FLDN26 • Florida Dentists 2025-2026

Table of Contents

FLDN26 • Florida Dentists 2025-2026

How to Receive Credit

NetCE 2 Hour Course #51334 • Medical Error Prevention and Root Cause Analysis

51334 • Medical Error Prevention and Root Cause Analysis

1. INTRODUCTION

2. DEFINING "MEDICAL ERROR"

3. ROOT CAUSE ANALYSIS PROCESS

4. ERROR REDUCTION AND PREVENTION

5. OTHER CONSIDERATIONS FOR PATIENT SAFETY

6. CONCLUSION

Works Cited

NetCE 2 Hour Course #57923 • Domestic Violence: The Florida Requirement

57923 • Domestic Violence: The Florida Requirement

1. INTRODUCTION

2. DEFINING DOMESTIC VIOLENCE

3. NATIONAL AND STATE STATISTICS AND LEGISLATION

4. IDENTIFYING GROUPS AT RISK FOR DOMESTIC VIOLENCE

5. CHARACTERISTICS OF PERPETRATORS OF DOMESTIC VIOLENCE

6. SCREENING FOR DOMESTIC VIOLENCE AND ABUSE

7. ASSESSING DOMESTIC VIOLENCE AND ABUSE

8. INTERVENTIONS FOR DOMESTIC VIOLENCE AND ABUSE

9. DOCUMENTATION AND FOLLOW-UP

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 2 Hour Course #55122 • Strategies for Appropriate Opioid Prescribing: The Florida Requirement

55122 • Strategies for Appropriate Opioid Prescribing: The Florida Requirement

1. INTRODUCTION

2. DEFINITIONS

3. EPIDEMIOLOGY OF CHRONIC PAIN AND OPIOID MISUSE

4. INITIATION AND MANAGEMENT OF THE PATIENT WITH PAIN

5. CRISIS INTERVENTION: MANAGEMENT OF OVERDOSE

6. COMPLIANCE WITH STATE AND FEDERAL LAWS

7. IDENTIFICATION OF DRUG DIVERSION/SEEKING BEHAVIORS

8. INTERVENTIONS FOR SUSPECTED OR KNOWN DRUG DIVERSION

9. CASE STUDY

10. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 8 Hour Course #56741 • Dental Treatment of Patients with Mental Disorders

56741 • Dental Treatment of Patients with Mental Disorders

1. INTRODUCTION

2. MOOD DISORDERS

3. ANXIETY DISORDERS

4. POST-TRAUMATIC STRESS DISORDER

5. SCHIZOPHRENIA

6. SOMATIC SYMPTOMS AND RELATED DISORDERS

7. SUBSTANCE USE DISORDERS

8. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 10 Hour Course #50201 • Botulinum Toxin and Dermal Fillers for Facial Aging

50201 • Botulinum Toxin and Dermal Fillers for Facial Aging

1. INTRODUCTION

2. TERMINOLOGY

3. BACKGROUND

4. THE PROCESSES OF FACIAL AGING

5. BOTULINUM TOXIN

6. SOFT TISSUE (DERMAL) FILLERS

7. DEOXYCHOLIC ACID

8. INDIVIDUALIZED ASSESSMENT AND TREATMENT PLANNING

9. THE MINIMALLY INVASIVE TREATMENT APPROACH

10. PATIENT SELECTION AND EVALUATION

11. ADVERSE EFFECTS

12. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

FLDN26 • Florida Dentists 2025-2026

Marjorie Conner Allen, BSN, JD

Alice Yick Flanagan, PhD, MSW

Mark Rose, BS, MA, LP

www.netce.com

Copyright © 2025 NetCE, All rights reserved.

FLDN26 • Florida Dentists 2025-2026

Expiration Date: 04/30/2026

How to Receive Credit

To complete this Special Offer for continuing education credit please go to http://www.netce.com/specials in your browser.

For assistance with receiving continuing education credit, please contact us at help@netce.com.

51334 • Medical Error Prevention and Root Cause Analysis

Marjorie Conner Allen, BSN, JD

www.netce.com

Copyright © 2022 NetCE, All rights reserved.

The Institute of Medicine's (IOM) 1999 publication To Err is Human: Building a Safer Health System, illuminated the unfortunate reality of medical errors in the healthcare industry. The report reviewed the prevalence of medical errors in the United States and highlighted measures that should be taken to prevent them. Specifically, the authors of the report noted that at least 44,000 and perhaps as many as 98,000 Americans were dying in hospitals each year as a result of medical errors. A 2016 report stated that the average number of annual in-hospital deaths attributable to medical error might actually be much higher, at around 400,000. Certainly, these numbers must be balanced against the millions of admissions to hospitals in the United States, which is in excess of 35 million annually. Healthcare professionals should commit to continuing to pay attention to evaluating current approaches for reducing errors and to building new systems to reduce the incidence of medical errors.

Table of Contents

51334 • Medical Error Prevention and Root Cause Analysis

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planner

Division Planner Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. DEFINING "MEDICAL ERROR"

3. ROOT CAUSE ANALYSIS PROCESS

FLORIDA LAW

4. ERROR REDUCTION AND PREVENTION

PATIENT FALLS

DELAYS IN TREATMENT

UNINTENDED RETENTION OF A FOREIGN BODY

WRONG-SITE SURGERY

PATIENT SUICIDE

OPERATIVE AND POSTOPERATIVE COMPLICATIONS

MEDICATION ERRORS

COMMON MISDIAGNOSES

5. OTHER CONSIDERATIONS FOR PATIENT SAFETY

USE OF AN INTERPRETER

6. CONCLUSION

Works Cited

51334 • Medical Error Prevention and Root Cause Analysis

Education Category. Management

Release Date. 09/01/2022

Review Date. 04/15/2025

Expiration Date. 08/31/2026

Course Overview

The Institute of Medicine's (IOM) 1999 publication To Err is Human: Building a Safer Health System, illuminated the unfortunate reality of medical errors in the healthcare industry. The report reviewed the prevalence of medical errors in the United States and highlighted measures that should be taken to prevent them. Specifically, the authors of the report noted that at least 44,000 and perhaps as many as 98,000 Americans were dying in hospitals each year as a result of medical errors. A 2016 report stated that the average number of annual in-hospital deaths attributable to medical error might actually be much higher, at around 400,000. Certainly, these numbers must be balanced against the millions of admissions to hospitals in the United States, which is in excess of 35 million annually. Healthcare professionals should commit to continuing to pay attention to evaluating current approaches for reducing errors and to building new systems to reduce the incidence of medical errors.

Audience

This course is designed for all licensed dental professionals.

Accreditations & Approvals

NetCE Nationally Approved PACE Program Provider for FAGD/MAGD credit. Approval does not imply acceptance by any regulatory authority or AGD endorsement. 10/1/2021 to 9/30/2027 Provider ID #217994. NetCE is an ADA CERP Recognized Provider. ADA CERP is a service of the American Dental Association to assist dental professionals in identifying quality providers of continuing dental education. ADA CERP does not approve or endorse individual courses or instructors, nor does it imply acceptance of credit hours by boards of dentistry. Concerns or complaints about a CE provider may be directed to the provider or to ADA CERP at www.ada.org/cerp. NetCE is approved as a provider of continuing education by the Florida Board of Dentistry, Provider #50-2405. NetCE is a Registered Provider with the Dental Board of California. Provider Number RP3841. Completion of this course does not constitute authorization for the attendee to perform any services that he or she is not legally authorized to perform based on his or her license or permit type.

Designations of Credit

NetCE designates this activity for 2 continuing education credits. AGD Subject Code 159. This course meets the Dental Board of California's requirements for 2 unit(s) of continuing education. Dental Board of California course #02-3841-25359.

Special Approvals

This course fulfills the Florida requirement for 2 hours of education on the Prevention of Medical Errors.

Course Objective

The purpose of this course is to satisfy the requirement of the Florida law and provide all licensed dental professionals with information regarding the root cause process, error reduction and prevention, and patient safety.

Learning Objectives

Upon completion of this course, you should be able to:

1. Describe how the Institute of Medicine defines "medical error."

2. Describe the types of sentinel events the Joint Commission has identified.

3. Discuss what factors must be included in a root cause analysis in order for the Joint Commission to consider it "thorough" and "credible."

4. Identify what types of adverse incidents must be reported to the Florida Agency for Healthcare Administration.

5. Identify the most common sentinel events reported to the Joint Commission.

6. Evaluate the most common misdiagnoses, as recognized by the Florida Board of Medicine, and outline the safety needs of special populations, including non-English-proficient patients.

Faculty

Marjorie Conner Allen, BSN, JD, received her Bachelor of Science in Nursing degree from the University of Florida, Gainesville, in 1984. She began her nursing career at Shands Teaching Hospital and Clinics at the University of Florida, Gainesville. While practicing nursing at Shands, she gave continuing education seminars regarding the nursing implications for dealing with adolescents with terminal illness. In 1988, Ms. Allen moved to Atlanta, Georgia where she worked at Egleston Children’s Hospital at Emory University in the bone marrow transplant unit. In the fall of 1989, she began law school at Florida State University. After graduating from law school in 1992, Ms. Allen took a two-year job as law clerk to the Honorable William Terrell Hodges, United States District Judge for the Middle District of Florida. After completing her clerkship, Ms. Allen began her employment with the law firm of Smith, Hulsey & Busey in Jacksonville, Florida where she has worked in the litigation department defending hospitals and nurses in medical malpractice actions. Ms. Allen resides in Jacksonville and is currently in-house counsel to the Mayo Clinic Jacksonville.

Faculty Disclosure

Contributing faculty, Marjorie Conner Allen, BSN, JD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planner

Mark J. Szarejko, DDS, FAGD

Division Planner Disclosure

The division planner has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

The Institute of Medicine's (IOM) 1999 publication To Err is Human: Building a Safer Health System, illuminated the unfortunate reality of medical errors in the healthcare industry. The report reviewed the prevalence of medical errors in the United States and highlighted measures that should be taken to prevent them. Specifically, the authors of the report noted that at least 44,000 and perhaps as many as 98,000 Americans were dying in hospitals each year as a result of medical errors and many more were being seriously injured [1]. They further noted that, even when using the lower estimate of 44,000, deaths in hospitals due to medical errors exceeded the annual deaths attributable to motor vehicle accidents (43,458), breast cancer (42,297), or AIDS (16,516) [1]. A 2016 report stated that the average number of annual in-hospital deaths attributable to medical error might actually be much higher, at around 400,000 [2]. This report places medical errors as the third leading cause of death in the United States. Certainly, these numbers must be balanced against the millions of admissions to hospitals in the United States, which is in excess of 33 million annually [1,3].

It does appear that some progress has been made in the past decade. The Agency for Healthcare Research and Quality found a 17% decline in hospital-acquired conditions between 2014 and 2017, or 910,000 fewer conditions and 20,500 fewer deaths than if the 2014 rate had remained steady [4]. Though the precise mechanism(s) responsible for this decline is not clear, it occurred following a concerted effort by federal agencies, organizations, and individual providers to curtail medical errors. However, the statistics indicate that medical errors continue to be an issue. Healthcare professionals should commit to continuing to pay greater attention to evaluating approaches for reducing errors and to building new systems to reduce the incidence of medical errors.

Spurred by a commitment to reducing medical error incidents, the Florida Legislature mandates that all healthcare professionals in Florida complete a two-hour course on the topic of prevention of medical errors [5]. This continuing education course is designed to satisfy the requirements of the Florida law and provide all licensed healthcare professionals with information regarding the root cause analysis process, error reduction and prevention, and patient safety, as well as information regarding the five most misdiagnosed conditions as determined by the Florida Board of Medicine.

2. DEFINING "MEDICAL ERROR"

The IOM Committee on Quality of Healthcare in America defines error as "the failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim" [1]. It is important to note that medical errors are not defined as intentional acts of wrongdoing and that not all medical errors rise to the level of medical malpractice or negligence. Errors depend on two kinds of failures: either the correct action does not proceed as intended, which is described as an "error of execution," or the original intended action is not correct, which is described as an "error of planning" [1]. A medical error can occur at any stage in the process of providing patient care, from diagnosis to treatment, and even while providing preventative care. Not all errors will result in harm to the patient. Medical errors that do result in injury are sometimes called preventable adverse events or sentinel events—sentinel because they signal the need for immediate investigation and response [6].

Preventable adverse events or sentinel events are defined as those events that cause an injury to a patient as a result of medical intervention or inaction on the part of the healthcare provider whereby the injury cannot reasonably be said to be related to the patient's underlying medical condition. Thus, for example, if a patient has a surgical procedure and dies postoperatively from pneumonia, the patient has suffered an adverse event. But was that adverse event preventable; was it caused by medical intervention or inaction? The specific facts of this case must be analyzed to determine whether the patient acquired the pneumonia as a result of poor handwashing techniques of the medical staff (i.e., an error of execution), which would indicate a preventable adverse event, or whether the patient acquired the pneumonia because of age and comorbidities, which would indicate a nonpreventable adverse event.

Healthcare professionals can learn much by closely scrutinizing and evaluating adverse events that lead to serious injury or death. The evaluation of such events would also enable healthcare professionals to improve the delivery of health care and reduce future mistakes. In addition, healthcare professionals should have a process in place to evaluate those instances in which a medical error occurred and did not cause harm to the patient. By reviewing these processes, healthcare professionals are afforded the unique opportunity to identify system improvements that have the potential to prevent future adverse events. The Joint Commission, recognizing the importance of analyzing both preventable adverse events and near-misses, has established guidelines for recognizing these events and requires healthcare facilities to conduct a root cause analysis to determine the underlying cause of the event [7].

3. ROOT CAUSE ANALYSIS PROCESS

The Joint Commission is a national organization with a mission to improve the quality of care provided at healthcare institutions in the United States. It accomplishes this mission by providing accredited status to healthcare facilities. Accreditors play an important role in encouraging and supporting actions within healthcare organizations by holding them accountable for ensuring a safe environment for patients. Healthcare organizations should actively engage in a cooperative relationship with the Joint Commission through this accreditation process and participate in the process to reduce risk and facilitate desired outcomes of care.

Root cause analysis, as defined by the Joint Commission, is "a process for identifying the basic or causal factors that underlie variation in performance, including the occurrence or possible occurrence of a sentinel event" [6]. In the 2022 update, the Joint Commission defines a sentinel event as a "patient safety event (not primarily related to the natural course of the illness or underlying condition) that reaches a patient and results in death, severe harm (regardless of duration of harm), or permanent harm (regardless of severity of harm)" [6,10]. Furthermore, the Joint Commission revision clarified the terms "severe" and "permanent" harm with regard to sentinel events. "Severe harm" is an event or condition that reaches the individual, resulting in life-threatening bodily injury (including pain or disfigurement) that interferes with or results in loss of functional ability or quality of life that requires continuous physiologic monitoring or a surgery, invasive procedure, or treatment to resolve the condition [6,10]."Permanent harm" is an event or condition that reaches the individual, resulting in any level of harm that permanently alters and/or affects an individual's baseline [6,10].

The following subsets of sentinel events are subject to review by the Joint Commission [6,11]:

- The event has resulted in an unanticipated death or major permanent loss of function, not related to the natural course of the patient's illness or underlying condition

or

- The event is one of the following (even if the outcome was not death or major permanent loss of function unrelated to the natural course of the patient's illness or underlying condition):

- Suicide of any patient receiving care, treatment, and services in a staffed around-the-clock care setting or within 72 hours of discharge

- Unanticipated death of a full-term infant

- Abduction of any patient receiving care, treatment, and services

- Any elopement (i.e., unauthorized departure) of a patient from a staffed around the-clock care setting (including the emergency department), leading to death, permanent harm, or severe temporary harm to the patient

- Discharge of an infant to the wrong family

- Rape, assault (leading to death or permanent loss of function), or homicide of any patient receiving care, treatment, and services

- Rape, assault (leading to death or permanent loss of function), or homicide of a staff member, licensed independent practitioner, visitor, or vendor while on site at the healthcare organization

- Hemolytic transfusion reaction involving administration of blood or blood products having major blood group incompatibilities (e.g., ABO, Rh, other blood groups)

- Invasive procedure, including surgery, on the wrong patient or wrong site

- Unintended retention of a foreign object in a patient after surgery or other invasive procedures

- Severe neonatal hyperbilirubinemia (bilirubin >30 mg/dL)

- Fluoroscopy resulting in permanent tissue injury when clinical and technical optimization were not implemented and/or recognized practice parameters were not followed

- Fire, flame, or unanticipated smoke, heat, or flashes occurring during an episode of patient care

- Any intrapartum (related to the birth process) maternal death

- Severe maternal morbidity

- Fall resulting in: any fracture; surgery, casting, or traction; required consult/management or comfort care for a neurological or internal injury; a patient with coagulopathy who receives blood products as a result of the fall; or death or permanent harm as a result of injuries sustained from the fall (not from physiologic events causing the fall)

Alternatively, the following examples are events that are NOT considered reviewable under the Joint Commission's sentinel event policy [6]:

- Any close call ("near miss")

- Full or expected return of limb or bodily function to the same level as prior to the adverse event by discharge or within two weeks of the initial loss of said function, whichever is the longer period

- Any sentinel event that has not affected a recipient of care (e.g., patient, individual, resident)

- Medication errors that do not result in death or major permanent loss of function

- Suicide other than in an around-the-clock care setting or following elopement from such a setting

- A death or loss of function following a discharge against medical advice

- Unsuccessful suicide attempts unless resulting in major permanent loss of function

- Minor degrees of hemolysis not caused by a major blood group incompatibility and with no clinical sequelae

For further definition of terms, please refer to the Joint Commission's Sentinel Event Policy and Procedures at https://www.jointcommission.org/resources/patient-safety-topics/sentinel-event/sentinel-event-policy-and-procedures.

As part of the accreditation requirement, the Joint Commission requires that healthcare organizations have a process in place to recognize these sentinel events, conduct thorough and credible root cause analyses that focus on process and system factors, and document a risk-reduction strategy and internal corrective action plan that includes measurement of the effectiveness of process and system improvements to reduce risk [6]. This process must be completed within 45 business days of the organization having become aware of the sentinel event.

The Joint Commission will consider a root cause analysis acceptable for accreditation purposes if it focuses primarily on systems and processes, not individual performance [6]. In other words, the healthcare organization should minimize the individual blame or retribution for involvement in a medical error. In addition, the root cause analysis should progress from special causes in clinical processes to common causes in organizational processes, and the analysis should repeatedly dig deeper by asking why, then, when answered, why again, and so on. The analysis should also identify changes that can be made in systems and processes, either through redesign or development of new systems or processes, which would reduce the risk of such events occurring in the future. The Joint Commission requires that the analysis be thorough and credible. To be considered thorough, the root cause analysis must include [6]:

- A determination of the human and other factors most directly associated with the sentinel event and the process(es) and systems related to its occurrence

- Analysis of the underlying systems and processes through a series of "why" questions to determine where redesign might reduce risk

- Inquiry into all areas appropriate to the specific type of event

- Identification of risk points and their potential contributions to this type of event

- A determination of potential improvement in processes or systems that would tend to decrease the likelihood of such events in the future, or a determination, after analysis, that no such improvement opportunities exist

To be considered credible, the root cause analysis must meet the following standards [6]:

- The organization's leadership and the individuals most closely involved in the process and systems under review must participate in the analysis.

- The analysis must be internally consistent; that is, it must not contradict itself or leave obvious questions unanswered.

- The analysis must provide an explanation for all findings of "not applicable" or "no problem."

- The analysis must include consideration of any relevant literature.

Finally, as previously discussed, after conducting this root cause analysis, the organization must prepare an internal corrective action plan. The Joint Commission will accept this action plan if it identifies changes that can be implemented to reduce risk or formulate a rationale for not undertaking such changes, and if, where improvement actions are planned, it identifies who is responsible for implementation, when the action will be implemented, and how the effectiveness of the actions will be evaluated [6].

FLORIDA LAW

Healthcare professionals have an obligation to report adverse events to leadership and ensure that organizations have processes in place to satisfy the Joint Commission requirement. In Florida, certain serious adverse incidents must also be reported to Florida's Agency for Health Care Administration (AHCA). Florida law requires that licensed facilities, such as hospitals, establish an internal risk management program. As part of that program, licensed facilities must develop and implement an incident reporting system, which requires the development of appropriate measures to minimize the risk of adverse incidents to patients, as well as imposes an affirmative duty on all healthcare providers and employees of the facility to report adverse incidents to the risk manager or to his or her designee. The risk manager must receive these incident reports within 3 business days of the incident, and depending on the type of incident, the risk manager may have to report the incident to AHCA within 15 days of receipt of the report.

Florida Statute 395.0197 specifically defines an adverse incident as [8]:

For purposes of reporting to the agency pursuant to this section, the term "adverse incident" means an event over which health care personnel could exercise control and which is associated in whole or in part with medical intervention, rather than the condition for which such intervention occurred, and which:

a) Results in one of the following injuries:

1. Death;

2. Brain or spinal damage;

3. Permanent disfigurement;

4. Fracture or dislocation of bones or joints;

5. A resulting limitation of neurological, physical, or sensory function which continues after discharge from the facility;

6. Any condition that required specialized medical attention or surgical intervention resulting from nonemergency medical intervention, other than an emergency medical condition, to which the patient has not given his or her informed consent; or

7. Any condition that required the transfer of the patient, within or outside the facility, to a unit providing a more acute level of care due to the adverse incident, rather than the patient's condition prior to the adverse incident

b) Was the performance of a surgical procedure on the wrong patient, a wrong surgical procedure, a wrong-site surgical procedure, or a surgical procedure otherwise unrelated to the patient's diagnosis or medical condition;

c) Required the surgical repair of damage resulting to a patient from a planned surgical procedure, where the damage was not a recognized specific risk, as disclosed to the patient and documented through informed-consent process; or

d) Was a procedure to remove unplanned foreign objects remaining from a surgical procedure.

In 2021, the Florida AHCA reported that a total of 184 deaths occurred as a result of hospital error, 21.4% of 859 adverse incidents reported for the year. The next most common incidents during this period were transfer of the patient to a unit providing a more acute level of care due to the adverse incident (18.7%), fracture or dislocation of bones or joints (17.0%), surgical procedures unrelated to the patient's diagnosis or medical needs (10.4%), surgical procedure to remove foreign object from a previous surgical procedure (10.2%), brain or spinal damage (5.0%), and surgical procedure performed on wrong site (4.3%) [9]. The following adverse incidents must be reported to the AHCA within 15 calendar days after their occurrence [8]:

- The death of a patient

- Brain or spinal damage to a patient

- The performance of a surgical procedure on the wrong patient

- The performance of a wrong-site surgical procedure

- The performance of a wrong surgical procedure

- The performance of a surgical procedure that is medically unnecessary or otherwise unrelated to the patient's diagnosis or medical condition

- The surgical repair of damage resulting to a patient from a planned surgical procedure, where the damage is not a recognized specific risk, as disclosed to the patient and documented through the informed-consent process

- The performance of procedures to remove unplanned foreign objects remaining from a surgical procedure

Each incident will be reviewed by the AHCA, who will then determine the penalty to be imposed upon the responsible party [8]. All Florida healthcare professionals who practice in licensed facilities should familiarize themselves with these requirements and ensure that the facility in which they practice has processes in place to ensure compliance.

Unlike Florida's mandatory reporting of serious adverse incidents, the Joint Commission recommends that healthcare organizations voluntarily report sentinel events, and it encourages the facilities to communicate the results of their root cause analyses and their corrective action plans. As a result of the sentinel events that have been reported, the Joint Commission has compiled Sentinel Event Alerts. These alerts are intended to provide healthcare organizations with important information regarding reported trends and, by doing so, highlight areas of potential concern so an organization may review its own internal processes to maximize error reduction and prevention with regard to a particular issue [7].

4. ERROR REDUCTION AND PREVENTION

Between 2005 and 2021, the Joint Commission reviewed 14,731 sentinel events [11]. Some events, such as fire, impacted multiple patients. Sentinel event reviews during this time period were frequently conducted for patient fall; delay in treatment; unintended retention of a foreign body; wrong-patient, wrong-site, wrong-procedure surgery; patient suicide; operative and postoperative complications; and medication error [11].

PATIENT FALLS

In 2021, the Joint Commission introduced a separate sentinel event line item for patient falls, making it the most frequently reported sentinel event that year. Patients who are at highest risk include the elderly, those who have an altered mental status due to chronic mental illness or acute intoxication, and those who have a history of prior falls. Additionally, the Joint Commission calls for an increased awareness to an under-recognized population at risk for falls. Newborns and infants are at risk for falls and/or drops, often due to maternal risk factors such as cesarean birth, use of pain medication within four hours, second or third postpartum night (specifically around midnight to early morning hours), and drowsiness associated with breastfeeding. It is obvious from these factors that a thorough and complete patient history may be the key to identifying those at risk.

The root causes of patient falls that healthcare facilities identified as sentinel events and reported to the Joint Commission included inadequate assessment; communication failures; lack of adherence to protocols and safety practices; inadequate staff orientation, supervision, staffing levels, or skill mix; deficiencies in the physical environment; and lack of leadership [19]. Risk reduction strategies to these root causes are fairly straightforward, although in practice, preventing falls is difficult. The most important are the use of a standardized assessment tool to identify fall and injury risk factors, assessing an individual patient's risks that may not have been captured through the tool, and interventions tailored to an individual patient's identified risks [19].

Because patient falls often result in morbidity, mortality, immobility, and early nursing home placement for patients, it is imperative that healthcare facilities initiate adequate fall prevention programs, which will ultimately reduce injuries. Failure to do so will result in a spiraling increase in the number of falls in healthcare facilities, particularly among the elderly who are at highest risk. As more Americans live beyond 65 years of age, the need to develop mobility protocols and programs to reduce the risk of falls and injuries for the older adult grows more urgent.

DELAYS IN TREATMENT

According to the Joint Commission, more than half of all reported delay in treatment sentinel events in 2010–2014 resulted in patient death [16]. It is important to keep in mind that delays in treatment can occur in any healthcare setting. The most common reason for a delay in treatment is misdiagnosis; however, delays can also result from delayed test results, lack of physician availability, delayed administration of ordered care, incomplete treatment, and even inability to get an initial appointment or follow-up appointment in a timely manner [16]. The main root causes contributing to delays in treatment are inadequate assessments, poor planning, communication failures, and human factors. Additionally, 48% of patients self-reported a delay in accessing healthcare during the COVID-19 pandemic. One study suggests that delays in treatment are likely due to widespread public health messages to avoid unnecessary visits, triage uncertainty, lack of providers, and lack of resources [36]. Recommendations from the Joint Commission include avoiding cognitive shortcuts, improving health information technology, incorporating diagnostic checklists into the electronic record, promoting provider-to-provider communication, engaging leadership in developing solutions, focusing organization attention on the scheduling process and on ordering tests and reporting test results, improving access to care, implementing a standardized communications method, maintaining adequate staffing levels, and increasing patient and family engagement/activation [16].

UNINTENDED RETENTION OF A FOREIGN BODY

In 2021, unintended retained foreign objects were the third most frequently reported sentinel event reported to the Joint Commission [11]. The prevalence of these events has remained relatively stable since 2009, indicating that preventing these errors remains difficult for practitioners and facilities. The most commonly retained items are sponges, followed by catheter guidewires and other (a broad category encompassing a wide variety of items) [11].

In addition to harming patients and contributing to distrust in the medical system, the unintended retention of foreign objects significantly contributes to patient care costs [13]. The average total cost of care related to unintended retained foreign objects is $166,000 to $200,000 [13].

According to the sentinel event data, the most common root causes of unintended retained foreign objects reported to the Joint Commission are [13]:

- The absence of policies and procedures

- Failure to comply with existing policies and procedures

- Problems with hierarchy and intimidation

- Failure in communication with physicians

- Failure of staff to communicate relevant patient information

- Inadequate or incomplete education of staff

WRONG-SITE SURGERY

Operating on the wrong part of a patient's body is an obvious sign that there is a problem in the operating room system. Interestingly, wrong-site surgery occurred more commonly in orthopedic procedures than in all other surgical specialties combined. The American Academy of Orthopaedic Surgeons takes this issue seriously, and it has taken special steps to eliminate the problem. For example, it recommends that a surgeon sign their initials at the correct site of surgery with an indelible pen. Unless the initials are visible, the surgeon should not make an incision [12]. Writing "NO" in large black letters on the side not to be operated on was suggested in the past, but this is discouraged due to possible confusion with the surgeon's initials. In spinal surgery, the Academy recommends that an intraoperative radiograph and radiopaque marker be used to determine the exact vertebral level of spinal surgery [12]. Whatever the mechanism used to prevent and reduce the incidence of this error, it is clear that this is not just the surgeon's problem. All operating room personnel, including physicians, nurses, technicians, anesthesiologists, and other preoperative allied health personnel, should monitor procedures to ensure verification procedures are followed, especially for high-risk procedures.

Due to the prevalence of wrong-site, wrong-procedure, and wrong-person surgeries, the Joint Commission, along with more than 50 professional healthcare organizations, convened two summits to help reduce the occurrence of these errors. The first summit, convened in 2003, developed a Universal Protocol that consisted of the following: a preprocedure verification process; marking the operative/procedure site with an indelible marker; taking a "time-out" with all team members immediately before starting the procedure; and adaptation of the requirements to all procedure settings, including bedside procedures. However, the incidence of wrong-site surgeries continued to increase, and in 2007 and 2010, additional summits were organized to pinpoint barriers in compliance and discover new strategies to eliminate these errors [14]. As of 2019, the Universal Protocol has been incorporated into the National Patient Safety Goal chapter of the Joint Commission accreditation manual [15].

PATIENT SUICIDE

It is estimated that between 48 and 65 hospital inpatient suicides occur per year in the United States. Most of these cases (31 to 52) occur in psychiatric units or involve psychiatric inpatients. The most common method is hanging [50]. Times of care transition are particularly risky, with a 200% increase in risk in the week after discharge from a psychiatric facility; the elevated risk continues for four years [18]. Other risk factors include previous suicide attempt or self-injury, mental or emotional disorders, history of trauma or loss, serious illness or chronic pain, substance use disorder, social isolation, and access to lethal means.

The most common root cause documented for patient suicide reported between 2010 and 2014 was shortcomings in assessment, most commonly psychiatric assessment [18]. In addition, nearly 25% of behavioral health facilities accredited by the Joint Commission were found noncompliant with the requirement to conduct an adequate suicide risk assessment in 2014.

The Joint Commission has recommended a number of suicide risk reduction strategies, including [18]:

- Review each patient's personal and family medical history for suicide risk factors.

- Screen all patients for suicide ideation, using a brief, standardized, evidence-based screening tool.

- Review screening questionnaires before the patient leaves the appointment or is discharged.

- Establish a collaborative, ongoing, and systematic assessment and treatment process with the patient involving the patient's other providers, family, and friends, as appropriate.

- To improve outcomes for at-risk patients, develop treatment and discharge plans that directly target suicidality.

- Educate all staff in patient care settings about how to identify and respond to patients with suicide ideation.

- Document decisions regarding the care and referral of patients with suicide risk.

A simple review of these measures demonstrates that healthcare providers can avoid the devastating impact of an inpatient suicide by implementing routine preventative strategies, such as removing harmful items and careful screening through the admission and discharge processes.

OPERATIVE AND POSTOPERATIVE COMPLICATIONS

Many of the sentinel events reported to the Joint Commission regarding operative and postoperative complications occurred in relation to nonemergent procedures, such as interventional imaging and/or endoscopy, tube or catheter insertion, open abdominal surgery, head and neck surgery, orthopedic surgery, and thoracic surgery [17]. The majority of the reporting healthcare facilities cited miscommunication as the primary root cause. Other identified causes include failure to follow established procedures, incomplete preoperative assessment, inconsistent postoperative monitoring procedures, and failure to question inappropriate orders. In order to reduce the risk, reporting facilities have identified a number of strategies, including improving staff orientation and training, increasing educational opportunities for physicians, clearly defining expected channels of communication, and monitoring consistency of compliance with procedures. Healthcare facilities should review postoperative patient monitoring procedures to ensure an adequate level appropriate to the needs of the patient, regardless of the setting (e.g., operating room, endoscopy suite, radiology department) [17]. Based upon these findings, it is clear that direct communication among healthcare providers is key to preventing operative and postoperative complications. Healthcare facilities should provide more staff education regarding preventative measures, and healthcare providers can do their part by engaging in a healthy and mutual respect for all of the members of the healthcare team [17].

MEDICATION ERRORS

Unquestionably, medication errors are one of the most common causes of avoidable harm to patients. These errors may occur at any of these critical points: when ordered or prescribed by a physician; during documentation; while transcribing; when dispensed by a pharmacist; when administered by a nurse; or during monitoring.

The National Coordinating Council for Medication Error Reporting and Prevention defines a medication error as [20]:

Any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional, patient or consumer. Such events may be related to professional practice, healthcare products, procedures, and systems, including prescribing: order communication; product labeling; packaging, and nomenclature; compounding; dispensing; distribution; administration; education; monitoring; and use.

It has been estimated that up to 50% of medication errors are caused by a provider writing the wrong medication, the wrong route or dose, or the wrong frequency, and nearly 75% of medication errors have been attributed to distraction of the care provider [24]. In addition, a number of medication errors can be linked to the prescriber who continually uses potentially dangerous abbreviations and dose expressions. Despite repeated warnings by the Institute for Safe Medication Practices about the dangers associated with using certain abbreviations when prescribing medications, this practice continues. To eliminate this factor, there are fairly simple steps that can eliminate much confusion. Prescribers should [21]:

- Avoid the use of the symbol "U" or "u" but rather spell "units" when ordering drugs, such as insulin.

- Spell out medication names completely rather than using abbreviations and acronyms.

- Avoid using abbreviations for "daily" (QD), "every other day" (QOD), or "four times daily" (QID), which are easily confused.

- Use leading zeros before a decimal point (e.g., 0.2 mg instead of .2 mg), and do not use trailing zeros (e.g., 2 mg instead of 2.0 mg).

- Write out "morphine sulfate" and "magnesium sulfate" instead of using the abbreviations (MS, MSO_4, MgSO_4).

The Institute for Safe Medication Practices publishes a list of error-prone abbreviations, symbols, and dose designations online at https://www.ismp.org/recommendations/error-prone-abbreviations-list.

Other factors contributing to prescriber errors are illegible or confusing handwriting and, a frequently cited cause of many adverse and sentinel events, the failure of healthcare providers to assess risk and prevent errors. Addressing illegibility may include developing appropriate policies and procedures, tracking and trending patterns, and evaluating results through peer review committees. Improving communication might include developing protocols for the use of verbal orders to assure that those from an onsite practitioner would be limited to an emergency situation only. No verbal orders should be taken for certain medications, such as for chemotherapy, and all verbal orders should be repeated for clarification and, whenever possible, reiterated to a third person. Another method of improving communication might involve reviewing the hospital formulary in collaboration with the Pharmacy and Therapeutics Committee of the medical staff to limit, where appropriate, the number of therapeutically and generically equivalent products [22].

It has been estimated that between 0.2% and 10% of prescriptions are dispensed incorrectly [23]. The three most common dispensing errors are: dispensing an incorrect medication, dosage strength, or dosage form; miscalculating a dose; and failing to identify drug interactions or contraindications [24]. Safe medication dispensing practices may include a number of risk reduction strategies to reduce the incidence of errors that may cause harm to patients [22,25,54,61]:

- Ensure that appropriate and current drug reference texts and/or online resources are immediately available to pharmacy personnel.

- Ensure that essential patient information, such as allergies, age, weight, current diagnoses, pertinent lab values, and current medication regimen, is available to the pharmacist prior to the dispensing of a new medication order.

- Require clarification of any order that is incomplete, illegible, or otherwise questionable using an established process for resolving questions.

- Whenever possible, dispense dosage units in a ready-to-administer form.

- Dispense single-dose vials and ampoules rather than multidose vials.

- Select oral rather than injectable routes, when possible.

- Require that a pharmacist double-check all mathematical calculations for neonatal and pediatric dilutions, parenteral nutrition solutions, and other compounded pharmaceutical products.

- Create an environment for the dispensing area that minimizes distractions and interruptions, provides appropriate lighting, air conditioning, and air flow, safe noise levels, and includes ergonomic consideration of equipment, fixtures, and technology.

- Require that a second pharmacist double-check the accuracy of order entry and dose calculations for all orders involving antineoplastic agents and other high-risk drugs dispensed by the pharmacy.

- Enhance the awareness of look-alike and sound-alike medications, and use warning signs to help differentiate medications from one another, especially when confusion exists between or among strengths, similar looking labels, or similar sounding names.

- Separate look-alike and sound-alike medications in pharmacy dispensing areas or consider repackaging or using different vendors.

- Follow-up and periodically evaluate the need for continued drug therapy for individual patients.

Once again, communication is likely the key to avoiding dispensing errors. Pharmacists should work closely with their staff to ensure that proper protocols are followed, and most importantly, when questions arise regarding a prescription, the pharmacist should take the time to contact the prescriber directly to obtain clarification.

The healthcare provider who has the responsibility to administer a medication has the final opportunity to avoid a mistake. In most cases, particularly in inpatient settings, this responsibility falls to the nurse. Nurses are often taught in nursing school to review the five "rights" prior to administering any medication: the right patient is given the right drug in the right dose by the right route at the right time [26]. Medication errors generally fall into four categories, which mimic these five "rights." The first is the failure to follow procedural safeguards, such as ensuring that essential patient information, including allergies, age, weight, and current medication regimen, is available. The second is unfamiliarity with a drug. In one case, a jury determined that a nurse was negligent for giving a drug without having reviewed the literature, which stated that the necessary precautions for the administration of the drug required the specialized skill of an anesthesiologist. The third category of drug administration is failure to use the correct mode of administration. A nurse in Delaware was held liable for administering a medication by injection after an order had been written to change the route to oral. The final category involves failure to obtain clarification if an order is incomplete, illegible, or otherwise questionable. In a case tried in Louisiana, a nurse was held liable for administering a medication that a physician ordered, notwithstanding that the dose was excessive. The nurse's administration of the drug led to the patient's death [27].

In addition, healthcare facilities should implement appropriate guidelines, policies, and procedures to ensure safe medication administration practice. These policies should require that staff members who administer medications [24,25,54,61]:

- Are knowledgeable about the drug's uses, precautions, contraindications, potential adverse reactions, interactions, and proper method of administration

- Resolve questions prior to medication administration

- Only administer medications that have been properly labeled with medication name, dose to be administered, dosage form, route, and expiration date

- Utilize a standard medication administration time schedule and receive education on how and when to incorporate newly started medication orders safely into the standardized schedule

- Have a second person verify a dosage calculation if a mathematical calculation of a dose is necessary

- Receive adequate education on the operation and use of devices and equipment used for medication administration (for example, patient-controlled anesthesia pumps and other types of infusion pumps)

- Have another person double-check infusion pump settings when critical, high-risk drugs are infused

- Document all medications immediately after administration

Finally, healthcare facilities should have proper quality assurance measures in place to monitor medication administration practices. Included among these would be protocols and guidelines for use with critical and problem-prone medications to help optimize therapies and minimize the possibility of adverse events and to integrate "triggers" to indicate the need for additional clinical monitoring [25].

It is important to note that the pediatric population is especially vulnerable to medication errors. When children are prescribed adult medications, care must be taken to adjust dosage according to weight, requiring the physician to use pediatric-specific calculations. Also, many healthcare settings are not trained to care for the pediatric patient. Intolerance due to physiologic immaturity is also a factor in adverse response to medications, and in many cases, this population cannot communicate their discomfort due to adverse reactions. Risk reduction strategies include standardizing and effectively identifying medications and processes for drug administration, ensuring pharmacy oversight, and using technology, such as medication dispensing programs, infusion pumps, and bar-coding, judiciously [28].

COMMON MISDIAGNOSES

As Florida healthcare professionals, it is important to be aware that in addition to wrong-site/wrong-procedure surgery, several medical conditions also continue to be misdiagnosed. As of 2024, the Florida Board of Medicine has determined the five most misdiagnosed conditions to be [29]:

- Oncology-related conditions

- Gastroenterology-related issues

- Cardiology-related issues

- Neurologic conditions

- Infectious disease-related conditions

It is important to be aware of the possibility of misdiagnosis and incorporate this knowledge into practice.

Oncology-Related Conditions

The early detection and diagnosis of cancers is crucial for selecting the appropriate treatment approach and to ensure an optimum outcome. However, an estimated 12% of cancer patients are initially misdiagnosed, and the missed or delayed diagnosis of cancers remains a significant cause of medical malpractice claims [30,31]. The causes of missed diagnoses vary widely among cancers in different parts of the body. In many cases, patients who do not fit the typical profile for a specific cancer (e.g., young age) may be underdiagnosed, and it is important that cancer is considered as part of the differential diagnosis in ambiguous cases [31,32,33]. In order to prevent missed or delayed cancer diagnosis, practitioners may take steps to ensure adherence to clinical guidelines for screening and diagnosis, use tools to facilitate communication, and engage strategies to ensure appropriate follow-up [55].

Gastroenterology-Related Conditions

Gasteroenterologic conditions may present with nonspecific complaints (e.g., abdominal pain, nausea) common to a variety of illnesses, complicating and delaying diagnosis. In one study of patients with pancreatic cancer, more than 30% were initially misdiagnosed, most commonly with gall bladder disease [58]. Diagnosis and screening for gastrointestinal disorders may be complicated by a lack of definitive test (e.g., irritable bowel syndrome) or by limits on screening recommendations (e.g., colorectal cancer). However, delayed diagnosis can lead to worsening conditions and poorer prognosis.

In general, gastrointestinal syndromes/symptoms may be classified into three general diagnostic categories: organic, motility, or functional disorders [59,60]. Functional GI disorders are idiopathic disorders of gut-brain interaction and, unlike organic and motility disorders, diagnosis involves identification of symptom clusters. As such, misdiagnosis is more common.

Another important consideration is GI symptom-specific anxiety, an important perpetuating factor that describes threatening interpretation and out-of-proportion behavioral response to GI sensations. This anxiety to real GI symptoms and the frequency of psychiatric comorbidity can lead to functional GI syndromes being dismissed as psychological or psychosomatic in nature.

Cardiology-Related Issues

The clinical presentation of chest pain has many possible etiologies, ranging from benign (e.g., panic/anxiety, pneumonia, peptic ulcer, gastroesophageal reflux disease, and pericarditis) to life-threatening (e.g., pulmonary embolism, acute coronary syndrome [ACS], aortic dissection, and pneumothorax). In many cases, it is best to rule out the more urgently threatening possibilities before testing for other causes.

Of the potentially life-threatening causes of chest pain, ACS is the most prevalent. Although a large percentage of individuals with suspected ACS will be seen initially in emergency departments, patients in any healthcare setting, regardless of other diagnoses, may abruptly develop chest pain suspicious for ACS. When a patient presents with clinical signs suspicious for myocardial infarction, immediate medical intervention is directed at confirming a diagnosis and stratifying the person's risk for adverse events such as cardiac arrest and severe/significant damage to the myocardium [41]. It is important to note that while some patients will present with classic ACS-related chest pain (tightness, sensation of pressure, heaviness, crushing, vise-like, aching pain in the substernal or upper left chest), many patients, particularly women and older patients, will present with "atypical" ACS-related chest pain [45,46]. Words commonly used to describe "atypical" chest pain associated with ACS include numbness, tingling, burning, stabbing, or pricking. Atypical chest pain location includes any area other than substernal or left sided, such as the back, area between shoulder blades, upper abdomen, shoulders, elbows, axillae, and ears [43,44,45,46]. Aside from atypical clinical presentation, other possible causes of missed ACS diagnosis include failure of interpretation of the history, failure to correctly interpret the electrocardiogram, failure to perform an electrocardiogram when necessary, and lack of proper use of cardiac enzyme test [47].

Neurologic-Related Conditions

Delayed or missed diagnoses of neurologic conditions may result in serious morbidity and mortality. Headaches are a common presenting condition in acute and primary care, and an estimated 5% of all patients admitted to emergency departments have neurologic symptoms [34]. Acute headache with neurologic symptoms may be misdiagnosed as stroke [35,64]. In addition, missed spinal fracture diagnoses are one of the leading causes of malpractice claims against radiologists [48].

One of the most common neurologic conditions is headache; however, it has been estimated that 50% of migraine patients remain undiagnosed or misdiagnosed, and only a small number (8% to 10%) of individuals with migraine take migraine-specific medications such as triptans or ergotamines [65,66]. Patients suffering from daily migraines may be misdiagnosed with chronic sinusitis or rhinitis and repeatedly and unsuccessfully treated with broad-spectrum antibiotics [62,63]. The diagnosis of migraine is based solely on a constellation of signs and symptoms, and a comprehensive medical and neurological examination is required to exclude secondary headache [56]. Useful evidence-based clinical guidelines for migraine screening have been developed and are summarized in the mnemonic POUND: pulsatile headache; one-day duration (4 to 72 hours); unilateral location; nausea or vomiting; and disabling intensity [57]. Competence of the clinician and effective communication with the patient play a crucial role in the diagnosis of migraine.

Infectious Disease-Related Conditions

Acute infection was the most commonly misdiagnosed disease in one study, with the potential adverse outcomes of sepsis, organ damage, and even death [37]. The presentation of infectious diseases may be atypical in certain populations (e.g., the elderly), making detection even more difficult. In one survey of physicians, delayed diagnoses were found to commonly occur with tuberculosis, nontuberculous mycobacterial infections, syphilis, epidural abscess, infective endocarditis, and endemic fungal infections (e.g., histoplasmosis, blastomycosis) [38]. Diseases with general symptoms and varied presentations (e.g., Lyme disease) also present complicated clinical pictures. Adherence to established guidelines for the diagnosis and treatment of specific infectious diseases and attentive patient assessment and history are recommended in order to improve diagnostic accuracy [39,40,42]. In addition, early consultation with an infectious disease specialist has been identified as potentially mitigating factor [38].

5. OTHER CONSIDERATIONS FOR PATIENT SAFETY

The most important issue to improving patient safety is being aware of the particular safety hazards that may exist for various patient populations and on particular specialty units. In addition, education of the patient and the family should be a priority.

Infants and young children are not developmentally or cognitively able to participate in care and decision making, thus putting them at higher risk, especially for medication errors. In addition, when a medication error occurs in this population, infants and young children are at higher risk because of their physical immaturity and increased sensitivity to the effects of drugs. The family or guardian of a pediatric patient should be encouraged to ask questions, especially if something seems wrong. In addition, a meta-analysis found that computerized provider order entry with clinical decision support reduced pediatric medication errors by 36% to 87% [51]. As such, the adoption of electronic support systems may help to reduce or eliminate these errors.

An estimated 30% of individuals 65 years of age or older who are living in the community fall each year [52]. Older patients may have poor vision, as a result of cataracts, glaucoma, and/or macular degeneration, and cardiovascular problems, which might result in syncope or postural hypotension. These conditions may affect patients' balance and stability. Bladder dysfunction, such as nocturia, may cause an elderly patient to have to ambulate more during the night in an unfamiliar environment, thereby increasing the risk of a fall. Lower extremity dysfunctions, such as arthritis, muscle weakness, or peripheral neuropathy, may make it more difficult to ambulate at any time. In addition to being at greater risk for falls, the elderly are also more prone to medication errors as their ability to understand instructions or to recognize an unfamiliar medication may be affected by dementia or other cognitive disorders. Interventions that can help prevent falls in the elderly include exercise programs, tai chi, vision improvement (e.g., first cataract surgery), and multifactorial assessment and intervention [52].

There are also unique factors that increase the risk of medical errors on specialty units. For instance, in critical care units, patients may be suffering from environmental psychosis, which could inhibit participation in their care. This is also true of lethargic and comatose patients. These patients are at particular risk because they cannot participate in the identification process. On psychiatric wards, patients may be suicidal or depressed, which may cause them to act out or attempt to harm themselves or others. Patients may also experience orthostatic side effects due to certain psychiatric medications, which may increase the incidence of falls. Obstetric patients are at higher risk for falls because they may have decreased sensation and mobility due to administration of epidural anesthesia, and they may also suffer from excessive blood loss, which could lead to postural hypotension [49]. Again, the key is identifying the unique needs of the particular population.

With regard to education, a number of organizations have developed guidelines to facilitate the role of patients as their own safety advocates. These guidelines are not intended to shift the burden of monitoring medical error to patients. Rather, they encourage patients to share responsibility for their own safety. As healthcare professionals, we should ensure that all of our patients are familiar with these guidelines. The Agency for Healthcare Research and Quality has developed a "Patient Fact Sheet" that outlines 20 tips for patients to help prevent medical errors [53]. Although some of these suggestions may seem extreme, many patients now desire to have a more active role in their care. Some of these items have become routine or are currently required, such as consultations by pharmacists when a patient picks up a prescribed medication.

USE OF AN INTERPRETER

As a result of the evolving racial and immigration demographics in the United States, interaction with patients for whom English is not a native language is inevitable. Because patient education is such a vital aspect of preventing medical errors, it is each practitioner's responsibility to ensure that information and instructions are explained in such a way that allows for patient understanding. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required.

Interpreters are more than passive agents who translate and transmit information back and forth from party to party. They should be professionally trained in ethics, accuracy, completeness, and impartiality. Furthermore, it is the interpreter's role to negotiate cultural differences and promote culturally responsive communication and practice. When they are enlisted and treated as part of the interdisciplinary clinical team, they serve as cultural brokers, who ultimately enhance the clinical encounter. In any case in which information regarding diagnostic procedures, treatment options, or medication/treatment measures is being provided, the use of an interpreter should be considered.

6. CONCLUSION

Although the United States has one of the top healthcare systems in the world, it is apparent that the numbers of medical errors are at unacceptably high levels. The consequences of medical errors are often more severe than the consequences of mistakes in other industries. They may lead to death or to serious and long-term disability, which underscores the need for aggressive action in this area. As a starting point, we should become an active part of the solution. This will only happen if all healthcare professionals voice their concerns when they identify problems in a system or process. In addition, we should actively participate in the root cause analysis process, understanding that the goal is not to assign blame, but rather to identify how we can improve the process to provide the best quality care to our patients. Medical errors are costly, not only because patients may lose their lives or livelihoods, but also because patients lose trust in the system and colleagues lose faith in each other. To preserve the integrity of our system, we must correct this problem, and the solution begins with each of us.

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57923 • Domestic Violence: The Florida Requirement

Marjorie Conner Allen, BSN, JD

Alice Yick Flanagan, PhD, MSW

www.netce.com

Copyright © 2022 NetCE, All rights reserved.

Domestic violence continues to be a prevalent problem in the United States today. Because of the number of individuals affected, it is likely that most healthcare professionals will encounter patients in their practice who are victims. Accordingly, it is essential that healthcare professionals are taught to recognize and accurately interpret behaviors associated with domestic violence. It is incumbent upon the healthcare professional to establish and implement protocols for early identification of domestic violence victims and their abusers. In order to prevent domestic violence and promote the well-being of their patients, healthcare professionals in all settings must take the initiative to properly assess all women for abuse during each visit and, for those women who are or may be victims, to offer education, counseling, and referral information.

Table of Contents

57923 • Domestic Violence: The Florida Requirement

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planner

Division Planner Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. DEFINING DOMESTIC VIOLENCE

3. NATIONAL AND STATE STATISTICS AND LEGISLATION

FLORIDA

4. IDENTIFYING GROUPS AT RISK FOR DOMESTIC VIOLENCE

PREGNANT WOMEN

CHILDREN

ELDERLY

MEN

LESBIAN, GAY, BISEXUAL, TRANSGENDER, AND QUEER/QUESTIONING VICTIMS

5. CHARACTERISTICS OF PERPETRATORS OF DOMESTIC VIOLENCE

6. SCREENING FOR DOMESTIC VIOLENCE AND ABUSE

7. ASSESSING DOMESTIC VIOLENCE AND ABUSE

CULTURALLY SENSITIVE ASSESSMENT

8. INTERVENTIONS FOR DOMESTIC VIOLENCE AND ABUSE

9. DOCUMENTATION AND FOLLOW-UP

Works Cited

Evidence-Based Practice Recommendations Citations

57923 • Domestic Violence: The Florida Requirement

Education Category. Ethics - Human Rights

Release Date. 08/01/2022

Review Date. 04/15/2025

Expiration Date. 07/31/2026

Course Overview

Domestic violence continues to be a prevalent problem in the United States today. Because of the number of individuals affected, it is likely that most healthcare professionals will encounter patients in their practice who are victims. Accordingly, it is essential that healthcare professionals are taught to recognize and accurately interpret behaviors associated with domestic violence. It is incumbent upon the healthcare professional to establish and implement protocols for early identification of domestic violence victims and their abusers. In order to prevent domestic violence and promote the well-being of their patients, healthcare professionals in all settings must take the initiative to properly assess all women for abuse during each visit and, for those women who are or may be victims, to offer education, counseling, and referral information.

Audience

This course is designed for all Florida dental professionals required to complete domestic violence education.

Accreditations & Approvals

NetCE Nationally Approved PACE Program Provider for FAGD/MAGD credit. Approval does not imply acceptance by any regulatory authority or AGD endorsement. 10/1/2021 to 9/30/2027 Provider ID #217994. NetCE is an ADA CERP Recognized Provider. ADA CERP is a service of the American Dental Association to assist dental professionals in identifying quality providers of continuing dental education. ADA CERP does not approve or endorse individual courses or instructors, nor does it imply acceptance of credit hours by boards of dentistry. Concerns or complaints about a CE provider may be directed to the provider or to ADA CERP at www.ada.org/cerp. NetCE is approved as a provider of continuing education by the Florida Board of Dentistry, Provider #50-2405. NetCE is a Registered Provider with the Dental Board of California. Provider Number RP3841. Completion of this course does not constitute authorization for the attendee to perform any services that he or she is not legally authorized to perform based on his or her license or permit type.

Designations of Credit

NetCE designates this activity for 2 continuing education credits. AGD Subject Code 156. This course meets the Dental Board of California's requirements for 2 unit(s) of continuing education. Dental Board of California course #02-3841-25358.

Special Approvals

This course fulfills the Florida requirement for 2 hours of Domestic Violence education every third renewal period.

Course Objective

The purpose of this course is to enable dental professionals in all practice settings to define domestic violence and identify those who are affected by domestic violence in the United States. This course describes how a victim can be accurately diagnosed and identifies the community resources available in the state of Florida for domestic violence victims.

Learning Objectives

Upon completion of this course, you should be able to:

1. Define domestic violence and its impact on health care.

2. Cite the general prevalence of domestic violence on a national and state level and identify state laws pertaining to the issue.

3. Describe how to screen and assess individuals who may be victims or perpetrators of domestic violence, including the importance of conducting a culturally sensitive assessment.

4. Identify community resources presently available for domestic violence victims and their perpetrators throughout Florida concerning legal aid, shelter, victim and batterer counseling, and child protection services.

Faculty

Marjorie Conner Allen, BSN, JD, received her Bachelor of Science in Nursing degree from the University of Florida, Gainesville, in 1984. She began her nursing career at Shands Teaching Hospital and Clinics at the University of Florida, Gainesville. While practicing nursing at Shands, she gave continuing education seminars regarding the nursing implications for dealing with adolescents with terminal illness. In 1988, Ms. Allen moved to Atlanta, Georgia where she worked at Egleston Children’s Hospital at Emory University in the bone marrow transplant unit. In the fall of 1989, she began law school at Florida State University. After graduating from law school in 1992, Ms. Allen took a two-year job as law clerk to the Honorable William Terrell Hodges, United States District Judge for the Middle District of Florida. After completing her clerkship, Ms. Allen began her employment with the law firm of Smith, Hulsey & Busey in Jacksonville, Florida where she has worked in the litigation department defending hospitals and nurses in medical malpractice actions. Ms. Allen resides in Jacksonville and is currently in-house counsel to the Mayo Clinic Jacksonville.

Alice Yick Flanagan, PhD, MSW, received her Master’s in Social Work from Columbia University, School of Social Work. She has clinical experience in mental health in correctional settings, psychiatric hospitals, and community health centers. In 1997, she received her PhD from UCLA, School of Public Policy and Social Research. Dr. Yick Flanagan completed a year-long post-doctoral fellowship at Hunter College, School of Social Work in 1999. In that year she taught the course Research Methods and Violence Against Women to Masters degree students, as well as conducting qualitative research studies on death and dying in Chinese American families.

Previously acting as a faculty member at Capella University and Northcentral University, Dr. Yick Flanagan is currently a contributing faculty member at Walden University, School of Social Work, and a dissertation chair at Grand Canyon University, College of Doctoral Studies, working with Industrial Organizational Psychology doctoral students. She also serves as a consultant/subject matter expert for the New York City Board of Education and publishing companies for online curriculum development, developing practice MCAT questions in the area of psychology and sociology. Her research focus is on the area of culture and mental health in ethnic minority communities.

Faculty Disclosure

Contributing faculty, Marjorie Conner Allen, BSN, JD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Contributing faculty, Alice Yick Flanagan, PhD, MSW, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planner

Mark J. Szarejko, DDS, FAGD

Division Planner Disclosure

The division planner has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

Domestic violence continues to be a prevalent problem in the United States today. Because of the number of individuals affected, it is likely that most healthcare professionals will encounter patients in their practice who are victims. Accordingly, it is essential that healthcare professionals are taught to recognize and accurately interpret behaviors associated with domestic violence. It is incumbent upon the healthcare professional to establish and implement protocols for early identification of domestic violence victims and their abusers. In order to prevent domestic violence and promote the well-being of their patients, healthcare professionals in all settings should take the initiative to properly assess all women for abuse during each visit and, for those women who are or may be victims, to offer education, counseling, and referral information.

Victims of domestic violence suffer emotional, psychologic, and physical abuse, all of which can result in both acute and chronic signs and symptoms of physical and mental disease, illness, and injury. Frequently, the injuries sustained require abused victims to seek care from healthcare professionals immediately after their victimization. Subsequently, physicians and nurses are often the first healthcare providers that victims encounter and are in a critical position to identify domestic violence victims in a variety of clinical practice settings where victims receive care. Accordingly, each healthcare professional should educate himself or herself to enhance awareness of the presence of abuse victims in his or her particular practice or clinical setting.

Specifically, healthcare professionals should be aware of the signs and symptoms associated with domestic violence. In addition, when family violence cases are identified, there should be a plan of action that includes providing information on, and referral to, local community resources related to legal aid, sheltering, victim counseling, batterer counseling, advocacy groups, and child protection.

2. DEFINING DOMESTIC VIOLENCE

Domestic violence, which is sometimes also referred to as spousal abuse, battering, or intimate partner violence (IPV), refers to the victimization of an individual with whom the abuser has or has had an intimate or romantic relationship. Researchers in the field of domestic violence have not agreed on a uniform definition of what constitutes violence or an abusive relationship. The Centers for Disease Control and Prevention (CDC) defines IPV as, "violence or aggression that occurs in a romantic relationship" [1]. According to the Florida Department of Children and Families, domestic violence is "a pattern of abusive behaviors that adults use to maintain power and control over their intimate partners or former partners. People who abuse their partners use a variety of tactics to coerce, intimidate, threaten, and frighten their victims" [2]. Domestic violence may include physical violence, sexual violence, emotional abuse, economic abuse, isolation, pet abuse, threats relating to children, and a variety of other behaviors meant to increase fear, intimidation, and power over the victim [2]. Florida law defines domestic violence as "any assault, aggravated assault, battery, aggravated battery, sexual assault, sexual battery, stalking, aggravated stalking, kidnapping, false imprisonment, or any criminal offense resulting in physical injury or death of one family or household member by another family or household member" [3]. Family or household members, according to Florida definition, must "be currently residing or have in the past resided together in the same single dwelling unit" [3]. Domestic violence knows no boundaries. It occurs in intimate relationships regardless of race, religion, culture, or socioeconomic status [2].

Whatever the definition, it is important for healthcare professionals to understand that domestic violence, in the form of emotional and psychologic abuse, sexual abuse, and physical violence, is prevalent in our society. Because of the similar nature of the definitions, this course will use the terms "domestic violence" and "IPV" interchangeably.

3. NATIONAL AND STATE STATISTICS AND LEGISLATION

Domestic violence is one of the most serious public health problems in the United States [4]. More than 36.4% of women and 33.6% of men have a lifetime history of IPV [4]. In Florida, the weighted lifetime prevalence of IPV (including rape, physical violence, and/or stalking) is 37.4% among women and 29.3% among men [5]. Although many of these incidents are relatively minor and consist of pushing, grabbing, shoving, slapping, and hitting, IPV resulted in approximately 1,500 deaths in the United States in 2019, with 214 of those deaths occurring in Florida in the same year. Statistics indicate a slightly higher rate in 2020, with 217 deaths in Florida in 2020 [7,8]. One of the difficulties in addressing the problem is that abuse is prevalent in all demographics, regardless of age, ethnicity, race, religious denomination, education, or socioeconomic status [2].

Victims of abuse often suffer severe physical injuries and will likely seek care at a hospital or clinic. The health and economic consequences of domestic violence are significant. Statistics vary from report to report, and due to the lack of studies on the national cost of domestic violence, the U.S. Congress funded the CDC to conduct a study to determine the cost of domestic violence on the healthcare system [9]. The 2003 CDC report, which relied on data from the National Violence Against Women Survey conducted in 1995, estimated the costs of IPV by measuring how many female victims were nonfatally injured; how many women used medical and mental healthcare services; and how many women lost time from paid work and household chores. The estimated total annual cost of IPV against women in the 1995 survey was more than $5.8 billion [9]. When updated to 2017 dollars, the amount was more than $9.3 billion annually. The costs associated with IPV at this time would be considerably more, but no further studies have been conducted [10]. It should be noted that the costs of any one victimization may continue for years; therefore, these statistics most likely underestimate the actual cost of IPV [9].

The national rate of nonfatal domestic violence against women declined 72% between 1993 and 2011 [11]. The rate of overall violent crime fell by nearly 60% in this same time period [11]. Studies reveal that several factors may have contributed to the reduction in violence, including a decline in the marriage rate and decrease of domesticity, better access to federally funded domestic violence shelters, improvements in women's economic status, and demographic trends, such as the aging of the population [13,14]. Of note, declines in the economy and stress associated with financial hardship and unemployment are significant contributors to IPV in the United States. Following the economic downturn in late 2008, there was a significant increase in the use of the National Domestic Violence Hotline in 2009, with more than half of victims reporting a change in household financial situation in the last year [15]. This trend continued with the COVID-19 pandemic, with stressors from lockdown orders, unemployment, financial insecurity, childcare and homeschool responsibilities, and poor coping strategies (e.g., substance abuse) increasing the rate of domestic violence. Reports showed a 9.7% increase in domestic violence calls for service in the first two months state-mandated lockdowns were imposed; furthermore, the National Commission on COVID-19 and Criminal Justice reported an increase of 8.1% in domestic violence incidents within the first months of mandated stay-at-home orders [6].

FLORIDA

In response to troubling domestic violence statistics, Governor Lawton Chiles appointed a Task Force on Domestic Violence on September 28, 1993, to investigate the problems associated with domestic violence in Florida and to compile recommendations as to how the problems should be approached and ultimately resolved. On January 31, 1994, the Task Force issued its first report on domestic violence. This report recommended standards to accurately measure the extent of domestic violence and strategies for increasing public awareness and education. It identified programs and resources that are available to victims in Florida, made legislative and budgetary suggestions for needed changes, provided a methodology for implementing these changes, and identified areas of domestic violence that require further study.

As a result of this report, Florida enacted legislation during the 1995 session implementing various suggestions of the Task Force. Specifically, the Legislature amended Section 455.222 of the Florida Statutes to require that all physicians, osteopaths, nurses, dentists, dental hygienists, midwives, psychologists, and psychotherapists obtain, as part of their biennial continuing education requirements, a one-hour continuing education course on domestic violence [17]. In June of 2006, Governor Jeb Bush signed into law House Bill 699. The bill, which went into effect July 1, 2006, changed the domestic violence continuing education requirement from one hour every renewal period to two hours every third renewal period.

In 1997, at the request of the Governor's Task Force, a workgroup was established by the Florida Department of Law Enforcement (FDLE) to evaluate the feasibility of tracking incidents of domestic violence in the state [18]. This resulted in the creation of the Domestic Violence Data Resource Center (DVDRC). The original mission of the DVDRC was to collect information related to domestic violence and to report and maintain the information in a statewide tracking system [19]. Domestic Violence Fatality Review Teams were established to examine those cases of domestic violence that resulted in a fatality and identify potential changes in policy or procedure that might prevent future deaths. The teams were comprised of representatives from law enforcement, the courts, social services, state attorneys, domestic violence centers, and others who may come into contact with domestic violence victims and perpetrators [20]. In 2000, the creation of Florida Statute 741.316 required the FDLE to annually publish a report based on the data gathered by the Fatality Review Teams [19]. Due to budgetary constraints, responsibility of compiling this data transferred to the Department of Children and Families in 2008 [21].

As part of Governor Jeb Bush's initiative, the "Family Protection Act" was signed into law in 2001. The act requires a 5-day mandatory jail term for any crime of domestic battery in which the perpetrator deliberately injures the victim. The law also makes a second battery crime a felony offense, treating offenders as serious criminals. Additional legislation, signed into law in 2002, includes Senate Bills 716 and 1974. Senate Bill 716 protects domestic violence victims by including dating relationships of six months in the definition of domestic violence laws. Senate Bill 1974 requires judges to inform victims of their rights, including the right to appear, be notified, seek restitution, and make a victim-impact statement. Governor Bush also created the Violence Free Florida campaign to increase public awareness of domestic violence issues [22].

In 2003, Governor Bush signed House Bill 1099, which transferred funding authority of the Florida Domestic Violence Trust Fund from the Department of Children and Families to the Florida Coalition Against Domestic Violence. According to the Domestic Violence in Florida 2010–2011 Annual Report to the Legislature, this has strengthened domestic violence services provided by streamlining the process of allocating funds [23].

In 2007, the Domestic Violence Leave Act was signed into law by Governor Charlie Crist [21]. This law requires employers with 50 or more employees to provide guaranteed leave for domestic violence issues.

In 2020, the FDLE reported 106,736 domestic violence offenses [8]. In general, domestic violence rates have been declining since 1998. An estimated 19.5% of domestic violence incidents involved spouses and 27.8% involved cohabitants; 11.6% of the victims were parents of the offenders. Domestic violence offenses resulted in the death of 217 victims in Florida in 2020, a number that has been decreasing since 2014 [8]. Domestic violence accounted for 16.9% of the state's murders in 2020 [8].

In their 2019 Annual Report, Fatality Review Teams summarized 31 cases of domestic violence fatalities and near fatalities [49]. The most significant findings included the following observations [49]:

- The perpetrators were predominantly male (94%) with female victims (90%) and had prior criminal histories, non-domestic-violence-related (67%) and for domestic violence specifically (69%).

- In 31% of fatalities, the perpetrators had a known "do not contact" order filed against them, and 13% of perpetrators had a known permanent injunction for protection against them filed by someone other than the victim.

- Substance abuse histories by the perpetrator was identified in 77% of the cases and diagnosed mental health disorders in 45%.

- In most cases, neither the decedent nor perpetrator sought help from the various intervention programs available to them.

To obtain a copy of the most current Florida Statewide Domestic Violence Fatality Review report, please visit https://www.myflfamilies.com/service-programs/domestic-violence/publications.shtml.

4. IDENTIFYING GROUPS AT RISK FOR DOMESTIC VIOLENCE

Healthcare professionals are in a critical position to identify domestic violence victims in a variety of clinical practice settings. Nurses are often the first healthcare provider a victim of domestic violence will encounter in a healthcare setting and should therefore be prepared to provide care and support for these victims. Although women are most often the victims, domestic violence extends to others in the household as well. For example, domestic violence includes abused men, children abused by their parents or parents abused by their children, elder abuse, and abuse among siblings [3].

Many victims of abuse sustain injuries that lead them to present to hospital emergency departments. Research has found that 49.6% of women seen in emergency departments reported a history of abuse and 44% of women who were ultimately killed by their abuser had sought help in an emergency department in the two years prior to their death [25,50]. Another study of 993 police-identified female victims of IPV found that only 28% of the women were identified in the emergency department as being victims of IPV [26]. These alarming statistics demonstrate that healthcare professionals who work in acute care, such as hospital emergency rooms, should maintain a high index of suspicion for battering of the patients that they see. Healthcare professionals who work in these settings should work with hospital administrators to establish and institute assessment mechanisms to accurately detect these victims.

For every victim of abuse, there is also a perpetrator. Like their victims, perpetrators of domestic violence come from all socioeconomic backgrounds, races, religions, and walks of life [1,4]. Accordingly, healthcare professionals should likewise be aware that seemingly supportive family members may, in fact, be abusers.

PREGNANT WOMEN

Because a gynecologist or obstetrician is frequently a woman's primary care physician, the American College of Obstetricians and Gynecologists (ACOG) recommends that all women be routinely assessed for signs of IPV (i.e., physical and psychologic abuse, reproductive coercion, and progressive isolation), including during prenatal visits, and providers should offer support and referral information for those being abused [25]. According to the ACOG, IPV affects as many as 324,000 pregnant women each year [25]. A meta-analysis of 92 independent studies found that the average reported prevalence of emotional abuse during pregnancy was 28.4%, physical abuse was 13.8%, and sexual abuse was 8% [51]. As with all domestic violence statistics, these estimates are presumed to be lower than the actual incidence as a result of under-reporting and lack of data on women whose pregnancies ended in fetal or maternal death. This makes IPV more prevalent among pregnant women than some of the health conditions included in prenatal screenings, including pre-eclampsia and gestational diabetes [25]. Because 96% of pregnant women receive prenatal care, this is an optimal time to assess for domestic violence and develop trusting relationships with the women. Possible factors that may predispose pregnant women to IPV include being unmarried, lower socioeconomic status, young maternal age, unintended pregnancy, delayed prenatal care, lack of social support, and use of tobacco, alcohol, or illegal drugs [25,51].

The overarching problem of violence against pregnant women cannot be ignored, especially as both mother and fetus are at risk. At this particularly vulnerable time in a woman's life, an organized clinical construct leading to immediate diagnosis and medical intervention will ensure that therapeutic opportunities are available to the pregnant woman and will reduce the potential negative outcomes [29]. Healthcare professionals should also be aware of the possible psychologic consequences of abuse during pregnancy. There is a higher risk of stress, depression, and addiction to alcohol and drugs in abused women. These conditions may result in damage to the fetus from tobacco, drugs, and alcohol and a loss of interest on the part of the mother in her or her baby's health [16,30]. Possible direct injuries to the fetus may result from maternal trauma [25].

Control of reproductive or sexual health is also a recognized trend in IPV. This type of abuse includes trying to impregnate or become pregnant against a partner's wishes, refusal to use birth control (e.g., condoms, oral contraceptives), or stopping a partner from using birth control [4].

CHILDREN

Children exposed to family violence are at high risk for abuse and for emotional damage that may affect them as they grow older. The Department of Justice estimates that of the 76 million children in the United States, 46 million will be exposed to some type of violence during their childhood [52]. Results of the National Survey of Children's Exposure to Violence indicated that 11% of children were exposed to IPV at home within the last year, and as many as 26% of children were exposed to at least one form of family violence during their lifetimes [31]. Of those children exposed to IPV, 90% were direct eyewitnesses of the violence; the remaining children were exposed by either hearing the violence or seeing or being told about injuries [31]. Of note, according to Florida criminal law, witnessing domestic violence is defined as "violence in the presence of a child if an offender is convicted of a primary offense of domestic violence, and that offense was committed in the presence of a child under age 16 who is a family or household member with the victim or perpetrator" [32].

A number of studies indicate that child witnesses are at increased risk for post-traumatic stress disorder, impaired development, aggressive behavior, anxiety, difficulties with peers, substance abuse, and academic problems than the average child [33,54,55]. Children exposed to violence may also be more prone to dating violence (as a perpetrator or a victim), and the ability to effectively cope with partnerships and parenting later in life may be affected, continuing the cycle of violence into the next generation [34,56].

In addition to witnessing violence, various studies have shown that these children may also become direct victims of violence, and children who both witness and experience violence are at the greatest risk for adverse psychosocial outcomes [53]. Research indicates that between 30% and 65% of husbands who batter their wives also batter their children [27,35]. Moreover, victims of abuse will often turn on their children; statistics demonstrate that 85% of domestic violence victims abuse or neglect their children. The 2020 Crime in Florida report found that more than 13% of domestic homicide victims were children killed by a parent [8]. Teenage children are also victimized. According to the U.S. Department of Justice, between 1980 and 2008, 17.5% of all homicides against female adolescents 12 to 17 years of age were committed by an intimate partner [36]. Among young women (18 to 24 years of age), the rate is estimated to be 43% in the United States and 8% to 57% globally. Abused teens often do not report the abuse. Individuals 12 to 19 years of age report only 35.7% of crimes against them, compared with 54% in older age groups [28,37]. Accordingly, healthcare professionals who see young children and adolescents in their practice (e.g., pediatricians, family physicians, school nurses, pediatric nurse practitioners, community health nurses) should have the tools necessary to detect these "silent victims" of domestic violence and to intervene quickly to protect young children and adolescents from further abuse. Without such critical intervention, the cycle of violence will never end.

ELDERLY

Abused and neglected elders, who may be mistreated by their spouses, partners, children, or other relatives, are among the most isolated of all victims of family violence. In a national study conducted by the National Institute of Justice in 2010, 4.6% of participants (community dwelling adults 60 years of age or older) were victims of emotional abuse in the past year, 1.6% physical abuse, 0.6% sexual abuse, 5.1% potential neglect, and 5.2% current financial abuse by a family member [38]. A 2017 study found a self-reported incidence of 11.6% psychological abuse, 2.6% physical abuse, 6.8% financial abuse, 4.2% neglect, and 0.9% sexual abuse [59]. The estimated annual incidence of all elder abuse types is 2% to 10%, but it is believed to be severely under-measured. According to one study, only 1 in 24 cases of elder abuse are reported to the authorities [39].

The prevalence rate of elder abuse in institutional settings is not clear. However, in a 2019 review of nine studies, 64% of elder care facility staff disclosed to having perpetrated abuse against an elderly resident in the past year [40]. In a random sample survey, 24.3% of respondents reported at least one incident of elder physical abuse perpetrated by a nursing home staff member [57].

Evidence Based Practice Recommendation

The U.S. Preventive Services Task Force concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for abuse and neglect in all older or vulnerable adults.

https://jamanetwork.com/journals/jama/fullarticle/2708121

Last Accessed: July 26, 2022

Strength of Recommendation: I (Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.)

As healthcare professionals in Florida, which leads the nation in percentage of older residents, it is important to understand that the needs of older Floridians will increase as will the numbers of elder victims of domestic violence. Because elder abuse can occur in family homes, nursing homes, board and care facilities, and even medical facilities, healthcare professionals should remain keenly aware of the potential for abuse. When abuse occurs between elder partners, it is primarily manifested in one of two ways: either as a long-standing pattern of marital violence or as abuse originating in old age. In the latter case, abuse may be precipitated by issues related to advanced age, including the stress that accompanies disability and changing family relationships [39].

It is important to understand that the domestic violence dynamic involves not only a victim but a perpetrator as well. For example, an adult son or daughter who lives in the parents' home and depends on the parents for financial support may be in a position to inflict abuse. This abuse may not always manifest itself as violence but can lead to an environment in which the elder parent is controlled and isolated. The elder may be hesitant to seek help because the abuser's absence from the home may leave the elder without a caregiver [39]. Because these elderly victims are often isolated, dependent, infirm, or mentally impaired, it is easy for the abuse to remain undetected. Healthcare professionals in all settings should remain aware of the potential for abuse and keep a watchful eye on this particularly vulnerable group.

MEN

Statistics confirm that domestic violence is predominantly perpetrated by men against women; however, there is evidence that women also exhibit violent behavior against their male partners [4]. Studies demonstrate approximately 5% of homicides against men are perpetrated by intimate partners [36]. It is persuasively argued that the impact on the health of female victims of domestic violence is generally much more severe than the impact on the health of male victims [42]. Approximately 512,770 women were raped and/or physically assaulted by an intimate partner in 2008, compared to 101,050 men [58]. In addition, 1 in 4 women has been physically assaulted, raped, and/or stalked by an intimate partner, compared with 1 out of every 10 men [1]. Rape, non-contact unwanted sexual experiences, and stalking against men are primarily perpetrated by other men, while other forms of violence against men were perpetrated mostly by women [5]. Male victims of IPV experienced 3 victimizations per 1,000 boys and men 12 years of age or older in 1994, and this rate decreased by 64%, to 1.1 per 1,000, in 2010 [11]. Of all homicides committed against men between 1980 and 2008, 7.1% were committed by an intimate partner [36]. Although women are more often victims of IPV, healthcare professionals should always keep in mind that men can also be victimized and assess accordingly.

LESBIAN, GAY, BISEXUAL, TRANSGENDER, AND QUEER/QUESTIONING VICTIMS

Domestic violence exists in lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) communities, and the rates are thought to mirror those of heterosexual women—approximately 25% [43]. However, women living with female intimate partners experience less IPV than women living with men [8]. Conversely, men living with male intimate partners experience more IPV than do men who live with female intimate partners [8]. In addition, 78% of IPV homicide victims reported in 2017 were transgender women or cisgender men [24]. This supports other statistics indicating that IPV is perpetrated primarily by men. A form of abuse specific to the gay community is for an abuser to threaten or to proceed with "outing" a partner to others [41,43].

Transgender individuals appear to be at particular risk for violence. According to a large national report, transgender victims of IPV were 1.9 times more likely to experience physical violence and 3.9 times more likely to experience discrimination than other members of the LGBTQ+ community [24].

In 2017, an annual national report recorded 52 incidences of hate violence-related homicides of LGBTQ+ people, the highest incident number recorded in its 20-year history [24]. This increasing prevalence of anti-LGBTQ+ violence can exacerbate IPV in LGBTQ+ communities. For example, a person who loses their job because of anti-trans bias may be more financially reliant on an unhealthy relationship. An abusive partner may also use the violence that an LGBTQ+ person experiences from their family as a way of isolating that person further [24].

Because of the stigma of being LGBTQ+, victims may be reticent to report abuse and afraid that their sexual orientation or biologic sex will be revealed. In one study, the three major barriers to seeking help were a limited understanding of the problem of LGBTQ+ IPV, stigma, and systemic inequities [41]. Many in this community feel that support services (e.g., shelters, support groups, crisis hotlines) are not available to them due to homophobia of the service providers. Unfortunately, this results in the victim feeling isolated and unsupported. Healthcare professionals should strive to be sensitive and supportive when working with homosexual patients.

5. CHARACTERISTICS OF PERPETRATORS OF DOMESTIC VIOLENCE

Abuser characteristics have been studied far less frequently than victim characteristics. Some studies suggest a correlation between the occurrence of abuse and the consumption of alcohol. A man who abuses alcohol is also likely to abuse his mate, although the abuser may not necessarily be inebriated at the time the abuse is inflicted [44]. Domestic violence assessment questionnaires should include questions that explore social drinking habits of both victims and their mates.

Other studies demonstrate that abusive mates are generally possessive and jealous. Another characteristic related to the abuser's dependency and jealousy is extreme suspiciousness. This characteristic may be so extreme as to border on paranoia [12]. Domestic violence victims frequently report that abusers are extremely controlling of the everyday activities of the family. This domination is generally all encompassing and often includes maintaining complete control of finances and activities of the victim (e.g., work, school, social interactions) [12].

In addition, abusers often suffer from low self-esteem and their sense of self and identity is directly connected to their partner [12]. Extreme dependence is common in both abusers and those being abused. Due to low self-esteem and self-worth, emotional dependence often occurs in both partners, but even more so in the abuser. Emotional dependence in the victim stems from both physical and psychologic abuse, which results in a negative self-image and lack of self-worth. Financial dependence is also very common, as the abuser often withholds or controls financial resources to maintain power over the victim [1,4].

6. SCREENING FOR DOMESTIC VIOLENCE AND ABUSE

Evidence Based Practice Recommendation

The U.S. Preventive Services Task Force recommends that that clinicians screen for intimate partner violence (IPV) in women of reproductive age and provide or refer women who screen positive to ongoing support services.

https://jamanetwork.com/journals/jama/fullarticle/2708121

Last Accessed: July 26, 2022

Strength of Recommendation: B (There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.)

There is no universal guideline for identifying and responding to domestic violence, but it is universally accepted that a plan for screening, assessing, and referring patients of suspected abuse should be in place at every healthcare facility. Guidelines should review appropriate interview techniques for a given setting and should also include the utilization of assessment tools. Furthermore, protocols within each facility or healthcare setting should include referral, documentation, and follow-up. This section relies heavily on the guidelines outlined in the Family Violence Prevention Fund's National Consensus Guidelines on Identifying and Responding to Domestic Violence Victimization in Health Care Settings; however, protocols should be customized based on individual practice settings and resources available [35]. The CDC has provided a compilation of assessment tools for healthcare workers to assist in recognizing and accurately interpreting behaviors associated with domestic violence and abuse, which may be accessed at https://www.cdc.gov/violenceprevention/pdf/ipv/ipvandsvscreening.pdf [45].

Several barriers to screening for domestic violence have been noted, including a lack of knowledge and training, time constraints, lack of privacy for asking appropriate questions, and the sensitive nature of the subject [35]. Although awareness and assessment for IPV has increased among healthcare providers, many are still hesitant to inquire about abuse [46]. At a minimum, those exhibiting signs of domestic violence should be screened. Although victims of IPV may not display typical signs and symptoms when they present to healthcare providers, there are certain cues that may be attributed to abuse. The obvious cues are physical. Injuries range from bruises, cuts, black eyes, concussions, broken bones, and miscarriages to permanent injuries such as damage to joints, partial loss of hearing or vision, and scars from burns, bites, or knife wounds. Typical injury patterns include contusions or minor lacerations to the head, face, neck, breast, or abdomen and musculoskeletal injuries. These are often distinguishable from accidental injuries, which are more likely to involve the extremities of the body. Abuse victims are also more likely to have multiple injuries than accident victims. When this pattern of injuries is seen, particularly in combination with evidence of old injury, physical abuse should be suspected [44].

In addition to physical signs and symptoms, domestic violence victims also exhibit psychologic cues that resemble an agitated depression. As a result of prolonged stress, various psychosomatic symptoms that generally lack an organic basis often manifest. For example, complaints of backaches, headaches, and digestive problems are common. Often, there are reports of fatigue, restlessness, insomnia, or loss of appetite. Great amounts of anxiety, guilt, and depression or dysphoria are also typical. Women who experienced IPV are also more likely to report asthma, irritable bowel syndrome, and diabetes [4]. Healthcare professionals should look beyond the typical symptoms of a domestic violence victim and work within their respective practice settings to develop appropriate assessment mechanisms to detect victims who exhibit less obvious symptoms.

The unique relationship dynamics of the abuser and abused are not easily detected under the best of circumstances. They may be especially difficult to uncover in circumstances in which the parties are suspicious and frightened, as might be expected when a victim presents to the emergency department. The key to detection, however, is to establish a proper assessment tool that can be utilized in the particular setting and to maintain a keen awareness for the cues described in this course. Screening for IPV should be carried out at the entry points of contact between victims and medical care (e.g., primary care, emergency services, obstetric and gynecologic services, psychiatric services, and pediatric care) [35].

The key to an initial assessment is to obtain an adequate history. Establishing that a patient's injuries are secondary to abuse is the first task. Clearly, there will be times when a victim is injured so severely that treatment of these injuries becomes the first priority. After such treatment is rendered, however, it is important that healthcare professionals not ignore the reasons that brought the victim to the emergency department [35].

7. ASSESSING DOMESTIC VIOLENCE AND ABUSE

Healthcare providers have reported that even if routine screening and inquiry results in a positive identification of IPV, the next steps of assessing and referring are often difficult, and many feel that they are not adequately prepared [46]. According to the Family Violence Prevention Fund, the goals of the assessment are to create a supportive environment, gather information about health problems associated with the abuse, and assess the immediate and long-term health and safety needs for the patient to develop an intervention [35].

Assessment of domestic violence victims should occur immediately after disclosure of abuse and at any follow-up appointments. Assessing immediate safety is priority. Having a list of questions readily available and well-practiced can help alleviate the uncertainty of how to begin the assessment (Table 1). If the patient is in immediate danger, referral to an advocate, support system, hotline, or shelter is indicated [35].

Table 1: ASSESSMENT OF IMMEDIATE SAFETY FOR DOMESTIC VIOLENCE VICTIMS

Are you in immediate danger?

Is your partner at the health facility now?

Do you want to (or have to) go home with your partner?

Do you have somewhere safe to go?

Have there been threats or direct abuse of the child(ren) (if applicable)?

Are you afraid your life may be in danger?

Has the violence gotten worse or is it getting scarier? Is it happening more often?

Has your partner used weapons, alcohol, or drugs?

Has your partner ever held you or your child(ren) against your will?

Does your partner ever watch you closely, follow you or stalk you?

Has your partner ever threatened to kill you, him/herself or your child(ren)?

Source: [35]

If the patient is not in immediate danger, the assessment may continue with a focus on the impact of IPV on the patient's mental and physical health and the pattern of history and current abuse [35]. These responses will help formulate an appropriate intervention.

CULTURALLY SENSITIVE ASSESSMENT

During the assessment process, a practitioner should be open and sensitive to the patient's worldview, cultural belief systems and how he/she views the illness [47]. This may reduce the tendency to over-pathologize or minimize health concerns of ethnic minority patients.

Pachter proposed a dynamic model that involves several tiers and transactions [48]. The first component of Pachter's model calls for the practitioner to take responsibility for cultural awareness and knowledge. The professional should be willing to acknowledge that he/she does not possess enough or adequate knowledge in health beliefs and practices among the different ethnic and cultural groups he/she comes in contact with. Reading and becoming familiar with medical anthropology is a good first step.

The second component emphasizes the need for specifically tailored assessment [48]. Pachter advocates the notion that there is tremendous diversity within groups. For example, one cannot automatically assume that a Cuban immigrant adheres to traditional beliefs. Often, there are many variables, such as level of acculturation, age at immigration, educational level, and socioeconomic status, that influence health ideologies. Finally, the third component involves a negotiation process between the patient and the professional [48]. The negotiation consists of a dialogue that involves a genuine respect of beliefs. It is important to remember that these beliefs may affect symptoms or appropriate interventions in the case of domestic violence.

Culturally sensitive assessment involves a dynamic framework whereby the practitioner engages in a continual process of questioning. By incorporating cultural sensitivity into the assessment of individuals with a history of being victims or perpetrators of domestic violence, it may be possible to intervene and offer treatment more effectively.

8. INTERVENTIONS FOR DOMESTIC VIOLENCE AND ABUSE

After the assessment is complete, the patient may or may not want immediate assistance or referral. It is important for healthcare providers to assure patients in a nonjudgmental manner that the decision of what they would like in terms of assistance is their choice and that the provider will help regardless of the decisions they are currently ready to make [35].

If the patient would like to immediately implement a plan of action, information for referral to a local domestic violence shelter to assist the victim and the victim's family should be readily available. The acute situation should be referred immediately to local law enforcement officials. Other resources in an acute situation include crisis hotlines and rape relief centers. After a victim is introduced into the system, counseling and follow-up are generally available by individual counselors who specialize in the care of battered women and their spouses and children. These may include social workers, psychologists, psychiatrists, other mental health workers, and community mental health services. The goals are to make the resources accessible and safe and to enhance support for those who are unsure of their options [35].

In Florida, a 24-hour domestic violence hotline is available for toll-free counseling and information. The number is 800-500-1119. The counselors answering the toll-free line may refer the victim to her or his local domestic violence center. A list of Florida certified domestic violence centers organized by county may also be found on the Florida Department of Children and Families website at https://www.myflfamilies.com/service-programs/domestic-violence. Florida's domestic violence centers provide information and referral services, counseling and case management services, a 24-hour hotline, temporary emergency shelter for more than 24 hours, educational services for community awareness relative to domestic violence, assessment and appropriate referral of resident children, and training for law enforcement personnel.

9. DOCUMENTATION AND FOLLOW-UP

It is imperative that healthcare professionals document all findings and recommendations regarding domestic violence in the victim's medical record, including a patient's denial of abuse, if applicable. If domestic violence is disclosed, documentation should include relevant history, results of the physical examination, findings of laboratory and other diagnostic procedures, and results of the assessment, intervention, and referral. The medical record can be an invaluable document in establishing the credibility of the victim's story when seeking legal aid [35].

Healthcare professionals should offer a follow-up appointment if disclosure of past or current abuse is present. Reassurance that assistance is available to the patient at any time is critical in helping to break the cycle of abuse [35].

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Evidence-Based Practice Recommendations Citations

1. U.S. Preventive Services Task Force. Screening for intimate partner violence, elder abuse, and abuse of vulnerable adults: U.S. Preventive Services Task Force recommendation statement. JAMA. 2018;320(16):1678-1687. Available at https://jamanetwork.com/journals/jama/fullarticle/2708121. Last accessed July 26, 2022.

55122 • Strategies for Appropriate Opioid Prescribing: The Florida Requirement

Mark Rose, BS, MA, LP

www.netce.com

Copyright © 2024 NetCE, All rights reserved.

Opioid analgesic medications can bring substantial relief to patients suffering from pain. However, the inappropriate use, abuse, and diversion of prescription drugs in America, particularly prescription opioids, has increased dramatically in recent years and has been identified as a national public health epidemic. A set of clinical tools, guidelines, and recommendations are now available for prescribers who treat pain patients with opioids. By implementing these tools, clinicians can effectively address issues related to the clinical management of opioid prescribing, opioid risk management, regulations surrounding the prescribing of opioids, and problematic opioid use by patients. In doing so, dental professionals are more likely to achieve a balance between the benefits and risks of opioid prescribing, optimize patient attainment of therapeutic goals, and avoid the risk to patient outcome, public health, and viability of their own practice imposed by deficits in knowledge.

Table of Contents

55122 • Strategies for Appropriate Opioid Prescribing: The Florida Requirement

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planner

Division Planner Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. DEFINITIONS

3. EPIDEMIOLOGY OF CHRONIC PAIN AND OPIOID MISUSE

OPIOID MISUSE IN FLORIDA

4. INITIATION AND MANAGEMENT OF THE PATIENT WITH PAIN

ACUTE PAIN

PATIENT EVALUATION AND ASSESSMENT OF ADDICTION RISK

CREATING A TREATMENT PLAN

PERIODIC REVIEW AND MONITORING

CONCURRENT USE OF BENZODIAZEPINES

CONSULTATION AND REFERRAL

MEDICAL RECORDS

PATIENT EDUCATION ON THE USE AND DISPOSAL OF OPIOIDS

DISCONTINUING OPIOID THERAPY

CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

5. CRISIS INTERVENTION: MANAGEMENT OF OVERDOSE

OPIOID ANTAGONISTS

6. COMPLIANCE WITH STATE AND FEDERAL LAWS

CONTROLLED SUBSTANCES LAWS/RULES

THE ELECTRONIC FLORIDA ONLINE REPORTING OF CONTROLLED SUBSTANCES EVALUATION PROGRAM

7. IDENTIFICATION OF DRUG DIVERSION/SEEKING BEHAVIORS

8. INTERVENTIONS FOR SUSPECTED OR KNOWN DRUG DIVERSION

9. CASE STUDY

ASSESSMENT

FOLLOW-UP

10. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

55122 • Strategies for Appropriate Opioid Prescribing: The Florida Requirement

Education Category. Pharmacology

Release Date. 09/01/2024

Expiration Date. 08/31/2027

Course Overview

Opioid analgesic medications can bring substantial relief to patients suffering from pain. However, the inappropriate use, abuse, and diversion of prescription drugs in America, particularly prescription opioids, has increased dramatically in recent years and has been identified as a national public health epidemic. A set of clinical tools, guidelines, and recommendations are now available for prescribers who treat pain patients with opioids. By implementing these tools, clinicians can effectively address issues related to the clinical management of opioid prescribing, opioid risk management, regulations surrounding the prescribing of opioids, and problematic opioid use by patients. In doing so, dental professionals are more likely to achieve a balance between the benefits and risks of opioid prescribing, optimize patient attainment of therapeutic goals, and avoid the risk to patient outcome, public health, and viability of their own practice imposed by deficits in knowledge.

Audience

This course is designed for all dental professionals who may alter prescribing practices or intervene to prevent drug diversion and inappropriate opioid use.

Accreditations & Approvals

NetCE Nationally Approved PACE Program Provider for FAGD/MAGD credit. Approval does not imply acceptance by any regulatory authority or AGD endorsement. 10/1/2021 to 9/30/2027 Provider ID #217994. NetCE is an ADA CERP Recognized Provider. ADA CERP is a service of the American Dental Association to assist dental professionals in identifying quality providers of continuing dental education. ADA CERP does not approve or endorse individual courses or instructors, nor does it imply acceptance of credit hours by boards of dentistry. Concerns or complaints about a CE provider may be directed to the provider or to ADA CERP at www.ada.org/cerp. NetCE is approved as a provider of continuing education by the Florida Board of Dentistry, Provider #50-2405. NetCE is a Registered Provider with the Dental Board of California. Provider Number RP3841. Completion of this course does not constitute authorization for the attendee to perform any services that he or she is not legally authorized to perform based on his or her license or permit type.

Designations of Credit

NetCE designates this activity for 2 continuing education credits. AGD Subject Code 200. This course meets the Dental Board of California's requirements for 2 unit(s) of continuing education. Dental Board of California course #02-3841-25433.

Special Approvals

This course is approved by the Florida Board of Dentistry to fulfill the Florida requirement for 2 hours on the safe and effective prescribing of controlled substance medications.

Course Objective

The purpose of this course is to provide dental professionals who prescribe or distribute opioids with an appreciation for the complexities of opioid prescribing and the dual risks of litigation due to inadequate pain control and drug diversion or misuse in order to provide the best possible patient care and to prevent a growing social problem.

Learning Objectives

Upon completion of this course, you should be able to:

1. Define opioid prescribing and opioid misuse.

2. Apply epidemiologic trends in opioid use and misuse to current practice so at-risk patient populations can be more easily identified, assessed, and treated.

3. Create comprehensive treatment plans for patients with chronic pain that address patient needs as well as drug diversion prevention.

4. Identify state and federal laws governing the proper prescription and monitoring of controlled substances.

5. Evaluate behaviors that may indicate drug seeking or diverting as well as approaches for patients suspected of misusing opioids.

Faculty

Mark Rose, BS, MA, LP, is a licensed psychologist in the State of Minnesota with a private consulting practice and a medical research analyst with a biomedical communications firm. Earlier healthcare technology assessment work led to medical device and pharmaceutical sector experience in new product development involving cancer ablative devices and pain therapeutics. Along with substantial experience in addiction research, Mr. Rose has contributed to the authorship of numerous papers on CNS, oncology, and other medical disorders. He is the lead author of papers published in peer-reviewed addiction, psychiatry, and pain medicine journals and has written books on prescription opioids and alcoholism published by the Hazelden Foundation. He also serves as an Expert Advisor and Expert Witness to law firms that represent disability claimants or criminal defendants on cases related to chronic pain, psychiatric/substance use disorders, and acute pharmacologic/toxicologic effects. Mr. Rose is on the Board of Directors of the Minneapolis-based International Institute of Anti-Aging Medicine and is a member of several professional organizations.

Faculty Disclosure

Contributing faculty, Mark Rose, BS, MA, LP, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planner

Mark J. Szarejko, DDS, FAGD

Division Planner Disclosure

The division planner has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

Pain is the leading reason for seeking medical care, and pain management is a large part of many healthcare professionals' practice. Opioid analgesics are approved by the U.S. Food and Drug Administration (FDA) for moderate and severe pain and are broadly accepted in acute pain, cancer pain, and end-of-life care, but are controversial in chronic noncancer pain. In response to the long-standing neglect of severe pain, indications for opioid analgesic prescribing were expanded in the 1990s, followed by inappropriate prescribing and increasing abuse, addiction, diversion, and overdose through the 2000s. In tandem with the continued under-treatment of pain, these practice patterns led to needless suffering from uncontrolled pain, opioid analgesic addiction, and overdose. Opioid analgesic prescribing and associated overdose peaked in 2011 with both now in multi-year decline, but information on these important trends is largely absent in the medical literature and media reporting.

Patients show substantial opioid response variations in analgesia and tolerability and may exhibit a range of psychologic, emotional, and behavioral responses that reflect inadequate pain control, an emerging opioid use problem, or both. Clinician delivery of best possible care to patients with pain requires appreciation of the complexities of opioid prescribing and the dual risks of inadequate pain control and inappropriate use, drug diversion, or overdose. A foundation for appropriate opioid prescribing is the understanding of factual data that clarify the prevalence, causality, and prevention of serious safety concerns with opioid prescribing.

2. DEFINITIONS

Definitions and use of terms describing opioid analgesic misuse, abuse, and addiction have changed over time, and their current correct use is inconsistent not only among healthcare providers, but also by federal agencies reporting epidemiologic data, such as prevalence of opioid analgesic misuse, abuse, or addiction. Misuse and misunderstanding of these concepts and their correct definitions have resulted in misinformation and represent an impediment to proper patient care.

Inappropriate opioid analgesic prescribing for pain is defined as the non-prescribing, inadequate prescribing, excessive prescribing, or continued prescribing despite evidence of ineffectiveness of opioids[1]. Appropriate opioid prescribing is essential to achieve pain control; to minimize patient risk of abuse, addiction, and fatal toxicity; and to minimize societal harms from diversion. The foundation of appropriate opioid prescribing is thorough patient assessment, treatment planning, and follow-up and monitoring. Essential for proper patient assessment and treatment planning is comprehension of the clinical concepts of opioid abuse and addiction, their behavioral manifestations in patients with pain, and how these potentially problematic behavioral responses to opioids both resemble and differ from physical dependence and pseudo-addiction. Prescriber knowledge deficit has been identified as a key obstacle to appropriate opioid prescribing and, along with gaps in policy, treatment, attitudes, and research, contributes to widespread inadequate treatment of pain [2]. For example, a survey measuring 200 primary care physicians' understanding of opioids and addiction found that [3]:

- 35% admitted knowing little about opioid addiction.

- 66% and 57% viewed low levels of education and income, respectively, as causal or highly contributory to opioid addiction.

- 30% believed opioid addiction "is more of a psychologic problem," akin to poor lifestyle choices rather than a chronic illness or disease.

- 92% associated prescription analgesics with opioid addiction, but only 69% associated heroin with opioid addiction.

- 43% regarded opioid dependence and addiction as synonymous.

This last point is very important because confusion and conflation of the clinical concepts of dependence and addiction has led to accusations of non-addicted patients with chronic pain of misusing or abusing their prescribed opioid and in the failure to detect treatment-emergent opioid problems. Knowledge gaps concerning opioid analgesics, addiction, and pain are related to attitude gaps, and negative attitudes may interfere with appropriate prescribing of opioid analgesics. For example, when 248 primary care physicians were asked of their prescribing approach in patients with headache pain with either a past or current history of substance abuse, 16% and 42%, respectively, would not prescribe opioids under any circumstance [5]. Possibly contributing to healthcare professionals' knowledge deficit in pain treatment is the extent of educational exposure in school. A 2011 study found that U.S. medical school students received a median 7 hours of pain education and Canadian medical students a median 14 hours, in contrast to the median 75 hours received by veterinarian school students in the United States [6].

In 2011, the American Society of Addiction Medicine (ASAM) published their latest revision in defining the disease of addiction. In 2018, ASAM's board recognized the need for an updated definition of addiction that would be more accessible to its stakeholder groups, including patients, the media, and policymakers. Accordingly, the Board appointed a Task Force that revised the definition of addiction for use in ASAM's policy statements. The revised definition states that [10]:

Addiction is a treatable, chronic medical disease involving complex interactions among brain circuits, genetics, the environment, and an individual's life experiences. People with addiction use substances or engage in behaviors that become compulsive and often continue despite harmful consequences. Prevention efforts and treatment approaches for addiction are generally as successful as those for other chronic diseases.

3. EPIDEMIOLOGY OF CHRONIC PAIN AND OPIOID MISUSE

Chronic pain affects about 100 million American adults—more than the total affected by heart disease, cancer, and diabetes combined [2]. It also costs the nation up to $635 billion each year in medical treatment and lost productivity and is the leading reason for receiving disability insurance [3,11]. The lifetime prevalence of chronic pain ranges from 54% to 80%, and among adults 21 years of age and older, 14% report pain lasting 3 to 12 months and 42% report pain that persists longer than one year [2]. While 5 to 8 million Americans receive long-term opioids for the management of chronic pain, an estimated 41% of patients with chronic pain report their pain is uncontrolled, and 10% of all adults with pain suffer from severe, disabling chronic pain [11].

The increasing prevalence of chronic pain is the result of multiple factors, including the aging population; rising rates of obesity and obesity-related pain conditions, such as joint deterioration; advances in life-saving trauma interventions; poorly managed post-surgical pain; and greater public awareness of pain as a condition warranting medical attention [2]. In addition, many armed forces veterans have been returning from military action in Afghanistan and Iraq with traumatic injuries and chronic pain, and veterans' care clinicians have been reporting the perception that long-term pain management is lacking support in the veteran healthcare infrastructure [12].

There is a widespread misperception that opioid analgesic prescribing and overdose continues to grow, fueling an opioid epidemic [13,14,15,16,17]. This is refuted by the following data showing that national opioid analgesic prescribing and overdose peaked in 2011 and are in multiyear decline.

According to a report from the National Forensic Laboratory Information System (NFLIS), prescription reports for hydrocodone increased dramatically from 2001 to 2010, but then steadily decreased through 2019. Oxycodone reports increased steadily from 2001 to 2004, and again from 2006 to 2010, and then steadily declined through 2019 [18]. Methadone prescribing data were not captured in the report.

Opioid analgesic-associated overdose fatalities have also decreased since 2011, despite published Centers for Disease Control and Prevention (CDC) data reporting a sharp rise in opioid analgesic fatalities in 2014 [19]. This increase was the result of the CDC adding clandestine fentanyl fatalities to figures for prescription opioids in 2014, a difference of more than 4,000 fatalities [20]. The CDC acknowledged this and presented revised 2014 figures with clandestine fentanyl overdoses removed, which supports the belief that opioid analgesic-associated overdose fatalities peaked in 2011 [21,22,23].

Opioid analgesic prescribing in the United States has declined from the 2011 peak but remains substantially higher than 1990. Before 1990, physicians seldom prescribed opioids for chronic noncancer pain. By the mid-2000s, 1 of 25 adults was prescribed an opioid for chronic pain, and annual opioid analgesic sales totaled more than $9 billion [25]. There is nearly universal agreement that opioid analgesics were injudiciously overprescribed during the 2000s. Interpretation of the broader trend of increased prescribing from 1990 might be viewed by public health professionals as entirely problematic and by pain medicine professionals as necessary in part, given the past neglect of patients in pain. This reflects the polarized nature of pain care and opioid analgesic prescribing in particular. Efforts to reduce opioid analgesic overprescribing and associated overdose have been successful but have come at a cost to patients who have faced increasing barriers to access, including stigma and abuse in a healthcare system, tapering of opioids without consideration for pain or functional improvements, and difficulty finding a physician [14,26].

Many prescribed opioid analgesic fatalities result from the co-ingestion central nervous system (CNS)/respiratory depressants (especially benzodiazepines) or prescribed methadone. According to the National Institute on Drug Abuse (NIDA), deaths involving benzodiazepines rose from 1,135 in 1999 to 11,537 in 2017. In 2021, nearly 14% of persons who died of an opioid overdose also tested positive for benzodiazepines [30,31]. A Canadian study evaluated 607,156 adults prescribed opioids for noncancer pain, and of those whose deaths were related to opioids, co-prescribed benzodiazepines were detected in 84.5% [32]. This is significant considering that dispensed benzodiazepine prescriptions increased more than 36% between 1996 and 2013 [34]. Additionally, many users obtain benzodiazepines by getting prescriptions from more than one doctor, forging prescriptions, or buying the drugs illicitly. Alprazolam and clonazepam are the two most frequently encountered benzodiazepines on the illicit market [18].

OPIOID MISUSE IN FLORIDA

In Florida, misuse of prescription opioids became a serious problem in the 1990s and 2000s, but efforts to stem the problem appear to be working. The rate of drug overdose deaths increased 58.9% during 2003–2010, and in 2009, one in eight deaths in Florida was attributable to drug overdose [35,36]. In 2022, opioids accounted for 79% of fatal drug overdoses in the state [35]. In 2015, Florida experienced an increase in oxycodone-caused deaths, the first in six years [27]. These trends resulted in the enactment of several measures to address prescribing that was inconsistent with best practices, and partnership with the U.S. Drug Enforcement Administration (DEA) to close and prevent "pill mills" from introducing millions of opioid dose units into illicit markets [37,38]. In May 2017, Governor Rick Scott signed an executive order declaring the opioid epidemic a public health emergency, providing additional funding and empowering state health professions to take steps to address this pressing issue [38]. As part of this order, the State Health Officer has issued a standing order for opioid antagonists to ensure emergency responders have access [38]. In 2022, the Florida Department of Health issued a statewide Standing Order for Naloxone, which authorizes pharmacists to dispense certain naloxone formulations to emergency responders for administration to persons exhibiting signs of opioid overdose [24].

An influx of clandestine fentanyl into Florida in early 2014, and several fentanyl analogs and other novel non-pharmaceutical opioids more recently, has largely driven the increases in opioid overdose fatalities. Analyses of data from 2013–2015 indicate sharp increases in overdose fatalities in Florida linked to counterfeit alprazolam, oxycodone, and hydrocodone tablets that contained fentanyl [39]. The decrease in prescription opioid fatalities, offset by increasing overdose fatalities from other opioid and non-opioid agents, reflects the intervention focus on the supply side ("pill mill laws") and neglect of treatment funding that would address the demand side of problematic drug use [40].

In Florida, fatalities with benzodiazepines present peaked in 2010 with 6,188, falling to 1,761 in 2023 (32% were alprazolam) [41]. Other primary contributors to opioid analgesic-related fatalities include alcohol and prescribed methadone [30,42].

In addition to the executive order issued in 2017, several new state laws were passed in 2018 to impose additional legal requirements on controlled substance prescribers [43]. These laws will be discussed in detail later in this course.

4. INITIATION AND MANAGEMENT OF THE PATIENT WITH PAIN

In 2016, the CDC issued updated opioid prescribing guidelines for chronic pain that address when to initiate or continue opioids for chronic pain; opioid selection, dosage, duration, follow-up, and discontinuation; and assessing risk and addressing harms of opioid use [44]. In addition, the CDC further updated guidance against the misapplication of this guideline in 2019, noting that some policies and practices attributed to the guideline were inconsistent with the recommendations [45]. In response to this and to the availability of new evidence, the CDC published an updated guideline in 2022 [4]. The updated clinical practice guideline is intended to achieve improved communication between clinicians and patients about the risks and benefits of pain treatment, including opioid therapy for pain; improved safety and effectiveness for pain treatment, resulting in improved function and quality of life for patients experiencing pain; and a reduction in the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death [4]. It is important to remember that inappropriately limiting necessary opioid medications to address patients' pain can be damaging and should be avoided. A central tenet of the updated 2022 guideline is that acute, subacute, and chronic pain needs to be appropriately and effectively treated regardless of whether opioids are part of a treatment regimen [4].

However, many guidelines do share common recommendations. These represent the current "conventional wisdom" in opioid analgesic prescribing and can inform healthcare professionals of the best clinical practices in opioid prescribing that include approaches to the assessment of pain and function and pain management modalities. Pharmacologic and nonpharmacologic approaches should be used on the basis of current evidence or best clinical practice. Patients with moderate-to-severe chronic pain without adequate pain relief from non-opioid or nonpharmacologic therapy can be considered for a trial of opioid therapy [44,52]. Initial treatment should always be considered individually determined and as a trial of therapy, not a definitive course of treatment [53].

ACUTE PAIN

Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids in a quantity no greater than that needed for the expected duration of severe pain. In most cases, three days or less will be sufficient; more than seven days will rarely be needed [44]. However, payers and health systems should not use the 2022 guideline to set rigid standards related to dosage or duration of opioid therapy. The guideline is not a replacement for clinical judgment or individualized, patient-centered care [5].

Florida law dictates that, for the treatment of acute pain, a prescription for an opioid drug may not exceed a three-day supply; an exception may be made for a seven-day supply if [54]:

- The prescriber, in his or her professional judgment, believes that more than a three-day supply of such an opioid is medically necessary to treat the patient's pain as an acute medical condition.

- The prescriber indicates "ACUTE PAIN EXCEPTION" on the prescription. (For the treatment of pain other than acute pain, a practitioner must indicate "NONACUTE PAIN" on a prescription.)

- The prescriber adequately documents in the patient's medical records the acute medical condition and lack of alternative treatment options that justify deviation from the three-day supply limit.

With postoperative, acute, or intermittent pain, analgesia often requires frequent titration, and the two- to four-hour analgesic duration with short-acting hydrocodone, morphine, and oxycodone is more effective than extended-release formulations. Short-acting opioids are also recommended in patients who are medically unstable or with highly variable pain intensity [55,56,57].

As part of House Bill 21, passed in 2018, the Florida Board of Medicine and the Board of Osteopathic Medicine are required to establish guidelines for prescribing controlled substances for acute pain; these guidelines are forthcoming [54].

PATIENT EVALUATION AND ASSESSMENT OF ADDICTION RISK

Information obtained by patient history, physical examination, and interview, from family members, a spouse, or state prescription drug monitoring program (PDMP), and from the use of screening and assessment tools can help the clinician to stratify the patient according to level of risk for developing problematic opioid behavioral responses (Table 1). Low-risk patients receive the standard level of monitoring, vigilance, and care. Moderate-risk patients should be considered for an additional level of monitoring and provider contact, and high-risk patients are likely to require intensive and structured monitoring and follow-up contact, additional consultation with psychiatric and addiction medicine specialists, and limited supplies of short-acting opioid formulations [44,58].

Table 1: RISK STRATIFICATION FOR PATIENTS PRESCRIBED OPIOIDS

Low Risk

No or well-defined and controlled personal or family history of alcohol/substance use disorder

No or minimal co-occurring psychiatric disorders or medical comorbidities

Age 45 years or older

High levels of pain acceptance and active coping strategies

High motivation and willingness to participate in multimodal therapy, attempting to function at normal levels

Medium Risk

Moderate concomitant psychiatric disorders, well controlled by therapy

Moderate coexisting medical disorders well-controlled by medical therapy and not affected by chronic opioid therapy (e.g., central sleep apnea)

History of personal or family alcoholism/substance abuse/addiction

Willing to participate in multimodal therapy, attempting to function in normal daily life

Pain involving more than three regions of the body

High Risk

Widespread pain without objective signs and symptoms

Pain involving more than three regions of the body

Aberrant drug-related behavior

History of alcoholism or drug misuse, abuse, addiction, diversion, dependency, tolerance, or hyperalgesia

Major psychologic disorders

Age younger than 45 years

Unwilling to participate in multimodal therapy, not functioning close to a near normal lifestyle

Source: [1,59,60,61]

Anxiety disorders, major depressive disorder, and intense emotional distress alter pain perception and response. Intensity and perception of reported pain is also influenced by factors such as mood, cultural background, social supports, and financial resources. A biopsychosocial model is required to inform pain assessment in order to address the biologic basis of pain and presence of social and psychologic contributors [51].

Before deciding to prescribe an opioid analgesic, clinicians should perform and document a detailed patient assessment that includes [1]:

- Pain indications for opioid therapy

- Nature and intensity of pain

- Past and current pain treatments and patient response

- Comorbid conditions

- Pain impact on physical and psychologic function

- Social support, housing, and employment

- Home environment (i.e., stressful or supportive)

- Pain impact on sleep, mood, work, relationships, leisure, and substance use

- Patient history of physical, emotional, or sexual abuse

Depression is perhaps the single most important comorbidity in patients with chronic pain and is vastly underdiagnosed and untreated. Patients with unrecognized and untreated depression are unlikely to respond to opioids and other pain therapies, but successful treatment of depression can promote analgesia [62].

If substance abuse is active, in remission, or in the patient's history, consult an addiction specialist before starting opioids [1]. In active substance abuse, do not prescribe opioids until the patient is engaged in a treatment/recovery program or other arrangements made, such as addiction professional co-management and additional monitoring. When considering an opioid analgesic (particularly those that are extended-release or long-acting), one must always weigh the benefits against the risks of overdose, abuse, addiction, physical dependence and tolerance, adverse drug interactions, and accidental exposure by children [44,63].

Screening and assessment tools can help guide patient stratification according to risk level and inform the appropriate degree of structure and monitoring in the treatment plan. It should be noted that despite widespread endorsement of screening tool use to help determine patient risk level, most tools have not been extensively evaluated, validated, or compared to each other, and evidence of their reliability is poor [64].

Opioid Risk Tool (ORT)

The Opioid Risk Tool (ORT) is a five-item assessment to help predict aberrant drug-related behavior. The ORT is also used to establish patient risk level through categorization into low, medium, or high levels of risk for aberrant drug-related behaviors based on responses to questions of previous alcohol/drug abuse, psychologic disorders, and other risk factors [65,66].

Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R)

The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) is a patient-administered, 24-item screen with questions addressing history of alcohol/substance use, psychologic status, mood, cravings, and stress. Like the ORT, the SOAPP-R helps assess risk level of aberrant drug-related behaviors and the appropriate extent of monitoring [67,68].

Screening Instrument or Substance Abuse Potential (SISAP)

The Screening Instrument or Substance Abuse Potential (SISAP) tool is a self-administered, five-item questionnaire addressing history developed to predict the risk of opioid misuse. The SISAP is used to identify patients with a history of alcohol/substance abuse and improve pain management by facilitating focus on the appropriate use of opioid analgesics and therapeutic outcomes in the majority of patients who are not at risk of opioid abuse, while carefully monitoring those who may be at greater risk [69].

CAGE and CAGE-AID

The original CAGE (Cut down, Annoyed, Guilty, and Eye-opener) Questionnaire consisted of four questions designed to help clinicians determine the likelihood that a patient was misusing or abusing alcohol. These same four questions were modified to create the CAGE-AID (adapted to include drugs), revised to assess the likelihood of current substance abuse [70].

Diagnosis, Intractability, Risk, and Efficacy (DIRE) Tool

The Diagnosis, Intractability, Risk, and Efficacy (DIRE) risk assessment tool is a clinician-rated questionnaire that is used to predict patient compliance with long-term opioid therapy [71]. Patients scoring lower on the DIRE tool are poor candidates for long-term opioid analgesia.

Mental Health Screening Tool

The Mental Health Screening Tool is a five-item screen that asks about a patient's feelings of happiness, calmness, peacefulness, nervousness, and depression in the past month [72]. A lower score on this tool is an indicator that the patient should be referred to a specialist for pain management.

CREATING A TREATMENT PLAN

Opioid therapy should be presented as a trial for a pre-defined period (e.g., ≤30 days). The goals of treatment should be established with all patients prior to the initiation of opioid therapy, including reasonable improvements in pain, function, depression, anxiety, and avoidance of unnecessary or excessive medication use [1,44]. The treatment plan should describe therapy selection, measures of progress, and other diagnostic evaluations, consultations, referrals, and therapies. All patients prescribed an opioid for pain related to a traumatic injury (severity score ≥9) should be concurrently prescribed an antagonist (e.g., naloxone) [54].

In opioid-naïve patients, start at the lowest possible dose and titrate to effect. Dosages for opioid-tolerant patients should always be individualized and titrated by efficacy and tolerability [1]. The need for frequent progress and benefit/risk assessments during the trial should be included in patient education. Patients should also have full knowledge of the warning signs and symptoms of respiratory depression.

Prescribers should be knowledgeable of federal and state opioid prescribing regulations. Issues of equianalgesic dosing, close patient monitoring during all dose changes, and incomplete cross-tolerance with opioid conversion should be considered. If necessary, treatment may be augmented, with preference for nonopioid and immediate-release opioids over long-acting/extended-release opioids. Taper opioid dose when no longer needed [63].

Non-Opioid Pain Management Options

Nonpharmacologic Approaches

Several nonpharmacologic approaches are therapeutic complements to pain-relieving medication, lessening the need for higher doses and perhaps minimizing side effects. These interventions can help decrease pain or distress that may be contributing to the pain sensation. Approaches include palliative radiotherapy, complementary/alternative methods, manipulative and body-based methods, and cognitive/behavioral techniques. The choice of a specific nonpharmacologic intervention is based on the patient's preference, which, in turn, is usually based on a successful experience in the past.

Methods to provide distraction from pain come in a wide variety of methods, including reciting poetry, meditating with a calm phrase, watching television or movies, playing cards, visiting with friends, or participating in crafts. Music therapy and art therapy are also becoming more widely used as nonpharmacologic options for pain management.

Non-Opioid Analgesics

Nonopioid analgesics, such as aspirin, acetaminophen (Tylenol), and nonsteroidal anti-inflammatory drugs (NSAIDs), are primarily used for mild pain and may also be helpful as coanalgesics for moderate and severe pain. Acetaminophen is among the safest of analgesic agents, but it has essentially no anti-inflammatory effect. Toxicity is a concern at high doses, and the maximum recommended dose is 3–4 g per day [73]. Acetaminophen should be avoided or given at lower doses in people with a history of alcohol abuse or renal or hepatic insufficiency [73].

NSAIDs are most effective for pain associated with inflammation. Among the commonly used NSAIDs are ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn), and indomethacin (Indocin). There are several classes of NSAIDs, and the response differs among patients; trials of drugs for an individual patient may be necessary to determine which drug is most effective [74]. NSAIDs inhibit platelet aggregation, increasing the risk of bleeding, and also can damage the mucosal lining of the stomach, leading to gastrointestinal bleeding. There is a ceiling effect to the nonopioid analgesics; that is, there is a dose beyond which there is no further analgesic effect. In addition, many side effects of nonopioids can be severe and may limit their use or dosing.

Informed Consent and Treatment Agreements

The initial opioid prescription is preceded by a written informed consent or "treatment agreement" [1]. This agreement should address potential side effects, tolerance and/or physical dependence, drug interactions, motor skill impairment, limited evidence of long-term benefit, misuse, dependence, addiction, and overdose. Informed consent documents should include information regarding the risk/benefit profile for the drug(s) being prescribed. The prescribing policies should be clearly delineated, including the number/frequency of refills, early refills, and procedures for lost or stolen medications.

The treatment agreement also outlines joint physician and patient responsibilities. The patient agrees to using medications safely, refraining from "doctor shopping," and consenting to routine urine drug testing (UDT). The prescriber's responsibility is to address unforeseen problems and prescribe scheduled refills. Reasons for opioid therapy change or discontinuation should be listed. Agreements can also include sections related to follow-up visits, monitoring, and safe storage and disposal of unused drugs.

PERIODIC REVIEW AND MONITORING

Evidence Based Practice Recommendation

The CDC recommends that clinicians should evaluate benefits and risks with patients within one to four weeks of starting opioid therapy for subacute or chronic pain or of dosage escalation. Clinicians should regularly re-evaluate benefits and risks of continued opioid therapy with patients.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm

Last Accessed: August 23, 2024

Strength of Recommendation/Level of Evidence: A4 (Most patients should receive based on clinical experience and observations, observational studies with important limitations, or randomized clinical trials with several major limitations)

When implementing a chronic pain treatment plan that involves the use of opioids, the patient should be frequently reassessed for changes in pain origin, health, and function [1]. This can include input from family members and/or the state PDMP. During the initiation phase and during any changes to the dosage or agent used, patient contact should be increased. At every visit, chronic opioid response may be monitored according to the "5 A's" [1,75]:

- Analgesia

- Activities of daily living

- Adverse or side effects

- Aberrant drug-related behaviors

- Affect (i.e., patient mood)

Signs and symptoms that, if present, may suggest a problematic response to the opioid and interference with the goal of functional improvement include [76]:

- Excessive sleeping or days and nights turned around

- Diminished appetite

- Short attention span or inability to concentrate

- Mood volatility, especially irritability

- Lack of involvement with others

- Impaired functioning due to drug effects

- Use of the opioid to regress instead of re-engaging in life

- Lack of attention to hygiene and appearance

The decision to continue, change, or terminate opioid therapy is based on progress toward treatment objectives and absence of concerning adverse effects and risks of overdose or diversion [1]. Satisfactory therapy is indicated by improvements in pain, function, and quality of life. It is important to remember that for some patients with severe chronic pain, improved function may take longer than pain control or either pain or function (not both) will improve. In some cases, preventing worsening pain/functional impairment is the best achievable outcome. Brief assessment tools to assess pain and function may be useful, as may UDTs. Treatment plans may include periodic pill counts to confirm adherence and minimize diversion.

Involvement of Family

Family members or the partner of the patient can provide the clinician with valuable information that better informs decision making regarding continuing opioid therapy. Family members can observe whether a patient is losing control of his or her life or becoming less functional or more depressed during the course of opioid therapy. They can also provide input regarding positive or negative changes in patient function, attitude, and level of comfort. The following questions can be asked of family members or a spouse to help clarify whether the patient's response to opioid therapy is favorable or unfavorable [76]:

- Is the person's day centered around taking the opioid medication? Response can help clarify long-term risks and benefits of the medication and identify other treatment options.

- Does the person take pain medication only on occasion, perhaps three or four times per week? If yes, the likelihood of addiction is low.

- Have there been any other substance (alcohol or drug) abuse problems in the person's life? An affirmative response should be taken into consideration when prescribing.

- Does the person in pain spend most of the day resting, avoiding activity, or feeling depressed? If so, this suggests the pain medication is failing to promote rehabilitation. Daily activity is essential, and the patient may be considered for enrollment in a graduated exercise program.

- Is the person in pain able to function (e.g., work, do household chores, play) with pain medication in a way that is clearly better than without? If yes, this suggests the pain medication is contributing to wellness.

Assessment Tools

VIGIL

VIGIL is the acronym for a five-step risk management strategy designed to empower clinicians to appropriately prescribe opioids for pain by reducing regulatory concerns and to give pharmacists a framework for resolving ambiguous opioid analgesic prescriptions in a manner that preserves legitimate patient need while potentially deterring diverters. The components of VIGIL are [77]:

- Verification: Is this a responsible opioid user?

- Identification: Is the identity of this patient verifiable?

- Generalization: Do we agree on mutual responsibilities and expectations?

- Interpretation: Do I feel comfortable allowing this person to have controlled substances?

- Legalization: Am I acting legally and responsibly?

The foundation of VIGIL is a collaborative physician/pharmacist relationship [77,78].

Current Opioid Misuse Measure (COMM)

The Current Opioid Misuse Measure (COMM) is a 17-item patient self-report assessment designed to help clinicians identify misuse or abuse in patients with chronic pain. Unlike the ORT and the SOAPP-R, the COMM identifies aberrant behaviors associated with opioid misuse in patients already receiving long-term opioid therapy [58]. Sample questions include: In the past 30 days, how often have you had to take more of your medication than prescribed? In the past 30 days, how much of your time was spent thinking about opioid medications (e.g., having enough, taking them, dosing schedule)?

Pain Assessment and Documentation Tool (PADT)

Guidelines by the CDC, the Federation of State Medical Boards (FSMB), and the Joint Commission stress the importance of documentation from both a healthcare quality and medicolegal perspective. Research has found widespread deficits in chart notes and progress documentation for patients with chronic pain who are receiving opioid therapy, and the Pain Assessment and Documentation Tool (PADT) was designed to address these shortcomings [79]. The PADT is a clinician-directed interview, with most sections (e.g., analgesia, activities of daily living, adverse events) consisting of questions asked of the patient. However, the potential aberrant drug-related behavior section must be completed by the physician based on his or her observations of the patient [80].

The Brief Intervention Tool

The Brief Intervention Tool is a 26-item, "yes-no," patient-administered questionnaire used to identify early signs of opioid abuse or addiction. The items assess the extent of problems related to drug use in several areas, including drug use-related functional impairment [72].

Urine Drug Tests

UDTs may be used to monitor adherence to the prescribed treatment plan and to detect unsanctioned drug use. They should be used more often in patients receiving addiction therapy, but clinical judgment is the ultimate guide to testing frequency (Table 2) [81]. The CDC 2016 guideline recommends clinicians should use UDT before starting opioid therapy and consider UDT at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs [44]. However, this recommendation was based on low-quality evidence that indicates little confidence in the effect estimate, and it is not included in the 2022 updated guideline [4].

Table 2: PATIENT RISK LEVEL AND FREQUENCY OF MONITORING

Monitoring Tool

Patient Risk Level

Low

Medium

High

Urine drug test

Every one to two years

Every 6 to 12 months

Every three to six months

State prescription drug monitoring program

Twice per year

Three times per year

Four times per year

Source: [81]

CONCURRENT USE OF BENZODIAZEPINES

In 2021, nearly 14% of persons who died of an opioid overdose also tested positive for benzodiazepines, a class of sedative medication commonly prescribed for anxiety, insomnia, panic attack, and muscle spasm [8]. Benzodiazepines work by raising the level of the neurotransmitter gamma-aminobutyric acid (GABA) in the brain. Common formulations include diazepam, alprazolam, and clonazepam. Combining benzodiazepines with opioids is unsafe because both classes of drug cause central nervous system depression and sedation and can decrease respiratory drive—the usual cause of overdose fatality. Both classes have the potential for drug dependence and addiction.

The CDC recommends that healthcare providers use caution when prescribing benzodiazepines concurrently with opioids whenever possible [4]. If a benzodiazepine is to be discontinued, the clinician should taper the medication gradually, because abrupt withdrawal can lead to rebound anxiety and complications such as hallucinations, seizures, delirium tremens, and, in rare instances, death. The rate of tapering should be individualized [4].

CONSULTATION AND REFERRAL

It is important to seek consultation or patient referral when input or care from a pain, psychiatry, addiction, or mental health specialist is necessary. Clinicians who prescribe opioids should become familiar with opioid addiction treatment options (including licensed opioid treatment programs for methadone and office-based opioid treatment for buprenorphine) if referral is needed [1].

Ideally, providers should be able to refer patients with active substance abuse who require pain treatment to an addiction professional or specialized program. In reality, these specialized resources are scarce or non-existent in many areas [1]. Therefore, each provider will need to decide whether the risks of continuing opioid treatment while a patient is using illicit drugs outweigh the benefits to the patient in terms of pain control and improved function [82].

MEDICAL RECORDS

As noted, documentation is a necessary aspect of all patient care, but it is of particular importance when opioid prescribing is involved. All clinicians should maintain accurate, complete, and up-to-date medical records, including all written or telephoned prescription orders for opioid analgesics and other controlled substances, all written instructions to the patient for medication use, and the name, telephone number, and address of the patient's pharmacy [1]. Good medical records demonstrate that a service was provided to the patient and that the service was medically necessary. Regardless of the treatment outcome, thorough medical records protect the prescriber.

PATIENT EDUCATION ON THE USE AND DISPOSAL OF OPIOIDS

Patients and caregivers should be counseled regarding the safe use and disposal of opioids. As part of its mandatory Risk Evaluation and Mitigation Strategy (REMS) for extended-release/long-acting opioids, the FDA has developed a patient counseling guide with information on the patient's specific medications, instructions for emergency situations and incomplete pain control, and warnings not to share medications or take them unprescribed [63]. A copy of this form may be accessed online at https://www.accessdata.fda.gov/drugsatfda_docs/rems/ERLA_opioids_2016-04-26_Patient_Counseling_Document.pdf[83].

When prescribing opioids, clinicians should provide patients with the following information [63]:

- Product-specific information

- Taking the opioid as prescribed

- Importance of dosing regimen adherence, managing missed doses, and prescriber contact if pain is not controlled

- Warning and rationale to never break or chew/crush tablets or cut or tear patches prior to use

- Warning and rationale to avoid other central nervous system depressants, such as sedative-hypnotics, anxiolytics, alcohol, or illicit drugs

- Warning not to abruptly halt or reduce the opioid without physician oversight of safe tapering when discontinuing

- The potential of serious side effects or death

- Risk factors, signs, and symptoms of overdose and opioid-induced respiratory depression, gastrointestinal obstruction, and allergic reactions

- The risks of falls, using heavy machinery, and driving

- Warning and rationale to never share an opioid analgesic

- Rationale for secure opioid storage

- Warning to protect opioids from theft

- Instructions for disposal of unneeded opioids, based on product-specific disposal information

There are no universal recommendations for the proper disposal of unused opioids, and patients are rarely advised of what to do with unused or expired medications [84]. According to the Office of National Drug Control Policy, most medications that are no longer necessary or have expired should be removed from their containers, mixed with undesirable substances (e.g., cat litter, used coffee grounds), and put into an impermeable, nondescript container (e.g., disposable container with a lid or a sealed bag) before throwing in the trash [85]. Any personal information should be obscured or destroyed. The FDA recommends that certain medications, including oxycodone/acetaminophen (Percocet), oxycodone (OxyContin tablets), and transdermal fentanyl (Duragesic Transdermal System), be flushed down the toilet instead of thrown in the trash [85]. The FDA provides a free toolkit of materials (e.g., social media images, fact sheets, posters) to raise awareness of the serious dangers of keeping unused opioid pain medicines in the home and with information about safe disposal of these medicines. The Remove the Risk Outreach toolkit is updated regularly and can be found at https://www.fda.gov/drugs/ensuring-safe-use-medicine/safe-opioid-disposal-remove-risk-outreach-toolkit[86]. Patients should be advised to flush prescription drugs down the toilet only if the label or accompanying patient information specifically instructs doing so and no other disposal method is appropriate. In 2023, the FDA issued a letter requiring all manufacturers of opioid analgesics dispensed in outpatient settings to submit a proposed modification to the Opioid Analgesic REMS. The modification requires manufacturers to make available prepaid mail-back envelopes to outpatient pharmacies and other opioid dispensers as an opioid analgesic disposal option for patients [9].

The American College of Preventive Medicine has established best practices to avoid diversion of unused drugs and educate patients regarding drug disposal [84]:

- Consider writing prescriptions in smaller amounts.

- Educate patients about safe storing and disposal practices.

- Give drug-specific information to patients about the temperature at which they should store their medications. Generally, the bathroom is not the best storage place. It is damp and moist, potentially resulting in potency decrements, and accessible to many people, including children and teens, resulting in potential theft or safety issues.

- Ask patients not to advertise that they are taking these types of medications and to keep their medications secure.

- Refer patients to community "take back" services overseen by law enforcement that collect controlled substances, seal them in plastic bags, and store them in a secure location until they can be incinerated. Contact your state law enforcement agency or visit https://www.dea.gov to determine if a program is available in your area.

DISCONTINUING OPIOID THERAPY

The decision to continue or end opioid prescribing should be based on a physician-patient discussion of the anticipated benefits and risks. An opioid should be discontinued with resolution of the pain condition, intolerable side effects, inadequate analgesia, lack of improvement in quality of life despite dose titration, deteriorating function, or significant aberrant medication use [1,44].

Clinicians should provide physically dependent patients with a safely structured tapering protocol. Withdrawal is managed by the prescribing physician or referral to an addiction specialist. Patients should be reassured that opioid discontinuation is not the end of treatment; continuation of pain management will be undertaken with other modalities through direct care or referral.

As a side note, cannabis use by patients with chronic pain receiving opioid therapy has traditionally been viewed as a treatment agreement violation that is grounds for termination of opioid therapy. However, some now argue against cannabis use as a rationale for termination or substantial treatment and monitoring changes, especially considering the increasing legalization of medical use at the state level [82].

CONSIDERATIONS FOR NON-ENGLISH-PROFICIENT PATIENTS

For patients who are not proficient in English, it is important that information regarding the risks associated with the use of opioids and available resources be provided in their native language, if possible. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required. Interpreters can be a valuable resource to help bridge the communication and cultural gap between patients and practitioners. Interpreters are more than passive agents who translate and transmit information back and forth from party to party. When they are enlisted and treated as part of the interdisciplinary clinical team, they serve as cultural brokers who ultimately enhance the clinical encounter. In any case in which information regarding treatment options and medication/treatment measures are being provided, the use of an interpreter should be considered. Print materials are also available in many languages, and these should be offered whenever necessary.

5. CRISIS INTERVENTION: MANAGEMENT OF OVERDOSE

Individuals who have first contact with persons suspected of experiencing an opioid-related overdose are in the position to intervene to prevent the potentially devastating consequences. In these cases, care begins with crisis intervention directed at immediate survival by reversing the potentially lethal effects of overdose with an opioid antagonist.

Opioid antagonists have obvious therapeutic value in the treatment of opioid overdose. A 2012 study found that wider distribution of naloxone and training in its administration might have prevented numerous deaths from opioid overdoses in the United States [87]. Since the first community-based opioid overdose prevention program began distributing naloxone in 1996, more than 10,000 overdoses have been reversed [87].

In Florida, licensed healthcare providers may prescribe and pharmacists may dispense opioid antagonists (even as a standing order) for at-risk individuals, these individuals' relatives or other caregivers, and emergency responders to be used in their course of duties [88]. Emergency responders include (but are not limited to) law enforcement officers, paramedics, and emergency medical technicians [88]. As noted, there is a statewide standing order for naloxone for all emergency responders in Florida [38].

OPIOID ANTAGONISTS

Relatively minor changes in the structure of an opioid can convert an agonist drug into one with antagonistic actions at one or more opioid receptor types. Opioid antagonists include naloxone, naltrexone, and nalmefene. Interestingly, naloxone also appears to block the analgesic effects of placebo medications and acupuncture. These agents have no abuse potential [89].

In response to acute overdose, the short-acting opioid antagonist naloxone is considered the gold standard, and it remains the most widely used opioid antagonist for the reversal of overdose and opioid-related respiratory depression. It acts by competing with opioids at receptor sites in the brain stem, reversing desensitization to carbon dioxide, and reversing or preventing respiratory failure and coma. There is no evidence that subcutaneous or intramuscular use is inferior to intravenous naloxone. This has prompted some states to pass laws allowing opioid antagonists to be available to the general public for administration outside the healthcare setting to treat acute opioid overdose [90]. In 2014, the FDA approved naloxone as an autoinjector dosage form for home use by family members or caregivers, and in 2015, the agency approved intranasal naloxone after a fast-track designation and priority review. Intranasal naloxone is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression [91,92].

When used for opioid overdose, a dose of 0.4–2 mg of naloxone is administered intravenously, intramuscularly, or subcutaneously [93]. If necessary, the dose may be repeated every two to three minutes for full reversal. For ease of use, naloxone is also available in a pre-filled auto-injection device. The intranasal formulation is available in doses of 2 mg, 4 mg, or 8 mg [93]. In 2023, the FDA approved Narcan, the first over-the-counter naloxone nasal spray [69]. Narcan is available as a 3-, 4-, or 8 -mg single dose, administered in one nostril [93]. It is important that standard Advanced Cardiac Life Support (ACLS) protocols be continued while naloxone is being administered and that medical treatment (at a healthcare facility) be given immediately.

6. COMPLIANCE WITH STATE AND FEDERAL LAWS

In response to the rising incidence in prescription opioid abuse, addiction, diversion, and overdose in the late 1990s and 2000s, the FDA has mandated opioid-specific REMS to reduce the potential negative patient and societal effects of prescribed opioids. Other elements of opioid risk mitigation include FDA partnering with other governmental agencies, state professional licensing boards, and societies of healthcare professionals to help improve prescriber knowledge of appropriate and safe opioid prescribing and safe home storage and disposal of unused medication [76].

Several regulations and programs at the state level have been enacted in an effort to reduce prescription opioid abuse, diversion, and overdose, including [94]:

- Physical examination required prior to prescribing

- Tamper-resistant prescription forms

- Pain clinic regulatory oversight

- Prescription limits

- Prohibition from obtaining controlled substance prescriptions from multiple providers

- Patient identification required before dispensing

- Immunity from prosecution or mitigation at sentencing for individuals seeking assistance during an overdose

CONTROLLED SUBSTANCES LAWS/RULES

The DEA is responsible for formulating federal standards for the handling of controlled substances. In 2011, the DEA began requiring every state to implement electronic databases that track prescribing habits, referred to as PDMPs. Specific policies regarding controlled substances are administered at the state level [95].

According to the DEA, drugs, substances, and certain chemicals used to make drugs are classified into five distinct categories or schedules depending upon the drug's acceptable medical use and the drug's abuse or dependency potential [96]. The abuse rate is a determinate factor in the scheduling of the drug; for example, Schedule I drugs are considered the most dangerous class of drugs with a high potential for abuse and potentially severe psychologic and/or physical dependence.

In Florida, the prescribing, dispensing, and consumption of certain controlled substances are governed by Chapter 893 of the Florida Statutes [97]. This law establishes the standards for controlled substance prescribing, including reporting system requirements, for prescribers and pharmacists in Florida. At the time of publication of this course, the Florida schedule of controlled substances aligns with the DEA schedule [43].

THE ELECTRONIC FLORIDA ONLINE REPORTING OF CONTROLLED SUBSTANCES EVALUATION PROGRAM

Emerging trends and patterns of prescription opioid abuse, addiction, and overdose are monitored by several industry and government agencies through data collection from a variety of sources. These include health insurance claims; the Automation of Reports and Consolidated Orders System, a DEA-run program that monitors the flow of controlled substances from manufacturing through distribution to retail sale or dispensing; the Treatment Episode Data Set, which monitors treatment admissions; the National Center for Health Statistics state mortality data; and the Researched Abuse, Diversion, and Addiction-Related Surveillance System, which monitors prescription drug abuse, misuse, and diversion [98].

Almost all states, including Florida, have enacted PDMPs to facilitate the collection, analysis, and reporting of information on controlled substances prescribing and dispensing [1]. All prescribers must consult the Electronic Florida Online Reporting of Controlled Substances Evaluation (E-FORCSE) to review a patient's controlled substance dispensing history before prescribing or dispensing a controlled substance to a patient 16 years of age or older [99]. This is mandated even for existing patients and should be done each time a controlled substance is prescribed or dispensed [43]. If the system is nonoperational or cannot be accessed due to a temporary technologic or electrical failure, the prescription may be issued (with documentation of the exception) for up to a maximum three-day supply.

All clinicians who dispense controlled substances are required to report the action to E-FORCSE as soon as possible, but no later than the close of the next business day [99]. This should be repeated each time the substance is dispensed. This reporting requirement is waived in certain circumstances, including for [99]:

- All acts of administration of a controlled substance

- The dispensing of a controlled substance in the healthcare system of the Department of Corrections

- The dispensing of a controlled substance to a person younger than 16 years of age

7. IDENTIFICATION OF DRUG DIVERSION/SEEKING BEHAVIORS

Research has more closely defined the location of prescribed opioid diversion into illicit use in the supply chain from the manufacturer to the distributor, retailer, and the end user (the patient with pain). This information carries with it substantial public policy and regulatory implications. The 2021 National Survey on Drug Use and Health asked non-medical users of prescription opioids how they obtained their most recently used drugs [100]. Among persons 12 years of age or older, 33.9% obtained their prescription opioids from a friend or relative for free, 39.3% got them through a prescription from one doctor (vs. 17.3% in 2009–2010), 7.3% bought them from a friend or relative, and 3.7% took them from a friend or relative without asking [100]. Other sources included a drug dealer or other stranger (7.9%); multiple doctors (3.2%); and theft from a doctor's office, clinic, hospital, or pharmacy (0.7%) [100].

As discussed, UDTs can give insight into patients who are misusing opioids. A random sample of UDT results from 800 patients with pain treated at a Veterans Affairs facility found that 25.2% were negative for the prescribed opioid while 19.5% were positive for an illicit drug/unreported opioid [50]. Negative UDT results for the prescribed opioid do not necessarily indicate diversion but may indicate the patient halted his/her use due to side effects, lack of efficacy, or pain remission. The concern arises over the increasingly stringent climate surrounding clinical decision-making regarding aberrant UDT results and that a negative result for the prescribed opioid or a positive UDT may serve as the pretense to terminate a patient rather than guide him/her into addiction treatment or an alternative pain management program [49].

In addition to aberrant urine screens, there are certain behaviors that are suggestive of an emerging opioid use disorder. The most suggestive behaviors are [47,48,82]:

- Selling medications

- Prescription forgery or alteration

- Injecting medications meant for oral use

- Obtaining medications from nonmedical sources

- Resisting medication change despite worsening function or significant negative effects

- Loss of control over alcohol use

- Using illegal drugs or non-prescribed controlled substances

- Recurrent episodes of:

- Prescription loss or theft

- Obtaining opioids from other providers in violation of a treatment agreement

- Unsanctioned dose escalation

- Running out of medication and requesting early refills

Behaviors with less association with opioid misuse include [47,48,82]:

- Aggressive demands for more drug

- Asking for specific medications

- Stockpiling medications during times when pain is less severe

- Using pain medications to treat other symptoms

- Reluctance to decrease opioid dosing once stable

- In the earlier stages of treatment:

- Increasing medication dosing without provider permission

- Obtaining prescriptions from sources other than the pain provider

- Sharing or borrowing similar medications from friends/family

8. INTERVENTIONS FOR SUSPECTED OR KNOWN DRUG DIVERSION

There are a number of actions that prescribers and dispensers can take to prevent or intervene in cases of drug diversion. These actions can be generally categorized based on the various mechanisms of drug diversion.

Prevention is the best approach to addressing drug diversion. As noted, the most common source of nonmedical use of prescribed opioids is from a family member or friend, through sharing, buying, or stealing. To avoid drug sharing among patients, healthcare professionals should educate patients on the dangers of sharing opioids and stress that "doing prescription drugs" is the same as "using street drugs" [84]. In addition, patients should be aware of the many options available to treat chronic pain aside from opioids. To prevent theft, patients should be advised to keep medications in a private place and to refrain from telling others about the medications being used.

Communication among providers and pharmacies can help to avoid inappropriate attainment of prescription drugs through "doctor shopping." Prescribers should keep complete and up-to-date records for all controlled substance prescribing. When possible, electronic medical records should be integrated between pharmacies, hospitals, and managed care organizations [84]. It is also best practice to periodically request a report from the E-FORCSE to evaluate the prescribing of opioids to your patients by other providers [84].

When dealing with patients suspected of drug seeking/diversion, first inquire about prescription, over-the-counter, and illicit drug use and perform a thorough examination [46,84]. Pill counting and/or UDT may be necessary to investigate possible drug misuse. Photo identification or other form of identification and social security number may be required prior to dispensing the drug, with proof of identity documented fully. If a patient is displaying suspicious behaviors, consider prescribing for limited quantities [46].

If a patient is found to be abusing prescribed opioids, this is considered a violation of the treatment agreement and the clinician must make the decision whether or not to continue the therapeutic relationship. If the relationship is terminated, it must be done ethically and legally. The most significant issue is the risk of patient abandonment, which is defined as ending a relationship with a patient without consideration of continuity of care and without providing notice to the patient. The American Medical Association Code of Ethics states, "Physicians have an obligation to support continuity of care for their patients. While physicians have the option of withdrawing from a case, they cannot do so without giving notice to the patient, the relatives, or responsible friends sufficiently long in advance of withdrawal to permit another medical attendant to be secured" [33]. The notice of termination should be sent in writing, should specifically note the causes for the termination, and should give a period of time prior to termination, usually 30 days [29]. Patients may also be given resources and/or recommendations to help them locate a new clinician.

Patients with chronic pain found to have an ongoing substance abuse problem or addiction should be referred to a pain specialist for continued treatment. Theft or loss of controlled substances is reported to the DEA. If drug diversion has occurred, the activity should be documented and a report to law enforcement should be made [28].

9. CASE STUDY

An unemployed man, 64 years of age, is brought to an emergency department by ambulance, after his wife returned from work to find him lying on the couch, difficult to arouse and incoherent. He has a past history of hypertension, diabetes (non-insulin dependent), mild chronic obstructive pulmonary disease, and chronic back and shoulder pain, for which he has been prescribed hydrocodone/acetaminophen for many years. His wife reports that while he seemed his usual self when she left for work that morning, he had, in recent weeks, been more withdrawn socially, less active, and complained of greater discomfort from the back and shoulder pain. She knows little about his actual medication usage and expresses concern that he may have been taking more than the prescribed amount of "pain medicine."

On evaluation, the patient is somnolent and arouses to stimulation but is non-communicative and unable to follow commands. His blood pressure is normal, he is afebrile, and there are no focal neurologic deficits. Oxygen saturation, serum glucose, and routine laboratory studies (blood counts and metabolic profile) are normal except for mild elevation in blood urea nitrogen (BUN) and creatinine; the urine drug screen is negative except for opioids. Additional history from the family indicates that the patient has been admitted to other hospitals twice in the past three years with a similar presentation and recovered rapidly each time "without anything being found."

Following admission, the patient remains stable-to-improved over the next 12 to 18 hours. By the following day, he is awake and conversant and looks comfortable. On direct questioning, he reports recent symptoms of depression but no suicidal ideation. The patient describes an increased preoccupation with his pain syndrome, difficulty sleeping at night, and little physical activity during the day, in part because of physical discomfort. He is vague about his medication regimen and admits to taking "occasional" extra doses of hydrocodone for pain relief.

The family is instructed to bring in all his pill bottles from home, which they do. In addition to the hydrocodone prescribed by his primary care physician, there is a recent refill of a prescription for the medication given to the patient at the time of his last hospital discharge six months earlier.

ASSESSMENT

A full evaluation, including radiographic studies and consultation with psychiatry and physical therapy, is completed. The working diagnosis for the patient's acute illness is toxic encephalopathy caused by the sedative side effects of opioid medication on the CNS. It is explained that the combination of his advancing age and diabetes likely reduced the efficiency of his kidneys in clearing the medication and its metabolites, making him more susceptible to CNS sedation. It is noted that the patient and his wife have little understanding of the rationale, proper use and safeguards, potential side effects, and limited effectiveness of opioid use for chronic pain.

In addition, the patient is diagnosed with poorly controlled chronic pain syndrome secondary to osteoarthritis and degenerative disc disease; exacerbating factors include deconditioning and reactive depression. The use of an opioid analgesic, at least for the near term, is considered appropriate, if dosed properly, monitored closely, and integrated into a comprehensive, multidisciplinary plan that includes treatment of depression and the use of adjunctive, nonpharmacologic modalities of care. In the setting of possible early diabetic nephropathy, the option of utilizing an NSAID, except for very brief periods of break-through pain, is not considered to be a safe option.

At discharge, and in consultation with his primary care physician, a written treatment and management plan addressing all aspects of the patient's care is presented to the patient and his wife for discussion and consent. Among the key issues addressed are:

- Goals: Improvement in subjective pain experience; improved function of daily living manifested by regular walking exercise and improved social interaction with family and friends; relief of depression; and in the long-term, anticipated withdrawal of opioid medication and resumption of part-time work and/or volunteer community activity

- Outpatient physical therapy and back exercise program to increase core muscular strength, improve flexibility, reduce pain, and increase exercise tolerance

- Patient and family counseling regarding the safe use, dosage regulation, side effects, and proper disposal of opioid medication

- Joint patient-physician responsibilities as regards to regular follow-up, monitoring of goals and treatment effectiveness, avoidance of "doctor-shopping," and assent to single provider for prescription medication

FOLLOW-UP

On follow-up six weeks after discharge, the patient is noticeably improved. He reports that he feels stronger and is sleeping better. His affect is brighter, and he is getting out more. He has maintained his physical therapy and exercise routine and is compliant with his medication. Though he still has pain, it is noticeably less and he is coping better. He and his wife are encouraged by his progress, particularly in regard to his improved functional status.

10. CONCLUSION

For patients suffering from pain, prescribed opioid analgesics may substantially lessen pain, distress, and impairment. Inappropriate overprescribing and overdose related to opioid analgesics increased dramatically in the 2000s. These trends are in multi-year reversal, but patient safety and risk mitigation remains no less important, and clinical tools, guidelines, and recommendations are available for use when prescribing opioids to patients with pain. By implementing these tools, the clinician can effectively address issues related to the clinical management of opioid prescribing, opioid risk management, regulations surrounding the prescribing of opioids, and problematic opioid use by patients. In doing so, healthcare professionals are more likely to achieve a balance between the benefits and risks of opioid prescribing, optimize patient attainment of therapeutic goals, and avoid the risk to patient outcome, public health, and viability of their own practice imposed by deficits in knowledge.

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37. Johnson H, Paulozzi L, Porucznik C, Mack K, Herter B. Decline in drug overdose deaths after state policy changes—Florida, 2010–2012. MMWR. 2014;63(26):569-574.

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42. Jones CM, Paulozzi LJ, Mack KA. Alcohol involvement in opioid pain reliever and benzodiazepine drug abuse-related emergency department visits and drug-related deaths—United States, 2010. MMWR. 2014;63(40):881-885.

43. Scott J. Florida's New Law on Controlled Substance Prescribing. Available at https://www.flmedical.org/Florida/Florida_Public/Docs/FMA-Opioid-HB21.pdf. Last accessed August 22, 2024.

44. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR. 2016;65(1):1-49.

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46. U.S. Department of Justice Diversion Control Division. Recognizing the Drug Abuser. Available at https://www.deadiversion.usdoj.gov/GDP/(DEA-DC-3)%20Recognizing%20the%20Drug%20Abuser.pdf. Last accessed August 22, 2024.

47. Holliday S, Hayes C, Dunlop A. Opioid use in chronic non-cancer pain. Part 2: prescribing issues and alternatives. Australian Fam Physician. 2013;42:104-111.

48. Passik SD. Issues in long-term opioid therapy: unmet needs, risks, and solutions. Mayo Clin Proc. 2009;84:593-601.

49. Meier B. Increase in Urine Testing Raises Ethical Questions. Available at https://www.nytimes.com/2013/08/02/business/increase-in-urine-testing-raises-ethical-questions.html?_r=0. Last accessed August 22, 2024.

50. Sekhon R, Aminjavahery N, Davis CN Jr, et al. Compliance with opioid treatment guidelines for chronic non-cancer pain (CNCP) in primary care at a Veterans Affairs Medical Center (VAMC). Pain Med. 2013;14(10):1548-1556.

51. Wallwork RS, Chipidza FE, Stern TA. Obstacles to the prescription and use of opioids. Prim Care Companion CNS Disord. 2016;18(1):10.

52. Management of Opioid Therapy for Chronic Pain Working Group. VA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain. Washington, DC: Department of Veterans Affairs, Department of Defense; 2017.

53. Chou R, Fanciullo GJ, Fine PG, et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009;10(2):113-130.

54. The Florida Senate. CS/CS/HB 21: Controlled Substances. Available at https://www.flsenate.gov/Session/Bill/2018/21. Last accessed August 21, 2024.

55. Argoff CE, Silvershein DI. A comparison of long- and short-acting opioids for the treatment of chronic noncancer pain: tailoring therapy to meet patient needs. Mayo Clin Proc. 2009;84(7):602-612.

56. McCarberg BH, Barkin RL. Long-acting opioids for chronic pain: pharmacotherapeutic opportunities to enhance compliance, quality of life, and analgesia. Am J Ther. 2001;8(3):181-186.

57. National Comprehensive Cancer Network. Adult Cancer Pain. Version 2.2024. Available at https://www.nccn.org/professionals/physician_gls/PDF/pain.pdf. Last accessed August 22, 2024.

58. Sundwall DN, Utah Department of Health. Utah Clinical Guidelines on Prescribing Opioids for Treatment of Pain. Salt Lake City, UT: Utah Department of Health; 2009.

59. Sloan P. Update on extended-release opioids in pain management. Expert Opin Drug Deliv. 2014;11(2):155-158.

60. Federation of State Medical Boards. Model Policy for the Use of Opioid Analgesics in the Treatment of Chronic Pain. Washington, DC: Federation of State Medical Boards; 2013.

61. Cheatle MD, Barker C. Improving opioid prescription practices and reducing patient risk in the primary care setting. J Pain Res. 2014;7:301-311.

62. Nadeau SE. Opioids for chronic noncancer pain. To prescribe or not to prescribe: what is the question? Neurology. 2015;85(7):646-651.

63. U.S. Food and Drug Administration. Medication Guides: Distribution Requirements and Inclusion in Risk Evaluation and Mitigation Strategies (REMS). Available at https://www.fda.gov/media/79776/download. Last accessed August 22, 2024.

64. Manchikanti L, Abdi S, Atluri S, et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: part 2—guidance. Pain Physician. 2012;15(3 Suppl):S67-S116.

65. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the opioid risk tool. Pain Med. 2005;6(6):432-442.

66. Opioid Risk Tool. Available at https://www.drugabuse.gov/sites/default/files/opioidrisktool.pdf. Last accessed August 22, 2024.

67. Butler SF, Budman SH, Fernandez KC, Fanciullo GJ, Jamison RN. Cross-validation of a Screener to Predict Opioid Misuse in Chronic Pain Patients (SOAPP-R). J Addict Med. 2009;3(2):66-73.

68. Screener and Opioid Assessment for Patients with Pain – Revised (SOAPP-R). Available at https://ddph-materials.s3.amazonaws.com/HelpIsHere/SOAPP-Tool.pdf. Last accessed August 22, 2024.

69. Cheattle MD. Risk Assessment: Safe Opioid Prescribing Tools. Available at https://www.medcentral.com/pain/chronic/risk-assessment-safe-opioid-prescribing-tools. Last accessed August 21, 2024.

70. Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004.

71. Fine PG, Finnegan T, Portenoy RK. Protect your patients, protect your practice: practical risk assessment in the structuring of opioid therapy in chronic pain. J Fam Pract. 2010;59(9 Suppl 2):S1-S16.

72. Katz NP. Opioid Prescribing Toolkit: A Workbook for Clinicians. New York, NY: Oxford University Press; 2010.

73. Dalal S, Bruera E. Assessment and management of pain in the terminally ill. Prim Care Clin Office Pract. 2011;38:195-223.

74. Berger AM, Shuster JL, Von Roenn JH (eds). Principles & Practice of Palliative Care & Supportive Oncology. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013.

75. American Chronic Pain Association. ACPA – Stanford Resource Guide to Pain Management: 2024 Edition. Available at https://www.acpanow.com/acpa-stanford-guide.html. Last accessed August 21, 2024.

76. Strickland JM, Huskey A, Brushwood DB. Pharmacist-physician collaboration in pain management practice. J Opioid Manag. 2007;3:295-301.

77. Tanzi MG. Screening pain prescriptions for safe use with VIGIL. Safeuse. 2015;21(9):68.

78. Crespi-Lofton J. VIGIL: answer the question "Is it legitimate?" Pharmacy Today. 2006;12(1):1.

79. Passik SD, Kirsh KL, Whitcomb L, et al. A new tool to assess and document pain outcomes in chronic pain patients receiving opioid therapy. Clin Ther. 2004;26:552-561.

80. Pain Assessment and Documentation Tool. Available at https://www.capc.org/documents/download/38/. Last accessed August 21, 2024.

81. Atluri SL, Akbik H, Sudarshan G. Prevention of opioid abuse in chronic non-cancer pain: an algorithmic, evidence-based approach. Pain Physician. 2012;15:ES177-ES189.

82. Baxter J. Minimizing the Misuse of Prescription Opioids in Patients with Chronic Nonmalignant Pain. Available at https://nida.nih.gov/sites/default/files/minimizingmisuse_part1.pdf. Last accessed August 21, 2024.

83. Patient Counseling Document. Available at https://www.accessdata.fda.gov/drugsatfda_docs/rems/ERLA_opioids_2016-04-26_Patient_Counseling_Document.pdf. Last accessed August 22, 2024.

84. American College of Preventive Medicine. Use, Abuse, Misuse and Disposal of Prescription Pain Medication Clinical Reference. Available at https://cdn.ymaws.com/acpm.site-ym.com/resource/resmgr/timetools-files/painmedsclinicalreference.pdf. Last accessed August 22, 2024.

85. Office of National Drug Control Policy. Proper Disposal of Prescription Drugs. Available at https://www.ojp.gov/pdffiles1/ondcp/prescrip_disposal.pdf. Last accessed August 22, 2024.

86. U.S. Food and Drug Administration. Safe Opioid Disposal: Remove the Risk Outreach Toolkit. Available at https://www.fda.gov/drugs/ensuring-safe-use-medicine/safe-opioid-disposal-remove-risk-outreach-toolkit. Last accessed August 22, 2024.

87. Wheeler E, Davidson PJ, Jones TS, Irwin KS. Community-based opioid overdose prevention programs providing naloxone—United States, 2010. MMWR. 2012;61(6):101-105.

88. Florida Legislature. 381.887 Emergency Treatment for Suspected Opioid Overdose. Available at http://www.leg.state.fl.us/statutes/index.cfm?App_mode=Display_Statute&Search_String=&URL=0300-0399/0381/Sections/0381.887.html. Last accessed August 22, 2024.

89. Gutstein HB, Akil H. Opioid analgesics. In: Brunton L, Parker K, Lazo J, Buxton I, Blumenthal D (eds). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill; 2011: 547-590.

90. van den Brink W, Haasen C. Evidence-based treatment of opioid-dependent patients. Can J Psychiatry. 2006;51(10):635-646.

91. Cassels C. FDA Okays Handheld Autoinjector for Opioid Overdose. Available at https://www.medscape.com/viewarticle/823039. Last accessed August 22, 2024.

92. U.S. Food and Drug Administration. FDA News Release [Archive]. FDA Moves Quickly to Approve Easy-To-Use Nasal Spray to Treat Opioid Overdose. Available at https://wayback.archive-it.org/7993/20180125101447/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm473505.htm. Last accessed August 22, 2024.

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94. Centers for Disease Control and Prevention. Risk for overdose from methadone used for pain relief—United States, 1999–2010. MMWR. 2012;61(26):493-497.

95. Hannon K. The Prescription Drug Crisis in New York State: A Comprehensive Approach. Available at https://www.scribd.com/doc/82474334/Prescription-Drug-Abuse-Crisis-in-NYS-Comprehensive-Approach-New. Last accessed August 22, 2024.

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Evidence-Based Practice Recommendations Citations

1. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical practice guideline for prescribing opioids for pain—United States, 2022. MMWR. 2022;71(3):1-95. Available at https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm. Last accessed August 23, 2024.

56741 • Dental Treatment of Patients with Mental Disorders

Mark J. Szarejko, DDS, FAGD

www.netce.com

Copyright © 2024 NetCE, All rights reserved.

The human mind is complex, and there are many forms of mental illness that affect millions of people in the United States and throughout the world. While strides have been made awareness and treatment of mental illness, stigma and lack of social acceptance remain. Aside from the fact that these conditions are medical illnesses that should be considered in any patient, they can also have systemic and oral effects that specifically impact the provision of dental care. As such, it is incumbent to include discussion and documentation of patients' mental illness and related pharmacotherapy as a part of their medical history. A collaborative effort by the entire interprofessional team in the treatment of patients with mental illness ensure that patients are able to maintain optimal oral health and a high quality of life.

Table of Contents

56741 • Dental Treatment of Patients with Mental Disorders

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. MOOD DISORDERS

BIPOLAR DISORDER

MAJOR DEPRESSIVE DISORDER

3. ANXIETY DISORDERS

GENERALIZED ANXIETY DISORDER

PANIC DISORDER

SPECIFIC PHOBIA

4. POST-TRAUMATIC STRESS DISORDER

MEDICAL TREATMENT

ORAL HEALTH IMPLICATIONS AND DENTAL TREATMENT MODIFICATIONS

5. SCHIZOPHRENIA

MEDICAL TREATMENT

ORAL HEALTH IMPLICATIONS AND DENTAL TREATMENT MODIFICATIONS

6. SOMATIC SYMPTOMS AND RELATED DISORDERS

MEDICAL TREATMENT

ORAL HEALTH IMPLICATIONS AND DENTAL TREATMENT MODIFICATIONS

7. SUBSTANCE USE DISORDERS

OPIOID USE DISORDER

BENZODIAZEPINE USE DISORDER

ALCOHOL USE DISORDER

NICOTINE (TOBACCO) USE DISORDER

CANNABIS USE DISORDER

COCAINE USE DISORDER

METHAMPHETAMINE USE DISORDER

8. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

56741 • Dental Treatment of Patients with Mental Disorders

Education Category. Psychiatric / Mental Health

Release Date. 03/01/2024

Expiration Date. 02/28/2027

Course Overview

The human mind is complex, and there are many forms of mental illness that affect millions of people in the United States and throughout the world. While strides have been made awareness and treatment of mental illness, stigma and lack of social acceptance remain. Aside from the fact that these conditions are medical illnesses that should be considered in any patient, they can also have systemic and oral effects that specifically impact the provision of dental care. As such, it is incumbent to include discussion and documentation of patients' mental illness and related pharmacotherapy as a part of their medical history. A collaborative effort by the entire interprofessional team in the treatment of patients with mental illness ensure that patients are able to maintain optimal oral health and a high quality of life.

Audience

This course is designed for all dental professionals in all practice settings.

Accreditations & Approvals

NetCE Nationally Approved PACE Program Provider for FAGD/MAGD credit. Approval does not imply acceptance by any regulatory authority or AGD endorsement. 10/1/2021 to 9/30/2027 Provider ID #217994. NetCE is an ADA CERP Recognized Provider. ADA CERP is a service of the American Dental Association to assist dental professionals in identifying quality providers of continuing dental education. ADA CERP does not approve or endorse individual courses or instructors, nor does it imply acceptance of credit hours by boards of dentistry. Concerns or complaints about a CE provider may be directed to the provider or to ADA CERP at www.ada.org/cerp. NetCE is approved as a provider of continuing education by the Florida Board of Dentistry, Provider #50-2405. NetCE is a Registered Provider with the Dental Board of California. Provider Number RP3841. Completion of this course does not constitute authorization for the attendee to perform any services that he or she is not legally authorized to perform based on his or her license or permit type.

Designations of Credit

NetCE designates this activity for 8 continuing education credits. AGD Subject Code 153. This course meets the Dental Board of California's requirements for 8 unit(s) of continuing education. Dental Board of California course #08-3841-25413.

Course Objective

In dentistry, mental health disorders are commonly encountered in patients and can impact oral health and the level of care that can be provided. The purpose of this course is to provide dental professionals with the information necessary to identify mental health disorders and to address these issues appropriately.

Learning Objectives

Upon completion of this course, you should be able to:

1. Describe the most frequently diagnosed mood disorders and potential impact on oral health.

2. Identify anxiety disorders and considerations for anxiety during dental treatment.

3. Discuss the presentation of post-traumatic stress disorder (PTSD) and impact on dental care.

4. Review considerations for dental patients with schizophrenia.

5. Analyze necessary modifications to dental treatment to accommodate the needs of patients with somatoform disorders.

6. Describe alterations in oral health that may arise from substance use disorders or medications used in their treatment.

Faculty

Mark J. Szarejko, DDS, FAGD, received his dental degree from the State University of New York at Buffalo in 1985. He received fellowship from the Academy of General Dentistry in 1994.

Faculty Disclosure

Contributing faculty, Mark J. Szarejko, DDS, FAGD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

Providing optimum treatment to dental patients requires a comprehensive understanding of the entire spectrum of their medical history. Systemic illnesses, including mental illnesses, can have a direct impact on oral health or an indirect impact via medications used in treatment. While awareness and general acceptance of mental health issues have improved in recent decades, current mental health issues coupled with historical stigma may prevent many patients from seeking treatment, thus leading to poorer dental and overall health, and a reduced quality of life.

Mental disorders are diagnosed or systemic conditions that can alter thought, mood, or behavior (individually or collectively) and that cause distress and impair function. It is estimated that nearly 25% of adults in the United States are currently experiencing a mental illness and that 50% of adults in the United States will experience at least one mental illness during their lifetime[1]. This represents a large portion of the U.S. population, many of whom will seek dental care.

This course will serve as an introduction to common mental illnesses in the United States, including a description of the most prevalent symptoms of each. Further, potentially adverse oral and dental effects of mental disorders and/or treatments will be explored. A review of dental treatment modifications that may be required will be provided. Although this course focuses on a selected group of mental disorders, it should provide insight into the varying needs of patients and the necessity for considering mental health in all dental patients.

2. MOOD DISORDERS

BIPOLAR DISORDER

Bipolar disorder, also known as manic depressive disorder, is a mood disorder that affects approximately 2.8% of the adult population, without a statistically significant difference of occurrence between men and women [3]. Bipolar disorder I features alternation of major depressive episodes with full manic episodes; bipolar disorder II is characterized by major depressive episodes and manic episodes that are less severe than those seen in bipolar I disorder [4]. A manic episode is defined in the revised fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) with the following criteria[5]:

- A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy, lasting at least one week and present most of the day, nearly every day (or any duration if hospitalization is necessary)

- During the period of mood disturbance and increased energy or activity, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree and represent a noticeable change from usual behavior:

- Inflated self-esteem or grandiosity

- Decreased need for sleep

- More talkative than usual or pressure to keep talking (pressured speech)

- Flight of ideas or subjective experience that thoughts are racing

- Increase in goal-directed activity or psychomotor agitation

- Excessive involvement in pleasurable or hedonistic activities with a high potential for painful consequences

- The mood disturbance is sufficiently severe to cause marked impairment in social or occupational functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features

- The episode is not attributable to the physiologic effects of a substance (e.g., an illicit drug, a medication, other treatment) or to another medical condition

At least one lifetime manic episode is required for the diagnosis of bipolar I disorder [5]. The elation and euphoria of this phase can be of such a magnitude that the patient may feel that he/she is cured of bipolar disorder and may discontinue the use of their medication(s).

Common characteristics of the depressive phase include lethargy, prolonged sadness, decreased self-esteem, contemplation of death or suicide, problems with concentration and memory, insomnia, loss of interest in activities that were previously enjoyable, and loss of appetite [7].

The duration of time in between episodes and the actual time in a manic or depressive phase varies considerably among patients. Some patients cycle between mania and depression several times during the course of a day or a week, while other patients may experience bipolar episodes only a few times each year. Other patients may remain in either the manic or the depressive phase for weeks or months at a time. Patients who experience bipolar episodes at least four times per year are known as "rapid cyclers." These patients are more resistant to conventional medical treatment [7].

The initial diagnosis of bipolar disorder is usually made during adolescence or early adulthood, when the patient exhibits a first manic episode. This may precede a depressive episode.

The underlying etiology of bipolar disorder is not completely understood. A genetic predisposition is hypothesized to play a role, as studies with monozygotic (identical) twins yield concordance rates of 60% to 80% while the rates decline to 14% to 23% for dizygotic (fraternal) twins [8]. Other researchers have suggested that problems with mitochondrial energy production may contribute to the development of the disorder [9].

Medical Treatment

There is no current cure for bipolar disorder, and long-term treatment is designed to allow for better control of manic/depressive swings. Treatment plans generally consist of pharmacotherapy, psychotherapy, and lifestyle modification that can be encouraged with family and peer support.

Mood stabilizers have long been the first choice for the pharmacologic management of bipolar disorder. Among these medications, lithium is most frequently prescribed. This agent helps to prevent manic episodes and to decrease the risk of suicidal behavior [13]. However, it is not always effective and its side effects can preclude its use.

The long-term use of lithium can cause adverse cardiovascular, central nervous, endocrine, hematologic, and neuromuscular effects [13]. In oral health, perhaps the most significant adverse effect of long-term lithium use is xerostomia (dry mouth). Interventions for xerostomia (dry mouth) include artificial saliva substitutes, frequent sips of water, or cholinergic medications, such as pilocarpine. Immunoglobulins and other compounds present in saliva that support immune functions will have a decreased output and can subject patients to recurring opportunistic infections, such as oral candidiasis. Impaired salivary flow will also cause a decrease in saliva's cleansing action upon the teeth. Further, the ability of salivary components to maintain the pH of saliva as a mild base is altered, which causes the oral environment to become more acidic.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) such ibuprofen and naproxen to manage dental or oral pain is common, but these medications can decrease the renal clearance of lithium and increase its serum concentration to toxic levels. As such, concurrent use of NSAIDs and lithium should be avoided in favor of acetaminophen-based analgesics, if appropriate. Patients taking lithium should also be cautioned to avoid over-the-counter NSAIDs [13].

The antibiotic metronidazole is occasionally used as a single agent or in conjunction with beta-lactam antibiotics (e.g., amoxicillin) to treat odontogenic infections. Metronidazole can also decrease the renal clearance of lithium and cause subsequent elevation in its plasma concentration, increasing the risk for lithium toxicity. As such, an antibiotic that is compatible with the patient's medical history should be used instead [13].

If lithium is ineffective or causes unacceptable side effects, valproic acid or carbamazepine may be used as a second-line option for patients with bipolar disorder. Valproic acid can potentiate central nervous system (CNS) depression seen with opioid analgesics and benzodiazepines (e.g., diazepam). Carbamazepine can decrease plasma concentrations of acetaminophen and tramadol and decrease their analgesic efficacy [14].

Macrolide antibiotics (e.g., erythromycin, azithromycin, clarithromycin) can increase the plasma concentration of valproic acid and carbamazepine, which can lead to systemic toxicity [13]. Alternative effective antibiotics should be used. Any other prescribed or over-the-counter medications that are used by the patient should be evaluated for potential adverse drug interactions with those used adjunctive to dental treatment.

Dental Treatment Modifications

As with any patient, dental treatment of a patient with bipolar disorder begins with a thorough review of the patient's current state and medical history. Patients experiencing a manic episode may display signs of hyperactivity, including grinding of teeth and excessive frequency and application of force during tooth brushing, which can lead to cervical abrasion and trauma to the gingival tissues. The subsequent sensitivity from the exposed dentin can discourage the patient from proper oral hygiene practices and increase the risk of caries and periodontal disease. Dental staff should provide the patient with a mirror view of any area of cervical abrasion and provide individualized oral hygiene instructions to maintain optimal oral hygiene without perpetuating the cycle of abrasion.

Patients experiencing a depressive episode may disregard oral hygiene. If this phase is extensive and oral hygiene is neglected for an extended period, caries and periodontal disease may develop or worsen. Patients with partial or complete dentures may neglect daily maintenance, with a consequent accumulation of food debris and micro-organisms that can cause inflammation of the underlying tissues and preclude the ability to wear the prostheses.

If possible, dental appointments should be scheduled between bipolar episodes, as patients who are in a manic or depressive phase may have difficulty enduring dental appointments or comprehending complex treatment plans, financial arrangements, and/or issues related to informed consent. The patient's physician should be contacted before initiation of treatment if there is any concern about the patient's ability to endure the proposed dental treatment plan.

MAJOR DEPRESSIVE DISORDER

Depressive disorders afflict approximately 17.3 million Americans each year [16]. MDD affects approximately 21 million American adults, or about 8% of the U.S. population 18 years of age and older in a given year. The lifetime incidence of depression in the United States is approximately 24% in women and 13% in men, or nearly 20% of all Americans. Depression is more common in persons with medical illnesses, with 11% to 36% of general medical inpatients fulfilling diagnostic criteria for MDD [17]. The DSM-5-TR umbrella of depressive disorders includes MDD (including major depressive episode), persistent depressive disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, depressive disorder due to another medical condition, other specified depressive disorder, unspecified depressive disorder, and disruptive mood dysregulation disorder, a new diagnosis added to address concerns about the potential overdiagnosis of and treatment for bipolar disorder in children up to 12 years of age [5]. Of these types, MDD is the most common type.

To meet the diagnosis of MDD, a person must have at least five of the following symptoms for at least two weeks' duration and represent a change from previous functioning. At least one of the symptoms must be either depressed mood or loss of interest or pleasure [5]:

- Depressed mood most of the day, nearly every day

- Markedly diminished interest or pleasure in all or almost all activities most of the day or nearly every day

- Significant weight loss or gain (>5% body weight) or increase or decrease in appetite

- Insomnia/hypersomnia nearly every day

- Psychomotor agitation or retardation nearly every day

- Fatigue/loss of energy nearly every day

- Feelings of worthlessness or inappropriate guilt nearly every day

- Diminished concentration or indecisiveness nearly every day

- Recurrent thoughts of death or suicide, suicide attempt, or a specific plan for committing suicide

In addition, MDD diagnosis requires that the symptoms must not meet the criteria for a mixed episode and there is no previous experience of a manic, mixed, or hypomanic episode. Symptoms of MDD cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Additionally, the symptoms may not be due to the direct physiologic effects of a recreational or prescribed drug or be better accounted for by bereavement (i.e., after the loss of a loved one, the symptoms persist for longer than two months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation) [5].

The diagnostic symptoms of MDD represent the domains of affective, behavioral, cognitive, and somatic impairment. Affective or mood symptoms include depressed mood and feelings of worthlessness or guilt, while behavioral symptoms include social withdrawal and agitation. Cognitive symptoms include difficulties with concentration or decision making, and somatic or physical symptoms include insomnia or fatigue.

The DSM-5-TR diagnostic criteria for MDD also include several specifiers to further describe the nature of the current episode of MDD. These specifiers include [5]:

- Anxious distress

- Mixed features

- Melancholic features

- Atypical features

- Mood-congruent psychotic features

- Mood-incongruent psychotic features

- Catatonic features

- Peripartum onset

- Seasonal pattern

Pharmacotherapy

Selective Serotonin Reuptake Inhibitors

Selective serotonin reuptake inhibitors (SSRIs) have advantages of low overdose lethality and better tolerability than first-generation antidepressants, which can improve adherence. SSRIs are particularly effective in patients with obsessive-compulsive symptoms, but may initially worsen anxiety or panic symptoms [22,23]. This class includes the agents fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro), and vortioxetine (Brintellix). Citalopram may have fewer drug-drug interactions than other SSRIs, and fluoxetine may be a better choice in patients with poorer adherence due to its long half-life [22,23].

The most common side effects with SSRIs are gastrointestinal (nausea, vomiting, and diarrhea), activation/insomnia (restlessness, agitation, anxiety, akathisia, and sleep disturbances), sexual, headache, fatigue, and weight gain [22,23]. Xerostomia can also occur with the use of SSRIs. Many of these side effects dissipate over time.

Platelet aggregation can be impaired due to platelet serotonin depletion, which can interfere with the ability to achieve hemostasis during oral or periodontal surgery or root planing and curettage procedures. The concurrent use of NSAIDs or daily aspirin as a cardioprotective measure can exacerbate this problem and should be avoided, particularly if invasive dental procedures are planned. SSRI-induced bruxism (the involuntary grinding or clenching of the teeth) has been reported [13]. For patients prescribed SSRIs who have dental phobia or anxiety, anxiolytic medications should only be given following consultation with the patient's physician, as this combination can potentiate CNS depression and increase the risk for respiratory arrest.

If an SSRI or tricyclic antidepressant (TCA) is combined with tramadol (an analgesic used for moderate-to-severe pain), serotonin syndrome may develop. Mild cases of serotonin syndrome present with signs and symptoms such as anxiety, diaphoresis, and gastrointestinal complaints. Severe cases can present with confusion, hypertension, hyperthermia, hyper-reflexia, and seizures [24]. The serotonin toxidrome has a variable presentation and can be difficult to detect. The most distinguishing features are clonus, fever, and hyper-reflexia, but the most important diagnostic clue is a history of exposure to serotonergic drugs. Given the potentially serious and even deadly effects of combining these medications, tramadol should be avoided and another analgesic chosen for these patients.

SSRIs have also been associated with alteration in taste (dysgeusia), sialadenitis (inflammation of the salivary glands), stomatitis (inflammation of the mucosal lining of any of the structures of the mouth), and edema of the tongue. Patients who experience dysgeusia may use extra salt or sugar to compensate for the decreased ability to taste. These compensatory mechanisms are contrary to good general and oral health. The pain associated with stomatitis can discourage patients from maintaining optimal oral hygiene [13,25].

While these adverse oral effects will resolve upon cessation of SSRI use, halting the medication suddenly is dangerous. Titration or switching to another class of antidepressant should only be attempted by the patient's physician.

Serotonin-Norepinephrine Reuptake Inhibitors

Most serotonin-norepinephrine reuptake inhibitors (SNRIs), including venlafaxine (Effexor), desvenlafaxine (Pristiq), levomilnacipran (Fetzima), and duloxetine (Cymbalta), are several-fold more selective for serotonin than norepinephrine. Safety, tolerability, and side effect profiles of SNRIs resemble SSRIs, with the exception that the SNRIs have been associated (rarely) with sustained elevated blood pressure [22,23]. As such, patients taking SNRIs are at risk for xerostomia, bruxism, and drug-drug interactions.

Tricyclic Antidepressants

TCAs are predominantly serotonin and/or norepinephrine reuptake inhibitors that act by blocking the serotonin transporter and the norepinephrine transporter, respectively, which results in an elevation of the extracellular concentrations of these neurotransmitters, and therefore an enhancement of neurotransmission. TCAs also have varying but typically high affinity for the H1 and H2 histamine receptors and muscarinic acetylcholine receptors. As a result, they also act as potent antihistamines and anticholinergics. These properties are generally undesirable in antidepressants, however, and likely contribute to their large side effect profiles [13,25].

TCAs are comparable in efficacy to SSRIs/SNRIs, but their side effect profile makes them seldom used as first-line therapy [22,23]. TCAs may initially worsen anxiety or panic symptoms. Due to side effect potential of cardiac arrhythmia, TCAs should be used very cautiously, if at all, in patients with heart problems. Issues with orthostatic hypotension and sedation, particularly in elderly patients, also arise and may be a concern following dental appointments.

Anticholinergic and antihistamine activity accounts for many side effects, including xerostomia, blurred vision, reduced gastrointestinal motility or constipation, urinary retention, cognitive and/or memory impairment, and increased body temperature [22,23]. Other side effects may include drowsiness, anxiety, emotional blunting (apathy/anhedonia), confusion, restlessness, dizziness, akathisia, hypotension, tachycardia, and arrhythmia. As with SSRIs, patients taking TCAs may develop dysgeusia, sialadenitis, stomatitis, and lingual edema. Tolerance to side effects often occurs if treatment is continued. Side effects may also be less troublesome if treatment is initiated with low doses and gradually increased [13,25].

The prolonged use of TCAs can cause suppression of the production of the formed elements of human blood, and this decreased production of platelets can result in coagulation problems after invasive dental procedures [14]. Similarly, decreased production of granular and agranular leukocytes can lead to an increased potential for opportunistic oral infections and delayed healing of intraoral surgical sites. A complete blood count (CBC) with differential and adjunctive laboratory tests (e.g., prothrombin time [PT], partial thromboplastin time [PTT]) are advisable prior to any dental procedure in which the ability to achieve hemostasis is required.

TCAs may also accentuate the effects of vasoconstrictors in local anesthetic solutions (e.g., epinephrine, levonordefrin), which can culminate in a rare but serious hypertensive crisis. This potential adverse effect is more pronounced when a TCA is combined with levonordefrin [28]. If appropriate, a local anesthetic solution without a vasoconstrictor (e.g., mepivacaine, prilocaine) should be used for these patients, keeping in mind that the duration and depth of anesthesia will be reduced. If a local anesthetic with a vasoconstrictor is used in a patient also taking a TCA, a cautious and conservative approach is mandatory.

Suicide

The rate of suicide is significantly higher among persons with a mood disorder than the general population. One long-term study found that 12% to 20% of individuals diagnosed with a major mood disorder (including schizophrenia, anxiety, depression, dementia, and/or substance abuse), ultimately died by suicide. The first three months after diagnosis is the period of highest risk for a first attempt, with the three months following the first attempt being the highest risk period for a second attempt [26].

Most people who are suicidal exhibit warning signs, whether or not they are in an acute suicide crisis. These warning signs should be taken seriously and include observable signs of serious depression; withdrawal from friends and/or social activities; sleep problems; and loss of interest in personal appearance, hobbies, work, and/or school [27]. Although dental professionals may feel uncomfortable with suicidal patients, it is essential not to ignore or deny the suspicion of suicide risk. The first and most immediate step is to allocate adequate time to the patient, even though many others may be scheduled, in order to show empathy and build rapport. Patients at risk for suicide should be referred to a behavioral health provider and provided the National Suicide and Crisis Lifeline phone number, 988. If suicide is an imminent risk, contacting emergency medical services may be warranted.

Dental Treatment Modifications

As discussed, the oral health of patients with major depressive disorder can be compromised by the direct and indirect effects of the medications that are used in its treatment and by the manner in which this disorder affects the patient's motivation to maintain optimal oral hygiene and attend periodic dental recall appointments. However, there are no universal modifications that apply to the dental treatment for these patients. Motivation of the patient to maintain optimal oral hygiene at home and to continue attendance at periodic recall appointments is a challenge, although this is an issue for many patients without depression as well. The length of a dental appointment should reflect the patient's ability to withstand dental treatment. Longer appointments and more complex dental procedures should only be scheduled if necessary. If there is any doubt about the degree to which major depressive disorder affects a patient's ability to commit to a treatment plan, withstand dental treatment, or tolerate medications, consultation with the patient's physician or psychiatrist is recommended.

3. ANXIETY DISORDERS

Anxiety disorders are characterized by states of chronic, excessive dread or fear of everyday situations. The fear and avoidance can be life-impairing and disabling. Anxiety disorders result from the interaction of biopsychosocial factors, whereby genetic vulnerability interacts with situations, stress, or trauma to produce clinically significant syndromes. The influence of hereditary factors and adverse psychosocial experiences on pathogenesis and pathophysiology is complex, but neuroscience advances have greatly improved the understanding of the underlying factors in the development and maintenance of anxiety disorders. Each year in the United States, anxiety disorders impact approximately 40 million adults (19.1% of total population) [29].

While there are many disorders under the umbrella of anxiety disorders, the conditions with the most impact on dental care are generalized anxiety, panic disorder, and specific phobia.

GENERALIZED ANXIETY DISORDER

The National Health Interview Study found that the annual incidence of generalized anxiety disorder was approximately 15% in adults in the United States in 2019; moderate-to-severe symptoms occurred in approximately 6% of individuals [30]. The majority of persons with generalized anxiety disorder diagnoses were female (19.5% compared with 11.2% in men). Childhood or adolescent onset was found in more than 50% of those seeking help for anxiety, reflecting the chronicity of the disease [5,30].

Generalized anxiety disorder is characterized by excessive and inappropriate worrying that is persistent and not restricted to particular circumstances. Patients have physical anxiety symptoms and key psychologic symptoms. Generalized anxiety disorder is often comorbid with major depressive disorder, panic disorder, phobia, health anxiety, and obsessive-compulsive disorder [31]. The diagnostic criteria for generalized anxiety disorder are [5]:

- Excessive anxiety and worry (apprehensive expectation) over a number of everyday concerns (e.g., school/work performance)

- Individual finds it difficult to control the worry

- Excessive anxiety and worry are associated with three or more of the following six symptoms, with at least some occurring more days than not for at least six months:

- Restlessness, feeling "on edge"

- Easily fatigued

- Difficulty concentrating

- Irritability

- Muscle tension

- Sleep disturbance (difficulty falling or staying asleep, restless sleep)

- The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning

- Symptoms not better explained by another mental disorder

- The disturbance is not attributable to the physiologic effects of a substance or another medical condition

Medical Treatment

The primary goals of generalized anxiety disorder treatment are reduction of anxiety symptoms and reduction or elimination of disability. Pharmacotherapy and CBT or cognitive therapy are equal as first-line options.

The Anxiety Disorders Association of Canada and the Anxiety and Depression Association of America have created guidelines for the selection of appropriate pharmacotherapy in the treatment of generalized anxiety disorder with differing recommendations regarding first- and second-line medications [33,34]. The Anxiety Disorders Association of Canada recommends agomelatine, pregabalin, venlafaxine XR, duloxetine, escitalopram, paroxetine, or sertraline as first-line options, while the Anxiety and Depression Association of America suggests venlafaxine XR, duloxetine, paroxetine, escitalopram, sertraline, or fluoxetine [33,34].

Oral Health Implications and Dental Treatment Modifications

As discussed, depression of the respiratory system and the CNS can occur with the use of benzodiazepines, especially in conjunction with alcohol or opioid analgesics. Dental clinicians should use non-opioid analgesics to treat pain if a patient is being treated with a benzodiazepine. Some dental practices use benzodiazepines to help calm apprehensive patients so they may receive treatment (marketed as "sleep dentistry"). Patients who are already taking a benzodiazepine to treat generalized anxiety disorder should not take an additional dose of any other benzodiazepine medication as an anxiolytic before dental treatment, as this combination can also potentiate respiratory and CNS depression.

Macrolide antibiotics (e.g., erythromycin, clarithromycin, azithromycin) used to treat odontogenic infections can increase blood plasma levels of alprazolam, with the potential for systemic toxicity. So, the simultaneous use of these medications is contraindicated [14]. Instead, alternative antibiotics (e.g., penicillin, amoxicillin, clindamycin) compatible with the patient's medical history should be used.

The pharmacokinetics of benzodiazepines should also be considered when medications are used adjunctive to dental treatment. Specifically, the half-life (i.e., the interval of time required to achieve a 50% reduction in blood plasma concentration) of benzodiazepines can be affected by drug interactions. An extended half-life results in a lingering drug effect [13].

Diazepam (via its active metabolite desmethyldiazepam) has a half-life that can range from 50 to 100 hours, compared with 40 hours for lorazepam and 11.2 hours for alprazolam [13]. Thus, the adverse interactions between diazepam and opioids can occur for approximately four days after the last dose of diazepam is taken. Although the half-lives of lorazepam and alprazolam are considerably less than that of diazepam, precaution for the expected half-lives of those drugs is also recommended.

Dental treatment modifications for patients with generalized anxiety disorder should be customized to reflect the degree to which the disorder affects their lives. Whether patients with generalized anxiety disorder have anxiety or phobias about dental treatment or not, dental treatment should progress at a pace and for a duration that does not challenge their emotional endurance. Oral manifestations of long-term anxiety can include destructive parafunctional habits such as bruxism, which can cause excessive wear of the teeth, fractures of existing restorations, temporomandibular joint disorders, and a decrease in the vertical dimension of occlusion. The fabrication of splints or night guards may be required to address these issues.

Anxiety can detract from the patient's desire and ability to maintain optimal oral hygiene. Dental staff should be supportive and use a non-judgmental motivational approach to encourage the patient to maintain an appropriate oral hygiene regimen that may include more frequent recall appointments. Alcohol, prescription drug, and/or illicit drug use may co-occur in patients with generalized anxiety disorder, which can lead to worsening symptoms and a high degree of morbidity and even mortality if left untreated. It is incumbent that dental clinicians discuss their concerns with the patient in an appropriate way and make referrals to mental health care.

PANIC DISORDER

In the United States, 4% to 28% of the population experience panic attacks at some time during their life. The 2.4% annual incidence of panic disorder in the United States is one of the highest prevalence rates worldwide [36,37].

Panic attacks are most likely to develop in patients who are in their mid-20s and slightly earlier in men than women. Panic disorder age of onset is usually between late adolescence and 35 years of age, while the age of onset for panic disorder with agoraphobia spans the early 20s to early 30s. Panic disorder is more common among women, with a 2:1 ratio and increasing to 3:1 with panic disorder with agoraphobia [36,37].

The diagnostic criteria for panic disorder require [5]:

- Recurrent unexpected panic attacks

- One or more of the attacks followed by at least one month of one or both of the following:

- Persistent concern or worry about additional panic attacks or their consequences

- Significant maladaptive change in behavior related to the attacks

The symptoms must not be attributable to substance-related effects, other medical conditions, or other psychiatric disorders. Up to 70% of patients report a history of at least one nocturnal panic attack [38]. Patients may present with symptoms suggestive of heightened sympathetic nervous system activity such as palpitations, increased systolic blood pressure, hyperventilation, sweating, or flushing. Other common symptoms include chest pain and discomfort, dizziness, and paraesthesias, while gastrointestinal symptoms such as nausea and vomiting are more common among men [5,39].

Criteria for panic attacks specify an abrupt surge of intense fear or intense discomfort that reaches a peak within minutes and includes four or more of the following symptoms [5]:

- Palpitations, pounding heart, or accelerated heart rate

- Sweating

- Trembling or shaking

- Sensations of shortness of breath or smothering

- Feelings of choking

- Chest pain or discomfort

- Nausea or abdominal distress

- Feeling dizzy, unsteady, light-headed, or faint

- Chills or heat sensations

- Paresthesia (numbness or tingling sensations)

- Derealization (feelings of unreality) or depersonalization (being detached from oneself)

- Fear of losing control or going crazy

- Fear of dying

Panic attack is not classified as a mental disorder and does not have a diagnostic code. Instead, an attack can occur with other mental disorders, such as depressive and anxiety disorders, and can also co-occur with physical disorders.

Medical Treatment

Combined treatment is superior in panic disorder, with effects of combined psycho- and pharmacotherapy treatment versus placebo about twice as large as pharmacotherapy alone versus placebo [40]. The first-line drugs recommended for the treatment of panic disorder are SSRIs or venlafaxine XR [33]. Research suggests that the largest effect size is found with clonazepam, followed by venlafaxine and fluoxetine [41].

The use of medications can only reduce the frequency and intensity of a panic attack but cannot eliminate the situations or places that precipitated the attack. The goal of psychotherapy such as cognitive therapy is to discern the patient's beliefs and perceptions that may serve as the trigger for a panic attack and eliminate them as a source of the heightened anxiety from which a panic attack evolves [42]. The use and duration of medications and psychotherapy will vary according to individual needs.

Oral Health Implications and Dental Treatment Modifications

As discussed, the drugs used to treat panic disorder, specifically antidepressants and benzodiazepines, can interact with other drugs used in dental treatment and result in adverse or unintended effects. These potential interactions should be considered whenever prescribing or administering a medication to these patients.

Dental treatment of patients with panic disorder should begin with a discussion of the patient's medical history that includes the details of the places or situations that have served as triggers for panic attacks. It is also possible that a patient may be unaware that he or she is experiencing what might be a first panic attack. Further complicating the matter, the signs and symptoms can resemble those of serious medical emergencies, including myocardial infarction (heart attack), acute asthmatic attack, or hypoglycemic crisis. In these situations, emergency medical services should be summoned; distinguishing between a panic attack and a medical emergency is beyond the ability of dental professionals.

Conversely, patients with a known history of panic disorder may develop a medical emergency that mimics a panic attack. Patients believed to be experiencing a panic attack should never be left alone, and if there is any doubt as to the origin of the acute symptomatology, emergency medical services should be called.

Patients who experience a panic attack in a dental setting may defer or avoid dental treatment completely and increase their risk of the development of carious lesions and periodontal disease. These patients should be encouraged to continue to seek dental care, with the reassurance that steps can be taken to make the experience less triggering.

SPECIFIC PHOBIA

Specific, simple, or isolated phobia is the excessive or unreasonable fear of (and is restricted to) animals, objects, or specific situations (e.g., dentists, spiders, elevators, flying, seeing blood) [31]. Intense anxiety or unexpected panic responses in the presence of specific objects or situations can mark phobia onset but are not the sole causal route. Disgust, either alone or combined with fear, may trigger the onset and maintenance of animal (particularly spiders, snakes, and worms) or blood-injection-injury phobias. This is the most common type of anxiety disorder, with a lifetime prevalence of 15.6% and a past-year prevalence of 12.1% [36].

Women are two- to three-times more likely to develop phobias than men, with the exception of blood-injection-injury phobia, which is evenly distributed by sex. Roughly 70% of those with specific phobia report more than one clinically relevant fear. Animals and heights are the most common stimuli, followed by flying, enclosed spaces, and blood-injection-injury. The average age of onset is 7 to 10 years, with declining probabilities of onset into later adulthood. The majority of animal phobias develop before 8 years of age [5,45,46]. The average age of treatment engagement is 31 years, although only 8% of persons with specific phobia are reported to seek treatment [46].

Specific, simple, or isolated phobia describes excessive or unreasonable fear in the presence of phobic stimuli, typically involving specific animals, objects, or situations (e.g., dentists, spiders, elevators, flying, seeing blood). Phobic stimuli are either avoided or are endured with significant personal distress [31]. This fear or anxiety must be markedly stronger than the actual threat of the object or situation (e.g., likelihood of being stuck on a well-maintained elevator) [5].

Specific phobias can develop after a traumatic event or from witnessing traumatic events. The fear or anxiety happens every time the person is exposed to the stimulus and may include panic attack symptoms.

The median age of onset with specific phobia is 13 years [5]. According to the DSM-5-TR, specific phobia is diagnosed when the following criteria are met [5]:

- Marked fear or anxiety about a specific object or situation (e.g., flying, seeing blood)

- Phobic object or situation almost always provokes immediate fear or anxiety and is actively avoided or endured with marked fear or anxiety

- Fear or anxiety out of proportion to the actual danger posed by the specific object or situation

- The fear, anxiety, or avoidance is persistent, typically at least six months

- Marked distress or functional impairment

Specific phobia subtypes are organized by phobia categories:

- Animal: Dogs, snakes, insects

- Natural environment: Storms, heights, dark

- Blood-injection-injury: Injections, blood draws, medical/dental procedures

- Situational: Driving, flying, enclosed spaces

- Other: Choking, vomiting, clowns

Medical Treatment

Patients with specific phobias generally do not consult medical professionals when able to avoid the specific feared situations or objects. Exposure therapy is effective in treating specific phobia and is the favored approach. For blood-injection-injury phobias, an effective approach is combining exposure therapy with muscle tension exercises (applied tension) designed to prevent fainting. Using stress-reducing medical devices, such as decorated butterfly needles and syringes, has significantly reduced needle phobia and stress in pediatric and adult patients. With dental phobias, use of cognitive-behavioral therapy can reduce avoidance of oral injections and decrease patient anxiety [42,47].

Oral Health Implications and Dental Treatment Modifications

It is essential that a discussion that is based on empathy and compassion reveals situations within the dental setting that cause anxiety of such a magnitude that they have precipitated phobia and/or a panic attack in the past for the patient and have the potential to do so in subsequent dental appointments. As noted, modifying treatment and/or devises to reduce stress is recommended to allow dental treatment to proceed.

4. POST-TRAUMATIC STRESS DISORDER

Post-traumatic stress disorder (PTSD) is a severe, potentially chronic and disabling disorder that develops in some persons following exposure to a traumatic event involving actual or threatened death, serious injury, or sexual assault [49]. Some common symptoms include intrusive thoughts, nightmares and flashbacks of traumatic events, avoidance of trauma reminders, hypervigilance, and sleep disturbance. These symptoms can be highly distressing and substantially impair social, occupational, and interpersonal functioning. The intensely distressing and impairing symptoms of traumatic stress are highly prevalent immediately following traumatic exposure and dissipate over the following days and weeks in most people. Persistence beyond one month post-trauma suggests PTSD [49].

Large community surveys indicate that 50% to 75% of people report experiencing at least one lifetime traumatic event [50]. A U.S. survey from 2001–2003 of 5,692 participants 18 years of age or older found lifetime PTSD prevalence rates of 6.8% overall—3.6% in men and 9.7% in women. Also found were past-year prevalence rates of 3.5% overall, with 1.8% in men and 5.2% in women. These rates were very similar to those of a large survey in the early 1990s that found a lifetime PTSD prevalence rate of 7.8% overall, with 5% in men and 10.4% in women [50].

MEDICAL TREATMENT

The overall objective of PTSD therapy is to treat the four core symptom clusters of intrusive re-experiencing, avoidance, negative alterations in cognitions and mood, and hyperarousal. Psychotherapy is the backbone of PTSD therapy, with pharmacotherapy used as an adjunct if necessary. Primary care clinicians should be aware of the range of therapeutic options along with their advantages and disadvantages (e.g., time commitment, side effects, risks) and be able to explain these to the patient.

Therapies for PTSD are broadly divided into psychotherapies, pharmacotherapies, and adjunctive or supplemental treatment modalities. Selection of the initial pharmacologic approach is based on clinician and patient choice and guided by the manifesting symptoms of PTSD, other disorders, and patient preference, with polypharmacy choice dictated by clinical presentation and co-occurring psychiatric disorders [51]. SSRIs are widely recommended as first-line agents in the treatment of PTSD [51]. Other possible drug choices include SNRIs, TCAs, monoamine oxidase inhibitors, sympatholytics, benzodiazepines, anticonvulsants, and atypical antipsychotics.

ORAL HEALTH IMPLICATIONS AND DENTAL TREATMENT MODIFICATIONS

Dental clinicians should be aware of these potential adverse drug interactions and side effects of the medications used to treat PTSD when they perform dental procedures and prescribe medications adjunctive to dental treatment. Paroxetine is an SSRI that has been found effective in the short-term treatment of PTSD; however, it has been associated with xerostomia. Normal salivary flow resumes upon discontinuation. The concurrent use of paroxetine and NSAIDs (e.g., ibuprofen, naproxen) can decrease platelet aggregation, and should be avoided if possible. Opioid analgesics may potentiate the effect and toxicity of paroxetine, so their concurrent use should be minimized or avoided [13].

Prior to the initiation of dental treatment for patients with PTSD, it is essential to establish an atmosphere of trust and open communication. In some cases, paranoia or heightened startle reflexes may be present. Patients may associate being placed in a supine position in the dental chair and having their personal space encroached upon by a dental professional with the loss of control experienced during their trauma. An open line of communication will allow for disclosure of these issues and provide a means for resolution.

The efficacy of the patient's oral hygiene should be evaluated at each recall visit, as medication-induced xerostomia can compromise ability to maintain optimal oral hygiene. Hygiene instructions and recall appointments should be tailored to the needs of the patient. Concurrent use and/or misuse of alcohol or recreational/prescribed medications should also be evaluated. A team approach involving the dental and medical team should be used to restore the patient to an ideal level of physical, mental, and emotional health.

5. SCHIZOPHRENIA

Schizophrenia is a complex psychotic disorder that affects less than 1% of the population, with a nearly equal distribution between men and women. Onset occurs later in women compared with men [54]. Symptoms of schizophrenia comprise three broad categories: positive, negative, and cognitive.

Positive symptoms include auditory (most common), olfactory, visual, or tactile hallucinations. Paranoid delusions, delusions of persecution, and grandiose delusions also occur. Thought disorders, characterized by a dysfunctional pattern of thinking, are another type of positive symptom. Finally, movement disorders commonly occur and tend to feature exaggerated and/or agitated body movements.

Negative symptoms are disruptions in normal emotions and behaviors. This may manifest in a variety of emotional issues and behaviors such as flat affect, anhedonia (i.e., a loss of pleasure in the activities of daily life), and difficulty initiating and sustaining activities. Less commonly, patients may display catatonia, with markedly depressed or absent movement and responses.

Cognitive symptoms tend to be more difficult to discern and include poor executive functioning (i.e., ability to understand information and use it to make decisions), difficulty concentrating, and memory issues [54]. A diagnosis of schizophrenia is made when a patient has two or more of the following symptoms for at least one month [5]:

- Hallucinations

- Catatonic movements

- Delusions

- Disorganized speech patterns

- Flattened affect

- Alogia (restricted amount and/or content of speech)

- Disruptions in social or occupational abilities

The exact cause of schizophrenia remains unclear, although a combination of biochemical factors and a genetic influence may contribute. The chance of a child developing schizophrenia is 10% to 13% if one parent has schizophrenia but escalates to 46% if both parents have schizophrenia [55].

MEDICAL TREATMENT

Schizophrenia is a disease with periods of remissions or mild symptoms, but for most patients, it is a long-term, recurring condition. As such, treatment generally continues throughout a patient's life.

Treatment of schizophrenia involves a combination of pharmacotherapy and psychosocial therapy. Most often, medications include typical (first generation) and atypical (second generation) antipsychotics [56]. The most frequently used typical antipsychotics are chlorpromazine, haloperidol, and perphenazine. These medications will address the positive symptoms of schizophrenia, but they do not ameliorate negative symptoms.

ORAL HEALTH IMPLICATIONS AND DENTAL TREATMENT MODIFICATIONS

Xerostomia is a potential adverse effect of antipsychotic medications, with a resumption of normal salivary production upon cessation of use. However, because pharmacotherapy will continue indefinitely, efforts should be made to improve comfort and oral health with saliva substitutes and other palliative interventions.

A more pronounced adverse effect of typical antipsychotic medications is tardive dyskinesia— involuntary movements of the tongue, lips, facial muscles, limbs, and trunk of the body [57]. This adverse effect can take months or years to develop and although it occurs predominantly with the use of the typical antipsychotics, it can also occur with the use of atypical agents.

Tardive dyskinesia is usually mild and reversible; however, it can become severe and irreversible in a small percentage of patients. Benzodiazepines and anticholinergics (e.g., diphenhydramine) can decrease the intensity of the symptoms, but these agents are also associated with oral and systemic adverse effects. Discontinuing a typical antipsychotic to alleviate the symptoms of tardive dyskinesia can increase the severity of the patient's schizophrenia and should only be done under psychiatric supervision.

In terms of oral health, the involuntary movements of the oral musculature seen with tardive dyskinesia can complicate the patient's ability to eat, speak, swallow, and remain stationary during dental procedures. Spasmodic activity of the intrinsic and extrinsic muscles of the tongue, cheeks, and floor of the mouth can preclude the use of mandibular partial or complete dentures, which rely on a balance of muscular control for their retention. Involuntary movement of the muscles of the soft palate can disrupt the suction seal at the posterior border of a maxillary denture and compromise the patient's ability to wear this prosthesis. Involuntary muscular activity of the fingers and the hands can present a challenge to maintain optimal levels of oral hygiene, increasing the risk for plaque deposits, dental caries, and periodontal disease. The frequency of recall appointments should reflect the patient's ability to maintain an appropriate level of oral hygiene in the presence of medication-induced xerostomia and/or tardive dyskinesia.

Typical antipsychotics can result in leukopenia, a condition characterized by decreased production of white blood cells (leukocytes) and particularly granulocytic leukocytes (i.e., neutrophils, basophils, and eosinophils) (referred to as agranulocytosis) [13]. Leukocytes are a critical component of an intact immune system and a decrease in production increases the risk for opportunistic oral and systemic infections. For example, impaired immune function can result in the overgrowth of the resident oral fungal organism Candida albicans, leading to oral candidiasis. This infection can be refractory to oral antifungal suspensions and systemic antifungal medications. Unchecked, it may extend regionally or systemically, with a high degree of morbidity and even mortality. Similarly, reactivation of herpes simplex virus-1 (HSV) and the development of recurrent herpes labialis is likely with impaired immunity.

Before invasive dental procedures are performed, a complete blood count with differential should be ordered for patients with schizophrenia who are prescribed a typical antipsychotic. The results can help guide decisions to decrease the risk of postsurgical infections and prolong healing.

Chlorpromazine, perphenazine, and haloperidol can potentiate the systemic depressant effects of opioids [14]. If possible, other pain relief methods should be used for patients who use these antipsychotics. Weight gain, dizziness, insomnia, and fatigue are among the more frequently occurring adverse effects of atypical antipsychotics.

Akathisia (a general sense of restlessness) may develop and can interfere with a patient's ability to remain stationary or seated [58]. Even aside from drug side effects, patients with schizophrenia may find it difficult or impossible to remain still in a dental chair for long appointments. As such, shorter appointments may be necessary to complete required dental treatment.

Dysphagia (difficulty swallowing), dysgeusia (distorted perception of taste), and stomatitis (generalized inflammation of the mucosal surfaces of the oral cavity) are also among the potential adverse effects of atypical antipsychotic medications [55]. Patients who wear partial or complete dentures may be unable to use these prostheses in the presence of stomatitis. If eating or swallowing are painful or impossible, liquid nutritional supplements may be necessary. Erosive areas of stomatitis can serve as portals of entry for pathogenic oral microbes, which can lead to local, regional, or systemic infections.

The concurrent use of anxiolytic medications or opioids with risperdone or olanzapine can exacerbate the respiratory depressive effects of the medications, increasing the risk of respiratory arrest [60]. Therefore, these combinations should only be attempted if absolutely necessary and upon approval of the patient's physician.

Dental treatment modifications of schizophrenic patients should be individualized, with consideration of the stability of the patient, current medication(s), and the presence of comorbidities. Consultation with the patient's physician and/or psychiatrist is advisable before beginning dental treatment.

Atypical antipsychotics have been associated with orthostatic hypotension [61]. This can be exacerbated when a patient in a dental chair is raised abruptly from supine to upright position. With this in mind, patients should be raised in a slow, incremental fashion to allow for appropriate regulation of blood pressure.

6. SOMATIC SYMPTOMS AND RELATED DISORDERS

Somatic symptoms and related disorders are a group of psychiatric conditions in which the patient presents with physical symptoms for which no underlying medical or organic cause can be identified. Previously known as somatoform disorders, the DSM-5-TR consolidated the number and description of these disorders under the title of Somatic Symptoms and Related Disorders, which will be the term used for this course. The prevalence of somatic symptoms and related disorders is 16.1% to 21.9% in the general population [62]. In order to establish a diagnosis of somatic symptoms and related disorders, the symptoms must [5]:

- Not be explained by a known medical condition, another mental disorder, or by the use of a medication or another substance

- Not be the result of malingering or factitious disorder

- Cause impairment with occupational and social activities or in the activities of daily living

Even with these criteria, establishing a diagnosis of somatic symptoms and related disorders is challenging.

MEDICAL TREATMENT

Treatment for somatic symptoms/disorders involves psychotherapy to identify the ultimate psychogenic etiology. The primary dental treatment concern is the avoidance of unnecessary treatment and referral to the appropriate specialists for patients with these disorders when oral or odontogenic pathology cannot be discerned from a comprehensive clinical and radiographic examination or when these problems are successfully resolved and symptoms persist.

ORAL HEALTH IMPLICATIONS AND DENTAL TREATMENT MODIFICATIONS

Pain Disorder

Pain disorder is considered a somatic disorder characterized by pain for which no organic or physical etiology can be identified. In patients with this disorder, psychologic factors such as stress, anxiety, and depression usually precede the onset of pain and can influence its severity and duration. The perception of pain can occur anywhere, including the oral and maxillofacial complex. Patients may complain of odontogenic pain even after a complete radiographic survey and clinical examination rules out dental caries, endodontic pathology, and defective restorations.

Atypical facial pain can be of varying durations and can occur in varying locations. Common oral manifestations of pain disorder include atypical facial pain and oral dysesthesia [64]. The pain may be described as burning or tingling, sharp, dull, or as a sensation of pressure or crushing [65]. Other conditions that can cause an oral burning sensation (e.g., vitamin B12 deficiency, erythematous candidiasis) should be ruled out before a somatic disorder is considered.

It is important not to equate the absence of obvious oral or odontogenic pathology with a somatic disorder. Likewise, providing dental treatment and/or analgesic prescriptions is not recommended without knowledge of the underlying cause of pain. When there is no apparent etiology for expressed pain, referral to another healthcare professional (e.g., an oral surgeon, primary care physician, neurologist) should be given to determine if the pain has an etiology beyond the oral and maxillofacial complex.

Hypochondriasis

Hypochondriasis is a somatic disorder in which the patient is convinced that his/her physical symptoms are indicative of a life-threatening medical condition. Hypochondriasis affects 1% to 8% of the population, and its diagnosis is made if the patient maintains a nondelusional preoccupation with the symptoms for at least six months [63]. In the dental setting, a patient who has pain in the oral-pharyngeal area may be convinced the pain originates from malignancy.

If a thorough clinical and radiographic exam detects pathology (e.g., caries, periodontal disease, oral lesions, endodontic pathology), these issues should be treated first. If a patient's symptoms persist upon the successful resolution of these problems and in the absence of any other evident pathology, the patient should be referred to a specialist. Patients with hypochondriasis may not be reassured even if clinical examinations and tests do not reveal any further pathology.

7. SUBSTANCE USE DISORDERS

Substance use disorder (SUD) is considered a mental illness and can undermine individuals' physical, psychologic, social, and emotional health and safety. The DSM-5-TR identifies 10 classes of drugs that may be linked to an SUD: alcohol, caffeine, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics or anxiolytics, stimulants, and nicotine (tobacco) [5]. Although they are outlined individually, individuals may have more than one SUD concurrently.

Diagnosis of SUD is made when at least two of the following symptoms within a 12-month period [5]:

- Use or consumption of more of a substance than planned

- Inability to control or stop use

- Spending an extensive amount of time using the substance(s) and using any means to obtain it/them

- Continued substance use results in failure to fulfill personal and professional obligations

- Cravings for the substances(s)

- Continued use of the substance(s) despite emerging or worsening health problems

- Continued use of the substance(s) despite a negative impact on personal or professional relationships

- Use of the substance(s) in dangerous situations such as driving or using heavy machinery

- Withdrawing from activities because of substance use

- Developing a tolerance to the substance(s), defined by:

- A need for markedly increased amounts to achieve intoxication or desired effect

- A markedly diminished effect with continued use of the same amount

- Experiencing withdrawal symptoms when the use of the substance(s) stops

SUDs transcend geographic boundaries, sex/gender, race, ethnicity, and socioeconomic status. It is important to remember that SUD is a mental illness and not a character flaw or the result of a lack of willpower. Patients with a SUD should be treated with the same empathy and concern conveyed to any patient with a mental illness.

It is important to understand some of the most common terms used when discussing SUDs. Addiction is defined by the American Society of Addiction Medicine (ASAM) as a "treatable, chronic medical disease involving complex interactions among brain circuits, genetics, the environment, and an individual's life experiences. People with addiction use substances or engage in behaviors that become compulsive and often continue despite harmful consequences" [66]. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. The ASAM also notes as part of their definition of addiction that "prevention efforts and treatment approaches for addiction are generally as successful as those for other chronic diseases" [66].

Tolerance refers to the diminishing effect of a substance over time. A patient has developed tolerance if it takes an increased dose of the drug to illicit the same effects. The term dependence has replaced the term "addiction" in some contexts. Substance dependence refers to both psychologic dependence (or addiction) and physical dependence. Physical dependence consists of neurobiologic adaptation (development of tolerance) from chronic exposure.

Most dental clinicians will treat a patient with a SUD during their careers. If a patient is suspected of having an SUD, it is imperative to be non-judgmental and empathetic in discussions with the patient and to provide a pathway for the patient to receive appropriate treatment.

Specific drugs of abuse will have different effects on users. All dental professionals should have knowledge of the most commonly abused drugs, their systemic and oral effects, and best practices when providing care to these patients. The following sections introduce the most common SUDs encountered in dental practice.

OPIOID USE DISORDER

Few medications have been highlighted as much in recent years as opioid analgesics. This is largely due to the high risk of misuse and diversion associated with these medications. However, the first reference to opium is found in the 3rd century B.C.E. The use of opium was well-understood by Arab physicians, and Arab traders introduced the drug to Asia, where it was utilized primarily for the control of dysentery [67].

The isolation of morphine from opium was achieved in 1806 and was named for Morpheus, the Greek god of dreams [67]. The discovery of other alkaloids in opium followed: codeine in 1832 and papaverine in 1848. By the mid-nineteenth century, pure alkaloids were used in medical practice in place of crude opium preparations [67].

In addition to the highly beneficial therapeutic effects, the toxic side effects and addictive potential of opioids have been known for centuries. These undesired effects have prompted a search for a potent synthetic opioid analgesic free of addictive potential and other complications. However, all synthetic opioids introduced into medical use share the same liabilities of the classical opioids. The search for new opioid therapeutics has resulted in the synthesis of opioid antagonists and compounds with mixed agonist-antagonist properties, such as buprenorphine, which has expanded therapeutic options and provided the basis of expanded knowledge of opioid mechanisms [67].

Nonmedical use of prescription opioids was reported in literature as early as 1880. A report in 1928 documented that injection of opioids contributed to the development of nonmedical use and misuses of prescription opioids. Before 1930, the prevalence of nonmedical opioid injecting in the United States was low. But by the mid-1940s, more than one-half the admissions to the National Institute of Mental Health's Lexington Hospital were for the misuse of prescription opioids [68].

Opioid broadly refers to all compounds related to opium. The term opium is derived from opos, the Greek word for "juice," as the drug is derived from the latex sap of the opium poppy Papaver somniferum. Drugs derived from opium, including the natural products morphine, codeine, and thebaine, may be referred to as opiates [67]. However, for the purposes of simplification, all compounds will be referred to as opioids in this course.

Morphine is the reference against which other opioids are compared, and analgesic potency is calculated as dose equivalence to morphine (i.e., morphine milligram equivalent or MME). Table 1 shows a typical equianalgesic-dose table with figures validated for acute pain in opioid-naïve patients and conversions for opioid-tolerant patients [69,70].

Table 1: OPIOID ANALGESIC APPROXIMATE DOSE EQUIVALENTS

Opioid Analgesic

Oral Dose

Parenteral Dose

Morphine Equipotency Ratio, Oral

Morphine

30 mg

10 mg

Reference opioid

Codeine

200 mg

100 mg

Not established

Fentanyl (transdermal)

Not applicable

100 mcg

Not applicable

Hydrocodone (Zohydro ER)

30–45 mg

Not applicable

1.5:1

Hydromorphone (Exalgo ER)

8 mg

2 mg

5:1

Levorphanol

4 mg

2 mg

Not established

Oxycodone (OxyContin ER)

20–30 mg

10–15 mg

2:1

Source: [69,70]

Morphine and most other opioid agonists share in common the following physiologic effects [67]:

- Analgesia

- Changes in mood and reward behavior

- Disruption of neuroendocrine function

- Alteration of respiration

- Changes in gastrointestinal and cardiovascular function

Pharmacology

Opioids have been the mainstay of pain treatment for thousands of years, exerting their effects by mimicking naturally occurring endogenous opioid peptides or endorphins [67]. Although many new opioids have been developed with pharmacologic properties similar to morphine, morphine remains the standard against which new analgesics are measured [67].

Endogenous Opioid Peptides

The endogenous opioid system is complex and subtle, with diverse functions. The system plays a sensory role, which is prominent in inhibiting response to painful stimuli; a modulatory role in gastrointestinal, endocrine, and autonomic functions; an emotional role evidenced by the powerful rewarding and addicting properties of opioids; and a cognitive role involving modulation of learning and memory [67].

There are three distinct families of classical opioid peptides: enkephalins, endorphins, and dynorphins. Each of these families is derived from a distinct precursor protein and has a characteristic anatomical distribution. The precursor proteins, preproenkephalin, pro-opiomelanocortin (POMC), and preprodynorphin are encoded by three corresponding genes. The primary opioid peptide derived from POMC is beta-endorphin. The POMC precursor is also processed into the non-opioid peptides adrenocorticotropic hormone (ACTH), melanocyte-stimulating hormone (alpha-MSH), and beta-lipotropin (beta-LPH), suggesting a common precursor for the stress hormone ACTH and the opioid peptide beta-endorphin. This association indicates a shared physiologic linkage between the stress axis and opioid systems, which has been validated by the observation of stress-induced analgesia [67].

Opioid Receptors

Opioids produce their effects through activity at three major receptor subtypes: mu, kappa, and delta. These G-protein-coupled receptors are linked to adenylate cyclase. The endogenous ligands for these receptors, beta-endorphin, enkephalin, and dynorphin, are expressed heterogeneously throughout the central and peripheral nervous systems, with a distribution pattern parallel with that of opioid receptors. Opioid receptors are also found in the central respiratory centers. Functional studies have revealed substantial parallels between mu and delta receptors and dramatic contrasts between mu/delta and kappa receptors [71].

Most opioid therapeutics, and all opioids with abuse potential, are selective for mu receptors, reflecting their similarity to morphine. However, drugs that are relatively selective at standard doses can interact with additional receptor subtypes at higher doses, resulting in divergent pharmacologic profiles [67]. A large number of endogenous ligands activate a small number of opioid receptors, a pattern strikingly different from most other neurotransmitter systems, in which a single ligand interacts with a large number of receptors that have different structures and second messengers [67].

Absorption, Distribution, Metabolism, and Elimination

Typically, opioids are readily absorbed from the gastrointestinal tract. The more lipophilic opioids are easily absorbed through the nasal or buccal mucosa. The most lipophilic opioids can be absorbed transdermally [67]. Most opioids, including morphine, undergo variable but significant hepatic first-pass metabolism, limiting oral bioavailability relative to parenteral administration. Most opioids act quickly when given intravenously. Compared with more lipid-soluble opioids, such as codeine, heroin, and methadone, morphine crosses the blood-brain barrier at a considerably lower rate [67].

Risk Factors for Opioid Use Disorder

Persons at heightened risk for opioid misuse or dependence include those who have a current or past history of substance misuse/abuse, individuals with untreated psychiatric disorders, and those with social or family environments that facilitate or encourage misuse [72]. It is estimated that approximately 6.7 to 7.6 million adolescents and adults in the United States are living with opioid use disorder at any given time [73].

The expected drug effect and the setting of use (context of administration) play important roles in the social learning of drug use. Because opioids, like other drugs that increase dopamine turnover, lead to conditional responses, the use of opioids may become conditioned to the activities of daily living. As a result, environmental stimuli become powerfully associated with opioid use, which can trigger cravings for the drug. The visibility of pharmaceutical marketing and advertising of medications may also play a role by changing the attitudes towards ingestion of these agents.

For youth, a social learning aspect to drug use is likely, based on the modeling of drug use by adults in their families and social networks [72]. Studies have found that 15% of high school students reported having ever used select illicit or injection drugs (i.e., cocaine, inhalants, heroin, methamphetamines, hallucinogens, or ecstasy); in addition, 14% of students reported misusing prescription opioids [74]. Individuals who use nonmedical prescription opioids before 13 years of age are more likely to become addicts than those who initiated use at 21 years of age or older. The odds of becoming an addict are reduced 5% each year after 13 years of age [75]. Additionally, it is a commonly held view among adolescents (27%) that prescription drugs are "much safer" than street drugs [76]. This belief is undoubtedly shared with much of the adult population and has led to the extraordinary rise in recreational prescription drug users.

Dental Treatment Considerations

Responsible prescribing of opioids is an essential measure to avoid contributing to and escalating the opioid crisis in the United States. Opioid analgesics are generally not used as first-line analgesic therapy; non-drug and non-opioid drug alternatives should be considered first. Opioids may be initiated when benefits are likely to outweigh risks, when other approaches to analgesia are ineffective or unlikely to be effective, and with a treatment plan designed to mitigate the risks of addiction, toxicity, and other adverse effects.

Dental pain after oral or periodontal surgery is caused by the release of prostaglandins from injured tissues. This type of pain is generally best managed by nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit prostaglandin formation. NSAIDs act locally while opioids act centrally, which results in greater and more dangerous side effects. Several controlled studies have concluded that NSAIDs, with or without adjunctive acetaminophen, provide equivalent or superior dental pain relief when compared to opioids [77]. The recommended dose of ibuprofen for mild post-procedural dental pain is 200–400 mg every four to six hours; alternatively, 400–600 mg ibuprofen combined with 500 mg acetaminophen every six hours may be used. If severe pain develops and an opioid analgesic is indicated, it is vital to start with the lowest possible dose for three days, after which the patient can be switched to ibuprofen with or without acetaminophen [78]. The American Dental Association supports statutory limits on the dosage and duration of opioid analgesics of no more than seven days for the treatment of acute dental pain [79]. Dental clinicians can also use techniques, including atraumatic surgical technique and long-lasting local anesthetics (e.g. bupivacaine), to minimize postprocedural pain and the need for analgesia.

If an opioid use disorder is disclosed or suspected, steps should be taken to increase patient safety and minimize the risk of misuse and dependence. In patients with opioid use disorder, nitrous oxide inhalation analgesia should be avoided, as it creates a similar pleasurable effect to opioids and can increase cravings. Benzodiazepines have become a popular adjunct medication to reduce dental-related anxiety ("sleep dentistry"), but coingestion of opioids and this class of medications elevates the risk of pronounced respiratory depression and fatality [80].

Patients with opioid use disorder are more prone to the development of xerostomia, caries, periodontal disease, and oral infections [61]. As discussed, the decreased flow and volume of saliva associated with xerostomia reduces the self-cleaning action of the teeth, increasing the risk of dental caries and periodontal disease.

Although the patient's medical history is reviewed prior to any dental treatment, he or she may not disclose current or historical opioid misuse or addiction. If a patient has a suspected opioid use disorder, the clinician should initiate an open, judgement-free discussion that focuses on the long-term well-being of the patient. Through responsible prescribing practices and patient referral, if appropriate, dental clinicians can help address the opioid crisis and provide the best level of patient care.

BENZODIAZEPINE USE DISORDER

For years, anxiolytic medications have been used in dental practice to decrease anxiety and allow treatment to be provided comfortably. Benzodiazepines provide a level of sedation that allows for significant relaxation but continued response to verbal commands and questions. Outside of dental practice, these agents may be used in the treatment of insomnia, generalized anxiety disorders, convulsive disorders, and seizure disorders. However, benzodiazepines are associated with potential problems with abuse and addiction.

Benzodiazepines are CNS depressants that enhance the major inhibitory neurotransmitter gammaaminobutyric acid (GABA) and decrease brain activity [82]. Benzodiazepines are distinct in their potentially lengthy duration of action; some agents produce active metabolites that extend their pharmacologic effect.

When used in dental practice, benzodiazepines are prescribed for a short period, usually just the night before and/or immediately preceding the appointment. Often, diazepam 5–10 mg is used for this purpose. The primary concern with diazepam is its extended duration of action, especially if opioids are also prescribed for postprocedural pain. Diazepam is metabolized as the active metabolite desmethyldiazepam, the half-life of which is 100 hours [13]. This prolonged duration of action far exceeds the duration of a dental appointment and can leave the patient in a sedated state with decreased mental acuity. It can also interact with opioid analgesics to potentiate the sedating and respiratory depression effects.

The ideal anxiolytic medication for dental appointments would provide adequate sedation with a short half-life. As such, triazolam is a better option, with a plasma half-life of two to three hours and rapid clearance that allows the patient to resume regular activities quickly [83]. Patients should be advised to refrain from alcohol while taking benzodiazepines because of the risk for CNS depression.

At the dose and duration benzodiazepines are used in dental practice, addiction and withdrawal symptoms are unlikely. However, some dental patients are on long-term benzodiazepine therapy for a mental health disorder (e.g., generalized anxiety disorder). The long-term use of these medications is associated with the potential for tolerance, physical dependence, addiction, and withdrawal symptoms.

Among patients who have used benzodiazepines for longer than six months, approximately 40% will experience moderate-to-severe withdrawal symptoms; the remaining 60% will experience mild symptoms upon abrupt cessation [84]. The most common benzodiazepine withdrawal symptoms include anxiety, panic attacks, insomnia, nightmares, depression, night sweats, heart palpitations, muscle pain, and problems with memory and concentration [85].

Dental Treatment Considerations

If a dental patient is known to be on long-term benzodiazepine therapy, consultation with the individual's physician or psychiatrist may be required to ensure that the medication can be safely continued or halted. As discussed, opioid analgesics should be avoided if possible in these patients. Similarly, nitrous oxide inhalation sedation can enhance the CNS depressant effects of benzodiazepines and should be avoided.

Withdrawal from benzodiazepines must be done under medical supervision and usually features a gradually decreasing dose. The expected severity of withdrawal from benzodiazepines can be assessed using the Clinical Institute Withdrawal Assessment—Benzodiazepines (CIWA-B) tool, which consists of 22 items. Higher scores indicate increasing difficulty and morbidity with the withdrawal symptoms [85].

Although there are no oral lesions specific to benzodiazepine use, xerostomia is a potential adverse oral effect. Personalized oral hygiene instructions and a more frequent recall schedule can promote optimal oral health for patients who experience this adverse effect. Consultation with the patient's physician should be sought if there is any concern about the patient's ability to withstand dental treatment.

ALCOHOL USE DISORDER

No substance, legal or illegal, has a more paradoxical mythology than alcohol. It is undeniably one of the most widely and safely used intoxicants in the world; however, it is also potent and dangerous, both from a psychologic and a physiologic viewpoint. Alcohol is currently responsible for more deaths and personal destruction than any other known substance of abuse, with the exception of tobacco. Substances of abuse are often put into categories based on their effects. Alcohol has effects similar to other depressants. Characteristics include:

- Decreased cognitive function while intoxicated

- Decreased inhibition and increased impulsivity

- Risk of overdose

- Development of depressive symptoms in heavy users

- Withdrawal symptoms similar to other depressants

- Symptoms of anxiety during withdrawal

- Substance-induced psychoses in some heavy users

There are several known risk factors for alcohol use disorders, including [86,87]:

- Temperament: Moodiness, negativity, and provocative behavior may lead to a child being criticized by teachers and parents. These strained adult-child interactions may increase the chances that a child will drink.

- Hyperactivity: Hyperactivity in childhood is a risk factor for the development of adult alcohol use disorders. Children with attention deficit hyperactivity disorder (ADHD) and conduct disorders have increased risk of developing an alcohol use disorder. Childhood aggression also may predict adult alcohol abuse.

- Parents: The most compelling and largest body of research shows parents' use and attitudes toward use to be the most important factor in an adolescent's decision to drink.

- Gender: Among adults, heavy alcohol use is almost three times more common among men than women and also more common among boys in middle or high school than among girls. Men with ADHD and/or conduct disorders are more likely to use alcohol than men without these disorders, while women who experience more depression, anxiety, and social avoidance as children are more likely to begin using alcohol as teens than women who do not experience these negative states.

- Psychology: Bipolar disorder, schizophrenia, antisocial personality disorder, and panic disorder all also increase the risk of a future alcohol use disorder.

Alcohol use disorder is a primary and chronic disease that is progressive and often fatal; it is not a symptom of another physical or mental condition. It is a disease in itself, like cancer or heart disease, with a very recognizable set of symptoms that are shared by others with the same disorder. About 29.5 million people (12 years of age and older) in the United States met DSM-5-TR criteria for alcohol use disorder in 2022 [88].

Dental professionals should understand the criteria and warning signs of alcohol use disorder. This enables safe patient care and earlier confrontation and intervention. Verifying the facts that show a person is at risk for alcohol use disorder and confronting the impaired individual with those facts is the definition of an office or brief intervention. Brief intervention is most effective before dependence is reached. Once diagnosable, the patient needs more comprehensive intervention.

Dental Treatment Considerations

Alcohol consumption can affect a variety of physiologic and psychologic processes, and persons who are currently inebriated should have dental treatment deferred. Although alcohol use disorder is not associated with any specific oral lesions, there are several areas of oral involvement that may be associated with excessive and/or long-term alcohol consumption. Excessive drinking may interfere with the absorption, digestion, metabolism, and utilization of nutrients, particularly vitamins. Individuals with alcohol use disorder often use alcohol as a source of calories to the exclusion of other food sources, which may also lead to a nutrient deficiency and malnutrition. In the late stage of the disease, patients may develop anorexia or severe loss of appetite, and refuse to eat. Persons with alcohol use disorder account for a significant proportion of patients hospitalized for malnutrition [89].

Direct toxic effects of alcohol on the small bowel causes a decrease in the absorption of water-soluble vitamins (e.g., thiamine, folate, B6). Studies have suggested that alcoholism is the most common cause of vitamin and trace-element deficiency in adults in the United States. Alcohol's effects are dose dependent and the result of malnutrition, malabsorption, and ethanol toxicity [90]. Vitamins A, C, D, E, K, and the B vitamins are deficient in some individuals with alcohol use disorder. All of these vitamins are involved in wound healing and cell maintenance. Because vitamin K is necessary for blood clotting, deficiencies can cause delayed clotting and result in excess bleeding. Vitamin A deficiency can be associated with night blindness, and vitamin D deficiency is associated with softening of the bones. Deficiencies of other vitamins involved in brain function can cause severe neurologic damage (e.g., deficiencies of folic acid, pyridoxine, thiamine, iron, zinc). Thiamine deficiency from chronic heavy alcohol consumption can lead to devastating neurologic complications, including Wernicke-Korsakoff syndrome, cerebellar degeneration, dementia, and peripheral neuropathy [91].

Alcohol abuse is a major risk factor for many infectious diseases. While respiratory infections are the most common, opportunistic oral infections may also occur, including candidiasis, angular cheilitis, necrotizing ulcerative gingivitis, and recurrent herpes labialis. Odontogenic infections of pulpal and/or periodontal origin are more virulent in persons with compromised immune systems and can have an aggressive extension into deeper fascial and muscle layers, with the potential for serious morbidity. Infections of rapid onset and regional dissemination require intravenous antibiotics and may require hospital admission. Dental clinicians who observe these opportunistic oral infections should discuss the finding with the patient.

Chronic alcohol abuse can also have an adverse effect on the salivary glands. In some cases, this manifests as bilateral enlargement of the parotid glands, known as sialosis. Sialosis is the result of peripheral neuropathy induced by chronic exposure to ethanol and reduced salivary flow [61].

A decrease in the buffering ability of the saliva results in a more acidic environment and proliferation of caries and Candida albicans. Prescription-strength fluoride toothpaste or gels can help reduce this risk.

The teeth of an individual with alcohol use disorder may be eroded due to the repetitive chemical (acidic) exposure to alcoholic drinks or vomit, resulting in perimolysis. The process of dental erosion can affect any tooth but the palatal surfaces of the maxillary teeth are most frequently affected. The classic presentation of an eroded tooth surface is smooth and shiny surface dentin. This exposed dentin can be sensitive to thermal changes and sweets. Erosive wear can undermine dental restorations and lead to a progressive loss of the vertical dimension of occlusion. Teeth with extensive loss of enamel can be difficult to restore.

The long-term abuse of alcohol has been shown to cause bone marrow suppression [93]. This can lead to a diminished number of neutrophils, which have a critical role in phagocytize bacteria associated with periodontal disease. This deficiency can predispose individuals with alcohol use disorder to opportunistic infections and more severe periodontal disease.

A deficiency in the quantity or the quality of platelets can impair the ability to obtain hemostasis after oral surgery, periodontal surgery, or root planing and curettage. Conducting a complete blood count (CBC) with differential can determine if platelet levels are sufficient to obtain hemostasis. However, these tests are not easily accessible for many dental practices. Patients should be asked if they bruise easily, if they experience problems with postprocedural bleeding after other invasive procedures, if they have a history of spontaneous nose bleeds, or if a small cut requires an extended time to coagulate. A positive response to any of these questions could indicate a problem with coagulation/healing and should prompt referral to a physician for further testing. Any invasive dental procedures should be deferred.

The liver is a particularly vulnerable organ to alcohol consumption, in large part because it is where alcohol is metabolized prior to elimination from the body. The most common manifestation among persons with alcohol use disorder is called "fatty liver." Among heavy drinkers, the incidence of fatty liver is almost universal. For some, a fatty liver may precede the onset of alcoholic cirrhosis.

The liver is the most critical organ for the metabolism of medications most commonly used in dental treatment, including analgesics, antibiotics, and local anesthetics. Amide-type local anesthetics (e.g., lidocaine, mepivacaine, prilocaine bupivacaine) are metabolized in the liver, and compromised hepatic function can cause plasma levels of local anesthetic to increase to toxic levels. As such, the lowest dose of local anesthetics should be used for these patients. Articaine is technically classified as an amide, but approximately 90% to 95% is metabolized by plasma esterases [13]. So, articaine is preferred for patients with compromised hepatic function, if appropriate.

Chronic heavy drinking appears to activate the enzyme CYP2E1, which may be responsible for transforming the over-the-counter pain reliever acetaminophen into toxic metabolites that can cause liver damage. Even when acetaminophen is taken in standard therapeutic doses, liver damage has been reported in this population [94]. A review of studies of liver damage resulting from acetaminophen-alcohol interaction reported that, in individuals with alcohol use disorder, these effects may occur with as little as 2.6 grams of acetaminophen (four to five "extra-strength" pills) taken over the course of the day by persons consuming varying amounts of alcohol [95]. The damage caused by alcohol-acetaminophen interaction is more likely to occur when acetaminophen is taken after, rather than before, the alcohol has been metabolized [94]. Moderate drinkers should also be made aware of this potential for interaction. There is now a warning label on the bottle that states, "If you consume three or more alcoholic drinks every day, ask your doctor whether you should take acetaminophen or other pain relievers/fever reducers." Further, in 2014, the FDA issued a statement that combination prescription pain relievers containing more than 325 mg acetaminophen per dosage unit should no longer be prescribed due to reported severe liver injury with acetaminophen in patients who took more than the prescribed dose in a 24-hour period; took more than one acetaminophen-containing product at the same time; or drank alcohol while taking acetaminophen products [96].

NICOTINE (TOBACCO) USE DISORDER

Nicotine dependence is considered a SUD and is the component of all tobacco products. Most commonly, nicotine is self-administered via cigarette smoking. Cigarette smoking is on the decline in the United States, but use of other tobacco products continues to increase annually . In addition to a rise in use of smokeless tobacco, people across the United States (especially youth) are using e-cigarettes (also referred to as e-cigs, vapes, e-hookahs, vape pens, and electronic nicotine delivery systems or ENDS), cigars, cigarillos (small cigars), hookahs, kreteks, pipes, and bidis (or beedis). Unfortunately, each of these products is just as dangerous (if not more so) as the use of cigarettes [101].

The rise of e-cigarettes in the past decade has introduced new variables in the prevention and treatment of nicotine addiction. Originally marketed as a smoking cessation tool, e-cigarettes are electronic products that typically deliver nicotine in the form of an aerosol [101].

Cigarette smoke is a complex mixture of more than 7,000 components, including nicotine, aromatic hydrocarbons, sterols and oxygenated isoprenoid compounds, aldehydes, nitriles, cyclic ethers, and sulfur compounds. At least 70 of these components are known to cause cancer [107].

Because nicotine can be absorbed through the oral mucosa, it does not have to be inhaled to enter the bloodstream [61]. In fact, smokeless tobacco users absorb two to three times the amount of nicotine absorbed from smoking. Smokeless tobacco is defined as tobacco products that are sucked or chewed (not burned) and includes chewing tobacco, snuff, and dissolvables. An estimated 8.6% of rural adults use smokeless tobacco, compared with 6% of urban adults [108]. Rates of smokeless tobacco use are greatest in states with large rural areas; Wyoming, West Virginia, Mississippi, and Kentucky have the highest use of smokeless tobacco [2]. Results of studies suggest that factors other than age, gender, poverty level, and region are driving urban-rural differences in tobacco use. In one study, the most likely reasons given for smokeless tobacco use were affordability, choice of flavors, ability to use in public places (as opposed to smoking), and safety to persons around the user (i.e., no secondhand smoke) [6]. As noted, while there may be a perception that these products are safer than smoked tobacco, they contain nicotine, are highly addictive, and have been linked to oral, esophageal, and pancreatic cancers [10].

Cigarettes deliver nicotine in a pulsatile manner, with plasma concentrations reaching their peak within 1.5 to 3 minutes of the commencement of smoking and gradually returning toward baseline within two to three hours [11]. Thus, nicotine levels rise and fall throughout the day with each cigarette smoked, declining to minimum amounts found in nonsmokers in the morning after the extended abstinence period of sleep. Such continuous flux in blood nicotine levels locks the user into an endless cycle of ups and downs and is thought to lead to the commonly held notion that smoking has a positive effect on mood. Considering smokers begin to experience withdrawal symptoms within hours of their last cigarette, and because these unpleasant effects are almost completely alleviated by smoking, this perception is hardly surprising. Daily repetition of this process links these perceived positive health benefits to the act of smoking in the smoker's mind and often results in the false identification of cigarettes as an effective form of self-medication [12].

Smoking and tobacco use is associated with a variety of chronic and potentially fatal illnesses. In particular, smoking has been implicated in the development of malignant and nonmalignant lung disease, including chronic obstructive pulmonary disease, bronchitis, influenza, emphysema, pneumonia, and lung cancer. Cardiovascular disease, defined as acute myocardial infarction (MI) and stroke, is strongly related to smoking and comprises 34% of smoking-related mortality; conversely, smoking yields 16% of cardiovascular-related mortality [105].

Oral Implications

In addition to the many deleterious systemic effects of nicotine and smoking, tobacco can have serious adverse effects on oral health as well. Some are reversible and relatively mild, such as teeth staining, while others can result in serious morbidity and mortality, including oral and oropharyngeal squamous cell carcinoma.

Evidence Based Practice Recommendation

The American Dental Association asserts potentially malignant disorders can be diagnosed clinically as leukoplakia, erythroplakia, erythroleukoplakia, or submucous fibrosis, and these lesions may occur among heavy tobacco and alcohol users.

https://jada.ada.org/article/S0002-8177(17)30701-8/fulltext?dgcid=PromoSpots_EBDsite_Oralcancer

Last Accessed: February 19, 2024

Level of Evidence: Expert Opinion/Consensus Statement

Tobacco residue leaves a sticky film on the teeth, which causes staining but also can retain bacterial plaque and increase the risk of caries and periodontal disease. Composite restorations can also be stained by tobacco, especially if there are surface porosities and/or irregularities. Depending on the depth and extent of staining, it may be necessary to replace restorations. Smokers should be advised to adhere to strict oral hygiene practices and recall schedule.

The soft tissues of the oral cavity and throat are also affected by prolonged exposure to tobacco via smoking or chewing. Some of the most common adverse effects associated with tobacco use are gingival recession, mucosal lesions (e.g., leukoplakia), delayed healing of surgical sites, and discoloration of the dorsum of the tongue [15]. Nicotine stomatitis (a widespread palatal keratosis) is most common among heavy pipe and cigar smokers and is a chronic inflammatory response of the palatal minor salivary glands.

Of course, the most dire oral consequence of tobacco use is oral cavity squamous cell carcinoma (OCSCC). Each year, there are more than 58,450 new cases and 12,230 deaths from OCSCC or related complications [18]. Many cases of OCSCC are diagnosed at advanced stages with significant local and regional metastases, and the related surgical resection and radiation therapy necessary for advanced-stage OCSCC are associated with a high degree of morbidity and mortality. Tobacco use is the most commonly identified risk factor for the development of OCSCC, and tobacco users have a 5- to 25-fold higher risk of the development of these malignancies compared with nonusers [19]. While both smoking and chewing tobacco increase the risk for oral malignancy, the sustained direct exposure seen with smokeless tobacco use is a greater risk. This risk is increased with concurrent alcohol consumption, as alcohol desiccates the mucosal surface and allows the carcinogens in tobacco to have an extended contact time with the tissues.

Early identification of the lesions of OCSCC is essential. Dental clinicians should provide thorough oral cancer screenings on all of their patients, and lesions that have not healed within two weeks after discovery or those that are highly suspicious should be biopsied. Unfortunately, the lesions of OCSCC can present in a variety of ways—there is no characteristic or diagnostic lesion. Leukoplakic (white) lesions are more common than the erythroplakic (red) lesions, but the latter has a much higher potential for malignant transformation.

Other possible adverse oral effects of smokeless tobacco use include gingival recession, halitosis, enamel erosion, damage to the alveolar bone, and periodontal disease. There is also an increased risk for coronal and root surface dental caries, because sugar is added to smokeless tobacco products [20].

Given the extensive potentially detrimental effects of tobacco use, all healthcare professionals, including dental professionals, should counsel their patients to stop tobacco use. U.S. Public Health Service guidelines recommend that all patients be asked [20]:

- Do you smoke or chew tobacco?

- Would you like to quit?

If a patient wants to quit, draw upon the same armament of strategies used to help motivate other health behavior change, such as brushing, flossing, and attending recall appointments. In addition, tobacco cessation programs and pharmacologic agents are often effective. For patients who are not ready to quit, employ the strategies for people in the precontemplative stage of change—remain nonjudgmental and find neutral ways to raise awareness of the problem.

Nicotine replacement therapy is effective in helping people stop tobacco use. This includes patches, gum, lozenges, inhalers, and nasal spray. Bupropion was the first non-nicotine pharmacotherapy for the treatment of tobacco dependence with proven efficacy [21]. Cessation rates have been reported to improve when drug therapy combines nicotine replacement with the antidepressant bupropion [32,35]. However, in its 2020 guideline for initiating pharmacologic treatment of tobacco-dependent adults, the American Thoracic Society (ATS) recommends varenicline over both bupropion and a nicotine patch for tobacco-dependent adults. In adults who are not ready to discontinue tobacco use, the ATS recommends beginning treatment with varenicline rather than waiting until patients are ready to stop tobacco use [21]. It is important to note that these medications have been associated with adverse effects, including an increased risk for depression and suicide [13].

Not surprisingly, tobacco cessation has high rates of relapse, and most people require multiple quit attempts to remain permanently tobacco-free. After 12 weeks of abstinence, about 43% of people return to regular use. However, longer periods of abstinence increase long-term success rates. After five years of abstinence, relapse rates drop to about 7% [43]. This presents an opportunity to help patients understand that tobacco cessation is a long-term process and previous attempts provide learning opportunities for the next attempt.

CANNABIS USE DISORDER

Cannabis products such as marijuana and hashish comprise the most widely used recreational drugs both in the United States and worldwide [44]. Although, with a few exceptions, these drugs lack the liability of abuse and dependence seen with other illicit drugs, such as cocaine, methamphetamine, and heroin, physical and psychologic withdrawal symptoms can occur with cannabis products, posing an additional consideration in the management of these patients.

There are several species of cannabis, including Cannabis sativa,Cannabis indica, and Cannabis ruderalis. Cannabis sativa is the most widely used variety and can be cultivated in a variety of climates [48,52]. The two main derivatives of cannabis are marijuana and hashish. The term marijuana originated in Mexico to describe cheap tobacco; today, it refers to the dried leaves and flowers of the Cannabis plant. Hashish, an Arabic term, is the viscous resin of the plant [48,52].

Cannabis contains more than 480 known chemicals, more than 100 of which are grouped under the category of cannabinoids [48,53]. The primary psychoactive ingredient is delta-9-tetrahydrocannabinol (delta-9-THC), which accounts for up to 25% of the total dry weight of high-potency strains [59]. Other cannabinoids, including delta-8-THC, cannabinol, cannabicyclol, cannabichromene, and cannabigerol, are present in small quantities (typically less than 5% dry weight) and have no significant psychotropic effects compared to THC. It is unknown whether these compounds may have an impact on the overall effect of cannabis [48]. One notable exception is cannabidiol (CBD), which in some cannabis strains can account for up to 5% dry weight and has demonstrated therapeutic efficacy for psychosis, anxiety, and other disorders [59,81,92].

Cannabis use disorder is best described as a chronic relapsing disease characterized by compulsive seeking and use of cannabis, accompanied by functional and molecular changes to the brain [5]. The single most defining aspect of cannabis use disorder is the salience of the relationship with the drug. The stronger the relationship, the more likely the patient will continue problematic use despite internal and external consequences.

As with many drugs, cannabis can enhance or attenuate the effects of other medications. A combination of dronabinol (a cannabinoid) and prochlorperazine is more effective in reducing chemotherapy-associated nausea and vomiting than prochlorperazine alone [97]. Cannabis can also augment the sedating effects of other psychotropic substances, such as alcohol and benzodiazepines. A number of synergistic effects may be therapeutically desirable, such as the enhancement of:

- Muscle relaxants, bronchodilators, and antiglaucoma medication

- Opioid analgesia

- Phenothiazines' antiemetic effect

- Benzodiazepines' antiepileptic action

The cyclooxygenase inhibitors, indomethacin, acetylsalicylic acid, and other NSAIDs antagonize THC effects, reflecting the involvement of cyclooxygenase activity in several THC effects [98].

Cannabis should not be considered as a safe alternative to tobacco products, as it contains many of the same carcinogens as tobacco products [100]. There is some evidence that frequent and/or heavy cannabis use may promote oral cancer development [104]. While there are no oral manifestations specific to prolonged cannabis use, smoking and/or chewing cannabis can cause an alteration in the oral epithelium known as cannabis stomatitis, which is characterized by chronic inflammation of the oral mucosa with hyperkeratosis and leukoplakia. Compared with the general population, chronic cannabis smokers have poorer oral health, more decayed teeth, more plaque accumulation, and poorer gingival health [102].

Aside from the direct effects of cannabis on the oral tissues, the appetite stimulant effects of THC can result in the consumption of cariogenic snack foods. The caries pattern among these patients typically involves the smooth outer or inner surfaces of the teeth [103].

Some habitual cannabis users experience a decrease in salivary flow and in the pH of the oral environment [106]. As discussed, xerostomia has a variety of adverse oral effects that should be addressed, if present.

COCAINE USE DISORDER

Stimulant drugs are substances that activate the central nervous system (CNS) and peripheral nervous system. There are two main categories of commonly used illicit stimulants: cocaine and amphetamine and its derivatives and analogs, such as methamphetamine. Cocaine, a tropane alkaloid, is extracted from the leaves of Erythroxylumcoca bush, which contain 0.6% to 1.8% of the alkaloid [109,110].

Cocaine's specific mechanism of action involves increasing the synaptic transmission of dopamine, serotonin, and norepinephrine by interaction with plasma membrane transporters to block presynaptic reuptake. Action involving the dopamine transporter is the most important in producing the reinforcing effects, which lead to dependence [109,110].

Cocaine can be absorbed through any mucous membrane. Different routes of cocaine delivery into the body produce different patterns and levels of blood cocaine concentration. Intranasally administered (snorted) cocaine is absorbed and distributed into the body gradually, while the onset of effect is rapid when smoked or injected. The effect of cocaine is experienced most rapidly and intensely when smoked, with an onset of effects typically occurring within 8 to 10 seconds; thus, cocaine is most addictive when smoked. Injected cocaine takes twice as long to enter the brain (i.e., 16 to 20 seconds), and snorted cocaine begins to act in three to five minutes. The lungs are the most rapid and efficient cocaine delivery modality because of the large surface area of absorption and rapidity of arterial circulation to the brain [109,110,111].

Peak plasma levels of cocaine occur 20 to 40 minutes following intranasal ingestion, with a typical concentration of 100–500 mcg/L. Toxicity is rarely seen at this dose level. Plasma half-life ranges from 31 to 82 minutes, with a mean of 38 minutes [109,111].

Subjective and behavioral effects from single- and multiple-dose acute ingestion of cocaine include euphoria, increased heart rate, restlessness, anxiety and panic, delusions, heightened alertness, and insomnia. Over time, chronic users may develop dysphoria, anxiety, restlessness, and paranoia. The risk of toxicity/overdose increases with continued use as well. Withdrawal from cocaine can also have a blend of physical and behavioral symptoms, including fatigue, decreased ability to concentrate, depression, anxiety, cravings, generalized body aches, chills, and tremors [111].

Patients are unlikely to volunteer use of cocaine during a dental appointment. However, if any common signs or symptoms of cocaine use or cocaine withdrawal are observed, clinicians should have an open, nonjudgmental discussion focusing on the patient's well-being. If appropriate, referral information should be provided.

In patients who may be taking cocaine, local anesthetics with a vasoconstrictor (e.g., 1:100,000 epinephrine) should be avoided. Concurrent use within 24 hours of last cocaine dose potentiates the stimulant effects and can lead to a hypertensive crisis, cerebrovascular accident (stroke), or myocardial infarction (heart attack) [61].

Snorting cocaine can lead to necrosis and perforation of the nasal septum and palate; surgical repair of these defects can be very challenging [112]. Possible oral effects of cocaine use include decay, erosion, gingival recession, decreased salivary pH, periodontal disease, and ulcerated and erythematous gingival tissues from intraoral cocaine deposition [113]. Oral and maxillofacial symptoms of cocaine abuse include xerostomia, bruxism, and temporomandibular joint pain [114].

METHAMPHETAMINE USE DISORDER

Like cocaine, methamphetamine is a CNS stimulant and induces temporary improvements in mental acuity and physical function. The widespread use of methamphetamine stems largely from its potential to produce euphoria, reduce fatigue, enhance performance, suppress appetite, and induce weight loss, coupled with multiple interacting social, biologic, cultural, and psychologic factors. Unlike cocaine and heroin, which are plant-derived and whose synthesis is complex, methamphetamine is easily prepared from simple chemical precursors [110,116].

Evidence Based Practice Recommendation

According to the Department of Veterans Affairs, there is insufficient evidence to recommend for or against the use of any pharmacotherapy for the treatment of methamphetamine use disorder.

https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPG.pdf

Last Accessed: February 19, 2024

Level of Evidence: Expert Opinion/Consensus Statement

Methamphetamine stimulates the release and blocks the presynaptic reuptake of serotonin, dopamine, and norepinephrine. It is metabolized at a much slower rate than some other stimulants, such as cocaine. Methamphetamine is primarily available as [110,115,116]:

- "Speed," a low-grade, locally manufactured powder that is snorted or injected

- Pills that are often combined with other drugs, such as ketamine

- "Base" or "paste," an often locally manufactured, glue-like substance

- "Crystal meth" and "ice," which are highly pure, crystalline forms that are smoked or injected

In addition to euphoria, hyperactivity, and energy, other acute effects of methamphetamine use can include increased confidence and self-esteem, grandiosity, feeling of well-being, heightened attentiveness, elevated body temperature, profuse sweating, restlessness, tremors, aggressive behavior, and uncontrollable jaw clenching. Chronic effects can include paranoia, insomnia, psychotic or violent behavior, pronounced fatigue, poor coping abilities, sexual dysfunction, and dermatologic conditions.

"Meth mouth" is widespread among certain populations of methamphetamine users, particularly those incarcerated for methamphetamine-related offenses. "Meth mouth" (dental deterioration) is a constellation of signs and symptoms associated with chronic use of methamphetamine and is caused by methamphetamine-induced vasoconstriction and reduced salivary flow, methamphetamine-induced vomiting, jaw clenching, the high intake of sugary beverages often seen with methamphetamine users, and abandonment of oral hygiene. This condition is characterized by widespread tooth decay and tooth loss, advanced tooth wear and fracture, and oral soft tissue inflammation and breakdown [117].

The American Dental Association recommends that practitioners be particularly aware of the following signs, which may indicate that dental deterioration is linked to methamphetamine use [117]:

- Unaccounted for and accelerated decay in adolescents and young adults

- Distinctive pattern of decay on the buccal smooth surface of the teeth and the interproximal surfaces of the anterior teeth

- Malnourished appearance of heavy users

The acute effects of methamphetamine can include irritability, agitation, hypervigilance, and possibly violent outbursts, and chronic use of methamphetamine has a greater association with violent behavior than any other psychoactive drug. Users of methamphetamine are also at high risk for being recipients of violence [115]. As such, they may present with dental or oral trauma, the healing of which can be complicated by the oral effects of the drug. As always, dental clinicians and staff should take steps to ensure their own safety and the safety of all of their patients, and protocols should be in place to manage patients who appear agitated or disturbed.

8. CONCLUSION

The human mind is complex, and there are many forms of mental illness that affect millions of people in the United States and throughout the world. While strides have been made awareness and treatment of mental illness, stigma and lack of social acceptance remain. Aside from the fact that these conditions are medical illnesses that should be considered in any patient, they can also have systemic and oral effects that specifically impact the provision of dental care. As such, it is incumbent to include discussion and documentation of patients' mental illness and related pharmacotherapy as a part of their medical history.

If serious mental illness is present, the patient's physician and/or psychiatrist should be consulted. A collaborative effort by the entire interprofessional team in the treatment of patients with mental illness ensure that patients are able to maintain optimal oral health and a high quality of life.

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Evidence-Based Practice Recommendations Citations

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50201 • Botulinum Toxin and Dermal Fillers for Facial Aging

Mark Rose, BS, MA, LP

www.netce.com

Copyright © 2024 NetCE, All rights reserved.

The importance for primary care clinicians to understand aesthetic medicine, patient variables, and market factors is brought to light by the increasing rates of aesthetic injections performed by non-board-certified physicians, nurses, and minimally trained aestheticians at inadequately equipped clinics, office settings, and spas. Primary care providers are well-placed to importantly inform their patients about many aspects related to aesthetic medicine but benefit from educational intervention to become most effective in this role.

Table of Contents

50201 • Botulinum Toxin and Dermal Fillers for Facial Aging

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planner

Division Planner Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. TERMINOLOGY

3. BACKGROUND

INCREASING CONCERNS

4. THE PROCESSES OF FACIAL AGING

THE TWO-DIMENSIONAL MODEL

THE 3-D MODEL: NORMAL ANATOMY OF FACIAL TISSUE

THE INTEGRATIVE AND AESTHETIC UNITS PERSPECTIVES

5. BOTULINUM TOXIN

DISCOVERY AND DEVELOPMENT

MECHANISM OF ACTION

AVAILABLE PRODUCTS AND FORMULATIONS

CLINICAL USE OF BOTULINUM TOXIN

6. SOFT TISSUE (DERMAL) FILLERS

HYALURONIC ACID

CALCIUM HYDROXYLAPATITE

POLY-L-LACTIC ACID

POLYMETHYLMETHACRYLATE MICROSPHERES

FILLER SELECTION

7. DEOXYCHOLIC ACID

8. INDIVIDUALIZED ASSESSMENT AND TREATMENT PLANNING

KEY ASSESSMENT ELEMENTS

ETHNIC CONSIDERATIONS

GENDER CONSIDERATIONS

AGE CONSIDERATIONS

9. THE MINIMALLY INVASIVE TREATMENT APPROACH

RECOMMENDED THERAPY COMBINATIONS

RECOMMENDED THERAPY SEQUENCE

PATIENT-TAILORED TREATMENT

THE TRI-VECTOR TECHNIQUE

THE UPPER FACE

THE MIDFACE

THE LOWER FACE AND NECK

THE NECK

10. PATIENT SELECTION AND EVALUATION

SCREENING AND SELECTION

PATIENT EVALUATION AND CONSENT

11. ADVERSE EFFECTS

PREVENTION AND RISK REDUCTION

COMMON ACUTE SIDE EFFECTS

INFREQUENT ACUTE ADVERSE EVENTS

VASCULAR COMPROMISE

ALLERGIC/HYPERSENSITIVITY REACTIONS

DELAYED COMPLICATIONS: INFLAMMATION OR INFECTION?

12. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

50201 • Botulinum Toxin and Dermal Fillers for Facial Aging

Education Category. Medical / Surgical

Release Date. 04/01/2024

Expiration Date. 03/31/2027

Course Overview

The importance for primary care clinicians to understand aesthetic medicine, patient variables, and market factors is brought to light by the increasing rates of aesthetic injections performed by non-board-certified physicians, nurses, and minimally trained aestheticians at inadequately equipped clinics, office settings, and spas. Primary care providers are well-placed to importantly inform their patients about many aspects related to aesthetic medicine but benefit from educational intervention to become most effective in this role.

Audience

This course is designed for dental professionals who may administer or care for patients who have undergone aesthetic procedures.

Accreditations & Approvals

NetCE Nationally Approved PACE Program Provider for FAGD/MAGD credit. Approval does not imply acceptance by any regulatory authority or AGD endorsement. 10/1/2021 to 9/30/2027 Provider ID #217994. NetCE is an ADA CERP Recognized Provider. ADA CERP is a service of the American Dental Association to assist dental professionals in identifying quality providers of continuing dental education. ADA CERP does not approve or endorse individual courses or instructors, nor does it imply acceptance of credit hours by boards of dentistry. Concerns or complaints about a CE provider may be directed to the provider or to ADA CERP at www.ada.org/cerp. NetCE is approved as a provider of continuing education by the Florida Board of Dentistry, Provider #50-2405. NetCE is a Registered Provider with the Dental Board of California. Provider Number RP3841. Completion of this course does not constitute authorization for the attendee to perform any services that he or she is not legally authorized to perform based on his or her license or permit type.

Designations of Credit

NetCE designates this activity for 10 continuing education credits. AGD Subject Code 780. This course meets the Dental Board of California's requirements for 10 unit(s) of continuing education. Dental Board of California course #10-3841-25415.

Course Objective

The purpose of this course is to provide clinicians with the knowledge necessary to provide minimally invasive aesthetic procedures and to care for patients who have undergone these procedures.

Learning Objectives

Upon completion of this course, you should be able to:

1. Outline the background of aesthetic medicine and botulinum toxin/filler use.

2. Describe the process of usual facial aging.

3. Discuss the mechanism of action and clinical use of botulinum toxin for the treatment of facial aging.

4. Compare and contrast the classes of dermal filling agents available.

5. Analyze components that affect the appropriate selection of dermal filling agent.

6. Describe key aspects of individualized assessment of patients seeking aesthetic treatments for facial aging.

7. Outline the minimally invasive approach to the treatment of facial aging.

8. Evaluate patient-related factors affecting suitability for various aesthetic treatments.

9. Identify acute and potentially severe side effects of botulinum toxin/filler use.

10. Discuss the role of biofilm infections in delayed reactions to dermal fillers.

Faculty

Mark Rose, BS, MA, LP, is a licensed psychologist in the State of Minnesota with a private consulting practice and a medical research analyst with a biomedical communications firm. Earlier healthcare technology assessment work led to medical device and pharmaceutical sector experience in new product development involving cancer ablative devices and pain therapeutics. Along with substantial experience in addiction research, Mr. Rose has contributed to the authorship of numerous papers on CNS, oncology, and other medical disorders. He is the lead author of papers published in peer-reviewed addiction, psychiatry, and pain medicine journals and has written books on prescription opioids and alcoholism published by the Hazelden Foundation. He also serves as an Expert Advisor and Expert Witness to law firms that represent disability claimants or criminal defendants on cases related to chronic pain, psychiatric/substance use disorders, and acute pharmacologic/toxicologic effects. Mr. Rose is on the Board of Directors of the Minneapolis-based International Institute of Anti-Aging Medicine and is a member of several professional organizations.

Faculty Disclosure

Contributing faculty, Mark Rose, BS, MA, LP, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planner

Mark J. Szarejko, DDS, FAGD

Division Planner Disclosure

The division planner has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

Visibly apparent aging and loss of youthful appearance are frequent concerns of patients seeking cosmetic treatment. Botulinum toxin and dermal (soft tissue) fillers are minimally invasive (i.e., injection-delivered) therapies that, along with knowledge advances, have revolutionized cosmetic treatment of aging features.

The clinical features of aging are the result of bone resorption; ligament laxity; redistribution, volume loss, and descent of facial soft tissue; and formation of lines and folds in inelastic, sagging skin. This complexity is not amenable to single-modality treatment; current practice combines botulinum toxin and fillers as the core approach, with other therapies added. Filling isolated lines or creases is de-emphasized.

In carefully selected patients with strict adherence to safety standards, desired results can be achieved with a low risk to safety. With increasing consumer demand, injector backgrounds and settings have expanded beyond oversight. Rises in catastrophic complications are largely unknown, as the "risk-free" perception of botulinum toxin and fillers continues. Clinicians and patients may be unaware of the range of U.S. Food and Drug Administration (FDA)-approved minimally invasive options, advances in the understanding and addressing facial aging with these therapies, and the potential of serious complications with incorrect use. These areas are the focus of this course.

Beyond the scope of this course are cosmetic surgery (e.g., rhinoplasty, face-lift), reconstructive or rehabilitative surgery, cosmetic concerns of systemic origin (e.g., lipoatrophy from antiretroviral therapy), and nonfacial cosmetic concerns. Laser, energy, and topical therapies are noninvasive interventions for sun-damaged, aged skin and acne scars, but they will not be the focus of this course. Cosmetic medicine is a point of convergence for diverse psychological, social, cultural, and racial factors, all of which should be considered for each patient. The properties of products discussed in this course are unique. This requires reference by commercial brand, but should not be construed as endorsement of any commercial product.

2. TERMINOLOGY

Plastic surgery includes subfields of reconstructive or rehabilitative surgery for congenital malformations or acquired disfigurements, and cosmetic surgery for correction, restoration, or enhancement of appearance[1]. "Aesthetic medicine" was coined to replace "cosmetic medicine/surgery," but the terms remain interchangeable [2].

The cosmetic medicine literature describes features with terms (e.g., defect, defective, deformity, deformation) that carry different meanings outside of this highly specialized professional audience. It is not the intent of this course to imply that normal aging of the face or skin is in any way a defect aside from the patient's perception or desires in terms of appearance. Beauty is a standard that varies by culture, time, age, and personal experiences, and there is no one standard for any facial feature or individual.

Therapeutic goals are variously described as volumizing, re-volumizing, rejuvenation, restoration, harmonization, resurfacing, correction, and others, with little consistency. This course will not attempt to modify terminology used in the published literature, except to improve logical consistency.

3. BACKGROUND

Until the 1990s, facial aging was attributed to gravitational effects that required surgical lifting and tightening to defy soft-tissue descent. Facial aging as a multi-tissue process of descent, volume loss, and resorption was first described in 1965 but remained obscure, and the focus on superficial tissue descent and correction persisted [3,4,5,6].

Botulinum toxin and dermal fillers were introduced to correct cosmetic defects without the need for surgery. Earlier use to spot-correct isolated wrinkles and creases led to temporary but limited benefits, with no advantage over surgical facelift for persons with moderate or advanced aging features [4,5,6,7].

Studies identified soft tissue volume loss and hard tissue resorption as causal to facial aging. This prompted filler injection into deep tissue for re-volumizing; new fillers designed for specific tissue placement; use of lower-dose botulinum toxin to improve outcomes; advances in lasers and energy devices for resurfacing or tightening with minimal recovery time; and evidence of synergistic efficacy and superior cosmetic outcomes with combined therapies [6,7,8]. These advances brought a paradigm shift from "wrinkle-chasing," with isolated clinical benefit, to recognition of facial aging as a complex interaction of extrinsic and intrinsic factors across multiple tissue planes requiring a three-dimensional, multilayered treatment approach [9,10]. Surgical facelift requires patients to wait until visible aging is sufficient to warrant surgery, often with sudden, sometimes unnatural, changes in appearance. Minimally invasive therapy offers a more gradual, natural-looking harmonization preferred by many patients [7].

Botulinum toxin and dermal filler injection techniques are constantly evolving; what was considered state-of-the-art 5 to 10 years ago no longer represents a practice standard [11]. Every year, the American Society of Plastic Surgeons (ASPS) and the American Society for Dermatologic Surgery (ASDS) separately publish the number of procedures performed by their board-certified members. In 2020, ASPS members performed 15.6 million cosmetic procedures—13.2 million nonsurgical (92% female)—at a total cost of $16.7 billion. Among patients who received cosmetic procedures, 66% were White, 12% were Hispanic, 9% were Black/African American, 7% were Asian, and 6% were other [12]. The 4.4 million botulinum toxin and 3.4 million dermal filler procedures reported by ASPS in 2020 represent an increase of 459% compared with 2000 [12]. ASDS members in 2019 performed an additional 2.3 million botulinum toxin (88% female) and 1.6 million filler (90% female) procedures, a 60% and 78% increase from 2012, respectively [13]. The number of cosmetic procedures was down significantly in all categories in 2020 (compared with 2019), likely due to COVID-19.

Between 2012 and 2017, there was a 50% increase in cosmetic procedure requests by persons younger than 30 years of age (90% female), and in 2016, more than 229,000 cosmetic procedures were performed in patients 18 years of age or younger [14,15]. The annual figures by ASPS/ASDS are considered the benchmark for cosmetic procedures, trends, and demand, but they significantly under-represent the actual number of minimally invasive procedures performed outside of their membership [16,17,18,19,20].

INCREASING CONCERNS

As cosmetic treatment methods have evolved, provider backgrounds expanded from specialists in plastic surgery (traditional) to dermatology, ophthalmology, and otolaryngology, then to dentists and registered nurses, followed by licensed aestheticians, unsanctioned medical personnel (e.g., medical assistants), and lay practitioners [17]. As such, the experience and qualifications of injectors is increasingly questionable and unpredictable. A large and growing proportion is performed in medical spas, spas, hair salons, other commercial settings, and at "Botox and filler parties" in private homes by non-healthcare professionals, sometimes without written informed consent [16,17].

There is an increasing number of filler complications from intravascular injection, an immediate, severe event that can result in blindness, tissue necrosis, or stroke, and from bacterial biofilm infection, when filler injection seeds skin-surface bacteria into tissue with the filler product [19]. Biofilm infections may become disfiguring, are often antibiotic-resistant, and are potentially a methicillin-resistant Staphylococcus aureus (MRSA) infection [21]. The increasingly unregulated state of botulinum toxin and filler injection practice, the absence of a universal adverse event reporting mechanism, and potentially powerful financial incentives to conceal complications have prompted calls for greater regulation of providers and practice and for relabeling of filler injections as "dermal implants" to accurately reflect the risks inherent in placing an inanimate object into human tissue [16,17,18,22,23].

The face ages in a unique but relatively consistent manner, creating a distinct but recognizable ''aged'' appearance. As people age, many are left with the feeling that their physical appearance is no longer an accurate representation of their mental state. Some opt to pursue cosmetic procedures for ''matching their outsides with their insides'' [24]. In skilled hands with diligent execution of precautions, the results attainable without surgery can be impressive, with a good safety margin. Improper patient selection, preparation, or technique invites problems ranging from patient dissatisfaction and poor cosmetic outcomes to increased risks of serious and potentially catastrophic complications of intravascular injection or delayed bacterial infections. The idea that botulinum toxin and fillers are risk-free cosmetic treatments is thoroughly dispelled.

4. THE PROCESSES OF FACIAL AGING

In the face, the process of aging that culminates in cosmetic concerns is complex. Changes of the facial skeleton, soft tissue, retaining ligaments, fat compartments, and the skin contribute to the features of facial aging in varying degrees, influenced by intrinsic (e.g., genetic) and extrinsic (e.g., sun exposure) factors [25]. To understand facial aging and appropriate interventions requires multidimensional knowledge of the normal anatomy and physiology of facial tissue layers, age-related changes in histology and morphology in each plane, and their multilevel interactions to form cosmetic features of aging.

Perceptual models used in cosmetic medicine can assist in conceptualizing these changes. Each model views facial aging from a different perspective. Presented in sequence, the models break down the complex, dynamic, multidimensional process into its dimensional components. The predominant models are [4,26,27,28,29,30,31,32]:

- The two-dimensional (2-D) model: Organizes the surface anatomy and superficial cosmetic defects into horizontal zones that anchor morphologic features to familiar anatomic boundaries

- The three-dimensional (3-D) model: Delineates facial anatomy into its underlying tissue layers to describe normal and age-related changes in structure/function at each facial tissue level

- The integrative model: "Zooms out" from the 3-D model to describe how tissue-level changes interact to form the visible features of facial aging

- The aesthetic zones/units model: Describes cosmetic defects of facial aging as changes in underlying and surrounding tissue within anatomically compartmentalized units

All four models will be used later in this course to describe the cosmetic features of facial aging and recommended minimally invasive interventions.

THE TWO-DIMENSIONAL MODEL

To describe the anatomic locations of common cosmetic concerns widely referenced in this course (Table 1), the face is divided into three horizontal zones with defined anatomic boundaries [4,30,31,32]:

Table 1: FACIAL AGING FEATURES

Zone

Cosmetic feature

Description

Upper face

Glabellar rhytides

Vertical lines between the eyebrows

Horizontal forehead rhytides

Horizontal creases on the forehead, exacerbated during brow elevation

Lateral canthal rhytides ("crow's feet")

Multiple periocular lines and wrinkles that radiate lateral to the eye, more prominent when smiling

Brow ptosis (drooping)

Tissue descent that can mimic angry or scowling expressions

Temporal fossa wasting

Concavity of the temple area

Midface

Nasojugal fold (tear trough depression)

Depression between the rim of the orbital bone and the nasal sidewall

"Bunny lines"

Wrinkles on the dorsal and lateral nose during contraction of the upper nasalis muscle

Nasolabial foldsa

Creases extending from the lateral nasal alae to the lateral mouth

Lower face

Perioral lip rhytides ("whistler's wrinkles")

Vertical wrinkles extending from the lip border

Mouth frown

A downward turn of the corners of the mouth

Melomental folds ("marionette lines")

Facial lines extending from the corners of the mouth to the mandible (jaw)

Mental crease

A horizontal groove present on the chin

Peau d'orange chin

Multiple dimples on the chin during contraction of the mentalis muscle

Masseteric hypertrophy

Square appearance to the jawline

Gingival (gummy) smile

Significant upper gum display during smilingb

Neckc

Platysmal bands

Vertical linear bands present on the anterior neck

Horizontal neck lines

Horizontal bands present on the upper neck

aSometimes assigned to the lower face.

bNot necessarily age-related.

cThe neck is usually included in the lower face for three horizontal zones.

Source: [10,33,34]

- The upper face: Forehead, glabella (smooth area between eyebrows), periocular (lateral to the eyes) areas, and temples

- The midface: Between the glabella and tip of nose, lateral to the zygoma (cheekbone). The malar area is highly relevant, as the malar is the cheekbone prominence. The submalar is the bony area underneath the cheekbone.

- The lower face: The perioral area (lips), mandible, chin, and neck

THE 3-D MODEL: NORMAL ANATOMY OF FACIAL TISSUE

The two-dimensional model is a good descriptive framework for cosmetic concerns but does not describe the aging processes of underlying facial tissue that inform their minimally invasive correction. This area is addressed by the three-dimensional model.

The Skin

The skin consists of the epidermis and dermis, mutually dependent layers that rest on the superficial fat layer [35].

Epidermis

The epidermis is the most superficial layer, composed of stratified squamous cells or keratinocytes (90%) and melanocytes (approximately 8%). The epidermis is directly exposed to the environment and its damaging effects. To replace damaged cells, new cells must constantly form and migrate to the surface over two to four weeks [35,36].

Melanocytes produce melanin, which gives pigment to the skin and absorbs ultraviolet (UV) light to prevent DNA damage. Absolute numbers of melanocytes are constant across races. The amount of melanin produced, size of melanosomes, and extent of aggregation account for differences in pigmentation. Epidermal melanocyte density declines with aging [35,36,37].

Dermis

The superficial papillary dermis (20% of the dermis) is loose connective tissue with capillaries, reticular fibers, and some collagen. Small projections (dermal papillae) into the epidermis maintain adhesion between the layers and nourish the epidermis [35,36].

The deeper reticular dermis is dense connective tissue, and the deepest level borders the superficial fat layer. Collagen makes up most of the dermis (75% is collagen type I), providing strength and structure to the skin. Elastin fibers, synthesized by fibroblasts and keratinocytes, give elasticity and resilience. Fibroblasts, the major cell type of the dermis, produce procollagen and elastin fibers [35].

Filling the spaces between collagen and elastin fibers is an extracellular matrix of glycosaminoglycans (hyaluronic acid), chondroitin sulfates, and glycoproteins (carbohydrates or amino sugars linked to a protein) [35,36,38].

The Superficial Fat Layer

The superficial fat layer, consisting of adipose tissue and collagen network, contributes to thermoregulation, shock absorption, wound healing, and immune function. The adipocytes can transform into myofibroblasts to influence local collagen synthesis [39]. Fibrous partitions separate the superficial fat into perioral (around the lips), nasolabial, cheek, and periorbital (around the eye sockets) compartments [40].

In the midface, the malar fat is composed of superficial fat compartments that lie above the superficial fascia. From medial to lateral, they are [25,41]:

- The nasolabial fat

- The superficial medial cheek, middle cheek, and lateral temporal cheek fat

- The inferior infraorbital fat, where under-eye "bags" appear, above the superficial medial cheek

Superficial Musculo-Aponeurotic System

The soft tissue is complex, because active movement over and around the orbital and oral cavities requires a muscle layer within soft tissues that connects with the overlying skin [42]. The superficial musculo-aponeurotic system is an organized fibrous network comprised of the platysma muscle, parotid fascia, and fibromuscular layer covering the cheek. The superficial musculo-aponeurotic system divides the deep and superficial fat, connects the facial muscles to the dermis in a moveable continuous plane, and functions to transmit, distribute, and amplify the activity of all facial muscles [43,44].

Muscles and Ligaments

Muscles of facial expression and muscles that facilitate chewing, smiling, speaking, and blinking alter the tension in adjacent skin, unlike other muscles that attach to bones or tendons. Muscles of facial expression significantly impact facial aesthetics, as repeated contraction can form dynamic rhytids and static lines [44,45,46,47].

The Deep Fat Layer

The deep fat layer is separated from superficial fat by the superficial musculo-aponeurotic system in the midface, platysma in the neck, and superficial temporal fascia in the temples, forming deep fat pads with fibrous ligament partitions [39,40]. Deep fat compartments in the midface are [25,41]:

- The deep cheek fat, which divides into medial (deep and medial to nasolabial fat) and lateral (deep to superficial medial cheek fat) parts. The deep medial cheek extends medially almost to the lateral incisor tooth.

- Medial portion of the buccal fat pad, just lateral to the deep lateral cheek

- The medial and lateral suborbicularis oculi fat, deep to the orbicularis oculi muscle of the lower eyelid

The Deep Fascia

The deep fascia layers are interconnected and secured to the facial skeleton in specific areas by a network of retaining ligaments, perpendicular to the layers and connect all layers to the deep fascia. The deep fascia provides the attachment for ligament origins and is formed by the periosteum on the facial skeleton and by deep muscle fascia where the skeleton is overlain by the masticatory structures [42].

The Facial Skeleton

The facial skeleton forms the scaffold on which soft tissues are draped and has a substantial effect on appearance. The primary bones of the facial skeleton by horizontal zone are [31,46,48]:

- Upper face: The frontal bone (forehead), bordered below by the glabella (smooth area between eyebrows) and frontonasal groove, and laterally by the supra-orbital (above-eye) ridges.

- Midface: Medial and middle thirds of the midface skeleton formed by the maxilla (houses roof of the mouth, extends upward to orbital floor). The lateral third is formed by the zygoma (cheekbone) body and arch.

- Lower face: The mandible (jaw bone) is the primary bone.

The 3-D Model: Age-Related Alteration

Age-related physiologic processes lead to morphologic changes of the facial skeleton, soft tissue, retaining ligaments, fat compartments, and skin. The three-dimensional alterations of facial aging require accurate evaluation to provide patients the optimal aesthetic strategy [25,30,42].

The Facial Skeleton

From prominent bone formation in youth, age-related changes in the relative dynamics of bone expansion and bone loss lead to predominant bone resorption in the aging craniofacial skeleton, an important contributor to facial aging [42,49]. Skeletal resorption and atrophy is uneven, and bone reduction is greatest in facial areas where prominent aging stigmata appear [4,25,31,42,50]. The maxilla has the greatest resorption; substantial reduction in its anterior projection largely contributes to aged appearance. The periorbital bones and anterior and inferior mandible (prejowl area) resorb extensively; the chin becomes shorter. The posterior and superior mandible undergo bone formation, increasing the mandible angle from 97º in younger skulls to 135º in older skulls. Maxilla and mandible resorption appreciably reduces the facial height. The midface recedes, but the forehead continuously expands.

Local changes in soft tissue and mechanical needs can also induce bone remodeling [50]. Mechano-transduction transforms mechanical energy into electro-chemical signaling to tissues or cells. Through this process, chronic facial muscle tension or overuse contributes to skeletal changes by impacting molecular signaling pathways, which alters bone remodeling patterns [51].

Reduction of anterior projection in the aging facial skeleton occurs immediately beneath the periosteum attached to the bone surface. The periosteum recedes with the bone; ligament origins recede with the periosteum [42].

Facial Fat

Superficial and deep facial fat is highly compartmentalized. Aging significantly alters the volume, structure, and position of facial fat compartments. Typically, deep fat atrophies and superficial fat may be unchanged or hypertrophy. Assessment of the fat depletion pattern is crucial for volumetric restoration. With attention to ligament involvement, the pattern is fairly predictable [8,25,30,41,42,50,52]. It occurs first in the periorbital and malar fat. The most extensive loss of deep fat occurs in the lateral and medial orbital fat and medial cheek fat. Likewise, the most extensive loss of superficial fat occurs with lateral temporal and preauricular fat.

Ligaments

Ligaments confine the fat areas; retaining ligaments anchor and stabilize the skin and facial fascia. With aging, medial ligaments of the center face keep their strength with strong fixation points, but lateral ligaments weaken and lose ability to prevent movement of fat compartments (though they may retain the borders). With loss of lateral fat volume and ligament support, the malar fat moves inferomedially and the superficial nasolabial and superior/inferior jowl fat move medially.

Superficial Musculo-Aponeurotic System and Muscles

The ligaments also transmit the effect of skeleton resorption by strongly connecting the skeleton with the superficial musculo-aponeurotic system. Glabella and masseter muscles can become hypo- or hypertonic. Chronic muscle use in facial expressions can aggravate some features of aging. Atrophy is prominent in masticatory muscles.

Epidermis and Dermis

Aging substantially alters the skin. Dermal collagen content declines by roughly 1% every year starting at around 40 years of age in women and 50 years of age in men. The remaining collagen fibers become disorganized, compact, and fragmented. Elastic fibers decrease in number and diameter. Epidermal thinning, collagen loss, and dermal elastosis contribute to fine rhytids of the aging face. Loss of muscle tone, skin elasticity, and thickness leads to sagging [41,49].

These dermal changes trigger a cascade of secondary events that greatly influence surrounding tissues. Wrinkles and furrows, a main focus of patients seeking cosmetic treatment for aging, develop from a slow, progressive alteration of all facial structures [49]. UV radiation from sun exposure substantially contributes to skin changes in aging.

THE INTEGRATIVE AND AESTHETIC UNITS PERSPECTIVES

The two- and three-dimensional models describe age-related changes within facial tissue layers. However, the integrative and aesthetic units models describe how these changes interact and combine into the cosmetic features of facial aging [4,25,30,41,42,53].

As noted, bone resorption is extensive in orbital and periorbital, malar, submalar, and mandibular areas. Soft tissue loss occurs in periorbital, forehead, glabellar, temporal, malar, perioral, mandibular, and mental areas. Retaining ligaments of fat compartments weaken; facial fat and soft tissue descent forms malar bags, folds, and sagging in nasolabial, jowl, and submental areas.

Increased orbit size and posterior maxillary resorption promote inferior displacement of the malar fat, accentuation of nasolabial folds, a blunted midface, and loss of support for periorbital tissues that contributes to perioral lines. Infraorbital volume loss exposes the inferior border of the orbicularis oculi muscle that helps form a malar crescent over the zygomatic eminence (lateral) and the nasojugal fold (medial); formerly concealed infraorbital fat pads ("palpebral bags") emerge.

Periorbital and perioral skin wrinkling from repeated muscle action progress from dynamic rhytids to static rhytids as the skin changes become permanent. Volume loss, distributional changes, and sagging disrupt the defining arcs and convexities of youth and contribute to the distinct morphology of the aging face.

Youthful Appearance and Aging

Loss of youthful features and development of aging features are frequent cosmetic concerns of patients. Expert plastic surgeons and cosmetic dermatologists are broadly uniform in characterizing youthful features and age-related changes. The following section specifically describes female features; male features will discussed later in the course [4,29,32,49,54,55,56,57,58].

The youthful face has a diffuse, balanced distribution of superficial and deep fat, conferring a smooth, three-dimensional topography delineated by a series of arcs and convexities, without clear distinction between temple, eyelid, and malar areas. On frontal view, the primary arc of the jawline, convexities of the temples, and multiple smaller secondary arcs of the lips are evident. In profile, the definitive features of youth are the lateral cheek projection, extending as an unbroken convex line from the lower eyelid to the cheek (the "ogee" curve).

Youthful features converge on the malar area. Prominent malar eminences are a hallmark of beauty in many cultures, and malar area convexity (roundness) is a defining feature of a youthful face. With aging, the malar fat position over the zygoma and orbital rim diminishes and descends. Ptotic cheek fat, and descent of malar soft tissue, produces sunken cheeks and shadows, leaving behind a cheek concavity accentuated by depletion of malar fullness.

From the front, the jawline appears scalloped; the temporal, buccal, and suborbital areas hollow; and the lips straight and angular. In profile, the primary arc of the cheek is broken, the mandibular arc replaced by a jowl line, and the forehead and brow lose their anterior projection.

Youthful features and age-related changes have agreement, but the extent of cosmetic correction is debated. A multinational panel of cosmetic medicine experts recommended an age-appropriate approach as the criterion standard, with a conservative approach preferable [52].

The Facial Aesthetic Units Perspective

The aesthetic units perspective informs how some visibly apparent aging features develop and directs cosmetic intervention. The surface and subsurface structural changes in skin thickness, composition of subcutaneous tissue, contour of the facial skeleton, and location and integrity of retaining ligaments contribute to variability of bony landmarks, formation of lines and wrinkles, variable skin pigmentation, and overall discontinuity of the facial region, termed "facial aesthetic units" [28].

In younger persons, facial aesthetic units flow together, appearing as a smoothly contoured, single dynamic structure without perceptible division. With aging, the redistribution of facial fat, loss of tissue volume, and retention of ligament borders induce a demarcation of the underlying facial structures. The compartmentalized aesthetic units become distinct as changes within and between distinct aesthetic units collectively contribute to an overall aged facial appearance [4,28].

A strong correlation was found between observer judgment of age and visually obvious separation of facial aesthetic units, suggesting it may serve as a psychophysical cue fundamental to perception of facial aging. This finding also aligns with current practice. Facial rejuvenation can include creation of more homogeneous skin tones, texture, and facial symmetry, and smooth contours between anatomical regions by blending the transition of facial aesthetic units for a harmonious and youthful facial appearance [28].

5. BOTULINUM TOXIN

DISCOVERY AND DEVELOPMENT

Botulinum toxin is derived from neurotoxins produced by Clostridium botulinum, the gram-positive bacillus that causes botulism. Subsequent to the 1897 discovery of C. botulinum as etiologic agent of botulism, seven botulinum toxin serotypes (A, B, C1, D, E, F, and G) with differing pharmacologic properties have been identified. Only serotypes A and B are used clinically, with type A (botulinum toxin-A) the most widely used for both medical and aesthetic indications [59].

During the late 1960s and early 1970s, the clinical value of botulinum toxin became evident in the treatment of strabismus. This was followed by demonstrated benefit in blepharospasm, hemifacial spasm, cervical dystonia, and other disorders of muscle hyperactivity and spasticity. From the first report of botulinum toxin-A injection for a cosmetic indication (glabellar frown lines) in 1992, its use has expanded to become the most requested procedure in aesthetic medicine. One commercial brand of botulinum toxin-A, Botox, has become popularized as the generic reference for all cosmetic botulinum toxin [60,61].

Botulinum toxin-A is the primary form used for cosmetic treatment. While less extensively studied for cosmetic indications, botulinum toxin-B also appears to be effective [59].

MECHANISM OF ACTION

Botulinum toxins block the release of acetylcholine from motor neurons at the neuromuscular junction. By inhibiting acetylcholine neurotransmission between peripheral nerve endings and muscle fibers, botulinum toxin weakens or paralyzes skeletal muscle and, in aesthetic medicine, weakens muscular contraction [10].

Botulinum toxin blocks presynaptic acetylcholine release, causing reduced or diminished muscle contraction. This results in temporary improvement in the appearance of the areas affected by lines and wrinkles, for facial contouring and improving the skin [62]. The inhibitory effect is temporary; recovery of muscular function is often evident by three months, but the cosmetic effect may persist longer [10,33].

AVAILABLE PRODUCTS AND FORMULATIONS

Four botulinum toxin formulations are approved by the FDA for aesthetic use (Table 2). The FDA recommends using specific names (e.g., ONA or ABO, Botox or Dysport), instead of serotypes (e.g., botulinum toxin-A), to prevent confusion between products [59]. Discussion in this course is limited to the five serotype A botulinum toxin products approved for cosmetic use; the off-label use of RIMA will not be explored. Unless a specific product is described, botulinum toxin is used to broadly reference the use of FDA-approved botulinum toxin-A formulations.

Table 2: BOTULINUM TOXIN PRODUCTS AND FORMULATIONS

Name, Serotype

Commercial Product

FDA-Approved Indications

Comments

ONA

type-A

Botox

Botox Cosmetic

Vistabel

Vistabex

Vacuum-dried powder (50 or 100 U/vial)

Glabellar, lateral canthal, and forehead lines

The original, most-studied formulation. Widely used off-label for treating other lines and facial contouring.

ABO

type-A

Dysport (300 or 500 U/vial)

Glabellar lines

First marketed in Europe

INCO

type-A

Bocouture or Xeomin (as lyophilized powder in 50 or 100 U)

Glabellar lines

Newer formulation. Free of complexing proteins. May reduce risks of sensitization and antibody formation.

PRA type-A

Jeuveau (4 U [0.1 mL] IM in each of five sites)

Glabellar lines

Newer formulation. Similar in efficacy to ONA.

RIMA

type-B

Myobloc, in liquid (5,000 U/mL)

No cosmetic indications

Less studied than type-A. Used in off-label facial lines. Distributed in the United States and Canada.

DAXI type-A

Daxxify (as lyophilized powder in 50 or 100 U)

Glabellar lines

New formulation (2022 FDA approval)

ABO = abobotulinumtoxinA, INCO = incobotulinumtoxinA, ONA = onabotulinumtoxinA, PRA = prabotulinumtoxinA, RIMA = rimabotulinumtoxinB, DAXI = daxibotulinumtoxinA, U = units.

Source: [59]

ONA, ABO, PRA, INCO, and DAXI must be reconstituted before using, with sterile, non-preserved saline recommended by their respective makers. In practice, many clinicians reconstitute these products in saline containing benzyl alcohol to reduce injection-site pain [63]. Compelling evidence now suggests that reconstitution using preserved saline dramatically improves patient comfort without compromising efficacy [18].

The formulations (i.e., ONA, INCO, PRA, ABO, and DAXI) are not interchangeable. The products differ in units, chemical properties, biologic activities, weight, and manufacturing process. Production process and conditions such as pH, temperature, formulation, and concentration are crucial; alterations in any can increase the likelihood of formation of inactivated toxoid proteins, which in turn may be immunogenic [62].

Dose conversions are not standardized. Dosing is not interchangeable, and the products and procedures should be selected and prescribed according to individual needs and aims of treatment [62].

CLINICAL USE OF BOTULINUM TOXIN

With aging, decreased skin elasticity and repeated muscle contraction cause hyper-functional facial lines, particularly in the glabellar and periorbital regions. Depressor muscles overpower the levators to result in ptosis of the brow and mid-cheek groove, and patients develop horizontal forehead rhytides, glabellar frown lines, or lateral canthal "crow's feet," indications for botulinum toxin use [64].

Botulinum toxin is also extensively used off-label for brow shaping, eyebrow lifting, opening the aperture of the eye, decreasing mouth frown, defining the jaw line, increasing lip show, decreasing gummy smile, reducing "bar-code" lines around the mouth, eliminating "golf ball" chin, reducing platysma bands, and softening a squared, masculine jaw [65].

Patients treated with botulinum toxin for aesthetic purposes can expect their results to last at least three months, but effects can persist four to five months depending on the area treated, dose, and formulation used. The results may last longer for some patients, especially after repeated treatment [62].

Long-term outcome data support practice trends in decreased dosing and increased botulinum toxin injection intervals. Patients treated for glabellar lines over an average of nine years reported high levels of satisfaction sustained by repeated treatment and greater reductions in their perceived age with increasingly longer treatment durations [6].

While botulinum toxin monotherapy of dynamic rhytides is effective, current practice favors botulinum toxin combined with fillers, lasers, and/or light- or energy-based devices for synergistic effects and superior and more durable improvements [10,33,59].

Dilution of FDA-approved botulinum toxin for off-label intradermal injection is used for reducing surface wrinkling by weakening superficial facial muscle activity but sparing deeper muscle function. This approach is also used for reducing upper face rhytides without affecting brow muscles [64,66].

Safe and effective use of botulinum toxin requires the understanding of anatomy, movement of muscles in isolation and in relation to other muscles, the concept of compensatory strengthening, and observant evaluation of the patient at rest (static) and with normal and exaggerated animation (dynamic). Every patient is unique, and inter-patient differences can be vast [65].

Patient Selection

To help determine botulinum toxin suitability, assess facial muscle function and tone in static and dynamic states looking for signs of stronger contraction (e.g., greater dynamic movement, deeper lines, larger apparent mass during use) [67]. Observing dynamic movement of the skin can help identify areas of stronger or weaker muscle contraction, why certain wrinkles are formed, and which muscles are creating them. The findings assign patients to one of the following categories [67]:

- Kinetic: Regular muscle contraction and wrinkles during active expression, but not at rest. Botulinum toxin very likely effective.

- Hyperkinetic: More excessive muscle contraction. May require more frequent, higher-dose botulinum toxin to achieve the desired effect.

- Hypertonic: Inability to relax specific muscles, visible wrinkles at rest. Some benefits may be possible with botulinum toxin, but adding filler injections may be necessary.

- Deep static lines with loss of skin elasticity: Unsuitable for botulinum toxin injection.

Side Effects and Safety

Compared with dermal fillers, prevention of botulinum toxin adverse effects is more straight-forward [18,33,59,62]. Common acute side effects include transient swelling, bruising, and headache. Ice or cooling is commonly used for post-injection comfort and to prevent bruising. Temperature seems to influence botulinum toxin uptake, suggesting that cooling the area might undermine efficacy.

Poor treatment response can result from insufficient or incorrect dosing, anatomical variation, or errors in drug handling during preparation, storage, or administration. Diffusion of toxin to untargeted areas from improper injection placement can result in excessive muscle weakness, cosmetic disfigurement, and/or functional deficits that persist for months.

Contraindications

Evidence Based Practice Recommendation

The Australasian College of Dermatologists strongly recommends that botulinum toxin-A treatment be avoided during pregnancy and breastfeeding owing to the lack of adequate data on the developmental risk to a human fetus from the use of these agents in pregnant women and evidence of reproductive toxicity in animal studies.

https://onlinelibrary.wiley.com/doi/full/10.1111/ajd.13273

Last Accessed: March 19, 2024

Level of Evidence: Expert Opinion/Consensus Statement

Injection-site infection, known hypersensitivity to any product component, and allergy to cow milk proteins for ABO only are all contraindications to botulinum toxin treatment [59]. Perioral botulinum toxin injections in professional speaker, vocalist, or musician patients require discussion of the potential functional impact from weakened or impaired muscle tone, a possible contraindication.

6. SOFT TISSUE (DERMAL) FILLERS

A variety of injectable soft tissue (dermal) filling agents are available for correction of prominent skin lines, fat atrophy, volume lost, and other contour changes of facial soft tissue (Table 3) [68]. Fillers are classed on different variables that inform appropriate selection and potential complications: biodegradability, longevity in the tissue, and histologic reaction [69,70,71].

Table 3: FDA-APPROVED DERMAL FILLERS AND CLINICAL USE

Product, Year Approved

Approved Indications

Hyaluronic acid: Galderma Labs

Restylanea, 2003

Correction of moderate-to-severe facial rhytides and/or folds

Lip augmentation

Restylane-L, 2012

Restylane Silk, 2014

Lip augmentation

Correction of perioral rhytides

Restylane Lyft, 2015

Correction of moderate-to-severe deep facial rhytides and folds

Restylane Defyne, 2016

Correction of moderate-to-severe facial rhytides and folds with age-related volume loss

Restylane Refyne, 2016

Correction of moderate-to-severe facial rhytides and folds

Restylane Kysse, 2020

Lip augmentation

Correction of perioral rhytides

Restylane Contour, 2021

Cheek augmentation, correction of midface contour deficiencies

Correction of perioral rhytides

Hyaluronic acid: Allergan

Juvéderm XC, 2006

Correction of moderate-to-severe facial rhytides and folds

Juvéderm Ultra XC, 2006

Juvéderm Ultra Plus XC, 2006

Juvéderm Ultra Plus XC, 2015

Lip augmentation

Correction of perioral rhytides

Juvéderm Voluma XC, 2013

Correction of age-related volume deficit in the midface

Cheek augmentation

Juvéderm Volbella XC, 2016

Lip augmentation

Correction of perioral rhytides

Juvéderm Vollure XC, 2017

Injection into the mid-to-deep dermis for correction of moderate-to-severe facial wrinkles and folds (e.g., nasolabial folds)

Hyaluronic acid: Merz Aesthetics

Belotero Balance, 2011

Correction of facial rhytides and folds, especially around the nose and mouth

Hyaluronic acid: Teoxane S.A.

RHA 2 and RHA 3, 2017

Injection into the mid-to-deep dermis for correction of moderate-to-severe dynamic facial wrinkles and folds (e.g., nasolabial folds)

RHA 4, 2017

Injection in deep dermis to superficial subcutaneous tissue for correction of moderate-to-severe dynamic facial wrinkles and folds (e.g., nasolabial folds)

Hyaluronic acid: Prollenium Medical Technologies, Inc.

Revanesse Versa, 2018

Injection in mid to deep dermis for correction of moderate-to-severe facial wrinkles and folds (e.g., nasolabial folds)

Calcium hydroxylapatite (CaHA): Merz Aesthetics

Radiessea, 2006

Correction of moderate-to-severe facial rhytides and folds

Radiesse(+), 2015

Poly-L-lactic acid (PLLA): Galderma Labs

Sculptra Aesthetic, 2009

Correction of shallow-to-deep nasolabial fold contour deficiencies and other facial rhytides

Polymethylmethacrylate (PMMA): Suneva Medical

Bellafill, 2006

Correction of volume deficits around the mouth (e.g., nasolabial folds)

Bellafill, 2015

Correction of acne scars

aDoes not contain lidocaine.

Source: [72,73]

The FDA designates fillers as either absorbable/temporary (e.g., hyaluronic acid, calcium hydroxyapatite [CaHA], poly-L-lactic acid [PLLA]) or non-absorbable/permanent (e.g., polymethylmethacrylate [PMMA]) based on the agent's biodegradability. If an agent absorbs within 18 months, it is considered temporary; if it does not absorb within 24 months, it is considered permanent. Some agents combine absorbable material for immediate effect and carrier until a nonabsorbable material induces fibroblast stimulatory effects (in more than 18 months). These agents are considered semipermanent. Agents with minimal tissue response are considered volumizers, while those that induce a strong tissue reaction are considered stimulators.

Temporary fillers use FDA-approved biodegradable materials absorbed by the body over time. Permanent fillers persist indefinitely in tissue. Some FDA-approved fillers, such as collagen-based products or avian-derived hyaluronic acid (Hylaform), remain available but are largely replaced by hyaluronic acid fillers with superior clinical properties and/or negligible allergenic potential [68,73,74].

Most acute side effects and potential serious adverse effects of FDA-approved dermal fillers are common across fillers. All filler agents are contraindicated in patients with known hypersensitivity to any product component specific to the product. There are a variety of other contraindications to the use of various dermal fillers (Table 4).

Table 4: CONTRAINDICATIONS TO DERMAL FILLERS

Contraindication

Specific Conditions

Relative and absolute contraindications

Allergic history

Multiple severe allergies

Anaphylaxis

Heightened immune responses to common inhaled and food allergens (atopy)

Allergy to latex, hyaluronic acid products, streptococcal/other gram-positive bacterial proteins, or lidocaine

Desensitization therapy during filler treatment

Scar-related

History of hypertrophic scarring or keloid formation

Scars at intended treatment site

Bleeding-related

Current anticoagulant or antiplatelet therapy

History of bleeding, clotting (hemophilia), or connective tissue disorders

Active autoimmune disease

Systemic lupus erythematosus

Rheumatoid arthritis

Hashimoto thyroiditis

Patient-related factors

Unattainable expectations

Pregnancy

Lactation

Contraindications unless fully resolved with treatment

Inflammatory skin diseases

Atopic dermatitis

Seborrheic dermatitis

Acne

Rosacea

Psoriasis

Skin infection or any unhealed facial wound

Impetigo

Folliculitis

Propionibacterium acnes

Viral warts

Perioral HPV

Molluscum contagiosa

Streptococci or staphylococci bacterial infections

Candida (yeast) infections

Local infection

ENT, oral cavity, or dental infections or abscess

Remote infection

Intestinal tract, urinary tract, or bladder infection

Inflammatory processes

Pimples

Hives

Rashes

Cysts

ENT = ear, nose, or throat, HPV = human papillomavirus.

Source: [19,75]

With all fillers, treatment should undercorrect the defect and avoid overcorrection. All treatment sites should be massaged immediately after injection to facilitate an even distribution.

HYALURONIC ACID

Hyaluronic acid is a glycosaminoglycan disaccharide and natural constituent of the dermal extracellular matrix, cartilage, and connective tissue. Hyaluronic acid is highly hydrophilic, enabling dermal hyaluronic acid to hydrate and cushion the skin and fill empty spaces within the extracellular matrix. Dermal hyaluronic acid content declines with skin aging, which reduces water-binding capacity and elasticity, induces volume loss, and promotes the development of rhytids and other aging features [72,73,76,77].

Unmodified hyaluronic acid readily dissolves in water to form a viscous gel, but injected into the dermis, it is quickly degraded by hyaluronidase and free radicals in the skin [76]. Most FDA-approved hyaluronic acid fillers use nonanimal stabilized hyaluronic acid synthesized from Streptococcus equi bacteria. Liquid nonanimal stabilized hyaluronic acid, as with native hyaluronic acid, is rapidly broken down [72,77]. To increase stability and longevity, manufacturers use crosslinking agents to bind hyaluronic acid polymer chains to each other, resulting in a gel that resists enzymatic and free radical breakdown. Most fillers use 1,4-butanediol diglycidyl ether (BDDE) as a cross-linker [76,77]. The hyaluronic acid modification process, proprietary to each maker, allows a portfolio of hyaluronic acid filler consistencies with varied rheologic properties (e.g., viscosity, gel hardness, lifting ability, tissue integration) that determine optimal tissue placement depth and product longevity [19,78,79].

Hyaluronic acid can bind 1,000 times its volume in water. This water-binding and space-filling effect underlies the volumizing efficacy of hyaluronic acid fillers [76]. Efficacy has been observed to persist beyond a time frame explained by space-filling effects alone. This led to research of other mechanisms, which identified induction of adipogenesis, neocollagenesis through mechanical tension on fibroblasts, and periosteal stem cell activation followed by new tissue formation with periosteal filler placement [52,80,81].

Hyaluronic acid fillers combined with botulinum toxin act synergistically to produce superior, more durable effects than either monotherapy. For example, the longevity of effects is improved when treating sites of dynamic wrinkles, such as glabellar lines. Reduced filler deformation due to botulinum-toxin induced local muscle relaxation at least partially accounts for this effect [68].

CALCIUM HYDROXYLAPATITE

Calcium hydroxylapatite (CaHA) is a mineral commonly found in human teeth and bones that functions as a scaffold for collagen ingrowth. CaHA filler contains CaHA microspheres as biodegradable particles suspended in an aqueous carboxymethylcellulose gel carrier. Once injected, the carrier gel gradually resorbs; the microspheres stimulate a fibroblastic response resulting in active physiologic remodeling of the extracellular matrix and long-term collagen deposition around the implant that promotes volumizing. The microspheres eventually degrade into calcium and phosphate ions and are excreted. The effects last around 18 months [10,73,79].

Radiesse (formerly Radiance) is the only FDA-approved CaHA filler, indicated for correcting moderate-to-severe soft-tissue defects, facial folds, and wrinkles, including nasolabial folds [72]. The viscoelastic filler is well suited for supraperiosteal and deep fat placement. When injected more superficially, it should be diluted 1:1 or 1:2 [10,68]. Radiesse(+), formulated with 0.3% lidocaine, was approved in 2015 to reduce pain without needing to premix before injection [82].

Radiesse is contraindicated in patients with a history of anaphylaxis or multiple severe allergies [68]. Radiesse injection of the lips risks forming nodules and should be avoided. Radiesse is visible on x-ray and may obscure underlying features [73].

POLY-L-LACTIC ACID

Poly-L-lactic acid (PLLA) is a biodegradable, biocompatible, synthetic polymer used for decades in resorbable sutures, orthopedic plates, and urologic stents. First approved in 1999 as a dermal filler in Europe, PLLA received FDA approval in 2004 for the treatment of HIV-associated lipoatrophy (Sculptra) and in 2009 for aesthetic treatment in immunocompetent patients (Sculptra Aesthetic) [49,72,73].

PLLA induces a subclinical inflammatory response that stimulates fibroblast proliferation, neocollagenesis, and type I collagen formation, leading to a progressive increase in dermal volume [68,72]. Each PLLA injection produces a gradual treatment effect with limited correction. Three injection sessions at six-week intervals are generally required, but improvements after the final injection can last up to two years. Patients should be counseled that final results can take months to achieve [83,84].

Treatment should aim to undercorrect, because the results progressively improve over time. Injections should be spaced at least three weeks apart because transient post-injection edema can mimic a full correction [68].

Injections should be placed into the deep dermis or subcutaneous fat. The lip and periorbital region should be avoided due to risk for nodule formation. Subcutaneous papules are a common adverse effect [68].

POLYMETHYLMETHACRYLATE MICROSPHERES

Polymethylmethacrylate (PMMA) is a non-biodegradable, biocompatible, synthetic polymer used in medical devices such as bone cement and intraocular lenses. As a soft tissue filler, PMMA microspheres are tiny, round, smooth particles suspended in a gel-like solution containing lidocaine and bovine collagen [73].

The collagen gel gives an initial volume but is resorbed over one to three months. The microspheres stimulate a local inflammatory reaction, followed by deposition of granulation tissue that encapsulate the microspheres and mature into connective tissue. By three months post-injection, the microspheres are surrounded by newly formed collagen, accounting for the observed volume-filling effect [74,79,84]. Tissue encapsulation of PMMA microspheres makes the results irreversible.

The PMMA filler Bellafill is the only FDA-approved permanent filler. Treatment of nasolabial folds and facial acne scars are the only approved cosmetic indications, but Bellafill is used off-label to volumize other mid- and lower-face contour defects [74,85].

The bovine collagen carries potential immunogenic issues. Clearance for Bellafill injection requires non-reactive response to skin-testing for bovine collagen hypersensitivity one month pre-procedure [74,79].

Good PMMA candidates are patients with well-defined lines and furrows and minimal excess skin [74,85]. PMMA use is not recommended in areas of thin skin (e.g., lower eyelid, neck), the lips, and in patients with generally thin, loose skin [74].

Bellafill is intended for deep tissue placement. A series of conservative injections can be required for optimal results, with touch-up injections performed one to three months after initial treatment [74]. Optimal results require 3 to 12 months for sufficient new collagen synthesis, and additional improvement beyond 12 months may occur [86].

FILLER SELECTION

Hyaluronic Acid Fillers

Unlike CaHA (Radiesse), PLLA (Sculptra), and PMMA (Bellafill) fillers, availability of numerous hyaluronic acid products requires judicious product selection based on rheologic properties. Each facial area and anatomic plane subjects filler to biomechanical stressors of compression, stretching, and lateral shearing from skin tension, muscle activity, and fat volume of varying intensity and frequency [78,87].

Rheology studies the flow and deformation of filler material subjected to biomechanical stressors to understand their clinical properties and behavior. Manufacturers crosslink and modify hyaluronic acid products (e.g., Hylacross, Vycross) using methods that determine gel rheology. The rheologic properties leverage the distinct tissue distribution patterns and clinical behaviors of hyaluronic acid products [76,77].

The clinical behavior of Radiesse is influenced by the same rheologic factors as hyaluronic acid fillers. Rheologic properties are unique to each hyaluronic acid and CaHA product, between filler families. The major rheologic properties are [9,29,53,76,78,88,89,90]:

- Shearing: Force pushing one part of a body in one direction and another part in the opposite direction

- Elasticity: Ability to resist deformation by external forces

- Viscosity: Ability to resist shearing forces

- Cohesivity: Ability to resist vertical compression and stretching

- Hydrophilicity (water-binding ability): Capacity to attract water and expand

- Particle size: Contributes to overall lifting and filling power

- Particle concentration and crosslinking: Influences durability by resisting enzymatic degradation.

Clinically, the elasticity of filler reflects the gel's firmness. The level of viscosity will determine the pattern and extent of tissue integration. High-viscosity agents resist tissue spread and shearing. Low-viscosity agents are ideal for superficial placement to treat shallow folds and lines and are best used where spread and softness is more important than volume (e.g., the lips) [53,76,77,78]. Conversely, high-elasticity and high-viscosity gels are best suited for deep placement to treat deep folds and restore volume loss by creating volume and lift in the mid- and lower face.

Cohesivity is spreading related to tissue depth and ability to hold form or shape under stress by overlying/underlying muscle and skin compression. Cohesivity increases with degree of cross-linking and hyaluronic acid concentration. Low-cohesivity gels are easier to mold and spread evenly in the skin, making them suited for correcting small rhytides. High-cohesivity gels are suited for revolumizing large areas of volume loss.

Restylane Lyft is an example of a high-elasticity, large-particle gel with greater filling power and resistance to degradation in deep-tissue volumizing. Juvéderm products use elasticity from highest to lowest in gels intended for deep (Voluma), midlevel (Vollure), and superficial (Volbella) tissue placement.

Calcium Hydroxylapatite

With a high lift capacity and results that last more than one year, Radiesse works well to fill volume loss in the midface and is placed in a manner similar to injection of hyaluronic acid products [84]. The use of Radiesse for melomental folds ("marionette lines") has been reported extensively, with effective and durable results [58].

Of note, Radiesse may be more likely than other fillers to result in intra-arterial complications, skin necrosis, and blindness. The increased propensity to cause vascular compromise could be related to particle size, with larger particles resulting in more proximal vessel obstruction. Certain particles may also stimulate the clotting cascade, ultimately resulting in skin necrosis [16]. This seems to elevate precautions in using this product near vascular danger zones.

Poly-L-Lactic Acid (Sculptra)

PLLA volumizes soft tissue in a gradual, progressive, and predictable manner, providing natural-looking restoration of facial volume [91]. Although it is categorized as biodegradable by the FDA, the duration of action is 12 to 24 months and, with repeat treatment, several years. As noted, PLLA is more accurately classed as a semipermanent dermal filler [84,92].

PLLA should be avoided in perioral and periocular areas; in the neck where thin skin requires superficial injection; and in mandibular ligament/platysma muscles [49,58]. Superficial injection in the dermis is also inappropriate. PLAA injection is recommended for the supraperiosteal in the temples, lateral brow, zygomatic area, maxillary area, mandibular area, and mental area [93]. It may also be used in the subcutaneous fat in the mid-cheek regions and preauricular area. More specifically, recommended PLLA injection sites are [49,58,93]:

- Temporal fossa: Supraperiosteal at the temporal muscle origin

- Lateral brow: Supraperiosteal at the tail of the brow

- Medial malar region: Supraperiosteal on the zygomatic bone, maxilla, and pyriform fossa

- Submalar/mid-cheek: Deep subcutaneous plane where bony background is absent

- Lateral third of the mandible/mandibular angle and lower lateral cheek: Superficial subcutaneous fat above the parotid gland and masseter muscle

- Mandible/chin: Supraperiosteal over the menton and prejowl sulcus

Sculptra may provide global volume restoration in lean patients who are too depleted for space-occupying fillers, an alternative to deep volumizing hyaluronic acid fillers that could be too expensive and difficult to use as scaffolding [94].

Polymethylmethacrylate (Bellafill)

Used as a deep tissue filler for mid- and lower-face volume loss, Bellafill seems comparable to other filler types in efficacy [84]. This shifts the basis for Bellafill selection to patient preference and appropriateness [34,74].

Persistent effects, possibly with a single treatment (or with minor touch-ups), can make Bellafill attractive, but treatment with permanent fillers requires careful screening. Patients who have histories of unsubstantiated dissatisfaction with cosmetic results, are unsure of their desired outcome, or are new to fillers are poor candidates for Bellafill [34,74].

Other Considerations in Filler Selection

Clinician experience influences the choice of filler. Improper use can result in an unacceptably high risk for adverse effects, and clinicians not trained in using specific fillers should refrain from their use [34,74]. Complications or unfavorable cosmetic results with permanent fillers may require surgical intervention and may be impossible to completely reverse.

The desired duration of effect should be considered. Fillers that eventually degrade in tissue (e.g., hyaluronic acid) offer the advantage of reversibility but require multiple subsequent treatments to maintain the desired effect. Adverse effects of products may not become apparent until post-market, making it prudent to select products with an established safety/adverse event profile from clinical use [95].

7. DEOXYCHOLIC ACID

Deoxycholic acid (Kybella) is FDA-approved for treatment of moderate-to-severe submental fullness/convexity ("double chin"). Injection into the subcutaneous fat below the chin area causes focal adipolysis and necrosis. This induces macrophages to clear cell membrane fragments, recruit fibroblasts, and stimulate neocollagenesis. Once destroyed, adipocytes cannot store or accumulate fat. Submental appearance is improved through subcutaneous fat reduction and tissue tightening [96,97].

Kybella is an alternative to liposuction for achieving an aesthetically pleasing jawline by submental fat reduction, but comparisons in clinical trials are lacking. Kybella is given in 0.2-mL injections, spaced 1 cm apart, until all sites in the planned treatment area are injected. Up to 50 injections, or 10 mL, are allowed per session. Several sessions spaced at least four weeks apart are usually required. In phase 3 clinical trials, the drug was effective and safe, although a significant number of patients experienced pain, transient bruising, edema, and numbness [98,99].

In the phase 3 trials, patients were injected with a mean 186 mg of drug as treatment. Cosmetic surgeons reported charging a mean $691 per 20-mg vial of deoxycholic acid, which would have cost the average study participant $6,426.35. In contrast, the average patient cost for submental liposuction is $2,976.56. While Kybella is cost-effective only for patients with mild-to-moderate submental liposis who require fewer injections and treatments, the avoidance of surgery for some patients may outweigh the greater expense [99].

With a 13% decrease in procedures performed in 2020 (135,586) compared with 2019 (156,153), Kybella uptake into cosmetic practice seems limited following its 2015 FDA approval [12].

8. INDIVIDUALIZED ASSESSMENT AND TREATMENT PLANNING

KEY ASSESSMENT ELEMENTS

Optimal assessment of facial aging begins with a thorough patient history and examination that assesses anatomical structure and age-related changes to the bone, fat, muscle, and skin. Specifically, this should include [10,49]:

- Skeletal changes

- Degree and location of volume loss

- Muscle anatomy and movement

- Appearance of lines and wrinkles

- Skin quality

- General facial appearance, symmetry, or any imbalance in facial proportions

The use of photonumeric scales are recommended for the objective assessment of facial aging features. Photonumeric scales have the advantage of providing a consistent visual frame of reference that minimizes variability in perception and subjectivity [100].

With these scales, assessment of the upper, mid, and lower face is performed, with specific aging features rated using a 0–4 scale (0: absent; 4: advanced) [101,102,103]. The score helps inform the appropriate level of intervention [10]:

- Early intervention: Individuals with minimal evidence of facial aging (Levels 0–1)

- Restoration: Individuals with moderate to advanced signs of aging (Levels 2–4)

The assessment lays the foundation for a detailed, individualized treatment plan that balances clinical experience with patient desires and expectations [10]. In this initial period, it is important to discuss treatment goals and ensure the patient understands the progressive nature of the aging process. Costs should also be reviewed, and in patients with limited financial means, treatment should focus on areas that will have the greatest impact. When the individualized treatment plan is formulated, the extent and sequence of procedures and/or treatments should be discussed. Clinicians should ensure the patient understands the maintenance involved in any type of facial restoration and that overtreatment and unnatural results (and likewise undertreatment and suboptimal results) will be avoided.

ETHNIC CONSIDERATIONS

Fundamental to individualized patient assessment is careful consideration of racial/ethnic and gender variation in facial aging features. In this course, the terms used to reference ancestry are Caucasian (European, North African, southwest Asian/Middle Eastern), African (sub-Saharan Africa), Latino/Hispanic (Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture), East Asian (China, Korea, Japan), Southeast Asian (Thailand, Singapore, Indonesia), and South Asian (the Indian subcontinent) [104].

People of all races have distinct ethnic features, yet cultural standards of beauty share remarkable similarity around the world, such as balance, proportion, and symmetry of facial features, and clear, unblemished, and youthful skin [105,106].

The aging process may manifest differently among various ethnic/racial group; aging promotes and accentuates intrinsic differences of facial morphology and structure. This leads to variations in aged features, such as "Caucasian corners" of lips that develop into marionette lines [94,105].

Relative to other ethnic/racial groups, the earlier onset and more extensive facial aging common in Caucasian patients reflects the interaction of morphologic features and skin quality. Bony remodeling, facial fat and soft tissue volume loss, deflation, and descent give rise to the same common signs of aging in all ethnic groups, making restoration of volume and correction of related sequelae fundamental strategies for every patient [53,105].

Skin Phototype

A powerful determinant of skin aging is the amount of melanin pigment in skin, which determines skin color or phototype. The Fitzpatrick Scale is a classification system that assigns individuals to one of six distinct phototypes based on skin complexion and response to UV radiation exposure (Table 5) [35,107]. Phototype is more tied to the equatorial proximity of one's ancestors than to specific ethnicity.

Table 5: FITZPATRICK SKIN PHOTOTYPES

Phototype

Unexposed Skin Color

Sun Exposure Responsea

Examples

I

Pale white

Always burns, never tans

Red hair with freckles

II

White

Burns easily, minimal tan

Fair-haired Caucasian, Northeast Asian

III

Olive to light brown

Burns minimally, gradually tans

Mediterranean Caucasian, East Asians

IV

Moderate brown

Burns minimally, tans well

Some Southwest Asian (Middle East) Caucasian, South Asian, Hispanic

V

Dark brown

Rarely burns, tans profusely

Darker Hispanic, some African

VI

Deeply pigmented dark brown to black

Never burns, tans deeply

Darker African, Indigenous Australian

aAfter one hour on sun-shielded, untanned skin.

Source: [107,108,109]

Variations in Aging Features

In phototypes IV–VI, the thicker, more compact dermis and higher melanin content delays the onset of skin aging, skin laxity, and sagging. In these individuals, aged skin presents with muscular or expressive lines instead of early fine wrinkling [10].

Craniofacial measurements of diverse racial/ethnic groups were originally compiled for reconstructive surgeons, who required normative data in treating congenital or post-traumatic facial disfigurements. These data inform cosmetic practice in diverse patients who age differently [110,111]. Unless otherwise stated, Caucasian facial characteristics are the point of reference for ethnic/racial variations discussed in the following sections [104]. This is the literature standard and should be taken as a guide rather than a determinate of beauty or value.

African

Compared with White individuals, persons of African descent have skin that maintains its structural integrity and youthful appearance. This bestows lower rates of facial rhytides, brow ptosis, lip aging, lip volume loss, and perioral rhytides formation [104,111].

Facial aging tends to show more prominently in the periorbital region and midface. Patients with African ancestry can exhibit pronounced sagging of the malar fat pads, soft-tissue laxity, and jowl formation of the midface. Unlike the laxity and descent of Caucasian skin, the thickness and weight of skin contribute to jowling in these patients [104].

Aging Black patients often have fewer issues requiring soft-tissue augmentation but may seek to restore the youthful fullness of their lips. Typically the upper lip alone is treated, as the lower lip usually maintains its volume [111].

Latino/Hispanic

This heterogeneous group encompasses individuals with any combination of White, Native American, and/or African-American features. For patients with predominately Native American characteristics, approaches for East Asians are recommended; when Caucasian characteristics predominate, approaches appropriate for this group are used [111].

Patients of Mexican or Central or South American origin tend to have rounder faces with heavy eyelids, a prominent malar eminence and midface area, broader nose, abbreviated nasal length, and a recessed chin. With aging, the mid-cheek area becomes thicker and heavier, with fat pad accumulation and more prominent nasolabial folds, along with eyebrow and eyelid drooping and lower lid fat accumulation [104].

East Asian

East Asians tend to have a wider face with wider bitemporal and bizygomatic width, shorter in vertical height, lower structural projection of the midface, and lack of brow, nasal, and chin projection. Aging is likely to present as central face retrusion; flattening of the anteromedial midface; recessed piriform fossa; and a flatter forehead. A flatter facial skeletal framework promotes greater soft-tissue descent of the midface, malar fat pad ptosis, and tear trough formation [53,105].

These features account for the prevalence of fillers of the medial midface, nose, chin, and forehead of younger Asian patients. In older patients, these regions are a priority, along with correcting age-related disharmonies. Volumizing is limited to the medial maxilla area to enhance central projection and to avoid further widening the midface. Lip augmentation is usually not needed, especially in patients of Southeast Asian origin who present greater lip fullness and may more likely desire lip reduction to balance the lower third of the face [53,104,111].

South Asian

South-Asian populations differ from Caucasian and East Asians, with smaller width of the malar prominences, smaller mandibular width and height, a much shorter lower third of the face compared with the middle and upper thirds, and smaller facial skeletal width compared with Caucasians. The downward medial descent of soft tissue is more aggressive due to higher volumes of facial fat pad over a smaller bone framework [56].

Bony changes and loss of lateral temple and cheek fat are best approached by volumizing the anterior mid-cheek and nasolabial fat pads, avoiding the deep medial midface fat pads. Nasolabial and medial midface correction should be very conservative, with emphasis on deep fat volumizer placement in lateral zones [56].

A concern of some patients is of repeated filler treatment producing an overtreated appearance and unsatisfying outcome. To address this concern, avoid volumizing the medial midface where soft tissue descent aggregates, compensating for this pattern by focusing on lateral midface volumizing [56].

GENDER CONSIDERATIONS

Men represent a small but growing proportion of cosmetic patients and distinctly differ from women in facial anatomy, physiology, and aging. Knowledge of sexual dimorphism (phenotypic differences between sexes) of the entire facial form, including the skeletal structure, musculature, vasculature, soft tissue, and skin is vital for aesthetic outcomes. Female facial characteristics remain the frame of reference for male variations [50,112,113,114,115].

Sexual dimorphism of skull characteristics is foundational to gender differences in facial features (Table 6). The facial vasculature of men is greater in density. Men have increased facial muscle mass, including the mimetic muscles, greater facial muscle movement, and greater upward vertical movement capacity in facial expressions (e.g., smiling, puckering of lips). Unlike the more curvilinear cheekbone in women, the male midface is more angled due to strong muscle insertions. Facial movement contributes to rhytid formation. Men have greater severity and distribution of facial rhytides; the perioral area is the only exception.

Table 6: SEXUAL DIMORPHISM OF THE SKULL

Area of the Face

Female

Male

Forehead

More straight

More oblique

Glabella

Curved and subtle

Frontonasal suture is more prominent

Supraorbital rim

Less conspicuous

More striking

Midface

Subtle angles

Irregular surface and little anterior projection

Zygoma

More prominent and curvilinear

Less prominent

Mandible

Lighter, with subtle angles

Larger, stronger, with clear-cut angles

Chin

Smaller and rounded shape

Larger and square-shaped

Source: [50]

Facial subcutaneous fat exhibits sexual dimorphism. The subcutaneous fat is 1.5 times thicker in the medial malar fat compartment of women, but the distribution is uniform in men. Men have less soft tissue in the cheek area overall, and the subcutaneous fat layer is thinner in men regardless of age.

The loss of subcutaneous fat, thicker skin, and more prominent facial musculature results in deeper expression lines and contributes to the greater severity of male rhytides. The prominent volume loss makes men appear older than their age, relative to women. Aging also causes a more significant downward shift of the lower eyelid in men.

Treatment Considerations

Understanding sexual dimorphism is crucial to prevent unwanted feminization of male features, a primary concern of male patients seeking aesthetic treatment [53,114,116,117]. In addition, cosmetic intervention that produces an exaggeration, rather than restoration, of typical male features can result in an aggressive or threatening appearance [115]. Of course, some men do wish to attain a more feminine or masculine appearance, but this is beyond the scope of this course, which focuses on cosmetic procedures to address unwanted facial changes associated with aging.

General approaches to minimally invasive correction of cosmetic concerns in older men vary by the area of the face [53,113,114,116,117].

Upper Face

Overfilling the temple should be avoided, because temporal hollowing is aesthetically appealing in many men. With botulinum toxin for rhytides, the lateral frontalis muscle is injected to prevent lateral brow arching and to maintain the flat male brow position. The frontalis may require more injections due to the larger forehead area. In a brow already lower with age, inferior frontalis injection requires caution to avoid ptosis (when brow position falls below the orbital rim) [53,113,114,116,117].

Midface

In the subcutaneous medial cheek fat compartment, uniform injection of filler replaces volume loss while maintaining a flatter and more angular cheek contour. The structural support may also improve the tear trough and palpebral malar groove. Fillers should be injected laterally along the zygomatic arch, avoiding a feminizing convexity from overvolumizing the anterior and medial cheeks [53,113,114,116,117].

Lower Face

Filler injections can restore or enhance the projection of the chin; increasing its forward projection helps tighten the jawline area, and increasing its lateral borders helps to square a recessed chin and add definition to the jawline. To restore volume or enhance shape, the supraperiosteal temporal-buccal fat pad is injected, which will project the jaw laterally and strengthen the jawline if a more square jaw is desired [53,113,114,116,117].

AGE CONSIDERATIONS

Aesthetic medicine professionals are confronted by increasing demand for cosmetic treatments by young patients. Treating this age group can be difficult to justify, but standard physiologic aging and individual concerns can guide age-appropriate cosmetic counseling, prevention, and intervention [118].

In patients younger than 20 years of age, minimally invasive cosmetic procedures are generally inappropriate. Emphasis is placed on prevention counseling (e.g., protection against sun damage) and addressing age-independent congenital characteristics or acquired disharmonies (e.g., acne scars) [53,118]. Cumulative exposures to UV radiation, smoking, and pollution can initiate early collagen decline, leading to noticeable fine lines and wrinkles in some patients in their 20s. Appropriate treatment includes noninvasive modalities or botulinum toxin, which is FDA-approved for rhytides in patients 18 years of age and older [118,119].

The typical age of patients who seek cosmetic procedures is between 30 and 50 years. When clinically indicated, fillers and toxin can demonstrably benefit older and younger patients. Patients between 30 and 50 years of age often achieve the most benefit from botulinum toxin treatment; a greater proportion of rhytides in older patients may be due to loss of skin elasticity, which is not alleviated by botulinum toxin [33]. There is no upper limit for age beyond which benefits cease, assuming that dose and injection sites are tailored to muscle mass and function [53].

9. THE MINIMALLY INVASIVE TREATMENT APPROACH

In the recommended practice of minimally invasive therapy for aging features, discussion begins with an overview of evidence that informs practice and the sequence of treatment delivery. Next, for each horizontal zone, the clinical features of aging are briefly reviewed and corresponding interventions are described.

The practice standard for facial aging is volume replacement, tissue tightening, and skin rejuvenation (resurfacing). Therapies for skin resurfacing include lasers/light (e.g., intense pulsed light, fractional laser), energy (e.g., microfocused ultrasound with visualization, radiofrequency) and topical (e.g., microdermabrasion, chemical peels) modalities. These mostly noninvasive therapies are mentioned by necessity as recommended components of multimodal treatment, but specifics of their use are beyond the scope of this course.

RECOMMENDED THERAPY COMBINATIONS

Improved understanding of facial aging and mechanisms of therapies inform their combination and sequence of use. With superior outcomes repeatedly demonstrated with combination therapy over monotherapy, this approach is now recommended for most patients [6,10,33,34,53,120].

Botulinum Toxin Plus Hyaluronic Acid Fillers

Botulinum toxin and hyaluronic acid fillers act synergistically for superior improvements and duration [34,53,79,87,120]. Recognition that hyperdynamic muscle activity leads to both soft tissue volume loss and rhytides has prompted botulinum toxin injection one to two weeks before fillers. Botulinum toxin increases filler efficacy by diminishing the dynamic muscle component of the target, and improves longevity by preventing filler breakdown from repetitive muscle activity. Fillers can extend botulinum toxin efficacy to six months.

Botulinum toxin is less effective in deep lines and creases (e.g., glabellar or forehead rhytides), and repetitive muscle contraction degrades filler efficacy to soften the appearance. Botulinum toxin/fillers overcome the respective monotherapy limitations to produce superior extent and duration of improvement, without increased bothersome or significant side effects. Outcomes are optimized by treating aesthetic units.

Botulinum Toxin/Hyaluronic Acid Fillers Plus Lasers/Light Therapies

Combined with energy-based therapies, the efficacy of botulinum toxin/fillers is superior to monotherapy, without increased spread of botulinum toxin, filler migration, or other untoward effects [10,94]. Botulinum toxin before laser resurfacing improves post-laser healing, collagen remodeling, and aesthetic results, while post-laser botulinum toxin reduces wrinkle recurrence, prolonging resurfacing efficacy.

Botulinum toxin added to intense pulsed-light treatment of photoaging increases overall aesthetic benefits. Microfocused ultrasound and radiofrequency stimulate fibroblast proliferation and new collagen for efficacy in cutaneous sagging, wrinkling, and marionette lines. Outcomes are usually more satisfactory combined with hyaluronic acid fillers.

RECOMMENDED THERAPY SEQUENCE

Ideally, all treatments should be spaced apart at least two weeks, with botulinum toxin given two weeks before filler injections in areas of static lines, dynamic rhytides, or deep folds. However, patients may prefer same-day botulinum toxin and filler injection for convenience. This is thought to be safe, with botulinum toxin injection before fillers to avoid toxin spread beyond the treated area [8,10,11,29,30,53,71]. In the four weeks before and after filler injection, lasers, intense pulsed light, chemical peels, microdermabrasion, and over-the-counter or prescription wrinkle treatments should be avoided. It is also important to avoid concurrent botulinum toxin with laser resurfacing or microfocused ultrasound; increased blood flow and edema may promote toxin diffusion and side effect risks.

The midface is treated first. Patients with nasolabial fold complaints may require education that correcting midface volume naturally and effectively treats overall aging features. The filler injection sequence is lateral, then middle, then medial fat compartments; in some cases, a sequence from deep to superficial tissue planes is suitable. New filler injection over previous fillers ("layering") is discouraged due to greater risk of potentially serious complications [8,10,11,29,30,53,71].

PATIENT-TAILORED TREATMENT

While minimally invasive procedures can improve facial texture and volumize, reduce, contour, lift, or reinforce soft tissue, optimal safety and aesthetic outcomes require individualized treatment planning based on assessment of skin changes, tissue quality, extent and pattern of muscle contraction, and soft/hard tissue volume loss [2,53]. These principles become obscured when rigid adherence to algorithms or cutaneous landmarks (which shift with age) supersedes a patient-tailored approach [53].

Declining tissue quality and skin laxity are indications for combining fillers with lasers or energy-based devices. In older patients, fewer injection sites and smaller toxin doses at each site may be indicated if muscle mass or function is reduced [53].

THE TRI-VECTOR TECHNIQUE

Patients present with varying levels of lipoatrophy regardless of age, and the tri-vector technique adapts practice standards into an easily patient-tailored framework [121]. In each horizontal zone, this approach initiates filler injections in lateral compartments, working from lateral to medial.

In this approach, step one is supra-periosteal filler injections. In the upper face, injections are made in the temporal fossa to address forehead atrophy, brow ptosis, and temporal volume loss. Filler in the midface addresses volume loss of preauricular (in front of ear) lateral cheek and mid-cheek fat, tear trough, and infra-nasal lines/folds; in the jawline, injections can address mandibular angle changes and maxilla and mandibular fat volume loss (also marionette lines).

The second step consists of deep dermis filler injections at three ligament support sites to provide fibrous fixation points and restrain facial skin against gravitational changes. These sites are:

- McGregor patch (posterior to zygomaticus minor muscle)

- Pyriform aperture (superior part of nasolabial fold)

- Modiolus (lateral to inferior part of nasolabial fold)

The final step in this approach is patient-specific. It may include filler injection in dermal or superficial fat layers to contour the face, soften any sharp angles (especially in jawline area), or address focal superficial lipoatrophy sites [121].

THE UPPER FACE

In each horizontal facial zone, there are compartmentalized anatomic regions that undergo changes and/or loss of volume and tissue integrity with age. Differences in underlying bony structure, weight, and soft-tissue quality influence inter-patient variations in specific aging changes [29,49].

The youthful upper face is characterized by a subtle convexity of the temple, forehead, and lateral brow and upper eyelid fullness [29]. The aged forehead skin, with loss of bone and fat support, is pulled by repetitive activity of depressor muscles and mimetic musculature to form horizontal rhytides. With temporal and forehead volume loss, glabellar rhytides deepen and lateral canthal rhytides (crow's feet) develop at rest and at smile [10].

The eyebrows, a powerful and versatile facial feature, greatly contribute to the perception of facial attractiveness, and fundamentally inform sexual dimorphism, facial recognition, and nonverbal communication [122]. Low medial brows, even without furrowed wrinkles, signal hostility and anger [65]. Brow ptosis develops as periorbital bone remodeling and temporal deep fat loss erode the support and fullness of the upper lid, causing the brow to descend to the superior orbital rim [4,29]. Fixed glabellar frown lines, transverse forehead furrows, temporal hollowing, skeletonized supraorbital rim, brow ptosis, and redundant upper eyelid skin combine to form an aged appearance to the upper face [4,29].

The forehead, glabella, and temples are treated as one aesthetic unit, with botulinum toxin for muscle modulation, fillers to improve temporal hollowing and contours of the forehead, and microfocused ultrasound to lift the ptotic brow and tighten the skin [10,11]. This "aesthetic unit" principle is underscored by inter-relationships of the brow elevator (frontalis) and depressor (corrugator, procerus, orbicularis oculi) muscles. With antagonistic function, botulinum toxin injection in one muscle causes unopposed strength in another [11,79].

Botulinum Toxin Treatment

Lines, furrows, and creases develop over time from hyperactive, repetitive use and contraction of various muscles. Botulinum toxin injection into culpable muscles can smooth vertical glabellar rhytides (glabellar complex muscles), horizontal forehead rhytides (frontalis muscle), and periorbital lateral canthal rhytides (lateral orbicularis oculi muscle) [33].

Horizontal Forehead Rhytides

The frontalis, the sole elevator muscle in the upper face, contracts to raise the eyebrows and upper eyelid to express surprise or fright. Frontalis contraction eventually forms horizontal forehead rhytides [33,67].

Horizontal forehead rhytides require simultaneous botulinum toxin injections of the frontalis and brow depressors. With frontalis muscle injection alone, unopposed activity of depressor muscles will induce a lowered, angry-looking brow ptosis. Frontalis injections are 2–3 cm above the brows; closer brow placement risks inhibition of facial expression and brow ptosis [11,33].

Glabellar Rhytides

Treatment of glabellar frown lines is an integral part of harmonizing the brow shape and eyebrow position. Glabellar lines are caused by contraction of the corrugator and orbicularis oculi muscles (move the brow medially) and the procerus and depressor supercilii muscles (pull the brow inferiorly). Botulinum toxin injection of corrugator and procerus muscles weakens the brow depressors to improve glabellar rhytides. Injections are made above the supraorbital rim to avoid upper eyelid ptosis. Men typically require higher doses due to greater muscle mass in this area [33].

Lateral Canthal Rhytides

Contraction of the lateral orbicularis oculi muscle produces lines (crow's feet) that radiate from the lateral canthus. These lines initially appear on smiling or squinting (dynamic) but can become static (at rest) due of aging, photodamage, and skin remodeling. Crow's feet are treated with multiple botulinum toxin injections into the lateral orbicularis oculi muscle, lateral to the orbital rim with the facial musculature at rest [11,33,79].

Brow Lift

Brow ptosis, a common feature of aging, can produce facial features at rest that mimic angry or scowling expressions. Brow shape and height are controlled by the opposing action of brow elevator (frontalis) and depressor muscles [33]. Botulinum toxin is injected as in treating glabellar lines (above), the lateral orbicularis oculi, and in the lateral corrugators 1–2 cm above the orbital rim to avoid the Mephisto or Spock eyebrow (quizzical look). Injections limited to the superolateral orbicularis oculi muscle (tail of the eyebrow) can give a lateral eyebrow elevation [10,11,33,79].

Hypertrophic Orbicularis Oculi

Botulinum toxin injection can widen the ocular aperture by weakening the orbicularis oculi muscle complex, producing a wider, rounder eye during smiling and at rest [33].

Dermal Fillers

Given the substantial variability in anatomy and aging of the upper face, reversible (hyaluronic acid) fillers may be preferred; clinicians with experience and a level of comfort may consider stimulatory (PLLA) fillers [10,11].

Fillers for temple and upper brow volume loss require elevated elasticity and viscosity for periosteal placement, to give structural and lifting support to overlying tissues with low risk of displacement (e.g., Restylane Lyft, Radiesse, Juvéderm Voluma-XC, Juvéderm Ultra Plus XC) [29]. Fillers for volumizing the upper lid, forehead, and crow's feet should have lower elasticity and viscosity for superficial placement (e.g., Restylane-L, Restylane-Silk, Belotero Balance, Juvéderm Ultra XC) [29].

The anatomic order of contouring influences the ultimate outcome of facial volumization. Augmenting the temple alone may provide lateral brow support and should be addressed before moving more caudally [29]. The upper face is a challenging area for fillers because of risk for serious complications [11].

Temple Volumization

Fillers for temporal volume loss and hollowing intend to eliminate concavity and achieve a uniform or slightly convex contour between the temporal fusion line and the zygomatic arch. Severe volume loss may require multiple treatment sessions [8,11].

Brow and Upper Lid

Volume loss occurs in bone and more superficial tissues including subcutaneous fat and the retro-orbicularis oculi fat pad. To correct this deficit, the initial filler injection is directly onto periosteum 1 cm superior to the upper lateral orbital rim or just above the superior lateral brow hairline [29].

Eyebrow Shaping

The position and/or shape of the eyebrow often changes with aging. Fillers can enhance eyebrow contour and volume and may improve elevation of the eyebrow tail when botulinum toxin provides insufficient eyebrow lifting [11].

Forehead Contouring

Dynamic forehead lines are usually treated with botulinum toxin, but fillers can treat deep horizontal lines to create a smooth contour across the forehead. The filler is injected at least 2 cm above the eyebrow, with the needle tip on bone [11]. For tightening eyelid skin, radiofrequency is preferred because of its efficacy and built-in safety features [10].

THE MIDFACE

In facial aesthetics, the midface is a main determinant of perceptions of facial attractiveness, influenced by synergy of the eyes, nose, lips, and cheekbones (central facial triangle). It is also the focal point for restoration of a youthful topography. As such, the midface should be treated first [4,10,122].

Degenerative changes occur in nearly all anatomic components of the midface. The mid-cheek manifests the most complex soft tissue changes with aging, and volume loss of the deep mid-facial fat is a primary determinant of an aged appearance. Fat within each compartment changes independently over time, losing volume and shifting as the facial ligaments attenuate and the bony skeleton recedes [10,31].

Loss of maxilla projection and skeletal support and inferior displacement of soft tissues contribute to the tear-trough deformity, malar mounds, and prominent nasolabial fold and groove. The cheeks lose projection to assume a sunken appearance. Prominent transitions between cheek fat pads and flattening of the malar prominence mark the deflated midface; the heart-shaped face of youth becomes distinctly pear shaped [10,29,31].

Accurate assessment of midface volume loss is the single most important factor for appropriate correction of facial volume; precise restoration may rejuvenate the upper and lower face [29]. To define these midface areas, draw one line from the lateral canthus to the lateral oral commissure and a second line from the tragus to the nasal ala. The lines intersect to form quadrants. Examine the upper-outer (zygomatico-malar region), upper-inner (anteromedial cheek), and lower-outer (submalar region) quadrants for volume loss and treat accordingly [84,123,124].

The medial suborbicularis oculi fat migrates inferiorly with aging. The medial part of the deep medial cheek fat extends almost to the lateral incisor tooth. Volumizing both medial fat pads is crucial for correcting cheek sagging—a major contributor to deep nasolabial folds [2,40].

Fillers are used for volumization and contouring the upper cheek and lid-cheek junction, the submalar and preauricular areas. Botulinum toxin plays a limited role [125]. Recommendations for the midface advise treating the malar area first; volumizing the malar and restoring its contours gives a lifting effect that may reduce or negate the need for filling other midface areas [30,55]. Careful attention should be paid to restorative effects on the lower lid, nasolabial fold, nasal base, and upper lip during malar augmentation [29].

Malar Area

Fillers are injected to create vertical pillars over the bone to support and lift the malar area. The following injection sequence is lateral to medial, to achieve a tenting effect with less filler needed for medial injection [8,30,94]:

- In the lateral midface, the zygomatic (cheekbone) arch and prominence (crucial for optimal cheek restoration)

- Lateral compartment of the superficial cheek fat pad and the preauricular superficial fat compartment

- Middle compartment of the superficial cheek fat (medial sub-orbicularis oculi fat)

A variety of fillers can volumize the malar/lateral cheek region with good results (e.g., hyaluronic acid, CaHA, PLLA, PMMA) [84].

Lower Lid

Volume restoration of tear trough deformity with filler injection is a difficult technique in a danger zone for vascular complications and should only be performed by experts [84].

Deep Medial Cheek

Volumizing the deep medial cheek fat increases anterior projection, reduces the nasolabial fold, and recreates a youthful cheek within its natural boundaries [25,40]. Juvéderm Voluma XC, Juvéderm Ultra Plus XC, Restylane Lyft, Radiesse, PLLA, and PMMA are all suited for deep midface volumizing [29,84]. Patients with significant orbital fat herniation may benefit more from surgery; fillers alone may be inadequate to reduce the transition between protuberant fat pad and concave tear trough [84].

Nasal Tip and Upper Nasolabial Fold

Deep volumizing of the nasal sill can provide support to the aging nasal tip, a natural correction of the upper nasolabial fold, and a minor lift to the upper lip. Treatment requires periosteal placement of high-elasticity, large-particle fillers [29].

Botulinum toxin can correct "bunny lines"—horizontal rhytides that traverse the nasal bridge and the downward slope of the nose when the patient is smiling—and elevation of the nasal tip [10,125]. In the midface, nasolabial folds are treated last [10].

Nasolabial Folds

Most fillers are indicated for treating nasolabial folds by the FDA, but unlike other midface areas, nasolabial folds hypertrophy with age. Thus, fillers are suggested to soften a prominent fold, not to volumize. First correct deficient malar volume, then soften residual nasolabial folds conservatively using moderate-elasticity and -viscosity filler (e.g., Restylane-L, Juvéderm Ultra XC) injections in the superficial fat just to the dermis [29].

Low-dose botulinum toxin into each lip elevator complex above the nasofacial groove can collapse the upper nasolabial fold but may vertically lengthen the upper lip, an aging-related feature. Botulinum toxin should not be directly injected into nasolabial folds, as this may result in an asymmetrical smile or lip ptosis [33].

After addressing volume loss, microfocused ultrasound treatment of the overlying superficial musculo-aponeurotic system and skin envelope addresses laxity and bridges the aesthetic unit compartments to create a smooth cheek contour [10,126].

THE LOWER FACE AND NECK

During the aging process, bony and soft-tissue structures in the lower face undergo significant alterations [4,10,29,58]. Malar and perioral fat volume loss, bone resorption, and ligament laxity cause increasingly lax skin to droop downward over a changing lower face structure. The general widening and loss of integrity of the lower face can appear as a relative increase in jowl volume with decreased jawline strength and perioral/lip volume.

Jowling is one of the most unwanted effects of aging and a primary concern of aging patients. The jowls become prominent with deflation of superficial fat exposing deeper fat pads, descent of deep fat pads, and increased septal laxity. Loss of volume in the prejowl sulcus, posterior jawline, and inferior preauricular region exacerbates the appearance of jowls.

Superficial and deep atrophy of the perioral area manifests as a lengthening and flattening of the upper lip complex, loss of vermillion and vermillion border volume, and formation of vertical perioral rhytides. The oral commissures turn down, and the mentalis region flattens or becomes ptotic. Protrusion of the central chin results from loss of lateral and inferior volume. These changes are superimposed on and intensified by mandibular bony changes that result in decreased vertical ramus height, a widening mandibular angle, and loss of anterior mandibular (mental) projection. Platysma muscle contraction from support of deeper neck and floor of mouth structures promotes vertical fibrous bands on the neck; laxity in overlying skin creates horizontal rhytides.

Botulinum toxin and filler combinations are especially effective in the lower face to address dynamic musculature, loss of volume and support, and skin laxity [10]. Some believe that fillers are more important than botulinum toxin and should be used first to provide structure and support before considering botulinum toxin for dynamic lines [127].

Jawline

Structural volumizing of the lower face should begin with correction of the jawline, using fillers with high elasticity (Restylane Lyft, Radiesse, Juvéderm Voluma XC, or Juvéderm Ultra Plus XC) [29]. Injector preference/experience will also determine filler choice [10].

Mandibular shrinkage and redistribution of fat leads to the emergence of jowls and loss of jawline definition. To smooth the jawline and camouflage the prejowl, the inferior mandibular border is injected in the supraperiosteal plane. Injection under the mandibular rim improves the prejowl concavity. The jowl is not directly injected, to avoid blood vessels [8,58].

A technique referred to as the "Nefertiti lift" involves small amounts of botulinum toxin injected along the jaw and into the lateral, upper platysmal band to improve the appearance of pouches. With skin laxity, the addition of microfocused ultrasound helps lift the jowls for a tighter appearance [10].

In women, an overly squared jaw can be undesired. If sagging is not an issue, botulinum toxin injection of the masseter results in a softening of the determined, clenched appearance and a more feminine face [65].

Chin

Botulinum toxin injections just anterior to the bony mentum on each side of the midline weaken the mentalis muscle contraction responsible for mental crease, and injections into the mentalis muscle at the prominence of the chin can help reduce a peau d'orange chin [33,65]. Fillers create definition and fill residual depressions. Injection is placed on the periosteum and deep subcutaneous tissue to create vertical pillars. Fillers with greater lift are preferred [8,58].

The perioral region is considered one aesthetic unit, comprising the lips, oral commissures, and melomental folds (marionette lines). Botulinum toxin is commonly used for perioral rhytides but requires caution, as improper injection may result in a flaccid cheek, an incompetent mouth, an asymmetrical smile, or speech pathology [10,79]. Perioral volumization may independently restore and support the lips by enhancing lip volume and should be precede direct mucosal lip volumizing in an aging face [29].

Moderate-elasticity fillers (e.g., Restylane-L, Restylane-L Silk, Juvéderm Ultra XC, Belotero Balance) are injected in the subcutaneous plane, first in the oral commissure until a subtle upturning is achieved, then in the upper and lower lip columns for volumizing support. This will improve the appearance of vertical lip rhytides and philtral columns [29].

Vertical perioral rhytides are common cosmetic concerns, induced or exacerbated by repetitive orbicularis oris muscle contraction. With fillers, a short-lived improvement and fairly rapid recurrence is likely caused by normal perioral animation. Low-dose botulinum toxin is injected adjacent to the vermillion border in the areas of rhytides, and lateral to the Cupid's bow area of the lip. Avoid injecting the oral commissures (corners of the lip) and the midline area to reduce the risk of a drooping lateral lip [33].

Mouth frown results when the depressor anguli oris muscle pulls the corners of the mouth downward, in opposition to the action of zygomaticus major/minor muscles, producing a frowning expression. Botulinum toxin injection weakens the depressor anguli oris, allowing the zygomaticus to elevate the corners of the mouth, which return to a horizontal position. Botulinum toxin is injected into the insertion point of the mentalis muscle, because upward pull of the mentalis contributes to mouth frown [33].

Melomental folds (marionette lines) are exacerbated by contraction of the depressor anguli oris muscle. This is treated by botulinum toxin injection into the posterior margin of each depressor anguli oris immediately above the mandible [33].

THE NECK

Platysmal bands, often the first sign of aging of the neck, appear as two vertical, bulky cords from the lower border of the mandible to the suprasternal region. Formerly thought to result from skin laxity and loss of platysma muscle tone, these vertical muscular bands are now attributed to platysma muscle activity, treated by denervating the platysma muscle with botulinum toxin instead of tightening the skin [128]. Very-low-dose botulinum toxin is injected superficially into only specific platysmal bands, to avoid dysphagia [79]. Improvement of the overall appearance of the neck requires fillers for structural support of the chin and jawline and botulinum toxin for the masseter, platysmal bands, or horizontal neck lines [33,127].

10. PATIENT SELECTION AND EVALUATION

As discussed, the careful assessment of patients forms the basis of individualized treatment planning. Because aesthetic procedures are elective, the benefits must clearly outweigh the risks. Healthcare providers have a responsibility to refuse requests in which the risk-benefit ratio is not in the patient's best interest, and to refer patients elsewhere for consideration of treatments the clinician cannot or prefers not to perform. Patients rely on the healthcare provider to act as a "learned intermediary" and to exercise fiduciary responsibility in advising the patient on the best course of action [95].

Patients should be carefully selected by thorough assessment of medical history, motivation, and expectations to identify contraindications. The increasing incidence of serious dermal filler complications has expanded the cutaneous and systemic contraindications to filler treatment, relevant to botulinum toxin because combined therapy is common.

Following screening, careful discussion addresses the specific cosmetic concerns and possible benefits and risks across a range of available options. A treatment plan is arrived at through shared decision-making; informed consent and documentation are made.

For those who are not proficient in English, it is important that the patient history and information regarding the risks associated with the use of botulinum toxin/dermal fillers be obtained in the patient's native language, if possible. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required.

SCREENING AND SELECTION

Screening and Assessment of Medical Contraindications

The patient may request a cosmetic therapy, but the aesthetic provider should ultimately "select" the patient. Most complications stem from inappropriate patient selection, inadequate antiseptic preparation, or improper treatment technique. Selecting appropriate patients, or perhaps more importantly, not treating inappropriate patients, is the first crucial step in avoiding complications [71].

A thorough history of skin conditions, allergies, systemic disease, current medication use, and previous cosmetic procedures is mandatory. Patients may not see important aspects of their history as relevant. To help ensure disclosure, assess skin-related and systemic conditions by linking to potential adverse effects [19,71].

Some skin disorders and local or remote infections can promote injection seeding of infective agents that populate the filler site, or hematogenous spread to implanted fillers and later biofilm formation or transition from infection to hypersensitivity [19,129,130]. These conditions require careful screening. Fillers have risks of injection-site keloid formation or hyperpigmentation; patients with these conditions should avoid fillers [75].

Screening may identify conditions whereby filler therapy is contraindicated, deferred until resolution, or considered cautiously. Significant comorbidity, polypharmacy, or use of immunomodulatory drugs can greatly complicate adverse effect management if it becomes necessary [22].

Screening and Assessment of Psychological Contraindications

Understanding the motivations for cosmetic treatment is vital to minimizing inappropriate patient selection. Unrealistic expectations, which are contraindications to cosmetic treatment, are prevalent in some psychological conditions [19,75]. Low self-esteem can lead to unrealistic goals and expectations. High neuroticism and/or anxiety may influence expectations, and outcomes tend to be poorer [131]. The most important mental disorder consideration is body dysmorphic disorder.

Body dysmorphic disorder is a psychiatric disorder characterized by preoccupation with an imagined defect in appearance or distorted perception of one's body image. These patients may be unduly invested in the cosmetic procedure as the solution to other life problems. Unrealistic expectations are followed by dissatisfaction with results that do not correlate with objective outcomes [132,133]. Dissatisfied patients with body dysmorphic disorder have been reported to retaliate against their cosmetic providers with lawsuits, threats of violence, physical assault, and in rare cases, homicide [134,135].

Compulsive behaviors have been described in patients who, driven by the quest for physical perfection, demand and obtain multiple sequential cosmetic injections despite the increasing risk. Compulsive demand for cosmetic procedures falls on a spectrum of dysmorphophobic behaviors [136,137]. Body dysmorphic disorder is also associated with "doctor-shopping" [131].

Whether the diagnostic threshold for body dysmorphic disorder is a contraindication to nonsurgical cosmetic procedures is unresolved, but many consider signs of body dysmorphic disorder a firm contraindication to cosmetic treatment [19,131,132,138]. Appropriate onward referral may be required when psychopathology is apparent [131,139].

PATIENT EVALUATION AND CONSENT

After the patient has been screened for medical and psychological contraindications to cosmetic treatment, the next step is to determine if treatment expectations can be met or managed with education and counseling. Following this, treatment options are explored and a plan is developed and documented.

Patient Motivation and Treatment Expectations

American healthcare consumers are both aging and youth-oriented [94]. A majority of the population is dissatisfied with their appearance, rates of cosmetic interventions continue to increase, and the expectations of many patients have risen proportionately [131].

Patient motivation for cosmetic therapy, benefits anticipated, and satisfaction with the outcome are closely inter-related. The expectations and motives for seeking treatment are complex and diverse. Patient dissatisfaction usually derives from failing to manage or meet expectations, underscoring the importance of identifying expectations at the first consultation and documenting this discussion [131]. The clinician should establish underlying motivations, differentiate patient wants from needs, and temper expectations within realistic goals [19].

Patient motivation is considered external when expecting physical changes to influence some aspect of their life (e.g., partner will love them more, career success). Unrealistic expectations with external motivation require discussion, as these patients are more likely to be dissatisfied with outcomes. In contrast, internally motivated patients (driven by a desire to look better for themselves) are good candidates [131,138].

Other factors can influence expectations [94,131]. Younger patients can be especially sensitive to peer group acceptance and social media images, but correction of an objectively undesired feature can also be therapeutic. Traditional and digital media promote unrealistic expectations of an idealized appearance, and along with marketing, this has led some patients to believe a youthful appearance can be maintained indefinitely, has a quick fix, or is guaranteed with a "miracle treatment." Partners, families, and friends can exert strong influences that can be helpful to separate from the patient's own expectations. Expectations tend to be higher among more educated patients.

Expectation Management

Patient expectations should be managed so they do not envisage an unrealistic outcome. The treatment of inadequately informed patients is fraught with potential problems and risks of dissatisfaction [71].

Patient education on the risks, potential benefits, and limitations of cosmetic procedures may modify expectations. Good information is associated with better outcomes, and hearing these details may lead the patient to prefer a different course of treatment than first proposed [131].

A 2016 guideline stresses the importance of giving prospective cosmetic patients time to reflect on what they learned during the initial consultation—a "cooling-off period" [140]. However, a 2015 consensus statement suggested initiating at least part of the treatment plan the same day to build patient confidence in aesthetic procedures and in the clinician [94]. It may be best to assess on a patient-by-patient basis which approach is appropriate.

The FACE-Q is a validated screening instrument that measures patient expectations of cosmetic treatment, such as appearance-related psychosocial distress and how they expect their appearance and quality of life to change after cosmetic treatment [141]. Use of the FACE-Q can help augment, but not replace, patient-clinician discussions of factors that influence expectations of cosmetic treatments [131].

An effective approach to expectation management is the mnemonic STEP [94]:

- Stress what can and cannot be done with minimally invasive aesthetic treatments.

- Target specific areas of patient concern.

- Envision what the effect of the aesthetic outcome would be like to the patient.

- Preframe the patient to the expected outcome.

Developing a Treatment Plan

The clinician should be both probing and empathetic. Patients may be ashamed they look older than their peers but too embarrassed to directly discuss it. Others may see their concerns as vain and frivolous. Many patients are unaware of the range and versatility of cosmetic procedures or believe their concerns are beyond remediation [94]. Keep the focus on cosmetic concerns rather than any preconceived treatment approach.

Educate the patient to focus on the underlying cause, not the superficial manifestation, of her/his cosmetic complaint. For example, sagging skin is often caused by volume loss, making volume augmentation the appropriate treatment [94].

Discuss realistic expectations for the results of specific treatments. For example, if a patient requests a specific treatment for prominent nasolabial folds with the goal of looking younger, explain that nasolabial folds can be treated directly, but would not produce a more youthful appearance—correcting the underlying volume loss could restore a youthful appearance, even with some residual folds [94].

Many patients have concerns about several facial areas. Asking: "If you could fix only one thing today, what would it be?" can help clarify their relative priorities to base a reasonable sequence of procedures [94].

Clarify expectations of time frame to determine what is realistic and feasible when patients require the desired effects before an important event, such as a wedding. Other patients may want progressive, rather than immediate, aesthetic improvement. Also understand the degree of patient risk tolerance in treatment selection [94].

Discuss the implications of botulinum toxin treatment of the orbicularis oris muscle. The reduction of fine motor control around the mouth may be detrimental to professional speakers, vocalists, or musicians [94].

Informed Consent and Documentation

The risk of malpractice claims is highest in cosmetic medicine. Most result from inadequate informed consent instead of procedural failures [16]. To fully inform decision-making and consent to treatment of patients, carefully discuss the possible benefits, disadvantages, and limitations over a broad range of options [7,95].

Beyond an unnatural look, the three main patient concerns are pain, complications, and costs. It is essential to discuss treatment costs, obtain financial consent, and plan over the long term to obviate financial stress. Addressing these issues upfront is instrumental in establishing the trust that underpins true patient satisfaction [19].

Shared decision-making, an essential element of evidence-based medicine, explores available treatment options, possible benefits and harms of each option, and best match to the patient's characteristics and preferences [142]. Obtaining signed informed consent is crucial in creating awareness and acceptance of potential complications. An informed consent document confirms patient understanding of the potential adverse effects and expected treatment outcome. The document should outline common and uncommon but serious adverse events. Supplying written pre- and post-instructions during the initial consultation can help to establish realistic expectations and minimize dissatisfaction [19,34].

Photographic documentation is essential for medico-legal purposes and appraisal of results. To ensure good quality pre- and post-treatment photographs, the patient should remove all makeup and jewelry and pull hair back or up using a hairband; a black/dark background is preferred. Multiple images at rest and during animation are recommended, including anterior, oblique, and lateral views with the head in a neutral, neck-extended, and neck-flexed position. Proper lighting, consistent angles, and a fixed camera distance are mandatory. A single-lens reflex camera and tripod are recommended instead of smartphones [19].

11. ADVERSE EFFECTS

As mentioned, there is increasing concern of serious adverse events involving dermal filler injections. Some experts noted that by 2010, the increasingly sophisticated training in nonsurgical cosmetic treatment was already neglecting adverse events and their management [22]. With the rapid growth in consumer demand for injection cosmetic therapies, the quality of training, skill, and credentialing of injectors and facilities are increasingly unclear. Along with inadequate regulation, the net effect is described as compromising not only patient safety but the reputation of the field [19,20,23].

With serious adverse events a focus of concern, there is an expansion of recommended measures to prevent, reduce, and manage adverse events before they become disastrous complications.

PREVENTION AND RISK REDUCTION

Several approaches are recommended before injection therapy to prevent or reduce complications by mitigating patient, clinician, or procedure risk factors.

Pretreatment Patient Management

Some complications may be prevented by careful pre-treatment patient management. Filler injection can reactivate latent herpes simplex virus (HSV) infection. Prophylactic antivirals (e.g., acyclovir, valaciclovir, famciclovir) are recommended with patient history of HSV in the intended injection area. Patients with a current outbreak of HSV should receive antivirals, with fillers deferred until resolution of herpes lesions [143,144]. For two to four weeks before and after filler treatment, patients should be counseled to avoid [92,143,144]:

- Dental procedures, oral hygienist visits, tooth bleaching/whitening

- Immunizations/vaccinations

- Other medical procedures

- Any facial procedure inducing inflammation or skin barrier disruption

In addition, products with blood-thinning effects should be avoided the week before filler treatment. This includes food/beverages (e.g., red wine, dark chocolate, grapefruit) and certain supplements/over-the-counter medications (e.g., vitamin E, gingko biloba, fish oils, St. John's wort, nonsteroidal anti-inflammatory drugs [NSAIDs]). Prescribed anticoagulants (e.g., aspirin, warfarin, clopidogrel, apixaban, rivaroxaban, dabigatran) should also be withheld, but only when cleared by the prescribing physician [92,143,144].

A pretreatment checklist should be provided to the patient that includes these points and explains the importance of having any infective or inflammatory conditions treated before the procedure; the treatment should be rescheduled if the pretreatment checklist is incomplete. The patient should receive the checklist with sufficient time to plan relevant medical visits around the treatment date. Contact patients one week pretreatment to ensure they possess and understand the checklist and have no precluding factors [19].

Procedure- and Clinician-Related Factors

Knowing previous surgical (e.g., rhinoplasty) or nonsurgical cosmetic procedures and locations is vital to prevent complications. Fixation, scarring, or alteration of underlying vasculature and anatomy at procedure sites can facilitate intravascular filler injection. "Layering" new fillers over a previously injected semi/fully intact filler can provoke dormant biofilm or inflammatory response [19,71,145].

Vascular Complications

Vascular occlusion from injected filler material may lead to potentially catastrophic complications of tissue necrosis, blindness, or stroke. Even with advanced knowledge of facial anatomy, vascular injury cannot be avoided with 100% certainty. However, measures can be taken to help reduce risks and mitigate intravascular adverse events if they develop. A key step is understanding the danger zones for vascular occlusion, areas where arteries have little or no collateral circulation, extensive anastomoses with the internal carotid artery, or are prone to external compression. Risk factors for vascular occlusion are summarized in Table 7[19,146,147]. Table 8 outlines strategies to mitigate these potential complications.

Table 7: RISK FACTORS FOR VASCULAR COMPLICATIONS DURING FILLER INJECTION

Factor

Description

Injection site danger zones

Injections to the nose, nasolabial fold, forehead, and glabella are at increased risk for blindness.

Injections to the glabellar region, nasal tip/alar triangle, and lips increase the risk for necrosis.

Injected volume

Bolus injections near danger zones increase risk of necrosis.

Filler type

Non-hyaluronic acid fillers cannot be dissolved.

Necrosis is more common with denser or more permanent fillers.

Needle gauge

Sharp needles puncture arteries more easily. Aspiration before injecting is suggested, but unreliable. Blunt cannulas are less likely to puncture vessels.

Scarring

Scarring from prior cosmetic procedures or trauma can alter the local vascular pattern.

Source: [70,145,146,147,148,149,150]

Table 8: RISK MITIGATION STRATEGIES FOR FILLER-RELATED VASCULAR COMPLICATIONS

Step

Recommended Strategy

Knowledge

Know injection-site vascular anatomy, and be aware of inter-patient variations.

"Go easy"

Inject slowly, and apply the least amount of pressure necessary. Keep the needle moving. Restrict bolus injections to periosteal plane.

Monitor closely

Watch for blanching or any changes in skin color.

Be aware

In a vascular occlusion, epinephrine can mask skin blanching, and local anesthetic or lidocaine can mask pain.

Listen to your patient

Immediately stop injecting if resistance is encountered, or if patient reports pain, discomfort, or changes in vision.

Have a plan

Onsite protocols for immediate, early, and late adverse events should be easily accessible.

Discharge instructions

Describe in writing the signs/symptoms of vessel occlusion and where and why to seek medical attention.

Staff education

Educate clinic staff on accurate assessment and appropriate referral of patients who report filler adverse events.

Report the incident

Report vascular compromise adverse events to the FDA and filler manufacturer.

Source: [70,145,146,147,148,149,150]

Infection Risk

To minimize infection, stringent aseptic technique is mandatory [19,151]. Prior to any intervention, it is vital to clean, degrease, and disinfect the patient's skin. Remove makeup and cleanse carefully with 2% chlorhexidine in 70% alcohol, avoiding ocular exposure. When treating the perioral area, consider antiseptic mouthwash containing chlorhexidine or povidone-iodine for sterilizing the oral cavity.

The clinician should remove all jewelry, wash hands with antiseptic cleanser, and use gloves for all injections. Once the syringe is held, sterility is lost and aseptic technique is crucial. Not touching any needle or cannula component that penetrates the skin may further reduce infective complications. Cleansing a broad area avoids infective risk from inadvertently resting a cannula on adjacent uncleaned skin. Frequently change needles/cannula when using multiple entry points.

Biopsy can play a crucial role in diagnosing and treating filler-related adverse events, but cosmetic patients strongly resist facial biopsy unless absolutely necessary. A medicolegal process is always justified [152].

After treatment is administered, it is important to assess the patient's response. Clinicians should routinely check perfusion in treated and watershed (e.g., glabella, nasal tip, upper lip) areas [19]. Consider that makeup can obscure skin tone and signs of vascular compromise. Patients should be furnished with written post-treatment instructions and contact numbers. A follow-up call to the patient should be made within 24 hours, and the clinician/clinic should be available by phone for 48 hours postprocedure [19].

All facilities should have easily accessible protocols for early and delayed-onset reactions [19]. Resuscitation measures (e.g., epinephrine, IV access, fluids) and an adequate supply of hyaluronidase should be kept on hand, with regular checks of expiration dates on emergency drugs. In addition, contact information for an ophthalmologist or oculoplastic surgeon experienced in treating retinal artery occlusion should be maintained.

Anesthesia/Analgesia

Pain control is crucial to ensuring a positive experience for patients [76]. Topical anesthetics or local nerve blocks are commonly used to reduce pain, although many fillers are also formulated with lidocaine. To reduce pain, use the smallest suitable needle, slow infiltration, and the least needle punctures necessary. Other measures to help reduce pain include ice application, skin vibration, patient distraction, and a relaxed, soothing treatment environment [34].

COMMON ACUTE SIDE EFFECTS

Pain, bruising, redness, itching, and swelling are common, self-limiting side effects following dermal filler injections. Persistence beyond seven days should be closely assessed [144].

Pain

Pain is relatively common and is more likely with multiple needle punctures. However, pain may also be a sign of impending vascular compromise, discussed in detail later in this course. Pain can be minimized by using slow needle introduction, ice anesthesia, and filler warmed to body temperature [70].

Erythema

Erythema (redness) usually resolves without treatment. Longer-lasting or persistent erythema suggests hypersensitivity reaction or infection and requires careful evaluation. Oral tetracycline, isotretinoin, topical tacrolimus, or medium-strength topical steroids are suggested for persistent erythema; long-term, high-potency topical steroids should be avoided. In severe cases, oral propranolol (20 mg) can make erythema less evident [70,143].

Edema

Evidence Based Practice Recommendation

If ice is used to control pain following botulinum toxin or dermal filler injection, the Australasian College of Dermatologists recommends placing it inside either a sterile glove or a nonsterile glove, then wiping the glove with alcohol or chlorhexidine to sterilize it, as ice is not sterile. Alternatively, frozen gel packs may be used in the same way.

https://onlinelibrary.wiley.com/doi/full/10.1111/ajd.13273

Last Accessed: March 19, 2024

Level of Evidence: Expert Opinion/Consensus Statement

Edema (swelling) in the first few days is normal with all fillers and can be managed by gentle pressure and ice packs [83]. Episodic swelling and edema following filler injection can occur after sun exposure, exercise, or saunas. It is important not to confuse normal edema with allergic reaction; manage with ice packs, topical steroids, and avoidance of vasodilating stimuli [70].

Ice is recommended and commonly applied on the injection site to prevent and manage pain and edema, but it has also been associated with infection. An Oregon plastic surgery clinic described an outbreak of facial Mycobacterium chelonae infection (presenting as swollen skin nodules with drainage or discoloration three to six weeks after inoculation) following filler injections. The infections required three to four months of multiple oral or IV antimicrobial agents to resolve. The source was traced to clinic tap water, used for ice applied immediately pre- or post-injection [153]. As such, cold packs rather than ice may be safer options.

Bruising

Bruising, hematoma, and ecchymosis can result from needle pricks and bleeding. This can be minimized by firm pressure on the needle insertion site and prevented by cessation of alcohol and supplements with anticoagulant effects one week before treatment. Intense pulsed light and vascular lasers have been used to treat persistent symptoms [70].

Lesions

Papulopustular lesions occur when filler injected too superficially in the papillary dermis occludes, or extrudes through, sebaceous or sweat gland openings and mimics bacterial infection or acneiform eruption. Post-injection massage can help in prevention, and topical astringents can help in their resolution [70].

Overcorrection can appear as bumps, nodules, or irregularities when too much material is injected. In these cases, hyaluronic acid products should be resolved using hyaluronidase. With non-hyaluronic acid fillers, puncture and drainage of excess product may suffice [70].

INFREQUENT ACUTE ADVERSE EVENTS

Dysesthesias and Paresthesia

Dysesthesias and paresthesia are symptoms of nerve injury following direct trauma, injection of filler into a nerve, or tissue compression by the product. Nerve damage is usually transient and reversible, infrequently permanent, with the infraorbital nerve the most common site [143].

Intracranial Penetration

For deep periosteal or supraperiosteal injections, the needle is advanced to the level of the bone and retracted slightly. Accidental intracranial penetration is a demonstrated risk, but the prevalence is unknown [70].

VASCULAR COMPROMISE

Vascular compromise is the result of vascular occlusion following inadvertent intravascular filler injection or vascular compression by adjacent filler material. Embolism occurs when filler material enters the vasculature, impeding blood flow. Vascular compromise can involve arterial or venous occlusion [70,143,150].

Areas at highest risk of embolism have minimal collateral circulation (the nose), terminal blood supply (the glabella), large vessels (the nasal artery), or large areas (forehead) supplied by a vessel with minimal collateral circulation (terminal supratrochlear artery) [154]. Embolization of filler material is a potentially catastrophic complication with possible sequelae of tissue necrosis, blindness, or cerebrovascular accident. The literature is replete with examples of permanent blindness following hyaluronic acid, PLLA, or CaHA filler injections [122,155]. Intravascular injection occurs more frequently than assumed. In a study of expert aesthetic physicians, 62% reported inducing one or more such events [156].

Tissue Necrosis

With embolism induced by intra-arterial injection, damage to endothelial cells leads to ischemic changes in the skin, tissue degradation, and necrosis [71]. Cells undergoing necrosis swell and then burst, releasing their contents to trigger a local inflammatory reaction, with swelling, pain, heat, and redness. Intra-arterial injection can lead to embolism, platelet aggregation, subsequent occlusion in a terminal branch, and delayed-onset necrosis [145].

Necrosis can follow vascular occlusion due to vessel compression by filler material or filler-induced tissue swelling, and onset can be delayed. Tissue necrosis can occur with all dermal filler types but is more likely with particulate fillers [83,145]. With blood supply reliant on a single arterial branch, the glabella, nasal ala, and nasolabial folds are most vulnerable to necrosis [70,83].

The cardinal features of vascular occlusion and necrosis are changes in skin color and pain [70,71,145,150]. Skin blanching and severe pain are immediate with arterial occlusion. However, as noted, epinephrine use may mask blanching, and pain may not fully appear until local anesthetic or nerve block wears off. If not swiftly resolved, the affected skin will develop reticulated erythema, purpura, ulceration, and scarring.

With venous occlusion, red/bluish skin color changes appear immediately to hours later, with or without pain, progressing to blisters, pustules, and tissue necrosis within a few days.

Blindness

The most feared complication of filler injections is blindness following occlusion of the central retinal artery, the final branch of the ophthalmic artery. Comparing average diameters, injected hyaluronic acid filler particles (400 mcm) easily move through the ophthalmic artery (2 mm) to block the central retinal artery (160 mcm) [122,154,157].

The routes to occlusion and blindness vary by proximal branch of the ophthalmic artery inadvertently injected. When the force of injection exceeds intra-arterial pressure, the injectate can move proximally in the angular artery and then proximal of the origin of the central retinal artery. With pressure on the syringe released, the material moves distally into the retinal artery. Central retinal artery occlusion follows injection into the glabellar region (through the supratrochlear artery into the supraorbital artery) or the nasolabial fold (in any anastomosis of the dorsal nasal artery from the ophthalmic artery) [154]. Blindness, visual field deficit, or blurring is instant, often with excruciating ocular pain [70,83,143].

Stroke

With greater pressure on the plunger or for a longer time, the filler may travel into the internal carotid artery and then enter cerebral circulation, producing a stroke [122,150]. Unilateral blindness and left-sided hemiplegia immediately following glabellar area injections are reported. However, these effects are rare with dermal fillers and more likely with autologous fat injections [70]. Pulmonary embolism and panophthalmoplegia have also been reported with filler injections [19].

Management of Vascular Compromise

Intense pain is considered an initial sign of intravascular filler injection, but as noted, it may be obscured by lidocaine in fillers or by local anesthetic. Vigilance for skin color change is mandatory [19]. With any suspicion of vascular occlusion from inappropriate pain, skin blanching, or mottled discoloration, immediately stop injecting and aspirate any product when withdrawing the needle (if possible). It is vital to facilitate an immediate, aggressive response to remove the product and promote blood flow [19,71].

Hyaluronidase Reversal

With hyaluronic acid fillers, hyaluronidase injection is the foundation of emergent therapy for most adverse events, a powerful advantage of these products, as no other dermal filler material has a reversing agent [19]. Hyaluronidase injection enzymatically dissolves the hyaluronic acid filler material [68].

Evidence Based Practice Recommendation

Hyaluronidase has also been shown to diffuse into the lumen of blood vessels even when injected external to it. According to the Aesthetic Complications Expert Group, for potential cases of necrosis due to intravascular deposition of hyaluronic acid, it is not essential to inject directly into the vessel—injection into the surrounding area is also likely to result in dissolution of the product.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057733

Last Accessed: March 19, 2024

Level of Evidence: Expert Opinion/Consensus Statement

Hyaluronidase is indispensable in resolving acute hyaluronic acid filler adverse events. All clinicians who provide hyaluronic acid filler injection should always have an adequate supply of hyaluronidase in the office for emergencies and regularly check the product expiration date [122].

Hyaluronidase is recommended in vascular compromise from all filler types to reduce edema and potentially decrease vessel-occluding pressure. When injected immediately, hyaluronidase degrades hyaluronan, a potent proinflammatory mediator associated with tissue necrosis [58,71].

High-dose hyaluronidase (500–1,000 IU) mixed with lidocaine is injected in the affected vessel, the surrounding path of the vessel, and its terminal branch; a large-bore cannula avoids bruising that obscures signs of improving skin color. Doses up to 1,500 U may be used if needed; the consequences of inadequate dosing are dire. Repeat hourly for three to four hours and daily for at least four days or as long as signs of ischemia persist [71,146,158,159].

Injecting high-dose hyaluronidase diluted with lidocaine induces vasodilation and hyaluronic acid dispersion and, with saline, allows coverage of a larger area [71]. Vigorously massage the treated area during and after all hyaluronidase injections to optimize the results and aid mechanical breakdown [158].

Because anaphylaxis is a potential side effect of hyaluronidase and skin testing for hypersensitivity reaction is not an option in emergencies, risk mitigation requires full resuscitation equipment on site and training in its use [34,95,158].

Promote Blood Flow to the Affected Area

Evidence Based Practice Recommendation

For necrosis following dermal filler injection, nitroglycerin paste (rectal paste, used off label) can be applied under an occlusive dressing for several days. The Aesthetic Complications Expert Group recommends applying for 12 hours and then removing for 12 hours until clinical improvement is seen or until it is no longer tolerated.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057733

Last Accessed: March 19, 2024

Level of Evidence: Expert Opinion/Consensus Statement

Apply warm compresses, and vigorously massage or tap the area. To limit platelet aggregation, clot formation, and further compromise, the patient should be administered two tablets (650 mg) of aspirin to chew and swallow, followed by 75 mg per day until necrosis resolves [19,71,145].

Some experts recommend nitroglycerin paste 2% to promote vasodilation [70,145,160,161]. However, others caution against its use before the hyaluronic acid has dissolved with two or three days of treatment, as dilation of adjacent unobstructed vascular pathways may propagate the embolus toward the orbital area [19]. Low-molecular-weight heparin has also been used in the management of patients with filler-induced vascular occlusion [34].

Additional Recommendations

Necrotic cells and tissue invite opportunistic infection. The measures needed to promote healing and prevent further complications depend on the extent of necrosis and range from appropriate dressing and wound care with topical and/or oral antibiotics to surgical debridement for removal of dead tissue. Susceptible patients may require antiherpetic medication with perioral-area necrosis [145].

Necrosis can be very painful, and pain management should be considered. While over-the-counter analgesics may be adequate in some cases, more severe pain can require opioids [145]. Because necrosis can cause significant scarring and distress to patients, practitioners should prepare for a possible malpractice claim filed by the patient [145].

Ophthalmic Events

An ophthalmic event is a medical emergency, with 60 to 90 minutes the absolute time window for saving vision. Blindness from central retinal artery occlusion is resolvable following hyaluronic acid filler injection only with rapid intervention by retrobulbar injection of hyaluronidase. Occlusion longer than 60 to 90 minutes is irreversible [19].

An ophthalmologist or oculoplastic surgeon should be contacted immediately and the patient transported to the clinic. The general emergency department is inappropriate [122].

To save vision, a needle is advanced in the inferotemporal quadrant of the orbit, inferior and lateral to the optic nerve, with hyaluronidase 2–4 cc (150–200 U/mL) injected into the inferolateral orbit [122]. Attempt rapid ocular pulsed massage. Having the patient hyperventilate in a paper bag may promote retinal vessel dilation. If possible, annotate the time of the vascular event and the visual acuity if lack of light perception or loss of vision occurs [19].

ALLERGIC/HYPERSENSITIVITY REACTIONS

Acute infections appear as acute inflammation or abscesses at the injection site. If left untreated, the initial reddening and hardening can result in fistula formation, discharge of pus and filler, and potentially permanent disfigurement [162].

Hypersensitivity/allergic reactions occur when injected filler material triggers an immune response. Etiology differs by post-injection onset: acute (minutes to hours) or delayed (within days) [19,71,143,163].

Acute Hypersensitivity Reaction

Type I hypersensitivity reactions, mediated by immunoglobulin E (IgE), may present with angioedema or anaphylaxis. Check vital signs; anaphylactic shock is a medical emergency. Angioedema can also progress to airway obstruction. Any systemic manifestation should be considered impending anaphylaxis and treated as such. This involves immediately administering IV epinephrine; if insufficient to maintain perfusion, consider additional vasopressor agents (e.g., dopamine, norepinephrine, glucagon). H1-receptor antagonists (plus cimetidine) are recommended for histamine-induced hypotension.

Hospital admission should be considered for more severe cases, as late-phase reactions may occur more than 36 hours after onset. If possible, remove the dermal filler using hyaluronidase as needed.

Delayed Hypersensitivity Reaction

Type IV hypersensitivity reactions, mediated by T lymphocytes and not antibodies, usually present with induration, erythema, edema, or various types of skin lesions, including painful erythematous nodules. Management consists of cold compresses for localized angioedema and H1-receptor antagonists for histamine-induced hypotension and pruritus. H2-receptor antagonists, oral corticosteroids, and ibuprofen are additional measures.

DELAYED COMPLICATIONS: INFLAMMATION OR INFECTION?

Understanding of delayed dermal filler adverse events and pathogenesis has been a slowly evolving process, impeded by the inconsistent terminology describing these adverse events [148,152]. Delayed filler adverse events have long been considered foreign body immune responses or type IV immunologic reactions to filler materials or contaminants from production, reinforced by negative bacterial culture tests of pus from nodules and the low-grade nature of most inflammations [69,144,150,164]. Sporadic findings of bacterial infection in late-onset nodules were often ascribed to departures from antiseptic standards in skin prep or handling of fillers [165,166]. However, steroid or high-dose NSAID therapy to suppress a presumed inflammatory/immune response led to worsened inflammation and abscesses in some patients, who often required IV antibiotics or surgery [22,162].

In 2009, molecular diagnostics with fluorescence in situ hybridization and advanced imaging established bacterial colonization of tissue and filler material as the causality of chronic inflammation and nodules [165,167,168]. In 2010, the role of biofilm in late filler complications gained attention, helping explain adverse reactions to steroid therapy. These dense bacterial colonies on surfaces secrete extracellular polymers, forming a protective matrix against host defenses and antibiotics. Knowledge of biofilm involvement improved the characterization of filler adverse events [152,162].

A foreign body granuloma results when immune response, unable to enzymatically degrade a foreign body, forms lymphocytic inflammation and fibrosis entrapping the body, preventing its migration. Foreign body granulomas are histologically distinct from inflammatory nodules [70,71,150].

Foreign body granuloma formation can involve biofilm which, protected from host immune response, remains semidormant until activated months or years later by host conditions that favor replication (e.g., new filler injection, dental/medical surgery, local or remote infection, trauma). Activated biofilm can cause an immune response, granulomatous inflammation, abscesses, or nodules, and flu-like illness can precede late-onset nodules [19,22,69].

Thus, late-onset nodules or granuloma may represent an immune/inflammatory response secondary to biofilm-colonized filler. Clinical differentiation is challenging. Foreign material in the dermis or sub-dermis can lead to sterile abscesses, granulomas, cellulitis, or nodules. Infection months or years after injection may have similar signs, varying from erythema, edema, inflammatory nodules, and pain/itching to systemic responses [165].

Therapy for late-onset nodules or granuloma consists of [19,68,69,150]:

- Oral antibiotics with immunomodulatory and anti-inflammatory efficacy, with a macrolide (e.g., clarithromycin) or a tetracycline (e.g., minocycline or doxycycline)

- Systematic and intralesional corticosteroids

- Topical tacrolimus (0.1%) or pimecrolimus (1%)

- Intralesional 5-fluorouracil

- Laser treatment

- Surgical excision

Biofilm in Dermal Filler Infections

Biofilm as an increasing concern is reflected in surgical and infectious disease practice guidelines; uptake in cosmetic/aesthetic medicine is more recent. The skin is understood as a microbiota ecosystem, colonized by diverse micro-organisms. In normal skin flora, most bacterial constituents are harmless. Some are beneficial, such as Staphylococcus epidermidis, which inhibits the growth of pathogenic Staphylococcus aureus[169,170].

Evidence Based Practice Recommendation

To minimize the risk of contamination and infection, the Australasian College of Dermatologists asserts that stringent hygiene, including the use of antiseptic non-touch technique at all times, is essential when fillers are injected. Because filler injections necessitate using hands to stabilize or pinch the skin, clinicians should perform antisepsis frequently during the procedure. They also note that sterile gloves may provide a false sense of security; therefore, they advocate changing gloves after preparing syringes for injection and marking the face.

https://onlinelibrary.wiley.com/doi/full/10.1111/ajd.13273

Last Accessed: March 19, 2024

Level of Evidence: Expert Opinion/Consensus Statement

S. aureus, the most commonly isolated pathogenic bacteria in surgical-site infections, colonizes tissue and artificial surfaces and is found on 30% to 60% of healthy Americans. A disturbed balance of the skin ecosystem can favor S. aureus proliferation and biofilm [171,172,173,174].

On unbroken skin, S. aureus can remain asymptomatic; on injection sites, it can seed infections. The needle breaks the skin barrier, picking up bacteria that are delivered into the dermal filler and setting up infection in the tissue. Preoperative skin preparation for open surgery fails to remove 20% of resident skin flora [21,165,175].

Dermal filler skin prep is less stringent than presurgical site prep. However, it is important to remember that Isopropyl alcohol, chlorhexidine, and povidone iodine are demonstrably insufficient in preventing S. aureus biofilm transfer to tissue during filler injection [165,170].

S. aureus biofilm-seeded hyaluronic acid injections have been linked to bacterial infection in studies comparing subjects who developed late infection to complication-free subjects, matched on age and hyaluronic acid treatment (e.g., filler properties, injections, volume). Bacterial skin flora were cultured from nasal swabs in both groups and filler injection sites in patients with late bacterial infection repeatedly over 12 months [164]. S. epidermidis dominated the bacterial flora on facial skin in 100% of subjects without complications, but pathogenic S. aureus and Klebsiella spp. dominated the bacterial flora on the facial skin of subjects with late bacterial infection. Late bacterial infection was diagnosed a mean 5.5 months after filler injection; pus and inflammatory tissue cultures were negative for bacterial growth. No subjects consented to biopsy, but exhaustive exclusion of other etiologies suggested bacterial biofilm infection [164].

Concerns of Antibiotic Resistance

Bacteria in a biofilm matrix exchange DNA mutations to spread antibiotic-resistant genes and biodiversity. As biofilms mature, antibiotic and antimicrobial resistance strengthens [162,172,173,175]. A lack of biofilm-specific biomarkers has made noninvasive detection and diagnosis very difficult [174].

Biofilms are very difficult to treat and can require antibiotic concentration over 32 times that necessary for planktonic bacteria. Even the highest tolerable antibiotic dose can be insufficient [176]. Filler explant may be needed, putting the patient at risk for tissue scarring, deformity, and nerve or structural damage. Minimally biodegradable fillers have higher rates of delayed-onset infection [165].

MRSA is a serious concern because few remaining antibiotics are effective. Vancomycin-resistant S. aureus has also emerged—a potentially incurable infection [174]. In the general U.S. population, 20% are persistently colonized with S. aureus (i.e., carriers) and 2% are MRSA carriers. MRSA carriage among surgical staff (4.5%) and healthcare workers (5%) is higher, and many studies support MRSA transmission from healthcare workers to patients [170,177]. As such, MRSA carriage screening and decolonization of surgical staff and patients can reduce MRSA surgical infections. However, no protocols or data are available on plastic surgeon MRSA carriage, association with filler-site infections, or decolonization [178,179].

Management of biofilm infection consists of oral antibiotics with immunomodulatory and anti-inflammatory efficacy [19,22,143,150]. The first-line choice is a macrolide (e.g., clarithromycin) or a tetracycline (e.g., minocycline or doxycycline) for two weeks. Second-line therapy is dual macrolide- and tetracycline-class therapy. The addition of a quinolone (e.g., ciprofloxacin) is reserved as third-line therapy due to potential serious class-wide adverse events. Patients with systemic symptoms or more severe local infection may require hospitalization and IV antibiotics.

Additional treatment options include hyaluronidase, laser, surgical drainage of the abscess, and filler excision. Note that intralesional hyaluronidase requires extreme caution, as it can facilitate the spread of active infection into adjacent tissues.

Another strategy for treating biofilm is low-dose triamcinolone injection mixed with 5-fluorouracil at regular intervals until resolution. The efficacy of 5-fluorouracil may involve its interaction with ariR, a regulatory gene that inhibits biofilm formation [34].

12. CONCLUSION

The importance for primary care clinicians to understand aesthetic medicine, patient variables, and market factors is brought to light by the increasing rates of aesthetic injections performed by non-board-certified physicians, nurses, and minimally trained aestheticians at inadequately equipped clinics, office settings, and spas [20]. Primary care providers are well-placed to importantly inform their patients about many aspects related to aesthetic medicine but benefit from educational intervention to become most effective in this role.

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1. Goodman GJ, Liew S, Callan P, Hart S. Facial aesthetic injections in clinical practice: pretreatment and posttreatment consensus recommendations to minimise adverse outcomes. Australas J Dermatol. 2020;61(3):217-225. Available at https://onlinelibrary.wiley.com/doi/full/10.1111/ajd.13273. Last accessed March 19, 2024.

2. King M. This month's guideline: management of necrosis. J Clin Aesthet Dermatol. 2018;11(7):E53-E57. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057733. Last accessed March 19, 2024.