Health Care Professional Distress and Mental Health: A Call to the Continuing Professional Development Community.

ABSTRACT: COVID-19 unleashed a maelstrom of distress on health care professionals. The pandemic contributed to a host of stressors for workers because of the need for rapid acquisition of new knowledge and skills to provide best treatment while simultaneously dealing with personal safety, limited resources, staffing shortages, and access to care issues. Concurrently, problems with systemic racial inequality and discrimination became more apparent secondary to difficulties with accessing health care for minorities and other marginalized groups. These problems contributed to many health care professionals experiencing severe moral injury and burnout as they struggled to uphold core values and do their jobs professionally. Some left or disengaged. Others died. As continuing professional development leaders focused on all health professionals, we must act deliberately to address health care professionals' distress and mental health. We must incorporate wellness and mental health as organizing principles in all we do. We must adopt a new mental model that recognizes the importance of learners' biopsychosocial functioning and commit to learners' wellness by developing activities that embrace a biopsychosocial point of view. As educators and influencers, we must demonstrate that the Institute for Healthcare Improvement's fourth aim to improve clinician well-being and safety (2014) and fifth aim to address health equity and the social determinants of health (2021) matter. It is crucial that continuing professional development leaders globally use their resources and relationships to accomplish this imperative call for action.

Pivoting Continuing Professional Development During the COVID-19 Pandemic: A Narrative Scoping Review of Adaptations and Innovations.

INTRODUCTION: Most formal continuing professional development (CPD) opportunities were offered in person until March 2020 when the COVID-19 pandemic disrupted traditional structures of CPD offerings. The authors explored the adaptations and innovations in CPD that were strengthened or newly created during the first 16 months of the pandemic. METHODS: The objectives of the narrative review were to answer the following questions: (1) what types of adaptations to CPD innovations are described? and (2) what may shape future innovations in CPD? The following databases were searched: Medline, Embase, CINAHL, and ERIC to identify the literature published between March 2020 to July 2021. The authors conducted a comprehensive search by including all study types that described adaptations and/or innovations in CPD during the stated pandemic period. RESULTS: Of the 8295 citations retrieved from databases, 191 satisfied the inclusion criteria. The authors found three categories to describe adaptations to CPD innovations: (1) creation of new online resources, (2) increased use of the existing online platforms/software to deliver CPD, and (3) use of simulation for teaching and learning. Reported advantages and disadvantages associated with these adaptations included logistical, interactional, and capacity building elements. The review identified five potential future CPD innovations: (1) empirical research on the effectiveness of virtual learning; (2) novel roles and ways of thinking; (3) learning from other disciplines beyond medicine; (4) formation of a global perspective; and (5) emerging wellness initiatives. DISCUSSION: This review provided an overview of the adaptations and innovations that may shape the future of CPD beyond the pandemic.

Paving the Way Forward for Evidence-Based Continuing Professional Development.

ABSTRACT: Continuing professional development (CPD) fosters lifelong learning and enables health care providers to keep their knowledge and skills current with rapidly evolving health care practices. Instructional methods promoting critical thinking and decision making contribute to effective CPD interventions. The delivery methods influence the uptake of content and the resulting changes in knowledge, skills, attitudes, and behavior. Educational approaches are needed to ensure that CPD meets the changing needs of health care providers. This article examines the development approach and key recommendations embedded in a CE Educator's toolkit created to evolve CPD practice and foster a learning experience that promotes self-awareness, self-reflection, competency, and behavioral change. The Knowledge-to-Action framework was used in designing the toolkit. The toolkit highlighted three intervention formats: facilitation of small group learning, case-based learning, and reflective learning. Strategies and guidelines to promote active learning principles in CPD activities within different modalities and learning contexts were included. The goal of the toolkit is to assist CPD providers to design educational activities that optimally support health care providers' self-reflection and knowledge translation into their clinical environment and contribute to practice improvement, thus achieving the outcomes of the quintuple aim.

Decision making in continuing professional development organisations during a crisis.

INTRODUCTION: Early in COVID-19, continuing professional development (CPD) providers quickly made decisions about program content, design, funding and technology. Although experiences during an earlier pandemic cautioned providers to make disaster plans, CPD was not entirely prepared for this event. We sought to better understand how CPD organisations make decisions about CPD strategy and operations during a crisis. METHODS: This is a descriptive qualitative research study of decision making in two organisations: CPD at the University of Toronto (UofT) and the US-based Society for Academic Continuing Medical Education (SACME). In March 2021, using purposive and snowball sampling, we invited faculty and staff who held leadership positions to participate in semi-structured interviews. The interview focused on the individual's role and organisation, their decision-making process and reflections on how their units had changed because of COVID-19. Transcripts were reviewed, coded and analysed using thematic analysis. We used Mazmanian et al.'s Ecological Framework as a further conceptual tool. RESULTS: We conducted eight interviews from UofT and five from SACME. We identified that decision making during the pandemic occurred over four phases of reactions and impact from COVID-19, including shutdown, pivot, transition and the 'new reality'. The decision-making ability of CPD organisations changed throughout the pandemic, ranging from having little or no independent decision-making ability early on to having considerable control over choosing appropriate pathways forward. Decision making was strongly influenced by the creativity, adaptability and flexibility of the CPD community and the need for social connection. CONCLUSIONS: This adds to literature on the changes CPD organisations faced due to COVID-19, emphasising CPD organisations' adaptability in making decisions. Applying the Ecological Framework further demonstrates the importance of time to decision-making processes and the relational aspect of CPD. To face future crises, CPD will need to embrace creative, flexible and socially connected solutions. Future scholarship could explore an organisation's ability to rapidly adapt to better prepare for future crises.

The Emerging Role of Reinforcement in the Clinician's Path from Continuing Education to Practice.

INTRODUCTION: Continuing education (CE) activities may affect clinicians' knowledge, skills, self-efficacy, and/or performance. Studies have suggested that self-efficacy may moderate or mediate the relationship between knowledge/competence and performance. Some results have shown that increases in knowledge/competence contributed to increases in self-efficacy. However, clinicians do not always learn something "new" when they participate in CE activities; rather, their knowledge or skills may be reinforced. This study examined whether self-efficacy was greater when clinicians reinforced what they already knew compared with when they learned something new. METHODS: Hierarchical linear modeling was conducted to examine the moderating role of status of knowledge/competence post-CE (reinforced/improved) in the relationship between post-CE knowledge/competence score and self-efficacy across 153 online continuing medical education- and/or CE-certified activities. RESULTS: The hierarchical linear modeling showed that learners with higher post-CE scores have higher post-self-efficacy ratings. Reinforced learners had higher post-CE-self-efficacy ratings than improved learners, controlling for post-CE score. DISCUSSION: This study contributes to an expanded understanding of the path from CE to practice. There was benefit to self-efficacy for learners who reinforced but did not improve their knowledge/competence. This study also suggests that pre-post questions can be considered part of the learning process.

'We are in for a culture change': continuing professional development leaders' perspectives on COVID-19, burn-out and structural inequities.

INTRODUCTION: The COVID-19 pandemic positioned healthcare systems in North America at the epicentre of the crisis, placing inordinate stress on clinicians. Concurrently, discussions about structural racism, social justice and health inequities permeated the field of medicine, and society more broadly. The confluence of these phenomena required rapid action from continuing professional development (CPD) leaders to respond to emerging needs and challenges. METHODS: In this qualitative study, researchers conducted 23 virtual semistructured interviews with CPD leaders in Canada and the USA. Interview audiorecordings were transcribed, deidentified and thematically analysed. RESULTS: This study revealed that the CPD leaders attributed the pandemic as illuminating and exacerbating problems related to clinician wellness; equity, diversity and inclusion; and health inequities already prevalent in the healthcare system and within CPD. Analysis generated two themes: (1) From heroes to humans: the shifting view of clinicians and (2) Melding of crises: an opportunity for systemic change in CPD. DISCUSSION: The COVID-19 pandemic increased recognition of burn-out and health inequities creating momentum in the field to prioritise and restrategise to address these converging public health crises. There is an urgent need for CPD to move beyond mere discourse on these topics towards holistic and sustainable actionable measures.

Pragmatic Systemic Solutions to the Wicked and Persistent Problem of the Unprofessional Disruptive Physician in the Health System.

We have always had and will always have "disruptive" or "dysfunctional" doctors behaving unprofessionally within healthcare institutions. Disruptive physician behaviour (also called "unprofessional behaviour") was described almost 150 years ago, but remains a persistent, wicked problem in healthcare, largely fuelled by systemic inaction. In this Commentary, we aim to explore the following aspects from a systemic lens: (i) the gaps in understanding systemic resistance and difficulty in addressing this issue; and (ii) pragmatic approaches to its management in the healthcare system. In doing so, we hope to shift the systemic effect from nihilism and despair, to one of hopeful realism about disruptive or unprofessional behaviour. We suggest that solutions lie in cultural change to ensure systemic awareness, responsiveness and early intervention, and an understanding of what systemic failure looks like in this context. Staff education, policies and procedures that outline a consistent reporting and review process including triaging the problem, its source, its effects, and the attempted solutions, are also crucial. Finally, assessment and intervention from appropriately mental-health-trained personnel are required, recognising that this is a complex mental health problem. We are not doing anyone any favours by ignoring, acting as bystanders, or otherwise turning a blind eye to disruptive or unprofessional behaviour; otherwise, we share culpability.

Assisting physicians who exhibit disruptive behavior: Understanding the costs, contributors, and corrections.

OBJECTIVE: The aim of this article is to discuss the etiology, prevalence, impact, and management of disruptive behavior in physicians. These various aspects will be examined at both the individual and system level, to provide appropriate perspective and detail effective approaches to address these behaviors. METHOD: Clinical experience and review of the authors' and other researchers' findings provide consensus on numerous key aspects of physician disruptive behavior. RESULTS: Physicians demonstrating disruptive behavior are often distressed. The behavior should be understood as arising from biopsychosocial contributors, knowledge gaps, insight, and systems factors. These contributors are inclusive and may interact with each other. CONCLUSIONS: A comprehensive approach is required which can include assessment/reassessment tools, individualized programming (therapy, coaching, instruction), deliberate practice, medical follow-up, and system intervention. Complications include the diversity of disruptive behaviors, the many contributory factors therein, disagreement about methodology/measurement, and the role of the system.

Motivate-to-move: development of an intervention promoting parental adherence to early power mobility programs.

PURPOSE: Parental/caregiver adherence has been identified as a barrier to implementation of early power mobility programs. Motivational interviewing (MI) may help in addressing this barrier. Two scoping reviews were conducted to gather concepts pertaining to parent-based or rehabilitation-based MI interventions and to develop a parent-based MI intervention to address parental/caregiver adherence to home-based early power mobility interventions for infants and young children. MATERIALS AND METHODS: Separate literature searches for parent-based MI and rehabilitation-based MI were conducted in PubMed, CINAHL Complete, PsycInfo, and Web of Science Core Collection. Inclusion criteria were [1]: focussed on/use of either a parent-based or a rehabilitation-based MI intervention and [2] MI interventions described in sufficient detail to be reproduced. Articles focussed on vaccinations, child abuse and neglect, mental health, or technology-based MI were excluded. Data regarding MI interventions and strategies were extracted from included articles. RESULTS: A total of 1130 unique titles were screened and 150 full-text articles were assessed for inclusion. Nineteen articles met the inclusion/exclusion criteria. Using a collaborative, consensus-based approach, a parent-based MI intervention incorporating specific MI strategies identified in the review was developed in collaboration with a psychologist. Future research exploring the application of this parent-based MI intervention is indicated. CONCLUSIONS: The parent-based MI interventions developed in this project may help to increase parental adherence to home-based early power mobility programs, thereby potentially addressing an identified barrier to implementation of early power mobility programs.IMPLICATIONS FOR REHABILITATIONTo our knowledge, this is the first study to develop MI scripts for the purpose of increasing parental/caregiver adherence to a power mobility training program for children.The MI interventions developed in this study are consistent with published suggestions to address perceived barriers to the implementation of early power mobility programs.Given the strategies of collaboration, autonomy, and empowerment embedded within the spirit of MI, parent-based MI interventions are congruous with and inclusive of the principles of family-centered care.

Measures of Skin Turgor in Humans: A Systematic Review of the Literature.

BACKGROUND: Many studies use similar methods to measure skin turgor, but there is no gold standard method that is being followed in clinics or hospitals. PURPOSE: The purpose of this systematic review was to determine if there is any consistent method to measure skin turgor in humans that is valid and reliable. METHODS: Topics of interest for turgor assessment included dehydration; skin integrity, including wounds and skin flaps; and fluid/electrolyte balance for adults 18 years and older. PubMed, ProQuest Medical, SPORTDiscus, PEDro, Web of Science Core Collection, and Cumulative Index of Nursing and Allied Health Literature complete databases were utilized. Levels of evidence were established with 2011 Oxford Centre for Evidence-Based Medicine scale. Methodological rigor was assessed with Quality Assessment of Diagnostic Accuracy Studies checklist. Two researchers graded rigor and level of evidence with a third researcher serving as a tie-breaker. RESULTS: Thirteen articles were included in the final analysis. Some researchers used skin turgor as a measure but did not give details regarding specifically how this measure was used. The pinch test was the most commonly used measure of skin turgor. There were 4 articles ranked as evidence level 2, 1 article as evidence level 3, and 8 articles as evidence level 4. Rigor scores ranged from 3 to 13/14. CONCLUSION: Skin turgor may not be the best assessment tool for some conditions or purposes in adults, such as dehydration, which could lead to a medical emergency.

Causal cascade of direct and indirect effects of anifrolumab on patient-reported outcomes: structural equation modelling of two Phase 3 trials.

OBJECTIVES: SLE significantly impairs health-related quality of life (HRQoL). In this post hoc analysis, structural equation modelling was used to examine the 'causal cascade' of interaction between anifrolumab, disease activity and patient-reported outcomes (PROs) in pooled data from the phase 3 TULIP-1 and TULIP-2 trials. METHODS: Data were pooled from the TULIP-1 (n = 364) and TULIP-2 (n = 362) randomized, placebo-controlled, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks for 48 weeks). We evaluated changes from baseline to week 24 and week 52 in four clinical (BICLA, BILAG-2004, SLEDAI-2K and changes in glucocorticoid dosage) and six PRO measures (SF-36, FACIT-F, EQ-5D, LupusQoL, PHQ-8 and pain NRS) in our hypothesized model of interactions. RESULTS: Our hypothesized model had an acceptable fit to the pooled TULIP trial data. At week 24, significant paths revealed that when compared with placebo, anifrolumab treatment improved disease activity as measured by BICLA, BILAG-2004, SLEDAI-2K and changes to glucocorticoid dosage. In turn, these clinical measures reduced pain, which improved fatigue, physical functioning, mood/emotions and HRQoL. When the model incorporated number of glucocorticoid tapers as the measure of change in glucocorticoid dosage, treatment effects of anifrolumab on glucocorticoid tapers were not retained at week 52. However, at week 52 treatment indirectly improved HRQoL through its direct effects on BICLA. CONCLUSIONS: Anifrolumab is associated with significant patient-reported improvements in aspects of HRQoL including pain, fatigue, mood and physical function. These benefits are from the direct effect of anifrolumab treatment on disease activity and reduction in glucocorticoid dosage.

A multivariable prediction model of a major treatment response for focal-onset seizures: A post-hoc analysis of Phase III trials of perampanel.

OBJECTIVE: Although 50 % reduction in seizure frequency is a common efficacy endpoint in clinical trials of antiepileptic drugs (AEDs), 75 % or greater reductions may be required to improve patients' health-related quality of life. Identification of clinical factors that are associated with high responder rates may help to inform clinicians on which patients may optimally benefit from treatment. We evaluated potential predictive factors for achieving major treatment responses (≥75 % reduction in seizure frequency per 28 days from study baseline) in patients with drug-resistant focal-onset seizures, with/without focal to bilateral tonic-clonic (FBTC) seizures in perampanel trials designed for regulatory approval. METHODS: Univariate analyses using logistic regression were performed using data from three double-blind, placebo-controlled Phase III studies of adjunctive perampanel (Studies 304 [NCT00699972], 305 [NCT00699582], 306 [NCT00700310]), and their open-label extension study (OLEx; Study 307 [NCT00735397]). For the double-blind studies, baseline seizure frequency, number of baseline AEDs, baseline seizure type, baseline concomitant enzyme-inducing AEDs (EIAEDs), baseline carbamazepine, lamotrigine, or valproic acid, age at diagnosis, time since diagnosis, etiology, and perampanel plasma concentration were included individually with study treatment. The same factors were included for the OLEx analysis except for plasma concentration and treatment. Variables found to be significant predictors for a major treatment response in univariate analyses were subsequently included in multivariable analyses using backwards and forwards selection. RESULTS: In the double-blind studies, 175/1374 patients had a major response to placebo (n = 25) or perampanel (n = 150). The best predictors of a major treatment response in multivariable models with forwards and backwards selection were: the presence of FBTC seizures during baseline (P = 0.0002), higher perampanel plasma concentration (P < 0.0001), older age at diagnosis (P = 0.0024 and 0.0045, respectively), and lower baseline seizure frequency (P = 0.0364 and 0.0127, respectively). In the OLEx, 217/1090 patients had a major treatment response. The best predictors of a major treatment response in the final multivariable model, regardless of backwards or forwards selection, were a lower baseline seizure frequency (P = 0.0022), the absence of focal impaired awareness seizures during baseline (P = 0.0011), the presence of FBTC seizures during baseline (P = 0.0164), lower number(s) of baseline AEDs (P = 0.0002), the absence of EIAEDs during baseline (P = 0.0059), an older age at diagnosis (P = 0.0054), and absence of structural etiologies (P = 0.0138). SIGNIFICANCE: These analyses of placebo-controlled and long-term extension trial data identified a number of potential predictive factors for patients with focal-onset seizures achieving a major treatment response. These factors may help guide clinicians when predicting a patient's response to treatment and optimizing individual treatment regimens.

Influence of titration of antiseizure medications on treatment selection: Results of an online survey with clinicians in the United States.

INTRODUCTION: Most antiseizure medications (ASM) need to be titrated before the optimal dose is achieved. Titration can last several weeks to months. We assessed the impact titration schedules have on ASM treatment-related decisions in the United States (US). METHODS: An online survey was conducted with different healthcare providers (HCPs) in the US involved in the treatment and management of patients with epilepsy. The survey contained three sections: the first section with screening questions; the second on key factors that influence a HCP's decision-making when selecting treatments for different types of seizures and different treatment lines; and the third on the HCP's knowledge and perceptions regarding ASM titration for the treatment of patients with epilepsy. RESULTS: One-hundred and fifty HCPs (63% neurologists) completed the survey. Most HCPs considered titration schedule to be important, with only 1-3% of HCPs, depending on type of seizure, considering the titration schedule to be "not important at all" when prescribing therapy. Healthcare providers' acceptance of titration increased with shorter durations (≥50% accepted titration periods of ≤2 weeks), and lower number of tablets/capsules per dose (≥50% accepted ≤3 tablets/capsules per dose), doses (≥50% accepted ≤2 doses/day), and steps (≥50% accepted ≤3 steps/dose change). Most HCPs (68-91% depending on type of seizure) considered a titration duration of 6 or more weeks only somewhat acceptable or somewhat or highly unacceptable. Almost all HCPs selected "somewhat familiar", "familiar", or "very familiar" as the attribute that best defines their knowledge level of titration, with only 4% selecting "a little familiar". While 87% of HCPs agreed or strongly agreed that they could easily understand titration schedules, only 27% of them agreed or strongly agreed that patients could easily understand titration schedules and 58% of HCPs considered that adhering to the titration schedule was difficult for patients. Most HCPs agreed or strongly agreed that a complex or long titration schedule renders it difficult to achieve their treatment objectives. CONCLUSIONS: Healthcare providers take into account the duration and complexity of the titration period in their ASM prescribing decision-making and prefer shorter and simpler titration schedules, particularly for patients who are experiencing convulsive seizures and starting monotherapy. There was a clear difference between the HCP's belief in their own ability to understand a titration schedule, and their belief that the patient would be able to follow the titration schedule appropriately.

Cognitive Screening Tools for Late Career Physicians: A Critical Review.

Screening measures are widely used in medicine to assess the increased probability that members of a defined population have a particular condition and therefore require more extensive assessment. The rationale for prospective screening of late career physicians (LCPs) is drawn from the following circumstances: Senior physicians-prone to the vicissitudes of aging-comprise nearly a third of the US physician workforce, physicians are poor at self-evaluation, data suggest many have clinically relevant cognitive decline, and screening is an evidence-based, method to detect individuals at risk and determine whether a comprehensive evaluation is necessary. A handful of professional organizations (eg, surgeons, obstetricians, and a growing number of medical staff credentialing committees) have developed policies in this arena. This focused review compares cognitive screening methods used or recommended for LCPs, with particular attention to the psychometric properties, ease of operational implementation, and appropriate application to physicians-a population selected for high cognitive reserve and skills. Further, we identify gaps in knowledge and practice, including the need for more career-span normative data on physicians' cognitive and work performance. Stakeholders can improve rehabilitation and other supports to LCPs in transition, calling upon the unique expertise of those neuropsychologists who are trained on conducting fitness for duty evaluations, as well as rehabilitation professionals who can assist in developing modifications to practice when indicated or facilitate graceful transitions to retirement when necessary.

Adverse Childhood Experiences in Trainees and Physicians With Professionalism Lapses: Implications for Medical Education and Remediation.

PURPOSE: Unprofessional behavior, which can include failure to engage, dishonest and/or disrespectful behavior, and poor self-awareness, can be demonstrated by medical trainees and practicing physicians. In the authors' experience, these types of behaviors are associated with exposure to adverse childhood experiences (ACEs). Given this overlap, the authors studied the percentage of ACEs among trainees and physicians referred for fitness-for-duty evaluations and patterns between the types of ACEs experienced and the reason for referral. METHOD: A final sample of 123 cases of U.S. trainees and physicians who had been referred to a Midwestern center for assessment and/or remediation of professionalism issues from 2013 to 2018 was created. Included professionalism lapses fell within 3 categories: boundary violation, disruptive behavior, or potential substance use disorder concerns. All participants completed a psychosocial developmental interview, which includes questions about ACE exposure. Overall rate of reported ACEs and types of ACEs reported were explored. RESULTS: Eighty-six (70%) participants reported at least 1 ACE, while 27 (22%) reported 4 or more. Compared with national data, these results show significantly higher occurrence rates of 1 or more ACEs and a lower occurrence rate of 0 ACEs. ACEs that predicted reasons for referral were physical or sexual abuse, feeling unwanted or unloved, witnessing abuse of their mother or stepmother, or caretaker substance use. CONCLUSIONS: In this sample, ACE exposure was associated with professionalism issues. Remediating individuals with professionalism issues and exposure to ACEs can be complicated by heightened responses to stressful stimuli, difficulties with collaboration and trust, and decreased self-efficacy. Adoption of a trauma-informed medical education approach may help those that have been impacted by trauma rebuild a sense of control and empowerment. The findings of this study may be useful predictors in identifying those at risk of problematic behavior and recidivism before a sentinel event.

Assessment of the long-term efficacy and safety of adjunctive perampanel in tonic-clonic seizures: Analysis of four open-label extension studies.

OBJECTIVE: This post hoc analysis evaluated long-term efficacy and safety in patients with focal to bilateral tonic-clonic seizures (FBTCS) or generalized tonic-clonic seizures (GTCS) who entered open-label extension (OLEx) studies to receive long-term adjunctive perampanel. METHODS: Patients aged 12 years and older who completed phase II or III randomized, double-blind, placebo-controlled studies could enter an OLEx study, each comprising a blinded conversion period followed by an open-label maintenance period (32-424 weeks; maximum perampanel dose = 12 mg/d). Exposure, seizure outcomes, and treatment-emergent adverse events (TEAEs) were analyzed. RESULTS: Baseline characteristics were generally balanced between patients with FBTCS (n = 720) and GTCS (n = 138). Mean (standard deviation) cumulative duration of perampanel exposure was 102.3 (70.3) weeks (FBTCS) and 83.9 (38.4) weeks (GTCS). Retention rates were 50.0% for up to 4 years (FBTCS) and 49.2% for up to 2 years (GTCS). Across OLEx treatment durations, median reductions in seizure frequency per 28 days were 66.7% (FBTCS) and 80.6% (GTCS). Fifty percent and 75% responder and seizure-freedom rates were 59.5%, 45.3%, and 18.4%, respectively (FBTCS), and 72.5%, 51.5%, and 16.7%, respectively (GTCS). Efficacy was sustained for up to 4 years (FBTCS) and up to 3 years (GTCS), even when accounting for early dropouts. TEAE incidence was highest during Year 1 (FBTCS, 85.3%; GTCS, 86.2%); most common were dizziness and somnolence. During Year 1, serious TEAEs were reported in 81 (11.3%; FBTCS) and 10 (7.2%; GTCS) patients. TEAEs were consistent with the known safety profile of perampanel; no new safety signals were identified with long-term treatment. SIGNIFICANCE: This post hoc analysis suggests long-term (up to 4 years) adjunctive perampanel (up to 12 mg/d) is efficacious and well tolerated in patients (aged 12 years and older) with FBTCS or GTCS.

Efficacy and safety of adjunctive perampanel in adolescent patients with epilepsy: Post hoc analysis of six randomized studies.

OBJECTIVE: This post hoc analysis of six randomized, double-blind, Phase II and III studies evaluated efficacy and safety of adjunctive perampanel (2-12 mg/day) in adolescent patients (aged ≥12 to ≤17 years) with uncontrolled partial-onset seizures, with or without secondarily generalized (SG) seizures, or primary generalized tonic-clonic (PGTC) seizures. METHODS: Adolescent patients from Studies 304 (NCT00699972), 305 (NCT00699582), 306 (NCT00700310), 335 (NCT01618695), 235 (NCT01161524), and 332 (NCT01393743) were included. Efficacy assessments (split by seizure type) included median percent change in seizure frequency per 28 days from baseline and seizure-freedom rates. Safety assessments (all seizure types combined) included monitoring of treatment-emergent adverse events (TEAEs). RESULTS: The Safety Analysis Set included 372 adolescent patients (placebo, n = 114; perampanel, n = 258); the Full Analysis Set included 346 patients with partial-onset seizures (placebo, n = 103; perampanel, n = 243), of whom 125 experienced SG seizures during baseline (placebo, n = 37; perampanel, n = 88), and 22 with PGTC seizures (placebo, n = 9; perampanel, n = 13). Compared with placebo, perampanel 8 and 12 mg/day conferred greater median percent reductions in seizure frequency per 28 days for partial-onset seizures (18.0% vs 35.9% and 53.8% [both P < 0.01]) and SG seizures (24.4% vs 72.8% [P < 0.001] and 57.8% [P < 0.01]), and greater seizure-freedom rates (partial-onset: 7.8% vs 13.2% and 11.8% [not statistically significant]; SG: 8.1% vs 40.7% [P < 0.001] and 41.7% [P < 0.01]). For PGTC seizures, and compared with placebo, perampanel 8 mg/day was also associated with greater median percent reductions in seizure frequency per 28 days (29.8% vs 88.0%) and greater seizure-freedom rates (11.1% vs 23.1%). Treatment-emergent adverse events were reported in 76 (66.7%) placebo- and 192 (74.4%) perampanel-treated patients (most common: dizziness, somnolence, headache, and nasopharyngitis). Serious TEAEs occurred in 5 (4.4%) placebo- and 11 (4.3%) perampanel-treated patients. CONCLUSIONS: Adjunctive perampanel was efficacious and generally well tolerated in adolescent patients with partial-onset, SG, or PGTC seizures and represents a potentially beneficial treatment option for adolescents with uncontrolled epilepsy.

Efficacy and safety of adjunctive perampanel 4 mg/d for the treatment of focal seizures: A pooled post hoc analysis of four randomized, double-blind, phase III studies.

OBJECTIVE: This post hoc analysis evaluated the efficacy and safety of adjunctive perampanel 4 mg/d received as modal dose, which may have differed from randomized dose, for treatment of focal seizures. METHODS: Data were pooled from four randomized, double-blind, placebo-controlled, phase III studies of adjunctive perampanel in patients (aged ≥12 years) with focal seizures, with/without focal to bilateral tonic-clonic (FBTC) seizures: studies 304 (NCT00699972), 305 (NCT00699582), 306 (NCT00700310), and 335 (NCT01618695). Efficacy assessments included median percentage reductions in seizure frequency per 28 days and seizure-freedom rates for patients receiving placebo and perampanel 4 mg/d (modal dose). Treatment-emergent adverse events (TEAEs) were assessed in patients receiving perampanel 4 mg/d at their TEAE onset. Outcomes were also assessed with/without enzyme-inducing antiseizure medications (EIASMs). RESULTS: The full analysis set included 979 patients with focal seizures (placebo: n = 616 [235 with FBTC seizures]; perampanel 4 mg/d: n = 363 [134 with FBTC seizures]). Compared with placebo, perampanel 4 mg/d conferred significantly greater median percentage reductions in seizure frequency per 28 days for focal (12.6% vs 21.1%; P = .0004) and FBTC seizures (17.4% vs 49.8%; P < .0001), and seizure-freedom rates for focal (0.8% vs 3.6%; P = .0018) and FBTC seizures (11.1% vs 18.7%; P = .0424). Seizure improvements with perampanel 4 mg/d were greater without EIASMs than with EIASMs. For assessment of TEAEs, overall 1376 patients with focal seizures received perampanel 4 mg/d at any time (FBTC seizures, n = 499). TEAEs with perampanel 4 mg/d occurred in 419 of 1376 (30.5%) and 148 of 499 (29.7%) patients with focal and FBTC seizures, respectively; most common was dizziness. The proportion of TEAEs was similar with or without EIASMs. SIGNIFICANCE: This post hoc analysis showed adjunctive perampanel 4 mg/d was efficacious and well tolerated in patients with focal seizures, with or without FBTC seizures. This dose may be a valuable treatment option in patients unable to tolerate higher perampanel doses up to 12 mg/d.

Understanding and Remediating Lapses in Professionalism: Lessons From the Island of Last Resort.

BACKGROUND: The literature on unprofessional behavior is reviewed. It is well accepted that unprofessional behavior, including a lack of civility and respect, can have a negative impact on patient safety and quality of care. METHODS: We used a focused review in the context of 20 years of experience of assessing, treating, and remediating unprofessional behavior. The review highlights that unprofessional behavior can stem from a variety of sources, including health, psychological/psychiatric issues, social functioning or support, or a combination of these. The review covers the challenges in the work environment and the relationship between outcome, as experienced by the physician, and the likelihood the physician will repeat or modify his or her behavior. RESULTS: Based on the evidence provided in the review and our clinical and research experience, we offer a new framework for the assessment, treatment, and remediation of physicians with professionalism transgressions: the Environmentally Valid Learning Approach. The approach is related to and expands on Miller's Pyramid by adding bio-psycho-social functioning and professional identity to the Pyramid. It emphasizes the dynamic and environmental characteristics of professional identity. CONCLUSIONS: Effective intervention is possible. Consideration of contributory factors, addressing/treating those factors, teaching/remediating skill deficiencies, and determining elements that need to be in place to foster implementation and maintenance of the developing skills are necessary components for successful resolution. The behavior is fully remediated when a self-sustaining alternative to the unprofessional behavior is established and the desired behavior becomes a permanent part of the physician's behavioral repertoire.