Creating an Unprotected Class: Addressing Legal Risks in the Era of Biologically-Defined Alzheimer's Disease.

Background: Documentation of preclinical biomarker tests for Alzheimer's disease (AD) in the medical record may expose patients to employment and insurance discrimination risks. There is a gap in research describing clinicians' approaches to documenting biomarker results. Objective: To evaluate discrimination risks faced by patients undergoing biomarker testing for AD through a qualitative analysis of clinician documentation practices. Methods: Semi-structured interviews using hypothetical patient scenarios. The qualitative analysis focused on interviewees' responses related to documentation and disclosure of results. Results: We collected and analyzed 17 interviews with dementia experts; and identified three approaches to documenting biomarkers as: an association with active AD, noninformative, and an increased susceptibility for AD. Those who associated biomarkers with active disease were more likely to favor disclosure to employers and insurers, which could increase discrimination risks. Conclusions: This study demonstrates the variety of documentation and disclosure practices likely to emerge for preclinical AD biomarker tests and highlights a need for guidelines in this area.

Hemimegalencephaly: A Systematic Comparison of Functional and Anatomic Hemispherectomy for Drug-Resistant Epilepsy.

BACKGROUND AND OBJECTIVES: Hemimegalencephaly (HME) is a rare diffuse malformation of cortical development characterized by unihemispheric hypertrophy, drug-resistant epilepsy (DRE), hemiparesis, and developmental delay. Definitive treatment for HME-related DRE is hemispheric surgery through either anatomic (AH) or functional hemispherectomy (FH). This individual patient data meta-analysis assessed seizure outcomes of AH and FH for HME with pharmacoresistant epilepsy, predictors of Engel I, and efficacy of different FH approaches. METHODS: PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were searched from inception to Jan 13th, 2023, for primary literature reporting seizure outcomes in >3 patients with HME receiving AH or FH. Demographics, neurophysiology findings, and Engel outcome at the last follow-up were extracted. Postsurgical seizure outcomes were compared through 2-tailed t -test and Fisher exact test. Univariate and multivariate Cox regression analyses were performed to identify independent predictors of Engel I outcome. RESULTS: Data from 145 patients were extracted from 26 studies, of which 89 underwent FH (22 vertical, 33 lateral), 47 underwent AH, and 9 received an unspecified hemispherectomy with a median last follow-up of 44.0 months (FH cohort) and 45.0 months (AH cohort). Cohorts were similar in preoperative characteristics and at the last follow-up; 77% (n = 66) of the FH cohort and 81% (n = 38) and of the AH cohort were Engel I. On multivariate analysis, only the presence of bilateral ictal electroencephalography abnormalities (hazard ratio = 11.5; P = .002) was significantly associated with faster time-to-seizure recurrence. A number-needed-to-treat analysis to prevent 1 additional case of posthemispherectomy hydrocephalus reveals that FH, compared with AH, was 3. There was no statistical significance for any differences in time-to-seizure recurrence between lateral and vertical FH approaches (hazard ratio = 2.59; P = .101). CONCLUSION: We show that hemispheric surgery is a highly effective treatment for HME-related DRE. Unilateral ictal electroencephalography changes and using the FH approach as initial surgical management may result in better outcomes due to significantly lower posthemispherectomy hydrocephalus probability. However, larger HME registries are needed to further delineate the predictors of seizure outcomes.

Reimagining a pass/fail clinical core clerkship: a US residency program director survey and meta-analysis.

Pass/fail (P/F) grading has emerged as an alternative to tiered clerkship grading. Systematically evaluating existing literature and surveying program directors (PD) perspectives on these consequential changes can guide educators in addressing inequalities in academia and students aiming to improve their residency applications. In our survey, a total of 1578 unique PD responses (63.1%) were obtained across 29 medical specialties. With the changes to United States Medical Licensure Examination (USMLE), responses showed increased importance of core clerkships with the implementation of Step 2CK cutoffs. PDs believed core clerkship performance was a reliable representation of an applicant's preparedness for residency, particularly in Accreditation Council for Graduate Medical Education's (ACGME)Medical Knowledge and Patient Care and Procedural Skills. PDs disagreed with P/F core clerkships because it more difficult to objectively compare applicants. No statistically significant differences in responses were found in PD preferential selection when comparing applicants from tiered and P/F core clerkship grading systems. If core clerkships adopted P/F scoring, PDs would further increase emphasis on narrative assessment, sub-internship evaluation, reference letters, academic awards, professional development and medical school prestige. In the meta-analysis, of 6 studies from 2,118 participants, adjusted scaled scores with mean difference from an equal variance model from PDs showed residents from tiered clerkship grading systems overall performance, learning ability, work habits, personal evaluations, residency selection and educational evaluation were not statistically significantly different than from residents from P/F systems. Overall, our dual study suggests that while PDs do not favor P/F core clerkships, PDs do not have a selection preference and do not report a difference in performance between applicants from P/F vs. tiered grading core clerkship systems, thus providing fertile grounds for institutions to examine the feasibility of adopting P/F grading for core clerkships.

Pediatric risk to orthotopic heart transplant (PRO) score: Insights from United Network for Organ Sharing (UNOS) waitlist mortality findings.

BACKGROUND: Pediatric heart transplant candidates on the waitlist have the highest mortality rate among all solid organ transplants. A risk score incorporating a candidate's individual risk factors may better predict mortality on the waitlist and optimize organ allocation to the sickest of those awaiting transplant. METHODS: Using the United Network for Organ Sharing (UNOS) database, we evaluated a total of 5542 patients aged 0-18 years old on the waitlist for a single, first time, heart transplant from January 2010 to June 2019. We performed a univariate analysis on two-thirds (N = 3705) of these patients to derive the factors most associated with waitlist mortality or delisting secondary to deterioration within 1 year. Those with a p <0.2 underwent a multivariate analysis and the resulting factors were used to build a prediction model using the Fine-Grey model analysis. This predictive scoring model was then validated on the remaining one-third of the patients (N = 1852). RESULTS: The Pediatric Risk to OHT (PRO) scoring model utilizes the following unique patient variables: blood type, diagnosis of congenital heart disease, weight, presence of ventilator support, presence of inotropic support, extracorporeal membrane oxygenation (ecmo) status, creatinine level, and region. A higher score indicates an increased risk of mortality. The PRO score had a predictive strength of 0.762 as measured by area under the ROC curve at 1 year. CONCLUSION: The PRO score is an improved predictive model with the potential to better assess mortality for patients awaiting heart transplant.

Gamma secretase activity modulates BMP-7-induced dendritic growth in primary rat sympathetic neurons.

Autonomic dysfunction has been observed in Alzheimer's disease (AD); however, the effects of genes involved in AD on the peripheral nervous system are not well understood. Previous studies have shown that presenilin-1 (PSEN1), the catalytic subunit of the gamma secretase (γ-secretase) complex, mutations in which are associated with familial AD function, regulates dendritic growth in hippocampal neurons. In this study, we examined whether the γ-secretase pathway also influences dendritic growth in primary sympathetic neurons. Using immunoblotting and immunocytochemistry, molecules of the γ-secretase complex, PSEN1, PSEN2, PEN2, nicastrin and APH1a, were detected in sympathetic neurons dissociated from embryonic (E20/21) rat sympathetic ganglia. Addition of bone morphogenetic protein-7 (BMP-7), which induces dendrites in these neurons, did not alter expression or localization of γ-secretase complex proteins. BMP-7-induced dendritic growth was inhibited by siRNA knockdown of PSEN1 and by three γ-secretase inhibitors, γ-secretase inhibitor IX (DAPT), LY-411575 and BMS-299897. These effects were specific to dendrites and concentration-dependent and did not alter early downstream pathways of BMP signaling. In summary, our results indicate that γ-secretase activity enhances BMP-7 induced dendritic growth in sympathetic neurons. These findings provide insight into the normal cellular role of the γ-secretase complex in sympathetic neurons.

Contribution of a positive psychology-based conceptual framework in reducing physician burnout and improving well-being: a systematic review.

BACKGROUND: The PERMA Model, as a positive psychology conceptual framework, has increased our understanding of the role of Positive emotion, Engagement, Relationships, Meaning, and Achievements in enhancing human potentials, performance and wellbeing. We aimed to assess the utility of PERMA as a multidimensional model of positive psychology in reducing physician burnout and improving their well-being. METHODS: Eligible studies include peer-reviewed English language studies of randomized control trials and non-randomized design. Attending physicians, residents, and fellows of any specialty in the primary, secondary, or intensive care setting comprised the study population. Eligible studies also involved positive psychology interventions designed to enhance physician well-being or reduce physician burnout. Using free text and the medical subject headings we searched CINAHL, Ovid PsychINFO, MEDLINE, and Google Scholar (GS) electronic bibliographic databases from 2000 until March 2020. We use keywords for a combination of three general or block of terms (Health Personnel OR Health Professionals OR Physician OR Internship and Residency OR Medical Staff Or Fellow) AND (Burnout) AND (Positive Psychology OR PERMA OR Wellbeing Intervention OR Well-being Model OR Wellbeing Theory). RESULTS: Our search retrieved 1886 results (1804 through CINAHL, Ovid PsychINFO, MEDLINE, and 82 through GS) before duplicates were removed and 1723 after duplicates were removed. The final review included 21 studies. Studies represented eight countries, with the majority conducted in Spain (n = 3), followed by the US (n = 8), and Australia (n = 3). Except for one study that used a bio-psychosocial approach to guide the intervention, none of the other interventions in this review were based on a conceptual model, including PERMA. However, retrospectively, ten studies used strategies that resonate with the PERMA components. CONCLUSION: Consideration of the utility of PERMA as a multidimensional model of positive psychology to guide interventions to reduce burnout and enhance well-being among physicians is missing in the literature. Nevertheless, the majority of the studies reported some level of positive outcome regarding reducing burnout or improving well-being by using a physician or a system-directed intervention. Albeit, we found more favorable outcomes in the system-directed intervention. Future studies are needed to evaluate if PERMA as a framework can be used to guide system-directed interventions in reducing physician burnout and improving their well-being.

The obesity paradox: Underweight patients are at the greatest risk of mortality after cholecystectomy.

BACKGROUND: Elevated body mass index is a risk factor for gallstone disease and cholecystectomy, but outcomes for low body mass index patients remain uncharacterized. We examined the association of body mass index with morbidity, mortality, and resource use after cholecystectomy. METHODS: The 2005 to 2016 American College of Surgeons National Surgical Quality Improvement Program was retrospectively analyzed for adult patients undergoing laparoscopic and open cholecystectomy. Patients were stratified into 5 groups: body mass index <18.5 (underweight), body mass index 18.5 to 24.9 (normal weight), body mass index 25 to 29.9 (overweight), body mass index 30 to 34.9 (class I obesity), body mass index 35 to 39.9 (class II obesity), and body mass index ≥40 (class III obesity). Multivariable regressions identified independent associations of covariates with 30-day mortality, complications, and resource use. RESULTS: Of 327,473 cholecystectomy patients, 1.0% were underweight, 19.5% normal weight, 30.3% overweight, 24.0% class I obesity, 13.5% class II obesity, and 11.7% class III obesity. After multivariable analysis, underweight patients had a higher risk of mortality (adjusted odds ratio = 1.53; P = .029) and postoperative bleeding (adjusted odds ratio = 1.45; P = .011) relative to normal weight patients. Conversely, class III obesity patients had lower mortality (adjusted odds ratio = 0.66; P = .005) but increased operative time (ß = 10.2 minutes; P < .001), wound infection (adjusted odds ratio = 1.38; P < .001), and wound dehiscence (adjusted odds ratio = 2.20; P < .001). Hospital duration of stay and readmission rates were highest for underweight patients. CONCLUSION: Underweight patients experience increased risk of mortality and readmission, while class III obesity patients have higher rates of wound infection and dehiscence as well as prolonged operative time. These findings may guide choice of intervention.

Impact of Payer Status on Delisting Among Liver Transplant Candidates in the United States.

Although socioeconomic disparities persist both pre- and post-transplantation, the impact of payer status has not been studied at the national level. We examined the association between public insurance coverage and waitlist outcomes among candidates listed for liver transplantation (LT) in the United States. All adults (age ≥18 years) listed for LT between 2002 and 2018 in the United Network for Organ Sharing database were included. The primary outcome was waitlist removal because of death or clinical deterioration. Continuous and categorical variables were compared using the Kruskal-Wallis and chi-square tests, respectively. Fine and Gray competing-risks regression was used to estimate the subdistribution hazard ratios (HRs) for risk factors associated with delisting. Of 131,839 patients listed for LT, 61.2% were covered by private insurance, 22.9% by Medicare, and 15.9% by Medicaid. The 1-year cumulative incidence of delisting was 9.0% (95% confidence interval [CI], 8.3%-9.8%) for patients with private insurance, 10.7% (95% CI, 9.9%-11.6%) for Medicare, and 10.7% (95% CI, 9.8%-11.6%) for Medicaid. In multivariable competing-risks analysis, Medicare (HR, 1.20; 95% CI, 1.17-1.24; P < 0.001) and Medicaid (HR, 1.20; 95% CI, 1.16-1.24; P < 0.001) were independently associated with an increased hazard of death or deterioration compared with private insurance. Additional predictors of delisting included Black race and Hispanic ethnicity, whereas college education and employment were associated with a decreased hazard of delisting. In this study, LT candidates with Medicare or Medicaid had a 20% increased risk of delisting because of death or clinical deterioration compared with those with private insurance. As more patients use public insurance to cover the cost of LT, targeted waitlist management protocols may mitigate the increased risk of delisting in this population.

Frailty Is Independently Associated With Worse Outcomes After Elective Anatomic Lung Resection.

BACKGROUND: Frailty has been widely recognized as a predictor of postoperative outcomes. Given the paucity of standardized frailty measurements in thoracic procedures, this study aimed to determine the impact of coding-based frailty on clinical outcomes and resource use after anatomic lung resection. METHODS: All adults undergoing elective, anatomic lung resections (segmentectomy, lobectomy, pneumonectomy) from 2005 to 2014 were identified using the National Inpatient Sample. Patients were categorized as either frail or nonfrail on the basis of the presence of any frailty-defining diagnoses defined by the Johns Hopkins Adjusted Clinical Groups. Multivariable models were used to assess the independent association of frailty with in-hospital mortality, nonhome discharge, complications, duration of stay, and costs. RESULTS: Of an estimated 366,357 hospitalizations for elective lung resection during the study period, 4.4% were in frail patients. Patients who underwent pneumonectomy or were treated at low-volume hospitals were more commonly frail. Relative to nonfrail patients, frailty was associated with increased unadjusted mortality (9.1% vs 1.7%; P < .001) and nonhome discharge (44.7% vs 10.5%; P < .001). Frail patients had 3.47 increased adjusted odds of mortality across resection types (95% confidence interval, 2.94 to 4.09). Frailty conferred the greatest increase in mortality, complications, and resource use after pneumonectomy relative to lobectomy or segmentectomy, although significant differences were evident for all 3 operations. CONCLUSIONS: Frailty exhibits a strong association with inferior clinical outcomes and increased resource use after elective lung resection, particularly pneumonectomy. This readily available tool may improve preoperative risk assessment and allow for better selection of treatment modalities for frail patients with pulmonary disorders.

National trends in postoperative infections across surgical specialties.

BACKGROUND: Despite the introduction of several measures to reduce incidence, postoperative infections have been reported to increase. We aimed to assess trends in the incidence and impact of postoperative infections using a recent national cohort. METHODS: Patients undergoing the most commonly performed elective inpatient procedures in 9 surgical specialties were identified from the 2006 to 2014 National Inpatient Sample. Diagnostic coding was utilized to identify patients with postoperative infections. To adjust for patient and operative differences in assessing outcomes, an inverse probability of treatment weighing protocol was used. RESULTS: Of an estimated 23,696,588 patients, 1,213,182 (5.1%) developed postoperative infections. Skin and soft tissue operations had the highest burden (12.9%) and endocrine the lowest (1.3%). During the study period, we found decreasing incidence, case fatality, and incremental cost of postoperative infections. Infection was associated with increased in-hospital mortality (1.4 vs 0.4%, P < .001), duration of stay (7.6 vs 3.7 days, P < .001), and costs ($27,597 vs $17,985, P < .001). Annually, postoperative infections led to an average incremental cost burden exceeding $700 million in the United States alone. CONCLUSION: During the study period there was a substantial decrease in the burden of postoperative infections. Despite encouraging trends, postoperative infections continue to serve as a suitable quality improvement target, particularly in specialties with a high burden of infections.