Citations

Abstract We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer’s disease (ADAD). A total of 550 variants in the APP, PSEN1 and PSEN2 genes were identified, of which 279 were classified as pathogenic or likely pathogenic based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria, utilizing data from the Dominantly Inherited Alzheimer Network (DIAN), literature and public databases. Symptomatic age at onset (AAO) data were estimated for 227 of these variants, allowing detailed characterization of their frequency, pathogenicity and AAO. Importantly, 226 variants met eligibility criteria for inclusion in disease-modifying clinical trials. Furthermore, we demonstrated the predictive value of mean variant AAO and parental AAO in predicting symptomatic AAO, validated against converters who became symptomatic during follow-up in the DIAN Observational Study. This dataset provides critical insights into the global landscape of ADAD and reveals the genetic and AAO heterogeneity of ADAD variants while refining variant trial eligibility criteria.

ABSTRACTObjectiveTo assess how patient and caregiver factors influence caregiver readiness for hospital discharge in palliative care patients.Study Setting and DesignThis transitional care study uses cross‐sectional data from a randomized controlled trial conducted from 2018 to 2023 testing an intervention for caregivers of hospitalized adult patients with a serious or life‐limiting illness who received a palliative care consult prior to transitioning out of the hospital.Data Sources and Analytical SampleCaregiver readiness was measured with the Family Readiness for Hospital Discharge Scale (n = 231). Caregiver demographic, intra‐ and interpersonal factors were self‐reported. Patient demographic, comorbidity score, and risk score for complicated discharge planning were extracted from electronic health records. Stepwise regression models estimated variance explained (r2) in caregiver readiness for patient hospital discharge.Principal FindingsPatient demographics and complexity were not statistically associated with caregiver readiness for discharge. Caregiver depressive symptoms, poor caregiver‐patient relationship quality, and fewer hours spent caregiving prior to hospitalization explained 29% of the variance in caregiver readiness.ConclusionsReliance on patient data may not be sufficient for explaining caregiver readiness for discharge. Assessing caregiver factors may be a better alternative for identifying caregivers at risk for low discharge readiness and those in need of additional support.Trial Registration: ClinicalTrials.gov on November 13, 2017, (No. NCT03339271)

Abstract Febrile infection–related epilepsy syndrome (FIRES) is a rare clinical presentation of refractory status epilepticus following a febrile infection. This study analyzes data from the NORSE/FIRES Family Registry, an international web‐based registry available in six languages with data entered by patients, families, and clinicians to explore clinical presentations, survivorship, and long‐term outcomes in adult and pediatric FIRES patients. We characterize and examine differences in demographics, prodromal symptoms, seizure frequency, anti‐seizure medications (ASMs), quality of life, cognition, mood, and anxiety in adults vs pediatric populations with FIRES. Eighty‐six participants were included in the study. Pediatric patients ( n = 54) were predominantly male (77.8%) and experienced a significantly higher post‐FIRES seizure burden than adult survivors (67.7% ≥12 seizures/month in pediatrics vs 11.8% in adults, p <.001). Adults ( n = 32) were more likely to be female (59.4%) and have flu‐like prodromal symptoms (90.6%). At ≥6 months post‐FIRES, both groups exhibited high ASM use, with the majority (87.5%) taking three or more medications. Pediatric patients reported worse mood and anxiety outcomes compared to adults ( p <.005). Self‐reported quality of life and cognition were rated as moderate across in adults (5.2/10) and pediatric (4.7/10) patients, although pediatric patients indicated poorer cognition. Our findings highlight the challenges in managing post‐FIRES outcomes across different age groups, particularly in pediatric patients who face a higher seizure burden and report worse cognitive outcomes.

Abstract Few studies have reliable estimates on costs of informal care following hospitalization, including health care use and out-of-pocket costs for family caregivers (FCGs) and their care recipients (CR). This presentation discusses results from a Transitional Palliative Care (TPC) intervention on healthcare use and out-of-pocket spending for both FCGs and CRs. The study used data from the Technology-Enhanced TPC study, a trial comparing the TPC intervention to support FCGs of seriously ill CRs to an attention control condition. TPC FCGs received teaching, guidance, and counseling via video calls for 8 weeks following CR hospital discharge. After discharge, a research assistant called FCGs once a month for up to 6 months or CR death to collect healthcare utilization (e.g. outpatient, emergency department, and hospital), out-of-pocket healthcare spending (e.g. deductibles and coinsurance), and health-related travel costs (e.g., transportation, lodging, food) for FCGs and CRs. Incidence rate ratios (IRR) were estimated using negative binomial regressions. The study included 282 FCG-CR dyads across 3 US states. TPC reduced nights in the hospital for CR (IRR = 0.75; 95% CI = 0.56 – 0. 99). Total out-of-pocket spending was not significantly different for TPC versus control; however, TPC dyads reported lower lodging costs (IRR = 0.71; 95% CI = 0.56-0.89). Across groups, mean out-of-pocket spending for dyads was $1401.85, with healthcare payments contributing $1048.58 and transportation expenses contributing $136.79. This study contributes to evidence that palliative care interventions reduce unnecessary hospitalization for seriously ill patients, yet the financial costs to caregivers remain high.

Abstract Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that profoundly impacts the lives of people with the condition and their family caregivers. Little is known about the experiences of care at home among individuals with ALS and their family caregivers. This qualitative study explored these experiences in 14 in-depth interviews that included seven persons with ALS and 13 family caregivers. The findings were organized based on the Salutogenic Model of Health. The main sources of stress reported included the overwhelming nature of getting an ALS diagnosis, inadequacy of health care teams in providing emotional support and promoting shared decision-making in regard to the management of ALS, high level of illness acuity, the intense nature of caregiving involved in ALS, high cost of treatments and equipment, difficulties navigating the healthcare system, unavailability of suitable medical equipment, scarcity of paid caregivers competent in managing ALS, and lack of adequate training for family caregivers. Perspectives on positive coping included mental toughness, maintaining a positive outlook about life and the future, being proactive in seeking support to maintain function and quality of life, proactively communicating with care teams, advanced care planning, having a sense of control over ALS management plan of care, and taking a break from caregiving. Instrumental and emotional support from family, friends, community organizations, and healthcare teams, as well as sufficient insurance and financial coverage for ALS treatments, facilitated better coping. Future research and policies should focus on identifying effective multisectoral strategies for supporting people with ALS and their caregivers.

Abstract Estimates of patient care costs often overlook the economic value of unpaid caregiving. This study aims to quantify the economic value of unpaid caregiving by rural FCGs. Using data from a multi-site randomized controlled trial evaluating Transitional Palliative Care (TPC) intervention for FCGs, this study quantifies the economic value of family caregiving in the six months following seriously ill care recipients’ hospital discharge using three valuation methods. Caregiving hours were self-reported by FCGs. The proxy cost approach assigned value to FCG hours using the national median home health aide wage. The unadjusted opportunity cost approach assigned value using the national median wage, by sex and education level. The adjusted opportunity cost approach assigned value by work force participation, using opportunity cost if employed and proxy cost otherwise. Of 282 FCGs, 94% were non-Hispanic White, 71% had a college degree, 56% were spouses, and 51% were in the workforce. FCG cost did not differ by treatment arm. FCGs of decedents compared to survivors reported significantly more hours per person-month (392 vs. 272, p&lt; 0.001), resulting in higher median opportunity cost ($12,653 vs. $8,843, p&lt; 0.001), proxy cost ($5,689 vs. $3,955, p&lt; 0.001), and adjusted opportunity cost ($9,490 vs. $6,443, p&lt; 0.001) per person-month. Proxy cost may undervalue FCG time, while opportunity cost may perpetuate labor market inequities. Policymakers must weigh trade-offs of different valuation methods. The high intensity of unpaid post-acute care, especially end-of-life, should be considered when designing policies and interventions to support unpaid FCG due to the economic impact on FCGs and employers.

Background and Objectives: Faculty members who are underrepresented in medicine (URM) may benefit from mentorship that is designed specifically to meet their unique needs and is focused on improving their career pathways in academic medicine. The Underrepresented in Medicine Mentorship Program (URM-MP) is an academic society-based mentorship program that pairs early career URM faculty with mid- to late-career faculty specifically trained to address URM issues. Methods: During the first 3 years of the program, mentors received web-based training on addressing oppression and marginalization of URM faculty in academic medicine. Mentor and mentee pairs met monthly for 1 year and received support from program leaders through web-based check-in meetings twice per year. Pre- and postassessment data were collected from mentees to help identify their needs and evaluate their experiences. Check-in meetings provided feedback about the program. Results: Fifty-seven URM faculty participated in years 1, 2, and 3. Results of pre- and postsurveys showed that mentees significantly improved their self-perceived effectiveness to enhance their careers, to find resources to perform their jobs, and to navigate the challenges of advancing in academic medicine. Qualitative analyses revealed themes of appreciation for mentors supporting their unique experiences as URM faculty. Check-in feedback further reinforced the relationship aspects of the mentorship as a significant benefit of this program. Conclusions: Society-based mentorship that involves specific training for mentors and fosters trusting mentor-mentee relationships can improve URM faculty’s confidence regarding their ability to succeed in academic medicine.

Importance Data are limited on the longitudinal implications of socioeconomic status (SES) for neurodevelopmental outcomes among persons with complex congenital heart disease (CHD). Objectives To examine the association of family SES, maternal educational level, and maternal IQ with the neurodevelopment of individuals with dextro-transposition of the great arteries (d-TGA) from age 1 to 16 years and to identify how SES-related disparities change with age. Design, Setting, and Participants This cohort study analyzed data of participants enrolled in the Boston Circulatory Arrest Study, a randomized clinical trial conducted in Boston, Massachusetts, from 1988 to 1992. Participants were infants with d-TGA who underwent arterial switch operation and, after operation, underwent in-person neurodevelopmental status evaluations at ages 1, 4, 8, and 16 years. Analyses were conducted from April 2021 to August 2024. Exposures Mean Hollingshead scores at birth, age 1 year, and age 4 years were used to assign participants to SES tertiles (lowest, middle, or highest). Main Outcomes and Measures Age-appropriate neurodevelopmental outcomes assessed at 4 study time points (ages 1, 4, 8, and 16 years) via in-person administration of a range of well-validated measures. Standardized neurodevelopmental composite scores from each evaluation were derived from principal component analysis and compared across SES tertiles, adjusting for birth and medical characteristics. These scores were used to categorize the sample into latent classes; patient and medical factors for a 3-class model were used to estimate latent class using multinomial regression. Results The sample included 164 patients with d-TGA (123 males [75%]; mean [SD] gestational age at birth, 39.8 [1.2] weeks; 3 with Asian [2%], 6 with Black [4%], 5 with Hispanic [3%], and 146 with White [89%] race and ethnicity) and their mothers (mean [SD] age at birth, 28.5 [5.2] years). Lower SES tertile was associated with worse scores on most individual neurodevelopmental tests and worse neurodevelopmental composite scores at ages 4, 8, and 16 years. For example, mean (SD) neurodevelopmental composite scores at age 4 years were –0.49 [0.83] for lowest, 0.00 [0.81] for middle, and 0.47 [1.10] for highest SES tertile ( F 2 = 15.5; P &amp;lt; .001). When measured at consecutive time points, differences between SES tertiles were of similar magnitude. A latent class analysis produced 2- and 3-class models representing patients with stable (103 [64%] and 85 [53%]), improving (20 [13%]), and declining (57 [36%] and 55 [34%]) neurodevelopmental status. Those experiencing declines in neurodevelopmental status were more likely to have younger maternal age at childbirth (26.6 [5.1] vs 29.6 [4.9] and 29.1 [5.1] years; P = .002), lower maternal IQ (91.0 [14.1] vs 100.1 [11.1] and 96.2 [11.0]; P &amp;lt; .001), and lower SES (35.2 [10.8] vs 40.9 [9.9] and 35.8 [10.1]; P = .003) compared with those with stable or improving status. Conclusions and Relevance This cohort study of individuals with d-TGA found an association between lower family SES and worse neurodevelopmental outcomes in childhood and continuing throughout adolescence as well as greater decline in neurodevelopmental status over time. Effective strategies are needed to improve access to neurodevelopmental monitoring and intervention services for children with CHD from lower socioeconomic backgrounds.