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At one time considered a possible form of neuromyelitis optica (NMO) spectrum disorder (NMOSD), it is now accepted that myelin oligodendrocyte glycoprotein (MOG) antibody (Ab)-associated disorder (MOGAD) is a distinct entity from either NMO or multiple sclerosis (MS) and represents a broad spectrum of clinical phenotypes. Whereas Abs targeting aquaporin-4 (AQP4) in NMO are pathogenic, the extent that anti-MOG Abs contribute to CNS damage in MOGAD is unclear. Both AQP4-specific Abs in NMO and MOG-specific Abs in MOGAD are predominantly IgG1, a T cell-dependent immunoglobulin (Ig) subclass. Key insights in neuroimmunology and MOGAD pathogenesis have been learned from MOG experimental autoimmune encephalomyelitis (EAE), described 2 decades before the term MOGAD was introduced. MOG-specific T cells are required in MOG EAE, and while anti-MOG Abs can exacerbate EAE and CNS demyelination, those Abs are neither necessary nor sufficient to cause EAE. Knowledge regarding the spectrum of MOGAD clinical and radiologic presentations is advancing rapidly, yet our grasp of MOGAD pathogenesis is incomplete. Understanding both the humoral and cellular immunology of MOGAD has implications for diagnosis, treatment, and prognosis.

BACKGROUND: Surgeons have come under increased scrutiny for postoperative pain management, particularly for opioid prescribing. To decrease opioid use but still provide pain control, nonopioid medications such as muscle relaxants are being used, which can be harmful in older adults. However, the prevalence of muscle relaxant prescribing, trends in use over time, and risk of prolonged use are unknown. STUDY DESIGN: Using a 20% representative Medicare sample, we conducted a retrospective analysis of muscle relaxant prescribing to patients ≥ 65 years of age. We merged patient data from Medicare Carrier, MedPAR, and Outpatient Files with Medicare Part D for the years 2013-2018. A total of 14 surgical procedures were included to represent a wide range of anatomic regions and specialties. RESULTS: The study cohort included 543,929 patients. Of the cohort, 8111 (1.5%) received a new muscle relaxant prescription at discharge. Spine procedures accounted for 12% of all procedures but 56% of postoperative prescribing. Overall, the rate of prescribing increased over the time period (1.4-2.0%, p < 0.001), with increases in prescribing primarily in the spine (7-9.6%, p < 0.0001) and orthopedic procedure groups (0.9-1.4%, p < 0.0001). Of patients discharged with a new muscle relaxant prescription, 10.7% had prolonged use. CONCLUSIONS: The use of muscle relaxants in the postoperative period for older adults is low, but increasing over time, especially in ortho and spine procedures. While pain control after surgery is crucial, surgeons should carefully consider the risks of muscle relaxant use, especially for older adults who are at higher risk for medication-related problems.

ImportanceMore than 70 000 Medicare beneficiaries receive care in long-term acute care hospitals (LTCHs) annually for prolonged acute illness. However, little is known about long-term functional and cognitive outcomes of middle-aged and older adults after hospitalization in an LTCH.ObjectiveTo describe survival, functional, and cognitive status after LTCH hospitalization and to identify factors associated with an adverse outcome.Design, setting, and participantsThis retrospective cohort study included middle-aged and older adults enrolled in the Health and Retirement Study (HRS) with linked fee-for-service Medicare claims. Included participants were aged 50 years or older with an LTCH admission between January 1, 2003, and December 31, 2016, with HRS interviews available before admission. Data were analyzed between November 1, 2021, and June 30, 2023.Main outcomes and measuresFunction and cognition were ascertained from HRS interviews conducted every 2 years. The primary outcome was death or severe impairment in the 2.5 years after LTCH hospitalization, defined as dependencies in 2 or more activities of daily living (ADLs) or dementia. Multivariable logistic regression was performed to evaluate associations with a priori selected risk factors including pre-LTCH survival prognosis (Lee index score), pre-LTCH impairment status, and illness severity characterized by receipt of mechanical ventilation and prolonged intensive care unit stay of 3 days or longer.ResultsThis study included 396 participants, with a median age of 75 (IQR, 68-82) years. Of the participants, 201 (51%) were women, 125 (28%) had severe impairment, and 318 (80%) died or survived with severe impairment (functional, cognitive, or both) within 2.5 years of LTCH hospitalization. After accounting for acute illness characteristics, prehospitalization survival prognosis as determined by the Lee index score and severe baseline impairment (functional, cognitive, or both) were associated with an increased likelihood of death or severe impairment in the 2.5 years after LTCH hospitalization (adjusted odds ratio [AOR], 3.2 [95% CI, 1.7 to 6.0] for a 5-point increase in Lee index score; and AOR, 4.5 [95% CI, 1.3 to 15.4] for severe vs no impairment).Conclusions and relevanceIn this cohort study, 4 of 5 middle-aged and older adults died or survived with severe impairment within 2.5 years of LTCH hospitalization. Better preadmission survival prognosis and functional and cognitive status were associated with lower risk of an adverse outcome, and these findings should inform decision-making for older adults with prolonged acute illness.

BACKGROUND: Management of elevated blood pressure (BP) during hospitalization varies widely, with many hospitalized adults experiencing BPs higher than those recommended for the outpatient setting. PURPOSE: To systematically identify guidelines on elevated BP management in the hospital. DATA SOURCES: MEDLINE, Guidelines International Network, and specialty society websites from 1 January 2010 to 29 January 2024. STUDY SELECTION: Clinical practice guidelines pertaining to BP management for the adult and older adult populations in ambulatory, emergency department, and inpatient settings. DATA EXTRACTION: Two authors independently screened articles, assessed quality, and extracted data. Disagreements were resolved via consensus. Recommendations on treatment targets, preferred antihypertensive classes, and follow-up were collected for ambulatory and inpatient settings. DATA SYNTHESIS: Fourteen clinical practice guidelines met inclusion criteria (11 were assessed as high-quality per the AGREE II [Appraisal of Guidelines for Research & Evaluation II] instrument), 11 provided broad BP management recommendations, and 1 each was specific to the emergency department setting, older adults, and hypertensive crises. No guidelines provided goals for inpatient BP or recommendations for managing asymptomatic moderately elevated BP in the hospital. Six guidelines defined hypertensive urgency as BP above 180/120 mm Hg, with hypertensive emergencies requiring the addition of target organ damage. Hypertensive emergency recommendations consistently included use of intravenous antihypertensives in intensive care settings. Recommendations for managing hypertensive urgencies were inconsistent, from expert consensus, and focused on the emergency department. Outpatient treatment with oral medications and follow-up in days to weeks were most often advised. In contrast, outpatient BP goals were clearly defined, varying between 130/80 and 140/90 mm Hg. LIMITATION: Exclusion of non-English-language guidelines and guidelines specific to subpopulations. CONCLUSION: Despite general consensus on outpatient BP management, guidance on inpatient management of elevated BP without symptoms is lacking, which may contribute to variable practice patterns. PRIMARY FUNDING SOURCE: National Institute on Aging. (PROSPERO: CRD42023449250).

COVID-19 disproportionally impacted the health and well-being of older adults--many of whom live with chronic conditions--due to their higher risk of dying and being hospitalized. It also created several secondary pandemics, including increased falls risk, sedentary behavior, social isolation, and physical inactivity due to limitations in mobility from lock-down policies. With falls as the leading cause of preventable death and hospitalizations, it became vital for in-person evidence-based falls prevention programs (EBFPPs) to pivot to remote delivery. In Spring 2020, many EBFPP administrators began re-designing programs for remote delivery to accommodate physical distancing guidelines necessitated by the pandemic. Transition to remote delivery was essential for older adults and persons with disabilities to access EBFPPs for staying healthy, falls and injury free, out of hospitals, and also keeping them socially engaged. We collaborated with the Administration on Community Living (ACL), the National Council on Aging (NCOA), and the National Falls Prevention Resource Center (NFPRC), for an in-depth implementation evaluation of remotely delivered EBFPPs. We examined the process of adapting and implementing four EBFPPs for remote delivery, best practices for implementing the programs remotely within the RE-AIM evaluation framework. This enhances NFPRC's ongoing work supporting dissemination, implementation, and sustainability of EBFPPs. We purposively sampled organizations for maximum variation in organization and provider type, geographic location, and reach of underserved older populations (Black, Indigenous, or other People of Color (BIPOC), rural, disabilities). This qualitative evaluation includes provider-level data from semi-structured interviews (N = 22) with program administrators, staff, and leaders. The interview guide included what, why, and how adaptations were made to EBFPP interventions and implementation strategies using Wiltsey-Stirman (2019) adaptations framework (FRAME), reach, and implementation outcomes (acceptability, feasibility, fidelity, and costs; Proctor et al., 2011), focusing on equity to learn for whom these programs were working and opportunities to address inequities. Findings demonstrate remote EBFPPs made planned and fidelity-consistent adaptations to remote delivery in partnership with researchers and community organizations, focusing on participant safety both in program content and delivery. Supports using and accessing technology were needed for delivery sites and leaders to facilitate engagement, and improved over time. While remote EBFPP delivery has increased access to EBFPPs for some populations from the perspective of program administrator, leaders, and staff (e.g., caregivers, rural-dwellers, persons with physical disabilities), the digital divide remains a barrier in access to and comfort using technology. Remote-delivered EBFPPs were acceptable and feasible to delivery organizations and leaders, were able to be delivered with fidelity using adaptations from program developers, but were more resource intensive and costly to implement compared to in-person. This work has important implications beyond the pandemic. Remote delivery has expanded access to groups traditionally underserved by in-person programming, particularly disability communities. This work will help answer important questions about reach, accessibility, feasibility, and cost of program delivery for older adults and people with disabilities at risk for falls, those living with chronic conditions, and communities most vulnerable to disparities in access to health care, health promotion programming, and health outcomes. It will also provide critical information to funders about elements required to adapt EBFPPs proven effective in in-person settings for remote delivery with fidelity to achieve comparable outcomes.

BackgroundPrescribing cascades are important contributors to polypharmacy. Little is known about which older adults are at highest risk of experiencing prescribing cascades. We explored which older veterans are at highest risk of the gabapentinoid (including gabapentin and pregabalin)-loop diuretic (LD) cascade, given the dramatic increase in gabapentinoid prescribing in recent years.MethodsUsing Veterans Affairs and Medicare claims data (2010-2019), we performed a prescription sequence symmetry analysis (PSSA) to assess loop diuretic initiation before and after gabapentinoid initiation among older veterans (≥66 years). To identify the cascade, we calculated the adjusted sequence ratio (aSR), which assesses the temporality of LD relative to gabapentinoid initiation. To explore high-risk groups, we used multivariable logistic regression with prescribing order modeled as a binary dependent variable. We calculated adjusted odds ratios (aORs), measuring the extent to which factors are associated with one prescribing order versus another.ResultsOf 151,442 veterans who initiated a gabapentinoid, there were 1,981 patients who initiated a LD within 6 months after initiating a gabapentinoid compared to 1,599 patients who initiated a LD within 6 months before initiating a gabapentinoid. In the gabapentinoid-LD group, the mean age was 73 years, 98% were male, 13% were Black, 5% were Hispanic, and 80% were White. Patients in each group were similar across patient and health utilization factors (standardized mean difference

BACKGROUND: Ublituximab is a novel anti-CD20 monoclonal antibody glycoengineered for enhanced antibody-dependent cellular cytotoxicity. The phase 3 ULTIMATE I and II studies showed significant improvements in annualized relapse rate, total number of gadolinium-enhancing (Gd+) T1 lesions, and total number of new or enlarging T2 at Week 96, as well as improvement in the proportion of participants with no evidence of disease activity (NEDA) from Weeks 24-96 with ublituximab vs. teriflunomide. METHODS: In ULTIMATE I (NCT03277261; www.clinicaltrials.gov) (N = 549) and II (NCT03277248; www.clinicaltrials.gov) (N = 545), participants with relapsing multiple sclerosis received ublituximab 450 mg intravenous infusion every 24 weeks (following Day 1 infusion of 150 mg and Day 15 infusion of 450 mg) or teriflunomide 14 mg oral once daily for 96 weeks. Pooled post hoc analyses evaluated NEDA by treatment epoch and participant subtype: age ( ≤ 38 or >38 years), early or later disease (3.5 at baseline. NEDA was defined as no confirmed relapses, no Gd+ T1 lesions, no new or enlarging T2 lesions, and no disability progression confirmed for ≥12 weeks. RESULTS: NEDA rates in the ublituximab vs. teriflunomide cohorts by treatment epoch were: Weeks 0-96, 44.6% vs. 12.4% (3.6 × improvement); Weeks 24-96 (re-baselined), 82.1% vs. 22.5% (3.6 × improvement); and Weeks 48-96 (re-baselined), 88.2% vs. 30.4% (2.9 × improvement) (all p < 0.0001). The primary driver of disease activity in ublituximab-treated participants was new or enlarging T2 lesions during Weeks 0-24. 41.8% of ublituximab-treated participants who had evidence of disease activity in the first year (Weeks 0-48) experienced NEDA in the second year of treatment (Weeks 48-96) compared with 17.3% of teriflunomide-treated participants. At Weeks 24-96 (re-baselined), rates of NEDA were significantly higher with ublituximab than teriflunomide in all participant subtypes (all p < 0.0001). CONCLUSIONS: ULTIMATE I and II pooled post hoc analyses demonstrated a consistent NEDA benefit among ublituximab-treated participants across treatment epochs and key participant subpopulations.

Human milk, due to its unique composition, is the optimal standard for infant nutrition. Osteopontin (OPN) is abundant in human milk but not bovine milk. The addition of bovine milk osteopontin (bmOPN) to formula may replicate OPNs concentration and function in human milk. To address safety concerns, we convened an expert panel to assess the adequacy of safety data and physiological roles of dietary bmOPN in infancy. The exposure of breastfed infants to human milk OPN (hmOPN) has been well-characterized and decreases markedly over the first 6 months of lactation. Dietary bmOPN is resistant to gastric and intestinal digestion, absorbed and cleared from circulation within 8-24 h, and represents a small portion (

This paper is an exploration of the pedagogic challenges experienced in teaching emerging Jewish educational leaders about how to lead with a diversity mindset and create inclusive spaces for teaching and learning. Employing elements of self-study and phenomenology, we identify felt difficulties, examining how those were evident in our planning and teaching of the course and in student work. From those challenges we name lessons to be learned and questions for further study about the professional development of Jewish educational leaders who are responsible for creating cultures of belonging in their institutions.

INTRODUCTION: Allogeneic hematopoietic cell transplantation (alloHCT) is increasingly offered to older adults, and its potential impact on cognition in this population is understudied. This work aims to evaluate the ability of cancer-specific geriatric assessments (cGA) and a global frailty index based on accumulation of deficits identified in the cGA to predict the risk of cognitive decline after alloHCT in older adults. MATERIALS AND METHODS: AlloHCT recipients aged 50 years or older completed a cGA, including a cognitive evaluation by the Blessed Orientation Memory Concentration (BOMC) test, at baseline prior to alloHCT and then at 3, 6, and 12 months after transplant. Baseline frailty was assessed using a deficit accumulation frailty index (DAFI) calculated from the cGA. A multinomial logit model was used to examine the association between predictors (individual cGA measures, DAFI) and the following three outcomes: alive with stable or improved cognition, alive with cognitive decline, and deceased. In post-hoc analyses, analysis of variance was used to compare BOMC scores at baseline, 3, 6, and 12 months across frailty categories. RESULTS: In total, 148 participants were included, with a median age of 62 (range 50-76). At baseline, 12% had cognitive impairment; at one year, 29% of survivors had improved BOMC scores, 33% had stable BOMC, and 37% had worse BOMC. Prior to transplant, 25% were pre-frail and 11% were frail. Individual baseline cGA measures were not associated with cognitive change at one year as assessed by BOMC. Adjusting for age, sex, and education, those who were frail at baseline were 7.4 times as likely to develop cognitive decline at one year than those who were non-frail, although this finding did not reach statistical significance (95% confidence interval [CI] 0.74-73.8, p = 0.09). The probability of being alive with stable/improved cognition at 12 months for the non-frail, pre-frail, and frail groups was 43%, 34%, and 8%, respectively. DISCUSSION: Baseline geriatric measures and frailty were not significantly associated with cognitive change as assessed by BOMC in adults aged 50 or older after alloHCT. However, the study was underpowered to detect clinically meaningful differences, and future work to elucidate potential associations between frailty and cognitive outcomes is warranted.

BACKGROUND: Persons with dementia (PWD) have high rates of polypharmacy. While previous studies have examined specific types of problematic medication use in PWD, we sought to characterize a broad spectrum of medication misuse and overuse among community-dwelling PWD. METHODS: We included community-dwelling adults aged ≥66 in the Health and Retirement Study from 2008 to 2018 linked to Medicare and classified as having dementia using a validated algorithm. Medication usage was ascertained over the 1-year prior to an HRS interview date. Potentially problematic medications were identified by: (1) medication overuse including over-aggressive treatment of diabetes/hypertension (e.g., insulin/sulfonylurea with hemoglobin A1c

Aquaporin-4 (AQP4)-specific Th17 cells are thought to have a central role in neuromyelitis optica (NMO) pathogenesis. When modeling NMO, only AQP4-reactive Th17 cells from AQP4-deficient (AQP4-/-), but not wild-type (WT) mice, caused CNS autoimmunity in recipient WT mice, indicating that a tightly regulated mechanism normally ensures tolerance to AQP4. Here, we found that pathogenic AQP4 T cell epitopes bind MHC II with exceptionally high affinity. Examination of T cell receptor (TCR) α/β usage revealed that AQP4-specific T cells from AQP4-/- mice employed a distinct TCR repertoire and exhibited clonal expansion. Selective thymic AQP4 deficiency did not fully restore AQP4-reactive T cells, demonstrating that thymic negative selection alone did not account for AQP4-specific tolerance in WT mice. Indeed, AQP4-specific Th17 cells caused paralysis in recipient WT or B cell-deficient mice, which was followed by complete recovery that was associated with apoptosis of donor T cells. However, donor AQP4-reactive T cells survived and caused persistent paralysis in recipient mice deficient in both T and B cells or mice lacking T cells only. Thus, AQP4 CNS autoimmunity was limited by T cell-dependent deletion of AQP4-reactive T cells. In contrast, myelin oligodendrocyte glycoprotein (MOG)-specific T cells survived and caused sustained disease in WT mice. These findings underscore the importance of peripheral T cell deletional tolerance to AQP4, which may be relevant to understanding the balance of AQP4-reactive T cells in health and in NMO. T cell tolerance to AQP4, expressed in multiple tissues, is distinct from tolerance to MOG, an autoantigen restricted in its expression.

Reproductive hormone profiles were described against physical characteristics during growth and development in male and female botos (Amazon River dolphins Inia geoffrensis) and during pregnancy. We determined hormone concentrations in 226 wild botos located in Mamirauá Reserve, Amazonas State, Brazil, as a part of the long-term population monitoring program known as Projeto Boto. Additionally, we applied receiver operator characteristic (ROC) analysis to compare diagnostic probabilities of using ultrasound, hormones, or combinations of these to detect pregnancy. Based on single-point analysis of serum testosterone (T), males with 5 ng ml-1 T and 227 cm as adult botos. For females, only progesterone (P4), T, relaxin (Rlx), and the combination of P4 × T2 were significantly different between non-pregnant and pregnant females, but androstenedione (A4) and the P4:T ratio were not. ROC analysis indicated that ultrasound and P4 × T2 were considered excellent as pregnancy diagnostic tests, and P4, T, and Rlx were classified as good predictors. Results indicated that negative and positive predictive probabilities from each diagnostic test could be used to accurately predict a pregnancy and calf loss rate of 13% for this population. Application of these methods for evaluating wild population reproductive success from a single serum sample can now be used for health evaluations of wild populations of boto and provide timely information for the development or evaluation of any conservation initiatives.

BackgroundCommonly prescribed antidepressants (paroxetine, fluoxetine, duloxetine, bupropion) inhibit bioconversion of several prodrug opioid medications to their active metabolite, potentially decreasing analgesic effect. There is a paucity of studies assessing the risk-benefit of concomitant administration of antidepressants and opioids.Research design and methodsObservational study of adult patients taking antidepressants prior to scheduled surgery using 2017-2019 electronic medical record data to assess perioperative use of opioids and to determine the incidence and risk factors for developing postoperative delirium. We conducted a generalized linear regression with the Gamma log-link to assess the association between use of antidepressants and opioids and a logistic regression to assess the association between antidepressants use and the likelihood of developing postoperative delirium.ResultsAfter controlling for patient demographic and clinical characteristics, and postoperative pain, use of inhibiting antidepressants was associated with 1.67 times greater use of opioids per hospitalization day (p = 0.00154), a two-fold increase in the risk for developing postoperative delirium (p = 0.0224), and an estimated average of four additional days of hospitalization (p

β-blockers are commonly used in heart failure with preserved ejection fraction (HFpEF), even in the absence of a compelling indication and despite the potential to cause harm. Identifying reasons for β-blocker prescription in HFpEF could permit the development of strategies to reduce unnecessary use and potentially improve medication prescribing patterns in this vulnerable population. We administered an online survey regarding β-blocker prescribing behavior to physicians trained in internal medicine or geriatrics (noncardiology physicians) and to cardiologists at 2 large academic medical centers. The survey assessed the reasons for β-blocker initiation, agreement regarding initiation and/or continuation of β-blockers by another clinician, and deprescribing behavior. The response rate was 28.2% (n = 231). Among respondents, 68.2% reported initiating β-blockers in patients with HFpEF. The most common reason for initiating a β-blocker was for treatment of an atrial arrhythmia. Notably, 23.7% of physicians reported initiating a β-blocker without an evidence-based indication. When a β-blocker was considered not necessary, 40.1% of physicians reported they were rarely or never willing to deprescribe. The most common reason for not deprescribing a β-blocker when the physician felt that a β-blocker was unnecessary was the concern about interfering with another physicians treatment plan (76.6%). In conclusion, a significant proportion of noncardiology physicians and cardiologists report prescribing β-blockers to patients with HFpEF, even when evidence-based indications are absent, and rarely deprescribe β-blockers in these scenarios.

Age determination of wild animals, including pinnipeds, is critical for accurate population assessment and management. For most pinnipeds, current age estimation methodologies utilize tooth or bone sectioning which makes antemortem estimations problematic. We leveraged recent advances in the development of epigenetic age estimators (epigenetic clocks) to develop highly accurate pinniped epigenetic clocks. For clock development, we applied the mammalian methylation array to profile 37,492 cytosine-guanine sites (CpGs) across highly conserved stretches of DNA in blood and skin samples (n = 171) from primarily three pinniped species representing the three phylogenetic families: Otariidae, Phocidae and Odobenidae. We built an elastic net model with Leave-One-Out-Cross Validation (LOOCV) and one with a Leave-One-Species-Out-Cross-Validation (LOSOCV). After identifying the top 30 CpGs, the LOOCV produced a highly correlated (r = 0.95) and accurate (median absolute error = 1.7 years) age estimation clock. The LOSOCV elastic net results indicated that blood and skin clock (r = 0.84) and blood (r = 0.88) pinniped clocks could predict age of animals from pinniped species not used for clock development to within 3.6 and 4.4 years, respectively. These epigenetic clocks provide an improved and relatively non-invasive tool to determine age in skin or blood samples from all pinniped species.

BackgroundHospitalizations among people with dementia (PWD) may precipitate behavioral changes, leading to the psychotropic medication use despite adverse outcomes and limited efficacy. We sought to determine the incidence of new psychotropic medication use among community-dwelling PWD after hospital discharge and, among new users, the proportion with prolonged use.MethodsThis was a retrospective cohort study using a 20% random sample of Medicare claims in 2017, including hospitalized PWD with traditional and Part D Medicare who were 68 years or older. The primary outcome was incident prescribing at discharge of psychotropics including antipsychotics, sedative-hypnotics, antiepileptics, and antidepressants. This was defined as new prescription fills (i.e., from classes not used in 180 days preadmission) within 7 days of hospital or skilled nursing facility discharge. Prolonged use was defined as the proportion of new users who continued to fill newly prescribed medications beyond 90 days of discharge.ResultsThe cohort included 117,022 hospitalized PWD with a mean age of 81 years; 63% were female. Preadmission, 63% were using at least 1 psychotropic medication; 10% were using medications from ≥3 psychotropic classes. These included antidepressants (44% preadmission), antiepileptics (29%), sedative-hypnotics (21%), and antipsychotics (11%). The proportion of PWD discharged from the hospital with new psychotropics ranged from 1.9% (antipsychotics) to 2.9% (antiepileptics); 6.6% had at least one new class started. Among new users, prolonged use ranged from 36% (sedative-hypnotics) to 63% (antidepressants); across drug classes, prolonged use occurred in 51%. Predictors of newly initiated psychotropics included length of stay (≥median vs. ConclusionsHospitalized PWD have a high prevalence of preadmission psychotropic medication use; against this baseline, discharge from the hospital with new psychotropics is relatively uncommon. Nevertheless, prolonged use of newly initiated psychotropics occurs in a substantial proportion of this population.

BackgroundUblituximab is a novel anti-CD20 monoclonal antibody glycoengineered for enhanced antibody-dependent cellular cytotoxicity. The phase 3 ULTIMATE I and II studies showed significant improvements in annualized relapse rate, total number of gadolinium-enhancing (Gd+) T1 lesions, and total number of new or enlarging T2 at Week 96, as well as improvement in the proportion of participants with no evidence of disease activity (NEDA) from Weeks 24–96 with ublituximab vs. teriflunomide.MethodsIn ULTIMATE I (NCT03277261; www.clinicaltrials.gov) (N = 549) and II (NCT03277248; www.clinicaltrials.gov) (N = 545), participants with relapsing multiple sclerosis received ublituximab 450 mg intravenous infusion every 24 weeks (following Day 1 infusion of 150 mg and Day 15 infusion of 450 mg) or teriflunomide 14 mg oral once daily for 96 weeks. Pooled post hoc analyses evaluated NEDA by treatment epoch and participant subtype: age ( ≤ 38 or >38 years), early or later disease (3.5 at baseline. NEDA was defined as no confirmed relapses, no Gd+ T1 lesions, no new or enlarging T2 lesions, and no disability progression confirmed for ≥12 weeks.ResultsNEDA rates in the ublituximab vs. teriflunomide cohorts by treatment epoch were: Weeks 0–96, 44.6% vs. 12.4% (3.6 × improvement); Weeks 24–96 (re-baselined), 82.1% vs. 22.5% (3.6 × improvement); and Weeks 48–96 (re-baselined), 88.2% vs. 30.4% (2.9 × improvement) (all p < 0.0001). The primary driver of disease activity in ublituximab-treated participants was new or enlarging T2 lesions during Weeks 0–24. 41.8% of ublituximab-treated participants who had evidence of disease activity in the first year (Weeks 0–48) experienced NEDA in the second year of treatment (Weeks 48–96) compared with 17.3% of teriflunomide-treated participants. At Weeks 24–96 (re-baselined), rates of NEDA were significantly higher with ublituximab than teriflunomide in all participant subtypes (all p < 0.0001).ConclusionsULTIMATE I and II pooled post hoc analyses demonstrated a consistent NEDA benefit among ublituximab-treated participants across treatment epochs and key participant subpopulations.

INTRODUCTION: Perceiving medication side effects but not reporting them to a clinician is common. Patterns of under-reporting and their implications are not well described. We aimed to address this gap by examining patterns of under-reporting perceived side effects of beta-blockers among patients with heart failure. METHODS: In 2016, a survey that evaluated medication-taking behavior was administered to 1114 participants (46.5% response rate) from The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort with prior adjudicated heart failure hospitalization or a heart failure Medicare claim. We examined the results of survey respondents who reported taking a beta-blocker to understand patterns of under-reporting perceived beta-blocker side effects. We defined an under-reporter as a participant who perceived experiencing a side effect from their beta-blocker but did not share it with their clinician (according to survey responses). We conducted a multivariable logistic regression analysis to identify determinants of being an under-reporter. Co-variates included age, sex, race, income, level of education, geographical location, and pill burden. We also examined whether under-reporters differed in self-reported medication adherence and willingness to take additional medication to prevent a future healthcare encounter compared to participants who reported perceived side effects to their clinicians and those who did not experience side effects. RESULTS: Among 310 respondents, 28% (n = 87) were under-reporters. Black race (odds ratio 2.11, confidence interval 1.21-3.67) and education less than college (odds ratio 2.00, confidence interval 1.09-3.67) were associated with being an under-reporter. Self-reported medication adherence was similar between groups (under-reporters: 46.3%; those who reported perceived side effects: 49.4%; those who did not experience side effects: 45.0%); under-reporters were more frequently unwilling to take additional medication to prevent a doctors visit (18.9% vs 12.1% vs 10.8%), emergency room visit (21.6% vs 13.3% vs 9.9%), and hospitalization (17.6% vs 10.8% vs 9.0%) compared with the other groups. CONCLUSION: We conclude that under-reporting perceived side effects of beta-blockers among adults with heart failure is common, is associated with Black race and low education, and may contribute to patient willingness to take additional medication to prevent future medical encounters.

BACKGROUND: Claims-based measures of multimorbidity, which evaluate the presence of a defined list of diseases, are limited in their ability to predict future outcomes. We evaluated whether claims-based markers of disease severity could improve assessments of multimorbid burden. METHODS: We developed 7 dichotomous markers of disease severity which could be applied to a range of diseases using claims data. These markers were based on the number of disease-associated outpatient visits, emergency department visits, and hospitalizations made by an individual over a defined interval; whether an individual with a given disease had outpatient visits to a specialist who typically treats that disease; and ICD-9 codes which connote more versus less advanced or symptomatic manifestations of a disease. Using Medicare claims linked with Health and Retirement Study data, we tested whether including these markers improved ability to predict ADL decline, IADL decline, hospitalization, and death compared to equivalent models which only included the presence or absence of diseases. RESULTS: Of 5012 subjects, median age was 76 years and 58% were female. For a majority of diseases tested individually, adding each of the 7 severity markers yielded minimal increase in c-statistic (≤0.002) for outcomes of ADL decline and mortality compared to models considering only the presence versus absence of disease. Gains in predictive power were more substantial for a small number of individual diseases. Inclusion of the most promising marker in multi-disease multimorbidity indices yielded minimal gains in c-statistics (

BACKGROUND: While depression is a leading cause of poor health, less than half of older adults receive adequate care. Inequities in both access and outcomes are even more pronounced for socially disadvantaged older adults. The collaborative care model (CCM) has potential to reduce this burden through community-based organizations (CBOs) who serve these populations. However, CCM has been understudied in diverse cultural and resource-constrained contexts. We evaluated the implementation and effectiveness of PEARLS, a home-based CCM adapted with and for community health workers/promotores (CHWs/Ps). METHODS: We used an instrumental case study design. Our case definition is a community-academic partnership to build CHW/P capacity for evidence-based depression care for older U.S. Latino adults in the Inland Empire region of California (2017-2020). We aimed to understand adaptations to fit local context; acceptability, feasibility, and fidelity; clinical effectiveness; and contextual determinants of implementation success or failure. Data sources included quantitative and qualitative administrative and evaluation data from participants and providers. We used descriptive statistics and paired t-tests to characterize care delivery and evaluate effectiveness post-intervention, and deductive thematic analysis to answer other aims. FINDINGS: This case study included 152 PEARLS participants and nine data sources (N = 67 documents). The CBO including their CHWs/Ps partnered with the external implementation team made adaptations to PEARLS content, context, and implementation strategies to support CHWs/Ps and older adults. PEARLS was acceptable, feasible and delivered with fidelity. Participants showed significant reductions in depression severity at 5 months (98% clinical response rate [mean (SD), 13.7 (3.9) drop in pre/post PHQ-9; p < 0.001] and received support for 2.6 social needs on average. PEARLS delivery was facilitated by its relative advantage, adaptability, and trialability; the teams collective efficacy, buy-in, alignment with organization mission, and ongoing reflection and evaluation during implementation. Delivery was challenged by weak partnerships with clinics for participant referral, engagement, reimbursement, and sustainability post-grant funding. DISCUSSION: This case study used existing data to learn how home-based CCM was adapted by and for CHWs/Ps to reduce health inequities in late-life depression and depression care among older Latino immigrants. The CBOs and CHWs/Ps strong trust and rapport, addressing social and health needs alongside depression care, and regular internal and external coaching and consultation, appeared to drive successful implementation and effectiveness.

Disease-modifying therapies for relapsing multiple sclerosis reduce relapse rates by suppressing peripheral immune cells but have limited efficacy in progressive forms of the disease where cells in the central nervous system play a critical role. To our knowledge, alemtuzumab, fumarates (dimethyl, diroximel, and monomethyl), glatiramer acetates, interferons, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, and teriflunomide are either limited to the periphery or insufficiently studied to confirm direct central nervous system effects in participants with multiple sclerosis. In contrast, cladribine and sphingosine 1-phosphate receptor modulators (fingolimod, ozanimod, ponesimod, and siponimod) are central nervous system-penetrant and could have beneficial direct central nervous system properties.

BACKGROUND: Measuring multimorbidity in claims data is used for risk adjustment and identifying populations at high risk for adverse events. Multimorbidity indices such as Charlson and Elixhauser scores have important limitations. We sought to create a better method of measuring multimorbidity using claims data by incorporating geriatric conditions, markers of disease severity, and disease-disease interactions, and by tailoring measures to different outcomes. METHODS: Health conditions were assessed using Medicare inpatient and outpatient claims from subjects age 67 and older in the Health and Retirement Study. Separate indices were developed for ADL decline, IADL decline, hospitalization, and death, each over 2 years of follow-up. We validated these indices using data from Medicare claims linked to the National Health and Aging Trends Study. RESULTS: The development cohort included 5012 subjects with median age 76 years; 58% were female. Claims-based markers of disease severity and disease-disease interactions yielded minimal gains in predictive power and were not included in the final indices. In the validation cohort, after adjusting for age and sex, c-statistics for the new multimorbidity indices were 0.72 for ADL decline, 0.69 for IADL decline, 0.72 for hospitalization, and 0.77 for death. These c-statistics were 0.02-0.03 higher than c-statistics from Charlson and Elixhauser indices for predicting ADL decline, IADL decline, and hospitalization, and