Mobility trajectories in multiple sclerosis: A comparative study of timed 25-foot walk and a patient-reported outcome measure.

BACKGROUND: Loss of mobility is common in persons with multiple sclerosis (PwMS), but little is known about this impairment from the patient's perspective. OBJECTIVE: The aim is to model longitudinal variation in a mobility patient-reported outcome (PRO) and compare trajectories to those observed for Timed 25-Foot Walk (T25FW) in a retrospective cohort. METHODS: Latent-class growth analysis was applied to 47,508 measures of Performance Scales© Mobility PRO (PS-Mobility) over ~4 years for 8524 PwMS. For 7347 PwMS, there were 41,988 T25FW measures during this period. Repeated measures correlation and concordance of trajectory assignment were evaluated. RESULTS: At the group level, PS-Mobility and T25FW linearly worsened and repeated-measures correlation was moderate. Eight latent classes with varying shapes that worsened described PS-Mobility variation, compared to six latent classes for T25FW that differed by intercept. The agreement between PS-Mobility and T25FW cluster assignment was modest. A higher proportion of individuals who were Black/African American, older, Medicaid beneficiaries, living in deprived neighborhoods, had longer disease duration, had progressive disease, and ever smokers were assigned to more impaired clusters. DISCUSSION: Cross-sectionally, PS-Mobility and T25FW were highly correlated, but longitudinally correlation was modest to moderate, underscoring the importance of considering both objective and subjective perspectives in evaluating mobility changes in PwMS.

A 6-month, prospective, randomized controlled trial of customized adherence enhancement versus a bipolar-specific educational control in poorly adherent adolescents and young adults living with bipolar disorder.

OBJECTIVE: Few studies have addressed medication adherence in adolescents and young adults (AYAs) with bipolar disorder (BD). This 6-month prospective randomized-controlled trial (RCT) tested customized adherence enhancement for adolescents and young adults (CAE-AYA), a behavioral intervention for AYAs versus enhanced treatment as usual (ETAU). METHODS: Inclusion criteria were AYAs age 13-21 with BD type I or II with suboptimal adherence defined as missing ≥20% of medications. Assessments were conducted at Screening, Baseline, and weeks 8, 12 and 24. Primary outcome was past 7 day self-reported Tablets Routine Questionnaire (TRQ) validated by electronic pillbox monitoring (SimpleMed). Symptom measures included the Hamilton Depression Rating Scale (HAM-D) and Young Mania Rating Scale (YMRS). RESULTS: The mean sample age (N = 36) was 19.1 years (SD = 2.0); 66.7% (N = 24) female, BD Type I (81%). The mean missed medication on TRQ for the total sample was 35.4% (SD = 28.8) at screening and 30.4% (SD = 30.5) at baseline. Both CAE-AYA and ETAU improved on TRQ from screening to baseline. Baseline mean missed medication using SimpleMed was 51.6% (SD = 38.5). Baseline HAM-D and YMRS means were 7.1 (SD = 4.7) and 6.0 (SD = 7.3), respectively. Attrition rate at week 24 was 36%. Baseline to 24-week change on TRQ, adjusting for age, gender, educational level, living situation, family history, race, and ethnicity, showed improvement favoring CAE-AYA versus ETAU of 15%. SimpleMed interpretation was limited due to substantial missing data. There was a significant reduction in depression favoring CAE-AYA. CONCLUSIONS: CAE-AYA may improve adherence in AYAs with BD, although conclusions need to be made cautiously given study limitations. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT04348604.

Clinical correlates of perceived stigma among people living with epilepsy enrolled in a self-management clinical trial.

BACKGROUND AND PURPOSE: Stigma is a pervasive barrier for people living with epilepsy (PLWE) and can have substantial negative effects. This study evaluated clinical correlates of perceived stigma in a research sample of PLWE considered to be at high risk due to frequent seizures or other negative health events. METHODS: Analyses were derived from baseline data from an ongoing Centers for Disease Control and Prevention (CDC)-funded randomized controlled trial (RCT) testing an epilepsy self-management approach. Standardized measures assessed socio-demographics, perceived epilepsy stigma, epilepsy-related self-efficacy, epilepsy self-management competency, health literacy, depressive symptom severity, functional status, social support and epilepsy-related quality of life. RESULTS: There were 160 individuals, mean age of 39.4, (Standard deviation/SD=12.2) enrolled in the RCT, 107 (66.9 %) women, with a mean age of epilepsy onset of 23.9 (SD 14.0) years. The mean seizure frequency in the prior 30 days was 6.4 (SD 21.2). Individual factors correlated with worse perceived stigma were not being married or cohabiting with someone (p = 0.016), lower social support (p < 0.0001), lower self-efficacy (p < 0.0001), and lower functional status for both physical health (p = 0.018) and mental health (p < 0.0001). Perceived stigma was associated with worse depressive symptom severity (p < 0.0001). Multivariable linear regression found significant independent associations between stigma and lower self-efficacy (ß -0.05; p = 0.0096), lower social support (ß -0.27; p = 2.4x10-5, and greater depression severity (ß 0.6; p = 5.8x10-5). CONCLUSIONS: Perceived epilepsy stigma was positively correlated with depression severity and negatively correlated with social support and self-efficacy. Providers caring for PLWE may help reduce epilepsy stigma by screening for and treating depression, encouraging supportive social relationships, and providing epilepsy self-management support. Awareness of epilepsy stigma and associated factors may help reduce some of the hidden burden borne by PLWE.

Risk Factors for Bacterial Keratitis and Severe Disease in Hydrogel Contact Lens Users: A Multicenter Case-Control Study and Case-Only Analysis.

PURPOSE: To assess risk factors for contact lens (CL)-related bacterial keratitis, cases and high-risk controls were enrolled. Using high-risk controls can help elucidate whether certain CL types or modalities are attributable to disease burden if risky wear patterns are similar between the cases and controls. This analysis identified whether such CL factors were associated with the occurrence of bacterial keratitis. In addition, a case-only analysis determined CL factors associated with severe disease. METHODS: From 2018 to 2021, 158 controls were enrolled at University Hospitals of Cleveland Eye Institute, and 153 bacterial keratitis cases were enrolled across 14 sites in the United States. Cases were soft CL wearers with either culture-proven bacterial keratitis or a corneal infiltrate with an overlying epithelial defect within the central 4 mm of the cornea, uveitis, or significant pain. Fungal, protozoan, or nonsoft CL wear-related microbial keratitis cases were excluded. Controls were recruited from high-risk CL wearers with no history of disease. All participants completed a questionnaire related to demographics, type of CL used, wearing schedule, lens handling practices, and storage case handling. Cases with ulcer/infiltrate size ≥2 mm in size, presence of hypopyon, or had fortified antibiotics prescribed were classified as severe keratitis. Univariate and multivariable logistic regression was used to assess association of CL variables with the occurrence of bacterial keratitis as well as occurrence of severe disease among the cases only. RESULTS: Compared with the control cohort, cases were older (mean age 45.6 vs. 38.9 years), had more males (42.5% vs. 23.6%), and had more current or former smokers (41.7% vs. 12.9%). There were no significant associations between CL material (silicone hydrogel vs. not) or CL type (daily disposable vs. reusable) and occurrence of bacterial keratitis. More than two-thirds (67.3%) of cases were classified as severe. Among cases only, univariate analyses found current smokers to have increased risk of severe disease (OR=2.87; 95% CI 1.13-7.26, P=0.03). Adjusting for age, sex, and smoking among the cases only, daily disposable lenses were protective against severe disease (OR=0.32; 95% CI 0.11-0.89, P=0.03). Reusable lenses increased risk of severe microbial keratitis between 3.0- and 4.4-fold compared with compliant daily disposability. DISCUSSION/CONCLUSION: Compared with a high-risk control cohort, no specific lens factors were associated with occurrence of CL-associated bacterial keratitis. Among cases only, current smokers and patients wearing reusable lenses are at increased risk of severe keratitis. Daily disposable lenses were protective even when noncompliance to daily disposability was considered.

Clinical correlates of medication adherence in individuals with bipolar disorder and comorbid hypertension.

OBJECTIVE: Individuals with bipolar disorder (BD) have high rates of suboptimal medication adherence, medical illness, and premature mortality, largely from cardiovascular causes. This analysis examined the association between adherence to antihypertensive and BD medications and clinical symptoms in patients with BD and comorbid hypertension (HTN) from an ongoing trial to optimize adherence. METHOD: Inclusion criteria were a BD diagnosis, treatment with antihypertensives, adherence challenges, and poorly controlled HTN. Adherence was measured via self-report using the Tablets Routine Questionnaire and using eCAP, an electronic pillcap which captures openings. Average systolic blood pressure (SBP) was calculated from 12 readings over 1 week. The Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Psychiatric Rating Scale (BPRS) assessed BD symptoms. RESULTS: A total of 83 participants with BD and HTN were included. Adherence to BD and antihypertensive medications were positively correlated. eCAP openings showed more missed doses than self-reported antihypertensive adherence. BD medication adherence was positively correlated with BPRS at baseline; antihypertensive adherence was negatively correlated with SBP at screening. Antihypertensive adherence improved and SBP decreased between screening and baseline. CONCLUSIONS: Adherence levels fluctuated over time and differed based on measurement method in people with comorbid BD and HTN. Self-reported BD adherence was positively related to global psychiatric symptoms and antihypertensive adherence was related to better SBP control. Monitoring both medication and blood pressure led to change in self-reported adherence. BD symptom severity may indicate poor adherence in patients with BD and should be considered in treatment planning.

A case study in science-to-service application of epilepsy self-management.

AIMS: Epilepsy self-management (ESM), the overall approach of reducing seizures and optimizing whole-health, is a targeted approach to improve population health for people with epilepsy (PWE). "Self-management for people with epilepsy and a history of negative health events" (SMART) is an 8-session group-format, remotely delivered ESM. This report describes the evolution of SMART development, testing and scale-up, taking advantage of ESM team expertise, community relationships and infrastructure established by social service agencies that deliver support to PWE. METHODS: This is a case-study dissemination and implementation (D&I) science-to-service model using the RE-AIM framework approach (Reach, Effectiveness, Adoption, Implementation, and Maintenance) focused on 5 dimensions of individual- and setting-level outcomes important to program adoption, impact and sustainability. Performance evaluations include participation representativeness, ESM attendance and acceptability as well as change in relevant health outcomes. RESULTS: SMART D & I is implemented via a collaboration of 3 unique regional, epilepsy-focused nonprofit social service organizations and a university team that developed SMART. The ongoing collaboration is expanding SMART delivery to PWE across 13 U.S. states. Thus far, we have trained 17 Nurse and Peer Educators (NEs and PEs). PEs (N = 10) have a mean age 51.1 (SD 10.4) years and a mean age of epilepsy diagnosis of 29.4 (SD 19.3). Of 128 participants offered SMART, and who provided age data (N = 86) mean age was 37.7 years (SD 14.4). Of participants who provided data on gender and race (N = 89), 65 were women (73.9 %), 18 African-American (20.2 %). Mean age of epilepsy diagnosis was 19.4 years (SD 16.6) and 59 (52.2 %) of PWE reported having seizures in the last 30 days pre-SMART sessions. Among those with attendance data (N = 103), mean number of SMART groups attended was 5.7 (SD 2.3). Mean values for past 30-day seizure frequency, 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Inventory (GAD-7) and 10-item Quality of Life in Epilepsy Scale (QOLIE-10) for PWE that provided both pre and post SMART data were 7.6 (SD 15.8) vs 2.8 (SD 3.4) p = 0.3, 7.63 (SD 6.6) vs 6.3 (SD 5.7) p = 0.95, 6.6 (SD 5.7) vs 6.67(SD 5.3) p = 0.47 and 2.8 (SD 0.8) vs 2.7 (SD 1.0) p = 0.07 respectively. CONCLUSIONS: Implementing ESM using a RE-AIM/Iterative RE-AIM framework links intervention developers and community partners. While PWE have substantial barriers to health, including frequent seizures, they are able engage in the SMART program. Although a major limitation to patient-level evaluation is challenges in collecting post-SMART follow-up data, preliminary findings suggest a trend for improved quality of life.

Association Between Symptom Severity and Medication Adherence in Adults with Bipolar Disorder Reporting Adherence Challenges.

Background: Given the importance of medication adherence among individuals with bipolar disorder (BD), this analysis from an ongoing randomized controlled trial (RCT) examined the relationship between BD symptoms, functioning and adherence in 69 poorly adherent adults with BD. Method: Study inclusion criteria included being ≥ 18 years old with BD Type 1 or 2, difficulties with medication adherence and actively symptomatic as measured by Brief Psychiatric Rating Scale (BPRS) score ≥ 36, Young Mania Rating Scale (YMRS) > 8 or Montgomery Asberg Depression Rating Scale (MADRS) > 8. Adherence was measured in 2 ways: 1) the self-reported Tablets Routine Questionnaire (TRQ) and 2) electronic pill container monitoring (eCap pillbox). BD symptoms and functioning were measured with the MADRS, YMRS, Clinical Global Impressions Scale (CGI), and Global Assessment of Functioning (GAF). Only screening and baseline data were examined. Results: Mean age was 42.32 (SD = 12.99) years, with 72.46% (n = 50) female and 43.48% (n = 30) non-white. Mean past 7-day percentage of days with missed BD medications using TRQ was 40.63% (SD = 32.61) and 30.30% (SD = 30.41) at screening and baseline, respectively. Baseline adherence using eCap was 42.16% (SD = 35.85) in those with available eCap data (n = 41). Worse adherence based on TRQ was significantly associated with higher MADRS (p = 0.04) and CGI (p = .03) but lower GAF (p = 0.02). eCAP measured adherence was not significantly associated with clinical variables. Conclusion: While depression and functioning were approximate markers of adherence, reliance on patient self-report or BD symptom presentation may give an incomplete picture of medication-taking behaviors.

Influence of social determinants of health and adversity on computerized neurocognitive assessment.

Introduction: Social determinants of health and adversity, including poverty, maltreatment, and neighborhood deprivation, are individual-level factors that may significantly affect baseline neurocognitive testing and management that have yet to be thoroughly explored within the computerized neurocognitive assessment.Objectives: Examine individual-level experiences of poverty, abuse, neighborhood deprivation, and social mobility on computerized cognitive testing.Methods: The sample included 3,845 student-athletes who completed a baseline Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and were enrolled in the Child-Household Integrated Longitudinal Data database. Multivariable linear regressions were used to assess independent variables of Supplemental Nutrition Assistance Program enrollment, abuse or neglect cases, Area Deprivation Index scores, and other demographic factors on four baseline ImPACT composite scores: verbal and visual memory, visuomotor, and reaction time.Results: Individual-level factors of persistent poverty and neighborhood deprivation were associated with lower composite scores; however, upward social mobility was not significantly associated with cognitive performance. The effects of mother's race on computerized cognitive testing performance were attenuated when accounting for measures of adversity.Conclusion: Findings highlight the importance of social determinants of health in computerized neurocognitive testing to ensure more culturally sensitive and precise understanding of athletic baselines.

Physical comorbidities of older age bipolar disorder (OABD) patients: A global replication analysis of prevalence and sex differences.

OBJECTIVES: To compare the prevalence of physical morbidities between older aged patients with bipolar disorder (OABD) and non-psychiatric comparisons (NC), and to analyze sex differences in prevalence. METHODS: OABD was defined as bipolar disorder among adults aged ≥50 years. Outcomes analyzed were the prevalence of diseases affecting the cardiovascular, respiratory, gastrointestinal, genitourinary, renal, musculoskeletal, and endocrine systems. The analysis used cross-sectional data of OABD participants (n = 878; mean age 60.9 ± 8.0 years, n = 496 (56%) women) from the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) dataset and NC participants recruited at the same sites (n = 355; mean age 64.4 ± 9.7 years, n = 215 (61%) women). RESULTS: After controlling for sex, age, education, and smoking history, the OABD group had more cardiovascular (odds ratio [95% confidence interval]: 2.12 [1.38-3.30]), renal (5.97 [1.31-43.16]), musculoskeletal (2.09 [1.30-3.43]) and endocrine (1.90 [1.20-3.05]) diseases than NC. Women with OABD had more gastrointestinal (1.56 [0.99-2.49]), genitourinary (1.72 [1.02-2.92]), musculoskeletal (2.64 [1.66-4.37]) and endocrine (1.71 [1.08-2.73]) comorbidities than men with OABD, when age, education, smoking history, and study site were controlled. CONCLUSIONS: This replication GAGE-BD study confirms previous findings indicating that OABD present more physical morbidities than matched comparison participants, and that this health burden is significantly greater among women.

A person-centered approach to characterizing longitudinal ambulatory impairment in Parkinson's disease.

Loss of ambulation is common and highly variable in Parkinson's disease (PD), and poorly understood from the perspectives of those with PD. Gaining insights to the anticipated perceived trajectories and their drivers, will facilitate patient-centered care. Latent class growth analysis, a person-centered mixture modelling approach, was applied to 16,863 people with PD stratified by early (N = 8612; < 3 years), mid (N = 6181; 3-10 years) and later (N = 2070; > 10 years) disease to discern clusters with similar longitudinal patterns of self-reported walking difficulty, measured by EuroQoL 5D-5L that is validated for use in PD. There were four clusters in early and mid-disease strata, with a fifth identified in later disease. Trajectories ranged from none to moderate walking difficulty, with small clusters with severe problems. The percentage of subjects with moderate (early = 17.5%, mid = 26.4%, later = 32.5%) and severe (early = 3.8%, mid = 7.4%, later = 15.4%) walking difficulty at baseline increased across disease duration groups. The trajectories tended to be stable with variability in moderate and severe groups. Across strata, clusters with moderate to severe problems were associated with more severe impairment, depression, anxiety, arthritis, higher BMI, lower income, and lower education, but no consistent race or gender differences. The findings reveal distinct longitudinal patterns in perceived difficulties in walking in PD.

Adaptive and Innate Immunity Are Key Drivers of Age at Onset of Multiple Sclerosis.

Background and Objectives: Multiple sclerosis (MS) age at onset (AAO) is a clinical predictor of long-term disease outcomes, independent of disease duration. Little is known about the genetic and biological mechanisms underlying age of first symptoms. We conducted a genome-wide association study (GWAS) to investigate associations between individual genetic variation and the MS AAO phenotype. Methods: The study population was comprised participants with MS in 6 clinical trials: ADVANCE (N = 655; relapsing-remitting [RR] MS), ASCEND (N = 555; secondary-progressive [SP] MS), DECIDE (N = 1,017; RRMS), OPERA1 (N = 581; RRMS), OPERA2 (N = 577; RRMS), and ORATORIO (N = 529; primary-progressive [PP] MS). Altogether, 3,905 persons with MS of European ancestry were analyzed. GWAS were conducted for MS AAO in each trial using linear additive models controlling for sex and 10 principal components. Resultant summary statistics across the 6 trials were then meta-analyzed, for a total of 8.3 × 10-6 single nucleotide polymorphisms (SNPs) across all trials after quality control and filtering for heterogeneity. Gene-based tests of associations, pathway enrichment analyses, and Mendelian randomization analyses for select exposures were also performed. Results: Four lead SNPs within 2 loci were identified (p < 5 × 10-8), including a) 3 SNPs in the major histocompatibility complex and their effects were independent of HLA-DRB1*15:01 and b) a LOC105375167 variant on chromosome 7. At the gene level, the top association was HLA-C (p = 1.2 × 10-7), which plays an important role in antiviral immunity. Functional annotation revealed the enrichment of pathways related to T-cell receptor signaling, autoimmunity, and the complement cascade. Mendelian randomization analyses suggested a link between both earlier age at puberty and shorter telomere length and earlier AAO, while there was no evidence for a role for either body mass index or vitamin D levels. Discussion: Two genetic loci associated with MS AAO were identified, and functional annotation demonstrated an enrichment of genes involved in adaptive and complement immunity. There was also evidence supporting a link with age at puberty and telomere length. The findings suggest that AAO in MS is multifactorial, and the factors driving onset of symptoms overlap with those influencing MS risk.

Clinical correlates of negative health events and disparities among adults with epilepsy enrolled in a self-management clinical trial.

AIMS: Despite advances in care, people with epilepsy experience negative health events (NHEs), such as seizures, emergency department (ED) visits and hospitalizations. This analysis using baseline data from an epilepsy self-management clinical trial targeting people from rural regions and other underserved populations assessed the relationship between demographic and clinical variables vs. NHEs. METHODS: Data to evaluate disparities and clinical correlates was collected using patient surveys from a baseline sample of 94 participants in a larger prospective study of 160 individuals with epilepsy who experienced an NHE within the last six months. Demographic characteristics, mental and physical functional status assessed using 36-Item Short Form Health Survey questionnaire version 2 (SF-36v2), depression assessed with the 9-item Patient Health Questionnaire (PHQ-9), quality of life assessed with the 10-item Quality of Life in Epilepsy Inventory (QOLIE-10), self-efficacy assessed the Epilepsy Self-Efficacy Scale (ESES), social support assessed with the Multidimensional Scale of Perceived Social Support (MSPSS), self-management assessed with the Epilepsy Self-Management Scale (ESMS), and stigma assessed with the Epilepsy Stigma Scale (ESS) were all examined in association with past 6-month total NHE frequency as well as NHE sub-categories of past 30-day and 6-month seizure counts, self-harm attempts, ED visits and hospitalizations. An exploratory evaluation of NHE correlates in relation to the Rural Urban Continuum Code (RUCC) residence classification compared 3 subgroups of increasing rurality. Descriptive statistics were generated for demographic and clinical variables and NHEs, and exploratory analyses compared the distribution of demographic, clinical, and NHE variables by RUCC categorization. RESULTS: The mean age was 38.5 years (SD 11.9), predominantly female (N= 62, 66.0%) and white (N=81, 86.2%). Just a little under half (N=43, 45.7%) of participants had annual incomes of less than $25,000, and 40% (N=38) were rural residents (RUCC >3). The past 6-month NHEs count was 20.4 (SD 32.0). Seizures were the most common NHE with a mean 30-day seizure frequency = 5.4 (SD 11.8) and 6-month seizure frequency of 18.7 (SD 31.6). Other NHE types were less common with a past 6-month self-harm frequency of 0.16 (SD 1.55), ED visit frequency of 0.72 (SD 1.10), and hospitalization frequency of 0.28 (SD 1.02). There were few significant demographic and clinical correlates for total and sub-categories of NHEs. Worse physical health status, as measured by the physical component summary (PCS) of the SF-36v2, was significantly associated with 6-month seizure counts (p=.04). There were no significant differences between the 3 RUCC subgroups on demographic variables. However, past 30-day seizure count, past 6-month seizure count and total past 6-month NHE counts were all higher among individuals from more rural settings (p-values <.01 for each). CONCLUSIONS: Rural adults with epilepsy were more likely to have a greater number of seizures and more epilepsy complications in general. Worse physical health function was also associated with more epilepsy complications. However, this analysis found few other demographic and clinical correlates of cumulative NHEs among adults with epilepsy. Additional efforts are needed to investigate health disparities among people with epilepsy who live in rural regions or who have poor physical health function.

Bipolar symptoms, somatic burden and functioning in older-age bipolar disorder: A replication study from the global aging & geriatric experiments in bipolar disorder database (GAGE-BD) project.

OBJECTIVES: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean ± standard deviation age 47.2 ± 13.5, 65% women, 49% aged over 50) dataset. DESIGN/METHODS: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601). RESULTS: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p ≤ 0.001, depression p ≤ 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning. CONCLUSIONS: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning.

Beta-defensin index: A functional biomarker for oral cancer detection.

There is an unmet clinical need for a non-invasive and cost-effective test for oral squamous cell carcinoma (OSCC) that informs clinicians when a biopsy is warranted. Human beta-defensin 3 (hBD-3), an epithelial cell-derived anti-microbial peptide, is pro-tumorigenic and overexpressed in early-stage OSCC compared to hBD-2. We validate this expression dichotomy in carcinoma in situ and OSCC lesions using immunofluorescence microscopy and flow cytometry. The proportion of hBD-3/hBD-2 levels in non-invasively collected lesional cells compared to contralateral normal cells, obtained by ELISA, generates the beta-defensin index (BDI). Proof-of-principle and blinded discovery studies demonstrate that BDI discriminates OSCC from benign lesions. A multi-center validation study shows sensitivity and specificity values of 98.2% (95% confidence interval [CI] 90.3-99.9) and 82.6% (95% CI 68.6-92.2), respectively. A proof-of-principle study shows that BDI is adaptable to a point-of-care assay using microfluidics. We propose that BDI may fulfill a major unmet need in low-socioeconomic countries where pathology services are lacking.

Cognition in older age bipolar disorder: An analysis of archival data across the globe.

BACKGROUND: Cognitive deficits in bipolar disorder (BD) impact functioning and are main contributors to disability in older age BD (OABD). We investigated the difference between OABD and age-comparable healthy comparison (HC) participants and, among those with BD, the associations between age, global cognitive performance, symptom severity and functioning using a large, cross-sectional, archival dataset harmonized from 7 international OABD studies. METHODS: Data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) database, spanning various standardized measures of cognition, functioning and clinical characteristics, were analyzed. The sample included 662 euthymic to mildly symptomatic participants aged minimum 50years (509 BD, 153 HC), able to undergo extensive cognitive testing. Linear mixed models estimated associations between diagnosis and global cognitive performance (g-score, harmonized across studies), and within OABD between g-score and severity of mania and depressive symptoms, duration of illness and lithium use and of global functioning. RESULTS: After adjustment for study cohort, age, gender and employment status, there was no significant difference in g-score between OABD and HC, while a significant interaction emerged between employment status and diagnostic group (better global cognition associated with working) in BD. Within OABD, better g-scores were associated with fewer manic symptoms, higher education and better functioning. LIMITATIONS: Cross-sectional design and loss of granularity due to harmonization. CONCLUSION: More research is needed to understand heterogenous longitudinal patterns of cognitive change in BD and understand whether particular cognitive domains might be affected in OABD in order to develop new therapeutic efforts for cognitive dysfunction OABD.

Male sexual and reproductive health in multiple sclerosis: a scoping review.

BACKGROUND: Multiple sclerosis (MS) is a chronic neuroinflammatory disease with highest incidence during the period of optimal reproductive health. This scoping review aimed to identify and summarize available data on sexual/reproductive health in males with MS (MwMS). METHODS: This review was based on PRISMA extension for Scoping Review. PubMed database was searched for keyword "multiple sclerosis" alongside keywords "sexual health", "reproductive health", "family planning", "male fertility", "male infertility", "sexual dysfunction", and "erectile dysfunction", iteratively using the "AND" logical operator. Descriptive analysis was performed on the included articles. RESULTS: Thirty-four studies were included, and four topics emerged: sexual dysfunction, erectile dysfunction, fertility, and family planning. Sexual dysfunction is common in MwMS (35-72%), yet only a minority of MwMS discuss their sexual health with their treatment teams. Both MS disability and depression were associated with sexual dysfunction in MwMS, with erectile dysfunction and decreased libido as the most prevalent aspects of sexual dysfunction. Positively, phosphodiesterase-5 inhibitors appear effective for treating erectile dysfunction and improving sexual quality of life in MwMS. There may also be a relationship between MS and male infertility, though changes in sexual behavior may underlie this association. Finally, a prominent knowledge gap was observed for disease-modifying therapy use and family planning in MwMS. CONCLUSION: Sexual dysfunction is common, impacted by MS severity, and associates with decreased quality of life in MwMS. Communication barriers regarding sexual and reproductive health appear to exist between MwMS and providers, as do literature gaps related to MS therapeutics and sexual/reproductive health.

Sociodemographic and clinical characteristics of people with oldest older age bipolar disorder in a global sample: Results from the global aging and geriatric experiments in bipolar disorder project.

OBJECTS: Studies of older age bipolar disorder (OABD) have mostly focused on "younger old" individuals. Little is known about the oldest OABD (OOABD) individuals aged ≥70 years old. The Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) project provides an opportunity to evaluate the OOABD group to understand their characteristics compared to younger groups. METHODS: We conducted cross-sectional analyses of the GAGE-BD database, an integrated, harmonized dataset from 19 international studies. We compared the sociodemographic and clinical characteristics of those aged <50 (YABD, n = 184), 50-69 (OABD, n = 881), and ≥70 (OOABD, n = 304). To standardize the comparisons between age categories and all characteristics, we used multinomial logistic regression models with age category as the dependent variable, with each characteristic as the independent variable, and clustering of standard errors to account for the correlation between observations from each of the studies. RESULTS: OOABD and OABD had lower severity of manic symptoms (Mean YMRS = 3.3, 3.8 respectively) than YABD (YMRS = 7.6), and lower depressive symptoms (% of absent = 65.4%, and 59.5% respectively) than YABD (18.3%). OOABD and OABD had higher physical burden than YABD, especially in the cardiovascular domain (prevalence = 65% in OOABD, 41% in OABD and 17% in YABD); OOABD had the highest prevalence (56%) in the musculoskeletal domain (significantly differed from 39% in OABD and 31% in YABD which didn't differ from each other). Overall, OOABD had significant cumulative physical burden in numbers of domains (mean = 4) compared to both OABD (mean = 2) and YABD (mean = 1). OOABD had the lowest rates of suicidal thoughts (10%), which significantly differed from YABD (26%) though didn't differ from OABD (21%). Functional status was higher in both OOABD (GAF = 63) and OABD (GAF = 64), though only OABD had significantly higher function than YABD (GAF = 59). CONCLUSIONS: OOABD have unique features, suggesting that (1) OOABD individuals may be easier to manage psychiatrically, but require more attention to comorbid physical conditions; (2) OOABD is a survivor cohort associated with resilience despite high medical burden, warranting both qualitative and quantitative methods to better understand how to advance clinical care and ways to age successfully with BD.

Prevalence of neuromyelitis optica spectrum disorder in the United States.

BACKGROUND: Neuromyelitis optic spectrum disorder (NMOSD) is a rare demyelinating, autoimmune disease and the burden in United States is not well characterized. OBJECTIVE: The objective of this study was to determine the 2022 US prevalence of NMOSD. METHODS: We constructed a cross-sectional study using aggregated electronic health record data for 25.7 million patients who had a 2022 clinical encounter. The data originated from the TriNetX US Collaborative Network of 55 healthcare organizations that span all 50 states. NMOSD prevalence was determined by querying for age-interval, sex, and race combinations, with direct standardization to the 2022 US Census data. RESULTS: There were 1772 NMOSD patients among 25,743,039 patients for a prevalence of 6.88/100,000. Prevalence was the highest in Blacks (12.99/100,000) who represented 27.7% of NMOSD patients, then Asians (9.41/100,000and Whites (5.58/100,000). Among females, the prevalence of NMOSD was 9.48/100,000, and Black and Asian females had a 2.65- and 1.94-times higher prevalence than White females. In males, the prevalence of NMOSD was 3.52/100,000 and it did not differ by race. We observed a 3/5:1 female-to-male ratio in NMOSD. The age- and sex-adjusted 2022 estimate of persons with NMOSD in the United States was 15,413 females and 6233 males. CONCLUSION: We estimate that there were near 22,000 Americans living with NMOSD in 2022.

Common Social and Health Disparities Contribute to Racial Differences in Ambulatory Impairment in Multiple Sclerosis.

BACKGROUND: We previously reported more rapid accrual of ambulatory impairments in Black compared to White individuals with relapsing remitting multiple sclerosis (RRMS) and higher body mass index (BMI). Hypertension and lower neighborhood socioeconomic status (SES) were associated with greater impairment, irrespective of race. We hypothesize that these common social and health inequities may explain a substantial portion of the racial differences in ambulation in American individuals with RRMS. METHODS: Causal mediation analyses investigated baseline and change-over-time mediators of ambulatory impairment differences between 1795 Black and White individuals with RRMS using a retrospective cohort study comprised of electronic health record data from 8491 clinical encounters between 2008 and 2015 where Timed 25-Foot Walk (T25FW) speeds without assistive devices were recorded. The hypothesis was that BMI, neighborhood SES, and hypertension were possible mediators. RESULTS: At baseline, Black individuals with RRMS (n = 175) had significantly slower T25FW speeds (5.78 vs 5.27 ft/s), higher BMI, a higher prevalence of hypertension, and they were more likely to live in lower-income neighborhoods than White individuals (n = 1,620). At baseline, a significant proportion (33.7%; 95% CI, 18.9%-59.4%) of the T25FW difference between Black and White individuals was indirectly due to a higher BMI (12.5%), hypertension burden (9.5%), and living in lower-income neighborhoods (11.2%). Once baseline mediation relationships were accounted for, there were no significant longitudinal mediation relationships. CONCLUSIONS: The findings implicate social and health disparities as prominent drivers of ambulatory differences between Black and White individuals with RRMS, suggesting that wellness and health promotion are essential components of MS care, particularly for Black individuals.

Sex Differences Among Older Adults With Bipolar Disorder: Results From the Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) Project.

OBJECTIVE: Sex-specific research in adult bipolar disorder (BD) is sparse and even more so among those with older age bipolar disorder (OABD). Knowledge about sex differences across the bipolar lifespan is urgently needed to target and improve treatment. To address this gap, the current study examined sex differences in the domains of clinical presentation, general functioning, and mood symptoms among individuals with OABD. METHODS: This Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) study used data from 19 international studies including BD patients aged ≥50 years (N = 1,185: 645 women, 540 men).A comparison of mood symptoms between women and men was conducted initially using two-tailed t tests and then accounting for systematic differences between the contributing cohorts by performing generalized linear mixed models (GLMMs). Associations between sex and other clinical characteristics were examined using GLMM including: age, BD subtype, rapid cycling, psychiatric hospitalization, lifetime psychiatric comorbidity, and physical health comorbidity, with study cohort as a random intercept. RESULTS: Regarding depressive mood symptoms, women had higher scores on anxiety and hypochondriasis items. Female sex was associated with more psychiatric hospitalizations and male sex with lifetime substance abuse disorders. CONCLUSION: Our findings show important clinical sex differences and provide support that older age women experience a more severe course of BD, with higher rates of psychiatric hospitalization. The reasons for this may be biological, psychological, or social. These differences as well as underlying mechanisms should be a focus for healthcare professionals and need to be studied further.