The timed 25-foot walk in a large cohort of multiple sclerosis patients.

BACKGROUND: The timed 25-foot walk (T25FW) is a key clinical outcome measure in multiple sclerosis patient management and clinical research. OBJECTIVES: To evaluate T25FW performance and factors associated with its change in the Multiple Sclerosis Outcome Assessments Consortium (MSOAC) Placebo Database (n = 2465). METHODS: We created confirmed disability progression (CDP) variables for T25FW and Expanded Disability Status Scale (EDSS) outcomes. We used intraclass correlation coefficients (ICCs) and Bland Altman plots to evaluate reliability. We evaluated T25FW changes and predictive validity using a mixed-effects model, survival analysis, and nested case-control analysis. RESULTS: The mean baseline score for the T25FW in this study population was 9.2 seconds, median = 6.1 (standard deviation = 11.0, interquartile range (IQR) = 4.8, 9.0). The T25FW measure demonstrated excellent test-retest reliability (ICC = 0.98). Walk times increased with age, disability, disease type, and disease duration; relapses were not associated with an increase. Patients with T25FW progression had a faster time to EDSS-CDP compared to those without (hazards ratio (HR): 2.6; confidence interval (CI): 2.2, 3.1). Changes in the T25FW were more likely to precede changes in EDSS. CONCLUSION: This research confirms the association of the T25FW with disability and provides some evidence of predictive validity. Our findings support the continued use of the T25FW in clinical practice and clinical trials.

Cardiovascular Diseases, Medications, and ALS: A Population-Based Case-Control Study.

INTRODUCTION: We investigated the associations between antecedent all-cause CVD diagnoses, cause-specific CVD diagnosis, and CVD medication prescriptions with the risk of developing amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: We conducted a population-based case-control study of U.S. Medicare enrollees from 2006 to 2013. The final sample included 3,714 incident ALS cases and 18,570 controls (matched on age, sex, enrollment length, and county). Information was collected from Medicare Parts A, B, and D administrative claims data on hypertension, ischemic heart disease, heart failure, acute myocardial infarction, atrial fibrillation, prescriptions of angiotensin-converting enzyme inhibitors, angiotensin II receptors blockers, calcium channel blockers, beta blockers, and antiarrhythmics. Associations were evaluated using conditional logistic regression adjusting for age, sex, race/ethnicity, geographical location, alcohol and tobacco use, and socioeconomic status. RESULTS: The odds ratio (OR) for having one or more ICD-9 codes for any cardiovascular disease diagnosis at least 24 months prior to the date of ALS diagnosis was 0.85 (95% confidence interval [CI]: 0.78-0.92). Cardiovascular conditions that were inversely associated with ALS included heart failure (OR = 0.79; 95% CI 0.70-0.89), atrial fibrillation (OR = 0.81; 95% CI 0.77-0.92), and hypertension (OR = 0.91; 95% CI 0.84-0.98). Exposures to several classes of cardiovascular medications were inversely associated with ALS risk even after adjusting for confounding by indication, including ACE inhibitors (OR = 0.84, 95% CI 0.77-0.91), calcium channel blockers (OR = 0.64, 95% CI 0.59-0.70), and beta blockers (OR = 0.76, 95% CI 0.71-0.83). DISCUSSION/CONCLUSION: These findings merit additional research, including animal studies and pilot clinical trials, to further evaluate and evidence the effects of ACEIs, CCBs, and BBs on the risk of developing and clinical expression of ALS.

Impact of Iowa's Prescription Monitoring Program on Opioid Pain Reliever Prescribing Patterns: An Interrupted Time Series Study 2003-2014.

OBJECTIVE: To evaluate the impact of Iowa's prescription monitoring program (PMP), implemented in 2009, on opioid pain reliever (OPR) prescribing patterns. METHODS: We conducted interrupted time series analyses using 2003-2014 health insurance claims from a private health insurer in Iowa. OPR prescriptions for all beneficiaries were included. Another data set included only OPR prescription for new opioid users required to have six months of insurance coverage. We evaluate four OPR prescribing patterns: 1) average daily dosage in morphine milligrams equivalents (MME), 2) MME per prescription, 3) average days' supply per prescription, and 4) prescription rate per 1,000 insured person-years. We examined confounding and effect measure modification of the relationship between PMP and prescribing patterns by age and sex. RESULTS: During the 12 years of follow-up, 1,512,388 insured Iowans contributed 6,169,634.92 person-years of follow-up. Of these, 505,274 patients filled 2,401,818 OPR prescriptions and 360,688 new OPR users filled as many first OPR prescriptions. The increasing trend of OPR prescription rates from 2003 to 2009 declined post-PMP. Similarly, there was a large decline in MME per day and MME per prescription. The OPR days' supply kept increasing post-PMP implementation, albeit at a slightly slower rate than pre-PMP implementation. There was no confounding by age and sex; however, we observed heterogeneity by age and sex; patients aged ≥50 years and females received higher doses and more prescriptions pre-PMP and experienced the greatest declines post-PMP. CONCLUSIONS: Our study suggests that Iowa PMP implementation may have resulted in declines in OPR prescribing, and this impact varies by patient age and sex.

Prevalence, Demographic, and Clinical Factors Associated With Cognitive Dysfunction in Patients With Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a chronic CNS demyelinating autoimmune disorder targeting the astrocyte antigen aquaporin-4 (AQP4), typically presenting with optic neuritis, transverse myelitis, and brain syndromes. Cognitive dysfunction (CD) in NMOSD is under-recognized and poorly understood. The purpose of this study was to evaluate the prevalence and clinical variables associated with CD in NMOSD. METHODS: This observational retrospective study with longitudinal follow-up describes a clinical cohort seen in the Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD. Serial Montreal Cognitive Assessments (MoCAs) were performed upon enrollment and at 6-month intervals to evaluate longitudinal cognitive function relative to demographic and disease-related factors. We used 2-tailed t test, analysis of variance, the χ2 test, linear regression for univariable and adjusted analyses and simultaneous linear regression and mixed-effects model for multivariable analyses. RESULTS: Thirty-four percent (75/219) of patients met criteria for CD (MoCA <26); 29% (64/219) showed mild dysfunction (MoCA 20-26/30), and 5% (11/219) showed moderate (MoCA <20/30) dysfunction. Patients with less neurologic disability and lower pain scores had higher MoCA scores (95% CI 0.24-0.65 and 95% CI 0.09-0.42, respectively). Patients with at least high school education scored higher on the MoCA (95% CI 2.2-5). When comparing patients dichotomized for CD, patients never on rituximab scored higher than patients only treated with rituximab (p < 0.029). There was no significant association between annualized relapse rate, age, sex, disease duration, AQP4 serostatus or brain lesions, and CD. CD was more pronounced among Black than White patients (95% CI -2.7 to -0.7). Multivariable analysis of serial MoCA did not indicate change (p = 0.715). Descriptive analysis of serial MoCA showed 30% (45/150) of patients with worsening MoCA performance had impaired language and verbal recall. DISCUSSION: To our knowledge, this is the largest study of diverse cohort to investigate CD in patients with NMOSD. Our findings demonstrate 34% of patients with NMOSD experience mild-to-moderate CD, while 30% of patients demonstrated decline on serial testing. The substantial prevalence of CD in this pilot report highlights the need for improved and validated screening tools and comprehensive measures to investigate CD in NMOSD.

Bringing Micro to the Macro: How Citizen Science Data Enrich Geospatial Visualizations to Advance Health Equity.

Social and spatial contexts affect health, and understanding nuances of context is key to informing successful interventions for health equity. Layering mixed methods and mixed scale data sources to visualize patterns of health outcomes facilitates analysis of both broad trends and person-level experiences across time and space. We used micro-scale citizen scientist-collected data from four Bay Area communities along with aggregate epidemiologic and population-level data sets to illustrate barriers to, and facilitators of, physical activity in low-income aging adults. These data integrations highlight the synergistic value added by combining data sources, and what might be missed by relying on either a micro- or macro-level data source alone. Mixed methods and granularity data integration can generate a deeper understanding of environmental context, which in turn can inform more relevant and attainable community, advocacy, and policy improvements.

Utilizing the AIM Curriculum to Improve Job Performance in an Educational Setting for Children With Autism and Related Disabilities.

The current study evaluated the effect of brief, daily present moment awareness activities on the work performance of paraprofessionals working at a school for children with disabilities. A nonconcurrent multiple-baseline design across three participants evaluated changes in staff-initiated interactions with students and staff's accuracy of data collection on student behavior. Relative to baseline, participants demonstrated an average increase in staff-initiated interactions and an increase in the average percentage accuracy of data collection. Participants averaged 10.02 (range 3.4-16.67) staff-initiated interactions during baseline and 15.38 (range 9.75-24.4) during the intervention phase. Relative to baseline, two of the three participants demonstrated an increase in their average accuracy of data collection on student behavior. Participants' average data collection accuracy was 56.9% (range 40%-86.67%) during baseline and 91.98% (range 86.41%-100%) during intervention. The average percentage of nonoverlapping data was 61.67% (range 25%-100%) for staff-initiated interactions and 33.33% (range 0%-100%) for data collection accuracy. Implications and possibilities for future research related to acceptance and commitment training interventions in workplace environments are discussed.

Using Relational Training to Improve Performance During Acceptance and Commitment Training Sessions.

The current study investigated the effect of relational training on improving engagement during acceptance and commitment training (ACT) sessions that aimed to reduce maladaptive behavior. Three female children diagnosed with autism participated in the current research. The relational training protocol involved eight programs designed to improve participants' ability to engage in relational responding. A concurrent multiple-baseline across-participants design was used, and participants' maladaptive behavior during ACT sessions was recorded. Results indicated a decrease in maladaptive behavior for one of the three participants, with a medium to large treatment effect. A secondary measure also showed improvement in all three participants' performance during ACT sessions. The percentage of nonoverlapping data and Cohen's d suggest a small to moderate treatment effect. Implications for implementing ACT with individuals diagnosed with autism are discussed.

Association Between Income Inequality and County-Level COVID-19 Cases and Deaths in the US.

Importance: Socioeconomically marginalized communities have been disproportionately affected by the COVID-19 pandemic. Income inequality may be a risk factor for SARS-CoV-2 infection and death from COVID-19. Objective: To evaluate the association between county-level income inequality and COVID-19 cases and deaths from March 2020 through February 2021 in bimonthly time epochs. Design, Setting, and Participants: This ecological cohort study used longitudinal data on county-level COVID-19 cases and deaths from March 1, 2020, through February 28, 2021, in 3220 counties from all 50 states, Puerto Rico, and the District of Columbia. Main Outcomes and Measures: County-level daily COVID-19 case and death data from March 1, 2020, through February 28, 2021, were extracted from the COVID-19 Data Repository by the Center for Systems Science and Engineering at Johns Hopkins University in Baltimore, Maryland. Exposure: The Gini coefficient, a measure of unequal income distribution (presented as a value between 0 and 1, where 0 represents a perfectly equal geographical region where all income is equally shared and 1 represents a perfectly unequal society where all income is earned by 1 individual), and other county-level data were obtained primarily from the 2014 to 2018 American Community Survey 5-year estimates. Covariates included median proportions of poverty, age, race/ethnicity, crowding given by occupancy per room, urbanicity and rurality, educational level, number of physicians per 100 000 individuals, state, and mask use at the county level. Results: As of February 28, 2021, on average, each county recorded a median of 8891 cases of COVID-19 per 100 000 individuals (interquartile range, 6935-10 666 cases per 100 000 individuals) and 156 deaths per 100 000 individuals (interquartile range, 94-228 deaths per 100 000 individuals). The median county-level Gini coefficient was 0.44 (interquartile range, 0.42-0.47). There was a positive correlation between Gini coefficients and county-level COVID-19 cases (Spearman ρ = 0.052; P < .001) and deaths (Spearman ρ = 0.134; P < .001) during the study period. This association varied over time; each 0.05-unit increase in Gini coefficient was associated with an adjusted relative risk of COVID-19 deaths: 1.25 (95% CI, 1.17-1.33) in March and April 2020, 1.20 (95% CI, 1.13-1.28) in May and June 2020, 1.46 (95% CI, 1.37-1.55) in July and August 2020, 1.04 (95% CI, 0.98-1.10) in September and October 2020, 0.76 (95% CI, 0.72-0.81) in November and December 2020, and 1.02 (95% CI, 0.96-1.07) in January and February 2021 (P < .001 for interaction). The adjusted association of the Gini coefficient with COVID-19 cases also reached a peak in July and August 2020 (relative risk, 1.28 [95% CI, 1.22-1.33]). Conclusions and Relevance: This study suggests that income inequality within US counties was associated with more cases and deaths due to COVID-19 in the summer months of 2020. The COVID-19 pandemic has highlighted the vast disparities that exist in health outcomes owing to income inequality in the US. Targeted interventions should be focused on areas of income inequality to both flatten the curve and lessen the burden of inequality.

Approximate Bayesian computation for spatial SEIR(S) epidemic models.

Approximate Bayesia n Computation (ABC) provides an attractive approach to estimation in complex Bayesian inferential problems for which evaluation of the kernel of the posterior distribution is impossible or computationally expensive. These highly parallelizable techniques have been successfully applied to many fields, particularly in cases where more traditional approaches such as Markov chain Monte Carlo (MCMC) are impractical. In this work, we demonstrate the application of approximate Bayesian inference to spatially heterogeneous Susceptible-Exposed-Infectious-Removed (SEIR) stochastic epidemic models. These models have a tractable posterior distribution, however MCMC techniques nevertheless become computationally infeasible for moderately sized problems. We discuss the practical implementation of these techniques via the open source ABSEIR package for R. The performance of ABC relative to traditional MCMC methods in a small problem is explored under simulation, as well as in the spatially heterogeneous context of the 2014 epidemic of Chikungunya in the Americas.

Randomized, controlled, double-blinded field trial to assess Leishmania vaccine effectiveness as immunotherapy for canine leishmaniosis.

Better tools are necessary to eliminate visceral leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic leishmaniasis. We performed a double-blinded, block-randomized, placebo-controlled, vaccine immunotherapy trial testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted, vaccine, LeishTec®, in owned hunting dogs infected with L. infantum. The primary outcome was reduction of clinical progression, with reduction of mortality as a secondary outcome. Vaccination as an immunotherapy reduced the risk of progression to clinically overt leishmaniasis by 25% in asymptomatic dogs (RR: 1.33 95% C.I. 1.009-1.786 p-value: 0.0450). Receiving vaccine vs. placebo reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95% C.I.: 1.185-8.502 p-value = 0.0245). Vaccination of infected-healthy animals with an anti-Leishmania vaccine significantly reduced clinical progression and decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be a tool for Leishmania control.

Spirituality and well-being: the relationship between religious coping and recovery from sexual assault.

Despite a growing body of literature documenting beneficial outcomes of religious coping, there are virtually no studies examining sexual assault survivors' use of religious coping. To fill this gap in the literature, the current study examines predictors and outcomes of positive and negative religious coping among 100 sexual assault survivors who believed in God. Results suggested that African American survivors were more likely to use both forms of religious coping than survivors from other ethnicities. Yet, results also suggest that positive religious coping is related to higher levels of psychological well-being and lower levels of depression, whereas negative religious coping is related to higher levels of depression, regardless of ethnicity. The only outcome where ethnicity makes a difference is posttraumatic growth with a stronger relationship between positive religious coping and posttraumatic growth among Caucasian survivors space. The implications of these findings for research and practice are discussed.