Neighborhood Resources and Health Outcomes Among Stroke Survivors in a Population-Based Cohort.

BACKGROUND: Stroke survivors believe neighborhood resources such as community centers are beneficial; however, little is known about the influence of these resources on stroke outcomes. We evaluated whether residing in neighborhoods with greater resource density is associated with favorable post-stroke outcomes. METHODS AND RESULTS: We included Mexican American and non-Hispanic White stroke survivors from the Brain Attack Surveillance in Corpus Christi project (2009-2019). The exposure was density of neighborhood resources (eg, community centers, restaurants, stores) within a residential census tract at stroke onset. Outcomes included time to death and recurrence, and at 3 months following stroke: disability (activities of daily living/instrumental activities of daily living), cognition (Modified Mini-Mental State Exam), depression (Patient Health Questionnaire-8), and quality of life (abbreviated Stroke-Specific Quality of Life scale). We fit multivariable Cox regression and mixed linear models. We considered interactions with stroke severity, ethnicity, and sex. Among 1786 stroke survivors, median age was 64 years (interquartile range, 56-73), 55% men, and 62% Mexican American. Resource density was not associated with death, recurrence, or depression. Greater resource density (75th versus 25th percentile) was associated with more favorable cognition (Modified Mini-Mental State Exam mean difference=0.838, 95% CI=0.092, 1.584) and among moderate-severe stroke survivors, with more favorable functioning (activities of daily living/instrumental activities of daily living=-0.156 [95% CI, -0.284 to 0.027]) and quality of life (abbreviated Stroke-Specific Quality of Life scale=0.194 [95% CI, 0.029-0.359]). CONCLUSIONS: We observed associations between greater resource density and cognition overall and with functioning and quality of life among moderate-severe stroke survivors. Further research is needed to confirm these findings and determine if neighborhood resources may be a tool for recovery.

Association of Neighborhood Recreation Centers and Poststroke Outcomes in a Population-Based Cohort.

BACKGROUND: Higher neighborhood socioeconomic status has been favorably associated with stroke outcomes. This may be due to these areas having more beneficial resources such as recreational centers. We aimed to determine if neighborhood density of recreation centers is favorably associated with stroke outcomes. METHODS: We conducted analyses of data from the Brain Attack Surveillance in Corpus Christi project, a cohort of stroke survivors ≥45 years of age residing in Nueces County, TX (2009-2020). We included non-Hispanic White and Mexican American incident stroke survivors, who were not institutionalized prestroke and completed baseline and follow-up assessments (N=1392). We calculated the density of fitness and recreational sports centers within their residential census tract during the year of their stroke. Outcomes included function (self-ratings on activities of daily living and instrumental activities of daily living), cognition (modified mini-mental state exam), depression (Patient Health Questionnaire-8), and quality of life (abbreviated Stroke-Specific Quality of Life Scale). We fit confounder-adjusted gamma-distributed mixed generalized linear models with a log link for each outcome and considered interaction with stroke severity. RESULTS: On average, participants were 65 years old, 53% male, and 63% Mexican American. Median recreational centers were 1.60 per square mile (interquartile range, 0.41-3.06). Among moderate-severe stroke survivors, greater density of recreation centers (75th versus 25th percentile) was associated with more favorable function and possibly quality of life (activities of daily living/instrumental activities of daily living, 4.8% change [95% CI, -0.11% to -9.27%]; Stroke-Specific Quality of Life Scale, 3.7% change [95% CI, -0.7% to 8.2%]). Minimal nonsignificant differences were observed among the overall stroke population and those with mild stroke. CONCLUSIONS: The availability of recreation centers may be beneficial for poststroke function and quality of life among those with moderate-severe stroke. If further research confirms recreation centers to be beneficial, this could inform rehabilitation following stroke.

Air Pollution and Maximum Temperature Are Associated with Neurodevelopmental Regressive Events in Autism Spectrum Disorder.

Neurodevelopmental regression (NDR) is an enigmatic event associated with autism spectrum disorder (ASD) during which a child loses previously acquired skills and develops ASD symptoms. In some, a trigger which precedes the NDR event, such as a fever, can be identified, but in many cases no trigger is obvious. We hypothesize that air pollution (PM2.5) may trigger NDR, especially in those children without an identified trigger. Average daily PM2.5, ozone, precipitation and maximum temperature (Tmax) were derived from Environmental Protection Agency models and National Oceanic and Atmospheric Administration monitors based on zip-code information from 83 ASD participants during the six-weeks following the onset month of an NDR event and a reference period defined as one year before and one year after the event. Seasonally adjusted logistic regression (LR) and linear mixed models (LMM) compared cases (with a history of NDR) and matched controls (without a history of NDR). LR models found that the risk of NDR was related to higher PM2.5 during 3 to 6 weeks of the NDR event period, particularly in those without a trigger. Overall, both models converged on NDR being related to a higher PM2.5 and lower Tmax both during the NDR event period as well as the reference period, particularly in those without a known trigger. This temporal pattern suggests that environmental triggers, particularly PM2.5, could be related to NDR, especially in those without an identifiable trigger. Further studies to determine the underlying biological mechanism of this observation could help better understand NDR and provide opportunities to prevent NDR.

The Influence of Diabetes Status on the Rate of Cataract Surgery Following Pars Plana Vitrectomy.

PURPOSE: We aimed to evaluate the association between diabetic status and the rates of cataract extraction (CE) following pars plana vitrectomy (PPV). DESIGN: Retrospective cohort, multicenter database study. PARTICIPANTS: Patients were selected from an insurance claims database (PharMetrics LifeLink) that included persons who had filed claims between 2006 and 2015 in the United States. METHODS: We analyzed the records of 22 146 patients who underwent PPV performed by 2705 retina physicians. The vitrectomy group included patients ≥18 years of age who had undergone PPV. The control group included patients who were matched to the vitrectomy group 1:2 based on sex, diabetes mellitus (DM) status, region of the United States, and Charleston Comorbidity Index. MAIN OUTCOME MEASURES: Hazard ratios (HRs) and rates of cataract surgery in patients with and without diabetes who had undergone prior PPV. RESULTS: The hazard ratio for post-PPV CE was lower among patients with diabetes (3.307; 95% confidence interval [CI], 3.051-3.583) than among patients without diabetes (4.889; 95% CI, 4.670-5.119). This association was significant for all subgroups of patients with diabetes except in patients with diabetes and without retinopathy (4.086; 95% CI, 3.511-4.754). There was a significantly longer time between PPV and CE in patients with diabetes (537 days; 95% CI, 459-677 days) compared with those without diabetes (295 days; 95% CI, 278-312 days). The type of DM (type 1 vs. type 2) did not influence the rate of post-PPV cataract surgery. In persons with diabetes who underwent PPV, we observed a trend for a lower HR of cataract surgery in eyes with proliferative retinopathy (0.903; 95% CI, 0.725-1.124), and nonproliferative retinopathy (0.965; 95% CI, 0.721-1.290) compared with eyes with no retinopathy. CONCLUSIONS: Eyes of patients with diabetes had a significantly decreased risk of undergoing CE after PPV surgery compared with eyes of patients without diabetes.

Intravenous immunoglobulin for the treatment of autoimmune encephalopathy in children with autism.

The identification of brain-targeted autoantibodies in children with autism spectrum disorder (ASD) raises the possibility of autoimmune encephalopathy (AIE). Intravenous immunoglobulin (IVIG) is effective for AIE and for some children with ASD. Here, we present the largest case series of children with ASD treated with IVIG. Through an ASD clinic, we screened 82 children for AIE, 80 of them with ASD. IVIG was recommended for 49 (60%) with 31 (38%) receiving the treatment under our care team. The majority of parents (90%) reported some improvement with 71% reporting improvements in two or more symptoms. In a subset of patients, Aberrant Behavior Checklist (ABC) and/or Social Responsiveness Scale (SRS) were completed before and during IVIG treatment. Statistically significant improvement occurred in the SRS and ABC. The antidopamine D2L receptor antibody, the anti-tubulin antibody and the ratio of the antidopamine D2L to D1 receptor antibodies were related to changes in the ABC. The Cunningham Panel predicted SRS, ABC, parent-based treatment responses with good accuracy. Adverse effects were common (62%) but mostly limited to the infusion period. Only two (6%) patients discontinued IVIG because of adverse effects. Overall, our open-label case series provides support for the possibility that some children with ASD may benefit from IVIG. Given that adverse effects are not uncommon, IVIG treatment needs to be considered cautiously. We identified immune biomarkers in select IVIG responders but larger cohorts are needed to study immune biomarkers in more detail. Our small open-label exploratory trial provides evidence supporting a neuroimmune subgroup in patients with ASD.

Comparison of Treatment for Metabolic Disorders Associated with Autism:Reanalysis of Three Clinical Trials.

Autism spectrum disorder (ASD) affects about 1 in 45 individuals in the United States, yet effective treatments are yet to be defined. There is growing evidence that ASD is associated with abnormalities in several metabolic pathways, including the inter-connected folate, methylation and glutathione pathways. Several treatments that can therapeutically target these pathways have been tested in preliminary clinical trials. The combination of methylcobalamin (mB12) with low-dose folinic acid (LDFA) and sapropterin, a synthetic form of tetrahydrobiopterin (BH4) have been studied in open-label trials while high-dose folinic acid has been studied in a double-blind placebo controlled trial. All of these treatments have the potential to positively affect folate, methylation and glutathione pathways. Although the effect of mB12/LDFA and BH4 on methylation and glutathione metabolism have been examined in the open-label studies, these changes have not been compared to controls who received a placebo in order to account for the natural variation in the changes in these pathways. Furthermore, the recent study using high-dose folinic acid (HDFA) did not analyze the change in metabolism resulting from the treatment. Thus, we compared changes in methylation and glutathione metabolism and biomarkers of chronic oxidative stress as a result of these three treatments to individuals receiving placebo. In general, mB12/LDFA treatment had a significant effect on glutathione and cysteine metabolism with a medium effect size while BH4 had a significant effect on methylation and markers of chronic oxidative stress with a large effect size. HDFA treatment did not significantly influence biomarkers of methylation, glutathione or chronic oxidative stress. One caveat was that participants in the mB12/LDFA and BH4 studies had significantly worse markers of glutathione metabolism and chronic oxidative stress at baseline, respectively. Thus, the participants selected in these two clinical trials may have been those with the most severe metabolic abnormalities and most expected to respond to these treatments. Overall this study supports the notion that metabolic abnormalities in individuals with ASD may be amenable to targeted treatments and provide some insight into the mechanism of action of these treatments.

Comparison of Three Clinical Trial Treatments for Autism Spectrum Disorder Through Multivariate Analysis of Changes in Metabolic Profiles and Adaptive Behavior.

Several studies associate autism spectrum disorder (ASD) pathophysiology with metabolic abnormalities related to DNA methylation and intracellular redox homeostasis. In this regard, three completed clinical trials are reexamined in this work: treatment with (i) methylcobalamin (MeCbl) in combination with low-dose folinic acid (LDFA), (ii) tetrahydrobiopterin, and (iii) high-dose folinic acid (HDFA) for counteracting abnormalities in the folate-dependent one-carbon metabolism (FOCM) and transsulfuration (TS) pathways and also for improving ASD-related symptoms and behaviors. Although effects of treatment on individual metabolites and behavioral measures have previously been investigated, this study is the first to consider the effect of interventions on a set of metabolites of the FOCM/TS pathways and to correlate FOCM/TS metabolic changes with behavioral improvements across several studies. To do so, this work uses data from one case-control study and the three clinical trials to develop multivariate models for considering these aspects of treatment. Fisher discriminant analysis (FDA) is first used to establish a model for distinguishing individuals with ASD from typically developing (TD) controls, which is subsequently evaluated on the three treatment data sets, along with one data set for a placebo, to characterize the shift of FOCM/TS metabolism toward that of the TD population. Treatment with MeCbl plus LDFA and, separately, treatment with tetrahydrobiopterin significantly shifted the metabolites toward the values of the control group. Contrary to this, treatment with HDFA had a lesser, though still noticeable, effect whilst the placebo group showed marginal, but not insignificant, variations in metabolites. A second analysis is then performed with non-linear kernel partial least squares (KPLS) regression to predict changes in adaptive behavior, quantified by the Vineland Adaptive Behavior Composite, from changes in FOCM/TS biochemical measurements provided by treatment. Incorporating the 74 samples receiving any treatment, including placebo, into the regression analysis yields an R 2 of 0.471 after cross-validation when using changes in six metabolic measurements as predictors. These results are suggestive of an ability to effectively improve pathway-wide FOCM/TS metabolic and behavioral abnormalities in ASD with clinical treatment.

The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder.

Treatment for mitochondrial dysfunction is typically guided by expert opinion with a paucity of empirical evidence of the effect of treatment on mitochondrial activity. We examined citrate synthase and Complex I and IV activities using a validated buccal swab method in 127 children with autism spectrum disorder with and without mitochondrial disease, a portion of which were on common mitochondrial supplements. Mixed-model linear regression determined whether specific supplements altered the absolute mitochondrial activity as well as the relationship between the activities of mitochondrial components. Complex I activity was increased by fatty acid and folate supplementation, but folate only effected those with mitochondrial disease. Citrate synthase activity was increased by antioxidant supplementation but only for the mitochondrial disease subgroup. The relationship between Complex I and IV was modulated by folate while the relationship between Complex I and Citrate Synthase was modulated by both folate and B12. This study provides empirical support for common mitochondrial treatments and demonstrates that the relationship between activities of mitochondrial components might be a marker to follow in addition to absolute activities. Measurements of mitochondrial activity that can be practically repeated over time may be very useful to monitor the biochemical effects of treatments.

A multicomponent motivational intervention to improve adherence among adolescents with poorly controlled type 1 diabetes: a pilot study.

OBJECTIVE: To adapt and pilot test a multicomponent motivational intervention that includes family-based contingency management (CM) for adolescents with poorly controlled type 1 diabetes. METHODS: A total of 17 adolescents, age 12-17 years (M = 14.8, SD = 1.5), with type 1 diabetes (duration M = 6.2 years, SD = 4.5) and mean HbA1c of 11.6% (SD = 2.5%) were enrolled. Adolescents and their parents received 14 weeks of motivational interviewing, clinic-based CM, and parent-directed CM that targeted increased blood glucose monitoring (BGM). RESULTS: Adolescents significantly increased their BGM (p < .001) and showed significantly improved HbA1c levels (glycemic control) from pre-to posttreatment (p < .0001). CONCLUSIONS: The magnitude of improvements in the frequency of BGM and glycemic control in adolescents with type 1 diabetes is encouraging and will be tested in a randomized controlled trial.