Mapping geographic disparities in treatment and clinical outcomes of high-grade aneurysmal subarachnoid hemorrhage in the United States.

BACKGROUND AND OBJECTIVE: Although high-grade (Hunt and Hess 4 and 5) aneurysmal subarachnoid hemorrhage (aSAH) typically portends a poor prognosis, early and aggressive treatment has previously been demonstrated to confer a significant survival advantage. This study aims to evaluate geographic, demographic, and socioeconomic determinants of high-grade aSAH treatment in the United States. METHODS: The National Inpatient Sample (NIS) was queried to identify adult high-grade aSAH hospitalizations during the period of 2015 to 2019 using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD) codes. The primary clinical endpoint of this analysis was aneurysm treatment by surgical or endovascular intervention (SEI), while the exposure of interest was geographic region by census division. Favorable functional outcome (assessed by the dichotomous NIS-SAH Outcome Measure, or NIS-SOM) and in-hospital mortality were evaluated as secondary endpoints in treated and conservatively managed groups. RESULTS: Among 99 460 aSAH patients identified, 36 795 (37.0%) were high-grade, and 9210 (25.0%) of these were treated by SEI. Following multivariable logistic regression analysis, determinants of treatment by SEI included female sex (adjusted OR (aOR) 1.42, 95% CI 1.35 to 1.51), transfer admission (aOR 1.18, 95% CI 1.12 to 1.25), private insurance (ref: government-sponsored insurance) (aOR 1.21, 95% CI 1.14 to 1.28), and government hospital ownership (ref: private ownership) (aOR 1.17, 95% CI 1.09 to 1.25), while increasing age (by decade) (aOR 0.93, 95% CI 0.91 to 0.95), increasing mortality risk (aOR 0.60, 95% CI 0.57 to 0.63), urban non-teaching hospital status (aOR 0.66, 95% CI 0.59 to 0.73), rural hospital location (aOR 0.13, 95% CI 0.7 to 0.25), small hospital bedsize (aOR 0.68, 95% CI 0.60 to 0.76), and geographic region (South Atlantic (aOR 0.72, 95% CI 0.63 to 0.83), East South Central (aOR 0.75, 95% CI 0.64 to 0.88), and Mountain (aOR 0.72, 95% CI 0.61 to 0.85)) were associated with a lower likelihood of treatment. High-grade aSAH patients treated by SEI experienced significantly greater rates of favorable functional outcomes (20.1% vs 17.3%; OR 1.20, 95% CI 1.13 to 1.28, P<0.001) and lower rates of mortality (25.8% vs 49.1%; OR 0.36, 95% CI 0.34 to 0.38, P<0.001) in comparison to those conservatively managed. CONCLUSION: A complex interplay of demographic, socioeconomic, and geographic factors influence treatment patterns of high-grade aSAH in the United States.

The gut-brain connection: Inflammatory bowel disease increases risk of acute ischemic stroke.

OBJECTIVES: Chronic inflammation of the gastrointestinal tract is a hallmark of inflammatory bowel disease (IBD). This increased inflammation is thought to induce a hypercoagulable state that increases the risk for stroke. However, few studies have examined the association between IBD and acute ischemic stroke (AIS). Thus, this study aims to investigate the incidence, treatments, complications, and outcomes of AIS in patients with IBD. MATERIALS & METHODS: ICD-9-CM and ICD-10-CM codes were used to query the National Inpatient Sample for AIS and IBD diagnosis. Baseline demographics, clinical characteristics, complications, treatments, and outcomes were assessed through descriptive statistics, multivariate regression, and propensity score matching (PSM) analysis. Acute stroke severity was assessed using the National Institute of Heath's Stroke Severity Score (SSS) as a template. RESULTS: 1,609,817 patients were diagnosed with AIS between 2010 through 2019. 7468 (0.46%) had concomitant diagnoses of IBD. AIS patients with IBS were younger, more likely to be white and female, but less likely to be obese. Although IBD patients had comparable stroke severities (p = 0.64) to their non-IBS counterparts, they received stroke intervention at statistically different rates than their non-IBD counterparts. Additionally, IBD patients had higher rates of in-hospital complications (p < 0.01) and longer lengths of stay (LOS) (p < 0.01). CONCLUSIONS: IBD patients develop AIS at a younger age with similar rates of stroke severity to their non-IBD counterparts, but receive higher rates of tissue plasminogen activator administration and decreased rates of mechanical thrombectomy. Our research shows that patients with IBD are at risk for AIS at an earlier age and are more likely to have complications. This underlies a connection between IBD and a hypercoagulable state that could predispose patients to AIS.

Effect of Behaviorally Designed Gamification With Social Incentives on Lifestyle Modification Among Adults With Uncontrolled Diabetes: A Randomized Clinical Trial.

Importance: Gamification is increasingly being used to promote healthy behaviors. However, it has not been well tested among patients with chronic conditions and over longer durations. Objective: To test the effectiveness of behaviorally designed gamification interventions to enhance support, collaboration, or competition to promote physical activity and weight loss among adults with uncontrolled type 2 diabetes. Design, Setting, and Participants: A 4-arm randomized clinical trial with a 1-year intervention was conducted from January 23, 2017, to January 27, 2020, with remotely monitored intervention. Analyses were conducted between February 10 and October 6, 2020. Participants included 361 adults with type 2 diabetes with hemoglobin A1c levels greater than or equal to 8% and body mass index greater than or equal to 25. Interventions: All participants received a wearable device, smart weight scale, and laboratory testing. Participants in the control group received feedback from their devices but no other interventions. Participants in the gamification arms conducted goal setting and were entered into a 1-year game designed using insights from behavioral economics with points and levels for achieving step goals and weight loss targets. The game varied by trial arm to promote either support, collaboration, or competition. Main Outcomes and Measures: Co-primary outcomes included daily step count, weight, and hemoglobin A1c level. Secondary outcome was low-density lipoprotein cholesterol level. Intention-to-treat analysis was used. Results: Participants had a mean (SD) age of 52.5 (10.1) years; hemoglobin A1c level, 9.6% (1.6%); daily steps, 4632 (2523); weight, 107.4 kg (20.8 kg); and body mass index, 37.1 (6.6). Of the 361 participants, 202 (56.0%) were women, 143 (39.6%) were White, and 185 (51.2%) were Black; with 87 (24.1%) randomized to control; 92 (25.4%) randomized to gamification with support and intervention; 95 (26.3%) randomized to gamification with collaboration; and 87 (24.1%) randomized to gamification with competition. Compared with the control group over 1 year, there was a significant increase in mean daily steps from baseline among participants receiving gamification with support (adjusted difference relative to control group, 503 steps; 95% CI, 103 to 903 steps; P = .01) and competition (606 steps; 95% CI, 201 to 1011 steps; P = .003) but not collaboration (280 steps; 95% CI, -115 to 674 steps; P = .16). All trial arms had significant reductions in weight and hemoglobin A1c levels from baseline, but there were no significant differences between any of the intervention arms and the control arm. There was only 1 adverse event reported that may have been related to the trial (arthritic knee pain). Conclusions and Relevance: Among adults with uncontrolled type 2 diabetes, a behaviorally designed gamification intervention in this randomized clinical trial significantly increased physical activity over a 1-year period when designed to enhance either support or competition but not collaboration. No differences between intervention and control groups were found for other outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02961192.

Disruption of Nrxn1α within excitatory forebrain circuits drives value-based dysfunction.

Goal-directed behaviors are essential for normal function and significantly impaired in neuropsychiatric disorders. Despite extensive associations between genetic mutations and these disorders, the molecular contributions to goal-directed dysfunction remain unclear. We examined mice with constitutive and brain region-specific mutations in Neurexin1α, a neuropsychiatric disease-associated synaptic molecule, in value-based choice paradigms. We found Neurexin1α knockouts exhibited reduced selection of beneficial outcomes and impaired avoidance of costlier options. Reinforcement modeling suggested that this was driven by deficits in updating and representation of value. Disruption of Neurexin1α within telencephalic excitatory projection neurons, but not thalamic neurons, recapitulated choice abnormalities of global Neurexin1α knockouts. Furthermore, this selective forebrain excitatory knockout of Neurexin1α perturbed value-modulated neural signals within striatum, a central node in feedback-based reinforcement learning. By relating deficits in value-based decision-making to region-specific Nrxn1α disruption and changes in value-modulated neural activity, we reveal potential neural substrates for the pathophysiology of neuropsychiatric disease-associated cognitive dysfunction.

Effectiveness of Behaviorally Designed Gamification Interventions With Social Incentives for Increasing Physical Activity Among Overweight and Obese Adults Across the United States: The STEP UP Randomized Clinical Trial.

Importance: Gamification, the use of game design elements in nongame contexts, is increasingly being used in workplace wellness programs and digital health applications. However, the best way to design social incentives in gamification interventions has not been well examined. Objective: To assess the effectiveness of support, collaboration, and competition within a behaviorally designed gamification intervention to increase physical activity among overweight and obese adults. Design, Setting, and Participants: This 36-week randomized clinical trial with a 24-week intervention and 12-week follow-up assessed 602 adults from 40 states with body mass indexes (calculated as weight in kilograms divided by height in meters squared) of 25 or higher from February 12, 2018, to March 17, 2019. Interventions: Participants used a wearable device to track daily steps, established a baseline, selected a step goal increase, were randomly assigned to a control (n = 151) or to 1 of 3 gamification interventions (support [n = 151], collaboration [n = 150], and competition [n = 150]), and were remotely monitored. The control group received feedback from the wearable device but no other interventions for 36 weeks. The gamification arms were entered into a 24-week game designed using insights from behavioral economics with points and levels for achieving step goals. No gamification interventions occurred during follow-up. Main Outcomes and Measures: The primary outcome was change in mean daily steps from baseline through the 24-week intervention period. Results: A total of 602 participants (mean [SD] age, 39 [10] years; mean [SD] body mass index, 30 [5]; 427 [70.9%] male) were included in the study. Compared with controls, participants had a significantly greater increase in mean daily steps from baseline during the intervention in the competition arm (adjusted difference, 920; 95% CI, 513-1328; P < .001), support arm (adjusted difference, 689; 95% CI, 267-977; P < .001), and collaboration arm (adjusted difference, 637; 95% CI, 258-1017; P = .001). During follow-up, physical activity remained significantly greater in the competition arm than in the control arm (adjusted difference, 569; 95% CI, 142-996; P = .009) but was not significantly greater in the support (adjusted difference, 428; 95% CI, 19-837; P = .04) and collaboration (adjusted difference, 126; 95% CI, -248 to 468; P = .49) arms than in the control arm. Conclusions and Relevance: All 3 gamification interventions significantly increased physical activity during the 24-week intervention, and competition was the most effective. Physical activity was lower in all arms during follow-up and only remained significantly greater in the competition arm than in the control arm. Trial Registration: ClinicalTrials.gov identifier: NCT03311230.

Behavioral Paradigms to Probe Individual Mouse Differences in Value-Based Decision Making.

Value-based decision making relies on distributed neural systems that weigh the benefits of actions against the cost required to obtain a given outcome. Perturbations of these systems are thought to underlie abnormalities in action selection seen across many neuropsychiatric disorders. Genetic tools in mice provide a promising opportunity to explore the cellular components of these systems and their molecular foundations. However, few tasks have been designed that robustly characterize how individual mice integrate differential reward benefits and cost in their selection of actions. Here we present a forced-choice, two-alternative task in which each option is associated with a specific reward outcome, and unique operant contingency. We employed global and individual trial measures to assess the choice patterns and behavioral flexibility of mice in response to differing "choice benefits" (modeled as varying reward magnitude ratios) and different modalities of "choice cost" (modeled as either increasing repetitive motor output to obtain reward or increased delay to reward delivery). We demonstrate that (1) mouse choice is highly sensitive to the relative benefit of outcomes; (2) choice costs are heavily discounted in environments with large discrepancies in relative reward; (3) divergent cost modalities are differentially integrated into action selection; (4) individual mouse sensitivity to reward benefit is correlated with sensitivity to reward costs. These paradigms reveal stable individual animal differences in value-based action selection, thereby providing a foundation for interrogating the neural circuit and molecular pathophysiology of goal-directed dysfunction.