Evaluation of a walking school bus program: a cluster randomized controlled trial.

BACKGROUND: The purpose of this study was to investigate the effects of a walking school bus intervention on children's active commuting to school. METHODS: We conducted a randomized controlled trial (RCT) in Houston, Texas (Year 1) and Seattle, Washington (Years 2-4) from 2012 to 2016. The study had a two-arm, cluster randomized design comparing the intervention (walking school bus and education materials) to the control (education materials) over one school year October/November - May/June). Twenty-two schools that served lower income families participated. Outcomes included percentage of days students' active commuting to school (primary, measured via survey) and moderate-to-vigorous physical activity (MVPA, measured via accelerometry). Follow-up took place in May or June. We used linear mixed-effects models to estimate the association between the intervention and outcomes of interest. RESULTS: Total sample was 418 students [Mage=9.2 (SD = 0.9) years; 46% female], 197 (47%) in the intervention group. The intervention group showed a significant increase compared with the control group over time in percentage of days active commuting (ß = 9.04; 95% CI: 1.10, 16.98; p = 0.015) and MVPA minutes/day (ß = 4.31; 95% CI: 0.70, 7.91; p = 0.02). CONCLUSIONS: These findings support implementation of walking school bus programs that are inclusive of school-age children from lower income families to support active commuting to school and improve physical activity. TRAIL REGISTRATION: This RCT is registered at clinicaltrials.gov (NCT01626807).

Household food insecurity and associations with hemoglobin A1c and acute diabetes-related complications in youth and young adults with type 1 diabetes: The SEARCH for Diabetes in Youth study.

AIMS: To examine, among youth and young adults (YYA) with type 1 diabetes (T1D), the association of household food insecurity (HFI) with: 1) HbA1c and 2) episodes of diabetic ketoacidosis (DKA) and severe hypoglycemia. METHODS: HFI was assessed using the U.S. Household Food Security Survey Module in SEARCH for Diabetes in Youth participants with T1D between 2016 and 2019. Linear and logistic regression models adjusted for age, diabetes duration, sex, race, ethnicity, clinic site, parent/participant education, household income, health insurance, and diabetes technology use. RESULTS: Of 1830 participants (mean age 20.8 ± 5.0 years, 70.0 % non-Hispanic White), HbA1c was collected for 1060 individuals (mean HbA1c 9.2 % ± 2.0 %). The prevalence of HFI was 16.4 %. In the past 12 months, 18.2 % and 9.9 % reported an episode of DKA or severe hypoglycemia, respectively. Compared to participants who were food secure, HFI was associated with a 0.33 % (95 % CI 0.003, 0.657) higher HbA1c level. Those with HFI had 1.58 (95 % CI 1.13, 2.21) times the adjusted odds of an episode of DKA and 1.53 (95 % CI 0.99, 2.37) times the adjusted odds of an episode of severe hypoglycemia as those without HFI. CONCLUSIONS: HFI is associated with higher HbA1c levels and increased odds of DKA in YYA with T1D.

Trends in Substance-Related Visits Among Youth to US Children's Hospitals, 2016-2021: An Analysis of the Pediatric Health Information System Database.

PURPOSE: This study evaluates recent trends in substance-related visits among youth visiting children's hospitals. METHODS: We conducted a cross-sectional study of substance-related visits to pediatric hospitals within the Pediatric Health Information System database of youth aged 12-21 years from 2016 through 2021. Substance-related visits were defined as acute visits for International Classification of Diseases, 10th Revision Clinical Modification codes related to substance 'use', dependence, or overdoses for alcohol, cannabis, nicotine, opioids, sedatives, stimulants, hallucinogens, or other substances. Cumulative growth rate and stratified substance-related trends were calculated using generalized estimating equations. Predicted number of visits during the COVID-19 pandemic was generated using an auto-regressive time series analysis. RESULTS: There were 106,793 substance-related visits involving 84,632 youth. From 2016 to 2021, substance-related visits increased by 47.9% and increased across all ages, demographics, regions, and payors. Visits of Hispanic youth experienced the greatest percentage growth (63.3%, p < .05) when compared to Non-Hispanic (NH) White (46.2%) or NH Black (49.8%) youth. All substances except sedatives experienced an increase in growth in visits. Cannabis accounted for the largest percentage of visits (52.2%) and experienced the greatest percentage growth during the study period (82.4%, p < .001). During the pandemic, publicly insured, female, NH Black, and Hispanic youth experienced a greater-than-predicted number of substance-related visits. DISCUSSION: Substance-related visits to children's hospitals are increasing for all demographics and nearly all substances. There were substantial increases in visits for most minoritized youth with a disproportionate rise among Hispanic youth. Visits over the pandemic were concentrated among publicly insured, female, NH Black, and Hispanic youth. Equitable large-scale investment is needed to address the rising morbidity of substance use among adolescents.

Properties of the Household Food Security Survey Module Scale in Young Adults with Diabetes.

BACKGROUND: The Household Food Security Survey Module (HFSSM) was not tailored to people with chronic diseases or young adults (YAs). OBJECTIVES: We aim to evaluate whether the 18-item HFSSM meets assumptions underlying the scale among YAs with diabetes. METHODS: Data from 1887 YAs with youth-onset type 1 diabetes or type 2 diabetes were used from the SEARCH for Diabetes in Youth Study, 2016-2019, and on 925 who returned for the SEARCH Food Security Cohort Study, 2018-2021, all of whom had completed the HFSSM. Guttman scaling properties (affirmation of preceding less severe items) and Rasch model properties (probability to answer an item based on difficulty level) were assessed. RESULTS: Items 3 (balanced meals) and 6 (eating less than one should) were affirmed more frequently than expected (nonmonotonic response pattern). At 1.2%-3.5%, item nonresponse was rare among type 1 diabetes but higher among type 2 diabetes (range: 3.1%-10.6%). Items 9 (not eating the whole day) and 3 did not meet the Guttman scaling properties. Rasch modeling revealed that item 3 had the smallest difficulty parameter. INFIT indices suggested that some responses to item 3 did not match the pattern in the rest of the sample. Classifying household food insecurity (HFI) based on items 1 and 2 compared with other 2-item combinations, including item 3, revealed a substantial undercount of HFI ranging from 5% to 8% points. CONCLUSIONS: Use of the HFSSM among YAs with diabetes could potentially result in biased HFI reporting and affect estimates of HFI prevalence in this population.

Self-Reported Food Security in Adolescents with Type 1 Diabetes: Association with Hemoglobin A1c and Mental Health Symptoms Independent of Household Food Security.

BACKGROUND: Typically, child exposure to food insecurity is assessed by caregiver reports of household food security. Child report has the potential for greater accuracy because it pertains only to the child whose experiences may differ from caregiver reports. OBJECTIVE: We assessed if adolescent-reported food insecurity was associated with levels of hemoglobin A1c (HbA1c), acute diabetes-related complications, depressive symptoms, and disordered eating behaviors in adolescents with type 1 diabetes, independently from household food security. METHODS: In a cross-sectional analysis of the multicenter SEARCH for Diabetes in Youth Cohort Study (phase 4, 2016-2019) including 601 adolescents aged 10-17 y with type 1 diabetes and their caregivers, household food security, and adolescent-reported food security were assessed using the 18-item Household Food Security Survey Module and the 6-item Child Food Security Assessment questionnaire. Age-stratified (10-13 and 14-17) regression models were performed to estimate independent associations, adjusting for sociodemographics, clinical factors, and household food security. RESULTS: Food insecurity was reported by 13.1% (n = 79) of adolescents and 15.6% (n = 94) of caregivers. Among adolescent-caregiver dyads, 82.5% (n = 496) of reports were concordant and 17.5% (n = 105) discordant, Cohen's κ= 0.3. Adolescent-reported food insecurity was not independently associated with HbA1c, diabetic ketoacidosis, and severe hypoglycemia, including in age-stratified analyses. Adolescent-reported food insecurity was independently associated with elevated odds of depressive symptoms [odds ratio (OR): 3.6; 95% confidence interval (CI): 1.3, 10.3] and disordered eating behaviors (OR: 2.5, 95% CI: 1.4, 4.6) compared with adolescents reporting food security; these associations remained in both age groups for disordered eating behaviors and in the older group for depressive symptoms. CONCLUSIONS: Adolescents with type 1 diabetes may experience food insecurity differently than caregivers. Adolescent-reported food insecurity was independently associated with depressive symptoms and disordered eating behaviors and thus may be an important attribute to assess in addition to household food security in adolescents with type 1 diabetes.

Household Food Insecurity Is Associated With Physical Activity in Youth and Young Adults With Diabetes: A Cross-Sectional Study.

BACKGROUND: Physical activity (PA) is essential for optimal diabetes management. Household food insecurity (HFI) may negatively affect diabetes management behaviors. The purpose of this study was to cross-sectionally examine the association between HFI and PA in youth and young adults (YYA) with type 1 (N = 1998) and type 2 (N = 391) diabetes from the SEARCH for Diabetes in Youth Study. METHODS: HFI was measured with the US Household Food Security Survey Module. PA was measured with the International Physical Activity Questionnaire Short Form. Walking, moderate-intensity PA (excluding walking), vigorous-intensity PA, moderate- to vigorous-intensity PA, and total PA were estimated as minutes per week, while time spent sitting was assessed in minutes per day. All were modeled with median regression. Meeting PA guidelines or not was modeled using logistic regression. RESULTS: YYA with type 1 diabetes who experienced HFI spent more time walking than those who were food secure. YYA with type 2 diabetes who experienced HFI spent more time sitting than those who were food secure. CONCLUSIONS: Future research should examine walking for leisure versus other domains of walking in relation to HFI and use objective PA measures to corroborate associations between HFI and PA in YYA with diabetes.

Humoral immune response after Ad26.COV2.S vaccination in patients with multiple sclerosis treated with natalizumab.

The immunomodulatory effects of disease-modifying therapies for multiple sclerosis might affect the immune response to vaccines for severe acute respiratory syndrome coronavirus 2. We analyzed the severe acute respiratory syndrome coronavirus 2-specific antibody response and lymphocyte profile before and after Ad26.COV2.S (Johnson & Johnson) vaccination in natalizumab-treated patients with multiple sclerosis. There was a 72-fold increase in mean anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G levels 4 weeks after vaccination and a 137-fold increase after 6 months. Other immune signals were within normal ranges. Natalizumab-treated patients with multiple sclerosis had a robust immune response to Ad26.COV2.S vaccine, and other immune signals were not significantly affected.

Whole blood miRNAs in relapsing MS patients treated with dimethyl fumarate in the phase 4 TREMEND trial.

We investigated the impact of dimethyl fumarate (DMF), an oral therapy for relapsing multiple sclerosis (MS), on blood microRNA (miRNA) signatures and neurofilament light (NFL) levels. DMF normalized miR-660-5p and modulated various miRNAs associated with the NF-kB pathway. These alterations reached a peak 4-7 months after treatment. Notably, particular miRNAs correlated with high or low NFL levels, implying their potential role as markers of treatment efficacy. Our findings broaden the understanding of DMF's immunomodulatory effects and may aid in predicting treatment responses.

Associations of Race and Ethnicity with Hepatocellular Carcinoma, Decompensation, and Mortality in US Veterans with Cirrhosis.

BACKGROUND: Among patients with cirrhosis, it remains unclear whether there are racial/ethnic differences in cirrhosis complications and mortality. We examined the associations between race/ethnicity and risk for hepatocellular carcinoma (HCC), cirrhosis decompensation, and all-cause mortality overall and by cirrhosis etiology. METHODS: US Veterans diagnosed with cirrhosis from 2001 to 2014 (n = 120,992), due to hepatitis C virus (HCV; n = 55,814), alcohol-associated liver disease (ALD; n = 36,323), hepatitis B virus (HBV; n = 1,972), nonalcoholic fatty liver disease (NAFLD; n = 17,789), or other (n = 9,094), were followed through 2020 for incident HCC (n = 10,242), cirrhosis decompensation (n = 27,887), and mortality (n = 81,441). Multivariable Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). RESULTS: Compared with non-Hispanic White patients, Hispanic patients had higher risk for HCC overall (aHR, 1.32; 95% CI, 1.24-1.41) and by cirrhosis etiology, particularly for ALD- (aHR, 1.63; 95% CI, 1.42-1.87) and NAFLD-cirrhosis (aHR, 1.76; 95% CI, 1.41-2.20), whereas non-Hispanic Black patients had lower HCC risk in ALD- (aHR, 0.79; 95% CI, 0.63-0.98) and NAFLD-cirrhosis (aHR, 0.54; 95% CI, 0.33-0.89). Asian patients had higher HCC risk (aHR, 1.70; 95% CI, 1.29-2.23), driven by HCV- and HBV-cirrhosis. Non-Hispanic Black patients had lower risk for cirrhosis decompensation overall (aHR, 0.71; 95% CI, 0.68-0.74) and by cirrhosis etiology. There was lower risk for mortality among all other racial/ethnic groups compared with non-Hispanic White patients. CONCLUSIONS: Race/ethnicity is an important predictor for risk of developing HCC, decompensation, and mortality. IMPACT: Future research should examine factors underlying these racial/ethnic differences to inform prevention, screening, and treatment for patients with cirrhosis.

Parent Behavior Management Training for Child ADHD Enhanced to Address Health Behaviors: Comparison of Telemedicine "Telegroup" Versus In-Person Delivery.

OBJECTIVE: ADHD is associated with suboptimal health behaviors including physical activity (PA). LEAP is a parent BMT group program enhanced to focus on health behaviors, integrated with mHealth technology. Little is known about implementing BMT via telemedicine "telegroups." METHODS: Children ages 5 to 10 with ADHD and their caregiver wore activity trackers and participated in an 8 to 9 week parent BMT and social media group emphasizing PA, sleep, and screen use. A 7-day child accelerometer-wear and parent and teacher measures were completed pre- and post-group. Groups were in-person prior to the COVID-19 pandemic and in telegroup format during the pandemic. RESULTS: Thirty-three families participated in person and 23 participated via virtual telegroup. Group attendance was superior for telegroup with equivalent satisfaction and skill use. Changes in health behavior and clinical outcomes were equivalent. CONCLUSIONS: LEAP is a feasible and novel BMT intervention that can be delivered in an accessible telegroup format with high participation and acceptability.

Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies.

INTRODUCTION: Dimethyl fumarate (DMF) showed favorable benefit-risk in patients with relapsing-remitting multiple sclerosis (MS) in phase 3 DEFINE and CONFIRM trials and in the ENDORSE extension study. Disease activity can differ in younger patients with MS compared with the overall population. METHODS: Randomized patients received DMF 240 mg twice daily or placebo (PBO; years 0-2 DEFINE/CONFIRM), then DMF (years 3-10; continuous DMF/DMF or PBO/DMF; ENDORSE); maximum follow-up (combined studies) was 13 years. This integrated post hoc analysis evaluated safety and efficacy of DMF in a subgroup of young adults aged 18-29 years. RESULTS: Of 1736 patients enrolled in ENDORSE, 125 were young adults, 86 treated continuously with DMF (DMF/DMF) and 39 received delayed DMF (PBO/DMF) in DEFINE/CONFIRM. Most (n = 116 [93%]) young adults completed DMF treatment in DEFINE/CONFIRM. Median (range) follow-up time in ENDORSE was 6.5 (2.0-10.0) years. Young adults entering ENDORSE who had been treated with DMF in DEFINE/CONFIRM had a model-based Annualized Relapse Rate (ARR; 95% CI) of 0.24 (0.16-0.35) vs. 0.56 (0.35-0.88) in PBO patients. ARR remained low in ENDORSE: 0.07 (0.01-0.47) at years 9-10 (DMF/DMF group). At year 10 of ENDORSE, EDSS scores were low in young adults: DMF/DMF, 1.9 (1.4); PBO/DMF, 2.4 (1.6). At ~ 7 years, the proportion of young adults with no confirmed disability progresion was 81% for DMF/DMF and 72% for PBO/DMF. Patient-reported outcomes (PROs) (SF-36 and EQ-5D) generally remained stable during ENDORSE. The most common adverse events (AEs) in young adults during ENDORSE were MS relapse (n = 53 [42%]). Most AEs were mild (n = 20 [23.3%], n = 7 [17.9%]) to moderate (n = 45 [52.3%], n = 23 [59.0%]) in the DMF/DMF and PBO/DMF groups, respectively. The most common serious AE (SAE) was MS relapse (n = 19 [15%]). CONCLUSION: The data support a favorable benefit-risk profile of DMF in young adults, as evidenced by well-characterized safety, sustained efficacy, and stable PROs. CLINICAL TRIAL INFORMATION: Clinical trials.gov, DEFINE (NCT00420212), CONFIRM (NCT00451451), and ENDORSE (NCT00835770).

Food Insecurity and Adequacy of Dietary Intake in Youth and Young Adults With Youth-Onset Type 1 and Type 2 Diabetes.

BACKGROUND: Household food insecurity is associated with poor dietary intake in the general population, but little is known about this association in persons with diabetes. OBJECTIVE: We examined the degree of adherence to the dietary reference intakes and 2020-2025 Dietary Guidelines for Americans overall and according to food security status and diabetes type among youth and young adults (YYA) with youth-onset diabetes. DESIGN, PARTICIPANTS, AND SETTING: The SEARCH for Diabetes in Youth study includes 1,197 YYA with type 1 diabetes (mean age = 21 ± 5 years) and 319 YYA with type 2 diabetes (25 ± 4 years). Participants (or parents if younger than age 18 years) completed the US Department of Agriculture Household Food Security Survey Module, wherein ≥3 affirmations indicate food insecurity. MAIN OUTCOME MEASURES: Diet was assessed via food frequency questionnaire and compared with age- and sex-specific dietary reference intakes for 10 nutrients and dietary components (calcium; fiber; magnesium; potassium; sodium; vitamins C, D, and E; added sugar; and saturated fat). STATISTICAL ANALYSES PERFORMED: Median regression models controlled for sex- and type-specific means for age, diabetes duration, and daily energy intake. RESULTS: Prevalence of guideline adherence was overarchingly poor, with <40% of participants meeting recommendations for eight of 10 nutrients and dietary components; however, higher adherence (>47%) was observed for vitamin C and added sugars. YYA with type 1 diabetes who were food insecure were more likely to meet recommendations for calcium, magnesium, and vitamin E (P < 0.05), and less likely for sodium (P < 0.05) than those with food security. In adjusted models, YYA with type 1 diabetes who were food secure had closer median adherence to sodium (P = 0.002) and fiber (P = 0.042) guidelines than those food insecure. No associations were observed in YYA with type 2 diabetes. CONCLUSIONS: Food insecurity is associated with lesser adherence to fiber and sodium guidelines in YYA with type 1 diabetes, which may lead to diabetes complications and other chronic diseases.

Measuring the Impact of the COVID-19 Pandemic on Health Behaviors and Health Care Utilization in Rural and Urban Patients with Cancer and Cancer Survivors.

Healthcare access and health behaviors differ between those living in urban and rural communities and contribute to inequitable cancer health outcomes. The COVID-19 pandemic led to significant disruptions in daily life and healthcare delivery. This cross-sectional survey aimed to measure the impact of the COVID-19 pandemic on the health behaviors of cancer patients and survivors, comparing outcomes for urban and rural respondents. Survey was administered from January 2021-June 2021 to cancer patients or survivors (treated within the last 5 years) at one of six cancer centers in Washington and Idaho. Respondent ZIP code was used to assess rurality using Rural-Urban Commuting Area designation. 515 rural (43.5% of those contacted) and 146 urban (40% of those contacted) cancer patients and survivors participated. Few differences between urban and rural cancer patients and cancer survivors were noted. Rural residents were older (69.2 years vs. 66.9 years). Rural respondents had higher mean alcohol consumption than urban respondents (4.4 drinks per week vs. 2.7 drinks per week). 12.2% of those who reported drinking in the last 30 days also reported increased alcohol consumption since the start of the pandemic, with no difference in reported increased alcohol consumption in rural vs. urban respondents. 38.5% reported decreased physical activity. 20.5% reported cancelling or delaying cancer care due to the COVID-19 pandemic. Delays in cancer healthcare services and worsening health behaviors due to the COVID-19 pandemic may contribute to poorer health outcomes, with few differences between rural and urban cancer patients and cancer survivors.

Household Food Insufficiency and Chronic Pain among Children in the US: A National Study.

This study aimed to determine the prevalence of pediatric chronic pain by household food sufficiency status and examine whether food insufficiency would be associated with greater risk for chronic pain. We analyzed data from the 2019-2020 National Survey of Children's Health of 48,410 children (6-17 years) in the United States. Across the sample, 26.1% (95% CI: 25.2-27.0) experienced mild food insufficiency and 5.1% (95% CI: 4.6-5.7) moderate/severe food insufficiency. The prevalence of chronic pain was higher among children with mild (13.7%) and moderate/severe food insufficiency (20.6%) relative to children in food-sufficient households (6.7%, p < 0.001). After adjusting for a priori covariates (individual: age, sex, race/ethnicity, anxiety, depression, other health conditions, adverse childhood events; household: poverty, parent education, physical and mental health; community: region of residence), multivariable logistic regression revealed that children with mild food insufficiency had 1.6 times greater odds of having chronic pain (95% CI: 1.4-1.9, p < 0.0001) and those with moderate/severe food insufficiency, 1.9 higher odds (95% CI: 1.4-2.7, p < 0.0001) relative to food-sufficient children. The dose-response relationship between food insufficiency and childhood chronic pain highlights the importance of further research to identify underlying mechanisms and evaluate the impact of food insufficiency on the onset and persistence of chronic pain across the lifespan.

COVID-19 Vaccine Response in People with Multiple Sclerosis Treated with Dimethyl Fumarate, Diroximel Fumarate, Natalizumab, Ocrelizumab, or Interferon Beta Therapy.

BACKGROUND: Some multiple sclerosis (MS) disease-modifying therapies (DMTs) impair responses to vaccines, emphasizing the importance of understanding COVID-19 vaccine immune responses in people with MS (PwMS) receiving different DMTs. METHODS: This prospective, open-label observational study enrolled 45 participants treated with natalizumab (n = 12), ocrelizumab (n = 16), fumarates (dimethyl fumarate or diroximel fumarate, n = 11), or interferon beta (n = 6); ages 18-65 years inclusive; stable on DMT for at least 6 months. Responder rates, anti-SARS-CoV-2 spike receptor-binding domain IgG (anti-RBD) geometric mean titers (GMTs), antigen-specific T cells, and vaccination-related adverse events were evaluated at baseline and 8, 24, 36, and 48 weeks after first mRNA-1273 (Moderna) dose. RESULTS: At 8 weeks post vaccination, all natalizumab-, fumarate-, and interferon beta-treated participants generated detectable anti-RBD IgG titers, compared to only 25% of the ocrelizumab cohort. At 24 and 36 weeks post vaccination, natalizumab-, fumarate-, and interferon beta-treated participants continued to demonstrate detectable anti-RBD IgG titers, whereas participants receiving ocrelizumab did not. Anti-RBD GMTs decreased 81.5% between 8 and 24 weeks post vaccination for the non-ocrelizumab-treated participants, with no significant difference between groups. At 36 weeks post vaccination, ocrelizumab-treated participants had higher proportions of spike-specific T cells compared to other treatment groups. Vaccine-associated side effects were highest in the ocrelizumab arm for most symptoms. CONCLUSIONS: These results suggest that humoral response to mRNA-1273 COVID-19 vaccine is preserved and similar in PwMS treated with natalizumab, fumarate, and interferon beta, but muted with ocrelizumab. All DMTs had preserved T cell response, including the ocrelizumab cohort, which also had a greater risk of vaccine-related side effects.

Street environments and crime around low-income and minority schools: Adopting an environmental audit tool to assess crime prevention through environmental design (CPTED).

Crime prevention through environmental design (CPTED) suggests an association between micro-scale environmental conditions and crime, but little empirical research exists on the detailed street-level environmental features associated with crime near low-income and minority schools. This study focuses on the neighborhoods around 14 elementary schools serving lower income populations in Seattle, WA to assess if the distribution of crime incidences (2013-2017) is linked with the street-level environmental features that reflect CPTED principles. We used a total of 40 audit variables that were included in the four domains derived from the broken windows theory and CPTED principles: natural surveillance (e.g., number of windows, balconies, and a sense of surveillance), territoriality (e.g., crime watch signs, trees), image/maintenance (e.g., graffiti and a sense of maintenance/cleanness), and geographical juxtaposition (e.g., bus stops, presence of arterial). We found that multiple crime types had significant associations with CPTED components at the street level. Among the CPTED domains, two image/maintenance features (i.e., maintenance of streets and visual quality of buildings) and two geographical juxtaposition features (i.e., being adjacent to multi-family housing and bus stops) were consistently associated with both violent and property crime. The findings suggest that local efforts to improve maintenance of streets and visual quality of buildings and broader planning efforts to control specific land uses near schools are important to improve safety in marginalized neighborhoods near schools that tend to be more vulnerable to crime. Our research on micro-scale environmental determinants of crime can also serve as promising targets for CPTED research and initiatives.

Dimethyl Fumarate Delays Multiple Sclerosis in Radiologically Isolated Syndrome.

OBJECTIVE: The radiologically isolated syndrome (RIS) represents the earliest detectable pre-clinical phase of multiple sclerosis (MS). This study evaluated the impact of therapeutic intervention in preventing first symptom manifestation at this stage in the disease spectrum. METHODS: We conducted a multi-center, randomized, double-blinded, placebo-controlled study involving people with RIS. Individuals without clinical symptoms typical of MS but with incidental brain MRI anomalies consistent with central nervous system (CNS) demyelination were included. Within 12 MS centers in the United States, participants were randomly assigned 1:1 to oral dimethyl fumarate (DMF) 240 mg twice daily or placebo. The primary endpoint was the time to onset of clinical symptoms attributable to a CNS demyelinating event within a follow-up period of 96 weeks. An intention-to-treat analysis was applied to all participating individuals in the primary and safety investigations. The study is registered at ClinicalTrials.gov, NCT02739542 (ARISE). RESULTS: Participants from 12 centers were recruited from March 9, 2016, to October 31, 2019, with 44 people randomized to dimethyl fumarate and 43 to placebo. Following DMF treatment, the risk of a first clinical demyelinating event during the 96-week study period was highly reduced in the unadjusted Cox proportional-hazards regression model (hazard ratio [HR] = 0.18, 95% confidence interval [CI] = 0.05-0.63, p = 0.007). More moderate adverse reactions were present in the DMF (34 [32%]) than placebo groups (19 [21%]) but severe events were similar (DMF, 3 [5%]; placebo, 4 [9%]). INTERPRETATION: This is the first randomized clinical trial demonstrating the benefit of a disease-modifying therapy in preventing a first acute clinical event in people with RIS. ANN NEUROL 2023;93:604-614.

Real-World Analysis Affirms the High Persistence and Adherence Observed with Diroximel Fumarate in Patients with Multiple Sclerosis.

INTRODUCTION: Adherence to disease-modifying therapies is key for achieving optimal outcomes in multiple sclerosis (MS). Diroximel fumarate (DRF) is an oral fumarate approved for treatment of relapsing forms of MS. It has the same pharmacologically active metabolite as dimethyl fumarate (DMF) and similar efficacy and safety profiles, but with demonstrated fewer gastrointestinal (GI) related adverse events (AEs). There are limited data characterizing persistence and adherence to DRF in the real world. METHODS: This retrospective analysis of the AcariaHealth Specialty Pharmacy Program included patients with MS initiating DRF from 1 December 2019 to 30 January 2021. This analysis evaluated persistence, measured as proportion of patients remaining on therapy; discontinuation rate due to GI AEs; and adherence measured by proportion of days covered (PDC). RESULTS: Overall, 1143 patients were included; 433 (37.9%) patients had been treated with prior DMF and switched to DRF. Persistence was high in both groups: the estimated proportion of patients remaining on DRF at 16 months was 82.3% [95% confidence internal (CI) 77.2-86.3%], and 90.1% (95% CI 82.2-94.6%) in the DMF to DRF group. Fifty-two (4.5%) patients overall and 15 (3.5%) in the DMF switch subgroup discontinued DRF due to GI AEs. Mean PDC was 90.8% (95% CI 89.2-92.5%), and 85.4% (95% CI 83.3-87.4%) of patients achieved PDC ≥ 80% in the overall population. In the DMF to DRF group, mean PDC was 90.7% (95% CI 88.0-93.5%), and 84.8% (95% CI 81.4-88.1%) of patients achieved PDC ≥ 80%. CONCLUSION: In this analysis of  > 1000 patients treated with DRF in real-world clinical practice, overall persistence at 16 months was high, treatment discontinuation due to GI AEs was low, and patients were highly adherent to therapy. Of 433 patients who switched from DMF to DRF, most (> 90%) were able to tolerate and persist on DRF after switching. Graphical abstract available for this article.

A Longitudinal View of Disparities in Insulin Pump Use Among Youth with Type 1 Diabetes: The SEARCH for Diabetes in Youth Study.

Objective: To evaluate changes in insulin pump use over two decades in a national U.S. sample. Research Design and Methods: We used data from the SEARCH for Diabetes in Youth study to perform a serial cross-sectional analysis to evaluate changes in insulin pump use in participants <20 years old with type 1 diabetes by race/ethnicity and markers of socioeconomic status across four time periods between 2001 and 2019. Multivariable generalized estimating equations were used to assess insulin pump use. Temporal changes by subgroup were assessed through interactions. Results: Insulin pump use increased from 31.7% to 58.8%, but the disparities seen in pump use persisted and were unchanged across subgroups over time. Odds ratio for insulin pump use in Hispanic (0.57, confidence interval [95% CI] 0.45-0.73), Black (0.28, 95% CI 0.22-0.37), and Other race (0.49, 95% CI 0.32-0.76) participants were significantly lower than White participants. Those with ≤high school degree (0.39, 95% CI 0.31-0.47) and some college (0.68, 95% CI 0.58-0.79) had lower use compared to those with ≥bachelor's degree. Those with public insurance (0.84, 95% CI 0.70-1.00) had lower use than those with private insurance. Those with an annual household income <$25K (0.43, 95% CI 0.35-0.53), $25K-$49K (0.52, 95% CI 0.43-0.63), and $50K-$74K (0.79, 95% CI 0.66-0.94) had lower use compared to those with income ≥$75,000. Conclusion: Over the past two decades, there was no improvement in the racial, ethnic, and socioeconomic inequities in insulin pump use, despite an overall increase in use. Studies that evaluate barriers or test interventions to improve technology access are needed to address these persistent inequities.