Search

ObjectiveTo assess our hypothesis that brain macrostructure is different in individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC), we conducted a comprehensive multicenter study using a uniform quantitative magnetic resonance imaging (qMRI) protocol, with analyses that account for the effects of disease phenotype, age, and cognition.MethodsBrain MRIs in 23 individuals with attenuated (MPS IA) and 38 with severe MPS I (MPS IH), aged 4-25 years, enrolled under the study protocol NCT01870375, were compared to 98 healthy controls.ResultsCortical and subcortical gray matter, white matter, corpus callosum, ventricular and choroid plexus volumes in MPS I significantly differed from HC. Thicker cortex, lower white matter and corpus callosum volumes were already present at the youngest MPS I participants aged 4-5 years. Age-related differences were observed in both MPS I groups, but most markedly in MPS IH, particularly in cortical gray matter metrics. IQ scores were inversely associated with ventricular volume in both MPS I groups and were positively associated with cortical thickness only in MPS IA.ConclusionsQuantitatively-derived MRI measures distinguished MPS I participants from HC as well as severe from attenuated forms. Age-related neurodevelopmental trajectories in both MPS I forms differed from HC. The extent to which brain structure is altered by disease, potentially spared by treatment, and how it relates to neurocognitive dysfunction needs further exploration.

BackgroundRace/ethnicity and low English proficiency healthcare disparities are well established in the United States. We sought to determine if there are race/ethnicity differences in anti-obesity medication (AOM) prescription rates among youth with severe obesity treated in a pediatric weight management clinic and if, among youth from non-primary English speaking families, there are differences in prescriptions between those using interpreters during visits versus not.MethodsWe reviewed electronic health records of 2- to 18-year-olds with severe obesity seen from 2012 to 2021. Race/ethnicity was self-report, and AOMs included topiramate, stimulants (e.g. phentermine, lisdexamfetamine), naltrexone (±bupropion), glucagon-like peptide-1 agonists, and orlistat. We used general linear regression models with log-link to compare incidence rate ratios (IRRs) within the first 1 and 3 years of being followed, controlling for age, percent of the 95th BMI percentile (%BMIp95), number of obesity-related comorbidities (e.g. insulin resistance, hypertension), median household income, and interpreter use. We repeated similar analyses among youth from non-primary English speaking families, comparing those using interpreters versus not.Results1,725 youth (mean age 11.5 years; %BMIp95 142%; 53% non-Hispanic White, 20% Hispanic/Latino, 16% non-Hispanic black; 6% used interpreters) were seen, of which 15% were prescribed AOMs within 1 year. The IRR for prescriptions was lower among Hispanic/Latino compared to non-Hispanic White youth at one (IRR 0.70; CI: 0.49-1.00; p = 0.047) but not 3 years. No other statistically significant differences by race/ethnicity were found. Among non-primary English speaking families, the IRR for prescriptions was higher at 1 year (IRR 2.49; CI: 1.32-4.70; p = 0.005) in those using interpreters versus not.ConclusionsAmong youth seen in a pediatric weight management clinic, AOM prescription incidence rates were lower in Hispanics/Latinos compared to non-Hispanic Whites. Interpreter use was associated with higher prescription incidence rates among non-primary English speakers. Interventions to achieve equity in AOM prescriptions may help mitigate disparities in pediatric obesity.

BackgroundCardiovascular disease frequently causes morbidity and mortality in mucopolysaccharidoses (MPS); however, cardiovascular anatomy and dysfunction in MPS IVA (Morquio A disease) is not well described. Consequently, the study aimed to compare carotid artery structure and elasticity of MPS IVA patients with other MPS patients and healthy control subjects, and quantitate frequency of MPS IVA cardiac structural and functional abnormalities.MethodsProspective, multi-center echocardiogram and carotid ultrasound evaluations of 12 Morquio A patients were compared with other MPS and healthy control subjects. Average differences between groups were adjusted for age, sex, and height with robust variance estimation for confidence intervals and P-values.ResultsMorquio A patients demonstrated significantly higher (P

PurposeAbnormalities in cerebrospinal fluid (CSF) have been reported in Hurler syndrome, a fatal neurodegenerative lysosomal disorder. While no biomarker has predicted neurocognitive response to treatment, one of these abnormalities, glycosaminoglycan nonreducing ends (NREs), holds promise to monitor therapeutic efficacy. A trial of intrathecal enzyme replacement therapy (ERT) added to standard treatment enabled tracking of CSF abnormalities, including NREs. We evaluated safety, biomarker response, and neurocognitive correlates of change.MethodsIn addition to intravenous ERT and hematopoietic cell transplantation, patients (N = 24) received intrathecal ERT at four peritransplant time points; CSF was evaluated at each point. Neurocognitive functioning was quantified at baseline, 1 year, and 2 years posttransplant. Changes in CSF biomarkers and neurocognitive function were evaluated for an association.ResultsOver treatment, there were significant decreases in CSF opening pressure, biomarkers of disease activity, and markers of inflammation. Percent decrease in NRE from pretreatment to final intrathecal dose posttransplant was positively associated with percent change in neurocognitive score from pretreatment to 2 years posttransplant.ConclusionIntrathecal ERT was safe and, in combination with standard treatment, was associated with reductions in CSF abnormalities. Critically, we report evidence of a link between a biomarker treatment response and neurocognitive outcome in Hurler syndrome.

ObjectivePrevious research suggests attention and white matter (WM) abnormalities in individuals with mucopolysaccharidosis type I (MPS I); this cross-sectional comparison is one of the first to examine the relationship of WM structural abnormalities as measured by corpus callosum (CC) volumes with attention scores to evaluate this relationship in a larger sample of patients with MPS I.MethodsVolumetric MRI data and performance on a computerized measure of sustained attention were compared for 18 participants with the severe form of MPS I (MPS IH), 18 participants with the attenuated form of MPS I (MPS IATT), and 60 typically developing age-matched controls.ResultsThe MPS I groups showed below-average mean attention scores (p < 0.001) and smaller CC volumes (p < 0.001) than controls. No significant associations were found between attention performance and CC volume for controls. Attention was associated with posterior CC volumes in the participants with MPS IH (p = 0.053) and total (p = 0.007) and anterior (p < 0.001) CC volumes in participants with MPS IATT.ConclusionsWe found that attention and CC volumes were reduced in participants with MPS I compared to typically developing controls. Smaller CC volumes in participants with MPS I were associated with decreased attention; such an association was not seen in controls. While hematopoietic cell transplantation used to treat MPS IH may compound these effects, attention difficulties were also seen in the MPS IATT group, suggesting that disease effects contribute substantially to the clinical attentional difficulties seen in this population.

Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but cardiovascular disease causes mortality in a significant percentage of survivors. Markers must be developed to predict MPS cardiac risk and monitor efficacy of investigational therapies.MPS patients underwent carotid artery ultrasonography from which carotid intima-media thickness (cIMT) and three measures of arterial stiffness were calculated: carotid artery distensibility (cCSD), compliance (cCSC), and incremental elastic modulus (cIEM). MPS carotid measurements were compared to corresponding data from pediatric and adult healthy cohorts. 33 MPS patients (17 MPS I, 9 MPS II, 4 MPS IIIA, and 3 MPS VI; mean age 12.5 ± 4.7 years), 560 pediatric controls (age 13.1 ± 4.0 years), and 554 adult controls (age 39.2 ± 2.2 years) were studied. Age and sex-adjusted aggregate MPS cIMT (0.56 ± 0.05 mm) was significantly greater than both pediatric (+0.12 mm; 95% CI +0.10 to +0.14 mm) and adult (+0.10 mm; 95% CI +0.06 to +0.14 mm) control cohorts; similar findings were observed for all MPS subtypes. Mean MPS cIMT approximated the 80th percentile of the adult cohort cIMT. MPS patients also demonstrated significantly increased adjusted arterial stiffness measurements, evidenced by reduced cCSD, cCSC, and increased cIEM, compared to pediatric and adult control cohorts. Regardless of treatment, MPS patients demonstrate increased cIMT and arterial stiffness compared to healthy pediatric and adult controls. These data suggest that relatively young MPS patients demonstrate a "structural vascular age" of at least 40 years old.

Given the increasing level and scope of biostatistics expertise needed at academic health centers today, we developed best practices guidelines for biostatistics units to be more effective in providing biostatistical support to their institutions, and in fostering an environment in which unit members can thrive professionally. Our recommendations focus on the key areas of: 1) funding sources and mechanisms; 2) providing and prioritizing access to biostatistical resources; and 3) interacting with investigators. We recommend that the leadership of biostatistics units negotiate for sufficient long-term infrastructure support to ensure stability and continuity of funding for personnel, align project budgets closely with actual level of biostatistical effort, devise and consistently apply strategies for prioritizing and tracking effort on studies, and clearly stipulate with investigators prior to project initiation policies regarding funding, lead time, and authorship.

Summary: Background: Anti‐obesity medications (AOMs) are promising lifestyle modification (LSM) adjuncts for obesity treatment, and phentermine is commonly prescribed in paediatric weight management clinics. Determining 'real‐world' AOM effectiveness and characteristics predicting response is important. Objectives: We sought to describe phentermine plus LSM effectiveness and identify baseline characteristics predicting response. Methods: This was a retrospective cohort study among youth seen in a US academic‐based weight management clinic from 2012 to 2020. Baseline characteristics (e.g., body mass index (BMI), liver transaminases, eating‐related behaviours) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, %BMI change, weight) were determined through electronic health records and intake surveys. Results: Among 91 youth prescribed phentermine plus LSM over 8 years (mean %BMIp95 150%), %BMIp95 was statistically significantly reduced at 1.5, 3, 6 and 12 months (peak reduction 10.9 percentage points at 6 months; p < 0.001). Considering multiple comparisons, the presence of baseline elevated alanine aminotransferase was associated with statistically significant smaller 1.5‐month %BMIp95 reductions (p = 0.001) and higher food responsiveness with smaller 3‐ (p = 0.001) and 6‐month (p < 0.001) reductions. Conclusions: Phentermine plus LSM reduced %BMIp95 among youth in a weight management clinic, and baseline characteristics may help determine those more or less likely to respond. Prospective studies are needed to further characterize effectiveness and confirm response predictors. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Whilst glucagon‐like peptide‐1 receptor agonists (GLP1‐RAs) are effective for treating adolescent obesity, weight loss maintenance (WLM; preventing weight regain) remains a challenge. Our goal was to investigate appetite/satiety hormones and eating behaviours that may predict WLM with exenatide (a GLP1‐RA) versus placebo in adolescents with severe obesity. Methods: Adolescents who had ≥5% body mass index (BMI) reduction with meal replacement therapy were randomized to 52 weeks of once‐weekly exenatide extended release or placebo. In this secondary analysis, eating behaviours and appetite/satiety regulation hormones post‐meal replacement therapy (pre‐randomization to exenatide or placebo) were evaluated as possible predictors of WLM. Percent change in BMI from randomization to 52 weeks served as the primary measure of WLM. Results: The analysis included 66 adolescents (mean age 16.0 years; 47% female). Lower leptin response to meal testing was associated with greater WLM in terms of BMI percent change in those receiving exenatide compared to placebo (p = 0.007) after adjusting for sex, age and BMI. There were no other significant predictors of WLM. Conclusions: Prior to exenatide, lower leptin response to meals was associated with improved WLM with exenatide compared to placebo. The mostly null findings of this study suggest that GLP1‐RA treatment may produce similar WLM for adolescents with obesity regardless of age, BMI, sex and eating behaviours. [ABSTRACT FROM AUTHOR]

Students Against Nicotine and Tobacco Addiction is a community-based participatory research project that engages local medical and mental health providers in partnership with students, teachers, and administrators at the Minnesota-based [...]

Financial strain and unmet social needs are associated with greater risk for lower urinary tract symptoms. Little research has examined financial strain and unmet social needs in relation to the more holistic concept of bladder health. This study utilizes baseline data from RISE FOR HEALTH: A U.S. Study of Bladder Health to examine whether financial strain, unmet social needs, and meeting specific federal poverty level threshold levels are associated with lower urinary tract symptoms and poorer perceived bladder health, well-being, and function. Participants were 18 years or older, born female or currently identified as a woman, and from the civilian, noninstitutionalized population residing in 50 counties in the United States that included or surrounded 9 recruitment centers. Data were collected through mailed or internet-based surveys. To address research questions, the 10-item Lower Urinary Tract Dysfunction Research Network - Symptom Index and selected Prevention of Lower Urinary Tract Symptoms Research Consortium bladder health scores were separately regressed on each financial strain, unmet social need, and federal poverty level variable, using linear regression adjusting for covariates (age, race/ethnicity, education, and vaginal parity) and robust variance estimation for confidence intervals (CI). Participants with no missing data for a given analysis were included (range of n=2564–3170). In separate sensitivity analyses, body mass index, hypertension, and diabetes were added as covariates and missing data were imputed. The mean age of participants was 51.5 years (standard deviation=18.4). Not having enough money to make ends meet, housing insecurity, food insecurity, unreliable transportation, and percent federal poverty levels of 300% or less were consistently associated with more reported lower urinary tract symptoms and poorer perceived bladder health. For example, compared to food secure participants, women who worried that their food would run out at the end of the month had a Lower Urinary Tract Dysfunction Research Network - Symptom Index score that was 3.4 points higher (95% CI: 2.5, 4.3), on average. They also had lower mean scores across different bladder health measures, each assessed using a 100-point scale: global bladder health (−8.2, 95% CI: −10.8, −5.7), frequency (−10.2, 95% CI: −13.8, −6.7), sensation (−11.6, 95% CI: −15.1, −8.2), continence (−13.3, 95% CI: −16.7, −9.9), and emotional impact of bladder health status (−13.2, 95% CI: −16.5, −9.9). Across analyses, associations largely remained significant after additional adjustment for body mass index, hypertension, and diabetes. The pattern of results when imputing missing data was similar to that observed with complete case analysis; all significant associations remained significant with imputation. Financial strain and unmet social needs are associated with worse LUTS and poorer bladder health. Longitudinal research is needed to examine whether financial strain and unmet social needs influence the development, maintenance, and worsening of lower urinary tract symptoms; different mechanisms by which financial strain and unmet social needs may impact symptoms; and the degree to which symptoms contribute to financial strain. If supported by etiologic research, prevention research can be implemented to determine whether the amelioration of financial strain and social needs, including enhanced access to preventative care, may promote bladder health across the life course. [ABSTRACT FROM AUTHOR]