Safety and preliminary efficacy on cognitive performance and adaptive functionality of epigallocatechin gallate (EGCG) in children with Down syndrome. A randomized phase Ib clinical trial (PERSEUS study)

Purpose: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance. Methods: A total of 73 children with DS (aged 6-12 years) were randomized. Participants received 0.5% EGCG (10 mg/kg daily dose) or placebo for 6 months with 3 months follow up after treatment discontinuation. Results: In total, 72 children were treated and 66 completed the study. A total of 38 participants were included in the EGCG group and 35 in the placebo group. Of 72 treated participants, 62 (86%) had 229 treatment-emergent adverse events (AEs). Of 37 participants in the EGCG group, 13 (35%) had 18 drug-related treatment-emergent AEs and 12 of 35 (34%) from the placebo group had 22 events. In the EGCG group, neither severe AEs nor increase in the incidence of AEs related to safety biomarkers were observed. Cognition and functionality were not improved compared with placebo. Secondary efficacy outcomes in girls point to a need for future work. Conclusion: The use of EGCG is safe and well-tolerated in children with DS, but efficacy results do not support its use in this population. (C) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Frailty and emergency department utilisation in adults with systemic lupus erythematosus ≤65 years of age: an administrative claims data analysis of Medicaid beneficiaries

Objective Frailty is a risk factor for adverse health in adults with SLE, including those &lt;65 years. Emergency department (ED) utilisation is high in adults with SLE, but to our knowledge, whether frailty is associated with ED use is unknown. In a large administrative claims dataset, we assessed risk of ED utilisation among frail adults with SLE ≤65 years of age relative to non-frail adults ≤65 years of age with SLE.Methods Using the MarketScan Medicaid subset from 2011 to 2015, we identified beneficiaries 18–65 years with SLE (≥3 SLE International Classification of Diseases, Ninth Revision codes ≥30 days apart). Comparators without a systemic rheumatic disease (SRD) were matched 4:1 on age and gender. Frailty status in 2011 was determined using two claims-based frailty indices (CFIs). We compared risk of recurrent ED utilisation among frail and non-frail beneficiaries with SLE using an extension of the Cox proportional hazard model for recurrent events data.Results Of 2262 beneficiaries with SLE and 9048 non-SRD comparators, 28.8% and 11.6% were frail, respectively, according to both CFIs. Compared with non-frail beneficiaries with SLE, frail beneficiaries with SLE had significantly higher hazard of recurrent ED use (HR 1.75, 95% CI 1.48 to 2.08).Conclusion Frailty increased hazard of recurrent ED visits in frail adults ≤65 years of age with SLE relative to comparable non-frail adults with SLE. Frailty is a potential target for efforts to improve quality of care in SLE

Living in immigrant communities does not impact total knee arthroplasty outcomes: experience from a high-volume center in the United States

Abstract Background Community characteristics such as poverty affect total knee arthroplasty (TKA) outcomes. However, it is unknown whether other community factors such as immigrant proportion (IP) also affect outcomes. Our objective was to determine the association of neighborhood IP on preoperative (pre-op) and 2-year postoperative (post-op) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function after elective TKA. Methods Patients in a high volume institutional TKA registry between May 2007 and February 2011 were retrospectively analyzed. Demographics, pre-op and 2-year post-op WOMAC pain and function scores, and geocodable addresses were obtained. Patient-level variables were linked to US Census Bureau census tract data. The effect of patient and neighborhood-level factors on WOMAC scores were analyzed using linear mixed effects models. Results 3898 TKA patients were analyzed. Pre-op and 2-year post-op WOMAC pain and function scores were between 2.75–4.88 WOMAC points worse in neighborhoods with a high IP (≥ 40%) compared to low IP (< 10%). In multivariable analyses, these differences were not statistically significant. Women had worse pre-op and 2-year post-op WOMAC scores (all p ≤ 0.04), but this difference was not influenced by neighborhood IP (all pinteraction NS). Conclusions Patients living in high (≥40%) IP neighborhoods do not have worse pre-op or 2-year post-op pain and function outcomes after TKA compared to those living in low (< 10%) IP neighborhoods. Although sex differences favoring males are notable, these differences are not associated with IP. High neighborhood IP do not appear to affect outcomes after TKA

Measuring the impact of steroid therapy on health-related quality of life in patients with rheumatic diseases: International development of a glucocorticoid treatment-specific patient reported outcome measure

Objectives: Glucocorticoids (GCs) (‘steroids’) are used to treat rheumatic diseases but adverse effects are common. We aimed to explore the impact of GC therapy on health-related quality of life (HRQoL), to inform the development of a treatment-specific Patient-Reported Outcome Measure (PROM) for use in clinical trials and practice. Methods: Semi-structured qualitative interviews were conducted with patients from the UK, USA and Australia, treated for a rheumatic condition with GCs in the last two years. Purposive sampling was used to select participants with a range of demographic and disease features. An initial conceptual framework informed interview prompts and cues. Interviews elicited GC-related physical and psychological symptoms and salient aspects of HRQoL in relation to GC therapy. Interview data were analysed inductively to develop initial individual themes and domains. Candidate questionnaire items were developed and refined. Results: Sixty semi-structured qualitative interviews were conducted (UK n=34, USA n=10, Australia n=16). Mean age 58 years; 39/60 female; 18 rheumatic diseases were represented. 126 individual themes were identified and organised into six domains: physical symptoms; psychological symptoms; psychological impact of steroids; impact of steroids on participation; impact of steroids on relationships; and benefits of steroids. Candidate questionnaire items were tested and refined by piloting with patient research partners, iterative rounds of cognitive interviews, and linguistic translatability assessment, informing a draft questionnaire. Conclusion: We describe an international qualitative study to develop candidate items for a treatment-specific PROM for patients with rheumatic diseases. A future survey will enable the validation of a final version of the PROM