Suspected Spontaneous Reports of Birth Defects in the UK Associated with the Use of Carbimazole and Propylthiouracil in Pregnancy

The concept of a carbimazole embryopathy underlies current Endocrine Society advice to avoid this drug in early pregnancy, favouring propylthiouracil as an alternative for the treatment of maternal hyperthyroidism. We aimed to establish whether suspected spontaneous reporting of adverse drug reactions in the UK via the Yellow Card Scheme supports a carbimazole embryopathy and the lack of association between propylthiouracil and congenital anomalies. All birth defects related to maternal treatment with carbimazole or propylthiouracil reported over a 47-year period via the Yellow Card Scheme were analysed. 57 cases with 97 anomalies were reported following in utero exposure to carbimazole. These anomalies included aplasia cutis, choanal atresia, tracheo-oesophageal fistula, and patent vitellointestinal duct, which have previously been reported in association with carbimazole/methimazole exposure in utero. Only 6 cases with 11 anomalies were reported for propylthiouracil, all within the last 15 years. Therefore, these findings may support a carbimazole embryopathy. There are few birth defects associated with propylthiouracil, but this should be interpreted in the context of higher historical prescription rates for carbimazole

Literature Review: Barriers to Participation in the Online Learning Environment: The Role of Race and Gender

As the number of adults participating in online learning continues to grow, it is important that adult educators, curriculum designers and the administrators of those programs understand the nature and characteristics of the adult learners filling those programs. Just as there are concerns about the efficacy of learning within traditional classrooms, there needs to be equal concerns about the effectiveness of learning in the online environment. An important question to be addressed--What is the significance of race, ethnicity and gender in the online learning environment

Pyrrolo[2,3D]Pyrimidine Compounds

Described herein is pyrrolo{2,3-d}pyrimidine compounds, their use as Janus Kinase (JAK) inhibitors, pharmaceutical compositions containing this compounds, and methods for the preparation of these compounds

Nurses Alumni Association Bulletin, Fall 1994

1994-1995 Meeting Dates Calendar 1995 Annual Luncheon - Meeting Notice Officers and Committee Chairs Bulletin Publication Committee 1994-1995 Meeting Dates Calendar The President\u27s Message Treasurer\u27s Report News About Our Graduates Fiftieth Anniversary Resume of Minutes of Alumni Association Meetings Department of Nursing 1993-1994 Alumni Office News Jefferson 2000 Fund The Women\u27s Center for Health Promotion Discount Parking for Alumni Cadet Nurse Corps Medical Anecdotes of Faith Ukranian-American Teacher Exchange Happy Birthday Committee Reports In Memoriam, Names of Deceased Graduates Luncheon Photos Class News Jefferson Alumni Identification Card Relief Fund Application Scholarship Application Membership Application Pins, Transcripts, Class Address Lists, Change of address Forms Campus Ma

Patterns of postmeal insulin secretion in individuals with sulfonylurea- treated KCNJ11 neonatal diabetes show predominance of non- KATP- channel pathways

Insulin secretion in sulfonylurea-treated KCNJ11 permanent neonatal diabetes mellitus (PNDM) is thought to be mediated predominantly through amplifying non-KATP-channel pathways such as incretins. Affected individuals report symptoms of postprandial hypoglycemia after eating protein/fat-rich foods. We aimed to assess the physiological response to carbohydrate and protein/fat in people with sulfonylurea-treated KCNJ11 PNDM.This article is freely available via Open Access. Click on the Publisher URL to access the full-text via the publisher's site

Nurses Alumni Association Bulletin, Fall 1995

1995-1996 Meeting Dates Calendar 1996 Annual Luncheon-Meeting Notice Officers and Committee Chairs Bulletin Publication Committee 1995-1996 Meeting Dates Calendar The President\u27s Message Financial Report What\u27s New Fiftieth Anniversary Resume of Minutes of Alumni Association Meetings Scholarship Funds at Work CAHS Alumni Board/Diploma School Alumni Office News Jefferson Health System Oldest Veteran Dies 1OOth Anniversary Pearl Harbor Remembered Memories Janet Hindson Retires Happy Birthday Scholarship Fund donors for 1994 Committee Reports By-Laws Development Bulletin Relief Fund Satellite Social Scholarship In Memoriam, Names of Deceased Graduates Class News Luncheon Photos Jefferson Alumni Identification Card The Diploma School of Nursing Alumni Association-Mabel C. Prevost Letter of Appreciation Tribute To a Mother An End Must Come Stuff For Senior Citizens to Chuckle Over Membership Application Relief Fund Application To Order: A Chronological History and Alumni Directory From TJU Bookstore Scholarship Fund Application Pins, Transcripts, Class Address List, Change of Address Forms, Alumni Identification Card Campus Map Picture - Class of 1893-189

Randomized trials fit for the 21st century. A joint opinion from the European Society of Cardiology, American Heart Association, American College of Cardiology, and the World Heart Federation

© The Author(s) 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. When citing this article, a citation from any of the journals listed is appropriate. For commercial re-use, please contact [email protected] controlled trials are the cornerstone for reliably evaluating therapeutic strategies. However, during the past 25 years, the rules and regulations governing randomized trials and their interpretation have become increasingly burdensome, and the cost and complexity of trials has become prohibitive. The present model is unsustainable, and the development of potentially effective treatments is often stopped prematurely on financial grounds, while existing drug treatments or non-drug interventions (such as screening strategies or management tools) may not be assessed reliably. The current ‘best regulatory practice’ environment, and a lack of consensus on what that requires, too often makes it unduly difficult to undertake efficient randomized trials able to provide reliable evidence about the safety and efficacy of potentially valuable interventions. Inclusion of underrepresented population groups and lack of diversity also remain among the challenges.info:eu-repo/semantics/publishedVersio

Long-term follow-up of glycemic and neurological outcomes in an international series of patients with sulfonylurea-treated ABCC8 permanent neonatal diabetes

This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this record OBJECTIVE ABCC8 mutations cause neonatal diabetes mellitus that can be transient (TNDM) or, less commonly, permanent (PNDM); ∼90% of individuals can be treated with oral sulfonylureas instead of insulin. Previous studies suggested that people with ABCC8-PNDM require lower sulfonylurea doses and have milder neurological features than those with KCNJ11-PNDM. However, these studies were short-term and included combinations of ABCC8-PNDM and ABCC8-TNDM. We aimed to assess the long-term glycemic and neurological outcomes in sulfonylurea-treated ABCC8-PNDM. RESEARCH DESIGN AND METHODS We studied all 24 individuals with ABCC8-PNDM diagnosed in the U.K., Italy, France, and U.S. known to transfer from insulin to sulfonylureas before May 2010. Data on glycemic control, sulfonylurea dose, adverse effects including hypoglycemia, and neurological features were analyzed using nonparametric statistical methods. RESULTS Long-term data were obtained for 21 of 24 individuals (median follow-up 10.0 [range 4.1–13.2] years). Eighteen of 21 remained on sulfonylureas without insulin at the most recent follow-up. Glycemic control improved on sulfonylureas (presulfonylurea vs. 1-year posttransfer HbA1c 7.2% vs. 5.7%, P = 0.0004) and remained excellent long-term (1-year vs. 10-year HbA1c 5.7% vs. 6.5%, P = 0.04), n = 16. Relatively high doses were used (1-year vs. 10-year dose 0.37 vs. 0.25 mg/kg/day glyburide, P = 0.50) without any severe hypoglycemia. Neurological features were reported in 13 of 21 individuals; these improved following sulfonylurea transfer in 7 of 13. The most common features were learning difficulties (52%), developmental delay (48%), and attention deficit hyperactivity disorder (38%). CONCLUSIONS Sulfonylurea treatment of ABCC8-PNDM results in excellent long-term glycemic control. Overt neurological features frequently occur and may improve with sulfonylureas, supporting early, rapid genetic testing to guide appropriate treatment and neurodevelopmental assessment.Wellcome Trus

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome

Sjögren’s syndrome is a common autoimmune disease (~0.7% of European Americans) typically presenting as keratoconjunctivitis sicca and xerostomia. In addition to strong association within the HLA region at 6p21 (Pmeta=7.65×10−114), we establish associations with IRF5-TNPO3 (Pmeta=2.73×10−19), STAT4 (Pmeta=6.80×10−15), IL12A (Pmeta =1.17×10−10), FAM167A-BLK (Pmeta=4.97×10−10), DDX6-CXCR5 (Pmeta=1.10×10−8), and TNIP1 (Pmeta=3.30×10−8). Suggestive associations with Pmeta<5×10−5 were observed with 29 regions including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2, and PHIP amongst others. These results highlight the importance of genes involved in both innate and adaptive immunity in Sjögren’s syndrome

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology