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Study design of Dal-GenE, a pharmacogenetic trial targeting reduction of cardiovascular events with dalcetrapib.
Tardif, JC, Dubé, MP, Pfeffer, MA, Waters, DD, Koenig, W, Maggioni, AP, McMurray, JJV, Mooser, V, White, HD, Heinonen, T, et al
American heart journal. 2020;:157-165
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Abstract
The objectives of precision medicine are to better match patient characteristics with the therapeutic intervention to optimize the chances of beneficial actions while reducing the exposure to unneeded adverse drug experiences. In a retrospective genome-wide association study of the overall neutral placebo-controlled dal-Outcomes trial, the effect of the cholesteryl ester transfer protein (CETP) modulator dalcetrapib on the composite of cardiovascular death, myocardial infarction or stroke was found to be influenced by a polymorphism in the adenylate cyclase type 9 (ADCY9) gene. Whereas patients with the AA genotype at position rs1967309 experienced fewer cardiovascular events with dalcetrapib, those with the GG genotype had an increased rate and the heterozygous AG genotype exhibited no difference from placebo. Measurements of cholesterol efflux and C-reactive protein (CRP) offered directionally supportive genotype-specific findings. In a separate, smaller, placebo-controlled trial, regression of ultrasonography-determined carotid intimal-medial thickness was only observed in dalcetrapib-treated patients with the AA genotype. Collectively, these observations led to the hypothesis that the cardiovascular effects of dalcetrapib may be pharmacogenetically determined, with a favorable benefit-risk ratio only for patients with this specific genotype. We describe below the design of dal-GenE, a precision medicine, placebo-controlled clinical outcome trial of dalcetrapib in patients with a recent acute myocardial infarction with the unique feature of selecting only those with the AA genotype at rs1967309 in the ADCY9 gene.
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Non-pharmacologic measures for gout management in the prospective GOSPEL cohort: Physicians' practice and patients' compliance profiles.
Chapron, A, Chopin, T, Esvan, M, Ea, HK, Lioté, F, Guggenbuhl, P
Joint bone spine. 2019;(2):225-231
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Abstract
OBJECTIVES Gout management includes non-pharmacological measures (NPM). The main objective of this study was to describe the NPM proposed by physicians and their implementation by patients after 3-6 months. The secondary objective was to identify NPM compliance profiles among these patients. METHODS Ancillary observational study using the GOSPEL French cohort of 1003 patients with gout, based on questionnaires for physicians and patients at inclusion and then after 3-6 months. Patients were included by a representative sample of 398 general practitioners (GP) and 109 private-practice rheumatologists. Modifiable risk factors of hyperuricemia and proposed NPM were compared. Patient compliance profiles were identified by multiple correspondence and hierarchical clustering analysis. RESULTS The study included 630 patients: 80.7% were obese or overweight, 51% reported excessive alcohol consumption. Physicians identified fewer modifiable risk factors than their real prevalence in the cohort. Physicians proposed NPM to 57% of patients, particularly diet modifications (46.4%). Increasing physical activity (P < 0.0001) was the best followed NPM. The physician's influence in the decision of starting NPM was more frequent among GPs' patients (P = 0.01). Three patients' compliance profiles were identified. "Very good responders" (55.8%) implemented all the proposed NPM. "Good responders" (12.7%) had a more severe disease and followed the proposed NPM, but for alcohol consumption. "Bad responders" (31.5%) did not modify their life style: these were older patients with a very recent gout diagnosis. CONCLUSION More personalized care about NPM requires adapting the practitioner's approach to patients' compliance profiles, especially elderly patients with recent gout.
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A Tailored Letter Based on Electronic Health Record Data Improves Gestational Weight Gain Among Women With Gestational Diabetes Mellitus: The Gestational Diabetes' Effects on Moms (GEM) Cluster-Randomized Controlled Trial.
Hedderson, MM, Brown, SD, Ehrlich, SF, Tsai, AL, Zhu, Y, Quesenberry, CP, Crites, Y, Ferrara, A
Diabetes care. 2018;(7):1370-1377
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OBJECTIVE Evaluate whether a tailored letter improved gestational weight gain (GWG) and whether GWG mediated a multicomponent intervention's effect on postpartum weight retention among women with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS A cluster-randomized controlled trial of 44 medical facilities (n = 2,014 women) randomized to usual care or a multicomponent lifestyle intervention delivered during pregnancy (tailored letter) and postpartum (13 telephone sessions) to reduce postpartum weight retention. The tailored letter, using electronic health record (EHR) data, recommended an end-of-pregnancy weight goal tailored to prepregnancy BMI and GWG trajectory at GDM diagnosis: total GWG at the lower limit of the IOM range if BMI ≥18.5 kg/m2 or the midpoint if <18.5 kg/m2 and weight maintenance if women had exceeded this. The outcomes for this study were the proportion of women meeting the Institute of Medicine (IOM) guidelines for weekly rate of GWG from GDM diagnosis to delivery and meeting the end-of-pregnancy weight goal. RESULTS The tailored letter significantly increased the proportion of women meeting the IOM guidelines (72.6% vs. 67.1%; relative risk 1.08 [95% CI 1.01-1.17]); results were similar among women with BMI <25.0 kg/m2 (1.07 [1.00-1.15]) and ≥25.0 kg/m2 (1.08 [0.98-1.18]). Thirty-six percent in the intervention vs. 33.0% in usual care met the end-of-pregnancy weight goal (1.08 [0.99-1.18]); the difference was statistically significant among women with BMI <25.0 kg/m2 (1.28 [1.05-1.57]) but not ≥25.0 kg/m2 (0.99 [0.87-1.13]). Meeting the IOM guidelines mediated the effect of the multicomponent intervention in reducing postpartum weight retention by 24.6% (11.3-37.8%). CONCLUSIONS A tailored EHR-based letter improved GWG, which mediated the effect of a multicomponent intervention in reducing postpartum weight retention.
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Evaluation of the efficacy of a short-course, personalized self-management and intensive spa therapy intervention as active prevention of musculoskeletal disorders of the upper extremities (Muska): a research protocol for a randomized controlled trial.
Lanhers, C, Pereira, B, Gay, C, Hérisson, C, Levyckyj, C, Dupeyron, A, Coudeyre, E
BMC musculoskeletal disorders. 2016;(1):497
Abstract
BACKGROUND Musculoskeletal disorders (MSDs) constitute a major occupational health problem in the working population, substantially impacting the quality of life of employees. They also cause considerable economic cost to the healthcare system, with, notably, the reimbursement of treatments and compensation for lost income. MSDs manifest as localized pain or functional difficulty in one or more anatomical areas, such as the cervical spine, shoulder, elbow, hand, and wrist. Although prevalence varies depending on the region considered and the method of assessment, a prevalence of 30% is found in different epidemiological studies. The disease needs to be prevented, not only for medical and economic reasons, but also for legal reasons, owing to the requirement of assessing occupational risks. The strategy envisaged may thus revolve around active, multimodal prevention that has employees fully involved at the heart of their care. Although physical exercise is widely recommended, few studies with a good level of evidence have enabled us to base a complete, well-constructed intervention on exercise that can be offered as secondary prevention in these disorders. METHODS A prospective, multicenter, comparative (intervention arm vs. control arm), randomized (immediate vs. later treatment) study using Zelen's design. This study falls under active prevention of MSDs of the upper extremities (UE-MSDs). Participants are workers aged between 18 and 65 years with latent or symptomatic MSDS, with any type of job or workstation, with or without an history of sick leave. The primary aim is to show the superiority at 3 months of a combination of spa therapy, exercise, and self-management workshops for 6 days over usual care in the management of MSDs in terms of employee functional capacity in personal and professional daily life. Secondary aims are to assess the benefit of the intervention in terms of pain, quality of life, and accumulated duration of sick leave. DISCUSSION This randomized controlled trial is the first that will aim to evaluate multidisciplinary management of UE-MSDs using nonpharmacological treatment combining exercise, self-management, and spa therapy. The originality of this intervention lies, in its short, intensive format, which is compatible with remaining in work; and in its multidisciplinary approach. This trial has the potential to demonstrate, with a good level of evidence, the benefits of a short course of spa therapy combined with a personalized self-management program on the functional capacity, pain, and quality of life of employees in their daily life. TRIAL REGISTRATION Clinical trial.gov NCT02702466 retrospectively registered. PROTOCOL Version 4 of 9/10/2015.