Beneficial and adverse effects of testosterone on the cardiovascular system in men

Context: The widespread use of T therapy, particularly in aging males, necessitates knowledge of the relationship between T and the cardiovascular system. Evidence Acquisition: The review is based on a 1970 to 2013 PubMed search with terms related to androgens in combination with cardiovascular disease, including T, dihydrotestosterone, trial, mortality, cardiovascular disease, myocardial infarction, blood pressure, endothelial function, dyslipidemia, thrombosis, ventricular function, and arrhythmia. Original articles, systematic reviews and meta-analyses, and relevant citations were screened. Evidence Synthesis: Low T has been linked to increased blood pressure, dyslipidemia, atherosclerosis, arrhythmia, thrombosis, endothelial dysfunction, as well as to impaired left ventricular function. On the one hand, a modest association is suggested between low endogenous T and incident cardiovascular disease or cardiovascular mortality, implying unrecognized beneficial T effects, residual confounding, or a relationship with health status. On the other hand, treatments with T to restore "normal concentrations" have so far not been proven to be beneficial with respect to cardiovascular disease; neither have they definitely shown specific adverse cardiovascular effects. The cardiovascular risk-benefit profile of T therapy remains largely evasive in view of a lack of well-designed and adequately powered randomized clinical trials. Conclusions: The important knowledge gap as to the exact relationship between T and cardiovascular disease would support a cautious, restrained approach to T therapy in aging men, pending clarification of benefits and risks by adequately powered clinical trials of sufficient duration

Sex Steroids Affect Triglyceride Handling, Glucose-Dependent Insulinotropic Polypeptide, and Insulin Sensitivity: A 1-week randomized clinical trial in healthy young men

OBJECTIVE- To evaluate metabolic effects of sex steroids in nonfasting and fasting conditions, independent from changes in body composition. RESEARCH DESIGN AND METHODS- A randomized clinical trial was performed to create contrasting sex steroid levels in healthy young men: by letrozole (aromatase inhibitor) to lower estradiol (E-2) and increase testosterone (group T, n = 10) versus letrozole plus E-2 patches to lower T and raise E-2 (group E, n = 10). Mixed meals and hyperinsulinemic-euglycemic clamps were performed before and after a 1-week treatment period. RESULTS- Following intervention, the postprandial triglyceride response displayed a diverging response with a decline in group T and an increase in group E; the postprandial glucose-dependent insulinotropic polypeptide (GIP) response increased in group T. Insulin sensitivity increased in group T but remained unaltered in group E. CONCLUSIONS- In healthy young men, short-term changes in sex steroids affect postprandial triglyceride and GIP response and insulin sensitivity

Dual-Decoder Consistency via Pseudo-Labels Guided Data Augmentation for Semi-Supervised Medical Image Segmentation

Medical image segmentation methods often rely on fully supervised approaches to achieve excellent performance, which is contingent upon having an extensive set of labeled images for training. However, annotating medical images is both expensive and time-consuming. Semi-supervised learning offers a solution by leveraging numerous unlabeled images alongside a limited set of annotated ones. In this paper, we introduce a semi-supervised medical image segmentation method based on the mean-teacher model, referred to as Dual-Decoder Consistency via Pseudo-Labels Guided Data Augmentation (DCPA). This method combines consistency regularization, pseudo-labels, and data augmentation to enhance the efficacy of semi-supervised segmentation. Firstly, the proposed model comprises both student and teacher models with a shared encoder and two distinct decoders employing different up-sampling strategies. Minimizing the output discrepancy between decoders enforces the generation of consistent representations, serving as regularization during student model training. Secondly, we introduce mixup operations to blend unlabeled data with labeled data, creating mixed data and thereby achieving data augmentation. Lastly, pseudo-labels are generated by the teacher model and utilized as labels for mixed data to compute unsupervised loss. We compare the segmentation results of the DCPA model with six state-of-the-art semi-supervised methods on three publicly available medical datasets. Beyond classical 10\% and 20\% semi-supervised settings, we investigate performance with less supervision (5\% labeled data). Experimental outcomes demonstrate that our approach consistently outperforms existing semi-supervised medical image segmentation methods across the three semi-supervised settings

Mediators of physical activity change in a behavioral modification program for type 2 diabetes patients

Background: Many studies have reported significant behavioral impact of physical activity interventions. However, few have examined changes in potential mediators of change preceding behavioral changes, resulting in a lack of information concerning how the intervention worked. Our purpose was to examine mediation effects of changes in psychosocial variables on changes in physical activity in type 2 diabetes patients.Methods: Ninety-two patients (62 ± 9 years, 30, 0 ± 2.5 kg/m, 69% males) participated in a randomized controlled trial. The 24-week intervention was based on social-cognitive constructs and consisted of a face-to-face session, telephone follow-ups, and the use of a pedometer. Social-cognitive variables and physical activity (device-based and self-reported) were collected at baseline, after the 24-week intervention and at one year post-baseline. PA was measured by pedometer, accelerometer and questionnaire.Results: Post-intervention physical activity changes were mediated by coping with relapse, changes in social norm, and social modeling from family members (p ≤ 0.05). One-year physical activity changes were mediated by coping with relapse, changes in social support from family and self-efficacy towards physical activity barriers (p ≤ 0.05). Conclusions: For patients with type 2 diabetes, initiatives to increase their physical activity could usefully focus on strategies for resuming regular patterns of activity, on engaging family social support and on building confidence about dealing with actual and perceived barriers to activity.Trial Registration: NCT00903500, ClinicalTrials.gov

Moxifloxacin dosing in post-bariatric surgery patients

Introduction Given the ever increasing number of obese patients and obesity related bypass surgery, dosing recommendations in the post-bypass population are needed. Using a population pharmacokinetic (PK) analysis and PK-pharmacodynamic (PD) simulations, we investigated whether adequate moxifloxacin concentrations are achieved in this population. Methods In this modelling and simulation study we used data from a trial on moxifloxacin PK. In this trial, volunteers who had previously undergone bariatric surgery (at least 6 months prior to inclusion), received two doses (intravenous and oral) of 400mg moxifloxacin administered on two occasions. Results In contrast to other papers, we found that moxifloxacin PK were best described by a three compartmental model using lean body mass (LBM) as a predictor for moxifloxacin clearance. Furthermore, we showed that the probability of target attainment for bacterial eradication against a hypothetical Streptococcus pneumoniae infection is compromised in patients with higher LBM, especially when targeting microorganisms with minimum inhibitory concentrations (MICs) of 0.5mgl-1 or higher (probability of target attainment (PTA) approaching zero). When considering the targets for suppression of bacterial resistance formation, even at MIC values as low as 0.25mgl-1, standard moxifloxacin dosing does not attain adequate levels in this population. Furthermore, for patients with a LBM of 78kg or higher, the probability of hitting this target approaches zero. Conclusions Throughout our PK-PD simulation study, it became apparent that, whenever optimal bacterial resistance suppression is deemed necessary, the standard moxifloxacin dosing will not be sufficient. Furthermore, our study emphasizes the need for a LBM based individualized dosing of moxifloxacin in this patient population

Manchester triage system in paediatric emergency care: prospective observational study

Objective To validate use of the Manchester triage system in paediatric emergency care

Interventions to promote medication adherence for chronic diseases in India: a systematic review

IntroductionCost-effective interventions that improve medication adherence are urgently needed to address the epidemic of non-communicable diseases (NCDs) in India. However, in low- and middle-income countries like India, there is a lack of analysis evaluating the effectiveness of adherence improving strategies. We conducted the first systematic review evaluating interventions aimed at improving medication adherence for chronic diseases in India.MethodsA systematic search on MEDLINE, Web of Science, Scopus, and Google Scholar was conducted. Based on a PRISMA-compliant, pre-defined methodology, randomized control trials were included which: involved subjects with NCDs; were located in India; used any intervention with the aim of improving medication adherence; and measured adherence as a primary or secondary outcome.ResultsThe search strategy yielded 1,552 unique articles of which 22 met inclusion criteria. Interventions assessed by these studies included education-based interventions (n = 12), combinations of education-based interventions with regular follow up (n = 4), and technology-based interventions (n = 2). Non-communicable diseases evaluated commonly were respiratory disease (n = 3), type 2 diabetes (n = 6), cardiovascular disease (n = 8) and depression (n = 2).ConclusionsAlthough the vast majority of primary studies supporting the conclusions were of mixed methodological quality, patient education by CHWs and pharmacists represent promising interventions to improve medication adherence, with further benefits from regular follow-up. There is need for systematic evaluation of these interventions with high quality RCTs and their implementation as part of wider health policy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022345636, identifier: CRD42022345636