Adverse cardiovascular events and mortality in men during testosterone treatment : an individual patient and aggregate data meta-analysis

Funding National Institute for Health Research Health Technology Assessment Programme. Acknowledgments This work was supported by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme (project no 17/68/01). The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR HTA Programme, or the Department of Health and Social Care, UK. The funders were not actively involved in the research process at any stage. The study design; collection, analysis, and interpretation of data; writing of the manuscript; and decision to submit for publication were performed independent of the funders. The Health Services Research Unit at the University of Aberdeen is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The Section of Endocrinology and Investigative Medicine at Imperial College London is funded by grants from the Medical Research Council, Biotechnology and Biological Sciences Research Council, NIHR, an Integrative Mammalian Biology Capacity Building Award, an FP7-HEALTH-2009-241592 EuroCHIP grant, and is supported by the NIHR Biomedical Research Centre Funding Scheme. The following authors are also funded as follows: NIHR Research Professorship (WSD), NIHR post-doctoral fellowship (CNJ). SBhasin receives National Institutes of Health research grant funding. The authors are grateful to Prakash Abraham, Alison Avenell, Craig Ramsay, Graham Scotland, Neil Scott, and Finlay MacKenzie for their advice; and to the many individuals from academia and industry who helped in the conduct of this study.Peer reviewedPublisher PD

Symptomatic benefits of testosterone treatment in patient subgroups : a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis

Acknowledgments This work was supported by the UK National Institute for Health and Care Research (NIHR)'s Health Technology Assessment Programme (project number 17/68/01). The views expressed herein are those of the authors and not necessarily those of the National Health Service, the NIHR Health Technology Assessment Programme, or the UK Department of Health and Social Care. The Health Services Research Unit at the University of Aberdeen is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The Section of Endocrinology and Investigative Medicine at Imperial College London is funded by grants from the Medical Research Council, the Biotechnology and Biological Sciences Research Council, NIHR, an Integrative Mammalian Biology Capacity Building Award, and an FP7-HEALTH-2009-241592 EuroCHIP grant, and is supported by the NIHR Biomedical Research Centre Funding Scheme. WSD is funded by an NIHR Research Professorship. CNJ is funded by an NIHR Post-Doctoral Fellowship. ShB receives NIH research grant funding. The authors are grateful to the clinical and methodological experts and patient partners who contributed to the advisory group for this study.Peer reviewedPublisher PD

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis

Background Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. Methods We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. Findings 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60–72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95–7·10]; τ²=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40–2·89]; τ²=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males’ Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory). Interpretation In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-mediumterm testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis

BACKGROUND: Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. METHODS: We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. FINDINGS: 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60-72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95-7·10]; τ 2=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40-2·89]; τ 2=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males' Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory). INTERPRETATION: In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-medium-term testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme

The effect of direct cognitive assessment in the Medicare annual wellness visit on dementia diagnosis rates

Objective: To evaluate the relationship between direct cognitive assessment introduced with the Medicare Annual Wellness Visit (AWV) and new diagnoses of dementia, and to determine if effects vary by race. Data Sources: Medicare Limited Data Set 5% sample claims 2003-2014 and the HRSA Area Health Resources Files. Study Design: Instrumental Variable approach estimating the relationship between AWV utilization and new diagnoses of dementia using county-level Welcome to Medicare Visit rates as an instrument. Data Collection/Extraction Methods: Three hundred twenty-four thousand three hundred and eighty-five fee-for-service Medicare beneficiaries without dementia when the AWV was introduced in 2011. Principal Findings: Annual Wellness Visit utilization was associated with an increased probability of new dementia diagnosis with effects varying by racial group (categorized as white, black, Hispanic/Latino, or Asian based on Social Security Administration data). Hazard ratios (95% confidence intervals) for new dementia diagnosis within 6 months of AWV utilization were as follows: 2.34 (2.13, 2.58) white, 2.22 (1.71, 2.89) black, 4.82 (2.94, 7.89) Asian, and 6.14 (3.70, 10.19) Hispanic (P <.001 for each). Our findings show that estimates that do not control for selection underestimate the effect of AWV on new diagnoses. Conclusions: Dementia diagnosis rates increased with AWV implementation with heterogenous effects by race and ethnicity. Current recommendations by the United States Preventive Services Task Force state that the evidence is insufficient to recommend for or against screening for cognitive impairment in older adults. © 2021 Health Research and Educational Trust12 month embargo; first published: 22 January 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Quantifying the impact of standardized assessment and symptom management tools on symptoms associated with cancer-induced anorexia cachexia syndrome

The objective of this study was to quantify the impact of standardized assessment and management tools on patient symptom scores in cancer-induced anorexia cachexia syndrome (ACS) using a within-group study design. Baseline assessments included the Patient Generated Subjective Global Assessment (PG-SGA) tool and an amended Symptoms and Concerns Checklist (SCC). Symptom management strategies, written for this project, were instigated. Follow-up SCC scores were collected at 2 and 4 weeks. Forty out of 79 patients referred were recruited; 29/79 (36.7%) were too unwell or had died prior to consent. At baseline, the PG-SGA tool revealed 250 active symptoms associated with ACS. Total PG-SGA score was above 9 for all patients. Predominant interventions involved simple dietary advice and prescription of artificial saliva, mouthwash and prokinetic antiemetics. Median total SCC score improved sequentially from 11 at baseline, to 7 and 4 at first and second review, respectively (visit 1 to 2, p = 0.001; visit 1 to 3, p < 0.001; and visit 2 to 3, p = 0.02). We conclude that patients with ACS are recognised late in their disease and have a considerable burden of active symptoms. A structured approach to assessment and management has a significant impact on symptom burden