201 research outputs found
How to interpret figures in reports of clinical trials
No full textA picture may be worth a thousand words but in medical research, caution Stuart Pocock, Thomas Travison, and Lisa Wruck, it is important to understand exactly what you are looking a
Effects of testosterone replacement on metabolic and inflammatory markers in men with opioid-induced androgen deficiency
No full textObjective: Symptomatic androgen deficiency is common in patients taking opioid analgesics, and testosterone replacement in these men improves libido, quality of life and body composition. However, the effects of testosterone replacement on metabolic and inflammatory markers in this setting have not been evaluated. This is important as opiate use itself has been associated with metabolic abnormalities. The objective of this investigation was to determine the effects of testosterone administration on metabolic and inflammatory markers in adult men with opioid-induced androgen deficiency. Methods: Sixty-four nondiabetic men aged 18 to 64 years using opioid analgesics for chronic noncancer pain with total testosterone levels <12 nmol/l were randomized to 14 weeks of transdermal testosterone gel or placebo gel daily. Total testosterone levels were measured by liquid chromatography mass spectrometry, and free testosterone was calculated using the law-of-mass-action equation. Metabolic parameters, inflammatory markers and oral glucose tolerance test (OGTT) were evaluated at baseline and 14 weeks. Results: Baseline characteristics were similar between the two groups. Testosterone concentrations increased from 7·7 ± 3·0 to 27 ± 19 nmol/l in the testosterone group, but did not meaningfully change in placebo group. Mean changes in metabolic and inflammatory markers during intervention did not differ significantly between groups and were not related to changes in on-treatment serum testosterone concentrations. Glucose and insulin response to the 75 g OGTT also did not differ between groups. Conclusion: In this 14-week trial, testosterone administration in men with opioid-induced androgen deficiency was not associated with worsening of metabolic and inflammatory markers
Figures in clinical trial reports: current practice & scope for improvement.
No full textBACKGROUND: Most clinical trial publications include figures, but there is little guidance on what results should be displayed as figures and how. PURPOSE: To evaluate the current use of figures in Trial reports, and to make constructive suggestions for future practice. METHODS: We surveyed all 77 reports of randomised controlled trials in five general medical journals during November 2006 to January 2007. The numbers and types of figures were determined, and then each Figure was assessed for its style, content, clarity and suitability. As a consequence, guidelines are developed for presenting figures, both in general and for each specific common type of Figure. RESULTS: Most trial reports contained one to three figures, mean 2.3 per article. The four main types were flow diagram, Kaplan Meier plot, Forest plot (for subgroup analyses) and repeated measures over time: these accounted for 92% of all figures published. For each type of figure there is a considerable diversity of practice in both style and content which we illustrate with selected examples of both good and bad practice. Some pointers on what to do, and what to avoid, are derived from our critical evaluation of these articles' use of figures. CONCLUSION: There is considerable scope for authors to improve their use of figures in clinical trial reports, as regards which figures to choose, their style of presentation and labelling, and their specific content. Particular improvements are needed for the four main types of figures commonly used
A subset of men with age-related decline in testosterone have gonadotroph autoantibodies
No full textContext: Age-related decline in serum testosterone (T) is being increasingly diagnosed. In most men, it associates with low or inappropriately normal gonadotropin levels, which suggests a hypothalamic-pituitary etiology. Autoantibodies against adenohypophyseal cells have been associated with pituitary dysfunction; however, the prevalence of pituitary autoimmunity in this age-related T decline has not been assessed. Objectives: This is a proof-of-concept study with the objective of determining the prevalence of antibodies to gonadotrophs in older men with age-related low T and compare it with healthy young and older eugonadal men. Study Design: This is a cross-sectional case-control study of 182 men. Cases included 100 older men (≥65 years) with age-related low T levels; the control groups were composed of 50 young and 32 older healthy eugonadal men. Serum antibodies against the anterior pituitary gland were measured using a two-step approach: 1) single indirect immunofluorescence (ie, participant serum only) to determine the pattern of cytosolic staining; and 2) double indirect immunofluorescence (ie, participant serum plus a commercial adenohypophyseal hormone antibody) to identify the anterior pituitary cell type recognized by the patient's antibodies). Results: In participants with positive antipituitary antibodies, the granular cytosolic pattern (highly predictive of pituitary autoimmunity) was only seen in older men with age-related low T (4%) and none in control groups (0%, P = .001). Double indirect immunofluorescence confirmed that pituitary antibodies were exclusively directed against the gonadotrophs. Conclusion: A subset of older men with age-related low T levels have specific antibodies against the gonadotrophs. Whether these antibodies are pathogenic and contributory to the age-related decline in T remains to be established
Resources, methods, and data infrastructure to promote research in dementia care, caregiving, and services
No full textBackgroundThe National Institute on Aging, in conjunction with the Department of Health and Human Services as part of the National Alzheimer’s Project Act, hosted a 2020 Dementia Care, Caregiving, and Services Research Summit Virtual Meeting Series on August 13, 2020. This article reflects three presentations related to Theme 6: Research Resources, Methods, and Data Infrastructure. Dr. Bynum discussed the challenges of identifying people for population‐ and healthcare‐based research, including how definitions of dementia have changed over time, the opportunities and challenges inherent in the use of electronic data sources, and the need to fit data collection strategies to research goals and questions. Dr. Travison provided an overview on the growing use of embedded pragmatic clinical trials (ePCTs) and how to enhance their impact in dementia research. Dr. Wendler presented on the ethical considerations relevant to consent for dementia research, including assessment of decisional capacity and the role of decisional surrogates.ConclusionsThe availability of claims data, electronic health records, and other sources of “existing” data has made the use and development of ePCTs both easier and more appealing. Among other things, they offer advantages in terms of lower cost and generalizability to real‐world settings. This is turn has necessitated the use of informatic and analytic approaches to account for some of the limitations and complexities of such data, including multilevel clustering and the need to link and jointly analyze data from the person with dementia and those of their care partner. As part of this process, it will be important to broaden the scope of who is assessed for decisional capacity, make those assessments more study specific, and assist surrogates in making decisions based on what the individual would have chosen for themselves if capacitated (i.e., substituted judgment).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168481/1/jgs17339_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168481/2/jgs17339.pd
The Method of Randomization for Cluster-Randomized Trials: Challenges of Including Patients with Multiple Chronic Conditions
No full textCluster-randomized clinical trials (CRT) are trials in which the unit of randomization is not a participant but a group (e.g. healthcare systems or community centers). They are suitable when the intervention applies naturally to the cluster (e.g. healthcare policy); when lack of independence among participants may occur (e.g. nursing home hygiene); or when it is most ethical to apply an intervention to all within a group (e.g. school-level immunization). Because participants in the same cluster receive the same intervention, CRT may approximate clinical practice, and may produce generalizable findings. However, when not properly designed or interpreted, CRT may induce biased results. CRT designs have features that add complexity to statistical estimation and inference. Chief among these is the cluster-level correlation in response measurements induced by the randomization. A critical consideration is the experimental unit of inference; often it is desirable to consider intervention effects at the level of the individual rather than the cluster. Finally, given that the number of clusters available may be limited, simple forms of randomization may not achieve balance between intervention and control arms at either the cluster- or participant-level. In non-clustered clinical trials, balance of key factors may be easier to achieve because the sample can be homogenous by exclusion of participants with multiple chronic conditions (MCC). CRTs, which are often pragmatic, may eschew such restrictions. Failure to account for imbalance may induce bias and reducing validity. This article focuses on the complexities of randomization in the design of CRTs, such as the inclusion of patients with MCC, and imbalances in covariate factors across clusters.Version of Recor
Influence of a six month endurance exercise program on the immune function of prostate cancer patients undergoing Antiandrogen or Chemotherapy: design and rationale of the ProImmun study
No full textBackground: Exercise seems to minimize prostate cancer specific mortality risk and treatment related side effects like fatigue and incontinence. However the influence of physical activity on the immunological level remains uncertain. Even prostate cancer patients undergoing palliative treatment often have a relatively long life span compared to other cancer entities. To optimize exercise programs and their outcomes it is essential to investigate the underlying mechanisms. Further, it is important to discriminate between different exercise protocols and therapy regimes.
Methods/Design: The ProImmun study is a prospective multicenter patient preference randomized controlled trial investigating the influence of a 24 week endurance exercise program in 80–100 prostate cancer patients by comparing patients undergoing Antiandrogen therapy combined with exercise (AE), Antiandrogen therapy without exercise (A), Chemotherapy with exercise(CE) or Chemotherapy without exercise (C). The primary outcome of the study is a change in prostate cancer relevant cytokines and hormones (IL-6, MIF, IGF-1, Testosterone). Secondary endpoints are immune cell ratios, oxidative stress and antioxidative capacity levels, VO2 peak, fatigue and quality of life. Patients of the intervention group exercise five times per week, while two sessions are supervised. During the supervised sessions patients (AE and CE) exercise for 33 minutes on a bicycle ergometer at 70-75% of their VO2 peak. To assess long term effects and sustainability of the intervention two follow-up assessments are arranged 12 and 18 month after the intervention.
Discussion: The ProImmun study is the first trial which primarily investigates immunological effects of a six month endurance exercise program in prostate cancer patients during palliative care. Separating patients treated with Antiandrogen therapy from those who are additionally treated with Chemotherapy might allow a more specific view on the influence of endurance training interventions and the impact of different therapy protocols on the immune function.
Trial registration: German Clinical Trials Register: DRKS0000473
Isometries for the induced c-norm on square matrices and some related results
No full textAbstractLet Fn be the linear space of column vectors with n coordinates over F = R or C. Denote by GP(n) the group of n × n generalized permutation matrices, i.e., matrices with exactly one nonzero entry with magnitude 1 in each row and column. Given a nonzero vector c = (c1…,cn)t ∈ Fn, define the c-norm of x = (x1,…,xn)t ∈ Fn by |x|c=max{|ctPx|:P∈GP(n)}, and the induced c-norm of A ∈ Fn×n by ||A||c=max{|Ay|c:|y|c⩽1}. We characterize, the isometries for induced c-norms. To achieve our goal, we study the geometric properties of Fn × n, and obtain some inequalities related to the induced c-norm as by-products. These results are of independent interest
Modulating Brain Activity to Improve Goal-directed Physical Activity in Older Adults: A Pilot Randomized Controlled Trial
No full textBackground: Insufficient physical activity in older adults remains a global health issue. Several interrelated factors contributing to inactivity are linked to the prefrontal cortex. We conducted a pilot study to assess the feasibility, acceptability, and effects of combining transcranial direct current stimulation (tDCS) and behavior counseling to improve physical activity in older adults. Methods: Inactive older adults living in subsidized housing participated in this randomized controlled trial. Baseline physical activity (daily steps) was measured with a Fitbit for 2 weeks. Participants then received an 8-week intervention, including 10 daily sessions of tDCS or Sham stimulation during the first 2 weeks, along with 4 biweekly behavior sessions. Functional outcomes were assessed at baseline, poststimulation, and after the entire intervention. Step counts were measured throughout the intervention and a 12-week retention period. Results: Twenty-eight participants completed the study. Compliance was 97%, 93%, and 92% for brain stimulation, behavior sessions, and follow-up assessments, respectively. Fitbit adherence was 96% and 71% during the intervention and retention periods. The tDCS arm, compared to Sham, exhibited greater increase in average daily steps (p .001). Participants increased 1 179 (+ 22%) and 550 (+ 15%) steps/day from baseline in the tDCS and Sham arms, respectively. Motivation (p .03) and self-reported walking performance (p .02) were also improved in the tDCS arm compared to Sham. Conclusions: Combining tDCS and personalized behavior counseling to improve physical activity was feasible, acceptable, and appeared to be effective in a cohort of inactive older adults living within subsidized housing. Larger and more definitive studies are warranted. © The Author(s) 2025. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved
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