Considerations for open-label randomized clinical trials: Design, conduct, and analysis.

Randomization and blinding are regarded as the most important tools to help reduce bias in clinical trial designs. Randomization is used to help guarantee that treatment arms differ systematically only by treatment assignment at baseline, and blinding is used to ensure that differences in endpoint evaluation and clinical decision-making during the trial arise only from the treatment received and not, for example, the expectation or desires of the people involved. However, given that there are times when it is not feasible or ethical to conduct fully blinded trials, we discuss what can be done to improve a trial, including conducting the trial as if it were a fully blinded trial and maintaining confidentiality of ongoing study results.

Complementary and Alternative Medicine Online Learning Intervention for Oncology Healthcare Providers: A Mixed-Methods Study.

Introduction: With the increased usage of complementary approaches in oncology comes the need for its integration into healthcare professional (HCP) education. The purpose of this single-arm, mixed-methods study was to examine the feasibility and benefits of a brief complementary and alternative medicine (CAM) learning intervention for improving HCP knowledge, attitudes, and practices regarding CAM use in cancer care, and explore the experiences of participating HCPs.

Methods: HCPs from the Tom Baker Cancer Centre in Alberta, Canada, were invited to participate in 3 online interactive learning modules that reviewed: (1) basic CAM information, (2) HCP-patient CAM communication, and (3) evidence-based CAM decision support.

Concept End Points Informing Design Considerations for Confirmatory Clinical Trials in Osteoarthritis.

Objective: There is an unmet need for therapies that target the underlying pathophysiology of osteoarthritis (OA). However, defining appropriate measures for clinical trials of such therapies is challenging. Our objective was to propose concept clinical end points that directly capture clinical benefit in this setting and evaluate the feasibility of their use.

Noninferiority Trials to Evaluate Drug Effects in Rheumatoid Arthritis.

Objective: The increased availability of highly effective treatments in rheumatoid arthritis (RA) necessitates a reexamination of study designs evaluating new treatments. We undertook this study to discuss possible specifications and considerations of noninferiority (NI) trials assessing drug effects in RA.

Methods: We focused on the use of approved tumor necrosis factor inhibitors (TNFi) as potential active controls and reviewed previous placebo-controlled studies.

"In the same boat"-a mixed-methods exploration of reasons why male gastrointestinal cancer patients joined a professionally led men-only cancer support group.

Purpose: Gastrointestinal (GI) cancer patients often suffer high rates of distress and social isolation, partially due to symptoms that are embarrassing or difficult to discuss with family or friends. Group support therapies mitigate illness-related stigma and standardization; however, men, in particular, are more averse to joining. Through an ongoing men-only GI cancer support group, this study sought to understand who joined the groups, what facilitated group uptake, and explore men's reasons for enrolling in the group.

Modality of exercise influences rate of decrease in depression for cancer survivors with elevated depressive symptomatology.

Purpose: This three-arm feasibility controlled trial examined whether different exercise modalities provide reductions in depression symptoms to cancer survivors with elevated depression.

Methods: Thirty-two participants (58.9 ± 9.

Avoiding bias and incorrect confidence interval coverage in prescription drug labeling.

Background: The primary purpose of prescription drug labeling is to give healthcare professionals the information needed to prescribe drugs appropriately. Therefore, labeling typically reports the effects that the treatment might be expected to have on several efficacy measures, including not only the primary endpoint used to establish effectiveness but also a number of key secondary endpoints that are important to practitioners and patients.

Methods: One possible regulatory approach to drug labeling is to include results on important secondary efficacy endpoints in labeling only if there is statistical evidence of a treatment effect and a clinically meaningful estimated effect.

Exercise Improves Physical Function and Mental Health of Brain Cancer Survivors: Two Exploratory Case Studies.

Background Malignant brain tumors are unpredictable and incurable, with 5-year survival rates less than 30%. The poor prognosis combined with intensive treatment necessitates the inclusion of complementary and supportive therapies that optimize quality of life and reduce treatment-related declines in health. Exercise therapy has been shown to be beneficial in other cancer populations, but no evidence is available for brain cancer survivors.

Surveys of Cancer Patients and Cancer Health Care Providers Regarding Complementary Therapy Use, Communication, and Information Needs.

Background: Complementary therapies (CTs) are increasingly utilized by cancer patients. Nonetheless, patients report insufficient support from health care practitioners (HCPs) and there is a general lack of patient-practitioner communication about CT use. Best care practices suggest that HCPs should address the needs of patients, including CT use.

An evaluation of inferential procedures for adaptive clinical trial designs with pre-specified rules for modifying the sample size.

Many papers have introduced adaptive clinical trial methods that allow modifications to the sample size based on interim estimates of treatment effect. There has been extensive commentary on type I error control and efficiency considerations, but little research on estimation after an adaptive hypothesis test. We evaluate the reliability and precision of different inferential procedures in the presence of an adaptive design with pre-specified rules for modifying the sampling plan.

Reliability of physiological attributes and their association with stochastic cycling performance.

Purpose: To assess the reliability of a 5-min-stage graded exercise test (GXT) and determine the association between physiological attributes and performance over stochastic cycling trials of varying distance.

Methods: Twenty-eight well-trained male cyclists performed 2 GXTs and either a 30-km (n = 17) or a 100-km stochastic cycling time trial (n = 9). Stochastic cycling trials included periods of high-intensity efforts for durations of 250 m, 1 km, or 4 km depending on the test being performing.

Estimating mean annual 25-hydroxyvitamin D concentrations from single measurements: the Multi-Ethnic Study of Atherosclerosis.

Background: The seasonal variation in circulating 25-hydroxyvitamin D [25(OH)D] concentrations is large relative to mean values. Single measurements may misclassify annual exposure, which may lead to bias in research and complicate clinical decision making.

Objective: We aimed to develop and validate a model for adjusting a single measurement of a serum 25(OH)D concentration to the time of year it was measured.

Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes.

Context: Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large, prospective community-based studies. Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity, and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D.

Objective: To investigate whether common variation within genes encoding the vitamin D-binding protein, megalin, cubilin, CYP27B1, CYP24A1, and the vitamin D receptor (VDR) modify associations of low 25-hydroxyvitamin D with major clinical outcomes.

Adaptive clinical trial designs with pre-specified rules for modifying the sample size: understanding efficient types of adaptation.

Adaptive clinical trial design has been proposed as a promising new approach that may improve the drug discovery process. Proponents of adaptive sample size re-estimation promote its ability to avoid 'up-front' commitment of resources, better address the complicated decisions faced by data monitoring committees, and minimize accrual to studies having delayed ascertainment of outcomes. We investigate aspects of adaptation rules, such as timing of the adaptation analysis and magnitude of sample size adjustment, that lead to greater or lesser statistical efficiency.

The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease.

Chronic kidney disease is characterized, in part, as a state of decreased production of 1,25-dihydroxyvitamin D (1,25(OH)(2)D); however, this paradigm overlooks the role of vitamin D catabolism. We developed a mass spectrometric assay to quantify serum concentration of 24,25-dihydroxyvitamin D (24,25(OH)(2)D), the first metabolic product of 25-hydroxyvitamin D (25(OH)D) by CYP24A1, and determined its clinical correlates and associated outcomes among 278 participants with chronic kidney disease in the Seattle Kidney Study. For eGFRs of 60 or more, 45-59, 30-44, 15-29, and under 15 ml/min per 1.

Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults: a cohort study.

Background: Circulating concentrations of 25-hydroxyvitamin D [25-(OH)D] are used to define vitamin D deficiency. Current clinical 25-(OH)D targets based on associations with intermediate markers of bone metabolism may not reflect optimal levels for other chronic diseases and do not account for known seasonal variation in 25-(OH)D concentration.

Objective: To evaluate the relationship of 25-(OH)D concentration with the incidence of major clinical disease events that are pathophysiologically relevant to vitamin D.

Variation in oral calcitriol response in patients with stages 3-4 CKD.

Background: Oral calcitriol decreases parathyroid hormone (PTH) concentrations in patients who have chronic kidney disease (CKD); however, treatment response is highly variable. We evaluated whether patient characteristics affect the PTH response to oral calcitriol in nondialysis patients with CKD in a clinic-based setting.

Study Design: Cohort study.

Seasonal variation in 25-hydroxyvitamin D concentrations in the cardiovascular health study.

Low circulating concentrations of 25-hydroxyvitamin D (25(OH)D) are associated with adverse health outcomes in diverse populations. However, 25(OH)D concentrations vary seasonally with varying exposure to sunlight, so single measurements may poorly reflect long-term 25(OH)D exposure. The authors investigated cyclical trends in average serum 25(OH)D concentrations among 2,298 individuals enrolled in the Cardiovascular Health Study of community-based older adults (1992-1993).

Glucose, insulin, and incident hypertension in the multi-ethnic study of atherosclerosis.

Diabetes mellitus and hypertension commonly coexist, but the nature of this link is not well understood. The authors tested whether diabetes and higher concentrations of fasting serum glucose and insulin are associated with increased risk of developing incident hypertension in the community-based Multi-Ethnic Study of Atherosclerosis. At baseline, 3,513 participants were free of hypertension, defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or use of antihypertensive medications to treat high blood pressure.

Effect of concurrent resistance and endurance training on physiologic and performance parameters of well-trained endurance cyclists.

The purpose of this study was to investigate the effect of concurrent resistance and endurance cycle training on physiologic and performance parameters of cyclists. Before and after a 6-week training intervention period, 14 well-trained male cyclists completed a maximal graded exercise test, a 30-km dynamic cycling test with 3 intermittent 250-m and 1-km sprints, and a 1 repetition maximum (1RM) squat test for the assessment of lower-limb strength. Subjects were allocated into 2 groups: a resistance training group (RT; n = 7) that completed a 6-week undulating, periodized resistance training program (3/wk) in conjunction with their regular cycle training and a control group (CON; n = 7) that maintained their usual cycle training.

A phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer.

Background: Androgen deprivation therapy (ADT) is accompanied by a number of adverse side effects including reduced bone mass and increased risk for fracture, reduced lean mass and muscle strength, mood disturbance and increased fat mass compromising physical functioning, independence, and quality of life. The purpose of this investigation is to examine the effects of long term exercise on reversing musculoskeletal-related side effects, and cardiovascular and diabetes risk factors in men receiving androgen deprivation for their prostate cancer. Specifically, we aim to investigate the effects of a 12-month exercise program designed to load the musculoskeletal system and reduce cardiovascular and diabetes disease progression on the following primary endpoints: 1) bone mineral density; 2) cardiorespiratory function and maximal oxygen capacity; 3) body composition (lean mass and fat mass); 4) blood pressure and cardiovascular function; 5) lipids and glycemic control; and 6) quality of life and psychological distress.

Allopurinol and mortality in hyperuricaemic patients.

Objectives: While studies have suggested that gout and hyperuricaemia are associated with the risk of premature death, none has investigated the role of urate-lowering therapy on this critical outcome. We examined the impact of allopurinol, the most commonly used urate-lowering drug, on the risk of mortality in hyperuricaemic patients.

Methods: From a population of hyperuricaemic veterans of [serum urate level >416 micromol/l (7.

Anthropometric, physiological and performance characteristics of elite team-handball players.

The objective of this study was to provide anthropometric, physiological, and performance characteristics of an elite international handball team. Twenty-one elite handball players were tested and categorized according to their playing positions (goalkeepers, backs, pivots, and wings). Testing consisted of anthropometric and physiological measures of height, body mass, percentage body fat and endurance (VO(2max)), performance measures of speed (5, 10, and 30 m), strength (bench press and squat), unilateral and bilateral horizontal jumping ability, and a 5-jump horizontal test.