An ethical review on the search for performance: evidence-based nutrology and the use without indication of anabolic steroids

This study aimed to evaluate what is new in the controversial use of testosterone, as an indication in pathologies such as hypogonadism or its use by athletes and bodybuilders in search of performance. Much is said about the subject and many myths were created without any scientific foundation, one of the objectives of the monograph is to show that when there is a precise clinical indication, testosterone is necessary and extremely beneficial to the patient. It was evaluated in current literature through books and articles, advances in physiology, regulation, treatment of late adult hypogonadism, incidence of use and the most common analogues used by athletes, the harms and benefits expected from the use of the hormone and especially what we have again on cardiovascular safety in testosterone use. After an extensive review, it is still not possible to affirm all the benefits and harms of using the hormone, many old studies are disputed in new studies and even presented results opposite to what was previously believed.

Cardiovascular safety of celecoxib in rheumatoid arthritis and osteoarthritis patients: A systematic review and meta-analysis

Objective To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo. Methods We included randomized controlled trials of oral celecoxib compared with a non-selective NSAID or placebo in rheumatoid arthritis and osteoarthritis patients. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database. Study selection and data extraction were done by two authors independently. The risk of bias was assessed using Cochrane’s risk-of-bias Tool for Randomized Trials. The effect size was presented as a risk ratio with their 95% confidence interval. Results Until July 22nd, 2021, our search identified 6279 records from which, after exclusions, 21 trials were included in the meta-analysis. The overall pooled risk ratio for Antiplatelet Trialists Collaboration cardiovascular events for celecoxib compared with any non-selective non-steroid anti-inflammatory drugs was 0.89 (95% confidence interval: 0.80–1.00). The pooled risk ratio for all-cause mortality for celecoxib compared with non-selective non-steroid anti-inflammatory drugs was 0.81 (95% confidence interval: 0.66–0.98). The cardiovascular mortality rate of celecoxib was lower than non-selective non-steroid anti-inflammatory drugs (risk ratio: 0.75, 95% confidence interval: 0.57–0.99). There was no significant difference between celecoxib and non-selective non-steroid anti-inflammatory drugs or placebo in the risk of other cardiovascular events. Conclusion Celecoxib is relatively safe in rheumatoid arthritis and osteoarthritis patients, independent of dose or duration. But it remains uncertain whether this would remain the same in patients treated with aspirin and patients with established cardiovascular diseases.

Cardiovascular Safety Assessment in Cancer Drug Development

The development of cardiovascular toxicity attributable to anticancer drugs is a pivotal event that is associated with cardiovascular morbidity as well as with worse cancer‐specific and overall outcomes. Although broad consensus exists regarding the importance of cardiovascular safety assessment in cancer drug development, real‐world data suggest that cardiovascular events are significantly underestimated in oncology trials. This drug safety discrepancy has profound implications on drug development decisions, risk‐benefit evaluation, formulation of surveillance and prevention protocols, and survivorship. In this article, we review the contemporary cardiovascular safety evaluation of new pharmaceuticals in hematology and oncology, spanning from in vitro pharmacodynamic testing to randomized clinical trials. We argue that cardiovascular safety assessment of anticancer drugs should be reformed and propose practical strategies, including development and validation of preclinical assays, expansion of oncology trial eligibility, incorporation of cardiovascular end points in early‐phase studies, and design of longitudinal multi‐institutional cardiotoxicity registries.

The effect of passive mobilization associated with blood flow restriction and combined with electrical stimulation on cardiorespiratory safety, neuromuscular adaptations, physical function, and quality of life in comatose patients in an ICU: a randomized controlled clinical trial

Background Intensive care unit-acquired atrophy and weakness are associated with high mortality, a reduction in physical function, and quality of life. Passive mobilization (PM) and neuromuscular electrical stimulation were applied in comatose patients; however, evidence is inconclusive regarding atrophy and weakness prevention. Blood flow restriction (BFR) associated with PM (BFRp) or with electrical stimulation (BFRpE) was able to reduce atrophy and increase muscle mass in spinal cord-injured patients, respectively. Bulky venous return occurs after releasing BFR, which can cause unknown repercussions on the cardiovascular system. Hence, the aim of this study was to investigate the effect of BFRp and BFRpE on cardiovascular safety and applicability, neuromuscular adaptations, physical function, and quality of life in comatose patients in intensive care units (ICUs). Methods Thirty-nine patients will be assessed at baseline (T0–18 h of coma) and randomly assigned to the PM (control group), BFRp, or BFRpE groups. The training protocol will be applied in both legs alternately, twice a day with a 4-h interval until coma awake, death, or ICU discharge. Cardiovascular safety and applicability will be evaluated at the first training session (T1). At T0 and 12 h after the last session (T2), muscle thickness and quality will be assessed. Global muscle strength and physical function will be assessed 12 h after T2 and ICU and hospital discharge for those who wake up from coma. Six and 12 months after hospital discharge, physical function and quality of life will be re-assessed. Discussion In view of applicability, the data will be used to inform the design and sample size of a prospective trial to clarify the effect of BFRpE on preventing muscle atrophy and weakness and to exert the greatest beneficial effects on physical function and quality of life compared to BFRp in comatose patients in the ICU. Trial registration Universal Trial Number (UTN) Registry UTN U1111-1241-4344. Retrospectively registered on 2 October 2019. Brazilian Clinical Trials Registry (ReBec) RBR-2qpyxf. Retrospectively registered on 21 January 2020, http://ensaiosclinicos.gov.br/rg/RBR-2qpyxf/

Cardiovascular Safety of Anti-Sclerostin Therapy in Chronic Kidney Disease

The significance of sclerostin for bone and cardiovascular health in patients with chronic kidney disease (CKD) is complex and incompletely understood. Experimental evidence suggests that anti-sclerostin therapy shows diminished efficacy on bone in the setting of CKD. Limited clinical evidence suggests that the osteoanabolic and anti-resorptive activity is attenuated, but hypocalcemia is more prevalent in patients with advanced CKD (eGFR < 30 mL/min) treated with anti-sclerostin (romosozumab) therapy as compared to patients without kidney disease. Furthermore, sclerostin is prominently expressed in uremic arteries. Whether the inhibition of sclerostin has adverse effects on cardiovascular health in CKD is currently unknown. This review summarizes the current understanding of the physiology and pathophysiology of sclerostin in CKD, with a focus on the cardiovascular safety of anti-sclerostin therapy in patients with or without CKD.