A practical approach for the compassionate use of convalescent plasma in patients with severe COVID-19 in developing countries.

The COVID-19 pandemic has affected 187 countries, representing a global public health problem. The increasing number of critically ill patients and deaths have fueled a desperate search for treatments that can halt the course of the disease. Currently, there are several experimental therapies with demonstrated in vitro activity against COVID-19 used in clinical practice, including hydroxychloroquine, remdesivir, interleukin-6 pathway inhibitors, and convalescent plasma; however, to date no agent has proven efficacy against COVID-19. In the case of convalescent plasma, this therapy consists in obtaining neutralizing antibodies from previously infected individuals by plasmapheresis and administering them to patients with severe disease. Recently, the use of convalescent plasma has shown promising results in preliminary studies, with case series reporting a decrease in temperature, and viral load, as well as improvement in clinical parameters among patients receiving this treatment. However, there are still unmet needs regarding the safety profile, tolerability, dosage, and timing this therapy should be given. Based on this, the objective of our study was to develop and propose a practical approach for the compassionate use of convalescent plasma for the treatment of patients with severe COVID-19, given the constrains and limitations of developing countries. We encourage health professionals in developing countries to use the current evidence and approaches to experimental treatments for patients with COVID-19, adapting them to their conditions, and always based on a thorough risk-benefit evaluation for each patient, and whenever possible to design and promote the much needed research in this field.

Intensive care unit and hospital mortality in patients with obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) is a common disorder affecting between 5% and 24% of men and women. The prevalence of OSA in the intensive care unit (ICU) population is unknown. This study was undertaken to determine the prevalence of OSA in patients admitted to the ICU and to determine if OSA is an independent predictor of mortality. METHODS: This is a retrospective study using an Acute Physiology and Chronic Health Evaluation III database cross-referenced to a comprehensive clinical database to identify patients with and without OSA admitted to medical, surgical, and mixed ICUs at a large academic medical center. RESULTS: Between January 2003 and December 2005, 15077 patients were admitted to the ICUs; and of these, 1183 (7.8%) had a physician-documented diagnosis of OSA. Eight hundred thirty-five (71%) patients had polysomnographic testing at our institution with a documented apnea-hypopnea index more than 5 per hour. Patients with OSA were younger (59.1 ± 14.0 vs 62.3 ± 18.0), male (58.9% vs 53.7%), and had lower Acute Physiology and Chronic Health Evaluation III scores (45.3 ± 24.1 vs 54.9 ± 27.7). Predicted mortality (10.3% ± 16.4% vs 16.3 ± 21.7), median ICU length of stay (1.13 vs 1.50 days), ICU mortality (2.4% vs 6.2%), and hospital mortality (3.9% vs 11.4%) were all reduced in patients with OSA, P values < .001. When adjusted for the severity of illness, OSA was independently associated with decreased hospital mortality, (0.408; 95% confidence interval, 0.298-0.557). CONCLUSIONS: Obstructive sleep apnea is common in patients admitted to the ICU. Obstructive sleep apnea was associated with a reduction in both ICU and hospital mortality.

A treatment decision aid may increase patient trust in the diabetes specialist. The Statin Choice randomized trial.

AIMS: Decision aids in practice may affect patient trust in the clinician, a requirement for optimal diabetes care. We sought to determine the impact of a decision aid to help patients with diabetes decide about statins (Statin Choice) on patients' trust in the clinician. METHODS: We randomized 16 diabetologists and 98 patients with type 2 diabetes referred to a subspecialty diabetes clinic to use the Statin Choice decision aid or a patient pamphlet about dyslipidaemia, and then to receive these materials from either the clinician during the visit or a researcher prior to the visit. Providers and patients were blinded to the study hypothesis. Immediately after the clinical encounter, patients completed a survey including questions on trust (range 0 to total trust = 100), knowledge, and decisional conflict. Researchers reviewed videotaped encounters and assessed patient participation (using the OPTION scale) and visit length. RESULTS: Overall mean trust score was 91 (median 97.2, IQR 86, 100). After adjustment for patient characteristics, results suggested greater total trust (trust = 100) with the decision aid [odds ratio (OR) 1.77, 95% CI 0.94, 3.35]. Total trust was associated with knowledge (for each additional knowledge point, OR 1.3, 95% CI 1.1, 1.6), patient participation (for each additional point in the OPTION scale, OR 1.1, 95% CI 1.1, 1.2), and decisional conflict (for every 5-point decrease in conflict, OR 1.5, 95% CI 1.2, 1.9). Total trust was not associated with visit length, which the decision aid did not significantly affect. There was no significant effect interaction across the trial factors. CONCLUSIONS: Preliminary evidence suggests that decision aids do not have a large negative impact on trust in the physician and may increase trust through improvements in the decision-making process.

Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials.

OBJECTIVE: To conduct a systematic review and meta-analysis of randomized placebo-controlled trials to measure the effect of testosterone use on sexual function in men with sexual dysfunction and varying testosterone levels. METHODS: Librarian-designed search strategies were used to search the MEDLINE (1966 to October 2004), EMBASE (1988 to October 2004), and Cochrane CENTRAL (inception to October 2004) databases. The MEDLINE search was rerun in March 2005. We also reviewed reference lists from included studies and content expert files. We selected randomized placebo-controlled trials of testosterone vs placebo that enrolled men with sexual dysfunction and measured satisfaction with erectile function and libido and overall sexual satisfaction. RESULTS: We included 17 trials (N = 862 participants) in this review. Trials that enrolled participants with low testosterone levels showed (1) a moderate nonsignificant and inconsistent effect of testosterone use on satisfaction with erectile function (random-effects pooled effect size, 0.80; 95% confidence interval [CI], -0.10 to 1.60), (2) a large effect on libido (pooled effect size, 1.31; 95% CI, 0.40 to 2.25), and (3) no significant effect on overall sexual satisfaction. Trials that enrolled patients with low-normal and normal testosterone levels at baseline showed testosterone that caused (1) a small effect on satisfaction with erectile function (pooled effect size, 0.34; 95% CI, 0.03 to 0.65), (2) moderate nonsignificant effect on libido (pooled effect size, 0.41; 95% CI, -0.01 to 0.83), and (3) no significant effect on overall sexual satisfaction. CONCLUSION: Testosterone use in men is associated with small improvements in satisfaction with erectile function and moderate improvements in libido. Unexplained inconsistent results across trials, wide CIs, and possible reporting bias weaken these inferences.

Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials.

OBJECTIVE: To conduct a systematic review and meta-analysis of randomized trials that assessed the effect of testosterone use on cardiovascular events and risk factors in men with different degrees of androgen deficiency. METHODS: Librarian-designed search strategies were used to search the MEDLINE (1966 to October 2004), EMBASE (1988 to October 2004), and Cochrane CENTRAL (inception to October 2004) databases. The database search was performed again in March 2005. We also reviewed reference lists from included studies and content expert files. Eligible studies were randomized trials that compared any formulation of commercially available testosterone with placebo and that assessed cardiovascular risk factors (lipid fractions, blood pressure, blood glucose), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, angina or claudication, revascularization, stroke), and cardiovascular surrogate end points (ie, laboratory tests indicative of cardiac or vascular disease). Using a standardized data extraction form, we collected data on participants, testosterone administration, and outcome measures. We assessed study quality with attention to allocation concealment, blinding, and loss to follow-up. RESULTS: The 30 trials included 1642 men, 808 of whom were treated with testosterone. Overall, the trials had limited reporting of methodological features that prevent biased results (only 6 trials reported allocation concealment), enrolled few patients, and were of brief duration (only 4 trials followed up patients for > 1 year). The median loss to follow-up across all 30 trials was 9%. Testosterone use in men with low testosterone levels led to inconsequential changes in blood pressure and glycemia and in all lipid fractions (total cholesterol: odds ratio [OR], -0.22; 95% confidence interval [CI], -0.71 to 0.27; high-density lipoprotein cholesterol: OR, -0.04; 95% CI, -0.39 to 0.30; low-density lipoprotein cholesterol: OR, 0.06; 95% CI, -0.30 to 0.42; and triglycerides: OR, -0.27; 95% CI, -0.61 to 0.08); results were similar in patients with low-normal to normal testosterone levels. The OR between testosterone use and any cardiovascular event pooled across trials that reported these events (n = 6) was 1.82 (95% CI, 0.78 to 4.23). Several trials failed to report data on measured outcomes. For reasons we could not explain statistically, the results were inconsistent across trials. CONCLUSION: Currently available evidence weakly supports the inference that testosterone use in men is not associated with important cardiovascular effects. Patients and clinicians need large randomized trials of men at risk for cardiovascular disease to better inform the safety of long-term testosterone use.

Testosterone use in men and its effects on bone health. A systematic review and meta-analysis of randomized placebo-controlled trials.

CONTEXT: Androgen-deficient men are at increased risk of osteoporosis. The extent to which testosterone can prevent and treat osteoporosis in men remains unclear. OBJECTIVE AND DESIGN: We performed a systematic review and meta-analysis of randomized placebo-controlled trials in men to estimate the effect of testosterone use on bone health outcomes. DATA SOURCES: The review encompassed librarian-designed search strategies using MEDLINE (1966 to March 2005), EMBASE (1988 to March 2005), and Cochrane CENTRAL (inception to March 2005); a review of reference lists from included studies; and content expert files. DATA COLLECTION: Independently and in duplicate, we assessed the methodological quality of the eligible trials and collected data on bone mineral density and bone fractures at the longest point of complete follow-up. DATA SYNTHESIS: We included eight trials enrolling 365 patients. Two trials followed patients for more than 1 yr. Meta-analysis of these trials showed that, compared with placebo, im testosterone was associated with an 8% (95% confidence interval, 4%, 13%) gain in lumbar bone mineral density and transdermal testosterone had no significant impact. Testosterone use was associated with a nonsignificant 4% (95% confidence interval, -2%, 9%) gain in femoral neck bone mineral density with unexplained differences in results across trials (26% of these differences were not explained by chance alone). No trials measured or reported the effect of testosterone on fractures. CONCLUSIONS: Intramuscular testosterone moderately increased lumbar bone density in men; the results on femoral neck bone density are inconclusive. Without bone fracture data, the available trials offer weak and indirect inferences about the clinical efficacy of testosterone on osteoporosis prevention and treatment in men.