Temperature control in critically ill patients with fever: A meta-analysis of randomized controlled trials.

PURPOSE: Fever is frequently encountered in ICU. It is unclear if targeted temperature control is beneficial in critically ill patients with suspected or confirmed infection. We conducted a systemic review and meta-analysis to answer this question. METHODS: We systematically reviewed major databases before January 2020 to identify randomized controlled trials (RCTs) that compared antipyretic with placebo for temperature control in non-neurocritical ill adult patients with suspected or confirmed infection. Outcomes of interest were 28-day mortality, temperature level, hospital mortality, length of stay, shock reversal, and patient comfort. RESULT: 13 RCTs enrolling 1963 patients were included. No difference in 28-day mortality between antipyretic compared with placebo (risk ratio [RR] 1.03; 95% CI 0.79-1.35). Lower temperature levels were achieved in the antipyretic group (MD [mean difference] -0.41; 95% CI -0.66 to -0.16). Antipyretic use did not affect the risk of hospital mortality (RR 0.97; 95% CI 0.73-1.30), ICU length of stay (MD -0.07; 95% CI -0.70 to 0.56), or shock reversal (RR 1.11; 95% CI 0.76-1.62). CONCLUSION: Antipyretic therapy effectively reduces temperature in non-neurocritical ill patients but does not reduce mortality or impact other outcomes.

Investigations and management of chronic cough: a 2020 update from the European Respiratory Society Chronic Cough Task Force.

Chronic cough affects approximately 10% of the general population, is highest amongst people aged 50 to 60 years, and is twice as common in women than men. It is described to last 8 weeks or longer in adults and does not respond well to treatment with over-the-counter medications and those targeting potential associated conditions. This is a debilitating condition with physical, social, and psychological consequences. The purpose of this review was to highlight the key messages on the management of chronic cough from the task force commissioned by the European Respiratory Society. The assessment of patients with chronic cough should include a thorough detailed history and examination to identify potential causes. The impact and severity can be assessed in a clinic using questionnaires. Potential causes of the condition vary and include, for example, angiotensin­converting enzyme inhibitors, smoking, asthma, nonasthmatic eosinophilic bronchitis, gastroesophageal reflux disease, and upper airways cough syndrome. In many patients, coughing is persistent despite optimum medical therapy of the underlying medical condition and is hence referred to as refractory chronic cough. In some cases, no cause can be found and the cough is classified as unexplained chronic cough. If treatment of any underlying disease is unsuccessful at controlling cough, then neuromodulatory treatment such as a low­dose opioid, gabapentin, pregabalin or speech and language therapy may be considered. There is no licensed treatment for chronic cough, but a new class of treatment targeting the purinergic P2X3 receptor is currently in phase 2 and 3 of development.

Accumulation of Deficits as a Key Risk Factor for Cardiovascular Morbidity and Mortality: A Pooled Analysis of 154 000 Individuals.

Background Frailty is associated with higher mortality in individuals at high cardiovascular disease (CVD) risk. We hypothesize that frailty is a more important prognostic factor than CVD risk factors and aim to determine the prognostic value of a cumulative deficit frailty index in patients with or at high risk for CVD. Methods and Results We conducted an individual-level pooled analysis of participants with or at risk for CVD, recruited in 14 multicenter clinical trials. The cumulative deficit index was calculated as the proportion of 26 deficits exhibited. Individuals were categorized as nonfrail, prefrail, or frail if they had indexes of ≤0.1, >0.1 to 0.21, or >0.21, respectively. CVD risk was assessed using the Framingham score. Outcomes included CVD event (new or recurrent myocardial infarction, stroke, or heart failure) and mortality. We studied 154 696 patients (mean age, 70.8 years; 63% men) with median follow-up of 3.2 years. There were 17 535 CVD events and 15 067 deaths. The frail group (n=13 872) had higher risk of a CVD event (incidence rate ratio, 1.97; 95% CI, 1.85-2.08), all-cause mortality (hazard ratio, 1.91; 95% CI, 1.79-2.03), and CVD mortality (hazard ratio, 1.91; 95% CI, 1.77-2.05) than the nonfrail group (n=101 343). Associations remained unchanged after adjusting for CVD risk factors. The index statistically outperformed the Framingham score in its ability to discriminate CVD events (C-statistic, 0.60 [95% CI, 0.60-0.61] versus 0.58 [95% CI, 0.57-0.58], respectively; P<0.001). Conclusions In individuals with or at high risk of developing CVD, the cumulative deficit index is associated with increased CVD events and mortality, independent of CVD risk factors, and adds incremental prognostic value.

Statin therapy in the treatment of active cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Preclinical evidence suggests statins may have anti-tumor properties. Large observational studies are also consistent with improved survival and cancer-specific outcomes among cancer patients on statins. We sought to evaluate the randomized controlled trials of statins in addition to usual anti-cancer therapy. METHODS: A systematic search of MEDLINE, Embase, CINAHL, Cochrane Library, Web of Science, Papers First and Clinicaltrials.gov was performed from inception through to July 4, 2017 to identify randomized clinical trials that investigated statin therapy in cancer patients. Our primary outcome was overall survival and our secondary outcome was progression-free survival. We calculated summary hazard ratio's (HR) and 95% confidence intervals (CI) based on random-effects models using aggregate data. PROSPERO (CRD42017065503). RESULTS: Ten studies with 1,881 individuals were included with 1,572 deaths and a median follow-up of 23 months. All trials included patients with advanced (stage 3 or higher) disease. There was minimal between-study statistical heterogeneity (I2 = 1.8%, for OS; I2 = 0%, for PFS). The pooled HR for overall survival in patients randomized to statins plus standard anti-cancer therapy versus standard therapy alone was 0.94 (95% CI, 0.85 to 1.04). In the 9 studies that reported progression-free survival (1,798 participants), the pooled HR for statin plus standard therapy versus standard therapy alone was 0.97 (95% CI, 0.87 to 1.07). CONCLUSIONS: In patients with advanced cancer and a prognosis <2 years, the addition of statins to standard anti-cancer therapy does not appear to improve overall survival or progression-free survival. Future research should assess if cancer patients with better prognosis benefit from longer-term statin therapy.