IMPORTANCE Progression-free survival (PFS) has become a commonly used outcome to assess the efficacy of new cancer drugs. However, it is not clear if delay in progression leads to improved quality of life with or without overall survival benefit. OBJECTIVE To evaluate the association between PFS and health-related quality of life (HRQoL) in oncology through a systematic review and quantitative analysis of published randomized clinical trials. Eligible trials addressed oral, intravenous, intraperitoneal, or intrapleural chemotherapy or biological treatments, and reported PFS or health-related quality of life. DATA SOURCES For this systematic review and quantitative analysis of randomized clinical trials of patients with cancer, we searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 2000, through May 4, 2016. STUDY SELECTION Paired reviewers independently screened citations, extracted data, and assessed risk of bias of included studies. DATA EXTRACTION AND SYNTHESIS We examined the association of difference in median PFS duration (in months) between treatment groups with difference in global, physical, and emotional HRQoL scores between groups (standardized to a range of 0-100, with higher scores representing better HRQoL) using weighted simple regressions. MAIN OUTCOME AND MEASURE The association between PFS duration and HRQoL. RESULTS Of 35 960 records screened, 52 articles reporting on 38 randomized clinical trials involving 13 979 patients across 12 cancer types using 6 different HRQoL instruments were included. The mean (SD) difference in median PFS between the intervention and the control arms was 1.91 (3.35) months. The mean (SD) differences in change of HRQoL adjusted to per-month values were −0.39 (3.59) for the global domain, 0.26 (5.56) for the physical domain, and 1.08 (3.49) for the emotional domain. The slope of the association between the difference in median PFS and the difference in change for global HRQoL (n = 30 trials) was 0.12 (95% CI, −0.27 to 0.52); for physical HRQoL (n = 20 trials) it was −0.20 (95% CI, −0.62 to 0.23); and for emotional HRQoL (n = 13 trials) it was 0.78 (95% CI, −0.05 to 1.60). CONCLUSIONS AND RELEVANCE We failed to find a significant association between PFS and HRQoL in cancer clinical trials. These findings raise questions regarding the assumption that interventions prolonging PFS also improve HRQoL in patients with cancer. Therefore, to ensure that patients are truly obtaining important benefit from cancer therapies, clinical trial investigators should measure HRQoL directly and accurately, ensuring adequate duration and follow-up.

New epidemiologic research confirms the potential harmful cardiovascular effects of heavy episodic alcohol use and does not support the previous observation that low-moderate alcohol use protects against stroke. Alcohol consumption also appears to have a continuous positive relationship with the risk of atrial fibrillation. In addition, Mendelian randomization analyses suggest that alcohol may have a direct causal role in adverse cardiovascular effects. Recent studies have confirmed that heavy alcohol use (>14 drinks per week in women and >21 drinks per week in men) and heavy episodic drinking are associated with an increased risk of mortality. New research raises concerns that even low-moderate alcohol use may not offer cardio- or cerebrovascular protection. Drinking ≥3 drinks per day on a regular basis or ≥5 drinks in any one episode should be discouraged.

Purpose: We aimed to determine the association between sepsis and long-term cardiovascular events. Methods:We conducted a systematic review of observational studies evaluating post-sepsis cardiovascular outcomes in adult sepsis survivors. MEDLINE, Embase, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched from inception until April 21st, 2021. Two reviewers independently extracted individual study data and evaluated risk of bias. Random-effects models estimated the pooled crude cumulative incidence and adjusted hazard ratios (aHRs) of cardiovascular events compared to either non-septic hospital survivors or population controls. Primary outcomes included myocardial infarction, stroke, and congestive heart failure; outcomes were analysed at maximum reported follow-up (from 30 days to beyond 5 years post-discharge).Results: Of 12,649 screened citations, 27 studies (25 cohort studies, 2 case-crossover studies) were included with a median of 4,289 (IQR 502-68,125) sepsis survivors and 18,399 (IQR 4,506) controls per study. The pooled cumulative incidence of myocardial infarction, stroke, and heart failure in sepsis survivors ranged from 3 to 9% at longest reported follow-up. Sepsis was associated with a higher long-term risk of myocardial infarction (aHR 1.77 [95% CI 1.26 to 2.48]; low certainty), stroke (aHR 1.67 [95% CI 1.37 to 2.05]; low certainty), and congestive heart failure (aHR 1.65 [95% CI 1.46 to 1.86]; very low certainty) compared to non-sepsis controls.Conclusions: Surviving sepsis may be associated with a long-term, excess hazard of late cardiovascular events which may persist for at least 5 years following hospital discharge.

ObjectivesCurrent guidelines suggest limiting the use of vasopressors following traumatic injury; however, wide variations in practice exist. Although excessive vasoconstriction may be harmful, these agents may help reduce administration of potentially harmful resuscitation fluids. This systematic review aims to compare early vasopressor use to standard resuscitation in adults with trauma-induced shock.DesignSystematic review.Data sourcesWe searched MEDLINE, EMBASE, ClinicalTrials.gov and the Central Register of Controlled Trials from inception until October 2016, as well as the proceedings of 10 relevant international conferences from 2005 to 2016.Eligibility criteria for selecting studiesRandomised controlled trials and controlled observational studies that compared the early vasopressor use with standard resuscitation in adults with acute traumatic injury.ResultsOf 8001 citations, we retrieved 18 full-text articles and included 6 studies (1 randomised controlled trial and 5 observational studies), including 2 published exclusively in abstract form. Across observational studies, vasopressor use was associated with increased short-term mortality, with unadjusted risk ratios ranging from 2.31 to 7.39. However, the risk of bias was considered high in these observational studies because patients who received vasopressors were systematically sicker than patients treated without vasopressors. One clinical trial (n=78) was too imprecise to yield meaningful results. Two clinical trials are currently ongoing. No study measured long-term quality of life or cognitive function.ConclusionsExisting data on the effects of vasopressors following traumatic injury are of very low quality according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. With emerging evidence of harm associated with aggressive fluid resuscitation and, in selected subgroups of patients, with permissive hypotension, the alternatives to vasopressor therapy are limited. Observational data showing that vasopressors are part of usual care would provide a strong justification for high-quality clinical trials of early vasopressor use during trauma resuscitation.Trial registration number CRD42016033437.