DESIGN: A post hoc subgroup analysis of the effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicenter, pragmatic, registry-based randomized trial.
SETTING: Eighty-five adult ICUs across 16 countries.
PATIENTS: Patients with obesity defined as a body mass index (BMI) greater than or equal to 30 kg/m 2 ( n = 425).
INTERVENTIONS: In the primary study, patients were randomized into a high-dose (≥ 2.2 g/kg/d) or usual-dose protein group (≤ 1.2 g/kg/d).
MEASUREMENTS AND MAIN RESULTS: Protein intake was monitored for up to 28 days, and outcomes (time to discharge alive [TTDA], 60-d mortality, days of mechanical ventilation [MV], hospital, and ICU length of stay [LOS]) were recorded until 60 days post-randomization. Of the 1301 patients in the primary study, 425 had a BMI greater than or equal to 30 kg/m 2 . After adjusting for sites and covariates, we observed a nonsignificant slower rate of TTDA with higher protein that ruled out a clinically important benefit (hazard ratio, 0.78; 95% CI, 0.58-1.05; p = 0.10). We found no evidence of difference in TTDA between protein groups when subgroups with different classes of obesity or patients with and without various nutritional and frailty risk variables were examined, even after the removal of patients with baseline acute kidney injury. Overall, 60-day mortality rates were 31.5% and 28.2% in the high protein and usual protein groups, respectively (risk difference, 3.3%; 95% CI, -5.4 to 12.1; p = 0.46). Duration of MV and LOS in hospital and ICU were not significantly different between groups.
CONCLUSIONS: In critically ill patients with obesity, higher protein doses did not improve clinical outcomes, including those with higher nutritional and frailty risk.
Methods: We searched PubMed-MEDLINE, Embase and Scopus, from inception to 20 Sep 2019, and reviewed major conferences' abstracts, for randomised controlled trials of ICI in advanced-stage NSCLC (Stage IIIB or IV) without EGFR mutation that reported hazard ratios (HRs) stratified by geographical region including the region "Asia" or "East Asia". The primary outcome measures were overall survival (OS) and progression-free survival (PFS). The pooled HR and its 95% confidence interval (CI) for OS and PFS in East Asians and non-East Asians were calculated using a random effect model and the difference compared using an interaction test.
Results: A total of 5,465 patients from 7 randomised controlled trials involving CTLA-4 and/or PD-1/L1 inhibitors were included, with 1,740 (32%) East Asians and 3,725 (68%) non-East Asians. ICI was associated with an improvement in OS and PFS for both East Asian (OS HR, 0.74; 95% CI, 0.65-0.85; PFS HR, 0.56; 95% CI, 0.40-0.79) and non-East Asian patients (OS HR, 0.78; 95% CI, 0.72-0.85; PFS HR, 0.69; 95% CI, 0.56-0.85), with no significant difference between the two groups (Pinteraction=0.55 for OS; Pinteraction=0.33 for PFS). Subgroup analyses showed a statistically significant superior PFS (but not OS) for East Asians than non-East Asians in trials that used immune checkpoint inhibitor in the first-line treatment (Pinteraction=0.02). No significant regional difference was found in further subgroups of pure ICI and combination of ICI with chemotherapy.
Conclusions: There is no significant difference in response to ICI between East Asians and non-East Asians with advanced stage NSCLC, and the statistically significant subgroup difference in PFS in the first line use of ICI may not be clinically significant.
METHODS: We linked pharmacy, custodial, death, case management, and HIV surveillance data from Connecticut Departments of Correction and Public Health to create a retrospective cohort of all adults with HIV released from jails and prisons in Connecticut between 2007 and 2014. We compared the mortality rate of adults with HIV released from incarceration with the general US and Connecticut populations, and modelled time-to-death from any cause after prison release with Cox proportional hazard models.
FINDINGS: We identified 1350 people with HIV who were released after 24 h or more of incarceration between 2007 and 2014, of whom 184 (14%) died after index release; median age was 45 years (IQR 39-50) and median follow-up was 5·2 years (IQR 3·0-6·7) after index release. The crude mortality rate for people with HIV released from incarceration was 2868 deaths per 100 000 person-years, and the standardised mortality ratio showed that mortality was higher for this cohort than the general US population (6·97, 95% CI 5·96-7·97) and population of Connecticut (8·47, 7·25-9·69). Primary cause of death was reported for 170 individuals; the most common causes were HIV/AIDS (78 [46%]), drug overdose (26 [15%]), liver disease (17 [10%]), cardiovascular disease (16 [9%]), and accidental injury or suicide (13 [8%]). Black race (adjusted hazard ratio [HR] 0·52, 95% CI 0·34-0·80), having health insurance (0·09, 0·05-0·17), being re-incarcerated at least once for 365 days or longer (0·41, 0·22-0·76), and having a high percentage of re-incarcerations in which antiretroviral therapy was prescribed (0·08, 0·03-0·21) were protective against mortality. Positive predictors of time-to-death were age (≥50 years; adjusted HR 3·65, 95% CI 1·21-11·08), lower CD4 count (200-499 cells per μL, 2·54, 1·50-4·31; <200 cells per μL, 3·44, 1·90-6·20), a high number of comorbidities (1·86, 95% CI 1·23-2·82), virological failure (2·76, 1·94-3·92), and unmonitored viral load (2·13, 1·09-4·18).
INTERPRETATION: To reduce mortality after release from incarceration in people with HIV, resources are needed to identify and treat HIV, in addition to medical comorbidities, psychiatric disorders, and substance use disorders, during and following incarceration. Policies that reduce incarceration and support integrated systems of care between prisons and communities could have a substantial effect on the survival of people with HIV.
FUNDING: US National Institutes of Health.
METHODS: Data of 3,100 Malaysian women with nonmetastatic breast cancer diagnosed between 2010 and 2017 were analyzed. Adherence to the Malaysian Clinical Practice Guidelines for Management of Breast Cancer second Edition was measured. Outcomes comprised overall survival and event-free survival.
RESULTS: Guideline adherence for chemotherapy, radiotherapy, hormonal therapy, and targeted therapy were 61.7%, 79.2%, 85.1%, and 26.2%, respectively. Older age was generally associated with lower adherence to guidelines. Compared with patients who were treated according to treatment guidelines, overall survival and event-free survival were substantially lower in patients who were not treated accordingly; hazard ratios for all-cause mortality were 1.69 (95% CI, 1.29 to 2.22), 2.59 (95% CI, 1.76 to 3.81), 3.08 (95% CI, 1.94 to 4.88), and 4.48 (95% CI, 1.98 to 10.13) for chemotherapy, radiotherapy, hormone therapy, and targeted therapy, respectively. Study inferences remain unchanged following sensitivity analyses.
CONCLUSION: Our study findings appear to suggest that adherence to treatment guidelines that have been adapted for resource-limited settings may still provide effective guidance in improving breast cancer outcomes.
METHODS: Six bibliographic databases were searched from their respective inception to 31 December 2021. Data were pooled using random-effects meta-analysis.
RESULTS: Of 5476 identified articles, 15 satisfied the inclusion criteria with a total sample size of 38 618 patients. Pooled findings showed that individuals with cytomegalovirus infection had a higher risk of tuberculosis disease compared to those not infected with cytomegalovirus (odds ratio [OR], 3.20; 95% confidence interval [CI], 2.18-4.70). Age was the only covariate that exerted a significant effect on the result of the association. Meta-analysis of risk estimates reported in individual studies showed a marked and significant correlation of cytomegalovirus infection with active tuberculosis (adjusted hazard ratio, 2.92; 95% CI, 1.34-4.51; adjusted OR, 1.14; 95% CI, .71-1.57). A clear dose-response relation was inferred between the levels of cytomegalovirus antibodies and the risks of tuberculosis events (OR for high levels of cytomegalovirus antibodies, 4.07; OR for medium levels of cytomegalovirus antibodies, 3.58).
CONCLUSIONS: The results suggest an elevated risk of tuberculosis disease among individuals with a prior cytomegalovirus infection.
METHODS: Bedtime was recorded based on self-reported habitual time of going to bed in 112,198 participants from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Participants were prospectively followed for 9.2 years. We examined the association between bedtime and the composite outcome of all-cause mortality, non-fatal myocardial infarction, stroke and heart failure. Participants with a usual bedtime earlier than 10PM were categorized as 'earlier' sleepers and those who reported a bedtime after midnight as 'later' sleepers. Cox frailty models were applied with random intercepts to account for the clustering within centers.
RESULTS: A total of 5633 deaths and 5346 major cardiovascular events were reported. A U-shaped association was observed between bedtime and the composite outcome. Using those going to bed between 10PM and midnight as the reference group, after adjustment for age and sex, both earlier and later sleepers had a higher risk of the composite outcome (HR of 1.29 [1.22, 1.35] and 1.11 [1.03, 1.20], respectively). In the fully adjusted model where demographic factors, lifestyle behaviors (including total sleep duration) and history of diseases were included, results were greatly attenuated, but the estimates indicated modestly higher risks in both earlier (HR of 1.09 [1.03-1.16]) and later sleepers (HR of 1.10 [1.02-1.20]).
CONCLUSION: Early (10 PM or earlier) or late (Midnight or later) bedtimes may be an indicator or risk factor of adverse health outcomes.
METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort study of individuals aged 35-70 years enrolled from 21 countries in five continents. Dietary intakes of dairy products for 136 384 individuals were recorded using country-specific validated food frequency questionnaires. Dairy products comprised milk, yoghurt, and cheese. We further grouped these foods into whole-fat and low-fat dairy. The primary outcome was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were calculated using multivariable Cox frailty models with random intercepts to account for clustering of participants by centre.
FINDINGS: Between Jan 1, 2003, and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major cardiovascular events [n=5855]) during the 9·1 years of follow-up. Higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of the composite outcome (HR 0·84, 95% CI 0·75-0·94; ptrend=0·0004), total mortality (0·83, 0·72-0·96; ptrend=0·0052), non-cardiovascular mortality (0·86, 0·72-1·02; ptrend=0·046), cardiovascular mortality (0·77, 0·58-1·01; ptrend=0·029), major cardiovascular disease (0·78, 0·67-0·90; ptrend=0·0001), and stroke (0·66, 0·53-0·82; ptrend=0·0003). No significant association with myocardial infarction was observed (HR 0·89, 95% CI 0·71-1·11; ptrend=0·163). Higher intake (>1 serving vs no intake) of milk (HR 0·90, 95% CI 0·82-0·99; ptrend=0·0529) and yogurt (0·86, 0·75-0·99; ptrend=0·0051) was associated with lower risk of the composite outcome, whereas cheese intake was not significantly associated with the composite outcome (0·88, 0·76-1·02; ptrend=0·1399). Butter intake was low and was not significantly associated with clinical outcomes (HR 1·09, 95% CI 0·90-1·33; ptrend=0·4113).
INTERPRETATION: Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort.
FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).
OBJECTIVES: Our aim was to assess the association of egg consumption with blood lipids, cardiovascular disease (CVD), and mortality in large global studies involving populations from low-, middle-, and high-income countries.
METHODS: We studied 146,011 individuals from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Egg consumption was recorded using country-specific validated FFQs. We also studied 31,544 patients with vascular disease in 2 multinational prospective studies: ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global End Point Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects with Cardiovascular Disease). We calculated HRs using multivariable Cox frailty models with random intercepts to account for clustering by study center separately within each study.
RESULTS: In the PURE study, we recorded 14,700 composite events (8932 deaths and 8477 CVD events). In the PURE study, after excluding those with history of CVD, higher intake of egg (≥7 egg/wk compared with <1 egg/wk intake) was not significantly associated with blood lipids, composite outcome (HR: 0.96; 95% CI: 0.89, 1.04; P-trend = 0.74), total mortality (HR: 1.04; 95% CI: 0.94, 1.15; P-trend = 0.38), or major CVD (HR: 0.92; 95% CI: 0.83, 1.01; P-trend = 0.20). Similar results were observed in ONTARGET/TRANSCEND studies for composite outcome (HR 0.97; 95% CI: 0.76, 1.25; P-trend = 0.09), total mortality (HR: 0.88; 95% CI: 0.62, 1.24; P-trend = 0.55), and major CVD (HR: 0.97; 95% CI: 0.73, 1.29; P-trend = 0.12).
CONCLUSIONS: In 3 large international prospective studies including ∼177,000 individuals, 12,701 deaths, and 13,658 CVD events from 50 countries in 6 continents, we did not find significant associations between egg intake and blood lipids, mortality, or major CVD events. The ONTARGET and TRANSCEND trials were registered at clinicaltrials.gov as NCT00153101. The PURE trial was registered at clinicaltrials.gov as NCT03225586.