METHODS: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults.
RESULTS: Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week).
DISCUSSION: This cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.
METHODS: This retrospective analysis included all new HIV diagnosis from 2016 to 2019 at the University of Malaya Medical Centre, Malaysia. Trends of HIV diagnosis was assessed using join point regression analysis, and characteristics between the older and younger adults were compared using χ 2 test or Mann-Whitney U test. Kaplan-Meier analysis and log-rank test were used to compare the survival probability in both age groups.
RESULTS: From a total of 594 new HIV diagnosis between 2016 and 2019, 11.5% (N = 68) were among older adults with an annual percent increase of 5.50%. Older adults were more likely ethnic Indians ( P < 0.001), acquired HIV through heterosexual contact ( P = 0.001), had late presentation to care ( P = 0.003), and multimorbidity ( P < 0.001). Immunological responses after 12 months on antiretroviral therapy were comparable in both the groups. Older adults had a higher probability of death compared with younger adults (adjusted hazard ratio 1.81, 95% confidence interval: 1.02 to 3.23, P = 0.043) after adjusting for sex, mode of HIV transmission, late presentation to care, antiretroviral therapy initiation, and multimorbidity.
CONCLUSION: Older adults diagnosed with HIV were associated with late care presentation and increased mortality. There is an urgent need to enhance uptake of HIV testing and linkage to care among older individuals in our setting.
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.
MATERIALS AND METHODS: Participants with an estimated glomerular filtration rate of 30 to <90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of >300-5,000 mg/g were randomized to 100 mg of canagliflozin or a placebo. The effects of canagliflozin treatment on pre-specified efficacy and safety outcomes were examined using Cox proportional hazards regression between participants from EA countries (China, Japan, Malaysia, the Philippines, South Korea and Taiwan) and the remaining participants.
RESULTS: Of 4,401 participants, 604 (13.7%) were from EA countries; 301 and 303 were assigned to the canagliflozin and placebo groups, respectively. Canagliflozin lowered the risk of primary outcome (composite of end-stage kidney disease, doubling of serum creatinine level, or renal or cardiovascular death) in EA participants (hazard ratio 0.54, 95% confidence interval 0.35-0.84). The effects of canagliflozin on renal and cardiovascular outcomes in EA participants were generally similar to those of the remaining participants. Safety outcomes were similar between the EA and non-EA participants.
CONCLUSIONS: In the CREDENCE trial, the risk of renal and cardiovascular events was safely reduced in participants from EA countries at high risk of renal events.
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 investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression.
RESULTS: Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62-1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22-3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17-0.85, p = 0.018).
CONCLUSIONS: Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.
DESIGN: Prospective cohort study.
SETTING: PURE study in 21 countries.
PARTICIPANTS: 148 858 participants with median follow-up of 9.5 years.
EXPOSURES: Country specific validated food frequency questionnaires were used to assess intakes of refined grains, whole grains, and white rice.
MAIN OUTCOME MEASURE: Composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios were estimated for associations of grain intakes with mortality, major cardiovascular events, and their composite by using multivariable Cox frailty models with random intercepts to account for clustering by centre.
RESULTS: Analyses were based on 137 130 participants after exclusion of those with baseline cardiovascular disease. During follow-up, 9.2% (n=12 668) of these participants had a composite outcome event. The highest category of intake of refined grains (≥350 g/day or about 7 servings/day) was associated with higher risk of total mortality (hazard ratio 1.27, 95% confidence interval 1.11 to 1.46; P for trend=0.004), major cardiovascular disease events (1.33, 1.16 to 1.52; P for trend<0.001), and their composite (1.28, 1.15 to 1.42; P for trend<0.001) compared with the lowest category of intake (<50 g/day). Higher intakes of refined grains were associated with higher systolic blood pressure. No significant associations were found between intakes of whole grains or white rice and health outcomes.
CONCLUSION: High intake of refined grains was associated with higher risk of mortality and major cardiovascular disease events. Globally, lower consumption of refined grains should be considered.