Body mass index, waist circumference, and mortality in subjects older than 80 years: a Mendelian randomization study.

BACKGROUND AND AIMS: Emerging evidence has raised an obesity paradox in observational studies of body mass index (BMI) and health among the oldest-old (aged ≥80 years), as an inverse relationship of BMI with mortality was reported. This study was to investigate the causal associations of BMI, waist circumference (WC), or both with mortality in the oldest-old people in China. METHODS: A total of 5306 community-based oldest-old (mean age 90.6 years) were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 1998 and 2018. Genetic risk scores were constructed from 58 single-nucleotide polymorphisms (SNPs) associated with BMI and 49 SNPs associated with WC to subsequently derive causal estimates for Mendelian randomization (MR) models. One-sample linear MR along with non-linear MR analyses were performed to explore the associations of genetically predicted BMI, WC, and their joint effect with all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. RESULTS: During 24 337 person-years of follow-up, 3766 deaths were documented. In observational analyses, higher BMI and WC were both associated with decreased mortality risk [hazard ratio (HR) 0.963, 95% confidence interval (CI) 0.955-0.971 for a 1-kg/m2 increment of BMI and HR 0.971 (95% CI 0.950-0.993) for each 5 cm increase of WC]. Linear MR models indicated that each 1 kg/m2 increase in genetically predicted BMI was monotonically associated with a 4.5% decrease in all-cause mortality risk [HR 0.955 (95% CI 0.928-0.983)]. Non-linear curves showed the lowest mortality risk at the BMI of around 28.0 kg/m2, suggesting that optimal BMI for the oldest-old may be around overweight or mild obesity. Positive monotonic causal associations were observed between WC and all-cause mortality [HR 1.108 (95% CI 1.036-1.185) per 5 cm increase], CVD mortality [HR 1.193 (95% CI 1.064-1.337)], and non-CVD mortality [HR 1.110 (95% CI 1.016-1.212)]. The joint effect analyses indicated that the lowest risk was observed among those with higher BMI and lower WC. CONCLUSIONS: Among the oldest-old, opposite causal associations of BMI and WC with mortality were observed, and a body figure with higher BMI and lower WC could substantially decrease the mortality risk. Guidelines for the weight management should be cautiously designed and implemented among the oldest-old people, considering distinct roles of BMI and WC.

Serum 25-Hydroxyvitamin D and Risk of Disability in Activities of Daily Living among the Oldest-Old: An Observational and Mendelian Randomization Study.

BACKGROUND: Vitamin D deficiency and disability are both prevalent among older adults. However, the association between them has rarely been investigated in the oldest-old subjects (aged ≥80 y), and the causality remains unclear. OBJECTIVE: This study aimed to elucidate the causal effect of vitamin D on the incident risk of disability in activities of daily living (ADL) among Chinese oldest-old based on the 2012-2018 Chinese Healthy Ageing and Biomarkers Cohort Study. METHODS: Serum 25-hydroxyvitamin D [25(OH)D] concentrations and ADL status at baseline and follow-up interviews were documented. Cox regression models were applied among 1427 oldest-old (mean age, 91.2 y) with normal baseline ADL status. One sample Mendelian randomization (MR) analyses were performed on a subset of 941 participants with qualified genetic data, using a 25(OH)D-associated genetic risk score as the genetic instrument. RESULTS: During a median follow-up of 3.4 y, 231 participants developed disability in ADL. Serum 25(OH)D concentration was inversely associated with the risk of disability in ADL [per 10 nmol/L increase hazard ratio (HR) 0.85; 95% CI: 0.75, 0.96]. Consistent results from MR analyses showed that a 10 nmol/L increment in genetically predicted 25(OH)D concentration corresponded to a 20% reduced risk of ADL disability (HR 0.80; 95% CI: 0.68, 0.94). Nonlinear MR demonstrated a monotonic declining curve, with the HRs exhibiting a more pronounced reduction among individuals with 25(OH)D concentrations below 50 nmol/L. Subgroup analyses showed that the associations were more distinct among females and those with poorer health conditions. CONCLUSIONS: Our study supports an inverse causal relationship between serum 25(OH)D concentration and the risk of disability in ADL among Chinese oldest-old. This protective effect was more distinct, especially for participants with vitamin D deficiency. Appropriate measures for improving vitamin D might help reduce the incidence of physical disability in this specific age group.

Transmission risk of asymptomatic SARS-CoV-2 infection: a systematic review and meta-analysis.

Background: Global evidence on the transmission of asymptomatic SARS-CoV-2 infection needs to be synthesized. Methods: A search of 4 electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science databases) as of January 24, 2021 was performed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Studies which reported the transmission rate among close contacts with asymptomatic SARS-CoV-2 cases were included, and transmission activities occurred were considered. The transmission rates were pooled by zero-inflated beta distribution. The risk ratios (RRs) were calculated using random-effects models. Results: Of 4923 records retrieved and reviewed, 15 studies including 3917 close contacts with asymptomatic indexes were eligible. The pooled transmission rates were 1.79 per 100 person-days (or 1.79%, 95% confidence interval [CI] 0.41%-3.16%) by asymptomatic index, which is significantly lower than by presymptomatic (5.02%, 95% CI 2.37%-7.66%; p<0.001), and by symptomatic (5.27%, 95% CI 2.40%-8.15%; p<0.001). Subgroup analyses showed that the household transmission rate of asymptomatic index was (4.22%, 95% CI 0.91%-7.52%), four times significantly higher than non-household transmission (1.03%, 95% CI 0.73%-1.33%; p=0.03), and the asymptomatic transmission rate in China (1.82%, 95% CI 0.11%-3.53%) was lower than in other countries (2.22%, 95% CI 0.67%-3.77%; p=0.01). Conclusions: People with asymptomatic SARS-CoV-2 infection are at risk of transmitting the virus to their close contacts, particularly in household settings. The transmission potential of asymptomatic infection is lower than symptomatic and presymptomatic infections. This meta-analysis provides evidence for predicting the epidemic trend and promulgating vaccination and other control measures. Registered with PROSPERO International Prospective Register of Systematic Reviews, CRD42021269446; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=269446.

Risk of SARS-CoV-2 reinfection: a systematic review and meta-analysis.

This meta-analysis aims to synthesize global evidence on the risk of reinfection among people previously infected with SARS-CoV-2. We systematically searched PubMed, Scopus, Embase and Web of Science as of April 5, 2021. We conducted: (1) meta-analysis of cohort studies containing data sufficient for calculating the incidence rate of SARS-CoV-2 reinfection; (2) systematic review of case reports with confirmed SARS-CoV-2 reinfection cases. The reinfection incidence was pooled by zero-inflated beta distribution. The hazard ratio (HR) between reinfection incidence among previously infected individuals and new infection incidence among infection-naïve individuals was calculated using random-effects models. Of 906 records retrieved and reviewed, 11 studies and 11 case reports were included in the meta-analysis and the systematic review, respectively. The pooled SARS-CoV-2 reinfection incidence rate was 0.70 (standard deviation [SD] 0.33) per 10,000 person-days. The incidence of reinfection was lower than the incidence of new infection (HR = 0.12, 95% confidence interval 0.09-0.17). Our meta-analysis of studies conducted prior to the emergency of the more transmissible Omicron variant showed that people with a prior SARS-CoV-2 infection could be re-infected, and they have a lower risk of infection than those without prior infection. Continuing reviews are needed as the reinfection risk may change due to the rapid evolution of SARS-CoV-2 variants.

SMetABF: A rapid algorithm for Bayesian GWAS meta-analysis with a large number of studies included.

Bayesian methods are widely used in the GWAS meta-analysis. But the considerable consumption in both computing time and memory space poses great challenges for large-scale meta-analyses. In this research, we propose an algorithm named SMetABF to rapidly obtain the optimal ABF in the GWAS meta-analysis, where shotgun stochastic search (SSS) is introduced to improve the Bayesian GWAS meta-analysis framework, MetABF. Simulation studies confirm that SMetABF performs well in both speed and accuracy, compared to exhaustive methods and MCMC. SMetABF is applied to real GWAS datasets to find several essential loci related to Parkinson's disease (PD) and the results support the underlying relationship between PD and other autoimmune disorders. Developed as an R package and a web tool, SMetABF will become a useful tool to integrate different studies and identify more variants associated with complex traits.

Treatment outcomes of HIV patients with hepatitis B and C virus co-infections in Southwest China: an observational cohort study.

BACKGROUND: Antiretroviral therapy (ART) has reduced mortality among people living with HIV (PLWH) in China, but co-infections of hepatitis B virus (HBV) and hepatitis C virus (HCV) may individually or jointly reduce the effect of ART. This study aimed to evaluate the impacts of HBV/HCV coinfections on treatment drop-out and mortality among PLWH on ART. METHODS: A retrospective cohort study analysis of 58 239 people living with HIV (PLWH) who initiated antiretroviral therapy (ART) during 2010-2018 was conducted in Guangxi Province, China. Data were from the observational database of the National Free Antiretroviral Treatment Program. Cox proportional hazard models were fitted to evaluate the effects of baseline infection of HBV or HCV or both on death and treatment attrition among PLWH. RESULTS: Our study showed high prevalence of HBV (11.5%), HCV (6.6%) and HBV-HCV (1.5%) co-infections. The overall mortality rate and treatment attrition rate was 2.95 [95% confidence interval (CI) 2.88-3.02] and 5.92 (95% CI 5.82-6.01) per 100 person-years, respectively. Compared with HIV-only patients, HBV-co-infected patients had 42% higher mortality [adjusted hazard ratio (aHR) = 1.42; 95% CI 1.32-1.54], HCV-co-infected patients had 65% higher mortality (aHR = 1.65; 95% CI 1.47-1.86), and patients with both HCV and HBV co-infections had 123% higher mortality (aHR = 2.23; 95% CI 1.87-2.66). CONCLUSIONS: HBV and HCV coinfection may have an additive effect on increasing the risk of all-cause death among PLWH who are on ART. It is suggested that there is need for primary prevention and access to effective hepatitis treatment for PLWH.

Association of HIV infection and cognitive impairment in older adults: A meta-analysis.

OBJECTIVE: To synthesize evidence on the association between human immunodeficiency virus (HIV) infection and cognitive impairment in older adults. DESIGN: Meta-analysis. PARTICIPANTS: Adults aged 50 years or older. METHODS: In this systematic literature review and meta-analysis, we searched PubMed, Scopus, Embase, and APA/PsycNet for studies published before July 21, 2020, that assessed the association between HIV-infection and cognitive impairment. We calculated pooled odds ratios (ORs) of cognitive impairment for people living with HIV (PLWH) and 95 % confidence intervals (CIs) using random-effect models and calculated pooled mean difference (MD) for major cognitive domains between PLWH and HIV-uninfected adults. We assessed risk of bias using the Newcastle-Ottawa scale. RESULTS: Of the 4432 studies identified, 21 cross-sectional studies were eligible for the meta-analysis, including 15 examining global cognitive impairment. The meta-analysis showed that older PLWH were more likely to be cognitively impaired than HIV-uninfected controls (OR = 2.44, 95 % CI = [1.69, 3.53], number of estimates (k) = 15, I2 = 71 %). This higher likelihood was shown in studies from high income countries (OR = 2.63, 95 % CI = [1.76, 3.94], k = 12, I2 = 55 %), but not from upper-middle income countries (OR = 1.96, 95 % CI = [0.26, 14.68], k = 3, I2 = 91 %). PLWH had lower scores than HIV-uninfected adults in 5 out of 7 major cognitive domains, including executive function (MD = -0.42, 95 % CI = [-0.72, -0.11], k = 5, I2 = 32 %), processing speed (MD = -0.33, 95 % CI = [-0.59, -0.08], k = 6, I2 = 16 %), verbal (MD=-0.29, 95 % CI = [-0.48, -0.10], k = 6, I2 = 0%), recall (MD = -0.24, 95 % CI = [-0.38, -0.10], k = 6, I2 = 0%) and motor/psychomotor (MD = -0.38, 95 % CI = [-0.59, -0.16], k = 5, I2 = 31 %) performance. CONCLUSIONS/IMPLICATIONS: Our meta-analysis provides empirical evidence that HIV infection is associated with an increased risk of cognitive impairment among older adults, especially in cognitive domains of executive function, processing speed, verbal, recall, and motor/psychomotor.