Supplementary Table S4 shows baseline characteristics of all participants by cancer diagnosis.

Supplementary Table S3 shows baseline characteristics of all study participants and those included in the main analysis.

Background Previous conventional epidemiological studies found a J-shape relationship between alcohol consumption and dementia, but this result was subject to confounding biases and reverse causation. Therefore, we aimed to investigate the potential linear or non-linear causal association between alcohol consumption and the incident risk of dementia in current drinkers. Methods This study used data from the UK Biobank to investigate the relationship between alcohol consumption and dementia risk. 313,958 White British current drinkers, who were free of dementia during 2006-2010, - 2010, were followed up until 2021. Alcohol consumption was self-reported and calculated according to the National Health Service guideline. The primary outcome was all-cause dementia identified fi ed through hospital and mortality records. We used multivariable Cox models with restricted cubic splines for conventional analysis and both non-linear and linear Mendelian Randomization (MR) analyses to assess causal relationships, employing a genetic score based on 95 SNPs identified fi ed from a meta-genome-wide association study of 941,280 people from Europe. Findings 313,958 current drinkers consumed an average of 13.6 [IQR: 7.1-25.2] - 25.2] units/week alcohol (men averaged 20.2 [11.1-33.9] - 33.9] units/week and women 9.5 [5.3-16.7] - 16.7] units/week). During a mean follow-up of 13.2 years, 5394 (1.7%) developed dementia. Multivariable Cox model with restricted cubic spline functions identified fi ed a J-shaped relationship between alcohol consumption and dementia risk, with the lowest risk at 12.2 units/week. The nonlinear MR failed to identify a significant fi cant non-linear causal relationship (p p = 0.45). Both individual-level (HR: 2.22 95%CI [1.06-4.66]) - 4.66]) and summary-level (1.89 [1.53-2.32]) - 2.32]) linear MR analyses indicated that higher genetically predicted alcohol consumption increased dementia risk. Interpretation This study identified fi ed a positive linear causal relationship between alcohol consumption and dementia among current drinkers. The J-shaped association found in conventional epidemiological analysis was not supported by non-linear MR analyses. Our fi ndings suggested that there was no safe level of alcohol consumption for dementia. Funding The Shenzhen Science and Technology Program and the Strategic Priority Research Program of Chinese Academy of Sciences. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Abstract Suicide-rates are highest among older adults. Yet, older-adult suicide has been under-studied, particularly in relation to suicide in other age-groups, and by sex and location. Age-standardized suicide-rates (ASSR) of older-adults (OA) (ages 60-years-and-older) and non-older-adults (NOA) (ages 10-59 years), and the ratio of OA-to-NOA ASSR, for the 1990-2019 period, were calculated based on 2019 Global-Burden-of-Disease (GBD) data. OA absolute and age-relative ASSR were examined by country/nation/territory Socio-Demographic Index (SDI). There was a significant negative-correlation between OA-to-NOA ASSR and SDI. OA-to-NOA ASSR-ratios were larger in women in many regions, though OA ASSR were lower among women. The finding that OA had higher age-relative suicide-rates in lower socioeconomic-position regions challenges the belief that OA-suicide is a problem of higher socioeconomic-position regions. The fact that in many regions OA age-relative suicide-rates were higher in women than in men challenge the belief that OA women are protected from suicide.

Background: Which life satisfaction components could be a target of positive psychological interventions for longevity is largely unknown. We aimed to investigate association of the composite measure of life satisfaction and its individual components with mortality. Methods: This cohort study included UK Biobank participants who responded to questions concerning five components of life satisfaction at baseline. We generated a composite score representing overall life satisfaction, ranging from 0 (lowest) to 5 (highest). The outcomes were all-cause and cause-specific mortality. We used multivariable Cox regression to estimate hazard ratios (HR) for the associations of interest. Results: Among 165,842 eligible participants, 12,261 all-cause deaths were observed over a median of 12.9-year follow-up. Overall life satisfaction was inversely associated with all-cause mortality (adjusted HR 0.94 [95% CI: 0.93-0.95] per 1 score increment). Health satisfaction showed the strongest association with all-cause mortality, with a fully adjusted HR of 0.52 (95% CI: 0.49-0.55) for high/extreme satisfaction and 0.63 (95% CI: 0.59-0.66) for moderate satisfaction, compared with unsatisfaction (P-trend<0.001), independent of other satisfaction components, regardless of physical health and sociodemographics. The association for family, friendship, work and financial satisfaction was attenuated when adjusted for other life satisfaction components. Similar findings were observed for cause-specific mortality. Limitations: Observational study with single baseline measurement of life satisfaction precludes the ability to establish causal relationship. Conclusions: Higher overall life satisfaction was associated with lower mortality. As the major contributor to lower mortality regardless of physical health and sociodemographics, health satisfaction could be an important target of positive psychological interventions for longevity.

Importance:Assessment of additional protection of a booster dose with an inactivated SARS-CoV-2 vaccine is key to developing vaccination strategies for billions of people worldwide who have received the primary 2-dose regimen. Objective:To estimate the relative effectiveness of a booster dose of an inactivated SARS-CoV-2 vaccine against Omicron infection. Design, Setting, and Participants:This cohort study was conducted among primary close contacts without previous SARS-CoV-2 infection identified in Shenzhen, China, between February and October 2022. Multiple strict nucleic acid testing and symptom surveillance for SARS-CoV-2 infection were regularly conducted during the 7-day centralized plus 7-day home-based quarantine. Exposure:A booster with an inactivated SARS-CoV-2 vaccine vs no booster after receipt of the primary 2-dose inactivated SARS-CoV-2 vaccine regimen. Main Outcomes and Measures:The primary outcomes were overall, symptomatic, and asymptomatic infections. Secondary outcomes were length of incubation and level of cycle threshold values. All the outcomes were assessed during the quarantine period. Results:Among 119 438 eligible participants (mean [SD] age, 37.6 [12.0] years; 66 201 men [55.4%]), 86 251 (72.2%) received a booster dose of an inactivated SARS-CoV-2 vaccine and 33 187 (27.8%) did not. A total of 671 cases infected with Omicron BA.2 were confirmed (464 symptomatic and 207 asymptomatic), and no severe infection or death events were observed. At a median (IQR) duration of 111 (75 to 134) days after booster vaccination, the relative effectiveness of a booster was 32.2% (95% CI, 11.3% to 48.2%) for overall infection, 23.8% (95% CI, -8.2% to 46.4%) for symptomatic infection, and 43.3% (95% CI, 12.3% to 63.3%) for asymptomatic infection. The effectiveness against overall infection changed nonlinearly over time following booster vaccination: 44.9% (95% CI, 4.9% to 68.1%) within 60 days, 50.4% (95% CI, 23.7% to 67.7%) at 61 to 120 days, 29.1% (95% CI, -4.8% to 52.1%) at 121 to 180 days, and 19.4% (95% CI, -14.4% to 43.2%) after 180 days (nonlinear P = .03). The effectiveness did not vary significantly according to the interval between booster vaccination and completion of primary vaccination. There was no association of booster vaccination with incubation or cycle threshold values. Conclusions and Relevance:In this cohort study, a booster dose of an inactivated SARS-CoV-2 vaccine provided additional moderate protection against mild infection for 120 days after receipt, but more research is needed to determine the optimal timing of a booster and its effectiveness in preventing severe infection for a longer duration.

BACKGROUND AND OBJECTIVES:The use of over-the-counter laxatives is common in the general population. The microbiome-gut-brain axis hypothesis suggests that the use of laxatives could be associated with dementia. We aimed to examine the association between the regular use of laxatives and the incidence of dementia in UK Biobank participants.METHODS:This prospective cohort study was based on UK Biobank participants aged 40-69 years without a history of dementia. Regular use of laxatives was defined as self-reported use in most days of the week for the last 4 weeks at baseline (2006-2010). The outcomes were all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD), identified from linked hospital admissions or death registers (up to 2019). Sociodemographic characteristics, lifestyle factors, medical conditions, family history, and regular medication use were adjusted for in the multivariable Cox regression analyses.RESULTS:Among the 502,229 participants with a mean age of 56.5 (SD 8.1) years at baseline, 273,251 (54.4%) were female, and 18,235 (3.6%) reported regular use of laxatives. Over a mean follow-up of 9.8 years, 218 (1.3%) participants with regular use of laxatives and 1,969 (0.4%) with no regular use developed all-cause dementia. Multivariable analyses showed that regular use of laxatives was associated with increased risk of all-cause dementia (hazard ratio [HR] 1.51; 95% CI 1.30-1.75) and VD (HR 1.65; 95% CI 1.21-2.27), with no significant association observed for AD (HR 1.05; 95% CI 0.79-1.40). The risk of both all-cause dementia and VD increased with the number of regularly used laxative types (p trend 0.001 and 0.04, respectively). Among the participants who clearly reported that they were using just 1 type of laxative (n = 5,800), only those using osmotic laxatives showed a statistically significantly higher risk of all-cause dementia (HR 1.64; 95% CI 1.20-2.24) and VD (HR 1.97; 95% CI 1.04-3.75). These results remained robust in various subgroup and sensitivity analyses.DISCUSSION:Regular use of laxatives was associated with a higher risk of all-cause dementia, particularly in those who used multiple laxative types or osmotic laxative.

IMPORTANCE Systematic reviews can help to justify a new randomized clinical trial (RCT), inform its design, and interpret its results in the context of prior evidence. OBJECTIVE To assess trends and factors associated with citing (a marker of the use of) prior systematic reviews in RCT reports. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study investigated 737 Cochrane reviews assessing health interventions to identify 4003 eligible RCTs, defined as those included in an updated version but not in the first version of a Cochrane review and published 2 years after the first version of the Cochrane review was published. MAIN OUTCOMES AND MEASURES The primary outcome was the citation of prior systematic reviews, Cochrane or others, as determined by screening references of eligible RCTs. Factors that may be associated with the citation of prior systematic reviews were also examined. RESULTS Among 4003 eligible RCTs, 1241 studies (31.0%) cited Cochrane reviews, 1698 studies (42.4%) cited prior non-Cochrane reviews, and 2265 studies (56.6%) cited either type of systematic review or both; 1738 RCTs (43.4%) cited no systematic reviews. The percentage of RCTs citing prior Cochrane reviews, non-Cochrane reviews, and either or both types of review increased from 28 studies (15.3%), 46 studies (25.1%), and 65 studies (35.5%) of 183 RCTs before 2008 to 42 studies (40.8%), 65 studies (64.1%), and 73 studies (71.8%) of 102 RCTs since 2020, respectively; the annual increases were 1.9% (95% CI, 1.4%-2.3%), 3.3%(95% CI, 2.9%-3.7%), and 3.0% (95% CI, 2.5%-3.5%), respectively. The proportion of RCTs citating prior systematic reviews varied considerably across clinical specialties, ranging from 28 of 106 RCTs (26.4%) in ophthalmology to 386 of 553 RCTs (69.8%) in psychiatry (P <.001). RCTs with 100 participants or more (risk ratio [RR], 1.16; 95% CI, 1.03-1.30), nonindustry funding (RR, 1.43; 95% CI, 1.27-1.61), and authors from high-income countries (RR, 1.10; 95% CI, 1.03-1.17) were more likely to cite systematic reviews than those with fewer than 100 participants, industry funding, and authors from low- and middle-income countries, respectively. A journal requirement to cite systematic reviews was not associated with the likelihood of citing a systematic review. CONCLUSIONS AND RELEVANCE This study found that the citation of prior systematic reviews in RCT reports improved over time, but approximately 40% of RCTs failed to do so. These findings suggest that reference to prior evidence for initiating, designing, and reporting RCTs should be further emphasized to assure clinical relevance, improve methodological quality, and facilitate interpretation of new results.

BACKGROUND:The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody concentrations can predict the efficacy is also uncertain. We aimed to assess the efficacy of these vaccines in preventing SARS-CoV-2 infections of different severities and the dose-response relationship between the antibody concentrations and efficacy. METHODS:We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, WHO, bioRxiv, and medRxiv for papers published between Jan 1, 2020 and Sep 12, 2022. RCTs on the efficacy of SARS-CoV-2 vaccines were eligible. Risk of bias was assessed using the Cochrane tool. A frequentist, random-effects model was used to combine efficacy for common outcomes (ie, symptomatic and asymptomatic infections) and a Bayesian random-effects model was used for rare outcomes (ie, hospital admission, severe infection, and death). Potential sources of heterogeneity were investigated. The dose-response relationships of neutralising, spike-specific IgG and receptor binding domain-specific IgG antibody titres with efficacy in preventing SARS-CoV-2 symptomatic and severe infections were examined by meta-regression. This systematic review is registered with PROSPERO, CRD42021287238. FINDINGS:28 RCTs (n=286 915 in vaccination groups and n=233 236 in placebo groups; median follow-up 1-6 months after last vaccination) across 32 publications were included in this review. The combined efficacy of full vaccination was 44·5% (95% CI 27·8-57·4) for preventing asymptomatic infections, 76·5% (69·8-81·7) for preventing symptomatic infections, 95·4% (95% credible interval 88·0-98·7) for preventing hospitalisation, 90·8% (85·5-95·1) for preventing severe infection, and 85·8% (68·7-94·6) for preventing death. There was heterogeneity in the efficacy of SARS-CoV-2 vaccines against asymptomatic and symptomatic infections but insufficient evidence to suggest whether the efficacy could differ according to the type of vaccine, age of the vaccinated individual, and between-dose interval (p>0·05 for all). Vaccine efficacy against symptomatic infection waned over time after full vaccination, with an average decrease of 13·6% (95% CI 5·5-22·3; p=0·0007) per month but can be enhanced by a booster. We found a significant non-linear relationship between each type of antibody and efficacy against symptomatic and severe infections (p<0·0001 for all), but there remained considerable heterogeneity in the efficacy, which cannot be explained by antibody concentrations. The risk of bias was low in most studies. INTERPRETATION:The efficacy of SARS-CoV-2 vaccines is higher for preventing severe infection and death than for preventing milder infection. Vaccine efficacy wanes over time but can be enhanced by a booster. Higher antibody titres are associated with higher estimates of efficacy but precise predictions are difficult due to large unexplained heterogeneity. These findings provide an important knowledge base for interpretation and application of future studies on these issues. FUNDING:Shenzhen Science and Technology Programs.

AbstractBackground:Previous studies indicated that glucosamine supplements may have a general anticancer effect. This study aimed to assess whether the potential effect differs across different types of cancers in a large prospective cohort study.Methods:All participants from the UK Biobank who were free of cancers and had complete information on glucosamine use at baseline were included and followed up from 2006 until 2021. Cox proportional hazards models were used to assess the associations between regular glucosamine use and different site-specific cancers. Subgroup analyses were performed to explore potential interactions. Several sensitivity analyses were conducted to assess the robustness of the main findings.Results:A total of 450,207 eligible participants (mean age: 56.2 years; females: 53.3%) were included, of whom 84,895 (18.9%) reported regular glucosamine use at baseline. During a median of 12.5 years follow-up, glucosamine use was significantly associated with an increased risk of overall cancer [HR, 1.04; 95% confidence interval (CI), 1.01–1.06], skin cancer (HR, 1.11; 95% CI, 1.07–1.15), and prostate cancer (HR, 1.07; 95% CI, 1.01–1.13), and with a reduced risk of lung cancer (HR, 0.88; 95% CI, 0.79–0.97) after adjusting for potential confounders. Statistical interaction was observed for gender, age, and education for the association of glucosamine use with overall cancer risk (all Pinteraction < 0.027). These results remained unchanged in the sensitivity analyses.Conclusions:Regular glucosamine use was associated with lower risk of lung cancer but higher risk of skin cancer, prostate cancer, and overall cancer.Impact:The roles of glucosamine use potentially differ in the development of different site-specific cancers.

Objectives: To examine whether and to what extent hospital strain will increase the risk of death from Covid-19. Design: Retrospective cohort study. Setting: England. Participants: Data on all the 147,276 Covid-19 deaths and 601,084 hospitalized Covid-19 patients in England during the period between 9 April 2020 and 11 March 2022 were extracted on a daily basis from the UK Health Security Agency. Main outcome measures: The number of Covid-19 patients currently in hospitals was used as the measure of hospital strain. Daily case fatality was estimated as the measure of risk of death from Covid-19. The study was divided into 4 periods, which represented largely the wild, Alpha, Delta and Omicron waves. Weighted linear regression models were used to assess the association between hospital strain and Covid-19 fatality with adjustment for potential confounders including vaccination score, hospital admission rate, percentage of deaths outside hospitals, study period and interaction between patients currently in hospitals and study period. Results: The daily case fatality from Covid-19 increased linearly as the number of patients currently in hospitals increased in the 4 study periods except the Omicron wave. After adjusting for potential confounders, an increase in 1000 patients currently in hospitals was associated with a relative increase of 6.3% (95% CI: 5.9%~6.8%), 1.4% (95% CI: 1.3% ~ 1.5%) and 12.7% (95% CI: 10.8%~14.7%) in daily case fatality during study periods 1, 2 and 3 respectively. Compared with the lowest number of patients currently in hospitals, the highest number was associated with a relative increase of 188.0% (95% CI: 165.9%~211.6%), 69.9% (95% CI: 59.0%~81.8%) and 58.2% (95% CI: 35.4%~89.0%) in daily case fatality in the first 3 study periods respectively. Sensitivity analyses using the number of patients in ventilation beds as the measure of hospital strain showed similar results. Conclusions: The risk of death from Covid-19 was linearly associated with the number of patients currently in hospitals, suggesting any (additional) effort to ease hospital strain or maintain care quality be beneficial during large outbreaks of Covid-19 and likely of other similar infectious diseases.

Background: Previous studies found that about 24% of the mild cognitive impairment (MCI) patients reverse to cognitive normal (CN) status. However, it is unclear which modifiable factors are associated with this reversion. Objective: To identify potential modifiable factors associated with the reversion of MCI to CN status. Methods: We conducted a prospective community-based cohort study based on 2002-2018 Chinese Longitudinal Health Longevity Survey (CLHLS). Multivariable Cox regression with least absolute shrinkage and selection operator (LASSO) penalty for variable selection was adopted to investigate the associations between reversion to CN and potential modifiable dietary/lifestyle, cardiometabolic, and psychological factors. Results: Our analysis included 7,422 MCI participants [average age: 90.0 (SD 9.5) years]. Among these participants, 1,604 (21.6%) reversed from MCI to CN with a mean (SD) follow-up of 2.9 (1.8) years. Several dietary/lifestyle factors, including daily consumption of fresh fruits (Hazard Ratio [HR]: 1.28, 95% CI: 1.15 to 1.42), engagement in reading (HR: 1.24, 95% CI: 1.00 to 1.54), housework (HR: 1.21, 95% CI: 1.08 to 1.35), and mah-jongg or other card games (HR: 1.23, 95% CI: 1.08 to 1.39), were positively associated with possibility of reversion. Cigarette smoking (HR: 0.92, 95% CI: 0.84 to 1.00) and duration of alcohol drinking (HR: 0.97, 95% CI: 0.94 to 0.99) were negatively associated with possibility of reversion. None of the modifiable cardiometabolic and psychological factors was found to be significantly associated with reversion to CN. Conclusion: This study identified several dietary/lifestyle factors associated with MCI reversion that may transfer into large-scale dementia prevention practices.

What is already known about this topic? During the coronavirus disease 2019 (COVID-19) pandemic, tremendous efforts have been made in countries to suppress epidemic peaks and strengthen hospital services to avoid hospital strain and ultimately reduce the risk of death from COVID-19. However, there is limited empirical evidence that hospital strain increases COVID-19 deaths. What is added by this report? We found the risk of death from COVID-19 was linearly associated with the number of patients currently in hospitals, a measure of hospital strain, before the Omicron period. This risk could be increased by a maximum of 188.0%. What are the implications for public health practice? These findings suggest that any (additional) effort to reduce hospital strain would be beneficial during early large COVID-19 outbreaks and possibly also others alike. During an Omicron outbreak, vigilance remains necessary to prevent excess deaths caused by hospital strain as happened in Hong Kong Special Administrative Region, China.

Predicting the probability of the reversion from mild cognitive impairment (MCI) to cognitively normal (CN) status can inform preventive treatments at individual, institutional and social level. This study aims to build a prediction model using a machine learning approach for reversion from MCI to CN status.

This is the first study examining the association between alcohol consumption and risk of cognitive impairment (CI) among Chinese older adults (65‐79 years).

It is unclear which modifiable factors are associated with reversion from mild cognitive impairment (MCI) to cognitively normal (CN) status. The study included 7,422 participants above 65 years old with MCI from Chinese Longitudinal Health Longevity Survey (CLHLS). Multivariable Cox regression with elastic net penalty was adopted to investigate the associations between reversion from MCI to CN and potential modifiable dietary/lifestyle, cardiometabolic, and psychological factors. 1,604 (21.6%) participants reversed from MCI to CN with a median follow-up of 2.8 years. Several dietary/lifestyle factors, including daily consumption of fresh fruits (HR: 1.28, 95% CI: 1.15-1.42), daily engagement in reading (HR: 1.24, 95% CI: 1.00-1.54), housework (HR: 1.21, 95% CI: 1.08-1.35), or mah-jong and other card games (HR: 1.23, 95% CI: 1.08-1.39), were associated with a higher possibility of reversion. This study identified several modifiable factors associated with MCI reversion that may transfer into large-scale preventive practice for dementia.

The negative effect of alcohol consumption on cognitive function is found to be J-shaped. We analyzed the association between alcohol consumption and the risk of dementia and examined the effect modification by APOE genotypes. 157,172 Participants with nearly equal alcohol consumption compared with ten years previously were included from UK Biobank cohort study. Levels of alcohol consumption were evaluated on both categorical scales such as abstainers, occasional drinkers, monthly drinkers, light-to-moderate drinkers (0- 14 units per week), and heavily drinkers (over 14 units per week) and continuous scales (total average weekly units of alcohol consumption), with Cox regression models and restricted cubic splines (RCS). Models over all participants and stratified on APOE genotypes were conducted to assess the risk of dementia, adjusted for sociodemographic, health behaviors, and health-related variables. 709 (0.45%) out of the 157,172 participants developed dementia over a mean follow-up of 11.4 years. Among all participants, abstainers (HR = 1.75, 95% CI 1.25 to 2.45) and occasional drinkers (1.45, 1.03 to 2.02) have an increased risk compared with light-to-moderate drinkers, whereas monthly drinkers (0.77, p = 0.25) and heavy drinkers (1.02, p = 0.86) do not show a significant difference. In the stratified analysis, among APOE ɛ4 allele carriers, there’s no significant difference between any category of drinkers and mildly weekly drinkers. In RCS with Cox models, 589 (0.44%) out of the 132,417 participants developed dementia over a mean follow-up of 11.4 years. A J-shape association between total average weekly alcohol consumption and dementia incidence was found only among APOE ɛ4 allele non-carriers. The effect of alcohol consumption on the risk of dementia differs between APOE ɛ4 carriers and non-carriers. The association between light-to-moderate alcohol consumption and dementia will be further examined.