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Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear.To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition.This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms.During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings.Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition.

Rationale Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods We constructed a polygenic risk score for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Results Of 430,582 participants, 712 developed severe COVID-19 as of February 22, 2021, of whom 19.8% had preexisting COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.09–1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18–1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12–1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35–3.04; P

Background Several guidelines have suggested alternative glycemic markers for hemoglobin A1c among older adults with limited life expectancy or multiple coexisting chronic illnesses. We evaluated associations between fructosamine, albumin-corrected fructosamine (AlbF), fasting plasma glucose (FPG), and mortality in the diabetic and nondiabetic subpopulations, and compared which marker better predicts mortality among participants aged 80 and older. Methods Included were 2 238 subjects from the Healthy Ageing and Biomarkers Cohort Study (2012–2018) and 207 participants had diabetes at baseline. Multivariable Cox proportional hazards regression models investigated the associations of fructosamine, AlbF, FPG, and all-cause, cardiovascular disease (CVD), and non-CVD mortality in the diabetic and nondiabetic subpopulations. Restricted cubic splines explored potential nonlinear relations. C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) evaluated the additive value of different glycemic markers to predict mortality. Results Overall, 1 191 deaths were documented during 6 793 person-years of follow-up. In the linear model, per unit increases of fructosamine, AlbF, and FPG were associated with a higher risk of mortality in nondiabetic participants, with hazard ratios of 1.02 (1.00, 1.05), 1.27 (1.14, 1.42), and 1.04 (0.98, 1.11) for all-cause mortality, and 1.04 (1.00, 1.07), 1.38 (1.19, 1.59), and 1.10 (1.01, 1.19) for non-CVD mortality, respectively. Comparisons indicated that AlbF better predicts all-cause and non-CVD mortality in nondiabetic participants with significant improvement in IDI and NRI. Conclusions Higher concentrations of fructosamine, AlbF, and FPG were associated with a higher risk of all-cause or non-CVD mortality among the very elderly where AlbF may constitute an alternative prospective glycemic predictor of mortality.

Objective To examine the association of incident type 2 diabetes (T2D) risk with sleep factors, genetic risk, and their combination effects. Design Large prospective population-based cohort study. Methods This population-based prospective cohort study included 360 403 (mean (s.d.) age: 56.6 (8.0) years) participants without T2D at baseline from the UK Biobank. Genetic risk was categorised as high (highest quintile), intermediate (quintiles: 2–4), and low (lowest quintile) based on a polygenic risk score for T2D. Sleep scores, including long or short sleep duration, insomnia, snoring, late chronotype, and excessive daytime sleepiness, were categorized as an unfavourable, intermediate, or favourable sleep and circadian pattern. Results During a median follow-up of 9.0 years, 13 120 incident T2D cases were recorded. Among the participants with an unfavourable sleep and circadian pattern, 6.96% (95% CI: 6.68–7.24%) developed T2D vs 2.37% (95% CI: 2.28–2.46%) of participants with a favourable sleep and circadian pattern (adjusted hazard ratio (HR): 1.53, 95% CI: 1.45–1.62). Of participants with a high genetic risk, 5.53% (95% CI: 5.36–5.69%) developed T2D vs 2.01% (95% CI: 1.91–2.11%) of participants with a low genetic risk (adjusted HR: 2.89, 95% CI: 2.72–3.07). The association with sleep and circadian patterns was independent of genetic risk strata. Participants in the lowest quintile with an unfavourable sleep and circadian pattern were 3.97-fold more likely to develop T2D than those in the lowest quintile with a favourable sleep and circadian pattern. Conclusions Sleep and circadian patterns and genetic risk were independently associated with incident T2D. These results indicate the benefits of adhering to a healthy sleep and circadian pattern in entire populations, independent of genetic risk.

Background The interplay between physical activity (PA) and air pollution in relation to type 2 diabetes (T2D) remains largely unknown. Based on a large population-based cohort study, this study aimed to examine whether the benefits of PA with respect to the risk of T2D are moderated by exposure to air pollution. Methods UK Biobank participants (n = 359,153) without diabetes at baseline were included. Information on PA was obtained using the International Physical Activity Questionnaire short form. Exposure to air pollution, including PM2.5, PMcoarse (PM2.5−10), PM10, and NO2, was estimated from land use regression models. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results During a median of 8.9 years of follow-up, 13,706 T2D events were recorded. Compared with a low PA level, the HRs for the risk of T2D among individuals with moderate and high PA were 0.82 (95% CI, 0.79–0.86) and 0.73 (95% CI, 0.70–0.77), respectively. Compared with low levels of air pollution, the HRs for risk of T2D for high levels of air pollution (PM2.5, PMcoarse, PM10, and NO2) were 1.19 (1.14–1.24), 1.06 (1.02–1.11), 1.13 (1.08–1.18), and 1.19 (1.14–1.24), respectively. There was no effect modification of the associations between PA and T2D by air pollution (all P-interactions > 0.05). The inverse associations between PA and T2D in each air pollution stratum were generally consistent (all P for trend Conclusion A higher PA and lower air pollution level were independently associated with a lower risk of T2D. The beneficial effects of PA on T2D generally remained stable among participants exposed to different levels of air pollution. Further studies are needed to replicate our findings in moderately and severely polluted areas.

Background To examine the association between regular use of proton pump inhibitors and the risk of incident dementia, including dementia subtypes, and whether the association differs between APOE genotypes. Methods Based on a prospective analysis of data from the UK Biobank, 501,002 individuals (female, 54.4%) aged between 40 and 70 years, who had no prevalent dementia at baseline, were enrolled between 2006 and 2010 and followed up to 2018. We compared all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) incidence rates between proton pump inhibitor users and non-users by the Cox proportional hazard model. Results During 4,438,839 person-years of follow-up (median length of follow-up, 9.0 years), there were 2505 incident cases of all-cause dementia, including 932 cases of AD and 524 cases of VaD. The incident rate of all-cause dementia among proton pump inhibitor users was 1.06 events per 1000 person-years, compared with 0.51 events per 1000 person-years among non-users. After adjustment for multiple confounders and indications, the hazard ratios (HRs) of the proton pump inhibitor users were 1.20 (95% CI, 1.07–1.35) for incident all-cause dementia, 1.23 (95% CI, 1.02–1.49) for incident AD, and 1.32 (95% CI, 1.05–1.67) for incident VaD. In addition, the association between proton pump inhibitor use and all-cause dementia differed by APOE genotype (P for interaction = 0.048). Among APOE ε4 heterozygotes, the fully adjusted HR of proton pump inhibitor use was 1.46 (95% CI, 1.22–1.75) and 1.68 (95% CI, 1.36–2.07), especially for individuals aged 65 years and older. Conclusions The finding of this large population-based cohort study indicates that the use of proton pump inhibitors is associated with an increased risk of incident dementia, particularly among APOE ε4 heterozygotes.

BackgroundGaps remained in the updated information of the firearm violence (FV) burden from a global landscape. Understanding the global burden of FV could contribute to decision-making.MethodsData on the FV burden, including physical violence by firearm (PVF), self-harm by firearm (SHF), and unintentional firearm injuries (UFI), were extracted from the Global Burden of Disease 2019. The temporal trends of age-standardized rate (ASR) were estimated using estimated annual percentage change (EAPC).ResultsIn 2019, PVF, SHF, and UFI reported 710.64 × 103, 335.25 × 103, and 2,133.88 × 103, respectively, incident cases worldwide. Their ASR (/100,000 people-years) were 9.31, 4.05, and 28.07. During 1990–2019, the overall incident ASRs of PVF presented an increasing trend (EAPC = 0.61, 95% confidence interval [CI]: 0.48 to 0.75). Notably, pronounced increasing trends were observed in Tropical Latin America, and North Africa and Middle East. However, incident trends of SHF and UFI declined globally, with the respective EAPCs being −0.68 (95% CI: −0.83 to −0.54) and −0.98 (95% CI: −1.19 to −0.77). In 2019, the ASR of death due to PVF, SHF, and UFI were 2.23, 0.65, and 0.26, and that of DALYs were 127.56, 28.10, and 17.64, respectively. Decreasing trends in the ASRs of FV were observed in most regions and countries worldwide over the past three decades, particularly that of PVF in Estonia.ConclusionThe FV burden was heterogeneous across regions and countries, which was deeply subjected to socioeconomic factors. The findings highlighted that specific prevention strategies and interventions were required, particularly in the high prevalent settings.

Background We investigated college students’ attitude and compliance towards a prevention strategy involving use of non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19). Methods We conducted a cross-sectional online survey in four universities in Guangdong Province (China) based on purposive sampling. A self-administered questionnaire was given to College students (CSs) to measure the supportive attitude towards an outbreak control strategy and adoption of NPIs in respondents. Results A total of 44,446 CSs participated between 31 January and 10 February 2020; 92.7% of respondents supported the outbreak control strategy. The proportion of respondents who avoided public places, wore a facemask, avoid gatherings, and washed hands more frequently than usual was 94.8, 92.8, 91.2 and 86.9%. respectively. A total of 76.5% respondents adopted all four measures. A supportive attitude was associated with NPI adoption. Students who were female, postgraduate, anxious, and not depressed tended to have a higher supportive attitude and higher chance of NPI adoption. Conclusions Higher supportiveness towards the disease control strategy for the Chinese public may lead to higher adoption rate of NPIs. Psychosocial factors were related to a supportive attitude and adoption of the NPI. We believe that our findings could aid policymakers to create NPIs to prevent and control emerging infectious diseases such as COVID-19.

Previous observational studies have suggested an association between coffee intake and reduced risk for death, but these studies did not distinguish between coffee consumed with sugar or artificial sweeteners and coffee consumed without.To evaluate the associations of consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee with all-cause and cause-specific mortality.Prospective cohort study.Data were extracted from the UK Biobank.A total of 171 616 participants (mean age, 55.6 years [SD, 7.9]) without cardiovascular disease (CVD) or cancer at baseline were eligible. Baseline demographic, lifestyle, and dietary data from the UK Biobank were used, with follow-up beginning in 2009 and ending in 2018.Dietary consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee was self-reported. All-cause, cancer-related, and CVD-related mortality were estimated.During a median follow-up of 7.0 years, 3177 deaths were recorded (including 1725 cancer deaths and 628 CVD deaths). Cox models with penalized splines showed U-shaped associations of unsweetened coffee, sugar-sweetened coffee, and artificially sweetened coffee with mortality. Compared with nonconsumers, consumers of various amounts of unsweetened coffee (0 to 1.5,1.5 to 2.5,2.5 to 3.5,3.5 to 4.5, and4.5 drinks/d) had lower risks for all-cause mortality after adjustment for lifestyle, sociodemographic, and clinical factors, with respective hazard ratios of 0.79 (95% CI, 0.70 to 0.90), 0.84 (CI, 0.74 to 0.95), 0.71 (CI, 0.62 to 0.82), 0.71 (CI, 0.60 to 0.84), and 0.77 (CI, 0.65 to 0.91); the respective estimates for consumption of sugar-sweetened coffee were 0.91 (CI, 0.78 to 1.07), 0.69 (CI, 0.57 to 0.84), 0.72 (CI, 0.57 to 0.91), 0.79 (CI, 0.60 to 1.06), and 1.05 (CI, 0.82 to 1.36). The association between artificially sweetened coffee and mortality was less consistent. The association of coffee drinking with mortality from cancer and CVD was largely consistent with that with all-cause mortality. U-shaped associations were also observed for instant, ground, and decaffeinated coffee.Exposure assessed at baseline might not capture changes in intake over time.Moderate consumption of unsweetened and sugar-sweetened coffee was associated with lower risk for death.National Natural Science Foundation of China, Young Elite Scientist Sponsorship Program by CAST, and Project Supported by Guangdong Basic and Applied Basic Research Foundation.

As one of the fatal complications, venous thromboembolism (VTE) is associated with increased mortality. However, the combined effects of adopting multiple healthy lifestyles have not been firmly demonstrated. This study was to evaluate the association of combined healthy lifestyles and genetic risk factors with VTE and to investigate their interaction. A prospective cohort study from UK Biobank with a total of 442,963 men and women aged between 38 to 73 years were recruited from 2006 to 2010 and followed up through 2017 or 2018. A polygenic risk score was constructed and a weighted healthy lifestyle score, including no current smoking, regular physical exercises, healthy diet, and healthy body mass index, was categorized. During a median follow-up 9.0 years (3,912,396 person-years), there were 6,736 (172 per 100,000 person-years) incident VTE cases recorded. Among the participants with an unfavorable lifestyle, 1.80% developed VTE, versus 1.03% of the participants with a favorable lifestyle (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.48–1.68). Of the participants with high genetic risk, 2.42% developed VTE, versus 0.97% of the participants with low genetic risk (HR: 2.60; 95% CI: 2.39–2.81). Moreover, of the participants with high genetic risk and unfavorable lifestyle, 2.90% developed VTE, versus 0.66% of the participants with low genetic risk and favorable lifestyle (HR: 4.09; 95% CI: 3.48–4.79). No significant interaction between genetic risk and lifestyle factors was observed (p for interaction = 0.727). An unfavorable lifestyle was associated with a substantially higher risk of VTE, regardless of the genetic risk strata.

Exposure to trichloroacetic acid (TCAA) has been associated with impaired semen quality; however, its association with spermatozoa apoptosis and DNA damage remains unclear. We, therefore, collected single semen and repeated urine samples from male partners of couples attending a reproductive center, which were measured for spermatozoa apoptosis and DNA damage parameters and TCAA concentrations, respectively. Multivariable linear regression models were used to explore the associations between urinary TCAA concentrations and spermatozoa apoptosis (

Background Candidate genes of neuromuscular junction (NMJ) pathway increased risk of frailty, but the extent and whether can be offset by exercises was unclear. The aim of this study was to investigate the association between aerobic exercises and incident frailty regardless of NMJ pathway‐related genetic risk. Methods A cohort study on participants from Chinese Longitudinal Healthy Longevity Survey was conducted from 2008 to 2011. A total of 7006 participants (mean age of 80.6 ± 10.3 years) without frailty at baseline were interviewed to record aerobic exercise status, and 4053 individuals among them submitted saliva samples. NMJ pathway‐related genes were genotyped and weighted genetic risk scores were constructed. Results During a median follow‐up of 3.1 years (19 634 person‐years), there were 1345 cases (19.2%) of incident frailty. Persistent aerobic exercises were associated with a 26% lesser frailty risk [adjusted hazard ratio (HR) = 0.74, 95% confidence interval (CI) = 0.64–0.85]. This association was stronger in a subgroup of 1552 longevous participants (age between 90 and 111 years, adjusted HR = 0.72, 95% CI = 0.60–0.87). High genetic risk was associated with a 35% increased risk of frailty (adjusted HR = 1.35, 95% CI = 1.16–1.58). Of the participants with high genetic risk and no persistent aerobic exercises, there was a 59% increased risk of frailty (adjusted HR = 1.59, 95% CI = 1.20–2.09). HRs for the risk of frailty increased from the low genetic risk with persistent aerobic exercise to high genetic risk without persistent aerobic exercise (P trend

Objective we aimed to investigate the association of smoking cessation with risk of all-cause mortality amongst oldest old people (aged ≥ 80 years). Design this was a prospective cohort study. Setting the Chinese Longitudinal Healthy Longevity Survey, implemented in 23 provinces of China. Participants a total of 28,643 community-dwelling oldest old people (mean age, 92.9 ± 7.5 years) were included. Methods in this community-based cohort study, Cox proportional hazards models were used to examine the association of smoking cessation with risk of all-cause mortality. Results during 136,585 person-years of follow-up from baseline to 1 September 2014, compared with never smokers, hazard ratios and 95% confidence intervals for all-cause mortality were 1.06 (1.02–1.10) for current smokers, 1.23 (1.09–1.39) for transient quitters (≤1 consecutive years since smoking cessation), 1.22 (1.12–1.32) for recent quitters (2–6 consecutive years since smoking cessation) and 1.11 (1.02–1.22) for long-term quitters (>6 consecutive years since smoking cessation). Cox models with penalised splines revealed an increased risk of all-cause mortality after smoking cessation; the highest mortality risk was observed within 2–4 years after smoking cessation and the risk gradually decreased with duration of smoking cessation. We further conducted subgroup analyses and sensitivity analyses to reduce the impact of reverse causation. Conclusions smoking is harmful to health in all populations. Our study findings indicated smoking cessation in late life to be associated with increased risk of all-cause mortality amongst oldest old people who have smoked for a long time.

As the proportion of the elderly population increases, more and more people suffer from aging-related diseases. Even if aging is inevitable, prolonging the time of healthy aging, delaying the progression of aging-related diseases, and the incidence of morbidity can greatly alleviate the pressure on individuals and society. Current research and exploration in the field of materials related to aging are expanding tremendously. Here, we present a summary of recent research in the field of nanomaterials relevant to aging. Some nanomaterials, such as silica nanomaterials (NMs) and carbon nanotubes, cause damage to the cells similar to aging processes. Other nanomaterials such as fullerenes and metalbased nanomaterials can protect the body from endogenous and exogenous harmful substances such as ROS by virtue of their excellent reducing properties. Another new type of nucleic acid nanomaterial, tetrahedral framework nucleic acids, works effectively against cell damage. This material selectively clears existing senescent cells in the tissue and thus prevents the development of the chronic inflammatory environment caused by senescent cells secreting senescence-associated secretory phenotype to the surroundings. We believe that nanomaterials have tremendous potential to advance the understanding and treatment of aging-related disorders, and today's research only represents the beginning stages.

BackgroundThe association between high-sensitivity C-reactive protein (hsCRP) levels and all-cause mortality for the oldest-old (aged 80 years or older) remains unclear. We aimed to investigate the associations between hsCRP concentrations and the risks of all-cause mortality, and further identify the potential modifying factors affecting these associations among the oldest-old.MethodsThis prospective, community-based cohort study included 2,206 participants aged 80 years or older (median age 93.0 years) from the Healthy Aging and Biomarkers Cohort Study. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidential intervals (95% CIs) for all-cause mortality according to hsCRP quartiles and recommendation for relative risk categories of hsCRP levels (< 1.0, 1.0–3.0, and > 3.0 mg/L), with adjustment for sociodemographic information, lifestyle, physical examination, medical history, and other potential confounders.ResultsDuring a median follow-up period of 3.1 years (IQR: 1.6–3.9 years), 1,106 deaths were verified. After full adjustment for potential confounders, a higher hsCRP concentration was positively associated with an increased risk of all-cause mortality (P for trend < 0.001). Compared with the lowest quartile, the fully adjusted HRs of the second, third, and fourth quartiles were 1.17 (95% CI: 0.94, 1.46), 1.28 (95% CI: 1.01, 1.61), and 1.49 (95% CI: 1.20, 1.87), respectively. The association of hsCRP with all-cause mortality was modified by smoking status (P for interaction = 0.011), an increased risk of hsCRP with all-cause mortality showed among non-current smokers (HR: 1.17; 95% CI: 1.07, 1.28), but no significance was observed in current smokers (HR: 0.83; 95% CI: 0.66, 1.18).ConclusionsOur study indicated that elevated hsCRP concentrations were associated with a higher risk of all-cause mortality among Chinese oldest-old. Future studies investigating additional factors of disease and aging processes are needed to obtain a better understanding of the mechanisms.

Background To investigate whether the mitochondrial transcription factor A (TFAM) rs1937 single nucleotide polymorphism (SNP) is associated with longevity. Methods We conducted a case-control study among Chinese long-lived individuals (≥90 years). Data were obtained on 3294 participants who were able to voluntarily provided a saliva sample during 2008–2009 from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). In this study, 1387 young elderly (65–74 years) were allocated to the control group, and 1907 long-lived individuals were recruited as the case group. SNP rs1937 on TFAM were genotyped. Logistic regression models were applied to evaluate the association between rs1937 SNP and longevity. Results The genotype frequency of the SNP of rs1937 in the two groups had a significant difference (p = 0.003). Binary logistic regression analysis showed that compared to younger elderly, the long-lived individuals with “CC genotype” of rs1937 were more closely related to increased longevity than those with “GG genotype” (OR: 1.989, 95% CI: 1.160–3.411). The positive association between rs1937 SNP and longevity was robust in stratified analyses and sensitivity analyses. Conclusions We found the SNP of rs1937 may be a potential biomarker for longer human life span. Further studies are necessary to elucidate the biological mechanism of rs1937 on TFAM with promoting longevity.

Evidence suggests that there is a close association between myeloperoxidase (MPO) gene rs2333227 G>A polymorphism with Alzheimer’s disease (AD) susceptibility. We conducted a meta-analysis to explore the precise association between MPO rs2333227 G>A polymorphism and AD susceptibility. Online databases were searched and the relevant information was collected. Crudeodds ratios with 95% confidence intervals were calculated. Trial sequential analysis (TSA), heterogeneity analyses, accumulative analyses, sensitivity analyses, and publication biasestests were performed. Overall, nine publications (ten independent case-controls) were included in this meta-analysis, involving 3260 participants. Pooled results revealed no significant association between MPO rs2333227 G>A polymorphism and AD susceptibility was observed. TSA showed that the present meta-analysis remained inconclusive due to insufficient evidence. In summary, the current meta-analysis indicated that the MPO rs2333227 G>A polymorphism may not be acausalfactor in the development of AD.

Highlights • The prevalence of anxiety and depression symptoms was 3.4% and 22.8% among workers during the COVID-19 epidemic in China. • Epidemic-related factors especially having confirmed cases in the community and having confirmed friends were associated with the higher risk of anxiety and depression symptoms. • Major traditional risk factors, such as general or poor health status and always drinking alcohol, were found still to be the dominant factors associating with the increased risk of anxiety and depression symptoms. • Approximately 67.3% and 26.8% of workers reported demand for psychological education and interventions, respectively., Background COVID-19 has gained intense attention globally. However, little is known about the COVID-19-ralated mental health status among workers. Methods The cross-sectional online survey with 123,768 workers was conducted from February 2, 2020 to February 7, 2020 on a mega-size labor-intensive factory in Shenzhen, China. Oral consent was obtained prior to the questionnaire survey. The information collected in the survey included demographic characteristics, psychological symptoms, COVID-19-related information, and demands for psychological education and interventions. Symptoms of anxiety and depression were measured by the Zung's Self-Rating Anxiety Scale and Self-Rating Depression Scale. Logistic regression models were performed to determine the association between related factors and mental health status. Results The prevalence of anxiety and depression symptoms was 3.4% and 22.8%, respectively. The dominant epidemic-related factors were having confirmed cases in the community (odds ratio [OR], 2.75, 95% CI, 2.37–3.19) and having confirmed friends (OR, 2.44; 95% CI, 1.69–3.52) for the increased risk of anxiety and depression symptoms, respectively. Nevertheless, major traditional risk factors such as general or poor health status and always drinking alcohol were still the dominant factors associated with the increased risk of anxiety and depression symptoms. Overall, 67.3% and 26.8% workers reported desire for psychological education and interventions, respectively. Limitations All assessments were self-reported, resulting in a risk of method bias. Conclusions Our findings show a relatively low prevalence of anxiety symptoms, a relatively high prevalence of depression symptoms, and urgent demand for psychological education and interventions among workers during the COVID-19 outbreak.

Cyclodextrins are widely used pharmaceutical excipients, particularly for insoluble compounds dosed orally, such as the oral solution of itraconazole, which is frequently used in clinical drug-drug interaction studies to inhibit cytochrome P450 3A. Since cyclodextrins act by forming inclusion complexes with their coformulated drug, they could have an unintended consequence of affecting absorption if they form a strong complex with the potential victim drug in an itraconazole drug-drug interaction study. This observation was made in a drug-drug interaction study with the Bruton's tyrosine kinase (BTK) inhibitor fenebrutinib and itraconazole, in which, relative to the control group, the expected increase in fenebrutinib maximum plasma concentration (Cmax ) was not observed in the itraconazole group, and a delay in time to reach maximum plasma concentration (Tmax ) was observed in the itraconazole group. The in vitro binding constant between fenebrutinib and hydroxypropyl-β-cyclodextrin was determined to be 2 × 105 M-1 , and the apparent permeability of fenebrutinib across a Madin-Darby canine kidney cell monolayer decreased in a cyclodextrin concentration-dependent manner. This observation was confirmed in vivo, in a pentagastrin-pretreated dog model, in which fenebrutinib was administered with or without cyclodextrin; a reduction in Cmax , a prolonged Tmax , and increased fenebrutinib recovery in feces replicated the previous observation in healthy volunteers and supported the hypothesis that complexation with cyclodextrin decreased rate and extent of fenebrutinib absorption. Physiologically-based pharmacokinetic modeling was used to translate the in vitro effect of cyclodextrin on fenebrutinib apparent permeability to the in vivo effect on absorption, which was then confirmed using the in vivo dog pharmacokinetic data.

In order to explore frailty subtypes and find their associated risk factors, we conducted cross-sectional surveys of 5,341 seniors aged 60 and over in China using the Frailty Index (FI) scale. We identified four frailty subtypes, namely multi-frail, cognitive and functionally frail, psychologically frail and physiologically frail. Old age and low education level were the common risk factors among the four subtypes. Being widowed, divorced or unmarried was a risk factor for multi-frail, cognitive and functionally frail and psychologically frail, and male sex was a protective factor against cognitive and functionally frail and psychologically frail subtypes. Having a harmonious relationship with family was a protective factor against multi-frail, and fewer visits to the elderly by their children was a risk factor for psychologically frail. Dissatisfaction with their housing was a risk factor for cognitive and functionally frail, psychologically frail and physiologically frail, and a pension being the main source of income was a risk factor for cognitive and functionally frail and psychologically frail. Exercising every day was a protective factor against multi-frail and cognitive and functionally frail, and a lower level of physical activity was a risk factor for all four frailty subtypes. Our findings confirm the heterogeneity of frailty and suggest that different frail elderly individuals need more targeted care interventions.

Background Evidence of the trend of the incidence of activities of daily living (ADL) disability among Chinese older people is limited. We aimed to investigate the time trends and potential risk factors for the incidence of ADL disability among Chinese older people (≥65 years). Methods We established two consecutive and nonoverlapping cohorts (6,857 participants in the 2002 cohort and 5,589 participants in the 2008 cohort) from the Chinese Longitudinal Healthy Longevity Survey. ADL disability was defined as the need for assistance with at least one essential activity (dressing, bathing, toileting, eating, indoor activities, and continence). Cox proportional hazards models were used to identify factors associated with the trend in the incidence of ADL disability from 2002 to 2014. Results The incidence (per 1,000 person-years) of ADL disability decreased significantly from 64.2 in the 2002 cohort to 46.6 in the 2008 cohort (p < .001), and decreasing trends in the incidence of ADL disability were observed for all sex, age, and residence subgroups (all p < .001), even after adjusting for multiple potential confounding factors. Moreover, we found that adjustment for sociodemographic, lifestyle information, and cardiovascular risk factors (hypertension, diabetes, heart disease, and stroke) explained less of the decline in ADL disability during the period from 2002 to 2014. Conclusion The incidence of ADL disability among the older adults in China appears to have decreased during the study period, and this finding cannot be explained by existing sociodemographic and lifestyle information and cardiovascular risk factors.

Background Carefully conducted systematic reviews (SRs) can provide reliable evidence on the effectiveness of treatment strategies for Alzheimer’s disease (AD). Nevertheless, the reliability of SR results can be limited by methodological flaws. This cross-sectional study aimed to examine the methodological quality of SRs on AD treatments, along with potentially relevant factors. Methods To identify eligible SRs on AD treatments, four databases including the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, and PsycINFO were searched. The Assessing the Methodological Quality of Systematic Reviews 2 instrument was used for quality appraisal of SRs. Multivariable regression analyses were used to examine factors related to methodological quality. Results A total of 102 SRs were appraised. Four (3.90%) SRs were considered as high quality; 14 (13.7%), 48 (47.1%), and 36 (35.3%) were as moderate, low, and critically low quality, respectively. The following significant methodological limitations were identified: only 22.5% of SRs registered protocols a priori, 6.9% discussed the rationales of chosen study designs, 21.6% gave a list of excluded studies with reasons, and 23.5% documented funding sources of primary studies. Cochrane SRs (adjusted odds ratio (AOR): 31.9, 95% confidence interval (CI): 3.81–266.9) and SRs of pharmacological treatments (AOR: 3.96, 95%CI: 1.27–12.3) were related to the higher overall methodological quality of SRs. Conclusion Methodological quality of SRs on AD treatments is unsatisfactory, especially among non-Cochrane SRs and SRs of non-pharmacological interventions. Improvement in the following methodological domains requires particular attention due to poor performance: registering and publishing protocols a priori, justifying study design selection, providing a list of excluded studies, and reporting funding sources of primary studies.

Introduction: The association patterns of hemoglobin (HB) concentrations with mortality among the longevity older adults are unclear. We aimed to evaluate the relationship among older adults form Chinese longevity regions.Methods: We included 1,785 older adults aged ≥65 years (mean age, 86.7 years; 1,002 women, 783 men) from the community-based Chinese Longitudinal Healthy Longevity Survey. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality using multivariable Cox proportional hazards models and Cox models with restricted cubic spline.Results: In total, 999 deaths occurred during a median follow-up of 5.4 years from 2011 to 2017. Restricted cubic spline analysis found no non-linear association between HB concentrations and all-cause mortality after a full adjustment for covariates among the older adults form longevity regions (p > 0.05 for non-linearity). The risk for all-cause mortality was significantly higher in the groups with HB concentration of Conclusions: Among older adults form Chinese longevity regions, HB concentrations were found to be inversely and linearly associated with all-cause mortality. Further prospective intervention trials are needed to confirm whether higher HB concentrations had a lower risk of mortality in these older adults.

Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29–9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.

BackgroundNon-pharmaceutical interventions were implemented in most countries to reduce the transmission of COVID-19. We aimed to describe the incidence of influenza in four countries in the 2019–2020 season and examined the effect of these non-pharmaceutical interventions on the incidence of influenza.MethodsWe used the network surveillance data from 2015 to 2020 to estimate the percentage increase in influenza cases to explore the effect of non-pharmaceutical interventions implemented to control the COVID-19 on the incidence of influenza in China, the United States, Japan, and Singapore.ResultsWe found that the incidence of influenza has been almost zero and reached a persistent near-zero level for a continuous period of six months since epidemiologic week 14 of 2020 in the four countries. Influenza incidence decreased by 77.71% and 60.50% in the early days of COVID-19 in the 2019–2020 season compared to the same period in preceding years in Japan and Singapore, respectively. Furthermore, influenza incidence decreased by 60.50–99.48% during the period of compulsory interventions in the 2019–2020 season compared to the same period in preceding years in the four countries.ConclusionThese findings suggest that the application of non-pharmaceutical interventions, even everyday preventive action, was associated with a reduction of influenza incidence, which highlights that more traditional public health interventions need to be reasserted and universalized to reduce influenza incidence.

Background While well-conducted systematic reviews (SRs) can provide the best evidence on the potential effectiveness of acupuncture, limitations on the methodological rigour of SRs may impact the trustworthiness of their conclusions. This cross-sectional study aimed to evaluate the methodological quality of a representative sample of SRs on acupuncture effectiveness. Methods Cochrane Database of Systematic Reviews, MEDLINE, and EMBASE were searched for SRs focusing on the treatment effect of manual acupuncture or electro-acupuncture published during January 2018 and March 2020. Eligible SRs must contain at least one meta-analysis and be published in English language. Two independent reviewers extracted the bibliographical characteristics of the included SRs with a pre-designed questionnaire and appraised the methodological quality of the studies with the validated AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews 2). The associations between bibliographical characteristics and methodological quality ratings were explored using Kruskal-Wallis rank tests and Spearman’s rank correlation coefficients. Results A total of 106 SRs were appraised. Only one (0.9%) SR was of high overall methodological quality, zero (0%) was of moderate-quality, six (5.7%) and 99 (93.4%) were of low-quality and critically low-quality respectively. Among appraised SRs, only ten (9.4%) provided an a priori protocol, four (3.8%) conducted a comprehensive literature search, five (4.7%) provided a list of excluded studies, and six (5.7%) performed meta-analysis appropriately. Cochrane SRs, updated SRs, and SRs that did not search non-English databases had relatively higher overall quality. Conclusions Methodological quality of SRs on acupuncture is unsatisfactory. Future reviewers should improve critical methodological aspects of publishing protocols, performing comprehensive search, providing a list of excluded studies with justifications for exclusion, and conducting appropriate meta-analyses. These recommendations can be implemented via enhancing the technical competency of reviewers in SR methodology through established education approaches as well as quality gatekeeping by journal editors and reviewers. Finally, for evidence users, skills in SR critical appraisal remain to be essential as relevant evidence may not be available in pre-appraised formats.

Background Genetic variation increases the risk of lung cancer, but the extent to which smoking amplifies this effect remains unknown. Therefore, we aimed to investigate the risk of lung cancer in people with different genetic risks and smoking habits. Methods This prospective cohort study included 345,794 European ancestry participants from the UK Biobank and followed up for 7.2 [6.5–7.8] years. Results Overall, 26.2% of the participants were former smokers, and 9.8% were current smokers. During follow-up, 1687 (0.49%) participants developed lung cancer. High genetic risk and smoking were independently associated with an increased risk of incident lung cancer. Compared with never-smokers, HR per standard deviation of the PRS increase was 1.16 (95% CI, 1.11–1.22), and HR of heavy smokers (≥40 pack-years) was 17.89 (95% CI, 15.31–20.91). There were no significant interactions between the PRS and the smoking status or pack-years. Population-attributable fraction analysis showed that smoking cessation might prevent 76.4% of new lung cancers. Conclusions Both high genetic risk and smoking were independently associated with higher lung cancer risk, but the increased risk of smoking was much more significant than heredity. The combination of traditional risk factors and additional PRS provides realistic application prospects for precise prevention.

Background The coronavirus disease 2019 (COVID-19) pandemic is a worldwide public health emergency that began in late 2019 and is still ongoing. Medical staff are at a particularly high risk of mental stress due to their close contact with infected patients. This study aimed to assess medical staff anxiety and depression levels from different risk-level areas in China during the early period of the COVID-19 outbreak and identify the main factors that might affect their mental health. Methods From February 22 to March 9, 2020, we conducted a 4-part online questionnaire to survey medical staff across different Chinese provinces about their anxiety and depression levels during the initial COVID-19 outbreak. The survey considered different demographic characteristics, anxiety (General Anxiety Disorder-7) scores, depression (Patient Health Questionnaire-9) scores, and occupational protection scores. Snowball sampling via a WeChatTM group was performed to collect the data. Results Among the 7,413 respondents, the rates of anxiety and depression reported among medical staff were 33.74% [2,501] and 27.65% [2,050], respectively. The odds of being assessed with severe anxiety were higher among nurses, those who were widowed, those in poor physical health, those working in COVID-19 designated facilities, and those receiving more than 50% negative/false information every day; the odds decreased by 5.8% with every 1-point increase in occupational protection. The odds of being assessed with moderate to severe depression or above were higher for the 18-30-year-old group, divorcees, those in poor physical health, and those receiving more than 50% of negative/false information every day; these odds decreased by 4.5% with every 1-point increase in occupational protection. Medical staff working in areas with a low exposure risk were at high risk of both anxiety and depression. Conclusions During the outbreak of COVID-19 in China, a significant proportion of medical staff faced psychological problems, even those in areas with a low exposure risk. Targeted interventions should focus more on nurses, widowed /divorced, and medical staff with poor physical health, less clinical experience, or insufficient occupational protection. The authenticity and orientation of media also showed a correlation with the mental state of medical staff.

To evaluate the associations of sarcopenia, handgrip strength and calf circumference with cognitive impairment among Chinese older adults.Totally 2,525 older adults were recruited from the Healthy Aging and Biomarkers Cohort Study. Cognitive impairment was assessed by the Chinese Mini-Mental State Examination. Handgrip strength was calculated from the means of the right and left hand values. Calf circumference was measured at the site of maximum circumference of the non-dominant leg. The formula developed by Ishii was used to define sarcopenia. Multiple logistic regression was performed to evaluate the associations of sarcopenia, handgrip strength, and calf circumference with cognitive impairment.The prevalence of cognitive impairment was 34.36%. The adjusted odds ratio (Sarcopenia, identified by low handgrip strength and low calf circumference, was positively associated with cognitive impairment.

ObjectiveTo evaluate whether evidence-based, individualised (EBI) counselling regarding hypertension and the treatment would affect medication use in insured patients with mild hypertension in China.MethodsWe conducted a parallel-group, randomised controlled trial in two primary care centres in Shenzhen, a metropolitan city in China. Patients with mild primary hypertension, 10-year risk of cardiovascular diseases (CVDs) lower than 20% and no history of CVDs were recruited and randomly allocated to two groups. EBI plus general counselling was provided to the intervention group and general counselling alone to the control group. EBI counselling included information on the 10-year CVD risk and treatment benefit in terms of absolute risk reduction estimated for each individual and information on average side effects and costs of antihypertensive drugs. The outcomes included use of antihypertensive drugs and adherence to the treatment at 6-month follow-up, with the former being primary outcome.ResultsTwo hundred and ten patients were recruited, with 103 and 107 allocated to the intervention and control groups, respectively. At baseline, 62.4% of the patients were taking antihypertensive drugs that were all covered by health insurance. At the end of 6-month follow-up, there was no statistically significant difference in the rate of medication use between the intervention group and the control group (65.0% vs 57.9%; OR=1.35, 95% CI: 0.77 to 2.36). The difference in adherence rate between the two groups was not statistically significant either (43.7% vs 40.2%; OR=1.15, 95% CI 0.67 to 2.00]). The results were robust in sensitivity analyses that used different cutoffs to define the two outcomes.ConclusionsThe EBI counselling by health educators other than the caring physicians had little impact on treatment choices and drug-taking behaviours in insured patients with mild primary hypertension in this study. It remains unclear whether EBI counselling would make a difference in uninsured patients, especially when conducted by the caring physicians.Trial registration numberChiCTR-TRC-14004169.

Background The aim of this study was to examine the trends in impairment regarding activities of daily living (ADL), physical performance, and cognitive function among the oldest-old (those aged 80 and older) in China between 1998 and 2014. Methods We used data on 34,297 oldest-old individuals from the seven waves of the Chinese Longitudinal Healthy Longevity Study. We estimated age, period, and cohort effects on the prevalence of self-reported ADL impairment, tested physical performance and cognitive function impairment using the age–period–cohort model. Results Regarding age, the prevalence of ADL, physical performance, and cognitive function impairment were highest in the centenarians, but they did not increase with age in this population. Among the literate subgroup, the prevalence of cognitive impairment increased more rapidly with age than that in the illiterate subgroup. Regarding period, the prevalence of self-reported and tested physical impairment slowly increased between 1998 and 2014, but cognitive impairment remained stable. Regarding cohort, ADL impairment continuously decreased. However, physical and cognitive impairment remained stable after a brief decline in the early birth cohorts. Conclusions The results suggest that the age effect is still the most obvious effect regarding several types of functional impairment. The likelihood of a younger person experiencing functional impairment may not change significantly, but ADL is likely to be amenable to improvement resulting from improved medical and social care. Therefore, increased care for the oldest-old may considerably improve their quality of life, particularly regarding their basic ADL.

BACKGROUND: High concentrations of plasma 25-hydroxyvitamin D [25(OH)D], a marker of circulating vitamin D, have been associated with a lower risk of mortality in epidemiologic studies of multiple populations, but the association for Chinese adults aged ≥80 y (oldest old) remains unclear. OBJECTIVE: We investigated the association between plasma [25(OH)D] concentration and all-cause mortality among Chinese adults aged ≥80 y. DESIGN: The present study is a prospective cohort study of 2185 Chinese older adults (median age: 93 y). Prospective all-cause mortality data were analyzed for survival in relation to plasma 25(OH)D using Cox proportional hazards regression models, with adjustments for potential sociodemographic and lifestyle confounders and biomarkers. The associations were measured with HR and 95% CIs. RESULTS: The median plasma 25(OH)D concentration was 34.4 nmol/L at baseline. Over the 5466 person-year follow-up period, 1100 deaths were identified. Men and women were analyzed together as no effect modification by sex was found. After adjusting for multiple potential confounders, the risk of all-cause mortality decreased as the plasma 25(OH)D concentration increased (P-trend

Background: Little is known about the role of specific leisure activities in affecting cognitive functions. We aim to examine the associations of specific leisure activities with the risk of cognitive impairment among oldest-old people in China. Methods: This community-based prospective cohort study included 10,741 cognitively normal Chinese individuals aged 80 years or older (median age 88 years) from the Chinese Longitudinal Healthy Longevity Survey. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Cox proportional hazards models were utilized to estimate the effects of specific leisure activities on cognitive impairment outcome. Results: During a median follow-up time of 3.4 years (41,760 person-years), 2,894 participants developed cognitive impairment. Compared to those who “never” engaged in watching TV or listening to radio, reading books or newspapers, and playing cards or mah-jong, those who engaged in such activities “almost every day” reduced their risk of cognitive impairment, the fully-adjusted hazard ratios were 0.56 (0.51–0.61), 0.64 (0.53–0.78), and 0.70 (0.56–0.86), respectively. The association between the risk of cognitive impairment and watching TV and listening to the radio, playing cards or mah-jong, and reading books or newspapers were stronger among those who had two or more years of education. Moreover, the association between risk of cognitive impairment and watching TV and listening to radio was stronger in men than in women. Conclusions: In conclusion, a greater frequency of TV watching or radio listening, reading books or newspapers, and playing cards or mah-jong may decrease the risk of cognitive impairment among the oldest-old.

Context The patterns of associations between glycated Hb (HbA1c) and mortality are still unclear. Objective To explore the extent to which ranges of HbA1c levels are associated with the risk of mortality among participants with and without diabetes. Design, Setting, and Patients This was a nationwide, community-based prospective cohort study. Included were 15,869 participants (median age 64 years) of the Health and Retirement Study, with available HbA1c data and without a history of cancer. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for mortality. Results A total of 2133 participants died during a median follow-up of 5.8 years. In participants with diabetes, those with an HbA1c level of 6.5% were at the lowest risk of all-cause mortality. When HbA1c level was 7.4%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 6.5%. As for participants without diabetes, those with an HbA1c level of 5.4% were at the lowest risk of all-cause mortality. When the HbA1c level was Conclusions A U-shaped and reverse J-shaped association for all-cause mortality was found among participants with and without diabetes. The corresponding optimal ranges for overall survival are predicted to be 5.6% and 7.4% and 5.0% and 6.5%, respectively.

The patterns of the association between high-density lipoprotein cholesterol (HDL-C) concentrations and mortality among the elderly are still unclear.To examine the association of HDL-C concentrations with mortality and to identify the optimal HDL-C concentration range that predicts the lowest risk of all-cause mortality among the elderly.This was a nationwide, community-based, prospective cohort study.This study included 7766 elderly individuals (aged ≥65 years; mean age: 74.4 years) from the Health and Retirement Study. Cox proportional hazards models and Cox models with penalized smoothing splines were used to estimate hazard ratios (HRs) with 95% CI for all-cause and cause-specific mortality.During a median follow-up of 5.9 years, 1921 deaths occurred. After a full adjustment for covariates, a nonlinear (P0.001 for nonlinearity) association was found between HDL-C and all-cause mortality [minimum mortality risk at 71 mg/dL (1.84 mM)]; the risk for all-cause mortality was significantly higher in the groups with HDL-C concentration61 mg/dL (1.58 mM; HR: 1.18; 95% CI: 1.05 to 1.33) and with HDL-C concentration87 mg/dL (2.25 mM; HR: 1.56; 95% CI: 1.17 to 2.07) than in the group with HDL-C concentrations ranging from 61 to 87 mg/dL (1.58 to 2.25 mM). Nonlinear associations of HDL-C concentrations with both cardiovascular and noncardiovascular mortality were also observed (both P0.001 for nonlinearity).Among the elderly, nonlinear associations were found between HDL-C and all-cause and cardiovascular mortality. The single optimal HDL-C concentration and range were 71 mg/dL and 61 to 87 mg/dL, respectively.

With the explosive growth of medical information, it is almost impossible for healthcare providers to review and evaluate all relevant evidence to make the best clinical decisions. Meta‐analyses, which summarize all existing evidence and quantitatively synthesize individual studies, have become the best available evidence for informing clinical practice. This article introduces the common methods, steps, principles, strengths and limitations of meta‐analyses and aims to help healthcare providers and researchers obtain a basic understanding of meta‐analyses in clinical practice and research., This article introduces the common methods, principles, steps, strengths and limitations of meta‐analyses and aims to help clinicians and researchers obtain a basic understanding of meta‐analyses in clinical practice and research.

Background: The goals of improving quality of life and increasing longevity are receiving growing amounts of attention. Body weight and lipid metabolism are closely related to various complications of diabetes. The aim of this study was to rank SGLT inhibitors according to their efficacy with regard to weight and evaluate the effect of SGLT inhibitors on lipid metabolism at 24 weeks of treatment. Methods: The Web of Science, PubMed, Cochrane Library, Embase, and Clinical Trials databases were electronically searched to collect randomized controlled trials involving patients with type 2 diabetes mellitus through June 2020. Two researchers independently screened and evaluated the selected studies and extracted the outcome indexes. ADDIS 1.16.5 and STATA 16 software were used to perform the network meta-analysis and draw the plots. Results: Ultimately, 36 studies were selected and included in this study. We found that all SGLT inhibitors were effective at reducing weight; canagliflozin was the most effective. SGLT inhibitors and placebo were not associated with significantly different serum cholesterol levels. SGLT inhibitors lowered serum triglyceride levels and increased serum high-density and low-density lipoprotein cholesterol levels. SGLT inhibitors also reduced the level of alanine aminotransferase. Conclusions: SGLT inhibitors can bring about weight loss in patients with T2DM and can also improve lipid metabolism. Therefore, patients with hyperlipidemia who have been unsuccessful at losing weight should consider taking SGLT inhibitors. In addition, SGLT inhibitors are hepatoprotective and appear to be safe for patients with mild to moderate liver dysfunction. Trial Registration: CRD42020198516.

Summary Background & aims The association between dietary diversity (DD) changes and mortality remains unclear. We aimed to investigate the association between DD changes and all-cause mortality among older people. Methods A total of 17,959 participants with a mean age of 84.8 years old were enrolled at baseline. Food groups were collected at baseline and follow-up using simplified food frequency questionnaire (FFQ), and then overall, plant-based and animal-based dietary diversity score (DDS) were calculated. DDS changes were calculated using DDS at baseline and the first follow-up. The association between three DDS changes (overall, plant-based and animal-based DDS) and subsequent all-cause mortality were evaluated. Nonparametrically restricted cubic splines and a multivariable-adjusted Cox proportional hazards model were used to estimate HRs and 95% CIs. Results We documented 12,974 deaths over a 129,590 person-years of follow up. Compared with high-to-high DDS pattern, participants with lower overall DDS patterns had increased mortality risk with HRs (95%CI) of 1.39 (1.29–1.49), 1.53 (1.37–1.70), 1.38 (1.18–1.60) and 1.55 (1.31–1.83) for medium-to-medium, low-to-low, low-to-high and high-to-low patterns, respectively. And compared with high-to-high DDS pattern, the estimates were 1.34 (1.23–1.46), 1.49 (1.35–1.65), 1.43 (1.23–1.67) and 1.62 (1.40–1.88) for plant-based DDS, and 1.23 (1.15–1.31), 1.29 (1.20–1.40), 1.24 (1.12–1.37) and 1.28 (1.15–1.44) for animal-based DDS for medium-to-medium, low-to-low, low-to-high and high-to-low patterns, respectively. There was a U-shaped association between DDS change scores and mortality, and compared with participants with whose DDS remained stable, those with extreme declines and extreme improvements had higher risks of mortality with HRs (95% CI) of 1.15 (1.09–1.22) and 1.11 (1.04–1.17). Conclusions Maintaining a lower DDS, extreme declines and extreme improvements in DDS were all associated with an increased risk of all-cause mortality.

Background: To evaluate dapagliflozin, canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin according to their effect on the glycated hemoglobin A1c (HbA1c) level in patients with type 2 diabetes mellitus. Methods: The Web of Science, PubMed, Cochrane Library, EMBASE, and Clinical Trials databases were electronically searched to collect randomized controlled trials of patients with type 2 diabetes mellitus through June 2020. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software was used to perform the meta-analysis and to create plots. Results: Finally, 27 studies were selected and included in this study. The meta-analysis results showed that sodium-dependent glucose transporter (SGLT) inhibitors significantly reduced the HbA1c level in patients with type 2 diabetes mellitus. However, these results were highly heterogeneous, so we conducted a subgroup analysis. The results of the subgroup analysis suggested that by dividing populations into different subgroups, the heterogeneity of each group could be reduced. Conclusions: SGLT inhibitors had a good effect on the HbA1c level in patients with type 2 diabetes mellitus, but there might be differences in the efficacy of SGLT inhibitors in different populations. It is hoped that more studies will be conducted to evaluate the efficacy and safety of SGLT inhibitors in different populations. Registration Number: CRD42020185025.

Evidence regarding alcohol consumption and cognitive impairment is controversial. Whether cessation of drinking alcohol by non-dependent drinkers alters the risk of cognitive impairment remains unknown. This study prospectively evaluated the potential association between the history of lifetime alcohol cessation and risk of cognitive impairment.This study included 15,758 participants age 65 years or older, selected from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) that covered 23 provinces in China. Current alcohol use status, duration of alcohol cessation, and alcohol consumption before abstinence were self-reported by participants; cognitive function was evaluated using Mini-mental State Examination (MMSE). Cause-specific hazard models and restricted cubic splines were applied to estimate the effect of alcohol use on cognitive impairment.Among the 15,758 participants, mean (± SD) age was 82.8 years (± 11.9 years), and 7,199 (45.7%) were males. During a mean of 3.9 years of follow-up, 3,404 cases were identified as cognitive impairment. Compared with current drinkers, alcohol cessation of five to nine years [adjustedA longer duration of alcohol cessation was associated with a lower risk of cognitive impairment assessed by MMSE. Alcohol cessation is never late for older adults to prevent cognitive impairment.

Highlights • The prevalence of anxiety and depression symptom was 7.7% and 12.2%, respectively. • Having confirmed and suspected cases in family members or relatives was associated with the higher risk of depression symptom. • Self-reported health condition was strongly associated with risk of anxiety and depression symptom., Background : Although studies have suggested experiencing the epidemic of severe infectious diseases increased the prevalence of mental health problems, the association between COVID-19 epidemic and risk of anxiety and depression symptom in college students in China was unclear. Methods : A large cross-sectional online survey with 44,447 college students was conducted in Guangzhou, China. The Zung's Self-rating Anxiety Scale (SAS) and the Center for Epidemiologic Studies Depression Scale (CES-D Scale) were used to define the anxiety and depression symptom, respectively. Multivariable logistic regression models were used to analyze the association between COVID-19 epidemic and risk of anxiety and depression symptom. Results : The prevalence of anxiety and depression symptom was 7.7% (95% confidence interval [CI]: 7.5%, 8.0%) and 12.2% (95%CI: 11.9%, 12.5%), respectively. Compared with students who reported have not infected or suspected cases in family members and relatives, students who reported having confirmed (OR=4.06; 95%CI: 1.62, 10.19; P=0.003), and suspected (OR=2.11; 95%CI: 1.11, 4.00; P=0.023) cases in family members and relatives had higher risk of depression symptom. Additionally, the proportions of students with anxiety and depression symptom reported more demand of psychological knowledge and interventions than those without (P

Background: Little is known about the role of dietary diversity changes in affecting cognitive function among older people. Therefore, we aimed to evaluate the associations between dietary diversity scores (DDS) changes with cognitive impairment among older adults in a large prospective cohort. Methods: Cognitive function was assessed using the Mini-Mental State Examination questionnaire at baseline and follow-up. A total of 9726 participants without Parkinson’s disease, dementia, or cognitive impairment were enrolled at baseline. Nine food groups were collected using simplified FFQ at baseline and follow-up surveys. Then nine food groups change patterns and DDS change patterns (overall, plant-based and animal-based) were assessed. The associations of above DDS changes patterns with subsequent cognitive impairment were evaluated. A multivariable-adjusted Cox proportional hazards model was used to estimate HRs and 95%CIs. Results: We documented 2805 cognitive impairments during 52,325 person-years of follow-up. Compared to high-to-high overall DDS change patterns, the multivariable adjusted HRs (95%CI) for high-to-medium, medium-to-medium, medium-to-low, low-to-medium and low-to-low DDS change patterns were 1.33 (1.12–1.57), 1.11 (0.94–1.32), 1.61 (1.39–1.86), 2.00 (1.66–2.40), 2.30 (1.90–2.78) and 2.80 (2.23–3.53), respectively. Compared with participants with stable DDS change pattern, those who in large improvement of DDS had a 13% lower risk of cognitive impairment (HRs, 0.87; 95%CI: 0.78–0.98). The associations of plant-based DDS, animal-based DDS, or nine food groups DDS change patterns with cognitive impairment were in a similar direction to the main result. Conclusions: Protective associations between maintaining high DDS and a reduced risk of cognitive impairment were observed. In contrast, lowering or maintaining a lower DDS increases the risk of cognitive impairment.

The purpose of this study is to assess the prevalence of funnel flow pattern for common pharmaceutical powder blends, upon discharging from modern intermediate bulk containers (IBCs) in drug product manufacturing. The estimation was built upon Jenike’s original radial stress field theory. It was modified to account for the stress-dependence of wall friction angle commonly observed in pharmaceutical powders. A total of 260 flow pattern estimations, based on 20 real-life IBCs and 13 investigational powder blends, were made. The estimated results showed that the mass flow pattern is present in less than 5% of all cases. Funnel flow pattern is clearly prevalent among pharmaceutical powder blends. The prevalence of funnel flow stems from several factors: 1) relatively shallow hopper section shared by all IBCs, 2) the common transition-type geometry, leading to even shallower hopper inclination at the edge of the hopper section, and 3) relatively high wall friction angles resulting from low wall normal stresses. This conclusion was verified through at-scale experiments, by discharging multiple pharmaceutical powder blends from a representative IBC. In general, our study suggests that, unless the powder wall friction can be substantially reduced, pharmaceutical powders are likely to discharge under funnel flow from modern IBCs.

Coronavirus disease 2019 (COVID-19) has recently emerged as a global threat. Understanding workers’ knowledge, attitudes, and practices (KAP) regarding this new infectious disease is crucial to preventing and controlling it. This study aimed to assess KAP regarding COVID-19 during the outbreak among workers in China. The present study was part of a cross-sectional online survey study conducted based on a large labor-intensive factory, which has 180,000 workers from various Chinese provinces, from 2 February 2020 to 7 February 2020. KAP related to COVID-19 were measured by 32 items, each item was measured with an agree/disagree/unclear format, and only correct responses were given 1 point. KAP regarding COVID-19 were measured with 20 items, 6 items and 6 items, respectively. A total of 123,768 valid responses (68.8%) were included in the analysis. Generally, the levels of knowledge (mean: 16.3 out of 20 points), attitudes (mean: 4.5 out of 6 points), and practices (mean: 5.8 out of 6 points) related to COVID-19 were high. Only 36,373 respondents (29.4%) disagreed that gargling with salt water is effective in protecting against COVID-19. Moreover, older respondents had decreased levels of knowledge and practices related to COVID-19 (both P values for the trend, Author summary The Coronavirus disease 2019 (COVID-19) has recently emerged as a global threat. It is important to understanding workers’ knowledge, attitudes, and practices (KAP) related to COVID-19. In this study, we conducted a large cross-sectional online survey base on a large labor-intensive factory to determine the status of COVID-19-related KAP during the outbreak among workers in China. We found that Chinese workers had strong awareness of COVID-19 but also had some misconceptions. Moreover, this study indicated that lower levels of knowledge and practices related to COVID-19 among older and less-educated workers. The results suggested that health authorities still need to ensure correct information on COVID-19 prevention and strengthen health interventions, particularly for older and less-educated workers.

Background: Research on the relationship between long-term exposure to particulate matter with aerodynamic diameter ≤2.5μm (PM2.5) and poor cognitive function is lacking in developing countries, especially in highly polluted areas. Objectives: We evaluated associations of long-term exposure to PM2.5 with poor cognitive function in a diverse, national sample of older adults in China. Methods: This analysis included data on 13,324 older adults (5,879 who were 65–79 years of age, 3,052 who were 80–89 years of age, 2,634 who were 90–99 years of age, and 1,759 who were ≥100 years of age) with normal cognitive function at baseline from March 2002 to September 2014, with 64,648 person-years of follow-up. We used a geographic information system analysis to estimate the annual average satellite-derived PM2.5 concentration for the geocoded location of the participants’ baseline residences. Poor cognitive function was defined as a score of less than 18 on the Chinese version of the Mini-Mental State Examination (MMSE). Competing risk models were performed to explore the association of PM2.5 with poor cognitive function. Results: Each 10-μg/m3 increase in PM2.5 was associated with a 5.1% increased risk of poor cognitive function [adjusted hazard ratio (HR): 1.051; 95% confidence interval (CI): 1.023, 1.079]. Compared to the lowest quartile of PM2.5 (

OBJECTIVE: To survey the residents for their understanding of Coronavirus Disease 2019 (COVID-19)-related knowledge, attitude and practices (KAP) in two hard hit provinces of China to facilitate the governmental decisions on strategies against the disease. METHODS: We invited the participants from Hubei and Henan Provinces of China for an internetbased survey starting from 12:00 on February 21, 2020 to 12:00 on February 23. The survey included the general conditions, KAP of COVID-19, psychological status and living conditions of the residents. RESULTS: The effective response rate of the questionnaire was 98.9%. The mean (P25, P75) age of the participants was 19 (16, 40) years, and 54.3% of them were students. Social media were the most important source of information concerning the pandemic of the respondents. The respondents had a high awareness of person-to-person transmission of the virus through the respiratory tract or droplets but showed a relatively low level of awareness of the population susceptible to COVID-19 and its specific symptoms. The results of multivariate analysis showed that women, undergraduate students (including college students) and higher degree holders had better knowledge of COVID-19 (P < 0.05); the proportion of respondents who expressed to have different levels of psychological stressed such as worry, anxiety and panic reached 77.2%; 16.7% of the responders considered psychological interventions necessary for their psychological conditions; 63.6% of the respondents confessed a bias against the people returning from Hubei and Henan provinces, while 22.4% worried that they might be biased because of their residence in Hubei and Henan. The rate of personal protective equipment shortage was as high as 69.4%; the rates of the responders who would "covering the mouth and nose when coughing or sneezing", "properly use masks in accordance with regulations", "maintain proper hand hygiene ", "avoid gatherings with relatives and friends" and "refrain from going to public places" were 92.4%, 95.9%, 93.5%, 88.8% and 93.1%, respectively. Women and groups with good knowledge of the disease reported better protective behaviors against the diseases (P < 0.05). CONCLUSIONS: The residents in Hubei and Henan Provinces have generally good KAP related to COVID-19, and the online platforms plays a positive role to in circulating epidemic-related information. It is essential to further increase the supply of the protective materials and pay more attention to the mental health of the residents during the pandemic, and psychological counseling and psychological protection should be provided if necessary.

We appreciated Safiri and Mansournia for their interest and comment on our recent study.1 2 Safiri et al 1 mentioned that we did not explain the steps for the selection of confounders that have been included in our fully adjusted models. We acknowledged that due to the limited number of the words for the manuscript required by the journal, the content for the explanation for selection of confounders was not included. Actually, all confounders in our study were selected according to the published literature,3–5 and these were the most important risk factors for mortality. In total, 27 …

Background: During the COVID-19 period, there was a huge gap in the understanding of masks between east and west. At the same time, the mechanism of the mask and the effect after use, also appeared differences. The Objective of this Meta-analysis is to systematically evaluate the efficacy of masks for influenza in the community. Methods: The Web of Science, PubMed, The Cochrane Library, EMBASE and Clinical Trials will be electronically searched to collect randomized controlled trials regarding the efficacy of masks for influenza in the community through Apr 2020. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. Revman 5.3 software will be used for the meta-analysis. Results: The outbreak is continuing, and we need to be prepared for a long fight. If masks are effective, we need to promote their use as soon as possible. If masks are ineffective, strong evidence should be given. This is an urgent task and our team will finish it as soon as possible. Conclusion: Provide stronger evidence to solve the problem, should we wear masks or not right now.

Background Dementia is a serious and growing health problem, and since most people with dementia live at home, caring responsibilities generally fall on family members. Caregivers are often inadequately supported by formal health services and have poorer psychological and physical health. Our study aimed to compare the contributions of publications from different countries, institutions and authors and present a bibliometric analysis to determine the hotspots and trends in research concerning the health of and interventions for family dementia caregivers. Methods Studies published during 1988–2018 were extracted from the Science Citation Index Expanded of the Web of Science. Each abstract of publications was evaluated to obtain the basic information. A bibliometric analysis was used to evaluate the number or cooperation networks of publications, countries, institutions, journals, citations, authors, references, and keywords. The resulting articles were analyzed descriptively, and the publication keywords were visualized using VOSviewer. Results Five hundred forty-two articles were identified. The annual number of relevant publications has steadily increased since approximately 2006. The USA has the highest number of publications (36.2%), followed by the UK (12.9%). China entered the field late, but research conducted in China has rapidly developed. The most productive institution, journal, and author in this field are University College London, the Journal of the American Geriatrics Society, and Orrell M from the UK, respectively. A co-occurrence analysis of the keywords reveals a mainstream research focus on burden, depression, quality of life, and corresponding interventions for people with dementia caregivers. The keywords “psychosocial intervention”, “long-term”, “e-learning/online”, “communication”, and “qualitative research” reflect the latest hotspots, appearing in approximately 2017–2018. Conclusion Our study details the performance statistics, main topics and trends research on the health of and interventions for dementia caregivers from 1988 to 2018 and provides a comprehensive analysis.