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Diabetic retinopathy (DR), the primary retinal vascular complication of diabetes mellitus (DM), is a leading cause of vision impairment and blindness in working-age population globally. Despite mounting concerns about the emergence of DM as a major public health problem in the largest developing country, China, much remains to be understood about the epidemiology of DR. We aimed to investigate the prevalence of and risk factors for DR, and estimate the burden of DR in China in 2010. China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedicine Literature Database (CBM-SinoMed), PubMed, Embase and Medline were searched for studies that reported the prevalence of and risk factors for DR in Chinese population between 1990 and 2017. A random-effects meta-analysis model was adopted to pool the overall prevalence of DR. Variations in the prevalence of DR in different age groups, DM duration groups and settings were assessed by subgroup meta-analysis and meta-regression. Odds ratios (ORs) of major risk factors were pooled using random-effects meta-analysis. The number of people with DR in 2010 was estimated by multiplying the age-specific prevalence of DR in people with DM with the corresponding number of people with DM in China. Finally, the national number of people with DR was distributed into six geographic regions using a risk factor-based model. A total of 31 studies provided information on the prevalence of DR and 21 explored potential risk factors for DR. The pooled prevalence of any DR, nonproliferative DR (NPDR) and proliferative DR (PDR) was 1.14% (95% CI = 0.80-1.52), 0.90% (95% CI = 0.56-1.31) and 0.07% (95% CI = 0.02-0.14) in general population; In people with DM, the pooled prevalence rates were 18.45% (95% CI = 14.77-22.43), 15.06% (95% CI = 11.59-18.88) and 0.99% (95% CI = 0.40-1.80) for any DR, NPDR and PDR, respectively. The prevalence of any DR in DM patients peaked between 60 and 69 years of age, and increased steeply with the duration of DM. DM patients residing in rural China were at a higher risk to have DR than those in urban areas. In addition, insulin treatment, elevated FBG level and higher HbA1c concentration were confirmed to be associated with a higher prevalence of DR in people with DM, with meta-ORs of 1.99 (95% CI = 1.34-2.95), 1.33 (95% CI = 1.12-1.59) and 1.15 (95% CI = 1.09-1.20) respectively. In 2010, a total of 13.16 million (95% CI = 8.95-18.00) Chinese aged 45 years and above were living with DR, among whom the most were in South Central China and the least were in Northwest China. DR has become a serious public health problem in China. Optimal screening of and interventions on DR should be implemented. Improved epidemiological studies on DR are still required.

AbstractObjectiveTo review the evidence on the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, CINAHL, Biosis, Joanna Briggs, Global Health, and World Health Organization COVID-19 database (preprints).Eligibility criteria for study selectionObservational and interventional studies that assessed the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality.Main outcome measuresThe main outcome measure was incidence of covid-19. Secondary outcomes included SARS-CoV-2 transmission and covid-19 mortality.Data synthesisDerSimonian Laird random effects meta-analysis was performed to investigate the effect of mask wearing, handwashing, and physical distancing measures on incidence of covid-19. Pooled effect estimates with corresponding 95% confidence intervals were computed, and heterogeneity among studies was assessed using Cochran’s Q test and the I2 metrics, with two tailed P values.Results72 studies met the inclusion criteria, of which 35 evaluated individual public health measures and 37 assessed multiple public health measures as a “package of interventions.” Eight of 35 studies were included in the meta-analysis, which indicated a reduction in incidence of covid-19 associated with handwashing (relative risk 0.47, 95% confidence interval 0.19 to 1.12, I2=12%), mask wearing (0.47, 0.29 to 0.75, I2=84%), and physical distancing (0.75, 0.59 to 0.95, I2=87%). Owing to heterogeneity of the studies, meta-analysis was not possible for the outcomes of quarantine and isolation, universal lockdowns, and closures of borders, schools, and workplaces. The effects of these interventions were synthesised descriptively.ConclusionsThis systematic review and meta-analysis suggests that several personal protective and social measures, including handwashing, mask wearing, and physical distancing are associated with reductions in the incidence covid-19. Public health efforts to implement public health measures should consider community health and sociocultural needs, and future research is needed to better understand the effectiveness of public health measures in the context of covid-19 vaccination.Systematic review registrationPROSPERO CRD42020178692.

China is increasingly facing the challenge of control of the growing burden of non-communicable diseases. We assessed the epidemiology of Alzheimer's disease and other forms of dementia in China between 1990, and 2010, to improve estimates of the burden of disease, analyse time trends, and inform health policy decisions relevant to China's rapidly ageing population. In our systematic review we searched for reports of Alzheimer's disease or dementia in China, published in Chinese and English between 1990 and 2010. We searched China National Knowledge Infrastructure, Wanfang, and PubMed databases. Two investigators independently assessed case definitions of Alzheimer's disease and dementia: we excluded studies that did not use internationally accepted case definitions. We also excluded reviews and viewpoints, studies with no numerical estimates, and studies not done in mainland China. We used Poisson regression and UN demographic data to estimate the prevalence (in nine age groups), incidence, and standardised mortality ratio of dementia and its subtypes in China in 1990, 2000, and 2010. Our search returned 12 642 reports, of which 89 met the inclusion criteria (75 assessed prevalence, 13 incidence, and nine mortality). In total, the included studies had 340 247 participants, in which 6357 cases of Alzheimer's disease were recorded. 254 367 people were assessed for other forms of dementia, of whom 3543 had vascular dementia, frontotemporal dementia, or Lewy body dementia. In 1990 the prevalence of all forms of dementia was 1·8% (95% CI 0·0–44·4) at 65–69 years, and 42·1% (0·0–88·9) at age 95–99 years. In 2010 prevalence was 2·6% (0·0–28·2) at age 65–69 years and 60·5% (39·7–81·3) at age 95–99 years. The number of people with dementia in China was 3·68 million (95% CI 2·22–5·14) in 1990, 5·62 million (4·42–6·82) in 2000, and 9·19 million (5·92–12·48) in 2010. In the same period, the number of people with Alzheimer's disease was 1·93 million (1·15–2·71) in 1990, 3·71 million (2·84–4·58) people in 2000, and 5·69 million (3·85–7·53) in 2010. The incidence of dementia was 9·87 cases per 1000 person-years, that of Alzheimer's disease was 6·25 cases per 1000 person-years, that of vascular dementia was 2·42 cases per 1000 person-years, and that of other rare forms of dementia was 0·46 cases per 1000 person-years. We retrieved mortality data for 1032 people with dementia and 20 157 healthy controls, who were followed up for 3–7 years. The median standardised mortality ratio was 1·94:1 (IQR 1·74–2·45). Our analysis suggests that previous estimates of dementia burden, based on smaller datasets, might have underestimated the burden of dementia in China. The burden of dementia seems to be increasing faster than is generally assumed by the international health community. Rapid and effective government responses are needed to tackle dementia in low-income and middle-income countries. Nossal Institute of Global Health (University of Melbourne, Australia), the National 12th Five-Year Major Projects of China, National Health and Medical Research Council Australia–China Exchange Fellowship, Importation and Development of High-Calibre Talents Project of Beijing Municipal Institutions, and the Bill & Melinda Gates Foundation.

The joint associations across genetic risk, modifiable lifestyle factors, and inflammatory bowel disease (IBD) remains unclear. Genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) was estimated by polygenic risk scores and further categorized into high, intermediate, and low genetic risk categories. Weighted healthy lifestyle scores were constructed based on 5 common lifestyle factors and categorized into favorable (4 or 5 healthy lifestyle factors), intermediate (3 healthy lifestyle factors), and unfavorable (0-2 healthy lifestyle factors) groups. Cox proportional hazards regression model was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for their associations. During the 12-year follow-up, 707 cases with CD and 1576 cases with UC were diagnosed in the UK Biobank cohort. Genetic risk and unhealthy lifestyle categories were monotonically associated with CD and UC risk with no multiplicative interaction between them. The HR of CD and UC were 2.24 (95% CI 1.75-2.86) and 2.15 (95% CI 1.82-2.53) for those with a high genetic risk, respectively. The HR of CD and UC for individuals with an unfavorable lifestyle were 1.94 (95% CI 1.61-2.33) and 1.98 (95% CI 1.73-2.27), respectively. The HR of individuals with a high genetic risk but a favorable lifestyle (2.33, 95% CI 1.58-3.44 for CD, and 2.05, 95% CI 1.58-2.66 for UC) were reduced nearly by half, compared with those with a high genetic risk but an unfavorable lifestyle (4.40, 95% CI 2.91-6.66 for CD and 4.44, 95% CI 3.34-5.91 for UC). Genetic and lifestyle factors were independently associated with susceptibility to incident CD and UC. Adherence to a favorable lifestyle was associated with a nearly 50% lower risk of CD and UC among participants at a high genetic risk.

Understanding the role of children in the transmission of SARS-CoV-2 is urgently required given its policy implications in relation to the reopening of schools and intergenerational contacts. We conducted a rapid review of studies that investigated the role of children in the transmission of SARS-CoV-2. We synthesized evidence for four categories: 1) studies reporting documented cases of SARS-CoV-2 transmission by infected children; 2) studies presenting indirect evidence on the potential of SARS-CoV-2 transmission by (both symptomatic and asymptomatic) children; 3) studies reporting cluster outbreaks of COVID-19 in schools; 4) studies estimating the proportions of children infected by SARS-CoV-2, and reported results narratively. A total of 16 unique studies were included for narrative synthesis. There is limited evidence detailing transmission of SARS-CoV-2 from infected children. We found two studies that reported a 3-month-old whose parents developed symptomatic COVID-19 seven days after caring for the infant and two children who may have contracted COVID-19 from the initial cases at a school in New South Wales. In addition, we identified six studies presenting indirect evidence on the potential for SARS-CoV-2 transmission by children, three of which found prolonged virus shedding in stools. There is little data on the transmission of SARS-CoV-2 in schools. We identified only two studies reporting outbreaks of COVID-19 in school settings and one case report of a child attending classes but not infecting any other pupils or staff. Lastly, we identified six studies estimating the proportion of children infected; data from population-based studies in Iceland, Italy, South Korea, Netherlands, California and a hospital-based study in the UK suggest children may be less likely to be infected. Preliminary results from population-based and school-based studies suggest that children may be less frequently infected or infect others, however current evidence is limited. Prolonged faecal shedding observed in studies highlights the potentially increased risk of faeco-oral transmission in children. Further seroprevalence studies (powered adequately for the paediatric population) are urgently required to establish whether children are in fact less likely to be infected compared to adults. We plan to update this rapid review as new data becomes available. These updates are available at https://www.ed.ac.uk/usher/uncover/completed-uncover-reviews.

This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, and at journal editors and reviewers seeking to assess Mendelian randomization manuscripts. The guidelines are divided into nine sections: motivation and scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary and sensitivity analyses (one section on robust statistical methods and one on other approaches), data presentation, and interpretation. These guidelines will be updated based on feedback from the community and advances in the field. Updates will be made periodically as needed, and at least every 18 months.

Diarrhoea and pneumonia are the leading infectious causes of childhood morbidity and mortality. We comprehensively reviewed the epidemiology of childhood diarrhoea and pneumonia in 2010–11 to inform the planning of integrated control programmes for both illnesses. We estimated that, in 2010, there were 1·731 billion episodes of diarrhoea (36 million of which progressed to severe episodes) and 120 million episodes of pneumonia (14 million of which progressed to severe episodes) in children younger than 5 years. We estimated that, in 2011, 700 000 episodes of diarrhoea and 1·3 million of pneumonia led to death. A high proportion of deaths occurs in the first 2 years of life in both diseases—72% for diarrhoea and 81% for pneumonia. The epidemiology of childhood diarrhoea and that of pneumonia overlap, which might be partly because of shared risk factors, such as undernutrition, suboptimum breastfeeding, and zinc deficiency. Rotavirus is the most common cause of vaccine-preventable severe diarrhoea (associated with 28% of cases), and Streptococcus pneumoniae (18·3%) of vaccine-preventable severe pneumonia. Morbidity and mortality from childhood pneumonia and diarrhoea are falling, but action is needed globally and at country level to accelerate the reduction.

Background The proteome is a major source of therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) study to identify candidate protein markers and therapeutic targets for colorectal cancer (CRC). Methods Protein quantitative trait loci (pQTLs) were derived from seven published genome-wide association studies (GWASs) on plasma proteome, and summary-level data were extracted for 4853 circulating protein markers. Genetic associations with CRC were obtained from a large-scale GWAS meta-analysis (16,871 cases and 26,328 controls), the FinnGen cohort (4957 cases and 304,197 controls), and the UK Biobank (9276 cases and 477,069 controls). Colocalization and summary-data-based MR (SMR) analyses were performed sequentially to verify the causal role of candidate proteins. Single cell-type expression analysis, protein-protein interaction (PPI), and druggability evaluation were further conducted to detect the specific cell type with enrichment expression and prioritize potential therapeutic targets. Results Collectively, genetically predicted levels of 13 proteins were associated with CRC risk. Elevated levels of two proteins (GREM1, CHRDL2) and decreased levels of 11 proteins were associated with an increased risk of CRC, among which four (GREM1, CLSTN3, CSF2RA, CD86) were prioritized with the most convincing evidence. These protein-coding genes are mainly expressed in tissue stem cells, epithelial cells, and monocytes in colon tumor tissue. Two interactive pairs of proteins (GREM1 and CHRDL2; MMP2 and TIMP2) were identified to be involved in osteoclast differentiation and tumorigenesis pathways; four proteins (POLR2F, CSF2RA, CD86, MMP2) have been targeted for drug development on autoimmune diseases and other cancers, with the potentials of being repurposed as therapeutic targets for CRC. Conclusions This study identified several protein biomarkers to be associated with CRC risk and provided new insights into the etiology and promising targets for the development of screening biomarkers and therapeutic drugs for CRC.

BackgroundSubstantial evidence indicates that dysbiosis of the gut microbial community is associated with colorectal neoplasia. This review aims to systematically summarise the microbial markers associated with colorectal neoplasia and to assess their predictive performance.MethodsA comprehensive literature search of MEDLINE and EMBASE databases was performed to identify eligible studies. Observational studies exploring the associations between microbial biomarkers and colorectal neoplasia were included. We also included prediction studies that constructed models using microbial markers to predict CRC and adenomas. Risk of bias for included observational and prediction studies was assessed.ResultsForty-five studies were included to assess the associations between microbial markers and colorectal neoplasia. Nine faecal microbiotas (i.e., Fusobacterium, Enterococcus, Porphyromonas, Salmonella, Pseudomonas, Peptostreptococcus, Actinomyces, Bifidobacterium and Roseburia), two oral pathogens (i.e., Treponema denticola and Prevotella intermedia) and serum antibody levels response to Streptococcus gallolyticus subspecies gallolyticus were found to be consistently associated with colorectal neoplasia. Thirty studies reported prediction models using microbial markers, and 83.3% of these models had acceptable-to-good discrimination (AUROC > 0.75). The results of predictive performance were promising, but most of the studies were limited to small number of cases (range: 9–485 cases) and lack of independent external validation (76.7%).ConclusionsThis review provides insight into the evidence supporting the association between different types of microbial species and their predictive value for colorectal neoplasia. Prediction models developed from case-control studies require further external validation in high-quality prospective studies. Further studies should assess the feasibility and impact of incorporating microbial biomarkers in CRC screening programme.

Background There is a clear need for systematic appraisal of models/factors predicting colorectal cancer (CRC) metastasis and recurrence because clinical decisions about adjuvant treatment are taken on the basis of such variables. Methods We conducted an umbrella review of all systematic reviews of observational studies (with/without meta-analysis) that evaluated risk factors of CRC metastasis and recurrence. We also generated an updated synthesis of risk prediction models for CRC metastasis and recurrence. We cross-assessed individual risk factors and risk prediction models. Results Thirty-four risk factors for CRC metastasis and 17 for recurrence were investigated. Twelve of 34 and 4/17 risk factors with p  < 0.05 were estimated to change the odds of the outcome at least 3-fold. Only one risk factor ( vascular invasion for lymph node metastasis [LNM] in pT1 CRC ) presented convincing evidence. We identified 24 CRC risk prediction models. Across 12 metastasis models, six out of 27 unique predictors were assessed in the umbrella review and four of them changed the odds of the outcome at least 3-fold. Across 12 recurrence models, five out of 25 unique predictors were assessed in the umbrella review and only one changed the odds of the outcome at least 3-fold. Conclusions This study provides an in-depth evaluation and cross-assessment of 51 risk factors and 24 prediction models. Our findings suggest that a minority of influential risk factors are employed in prediction models, which indicates the need for a more rigorous and systematic model construction process following evidence-based methods.