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Guoshuai Shi,1 Ni Zhu,2 Lin Qiu,3 Hong Yan,1,4 Lingxia Zeng,1 Duolao Wang,5 Shaonong Dang,1 Zhaoqing Li,1 Yijun Kang,1 Tao Chen,6 Chao Li1 1Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China; 2Department of Communicable Disease Control and Prevention, Shaanxi Provincial Center for Disease Control and Prevention, Xi’an, Shaanxi, People’s Republic of China; 3Department of Chronic and Noncommunicable Disease Control and Prevention, Shaanxi Provincial Center for Disease Control and Prevention, Xi’an, Shaanxi, People’s Republic of China; 4Nutrition and Food Safety Engineering Research Center of Shaanxi Province, Xi’an, Shaanxi, People’s Republic of China; 5Department of Clinical Sciences, Liverpool School of Tropical Medicine Pembroke Place, Liverpool, Merseyside, L3 5QA, UK; 6Department of Public Health, Policy & Systems, Institute of Population Health, The University of Liverpool, Liverpool, L69 3GB, UKCorrespondence: Chao LiDepartment of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of ChinaEmail lcxjtu@xjtu.edu.cnTao ChenDepartment of Public Health, Policy & Systems, Institute of Population Health, The University of Liverpool, Whelan Building, Quadrangle, Liverpool, L 69 3GB, UKEmail Tao.chen@liverpool.ac.ukPurpose: This study aimed to estimate the impact of the 2020 China Diabetes Society’s (CDS) guideline on the prevalence of diabetes mellitus and eligibility for antidiabetic treatment in China.Material and Methods: Baseline data from the China Health and Retirement Longitudinal Study (CHARLS, 2011– 2012) were used to estimate the prevalence of diabetes mellitus and compare the recommendations for antidiabetic medication and intensification of therapy between the 2017 and 2020 CDS guidelines.Results: According to the 2017 CDS guideline, the prevalence of diabetes mellitus was 12.56% among Chinese adults who were ≥ 45 years of age. However, according to the 2020 CDS guideline, 0.65% (0.35%, 1.20%), or 3.54 (2.50, 4.57) million Chinese adults who were ≥ 45 years would additionally be diagnosed with diabetes mellitus. Among Chinese adults not taking antidiabetic medications, 1.06% (0.87%, 1.28%), or 5.37 (4.36, 6.38) million Chinese adults with diabetes mellitus were recommended to start antidiabetic medication according to the 2017 CDS guideline, while 1.27% (1.01%, 1.58%), or 6.44 (5.29, 7.60) million Chinese adults with diabetes would be recommended to initiate antidiabetic medication according to the 2020 CDS guideline. Among Chinese adults taking antidiabetic medication, 51.59% (44.19%, 58.93%), or 18.35 (15.58, 21.12) million Chinese adults with diabetes received antidiabetic treatment but had a hemoglobin A1c (HbA1c) level higher than that mentioned in the 2017 and 2020 CDS guidelines.Conclusion: The addition of HbA1c in the 2020 CDS guideline will result in a modest increase in the number of Chinese adults who are diagnosed with diabetes and diabetes patients recommended for antidiabetic medication; however, the 2020 CDS guideline does not affect the number of diabetes patients eligible for intensification of treatment.Keywords: China Diabetes Society, diabetes, glycated hemoglobin A1c

Objectives This study sought to determine if percutaneous coronary intervention (PCI) prior to transcatheter aortic valve replacement (TAVR) in patients with significant coronary artery disease would produce noninferior clinical results when compared with no PCI (control arm). Background PCI in patients undergoing TAVR is not without risk, and there are no randomized data to inform clinical practice. Methods Patients with severe symptomatic aortic stenosis and significant coronary artery disease with Canadian Cardiovascular Society class ≤2 angina were randomly assigned to receive PCI or no PCI prior to TAVR. The primary endpoint was a composite of all-cause death or rehospitalization at 1 year. Noninferiority testing (prespecified margin of 7.5%) was performed in the intention-to-treat population. Results At 17 centers, 235 patients underwent randomization. At 1 year, the primary composite endpoint occurred in 48 (41.5%) of the PCI arm and 47 (44.0%) of the no-PCI arm. The requirement for noninferiority was not met (difference: -2.5%; 1-sided upper 95% confidence limit: 8.5%; 1-sided noninferiority test P = 0.067). On analysis of the as-treated population, the difference was -3.7% (1-sided upper 95% confidence limit: 7.5%; P = 0.050). Mortality was 16 (13.4%) in the PCI arm and 14 (12.1%) in the no-PCI arm. At 1 year, there was no evidence of a difference in the rates of stroke, myocardial infarction, or acute kidney injury, with higher rates of any bleed in the PCI arm (P = 0.021). Conclusions Observed rates of death and rehospitalization at 1 year were similar between PCI and no PCI prior to TAVR; however, the noninferiority margin was not met, and PCI resulted in a higher incidence of bleeding. (Assessing the Effects of Stenting in Significant Coronary Artery Disease Prior to Transcatheter Aortic Valve Implantation; ISRCTN75836930 )

BackgroundIntravenous recombinant tissue plasminogen activator (r-tPA) and urokinase (UK) are both recommended for the treatment of acute ischaemic stroke (AIS) in China, but with few comparative outcome data being available. We aimed to compare the outcomes of these two thrombolytic agents for the treatment of patients within 4.5 hours of onset of AIS in routine clinical practice in China.MethodsA pre-planned, prospective, nationwide, multicentre, real-world registry of consecutive patients with AIS (age ≥18 years) who received r-tPA or UK within 4.5 hours of symptom onset according to local decision-making and guideline recommendations during 2017–2019. The primary effectiveness outcome was the proportion of patients with an excellent functional outcome (defined by modified Rankin scale scores 0 to 1) at 90 days. The key safety endpoint was symptomatic intracranial haemorrhage according to standard definitions. Multivariable logistic regression was used for comparative analysis, with adjustment according to propensity scores to ensure balance in baseline characteristics.ResultsOverall, 4130 patients with AIS were registered but 320 had incomplete or missing data, leaving 3810 with available data for analysis of whom 2666 received r-tPA (median dose 0.88 (IQR 0.78–0.90) mg/kg) and 1144 received UK (1.71 (1.43–2.00)×104 international unit per kilogram). There were several significant intergroup differences in patient characteristics: r-tPA patients were more educated, had less history of stroke, lower systolic blood pressure, greater neurological impairment and shorter treatment times from symptom onset than UK patients. However, in adjusted analysis, the frequency of excellent outcome (OR 1.18, 95% CI 1.00 to 1.40, p=0.052) and symptomatic intracranial haemorrhage (OR 0.70, 95% CI 0.33 to 1.47, p=0.344) were similar between groups.ConclusionsUK may be as effective and carry a similar safety profile as r-tPA in treating mild to moderate AIS within guidelines in China.Registrationhttp://www.clinicaltrials.gov. unique identifier: NCT02854592.

Primary percutaneous coronary intervention (PPCI), the preferred reperfusion strategy for all acute ST-segment elevation myocardial infarction (STEMI) patients, is not universally available in clinical practice. Pharmacoinvasive strategy has been proposed as a therapeutic option in patients with STEMI when timely PPCI is not feasible. However, pharmacoinvasive strategy has potential delay between clinical patency and complete myocardial perfusion. The optimal reperfusion strategy for STEMI patients with anticipated PPCI delay according to current practice is uncertain. OPTIMAL-REPERFUSION is an investigator-initiated, prospective, multicenter, randomized, open-label, superiority trial with blinded evaluation of outcomes. A total of 632 STEMI patients presenting within 6 hours after symptom onset and with an expected time of first medical contact to percutaneous coronary intervention (PCI) ≥120 minute will be randomized to a reduced-dose facilitated PCI strategy (reduced-dose fibrinolysis combined with simultaneous transfer for immediate invasive therapy with a time interval between fibrinolysis to PCI

Background. Thrombocytopenia was intuitively considered to be associated with higher risk of bleeding and multiple comorbidities after percutaneous coronary intervention (PCI). However, controversial results exist, and the real-world clinical impact of thrombocytopenia in patients undergoing PCI is largely unknown. The aim of this study was to evaluate the influence of baseline thrombocytopenia on the prognosis of patients undergoing PCI. Methods. Using the West China Hospital Inpatient Sample database, patients who underwent PCI were identified from August 2012 to January 2019. Baseline thrombocytopenia was defined as a preprocedural platelet count of 100 × 10 9 / L or less obtained from a routine blood sample taken within 48 hours before coronary PCI. The clinical effect of the advanced thrombocytopenia group ( ≤ 85 × 10 9 / L ), according to the median value of platelet count in the thrombocytopenia cohort, was further assessed. The primary outcome was a composite of in-hospital death, bleeding events, and post-PCI transfusion. Results. Of 9531 patients enrolled in our study, 936 had baseline thrombocytopenia and 8595 patients did not have. There were no significant differences in the primary outcome between the two groups. However, advanced thrombocytopenia was independently associated with higher risk of primary outcome (OR 1.67, 95% CI 1.06 to 2.65, p = 0.029 ). Acute coronary syndrome (ACS) patients with thrombocytopenia were associated with higher odds of major bleeding ( BARC ≥ 2 ) (OR 2.56, 95% CI 1.24 to 5.44, p = 0.011 ). Compared with the nonthrombocytopenia group, the thrombocytopenia group with ticagrelor use had higher odds of major bleeding (OR 9.7, 95% CI 1.57 to 60.4 versus OR 0.22, 95% CI 0.03 to 1.69, interaction p = 0.025 ). Conclusions. It seems feasible for patients with thrombocytopenia to receive PCI, but close attention should be paid to advanced thrombocytopenia, the risk of postprocedure bleeding in ACS patients, and the use of more potent P2Y12 inhibitor.

OBJECTIVE: To evaluate the clinical features of disease progression among patients with COVID-19 to help early identification of patients at high risk.DESIGN: This was a retrospective, multi-centre cohort study. From 10 January to 29 February 2020, all cases diagnosed with COVID-19 at 24 hospitals (with complete medical records) in Jiangsu Province, China were recruited. The primary outcome was deterioration in condition, i.e., the dramatic progression from asymptomatic or mild or moderate status into severe or critically ill status during 14 days´ follow-up.RESULTS: Of the 625 patients in Jiangsu, none died; 597 patients were asymptomatic or had mild or moderate disease on admission, of whom 36 (6%) experienced disease deterioration to become severe or critically ill.CONCLUSION: Disease deterioration to severe or critically ill status was associated with age, pulmonary opacity score, lymphocyte count on admission and exposure to the pandemic centre in Wuhan.

Background Coronavirus Disease-2019 (COVID-19) pandemic has become a major health event that endangers people health throughout China and the world. Understanding the factors associated with COVID-19 disease severity could support the early identification of patients with high risk for disease progression, inform prevention and control activities, and potentially reduce mortality. This study aims to describe the characteristics of patients with COVID-19 and factors associated with severe or critically ill presentation in Jiangsu province, China. Methods Multicentre retrospective cohort study of all individuals with confirmed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections diagnosed at 24 COVID-19-designated hospitals in Jiangsu province between the 10th January and 15th March 2020. Demographic, clinical, laboratory, and radiological data were collected at hospital admission and data on disease severity were collected during follow-up. Patients were categorised as asymptomatic/mild/moderate, and severe/critically ill according to the worst level of COVID-19 recorded during hospitalisation. Results A total of 625 patients, 64 (10.2%) were severe/critically ill and 561 (89.8%) were asymptomatic/mild/moderate. All patients were discharged and no patients died. Patients with severe/critically ill COVID-19 were more likely to be older, to be single onset (i.e. not belong to a cluster of cases in a family/community, etc.), to have a medical history of hypertension and diabetes; had higher temperature, faster respiratory rates, lower peripheral capillary oxygen saturation (SpO2), and higher computer tomography (CT) image quadrant scores and pulmonary opacity percentage; had increased C-reactive protein, fibrinogen, and D-dimer on admission; and had lower white blood cells, lymphocyte, and platelet counts and albumin on admission than asymptomatic/mild/moderate cases. Multivariable regression showed that odds of being a severe/critically ill case were associated with age (year) (OR 1.06, 95%CI 1.03–1.09), lymphocyte count (109/L) (OR 0.25, 95%CI 0.08–0.74), and pulmonary opacity in CT (per 5%) on admission (OR 1.31, 95%CI 1.15–1.51). Conclusions Severe or critically ill patients with COVID-19 is about one-tenths of patients in Jiangsu. Age, lymphocyte count, and pulmonary opacity in CT on admission were associated with risk of severe or critically ill COVID-19.

Background Exposure to household air pollution is associated with an increased risk of pneumonia in children in low- and middle-income countries; however, exposure-response data are limited, and there are uncertainties around the extent to which biomass-fueled cookstoves can reduce these exposures. Research Question What is the association between exposure to household air pollution and pneumonia in children under the age of 5 years in rural Malawi and what are the effects of a biomass-fueled cookstove intervention on personal exposure to household air pollution? Study Design and Methods We measured personal exposure to carbon monoxide (CO; 48 hours of continuous measurement and transcutaneous carboxyhemoglobin) every 6 months in children who participated in a cluster-randomized controlled trial of a cleaner burning biomass-fueled cookstove intervention to prevent pneumonia in children under the age of 5 years in rural Malawi (the Cooking And Pneumonia Study). Exposure-response and multivariable analyses were done. Results We recruited 1805 (928 intervention; 877 control) children (mean age, 25.6 months; 50.6% female). We found no evidence of an association between exposure to CO (incident rate ratio, 1.0; 95% CI, 0.967 to 1.014; P = .53) or carboxyhemoglobin (incident rate ratio, 1.00; 95% CI, 0.993 to 1.003; P = .41) in children who experienced pneumonia vs those who did not. Median exposure to CO in the intervention and control groups was was 0.34 (interquartile range, 0.15 to 0.81) and 0.37 parts per million (interquartile range, 0.15 toa 0.97), respectively. The group difference in means was 0.46 (95% CI, −0.95 to 0.012; P = .06). Interpretation Exposure to CO in our population was low with no association seen between exposure to CO and pneumonia incidence and no effect of the Cooking And Pneumonia Study intervention on these exposures. These findings suggest that CO may not be an appropriate measure of household air pollution exposure in settings such as rural Malawi and that there is a need to develop ways to measure particulate matter exposures directly in young children instead. Clinical Trial Registration ISRCTN59448623.

In this study, we aimed to explore regional differences in maternal lifestyle during pregnancy related to congenital heart defects (CHD) in Shaanxi province, Northwestern China. A large-scale epidemiologic survey of birth defects among infants born during 2010–2013, was conducted in Shaanxi province. Non-spatial and geographic weighted logistic regression models were used for analysis. The spatial model indicated that passive smoking frequency was positively associated with CHD for 43.3% of participants (P P P

OBJECTIVES\ud The prevalence of childhood obesity has increased substantially. We aimed to characterize the effect of birth weight on body composition and overweight/obesity at early school age.\ud STUDY DESIGN\ud A total of 1669 children with available birth records from a double-blind cluster-randomized controlled trial exploring micronutrient supplementation during pregnancy were included. Data regarding school-aged body composition, social-demographic factors and health behaviours were prospectively collected.\ud RESULT\ud s: The study population consisted of 1004 boys and 665 girls aged between 7 and 10 years. The prevalence of overweight/obesity (>85th age-sex-specific percentiles) was 7.4% for boys and 5.0% for girls. Generalized estimating equation models were used to account for the cluster nature of the data. A significant upward trend across quintiles of birth weight was observed for fat mass index (boys: P for trend 0.002; girls: P for trend

Macrophage migration inhibitory factor (MIF) has been recognized as a major player in the pathogenesis of atherosclerosis. This study determined the association between polymorphisms of MIF gene and acute coronary syndrome (ACS). The polymorphism of MIF gene (rs755622, rs1007888 and rs2096525) was analyzed in 1153 healthy controls and 699 ACS cases in Chinese Han population. Plasma MIF level was also measured in part of ACS patients (139/19.9%) and healthy controls (129/11.2%) randomly. Most participants including healthy controls and ACS patients carried rs755622 GG (63.1% vs. 56.7%) and CG genotypes (33.1% vs. 38.9%) and G allele of rs755622 (79.6% vs. 76.1%, respectively), while CC genotype (3.8% vs. 4.4%) and C allele (20.4% vs. 23.9%) carriers were the lowest. Multivariate logistic regression analysis showed that carriers with rs755622 C allele had a higher risk of ACS compared to other genotypes (AOR = 1.278, 95% CI: 1.042–1.567). In addition, CC genotype carriers had the highest plasma levels of MIF than other genotype carriers. The MIF level in ACS patients with CC genotype was significantly higher than ACS patients carrying GG genotype and healthy controls carrying 3 different genotypes of MIF gene rs755622. Our findings indicate that MIF gene rs755622 variant C allele is associated with increased risk of ACS. Identification of this MIF gene polymorphism may help for predicting the risk of ACS.

Highlights • The timing and route of influenza vaccines effect symptom reporting in healthy adults. • Symptoms experienced by healthy adults were further affected by the presence of S. pneumoniae. • LAIV vaccination prior to S. pneumoniae exposure/colonisation led to reduced symptoms. • TIV vaccination prior to S. pneumoniae exposure/colonisation led to increased nasal symptoms compared to LAIV., Background Nasopharyngeal colonisation by S. pneumoniae is a prerequisite for invasive pneumococcal infections. Influenza co-infection leads to increased susceptibility to secondary pneumonia and mortality during influenza epidemics. Increased bacterial load and impaired immune responses to pneumococcus caused by influenza play a role in this increased susceptibility. Using an Experimental Human Challenge Model and influenza vaccines, we examined symptoms experienced by healthy adults during nasal co-infection with S. pneumoniae and live attenuated influenza virus. Methods Randomised, blinded administration of Live Attenuated Influenza Vaccine (LAIV) or Tetravalent Inactivated Influenza Vaccine (TIV) either preceded bacterial inoculation or followed it, separated by a 3-day interval. The presence and density of S. pneumoniae was determined from nasal washes. Participants completed a symptom questionnaire from the first intervention until 6 days post second intervention. Results The timing and type of influenza vaccination and presence of S. pneumoniae in the nasopharynx significantly affected symptom reporting. In the study where influenza vaccination preceded bacterial inoculation: nasal symptoms were less common in the LAIV group than the TIV group (OR 0.57, p

Background Randomized trials have shown that complete revascularization in patients with ST-segment elevation myocardial infarction (MI) with multivessel disease results in lower major adverse cardiovascular events (MACE) (all-cause death, MI, ischemia-driven revascularization, heart failure). Objectives The goal of this study was to determine whether the benefits of complete revascularization are sustained long-term and their impact on hard endpoints. Methods CvLPRIT (Complete versus Lesion-only Primary PCI Trial) was a randomized trial of complete inpatient revascularization versus infarct-related artery revascularization only at the index admission. Randomized patients have been followed longer-term. The components of the original primary endpoint were collected from physical and electronic patient records, and from local databases for all readmissions. Results The median follow-up (achieved in >90% patients) from randomization to first event or last follow-up was 5.6 years (0.0 to 7.3 years). The primary MACE endpoint rate at this time point was 24.0% in the complete revascularization group but 37.7% of the infarct-related artery–only group (hazard ratio: 0.57; 95% confidence interval: 0.37 to 0.87; p = 0.0079). The composite endpoint of all-cause death/MI was 10.0% in the complete revascularization group versus 18.5% in the infarct-related artery–only group (hazard ratio: 0.47; 95% confidence interval: 0.25 to 0.89; p = 0.0175). In a landmark analysis (from 12 months to final follow-up), there was no significant difference between MACE, death/MI, and individual components of the primary endpoint. Conclusions Long-term follow-up of the CvLPRIT trial shows that the significantly lower rate of MACE in the complete revascularization group, previously seen at 12 months, is sustained to a median of 5.6 years. A significant difference in composite all-cause death/MI favoring the complete revascularization was also observed. (Complete versus Lesion-only Primary PCI Trial; ISRCTN70913605)

Research question Is pre-pregnancy maternal underweight associated with perinatal outcomes of singletons who were conceived through assisted reproductive technology (ART)? Design A 10-year (2006–2015) Chinese sample of 6538 women and their singleton infants who were conceived through ART was used to examine the association between pre-pregnancy maternal underweight and perinatal outcomes. Propensity scores for underweight were calculated for each participant using multivariable logistic regression, which was used to match 740 (91.36% of 810) underweight women with 740 normal weight women; the effects of underweight on birth weight and gestational age were then assessed by generalized estimating equation model. Results After propensity score matching, the birth weight was lower (difference –136.83 g, 95% CI –184.11 to –89.55 g) in the underweight group than in the normal weight group. The risks of low birth weight (LBW) and small for gestational age (SGA) were increased in the underweight group compared with those in the normal weight group (LBW: RR 1.64, 95% CI 1.01 to 2.67; SGA: RR 1.46, 95% CI 1.06 to 2.02). The risks of fetal macrosomia and being large for gestational age (LGA) were decreased in the underweight group compared with those in the normal weight group (macrosomia: RR 0.39, 95% CI 0.26 to 0.61; LGA: RR 0.36, 95% CI 0.24 to 0.53). The associations between underweight, gestational age and preterm birth were not statistically significant. Conclusions Among women undergoing ART, pre-pregnancy maternal underweight was associated with lower birth weight, increased LBW and SGA risks, and decreased fetal macrosomia and LGA risks in singleton infants.

Background Ivermectin is being considered for mass drug administration for malaria, due to its ability to kill mosquitoes feeding on recently treated individuals. In a recent trial, 3-day courses of 300 and 600 mcg/kg/day were shown to kill Anopheles mosquitoes for at least 28 days post-treatment when fed patients’ venous blood using membrane feeding assays. Direct skin feeding on humans may lead to higher mosquito mortality, as ivermectin capillary concentrations are higher. We compared mosquito mortality following direct skin and membrane feeding. Methods We conducted a mosquito feeding study, nested within a randomized, double-blind, placebo-controlled trial of 141 adults with uncomplicated malaria in Kenya, comparing 3 days of ivermectin 300 mcg/kg/day, ivermectin 600 mcg/kg/day, or placebo, all co-administered with 3 days of dihydroartemisinin-piperaquine. On post-treatment day 7, direct skin and membrane feeding assays were conducted using laboratory-reared Anopheles gambiae sensu stricto. Mosquito survival was assessed daily for 28 days post-feeding. Results Between July 20, 2015, and May 7, 2016, 69 of 141 patients participated in both direct skin and membrane feeding (placebo, n = 23; 300 mcg/kg/day, n = 24; 600 mcg/kg/day, n = 22). The 14-day post-feeding mortality for mosquitoes fed 7 days post-treatment on blood from pooled patients in both ivermectin arms was similar with direct skin feeding (mosquitoes observed, n = 2941) versus membrane feeding (mosquitoes observed, n = 7380): cumulative mortality (risk ratio 0.99, 95% confidence interval [CI] 0.95–1.03, P = .69) and survival time (hazard ratio 0.96, 95% CI 0.91–1.02, P = .19). Results were consistent by sex, by body mass index, and across the range of ivermectin capillary concentrations studied (0.72–73.9 ng/mL). Conclusions Direct skin feeding and membrane feeding on day 7 resulted in similar mosquitocidal effects of ivermectin across a wide range of drug concentrations, suggesting that the mosquitocidal effects seen with membrane feeding accurately reflect those of natural biting. Membrane feeding, which is more patient friendly and ethically acceptable, can likely reliably be used to assess ivermectin’s mosquitocidal efficacy. Clinical Trials Registration NCT02511353., Ivermectin is being considered for mass drug administration for malaria, due to its ability to kill mosquitoes feeding on recently-treated individuals. Membrane feeding, which is more patient friendly, likely reflects the effects of direct-skin feeding in assessing ivermectin’s mosquitocidal efficacy.

BackgroundHIV, diabetes and hypertension have a high disease burden in sub-Saharan Africa. Healthcare is organised in separate clinics, which may be inefficient. In a cohort study, we evaluated integrated management of these conditions from a single chronic care clinic.ObjectivesTo determined the feasibility and acceptability of integrated management of chronic conditions in terms of retention in care and clinical indicators.Design and settingProspective cohort study comprising patients attending 10 health facilities offering primary care in Dar es Salaam and Kampala.InterventionClinics within health facilities were set up to provide integrated care. Patients with either HIV, diabetes or hypertension had the same waiting areas, the same pharmacy, were seen by the same clinical staff, had similar provision of adherence counselling and tracking if they failed to attend appointments.Primary outcome measuresRetention in care, plasma viral load.FindingsBetween 5 August 2018 and 21 May 2019, 2640 patients were screened of whom 2273 (86%) were enrolled into integrated care (832 with HIV infection, 313 with diabetes, 546 with hypertension and 582 with multiple conditions). They were followed up to 30 January 2020. Overall, 1615 (71.1%)/2273 were female and 1689 (74.5%)/2266 had been in care for 6 months or more. The proportions of people retained in care were 686/832 (82.5%, 95% CI: 79.9% to 85.1%) among those with HIV infection, 266/313 (85.0%, 95% CI: 81.1% to 89.0%) among those with diabetes, 430/546 (78.8%, 95% CI: 75.4% to 82.3%) among those with hypertension and 529/582 (90.9%, 95% CI: 88.6 to 93.3) among those with multimorbidity. Among those with HIV infection, the proportion with plasma viral load ConclusionIntegrated management of chronic diseases is a feasible strategy for the control of HIV, diabetes and hypertension in Africa and needs evaluation in a comparative study.

Introduction HIV programmes in sub-Saharan Africa are well funded but programmes for diabetes and hypertension are weak with only a small proportion of patients in regular care. Healthcare provision is organised from stand-alone clinics. In this cluster randomised trial, we are evaluating a concept of integrated care for people with HIV infection, diabetes or hypertension from a single point of care. Methods and analysis 32 primary care health facilities in Dar es Salaam and Kampala regions were randomised to either integrated or standard vertical care. In the integrated care arm, services are organised from a single clinic where patients with either HIV infection, diabetes or hypertension are managed by the same clinical and counselling teams. They use the same pharmacy and laboratory and have the same style of patient records. Standard care involves separate pathways, that is, separate clinics, waiting and counselling areas, a separate pharmacy and separate medical records. The trial has two primary endpoints: retention in care of people with hypertension or diabetes and plasma viral load suppression. Recruitment is expected to take 6 months and follow-up is for 12 months. With 100 participants enrolled in each facility with diabetes or hypertension, the trial will provide 90% power to detect an absolute difference in retention of 15% between the study arms (at the 5% two-sided significance level). If 100 participants with HIV infection are also enrolled in each facility, we will have 90% power to show non-inferiority in virological suppression to a delta=10% margin (ie, that the upper limit of the one-sided 95% CI of the difference between the two arms will not exceed 10%). To allow for lost to follow-up, the trial will enrol over 220 persons per facility. This is the only trial of its kind evaluating the concept of a single integrated clinic for chronic conditions in Africa. Ethics and dissemination The protocol has been approved by ethics committee of The AIDS Support Organisation, National Institute of Medical Research and the Liverpool School of Tropical Medicine. Dissemination of findings will be done through journal publications and meetings involving study participants, healthcare providers and other stakeholders. Trial registration number NCT43896688.

Background Angiotensin receptor neprilysin inhibitor (ARNI) sacubitril-valsartan has been recommended as one of the first-line therapies in heart failure with reduced ejection fraction. However, whether ARNI could benefit patients with ST-segment elevation myocardial infarction (STEMI) by improving left ventricular (LV) remodeling remains unknown. The primary objective of the PERI-STEMI trial is to assess whether sacubitril-valsartan is more effective in preventing adverse LV remodeling for patients with STEMI than enalapril. Hypothesis We hypothesize that sacubitril/valsartan is superior to enalapril in preventing adverse LV remodeling evaluated by cardiovascular magnetic resonance imaging at the 6-month follow-up. Methods PERI-STEMI is an investigator-initiated, prospective, multi-center, randomized, open-label, superiority trial with blinded evaluation of outcomes. A total of 376 first-time STEMI patients with primary percutaneous coronary intervention (PPCI) within 12 h after symptom onset will be randomized to sacubitril-valsartan or enalapril treatment. All the patients will receive a baseline cardiovascular magnetic resonance (CMR) examination at 4–7 days post-PPCI. The primary endpoint is the change of indexed LV mass at the 6-month follow-up CMR. Results Enrollment of the first patient is planned in November 2021. Recruitment is anticipated to last for 12–18 months and patients will be followed for 5 years after randomization. The study is expected to complete in June 2027. Conclusions The results of the PERI-STEMI trial are expected to provide CMR evidence on whether ARNI could benefit patients with STEMI, so as to facilitate the strategy of CMR-based risk stratification and therapy selection for these patients. PERI-STEMI is registered at ClinicalTrials.gov (NCT04912167).

In a double-blind, randomised, parallel-group, placebo-controlled study, healthy school children aged 3-10 years received a probiotic based supplement daily for 6 months to assess the impact on the incidence and duration of upper respiratory tract infection (URTI) symptoms. The intervention comprised Lab4 probiotic (Lactobacillus acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20 and Bifidobacterium animalis subsp. lactis CUL34) at 12.5 billion cfu/day plus 50 mg vitamin C or a matching placebo. 171 children were included in the analysis (85 in placebo and 86 in active group). Incidence of coughing was 16% (P=0.0300) significantly lower in the children receiving the active intervention compared to the placebo. No significant differences in the incidence rate of other URTI symptoms were observed. There was significantly lower risk of experiencing five different URTI related symptoms in one day favouring the active group (Risk ratio: 0.31, 95% confidence interval: 0.12, 0.81, P=0.0163). Absenteeism from school and the use of antibiotics was also significantly reduced for those in the active group (-16%, P=0.0060 and -27%, P=0.0203, respectively). Our findings indicate that six months daily supplementation with the Lab4 probiotic and vitamin C combination reduces the incidence of coughing, absenteeism and antibiotic usage in 3 to 10 year old children.

BACKGROUND\ud China's rapid urbanization has created a large number of labour transferring from rural to urban areas and large numbers of college students with left-behind experience (LBE). LBE was an important influencing factor on college students' mental health.\ud \ud METHODS\ud A mixed method involving quantitative survey and qualitative interview was emplyed to explore the influence of LBE on mental health of college students. In the quantitative survey, 1605 college students from three different universities of Shandong province in China were recruited. Their mental health status was measured using Symptom Check-list 90(SCL-90 scale) compiled by American psychologist Derogatis. In the qualitative interview, 40 college students with left-behind experience from the same three universities were interviewed.\ud \ud RESULTS\ud The prevalence estimate of total mental health problems among left-behind students was 2.14 times higher than that among those without left-behindexperience. LBE increased the problems of somatization, obsessive-compulsion (Ocd), international sensitivity, depression, anxiety, hostility, terror, paranoia, psychoticism and other symptoms. The result of qualitative interview showed the mental health problems of the college students with left-behind experience were mainly on anxiety, depression, Ocd, interpersonal sensitive and hostility, which was consistent with the results of quantitative survey.\ud \ud LIMITATION\ud Representativeness of the sample is the major limitation of our study. Due to rare similar studies performed in other countries, we could not compare the results in China to that in other countries.\ud \ud CONCLUSION\ud Left-behind experience was an important factor associated with the mental health of college students. The mental health of college students with LBE needs more attention.

Background: Considerable attention has focused on omega-3 polyunsaturated fatty acids (PUFA) role in protect against the development of cardiometabolic diseases, which has led to dietary recommendations to increase omega-3 fatty acid intake.Methods: MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and reference lists were searched for articles from inception to May 2020. Random-effects model was used to estimate the pooled relative risk (RR) and 95% confidence intervals (CIs) for the association of omega-3 PUFAs, including α-linoleic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), with risk of developing type 2 diabetes (T2D), cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, cancer, and mortality.Results: 66 prospective studies comprised of 211,600 participants were identified. Individual omega-3 PUFAs showed divergent associations with the study outcomes of interest. An inverse association with risk of T2D was observed comparing extreme categories of ALA concentration (RR,0.91;95%CI,0.83-0.99), but not for the marine-origin omega-3 fatty acids biomarkers. The marine-origin omega-3 fatty acids biomarkers, but not ALA, were significantly associated with lower risks of total CVD, CHD, and overall mortality, with RRs ranging from 0.70 for DHA-CHD association to 0.85 for EPA-CHD association. Lower risk of colorectal cancer was observed at higher levels of DPA (RR,0.76;95%CI:0.59-0.98) and DHA (RR,0.80;95%CI:0.65-0.99). In dose-response analyses, inverse linear associations were observed between EPA, DPA, and DHA biomarkers and CVD or CHD risk, except for DHA-CVD association which showed a nonlinearity association.Conclusion: Higher concentrations of marine-derived omega-3 PUFA biomarkers were associated with a significantly reduced risk of total CVD, CHD, certain types of cancer, and total mortality. Levels of ALA were inversely with a lower risk of T2D but not CVD-related outcomes. These data support the dietary recommendations advocating the role of omega-3 PUFAs in maintaining an overall lower risk of developing cardiovascular disease and premature deaths.

Faecal volatile organic compounds (VOCs) result from the metabolism of the intestinal mucosa, gut microbiota and the environment. Profiling of faecal VOCs in children with different IBD sub-types and disease distribution and activity may shed light on underlying disease mechanisms. Method We assessed faecal VOCs by gas chromatography-mass spectrometry in a prospective, observational study of children with suspected inflammatory bowel disease (IBD) attending 3 specialist clinics. We tested whether the abundance of faecal VOCs differed according to IBD versus other gastrointestinal disorders, IBD subtype and response to treatment in IBD. Results We characterised faecal VOCs in 132 children in whom IBD was diagnosed and 132 non-IBD controls. 162 (61.4%) were boys. Mean age was 12.2 years (SD 3.0). In total 214 (81.1%) were white, 35 (13.3%) were Asian and 15 (5.7%) of other ethnic background. There were 78 (29.5%) children with Crohn’s disease (CD), 38 (14.4%) with ulcerative colitis (UC) and 16 (6.1%) IBD-unclassified. The most common diagnosis in controls was a functional gastrointestinal disorder. The mean abundance of 16 VOCs was significantly lower in IBD than controls whereas phenol and propan-1-ol were higher in IBD (p=0.001). Some short chain fatty acids (butanoic, pentanoic and hexanoic acids) were lower in IBD than controls (p The two compounds that were more abundant in IBD than control (propan-1-ol and phenol) returned to control levels post-treatment (figure 1). Within IBD, the subtype (CD versus colitis (UC and IBD-unclassified)) described a small amount of variation (3%, p=0.006), with three faecal VOCs (6-methylhept-5-en-2-one; benzaldehyde; 4-methylphenol) significantly different in abundance between CD and colitis (t-test, p Conclusion/interpretation Propan-1-ol and phenol, higher in abundance in IBD than controls and returning to control levels post-treatment, may indicate abnormal amino-acid metabolism in pre-treatment IBD; phenol may be pro-inflammatory. Further analysis of VOCs may provide insights into underlying disease mechanisms in paediatric IBD.

AimsThis study aimed to assess the clinical characteristics and long-term survival outcome in patients with Takayasu’s arteritis-associated pulmonary hypertension (TA-PH).Methods and resultsWe conducted a nationally representative cohort study of TA-PH using data from the National Rare Diseases Registry System of China. Patients with pulmonary artery involvement who fulfilled the diagnostic criteria of Takayasu’s arteritis and pulmonary hypertension were included. The primary outcome was the time from diagnosis of TA-PH to the occurrence of all-cause death. Between January 2007 and January 2019, a total of 140 patients were included, with a mean age of 41.4 years at diagnosis, and a female predominance (81%). Patients with TA-PH had severely haemodynamic and functional impairments at diagnosis. Significant improvements have been found in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and haemodynamic profiles in patients with TA-PH receiving drugs approved for pulmonary arterial hypertension. The overall 1-, 3-, and 5-year survival rates in TA-PH were 94.0%, 83.2%, and 77.2%, respectively. Predictors associated with an increased risk of all-cause death were syncope [adjusted hazard ratio (HR) 5.38 (95% confidence interval 1.77–16.34), P = 0.003], NT-proBNP level [adjusted HR 1.04 (1.03–1.06), P ConclusionPatients with TA-PH were predominantly female and had severely compromised haemodynamics. More than 80% of patients in our cohort survived for at least 3 years. Medical treatment was based on investigators’ personal opinions, and no clear risk-to-benefit ratio can be derived from the presented data.

Gut microbiome manipulation to alter the gut-lung axis may potentially protect humans against respiratory infections, and clinical trials of probiotics show promise in this regard in healthy adults and children. However, comparable studies are lacking in overweight/obese people, who have increased risks in particular of viral upper respiratory tract infections (URTI). This Addendum further analyses our recent placebo-controlled trial of probiotics in overweight/obese people (focused initially on weight loss) to investigate the impact of probiotics upon the occurrence of URTI symptoms. As well as undergoing loss of weight and improvement in certain metabolic parameters, study participants taking probiotics experienced a 27% reduction in URTI symptoms versus control, with those ≥45 years or BMI ≥30 kg/m2 experiencing greater reductions. This symptom reduction is apparent within 2 weeks of probiotic use. Gut microbiome diversity remained stable throughout the study in probiotic-treated participants. Our data provide support for further trials to assess the potential role of probiotics in preventing viral URTI (and possibly also COVID-19), particularly in overweight/obese people.

Background The Systolic Blood Pressure Intervention Trial (SPRINT) showed significant reductions in death and cardiovascular disease (CVD) risk with a systolic blood pressure (SBP) goal of, Tao Chen and colleagues estimate the cost-effectiveness of intensive blood pressure intervention in Chinese populations at high risk for cardiovascular disease., Author summary Why was this study done? The Systolic Blood Pressure Intervention Trial (SPRINT) has previously demonstrated significant reductions in death and cardiovascular disease (CVD) risk with a systolic blood pressure (SBP) goal of < 120 mm Hg (intensive treatment) compared with a SBP goal of

Background: ST2 is a circulating biomarker that is well established for predicting outcome in heart failure (HF). This is the first study to look at ST2 concentrations in optimally treated patients with stable but significant left ventricular systolic dysfunction (LVSD) compared to patients with severe aortic stenosis (AS). Methods: Two cohorts were retrospectively studied: 94 patients undergoing transcatheter aortic valve implantation for severe AS (63 with normal ejection fraction [EF] and 31 with reduced EF), and 50 patients with severe LVSD from non-valvular causes. ST2 pre-procedural samples were taken, and repeated again at 3 and 6 months. Patients were followed-up for 2 years. Data was analyzed using SPSS software. Results: Baseline concentrations of soluble ST2 did not differ significantly between the HF group and AS group with normal EF (EF ≥ 50%). However, in the AS group with a low EF (EF < 50%) ST2 concentrations were significantly higher that the HF group (p = 0.009). New York Heart Association class IV HF, baseline N-terminal pro-B-type natriuretic peptide and gender were all independent predictors of soluble ST2 (sST2) baseline concentrations. Conclusions: Raised ST2 concentrations in the context of severe AS may be a marker for subclinical or clinical left ventricular dysfunction. More research is required to assess its use for assessment of prognosis and response to treatment.

ObjectiveD-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. Few studies explore the association between baseline D-dimer levels and the incidence of heart failure (HF), all-cause mortality in an acute myocardial infarction (AMI) population. We aimed to explore this association.MethodsWe enrolled 4504 consecutive patients with AMI with complete data in a prospective cohort study and explored the association of plasma D-dimer levels on admission and the incidence of HF, all-cause mortality.ResultsOver a median follow-up of 1 year, 1112 (24.7%) patients developed in-hospital HF, 542 (16.7%) patients developed HF after hospitalisation and 233 (7.1%) patients died. After full adjustments for other relevant clinical covariates, patients with D-dimer values in quartile 3 (Q3) had 1.51 times (95% CI 1.12 to 2.04) and in Q4 had 1.49 times (95% CI 1.09 to 2.04) as high as the risk of HF after hospitalisation compared with patients in Q1. Patients with D-dimer values in Q4 had more than a twofold (HR 2.34; 95% CI 1.33 to 4.13) increased risk of death compared with patients in Q1 (pConclusionsD-dimer was found to be associated with the incidence of HF after hospitalisation and all-cause mortality in patients with AMI.

This study was a retrospective multicentre cohort study of patients with coronavirus disease 2019 (COVID-19) diagnosed at 24 hospitals in Jiangsu province, China as of 15 March 2020. The primary outcome was the occurrence of acute respiratory failure during hospital stay. Of 625 patients, 56 (9%) had respiratory failure. Some selected demographic, epidemiologic, clinical and laboratory features as well as radiologic features at admission and treatment during hospitalisation were significantly different in patients with and without respiratory failure. The multivariate logistic analysis indicated that age (in years) (odds ratio [OR], 1.07; 95% confidence interval [CI]: 1.03–1.10; P = 0.0002), respiratory rate (breaths/minute) (OR, 1.23; 95% CI: 1.08–1.40; P = 0.0020), lymphocyte count (109/l) (OR, 0.18; 95% CI: 0.05–0.69; P = 0.0157) and pulmonary opacity score (per 5%) (OR, 1.38; 95% CI: 1.19–1.61; P < 0.0001) at admission were associated with the occurrence of respiratory failure. Older age, increased respiratory rate, decreased lymphocyte count and greater pulmonary opacity score at admission were independent risk factors of respiratory failure in patients with COVID-19. Patients having these risk factors need to be intensively managed during hospitalisation.

Faecal volatile organic compounds (VOCs) result from the metabolism of the intestinal mucosa, gut microbiota and the environment. Faecal VOCs may provide novel insights into the pathogenesis of gastrointestinal disorders. Method We assessed faecal VOCs by gas chromatography-mass spectrometry in a prospective, observational study of children with suspected inflammatory bowel disease (IBD) attending 3 specialist clinics. We tested whether the abundance of faecal VOCs differed according to IBD versus other gastrointestinal disorders, IBD subtype and response to treatment in IBD. Results We characterised faecal VOCs in 132 children in whom IBD was diagnosed and 132 non-IBD controls. 162 (61.4%) were boys. Mean age was 12.2 years (SD 3.0). In total 214 (81.1%) were white, 35 (13.3%) were Asian and 15 (5.7%) of other ethnic background. There were 78 (29.5%) children with Crohn’s disease (CD), 38 (14.4%) with ulcerative colitis (UC) and 16 (6.1%) IBD-unclassified. The most common diagnosis in controls was a functional gastrointestinal disorder. The abundance of 18/30 (60.0%) faecal VOCs differed significantly between IBD and controls (t-test; p Within IBD, the subtype (CD versus colitis (UC and IBD-unclassified)) described a small amount of variation (3%, p=0.006), with three faecal VOCs (6-methylhept-5-en-2-one; benzaldehyde; 4-methylphenol) significantly different in abundance between CD and colitis (t-test, p Conclusion/Interpretation Characterisation of faecal VOCs may advance the understanding of the pathogenesis of IBD, disease sub-types and response to treatment.

BACKGROUND Children who have been hospitalized with severe anemia in areas of Africa in which malaria is endemic have a high risk of readmission and death within 6 months after discharge. No prevention strategy specifically addresses this period. METHODS We conducted a multicenter, two-group, randomized, placebo-controlled trial in nine hospitals in Kenya and Uganda to determine whether 3 months of malaria chemoprevention could reduce morbidity and mortality after hospital discharge in children younger than 5 years of age who had been admitted with severe anemia. All children received standard in-hospital care for severe anemia and a 3-day course of artemether–lumefantrine at discharge. Two weeks after discharge, children were randomly assigned to receive dihydroartemisinin–piperaquine (chemoprevention group) or placebo, administered as 3-day courses at 2, 6, and 10 weeks after discharge. Children were followed for 26 weeks after discharge. The primary outcome was one or more hospital readmissions for any reason or death from the time of randomization to 6 months after discharge. Conditional risk-set modeling for recurrent events was used to calculate hazard ratios with the use of the Prentice–Williams–Peterson total-time approach. RESULTS From May 2016 through May 2018, a total of 1049 children underwent randomization; 524 were assigned to the chemoprevention group and 525 to the placebo group. From week 3 through week 26, a total of 184 events of readmission or death occurred in the chemoprevention group and 316 occurred in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.54 to 0.78; P

The impact of diet on the metabolic syndrome (MetS) and CVD has been investigated widely, but few studies have investigated the association between dietary patterns (DP) and the predicted CVD, derived from reduced rank regression (RRR). The objectives of this study were to derive DP using RRR and principal component analysis (PCA) and investigate their associations with the MetS and estimated 10-year atherosclerotic CVD (ASCVD). We used the baseline dataset from the Xinjiang multi-ethnic cohort study in China, collected from June 2018 to May 2019. A total of 14 982 subjects aged 35–74 years from Urumqi, Huo Cheng and Mo Yu were included in the analysis. The 10-year ASCVD risk was estimated using the Chinese ASCVD risk equations. The associations of DP with the MetS and 10-year ASCVD were determined using multivariable logistic regression models. In Urumqi and Mo Yu, the increased RRR DP score was associated with a higher OR of having the MetS and with a higher OR of elevated 10-year ASCVD risk. However, only the first DP determined by PCA in Urumqi was inversely associated with the MetS and elevated 10-year ASCVD risk. The prevalence of the MetS and elevated ASCVD risk in urban population is higher than that in rural areas. Our results may help nutritionists develop more targeted dietary strategies to prevent the MetS and ASCVD in different regions in China.

Background: Perinatal depression is a maternal mental health condition that is associated with various adverse health outcomes both for the mothers and the babies. The study aim was to estimate the prevalence of perinatal depression and its risks and determinants in Mainland China.\ud \ud Methods: Systematic searches were conducted in 10 major databases and random effect meta-analysis was performed to achieve the pooled variance of perinatal depression. Subgroup analyses were conducted based on region, scale, methods of diagnosis and study design. Meta-regression was performed with the variables such as age, quality assessment score and gross domestic product (GDP) of the province.\ud \ud Results: Pooled prevalence of perinatal depression was 16.3% (CI=95%; 14.7% to 18.2%, P < 0.001), with antenatal depression 19.7% (CI=95%; 15.8% to 24.2%, P < 0.001) and postnatal depression 14.8% (CI=95%; 13.1% to 16.6%, P < 0.001). Significant publication bias was found and heterogeneity was I2= 98.13%. Lower socioeconomic status, poor physical health, anxiety about pregnancy and reduced social support were major risk factors while better living conditions and education were protective factors. The prevalence of perinatal depression showed a significant increasing trend in the last decade.\ud \ud Limitations: The review does not include studies with small sample size (n

Background Both pulmonary tuberculosis (PTB) and diabetes mellitus (DM) are major global public health problems. We estimated the global, regional, and national prevalence of diabetes mellitus in a population with PTB. Methods We searched for observational studies of DM in people with PTB using the PubMed and Embase electronic bibliographic databases, focusing on articles published in the English language from database inception until March 31, 2021. We included original research that reported the prevalence of DM in PTB or those that had sufficient data to compute these estimates. Studies were excluded if they did not provide primary data or were case studies or reviews. Two authors independently extracted the articles and collected detailed information using a predefined questionnaire. A country-specific random-effects meta-analysis was used for countries with two or more available studies, and a fractional response regression model was employed to predict the prevalence of DM in PTB for countries with one or no study. The study was registered with the International Prospective Register of Systematic Reviews, using the registration number CRD42018101989. Results We identified 22,658 studies, and 153, across 51 countries, were retained for data extraction. The global prevalence of DM among patients with PTB was estimated to be 13.73% (95% confidence interval [CI] 12.51–14.95). The prevalence rates were 19.32% (95% CI 13.18–25.46) in the region of the Americas, 17.31% (95% CI 12.48–22.14) in the European region, 14.62% (95% CI 12.05–17.18) in Southeast Asia, 13.59% (95% CI 7.24–19.95) in the western Pacific region, 9.61% (95% CI 4.55–14.68) in the eastern Mediterranean region, and 9.30% (95% CI 2.83–15.76) in the African region. The country with the highest estimated prevalence was the Marshall Islands (50.12%; 95% CI 4.28–95.76). Conclusion Comorbid PTB and DM remain prevalent worldwide.

Background Previous studies have suggested that maternal stress could increase the risk of some adverse pregnancy outcomes, but evidence on congenital heart disease (CHD) is limited. We aimed to explore the association between maternal exposure to life events during pregnancy and CHD in offspring. Methods The data was based on an unmatched case-control study about CHD conducted in Shaanxi province of China from 2014 to 2016. We included 2280 subjects, 699 in the case group and 1581 in the control group. The cases were infants or fetuses diagnosed with CHD, and the controls were infants without any birth defects. The life events were assessed by the Life Events Scale for Pregnant Women, and were divided into positive and negative events for synchronous analysis. A directed acyclic graph was drawn to screen the confounders. Logistic regression was employed to estimate the odds ratio and 95% confidence interval for the effects of life events on CHD. Results After controlling for the potential confounders, the pregnant women experiencing the positive events during pregnancy had lower risk of CHD in offspring than those without positive events (OR = 0.38, 95%CI: 0.30 ~ 0.48). The risk of CHD in offspring could increase by 62% among the pregnant women experiencing the negative events compared to those without (OR = 1.62, 95%CI: 1.29 ~ 2.03). Both effects showed a certain dose-response association. Besides, the positive events could weaken the risk impact of negative events on CHD. Conclusion It may suggest that maternal exposure to negative life events could increase the risk of CHD in offspring, while experiencing positive events could play a potential protective role.

ObjectivesTo determine the age-specific clinical presentations and incidence of adverse outcomes among patients with COVID-19 in Jiangsu, China.Design and settingRetrospective, multicentre cohort study performed at 24 hospitals in Jiangsu, China.Participants625 patients with COVID-19 enrolled between 10 January and 15 March 2020.ResultsOf the 625 patients (median age, 46 years; 329 (52.6%) men), 37 (5.9%) were children (18 years or younger), 261 (41.8%) young adults (19–44 years), 248 (39.7%) middle-aged adults (45–64 years) and 79 (12.6%) elderly adults (65 years or older). The incidence of hypertension, coronary heart disease, chronic obstructive pulmonary disease and diabetes comorbidities increased with age (trend test, p2test, p=0.0008, 0.0146 and 0.0282, respectively). The quadrant score and pulmonary opacity score increased with age (trend test, both p2test p2test p2test pConclusionsElderly (≥65 years) patients with COVID-19 had the highest risk of severe or critical illness, intensive care use, respiratory failure and the longest hospital stay, which may be due partly to their having a higher incidence of comorbidities and poor immune responses to COVID-19.

BACKGROUNDThe risk factors for mortality of COVID-19 classified as critical type have not been well described.OBJECTIVESThis study aimed to described the clinical outcomes and further explored risk factors of in-hospital death for COVID-19 classified as critical type.METHODSThis was a single-center retrospective cohort study. From February 5, 2020 to March 4, 2020, 98 consecutive patients classified as critical COVID-19 were included in Huo Shen Shan Hospital. The final date of follow-up was March 29, 2020. The primary outcome was all-cause mortality during hospitalization. Multivariable Cox regression model was used to explore the risk factors associated with in-hospital death.RESULTSOf the 98 patients, 43 (43.9%) died in hospital, 37(37.8%) discharged, and 18(18.4%) remained in hospital. The mean age was 68.5 (63, 75) years, and 57 (58.2%) were female. The most common comorbidity was hypertension (68.4%), followed by diabetes (17.3%), angina pectoris (13.3%). Except the sex (Female: 68.8% vs 49.1%, P=0.039) and angina pectoris (20.9% vs 7.3%, P = 0.048), there was no difference in other demographics and comorbidities between non-survivor and survivor groups. The proportion of elevated alanine aminotransferase, creatinine, D-dimer and cardiac injury marker were 59.4%, 35.7%, 87.5% and 42.9%, respectively, and all showed the significant difference between two groups. The acute cardiac injury, acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS) were observed in 42.9%, 27.8% and 26.5% of the patients. Compared with survivor group, non-survivor group had more acute cardiac injury (79.1% vs 14.5%, PPCONCLUSIONSCOVID-19 classified as critical type had a high prevalence of acute cardiac and kidney injury, which were associated with a higher risk of in-hospital mortality.

OBJECTIVES\ud The purpose of this study was to parameterize mid-trimester drop in blood pressure (BP) trajectory during pregnancy and to evaluate its utility for predicting preeclampsia.\ud METHODS\ud To develop parametric models for BP trajectory during pregnancy, we used data from 7923 Chinese pregnant women with 24 810 routine antenatal care visits. Then, we evaluated the utility of BP trajectory parameters for predicting clinician-diagnosed preeclampsia in a separate sample of 3524 pregnant women from a randomized controlled trial of prenatal vitamin supplementation conducted in the same area. We focused on parameters related to the mid-trimester BP drop, including the gestational age and BP value at the nadir (lowest point), change in BP, velocity, and area under curve during two periods (from 12 weeks of gestation to the nadir and from the nadir to 33 weeks of gestation).\ud RESULTS\ud All participants in our analysis had a mid-pregnancy drop in their SBP, DBP, and mean arterial pressure (MAP) trajectories. There were high correlations (|r| > 0.90) among trajectory parameters of the same BP measure. The final prediction model included selective parameters of SBP, DBP, and MAP trajectories, prepregnancy BMI and gestational age at the first antenatal care visit. The area under the receiver-operating curve for predicting preeclampsia was 0.886 (95% confidence interval 0.846--0.926) in the training dataset and 0.802 (0.708--0.895) in the validation dataset.\ud CONCLUSION\ud Our novel BP trajectory parameters are informative and can predict preeclampsia at a clinically acceptable level.

BACKGROUND: It is known that personality has an influence on the outcome of mental state disorders, but detailed studies on its long-term impact are few. We examined the influence of personality status on the 8-year outcome of health anxiety and its relationship to the effects of cognitive behaviour therapy in a randomized controlled trial. AIMS: This study aims to examine both the usefulness of the diagnosis of personality disorder and an additional measure of pathological dependence, in predicting the outcome of medical patients with health anxiety treated with cognitive behaviour therapy. Because the influence of personality is often shown in the long term, these assessments covered the period of 8 years after randomization. An additional aim is to examine the costs of different levels of personality dysfunction in each treatment group. METHOD: Personality dysfunction, using both ICD-10 and ICD-11 classifications of severity, was assessed at baseline by interview in a randomized controlled trial. Patients were also assessed for pathological dependence using the Dependent Personality Questionnaire, also scored along a severity dimension. Four hundred forty-four patients from medical clinics with pathological health anxiety were treated with a modified form of cognitive behaviour therapy for health anxiety (CBT-HA) or standard care. Total costs over follow-up were calculated from hospital data and compared by personality group. RESULTS: At baseline, 381 (86%) had some personality dysfunction, mainly at the lower level of personality difficulty (not formally a disorder). One hundred eighty four (41%) had a personality disorder. A similar proportion was found with regard to dependent personality. Using the ICD-10 classification, 153 patients (34.6%) had a personality disorder, with 83 (54.2%) having anxious or dependent personality disorder, 20 (13.1%) having an anankastic disorder, but also with 66 (43.1%) having mixed disorder. During initial treatment, those with personality disorder adhered more closely to CBT-HA, and after 8 years, they had a significantly better outcome than those with personality difficulty and no personality disorder (p

Objectives To determine the age-specific clinical presentations and incidence of adverse outcomes among patients with COVID-19 in Jiangsu, China. Design and setting This is a retrospective, multi-center cohort study performed at twenty-four hospitals in Jiangsu, China. Participants From January 10 to March 15, 2020, 625 patients with COVID-19 were involved. Results Of the 625 patients (median age, 46 years; 329 [52.6%] males), 37 (5.9%) were children (18 years or less), 261 (40%) young adults (19-44 years), 248 (39.7%) middle-aged adults (45-64 years), and 79 (12.6%) elderly (65 years or more). The incidence of hypertension, coronary heart disease, chronic obstructive pulmonary disease, and diabetes comorbidities increased with age (trend test, P < .0001, P = 0.0003, P < .0001, and P < .0001 respectively). Fever, cough, and shortness of breath occurred more commonly among older patients, especially the elderly, compared to children (Chi-square test, P = 0.0008, 0.0146, and 0.0282, respectively). The quadrant score and pulmonary opacity score increased with age (trend test, both P < .0001). Older patients had significantly more abnormal values in many laboratory parameters than younger patients. Elderly patients contributed the highest proportion of severe or critically-ill cases (33.0%, Chi-square test P < 0.001), intensive care unit (ICU) (35.4%, Chi-square test P < 0.001), and respiratory failure (31.6%, Chi-square test P = 0.0266), and longest hospital stay (21 days, ANOVA-test P < 0.001). Conclusions Elderly (≥65) patients with COVID-19 had the highest risk of severe or critical illness, intensive care use, respiratory failure, and the longest hospital stay, which may be due partly to that they had higher incidence of comorbidities and poor immune responses to COVID-19.

BackgroundLittle is known about the impact of socioeconomic status (SES) on incidence of stroke in China. This study aimed to examine the association of SES, which was measured by different indicators, with incidence of stroke and gender differences in the association.Methods and resultsTwo prospective cohort studies were conducted including 2852 participants aged ≥60 years in Anhui province and 3016 participants in four other provinces in China. During a median follow-up of 7.1 years, 211 incident stroke cases occurred in the Anhui cohort. The risk of stroke increased with living in rural areas (adjusted HR 2.49, 95% CI 1.19 to 5.22; women 3.64, 95% CI 1.17 to 11.32, men 2.23, 95% CI 0.81 to 6.19), but not significantly with educational level, occupational class, satisfactory income and financial problems (except for women with low education). The four-province cohort had 113 incident stroke cases over the 3.1 years’ follow-up. The five SES indicators were not significantly associated with incident stroke (except for increased risk in men with high occupation), but additional measurement for actual income showed that incident stroke increased in women with low personal income and in men with high family income. Pooled data from the two cohorts demonstrated the impacts of rural living (1.66, 95% CI 1.08 to 2.57) and having high occupational class (1.56, 95% CI 1.01 to 2.38), and gender differences for women with low education (2.26, 95% CI 1.19 to 4.27).ConclusionsRural living and being female with low SES are associated with increased stroke risk in China. Strategies to improve public health in the rural communities and gender-specific targets for health inequality should be an integral component of stroke interventions.

IntroductionTo investigate the relationship between long-term change trajectory in body mass index (BMI) and the hazard of type 2 diabetes among Chinese adults.Research design and methodsData were obtained from the China Health and Nutrition Survey (CHNS). Type 2 diabetes was reported by participants themselves in each survey wave. The duration of follow-up was defined as the period from the first visit to the first time self-reported type 2 diabetes, death, or other loss to follow-up from CHNS. The patterns of change trajectories in BMI were derived by latent class trajectory analysis method. The Fine and Gray regression model was used to estimate HRs with corresponding 95% CIs for type 2 diabetes.ResultsFour patterns of the trajectories of change in BMI were identified among Chinese adults, 42.7% of participants had stable BMI change, 40.8% for moderate BMI gain, 8.9% for substantial BMI gain and 7.7% for weight loss. During the follow-up with mean 11.2 years (158 637 person-years contributed by 14 185 participants), 498 people with type 2 diabetes (3.7%) occurred. Risk of type 2 diabetes was increased by 47% among people who gained BMI more substantially and rapidly (HR: 1.47, 95% CI 1.08 to 2.02, p=0.016) and increased by 20% among those in people with the moderate BMI gain (HR: 1.20, 95% CI 0.98 to 1.48, p=0.078), compared with those with stable BMI change.ConclusionsLong-term substantial gain of BMI was significantly associated with an increased risk of type 2 diabetes in the Chinese adults.

Introduction\ud Pneumococcal colonisation is regarded as a pre-requisite for developing pneumococcal disease. In children previous studies have reported pneumococcal colonisation to be a symptomatic event and described a relationship between symptom severity/frequency and colonisation density. The evidence for this in adults is lacking in the literature. This study uses the experimental human pneumococcal challenge (EHPC) model to explore whether pneumococcal colonisation is a symptomatic event in healthy adults.\ud \ud Methods\ud Healthy participants aged 18–50 were recruited and inoculated intra-nasally with either Streptococcus pneumoniae (serotypes 6B, 23F) or saline as a control. Respiratory viral swabs were obtained prior to inoculation. Nasal and non-nasal symptoms were then assessed using a modified Likert score between 1 (no symptoms) to 7 (cannot function). The rate of symptoms reported between the two groups was compared and a correlation analysis performed.\ud \ud Results\ud Data from 54 participants were analysed. 46 were inoculated with S. pneumoniae (29 with serotype 6B, 17 with serotype 23F) and 8 received saline (control). In total, 14 became experimentally colonised (30.4%), all of which were inoculated with serotype 6B. There was no statistically significant difference in nasal (p = 0.45) or non-nasal symptoms (p = 0.28) between the inoculation group and the control group. In those who were colonised there was no direct correlation between colonisation density and symptom severity. In the 22% (12/52) who were co-colonised, with pneumococcus and respiratory viruses, there was no statistical difference in either nasal or non-nasal symptoms (virus positive p = 0.74 and virus negative p = 1.0).\ud \ud Conclusion\ud Pneumococcal colonisation using the EHPC model is asymptomatic in healthy adults, regardless of pneumococcal density or viral co-colonisation.

Contains fulltext : 220640.pdf (Publisher’s version ) (Closed access) BACKGROUND: Late initiation of HIV antiretroviral therapy (ART) in pregnancy is associated with not achieving viral suppression before giving birth and increased mother-to-child transmission of HIV. We aimed to investigate virological suppression before giving birth with dolutegravir compared with efavirenz, when initiated during the third trimester. METHODS: In this randomised, open-label trial, DolPHIN-2, we recruited pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating ART in third trimester. Participants were randomly assigned (1:1) to dolutegravir-based or efavirenz-based therapy. HIV viral load was measured 7 days and 28 days after antiretroviral initiation, at 36 weeks' gestation, and at the post-partum visit (0-14 days post partum). The primary efficacy outcome was a viral load of less than 50 copies per mL at the first post-partum visit, and the primary safety outcome was the occurrence of drug-related adverse events in mothers and infants until the post-partum visit. Longer-term follow-up of mothers and infants continues. This study is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23, and Aug 15, 2018, we randomly assigned 268 mothers to dolutegravir (135) or efavirenz (133). All mothers and their infants were included in the safety analysis, and 250 mothers (125 in the dolutegravir group, 125 in the efavirenz group) and their infants in efficacy analyses, by intention-to-treat analyses. The median duration of maternal therapy at birth was 55 days (IQR 33-77). 89 (74%) of 120 in the dolutegravir group had viral loads less than 50 copies per mL, compared with 50 (43%) of 117 in the efavirenz group (risk ratio 1·64, 95% CI 1·31-2·06). 30 (22%) of 137 mothers in the dolutegravir group reported serious adverse events compared with 14 (11%) of 131 in the efavirenz group (p=0·013), particularly surrounding pregnancy and puerperium. We found no differences in births less than 37 weeks and less than 34 weeks gestation (16·4% vs 3·3%, across both groups). Three stillbirths in the dolutegravir group and one in the efavirenz group were considered unrelated to treatment. Three infant HIV infections were detected, all in the dolutegravir group, and were considered likely to be in-utero transmissions. INTERPRETATION: Our data support the revision to WHO guidelines recommending the transition to dolutegravir in first-line ART for all adults, regardless of pregnancy or child-bearing potential. FUNDING: Unitaid.

Objective. To classify the infection risk of human papillomavirus (HPV) among human immunodeficiency virus- (HIV-) negative men who have sex with men (MSM) using group-based trajectory modeling (GBTM). Methods. This study collected data on demographic and sexual behavior characteristics by questionnaires at semiannual visits from March 1st, 2016 to December 31th, 2017. Researchers collected anal exfoliated cells to finish HPV testing and blood samples to finish HIV testing at baseline and follow-up visits. Accumulative infection numbers of different types of HPV as the primary outcome and the follow-up visits as the independent predicator to build a GBTM model. Results. There were 500 potentially eligible HIV-negative participants at baseline, 361 (72.2%) of whom were included in this study after screening. Three trajectory groups were identified as the best-fitted GBTM model. Trajectory 1, defined as decreased group (DG) accounted for 44.6% (161/361) of the sample, showed a declining pattern with visits. Trajectory 2, defined as flat group (FG) accounted for 49.6% (179/361) of the sample, showed a flat pattern with visits. Trajectory 3, regarded as the increased group (IG) accounted for 5.8% (21/361) of the sample, showed an uptrend. Compared to the DG, risk factors for the FG included receptive anal intercourse (AOR, 2.24; 95% CI, 1.36-3.71), occasional condom use in anal sex during the past six months (AOR, 1.90; 95% CI, 1.16-3.14), experience of transactional sex with males in the past year (AOR, 3.60; 95% CI, 1.12-11.54), and substance use (AOR, 1.81; 95% CI, 1.08-3.04). Risk factors for the IG included receptive anal intercourse (AOR, 2.81; 95% CI, 1.04-7.70), occasional condom use in anal sex during the past six months (AOR, 3.93; 95% CI, 1.40-11.01), and history of other STIs (AOR, 5.72; 95% CI, 1.40-23.46). Conclusion. The MSM data in this study showed three distinct developmental trajectories (DG, FG, and IG) of HPV infection among HIV-negative MSM, with receptive anal intercourse and occasional condom use in anal sex during the past six months being the risk factors associated with FG and IG.

The aim of this study was to assess the effect of low maternal weight at pre-pregnancy and the average gestational weight gain on undernourished children and their intellectual development. From October 2012 to September 2013, we followed 1744 offspring of women who participated in a trial conducted from 2002 to 2006. Pregnant women recruited in the original trial could receive three prenatal health checks for free, at which maternal weight and height were measured. WISC-IV was used to estimate the intellectual development of children. Weight and height of both pregnant women and children were measured by trained anthropometrists using standard procedures. Having low maternal weight at pre-pregnancy was associated with an increased risk of undernutrition amongst children (underweight: OR = 2.02, 95%CI: 1.14–3.56, thinness: OR = 2.79, 95%CI: 1.50–5.17) and a decrease in verbal comprehension index (−2.70 points, 95%CI: −4.95–0.44) of children. The effect of average gestational weight gain on occurrences of underweight children (OR = 0.08, 95%CI: 0.01–0.55) was also found. We identified the effect of maternal pre-pregnancy underweight on impairment of the separate intellectual domains (verbal comprehension index) and increasing occurrence of undernourished children. Average gestational weight gain was positively associated with a decreased prevalence of underweight children but not with the intellectual development of children in rural China.

Background: Ivermectin is being considered for mass drug administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals. However, standard, single doses of 150–200 μg/kg used for onchocerciasis and lymphatic filariasis have a short-lived mosquitocidal effect (2 ; women: 2 ), with permuted blocks of three, to receive 3 days of ivermectin 300 μg/kg per day, ivermectin 600 μg/kg per day, or placebo, all co-administered with 3 days of dihydroartemisinin-piperaquine. Blood of patients taken on post-treatment days 0, 2 + 4 h, 7, 10, 14, 21, and 28 was fed to laboratory-reared Anopheles gambiae sensu stricto mosquitoes, and mosquito survival was assessed daily for 28 days after feeding. The primary outcome was 14-day cumulative mortality of mosquitoes fed 7 days after ivermectin treatment (from participants who received at least one dose of study medication). The study is registered with ClinicalTrials.gov, number NCT02511353. Findings: Between July 20, 2015, and May 7, 2016, 741 adults with malaria were assessed for eligibility, of whom 141 were randomly assigned to receive ivermectin 600 μg/kg per day (n=47), ivermectin 300 μg/kg per day (n=48), or placebo (n=46). 128 patients (91%) attended the primary outcome visit 7 days post treatment. Compared with placebo, ivermectin was associated with higher 14 day post-feeding mosquito mortality when fed on blood taken 7 days post treatment (ivermectin 600 μg/kg per day risk ratio [RR] 2·26, 95% CI 1·93–2·65, p

Background: A reduction in the density of capillaries (rarefaction) is known to occur in many tissues in patients with essential hypertension and play a role in increasing Blood Pressure (BP). The aim of this trial was to assess in a randomized, double blind, design the effects of treatment of hypertension with candesartan versus amlodipine on microvascular rarefaction and other indices of vascular function.\ud \ud Methods: We recruited twenty-two individuals with mild-to-moderate hypertension. After a 2-week placebo run-in period, patients who remained hypertensive (≥140/90 mmHg) were randomized to 8-weeks treatment with Candesartan tablets 8mg daily (with forced titration to 16mg) or Amlodipine tablets 5mg daily (with forced titration to 10mg). The capillary microcirculation was studied using CapiScope system CAM1. Pulse wave velocity, central BP and aortic Augmentation Index were also measured.\ud \ud Results: We observed significant reductions in brachial BP, and central BP after 4 and 8 weeks treatment with either candesartan or amlodipine but there was no significant effect on basal (functional) or maximal (structural) capillary densities, or pulse wave velocity.\ud \ud Conclusion: Eight weeks treatment of hypertension with either amlodipine or candesartan significantly reduced brachial and central BP but was not sufficient to induce a regression in functional or structural microvascular abnormalities.

Background Adolescence is a sensitive time for girls’ sexual and reproductive health (SRH), as biological changes occur concurrently with heightening pressures for sexual activity. In western Kenya, adolescent girls are vulnerable to acquiring sexually transmitted infections (STIs), such as HIV and herpes simplex virus type 2 (HSV-2), and to becoming pregnant prior to reaching adulthood. This study examines associations between individual, household, and partner-related risk factors and the prevalence of sex, adolescent pregnancy, HIV, and HSV-2. Methods and findings We report baseline findings among 4,138 girls attending secondary school who were enrolled between 2017 and 2018 in the Cups or Cash for Girls (CCG) cluster randomized controlled trial in Siaya County, rural western Kenya. Laboratory confirmed biomarkers and survey data were utilized to assess the effects of girls’ individual, household, and partner characteristics on the main outcome measures (adolescent reported sex, prior pregnancy, HIV, and HSV-2) through generalized linear model (GLM) analysis. Complete data were available for 3,998 girls (97%) with median age 17.1 years (interquartile range [IQR] 16.3 to 18.0 years); 17.2% were HSV-2 seropositive (n = 686) and 1.7% tested positive for HIV (n = 66). Sexual activity was reported by 27.3% girls (n = 1,090), of whom 12.2% had been pregnant (n = 133). After adjustment, orphanhood (adjusted risk ratio [aRR] 2.81, 95% confidence interval [CI] 1.18 to 6.71, p-value [p] = 0.020), low body mass index (BMI) (aRR 2.07; CI: 1.00 to 4.30, p = 0.051), and age (aRR 1.34, 1.18 to 1.53, p < 0.001) were all associated with HIV infection. Girls reporting light menstrual bleeding (aRR 2.42, 1.22 to 4.79, p = 0.012) for fewer than 3 days (aRR 2.81, 1.16 to 6.82, p = 0.023) were over twice as likely to have HIV. Early menarche (aRR 2.05, 1.33 to 3.17, p = 0.001) was associated with adolescent pregnancy and HSV-2–seropositive girls reported higher rates of pregnancy (aRR 1.62, CI: 1.16 to 2.27, p = 0.005). High BMI was associated with HSV-2 (aRR 1.24, 1.05 to 1.46, p = 0.010) and sexual activity (aRR 1.14, 1.02 to 1.28, p = 0.016). High levels of harassment were detected in the cohort (41.2%); being touched indecently conveyed the strongest association related to reported sexual activity (aRR 2.52, 2.26 to 2.81, p < 0.001). Study limitations include the cross-sectional design of the study, which informs on the SRH burdens found in this population but limits causal interpretation of associations, and the self-reported exposure ascertainment, which may have led to possible underreporting of risk factors, most notably prior sexual activity. Conclusions Our findings indicate that adolescent girls attending school in Kenya face frequent harassment for sex and are at high risk of pregnancy and HSV-2, with girls experiencing early menarche particularly vulnerable. Targeted interventions, such as earlier sexual education programs, are warranted to address their vulnerability to SRH harms. Trial registration ClinicalTrials.gov NCT03051789., In a cross sectional analysis, Garazi Zulaika and colleagues study associations between risk factors and prevalence of sexual activity, pregnancy, and HIV and HSV-2 infections among adolescent girls in rural Kenya., Author summary Why was this study done? Girls in low- and middle-income countries (LMICs) face severe health risks from becoming pregnant prior to reaching adulthood and from exposure to sexually transmitted infections (STIs) such as HIV and herpes simplex virus type 2 (HSV-2). Key factors found to be linked to adolescent sexual and reproductive health (SRH) in LMICs include household wealth, age at first sex, and schooling. Evidence of a positive association between girls’ SRH, and their education and economic potential has strengthened international resolve to identify risks and improve conditions that adolescent girls face in these settings. What did the researchers do and find? We collected data from 3,998 girls attending 96 public secondary day schools in 2017 and 2018 as part of the baseline assessment of a randomized controlled study. We explored whether girls’ personal characteristics were associated with SRH harms, namely adolescent sex, early pregnancy, and acquisition of HIV and HSV-2. We found biological factors including girls experiencing early menarche, having lighter periods, and body mass index (BMI); household level factors including being unhappy at home, being orphaned, and coming from poorer households; and social factors including experiencing harassment for sex both in and out of school or being touched indecently were significantly associated with girls’ sexual and reproductive harms, such as pregnancy, HSV-2, and/or HIV. What do these findings mean? These findings illustrate that the burden of SRH harms faced by adolescent girls attending school in rural western Kenya is high. Interventions and programs to improve SRH and continued education need to address both environmental and biological risk factors among vulnerable populations.

The geographical variation of maternal dietary patterns related to birth outcomes is important for improving the health of mothers and children; however, it is currently unknown. Thus, the objective of the study was to investigate geographical variations of maternal dietary pattern during pregnancy, and evaluate the spatial varying association of maternal dietary patterns in pregnancy with abnormal birth weight. A population-based cross-sectional study was conducted in Shaanxi province in Northwest China in 2013 to evaluate the relationship between abnormal birth weight and dietary pattern using the Geographically Weighted Logistic Regression (GWLR). Three dietary patterns during pregnancy were extracted through factor analysis, explaining approximately 45.8% of the variability of food intake. Approximately 81.6% of mothers with higher scores on the equilibrium pattern was more unlikely to have small for gestational age (SGA) infants, with the lower OR observed in Central and South Shaanxi. The snacks pattern was positively associated with low birth weight (LBW) for 23.2% of participants, with the highest OR in Central Shaanxi. Among about 80.0% of participants with higher scores on the snacks pattern living in South and Central Shaanxi, there was a higher risk for SGA. The OR values tend to descend from South to North Shaanxi. The OR values of the negative association between prudent pattern and LBW decreased from South to North Shaanxi among approximately 59.3% of participants. The prudent pattern was also negatively associated with the increasing risk of fetal macrosomia among 19.2% of participants living mainly in South Shaanxi. The association of maternal dietary patterns during pregnancy with abnormal birth weight varied geographically across Shaanxi province. The findings emphasize the importance of geographical distribution to improve the dietary patterns among disadvantaged pregnant women.

IntroductionCalcium dobesilate (CaD) has been used in the treatment of diabetic retinopathy (DR) due to its potential in protecting against retinal vascular damage. However, there is limited evidence exploring its efficacy in combating DR progression. This study is aimed at evaluating whether CaD could prevent DR progression into an advanced stage among Chinese patients with mild-to-moderate non-proliferative DR (NPDR).Methods and analysisThis study is a single-blind, multicentre, cluster-randomised, controlled superiority trial. A total of 1272 patients with mild-to-moderate NPDR will be enrolled and randomly assigned at a 1:1 ratio into the control group (conventional treatment group) and the intervention group (conventional treatment plus CaD (500 mg three times per day) for 12 months). Patients will be followed at 1, 3, 6 and 12 months after randomisation and receiving treatments, with the severity of DR assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. The primary endpoint is the progression of DR during follow-up, which is defined as an increase of two or more steps in the ETDRS scale. The secondary endpoints include the concomitant changes in visual acuity, presence, number, location and type of retinal lesions, and retinal blood vessel diameter as well as the arteriovenous ratio at different visits.Ethics and disseminationEach local ethics committee (first Vote: Ethical Review Committees of Zhongda Hospital of Southeast University (2019ZDSYLL132-P01)) has approved the study. The results will be published in high impact peer-reviewed scientific journals aimed at the general reader.Trial registration numbersNCT04283162.