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Background\ud The use of accurate prediction tools and early intervention are important for addressing severe coronavirus disease 2019 (COVID-19). However, the prediction models for severe COVID-19 available to date are subject to various biases. This study aimed to construct a nomogram to provide accurate, personalized predictions of the risk of severe COVID-19.\ud \ud Methods\ud This study was based on a large, multicenter retrospective derivation cohort and a validation cohort. The derivation cohort consisted of 496 patients from Jiangsu Province, China, between January 10, 2020, and March 15, 2020, and the validation cohort contained 105 patients from Huangshi, Hunan Province, China, between January 21, 2020, and February 29, 2020. A nomogram was developed with the selected predictors of severe COVID-19, which were identified by univariate and multivariate logistic regression analyses. We evaluated the discrimination of the nomogram with the area under the receiver operating characteristic curve (AUC) and the calibration of the nomogram with calibration plots and Hosmer-Lemeshow tests.\ud \ud Results\ud Three predictors, namely, age, lymphocyte count, and pulmonary opacity score, were selected to develop the nomogram. The nomogram exhibited good discrimination (AUC 0.93, 95% confidence interval [CI] 0.90–0.96 in the derivation cohort; AUC 0.85, 95% CI 0.76–0.93 in the validation cohort) and satisfactory agreement.\ud \ud Conclusions\ud The nomogram was a reliable tool for assessing the probability of severe COVID-19 and may facilitate clinicians stratifying patients and providing early and optimal therapies.

Summary Background & aims Epidemiologic studies are inconsistent regarding the association of dietary omega-3 polyunsaturated fatty acids (PUFA) and/or fish intake with risk of age-related macular degeneration (AMD) incidence and progression. The objective was to determine these associations by conducting a meta-analysis of available studies. Methods Three electronic databases were searched for studies that quantified dietary omega-3 PUFA and/or fish intake from inception to December 2020 without language restriction. Three investigators independently assessed for inclusion and extracted data. Study-specific risk estimates were combined using random-effects model. Potential dose–response associations were explored with the use of generalized least-squares trend estimation. Results 21 studies were included in the meta-analysis. Higher dietary intakes of omega-3 PUFA was significantly associated with 14% (relative risk [RR]: 0.86, 95% confidence interval [CI]: 0.77, 0.96) and 29% (RR: 0.71, 95% CI: 0.55, 0.91) lower risk of early and late AMD, respectively. The dose–response analysis showed a 6% and 22% decrease in the risk of early and late AMD for each additional 1 g/d omega-3 PUFA intake. For individual omega-3 PUFA, the intake of eicosapentaenoic acid and docosahexaenoic acid was inversely associated with lower AMD risk, whereas no association was found for the alpha-linolenic acid. Consistent inverse associations were also found between fish intake and AMD. The pooled RRs comparing extreme categories of fish intake were 0.79 (95% CI: 0.70, 0.90) and 0.71 (95% CI: 0.60, 0.85) for early and late AMD risk, respectively. Every 15 g/d of fish consumption was associated with 13% and 14% lower early and late AMD. In addition, fish intake was associated with a significantly reduced risk of AMD progression (RR: 0.73, 95% CI: 0.53, 1.00). Conclusions A high intake of dietary omega-3 PUFA or fish was associated with a reduced risk of developing of AMD, which further supports that consumption of omega-3 PUFA-rich foods may be a new avenue nutritional approach to preventing AMD.

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 )

Tian Tian,1,* Xiaobo Zhang,1,* Tao Luo,1 Duolao Wang,2 Yuping Sun,3 Jianghong Dai1 1Department of Epidemiology and Biostatistics, School of Public Health, Xinjiang Medical University, Urumqi, 830001, People’s Republic of China; 2Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, L35QAUK, UK; 3School of Basic Medicine, Xinjiang Medical University, Urumqi, 830001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianghong Dai Tel +86-991-4365530Email epidjh@163.comAbstract: Gut microbiota are critical to many aspects of human health including immune and metabolic health. Long-term diet influences the community structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how the human gut microbiome responds to short-term intervention with dietary fiber. This study explored the effects of mixed dietary fibers on gut microbiota in young, healthy people. Twelve healthy, young adults participated in a randomized, crossover trial comparing the effects of polyglucan, inulin and resistant malt dextrin on gut microbiota composition and bacterial abundances. During the study, the subjects followed their normal diets without any constraints. Microbial community profiles were determined by absolute quantification 16S rRNA gene amplicon sequencing. Mixed model analysis did not reveal an effect of dietary intervention on microbial community structure. At the genus level, dietary fiber intervention for 4 days significantly promoted the growth of Alloprevotella, Parabacteroides and Parasutterella and inhibited the growth of Adlercreutzia, Anaerovorax, Enterococcus, Intestinibacter and Ruminococcus 2 compared with the baseline. Addition of whey albumen powder for 4 days promoted the growth of Corynebacterium, Collinsella, Olsenella and Lactococcus but interfered with the growth of Megasphaera. Our results should be corroborated by randomized clinical trials with large sample size.Keywords: dietary fiber, gut microbiota, short-term intervention

This study investigated associations between chest computed tomography (CT) pulmonary opacity score on admission and clinical features and outcomes in COVID-19 patients. The retrospective multi-center cohort study included 496 COVID-19 patients in Jiangsu province, China diagnosed as of March 15, 2020. Patients were divided into four groups based on the quartile of pulmonary opacity score: ≤ 5%, 6-20%, 21-40% and 41% +. CT pulmonary opacity score was independently associated with age, single onset, fever, cough, peripheral capillary oxygen saturation, lymphocyte count, platelet count, albumin level, C-reactive protein (CRP) level and fibrinogen level on admission. Patients with score ≥ 41% had a dramatic increased risk of severe or critical illness [odds ratio (OR), 15.58, 95% confidence interval (CI) 3.82-63.53), intensive care unit (ICU)] admission (OR, 6.26, 95% CI 2.15-18.23), respiratory failure (OR, 19.49, 95% CI 4.55-83.40), and a prolonged hospital stay (coefficient, 2.59, 95% CI 0.46-4.72) compared to those with score ≤ 5%. CT pulmonary opacity score on admission, especially when ≥ 41%, was closely related to some clinical characteristics and was an independent predictor of disease severity, ICU admission, respiratory failure and long hospital stay in patients with COVID-19.

Background Globally, there is a large documented gap between needs of families and children with developmental disorders and available services. We adapted the World Health Organization’s mental health Gap-Intervention Guidelines (mhGAP-IG) developmental disorders module into a tablet-based android application to train caregivers of children with developmental disorders. We aimed to evaluate the effectiveness of this technology-assisted, family volunteers delivered, parents’ skills training intervention to improve functioning in children with developmental disorders in a rural community of Rawalpindi, Pakistan. Methods In a single-blinded, cluster randomized controlled trial, 30 clusters were randomised (1:1 ratio) to intervention (n = 15) or enhanced treatment as usual (ETAU) arm (n = 15). After screening, 540 children (18 participants per cluster) aged 2–12 years, with developmental disorders and their primary caregivers were recruited into the trial. Primary outcome was child’s functioning, measured by Childhood Disability Assessment Schedule for Developmental Disorders (DD-CDAS) at 6-months post-intervention. Secondary outcomes were parents’ health related quality of life, caregiver-child joint engagement, socio-emotional well-being of children, family empowerment and stigmatizing experiences. Intention-to-treat analyses were done using mixed-models adjusted for covariates and clusters. Results At 6-months post-intervention, no statistically significant mean difference was observed on DD-CDAS between intervention and ETAU (mean [SD], 47.65 [26.94] vs. 48.72 [28.37], Adjusted Mean Difference (AMD), − 2.63; 95% CI − 6.50 to 1.24). However, parents in the intervention arm, compared to ETAU reported improved health related quality of life (mean [SD] 65.56 [23.25] vs. 62.17 [22.63], AMD 5.28; 95% CI 0.44 to 10.11). The results were non-significant for other secondary outcomes. Conclusions In the relatively short intervention period of 6 months, no improvement in child functioning was observed; but, there were significant improvements in caregivers’ health related quality of life. Further trials with a longer follow-up are recommended to evaluate the impact of intervention. Trial registration Clinicaltrials.gov, NCT02792894. Registered April 4, 2016, https://clinicaltrials.gov/ct2/show/NCT02792894

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.

Background In many low resource settings, the provision of government mental health care services is limited to specialized psychiatry units in urban hospital care facilities, where the most common treatment for common mental disorders (CMDs) is pharmacotherapy, occasionally with adjunct nonspecific psychological support. We aimed to evaluate the effectiveness of adding a low intensity, psychological intervention, Problem Management Plus (PM+) for CMDs into routine care in a specialized mental health care facility in Pakistan. Methods A two arm, single-blind individual randomized controlled trial (RCT) was carried out with adults (N = 192), referred for psychological support by psychiatrists. The study participants were randomized (1:1) to PM + plus Treatment as Usual (TAU) (n = 96) or TAU only (n = 96). The primary outcomes were symptoms of anxiety and depression, measured by the Hospital Anxiety and Depression Scale (HADS) and functional impairment as measured by WHO Disability Assessment Schedule (WHODAS 2.0) at 20 weeks after baseline. Results The analysis was done on intention-to-treat principle. The linear mixed model analysis showed that at 20 weeks after baseline, there was a significant reduction in symptoms of anxiety and depression (mean [SD], 16.23 [8.81] vs 19.79 [7.77]; AMD, − 3.10; 95% CI, − 0.26 to − 5.76); p = 0.03 and improvement in functioning (mean [SD], 22.94 [9.37] vs 27.37 [8.36]; AMD, − 4.35; 95% CI, − 1.45 to − 7.24); p = 0.004 in PM + plus TAU versus TAU arm. The follow-up rate was 67% at primary end-point. Conclusions Specialized care facilities in LMICs may consider adding brief, evidence-based psychological treatments for CMDs to their routine care. Trial Registration Australian New Zealand Clinical Trials Registry, ACTRN12616000381482. Registered March 23, 2016. Retrospectively registered, https://www.anzctr.org.au/Default.aspx/ ACTRN12616000381482

This 9-month randomised, parallel, double-blind, single-centre, placebo-controlled study (PROBE, ISRCTN18030882) assessed the impact of probiotic supplementation on bodyweight. Seventy overweight Bulgarian participants aged 45–65 years with BMI 25–29.9 kg/m2 received a daily dose of the Lab4P probiotic comprising lactobacilli and bifidobacteria (50 billion cfu/day). Participants maintained their normal diet and lifestyle over the duration of the study. The primary outcome was change from baseline in body weight and secondary outcomes included changes in waist circumference, hip circumference and blood pressure. A significant between group decrease in body weight (3.16 kg, 95% CI 3.94, 2.38, p p p

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 Adolescent girls in sub-Saharan Africa are disproportionally vulnerable to sexual and reproductive health (SRH) harms. In western Kenya, where unprotected transactional sex is common, young females face higher rates of school dropout, often due to pregnancy, and sexually transmitted infections (STIs), including HIV. Staying in school has shown to protect girls against early marriage, teen pregnancy, and HIV infection. This study evaluates the impact of menstrual cups and cash transfer interventions on a composite of deleterious outcomes (HIV, HSV-2, and school dropout) when given to secondary schoolgirls in western Kenya, with the aim to inform evidence-based policy to improve girls’ health, school equity, and life-chances. Methods Single site, 4-arm, cluster randomised controlled superiority trial. Secondary schools are the unit of randomisation, with schoolgirls as the unit of measurement. Schools will be randomised into one of four intervention arms using a 1:1:1:1 ratio and block randomisation: (1) menstrual cup arm; (2) cash transfer arm, (3) cups and cash combined intervention arm, or (4) control arm. National and county agreement, and school level consent will be obtained prior to recruitment of schools, with parent consent and girls’ assent obtained for participant enrolment. Participants will be trained on safe use of interventions, with all arms receiving puberty and hygiene education. Annually, the state of latrines, water availability, water treatment, handwashing units and soap in schools will be measured. The primary endpoint is a composite of incident HIV, HSV-2, and all-cause school dropout, after 3 years follow-up. School dropout will be monitored each term via school registers and confirmed through home visits. HIV and HSV-2 incident infections and risk factors will be measured at baseline, mid-line and end-line. Intention to treat analysis will be conducted among all enrolled participants. Focus group discussions will provide contextual information on uptake of interventions. Monitoring for safety will occur throughout. Discussion If proved safe and effective, the interventions offer a potential contribution toward girls’ schooling, health, and equity in low- and middle-income countries. Trial registration ClinicalTrials.gov NCT03051789, 15th February 2017.

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).

Background An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) before presentation. There is some evidence suggesting an increased 2-week mortality in those receiving ART for 14 days. However, presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or nonadherence, are not well described. Methods Six hundred seventy-eight adults with a first episode of cryptococcal meningitis recruited into a randomized, noninferiority, multicenter phase 3 trial in 4 Sub-Saharan countries were analyzed to compare clinical presentation and 2- and 10-week mortality outcomes between ART-naïve and -experienced patients and between patients receiving ART for varying durations before presentation. Results Over half (56%; 381/678) the study participants diagnosed with a first episode of cryptococcal meningitis were ART-experienced. All-cause mortality was similar at 2 weeks (17% vs 20%; hazard ratio [HR], 0.85; 95% CI, 0.6–1.2; P = .35) and 10 weeks (38% vs 36%; HR, 1.03; 95% CI, 0.8–1.32; P = .82) for ART-experienced and ART-naïve patients. Among ART-experienced patients, using different cutoff points for ART duration, there were no significant differences in 2- and 10-week mortality based on duration of ART. Conclusions In this study, there were no significant differences in mortality at 2 and 10 weeks between ART-naïve and -experienced patients and between ART-experienced patients according to duration on ART.

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.

We aim to study kinetics of anti-SARS-CoV-2 IgG antibody levels in subjects with COVID-19 for up to 11 months and the potential influential factors. The study was a prospective longitudinal study. The analyses were based on 77 serum/plasma samples with a mean of 4 samples per participant (range 1 – 18) in 20 participants with at least one positive Polymerase Chain Reaction testing result from 19 March 2020 up to 10 February 2021. Among the subjects (median age 34.5 years, 65% male), IgG level declined with the follow-up time (per month; geometric mean ratio [GMR] 0.73; 95% CI, 0.72 – 0.74). In a small sample of subjects from the general population with COVID-19, IgG levels declined non-linearly from month 2 to 11 with individual heterogeneity in quantity and changing speed and may be associated with gender, race and the loss of smell and taste.

IntroductionMillions of children in low resource settings are at high risk of poor development due to factors such as under nutrition, inadequate stimulation and maternal depression. Evidence-based interventions to address these risk factors exist, but often as a separate and overlapping package. The current study aims to evaluate the effectiveness of a common elements-based intervention to improve mother–infant interaction at 12 months post-partum.Method and analysisA two-arm, single-blinded, individual randomised controlled trial is being carried out in the community settings of the rural subdistrict of Gujar Khan in Rawalpindi, Pakistan. 250 pregnant women in third trimester with distress (Self-Reporting Questionnaire, cut-off score >9) have been randomised on 1:1 allocation ratio into intervention (n=125) and treatment-as-usual arms (n=125). The participants in the intervention arm will receive 15 individual sessions of intervention on a monthly basis by non-specialist facilitators. The intervention involves components of early stimulation, learning through play, responsive feeding, guided discovery using pictures, behavioural activation and problem solving. The primary outcome is caregiver–infant interaction at 12 months postpartum. The secondary outcomes include maternal psychological well-being, quality of life, social support and empowerment. Infant secondary outcomes include growth, nutrition and development. The data will be collected at baseline, 6 and 12 months postpartum. A qualitative process evaluation will be conducted to inform the feasibility of intervention delivery.EthicsEthics approval for the present study was obtained from the Human Development Research Foundation Institutional Review Board, Islamabad Pakistan.DisseminationIf proven effective, the study will contribute to scale-up care for maternal and child mental health in low resource settings, globally. The findings of the present study will be published in peer-reviewed journals and presented at conferences and community forums.Trial registration numberNCT04252807.

Thepandemicof COVID-19 has rapidly spread to over 200 countries and territoriesin the past 4months. To save lives and minimizetransmission, millions of healthcareworkers are working in frontlines worldwidebut putting themselves at high risk from the disease. All of themare workingunder extreme pressuresandexperiencinggreat psychological distressin such a challenging situation.In addition to the huge psychological pressure, healthcare workers around the world face morale and burnout issues as they have to make impossible decisions(Greenberg, Docherty, Gnanapragasam, & Wessely, 2020).It is encouraging is that the World Health Organization (WHO) and manyinstitutions have proposedguidelinesto providepsychological assistance for healthcare workers duringthispandemic

We assessed the effect of COVID-19 lockdown on deliveries and neonatal admissions according to gestation in Lagos, Nigeria. During lockdown (April–June 2020), there was a marked fall of about 50% in in-hospital deliveries and admissions to the neonatal wards for both in and outborn infants compared with prelockdown (January–March 2020) and a comparison period (April–June 2019). However, the proportion of preterm infants was broadly similar in each period. Lockdown markedly reduced hospital deliveries and healthcare-seeking for sick newborns but did not influence the overall proportion of preterm births among in-house deliveries and outborn neonatal admissions.

Among 472 patients with human immunodeficiency virus-associated cryptococcal meningitis, 16% had severe visual loss at presentation, and 46% of these were 4-week survivors and remained severely impaired. Baseline cerebrospinal fluid opening pressure ≥40 cmH2O (adjusted odds ratio [aOR], 2.56; 95% confidence interval [CI], 1.36–4.83; P = .02) and fungal burden >6.0 log10 colonies/mL (aOR, 3.01; 95% CI, 1.58–5.7; P = .003) were independently associated with severe visual loss.

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.

The outbreak of the Ebola virus has resulted in significant morbidity and mortality in the affected areas, and Ebola virus RNA has been found in the semen of the survivors after 9 months of symptom onset. However, the role that sexual transmission played in the transmission is not very clear. In this paper, we developed a compartmental model for Ebola virus disease (EVD) dynamics, which includes three different infectious routes: contact with the infectious, contact with dead bodies, and transmission by sexual behaviour with convalescent survivors. We fitted the model to daily cumulative cases from the first reported infected case to October 25, 2014 for the epidemic in Sierra Leone, Liberia and Guinea. The basic reproduction numbers in these countries were estimated as 1.6726 (95%CI:1.5922–1.7573), 1.8162 (95%CI:1.7660–1.8329) and 1.4873 (95%CI:1.4770–1.4990), respectively. We calculated the contribution of sexual transmission to the basic reproduction number R0 as 0.1155 (6.9%), 0.0236 (2.8%) and 0.0546 (3.7%) in Sierra Leone, Liberia and Guinea, respectively. Sensitivity analysis shows that the transmission rates caused by contacts with alive patients and sexual activities with convalescent patients have stronger impacts on the R0. These results suggest that isolating the infectious individuals and advising the recovery men to avoid sexual intercourse are efficient ways for the eradication of endemic EVD.

Objective: To develop a nomogram to predict the probability of live birth on the basis of the association of patient characteristics in subfertile individuals or couples. Methods: A retrospective study was conducted from January 2014 to December 2015. A nomogram was built from a training cohort and tested on an independent validation cohort. A total of 2,257 patients who had undergone their first nondonor cycle of in vitro fertilization (IVF) (including intracytoplasmic sperm injection) were randomly split 2:1 into training (n = 1,527) and validation (n = 730) cohorts. Results: There were no statistically significant differences in the patients' baseline and cycle characteristics between the training and validation cohorts. On multiple logistic regression analysis, female age, antral follicle count, tubal factor, anovulation, ethnicity, unexplained fertility, and male factor were significantly associated with live birth. The nomogram had a C-index of 0.700 (95% confidence interval [CI]: 0.698–0.701) in the training cohort and 0.684 (95% CI: 0.681–0.687) in the validation cohort. Conclusions: Our nomogram can predict the probability of live birth for infertile women and can be used to guide clinicians and couples to decide on an IVF treatment option.

High‐dose ivermectin, co‐administered for 3 days with dihydroartemisinin‐piperaquine (DP), killed mosquitoes feeding on individuals for at least 28 days posttreatment in a recent trial (IVERMAL), whereas 7 days was predicted pretrial. The current study assessed the relationship between ivermectin blood concentrations and the observed mosquitocidal effects against Anopheles gambiae s.s. Three days of ivermectin 0, 300, or 600 mcg/kg/day plus DP was randomly assigned to 141 adults with uncomplicated malaria in Kenya. During 28 days of follow‐up, 1,393 venous and 335 paired capillary plasma samples, 850 mosquito‐cluster mortality rates, and 524 QTcF‐intervals were collected. Using pharmacokinetic/pharmacodynamic (PK/PD) modeling, we show a consistent correlation between predicted ivermectin concentrations and observed mosquitocidal‐effects throughout the 28‐day study duration, without invoking an unidentified mosquitocidal metabolite or drug‐drug interaction. Ivermectin had no effect on piperaquine's PKs or QTcF‐prolongation. The PK/PD model can be used to design new treatment regimens with predicted mosquitocidal effect. This methodology could be used to evaluate effectiveness of other endectocides.

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.

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: Previous studies have reported the important roles of the precuneus in mediating metacognition and the prefrontal cortex in decision-making tasks. However, the underlying mechanisms of metacognition are still not fully elucidated. Long echo time proton magnetic resonance spectroscopy (MRS) was used to further explore the neurocognitive correlates of metacognition. Methods: Metacognition was based on a self-report questionnaire of nursing students. Magnetic resonance (MR) spectra were recorded from bilateral precuneus and medial prefrontal cortex. Results: Significant positive correlation was discovered between total metacognitive score and academic score (p = 0.007). Precuneus N-acetyl aspartate/creatine plus phosphocreatine (NAA/Cr+PCr) ratios were corresponded to metacognitive ability. Moreover, the correlation between precuneus NAA/Cr+PCr ratios and metacognitive ability was established for the right precuneus and not left precuneus. Furthermore, linear regression suggested that for every increase in the right precuneus NAA/Cr+PCr ratios, there is a predicted decrease in total metacognitive score (p = 0.020). Conclusions: These findings further indicated that the right precuneal region plays an important role in metacognition and learning.

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.