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Jiang Liu,1,2,* Hao Hu,1,3,* Shanhu Qiu,4 Duolao Wang,5 Jianing Liu,1 Ziwei Du,1 Zilin Sun1 1Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2Department of Endocrinology, The Third Hospital of Nanchang, Nanchang, Jiangxi, People’s Republic of China; 3Department of Endocrinology, The First People’s Hospital of Xuzhou, Xuzhou, Jiangsu, People’s Republic of China; 4Department of General Practice, Zhongda Hospital; Institute of Diabetes, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 5Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK*These authors contributed equally to this workCorrespondence: Zilin Sun, Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China, Tel +8613951749490, Fax +862583262609, Email sunzilin1963@126.comPurpose: To investigate the prevalence and associated factors of diabetic retinopathy (DR) and advanced DR in Chinese adults with diabetes mellitus (DM).Patients and Methods: A cross-sectional study was performed on 4831 diabetic patients from 24 hospitals from April 2018 to July 2020. Non-mydriatic fundus of patients were interpreted by an artificial intelligence (AI) system. Fundus photos that were unsuitable for AI interpretation were interpreted by two ophthalmologists trained by one expert ophthalmologist at Beijing Tongren Hospital. Medical history, height, weight, body mass index (BMI), glycosylated hemoglobin (HbA1c), blood pressure, and laboratory examinations were recorded.Results: A total of 4831 DM patients were included in this study. The prevalence of DR and advanced DR in the diabetic population was 31.8% and 6.6%, respectively. In multiple logistic regression analysis, male (odds ratio [OR], 1.39), duration of diabetes (OR, 1.05), HbA1c (OR, 1.11), farmer (OR, 1.39), insulin treatment (OR, 1.61), region (northern, OR, 1.78; rural, OR, 6.96), and presence of other diabetic complications (OR: 2.03) were associated with increased odds of DR. The factors associated with increased odds of advanced DR included poor glycemic control (HbA1c > 7.0%) (OR, 2.58), insulin treatment (OR, 1.73), longer duration of diabetes (OR, 3.66), rural region (OR, 4.84), and presence of other diabetic complications (OR, 2.36), but overweight (BMI > 25 kg/m2) (OR, 0.61) was associated with reduced odds of advanced DR.Conclusion: This study shows that the prevalence of DR is very high in Chinese adults with DM, highlighting the necessity of early diabetic retinal screening.Keywords: diabetes mellitus, screening, artificial intelligence, glycemic control, rural region

Generalized pairwise comparisons and win statistics (i.e., win ratio, win odds and net benefit) are advantageous in analyzing and interpreting a composite of multiple outcomes in clinical trials. An important limitation of these statistics is their inability to adjust for covariates other than by stratified analysis. Because the win ratio does not account for ties, the win odds, a modification that includes ties, has attracted attention. We review and combine information on the win odds to articulate the statistical inferences for the win odds. We also show alternative variance estimators based on the exact permutation and bootstrap as well as statistical inference via the probabilistic index. Finally, we extend multiple-covariate regression probabilistic index models to the win odds with a univariate outcome. As an illustration we apply the regression models to the data in the CHARM trial.

Background. There are few reports on the relationship between dietary patterns and cardiovascular disease (CVD) risk in patients with type 2 diabetes (T2D). This study aimed to explore relationships between dietary patterns and CVD risk in the T2D population using multiple statistical analysis methods. Methods. A total of 2,984 patients with T2D from the Xinjiang Multi-Ethnic Cohort, 555 of whom were suffering from CVD, were enrolled in this study. Participants’ dietary intake was measured by the semiquantitative food frequency questionnaire (FFQ). Three statistical methods were used to construct dietary patterns, including principal component analysis (PCA) method, reduced-rank regressions (RRR) method, and partial least-squares regression (PLS) method. Then, the association between dietary patterns and CVD risk in T2D patients was analyzed by logistic regression. After excluding participants with CVD, the associations between dietary patterns and 10-year CVD risk scores were subsequently evaluated to reduce reverse causality. Results. In this study, four dietary patterns were identified by three methods. Adjustment for confounding factors, subjects with the highest scores on the “high-protein and high-carbohydrate” patterns derived from PCA, RRR, and PLS had higher odds of CVD than those with the lowest scores (OR: 2.89, 95% CI: 2.11–3.96, P t r e n d < 0.001 ; OR: 2.96, 95% CI: 2.17–4.03, P t r e n d < 0.001 ; OR: 2.01, 95% CI: 1.50–2.70, P t r e n d < 0.001 , respectively). However, the dietary pattern of PCA-prudent was not significantly related to the odds of having CVD in T2D patients (adjusted ORQ4vsQ1: 0.93, 95% CI: 0.70–1.24, P t r e n d = 0.474 ). Interestingly, we also found significant associations between “high-protein and high-carbohydrate” patterns and the elevated predicted 10-year CVD risk in T2D patients (all P t r e n d < 0.05 ). Conclusion. The positive correlation between “high-protein and high-carbohydrate” patterns and CVD risk in T2D patients was robust across all three data-driven approaches. These findings may have public health significance, encouraging an emphasis on food choices in the usual diet and promoting nutritional interventions for patients with T2D to prevent CVD.

Considerable attention has focused on the role of omega-3 polyunsaturated fatty acids (PUFA) in the prevention of cardiometabolic diseases, which has led to dietary recommendations to increase omega-3 fatty acid intake. A meta-analysis was conducted to summarize evidence from prospective studies regarding associations between omega-3 PUFA biomarkers and risk of developing major chronic diseases.Four electronic databases were searched for articles from inception to March 1, 2022. 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-linolenic 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. The Grades of Recommendation, Assessment, Development and Evaluation assessment tool was used to rates the confidence in estimates.A total of 67 prospective studies comprised of 310,955 participants were identified. Individual omega-3 PUFAs showed divergent associations with the study outcomes of interest. A significant inverse association with T2D risk was observed across categories of ALA (relative risk [RR]: 0.89, 95% confidence interval [CI]: 0.82-0.96), EPA (RR: 0.85, 95% CI: 0.72-0.99) and DPA (RR: 0.84, 95% CI: 0.73-0.96) biomarkers. The marine-origin omega-3 fatty acids biomarkers but not ALA was 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. A 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), whereas no association was noted for other outcomes. In addition, a dose-response relationship was observed between an increasing level of EPA, DPA, or DHA biomarker and lower risk of CVD.Higher concentrations of marine-derived omega-3 PUFA biomarkers were associated with a significantly reduced risk of total CVD, CHD, and total mortality. Levels of ALA were inversely associated 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.

Mechanistic studies have suggested that antioxidants have beneficial effects on age-related macular degeneration (AMD). This study aimed to investigate the association between the types and sources of dietary vitamin and carotenoid intakes and AMD risk in China. A matched case-control study of 260 patients who were clinically diagnosed with AMD and 260 matched controls was performed. The participants were interviewed for dietary information and potential confounders, and comprehensive ophthalmic examinations were performed. Conditional logistic models were used to estimate the odds ratio (OR) and 95% confidence interval (CI) across the categories of specific vitamins and carotenoids and their main sources. When comparing the extreme quartiles, the ORs(95% CI) were 0.30 (0.10, 0.88) for lutein and 0.28 (0.11, 0.74) for β-cryptoxanthin. The associations between AMD and other dietary vitamin and carotenoid intakes were generally weaker and non-significant. Higher intakes of spinach and egg, which are important sources of lutein, were associated with a reduced odds of AMD, with an OR comparing the highest and lowest categories of spinach being 0.42 (95%CI: 0.20, 0.88) and that comparing the highest and lowest categories of the egg being 0.52 (95% CI: 0.27, 0.98). Participants who were in the highest category of both egg intake and spinach intake had a much greater reduced odds of having AMD (OR: 0.23; 95%CI: 0.08, 0.71) than those in the lowest category of egg intake and spinach intake. In conclusion, a higher intake of lutein and lutein-rich foods was associated with a significantly decreased odds of AMD. These findings provide further evidence of the benefits of lutein and lutein-rich foods in the prevention of AMD.

Radivoj Arezina,1 Tao Chen,2 Duolao Wang3,4 1Department of Medical, Stridon Clinical Research, Richmond Upon Thames, London, UK; 2Department of Public Health, Policy & Systems, Institute of Population Health, University of Liverpool, Liverpool, Merseyside, UK; 3Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 4Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, Merseyside, UKCorrespondence: Duolao Wang, Email Duolao.Wang@lstmed.ac.ukAbstract: COPD (chronic obstructive pulmonary disease) is a major public health concern associated with significant morbidity and mortality worldwide. Current therapeutic guidelines for this disease recommend starting with an inhaled bronchodilator, stepping up to combination therapy as necessary, and/or adding inhaled corticosteroids as symptoms and airflow obstruction progress. However, no drug therapy exists to stop disease progression. The mechanistic definition underlying COPD pathogenesis remains poorly understood, it is generally accepted that oxidative stress and the altered immune response of low-grade airway inflammation are major factors contributing to COPD development. There are several potential therapeutic targets that are currently under investigation, including immune regulatory pathways in inflammation and lung-associated steroid resistance induced by oxidative stress signaling cascades. Patients with COPD have increased levels of inflammatory mediators, including lipid and peptide mediators, as well as a network of cytokines and chemokines that maintain inflammatory immune response and recruit circulating cells into the lungs. Many of these pro-inflammatory mediators are regulated by nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs), such as p38 MAPK. Increased oxidative stress is a key driving mechanism in perpetuating inflammation and lung injury. Furthermore, many proteases that degrade elastin fibres are secreted by airway resident infiltrating immune cells in COPD patients. In this perspective, we discuss novel aspects of signaling pathway activation in the context of inflammation and oxidative stress, and the broad view of potential effective pharmacotherapies that target the underlying mechanistic disease process in COPD.Keywords: COPD, mechanistic, pharmacotherapy

BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine is more effective than IPTp with sulfadoxine-pyrimethamine at reducing malaria infection during pregnancy in areas with high-grade resistance to sulfadoxine-pyrimethamine by Plasmodium falciparum in east Africa. We aimed to assess whether IPTp with dihydroartemisinin-piperaquine, alone or combined with azithromycin, can reduce adverse pregnancy outcomes compared with IPTp with sulfadoxine-pyrimethamine.METHODS: We did an individually randomised, double-blind, three-arm, partly placebo-controlled trial in areas of high sulfadoxine-pyrimethamine resistance in Kenya, Malawi, and Tanzania. HIV-negative women with a viable singleton pregnancy were randomly assigned (1:1:1) by computer-generated block randomisation, stratified by site and gravidity, to receive monthly IPTp with sulfadoxine-pyrimethamine (500 mg of sulfadoxine and 25 mg of pyrimethamine for 1 day), monthly IPTp with dihydroartemisinin-piperaquine (dosed by weight; three to five tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine once daily for 3 consecutive days) plus a single treatment course of placebo, or monthly IPTp with dihydroartemisinin-piperaquine plus a single treatment course of azithromycin (two tablets containing 500 mg once daily for 2 consecutive days). Outcome assessors in the delivery units were masked to treatment group. The composite primary endpoint was adverse pregnancy outcome, defined as fetal loss, adverse newborn baby outcomes (small for gestational age, low birthweight, or preterm), or neonatal death. The primary analysis was by modified intention to treat, consisting of all randomised participants with primary endpoint data. Women who received at least one dose of study drug were included in the safety analyses. This trial is registered with ClinicalTrials.gov, NCT03208179.FINDINGS: From March-29, 2018, to July 5, 2019, 4680 women (mean age 25·0 years [SD 6·0]) were enrolled and randomly assigned: 1561 (33%; mean age 24·9 years [SD 6·1]) to the sulfadoxine-pyrimethamine group, 1561 (33%; mean age 25·1 years [6·1]) to the dihydroartemisinin-piperaquine group, and 1558 (33%; mean age 24·9 years [6.0]) to the dihydroartemisinin-piperaquine plus azithromycin group. Compared with 335 (23·3%) of 1435 women in the sulfadoxine-pyrimethamine group, the primary composite endpoint of adverse pregnancy outcomes was reported more frequently in the dihydroartemisinin-piperaquine group (403 [27·9%] of 1442; risk ratio 1·20, 95% CI 1·06-1·36; p=0·0040) and in the dihydroartemisinin-piperaquine plus azithromycin group (396 [27·6%] of 1433; 1·16, 1·03-1·32; p=0·017). The incidence of serious adverse events was similar in mothers (sulfadoxine-pyrimethamine group 17·7 per 100 person-years, dihydroartemisinin-piperaquine group 14·8 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 16·9 per 100 person-years) and infants (sulfadoxine-pyrimethamine group 49·2 per 100 person-years, dihydroartemisinin-piperaquine group 42·4 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 47·8 per 100 person-years) across treatment groups. 12 (0·2%) of 6685 sulfadoxine-pyrimethamine, 19 (0·3%) of 7014 dihydroartemisinin-piperaquine, and 23 (0·3%) of 6849 dihydroartemisinin-piperaquine plus azithromycin treatment courses were vomited within 30 min.INTERPRETATION: Monthly IPTp with dihydroartemisinin-piperaquine did not improve pregnancy outcomes, and the addition of a single course of azithromycin did not enhance the effect of monthly IPTp with dihydroartemisinin-piperaquine. Trials that combine sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine for IPTp should be considered.FUNDING: European & Developing Countries Clinical Trials Partnership 2, supported by the EU, and the UK Joint-Global-Health-Trials-Scheme of the Foreign, Commonwealth and Development Office, Medical Research Council, Department of Health and Social Care, Wellcome, and the Bill-&-Melinda-Gates-Foundation.

Cluster analysis may assist in stratifying heterogeneous clinical presentations of type 2 diabetes (T2D). However, the association of cluster-based subgroups with diabetes-related outcomes such as diabetic retinopathy remains unclear. This study was aimed to address this issue with novel clusters of T2D derived from four simple parameters. We developed a k-means clustering model in participants with newly diagnosed T2D (N = 1910) from the SENSIBLE and SENSIBLE-Addition studies, based on body mass index (BMI), waist circumference (WC), mean arterial pressure (MAP), and hemoglobin A1c (HbA1c). Diabetic retinopathy was ascertained with the protocol from the Early Treatment of Diabetic Retinopathy Study. Participants (N = 515) without diabetic retinopathy at baseline were followed-up for 3 years. Logistic regression analyses were performed to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). Three clusters were identified, with cluster 0, 1 and 2 accounting for 48.2, 8.9 and 42.9%, respectively. Participants with T2D were featured by the lowest BMI, WC, MAP, and HbA1c in cluster 0, poor glycemic condition in cluster 1, and the highest BMI, WC, and MAP in cluster 2. Compared with cluster 0, cluster 1 was associated with increased odds of diabetic retinopathy in both the cross-sectional study (OR 6.25, 95% CI: 3.19-12.23) and the cohort study (OR 9.16, 95% CI: 2.08-40.34), while cluster 2 was not. Moreover, most participants remained their clusters unchanged during follow-up. Our cluster-based analysis showed that participants with poor glycemic condition rather than high blood pressure and obesity had higher risk of diabetic retinopathy.

Cardiac damage is commonly reported in patients with coronavirus disease 2019 (COVID-19) but its prevalence and impact on the long-term survival of patients remain uncertain. This study aimed to explore the prevalence of myocardial injury and assess its prognostic value in patients with COVID-19.A single-center, retrospective cohort study was performed at the Affiliated Hospital of Jianghan University. Data from 766 patients with confirmed COVID-19 who were hospitalized from December 27, 2019 to April 25, 2020 were collected. Demographic, clinical, laboratory, electrocardiogram, treatment data and all-cause mortality during follow-up were collected and analyzed.Of the 766 patients with moderate to critically ill COVID-19, 86 (11.2%) died after a mean follow-up of 72.8 days. Myocardial injury occurred in 94 (12.3%) patients. The mortality rate was 64.9% (61/94) and 3.7% (25/672) in patients with and without myocardial injury, respectively. Cox regression showed that myocardial injury was an independent risk factor for mortality (hazard ratio: 8.76, 95% confidence interval: 4.76-16.11,COVID-19 not only involves pneumonia but also cardiac damage. Myocardial injury is a common complication and an independent risk factor for mortality in COVID-19 patients.

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,&ast; Xiaobo Zhang,1,&ast; 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&ast;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

IntroductionEmotional problems are leading contributors to health burden among adolescents worldwide. There is an urgent need for evidence-based psychological interventions for young people. This study aims to evaluate the effectiveness of a school-based, group psychological intervention, Early Adolescent Skills for Emotions (EASE) developed by the WHO to improve psychosocial distress in Pakistani adolescents.Method and analysisA two-arm, single-blinded, cluster randomised controlled trial, with a wait-list control arm is being conducted in school settings of rural Pakistan. Forty eligible public-school clusters have been randomised (stratified by gender) on a 1:1 allocation ratio into intervention (n=20) and control arm (n=20). Following informed consent, 564 adolescents with psychosocial distress (Youth-reported Paediatric Symptoms Checklist, cut-off ≥28) from 40 schools have been enrolled into the trial (14±3 average cluster size) between 2 November 2021 and 30th November 2021. Participants in the intervention arm will receive EASE in 7-weekly adolescents and 3-biweekly caregivers group sessions in schools. The adolescent sessions involve the components of psychoeducation, stress management, behavioural activation, problem-solving and relapse prevention. Caregivers will receive training to learn and implement active listening; spending quality time and using praise as a strategy to help their children. The primary outcome is reduction in psychosocial distress at 3 months postintervention. Secondary outcomes include symptoms of depression and anxiety, caregiver–adolescent relationship and caregivers’ well-being. Outcomes will be assessed at baseline, immediate 1 week and 3-months postintervention. Qualitative process evaluation will explore barriers and facilitators to programme implementation in low-resource school settings.EthicsEthics approval has been obtained from Central Ethics Committee of University of Liverpool, UK, Ethics Review Committee of WHO Geneva and from the Institutional Review Board of Human Development Research Foundation (HDRF), Pakistan.DisseminationThe findings of the study will be disseminated by WHO and through peer-reviewed publications.Trial registration numberISRCTN17755448.

BackgroundThe social disparities in obesity may originate in early life and adult social class. There are various developmental trajectories of overweight/obesity in adulthood. It is unclear how the intergenerational mobility of socioeconomic status influences adult overweight/obesity in China.MethodsWe used longitudinal data from ten waves of the China Health and Nutrition Survey (CHNS) between 1989 and 2015 for our analysis. The group-based trajectory modeling was used to identify BMI trajectories in adulthood. Multinomial logistic regression was adopted to assess the associations between SES and adult BMI trajectories.ResultsAmong a total of 3,138 participants, three latent clusters, including normal-stable BMI (51.4%), progressive overweight group (39.8%), and progressive obesity group (8.8%), were identified. High father’s occupational position, high participants’ occupation position and educational attainment, respectively, were associated with greater obesity risk. Compared to a stable low life course SES trajectory, a stable high life course SES trajectory was associated with a 2.35-fold risk of obesity, and upward and downward social mobility trajectories increased the risk for overweight/obesity. Individuals in the highest relative to the lowest life course cumulative socioeconomic score group had around twice risk of obesity.ConclusionsThe results emphasize the role of the high SES in early life and life-course SES accumulation, in the obesity intervention in China.FundingAll the work was supported by the National Natural Science Foundation of China (Grant Nos. 72174167, 81602928) and Natural Science Foundation of Shaanxi (2021JM-031).

RationaleStreptococcus pneumoniae serotype 3 (SPN3) is a cause of invasive pneumococcal disease and associated with low carriage rates. Following the introduction of pediatric 13-valent pneumococcal conjugate vaccine (PCV13) programmes, SPN3 declines are less than other vaccine serotypes and incidence has increased in some populations coincident with a shift in predominant circulating SPN3 clade, from I to II. A human challenge model provides an effective means for assessing the impact of PCV13 on SPN3 in the upper airway.ObjectivesTo establish SPN3's ability to colonise the nasopharynx using different inoculum clades and doses and the safety of an SPN3 challenge model.MethodsIn a human challenge study involving three well characterised and antibiotic sensitive SPN3 isolates (PFESP306 [clade Ia], PFESP231 [no clade] and PFESP505 [clade II]), inoculum doses (10,000, 20,000, 80,000, 160,000 CFU/100μL) were escalated until maximal colonisation rates were achieved, with concurrent acceptable safety.Outcome measuresPresence and density of experimental SPN3 nasopharyngeal colonisation in nasal wash samples, assessed using microbiological culture and molecular methods, on days 2, 7 and 14 post-inoculation.Results96 healthy participants (median age 21, interquartile range 19-25) were inoculated (n=6-10 per dose group, 10 groups). Colonisation rates ranged from 30.0-70.0% varying with dose and isolate. 30.0% (29/96) reported mild symptoms (82.8% sore throat, [24/29]), one developed otitis media requiring antibiotics. No serious adverse events occurred.ConclusionsAn SPN3 human challenge model is feasible and safe with comparable carriage rates to an established SPN6B human challenge model. SPN3 carriage may cause mild upper respiratory symptoms. Clinical trial registration available at www. https://www.isrctn.com/, ID: ISRCTN11306486.

IntroductionDespite widely available vaccinations, Streptococcus pneumoniae (SPN) remains a major cause of morbidity and mortality worldwide, causing community-acquired pneumonia, meningitis, otitis media, sinusitis and bacteraemia. Here, we summarise an ethically approved protocol for a double-blind, randomised controlled trial investigating the effect of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23) on pneumococcal nasopharyngeal colonisation acquisition, density and duration using experimental human pneumococcal challenge (EHPC).Methods and analysisHealthy adult participants aged 18–50 years will be randomised to receive PCV13, PPV23 or placebo and then undergo one or two EHPCs involving intranasal administration of SPN at 1-month post-vaccination with serotype 3 (SPN3) and 6 months with serotype 6B (SPN6B). Participants randomised to PCV13 and placebo will also be randomised to one of two clinically relevant SPN3 strains from distinct lineages within clonal complex 180, clades Ia and II, creating five study groups. Following inoculation, participants will be seen on days 2, 7, 14 and 23. During the follow-up period, we will monitor safety, colonisation status, density and duration, immune responses and antigenuria. The primary outcome of the study is comparing the rate of SPN3 acquisition between the vaccinated (PCV13 or PPV23) and unvaccinated (placebo) groups as defined by classical culture. Density and duration of colonisation, comparison of acquisition rates using molecular methods and evaluation of the above measurements for individual SPN3 clades and SPN6B form the secondary objectives. Furthermore, we will explore the immune responses associated with these vaccines, their effect on colonisation and the relationship between colonisation and urinary pneumococcal antigen detection.Ethics and disseminationThe study is approved by the NHS Research and Ethics Committee (Reference: 20/NW/0097) and by the Medicines and Healthcare products Regulatory Agency (Reference: CTA 25753/0001/001–0001). Findings will be published in peer-reviewed journals.Trial registration numberISRCTN15728847, NCT04974294.

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.

Perinatal anxiety is among the most common mental health conditions that have a huge negative impact both on mothers and their children. This study aimed to establish summary estimates of the prevalence of perinatal anxiety and its influencing factors in Mainland China.A systematic search was carried out from nine major English and Chinese electronic databases to identify studies published up to August 20, 2022 with data on the prevalence of perinatal anxiety. Two reviewers conducted data extraction and quality assessment. Meta-analysis was performed using a random-effects model. Subgroup and meta-regression analyses were performed when possible.271 studies representing 369,477 women were included in the study. Pooled prevalence of perinatal anxiety was 17.4 % (95 % CI: 16.2 % to 18.7 %), with prenatal anxiety 17.4 % (95%CI: 16.1 % to 18.8 %) and postpartum anxiety 17.5 % (95%CI: 13.5 % to 22.4 %). However, the overall estimates presented substantial heterogeneity (IVery large heterogeneity among studies was observed in meta-synthesis, and all included studies used self-report scales to identify anxiety rather than diagnostic interviews.Varying degrees of perinatal anxiety is prevalent among Chinese women. Screening and evidence-based interventions are urgent and necessary to address this public concern and promote their health and well-being.

SUSPPUP, calculated as serum sodium [Na ] to urinary Na divided by (serum potassium [K ]) to urinary K , is a composite electrolyte index that reflects renal Na retention and K excretion. It remains unclear whether SUSPPUP and its components including serum or urinary Na or K , are associated with glucose metabolism. This study aimed to address their associations. We conducted a cross-sectional study enrolling 5,581 Chinese adults (1,269 with prediabetes, 1,044 with diabetes, and 3,268 with normoglycemia). Fasting serum and morning spot urine were used to measure electrolytes that included Na and K . SUSPPUP was higher in prediabetes and diabetes than normoglycemia. The odds of prediabetes and diabetes were increased by 21% and 39% for every 1-standard deviation increment of SUSPPUP after multivariable-adjustment. Multiple linear regression analysis showed that SUSPPUP correlated positively with fasting plasma glucose, 2 h plasma glucose after OGTT, and glycated hemoglobin A1c. Higher spot urinary Na was associated with lower odds of prediabetes and diabetes, while spot urinary K showed the opposite. Increases in Na retention and K excretion in the kidney, as reflected by an elevated SUSPPUP, are associated with increased prevalence of prediabetes and diabetes in Chinese community-dwellers.

Lens autofluorescence ratio (LFR) is a novel approach to detect advanced glycation end products in a time-saving and non-invasive manner. However, its associations with glycemia and diabetes remain unclear. We conducted this study to address this issue in Chinese adults. We enrolled a total of 4,705 participants aged 20-70 years in China between May 2020 and January 2021 in a cross-sectional study. LFR was determined by biomicroscopy (ClearPath DS-120). Diabetes was ascertained by oral glucose tolerance test, self-reported history, and/or antidiabetic medication use. Correlation and logistic regression analyses were performed. LFR was higher in participants with diabetes than those without (23.27 ± 6.51 vs. 19.45 ± 5.08, p < 0.001). LFR correlated with fasting plasma glucose and hemoglobin A1c in the overall and diabetes-stratified populations. The odds of diabetes was increased by 6% per one percent higher of LFR after multivariable-adjustment (odds ratio (OR) 1.06, 95% CI 1.04-1.08, p < 0.001). Participants in the highest quartile of LFR had higher odds of diabetes compared with those in the lowest quartile (OR 1.83, 95% CI 1.33-2.52, p < 0.001). Mediation analysis showed that, insulin resistance, as assessed by triglyceride-glucose index, may underline the relationship between high LFR and increased odds of diabetes. LFR, a non-invasive indirect measure of advanced glycation end products, appears to be associated with glycemia and the risk of developing diabetes in Chinese adults.

Conventional analyses of a composite of multiple time-to-event outcomes use the time to the first event. However, the first event may not be the most important outcome. To address this limitation, generalized pairwise comparisons and win statistics (win ratio, win odds, and net benefit) have become popular and have been applied to clinical trial practice. However, win ratio, win odds, and net benefit have typically been used separately. In this article, we examine the use of these three win statistics jointly for time-to-event outcomes. First, we explain the relation of point estimates and variances among the three win statistics, and the relation between the net benefit and the Mann-Whitney U statistic. Then we explain that the three win statistics are based on the same win proportions, and they test the same null hypothesis of equal win probabilities in two groups. We show theoretically that the Z-values of the corresponding statistical tests are approximately equal; therefore, the three win statistics provide very similar p-values and statistical powers. Finally, using simulation studies and data from a clinical trial, we demonstrate that, when there is no (or little) censoring, the three win statistics can complement one another to show the strength of the treatment effect. However, when the amount of censoring is not small, and without adjustment for censoring, the win odds and the net benefit may have an advantage for interpreting the treatment effect; with adjustment (e.g., IPCW adjustment) for censoring, the three win statistics can complement one another to show the strength of the treatment effect. For calculations we use the R package WINS, available on the CRAN (Comprehensive R Archive Network).

QT interval on an electrocardiogram (ECG) trace is a widely used surrogate parameter in drug development to detect the potential of drugs to cause life threatening cardiac arrhythmias. It changes inversely with the magnitude of heart rate (Heart rate=60/RR, RR stands for RR interval on an ECG reading) and is often corrected to a heart rate independent value known as the corrected QT interval (QTc). Various parametric QT correction formulae have been proposed by specifying the QT and heart rate relationships explicitly by a fixed number of parameters. This paper proposes to use the Box-Cox transformation to fit the QTRR relationship, and develops a new method for correcting the QT interval for heart rate. The six commonly used parametric models are the special cases of Box-Cox transformed model. We discuss the model parameter estimation and assess the performance of QT correction formulae derived from four types of Box-Cox transformations using four off-drug ECG datasets and one on-drug ECG dataset, as well as a simulated dataset. The results show that all four derived QT correction formulae from Box-Cox transformation generate a heart rate independent QTc and that the QT correction formula derived from transformation of both QT and RR generates QTc with smaller variations. The Box-Cox transformation represents a very flexible family for modelling QT-RR relationships including the six commonly used parameter models, thus providing a potentially better QT correction method than the existing parametric models.

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.

Objective: This study investigated emotional distress and associated factors among the general population in the aftermath of the COVID-19 lockdown in China. Design and sample: An online nationwide survey was conducted using a self-designed questionnaire, which included items related to demography, lifestyle, and experience of emotional distress during the previous month of the pandemic period. A total of 10,545 respondents completed the survey. Results: Over 30% of participants reported experiencing one or more symptoms of emotional distress to a moderate or higher degree. Increased emotional distress was associated with COVID-19-related impact on diet (β = −1.106, 95% CI: −1.187 to −1.026, p < 0.001), experiencing food shortage (β = 1.334, 95% CI: 1.117 to 1.551, p < 0.001), lack of physical exercise (β = −0.845, 95% CI: −1.024 to −0.667, p < 0.001), younger age (β = −0.050, 95% CI: −0.062 to −0.039, p < 0.001), being a smoker (β = 0.852, 95% CI: 0.604 to 1.100, p < 0.001), lower education level (β = −0.524, 95% CI: −0.702 to −0.346, p < 0.001), and lack of medical insurance (β = −0.742, 95% CI: −1.012 to −0.473, p < 0.001). Emotional distress was negatively associated time spent sleeping (β = −0.020, 95% CI: −0.027 to −0.013, p < 0.001). Conclusion: The levels of emotional distress are high in the aftermath of the lockdown and associated with a number of demographic and lifestyle factors.

Background: Rates of perinatal depression in China are high. The Thinking Healthy Programme is a WHO-endorsed, evidence-based psychosocial intervention for perinatal depression, requiring five days of face-to-face training by a specialist trainer. Given the paucity of specialist trainers and logistical challenges, standardized training of large numbers of nurses is a major challenge for scaling up. We developed an electronic training programme (e-training) which eliminates the need for specialist-led, face-to-face training. The aim of this study was to evaluate the effectiveness of the e-training compared to conventional face-to-face training in nursing students. Methods: A single blind, non-inferiority, randomized controlled trial was conducted. One hundred nursing students from two nursing schools were randomly assigned to either e-training or conventional face-to-face training. Results: E-training was not inferior to specialist-led face-to-face training immediately post-training [mean ENhancing Assessment of Common Therapeutic factors (ENACT) score (M) 45.73, standard deviation (SD) 4.03 vs. M 47.08, SD 4.53; mean difference (MD) −1.35, 95% CI; (−3.17, 0.46), p = 0.14]. There was no difference in ENACT scores at three months [M = 42.16, SD 4.85 vs. M = 42.65, SD 4.65; MD = −0.481, 95% CI; (−2.35, 1.39), p = 0.61]. Conclusions: E-training is a promising tool with comparative effectiveness to specialist-led face-to-face training. E-training can be used for training of non-specialists for evidence-based psychosocial interventions at scale and utilized where there is a shortage of specialist trainers, but practice under supervision is necessary to maintain competence. However, continued practice under supervision may be necessary to maintain competence.

Contains fulltext : 283104.pdf (Publisher’s version ) (Open Access) BACKGROUND: Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. METHODS: DolPHIN-2 was a randomised, open-label trial. 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 antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz group had a viral load of less than 50 copies per mL. Of 57 (21%) mothers with a severe adverse event, three (2%) in the dolutegravir group and five (4%) in the efavirenz group were related to the drug (dolutegravir drug-related events were one woman each with suicidal ideation, suicide attempt, herpes zoster meningitis; efavirenz drug-related events were one woman each with suicide attempt and liver cirrhosis, and three people with drug-induced liver injury). Of 136 (56%) infants in whom severe adverse events were recorded, none were related to the study drugs. In addition to the three infant HIV infections detected at birth in the dolutegravir group that have been previously reported, an additional transmission in the efavirenz group occurred during breastfeeding despite optimal maternal viral suppression and serial negative infant tests in the first year of life. INTERPRETATION: Dolutegravir was safe and well tolerated, supporting updated WHO treatment recommendations in pregnant and breastfeeding women. Infant HIV transmissions can occur during breastfeeding despite persistently undetectable maternal viral load highlighting the need for continued infant testing. FUNDING: Unitaid.

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.