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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.

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.

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 )

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.

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

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: COVID-19 has become a major health event that endangers public health throughout China and the world raising international concern This study aims

Background: Respiratory failure is the leading cause of death in patients with COVID-19. This study aimed to assess the incidence and risk factors for respiratory failure in patients with COVID-19 in Jiangsu province, China. Methods: We did a multicentre retrospective cohort study of all patients with COVID-19 diagnosed at 24 hospitals in Jiangsu province, China between 10 January and 18 February 2020. The demographic, clinical, laboratory, and radiologic features at admission were collected. Clinical outcomes were collected at 8 time points over 14 days from hospital admission. The primary outcome was the occurrence of acute respiratory failure within 14 days from admission, defined as oxygen saturation < 93% and/or partial pressure of oxygen in arterial blood < 60 mm Hg on room air and/or requirement of high-flow nasal cannula therapy, non-invasive or invasive mechanical ventilation. Findings: Of the 626 patients with confirmed COVID-19 infection during the study period, 620 (99.0%) had accessible medical records and were included in the study. Respiratory failure (mainly type I) occurred in 53 of 620 (8.6%) patients. As of 18 February 2020, no patients had died and 252 (40.6%) patients had been discharged. Some differences were observed in demographic and clinical characteristics, laboratory parameters, and radiological findings between patients with and without respiratory failure. Multivariate logistic analysis indicated that age (year) (odds ratio [OR], 1.07; 95% confidence interval [CI]: 1.04-1.11; p < 0.0001), respiratory rate (OR, 1.19; 95% CI: 1.05-1.35; p = 0.0052), lymphocyte count (10 -9 /L) (OR, 0.19; 95% CI: 0.06-0.64, p = 0.0089), and pulmonary opacity (per 5%) (OR, 1.29, 95% CI: 1.09-1.52; p = 0.0052) at admission were associated with the occurrence of respiratory failure. Interpretation: The rate of respiratory failure and death was lower in patients with COVID-19 in Jiangsu than in Wuhan city and lower than previously seen in patients with SARS and MERS. Age, lymphocyte count, respiratory rate, and pulmonary opacity score at admission were identified as independent risk factors for developing respiratory failure. Funding Statement: This work was supported, in part, by the research Grant 2020YFC0843700 67 from Ministry of Science and Technology of the People’s Republic of China. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The Ethics Committee of Zhongda Hospital Affiliated to Southeast University approved this study (2020ZDSYLL013–P01 and 2020ZDSYLL019–P01). Informed consent was waived due to the emergent event of the pandemic.

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

Background: The prevalence of perinatal depression is 16.3% in China and has shown a rising trend in the last decade. However, very few studies were found comparing and summarizing psychosocial interventions for perinatal depression. This study aimed at evaluating and characterizing psychosocial interventions for perinatal depression in Mainland China. Methods: In this systematic review and meta-analysis, ten major English and Chinese language electronic bibliographic databases were searched for randomized controlled trials examining the effect of psychosocial interventions for perinatal depressed women in Mainland China. Studies meeting eligibility criteria and published before 25th February 2019 were included, while those focusing on a very specific sub-population or reporting non-psychosocial interventions were excluded. Data was extracted from articles by a standard form. Meta-analysis was conducted to obtain a summary measure of the effectiveness of the interventions in reducing perinatal depressive symptoms. The theoretical underpinnings and implementation processes of the interventions were also characterised. Findings: A total of 6,857 articles were identified in the initial database searching, of which, 26 studies were eligible for data analysis, representing a sample size of 4,673. Meta-analysis indicated that psychosocial interventions in China significantly reduced perinatal depressive symptoms (standard difference in means 0·81, 95% confidence intervals -1·03 to -0·58, P

Increased nasopharyngeal colonization density has been associated with pneumonia. We used experimental human pneumococcal carriage to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. A total of 101 healthy subjects were screened for respiratory virus before pneumococcal intranasal challenge. Virus was associated with increased odds of colonization (75% virus positive became colonized vs. 46% virus-negative subjects; P=0.02). Nasal Factor H (FH) levels were increased in virus-positive subjects and were associated with increased colonization density. Using an in vitro epithelial model we explored the impact of increased mucosal FH in the context of coinfection. Epithelial inflammation and FH binding resulted in increased pneumococcal adherence to the epithelium. Binding was partially blocked by antibodies targeting the FH-binding protein Pneumococcal surface protein C (PspC). PspC epitope mapping revealed individuals lacked antibodies against the FH binding region. We propose that FH binding to PspC in vivo masks this binding site, enabling FH to facilitate pneumococcal/epithelial attachment during viral infection despite the presence of anti-PspC antibodies. We propose that a PspC-based vaccine lacking binding to FH could reduce pneumococcal colonization, and may have enhanced protection in those with underlying viral infection.

Objectives To describe the use of maternal health services according to the standards of the Chinese Ministry of Health, and assess socio-economic inequalities in usage in rural Shaanxi province, western China. Study design Cross-sectional survey. Methods Principal components analysis was used to measure the economic status of households. A concentration index (CI) approach was used as a measure of socio-economic inequalities in the use of maternal health services, and a decomposable CI was used to identify the factors that contributed to the socio-economic inequalities in usage. Results In total, 4760 women who had given birth in the preceding three years were selected at random to be interviewed in the five counties. Household wealth index was calculated by constructing a linear index from asset ownership indicators using principal components analysis to derive weights. The CI approach is a standard measure in the analysis of inequalities in health. If the CI for the use of maternal health services is positive, it is pro-rich; if it is negative, it is pro-poor. The decomposition method was used to estimate the contributions of individual factors to CI. The overall CI for five or more prenatal visits was 0.075. The household wealth index was found to make the greatest contribution to socio-economic inequalities for five or more prenatal visits (35.5%), followed by maternal education (28.8%), receipt of a health handbook during pregnancy (12.1%), age group (11.0%), distance from health facility (10.5%), family members (1.5%) and district of residence (0.6%). Conclusions Socio-economic inequalities in the use of prenatal health services were pro-rich in rural western China. Socio-economic inequalities in hospital delivery and postnatal health check-ups were not evident. Improving household economic status, providing prenatal health services for women with low income and low educational level, providing health handbooks and improving traffic conditions should be promoted as methods to eliminate socio-economic inequalities in the use of maternal health services.

Background: Micronutrient supplementation is often prescribed during pregnancy. The effects of prenatal iron and multimicronutrient supplementation on intellectual development in young school-aged children are less than clear. Objective: The aim of this study was to examine the long-term effects of prenatal iron plus folic acid or multiple micronutrient (including iron and folic acid) supplementation vs. folic acid supplementation on the intellectual development of young school-aged children in rural China. Methods: Young school-aged children (aged 7210 y, n = 1744) of women who had participated in a trial of prenatal supplementation with various combinations of micronutrients and remained residents in 2 rural counties in China were followed. We measured their intellectual development by Wechsler Intelligence Scale for Children Fourth Edition (WISCIV). The WISC-IV generated the Full-Scale Intelligence Quotient (FSIQ), Verbal Comprehension Index (VCI), Working Memory Index (WMI), Perceptual Reasoning Index (PRI), and Processing Speed Index (PSI). Multilevel analyses were used to assess the effect of prenatal micronutrient supplementation on the intellectual development of children. Results: The mean differences in FSIQ, VCI, WMI, PRI, and PSI, respectively, were not significant between prenatal folic acid supplementation and either iron plus folic acid [20.34 (P = 0.65), 20.06 (P = 0.95), 20.22 (P = 0.76), 20.01 (P = 0.99), and 21.26 (P = 0.11)] or multimicronutrient [20.39 (P = 0.60), 20.64 (P = 0.48), 0.11 (P = 0.87), 20.43 (P = 0.59), and 20.34; (P = 0.65)] supplementation after adjusting for confounders. Conclusions: No evidence suggests different effects on intellectual development between prenatal iron plus folic acid, multimicronutrient supplementation, and prenatal folic acid supplementation in children aged 7210 y. This trial was registered at www.isrctn.com as ISRCTN08850194. J Nutr doi: 10.3945/jn.114.207795.

Background: Health anxiety is common in medical settings and can be treated successfully by cognitive behaviour therapy. However it is not clear who might be best placed to deliver this therapy. Objectives: In a planned secondary analysis of data from a randomised trial of adapted cognitive behaviour therapy for health anxiety we compared outcomes of therapy delivered by nurses and other professional groups. Design: A randomised controlled trial with two treatment arms, 5-10 sessions of cognitive behaviour therapy adapted health anxiety or standard care. Setting: Cardiology, endocrine, gastroenterology, neurological and respiratory clinics in six general hospitals in the UK covering urban, suburban and rural areas. Participants: Medical patients attending the clinics who had pathological health anxiety and also scored for a diagnosis of hypochondriasis. Methods: Patients were randomised to one of two treatment arms, 5-10 sessions of cognitive behaviour therapy adapted health anxiety or standard care delivered by naive therapists (not randomised) who were trained in advance before delivering the treatment. Independent assessment of outcomes by researchers masked to allocation status at 3. m, 6. m, 12. m and 24. m. Results: 444 patients were randomised in the trial, 219 to cognitive behaviour therapy adapted health anxiety and 225 to standard care. 373 (84%) completed assessments after two years. Those treated by nurses (n = 66) had improvement in health anxiety, generalised anxiety and depression outcomes that were significantly better and twice as great as those of the professional groups of assistant psychologists (n = 87) and graduate workers (n = 66) (P

Summary Background Medical abortion is under-used in developing countries. We assessed whether early first-trimester medical abortion provided by midlevel providers (government-trained, certified nurses and auxiliary nurse midwives) was as safe and effective as that provided by doctors in Nepal. Methods This multicentre randomised controlled equivalence trial was done in five rural district hospitals in Nepal. Women were eligible for medical abortion if their pregnancy was of less than 9 weeks (63 days) and if they resided less than 90 min journey away from the study clinic. Women were ineligible if they had any contraindication to medical abortion. We used a computer-generated randomisation scheme stratified by study centre with a block size of six. Women were randomly assigned to a doctor or a midlevel provider for oral administration of 200 mg mifepristone followed by 800 μg misoprostol vaginally 2 days later, and followed up 10–14 days later. The primary endpoint was complete abortion without manual vacuum aspiration within 30 days of treatment. The study was not masked. Abortions were recorded as complete, incomplete, or failed (continuing pregnancy). Analyses for primary and secondary endpoints were by intention to treat, supplemented by per-protocol analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT01186302. Findings Of 1295 women screened, 535 were randomly assigned to a doctor and 542 to a midlevel provider. 514 and 518, respectively, were included in the analyses of the primary endpoint. Abortions were judged complete in 504 (97·3%) women assigned to midlevel providers and in 494 (96·1%) assigned to physicians. The risk difference for complete abortion was 1·24% (95% CI −0·53 to 3·02), which falls within the predefined equivalence range (−5% to 5%). Five cases (1%) were recorded as failed abortion in the doctor cohort and none in the midlevel provider cohort; the remaining cases were recorded as incomplete abortions. No serious complications were noted. Interpretation The provision of medical abortion up to 9 weeks' gestation by midlevel providers and doctors was similar in safety and effectiveness. Where permitted by law, appropriately trained midlevel health-care providers can provide safe, low-technology medical abortion services for women independently from doctors. Funding UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR), World Health Organization.

Subjective quality of life (SQOL) is an important outcome in the treatment of patients with schizophrenia. However, there is only limited evidence on factors influencing SQOL, and little is known about whether the same factors influence SQOL in patients with schizophrenia and other mental disorders. This study aimed to identify the factors associated with SQOL and test whether these factors are equally important in schizophrenia and other disorders. For this we used a pooled data set obtained from 16 studies that had used either the Lancashire Quality of Life Profile or the Manchester Short Assessment of Quality of Life for assessing SQOL. The sample comprised 3936 patients with schizophrenia, mood disorders, and neurotic disorders. After controlling for confounding factors, within-subject clustering, and heterogeneity of findings across studies in linear mixed models, patients with schizophrenia had more favourable SQOL scores than those with mood and neurotic disorders. In all diagnostic groups, older patients, those in employment, and those with lower symptom scores had higher SQOL scores. Whilst the strength of the association between age and SQOL did not differ across diagnostic groups, symptom levels were more strongly associated with SQOL in neurotic than in mood disorders and schizophrenia. The association of employment and SQOL was stronger in mood and neurotic disorders than in schizophrenia. The findings may inform the use and interpretation of SQOL data for patients with schizophrenia.

SummaryBackgroundExamination of bronchoalveolar lavage, induced sputum, and peripheral blood indicate that cysteinyl leukotriene receptor blockers decrease inflammatory cells in asthma but these do not examine airway tissue per se.ObjectivesOur objective was to determine the effect of montelukast, a leukotriene receptor antagonist, on airway tissue inflammatory cells by direct bronchoscopic examination of the bronchial mucosa.MethodsAdult subjects with mild asthma (pre-bronchodilator FEV1≥70% predicted; PC20 of ≤4mg/mL) were given 10mg/day oral montelukast (N=38) or placebo (N=37) for 6weeks. Bronchial mucosal eosinophils and mast cells were identified and counted.ResultsChange from baseline in numbers of biopsy EG2+ (“activated”) eosinophils was the primary endpoint; numbers of total (chromotrope 2R+) eosinophils and (tryptase+) mast cells were secondary. Unexpectedly, there were many patients with zero EG2+ eosinophils at baseline. There was a within-group decrease in EG2+ cells, from 13.54cells/mm (at baseline) to 0.79cells/mm at 6weeks in the montelukast group (LS mean change; 95% confidence interval=−13.59 [−25.45, −1.74]cells/mm; P

Objectives The goal of this study was to identify potentially novel laboratory markers of risk in chronic heart failure patients. Background Although a variety of prognostic markers have been described in heart failure, a systematic assessment of routine laboratory values has not been reported. Methods All 2,679 symptomatic chronic heart failure patients from the North American CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) program had a wide range of laboratory measures performed at a core facility, enabling us to assess the relationship between routine blood tests and outcomes using a Cox proportional hazards model. We then replicated our findings in a cohort of 2,140 heart failure patients from the Duke Databank. Results Among 36 laboratory values considered in the CHARM program, higher red cell distribution width (RDW) showed the greatest association with morbidity and mortality (adjusted hazard ratio 1.17 per 1-SD increase, p Conclusions In 2 large contemporary heart failure populations, RDW was found to be a very strong independent predictor of morbidity and mortality. Understanding how and why this marker is associated with outcome may provide novel insights into heart failure pathophysiology.

Objectives Short-term randomised trials suggest that patients with diabetes mellitus (DM), admitted with acute coronary syndromes (ACS) are at increased risk of subsequent adverse events. We tested whether this hypothesis was true for an unselected population of ACS patients with and without DM admitted with non-ST elevation MI or unstable angina, in a non-trial setting over a longer term of follow-up. Methods Prospective, centrally, coordinated multicenter registry involving 56 centers throughout the UK (half having angiographic facilities). Consecutive patients admitted with ACS without ST elevation on the presenting ECG were followed up to 6 months. A sub-group of patients were flagged with the UK Office for National Statistics and followed-up for death over 4 years. Results Data were collected on 1046 ACS patients of whom 170 (16%) had a prior diagnosis of DM. DM patients had higher baseline co-morbidities and unadjusted mortality rates at 6 months (11.8% vs. 6.4%, p =0.01). After correcting for clinical variables such as age, gender, smoking status and chest pain/ischaemic ECG changes on admission, prior history of any of myocardial infarction, heart failure, hypertension, hypercholesterolemia (on treatment), stroke or coronary revascularisation (PTCA or CABG), mortality rates for DM patients were no longer significantly raised (hazard ratio 1.35, 95% CI: 0.79–2.30; p =0.27 at 6 months and 1.15, 95% CI 0.72–1.83 at 4 years). 30% of diabetics were dead after 4 years of follow-up. Patients with DM were more likely to have been revascularised at 6 months and were more likely to receive ACE inhibitors. Based on the rate of recruitment and the population covered in the study, about 21,000 patients with DM will be admitted with non-ST elevation ACS each year in the UK. Conclusions DM is common amongst patients admitted with ACS without ST elevation and is associated with significant morbidity and mortality: approximately 1 in 8 will not survive up to 6 months and 1 in 3 to 4 years. DM patients should be managed aggressively to reduce their risk of future complications.

OBJECTIVES: The purpose of this study was to determine the pathologic basis of Q-wave (QW) and non-Q-wave (NQW) myocardial infarction (MI). BACKGROUND: The QW/NQW distinction remains in wide clinical use but the meaning of the difference remains controversial. We hypothesized that measurement of total MI size and transmural extent by late gadolinium enhancement cardiovascular magnetic resonance (CMR) would identify the pathologic basis of QWs. METHODS: A total of 100 consecutive patients with documented previous MI had electrocardiogram and CMR on the same day. Patients with acute MI within seven days were excluded. Left ventricular function and the size and transmural extent of MI were quantified in the three major arterial territories and correlated with the presence of QW. RESULTS: Subendocardial MI showed QW in 28%. Transmural MI showed NQW in 29%. Of all MIs, 48% were at some point transmural, and 99% of these were at some point non-transmural. As MI size and number of transmural segments increased, the probability of QW increased (anterior: total size chi-square = 53, p < 0.0001, transmural extent chi-square = 36, p < 0.0001; inferior: total size chi-square = 16, p = 0.001, transmural extent chi-square = 10, p = 0.001). These findings did not hold for lateral MI. In a multivariate model, the transmural extent of MI was not an independent predictor of QW when total size of MI was removed. The QW/NQW classification was a good test for size of MI (area under receiver operating characteristic curve: anterior 0.90, inferior 0.77). CONCLUSIONS: The QW/NQW distinction is useful, but it is determined by the total size rather than transmural extent of underlying MI.

This study examines patterns and differentials of contraceptive failure rates by method and characteristics of users, using the Chinese Two-per-Thousand Fertility Survey data. The results show that contraceptive failure rates for modern methods including sterilization are some of the highest in the world. The first year failure rates are 4.2% for male sterilization, 0.7% for female sterilization, 10.3% for IUD, 14.5% for pill, and 19.0% for condom. There are also some differentials in contraceptive failure rates by users' sociodemographic and fertility characteristics. Contraceptive failure rate declines with women's age for all reversible methods. Rural women have higher sterilization, IUD, and condom contraceptive failure rates than urban women. Women with two or more children have a higher failure rate for sterilization methods but have lower failure rates for other methods.

We read with interest the letter from Dr. Dastidar and colleagues in which they express their views and compare our report of the randomized CvLPRIT (Complete Versus Lesion-Only Primary PCI Trial) [(1)][1] with their in-house clinical experience. They suggest that the trial was not run according to