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Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is a major route of HBV transmission worldwide despite an existing immunoprophylaxis regimen. The implementation of immunoprophylaxis has been challenging, especially in low-income and middle-income countries, where MTCT is common, because of difficulty obtaining and delivering the monovalent HBV vaccine and the HBV immunoglobulin. Global control of the HBV epidemic will need improved prevention of MTCT. We discuss research gaps that hinder development of new options for the elimination of MTCT as well as policy changes that may help the current vaccine-based strategy to live up to its full potential. We propose that decreasing hepatitis B viral concentrations before delivery, along with HBV vaccine use, could provide an alternative strategy that would decrease MTCT of HBV.

ObjectivesThe coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19.Design, setting and participantsCross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO’s International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers.Main outcome(s)Trial intervention, sponsorship, critical design elements and specified outcomesResultsOverall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020.ConclusionsWhile accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.

Hepatitis B virus (HBV) infection remains a serious public health problem worldwide. Mother-to-child transmission (MTCT) of HBV is the major mode of transmission in HBV-endemic areas, including China, where little is known about pregnant women's knowledge of and attitudes towards HBV infection and MTCT. A cross-sectional survey, conducted in pregnant women in Guangdong Province, China, measured HBV knowledge and attitudes using a questionnaire, at one tertiary and two rural hospitals. The total response rate was 94.5% (737/780). Of the 11 knowledge questions, the mean score was 6.73 ± 3.04 (mean ± SD). Most pertinent to preventing MTCT, 53.3% of the respondents did not know that HBV can be transmitted through unprotected sexual intercourse and nearly 20% did not know that HBV can be transmitted from mother to infant. The results of the four attitude questions was better with 83% and 85% being willing to be screened for HBV and let their baby receive HBV vaccine and HBIg, respectively. However, only 16.5% of respondents agreed that they would be willing to take drugs that are known not to harm the fetus to prevent MTCT of HBV. In multivariable analysis, higher education level was associated with better knowledge and attitude scores. Knowledge about HBV among pregnant women was poor and needs to be improved to prevent MTCT of HBV. Health education needs to be directed towards pregnant mothers, particularly less educated mothers, in high HBV endemicity settings.

Background Central line-associated bloodstream infections (CLABSI) are a major source of sepsis in modern intensive care medicine. Some years ago bundle interventions have been introduced to reduce CLABSI. The use of checklists may be an additional tool to improve the effect of these bundles even in highly specialized institutions. In this study we investigate if the introduction of a checklist reduces the frequency of CLABSI. Methods During the study period from October 2011 to September 2012, we investigated the effect of implementing a checklist for the placement of central venous lines (CVL). Patients were allocated either to the checklist group or to the control group, roughly in a 1:2 ratio. The frequency of CLABSI was compared between the two groups. Results During the study period 4416 CVL were inserted; 1518 in the checklist group and 2898 in the control group. The use of the checklist during CVL placement resulted in a lower CLABSI frequency. The incidence in the checklist group was 3.8 per 1000 catheter days as compared to 5.9 per 1000 catheter days in the control group (IRR = 0.57; p  = 0.001). The use of the checklist also reduced the frequency of catheter colonisation significantly, 36.3 per 1000 catheter days in the checklist group vs 21.2 per 1000 catheter days in the control group, respectively (IRR = 0.58; p  < 0.001). Conclusion The introduction of a checklist to improve the adherence to hygiene standards while placement of central venous lines reduced the frequency of infections significantly.

Cardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) in patients without cardiovascular or renal disease, a majority of newly diagnosed patients with type 2 diabetes often excluded from clinical trials on this association, is poorly understood. Thus, we investigate the risk of major adverse cardiovascular events (MACE) associated with DPP-4i in low-risk patients with diabetes. Using a new-user retrospective cohort derived from IBM MarketScan Commercial Claims and Encounters (2010-2015), we identified patients aged 35-65 with type 2 diabetes, without cardiovascular or renal disease, initiating DPP-4i, sulfonylureas, or metformin. Primary composite outcome of time to first MACE was defined as the first of any of the following: myocardial infarction, cardiac arrest, coronary artery bypass graft, coronary angioplasty, heart failure, and stroke. Secondary outcomes were time to first heart failure, acute myocardial infarction, and stroke. We compared outcomes for DPP-4i versus sulfonylurea and DPP-4i versus metformin using propensity score weighted Cox proportional hazards, adjusting for demographics, baseline comorbidities, concomitant medications, and cumulative exposure. Of 445,701 individuals, 236,431 (53.0%) were male, median age was 51 (interquartile range: [44, 57]), 30,267 (6.79%) initiated DPP-4i, 52,138 (11.70%) initiated sulfonylureas, and 367,908 (82.55%) initiated metformin. After adjustment, DPP-4i was associated with lower risk of MACE than sulfonylurea (adjusted hazard ratio (aHR) = 0.87; 95% confidence interval (CI): 0.78-0.98), and similar risk to metformin (aHR = 1.07; 95% CI: 0.97-1.18). Risk for acute myocardial infarction (aHR = 0.70; 95% CI: 0.51-0.96), stroke (aHR = 0.57; 95% CI: 0.41-0.79), and heart failure (aHR = 0.57; 95% CI: 0.41-0.79) with DPP-4i was lower compared to sulfonylureas. Our findings show that for this cohort of low-risk patients newly treated for type 2 diabetes, DPP-4i exhibited 13% lower risk for MACE compared to sulfonylureas and similar risk for MACE compared to metformin, suggesting DPP-4i is a low cardiovascular risk option for low-risk patients initiating antihyperglycemic treatment.

Common mental disorders, particularly unipolar depressive disorders, rank among the top 5 with respect to the global burden of disease. As a major public health concern, antepartum depression and anxiety not only affects the individual woman, but also her offspring. Data on the prevalence of common mental disorders in pregnant women in sub-Saharan Africa are scarce. We provide results from Ghana and Côte d'Ivoire. We subsequently recruited and screened n = 1030 women in the third trimester of their pregnancy for depressed mood, general anxiety, and perceived disability using the Patient Health Questionnaire depression module (PHQ-9), the 7-item Anxiety Scale (GAD-7), and the World Health Organisation Disability Assessment Schedule II (WHO-DAS 2.0, 12-item version). In addition to estimates of means and prevalence, a hierarchical linear regression model was calculated to determine the influence of antepartum depression and anxiety on disability. In Ghana, 26.6% of women showed substantially depressed mood. In Côte d'Ivoire, this figure was even higher (32.9%). Clear indications for a generalized anxiety disorder were observed in 11.4% and 17.4% of pregnant women, respectively. Comorbidity of both conditions was common, affecting about 7.7% of Ghanaian and 12.6% of Ivorian participants. Pregnant women in both countries reported a high degree of disability regarding everyday activity limitations and participation restrictions. Controlled for country and age, depression and anxiety accounted for 33% of variance in the disability score. Antepartum depression and anxiety were highly prevalent in our sample and contributed substantially to perceived disability. These serious threats to health must be further investigated and more data are needed to comprehensively quantify the problem in sub-Saharan Africa.

Clinical trials investigating cardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) among patients with cardiovascular and renal disease rarely recruit patients with renal impairment, despite associations with increased risk for major adverse cardiovascular events (MACE). We investigated the risk of MACE associated with the use of DPP-4i among these high-risk patients. Using a new-user, retrospective, cohort design, we analyzed 2010–2015 IBM MarketScan Commercial Claims and Encounters for patients with diabetes, comorbid with cardiovascular disease and/or renal impairment. We compared time to first MACE for DPP-4i versus sulfonylurea and versus metformin. Of 113,296 individuals, 9146 (8.07%) were new DPP-4i users, 17,481 (15.43%) were new sulfonylurea users, and 88,596 (78.20%) were new metformin users. Exposure groups were not mutually exclusive. DPP-4i was associated with lower risk for MACE than sulfonylurea (aHR 0.84; 95% CI 0.74, 0.93) and similar risk for MACE to metformin (aHR 1.07; 95% CI [1.04, 1.16]). DPP-4i use was associated with lower risk for MACE compared to sulfonylureas and similar risk for MACE compared to metformin. This association was most evident in the first year of therapy, suggesting that DPP-4i is a safer choice than sulfonylurea for diabetes treatment initiation in high-risk patients.

To evaluate the association between the nature of findings and the switching of registered primary outcomes among randomized controlled trials (RCTs) from mainland China. This is a retrospective cohort study. We retrieved RCTs from trial registries and identified the corresponding journal articles from bibliographic databases until August 2019. Trial registries and journal articles were compared to evaluate whether registered primary outcomes with negative findings were more likely to be switched to secondary outcomes in the subsequent journal articles than those with positive findings. Switching of registered primary outcomes occurred in 131 (45%) of 294 RCTs. A total of 450 registered primary outcomes were matched to 522 (37%) primary outcomes and 871 (63%) secondary outcomes in the journal articles. Among RCTs registered before they started, the odds of switching primary outcomes with negative findings were 2.64 (95% CI: 1.16–6.02) times the odds of switching those with positive findings. Among RCTs registered when they were ongoing, the odds of switching primary outcomes with negative findings were 8.84 (95% CI: 3.62–25.93) times the odds of switching those with positive findings. The nature of findings may play a role in how likely a prespecified primary outcome is switched subsequently. •Primary outcome switching is prevalent among randomized trials from China.•Registered primary outcomes with negative findings are more likely to be switched.•The registration timing modifies this association.•Trial registration should be prompted to detect primary outcome switching.

The vast majority of research on mental health has been undertaken in high income countries. This study aimed at investigating the long-term course of maternal depressive symptoms and its association with various mother- and child-related characteristics in two West African lower middle income countries with focus on the relationship with long-term anxiety symptoms. In the Child Development Study, a prospective birth cohort study in Côte d'Ivoire and Ghana, the 9-item Patient Health Questionnaire (PHQ-9) was answered by N = 776 women 3 months antepartum, and 3, 12, and 24 months postpartum between April 2010 and March 2014. Growth mixture modeling was used to identify distinct trajectories of depressive symptoms. Several psychosocial, obstetric, and sociodemographic characteristics were assessed and multinomial regression analysis was performed to investigate the influence of these variables on the different depression trajectories. We found three distinct classes of depressive symptoms that were characterized by an asymptomatic trajectory (91.5%), by recurrent risk (4.3%) and by postnatal risk (4.3%). The longitudinal course of depressive symptoms was strongly associated with anxiety symptoms (χ2 = 258.54, df = 6, p < 0.001; φ = .577). Among other factors, higher levels of anxiety, new pregnancy 2 years after birth, economic stress, and family stress were associated with the risk classes. A substantial proportion of West African women in our sample developed unfavorable patterns of depressive symptoms during the vulnerable phase of pregnancy and early motherhood. Psychosocial factors, especially antepartum anxiety symptoms, played a decisive role in this process. Perceived economic hardship further exaggerated the mental health burden.

Background Synthetic oxytocin (sOT) is frequently administered during parturition. Studies have raised concerns that fetal exposure to sOT may be associated with altered brain development and risk of neurodevelopmental disorders. In a large and diverse sample of children with data about intrapartum sOT exposure and subsequent diagnoses of two prevalent neurodevelopmental disorders, i.e., attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), we tested the following hypotheses: (1) Intrapartum sOT exposure is associated with increased odds of child ADHD or ASD; (2) associations differ across sex; (3) associations between intrapartum sOT exposure and ADHD or ASD are accentuated in offspring of mothers with pre-pregnancy obesity. Methods The study sample comprised 12,503 participants from 44 cohort sites included in the Environmental Influences on Child Health Outcomes (ECHO) consortium. Mixed-effects logistic regression analyses were used to estimate the association between intrapartum sOT exposure and offspring ADHD or ASD (in separate models). Maternal obesity (pre-pregnancy BMI ≥ 30 kg/m 2 ) and child sex were evaluated for effect modification. Results Intrapartum sOT exposure was present in 48% of participants. sOT exposure was not associated with increased odds of ASD (adjusted odds ratio [aOR] 0.86; 95% confidence interval [CI], 0.71–1.03) or ADHD (aOR 0.89; 95% CI, 0.76–1.04). Associations did not differ by child sex. Among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of offspring ADHD (aOR 0.72; 95% CI, 0.55–0.96). No association was found among mothers without obesity (aOR 0.97; 95% CI, 0.80–1.18). Conclusions In a large, diverse sample, we found no evidence of an association between intrapartum exposure to sOT and odds of ADHD or ASD in either male or female offspring. Contrary to our hypothesis, among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of child ADHD diagnosis.