Safety and efficacy of antenatal milk expressing for women with diabetes in pregnancy: protocol for a randomised controlled trial

Many maternity providers recommend that women with diabetes in pregnancy express and store breast milk in late pregnancy so breast milk is available after birth, given (1) infants of these women are at increased risk of hypoglycaemia in the first 24 h of life; and (2) the delay in lactogenesis II compared with women without diabetes that increases their infant\u27s risk of receiving infant formula. The Diabetes and Antenatal Milk Expressing (DAME) trial will establish whether advising women with diabetes in pregnancy (pre-existing or gestational) to express breast milk from 36 weeks gestation increases the proportion of infants who require admission to special or neonatal intensive care units (SCN/NICU) compared with infants of women receiving standard care. Secondary outcomes include birth gestation, breastfeeding outcomes and economic impact

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Clinical outcomes for young people with screening-detected and clinically-diagnosed rheumatic heart disease in Fiji.

Echocardiographic screening is under consideration as a disease control strategy for rheumatic heart disease (RHD). However, clinical outcomes of young people with screening-detected RHD are unknown. We aimed to describe the outcomes for a cohort with screening-detected RHD, in comparison to patients with clinically-diagnosed RHD. A retrospective cohort study included all young people with screening-detected RHD in the Central Division of Fiji in the primary cohort. Screen-negative and clinically-diagnosed comparison groups were matched 1:1 to the primary cohort. Data were collected on mortality, clinical complications and healthcare utilisation from the electronic and paper health records and existing databases. Seventy participants were included in each group. Demographic characteristics of the groups were similar (median age 11years, 69% female, median follow-up 7years). There were nine (12.9%) RHD-related deaths in the clinically-diagnosed group and one (1.4%) in the screening-detected group (Incident Rate Ratio: 9.6, 95% CI 1.3-420.6). Complications of RHD were observed in 39 (55.7%) clinically-diagnosed cases, four (20%) screening-detected cases and one (1.4%) screen-negative case. There were significant differences in the cumulative complication curves of the groups (p<0.001). Rates of admission and surgery were highest in the clinically-diagnosed group, and higher in the screening-detected than screen-negative group. Young people with screening-detected RHD have worse health outcomes than screen-negative cases in Fiji. The prognosis of clinically-diagnosed RHD remains poor, with very high mortality and complication rates. Further studies in other settings will inform RHD screening policy. Comprehensive control strategies are required for disease prevention

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Change in bias in self-reported body mass index in Australia between 1995 and 2008 and the evaluation of correction equations

<p>Abstract</p> <p>Background</p> <p>Many studies have documented the bias in body mass index (BMI) determined from self-reported data on height and weight, but few have examined the change in bias over time.</p> <p>Methods</p> <p>Using data from large, nationally-representative population health surveys, we examined change in bias in height and weight reporting among Australian adults between 1995 and 2008. Our study dataset included 9,635 men and women in 1995 and 9,141 in 2007-2008. We investigated the determinants of the bias and derived correction equations using 2007-2008 data, which can be applied when only self-reported anthropometric data are available.</p> <p>Results</p> <p>In 1995, self-reported BMI (derived from height and weight) was 1.2 units (men) and 1.4 units (women) lower than measured BMI. In 2007-2008, there was still underreporting, but the amount had declined to 0.6 units (men) and 0.7 units (women) below measured BMI. The major determinants of reporting error in 2007-2008 were age, sex, measured BMI, and education of the respondent. Correction equations for height and weight derived from 2007-2008 data and applied to self-reported data were able to adjust for the bias and were accurate across all age and sex strata.</p> <p>Conclusions</p> <p>The diminishing reporting bias in BMI in Australia means that correction equations derived from 2007-2008 data may not be transferable to earlier self-reported data. Second, predictions of future overweight and obesity in Australia based on trends in self-reported information are likely to be inaccurate, as the change in reporting bias will affect the apparent increase in self-reported obesity prevalence.</p

The neighbourhood social environment and alcohol use among urban and rural Scottish adolescents

Funding for the Scottish Health Behaviour in School-aged Children was provided by NHS Scotland. This work was also supported by the 600th Anniversary Ph.D. Scholarship which was awarded to Gina Martin by the University of St Andrews.Objectives This research examined the relationship between neighbourhood social environmental characteristics and drinking outcomes among a sample of urban and rural adolescents. Methods From a sample of 1558 Scottish secondary schoolchildren, surveyed as part of the 2010 Health Behaviour in School-aged Children study, we modelled three drinking outcomes on a variety of neighbourhood conditions, including social cohesion, disorder, alcohol outlet density, deprivation, and urban/rurality. Nested and cross-classified multilevel logistic regressions were specified. Results An urban-to-rural gradient was found with non-urban adolescents exhibiting higher odds of having ever drank. Neighbourhood social cohesion related to having ever drank. Among drinkers, those living in accessible small towns had higher odds of weekly drinking and drunkenness compared to urban areas. Higher odds of drunkenness were also found in remote rural areas. Those residing in the least deprived areas had lower odds of weekly drinking. Conclusions In Scotland, inequalities exist in adolescent alcohol use by urban/rurality and neighbourhood social conditions. Findings support regional targeting of public health efforts to address inequalities. Future work is needed to develop and evaluate intervention and prevention approaches for neighbourhoods at risk.Publisher PDFPeer reviewe