Are routinely collected NHS administrative records suitable for endpoint identification in clinical trials? Evidence from the West of Scotland coronary prevention study

Background: Routinely collected electronic patient records are already widely used in epidemiological research. In this work we investigated the potential for using them to identify endpoints in clinical trials.<p></p> Methods: The events recorded in the West of Scotland Coronary Prevention Study (WOSCOPS), a large clinical trial of pravastatin in middle-aged hypercholesterolaemic men in the 1990s, were compared with those in the record-linked deaths and hospitalisations records routinely collected in Scotland.<p></p> Results: We matched 99% of fatal study events by date. We showed excellent matching (97%) of the causes of fatal endpoint events and good matching (.80% for first events) of the causes of nonfatal endpoint events with a slightly lower rate of mismatching of record linkage than study events (19% of first study myocardial infarctions (MI) and 4% of first record linkage MIs not matched as MI). We also investigated the matching of non-endpoint events and showed a good level of matching, with .78% of first stroke/TIA events being matched as stroke/TIA. The primary reasons for mismatches were record linkage data recording readmissions for procedures or previous events, differences between the diagnoses in the routinely collected data and the conclusions of the clinical trial expert adjudication committee, events occurring outside Scotland and therefore being missed by record linkage data, miscoding of cardiac events in hospitalisations data as ‘unspecified chest pain’, some general miscoding in the record linkage data and some record linkage errors.<p></p> Conclusions: We conclude that routinely collected data could be used for recording cardiovascular endpoints in clinical trials and would give very similar results to rigorously collected clinical trial data, in countries with unified health systems such as Scotland. The endpoint types would need to be carefully thought through and an expert endpoint adjudication committee should be involved.<p></p&gt

Triggered massive-star formation on the borders of Galactic HII regions. IV- Star formation at the periphery of Sh2-212

Aims: We wish to establish whether sequential star formation is taking place at the periphery of the Galactic HII region Sh2-212. Methods: We present CO millimetre observations of this region obtained at the IRAM 30-m telescope to investigate the distribution of associated molecular material. We also use deep JHK observations obtained at the CFHT to study the stellar content of the region, and radio observations obtained at the VLA to look for the presence of an ultra-compact (UC) HII region and for maser emission. Results: In the optical, Sh2-212 is spherically symmetric around its central exciting cluster. This HII region is located along a molecular filament. A thin, well-defined half ring of molecular material surrounds the brightest part of the HII region at the rear and is fragmented. The most massive fragment (~200 solar masses) contains a massive young stellar object displaying a near-IR excess; its spectral energy distribution indicates a high-mass (~14solar masses), high-temperature (~30000K), and high-luminosity (~17000 solar luminosities) source. This object ionizes a UC HII region. Conclusions: Sh2-212 is a good example of massive-star formation triggered via the collect and collapse process. The massive YSO observed at its periphery is a good candidate for a massive star formed in isolation.Comment: 12 pages, 14 figures. To be published in A&

Academic self-concept, gender and single-sex schooling

This paper assesses gender differences in academic self-concept for a cohort of children born in 1958 (the National Child Development Study). We address the question of whether attending single-sex or co-educational schools affected students’ perceptions of their own academic abilities (academic self-concept). Academic selfconcept was found to be highly gendered, even controlling for prior test scores. Boys had higher self-concepts in maths and science, and girls in English. Single-sex schooling reduced the gender gap in self-concept, while selective schooling was linked to lower academic self-concept overall

Poverty and mental health: the work of the female sanitary inspectors in Bradford (c. 1901–1912)

This is the final version of the article. Available from Palgrave Macmillan via the DOI in this record.Although there are many excellent studies of the work of pioneer women public health officers, few accounts dwell on mental health issues or discuss any relationship that such staff might have understood to exist between poverty and mental health in the early twentieth century. This is a remarkable omission considering that social and feminist historians have highlighted the problems created by the way early practitioners sought to manage poverty and arguably the poor. Drawing on records created by Female Sanitary Inspectors (FSIs) in Bradford, this study chronicles distressing economic and social conditions but also reveals encounters between the staff and people experiencing mental health problems and mental health crises. The ways in which the FSIs chose to both make and deny links between the abject poverty witnessed in the slum districts and cases of mental disorder forms an important strand to the analysis that follows. Interestingly, it is the well-being of the staff that emerges as a persistent and even over-riding concern.This work was generously supported by Wellcome Trust Grant 074999. This was a personal fellowship entitled 'The Medical Officer of Health and the Organisation of Health Visiting as a Comprehensive Community Health Service, 1906-1974'

The Effectiveness of Alcohol Screening and Brief Intervention in Emergency Departments: A Multicentre Pragmatic Cluster Randomized Controlled Trial

BACKGROUND: Alcohol misuse is common in people attending emergency departments (EDs) and there is some evidence of efficacy of alcohol screening and brief interventions (SBI). This study investigated the effectiveness of SBI approaches of different intensities delivered by ED staff in nine typical EDs in England: the SIPS ED trial. METHODS AND FINDINGS: Pragmatic multicentre cluster randomized controlled trial of SBI for hazardous and harmful drinkers presenting to ED. Nine EDs were randomized to three conditions: a patient information leaflet (PIL), 5 minutes of brief advice (BA), and referral to an alcohol health worker who provided 20 minutes of brief lifestyle counseling (BLC). The primary outcome measure was the Alcohol Use Disorders Identification Test (AUDIT) status at 6 months. Of 5899 patients aged 18 or more presenting to EDs, 3737 (63·3%) were eligible to participate and 1497 (40·1%) screened positive for hazardous or harmful drinking, of whom 1204 (80·4%) gave consent to participate in the trial. Follow up rates were 72% (n?=?863) at six, and 67% (n?=?810) at 12 months. There was no evidence of any differences between intervention conditions for AUDIT status or any other outcome measures at months 6 or 12 in an intention to treat analysis. At month 6, compared to the PIL group, the odds ratio of being AUDIT negative for brief advice was 1·103 (95% CI 0·328 to 3·715). The odds ratio comparing BLC to PIL was 1·247 (95% CI 0·315 to 4·939). A per protocol analysis confirmed these findings. CONCLUSIONS: SBI is difficult to implement in typical EDs. The results do not support widespread implementation of alcohol SBI in ED beyond screening followed by simple clinical feedback and alcohol information, which is likely to be easier and less expensive to implement than more complex interventions

Using ion mobility spectrometry-mass spectrometry to decipher the conformational and assembly characteristics of the hepatitis B capsid protein.

The structural and functional analysis of the core protein of hepatitis B virus is important for a full understanding of the viral life cycle and the development of novel therapeutic agents. The majority of the core protein (CP149) comprises the capsid assembly domain, and the C-terminal region (residues 150-183) is responsible for nucleic acid binding. Protein monomers associate to form dimeric structural subunits, and helices 3 and 4 (residues 50-111 of the assembly domain) have been shown to be important for this as they constitute the interdimer interface. Here, using mass spectrometry coupled with ion mobility spectrometry, we demonstrate the conformational flexibility of the CP149 dimer. Limited proteolysis was used to locate involvement in this feature to the C-terminal region. A genetically fused CP dimer was found to show decreased disorder, consistent with a more restricted C-terminus at the fusion junction. Incubation of CP149 dimer with heteroaryldihydropyrimidine-1, a small molecule known to interfere with the assembly process, was shown to result in oligomers different in shape to the capsid assembly-competent oligomers of the fused CP dimer. We suggest that heteroaryldihydropyrimidine-1 affects the dynamics of CP149 dimer in solution, likely affecting the ratio between assembly active and inactive states. Therefore, assembly of the less dynamic fused dimer is less readily misdirected by heteroaryldihydropyrimidine-1. These studies of the flexibility and oligomerization properties of hepatitis B virus core protein illustrate both the importance of C-terminal dynamics in function and the utility of gas-phase techniques for structural and dynamical biomolecular analysis

A <i>Herschel</i> and BIMA study of the sequential star formation near the W 48A H II region

We present the results of Herschel HOBYS (Herschel imaging survey of OB Young Stellar objects) photometric mapping combined with Berkeley Illinois Maryland Association (BIMA) observations and additional archival data, and perform an in-depth study of the evolutionary phases of the star-forming clumps in W 48A and their surroundings. Age estimates for the compact sources were derived from bolometric luminosities and envelope masses, which were obtained from the dust continuum emission, and agree within an order of magnitude with age estimates from molecular line and radio data. The clumps in W 48A are linearly aligned by age (east-old to west-young): we find a ultra-compact (UC) H II region, a young stellar object (YSO) with class II methanol maser emission, a YSO with a massive outflow and finally the NH2D prestellar cores from Pillai et al. This remarkable positioning reflects the (star) formation history of the region. We find that it is unlikely that the star formation in the W 48A molecular cloud was triggered by the UC H II region and discuss the Aquila supershell expansion as a major influence on the evolution of W 48A. We conclude that the combination of Herschel continuum data with interferometric molecular line and radio continuum data is important to derive trustworthy age estimates and interpret the origin of large-scale structures through kinematic information

Low mid-upper arm circumference identifies children with a high risk of death who should be the priority target for treatment

Background: Severe acute malnutrition (SAM) is currently defined by the WHO as either a low mid-upper arm circumference (i.e. MUAC <115 mm), a low weight-for-height z-score (i.e. WHZ <- 3), or bilateral pitting oedema. MUAC and WHZ do not always identify the same children as having SAM. This has generated broad debate, as illustrated by the recent article by Grellety & Golden (BMC Nutr. 2016;2:10). Discussion: Regional variations in the proportion of children selected by each index seem mostly related to differences in body shape, including stuntedness. However, the practical implications of these variations in relation to nutritional status and also to outcome are not clear. All studies that have examined the relationship between anthropometry and mortality in representative population samples in Africa and in Asia have consistently showed that MUAC is more sensitive at high specificity levels than WHZ for identifying children at high risk of death. Children identified as SAM cases by low MUAC gain both weight and MUAC in response to treatment. The widespread use of MUAC has brought enormous benefits in terms of the coverage and efficiency of programs. As a large high-risk group responding to treatment, children with low MUAC should be regarded as a public health priority independently of their WHZ. Conclusion: While a better understanding of the mechanism behind the discrepancy between MUAC and WHZ is desirable, research in this area should not delay the implementation of programs aiming at effectively reducing malnutrition-related deaths by prioritising the detection and treatment of children with low MUAC