Objectives To determine whether BCG vaccination protects against Mycobacterium tuberculosis infection as assessed by interferon γ release assays (IGRA) in children.Design Systematic review and meta-analysis. Searches of electronic databases 1950 to November 2013, checking of reference lists, hand searching of journals, and contact with experts. Setting Community congregate settings and households.Inclusion criteria Vaccinated and unvaccinated children aged under 16 with known recent exposure to patients with pulmonary tuberculosis. Children were screened for infection with M tuberculosis with interferon γ release assays. Data extractionStudy results relating to diagnostic accuracy were extracted and risk estimates were combined with random effects meta-analysis. ResultsThe primary analysis included 14 studies and 3855 participants. The estimated overall risk ratio was 0.81 (95% confidence interval 0.71 to 0.92), indicating a protective efficacy of 19% against infection among vaccinated children after exposure compared with unvaccinated children. The observed protection was similar when estimated with the two types of interferon γ release assays (ELISpot or QuantiFERON). Restriction of the analysis to the six studies (n=1745) with information on progression to active tuberculosis at the time of screening showed protection against infection of 27% (risk ratio 0.73, 0.61 to 0.87) compared with 71% (0.29, 0.15 to 0.58) against active tuberculosis. Among those infected, protection against progression to disease was 58% (0.42, 0.23 to 0.77). Conclusions BCG protects against M tuberculosis infection as well as progression from infection to disease.Trial registration PROSPERO registration No CRD42011001698 (www. crd.york.ac.uk/prospero/). IntroductionBCG vaccine has been the subject of numerous efficacy trials and epidemiological studies conducted over several decades. These trials indicate that BCG has 60-80% protective efficacy against severe forms of tuberculosis in children, particularly meningitis, 1 2 and its efficacy against pulmonary diseases varies geographically.3-5 BCG does not seem to protect against disease when it is given to people already infected or sensitised to environmental mycobacteria, which could explain the geographical variation.6-8 Until recently it was not possible to establish whether the protective effect of BCG vaccination against disease was from its action in preventing acquisition of infection or limited to prevention of progression from infection to clinical disease.The scarcity of evidence on whether the vaccine is effective against Mycobacterium tuberculosis infection was because of limitations of the tuberculin skin test. This test cannot distinguish a positive response caused by M tuberculosis infection from that caused by BCG vaccination or non-tuberculous In this systematic review we examined the evidence for the protective effect of BCG against M tuberculosis infection, as opposed to against disease, in settings where children can be presumed to have been exposed to M tu...

SUMMARYObjectives Many studies have investigated predictors of people with dementia entering 24-h care but this is the first to consider a comprehensive range of carer and care recipient (CR) characteristics derived from a systematic review, in a longitudinal cohort study followed up for several years. Methods We interviewed 224 people with Alzheimer's disease (AD) and their carers, recruited to be representative in terms of their severity, sex and living situation as part of the LASER-AD study; and determined whether they entered 24-h care in the subsequent 4.5 years. We tested a comprehensive range of characteristics derived from a systematic review, and used Cox proportional hazard regression to determine whether they independently predicted entering 24-h care.Results The main independent predictors of shorter time to enter 24-h care were the patient being: more cognitively or functionally impaired (hazard ratio (HR) ¼ 1.09; 95% CI ¼ 1.06-1.12) and (HR ¼ 1.04 95% CI ¼ 1.03-1.05), having a paid versus a family carer (HR ¼ 2.22; 95% CI ¼ 1.39-3.57), the carer being less educated (HR ¼ 1.43; 95% CI ¼ 1.12-1.83) and spending less hours caring (HR ¼ 1.01; 95% CI ¼ 1.00-1.01). Conclusion As having a family carer who spent more time caring (taking into account illness severity) delayed entry to 24-h care, future research should investigate how to enable carers to provide this. Other interventions to improve patients' impairment may not only have benefits for patients' health but also allow them to remain longer at home. This financial benefit could more than offset the treatment cost.

ObjectivesMedically unexplained symptoms (MUS) present frequently in healthcare, can be complex and frustrating for clinicians and patients and are often associated with overinvestigation and significant costs. Doctors need to be aware of appropriate management strategies for such patients early in their training. A previous qualitative study with foundation year doctors (junior doctors in their first 2 years postqualification) indicated significant lack of knowledge about this topic and appropriate management strategies. This study reviewed whether, and in what format, UK foundation training programmes for newly qualified doctors include any teaching about MUS and sought recommendations for further development of such training.DesignMixed-methods design comprising a web-based questionnaire survey and an expert consultation workshop.SettingNineteen foundation schools in England, Wales and Northern IrelandParticipantsQuestionnaire administered via email to 155 foundation training programme directors (FTPDs) attached to the 19 foundation schools, followed by an expert consultation workshop attended by 13 medical educationalists, FTPDs and junior doctors.ResultsThe 53/155 (34.2%) FTPDs responding to the questionnaire represented 15 of the 19 foundation schools, but only 6/53 (11%) reported any current formal teaching about MUS within their programmes. However, most recognised the importance of providing such teaching, suggesting 2–3 hours per year. All those attending the expert consultation workshop recommended case-based discussions, role-play and the use of videos to illustrate positive and negative examples of doctor–patient interactions as educational methods of choice. Educational sessions should cover the skills needed to provide appropriate explanations for patients’ symptoms as well as avoid unnecessary investigations, and providing information about suitable treatment options.ConclusionsThere is an urgent need to improve foundation level training about MUS, as current provision is very limited. An interactive approach covering a range of topics is recommended, but must be delivered within a realistic time frame for the curriculum.

Members of the clinical cohort recruitment and characterization group are listed in the Acknowledgements.

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