Screening of healthcare workers for tuberculosis: development and validation of a new health economic model to inform practice

Methods for determining cost-effectiveness of different treatments are well established, unlike appraisal of non-drug interventions, including novel diagnostics and biomarkers

Organisational interventions to reduce length of stay in hospital: a rapid evidence assessment

This is the final version of the report. Available from the publisher via the DOI in this record.BACKGROUND: Available evidence on effective interventions to reduce length of stay in hospital is wide-ranging and complex, with underlying factors including those acting at the health system, organisational and patient levels, and the interface between these. There is a need to better understand the diverse literature on reducing the length of hospital stay. OBJECTIVES: This study sought to (i) describe the nature of interventions that have been used to reduce length of stay in acute care hospitals; (ii) identify the factors that are known to influence length of stay; and (iii) assess the impact of interventions on patient outcomes, service outcomes and costs. DATA SOURCES: We searched MEDLINE (Ovid), EMBASE, the Health Management Information Consortium and System for Information on Grey Literature in Europe for the period January 1995 to January 2013 with no limitation of publication type. METHODS: We conducted a rapid evidence synthesis of the peer-reviewed literature on organisational interventions set in or initiated from acute hospitals. We considered evidence published between 2003 and 2013. Data were analysed drawing on the principles of narrative synthesis. We also carried out interviews with eight NHS managers and clinical leads in four sites in England. Results: A total of 53 studies met our inclusion criteria, including 19 systematic reviews and 34 primary studies. Although the overall evidence base was varied and frequently lacked a robust study design, we identified a range of interventions that showed potential to reduce length of stay. These were multidisciplinary team working, for example some forms of organised stroke care; improved discharge planning; early supported discharge programmes; and care pathways. Nursing-led inpatient units were associated with improved outcomes but, if anything, increased length of stay. Factors influencing the impact of interventions on length of stay included contextual factors and the population targeted. The evidence was mixed with regard to the extent to which interventions seeking to reduce length of stay were associated with cost savings. LIMITATIONS: We only considered assessments of interventions which provided a quantitative estimate of the impact of the given organisational intervention on length of hospital stay. There was a general lack of robust evidence and poor reporting, weakening the conclusions that can be drawn from the review. CONCLUSIONS: The design and implementation of an intervention seeking to reduce (directly or indirectly) the length of stay in hospital should be informed by local context and needs. This involves understanding how the intervention is seeking to change processes and behaviours that are anticipated, based on the available evidence, to achieve desired outcomes (‘theory of change’). It will also involve assessing the organisational structures and processes that will need to be put in place to ensure that staff who are expected to deliver the intervention are appropriately prepared and supported. With regard to future research, greater attention should be given to the theoretical underpinning of the design, implementation and evaluation of interventions or programmes. There is a need for further research using appropriate methodology to assess the effectiveness of different types of interventions in different settings. Different evaluation approaches may be useful, and closer relationships between researchers and NHS organisations would enable more formative evaluation. Full economic costing should be undertaken where possible, including considering the cost implications for the wider local health economyThe National Institute for Health Research Health Services and Delivery Research programme

Distinct Binding and Immunogenic Properties of the Gonococcal Homologue of Meningococcal Factor H Binding Protein

Neisseria meningitidis is a leading cause of sepsis and meningitis. The bacterium recruits factor H (fH), a negative regulator of the complement system, to its surface via fH binding protein (fHbp), providing a mechanism to avoid complement-mediated killing. fHbp is an important antigen that elicits protective immunity against the meningococcus and has been divided into three different variant groups, V1, V2 and V3, or families A and B. However, immunisation with fHbp V1 does not result in cross-protection against V2 and V3 and vice versa. Furthermore, high affinity binding of fH could impair immune responses against fHbp. Here, we investigate a homologue of fHbp in Neisseria gonorrhoeae, designated as Gonococcal homologue of fHbp (Ghfp) which we show is a promising vaccine candidate for N. meningitidis. We demonstrate that Gfhp is not expressed on the surface of the gonococcus and, despite its high level of identity with fHbp, does not bind fH. Substitution of only two amino acids in Ghfp is sufficient to confer fH binding, while the corresponding residues in V3 fHbp are essential for high affinity fH binding. Furthermore, immune responses against Ghfp recognise V1, V2 and V3 fHbps expressed by a range of clinical isolates, and have serum bactericidal activity against N. meningitidis expressing fHbps from all variant groups

Evaluation of telephone first approach to demand management in English general practice: observational study

Objective: To evaluate a “telephone first” approach, in which all patients wanting to see a general practitioner (GP) are asked to speak to a GP on the phone before being given an appointment for a face to face consultation. Design: Time series and cross sectional analysis of routine healthcare data, data from national surveys, and primary survey data. Participants: 147 general practices adopting the telephone first approach compared with a 10% random sample of other practices in England. Intervention: Management support for workload planning and introduction of the telephone first approach provided by two commercial companies. Main outcome measures: Number of consultations, total time consulting (59 telephone first practices, no controls). Patient experience (GP Patient Survey, telephone first practices plus controls). Use and costs of secondary care (hospital episode statistics, telephone first practices plus controls). The main analysis was intention to treat, with sensitivity analyses restricted to practices thought to be closely following the companies’ protocols. Results: After the introduction of the telephone first approach, face to face consultations decreased considerably (adjusted change within practices −38%, 95% confidence interval −45% to −29%; P<0.001). An average practice experienced a 12-fold increase in telephone consultations (1204%, 633% to 2290%; P<0.001). The average duration of both telephone and face to face consultations decreased, but there was an overall increase of 8% in the mean time spent consulting by GPs, albeit with large uncertainty on this estimate (95% confidence interval −1% to 17%; P=0.088). These average workload figures mask wide variation between practices, with some practices experiencing a substantial reduction in workload and others a large increase. Compared with other English practices in the national GP Patient Survey, in practices using the telephone first approach there was a large (20.0 percentage points, 95% confidence interval 18.2 to 21.9; P<0.001) improvement in length of time to be seen. In contrast, other scores on the GP Patient Survey were slightly more negative. Introduction of the telephone first approach was followed by a small (2.0%) increase in hospital admissions (95% confidence interval 1% to 3%; P=0.006), no initial change in emergency department attendance, but a small (2% per year) decrease in the subsequent rate of rise of emergency department attendance (1% to 3%; P=0.005). There was a small net increase in secondary care costs. Conclusions: The telephone first approach shows that many problems in general practice can be dealt with over the phone. The approach does not suit all patients or practices and is not a panacea for meeting demand. There was no evidence to support claims that the approach would, on average, save costs or reduce use of secondary care

Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells

Microsomal triglyceride transfer protein (MTP), an endoplasmic reticulum (ER) chaperone that loads lipids onto apolipoprotein B, also regulates CD1d presentation of glycolipid antigens in the liver and intestine. We show MTP RNA and protein in antigen-presenting cells (APCs) by reverse transcription–polymerase chain reaction and by immunoblotting of mouse liver mononuclear cells and mouse and human B cell lines. Functional MTP, demonstrated by specific triglyceride transfer activity, is present in both mouse splenocytes and a CD1d-positive mouse NKT hybridoma. In a novel in vitro transfer assay, purified MTP directly transfers phospholipids, but not triglycerides, to recombinant CD1d. Chemical inhibition of MTP lipid transfer does not affect major histocompatibility complex class II presentation of ovalbumin, but considerably reduces CD1d-mediated presentation of α-galactosylceramide (α-galcer) and endogenous antigens in mouse splenic and bone marrow–derived dendritic cells (DCs), as well as in human APC lines and monocyte-derived DCs. Silencing MTP expression in the human monocyte line U937 affects CD1d function, as shown by diminished presentation of α-galcer. We propose that MTP acts upstream of the saposins and functions as an ER chaperone by loading endogenous lipids onto nascent CD1d. Furthermore, our studies suggest that a small molecule inhibitor could be used to modulate the activity of NKT cells