The nuts and bolts of PROSPERO: an international prospective register of systematic reviews

The nuts and bolts of PROSPERO: an internationa

Medical Crises in Older People: cohort study of older people attending acute medical units, developmental work and randomised controlled trial of a specialist geriatric medical intervention for high-risk older people; cohort study of older people with mental health problems admitted to hospital, developmental work and randomised controlled trial of a specialist medical and mental health unit for general hospital patients with delirium and dementia; and cohort study of residents of care homes and interview study of health-care provision to residents of care homes

BackgroundThis programme of research addressed shortcomings in the care of three groups of older patients: patients discharged from acute medical units (AMUs), patients with dementia and delirium admitted to general hospitals, and care home residents.MethodsIn the AMU workstream we undertook literature reviews, performed a cohort study of older people discharged from AMU (Acute Medical Unit Outcome Study; AMOS), developed an intervention (interface geriatricians) and evaluated the intervention in a randomised controlled trial (Acute Medical Unit Comprehensive Geriatric Assessment Intervention Study; AMIGOS). In the second workstream we undertook a cohort study of older people with mental health problems in a general hospital, developed a specialist unit to care for them and tested the unit in a randomised controlled trial (Trial of an Elderly Acute care Medical and mental health unit; TEAM). In the third workstream we undertook a literature review, a cohort study of a representative sample of care home residents and a qualitative study of the delivery of health care to care home residents.ResultsAlthough 222 of the 433 (51%) patients recruited to the AMIGOS study were vulnerable enough to be readmitted within 3 months, the trial showed no clinical benefit of interface geriatricians over usual care and they were not cost-effective. The TEAM study recruited 600 patients and there were no significant benefits of the specialist unit over usual care in terms of mortality, institutionalisation, mental or functional outcomes, or length of hospital stay, but there were significant benefits in terms of patient experience and carer satisfaction with care. The medical and mental health unit was cost-effective. The care home workstream found that the organisation of health care for residents in the UK was variable, leaving many residents, whose health needs are complex and unpredictable, at risk of poor health care. The variability of health care was explained by the variability in the types and sizes of homes, the training of care home staff, the relationships between care home staff and the primary care doctors and the organisation of care and training among primary care doctors.DiscussionThe interface geriatrician intervention was not sufficient to alter clinical outcomes and this might be because it was not multidisciplinary and well integrated across the secondary care–primary care interface. The development and evaluation of multidisciplinary and better-integrated models of care is justified. The specialist unit improved the quality of experience of patients with delirium and dementia in general hospitals. Despite the need for investment to develop such a unit, the unit was cost-effective. Such units provide a model of care for patients with dementia and delirium in general hospitals that requires replication. The health status of, and delivery of health care to, care home residents is now well understood. Models of care that follow the principles of comprehensive geriatric assessment would seem to be required, but in the UK these must be sufficient to take account of the current provision of primary health care and must recognise the importance of the care home staff in the identification of health-care needs and the delivery of much of that care.Trial registrationCurrent Controlled Trials ISRCTN21800480 (AMIGOS); ClinicalTrials.gov NCT01136148 (TEAM)

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

Interview with Davina Gordon, 4 August 2010

Davina Gordon was born in 1933 and went to primary school during the Second World War. She remembered only large classes with very little history being taught. At Goldolphin & Latymer grammar school she was taught history chronologically, starting with Roman Britain. The teacher taught by talking. The girls sat listening to her without making notes but then used the textbook afterwards to make notes and write essays for homework. She was a very interesting teacher and Davina found it all fascinating and particularly remembered a lesson when they had to decide what they would have done to stabilise the country if they had been Elizabeth 1. After the war ended, soon after she went to the grammar school, there were trips to London museums and further afield. She did a course of general history for a year in the sixth form while doing a secretarial course at the school. There was now a new teacher who liked to bring in newspapers and talk about politics. After school she initially did secretarial work but then trained to be a gemmologist and worked in a jeweller’s shop for many years. Interviewed by Jenny Keating

Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function

Clinical studies of bone marrow (BM) cell therapy for liver cirrhosis are under way but the mechanisms of benefit remain undefined. Cells of the monocyte-macrophage lineage have key roles in the development and resolution of liver fibrosis. Therefore, we tested the therapeutic effects of these cells on murine liver fibrosis. Advanced liver fibrosis was induced in female mice by chronic administration of carbon tetrachloride. Unmanipulated, syngeneic macrophages, their specific BM precursors, or unfractionated BM cells were delivered during liver injury. Mediators of inflammation, fibrosis, and regeneration were measured. Donor cells were tracked by sex-mismatch and green fluorescent protein expression. BM-derived macrophage (BMM) delivery resulted in early chemokine up-regulation with hepatic recruitment of endogenous macrophages and neutrophils. These cells delivered matrix metalloproteinases-13 and -9, respectively, into the hepatic scar. The effector cell infiltrate was accompanied by increased levels of the antiinflammatory cytokine interleukin 10. A reduction in hepatic myofibroblasts was followed by reduced fibrosis detected 4 weeks after macrophage infusion. Serum albumin levels were elevated at this time. Up- regulation of the liver progenitor cell mitogen tumor necrosis factor-like weak inducer of apoptosis (TWEAK) preceded expansion of the progenitor cell compartment. Increased expression of colony stimulating factor-1, insulin-like growth factor-1, and vascular endothelial growth factor also followed BMM delivery. In contrast to the effects of differentiated macrophages, liver fibrosis was not significantly altered by the application of macrophage precursors and was exacerbated by whole BM. Conclusion: Macrophage cell therapy improves clinically relevant parameters in experimental chronic liver injury. Paracrine signaling to endogenous cells amplifies the effect. The benefits from this single, defined cell type suggest clinical potential