Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines).

Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this Review is to provide a summary of knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. This Review outlines what a placebo control entails and present understanding of this tool in the context of surgery. We consider when placebo controls in surgery are acceptable (and when they are desirable) in terms of ethical arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be done and interpreted. Use of placebo controls is justified in randomised controlled trials of surgical interventions provided there is a strong scientific and ethical rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with high risk of bias, particularly because of the placebo effect. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. This Review forms an outline for best practice and provides guidance, in the form of the Applying Surgical Placebo in Randomised Evaluations (known as ASPIRE) checklist, for those considering the use of a placebo control in a surgical randomised controlled trial.

The impact of closing emergency departments on mortality in emergencies: an observational study.

BACKGROUND: In England the demand for emergency care is increasing, while there is also a staffing shortage. This has implications for quality of care and patient safety. One solution may be to concentrate resources on fewer sites by closing or downgrading emergency departments (EDs). Our aim was to quantify the impact of such reorganisation on population mortality. METHODS: We undertook a controlled interrupted time series analysis to detect the impact of closing or downgrading five EDs, which occurred due to concerns regarding sustainability. We obtained mortality data from 2007 to 2014 using national databases. To establish ED resident catchment populations, estimated journey times by road were supplied by the Department for Transport. Other major changes in the emergency and urgent care system were determined by analysis of annual NHS Trust reports in each geographical area studied. Our main outcome measures were mortality and case fatality for a set of 16 serious emergency conditions. RESULTS: For residents in the areas affected by closure, journey time to the nearest ED increased (median change 9 min, range 0-25 min). We found no statistically reliable evidence of a change in overall mortality following reorganisation of ED care in any of the five areas or overall (+2.5% more deaths per month on average; 95% CI -5.2% to +10.2%; p=0.52). There was some evidence to suggest that, on average across the five areas, there was a small increase in case fatality, an indicator of the 'risk of death' (+2.3%, 95% CI +0.9% to+3.6%; p<0.001), but this may have arisen due to changes in hospital admissions. CONCLUSIONS: We found no evidence that reorganisation of emergency care was associated with a change in population mortality in the five areas studied. Further research should establish the economic consequences and impact on patient experience and neighbouring hospitals.

Development process of a consensus-driven CONSORT extension for randomised trials using an adaptive design.

BACKGROUND: Adequate reporting of adaptive designs (ADs) maximises their potential benefits in the conduct of clinical trials. Transparent reporting can help address some obstacles and concerns relating to the use of ADs. Currently, there are deficiencies in the reporting of AD trials. To overcome this, we have developed a consensus-driven extension to the CONSORT statement for randomised trials using an AD. This paper describes the processes and methods used to develop this extension rather than detailed explanation of the guideline. METHODS: We developed the guideline in seven overlapping stages: 1) Building on prior research to inform the need for a guideline; 2) A scoping literature review to inform future stages; 3) Drafting the first checklist version involving an External Expert Panel; 4) A two-round Delphi process involving international, multidisciplinary, and cross-sector key stakeholders; 5) A consensus meeting to advise which reporting items to retain through voting, and to discuss the structure of what to include in the supporting explanation and elaboration (E&E) document; 6) Refining and finalising the checklist; and 7) Writing-up and dissemination of the E&E document. The CONSORT Executive Group oversaw the entire development process. RESULTS: Delphi survey response rates were 94/143 (66%), 114/156 (73%), and 79/143 (55%) in rounds 1, 2, and across both rounds, respectively. Twenty-seven delegates from Europe, the USA, and Asia attended the consensus meeting. The main checklist has seven new and nine modified items and six unchanged items with expanded E&E text to clarify further considerations for ADs. The abstract checklist has one new and one modified item together with an unchanged item with expanded E&E text. The E&E document will describe the scope of the guideline, the definition of an AD, and some types of ADs and trial adaptations and explain each reporting item in detail including case studies. CONCLUSIONS: We hope that making the development processes, methods, and all supporting information that aided decision-making transparent will enhance the acceptability and quick uptake of the guideline. This will also help other groups when developing similar CONSORT extensions. The guideline is applicable to all randomised trials with an AD and contains minimum reporting requirements.

Paramedic Assessment of Older Adults After Falls, Including Community Care Referral Pathway: Cluster Randomized Trial.

STUDY OBJECTIVE: We aim to determine clinical and cost-effectiveness of a paramedic protocol for the care of older people who fall. METHODS: We undertook a cluster randomized trial in 3 UK ambulance services between March 2011 and June 2012. We included patients aged 65 years or older after an emergency call for a fall, attended by paramedics based at trial stations. Intervention paramedics could refer the patient to a community-based falls service instead of transporting the patient to the emergency department. Control paramedics provided care as usual. The primary outcome was subsequent emergency contacts or death. RESULTS: One hundred five paramedics based at 14 intervention stations attended 3,073 eligible patients; 110 paramedics based at 11 control stations attended 2,841 eligible patients. We analyzed primary outcomes for 2,391 intervention and 2,264 control patients. One third of patients made further emergency contacts or died within 1 month, and two thirds within 6 months, with no difference between groups. Subsequent 999 call rates within 6 months were lower in the intervention arm (0.0125 versus 0.0172; adjusted difference -0.0045; 95% confidence interval -0.0073 to -0.0017). Intervention paramedics referred 8% of patients (204/2,420) to falls services and left fewer patients at the scene without any ongoing care. Intervention patients reported higher satisfaction with interpersonal aspects of care. There were no other differences between groups. Mean intervention cost was $23 per patient, with no difference in overall resource use between groups at 1 or 6 months. CONCLUSION: A clinical protocol for paramedics reduced emergency ambulance calls for patients attended for a fall safely and at modest cost.

Acceptability of NHS 111 the telephone service for urgent health care: cross sectional postal survey of users' views.

BACKGROUND: In 2010, a new telephone service, NHS 111, was piloted to improve access to urgent care in England. A unique feature is the use of non-clinical call takers who triage calls with computerized decision support and have access to clinical advisors when necessary. Aim. To explore users' acceptability of NHS 111. DESIGN: Cross-sectional postal survey. SETTING: Four pilot sites in England. METHOD: A postal survey of recent users of NHS 111. RESULTS: The response rate was 41% (1769/4265), with 49% offering written comments (872/1769). Sixty-five percent indicated the advice given had been very helpful and 28% quite helpful. The majority of respondents (86%) indicated that they fully complied with advice. Seventy-three percent was very satisfied and 19% quite satisfied with the service overall. Users were less satisfied with the relevance of questions asked, and the accuracy and appropriateness of advice given, than with other aspects of the service. Users who were autorouted to NHS 111 from services such as GP out-of-hours services were less satisfied than direct callers. CONCLUSION: In pilot services in the first year of operation, NHS 111 appeared to be acceptable to the majority of users. Acceptability could be improved by reassessing the necessity of triage questions used and auditing the accuracy and appropriateness of advice given. User acceptability should be viewed in the context of findings from the wider evaluation, which identified that the NHS 111 pilot services did not improve access to urgent care and indeed increased the use of emergency ambulance services.

Direct risk standardisation: a new method for comparing casemix adjusted event rates using complex models.

BACKGROUND: Comparison of outcomes between populations or centres may be confounded by any casemix differences and standardisation is carried out to avoid this. However, when the casemix adjustment models are large and complex, direct standardisation has been described as "practically impossible", and indirect standardisation may lead to unfair comparisons. We propose a new method of directly standardising for risk rather than standardising for casemix which overcomes these problems. METHODS: Using a casemix model which is the same model as would be used in indirect standardisation, the risk in individuals is estimated. Risk categories are defined, and event rates in each category for each centre to be compared are calculated. A weighted sum of the risk category specific event rates is then calculated. We have illustrated this method using data on 6 million admissions to 146 hospitals in England in 2007/8 and an existing model with over 5000 casemix combinations, and a second dataset of 18,668 adult emergency admissions to 9 centres in the UK and overseas and a published model with over 20,000 casemix combinations and a continuous covariate. RESULTS: Substantial differences between conventional directly casemix standardised rates and rates from direct risk standardisation (DRS) were found. Results based on DRS were very similar to Standardised Mortality Ratios (SMRs) obtained from indirect standardisation, with similar standard errors. CONCLUSIONS: Direct risk standardisation using our proposed method is as straightforward as using conventional direct or indirect standardisation, always enables fair comparisons of performance to be made, can use continuous casemix covariates, and was found in our examples to have similar standard errors to the SMR. It should be preferred when there is a risk that conventional direct or indirect standardisation will lead to unfair comparisons.

Patients' experience and satisfaction with GP led walk-in centres in the UK; a cross sectional study.

BACKGROUND: GP led walk-in centres were established in the UK in 2009. Around 150 such clinics were initially planned to open. Their purpose is to provide a primary health care service to complement the urgent care services provided by Emergency Departments (ED), to reduce unnecessary patient attendance at ED, and to increase accessibility of health care services. The objectives of this study were to determine patient satisfaction and experiences with GP led walk-in centres in the UK. METHODS: A survey was conducted in two GP led walk-in centres in the North of England over three weeks during September and October 2011. A self reported, validated questionnaire was used to survey patients presenting at these centres. A short post visit questionnaire was also sent to those who agreed. Ethical approval for the study was obtained from an NHS ethical review committee. RESULTS: Based on a sample of 1030 survey participants (Centre A = 501; Centre B = 529), we found that 93% of patients were either highly or fairly satisfied with the service at centre A and 86% at centre B. The difference between centres was due to the longer reported waiting times which were seen in centre B. There was no difference in satisfaction between first time users and repeat users (P value = 0.8). Roughly 50% (n = 507) of patients reported that their reason for using the walk-in centre was having GP access without an appointment, and 9% (n = 87) reported that their GP surgery was closed. A further 20% of patients (n = 205) reported that they were not able to see their own GP because of their working hours.In the post visit survey (n = 258), nearly all patients reported complying with the advice given (around 90% at both study centres), and most of the patients (86%) reported their problem had resolved a few days later. In addition, 56% of patients at centre B and 58% at centre A reported that they had also visited another NHS service for the same problem, mostly their own GP (66%). CONCLUSIONS: The GP led walk-in centres increased access to GP care and most of the patients were satisfied with the service.

Did hospital mortality in England change from 2005 to 2010? A retrospective cohort analysis.

BACKGROUND: There is some evidence that hospital performance in England measured by the Dr Foster Hospital Standardised Mortality Ratio (HSMR) has improved substantially over the last 10 years. This study explores mortality in-hospital and up to 30 days post-discharge over a five year period to determine whether there have been improvements in case-mix adjusted mortality, to examine if any changes are due to changes in case-mix adjustment variables such as age, sex, method of admission and comorbidity, and to compare changes between hospital trusts. METHODS: Using Hospital Episode Statistics linked to mortality data from the Office for National Statistics the Summary Hospital-Level Mortality Index (SHMI) was calculated for all patients who were discharged or died in general acute hospital trusts in England for the period 01/04/2005 to 30/09/2010. RESULTS: During this five year period the number of admissions rose by 8% but deaths fell by 5%. The SHMI fell by 24% from 112 to 85 over the period, partly due to fewer deaths but partly due to increasing numbers predicted by the SHMI model. Excluding comorbidities from the model the SHMI fell by 18% from 108 to 89 over this period. The reduction was similar in emergency and elective admissions and in all other sub-groups examined. The average quarterly change in SHMI varied considerably between trusts (range: -4.4 to -0.2). CONCLUSIONS: As measured by the SHMI there has been a 24% improvement in mortality in acute general trusts in England over a period of five and a half years. Part of this improvement is an artificial effect caused by changes in the depth of coding of comorbidities and other effects due to change in case-mix or non-constant risk.

Health utility after emergency medical admission: a cross-sectional survey.

OBJECTIVES: Health utility combines health related quality of life and mortality to produce a generic outcome measure reflecting both morbidity and mortality. It has not been widely used as an outcome measure in evaluations of emergency care and little is known about the feasibility of measurement, typical values obtained or baseline factors that predict health utility. We aimed to measure health utility after emergency medical admission, to compare health utility to age, gender and regional population norms, and identify independent predictors of health utility. METHODS: We selected 5760 patients across three hospitals who were admitted to hospital by ambulance as a medical emergency. The EQ-5D questionnaire was mailed to all who were still alive 30 days after admission. Health utility was estimated by applying tariff values to the EQ-5D responses or imputing a value of zero for those who had died. Multivariable analysis was used to identify independent predictors of health utility at 30 days. RESULTS: Responses were received from 2488 (47.7%) patients, while 541 (9.4%) had died. Most respondents reported some or severe problems with each aspect of health. Mean health utility was 0.49 (standard deviation 0.35) in survivors and 0.45 (0.36) including non-survivors. Some 75% had health utility below their expected value (mean loss 0.32, 95% confidence interval 0.31 to 0.33) and 11% had health utility below zero (worse than death). On multivariable modelling, reduced health utility was associated with increased age and lower GCS, varied according to ICD10 code and was lower among females, patients with recent hospital admission, steroid therapy, or history of chronic respiratory disease, malignancy, diabetes or epilepsy. CONCLUSIONS: Health utility can be measured after emergency medical admission, although responder bias may be significant. Health utility after emergency medical admission is poor compared to population norms. We have identified independent predictors or health utility that need to be measured and taken into account in non-randomized evaluations of emergency care.

Patients' experiences and views of an emergency and urgent care system.

BACKGROUND: Surveys of patients' experiences and views of health care usually focus on single services. During an unexpected episode of ill health, patients may make contact with different services and therefore experience care within an emergency and urgent care system. We developed the Urgent Care System Questionnaire and used it to describe patients' experiences and views of an emergency and urgent care system in England. METHODS: A market research company used quota sampling and random digit dialling to undertake a telephone survey of 1000 members of the general population in July 2007. RESULTS: 15% (151/1000) of the population reported using the emergency and urgent care system in the previous 3 months. Two thirds of users (68%, 98/145) contacted more than one service for their most recent event, with a mean of 2.0 services per event. Users entered the system through a range of services: the majority contacted a daytime GP in the first instance (59%, 85/145), and 12% (18/145) contacted either a 999 emergency ambulance or an emergency department. Satisfaction with all aspects of care diminished when four or more services had been contacted. CONCLUSIONS: This is the first study to describe patients' experiences and views of the emergency and urgent care system. The majority of patients experienced a system of care rather than single service care. There was an indication that longer pathways resulted in lower levels of patient satisfaction. Health care organisations can undertake similar surveys to identify problems with their system or to assess the impact of changes made to their system.

The appropriateness of, and compliance with, telephone triage decisions: a systematic review and narrative synthesis.

AIM: This paper is a report of the synthesis of evidence on the appropriateness of, and compliance with, telephone triage decisions. BACKGROUND: Telephone triage plays an important role in managing demand for health care. Important questions are whether triage decisions are appropriate and patients comply with them. DATA SOURCES: CINAHL, Cochrane Clinical Trials Database, Medline, Embase, Web of Science, and Psyc Info were searched between 1980-June 2010. LITERATURE REVIEW: Rapid Evidence Synthesis. REVIEW METHODS: The principles of rapid evidence assessment were followed. RESULTS: We identified 54 relevant papers: 26 papers reported appropriateness of triage decision, 26 papers reported compliance with triage decision, and 2 papers reported both. Nurses triaged calls in most of the studies (n=49). Triage decisions rated as appropriate varied between 44-98% and compliance ranged from 56-98%. Variation could not be explained by type of service or method of assessing appropriateness. However, inconsistent definitions of appropriateness may explain some variation. Triage decisions to contact primary care may have lower compliance than decisions to contact emergency services or self care. CONCLUSION: Telephone triage services can offer appropriate decisions and decisions that callers comply with. However, the association between the appropriateness of a decision and subsequent compliance requires further investigation and further consideration needs to be given to the minority of calls which are inappropriately managed. We suggest that a definition of appropriateness incorporating both accuracy and adequacy of triage decision should be encouraged.

Why do patients with minor or moderate conditions that could be managed in other settings attend the emergency department?

OBJECTIVES: To estimate the potential of alternative providers of care for minor health problems to reduce demands on emergency departments (EDs). METHODS: Data were collected in a type 1 urban ED over a 2-month period in two stages: questionnaire to adult attendees presenting to the ED; and a notes review. RESULTS: The usable response rate was 68% (n=261/384). The notes review confirmed that more than two-thirds of the presenting conditions could have been managed in settings other than the ED. The attendees' reasons on the questionnaire indicated a strong belief that the only provider able to deal with their concerns at that time was the ED. For some users, the ED was not the first contact with a healthcare provider for the same health problem. Few believed that they would be seen quicker in the ED or that the ED was more convenient. The most frequent reason for presenting to the ED was 'being advised to attend by someone else'. The 'adviser' was more likely to be a health professional (doctor or nurse or NHS Direct) than to be 'friends or family'. CONCLUSIONS: Although there appears to be considerable potential for minor conditions to be managed in settings other than the ED, our findings indicate that patients will continue to present these conditions to the ED. Patient perceptions of the urgency of their treatment need, and also the availability and capacity of alternative services may be offsetting their potential to substitute for the ED. Advice from other services may be contributing to demands on the ED.

Measuring the impact introducing NHS 111 online had on the NHS 111 telephone service and the wider NHS urgent care system: an observational study.

OBJECTIVES: To explore what impact introducing the National Health Service (NHS) 111 online service had on the number of phone calls to the NHS 111 telephone service and the NHS urgent care system. DESIGN: Observational study using a dose-response interrupted time series model and random-effects meta- analysis to estimate the average effect. SETTING AND PARTICIPANTS: NHS 111 telephone and online contacts for 18 NHS 111 area codes in England. NHS 111 telephone and online contacts data were collected between October 2010 to December 2019 and January 2018 to December 2019, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome: the number of triaged calls to the NHS 111 telephone service following the introduction of NHS 111 online. SECONDARY OUTCOMES: total calls to the NHS 111 telephone service, total number of emergency ambulance referrals or advice to contact 999, total number of advice to attend an emergency department or other urgent care treatment facility, and total number of advice to contact primary care. RESULTS: For triaged calls, the overall incidence rate ratio (IRR) per 1000 online contacts was 1.013 (95% CI: 0.996 to 1.029, p=0.127). For total calls, the overall IRR per 1000 online contacts was 1.008 (95% CI: 0.992 to 1.025, p=0.313). For emergency ambulance referrals or advice to contact 999, the overall IRR per 1000 online contacts was 1.067 (95% CI: 1.035 to 1.100, p<0.001). For advice to attend an emergency department or other urgent care treatment facility, the overall IRR per 1000 online contacts is 1.050 (95% CI: 1.010 to 1.092, p=0.014). And finally, for those advised to contact primary care, the overall IRR per 1000 online contacts is 1.051 (95% CI: 1.027 to 1.076, p<0.001). CONCLUSIONS: It was found that the NHS 111 online service has little impact on the number of triaged and total calls, suggesting that the workload for the NHS 111 telephone service has not increased or decreased as a result of introducing NHS 111 online. However, there was evidence to suggest an increase in the overall number of disposition recommendations (ambulance, emergency department and primary care) for NHS 111 telephone and online services combined following the introduction of the NHS 111 online service.

Infective endocarditis following invasive dental procedures: IDEA case-crossover study.

BACKGROUND: Infective endocarditis is a heart infection with a first-year mortality rate of ≈ 30%. It has long been thought that infective endocarditis is causally associated with bloodstream seeding with oral bacteria in ≈ 40-45% of cases. This theorem led guideline committees to recommend that individuals at increased risk of infective endocarditis should receive antibiotic prophylaxis before undergoing invasive dental procedures. However, to the best of our knowledge, there has never been a clinical trial to prove the efficacy of antibiotic prophylaxis and there is no good-quality evidence to link invasive dental procedures with infective endocarditis. Many contend that oral bacteria-related infective endocarditis is more likely to result from daily activities (e.g. tooth brushing, flossing and chewing), particularly in those with poor oral hygiene. OBJECTIVE: The aim of this study was to determine if there is a temporal association between invasive dental procedures and subsequent infective endocarditis, particularly in those at high risk of infective endocarditis. DESIGN: This was a self-controlled, case-crossover design study comparing the number of invasive dental procedures in the 3 months immediately before an infective endocarditis-related hospital admission with that in the preceding 12-month control period. SETTING: The study took place in the English NHS. PARTICIPANTS: All individuals admitted to hospital with infective endocarditis between 1 April 2010 and 31 March 2016 were eligible to participate. INTERVENTIONS: This was an observational study; therefore, there was no intervention. MAIN OUTCOME MEASURE: The outcome measure was the number of invasive and non-invasive dental procedures in the months before infective endocarditis-related hospital admission. DATA SOURCES: NHS Digital provided infective endocarditis-related hospital admissions data and dental procedure data were obtained from the NHS Business Services Authority. RESULTS: The incidence rate of invasive dental procedures decreased in the 3 months before infective endocarditis-related hospital admission (incidence rate ratio 1.34, 95% confidence interval 1.13 to 1.58). Further analysis showed that this was due to loss of dental procedure data in the 2-3 weeks before any infective endocarditis-related hospital admission. LIMITATIONS: We found that urgent hospital admissions were a common cause of incomplete courses of dental treatment and, because there is no requirement to record dental procedure data for incomplete courses, this resulted in a significant loss of dental procedure data in the 2-3 weeks before infective endocarditis-related hospital admissions. The data set was also reduced because of the NHS Business Services Authority's 10-year data destruction policy, reducing the power of the study. The main consequence was a loss of dental procedure data in the critical 3-month case period of the case-crossover analysis (immediately before infective endocarditis-related hospital admission), which did not occur in earlier control periods. Part of the decline in the rate of invasive dental procedures may also be the result of the onset of illness prior to infective endocarditis-related hospital admission, and part may be due to other undefined causes. CONCLUSIONS: The loss of dental procedure data in the critical case period immediately before infective endocarditis-related hospital admission makes interpretation of the data difficult and raises uncertainty over any conclusions that can be drawn from this study. FUTURE WORK: We suggest repeating this study elsewhere using data that are unafflicted by loss of dental procedure data in the critical case period. TRIAL REGISTRATION: This trial is registered as ISRCTN11684416. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 28. See the NIHR Journals Library website for further project information.

Infective endocarditis is a life-threatening infection of the heart valves. Most people are at low risk of infective endocarditis. However, those with certain cardiac conditions are at moderate risk of infective endocarditis, and those with artificial or repaired heart valves, a history of infective endocarditis and certain congenital heart conditions are at high risk of infective endocarditis. In around 40­45% of cases, oral bacteria are the cause of infective endocarditis. For many years, those people at moderate or high risk of infective endocarditis were given antibiotics (antibiotic prophylaxis) before invasive dental procedures such as extractions to reduce the risk of infective endocarditis. There is no good-quality evidence, however, to support the effectiveness of antibiotic prophylaxis, or the link between invasive dental procedures and infective endocarditis. Many believe that the oral bacteria that cause infective endocarditis are more likely to enter the blood during daily activities (e.g. toothbrushing, flossing or chewing), particularly in those with poor oral hygiene, than on the rare occasions when invasive dental procedures are performed. The aim of this study was to link English NHS data on infective endocarditis-related hospital admissions and dental treatments to determine if infective endocarditis is more likely in the weeks immediately after an invasive dental procedure than at any other time. When we linked the data sets and plotted the occurrence of different dental treatments over the year before infective endocarditis-related hospital admission, we detected a problem in the way that dental data were recorded. Unfortunately, there was a failure to collect dental procedure data when courses of treatment were incomplete. As one of the most common reasons for not completing a course of treatment was emergency admission to hospital, this meant that the number of dental procedures recorded decreased in the weeks before any emergency hospital admission. We have attempted to correct for this, but the data loss has affected the data quality. Although the data suggest an association between invasive dental procedures and infective endocarditis in individuals at high risk of infective endocarditis, the certainty of this association has been weakened.

Analysis of Prosthetic Joint Infections Following Invasive Dental Procedures in England.

Importance: Dentists in the United States are under pressure from orthopedic surgeons and their patients with prosthetic joints to provide antibiotic prophylaxis before invasive dental procedures (IDP) to reduce the risk of late prosthetic joint infection (LPJI). This has been a common practice for decades, despite a lack of evidence for an association between IDP and LPJI, a lack of evidence of antibiotic prophylaxis efficacy, cost of providing antibiotic prophylaxis, and risk of both adverse drug reactions and the potential for promoting antibiotic resistance. Objective: To quantify any temporal association between IDP and subsequent LPJI. Design, Setting, and Participants: This cohort study used a case-crossover and time trend design to examine any potential association between IDP and LPJI. The population of England (55 million) was chosen because antibiotic prophylaxis has never been recommended to prevent LPJI in England, and any association between IDP and LPJI would therefore be fully exposed. All patients admitted to hospitals in England for LPJI from December 25, 2011, through March 31, 2017, and for whom dental records were available were included. Analyses were performed between May 2018 and June 2021. Exposures: Exposure to IDP. Main Outcomes and Measures: The main outcome was the incidence of IDP in the 3 months before LPJI hospital admission (case period) compared with the incidence in the 12 months before that (control period). Results: A total of 9427 LPJI hospital admissions with dental records (mean [SD] patient age, 67.8 [13.1] years) were identified, including 4897 (52.0%) men and 4529 (48.0%) women. Of these, 2385 (25.3%) had hip prosthetic joints, 3168 (33.6%) had knee prosthetic joints, 259 (2.8%) had other prosthetic joints, and 3615 (38.4%) had unknown prosthetic joint types. There was no significant temporal association between IDP and subsequent LPJI. Indeed, there was a lower incidence of IDP in the 3 months prior to LPJI (incidence rate ratio, 0.89; 95% CI, 0.82-0.96; P = .002). Conclusions and Relevance: These findings suggest that there is no rationale to administer antibiotic prophylaxis before IDP in patients with prosthetic joints.

Noninvasive ventilation in acute cardiogenic pulmonary edema.

BACKGROUND: Noninvasive ventilation (continuous positive airway pressure [CPAP] or noninvasive intermittent positive-pressure ventilation [NIPPV]) appears to be of benefit in the immediate treatment of patients with acute cardiogenic pulmonary edema and may reduce mortality. We conducted a study to determine whether noninvasive ventilation reduces mortality and whether there are important differences in outcome associated with the method of treatment (CPAP or NIPPV). METHODS: In a multicenter, open, prospective, randomized, controlled trial, patients were assigned to standard oxygen therapy, CPAP (5 to 15 cm of water), or NIPPV (inspiratory pressure, 8 to 20 cm of water; expiratory pressure, 4 to 10 cm of water). The primary end point for the comparison between noninvasive ventilation and standard oxygen therapy was death within 7 days after the initiation of treatment, and the primary end point for the comparison between NIPPV and CPAP was death or intubation within 7 days. RESULTS: A total of 1069 patients (mean [+/-SD] age, 77.7+/-9.7 years; female sex, 56.9%) were assigned to standard oxygen therapy (367 patients), CPAP (346 patients), or NIPPV (356 patients). There was no significant difference in 7-day mortality between patients receiving standard oxygen therapy (9.8%) and those undergoing noninvasive ventilation (9.5%, P=0.87). There was no significant difference in the combined end point of death or intubation within 7 days between the two groups of patients undergoing noninvasive ventilation (11.7% for CPAP and 11.1% for NIPPV, P=0.81). As compared with standard oxygen therapy, noninvasive ventilation was associated with greater mean improvements at 1 hour after the beginning of treatment in patient-reported dyspnea (treatment difference, 0.7 on a visual-analogue scale ranging from 1 to 10; 95% confidence interval [CI], 0.2 to 1.3; P=0.008), heart rate (treatment difference, 4 beats per minute; 95% CI, 1 to 6; P=0.004), acidosis (treatment difference, pH 0.03; 95% CI, 0.02 to 0.04; P<0.001), and hypercapnia (treatment difference, 0.7 kPa [5.2 mm Hg]; 95% CI, 0.4 to 0.9; P<0.001). There were no treatment-related adverse events. CONCLUSIONS: In patients with acute cardiogenic pulmonary edema, noninvasive ventilation induces a more rapid improvement in respiratory distress and metabolic disturbance than does standard oxygen therapy but has no effect on short-term mortality. (Current Controlled Trials number, ISRCTN07448447.)

South Yorkshire Cohort: a 'cohort trials facility' study of health and weight - protocol for the recruitment phase.

BACKGROUND: Growing levels of both obesity and chronic disease in the general population pose a major public health problem. In the UK, an innovative 'health and weight' cohort trials facility, the 'South Yorkshire Cohort', is being built in order to provide robust evidence to inform policy, commissioning and clinical decisions in this field. This protocol reports the design of the facility and outlines the recruitment phase methods. METHOD/DESIGN: The South Yorkshire Cohort health and weight study uses the cohort multiple randomised controlled trial design. This design recruits a large observational cohort of patients with the condition(s) of interest which then provides a facility for multiple randomised controlled trials (with large representative samples of participants, long term outcomes as standard, increased comparability between each trial conducted within the cohort and increased efficiency particularly for trials of expensive interventions) as well as ongoing information as to the natural history of the condition and treatment as usual.This study aims to recruit 20,000 participants to the population based South Yorkshire Cohort health and weight research trials facility. Participants are recruited by invitation letters from their General Practitioners. Data is collected using postal and/or online patient self completed Health Questionnaires. NHS numbers will be used to facilitate record linkage and access to routine data. Participants are eligible if they are: aged 16 - 85 years, registered with one of 40 practices in South Yorkshire, provide consent for further contact from the researchers and to have their information used to look at the benefit of health treatments. The first wave of data is being collected during 2010/12 and further waves are planned at 2 - 5 year intervals for the planned 20 year duration of the facility. DISCUSSION: The South Yorkshire Cohort combines the strengths of the standard observational, longitudinal cohort study design with a population based cohort facility for multiple randomised controlled trials in a range of long term health and weight related conditions (including obesity). This infrastructure will allow the rapid and cheap identification and recruitment of patients, and facilitate the provision of robust evidence to inform the management and self-management of health and weight.

Role of ambulance response times in the survival of patients with out-of-hospital cardiac arrest.

OBJECTIVES: To evaluate the role of ambulance response times in improving survival for out-of-hospital cardiac arrest (OHCA). METHODS: OHCAs were identified by sampling consecutive life-threatening category A emergency ambulance calls on an annual basis for the 5 years 1996/7-2000/1 from four ambulance services in England. From these, all calls where an ambulance arrived at the scene and treated or transported a patient were included in the study. These cohorts of patients were followed up to discharge from hospital. RESULTS: Overall, 30 (2.6%) of the 1161 patients with cardiac arrest survived to hospital discharge. If the patient arrested while the paramedics were on scene, survival to hospital discharge was 14%. The most important predictive factors for survival were response time, initial presenting heart rhythm in ventricular fibrillation and whether the arrest was witnessed. The estimated effect of a 1 min reduction in response time was to improve the odds of survival by 24% (95% CI 4% to 48%). The costs of reducing response times across the board by 1 at the time of this study were estimated at around £54 million. CONCLUSIONS: The arrival of a crew prior to OHCA means that the chance of surviving the arrest increases sevenfold. Overall it is possible that rapid response to patients in immediate risk of arrest may be at least as beneficial as rapid response to those who have arrested. Concentrating resources on reducing response times across the board to improve survival for those patients already in arrest is unlikely to be a cost-effective option to the U.K. National Health Service.

Health utility and survival after hospital admission with acute cardiogenic pulmonary oedema.

BACKGROUND: The aim of this study was to measure health utility and survival in patients with acute cardiogenic pulmonary oedema (ACPO), identify predictors of outcome and determine the effect of initial treatment with non-invasive ventilation (NIV) upon outcomes. METHODS: A randomised controlled trial was conducted at 26 hospitals in the UK. 1069 adults with ACPO were randomised to continuous positive airway pressure (CPAP), non-invasive positive pressure ventilation (NIPPV) or standard oxygen therapy. The main outcome measures were survival to 1-5 years, health utility measured using the EQ-5D survey at 1, 3 and 6 months, and quality-adjusted life years (QALYs). RESULTS: Median survival was 771 days (95% CI 669 to 875), with no difference between the three treatment groups (p = 0.827). Age (HR 1.042, 95% CI 1.031 to 1.052), chronic obstructive pulmonary disease (HR 1.13, 95% CI 1.06 to 1.62), cerebrovascular disease (HR 1.41, 95% CI 1.14 to 1.73) and diabetes mellitus (HR 1.31, 95% CI 1.01 to 1.63) independently predicted mortality. Mean EQ-5D scores were 0.578, 0.576 and 0.582 at 1, 3 and 6 months, respectively, with no significant difference between the treatment groups. Male gender (+0.045 QALYs, 95% CI 0.009 to 0.081) and cerebrovascular disease (-0.080 QALYs, 95% CI -0.131 to -0.029) independently predicted health utility. CONCLUSION: Patients with ACPO have high mortality and reduced health utility. Initial treatment with CPAP or NIPPV does not alter subsequent survival or health utility.