Effectiveness and cost effectiveness of pharmacological thromboprophylaxis for medical inpatients: decision analysis modelling study.

Objective: To determine the balance of costs, risks, and benefits for different thromboprophylaxis strategies for medical patients during hospital admission. Design: Decision analysis modelling study. Setting: NHS hospitals in England. Population: Eligible adult medical inpatients, excluding patients in critical care and pregnant women. Interventions: Pharmacological thromboprophylaxis (low molecular weight heparin) for all medical inpatients, thromboprophylaxis for none, and thromboprophylaxis given to higher risk inpatients according to risk assessment models (Padua, Caprini, IMPROVE, Intermountain, Kucher, Geneva, and Rothberg) previously validated in medical cohorts. Main outcome measures: Lifetime costs and quality adjusted life years (QALYs). Costs were assessed from the perspective of the NHS and Personal Social Services in England. Other outcomes assessed were incidence and treatment of venous thromboembolism, major bleeds including intracranial haemorrhage, chronic thromboembolic complications, and overall survival. Results: Offering thromboprophylaxis to all medical inpatients had a high probability (>99%) of being the most cost effective strategy (at a threshold of £20 000 (€23 440; $25 270) per QALY) in the probabilistic sensitivity analysis, when applying performance data from the Padua risk assessment model, which was typical of that observed across several risk assessment models in a medical inpatient cohort. Thromboprophylaxis for all medical inpatients was estimated to result in 0.0552 additional QALYs (95% credible interval 0.0209 to 0.1111) while generating cost savings of £28.44 (-£47 to £105) compared with thromboprophylaxis for none. No other risk assessment model was more cost effective than thromboprophylaxis for all medical inpatients when assessed in deterministic analysis. Risk based thromboprophylaxis was found to have a high (76.6%) probability of being the most cost effective strategy only when assuming a risk assessment model with very high sensitivity is available (sensitivity 99.9% and specificity 23.7% v base case sensitivity 49.3% and specificity 73.0%). Conclusions: Offering pharmacological thromboprophylaxis to all eligible medical inpatients appears to be the most cost effective strategy. To be cost effective, any risk assessment model would need to have a very high sensitivity resulting in widespread thromboprophylaxis in all patients except those at the very lowest risk, who could potentially avoid prophylactic anticoagulation during their hospital stay.

Randomised trials conducted using cohorts: a scoping review.

INTRODUCTION: Cohort studies generate and collect longitudinal data for a variety of research purposes. Randomised controlled trials (RCTs) increasingly use cohort studies as data infrastructures to help identify and recruit trial participants and assess outcomes. OBJECTIVE: To examine the extent, range and nature of research using cohorts for RCTs and describe the varied definitions and conceptual boundaries for RCTs using cohorts. DESIGN: Scoping review. DATA SOURCES: Searches were undertaken in January 2021 in MEDLINE (Ovid) and EBM Reviews-Cochrane Methodology Registry (Final issue, third Quarter 2012). ELIGIBILITY CRITERIA: Reports published between January 2007 and December 2021 of (a) cohorts used or planned to be used, to conduct RCTs, or (b) RCTs which use cohorts to recruit participants and/or collect trial outcomes, or (c) methodological studies discussing the use of cohorts for RCTs. DATA EXTRACTION AND SYNTHESIS: Data were extracted on the condition being studied, age group, setting, country/continent, intervention(s) and comparators planned or received, unit of randomisation, timing of randomisation, approach to informed consent, study design and terminology. RESULTS: A total of 175 full-text articles were assessed for eligibility. We identified 61 protocols, 9 descriptions of stand-alone cohorts intended to be used for future RCTs, 39 RCTs using cohorts and 34 methodological papers.The use and scope of this approach is growing. The thematics of study are far-ranging, including population health, oncology, mental and behavioural disorders, and musculoskeletal conditions.Authors reported that this approach can lead to more efficient recruitment, more representative samples, and lessen disappointment bias and crossovers. CONCLUSION: This review outlines the development of cohorts to conduct RCTs including the range of use and innovative changes and adaptations. Inconsistencies in the use of terminology and concepts are highlighted. Guidance now needs to be developed to support the design and reporting of RCTs conducted using cohorts.

Research priorities for the management of major trauma: an international priority setting partnership with the James Lind Alliance.

OBJECTIVE: The objective of this study is to determine research priorities for the management of major trauma, representing the shared priorities of patients, their families, carers and healthcare professionals. DESIGN/SETTING: An international research priority-setting partnership. PARTICIPANTS: People who have experienced major trauma, their carers and relatives, and healthcare professionals involved in treating patients after major trauma. The scope included chest, abdominal and pelvic injuries as well as major bleeding, multiple injuries and those that threaten life or limb. METHODS: A multiphase priority-setting exercise was conducted in partnership with the James Lind Alliance over 24 months (November 2021-October 2023). An international survey asked respondents to submit their research uncertainties which were then combined into several indicative questions. The existing evidence was searched to ensure that the questions had not already been sufficiently answered. A second international survey asked respondents to prioritise the research questions. A final shortlist of 19 questions was taken to a stakeholder workshop, where consensus was reached on the top 10 priorities. RESULTS: A total of 1572 uncertainties, submitted by 417 respondents (including 132 patients and carers), were received during the initial survey. These were refined into 53 unique indicative questions, of which all 53 were judged to be true uncertainties after reviewing the existing evidence. 373 people (including 115 patients and carers) responded to the interim prioritisation survey and 19 questions were taken to a final consensus workshop between patients, carers and healthcare professionals. At the final workshop, a consensus was reached for the ranking of the top 10 questions. CONCLUSIONS: The top 10 research priorities for major trauma include patient-centred questions regarding pain relief and prehospital management, multidisciplinary working, novel technologies, rehabilitation and holistic support. These shared priorities will now be used to guide funders and teams wishing to research major trauma around the globe.

Randomised controlled trial comparing intraoperative cell salvage and autotransfusion with standard care in the treatment of hip fractures: a protocol for the WHITE 9 study.

INTRODUCTION: People who sustain a hip fracture are typically elderly, frail and require urgent surgery. Hip fracture and the urgent surgery is associated with acute blood loss, compounding patients' pre-existing comorbidities including anaemia. Approximately 30% of patients require a donor blood transfusion in the perioperative period. Donor blood transfusions are associated with increased rates of infections, allergic reactions and longer lengths of stay. Furthermore, there is a substantial cost associated with the use of donor blood. Cell salvage and autotransfusion is a technique that recovers, washes and transfuses blood lost during surgery back to the patient. The objective of this study is to determine the clinical and cost effectiveness of intraoperative cell salvage, compared with standard care, in improving health related quality-of-life of patients undergoing hip fracture surgery. METHODS AND ANALYSIS: Multicentre, parallel group, two-arm, randomised controlled trial. Patients aged 60 years and older with a hip fracture treated with surgery are eligible. Participants will be randomly allocated on a 1:1 basis to either undergo cell salvage and autotransfusion or they will follow the standard care pathway. Otherwise, all care will be in accordance with the National Institute for Health and Care Excellence guidance. A minimum of 1128 patients will be recruited to obtain 90% power to detect a 0.075-point difference in the primary endpoint: EuroQol-5D-5L HRQoL at 4 months post injury. Secondary outcomes will include complications, postoperative delirium, residential status, mobility, allogenic blood use, mortality and resource use. ETHICS AND DISSEMINATION: NHS ethical approval was provided on 14 August 2019 (19/WA/0197) and the trial registered (ISRCTN15945622). After the conclusion of this trial, a manuscript will be prepared for peer-review publication. Results will be disseminated in lay form to participants and the public. TRIAL REGISTRATION NUMBER: ISRCTN15945622.

Research priorities for the management of complex fractures: a UK priority setting partnership with the James Lind Alliance.

OBJECTIVE: To determine research priorities for the management of complex fractures, which represent the shared priorities of patients, their families, carers and healthcare professionals. DESIGN/SETTING: A national (UK) research priority setting partnership. PARTICIPANTS: People who have experienced a complex fracture, their carers and relatives, and relevant healthcare professionals and clinical academics involved in treating patients with complex fractures. The scope includes open fractures, fractures to joints broken into multiple pieces, multiple concomitant fractures and fractures involving the pelvis and acetabulum. METHODS: A multiphase priority setting exercise was conducted in partnership with the James Lind Alliance over 21 months (October 2019 to June 2021). A national survey asked respondents to submit their research uncertainties which were then combined into several indicative questions. The existing evidence was searched to ensure that the questions had not already been sufficiently answered. A second national survey asked respondents to prioritise the research questions. A final shortlist of 18 questions was taken to a stakeholder workshop, where a consensus was reached on the top 10 priorities. RESULTS: A total of 532 uncertainties, submitted by 158 respondents (including 33 patients/carers) were received during the initial survey. These were refined into 58 unique indicative questions, of which all 58 were judged to be true uncertainties after review of the existing evidence. 136 people (including 56 patients/carers) responded to the interim prioritisation survey and 18 questions were taken to a final consensus workshop between patients, carers and healthcare professionals. At the final workshop, a consensus was reached for the ranking of the top 10 questions. CONCLUSIONS: The top 10 research priorities for complex fracture include questions regarding rehabilitation, complications, psychological support and return to life-roles. These shared priorities will now be used to guide funders and teams wishing to research complex fractures over the coming decade.

Warwick Hip Trauma Study: a randomised clinical trial comparing interventions to improve outcomes in internally fixed intracapsular fractures of the proximal femur. Protocol for the WHiT Study.

BACKGROUND: Controversy exists regarding the optimal treatment for patients with displaced intracapsular fractures of the proximal femur. The recognised treatment alternatives are arthroplasty and internal fixation. The principal criticism of internal fixation is the high rate of non-union; up to 30% of patients will have a failure of the fixation leading to revision surgery. We believe that improved fracture healing may lead to a decreased rate of failure of fixation. We therefore propose to investigate strategies to both accelerate fracture healing and improve fixation that may significantly improve outcomes after internal fixation of intracapsular femoral fractures. We aim to test the clinical effectiveness of the osteoinductive agent platelet rich plasma and conduct a pilot study of a novel fixed-angle fixation system. DESIGN: We have planned a three arm, single centre, standard-of-care controlled, double blinded, pragmatic, randomised clinical trial. The trial will include a standard two-way comparison between platelet-rich plasma and standard-of-care fixation versus standard-of-care fixation alone. In addition there will be a subsidiary pilot arm testing a fixed-angle screw and plate fixation system. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49197425.