Dmitri Nepogodiev

Meta-analysis of plasma to red blood cell ratios and mortality in massive blood transfusions for trauma §,§§

BACKGROUND The current military paradigm for blood transfusion in major trauma favours high plasma:RBC ratios. This study aimed determine whether high plasma:red blood cell (RBC) ratios during massive transfusion for trauma decrease mortality, using meta-analysis of contemporaneous groups matched for injury severity score. METHODS A systemic review of the published literature for massive blood transfusions in trauma was performed. Patients were categorised into groups based on plasma:RBC transfusion ratios. Meta-analysis was only performed when there were no significant differences in Injury Severity Score (ISS) between ratio groups within studies. The main endpoint was 30-day mortality. RESULTS Six observational studies reporting outcomes for 1885 patients were included in this meta-analysis. Five studies were from civilian environments and one from a military setting. Ratio cut-offs at 1:2 were the most commonly reported, demonstrating a survival advantage with higher ratios (OR 0.49, 95% CI 0.31-0.80, p=0.004). Ratios≥1:2 showed a significant reduction in mortality compared to lower ratios (OR 0.56, 95% CI 0.40-0.78, p<0.001). Reducing the cut-off level was still protective (ratios between 1:2.5 and 1:4, OR 0.41), although the confidence interval was wide (0.16-1.00, p=0.05) and data heterogenous (I(2)=78%). Ratios of 1:1 were not proven to confer additional benefit beyond ratios of 1:2 (OR 0.50, 95% CI 0.37-0.68, p<0.001). CONCLUSIONS In groups matched for ISS, there was a survival benefit with high plasma:RBC resuscitation ratios. No additional benefits of 1:1 over 1:2 ratios were identified.

A clinical and radiological assessment of incisional hernias following closure of temporary stomas.

AIMS The rate of incisional hernia at stoma closure sites is unclear. This study aimed to describe this rate in patients with closed stomas who had definitive post-operative imaging of their abdominal wall. METHODS A retrospective review of patients who had undergone stoma reversal and had a CT or MRI scan of the abdomen ≥2 months following reversal was performed. A radiologist, blinded to the original radiological report and clinical results, reviewed all scans for abdominal wall herniation. This was correlated to documented clinical findings. RESULTS Fifty-nine patients were included: 49 loop ileostomy and 10 end colostomy reversals. CT scans were performed for 57 patients and MRI for two. The median time from closure to imaging was 10 months (range 3-32 months). The combined clinical and radiological hernia rate was 34% (20/59). Imaging alone produced a rate of 31% (18/59). The clinical rate of hernia detection was 14% (8/59). Using the rate of clinical herniation as the detection standard, imaging had a low positive predictive value (33%, 6/18) but a high negative predictive value (95%, 39/41). Four patients required surgical repair of their stoma site hernia (20%, 4/20). CONCLUSIONS One in three patients undergoing stoma closure developed an incisional hernia. One in five of those with a hernia underwent surgical repair. Definitive imaging may provide an early surrogate marker for late clinically relevant hernias. Consideration of methods to prevent stoma closure site hernias should be considered.

Promoting research and audit at medical school: evaluating the educational impact of participation in a student-led national collaborative study.

BackgroundMedical students often struggle to engage in extra-curricular research and audit. The Student Audit and Research in Surgery (STARSurg) network is a novel student-led, national research collaborative. Student collaborators contribute data to national, clinical studies while gaining an understanding of audit and research methodology and ethical principles. This study aimed to evaluate the educational impact of participation.MethodsParticipation in the national, clinical project was supported with training interventions, including an academic training day, an online e-learning module, weekly discussion forums and YouTube® educational videos. A non-mandatory, online questionnaire assessed collaborators’ self-reported confidence in performing key academic skills and their perceptions of audit and research prior to and following participation.ResultsThe group completed its first national clinical study (“STARSurgUK”) with 273 student collaborators across 109 hospital centres. Ninety-seven paired pre- and post-study participation responses (35.5%) were received (male = 51.5%; median age = 23). Participation led to increased confidence in key academic domains including: communication with local research governance bodies (p < 0.001), approaching clinical staff to initiate local collaboration (p < 0.001), data collection in a clinical setting (p < 0.001) and presentation of scientific results (p < 0.013). Collaborators also reported an increased appreciation of research, audit and study design (p < 0.001).ConclusionsEngagement with the STARSurg network empowered students to participate in a national clinical study, which increased their confidence and appreciation of academic principles and skills. Encouraging active participation in collaborative, student-led, national studies offers a novel approach for delivering essential academic training.

Meta-analysis of predictive factors and outcomes for failure of non-operative management of blunt splenic trauma.

BACKGROUND This study aimed to analyse predictive factors and outcomes of failure of non-operative management (NOM) following blunt splenic trauma. METHODS A systematic review of the literature was performed for studies comparing failed NOM (fNOM) to successful NOM (sNOM) in adults (≥ 16 years). The main endpoints were fNOM and associated mortality. Between-study heterogeneity was assessed. Meta-analysis of high quality studies, identified using the Newcastle-Ottawa Scale, was performed using fixed or random models. RESULTS Four prospective and 21 retrospective studies were included. From 24,615 unselected patients, 3025 experienced fNOM (12%, range 4-52%). Meta-analysis of the high quality studies revealed that mortality was significantly higher with fNOM in unselected age groups (odds ratio 1.93, 95% confidence interval 1.04-3.57, p = 0.04, I(2) = 0%), in those <55 years old (OR 3.42, 95% CI 1.73-6.77, p = 0.02, I(2) = 0%) and in those ≥ 55 years old (OR 2.65, 95% CI 1.20-5.82, p = 0.02, I(2) = 0%). There was a significant improvement in sNOM following introduction of angioembolisation protocols (OR 0.26, 95% CI 0.13-0.53, p<0.002, I(2) = 51%), although these five studies were non-randomised. American Association for the Surgery of Trauma injury grades 4-5, the presence of moderate or large haemoperitoneum, increasing injury severity score and increasing age were all significantly associated with increased risk of fNOM. fNOM led to significantly longer intensive care unit and overall lengths of stay. CONCLUSIONS fNOM leads to increased resource use and increased mortality. Methods of preventing fNOM, such as angioembolisation, warrant further assessment. Patients with increasing age, AAST scores and moderate or large haemoperitoneums may benefit from closer monitoring.

Determining Surgical Complications in the Overweight (DISCOVER): a multicentre observational cohort study to evaluate the role of obesity as a risk factor for postoperative complications in general surgery

Introduction Obesity is increasingly prevalent among patients undergoing surgery. Conflicting evidence exists regarding the impact of obesity on postoperative complications. This multicentre study aims to determine whether obesity is associated with increased postoperative complications following general surgery. Methods and analysis This prospective, multicentre cohort study will be performed utilising a collaborative methodology. Consecutive adults undergoing open or laparoscopic, elective or emergency, gastrointestinal, bariatric or hepatobiliary surgery will be included. Day case patients will be excluded. The primary end point will be the overall 30-day major complication rate (Clavien-Dindo grade III–V complications). Data will be collected to risk-adjust outcomes for potential confounding factors, such as preoperative cardiac risk. This study will be disseminated through structured medical student networks using established collaborative methodology. The study will be powered to detect a two-percentage point increase in the major postoperative complication rate in obese versus non-obese patients. Ethics and dissemination Following appropriate assessment, an exemption from full ethics committee review has been received, and the study will be registered as a clinical audit or service evaluation at each participating hospital. Dissemination will take place through national and local research collaborative networks.

The effect of trainee research collaboratives in the UK

Trainee-led networks have pioneered a novel collaborative approach to research in the UK. Established at a similar time to the UK National Institute for Health Research in 2006, collaborative groups have developed new pathways for doctors in full-time specialty training to design, disseminate, and deliver high-quality, multicentre research. In parallel, the National Institute for Health Research set up Clinical Research Networks (CRNs) to coordinate delivery of research across 30 clinical specialties and 15 English regional networks. Analogous networks have also been established by the devolved administrations in Scotland, Northen Ireland, and Wales. CRNs provide infrastructure to promote and coordinate research, including funding research support staff and providing research skills training. Using gastrointestinal surgery as an example, we sought to quantify trainee-led collaborative research network engagement and compare hospital participation with CRN studies. We only considered CRN and trainee-led collaborative studies involving ten or more hospitals with information available about participating sites. We searched the CRN portfolio for closed gastrointestinal and general surgery studies. We contacted trainee networks via a national mailing list to identify trainee studies. We derived denominators from the total number of hospitals offering emergency or major elective gastrointestinal surgery. Overall, 238 (99%) of 241 UK hospitals providing general surgery services participated in one or more trainee-led collaborative studies over the past decade compared with 191 (79%) of 241 for CRN studies. With the three trainee-led studies that had been adopted into the CRN portfolio excluded, participation in trainee-led research remained similar, at 236 (98%) of 241. Trainee groups delivered 15 studies overall: 12 observational studies and three randomised controlled trials (RCTs), coordinated by five regional and two national trainee networks (appendix). These numbers compared with three observational studies and eight RCTs coordinated by the CRN. We noted strong participation in trainee collaborative studies, even in regions with low CRN coverage, with the mean number of studies per hospital greater for collaboratives than for CRNs (appendix). Regions with a Royal College of Surgeons Surgical Trials Centre had greater participation in both trainee and CRN studies: the mean number of studies per hospital was 8·2 versus 6·0 in regions without. Trainee-led collaboratives have driven substantial additional research participation across the UK, on top of that achievable through CRNs alone, and have engaged additional gastrointestinal surgery units with little infrastructure or associated costs. This success is now being replicated in other specialties, with the British Neurosurgical Trainee Research Collaborative engaging 26 of 30 UK adult trauma-receiving neurosurgical units in the RESCUE-ASDH RCT. As the collaborative model is extended globally, it offers a powerful opportunity to promote a collaborative research culture and grow capacity with minimal investment. Synergy between trainee-led networks and CRNs could maximise delivery of high-quality research across the UK.

Intraoperative cell salvage in a combat support hospital: a prospective proof of concept study.

BACKGROUND: Provision of transfusion support is an important element of contemporary military operations, but presents a considerable logistic burden. Intraoperative blood salvage (IBS) offers the potential to reduce dependency on donated red blood cell (RBC) supply. The aim of this study was to assess the feasibility of IBS in an operational environment.

Underreporting of Secondary Endpoints in Randomized Trials: Cross-sectional, Observational Study.

Objective: To determine if underreporting of secondary endpoints in randomized controlled trials occurs, using surgical site infection (SSI) as an example. Background: SSI is a commonly measured endpoint in surgical trials and can act as a proxy marker for primary and secondary endpoint assessments across trials in a range of medical specialties. Methods: Cross-sectional observational study of randomized trials including patients undergoing gastrointestinal surgery published in a representative selection of general medical and general surgical journals. Studies were included if SSI assessment was a prespecified endpoint. Adjusted binary logistic regression was used to identify factors associated with a high rate of SSI detection (≥10%). Results: From 216 trials including 45,633 patients, the pooled SSI rate was 7.7% (3519/45,633), which was significantly higher when assessed as a primary endpoint (12.6%, 1993/15,861, 49 studies) vs as a secondary endpoint (5.1%, 1526/29,772, 167 studies, P < 0.001). When assessed as a secondary outcome, standardized definitions and formal clinical reviews were used significantly less often. When adjusted for surgical contamination and methodological confounders, secondary assessment was associated with reduced SSI detection compared with primary assessment (adjusted odds ratio 0.24, 95% confidence interval 0.08–0.69, P = 0.008). Conclusions: Secondary endpoint assessment of SSI in randomized trials was associated with significantly reduced rigor and subsequent detection rates compared with assessment as a primary endpoint. Trial investigators should ensure that primary and secondary endpoint assessments are equally robust. PRISMA guidelines should be updated to promote the conduct of meta-analysis based only on primary outcomes from randomized controlled trials.

Surgical training and clinical trial involvement—the trainees’ view

As surgical trainees across multiple disciplines, it is our collective aim for all surgical patients to have the opportunity to participate in at least one clinical trial during their hospital episode.1 We recognise that most patients wish to have this option,2 and we want our training to facilitate this. Because patients have the right to be involved in improving surgical …

Meta-analysis protocols should be prospectively registered.

In the past three years, seven new randomised trials have evaluated the effectiveness of prophylactic mesh to prevent parastomal hernia. Since the most recent meta-analysis on this topic was published in 2012, an updated meta-analysis incorporating these new results was needed. Over the past year, seven such meta-analyses have been published on this exact topic (Table 1) [1–7] and another two groups are developing further reviews. A total of ten randomised controlled trials were included across the seven published meta-analyses. Only Cross et al. [5] pooled data from all ten trials, although Cornille et al. [1] did include all eight trials for which full results were available at the time of their literature search. Across the seven reviews, only four trials were included in every meta-analysis. The reasons for studies being excluded from analyses varied (Table 1); for example, Zhu et al. [4] and López-Cano et al. [7] only included trials evaluating the use of mesh for colostomies, whilst Wang et al. [2] only included patients having permanent end colostomies following resection for rectal cancer. Despite the differences in study inclusion, all seven meta-analyses drew identical conclusions; that prophylactic mesh is safe and may have a role in prevention of parastomal hernia. Most studies stressed that better evidence is needed to form a firm treatment recommendation, with only López-Cano et al. [7] stating that further trials are not needed. Simultaneous publication of similar reviews in multiple journals fails to make the best use of authors’ and editors’ time and resources. Unfortunately, overlap between metaanalyses is common, with two-thirds of published metaanalyses duplicating a similar previous review [20]. Such duplication represents a form of research waste, alongside previously identified wastes such as non-publication, study discontinuation and poor reporting. PROSPERO is an international prospective register of systematic reviews where researchers can register protocols for planned meta-analyses [21]. Only two of the reviews discussed here were registered on PROSPERO [3, 7]. If prospective registration of review protocols on PROSPERO were mandated by journal editors in the same way that all randomized controlled trials must be registered in clinical trials registries, duplication would be avoided.