Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718.).

Controlled-trials.com (ISRCTN46552265).

Background Late-stage isolated medial knee osteoarthritis can be treated with total knee replacement (TKR) or partial knee replacement (PKR). There is high variation in treatment choice and little robust evidence to guide selection. The Total or Partial Knee Arthroplasty Trial (TOPKAT) therefore aims to assess the clinical effectiveness and costeffectiveness of TKR versus PKR in patients with medial compartment osteoarthritis of the knee, and this represents an analysis of the main endpoints at 5 years. Methods Our multicentre, pragmatic randomised controlled trial was done at 27 UK sites. We used a combined expertise-based and equipoise-based approach, in which patients with isolated osteoarthritis of the medial compartment of the knee and who satisfied general requirements for a medial PKR were randomly assigned (1:1) to receive PKR or TKR by surgeons who were either expert in and willing to perform both surgeries or by a surgeon with particular expertise in the allocated procedure. The primary endpoint was the Oxford Knee Score (OKS) 5 years after randomisation in all patients assigned to groups. Health-care costs (in UK 2017 prices) and cost-effectiveness were also assessed. This trial is registered with ISRCTN (ISRCTN03013488) and ClinicalTrials.gov (NCT01352247). Findings Between Jan 18, 2010, and Sept 30, 2013, we assessed 962 patients for their eligibility, of whom 431 (45%) patients were excluded (121 [13%] patients did not meet the inclusion criteria and 310 [32%] patients declined to participate) and 528 (55%) patients were randomly assigned to groups. 94% of participants responded to the follow-up survey 5 years after their operation. At the 5-year follow-up, we found no difference in OKS between groups (mean difference 1•04, 95% CI-0•42 to 2•50; p=0•159). In our within-trial cost-effectiveness analysis, we found that PKR was more effective (0•240 additional quality-adjusted life-years, 95% CI 0•046 to 0•434) and less expensive (-£910, 95% CI-1503 to-317) than TKR during the 5 years of follow-up. This finding was a result of slightly better outcomes, lower costs of surgery, and lower follow-up health-care costs with PKR than TKR. Interpretation Both TKR and PKR are effective, offer similar clinical outcomes, and result in a similar incidence of re-operations and complications. Based on our clinical findings, and results regarding the lower costs and better costeffectiveness with PKR during the 5-year study period, we suggest that PKR should be considered the first choice for patients with late-stage isolated medial compartment osteoarthritis.

Objective To determine whether, from a health provider and patient perspective, surgical stabilisation of the spine is cost effective when compared with an intensive programme of rehabilitation in patients with chronic low back pain. Design Economic evaluation alongside a pragmatic randomised controlled trial. Setting Secondary care. Participants 349 patients randomised to surgery (n = 176) or to an intensive rehabilitation programme (n = 173) from 15 centres across the United Kingdom between June 1996 and February 2002. Main outcome measures Costs related to back pain and incurred by the NHS and patients up to 24 months after randomisation. Return to paid employment and total hours worked. Patient utility as estimated by using the EuroQol EQ-5D questionnaire at several time points and used to calculate quality adjusted life years (QALYs). Cost effectiveness was expressed as an incremental cost per QALY. Results At two years, 38 patients randomised to rehabilitation had received rehabilitation and surgery whereas just seven surgery patients had received both treatments. The mean total cost per patient was estimated to be £7830 (SD £5202) in the surgery group and £4526 (SD £4155) in the intensive rehabilitation arm, a significant difference of £3304 (95% confidence interval £2317 to £4291). Mean QALYs over the trial period were 1.004 (SD 0.405) in the surgery group and 0.936 (SD 0.431) in the intensive rehabilitation group, giving a non-significant difference of 0.068 ( − 0.020 to 0.156). The incremental cost effectiveness ratio was estimated to be £48 588 per QALY gained ( − £279 883 to £372 406). Conclusion Two year follow-up data show that surgical stabilisation of the spine may not be a cost effective use of scarce healthcare resources. However, sensitivity analyses show that this could change-for example, if the proportion of rehabilitation patients requiring subsequent surgery continues to increase.

OFG mainly presents in young adults with lip and buccal involvement. Abnormalities in inflammatory markers, hematology and oral features of ulceration, and buccal-sulcal involvement are factors more commonly associated with CD. Initial presentation of OFG does not necessarily predict development of CD, although this is more likely in childhood.

Non-variceal upper gastrointestinal bleeding (NVUGIB) is bleeding that develops in the oesophagus, stomach or proximal duodenum. Peptic ulcers, caused by Helicobacter pylori infection or use of NSAIDs and low-dose aspirin (LDA), are the most common cause. Although the incidence and mortality associated with NVUGIB have been decreasing owing to considerable advances in the prevention and management of NVUGIB over the past 20 years, it remains a common clinical problem with an annual incidence of ∼67 per 100,000 individuals in the United States in 2012. NVUGIB is a medical emergency, and mortality is in the range ∼1-5%. After resuscitation and initial assessment, early (within 24 hours) diagnostic and therapeutic endoscopy together with intragastric pH control with proton pump inhibitors (PPIs) form the basis of treatment. With a growing ageing population treated with antiplatelet and/or anticoagulant medications, the clinical management of NVUGIB is complex as the risk between gastrointestinal bleeding events and adverse cardiovascular events needs to be balanced. The best clinical approach includes identification of risk factors and prevention of bleeding; available strategies include continuous treatment with PPIs or H. pylori eradication in those at increased risk of developing NVUGIB. Treatment with PPIs and/or use of cyclooxygenase-2-selective NSAIDs should be implemented in those patients at risk of NVUGIB who need NSAIDs and/or LDA.

ObjectiveIn 2001, the National Institute for Health Research Cancer Research Network (NCRN) was established, leading to a rapid increase in clinical research activity across the English NHS. Using colorectal cancer (CRC) as an example, we test the hypothesis that high, sustained hospital-level participation in interventional clinical trials improves outcomes for all patients with CRC managed in those research-intensive hospitals.DesignData for patients diagnosed with CRC in England in 2001–2008 (n=209 968) were linked with data on accrual to NCRN CRC studies (n=30 998). Hospital Trusts were categorised by the proportion of patients accrued to interventional studies annually. Multivariable models investigated the relationship between 30-day postoperative mortality and 5-year survival and the level and duration of study participation.ResultsMost of the Trusts achieving high participation were district general hospitals and the effects were not limited to cancer ‘centres of excellence’, although such centres do make substantial contributions. Patients treated in Trusts with high research participation (≥16%) in their year of diagnosis had lower postoperative mortality (p<0.001) and improved survival (p<0.001) after adjustment for casemix and hospital-level variables. The effects increased with sustained research participation, with a reduction in postoperative mortality of 1.5% (6.5%–5%, p<2.2×10−6) and an improvement in survival (p<10−19; 5-year difference: 3.8% (41.0%–44.8%)) comparing high participation for ≥4 years with 0 years.ConclusionsThere is a strong independent association between survival and participation in interventional clinical studies for all patients with CRC treated in the hospital study participants. Improvement precedes and increases with the level and years of sustained participation.

Background Late-stage medial compartment knee osteoarthritis can be treated using total knee replacement or partial (unicompartmental) knee replacement. There is high variation in treatment choice and insufficient evidence to guide selection. Objective To assess the clinical effectiveness and cost-effectiveness of partial knee replacement compared with total knee replacement in patients with medial compartment knee osteoarthritis. The findings are intended to guide surgical decision-making for patients, surgeons and health-care providers. Design This was a randomised, multicentre, pragmatic comparative effectiveness trial that included an expertise component. The target sample size was 500 patients. A web-based randomisation system was used to allocate treatments. Setting Twenty-seven NHS hospitals (68 surgeons). Participants Patients with medial compartment knee osteoarthritis. Interventions The trial compared the overall management strategy of partial knee replacement treatment with total knee replacement treatment. No specified brand or subtype of implant was investigated. Main outcome measures The Oxford Knee Score at 5 years was the primary end point. Secondary outcomes included activity scores, global health measures, transition items, patient satisfaction (Lund Score) and complications (including reoperation, revision and composite ‘failure’ – defined by minimal Oxford Knee Score improvement and/or reoperation). Cost-effectiveness was also assessed. Results A total of 528 patients were randomised (partial knee replacement, n = 264; total knee replacement, n = 264). The follow-up primary outcome response rate at 5 years was 88% and both operations had good outcomes. There was no significant difference between groups in mean Oxford Knee Score at 5 years (difference 1.04, 95% confidence interval –0.42 to 2.50). An area under the curve analysis of the Oxford Knee Score at 5 years showed benefit in favour of partial knee replacement over total knee replacement, but the difference was within the minimal clinically important difference [mean 36.6 (standard deviation 8.3) (n = 233), mean 35.1 (standard deviation 9.1) (n = 231), respectively]. Secondary outcome measures showed consistent patterns of benefit in the direction of partial knee replacement compared with total knee replacement although most differences were small and non-significant. Patient-reported improvement (transition) and reflection (would you have the operation again?) showed statistically significant superiority for partial knee replacement only, but both of these variables could be influenced by the lack of blinding. The frequency of reoperation (including revision) by treatment received was similar for both groups: 22 out of 245 for partial knee replacement and 28 out of 269 for total knee replacement patients. Revision rates at 5 years were 10 out of 245 for partial knee replacement and 8 out of 269 for total knee replacement. There were 28 ‘failures’ of partial knee replacement and 38 ‘failures’ of total knee replacement (as defined by composite outcome). Beyond 1 year, partial knee replacement was cost-effective compared with total knee replacement, being associated with greater health benefits (measured using quality-adjusted life-years) and lower health-care costs, reflecting lower costs of the index surgery and subsequent health-care use. Limitations It was not possible to blind patients in this study and there was some non-compliance with the allocated treatment interventions. Surgeons providing partial knee replacement were relatively experienced with the procedure. Conclusions Both total knee replacement and partial knee replacement are effective, offer similar clinical outcomes and have similar reoperation and complication rates. Some patient-reported measures of treatment approval were significantly higher for partial knee replacement than for total knee replacement. Partial knee replacement was more cost-effective (more effective and cost saving) than total knee replacement at 5 years. Future work Further (10-year) follow-up is in progress to assess the longer-term stability of these findings. Trial registration Current Controlled Trials ISRCTN03013488 and ClinicalTrials.gov NCT01352247. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 20. See the NIHR Journals Library website for further project information.