Val Redman

Cost effectiveness of initial endoscopy for dyspepsia in patients over age 50 years : a randomised controlled trial in primary care

BACKGROUND Dyspepsia can be managed by initial endoscopy and treatment based on endoscopic findings, or by empirical prescribing. We aimed to determine the cost effectiveness of initial endoscopy compared with usual management in patients with dyspepsia over age 50 years presenting to their primary care physician. METHODS 422 patients were recruited and randomly assigned to initial endoscopy or usual management. Primary outcomes were effect of treatment on dyspepsia symptoms and cost effectiveness. Secondary outcomes were quality of life and patient satisfaction. Total costs were calculated from individual patients use of resources with unit costs applied from national data. Statistical analysis of uncertainty on incremental cost-effectiveness ratio (ICER) was done along with a sensitivity analysis on unit costs with cost-effectiveness acceptability curves. FINDINGS In the 12 months following recruitment, 213 (84%) patients had an endoscopy compared with 75 (41%) controls. Initial endoscopy resulted in a significant improvement in symptom score (p=0.03), and quality of life pain dimension (p=0.03), and a 48% reduction in the use of proton pump inhibitors (p=0.005). The ICER was Pound Sterling1728 (UK Pound Sterling) per patient symptom-free at 12 months. The ICER was very sensitive to the cost of endoscopy, and could be reduced to Pound Sterling165 if the unit cost of this procedure fell from Pound Sterling246 to Pound Sterling100. INTERPRETATION Initial endoscopy in dyspeptic patients over age 50 might be a cost-effective intervention.

Randomised controlled trials in primary care: case study

Editorial by Thomas Although over 90% of patient contacts within the NHS occur in primary care, many of the interventions used in this setting remain unproved.1 The relevance of research undertaken in secondary or tertiary care to general practice is questionable, and more research based in primary care is needed.2 Increasing research in primary care will inevitably increase demand for randomised controlled trials in this setting. Some of the trials will be of health service interventions (pragmatic trials),3 where the focus lies in assessing the cost effectiveness of an intervention rather than efficacy or safety. The difficulties experienced in doing randomised controlled trials in primary care have been reported4–6 and are not restricted to this setting. 7 8 We discuss some of the issues that must be considered when conducting and interpreting the results of trials in primary care using examples generated during a trial of the management of dyspepsia (box). #### Birmingham open access endoscopy study The study aimed to evaluate the effectiveness of two management strategies for patients presenting in primary care with symptoms of dyspepsia. Two randomised controlled trials were conducted concurrently, with eligibility being determined by the patients age at presentation. Randomisation was done at the individual patient level by using sealed opaque, sequentially numbered envelopes during a primary care consultation for dyspepsia. ##### Initial endoscopy trial Eligible patients— 50 years of age or older. Intervention— Referred for open access endoscopy. ##### Test and endoscopy trial Eligible patients— Under 50 years. Intervention —Tested for Helicobacter pylori antibodies with Helisal near patient test. Patients with positive results referred for open access endoscopy; those with negative results received symptomatic treatment only. Control arms (both trials)— Managed according to “usual practice” excluding open access endoscopy. This included antacids, H2 receptor antagonists, proton pump inhibitors, outpatient gastroenterology referral, facilitated or direct access endoscopy (for example, vetted by consultant), …

Impact of wound edge protection devices on surgical site infection after laparotomy: multicentre randomised controlled trial (ROSSINI Trial).

Objective To determine the clinical effectiveness of wound edge protection devices in reducing surgical site infection after abdominal surgery. Design Multicentre observer blinded randomised controlled trial. Participants Patients undergoing laparotomy at 21 UK hospitals. Interventions Standard care or the use of a wound edge protection device during surgery. Main outcome measures Surgical site infection within 30 days of surgery, assessed by blinded clinicians at seven and 30 days and by patient’s self report for the intervening period. Secondary outcomes included quality of life, duration of stay in hospital, and the effect of characteristics of the patient and operation on the efficacy of the device. Results 760 patients were enrolled with 382 patients assigned to the device group and 378 to the control group. Six patients in the device group and five in the control group did not undergo laparotomy. Fourteen patients, seven in each group, were lost to follow-up. A total of 184 patients experienced surgical site infection within 30 days of surgery, 91/369 (24.7%) in the device group and 93/366 (25.4%) in the control group (odds ratio 0.97, 95% confidence interval 0.69 to 1.36; P=0.85). This lack of benefit was consistent across wound assessments performed by clinicians and those reported by patients and across all secondary outcomes. In the secondary analyses no subgroup could be identified in which there was evidence of clinical benefit associated with use of the device. Conclusions Wound edge protection devices do not reduce the rate of surgical site infection in patients undergoing laparotomy, and therefore their routine use for this role cannot be recommended. Trial registration Current Controlled Trials ISRCTN 40402832

Randomised controlled trial of Helicobacter pylori testing and endoscopy for dyspepsia in primary care

Abstract Objective: To determine the cost effectiveness of a strategy of near patient Helicobacter pylori testing and endoscopy for managing dyspepsia. Design: Randomised controlled trial. Setting: 31 UK primary care centres. Participants: 478 patients under 50 years old presenting with dyspepsia of longer than four weeks duration. Interventions: Near patient testing for H pylori and open access endoscopy for patients with positive results. Control patients received acid suppressing drugs or specialist referral at general practitioners discretion. Main outcome measures: Cost effectiveness based on improvement in symptoms and use of resources at 12 months; quality of life. Results: 40% of the study group tested positive for H pylori. 45% of study patients had endoscopy compared with 25% of controls. More peptic ulcers were diagnosed in the study group (7.4% v 2.1%, P=0.011). Paired comparison of symptom scores and quality of life showed that all patients improved over time with no difference between study and control groups. No significant differences were observed in rates of prescribing, consultation, or referral. Costs were higher in the study group (£367.85 v £253.16 per patient). Conclusions: The test and endoscopy strategy increases endoscopy rates over usual practice in primary care. The additional cost is not offset by benefits in symptom relief or quality of life. What is already known on this topic Patients younger than 50 without H pylori infection are unlikely to have treatable disease detected at endoscopy Such patients can be managed by acid suppression and reassurance alone Test and endoscopy (referral of patients testing positive for H pyloriin primary care) has been recommended as a way to reduce endoscopic workload What this paper adds Applying a test and endoscopy strategy increased the endoscopy referral rate from 25% to 40% The strategy produced no significant differences in symptoms or quality of life compared with usual management The increased costs of this strategy cannot be justified

Factors affecting attitudes toward colorectal cancer screening in the primary care population.

Background:Colorectal cancer (CRC) is a major cause of death in the United Kingdom. Regular screening could significantly reduce CRC-related morbidity and mortality. However, screening programmes in the United Kingdom have to date seen uptake rates of less than 60%. Attitudes towards screening are the primary factors determining patient uptake.Methods:A questionnaire was sent to people aged 50–69 years who were registered with general practices in the West Midlands. A total of 11 355 people (53%) completed the questionnaire. Multivariable logistic regression analyses were performed to identify those factors (gender, age, ethnicity, deprivation, number of symptoms, and their duration) that most strongly contributed to negative/positive attitudes in the primary care population.Results:Fourteen percent of respondents had a negative attitude towards screening. Men, older people, and those with Indian ethnic backgrounds were more likely to have negative attitudes toward screening, whereas people with Black-Caribbean ethnic background, people with multiple symptoms and those reporting abdominal pain, bleeding, and tiredness were more likely to have a positive attitude.Conclusion:Culturally relevant screening strategies should aim to increase knowledge of the symptoms and signs related to bowel cancer among South Asian ethnic groups in the United Kingdom. It is also important to find ways to increase the acceptability of screening among asymptomatic patients.

Evaluation of the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population

BackgroundBowel cancer is common and is a major cause of death. Meta-analysis of randomised controlled trials estimates that screening for colorectal cancer using faecal occult blood (FOB) test reduces mortality from colorectal cancer by 16%. However, FOB testing has a low positive predictive value, with associated unnecessary cost, risk and anxiety from subsequent investigation, and is unacceptable to a proportion of the target population. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with colorectal cancer, and this can be measured from a blood sample. Serum MMP-9 is potentially an accurate, low risk and cost-effective population screening tool. This study aims to evaluate the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population.Methods/DesignPeople aged 50 to 69 years, who registered in participating general practices in the West Midlands Region, will be asked to complete a questionnaire that asks about symptoms. Respondents who describe any colorectal symptoms (except only abdominal bloating and/or anal symptoms) and are prepared to provide a blood sample for MMP9 estimation and undergo a colonoscopy (current gold standard investigation) will be recruited at GP based clinics by a research nurse. Those unfit for colonoscopy will be excluded. Colonoscopies will be undertaken in dedicated research clinics. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the colonoscopy findings, and the combination of factors (e.g. symptoms and MMP-9 level) that best predict a diagnosis of malignancy (invasive disease or polyps) will be determined.DiscussionColorectal cancer is a major cause of morbidity and mortality. Most colorectal cancers arise from adenomas and there is a period for early detection by screening, but available tests have risks, are unacceptable to many, have high false positive rates or are expensive.This study will establish the potential of serum MMP-9 as a screening test for colorectal cancer. If it is confirmed as accurate and acceptable, this serum marker has the potential to assist with reducing the morbidity and mortality from colorectal cancer.

Serum matrix metalloproteinase 9 and colorectal neoplasia: A community-based evaluation of a potential diagnostic test

Background:A blood test may be a more acceptable routine colorectal cancer (CRC) screening test than faecal occult blood test, flexible sigmoidoscopy or colonoscopy, and could be safer and cheaper. We evaluated the accuracy of a serum matrix metalloproteinase (MMP9) test for CRC in a non-presenting symptomatic population.Methods:A cohort, aged 50–69 with lower gastrointestinal symptoms, was identified by community-based survey. Accuracy of serum MMP9 was assessed by comparison with colonoscopy. Logistic regression identified predictors of neoplasia and receiver operating characteristic curve analyses determined the cutoff to maximise the sensitivity.Results:Data were available for 748 patients. Overall, 46 cases of neoplasia were identified. Univariate analysis demonstrated that demographic characteristics, behavioural factors, clinical symptoms and raised serum MMP9 concentration were all significantly associated with the presence of neoplasia. Our final logistic regression model had a sensitivity of 79% and specificity of 70%.Conclusion:We demonstrated a significant association between serum MMP9 concentration and the presence of neoplasia. Serum MMP9 levels are raised in those with cancer and high-risk adenomas, although MMP9 estimation is likely to have the greatest predictive utility when used as part of a panel of biomarkers. Further work is required to identify biomarkers that are sufficiently accurate for implementing into routine practice.

Reduction of surgical site infection using a novel intervention (ROSSINI): study protocol for a randomised controlled trial

BackgroundSurgical site infection (SSI) is a common complication following abdominal surgery. It is associated with considerable morbidity and mortality, and its management results in significant cost to health services within both primary and secondary care. Some surgeons believe that the use of a wound-edge protection device may reduce the incidence of SSI. Whilst there is some encouraging evidence showing that such devices may lead to a reduction in SSI, there are no controlled trials of sufficient size or quality to support their routine use.Methods/Design750 patients will be recruited from around 20 surgical units within the United Kingdom. Patients undergoing laparotomy through any major abdominal incision for any indication, elective or emergency, are eligible. Patients under the age of 18, those undergoing a laparoscopic assisted procedure or who have undergone laparotomy within the previous 3 months, and those who are unable to give informed consent will be excluded. Patients will be randomised (1:1 ratio) to the use of a wound-edge protection device or no wound-edge protection device during surgery.Follow up will consist of blinded clinical wound reviews at 5-7 days and 30-33 days postoperatively with a self-completed questionnaire covering the intervening period. Quality of life questionnaires will be completed prior to surgery and at the subsequent wound review points and information on resource usage will also be captured.The primary outcome measure is SSI within 30 days of surgery. Secondary outcomes include the impact of the degree of wound contamination, patient comorbidity, and operative characteristics on the efficacy of a wound-edge protection device in reducing SSI and whether the use of a wound-edge protection device has an effect on health-related quality of life or length of hospital stay and is cost-effective.DiscussionRossini is the first multicentre observer-blinded randomised controlled trial of sufficient size and quality to establish whether the use of a wound-edge protection device in adult patients undergoing abdominal surgery leads to a lower rate of SSI. The results of this study will be used to inform current surgical practice and may potentially benefit patients undergoing surgery in the future.Trial registration numberCurrent Controlled Trials ISRCTN: ISRCTN40402832

Establishing the added benefit of measuring MMP9 in FOB positive patients as a part of the Wolverhampton colorectal cancer screening programme

BackgroundBowel cancer is common and a major cause of death. The NHS is currently rolling out a national bowel cancer screening programme that aims to cover the entire population by 2010. The programme will be based on the Faecal Occult Blood test (FOBt) that reduces mortality from colon cancer by 16%. However, FOB testing has a relatively low positive predictive value, with associated unnecessary cost, risk and anxiety from subsequent investigation, and is unacceptable to a proportion of the target population. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP9) have been found to be associated with colorectal cancer, and this can be measured from a blood sample. MMP9 has potential for detecting those at risk of having colorectal cancer. The aim of this study is to assess whether MMP9 estimation enhances the predictive value of a positive FOBt.Methods and designFOBt positive people aged 60–69 years attending the Wolverhampton NHS Bowel Cancer Screening Unit and providing consent for colonoscopy will be recruited. Participants will provide a blood sample prior to colonoscopy and permission for collection of the clinical outcome from screening unit records. Multivariate logistic regression analyses will determine the independent factors (patient and disease related, MMP9) associated with the prediction of neoplasia.DiscussionColorectal cancer is a major cause of morbidity and mortality. Pilot studies have confirmed the feasibility of the national cancer screening programme that is based on FOBt. However, the test has high false positive rates. MMP9 has significant potential as a marker for both adenomas and cancers. This study is to examine whether using MMP9 as an adjunct to FOBt improves the accuracy of screening and reduces the number of false positive tests that cause anxiety and require invasive and potentially harmful investigation.