Su Mason

The eVALuate study: two parallel randomised trials, one comparing laparoscopic with abdominal hysterectomy, the other comparing laparoscopic with vaginal hysterectomy

Objective To compare the effects of laparoscopic hysterectomy and abdominal hysterectomy in the abdominal trial, and laparoscopic hysterectomy and vaginal hysterectomy in the vaginal trial. Design Two parallel, multicentre, randomised trials. Setting 28 UK centres and two South African centres. Participants 1380 women were recruited; 1346 had surgery; 937 were followed up at one year. Primary outcome Rate of major complications. Results In the abdominal trial laparoscopic hysterectomy was associated with a higher rate of major complications than abdominal hysterectomy (11.1% v 6.2%, P = 0.02; difference 4.9%, 95% confidence interval 0.9% to 9.1%) and the number needed to treat to harm was 20. Laparoscopic hysterectomy also took longer to perform (84 minutes v 50 minutes) but was less painful (visual analogue scale 3.51 v 3.88, P = 0.01) and resulted in a shorter stay in hospital after the operation (3 days v 4 days). Six weeks after the operation, laparoscopic hysterectomy was associated with less pain and better quality of life than abdominal hysterectomy (SF-12, body image scale, and sexual activity questionnaires). In the vaginal trial we found no evidence of a difference in major complication rates between laparoscopic hysterectomy and vaginal hysterectomy (9.8% v 9.5%, P = 0.92; difference 0.3%, -5.2% to 5.8%), and the number needed to treat to harm was 333. We found no evidence of other differences between laparoscopic hysterectomy and vaginal hysterectomy except that laparoscopic hysterectomy took longer to perform (72 minutes v 39 minutes) and was associated with a higher rate of detecting unexpected pathology (16.4% v 4.8%, P = < 0.01). However, this trial was underpowered. Conclusions Laparoscopic hysterectomy was associated with a significantly higher rate of major complications than abdominal hysterectomy. It also took longer to perform but was associated with less pain, quicker recovery, and better short term quality of life. The trial comparing vaginal hysterectomy with laparoscopic hysterectomy was underpowered and is inconclusive on the rate of major complications; however, vaginal hysterectomy took less time.

Effect of population screening and treatment for Helicobacter pylori on dyspepsia and quality of life in the community: a randomised controlled trial

BACKGROUND Infection with Helicobacter pylori is the main cause of peptic-ulcer disease. Treatment of this infection might lower the prevalence of dyspepsia in the community and improve quality of life. We investigated this possibility in a double-blind randomised controlled trial. METHODS Individuals aged 40-49 years were randomly selected from the lists of 36 primary-care centres. A researcher interviewed participants with a validated dyspepsia questionnaire and the psychological general wellbeing index (PGWB). H. pylori status was assessed by the carbon-13-labelled urea breath test. Infected participants were randomly assigned active treatment (omeprazole 20 mg, clarithromycin 250 mg, and tinidazole 500 mg, each twice daily for 7 days) or identical placebo. Participants were followed up at 6 months and 2 years. FINDINGS Of 32,929 individuals invited, 8455 attended and were eligible; 2324 were positive for H. pylori and were assigned active treatment (1161) or placebo (1163). 1773 (76%) returned at 2 years. Dyspepsia or symptoms of gastro-oesophageal reflux were reported in 247 (28%) of 880 in the treatment group and 291 (33%) of 871 in the placebo group (absolute-risk reduction 5% [95% CI 1-10]). H. pylori treatment had no significant effect on quality of life (mean difference in PGWB score between groups 0.86 [-0.33 to 2.05]). INTERPRETATION Community screening and treatment for H. pylori produced only a 5% reduction in dyspepsia. This small benefit had no impact on quality of life.

Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis

OBJECTIVE To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis. DESIGN A multicentre randomised double blind placebo controlled trial. SUBJECTS Infants admitted to hospital with their first episode of RSV positive bronchiolitis. INTERVENTION Randomisation to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12 months. MAIN OUTCOME MEASURES Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of antiwheeze medication during follow up. RESULTS 161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure. Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Pla, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (CI)), −2 (−14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), −1 (−2 to 0). Percentage of infants receiving at least one prescription for antiwheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), −10 (−26 to 6); bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), −7 (−22 to 8). CONCLUSIONS There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.

Evaluating complementary medicine: methodological challenges of randomised controlled trials

Complementary medicine is increasingly popular for treating many different problems. Doctors and patients need evidence about complementary treatments, but randomised controlled trials need to be carefully designed to take holism into account and avoid invalid results You think that by understanding one, you can understand two, for one and one is two. But to understand two, you must first understand “and.” Sufi saying1 Complementary medicine should be evaluated as rigorously as conventional medicine to protect the public from charlatans and unsafe practices,2–5 but many practitioners of complementary medicine are reticent about evaluation of their practice. Sceptics maintain that this is because of fear that investigations will find treatments ineffective and threaten livelihoods. In defence, many practitioners argue that research methods dissect their practice in a reductionist manner and fail to take into account complementary medicines holistic nature leading to invalid evaluation. #### Summary points Complementary medicine comprises many different disciplines, a wide spectrum of practices and philosophies which differ from conventional medicine. Conventional medicine traditionally aims to diagnose illness and treat, cure, or alleviate symptoms. Many complementary disciplines aim not only to relieve symptoms and restore wellness but also to help individuals in a process of self healing within a holistic view of health. In this view, individuals are more than just mind, body, and spirit in a social—family …

Randomised, controlled trial of alternating pressure mattresses compared with alternating pressure overlays for the prevention of pressure ulcers: PRESSURE (pressure relieving support surfaces) trial

Abstract Objective To compare whether differences exist between alternating pressure overlays and alternating pressure mattresses in the development of new pressure ulcers, healing of existing pressure ulcers, and patient acceptability. Design Pragmatic, open, multicentre, randomised controlled trial. Setting 11 hospitals in six NHS trusts. Participants 1972 people admitted to hospital as acute or elective patients. Interventions Participants were randomised to an alternating pressure mattress (n = 982) or an alternating pressure overlay (n = 990). Main outcome measures The proportion of participants developing a new pressure ulcer of grade 2 or worse; time to development of new pressure ulcers; proportions of participants developing a new ulcer within 30 days; healing of existing pressure ulcers; and patient acceptability. Results Intention to treat analysis found no difference in the proportions of participants developing a new pressure ulcer of grade 2 or worse (10.7% overlay patients, 10.3% mattress patients; difference 0.4%, 95% confidence interval - 2.3% to 3.1%, P = 0.75). More overlay patients requested change owing to dissatisfaction (23.3%) than mattress patients (18.9%, P = 0.02). Conclusion No difference was found between alternating pressure mattresses and alternating pressure overlays in the proportion of people who develop a pressure ulcer. Trial registration ISRCTN 78646179

A sequential randomised controlled trial comparing a dry visco-elastic polymer pad and standard operating table mattress in the prevention of post-operative pressure sores.

Four hundred and forty-six general, vascular and gynaecological surgical patients were recruited to a two centre, double triangular sequential randomised controlled trial to compare the post-operative pressure sore incidence in patients positioned on the standard operating table mattress with those positioned on the dry visco-elastic polymer pad (Action Products Inc.). Two hundred and twenty two patients were randomised to the experimental group and 224 to the standard mattress. The main endpoint failure rate (a pressure sore) was found to be 11% (22/205) for patients allocated to the dry visco-elastic polymer pad and 20% (43/211) for patients allocated to the standard operating table mattress. There was a significant reduction in the odds of developing a pressure sore on the dry visco-elastic polymer pad as compared to the standard, [symbol see text] = 0.46 with 95% confidence interval of (0.26, 0.82), P = 0.010. The adjusted point estimates of the probability of developing a pressure sore on the dry visco-elastic polymer pad and the standard operating table mattress were 0.11 and 0.21 respectively.

Representation of South Asian people in randomised clinical trials: analysis of trials' data

Excluding patients of ethnic minority groups from clinical trials is unethical,1 introduces substantial bias, and means that findings are based on unrepresentative populations.2 The National Institutes of Health Revitalization Act 1993 requires that all minority groups be represented in the sample in research projects supported by the National Institutes of Health, unless there is a clear and compelling justification not to do so. In the United Kingdom no such legislation exists. To determine the proportion of South Asian participants (the biggest minority ethnic group in Britain) included in clinical trials we investigated the ethnicity profile of six clinical trials recently conducted by the Northern and Yorkshire Clinical Trials and Research Unit, University of Leeds. All were phase III, multicentre, randomised, controlled trials and had recruited large numbers of participants and centres. Two were national breast cancer trials for which regional recruitment figures were available; two …

Pressure relieving support surfaces (PRESSURE) trial: cost effectiveness analysis

Abstract Objective To assess the cost effectiveness of alternating pressure mattresses compared with alternating pressure overlays for the prevention of pressure ulcers in patients admitted to hospital. Design Cost effectiveness analysis carried out alongside the pressure relieving support surfaces (PRESSURE) trial; a multicentre UK based pragmatic randomised controlled trial. Setting 11 hospitals in six UK NHS trusts. Participants Intention to treat population comprising 1971 participants. Main outcome measures Kaplan Meier estimates of restricted mean time to development of pressure ulcers and total costs for treatment in hospital. Results Alternating pressure mattresses were associated with lower overall costs (£283.6 per patient on average, 95% confidence interval - £377.59 to £976.79) mainly due to reduced length of stay in hospital, and greater benefits (a delay in time to ulceration of 10.64 days on average, - 24.40 to 3.09). The differences in health benefits and total costs for hospital stay between alternating pressure mattresses and alternating pressure overlays were not statistically significant; however, a cost effectiveness acceptability curve indicated that on average alternating pressure mattresses compared with alternating pressure overlays were associated with an 80% probability of being cost saving. Conclusion Alternating pressure mattresses for the prevention of pressure ulcers are more likely to be cost effective and are more acceptable to patients than alternating pressure overlays.

The cost-effectiveness of population Helicobacter pylori screening and treatment: a Markov model using economic data from a randomized controlled trial

Economic models have suggested that population Helicobacter pylori screening and treatment may be a cost‐effective method of reducing mortality from gastric cancer. These models are conservative as they do not consider that the programme may reduce health service peptic ulcer and other dyspepsia costs. We have evaluated the economic impact of population H. pylori screening and treatment over 2 years in a randomized controlled trial and have incorporated the results into an economic model exploring the impact of H. pylori eradication on peptic ulcer disease and gastric cancer.

Improving the quality of consent to randomised controlled trials by using continuous consent and clinician training in the consent process

Objective: To assess whether continuous consent, a process in which information is given to research participants at different stages in a trial, and clinician training in that process were effective when used by clinicians while gaining consent to the Total Body Hypothermia (TOBY) trial. The TOBY trial is a randomised controlled trial (RCT) investigating the use of whole-body cooling for neonates with evidence of perinatal asphyxia. Obtaining valid informed consent for the TOBY trial is difficult, but is a good test of the effectiveness of continuous consent. Methods: Semistructured interviews were conducted with 30 sets of parents who consented to the TOBY trial and with 10 clinicians who sought it by the continuous consent process. Analysis was focused on the validity of parental consent based on the consent components of competence, information, understanding and voluntariness. Results: No marked problems with consent validity at the point of signature were observed in 19 of 27 (70%) couples. Problems were found mainly to lie with the competence and understanding of the parents: mothers, particularly, had problems with competence in the early stages of consent. Problems in understanding were primarily to do with side effects. Problems in both competence and understanding were observed to reduce markedly, particularly for mothers, in the post-signature phase, when further discussion took place. Randomisation was generally understood but unpopular. Information was not always given by clinicians in stages during the short period available before parents gave consent. Most clinicians, however, were able to give follow-up information. Discussion: Consent validity was found to compare favourably with similar trials examined in the Euricon study. Conclusion: Adopting the elements of the continuous consent process and clinician training in RCTs should be considered by researchers, particularly when they have concerns about the quality of consent they are likely to obtain by using a conventional process.