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Biomedical subjects

D Braunholtz

Publications and source records attributed to D Braunholtz.

18 recordsLinked to original sources
PubMed2004

Trials in surgery.

BACKGROUND: Trials in surgery pose some special problems. This paper examines these with reference to 10 years of methodological research sponsored by the UK National Health Service Research and Development programme. METHODS: Solutions to common problems encountered in surgical studies were considered, such as issues of blinding, dependence of results on technical skill and continued evolution of technology. RESULTS: Numerous methodological developments are described, including the tracker trial concept in which trial design can be adapted to take account of technical developments and interim results. The governance of trials, solutions to ethical conundra and the rising importance of databases are also discussed. CONCLUSION: Like surgery itself, the methodological toolkit for evaluation of surgical procedures continues to evolve. The rules of statistical and scientific probity provide plenty of scope for imaginative design solutions for surgical trials.

Bias↗
PubMed2004

Randomisation in trials: do potential trial participants understand it and find it acceptable?

OBJECTIVE: To examine lay persons' ability to identify methods of random allocation and their acceptability of using methods of random allocation in a clinical trial context. DESIGN: Leaflets containing hypothetical medical, non-medical, and clinical trial scenarios involving random allocation, using material from guidelines for trial information leaflets. SETTING AND PARTICIPANTS: Adults attending further education colleges (n = 130), covering a wide range of ages, occupations, and levels of education. MAIN MEASURES: Judgements of whether each of five methods of allocation to two groups was random in a medical or non-medical scenario. Judgements of whether these allocation methods were acceptable in a randomised clinical trial scenario, with or without a scientific justification for randomisation. RESULTS: The majority of our group of participants judged correctly that allowing people their preference was not random, and that the following were random: using a computer with no information about the individual (recommended wording for MREC trial leaflets), tossing a coin, drawing a name out of a hat. Judgements were split over allocating people in turn (not a random allocation method but shares features with randomisation). Judgements were no different in medical and non-medical scenarios. Few of the correctly identified random methods were judged to be acceptable in a clinical trial scenario. Inclusion of a scientific justification for randomising significantly increased the acceptability of only one random method: allocation by computer. CONCLUSIONS: Current UK guidelines' recommended description of random allocation by computer seems warranted. However, while potential trial participants may understand what random allocation means, they may find it unacceptable unless offered an acceptable justification for its use.

Adolescent↗
PubMed2003

Helicobacter pylori infection in subjects with acute ischaemic stroke.

AIMS: To determine whether infection with Helicobacter pylori is a significant risk factor for stroke. SUBJECTS: A total 467 in-patients with clinical evidence of acute ischaemic stroke and 388 healthy controls with no evidence of cerebrovascular disease. METHODS: This was a case control study. The prevalence of Helicobacter pylori was measured by enzyme-linked immunosorbent assay in stroke patients and controls. A positive titre was defined as >15 U/ml and relationship with circulating plasma fibrinogen and social depravation was expressed using the Townsend Index. RESULTS: There were significantly more Helicobacter pylori positive individuals (274/398 (69%)) in the cases compared to the controls (206/352 (58.5%)). Fibrinogen levels were also significantly higher in Helicobacter pylori positive (mean 4.14, standard deviation 1.33) than negative individuals (mean 3.78, standard deviation 1.28). The association between Helicobacter pylori and stroke was lost in a logistic model controlling for socio-economic status. Furthermore, fibrinogen levels were not associated with Helicobacter pylori status in a linear regression model controlling for socio-economic status. CONCLUSIONS: Infection with Helicobacter pylori is associated with an increased risk of stroke and increased fibrinogen levels but these findings can be attributed to a confounding effect of socio-economic status.

Aged↗
PubMed2003

The measurement of active errors: methodological issues.

The value of research in any topic area turns on its validity. Patient safety research has revealed--or, at least, given renewed urgency to--a raft of methodological issues. The meaning and thus the value of empirical research in this field is contingent on getting the methodology right. The need for good methods for the measurement of error is necessary whenever an inference is intended and, since inferences lie at the heart of research and management, there is a huge need to understand better how to make measurements that are meaningful, precise, and accurate. In this paper we consider issues relating to the measurement of error and the need for more research.

Empirical Research↗
PubMed2003

Top-rated British business research: has the emperor got any clothes?

Business schools have great prestige and charge large amounts of money for their courses. But how good is the science on which they base their prescriptions for action? To find out we examined the published output from the only three British business schools with the highest (5*) research assessment ranking at the time the articles were published. We conclude that theory development and model construction are often elegant. However, the methods used to obtain primary empirical information to confirm or refute the theories or populate models are poor, at least from a positivist or pragmatic ontological perspective. Large scale comparative studies made up only a small proportion of research output from the business schools. Literature reviews were not systematic. The sampling frame and rationale for selection of cases for study are inadequately described. The methods of data collection were frequently not given in sufficient detail to enable the study to be replicated and the conclusions tended to go far beyond what the data by themselves could support. However, this does not have to be the case-there are excellent examples of research in social sciences. We conclude, therefore, that top-rated British business research is a scantily clad emperor.

Commerce↗
PubMed2002

The Leeds University Maternity Audit Project.

OBJECTIVES: To measure levels of and changes in compliance with evidence-based recommendations in obstetrics in the UK. To identify barriers to and factors associated with compliance. DESIGN: A quantitative case-note audit for 1988 and 1996, and a qualitative interview study of key staff. SETTING: Twenty maternity units, selected at random from all UK units SUBJECTS: Fifty consecutive cases of pre-term delivery (PTD), Caesarean section (CS), instrumental delivery (ID), and perineal repair (PR) operations in each period in each unit. The lead clinician, midwifery manager, a senior midwife, neonatologist, and middle-grade obstetrician in each unit. MAIN OUTCOME MEASURES: Maternal steroid use in PTD, antibiotic use in CS, use of the ventouse (vacuum extractor) rather than forceps as instrument of first choice for ID, and use of polyglycolic acid (PGA) sutures for PR in each time period. Facilities for implementing, staff attitudes to, and the degree of planning to follow each recommendation. MAIN RESULTS: The median proportion of ventouse as instrument of first choice in each unit was 8% (range 0-32%) in 1988, rising to 64% (range 0-98%) in 1996. PGA use for PR was 0% (range 0-30%) in 1988, and 72% (range 0-100%) in 1996. Steroid use for eligible PTD was median 0% (range 0-23%) in 1988, rising to 82% (range 63-95%) in 1996. Antibiotic use for CS was 7% (range 0-25%) rising to 84% (range 10-100%) in 1996. There was no relationship between unit size, type of unit, facilities, staff attitudes or degree of planning, and compliance with the recommendations, nor was the level of adherence to one standard typically correlated with adherence to the others. However, there was a positive correlation (R = 0.6, P < 0.005) between local availability of the Cochrane database of perinatal trials and unit compliance with the audit standards in the latter time period. CONCLUSIONS: We have documented a massive shift in practice in line with the evidence, although many units still have substantial room for improvement. About 2000 wound infections, 200 deaths due to prematurity, nearly 8000 women in pain from catgut sutures, and 1500 cases of severe perineal trauma from forceps remain preventable. The reasons why units vary remain obscure, although the qualitative interviews often revealed local factors such as key enthusiastic staff. There was no sign of evidence being positively driven into practice by any systematic managerial process. The relationship between Cochrane availability and high-standard care may be simply a marker of commitment to the evidence, but it remains plausible that if senior staff make Cochrane available for their juniors, audit compliance improves.

Adult↗
PubMed2000

The proportion of upper gastrointestinal symptoms in the community associated with Helicobacter pylori, lifestyle factors, and nonsteroidal anti-inflammatory drugs. Leeds HELP Study Group.

OBJECTIVE: Upper gastrointestinal disorders are common in the community, yet the determinants of these symptoms are poorly characterized. The association between upper gastrointestinal symptoms and Helicobacter pylori (H. pylori), socioeconomic status, nonsteroidal antiinflammatory drug (NSAID) use, smoking, alcohol, and coffee intake was assessed in a cross-sectional survey. METHODS: Subjects between the ages of 40-49 yr were randomly selected from the lists of 36 primary care centers. Participants attended their local primary care center and were interviewed by a researcher using a validated dyspepsia questionnaire. H. pylori status was determined by a nonfasting 13C-urea breath test. RESULTS: A total of 32,929 subjects were invited, and 8,407 (25%) attended and were eligible. Of these, 2,329 (28%) were H. pylori positive and 3,177 (38%) had dyspepsia. Also, 44% of H. pylori-infected participants reported dyspepsia compared with 36% of uninfected subjects [odds ratio = 1.39; 95% confidence interval (CI) 1.26-1.53]. H. pylori infection remained a significant risk factor for dyspepsia in a multiple logistic regression model (odds ratio = 1.21; 95% CI 1.09-1.34), suggesting that 5% of dyspepsia in the population is attributable to H. pylori. NSAIDs, low educational attainment, renting accommodation, absence of central heating, sharing a bed with siblings, and being married were also significantly associated with dyspepsia in this model. Smoking, but not drinking alcohol or coffee, was marginally associated with dyspepsia, but this finding was not robust. These factors were not associated with any dyspepsia subtype. CONCLUSIONS: H. pylori is significantly associated with dyspepsia and may be responsible for 5% of upper gastrointestinal symptoms in the community.

Adult↗
PubMed2000

Who's afraid of Thomas Bayes?

Sometimes direct evidence is so strong that a prescription for practice is decreed. Usually, things are not that simple-leaving aside the possibility that important trade offs may be involved, direct comparative data may be imprecise (especially in crucial sub-groups) or subject to possible bias, or there may be no direct comparative evidence; but still decisions have to be made. In these circumstances, indirect evidence-the plausibility of effects-enters the frame. But how should we describe the extent of plausibility and, having done so, how can this be integrated with any direct evidence that might exist. Also, how can allowance be made in a transparent (that is, explicit) way for perceptions of the size of bias in the direct evidence. Enter the Reverend Thomas Bayes; plausibility (however derived-laboratory experiment, qualitative study or just "experience") is captured numerically as degrees of belief ("prior" to the direct data) and updated (by the direct evidence) to yield "posterior" probabilities for use in decision making. The mathematical model used for this purpose must explicitly take account of assumptions about bias in the direct data. This paradigm bridges theory and practice, and provides the intellectual scaffold for those who recognise that (numerically definable) probabilities, and values (also numerically definable) underlie decisions, but who also realise that subjectivity is ineluctable in science.

Bayes Theorem↗
PubMed1998

The Leeds Dyspepsia Questionnaire: a valid tool for measuring the presence and severity of dyspepsia.

BACKGROUND: There is currently no validated questionnaire that assesses both the presence and severity of dyspepsia. AIM: To develop the Leeds Dyspepsia Questionnaire (LDQ) as a measure of the presence and severity of dyspepsia, and to assess the validity, reliability and responsiveness of this instrument. METHODS: Unselected patients attending either a hospital dyspepsia clinic or a general practice surgery were interviewed by a trained gastroenterologist or a general practitioner on the presence and severity of dyspepsia. This opinion was compared with the results of the nurse-administered LDQ. Test-retest reliability was assessed by the same research nurse re-administering the LDQ 4-7 days after the initial visit in a subgroup of hospital patients. In a further subgroup of patients one researcher interviewed the patients and a second researcher re-administered the LDQ within 30 min to evaluate inter-rater reliability. The responsiveness of the LDQ was measured by repeating it in patients with endoscopically proven peptic ulcer or oesophagitis 1 month after receiving appropriate therapy. RESULTS: The LDQ was administered to 99 general practice and 215 hospital patients. In the GP population 41/98 (42%) had dyspepsia according to the GP and the LDQ had a sensitivity of 80% (95% CI: 65-91%) and a specificity of 79% (95% CI: 66-89%). The weighted kappa statistic for the agreement between the LDQ and the clinician for the severity of dyspepsia was 0.58 in the GP population and 0.49 in hospital patients. The kappa statistic for test-retest reliability was 0.83 in 107 patients. The LDQ had excellent inter-rater reliability with a kappa statistic of 0.90 in 42 patients. The median LDQ score fell from 22.5 (range 9-36) to 4.5 (range 0-27) in 12 patients 1 month after receiving appropriate therapy (Wilcoxon signed rank test, P < 0.0001). CONCLUSION: The LDQ is a valid, reliable and responsive instrument for measuring the presence and severity of dyspepsia.

Adolescent↗
PubMed1997

Helicobacter pylori infection is related to atheroma in patients undergoing coronary angiography.

OBJECTIVES: Helicobacter pylori infection has been related to an increased risk of ischaemic heart disease (IHD) possibly by raising plasma fibrinogen. The evidence for this association is conflicting. Furthermore, no attempt has been made to distinguish between an effect on atheroma and thrombosis. We have determined the association of H. pylori status with IHD assessed by coronary angiography. We have also evaluated the influence of H. pylori infection on haemostatic factors. METHODS: Caucasian patients undergoing coronary angiography for suspected IHD were recruited. H. pylori status was determined by serology (Helico G). Plasma fibrinogen was measured by the Clauss assay. Coronary angiograms were assessed and significant atheroma defined as > or = 50% stenosis. A history of myocardial infarction was ascertained by WHO criteria. RESULTS: 292 patients were recruited (median age 59, 95 female); 204 (70%) patients had IHD and 185 (64%) of all patients were H. pylori-positive; 68% patients with IHD were H. pylori-positive compared with 50% without IHD (P = 0.003). When adjusted for other risk factors by logistic regression, H. pylori remained significantly associated with IHD (odds ratio = 2.4, 95% CI = 1.2-5.1, P = 0.02). H. pylori status was not related to a history of myocardial infarction. Circulating levels of PAI-1, vWF, Factor VII and fibrinogen were not related to H. pylori status. CONCLUSION: This study suggests that infection with H. pylori is associated with coronary atheroma, but that this relationship is unlikely to be mediated through raised plasma fibrinogen.

Adult↗
PubMed1997

Do patients need to fast for a 13C-urea breath test?

OBJECTIVE: The 13C-urea breath test (13C-UBT) is a useful non-invasive method of diagnosing Helicobacter pylori infection. One of its limitations, however, is that patients have to fast for 4 h before testing. We have compared the accuracy of a non-fasting 13C-UBT (NF13C-UBT) with a fasting 13C-UBT (F13C-UBT) test and against a gold standard. DESIGN: An unblinded prospective crossover study. METHODS: H. pylori status was assessed by histology, culture and rapid urease test. Patients were defined as H. pylori positive if two or more tests gave a positive result and negative if all tests were negative. H. pylori status was indeterminate if only one test gave a positive result. Following endoscopy patients had a F13C-UBT and then a further NF13C-UBT up to 14 days later after eating two slices of toast with jam or honey and tea or coffee. RESULTS: Of the 222 patients recruited to the study, 123 were gold standard H. pylori positive and 94 were negative with five patients having indeterminate status. Compared to this gold standard the NF13C-UBT had a 98% sensitivity and 96% specificity and the F13C-UBT had a 96% sensitivity and 97% specificity. The NF13C-UBT and F13C-UBT agreed in 217/222 (98%) cases. CONCLUSION: Relaxation of the fasting state does not reduce the accuracy of the 13C-UBT, making this test more convenient for patients.

Biopsy↗
PubMed1996

The statistical basis of public policy: a paradigm shift is overdue.

The recent controversy over the increased risk of venous thrombosis with third generation oral contraceptives illustrates the public policy dilemma that can be created by relying on conventional statistical tests and estimates: case-control studies showed a significant increase in risk and forced a decision either to warn or not to warn. Conventional statistical tests are an improper basis for such decisions because they dichotomise results according to whether they are or are not significant and do not allow decision makers to take explicit account of additional evidence--for example, of biological plausibility or of biases in the studies. A Bayesian approach overcomes both these problems. A Bayesian analysis starts with a "prior" probability distribution for the value of interest (for example, a true relative risk)--based on previous knowledge--and adds the new evidence (via a model) to produce a "posterior" probability distribution. Because different experts will have different prior beliefs sensitivity analyses are important to assess the effects on the posterior distributions of these differences. Sensitivity analyses should also examine the effects of different assumptions about biases and about the model which links the data with the value of interest. One advantage of this method is that it allows such assumptions to be handled openly and explicitly. Data presented as a series of posterior probability distributions would be a much better guide to policy, reflecting the reality that degrees of belief are often continuous, not dichotomous, and often vary from one person to another in the face of inconclusive evidence.

Attitude to Health↗
PubMed1995

Clinical trials and rare diseases: a way out of a conundrum.

Currently, clinical trials tend to be individually funded and applicants must include a power calculation in their grant request. However, conventional levels of statistical precision are unlikely to be obtainable prospectively if the trial is required to evaluate treatment of a rare disease. This means that clinicians treating such diseases remain in ignorance and must form their judgments solely on the basis of (potentially biased) observational studies experience, and anecdote. Since some unbiased evidence is clearly better than none, this state of affairs should not continue. However, conventional (frequentist) confidence limits are unlikely to exclude a null result, even when treatments differ substantially. Bayesian methods utilise all available data to calculate probabilities that may be extrapolated directly to clinical practice. Funding bodies should therefore fund a repertoire of small trials, which need have no predetermined end, alongside standard larger studies.

Bayes Theorem↗