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Biomedical subjects

Deborah Ashby

Publications and source records attributed to Deborah Ashby.

At least 19 recordsLinked to original sources
PubMed2007

Lack of effect of influenza immunisation on anticoagulant control in patients on long-term warfarin.

PURPOSE: The effect of influenza vaccination on oral anticoagulant control is uncertain but important to establish since anticoagulants are widely used and most patients taking them are candidates for immunisation because of age or underlying cardiac disease. We therefore prospectively evaluated the effect of influenza vaccination on International Normalised Ratio (INR) control in patients on long-term warfarin. METHODS: We undertook a prospective audit of patients on long-term warfarin attending a single hospital anticoagulant clinic who reported receiving influenza vaccination within the 10 days prior to a clinic visit. We compared the stability of anticoagulant control in the 12 months prior to and 10 days after immunisation, restricting analysis to those patients whose warfarin dosage was unchanged before and after vaccination. RESULTS: Of 106 consecutive patients who reported receiving influenza vaccination within the 10 days prior to a clinic visit, results were evaluable in 78 because the dose of warfarin was unchanged before and after vaccination. Influenza immunisation had no apparent effect on anticoagulant control. No bleeding or thrombotic complications were reported. CONCLUSIONS: Our findings suggest that it is not necessary to routinely monitor the INR more closely after influenza vaccination.

Aged↗
PubMed2006

Bayesian statistics in medicine: a 25 year review.

This review examines the state of Bayesian thinking as Statistics in Medicine was launched in 1982, reflecting particularly on its applicability and uses in medical research. It then looks at each subsequent five-year epoch, with a focus on papers appearing in Statistics in Medicine, putting these in the context of major developments in Bayesian thinking and computation with reference to important books, landmark meetings and seminal papers. It charts the growth of Bayesian statistics as it is applied to medicine and makes predictions for the future. From sparse beginnings, where Bayesian statistics was barely mentioned, Bayesian statistics has now permeated all the major areas of medical statistics, including clinical trials, epidemiology, meta-analyses and evidence synthesis, spatial modelling, longitudinal modelling, survival modelling, molecular genetics and decision-making in respect of new technologies.

Bayes Theorem↗
PubMed2006

Sample size for cluster randomized trials: effect of coefficient of variation of cluster size and analysis method.

BACKGROUND: Cluster randomized trials are increasingly popular. In many of these trials, cluster sizes are unequal. This can affect trial power, but standard sample size formulae for these trials ignore this. Previous studies addressing this issue have mostly focused on continuous outcomes or methods that are sometimes difficult to use in practice. METHODS: We show how a simple formula can be used to judge the possible effect of unequal cluster sizes for various types of analyses and both continuous and binary outcomes. We explore the practical estimation of the coefficient of variation of cluster size required in this formula and demonstrate the formula's performance for a hypothetical but typical trial randomizing UK general practices. RESULTS: The simple formula provides a good estimate of sample size requirements for trials analysed using cluster-level analyses weighting by cluster size and a conservative estimate for other types of analyses. For trials randomizing UK general practices the coefficient of variation of cluster size depends on variation in practice list size, variation in incidence or prevalence of the medical condition under examination, and practice and patient recruitment strategies, and for many trials is expected to be approximately 0.65. Individual-level analyses can be noticeably more efficient than some cluster-level analyses in this context. CONCLUSIONS: When the coefficient of variation is <0.23, the effect of adjustment for variable cluster size on sample size is negligible. Most trials randomizing UK general practices and many other cluster randomized trials should account for variable cluster size in their sample size calculations.

Cluster Analysis↗
PubMed2006

Oral protein energy supplements for children with cystic fibrosis: CALICO multicentre randomised controlled trial.

OBJECTIVE: To determine whether oral protein energy supplements, used long term in children with cystic fibrosis who are moderately malnourished, improve nutritional and other outcomes. DESIGN: Multicentre randomised controlled trial. SETTING: Seven specialist paediatric cystic fibrosis centres and their associated shared care clinics and seven smaller paediatric cystic fibrosis clinics. PARTICIPANTS: 102 children with cystic fibrosis, aged between 2 and 15 years, who were moderately malnourished. INTERVENTIONS: Oral protein energy supplements in addition to usual dietary advice compared with dietary advice alone, for 12 months. MAIN OUTCOME MEASURE: Change in body mass index centile over one year. RESULTS: Use of supplements was not associated with a change in body mass index centile (mean difference 2.99 centile points, 95% confidence interval -2.70 to 8.68) or other nutritional and spirometric outcomes in this group of children. CONCLUSIONS: Long term use of oral protein energy supplements did not result in an improvement in nutritional status or other clinical outcomes in children with cystic fibrosis who were moderately malnourished. Oral protein energy supplements should not be regarded as an essential part of the management of this group of children. TRIAL REGISTRATION: ISRCTN: 95744468.

Administration, Oral↗
PubMed2006

Is it exposure to cigarette smoke or to smokers which increases the risk of meningococcal disease in teenagers?

BACKGROUND: Passive smoking appears to increase the risk of meningococcal disease (MD) in adolescents. Whether this effect is attributable to exposure to cigarette smoke or contact with smokers is unknown. METHODS: We conducted a prospective population-based case-control study with age, sex matched-controls in 1:1 matching. Participants were 15-19 year old with MD recruited at hospital admission in six regions (65% of the population of England) from January 1999 through June 2000, and their matched controls. Data on potential risk factors were gathered by confidential interview, including seven passive smoking variables. Factor analysis was performed to assess the dimensionality of the passive smoking exposure variables. The data were analysed with univariate and multivariate conditional logistic regression. RESULTS: 144 case-control pairs were recruited (51% male; median age 17.6). Factor analysis identified two independent factors representing passive smoking (P < 0.01), one associated with 'exposure to smoke', the other with 'smoker contact'. Only smoker contact was a significant risk factor for MD (OR = 1.8; 95% CI 1.0-3.3; P = 0.05). In multivariate analysis this factor was still associated with MD independently of potential confounders such as active smoker status and household crowding. CONCLUSION: Contact with smokers is associated with increased risk of MD in adolescents. This is more likely to be due to higher carriage rates in smokers than to exposure to smoke and emphasizes the importance of public health measures to stop smoking. In epidemiological studies that assess risk from passive smoking, exposure to smoke should be differentiated where possible from contact with smokers.

Adolescent↗
PubMed2006

A systematic review of pain drawing literature: should pain drawings be used for psychologic screening?

OBJECTIVES: The use of pain drawings to identify the psychologic "state" of patients has been advocated. They are used for psychologic screening before considering treatments, such as surgery. For pain drawings to be clinically useful as a psychologic screen they need good positive and negative predictive values. We systematically reviewed the literature that directly compared pain drawing scoring systems with measures of psychologic state. METHOD: We searched 12 medical and social science databases, using key words and their derivatives. Nineteen articles were suitable for analysis. The majority focused on low back pain (79%) in secondary or tertiary care (90%). Pain drawings were evaluated against psychologic tools testing: somatization, depression, anxiety, and distress. RESULTS: Three studies concluded that the association between pain drawings and psychologic state was sufficient for clinical use; of these only 1 showed reasonable sensitivity and specificity data. Six reported a statistical association and 10/19 studies reported inconclusive results and weak association. The pooled median sensitivity score was 56% (range 24% to 93%), specificity 79.5% (range 44% to 91%), positive predictive value 71.5% (range 28% to 94%), and negative predictive value 88% (range 35% to 100%). The predictive data were too low, wide-ranging, and inconsistent to accept the pain drawing as a clinical diagnostic tool to predict psychologic state. CONCLUSIONS: We conclude that the available data do not support the assumption that unusual pain drawings or extensive marking indicate disturbed psychologic state. There is no high quality evidence to support pain-drawing use as a psychologic assessment tool; therefore, pain drawings are not recommended for this purpose.

Humans↗
PubMed2006

Variations in primary open-angle glaucoma prevalence by age, gender, and race: a Bayesian meta-analysis.

PURPOSE: To quantify the variation in primary open-angle glaucoma (OAG) prevalence with age, gender, race, year of publication, and survey methodology. METHODS: Medline, EMBASE, and PubMed were searched for studies of OAG prevalence. Studies with defined population samplings were sought. Forty-six published observational studies of OAG prevalence (103,567 participants with 2509 cases of OAG) were identified for inclusion in the systematic review and meta-analysis. Data on the number of people and the number of cases of OAG by age, race, and gender were sought for each study. Additional information was obtained regarding whether the definition of glaucoma relied on raised intraocular pressure (IOP) and whether visual field examination was performed routinely on all individuals. Bayesian meta-analysis was used to model the associations between the log odds of OAG and age, race, gender, year of publication, method of visual field testing, and effect of reliance on IOP in the definition of OAG. RESULTS: Black populations had the highest OAG prevalence at all ages, but the proportional increase in prevalence of OAG with age was highest in white populations. The odds ratio per decade increase in age was 2.05 in white populations (95% credible interval, 1.91 to 2.18), 1.61 (95% credible interval, 1.53 to 1.70) in black populations, and 1.57 (95% credible interval, 1.46 to 1.68) in Asian populations. The average estimated prevalence in those older than 70 years of age was 6% in white populations, 16% in black populations, and 3% in Asian populations. After adjusting for age, race, year of publication, and survey methods, men were 1.37 (95% credible interval, 1.22 to 1.53) times more likely than women to have OAG. The prevalence of OAG was one third lower in studies in which routine visual fields were not assessed and that used an IOP criterion in the definition of glaucoma; this effect was reduced to the null after adjustment for age, racial group, and year of publication. CONCLUSIONS: Although black populations had the highest prevalence of OAG at all ages, white populations showed the steepest increase in OAG prevalence with age. Men were more likely than women to have OAG.

Adult↗
PubMed2005

TOIB Study. Are topical or oral ibuprofen equally effective for the treatment of chronic knee pain presenting in primary care: a randomised controlled trial with patient preference study. [ISRCTN79353052].

BACKGROUND: Many older people have chronic knee pain. Both topical and oral non- steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat this. Oral NSAIDS are effective, at least in the short term, but can have severe adverse effects. Topical NSAIDs also appear to be effective, at least in the short term. One might expect topical NSAIDs both to be less effective and to have fewer adverse effects than oral NSAIDs. If topical NSAIDs have fewer adverse effects this may outweigh both the reduction in effectiveness and the higher cost of topical compared to oral treatment. Patient preferences may influence the comparative effectiveness of drugs delivered via different routes. METHODS: TOIB is a randomised trial comparing topical and oral ibuprofen, with a parallel patient preference study. We are recruiting people aged 50 or over with chronic knee pain, from 27 MRC General Practice Research Framework practices across the UK. We are seeking to recruit 283 participants to the RCT and 379 to the PPS. Participants will be followed up for up to two years (with the majority reaching one year). Outcomes will be assessed by postal questionnaire, nurse examination, laboratory tests and medical record searches at one and two years or the end of the study. DISCUSSION: This study will provide new evidence on the overall costs and benefits of treating chronic knee pain with either oral or topical ibuprofen. The use of a patient preference design is unusual, but will allow us to explore how preference influences response to a medication. In addition, it will provide more information on adverse events. This study will provide evidence to inform primary care practitioners, and possibly influence practice.

Administration, Oral↗
PubMed2005

High prevalence but low impact of data extraction and reporting errors were found in Cochrane systematic reviews.

BACKGROUND AND OBJECTIVE: Extracting data from primary articles is an essential component in conducting systematic reviews. Incorrect data extraction can lead to false conclusions. The objective of this study was to retrospectively repeat the data extraction in all systematic reviews conducted by the Cochrane Cystic Fibrosis and Genetic Disorders Group. STUDY DESIGN AND SETTING: For each review, data extraction was conducted, by an experienced statistician, for the same publications used by the reviewers. Results were compared with those obtained by the reviewers. RESULTS: Errors were found in 20 of 34 reviews, including incorrect calculations made when converting data in primary articles into data required for the review (2 reviews) and misinterpretation of data that were reported in the primary article (7 reviews). All data-handling errors led to changes in the summary results, but none of these affected the review conclusions. CONCLUSIONS: Important errors were identified in a high proportion of reviews. A variety of problems relating to the reporting of results within a review were identified, but these did not lead to substantial changes in any conclusion.

Cystic Fibrosis↗
PubMed2005

Attenuated Salmonella typhimurium SL3261 as a vaccine vector for recombinant antigen in rabbits.

Oral live Salmonella vaccine vectors expressing recombinant guest antigens help stimulate systemic, mucosal, humoral, and cell-mediated immune responses against Salmonella and recombinant antigens. It may be possible to use them effectively against Haemophilus ducreyi, the bacterium that causes chancroid, a sexually transmitted genital ulcer disease. This study aimed to test the feasibility of using oral Salmonella vaccine vectors for the evaluation of chancroid vaccine candidates in the temperature-dependent rabbit model of H. ducreyi infection, an in vivo quantitative virulence assay of inducible immunity. We identified 10(8) to 10(9) CFU to be a safe and immunogenic oral dose range of S. typhimurium SL3261, by monitoring post-administration onset and course of illness and antibody titre by enzyme immunoassay (EIA). We successfully transduced plasmid pTETnir15 into the strain to produce recombinant S. typhimurium SL3261(pTETnir15), successfully expressed tetanus toxin fragment C (TetC) in it, and elicited serum anti-TetC titres of 1:6400 by EIA, 4 weeks after inoculation. The course of experimentally induced H. ducreyi skin lesions in rabbits treated with SL3261(pTETnir15) was similar to that in saline-treated controls. We describe a framework that successfully uses Salmonella as a vector for recombinant control antigen in the rabbit model of H. ducreyi infection, and is suitable for pre-clinical evaluation of Salmonella vector-based H. ducreyi vaccine antigen candidates.

Administration, Oral↗
PubMed2005

Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review.

OBJECTIVE: To investigate whether selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with an increased risk of suicide related outcomes in adults. DESIGN: Meta-analysis of randomised controlled trials of SSRIs compared with placebo in adults submitted by pharmaceutical companies to the safety review of the Medicines and Healthcare products Regulatory Agency (MHRA). PARTICIPANTS: Over 40,000 individuals participating in 477 randomised controlled trials. MAIN OUTCOME MEASURES: Suicide, non-fatal self harm, and suicidal thoughts. RESULTS: An estimated 16 suicides, 172 episodes of non-fatal self harm, and 177 episodes of suicidal thoughts were reported. We found no evidence that SSRIs increased the risk of suicide, but important protective or hazardous effects cannot be excluded (odds ratio 0.85, 95% credible interval 0.20 to 3.40). We found weak evidence of an increased risk of self harm (1.57, 0.99 to 2.55). Risk estimates for suicidal thoughts were compatible with a modest protective or adverse effect (0.77, 0.37 to 1.55). The relative frequency of reported self harm and suicidal thoughts in the trials compared with suicide indicates non-fatal end points were under-recorded. CONCLUSION: Increased risks of suicide and self harm caused by SSRIs cannot be ruled out, but larger trials with longer follow up are required to assess the balance of risks and benefits fully. Any such risks should be balanced against the effectiveness of SSRIs in treating depression. When prescribing SSRIs, clinicians should warn patients of the possible risk of suicidal behaviour and monitor patients closely in the early stages of treatment.

Adult↗
PubMed2005

Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case-control study.

OBJECTIVE: To compare the risk of non-fatal self harm and suicide in patients taking selective serotonin reuptake inhibitors (SSRIs) with that of patients taking tricyclic antidepressants, as well as between different SSRIs and different tricyclic antidepressants. DESIGN: Nested case-control study. SETTING: Primary care in the United Kingdom. PARTICIPANTS: 146,095 individuals with a first prescription of an antidepressant for depression. MAIN OUTCOME MEASURES: Suicide and non-fatal self harm. RESULTS: 1968 cases of non-fatal self harm and 69 suicides occurred. The overall adjusted odds ratio of non-fatal self harm was 0.99 (95% confidence interval 0.86 to 1.14) and that of suicide 0.57 (0.26 to 1.25) in people prescribed SSRIs compared with those prescribed tricyclic antidepressants. We found little evidence that associations differed over time since starting or stopping treatment. We found some evidence that risks of non-fatal self harm in people prescribed SSRIs compared with those prescribed tricyclic antidepressants differed by age group (interaction P = 0.02). The adjusted odds ratio of non-fatal self harm for people prescribed SSRIs compared with users of tricylic antidepressants for those aged 18 or younger was 1.59 (1.01 to 2.50), but no association was apparent in other age groups. No suicides occurred in those aged 18 or younger currently or recently prescribed tricyclic antidepressants or SSRIs. CONCLUSION: We found no evidence that the risk of suicide or non-fatal self harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants. We found some weak evidence of an increased risk of non-fatal self harm for current SSRI use among those aged 18 or younger. However, preferential prescribing of SSRIs to patients at higher risk of suicidal behaviour cannot be ruled out.

Adolescent↗
PubMed2005

Informed patient consent to participation in cluster randomized trials: an empirical exploration of trials in primary care.

Cluster randomized trials are increasingly common. Obtaining informed patient consent to participation in these trials raises practical challenges and ethical issues. The aims of this paper were to 1) develop a typology of interventions employed in cluster randomized trials in primary care; 2) assess whether the likelihood of seeking individual consent to participation varies by intervension type; 3) assess whether this likelihood has increased over time; 4) assess evidence for under reporting of consent procedures; 5) articulate reasons for not obtaining consent; and 6) make recommendations for future trial investigators. We collected data on trial interventions and consent procedures from reports of 152 recently published trials, and 47 unpublished trials. We develop a typology of interventions based on reasons for adopting a clustered design. We examine proportions seeking individual consent to participation among trials involving different types of intervention, in different periods, and among published and unpublished trials. Two-thirds of the trials had multifaceted interventions. Trials involving different types of intervention had different propensities to seek consent, largely because of practical obstacles to obtaining consent. Obtaining consent can compromise internal validity. More recent trials are no more likely to obtain consent than past trials. There was no evidence of under-reporting of consent procedures in publications. In conclusion, future trial investigators should consider both practical reasons and scientific arguments for not obtaining individual patient consent for all interventions in their trials. Where feasible, they should allow patients to opt out of the trial. Lay individuals should represent trial participants as part of the process of cluster consent to participation, and lay individuals could also be involved in considering ethical issues during trial planning. A more public debate may clarify the general acceptability of not obtaining consent in certain situations.

Biomedical Research↗
PubMed2005

Where's the utility in Bayesian data-monitoring of clinical trials?

BACKGROUND: Data monitoring is now an established part of good practice in clinical trials. Bayesian procedures for data-monitoring of treatment trials have been proposed and used, but sometimes without explicit consideration of utilities. A natural statistical framework for evidence-based medicine is a Bayesian approach to decision-making that incorporates an integrated summary of the available evidence and associated uncertainty with assessment of utilities. METHODS: We explore this approach to data monitoring, explicitly addressing separately the individual, scientific and public health perspectives. The Data Monitoring Committee's decision can then be thought of as a weighted combination of these perspectives. These ideas are illustrated with a trial of treatments for oesophageal cancer. RESULTS: For a Bayesian approach without explicit utilities we show that a utility structure is, in fact, implicit, and that it may be viewed as a weighted sum of the individual and scientific utilities. CONCLUSIONS: We argue that explicit consideration of utilities leads to decision-making that is more transparent, and lays foundations for data monitoring of more complex trials.

Algorithms↗
PubMed2004

Adjusting for publication bias: modelling the selection process.

UNLABELLED: RATIONALE, AIMS AND BACKGROUND: Systematic review with meta-analysis, a statistical technique for combining results of several studies, is progressively being used to guide decisions in medicine. Publication bias is acknowledged as a threat to the validity of systematic reviews and its existence may lead to inappropriate decisions about patient management or health policy. It is said to occur when the results of research available in the literature are not representative of the totality of all research. The selection mechanism that causes publication bias is complex, yet despite an extensive literature of empirical research identifying risk factors for publication, little work has been done to improve models of selection. Methods METHODS: that adjust combined meta-analytic estimates for publication bias are compared and applied to a systematic review of oral rehydration solution in the treatment of dehydration. Within a weighted distributions framework models of the selection process are considered and developed further. CONCLUSIONS: Weighted distributions offer a flexible approach that allows the potential to modify the selection function to incorporate other factors. Methods that adjust combined estimates should not be used to provide an alternative answer but to consider the robustness of the combined estimate to publication bias.

Child↗
PubMed2004

Lessons for cluster randomized trials in the twenty-first century: a systematic review of trials in primary care.

BACKGROUND: Evidence suggests that cluster randomized trials are often poorly designed and analysed. There is little recent research on the methodologic quality of cluster randomized trials and none focuses on primary health care where these trials are increasingly common. METHODS: We conducted a systematic review of recent cluster randomized trials in primary health care, searching the Cochrane Controlled Trials Register. We also searched for unpublished trials in conference proceedings, and the UK National Research Register. We assess methodologic quality using a checklist, articulate problems facing investigators conducting these trials, and examine the extent to which carrying out a cluster randomized trial (as opposed to an individually randomized trial) in primary care may reduce power. RESULTS: We found 367 trial reports. Many trials were reported more than once. We characterize 152 independent cluster randomized trials in primary health care published between 1997 and 2000, and briefly describe 47 trials unpublished at December 2000. The quality of design and analysis was variable. Of published trials reporting sample size calculations 20% accounted for clustering in these calculations, 59% of published trials accounted for clustering in analyses. Unpublished trials were more recent and of higher quality. Reporting quality was better in journals reporting more cluster randomized trials. Many trial investigators reported problems with adherence to protocol, recruitment and type of intervention. CONCLUSIONS: Methodologic quality of cluster randomized trials in primary health care is variable and reporting needs improvement. The use of cluster randomization should be indicated in the title or abstract so these kinds of trials are easier to identify. Communicating appropriate methodology to health care researchers continues to be a challenge. Cluster randomized trials should always be piloted and information from pilots and unsuccessful trials shared more widely.

Cluster Analysis↗