Biomedical subjects

Paula R Williamson

Publications and source records attributed to Paula R Williamson.

16 recordsLinked to original sources

PubMed2006

Are we meeting the standards set for endoscopy? Results of a large-scale prospective survey of endoscopic retrograde cholangio-pancreatograph practice.

OBJECTIVE: To examine endoscopic retrograde cholangio-pancreatography (ERCP) services and training in the UK. DESIGN: Prospective multicentre survey. SETTING: Five regions of England. PARTICIPANTS: Hospitals with an ERCP unit. OUTCOME MEASURES: Adherence to published guidelines, technical success rates, complications and mortality. RESULTS: Organisation questionnaires were returned by 76 of 81 (94%) units. Personal questionnaires were returned by 190 of 213 (89%) ERCP endoscopists and 74 of 91 (81%) ERCP trainees, of whom 45 (61%) reported participation in <50 ERCPs per annum. In all, 66 of 81 (81%) units collected prospective data on 5264 ERCPs, over a mean period of 195 days. Oximetry was used by all units, blood pressure monitoring by 47 of 66 (71%) and ECG monitoring by 37 of 66 (56%) units; 1484 of 4521 (33%) patients were given >5 mg of midalozam. Prothrombin time was recorded in 4539 of 5264 (86%) procedures. Antibiotics were given in 1021 of 1412 (72%) cases, where indicated. Patients' American Society of Anesthesiology (ASA) scores were 3-5 in 670 of 5264 (12.7%) ERCPs, and 4932 of 5264 (94%) ERCPs were scheduled with therapeutic intent. In total, 140 of 182 (77%) trained endoscopists demonstrated a cannulation rate >/=80%. The recorded cannulation rate among senior trainees (with an experience of >200 ERCPs) was 222/338 (66%). Completion of intended treatment was done in 3707 of 5264 (70.4%) ERCPs; 268 of 5264 (5.1%) procedures resulted in a complication. Procedure-related mortality was 21/5264 (0.4%). Mortality correlated with ASA score. CONCLUSION: Most ERCPs in the UK are performed on low-risk patients with therapeutic intent. Complication rates compare favourably with those reported internationally. However, quality suffers because there are too many trainees in too many low-volume ERCP centres.

Adult↗

PubMed2006

In a systematic review, infrared ear thermometry for fever diagnosis in children finds poor sensitivity.

BACKGROUND AND OBJECTIVES: To investigate sensitivity and specificity of infrared ear thermometry compared to rectal thermometry to detect fever in children. METHODS: Systematic review of studies comparing rectal and infrared ear temperatures in children. RESULTS: Sensitivity and specificity estimates were highly heterogeneous, and displayed an inverse relationship suggestive of a threshold effect, due in part to the different offsets used to obtain adjusted tympanic temperatures depending on the ear thermometer mode. To account for this threshold effect, results from each study were summarized as a diagnostic odds ratio (DOR). These varied extensively across studies, suggesting that heterogeneity between study estimates is not fully explained by the threshold effect. Pooled estimates of sensitivity and specificity from random effects models were 63.7% (95% CI 55.6%, 71.8%) and 95.2% (95% CI 93.5%, 96.9%), respectively. CONCLUSION: Pooled estimates of measures of diagnostic accuracy from these studies suggest that infrared ear thermometry would fail to diagnose fever in three or four out of every 10 febrile children (with fever defined by a rectal temperature of 38 degrees C or above). These findings support our previous concerns about the use of infrared ear thermometers in situations where a failure to detect fever has serious implications.

Adolescent↗

PubMed2006

Clinical factors and ABCB1 polymorphisms in prediction of antiepileptic drug response: a prospective cohort study.

BACKGROUND: The ABCB1 3435C-->T single-nucleotide polymorphism (SNP) or a three-SNP haplotype containing 3435C-->T has been implicated in multidrug resistance in epilepsy in three retrospective case-control studies, but a further three have failed to replicate the association. We aimed to determine the effect of the ABCB1 gene on epilepsy drug response, using a unique large cohort of epilepsy patients with prospectively measured seizure and drug response outcomes. METHODS: The ABCB1 3435C-->T polymorphism and three-SNP haplotype, plus a comprehensive set of tag SNPs across ABCB1 and adjacent ABCB4, were genotyped in a cohort of 503 epilepsy patients with prospectively measured seizure and drug response outcomes. Clinical, demographic, and genetic data were analysed. Treatment outcome was measured in terms of time to 12-month remission, time to first seizure, and time to drug withdrawal due to inadequate seizure control or side-effects. Randomly selected genome-wide HapMap SNPs (n=129) were genotyped in all patients for genomic control. FINDINGS: Number of seizures before treatment was the dominant feature predicting seizure outcome after starting antiepileptic drug therapy, measured by both time to first seizure (hazard ratio 1.34, 95% CI 1.21-1.49, p<0.0001) and time to 12-month remission (0.83, 0.73-0.94, p=0.003). There was no association of the ABCB1 3435C-->T polymorphism, the three-SNP haplotype, or any gene-wide tag SNP with time to first seizure after starting drug therapy, time to 12-month remission, or time to drug withdrawal due to unacceptable side-effects or to lack of seizure control. INTERPRETATION: We found no evidence that ABCB1 common variation influences either seizure or drug withdrawal outcomes after initiation of antiepileptic drug therapy.

ATP-Binding Cassette Transporters↗

PubMed2006

HLA-B locus in Caucasian patients with carbamazepine hypersensitivity.

BACKGROUND: A strong pharmacogenetic association has been reported in Chinese patients between human leukocyte antigen (HLA)-B*1502 and carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS). METHODS: We have genotyped the HLA-B alleles in 56 Caucasian patients with varying severities of CBZ hypersensitivity and 43 controls on CBZ without adverse effects. RESULTS: None of our patients (including two with blistering skin rashes) were positive for the HLA-B*1502 allele. HLA-B*0702 allele may protect against severe CBZ hypersensitivity but warrants further study. Of secondary interest, the correlation between HLA-B*0801 and HLA-DR3, DQ2 and TNF -308 alleles (on the ancestral haplotype 8.1) is consistent with our previous findings. CONCLUSION: HLA-B*1502 does not seem to be a marker for all forms of CBZ-induced hypersensitivity in a Caucasian population.

Alleles↗

PubMed2005

Investigating heterogeneity in an individual patient data meta-analysis of time to event outcomes.

Differences across studies in terms of design features and methodology, clinical procedures, and patient characteristics, are factors that can contribute to variability in the treatment effect between studies in a meta-analysis (statistical heterogeneity). Regression modelling can be used to examine relationships between treatment effect and covariates with the aim of explaining the variability in terms of clinical, methodological, or other factors. Such an investigation can be undertaken using aggregate data or individual patient data. An aggregate data approach can be problematic as sufficient data are rarely available and translating aggregate effects to individual patients can often be misleading. An individual patient data approach, although usually more resource demanding, allows a more thorough investigation of potential sources of heterogeneity and enables a fuller analysis of time to event outcomes in meta-analysis. Hierarchical Cox regression models are used to identify and explore the evidence for heterogeneity in meta-analysis and examine the relationship between covariates and censored failure time data in this context. Alternative formulations of the model are possible and illustrated using individual patient data from a meta-analysis of five randomized controlled trials which compare two drugs for the treatment of epilepsy. The models are further applied to simulated data examples in which the degree of heterogeneity and magnitude of treatment effect are varied. The behaviour of each model in each situation is explored and compared.

Anticonvulsants↗

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

Individual patient data meta-analysis : Cervical stitch (cerclage) for preventing pregnancy loss in women.

BACKGROUND: Cervical cerclage is a surgical procedure involving suturing the cervix with a purse type stitch to keep it closed during pregnancy. This procedure has been used widely in the management of pregnancies considered at high risk of preterm delivery. Several observational studies into the efficacy of cervical cerclage have claimed high rates of successful pregnancy outcome in women with a poor obstetric history attributed to cervical incompetence. However, a recent aggregate data Cochrane review found no such conclusive evidence from seven included randomised studies. Current data suggests that cervical cerclage is likely to benefit women considered to be 'at very high risk' of a second trimester miscarriage due to a cervical factor, however identifying such women remains elusive and many women may be treated unnecessarily. Undertaking an individual patient data (IPD) meta-analysis of the studies will allow us to investigate whether treatment is more effective in particular subgroups. Such an analysis will also provide a more powerful analysis of the predictors of preterm delivery and pregnancy loss, including ultrasound measurement of cervical length, and will allow a more complete analysis of 'time to event' outcomes. METHODS/DESIGN: The analysis will include data from randomised trials comparing the intervention of elective cerclage versus no cerclage or bedrest to prevent miscarriage or pre-term labour. A specific list of data will be requested for each trial, including demographic and obstetric history data. The primary outcomes of interest will be neonatal mortality/morbidity. Attention will also be given to secondary outcomes such as time from randomisation to delivery, preterm delivery before 32 weeks and maternal morbidity. An intention to treat analysis will be performed, with attention paid to assessing clinical and statistical heterogeneity. Multilevel models with patients and trials as the two levels will be explored to investigate treatment effect on various outcomes. Patient-level covariates will be incorporated into the models in an attempt to account for statistical heterogeneity as well as to investigate interactions with treatment effect. DISCUSSION: Predictive models generated from our analysis should lead to more effective counselling of women at risk and a more cost effective use of cerclage.

Journal Article↗

PubMed2005

An overview of methods and empirical comparison of aggregate data and individual patient data results for investigating heterogeneity in meta-analysis of time-to-event outcomes.

Combining the results of individual studies using meta-analysis may be undertaken using either aggregate data (AD) or individual patient data (IPD). In any meta-analysis it is important to consider statistical heterogeneity between studies. Potential sources of heterogeneity can be explored using regression models with either AD or IPD. An overview of approaches and empirical assessment of how the results and conclusions differ from these analyses is undertaken using a meta-analysis of five randomized controlled trials comparing two antiepileptic drugs with time-to-event outcomes. Alternative meta-regression models using AD are compared to stratified Cox regression models using IPD. Age as a potential cause of heterogeneity is detected by both AD and IPD regression models. Time from first ever seizure to randomization is only identified by some AD models. A more thorough explanation of heterogeneity is obtained from the model using IPD but further empirical evidence comparing IPD and AD results are needed.

Clinical Trials as Topic↗

PubMed2004

Cervical cerclage for prevention of preterm delivery in women with short cervix: randomised controlled trial.

BACKGROUND: Cervical cerclage has been widely used in the past 50 years to prevent early preterm birth and its associated neonatal mortality and morbidity. Results of randomised trials have not generally lent support to this practice, but this absence of benefit may be due to suboptimum patient selection, which was essentially based on obstetric history. A more effective way of identifying the high-risk group for early preterm delivery might be by transvaginal sonographic measurement of cervical length. We undertook a multicentre randomised controlled trial to investigate whether, in women with a short cervix identified by routine transvaginal scanning at 22-24 weeks' gestation, the insertion of a Shirodkar suture reduces early preterm delivery. METHODS: Cervical length was measured in 47?123 women. The cervix was 15 mm or less in 470, and 253 (54%) of these women participated in the study and were randomised to cervical cerclage (127) or to expectant management (126). Primary outcome was the frequency of delivery before 33 completed weeks (231 days) of pregnancy. FINDINGS: The proportion of preterm delivery before 33 weeks was similar in both groups, 22% (28 of 127) in the cerclage group versus 26% (33 of 126) in the control group (relative risk=0.84, 95% CI 0.54-1.31, p=0.44), with no significant differences in perinatal or maternal morbidity or mortality. INTERPRETATION: The insertion of a Shirodkar suture in women with a short cervix does not substantially reduce the risk of early preterm delivery. Routine sonographic measurement of cervical length at 22-24 weeks identifies a group at high risk of early preterm birth.

Adult↗

PubMed2004

The value of a pilot study in breast-feeding research.

OBJECTIVE: To test the integrity of a protocol for a randomised controlled trial (RCT) to examine the effectiveness of skin-to-skin care compared to routine care on the initiation and duration of breast feeding and to provide data to be used in the power calculation for a proposed trial. DESIGN: Randomised pilot study. SETTING: Warrington Hospital, Cheshire, UK. PARTICIPANTS: Women at 36 weeks' gestation with healthy singleton pregnancies, who intended to breast feed, who had 'booked' for care at Warrington Hospital and had given informed consent to participate. Twenty-eight women were randomised in the pilot study. METHOD: Women were randomly allocated to receive either routine or skin-to-skin care following birth. The first breast feed was assessed using the Breast-feeding Assessment Tool (BAT). Mothers were followed up at discharge from hospital and again at four months to provide details of duration of breast feeding. FINDINGS: 66 women were approached to participate in the trial and 44 consented (67% consent rate). Twenty-eight women were randomised in the study and 26 breast feeds were observed (93%). The pilot study identified procedural changes that were required in the design of the main study, provided an estimate of recruitment rates and confirmed the previously calculated sample size. CONCLUSION: The pilot study demonstrated that a large RCT of skin-to-skin versus routine care was feasible. This is an example of how a pilot study has the ability to identify unforeseen challenges in the conduct of the trial as well as allowing necessary changes to be made to the design that will increase the quality of the subsequent research.

Adult↗

PubMed2004

Design and analysis of pilot studies: recommendations for good practice.

Pilot studies play an important role in health research, but they can be misused, mistreated and misrepresented. In this paper we focus on pilot studies that are used specifically to plan a randomized controlled trial (RCT). Citing examples from the literature, we provide a methodological framework in which to work, and discuss reasons why a pilot study might be undertaken. A well-conducted pilot study, giving a clear list of aims and objectives within a formal framework will encourage methodological rigour, ensure that the work is scientifically valid and publishable, and will lead to higher quality RCTs. It will also safeguard against pilot studies being conducted simply because of small numbers of available patients.

Pilot Projects↗

PubMed2003

A systematic review of randomised controlled trials evaluating the effect of mother/baby skin-to-skin care on successful breast feeding.

OBJECTIVE: to examine the effects of early skin-to-skin contact between mother and baby on the initiation and duration of breast feeding. REVIEW METHODS SEARCH STRATEGY: electronic databases--the Cochrane Library, MEDLINE,CINAHL and EMBASE. References of studies were examined to identify additional trials and contact was made with researchers in the field. Study selection criteria: randomised or quasi-randomised controlled trials in any language in which skin-to-skin contact between mothers and their healthy full-term newborn babies was compared to routine contact. Primary outcomes were success of first breast feed and duration of breast feeding. Secondary outcomes included, baby temperature and behaviour. STUDY-QUALITY ASSESSMENT: validity of included studies was assessed using criteria defined by the Cochrane Collaboration. Application of inclusion criteria, validity assessment and data extraction were carried out independently by two reviewers with a third reviewer to resolve differences. FINDINGS: seven randomised controlled trials were identified. Five studies assessed duration of breast feeding with mixed results. None of the studies assessed the success of the first breast-feeding experience. Study quality was variable with methods of randomisation and blinding of assessment unclear in four of the five studies providing relevant results. CONCLUSIONS: the findings of this systematic review fail to support the current initiatives to implement changes in clinical practice to include skin-to-skin contact. Methodological flaws within the included studies prohibit firm conclusions being reached with regard to the effect of skin-to-skin contact on the duration of breast feeding, timing of first breast feed or baby physiological factors. The review highlights the need for further primary research to assess the effect of skin-to-skin contact on the breast-feeding experience.

Breast Feeding↗

PubMed2002

Aggregate data meta-analysis with time-to-event outcomes.

In a meta-analysis of randomized controlled trials with time-to-event outcomes, an aggregate data approach may be required for some or all included studies. Variation in the reporting of survival analyses in journals suggests that no single method for extracting the log(hazard ratio) estimate will suffice. Methods are described which improve upon a previously proposed method for estimating the log(HR) from survival curves. These methods extend to life-tables. In the situation where the treatment effect varies over time and the trials in the meta-analysis have different lengths of follow-up, heterogeneity may be evident. In order to assess whether the hazard ratio changes with time, several tests are proposed and compared. A cohort study comparing life expectancy of males and females with cerebral palsy and a systematic review of five trials comparing two anti-epileptic drugs, carbamazepine and sodium valproate, are used for illustration.

Anticonvulsants↗

PubMed2002

Statistical issues in the assessment of the evidence for an interaction between factors in epilepsy trials.

We examine the common clinical belief that there is an interaction between epilepsy type and the two standard anti-epileptic drugs, valproate and carbamazepine, using data from several randomized clinical trials. Epilepsy type is not always easy to define, and three possible reclassifications are investigated to see whether misclassification of epilepsy type within the trials has potentially masked such an interaction. Regression modelling is employed to investigate whether heterogeneity between trial results can be explained by patient factors. Our work suggests that uncertainty in epilepsy type classification should be recognized in future studies. We also generate the hypothesis that the interaction of drug effect with age may reflect the perceived interaction with epilepsy type. We suggest that in any context where misclassification is likely, it is worth considering the use of an explicit 'unclassified' group, and investigating whether additional covariates can answer the substantive question.

Adolescent↗

PubMed2002

Infrared ear thermometry compared with rectal thermometry in children: a systematic review.

BACKGROUND: Infrared ear thermometry is frequently used in children, because this is a quick method of taking temperature and the ear is easily accessible. Our aim was to evaluate agreement between temperature measured at the rectum and ear in children. METHODS: We did a systematic review of studies comparing temperature measured at the rectum (the reference site) using mercury, electronic, or indwelling probe thermometers, with temperature measured at the ear (the test site) using infrared ear thermometers. Heterogeneity between studies was investigated by exploring subgroups according to the mode of the infrared ear thermometer. FINDINGS: 44 studies containing 58 comparisons (5935 children) were eligible for inclusion in this review. Outcome data were available in reports from 12 comparisons (2312 [39%] children), and data on individual patients were obtained for a further 19 comparisons (2129 [36%] children). 31 comparisons (4441 [75%] children) were therefore included in the meta-analysis. The pooled mean temperature difference (rectal minus ear) was 0.29 degrees C (95% limits of agreement -0.74 to 1.32). We pooled data by ear device mode and the mean temperature differences were rectal mode 0.15 degrees C (-0.95 to 1.25), actual 0.70 degrees C (-0.20 to 1.60), core 0.25 degrees C (-0.78 to 1.27), oral 0.34 degrees C (-0.86 to 1.54), tympanic 0.62 degrees C (-0.40 to 1.64) and mode not stated 0.32 degrees C (-0.57 to 1.21). There was significant residual heterogeneity in both mean differences and sample SDs within the groups of ear device mode. INTERPRETATION: Although the mean differences between rectal and ear temperature measurements were small, the wide limits of agreement mean that ear temperature is not a good approximation of rectal temperature, even when the ear thermometer is used in rectal mode. Our finding suggests that infrared ear thermometry does not show sufficient agreement with an established method of temperature measurement to be used in situations where body temperature needs to be measured with precision.

Body Temperature↗

PubMed2002

Carbamazepine versus valproate monotherapy for epilepsy: a meta-analysis.

PURPOSE: To provide an overview of the evidence comparing carbamazepine (CBZ) and valproate (VPA) monotherapy for epilepsy, investigating whether existing data support the current practice of preferring CBZ for partial-onset and VPA for generalized-onset seizures. METHODS: We performed meta-analysis of randomized controlled trials by using individual patient data. Our strategy included searches of (a) Medline, 1966-2000; (b) The Cochrane Library 2000, issue 4; and (c) the pharmaceutical industry. Outcome measures were time to discontinuation of allocated treatment, time to 12-month remission, and time to first seizure after randomization. Results are expressed as hazard ratios (HRs; 95% CI), where HR>1 indicates that an event is more likely with VPA. A test for an interaction between treatment and seizure type (partial vs. generalized onset) also was undertaken. RESULTS: Data were available for 1,265 patients from five trials. Overall results (HR, 95% CI) were Time to treatment discontinuation, 0.97 (0.79-1.18); 12-Month remission, 0.87 (0.74-1.02); and First seizure, 1.09 (0.96-1.25), suggesting no overall difference for these outcomes. The test for an interaction between Treatment and Seizure type was significant for time to first seizure, but for no other outcome. The age distribution of adults classified as having generalized seizures indicated that significant numbers of patients may have had their seizures misclassified. CONCLUSIONS: We found some evidence to support the preference of CBZ for partial-onset seizures, but no evidence to support the preference of VPA for generalized-onset seizures. Confidence intervals are too wide to infer equivalence. Misclassification of patients may have confounded our results and has important implications for future trials.

Adolescent↗