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Ian R White

Publications and source records attributed to Ian R White.

At least 19 recordsLinked to original sources
PubMed2007

Analysis of cluster randomized cross-over trial data: a comparison of methods.

In a cluster randomized cross-over trial, all participating clusters receive both intervention and control treatments consecutively, in separate time periods. Patients recruited by each cluster within the same time period receive the same intervention, and randomization determines order of treatment within a cluster. Such a design has been used on a number of occasions. For analysis of the trial data, the approach of analysing cluster-level summary measures is appealing on the grounds of simplicity, while hierarchical modelling allows for the correlation of patients within periods within clusters and offers flexibility in the model assumptions. We consider several cluster-level approaches and hierarchical models and make comparison in terms of empirical precision, coverage, and practical considerations. The motivation for a cluster randomized trial to employ cross-over of trial arms is particularly strong when the number of clusters available is small, so we examine performance of the methods under small, medium and large (6, 18, 30) numbers of clusters. One hierarchical model and two cluster-level methods were found to perform consistently well across the designs considered. These three methods are efficient, provide appropriate standard errors and coverage, and continue to perform well when incorporating adjustment for an individual-level covariate. We conclude that choice between hierarchical models and cluster-level methods should be influenced by the extent of complexity in the planned analysis.

Cluster Analysis↗
PubMed2006

Predicting the risk for sudden infant death syndrome from obstetric characteristics: a retrospective cohort study of 505,011 live births.

OBJECTIVE: We sought to develop a simple robust method for assessing the risk for sudden infant death syndrome (SIDS) on the basis of obstetric characteristics. METHODS: A population-based retrospective cohort study was conducted of data from the linked Scottish Morbidity Record, Stillbirth and Infant Death Enquiry and General Registrar's Office database of births and deaths, encompassing births in Scotland between 1992 and 2001. All women who had a singleton live birth between 24 and 43 weeks' gestation and for whom data were available (n = 505,011), divided into model development and validation samples, were studied. The main outcome measure was death of the infant in the first year of life as a result of SIDS. RESULTS: The risk for SIDS was modeled in the development sample using logistic regression with the following predictors: maternal age, parity, marital status, smoking, and the birth weight and the gender of the infant. When the model was evaluated in the validation sample, the area under the receiver operating characteristic curve was 0.84 and the incidence of SIDS was 0.7 per 10,000 (95% confidence interval: 0.3-1.4) among 126,253 women in the lower 50% of predicted risk and 29.7 per 10,000 (95% confidence interval: 23.4-37.2) among the 25,250 women in the top 10% of predicted risk. A logistic-regression model then was developed for the whole population, and the output was converted into adjusted likelihood ratios. These are tabulated and provide a simple method for assessing the risk for SIDS associated with any combination of obstetric characteristics. CONCLUSIONS: A model that uses maternal characteristics and outcome at birth is predictive of the risk for SIDS. This model is presented in a simple form that allows calculation of the individual risk for SIDS.

Birth Weight↗
PubMed2005

Eliciting and using expert opinions about influence of patient characteristics on treatment effects: a Bayesian analysis of the CHARM trials.

When randomized trial results are available for several different groups of patients, neither applying the overall results to each type of patient nor using group-specific results is entirely satisfactory. Instead, we estimate group-specific treatment effects using a Bayesian approach with informative priors for the treatment x group interactions. We describe how we elicited these prior beliefs about the effects of a new drug for the treatment of heart failure in three different patient groups. Using results from three trials, one in each patient group, the posterior mean treatment effects are very similar to the trial-specific maximum likelihood estimates, showing that in this case each trial effectively stands by itself. Our methods can also be applied to subgroup analyses in a single clinical trial, where subgroup-specific posterior means are likely to lie between the subgroup-specific maximum likelihood estimates and the pooled maximum likelihood estimates.

Bayes Theorem↗
PubMed2005

Intensive case management for severe psychotic illness: is there a general benefit for patients with complex needs? A secondary analysis of the UK700 trial data.

The UK700 trial failed to demonstrate an overall benefit of intensive case management (ICM) in patients with severe psychotic illness. This does not discount a benefit for particular subgroups, and evidence of a benefit of ICM for patients of borderline intelligence has been presented. The aim of this study is to investigate whether this effect is part of a general benefit for patients with severe psychosis complicated by additional needs. In the UK700 trial patients with severe psychosis were randomly allocated to ICM or standard case management. For each patient group with complex needs the effect of ICM is compared with that in the rest of the study cohort. Outcome measures are days spent in psychiatric hospital and the admission and discharge rates. ICM may be of benefit to patients with severe psychosis complicated by borderline intelligence or depression, but may cause patients using illicit drugs to spend more time in hospital. There was no convincing evidence of an effect of ICM in a further seven patient groups. ICM is not of general benefit to patients with severe psychosis complicated by additional needs. The benefit of ICM for patients with borderline intelligence is an isolated effect which should be interpreted cautiously until further data are available.

Critical Care↗
PubMed2005

Predicting cesarean section and uterine rupture among women attempting vaginal birth after prior cesarean section.

BACKGROUND: There is currently no validated method for antepartum prediction of the risk of failed vaginal birth after cesarean section and no information on the relationship between the risk of emergency cesarean delivery and the risk of uterine rupture. METHODS AND FINDINGS: We linked a national maternity hospital discharge database and a national registry of perinatal deaths. We studied 23,286 women with one prior cesarean delivery who attempted vaginal birth at or after 40-wk gestation. The population was randomly split into model development and validation groups. The factors associated with emergency cesarean section were maternal age (adjusted odds ratio [OR] = 1.22 per 5-y increase, 95% confidence interval [CI]: 1.16 to 1.28), maternal height (adjusted OR = 0.75 per 5-cm increase, 95% CI: 0.73 to 0.78), male fetus (adjusted OR = 1.18, 95% CI: 1.08 to 1.29), no previous vaginal birth (adjusted OR = 5.08, 95% CI: 4.52 to 5.72), prostaglandin induction of labor (adjusted OR = 1.42, 95% CI: 1.26 to 1.60), and birth at 41-wk (adjusted OR = 1.30, 95% CI: 1.18 to 1.42) or 42-wk (adjusted OR = 1.38, 95% CI: 1.17 to 1.62) gestation compared with 40-wk. In the validation group, 36% of the women had a low predicted risk of caesarean section (< 20%) and 16.5% of women had a high predicted risk (> 40%); 10.9% and 47.7% of these women, respectively, actually had deliveries by caesarean section. The predicted risk of caesarean section was also associated with the risk of all uterine rupture (OR for a 5% increase in predicted risk = 1.22, 95% CI: 1.14 to 1.31) and uterine rupture associated with perinatal death (OR for a 5% increase in predicted risk = 1.32, 95% CI: 1.02 to 1.73). The observed incidence of uterine rupture was 2.0 per 1,000 among women at low risk of cesarean section and 9.1 per 1,000 among those at high risk (relative risk = 4.5, 95% CI: 2.6 to 8.1). We present the model in a simple-to-use format. CONCLUSIONS: We present, to our knowledge, the first validated model for antepartum prediction of the risk of failed vaginal birth after prior cesarean section. Women at increased risk of emergency caesarean section are also at increased risk of uterine rupture, including catastrophic rupture leading to perinatal death.

Age Factors↗
PubMed2005

Randomised controlled trial of acute mental health care by a crisis resolution team: the north Islington crisis study.

OBJECTIVE: To evaluate the effectiveness of a crisis resolution team. DESIGN: Randomised controlled trial. PARTICIPANTS: 260 residents of the inner London Borough of Islington who were experiencing crises severe enough for hospital admission to be considered. INTERVENTIONS: Acute care including a 24 hour crisis resolution team (experimental group), compared with standard care from inpatient services and community mental health teams (control group). MAIN OUTCOME MEASURES: Hospital admission and patients' satisfaction. RESULTS: Patients in the experimental group were less likely to be admitted to hospital in the eight weeks after the crisis (odds ratio 0.19, 95% confidence interval 0.11 to 0.32), though compulsory admission was not significantly reduced. A difference of 1.6 points in the mean score on the client satisfaction questionnaire (CSQ-8) was not quite significant (P = 0.07), although it became so after adjustment for baseline characteristics (P = 0.002). CONCLUSION: Crisis resolution teams can reduce hospital admissions in mental health crises. They may also increase satisfaction in patients, but this was an equivocal finding.

Adolescent↗
PubMed2005

The effect of measurement error in risk factors that change over time in cohort studies: do simple methods overcorrect for 'regression dilution'?

BACKGROUND: The attenuation of the relationship between disease and a risk factor subject to error through 'regression dilution' is well recognized, and researchers often make attempts to adjust for its effects. However, the adjustment methods most often adopted in cohort studies make an implicit assumption that the relationship is driven exclusively by current error-free levels of the risk factor and not by past levels. Here we investigate the bias that is introduced if this assumption is invalid. METHODS: We model disease risk at a particular time in terms of error-free levels of the risk factor at that time and in past periods, and summarize the 'life-course' risk factor-disease relationship using crude current level, history adjusted current level and lifetime level associations. Using systolic blood pressure data from the Framingham Heart Study we show the impact of measurement error on these associations and investigate the biases that can occur with simple correction methods. RESULTS: A simple 'ratio of ranges' type correction factor overestimates the lifetime level association by 29% in the presence of a relatively modest dependency of current risk on past levels (levels 5 years ago half as predictive of current risk as current levels). CONCLUSIONS: Simple methods of correction for regression dilution bias can lead to substantial overcorrection if the risk factor-disease relationship is not short term.

Adult↗
PubMed2005

Assessing subgroup effects with binary data: can the use of different effect measures lead to different conclusions?

BACKGROUND: In order to use the results of a randomised trial, it is necessary to understand whether the overall observed benefit or harm applies to all individuals, or whether some subgroups receive more benefit or harm than others. This decision is commonly guided by a statistical test for interaction. However, with binary outcomes, different effect measures yield different interaction tests. For example, the UK Hip trial explored the impact of ultrasound of infants with suspected hip dysplasia on the occurrence of subsequent hip treatment. Risk ratios were similar between subgroups defined by level of clinical suspicion (P = 0.14), but odds ratios and risk differences differed strongly between subgroups (P < 0.001). DISCUSSION: Interaction tests on different effect measures differ because they test different null hypotheses. A graphical technique demonstrates that the difference arises when the subgroup risks differ markedly. We consider that the test of interaction acts as a check on the applicability of the trial results to all included subgroups. The test of interaction should therefore be applied to the effect measure which is least likely a priori to exhibit an interaction. We give examples of how this might be done. SUMMARY: The choice of interaction test is especially important when the risk of a binary outcome varies widely between subgroups. The interaction test should be pre-specified and should be guided by clinical knowledge.

Data Interpretation, Statistical↗
PubMed2005

Adjusting for partially missing baseline measurements in randomized trials.

Adjustment for baseline variables in a randomized trial can increase power to detect a treatment effect. However, when baseline data are partly missing, analysis of complete cases is inefficient. We consider various possible improvements in the case of normally distributed baseline and outcome variables. Joint modelling of baseline and outcome is the most efficient method. Mean imputation is an excellent alternative, subject to three conditions. Firstly, if baseline and outcome are correlated more than about 0.6 then weighting should be used to allow for the greater information from complete cases. Secondly, imputation should be carried out in a deterministic way, using other baseline variables if possible, but not using randomized arm or outcome. Thirdly, if baselines are not missing completely at random, then a dummy variable for missingness should be included as a covariate (the missing indicator method). The methods are illustrated in a randomized trial in community psychiatry.

Data Interpretation, Statistical↗
PubMed2005

Analyzing the duration of recurrent events in clinical trials: a comparison of approaches using data from the UK700 trial of psychiatric case management.

In studies of chronic disease the outcome measure may be based upon the duration of recurring illness. Our example is the UK700 trial of psychiatric case management, where the total number of days spent in hospital over a 2-year follow-up was the primary outcome. Investigations of treatment effect modifiers were undertaken using an analysis of that primary outcome, a comparison of length of hospitalizations, and also a multi-state modeling approach. The days in hospital outcome was relatively straightforward to analyze, and allowed the complete randomized treatment groups to be compared. In contrast, the comparison of length of hospitalizations included only hospitalized patients, with censored observations not being well accommodated. The multi-state model provided separate treatment effect estimates for admission and discharge, this being more informative about how any reduction in days spent in hospital is achieved. Estimation of the treatment effects through the use of proportional hazards regression allowed appropriate incorporation of censored observations. However, with the multi-state model approach treatment effect estimates are not based upon comparisons of complete randomized treatment groups, as individuals are removed from the risk set for admission whilst at risk for discharge, and vice versa. We conclude that total duration is an appropriate primary outcome for clinical trials, but that multi-state models deserve greater use as an informative secondary analysis.

Case Management↗
PubMed2005

Patch testing with a new fragrance mix - reactivity to the individual constituents and chemical detection in relevant cosmetic products.

UNLABELLED: A new fragrance mix (FM II), with 6 frequently used chemicals not present in the currently used fragrance mix (FM I), was evaluated in 6 dermatological centres in Europe, as previously reported. In this publication, test results with the individual constituents and after repeated open application test (ROAT) of FM II are described. Furthermore, cosmetic products which had caused a contact dermatitis in patients were analysed for the presence of the individual constituents. In 1701 patients, the individual constituents of the medium (14%) and the highest (28%) concentration of FM II were simultaneously applied with the new mix at 3 concentrations (break-down testing for the lowest concentration of FM II (2.8%) was performed only if the mix was positive). ROAT was performed with the concentration of the FM II which had produced a positive or doubtful (+ or ?+) patch test reaction. Patients' products were analysed for the 6 target compounds by gas chromatography-mass spectrometry (GC-MS). RESULTS: 50 patients (2.9%) showed a positive reaction to 14% FM II and 70 patients (4.1%) to 28% FM II. 24/50 (48%) produced a positive reaction to 1 or more of the individual constituents of 14% FM II and 38/70 (54.3%) to 28% FM II, respectively. If doubtful reactions to individual constituents are included, the break-down testing was positive in 74% and 70%, respectively. Patients with a positive reaction to 14% FM II showed a higher rate of reactions to the individual constituent of the 28% FM II: 36/50 (72%). Positive reactions to individual constituents in patients negative to FM II were exceedingly rare. If doubtful reactions are regarded as negative, the sensitivity, specificity, positive predictive value and negative predictive value for the medium concentration of FM II towards at least 1 individual constituent was 92.3% (exact 95% confidence interval 74.9-99.1%), 98.4% (97.7-99.0%), 48% (33.7-62.6%) and 99.9% (99.6-"100.0%), respectively. For the high concentration, the figures were very similar. The frequency of positive reactions to the individual constituents in descending order was the same for both FM II concentrations: hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral) > citral > farnesol > citronellol > alpha-hexyl-cinnamic aldehyde (AHCA). No unequivocally positive reaction to coumarin was observed. Lyral) was the dominant individual constituent, with positive reactions in 36% of patients reacting to 14% FM II and 37.1% to 28% FM II. 5/11 patients developed a positive ROAT after a median of 7 days (range 2-10). The 5 patients with a doubtful or negative reaction to 28% FM II were all ROAT negative except 1. There were 7 patients with a certain fragrance history and a positive reaction to either 28% or 14% FM II but a negative reaction to FM I. Analysis with GC-MS in a total of 24 products obtained from 12 patients showed at least 1-5 individual constituents per product: Lyral (79.2%), citronellol (87.5%), AHCA (58.3%), citral (50%) and coumarin (50%). The patients were patch test positive to Lyral, citral and AHCA. In conclusion, patients with a certain fragrance history and a negative reaction to FM I can be identified by FM II. Testing with individual constituents is positive in about 50% of cases reacting to either 14% or 28% FM II.

Acrolein↗
PubMed2005

Patch testing with a new fragrance mix detects additional patients sensitive to perfumes and missed by the current fragrance mix.

The currently used 8% fragrance mix (FM I) does not identify all patients with a positive history of adverse reactions to fragrances. A new FM II with 6 frequently used chemicals was evaluated in 1701 consecutive patients patch tested in 6 dermatological centres in Europe. FM II was tested in 3 concentrations - 28% FM II contained 5% hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral), 2% citral, 5% farnesol, 5% coumarin, 1% citronellol and 10%alpha-hexyl-cinnamic aldehyde; in 14% FM II, the single constituents' concentration was lowered to 50% and in 2.8% FM II to 10%. Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable, none. Positive reactions to FM I occurred in 6.5% of the patients. Positive reactions to FM II were dose-dependent and increased from 1.3% (2.8% FM II), through 2.9% (14% FM II) to 4.1% (28% FM II). Reactions classified as doubtful or irritant varied considerably between the 6 centres, with a mean value of 7.2% for FM I and means ranging from 1.8% to 10.6% for FM II. 8.7% of the tested patients had a certain fragrance history. Of these, 25.2% were positive to FM I; reactivity to FM II was again dose-dependent and ranged from 8.1% to 17.6% in this subgroup. Comparing 2 groups of history - certain and none - values for sensitivity and specificity were calculated: sensitivity: FM I, 25.2%; 2.8% FM II, 8.1%; 14% FM II, 13.5%; 28% FM II, 17.6%; specificity: FM I, 96.5%; 2.8% FM II, 99.5%; 14% FM II, 98.8%; 28% FM II, 98.1%. 31/70 patients (44.3%) positive to 28% FM II were negative to FM I, with 14% FM II this proportion being 16/50 (32%). In the group of patients with a certain history, a total of 7 patients were found reacting to FM II only. Conversely, in the group of patients without any fragrance history, there were significantly more positive reactions to FM I than to any concentration of FM II. In conclusion, the new FM II detects additional patients sensitive to fragrances missed by FM I; the number of false-positive reactions is lower with FM II than with FM I. Considering sensitivity, specificity and the frequency of doubtful reactions, the medium concentration, 14% FM II, seems to be the most appropriate diagnostic screening tool.

Acrolein↗
PubMed2005

Selected oxidized fragrance terpenes are common contact allergens.

Terpenes are widely used fragrance compounds in fine fragrances, but also in domestic and occupational products. Terpenes oxidize easily due to autoxidation on air exposure. Previous studies have shown that limonene, linalool and caryophyllene are not allergenic themselves but readily form allergenic products on air-exposure. This study aimed to determine the frequency and characteristics of allergic reactions to selected oxidized fragrance terpenes other than limonene. In total 1511 consecutive dermatitis patients in 6 European dermatology centres were patch tested with oxidized fragrance terpenes and some oxidation fractions and compounds. Oxidized linalool and its hydroperoxide fraction were found to be common contact allergens. Of the patients tested, 1.3% showed a positive reaction to oxidized linalool and 1.1% to the hydroperoxide fraction. About 0.5% of the patients reacted to oxidized caryophyllene whereas 1 patient reacted to oxidized myrcene. Of the patients reacting to the oxidized terpenes, 58% had fragrance-related contact allergy and/or a positive history for adverse reaction to fragrances. Autoxidation of fragrance terpenes contributes greatly to fragrance allergy, which emphasizes the need of testing with compounds that patients are actually exposed to and not only with the ingredients originally applied in commercial formulations.

Allergens↗
PubMed2005

Mode of delivery and the risk of delivery-related perinatal death among twins at term: a retrospective cohort study of 8073 births.

OBJECTIVE: To determine the risk of perinatal death among twins born at term in relation to mode of delivery. DESIGN: Retrospective cohort study. SETTING: Scotland 1985-2001. POPULATION: All twin births at or after 36 weeks of gestation, excluding antepartum stillbirths and perinatal deaths due to congenital abnormality (n= 8073). METHODS: The outcome of first and second twins was compared using McNemar's test and the outcome of twin pairs in relation to mode of delivery was compared using exact logistic regression. MAIN OUTCOME MEASURES: Intrapartum stillbirth or neonatal death of either twin. RESULTS: Overall, there were six deaths of first twins and 30 deaths of second twins (OR for second twin 5.00, 95% CI 2.00-14.70). The odds ratio for death of the second twin due to intrapartum anoxia was 21 (95% CI 3.4-868.5). The associations were similar for twins delivered following induction of labour and for sex discordant twins. However, there was no association between birth order and the risk of death among 1472 deliveries by planned caesarean section. There was death of either twin among 2 of 1472 (0.14%) deliveries by planned caesarean section and 34 of 6601 (0.52%) deliveries by other means (P= 0.05, odds ratio for planned caesarean section 0.26 [95% CI 0.03-1.03]). The association was similar when adjusted for potential confounders. Assuming causality, we estimate that 264 caesarean deliveries (95% CI 158-808) would be required to prevent each death. CONCLUSION: Planned caesarean section may reduce the risk of perinatal death of twins at term by approximately 75% compared with attempting vaginal birth. This is principally due to reducing the risk of death of the second twin due to intrapartum anoxia.

Adult↗
PubMed2005

Uses and limitations of randomization-based efficacy estimators.

In randomized trials with departures from allocated treatment, intention-to-treat analysis is important but not always sufficient. The most common supplement to intention-to-treat analysis is per-protocol analysis, whose assumption of comparability between different nonrandomized groups is often implausible. Randomization-based methods avoid making this assumption and are preferable. Situations where intention-to-treat analysis is insufficient and a randomization-based method is useful include provision of patient information, exploration of treatment-covariate and treatment-time interactions, meta-analysis, and equivalence trials.

Aged↗
PubMed2005

Standardized mean differences in individually-randomized and cluster-randomized trials, with applications to meta-analysis.

The magnitude of the effect of an intervention on a quantitative outcome may be expressed as a standardized mean difference by dividing the difference in means by the standard deviation of the outcome. This is useful to compare outcomes measured using different scales, especially in meta-analysis. However, uncertainty about the standard deviation leads to complicated formulae to avoid bias and to compute the correct standard error. We review approximate and exact formulae and argue for the use of the exact formulae. We then extend the formulae to cluster-randomized trials, and show how the calculations may be implemented using published results. We also describe methods for estimating the standard deviation. Various pitfalls are identified which can lead to major errors especially in the cluster-randomized setting.

Bias↗
PubMed2005

Outcomes of crises before and after introduction of a crisis resolution team.

BACKGROUND: Crisis resolution teams (CRTs) are being introduced throughout England, but their evidence base is limited. AIMS: To compare outcomes of crises before and after introduction of a CRT. METHOD: A new methodology was developed for identification and operational definition of crises. A quasi-experimental design was used to compare cohorts presenting just before and just after a CRT was established. RESULTS: Following introduction of the CRT, the admission rate in the 6 weeks after a crisis fell from 71% to 49% (OR 0.38, 95% CI 0.21-0.70). A difference of 5.6 points (95% CI 2.0-8.3) on mean Client Satisfaction Questionnaire (CSQ-8) score favoured the CRT. These findings remained significant after adjustment for baseline differences. No clear difference emerged in involuntary hospitalisations, symptoms, social functioning or quality of life. CONCLUSIONS: CRTs may prevent some admissions and patients prefer them, although other outcomes appear unchanged in the short term.

Adult↗