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Ian R White

Publications and source records attributed to Ian R White.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2004

Second-trimester maternal serum levels of alpha-fetoprotein and the subsequent risk of sudden infant death syndrome.

BACKGROUND: Unexplained stillbirth and the sudden infant death syndrome (SIDS) share some features. A raised maternal serum level of alpha-fetoprotein during the second trimester of pregnancy is a marker of placental dysfunction and a strong predictor of the risk of unexplained stillbirth. It is unknown whether alpha-fetoprotein levels also predict the risk of SIDS. METHODS: We linked a prenatal-screening database for women in western Scotland with databases of maternity, perinatal death, and birth and death certifications to assess the association between second-trimester levels of maternal serum alpha-fetoprotein and the subsequent risk of SIDS. RESULTS: Among 214,532 women with singleton births, there were 114 cases of SIDS (incidence, 2.7 per 10,000 births among women with alpha-fetoprotein levels in the lowest quintile and 7.5 per 10,000 births among those with levels in the highest quintile). When the lowest quintile was used as a referent, the unadjusted odds ratios for SIDS for the second through fifth quintiles were 1.7 (95 percent confidence interval, 0.8 to 3.5), 1.8 (95 percent confidence interval, 0.9 to 3.7), 2.5 (95 percent confidence interval, 1.3 to 4.8), and 2.8 (95 percent confidence interval, 1.4 to 5.4), respectively (P for trend = 0.001). The risk of SIDS varied inversely with the birth-weight percentile and the gestational age at delivery; after adjustment for these factors, the odds ratios for SIDS were 1.7 (95 percent confidence interval, 0.8 to 3.5), 1.7 (95 percent confidence interval, 0.8 to 3.5), 2.2 (95 percent confidence interval, 1.1 to 4.4), and 2.2 (95 percent confidence interval, 1.1 to 4.3), respectively (P for trend = 0.01). CONCLUSIONS: There is a direct association between second-trimester maternal serum alpha-fetoprotein levels and the risk of SIDS, which may be mediated in part through impaired fetal growth and preterm birth.

Adult↗
PubMed2004

Comparison of imputation and modelling methods in the analysis of a physical activity trial with missing outcomes.

BACKGROUND: Longitudinal studies almost always have some individuals with missing outcomes. Inappropriate handling of the missing data in the analysis can result in misleading conclusions. Here we review a wide range of methods to handle missing outcomes in single and repeated measures data and discuss which methods are most appropriate. METHODS: Using data from a randomized controlled trial to compare two interventions for increasing physical activity, we compare complete-case analysis; ad hoc imputation techniques such as last observation carried forward and worst-case; model-based imputation; longitudinal models with random effects; and recently proposed joint models for repeated measures data and non-ignorable dropout. RESULTS: Estimated intervention effects from ad hoc imputation methods vary widely. Standard multiple imputation and longitudinal modelling agree closely, as they should. Modifying the modelling method to allow for non-ignorable dropout had little effect on estimated intervention effects, but imputing using a common imputation model in both groups gave more conservative results. CONCLUSIONS: Results from ad hoc imputation methods should be avoided in favour of methods with more plausible assumptions although they may be computationally more complex. Although standard multiple imputation methods and longitudinal modelling methods are equivalent for estimating the treatment effect, the two approaches suggest different ways of relaxing the assumptions, and the choice between them depends on contextual knowledge.

Bias↗
PubMed2004

Parametric randomization-based methods for correcting for treatment changes in the assessment of the causal effect of treatment.

We develop parametric maximum likelihood methods to adjust for treatment changes during follow-up in order to assess the causal effect of treatment in clinical trials with time-to-event outcomes. The accelerated failure time model of Robins and Tsiatis relates each observed event time to the underlying event time that would have been observed if the control treatment had been given throughout the trial. We introduce a bivariate parametric frailty model for time to treatment change and time to trial endpoint. Estimating equations which respect the randomization are constructed and compared to maximum likelihood methods in a simulation study. The Concorde trial of immediate versus deferred zidovudine in HIV infection is used as a motivating example and illustration of the methods.

Anti-HIV Agents↗
PubMed2004

A statistical comparison of silver and SYPRO Ruby staining for proteomic analysis.

Silver staining has been the method most commonly employed for high sensitivity staining of proteins following two-dimensional gel electrophoresis. Whilst this method offers detection in the nanogram range it does have major drawbacks including a lack of linearity, nonstoichiometric staining of proteins, a lack of compatibility with the microchemical preparation of proteins for identification by mass spectrometric techniques, and a highly subjective assessment of the staining endpoint. SYPRO Ruby is a relatively new, ruthenium complex-based stain which is reported to offer advantages over silver, particularly in overcoming the limitations cited above. We describe a series of experiments where several protein staining procedures commonly employed are compared. To enable optimization of the in situ digestion procedure, a statistical approach has been undertaken. The effects of a variety of staining, digestion, and analysis protocols on the downstream processing of a test radiolabeled protein were studied. The data confirms that as well as offering sensitivity similar to silver, SYPRO Ruby staining is reproducible, linear, and offers a higher level of compatibility with the identification of proteins by mass spectrometry.

Coloring Agents↗
PubMed2004

Combined logistic and Bayesian modeling of cesarean section risk.

OBJECTIVE: This study was undertaken to develop a simple and robust method for predicting risk of cesarean section. STUDY DESIGN: Retrospective cohort study of singleton births at term between 1992 and1999 in 22 Scottish maternity hospitals among primigravid women induced with prostaglandin. The risk of emergency cesarean section was modeled by using multivariate logistic regression in a development sample (n = 14,968). The output of this model was converted into adjusted likelihood ratios by using a novel method and tested in a validation sample (n = 12,638). RESULTS: Maternal age, height, gestational age, and fetal sex were all predictive of the risk of emergency cesarean section after prostaglandin induction of labor (all P < .001). The area under the receiver operator characteristic (ROC) curve in the development group was 0.677. The derived Bayesian model was comparably predictive of cesarean section risk in the validation sample: ROC of 0.673 (95% CI 0.662-0.684). Among the 994 women (8%) with a predicted cesarean section risk of more than 40%, the expected proportion was 48.2% and the observed proportion was 47.2%. Among the 1439 (11.4%) with a predicted cesarean risk of less than 10%, the expected proportion was 7.9% and the actual proportion 8.6%. CONCLUSION: Women at low or high risk of cesarean section after prostaglandin induction of labor can be identified with the use a novel combination of logistic regression and Bayesian modeling. The method is simple, robust, and may be generally applicable for clinical estimation of risk.

Adult↗
PubMed2004

Strong irritants masquerading as skin allergens: the case of benzalkonium chloride.

Chemicals may possess a number of hazards to human health including the ability to cause skin irritation and contact allergy. Identification and characterization of these properties should fall within predictive toxicology, but information derived from human exposure, including clinical experience, is also of importance. In this context, it is of interest to review the case of benzalkonium chloride, a cationic surfactant. This chemical is a well-known skin irritant, but on occasions it has also been reported to have allergenic properties, typically on the basis of positive diagnostic patch test data. Because the accumulated knowledge concerning the properties of a chemical is employed as the basis for its regulatory classification (e.g. in Europe), as well as for informing the clinical community with respect to the diagnosis of irritant versus allergic contact dermatitis (ACD), it is important to distinguish properly which chemicals are simply irritants from those which are both irritant and allergenic on skin. A review of the information on benzalkonium chloride confirms that it is a significant skin irritant. However, both predictive test results and clinical data lead to the conclusion that benzalkonium chloride is, at most, an extremely rare allergen, except perhaps in the eye, but with many supposed cases of ACD being likely to arise from the misinterpretation of patch test data. As a consequence, this substance should not normally be regarded as, or classified as, a significant skin sensitizer.

Benzalkonium Compounds↗
PubMed2004

Mortality in England and Wales attributable to any drinking, drinking above sensible limits and drinking above lowest-risk level.

AIMS: To quantify mortality attributable to any alcohol consumption, and mortality attributable to consumption above different levels. DESIGN: We related all-cause mortality to alcohol consumption using cause-specific mortality models from a systematic review and using the distribution of alcohol consumption and causes of death by age and sex in England and Wales in 1997. We estimated the deaths and person-years of life lost to age 65 that were attributable: to any drinking; to drinking above the nadir (the level of alcohol consumption carrying the lowest risk); and to drinking more than the British Royal Colleges' recommended limits of 21 units/week in men and 14 units/week in women. FINDINGS: Ischaemic heart disease deaths prevented by alcohol consumption (11 276 in men, 4050 in women) roughly balanced other deaths attributable to alcohol consumption (9246 in men, 4216 in women). Overall, 0.8% of all deaths in men were prevented by alcohol consumption (95% confidence interval, 0.2% to 1.3%), while 0.1% of all deaths in women were attributable to alcohol consumption (95% confidence interval, - 0.3% to 0.4%); 2.1% (1.9-2.3%) of all deaths in men and 0.8% (0.6-1.0%) of all deaths in women were attributable to drinking more than the recommended limits, while 2.8% and 1.2% of deaths, respectively, were attributable to drinking above the nadir. Of all person-years of life lost to age 65, 10.3% in men and 5.6% in women were attributable to any drinking; 8.5% and 4.0% were attributable to drinking above the recommended limits; and 12.6% and 6.0% were attributable to drinking above the nadir. CONCLUSIONS: Although overall mortality risks and benefits of alcohol consumption appear roughly equal, drinking above recommended limits remains responsible for many deaths and a large loss of person-years of life.

Adolescent↗
PubMed2004

Are missing outcome data adequately handled? A review of published randomized controlled trials in major medical journals.

BACKGROUND: Randomized controlled trials almost always have some individuals with missing outcomes. Inadequate handling of these missing data in the analysis can cause substantial bias in the treatment effect estimates. We examine how missing outcome data are handled in randomized controlled trials in order to assess whether adequate steps have been taken to reduce nonresponse bias and to identify ways to improve procedures for missing data. METHODS: We reviewed all randomized trials published between July and December 2001 in BMJ, JAMA, Lancet and New England Journal of Medicine, excluding trials in which the primary outcome was described as a time-to-event. We focused on trial designs, how missing outcome data were described and the statistical methods used to deal with the missing outcome data, including sensitivity analyses. RESULTS: We identified 71 trials of which 63 (89%) reported having partly missing outcome data: 13 trials had more than 20% of patients with missing outcomes. In 26 trials that measured the outcome at a single time point, 92% performed a complete case analysis and 8% imputed the missing outcomes using baseline values or the worst case value. In 37 trials with repeated measures of the outcome, 46% performed complete case analyses, potentially excluding individuals with some follow-up data, while 14% performed a repeated measures analysis, 19% used the last observation carried forward, 11% imputed with the worst case value and 2% imputed using regression predictions. Thirteen (21%) of trials with missing data reported a sensitivity analysis. CONCLUSIONS: Our review shows that missing outcome data are a common problem in randomized controlled trials, and are often inadequately handled in the statistical analysis in the top tier medical journals. Authors should explicitly state the assumptions underlying the handling of the missing outcomes and justify them through data descriptions and sensitivity analyses.

Bias↗
PubMed2004

Allergic contact dermatitis from chlorhexidine.

Although chlorhexidine is a widely used substance, allergic contact dermatitis from chlorhexidine has rarely been reported. Our objective was to study all cases of allergic contact dermatitis from chlorhexidine that were seen at St John's Institute of Dermatology from January 1983 to June 2002. The case records of all patients with positive patch-test reactions to chlorhexidine during the study period were retrieved. The clinical presentation, strength, and relevance of the positive patch-test results as well as possible sources of exposure were studied. There were five cases of allergic contact dermatitis from chlorhexidine during the study period; three of these patients had positive patch-test reactions to chlorhexidine that were of current relevance. The possible sources of exposure included Hibisol, Hibiscrub, a chlorhexidine spray, and peri- and postoperative antiseptic solutions. We concluded that allergic contact dermatitis from chlorhexidine is rare. However, when it occurs, it may cause a severe dermatitis reaction.

Adult↗
PubMed2003

Choice of test for comparing two groups, with particular application to skewed outcomes.

We consider a clinical trial where a skewed outcome variable is to be compared between two groups. While comparison of sample means may lack power, we show that power also depends on the nature of the anticipated treatment effect. For any given distribution in the control arm, there is a family of true distributions in the intervention arm for which the most powerful test is a comparison of arithmetic means. Similar results hold for a comparison of geometric means, and approximately for the Wilcoxon rank sum test and a comparison of medians. We discuss how these methods could be used in planning the analysis of a clinical trial in which the intervention effect alters the shape of the distribution. These ideas are illustrated by a trial in community psychiatry, where the primary outcome (days in hospital) was highly skewed but the intervention was mainly expected to reduce the frequency of values in the tail. We show that a comparison of sample means is a reasonable choice in this case despite the skewness.

Bias↗