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P C Lambert

Publications and source records attributed to P C Lambert.

At least 19 recordsLinked to original sources
PubMed2007

An evaluation of bivariate random-effects meta-analysis for the joint synthesis of two correlated outcomes.

Often multiple outcomes are of interest in each study identified by a systematic review, and in this situation a separate univariate meta-analysis is usually applied to synthesize the evidence for each outcome independently; an alternative approach is a single multivariate meta-analysis model that utilizes any correlation between outcomes and obtains all the pooled estimates jointly. Surprisingly, multivariate meta-analysis is rarely considered in practice, so in this paper we illustrate the benefits and limitations of the approach to provide helpful insight for practitioners. We compare a bivariate random-effects meta-analysis (BRMA) to two independent univariate random-effects meta-analyses (URMA), and show how and why a BRMA is able to 'borrow strength' across outcomes. Then, on application to two examples in healthcare, we show: (i) given complete data for both outcomes in each study, BRMA is likely to produce individual pooled estimates with very similar standard errors to those from URMA; (ii) given some studies where one of the outcomes is missing at random, the 'borrowing of strength' is likely to allow BRMA to produce individual pooled estimates with noticeably smaller standard errors than those from URMA; (iii) for either complete data or missing data, BRMA will produce a more appropriate standard error of the pooled difference between outcomes as it incorporates their correlation, which is not possible using URMA; and (iv) despite its advantages, BRMA may often not be possible due to the difficulty in obtaining the within-study correlations required to fit the model. Bivariate meta-regression and further research priorities are also discussed.

Analysis of Variance↗
PubMed2005

Recalibration methods to enhance information on prevalence rates from large mental health surveys.

Comparisons between self-report and clinical psychiatric measures have revealed considerable disagreement. It is unsafe to consider these measures as directly equivalent, so it would be valuable to have a reliable recalibration of one measure in terms of the other. We evaluated multiple imputation incorporating a Bayesian approach, and a fully Bayesian method, to recalibrate diagnoses from a self-report survey interview in terms of those from a clinical interview with data from a two-phase national household survey for a practical application, and artificial data for simulation studies. The most important factors in obtaining a precise and accurate 'clinical' prevalence estimate from self-report data were (a) good agreement between the two diagnostic measures and (b) a sufficiently large set of calibration data with diagnoses based on both kinds of interview from the same group of subjects. From the case study, calibration data on 612 subjects were sufficient to yield estimates of the total prevalence of anxiety, depression or neurosis with a precision in the region of +/-2%. The limitations of the calibration method demonstrate the need to increase agreement between survey and reference measures by improving lay interviews and their diagnostic algorithms.

Adult↗
PubMed2003

Up-to-date estimates of long-term cancer survival in England and Wales.

Cancer survival in England and Wales has improved over the last 30 years. However, cohort survival estimates delay recognition of these improvements. Here we show that period survival estimates, based on survival in a recent time period, suggest a more optimistic pattern for England and Wales than cohort-based measures for most cancers.British Journal of Cancer (2003) 89, 74-76. doi:10.1038/sj.bjc.6600976 www.bjcancer.com

Adolescent↗
PubMed2003

Reporting of prognostic markers: current problems and development of guidelines for evidence-based practice in the future.

Prognostic markers help to stratify patients for treatment by identifying patients with different risks of outcome (e.g. recurrence of disease), and are important tools in the management of cancer and many other diseases. Systematic review and meta-analytical approaches to identifying the most valuable prognostic markers are needed because (sometimes conflicting) evidence relating to markers is often published across a number of studies. To investigate the practicality of this approach, an empirical investigation of a systematic review of tumour markers for neuroblastoma was performed; 260 studies of prognostic markers were identified, which considered 130 different markers. The reporting of these studies was often inadequate, in terms of both statistical analysis and presentation, and there was considerable heterogeneity for many important clinical/statistical factors. These problems restricted both the extraction of data and the meta-analysis of results from the primary studies, limiting feasibility of the evidence-based approach.Guidelines for reporting the results of primary prognostic marker studies in cancer, and other diseases, are given in order to facilitate both the interpretation of individual studies and the undertaking of systematic reviews, meta-analysis and, ultimately, evidence-based practice. General availability of full individual patient data is a necessary step forward and would overcome the majority of problems encountered, including poorly reported summary statistics and variability in cutoff level, outcome assessed and adjustment factors used. It would also limit the problem of reporting bias, although publication bias will remain a concern until studies are prospectively registered. Such changes in practice would help important evidence-based reviews to be conducted in order to establish the most appropriate prognostic markers for clinical use, which should ultimately improve patient care.

Biomarkers, Tumor↗
PubMed2003

A systematic review of molecular and biological markers in tumours of the Ewing's sarcoma family.

The aims of this study were to perform the first systematic review of molecular and biological tumour markers in tumours of the Ewing's sarcoma family (ESFT), and evaluate the current evidence for their clinical use. A well-defined, reproducible search strategy was used to identify the relevant literature from 1966 to February 2000. Papers were independently assessed for tumour markers used in the screening, diagnosis, prognosis or monitoring of patients with ESFT. Eighty-four papers studying the use of 70 different tumour markers in ESFT's were identified. Low-quality, inconsistent reporting limited meta-analysis to that of prognostic data for 28 markers. Patients with tumours lacking S-100 protein expression have a better overall survival (OS) (hazard ratio (HR)=0.41, 95% confidence interval (CI) 0.19, 0.89) than those with expression; patients with high levels of serum LDH had a worse OS and disease-free survival (DFS) (OS: HR=2.92, CI 2.16, 3.94, DFS: HR=3.38, 95% CI 2.28, 4.99); patients with localised disease and tumours expressing type 1 EWS-FLI1 fusion transcripts had an improved DFS compared with those with other fusion transcript types (HR=0.17, 95% CI 0.079, 0.37). The knowledge base formed should facilitate more informative future research. Improved statistical reporting and large, multicentre prospective studies are advocated.

Biomarkers, Tumor↗
PubMed2003

An adult model of exclusive viral wheeze: inflammation in the upper and lower respiratory tracts.

BACKGROUND: We have previously reported an experimental infection of young adults with a history of episodic and exclusive viral wheeze (EVW) using human coronavirus, in which 16 of 24 with EVW (15 atopic) and 11 of 19 healthy controls (seven atopic) developed a symptomatic cold with evidence of infection, but only those with EVW developed lower respiratory tract symptoms and increased airway responsiveness. OBJECTIVE: The aim of this study was to compare the EVW and control groups from this study for inflammatory changes occurring in the upper and lower respiratory tracts during the experimental infection, in particular, to determine whether eosinophil-driven inflammation was associated with EVW. METHODS: Nasal lavage and induced sputum were collected prior to inoculation (day 0) and 2, 4 and 17 days later. Differential cell counts were performed and supernatant was assayed for IL-8, IL-5, IFN-gamma, and eosinophilic cationic protein (ECP). RESULTS: There was no difference between the two groups in any measurement at baseline. In both groups, during colds the volume of nasal secretion increased as did leucocyte counts in both upper and lower respiratory tracts. A modest increase in nasal neutrophil count was seen in both EVW and control groups with symptomatic colds on day 2 (median (quartile) difference from baseline 5.4 (0.0, 11.0) and 1.8 (-1.1, 2.2)x10(4)/mL of secretions, respectively). The change in nasal neutrophil counts in all subjects correlated with nasal symptom scores. A significant relative increase in sputum differential neutrophil count was seen on day 4 in the EVW group with a cold but not in controls (mean difference (95% confidence interval) 20.4 (9.6, 31.1)% and 3.1 (-8.2, 14.5)%, respectively, P<0.01); however, this increase did not correlate with lower respiratory tract symptom scores. IL-8 increased in both the upper and lower respiratory tracts in both EVW and control subjects with colds, the largest change being seen on day 4 in the sputum of those with EVW (mean difference from baseline (95% confidence interval) 2.5 (0.55-4.46) ng/mL). Only modest changes were seen in IFN-gamma and no changes were seen in IL-5 or ECP. None of the results was influenced by the atopic status of the subjects in either group. CONCLUSIONS: EVW wheeze is characterized by neutrophilic inflammation in both the upper and lower respiratory tracts without eosinophilia (even in atopic subjects). IL-8 is likely to be an important chemokine in this process. Symptoms and airway responsiveness were correlated with change in neutrophils.

Common Cold↗
PubMed2002

A comparison of summary patient-level covariates in meta-regression with individual patient data meta-analysis.

OBJECTIVES: To compare meta-analysis of summary study level data with the equivalent individual patient data (IPD) analysis when interest lies in identification of binary patient characteristics related to treatment efficacy. DESIGN: A simulation study comparing meta-regression with IPD analyses of randomized controlled trials. METHODS: Twenty-seven different meta-analysis situations were simulated with 1000 repetitions in each case. The following parameters were varied: (1) the treatment effect magnitude for different patient risk groups; (2) sample sizes of individual studies; and (3) number of studies. The meta-regression and IPD results were then compared for each situation. RESULTS: The statistical power of meta-regression was dramatically and consistently lower than that of IPD analysis, with little agreement between the parameter estimates obtained from the two methods. Only in meta-analyses of large numbers of large trials, did meta-regression detect differential treatment effects between risk groups with any consistency. CONCLUSIONS: Meta-analysis of summary data may be adequate when estimating a single pooled treatment effect or investigating study level characteristics. However, when interest lies in investigating whether patient characteristics are related to treatment, IPD analysis will generally be necessary to discover any such relationships. In these situations practitioners should try to obtain individual-level data.

Humans↗
PubMed2002

Parents' accounts of wheeze and asthma related symptoms: a qualitative study.

AIMS: To examine parents' accounts of how they recognise and judge respiratory symptoms in children, and to investigate their interpretations of respiratory survey questions about wheeze, shortness of breath, and cough. METHODS: Qualitative study using semistructured interviews. Data were analysed using the constant comparative method. Nineteen parents of children aged under 6 years were recruited from a cohort of parents who had responded to an earlier respiratory symptom survey and from one general practice. RESULTS: Parents judged respiratory symptoms using a range of cues, including changes in the sound of breathing and changes in appearance and behaviour. Experiential resources and contextual factors played an important role in parents' judgements. Interpretations of questions about respiratory symptoms were varied, particularly in relation to the terms "attacks of wheeze" and "shortness of breath". Parents' descriptions of wheeze differed from descriptions of the sound of wheeze used in some survey questionnaires. Parents drew fine distinctions between different "types" of cough and identified a distinct "asthma" cough. CONCLUSIONS: Attention needs to be given to the complexity of reporting respiratory symptoms in children and to the importance of contextual factors in parents' judgements. We suggest that questions which require parents to report on children's internal feelings or states be avoided. Consideration should be given to providing parents with explicit direction on what cues to attend to or ignore in reporting symptoms, and to clarifying some questions that are currently used in clinical practice and in surveys.

Asthma↗
PubMed2001

Analysis of ambulatory blood pressure monitor data using a hierarchical model incorporating restricted cubic splines and heterogeneous within-subject variances.

Hypertensive disorders of pregnancy are associated with significant maternal and foetal morbidity. Measurement of blood pressure remains the standard way of identifying individuals at risk. There is growing interest in the use of ambulatory blood pressure monitors (ABPM), which can record an individual's blood pressure many times over a 24-hour period. From a clinical perspective interest lies in the shape of the blood pressure profile over a 24-hour period and any differences in the profile between groups. We propose a two-level hierarchical linear model incorporating all ABPM data into a single model. We contrast a classical approach with a Bayesian approach using the results of a study of 206 pregnant women who were asked to wear an ABPM for 24 hours after referral to an obstetric day unit with high blood pressure. As the main interest lies in the shape of the profile, we use restricted cubic splines to model the mean profiles. The use of restricted cubic splines provides a flexible way to model the mean profiles and to make comparisons between groups. From examining the data and the fit of the model it is apparent that there were heterogeneous within-subject variances in that some women tend to have more variable blood pressure than others. Within the Bayesian framework it is relatively easy to incorporate a random effect to model the between-subject variation in the within-subject variances. Although there is substantial heterogeneity in the within-subject variances, allowing for this in the model has surprisingly little impact on the estimates of the mean profiles or their confidence/credible intervals. We thus demonstrate a powerful method for analysis of ABPM data and also demonstrate how heterogeneous within-subject variances can be modelled from a Bayesian perspective.

Bayes Theorem↗
PubMed2001

A model of viral wheeze in nonasthmatic adults: symptoms and physiology.

Episodic wheezing associated with viral infections of the upper respiratory tract (URT) is a common problem in young children but also occurs in adults. It is hypothesized that an experimental infection with human coronavirus (HCoV), the second most prevalent common cold virus, would cause lower respiratory tract (LRT) changes in adults with a history of viral wheeze. Twenty-four viral wheezers (15 atopic) and 19 controls (seven atopic) were inoculated with HCoV 229E and monitored for the development of symptoms, changes in airway physiology and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20). At baseline, viral wheezers were similar to controls in PC20 (mean+/-SD log2PC20: 5.1+/-1.9 and 5.8+/-1.4 g x L(-1), respectively) but had a lower FEV1 than controls (mean+/-SD 85.8+/-11.4 and 95.6+/-13.2% predicted, respectively p < 0.05). Nineteen viral wheezers and 11 controls developed colds. Viral wheezers with colds reported significantly more URT symptoms than controls (median scores (interquartile range): 24 (10-37) and 6 (4-15), respectively p = 0.014). Sixteen viral wheezers and no controls reported LRT symptoms (wheeze, chest tightness and shortness of breath). The viral wheezers with colds had small (3-4%) reductions in FEV1 and peak expiratory flow on days with LRT symptoms (days 3-6), but a progressive reduction in PC20 from baseline on days 2, 4 and 17 after inoculation (by 0.82, 1.35 and 1.82 doubling concentrations, respectively). The fall in PC20 affected both atopic and nonatopic subjects equally. There were no changes in FEV1 or PC20 in controls. An adult model of viral wheeze that is independent of atopy and therefore, of classical atopic asthma was established.

Adult↗
PubMed2000

Birth weight and 24-hour ambulatory blood pressure in nonproteinuric hypertensive pregnancy.

OBJECTIVE: The aim of this study was to examine the relationship between maternal ambulatory blood pressure monitor measurements during pregnancy and birth weight in a population of women considered to have hypertension according to conventional antenatal clinic measurement. STUDY DESIGN: A prospective observational study was carried out within the obstetric departments of Leicester Royal Infirmary and Queen Charlotte's Hospital. A total of 237 women were found to have hypertension (blood pressure >/=140/90 mm Hg) without significant proteinuria during examination in the antenatal assessment area. Sequential-day unit blood pressure recordings and a 24-hour automated ambulatory blood pressure recording were performed, and the results were compared with the principal outcome measure of birth weight. RESULTS: A significant inverse association (gradient, -13.5; 95% confidence interval -23.4 to -3.6) was found between daytime ambulatory diastolic blood pressure measurement and birth weight. An increase of 5 mm Hg in daytime mean diastolic blood pressure was associated with a fall in birth weight of 68.5 g. This association remained after adjustment for potential confounders that included maternal age, maternal weight, smoking status, ethnicity, and gestational age at delivery. No such association was found between obstetric day unit assessment of blood pressure and birth weight. CONCLUSION: There is a significant association between blood pressure and birth weight in nonproteinuric hypertensive pregnancies. The best predictor of this association is the daytime mean ambulatory diastolic blood pressure measurement. This is further evidence that maternal blood pressure may be an important confounding and potentially genetic variable in the association between birth weight and subsequent adult hypertension.

Adult↗
PubMed1999

The role of observer error in antenatal dipstick proteinuria analysis.

OBJECTIVE: To determine the role of inter-observer error and the influence of training upon dipstick urine analysis. DESIGN: A two phase observational and training study. METHODS: Five standard solutions of serum albumin were used to test the accuracy of midwives and nursing auxiliaries involved in dipstick urine analysis at a maternity hospital. The standard solutions were chosen such that they should have resulted in negative (n = 2) and positive (n = 3) dipstick test results, respectively. SETTING: A teaching maternity hospital and academic department of obstetrics and gynaecology. PARTICIPANTS: Twenty midwives, 20 nursing auxiliaries and nine laboratory technicians. RESULTS: For the two nonproteinuric solutions, a higher false positive rate was observed for nursing auxiliaries (40% and 55%), compared with midwives (5% and 30%) (P = 0.020 and P = 0.20, respectively). Before training, laboratory technicians recorded high false positive rates (67% and 89%), but after training these were reduced to 0% and 22% (P = 0.25 and P = 0.023, respectively). Both nursing auxiliaries and midwives recorded false negative rates of between 10% and 45% for the three proteinuric solutions. CONCLUSIONS: Observer error may be reduced by assigning midwives to urine dipstick analysis or by the implementation of directed training. Classification of pre-eclampsia or other hypertensive diseases of pregnancy on the basis of the presence and degree of proteinuria should be confirmed with a 24-hour quantitative protein collection.

False Negative Reactions↗
PubMed1998

Recurrent cough: natural history and significance in infancy and early childhood.

We investigated the outcome for a sample of children in whom recurrent cough was reported in the preschool years to determine 1) whether they shared the characteristics attributed to cough variant asthma, and 2) the proportion who developed classical wheezy asthma at follow-up during the early school years. A cohort of children identified as having recurrent cough in the preschool period was reassessed during the early school years. Previously identified asymptomatic preschool children who remained symptom-free provided a comparison group with respect to current respiratory symptoms, lung function, bronchial reactivity to inhaled methacholine, atopic status, peak flow variability, and recorded night cough. The response rate was modest, with 41% attending the follow-up study; information on current symptoms was available from a further 16%. Ascertainment of current symptoms showed that 70 of 125 (56.0% [95% CI 47.3-64.5%]) were symptom-free at follow-up, 46 (36.8% [28.7-45.5%]) continued to have recurrent cough in the absence of colds, and 9 (7.2% [3.6-12.8%]) reported recent attacks of wheeze. When comparing the 46 children whose recurrent cough persisted from the preschool period through to follow-up with subjects from the asymptomatic comparison group, the former had significantly more night cough (50.0% vs. 16.8%; P< 0.01), were more likely to be treated (10.9% vs. 1.7%; P=0.01), or were diagnosed (26.1% vs. 5.7%; P < 0.001) as asthmatic. They also showed greater bronchial reactivity than their asymptomatic counterparts (1.23 mg/ml vs. 3.35 mg/ml; P=0.002). Atopic status and other indices of lung function were similar between groups. We conclude that there are a group of children with long-term recurrent cough who display features consistent with a diagnosis of cough variant asthma, but at 2-4 years of follow-up, few progress to develop asthma characterized by wheeze.

Asthma↗
PubMed1998

Automated, ambulatory, or conventional blood pressure measurement in pregnancy: which is the better predictor of severe hypertension?

OBJECTIVES: Our purpose was to investigate the benefit, if any, of automated blood pressure monitoring over obstetric day unit conventional blood pressure measurement in the assessment of hypertensive pregnancies. STUDY DESIGN: A prospective, observational study was carried out in two large teaching hospitals. Three hundred and forty-eight women with a confirmed clinic blood pressure of at least 140/90 mm Hg were recruited. Conventional blood pressure measurements (< or =5) were obtained on the day unit and simultaneously an ambulatory blood pressure monitor was applied for 24 hours. The predictive ability of day unit assessment (blood pressure > 140/90 mm Hg) and automated blood pressure monitoring (blood pressure > 130/85 mm Hg) was compared. Principal outcome measures included the occurrence of severe hypertension (> 160/110 mm Hg) and proteinuria (> 500 mg or 2+) within (a) 2 weeks and (b) the remainder of the pregnancy. Thompson's method was used to compare sensitivity and specificity of the day unit blood pressure and automated blood pressure monitoring. RESULTS: Three hundred and forty-eight women were recruited to the study. The comparison between automated blood pressure monitoring and conventional blood pressure measurement for both sensitivity and specificity for systolic and diastolic blood pressure revealed increased sensitivity and decreased specificity with automated blood pressure monitoring for all principal outcomes except development of proteinuria for systolic blood pressure. Sensitivity for the outcomes was increased with automated blood pressure monitoring by between 14% and 27% for systolic blood pressure and between 7% and 39% for diastolic blood pressure, with the greatest improvement seen for the development of severe hypertension within 2 weeks of assessment. CONCLUSIONS: In the assessment of hypertensive pregnancies, automated blood pressure measurement was a significantly better predictor (compared with conventional day unit assessment) for the development of severe hypertension within 2 weeks of assessment for both systolic and diastolic blood pressure.

Adult↗
PubMed1997

Automated blood pressure measurement as a predictor of proteinuric pre-eclampsia.

OBJECTIVES: To investigate the relation between antenatal clinic, obstetric day unit and 24-hour ambulatory blood pressure measurements and 24-hour proteinuria levels in hypertensive pregnancies. DESIGN: An observational study. PARTICIPANTS: Forty-eight women presenting with new hypertension after 20 weeks of gestation. RESULTS: The closest relation was found between ambulatory blood pressure measurements and 24-hour proteinuria levels. No significant relation was found between the conventional diastolic blood pressure threshold of 90 mmHg and 24-hour proteinuria levels. CONCLUSIONS: Ambulatory blood pressure measurement gives better information about disease status in pre-eclampsia as assessed by proteinuria than does conventional sphygmomanometry.

Adolescent↗
PubMed1996

Diurnal blood pressure difference in the assessment of preeclampsia.

OBJECTIVE: To evaluate diurnal variation in blood pressure (BP) in normal gravidas and those with preeclampsia, using ambulatory BP monitoring. METHODS: A cross-sectional comparative observational study was performed in three teaching hospital maternity units. Twenty-four normotensive and 24 preeclamptic women who were similar in age, weight, and mean duration of gestation (35 weeks) were studied. Diurnal variation and BP measurement were assessed using ambulatory BP monitors validated for use in pregnancy and for which normal reference ranges for pregnancy have been derived. RESULTS: At night, the BP fall was less in preeclamptic women than in normotensive women. The day-night BP difference decreased as average BP rose (diastolic gradient = -0.54 [95% confidence interval (CI) -0.77 to -0.31], systolic gradient = -0.36 [95% CI -0.58 to -0.14], where gradient denotes a unit increase in BP leading to an increase or decrease in the day-night difference). CONCLUSION: The decrease in day-night BP difference observed in preeclampsia is inversely related to average BP. This blunting of the day-night BP difference may be a useful adjunctive measure of disease severity in preeclampsia.

Adolescent↗