John Belcher

Development of OASYS-2: a system for the analysis of serial measurement of peak expiratory flow in workers with suspected occupational asthma.

BACKGROUND: Serial peak expiratory flow (PEF) measurement is usually the most appropriate first step in the confirmation of occupational asthma. Visual assessment of the plotted record is more sensitive and specific than statistical methods so far reported. The use of visual analysis is limited by lack of widespread expertise in the methods. A computer assisted diagnostic aid (OASYS-2) has been developed which is based on a scoring system developed from visual analysis. This removes the requirement for an experienced interpreter and should lead to the more widespread use of the technique. METHODS: PEF records were collected from workers attending an occupational lung disease clinic for investigation of suspected occupational asthma and from workers participating in a study of respiratory symptoms in a postal sorting office. PEF records were divided into two development sets and two gold standard sets. The latter consisted of records from workers in which a final diagnosis had been reached by a method other than PEF recording. An experienced observer scored individual work and rest periods for the two development set PEF records; linear discriminant analysis was used to compare measurements taken from development set 1 records with visual scores. Two equations were produced which allowed prediction of scores for individual work or rest periods. The development set 2 was used to determine how these scores should be used to produce a whole record score. The first gold standard set was used to determine the whole record score which best separated those with and without occupational asthma. The second set determined the sensitivity and specificity of the chosen score. RESULTS: Two hundred and sixty eight PEF records were collected from 169 workers and divided into two development sets (81 and 60 records) and two gold standard sets (60 and 67 records). Linear discriminant analysis produced equations predicting the score for work periods incorporating five indices of PEF change and one for rest periods using seven indices. These equations correctly predicted the score for development set 1 work and rest periods on 61% of occasions (kappa = 0.47). The whole record score for development set 2 records, after weighting for definite or definitely no occupational effect, correlated with the visual score (correlation coefficient 0.86). Comparison with gold standard set 1 identified a cut off which proved to have a sensitivity of 75% and a specificity of 94% for an independent diagnosis of occupational asthma when applied to gold standard set 2. CONCLUSIONS: These results suggest that the sensitivity and specificity of analysing PEF records for occupational asthma using OASYS-2 approaches that of visual analysis, but it should be absolutely reproducible. The performance of OASYS-2 is more specific and approaches the sensitivity of other statistical methods of analysis. The evaluation of a large number of PEF records from workers exposed to different sensitising agents suggests that these results should be robust and should be repeatable in clinical practice.

Development of an expert system for the interpretation of serial peak expiratory flow measurements in the diagnosis of occupational asthma. Midlands Thoracic Society Research Group.

If asthma is due to work exposures there must be a relation between these exposures and the asthma. Asthma causes airway hyperresponsiveness and obstruction; the obstruction can be measured with portable meters, which usually measure peak expiratory flow, or sometimes forced expiratory volume in 1 second (FEV1). These can be measured serially (for instance 2 hourly) over several weeks at and away from work. Once occupational asthma develops, the asthma will be induced by many non-specific triggers common to non-occupational asthma. The challenge is to identify changes in peak expiratory flow due to work among other non-occupational causes. Standard statistical tests have been found to be insensitive or non-specific, principally because of the variable period for deterioration to occur after exposure, and the sometimes prolonged time for recovery to occur, such that days away from work may initially have lower measurements than days at work. A computer assisted diagnostic aid (Oasys) has been developed to separate occupational from non-occupational causes of airflow obstruction. Oasys-2 is based on a discriminant analysis, and achieved a sensitivity of 75% and a specificity of at least 94%; therefore peak expiratory flow monitoring combined with Oasys-2 analysis is better to confirm than to exclude occupational asthma. A neural network version in development has improved on this. Both have been based on expert interpretation of peak flow measurements plotted as daily maximum, mean, and minimum, with the first reading at work taken as the first reading of the day. Oasys has been evaluated with independent criteria against measurements made in a wide range of occupational situations. Oasys is sufficiently developed to be the initial method for the confirmation, although less so for exclusion of occupational asthma.

Increased risk of vascular disease associated with gout: A retrospective, matched cohort study in the UK Clinical Practice Research Datalink

Objectives To determine whether gout increases risk of incident coronary heart disease (CHD), cerebrovascular (CVD) and peripheral vascular disease (PVD) in a large cohort of primary care patients with gout, since there have been no such large studies in primary care. Methods A retrospective cohort study was performed using data from the Clinical Practice Research Datalink (CPRD). Risk of incident CHD, CVD and PVD was compared in 8386 patients with an incident diagnosis of gout, and 39 766 age, sex and registered general practice-matched controls, all aged over 50 years and with no prior vascular history, in the 10 years following incidence of gout, or matched index date (baseline). Multivariable Cox Regression was used to estimate HRs and covariates included sex and baseline measures of age, Body Mass Index, smoking, alcohol consumption, Charlson comorbidity index, history of hypertension, hyperlipidaemia, chronic kidney disease, statin use and aspirin use. Results Multivariable analysis showed men were at increased risk of any vascular event (HRs (95% CIs)) HR 1.06 (1.01 to 1.12), any CHD HR 1.08 (1.01 to 1.15) and PVD HR 1.18 (1.01 to 1.38), while women were at increased risk of any vascular event, HR 1.25 (1.15 to 1.35), any CHD HR 1.25 (1.12 to 1.39), and PVD 1.89 (1.50 to 2.38)) but not any CVD. Conclusions In this cohort of over 50s with gout, female patients with gout were at greatest risk of incident vascular events, even after adjustment for vascular risk factors, despite a higher prevalence of both gout and vascular disease in men. Further research is required to establish the reason for this sex difference.

Variation in hydrogen cyanide production between different strains of Pseudomonas aeruginosa

There is increasing interest in using the cyanogenic properties of Pseudomonas aeruginosa to develop a nonmicrobiological method for its detection. Prior to this, the variation in cyanide production between different P. aeruginosa strains needs to be investigated. Hydrogen cyanide (HCN) released into the gas phase by 96 genotyped P. aeruginosa samples was measured using selected ion flow tube-mass spectrometry after 24, 48, 72 and 96 h of incubation. The HCN produced by a range of non-P. aeruginosa cultures and incubated blank plates was also measured. All P. aeruginosa strains produced more HCN than the control samples, which generated extremely low levels. Analysis across all time-points demonstrated that nonmucoid samples produced more HCN than the mucoid samples (p=0.003), but this relationship varied according to strain. There were clear differences in the headspace HCN concentration for different strains. Multivariate analysis of headspace HCN for the commonest strains (Liverpool, Midlands_1 and Stoke-on-Trent, UK) revealed a significant effect of strain (p<0.001) and a borderline interaction of strain and phenotype (p=0.051). This evidence confirms that all P. aeruginosa strains produce HCN but to varying degrees and generates interest in the possible future clinical applications of the cyanogenic properties of P. aeruginosa.

Increased cardiovascular mortality associated with gout: a systematic review and meta-analysis

Background Hyperuricaemia, the biochemical precursor to gout, has been shown to be an independent risk factor for mortality from cardiovascular disease (CVD), although studies examining the clinical phenomenon of gout and risk of CVD mortality report conflicting results. This study aimed to produce a pooled estimate of risk of mortality from cardiovascular disease in patients with gout. Design Systematic review and meta-analysis. Methods Electronic bibliographic databases were searched from inception to November 2012, with results reviewed by two independent reviewers. Studies were included if they reported data on CVD mortality in adults with gout who were free of CVD at time of entry into the study. Pooled hazard ratios (HRs) for this association were calculated both unadjusted and adjusted for traditional vascular risk factors. Results Six papers, including 223,448 patients, were eligible for inclusion (all (CVD) mortality n = 4, coronary heart disease (CHD) mortality n = 3, and myocardial infarction mortality n = 3). Gout was associated with an excess risk of CVD mortality (unadjusted HR 1.51 (95% confidence interval, CI, 1.17–1.84)) and CHD mortality (unadjusted HR 1.59, 95% CI 1.25–1.94)). After adjusting for traditional vascular risk factors, the pooled HR for both CVD mortality (HR 1.29, 95% CI 1.14–1.44) and CHD mortality (HR 1.42, 95% CI 1.22–1.63) remained statistically significant, but none of the studies reported a significant association with myocardial infarction. Conclusions Gout increases the risk of mortality from CVD and CHD, but not myocardial infarction, independently of vascular risk factors.

A systematic review of radiographic definitions of foot osteoarthritis in population-based studies

OBJECTIVE To identify the methods used in population-based epidemiological studies to diagnose radiographic foot osteoarthritis (OA) and to estimate the population prevalence of radiographic foot OA. METHOD Electronic databases searched included Medline, Embase, CINAHL and Ageline (inception to May 2009). The search strategy combined search terms for radiography, OA, foot, and specific foot joints. Predetermined selection criteria were applied. Data extracted from each paper included: sample population, radiographic views taken, foot joints examined, scoring system used, definition of OA applied, reliability of radiographic scoring and prevalence of radiographic OA in the foot. RESULTS Titles and abstracts of 1035 papers were reviewed and full-texts of 21 papers were obtained. Fifteen papers met inclusion criteria and a further 12 papers were included after screening references. Radiographic views were frequently not specified (NS) but a combination of antero-posterior (AP) and lateral (Lat) views was most commonly reported. The first metatarsophalangeal (MTP) joint was the most commonly examined joint (n=20, 74%). Nineteen studies (70%) used the Kellgren and Lawrence (K&L) grading system, 95% of which defined OA as K&L grade> or =2. Estimates of the prevalence of radiographic first MTP joint OA (defined as K&L> or =2) in middle-aged to older adults ranged from 6.3 to 39%. Significant statistical heterogeneity prevented pooling of prevalence estimates. CONCLUSION There are comparatively few studies examining radiographic foot OA. Existing studies mainly focus on the first MTP joint and use the K&L grading system. Future studies are needed to quantify the prevalence of radiographic OA at the different joint complexes within the foot.

The descriptive assessment for psychiatric art. A new way of quantifying paintings by psychiatric patients.

This pilot study reports the development of a coding system for quantitative analysis of paintings produced by psychiatric patients. Color, color intensity, quality of line, space covered, and subjectively judged emotional tone as characteristics of paintings were recorded in each section of a grid superimposed over the picture. A sample of 39 psychiatric patients were classified into 4 groups using ICD-10 criteria: depression, psychosis, brain injury, and drug abuse. Six independent raters achieved excellent reliability across all scales on each of eight pictures. Analysis of variance results show that each diagnostic group differed on 4 of 13 variables: yellow, orange, color intensity, and line (p < .02). The prospects for further research are discussed.

Procalcitonin versus C-reactive protein and immature-to-total neutrophil ratio as markers of infection after cardiopulmonary bypass in children

Objective: To document concentrations of procalcitonin (PCT), C-reactive protein (CRP), and immature-to-total neutrophil ratio (ITR), postcardiopulmonary bypass (CPB), and to test the hypothesis that PCT is a more reliable marker of infection than CRP or ITR in the post-CPB child. Design: Prospective cohort study. Setting: Pediatric intensive care units at Royal Children’s Hospital, Melbourne, Australia and Birmingham Children’s Hospital, UK. Patients: First stage: 283 post-CPB children; second stage: 65 post-CPB children with suspected infection. Interventions: In the first stage, PCT, ITR, and CRP were measured serially on the first, second, third, and fifth postoperative day (POD). In the second stage, PCT, ITR, and CRP were measured in the specimens taken in the period before and after the clinical diagnosis of infection. Measurements and Main Results: In children without infection, the median peak PCT concentration more than 5 PODs was 1.0 ng/mL, in children with local infection 1.0 ng/mL, and in children with definite sepsis 14.8 ng/mL. CRP increased in all subgroups of children studied, reaching a peak on POD 3 (median 51 mg/L). In definite sepsis, CRP was increased more than the other subgroups. ITR remained high with a median of 0.08 from POD 1 and gradually decreased, except in definite sepsis, where it remained high. In a receiver operating characteristic curve analysis, PCT was the most reliable variable for the diagnosis of probable/definite sepsis with area under the curve 0.84 (95% confidence interval, 0.75–0.92) compared with 0.73 (0.62–0.84) for ITR and 0.62 (0.52–0.73) for CRP. Conclusions: CRP was a poor marker of sepsis in this study. Children with a PCT <2.2 ng/mL or ITR <0.08 were unlikely to have definite or probable sepsis. However, only a third of children with high values of PCT and ITR had definite or probable sepsis.

Gout and risk of chronic kidney disease and nephrolithiasis: meta-analysis of observational studies

IntroductionTo determine the prevalence of chronic kidney disease and nephrolithiasis in people with gout, and the association between gout and prevalent or incident chronic kidney disease and nephrolithiasis.MethodsSystematic review and meta-analysis of epidemiological studies. Data sources; MEDLINE, EMBASE and CINAHL databases, hand-searched reference lists, citation history and contact with authors. Eligibility criteria: cohort, case–control or cross-sectional studies which examined the occurrence of chronic kidney disease or nephrolithiasis amongst adults with gout (with or without a non-gout comparator group) in primary care or general population samples. Prevalence and risk estimate meta-analyses were performed using a random-effects model.ResultsSeventeen studies were included in the meta-analysis (chronic kidney disease n = 7, nephrolithiasis n = 8, both n = 2). Pooled prevalence estimates of chronic kidney disease stage ≥3 and self-reported lifetime nephrolithiasis in people with gout were 24% (95% confidence interval 19% to 28%) and 14% (95% CI 12% to 17%) respectively. Gout was associated with both chronic kidney disease (pooled adjusted odds ratio 2.41, 95% confidence interval 1.86 to 3.11) and self-reported lifetime nephrolithiasis (1.77, 1.43 to 2.19).ConclusionsChronic kidney disease and nephrolithiasis are commonly found amongst patients with gout. Gout is independently associated with both chronic kidney disease and nephrolithiasis. Patients with gout should be actively screened for chronic kidney disease and its consequences.

Is cancer associated with polymyalgia rheumatica? A cohort study in the General Practice Research Database

Objective To investigate the incidence of new cancer diagnoses in a community sample of patients with polymyalgia rheumatica (PMR). Methods All incident cases of PMR in the UK General Practice Research Database (GPRD) (1987–99), without pre-existing cancer or vascular disease and treated with corticosteroids (n=2877) were matched with up to five age, sex and GP practice patients without PMR (n=9942). Participants were followed up until first cancer diagnosis, death, transfer out of the database or end of available records. Results The mean age of the sample was 71.6 years (SD 9.0), 73% were female. Median follow-up time was 7.8 years (IQR 3.4, 12.3). 667 (23.2%) people with a PMR diagnosis developed cancer compared with 1938 (19.5%) of those without PMR. There was an interaction between PMR status and time. In the first 6 months after diagnosis, those with a PMR diagnosis were significantly more likely to receive a cancer diagnosis (adjusted HR (95% CI): 1.69 (1.18 to 2.42)). The number of events was small, but occurrences of prostate, blood, lymph nodes, female reproductive and nervous system cancers may be more common in those with PMR in the first 6 months after PMR diagnosis. Conclusions An increase in the rate of cancer diagnoses was noted in the first 6 months of observation, but we were unable to determine whether the cancer incidence in PMR was different from controls, beyond this time point. Clinicians should ensure they fully exclude cancer as a cause of PMR-like symptoms and monitor patients for possible malignancies.