Pragmatic randomized controlled trial of an allergy intervention for children aged 6-16 with asthma and rhinitis in general practice.

BACKGROUND: It is widely believed that for allergic rhinitis and asthma, avoidance of specific triggers can improve symptom control. Whilst many children with asthma or rhinitis are sensitized to airborne allergens, primary care diagnostic and management decisions are often made without a detailed history of the allergic triggers or allergy testing. Thus, treatment decisions are empirical and allergen avoidance advice is either not given or, if given, not tailored to the child's sensitivities. OBJECTIVE: To ascertain whether allergy assessment and tailored advice in general practice enhances outcomes of children with asthma and rhinitis. METHOD: Pragmatic RCT of allergy intervention (structured allergy history, skin prick testing and appropriate allergy avoidance advice) vs. usual care in children with asthma and/or rhinoconjunctivitis. A blinded observer assessed outcomes at 12 months. Main outcome measures were symptom scores and disease-specific health-related QoL. Secondary outcomes were healthcare utilization, days unable to pursue usual activities and self-rated improvement. RESULTS: A total of 335 participants were randomized to formal allergy assessment or normal care. There were no differences in participants' demographic or clinical characteristics at baseline (all P > 0.05). At 12 months, participants receiving the allergy intervention had fewer rhinitis symptoms (MD - 3.14, 95% CI - 6.01, - 0.81) and an improvement in QoL (MD - 0.50, 95% CI 0.32, 0.68). There were no significant changes in asthma symptoms, healthcare utilization or number of days unable to pursue usual activities. CONCLUSION: Amongst children with known asthma and/or rhinitis in primary care, taking a structured allergy history with skin prick testing and tailored advice on allergy avoidance resulted in reduced symptoms of rhinitis and improved QoL.

Pragmatic randomized controlled trial of a structured allergy intervention for adults with asthma and rhinitis in general practice.

BACKGROUND: It is widely believed that in patients with allergic rhinitis and asthma, avoidance of specific triggers can help improve symptom control and reduce need for medication. Whilst most patients with asthma or rhinitis are sensitized to airborne allergens, primary care diagnostic and management decisions are often made without either obtaining a detailed history of the patient's allergic triggers or performing skin prick tests. Thus, management decisions are empirical and allergen avoidance advice is either not given or, if given, not tailored to the patient's sensitivities. METHOD: To ascertain whether allergy assessment and tailored advice in general practice for patients with asthma and rhinitis enhance well-being, we conducted a pragmatic, open, randomized controlled trial of allergy intervention (structured allergy history and skin prick testing and appropriate advice on allergy avoidance) versus usual care in adult patients with a working diagnosis of asthma and/or rhino-conjunctivitis. Outcomes were assessed after 12 months by an observer who was blinded to allocation. The main outcome measures were asthma and rhinitis symptoms, disease-specific health-related quality of life, generic quality of life and lung function. RESULTS: There were no significant differences in baseline demographics or disease characteristics between patients assigned to immediate or delayed skin prick testing. No significant differences were observed between groups for any measures of symptoms, quality of life or lung function at 12 months (all P > 0.05). CONCLUSION: Amongst adults with known asthma and/or rhinitis in primary care, taking a structured allergy history with skin prick tests and giving tailored advice on allergy avoidance made no difference to their symptoms, quality of life or lung function as measured twelve months later.

High-titre circulating tissue transglutaminase-2 antibodies predict small bowel villous atrophy, but decision cut-off limits must be locally validated.

Numerous studies suggest that high levels of circulating immunoglobulin (Ig)A tissue transglutaminase (TTG2) antibodies predict coeliac disease with high specificity. Accordingly, it has been suggested that duodenal biopsy may not be required routinely for diagnostic confirmation where quantitative serology identifies the presence of high antibody titres. However, defining a cut-off TTG2 threshold is problematic, as the multiple available assay methods are not harmonized and most studies have been focused on the paediatric population. Recent paediatric guidelines proposed a TTG2 antibody diagnostic cut-off at 10 × the upper limit of normal (ULN) for the method; however, concerns remain about errors of generalization, between both methods and laboratories. In this study, we used retrospective laboratory data to investigate the relationship between TTG2 antibody levels and Marsh 3 histology in the seropositive population of adults and children at a single centre. Among 202 seropositive patients with corresponding biopsies, it was possible to define a TTG2 antibody cut-off with 100% specificity for Marsh 3 histology, at just over 10 × ULN for the method. However, UK National External Quality Assurance Scheme returns during the study period showed a wide dispersion of results and poor consensus, both between methods and between laboratories using the same method. Our results support the view that high-titre TTG2 antibody levels have strong predictive value for villous atrophy in adults and children, but suggest that decision cut-offs to guide biopsy requirement will require local validation. TTG2 antibody assay harmonization is a priority, in order to meet the evolving requirements of laboratory users in this field.

Interleukin-6 for the diagnosis of ovarian torsion: a systematic review and meta-analysis.

Ovarian torsion may have significant fertility implications. Interleukin-6 is a pro-inflammatory cytokine, which may act as a helpful diagnostic test. Our objective was to investigate the accuracy of serum interleukin-6 in the diagnosis of ovarian torsion in women with ultrasonographic evidence of an ovarian cyst. An electronic search of published data, unpublished dissertations, theses and conference proceedings was performed. The systematic review involved observational studies. The studies had to provide data to construct 2 × 2 tables. A modified QUADAS tool was used to assess the quality of studies. Sensitivity, specificity, positive and negative predictive value, likelihood ratios and diagnostic odds ratios were calculated. Three studies were identified. Two were included in the meta-analysis. The prevalence of torsion was 30% (21/70). The pooled sensitivity was 85.1% and the pooled specificity was 84.1%. Although further cohort studies would be required, there may be a role for interleukin-6 in the diagnosis of ovarian torsion.

Determinants of long-term outcome in severe alcoholic hepatitis.

BACKGROUND: Although short-term outcome in severe alcoholic hepatitis (SAH) is well described, its long-term course remains uncharacterised. AIM: To assess determinants of long-term outcome in SAH. METHODS: Data were recorded from a cohort with SAH (admission Discriminant Function (DF) ≥32). Kaplan-Meier (KM) and Cox proportional hazards survival analyses were performed to determine predictors of outcome. RESULTS: One hundred and nine patients were included; 63.3% male, aged 49.6 ± 9.4 years with median follow-up of 40.7 months (95% CI 37.2-44.3). Median DF was 58, 86.2% had cirrhosis and 65.1% received corticosteroids and/or pentoxifylline. Overall mortality was 57.8%, 96.8% of deaths being liver-related and 65.1% occurring after the index hospitalisation. Estimated 5-year survival was 31.8%. Hepatorenal syndrome was the only baseline factor independently associated with mortality (HR 3.78, 95% CI 1.98-7.19, P < 0.0001), although it predicted short-term, rather than long-term outcome (median survival 0.52 months, 95% CI 0.43-0.61). Of the 87 patients (79.8%) who survived index hospitalisation, 65.1% experienced recidivism. Abstinence at last follow-up remained the only independent predictor of survival in multivariate analysis (HR 0.370, 95% CI 0.168-0.818, P = 0.014). Five-year survival was higher in abstainers (75.3%) compared with relapsed and continued drinkers (26.8% and 21.0%, respectively, P = 0.005). However, the survival benefit from abstinence only became statistically significant at 18 months postdischarge (HR 2.714, 95% CI 0.995-7.404, P = 0.051). CONCLUSIONS: Estimated 5-year survival after index hospitalisation with SAH is 31.8% with alcohol relapse occurring in two-thirds of patients. Abstinence remains the only independent predictor of long-term survival. Novel strategies to improve abstinence after admission with SAH are urgently needed.

Association of air pollution with daily GP consultations for asthma and other lower respiratory conditions in London.

BACKGROUND: Very few published studies have looked at the effects of air pollution on health in the primary care setting. As part of a large study to examine the association between air pollution and a number of health outcomes, the relationship between daily GP consultations for asthma and other lower respiratory diseases (LRD) and air pollution in London was investigated. METHODS: Time-series analysis of daily numbers of GP consultations controlling for time trends, seasonal factors, day of week cycles, influenza, weather, pollen levels, and serial correlation was performed. Consultation data were available from between 268 718 and 295 740 registered patients from 45-47 London practices contributing to the General Practice Research Database during 1992-4. RESULTS: Positive associations, weakly significant and consistent across lags, were observed between asthma consultations and nitrogen dioxide (NO2) and carbon monoxide (CO) in children and particulate matter of less than 10 microm in diameter (PM10) in adults, and between other LRD consultations and sulphur dioxide (SO2) in children. A consistently negative association with ozone in children was observed in both disease categories. The effect estimates of most pollutants were much larger when analysed separately by season, particularly in the children: percentage change in asthma consultations during the warm season (April-September) for a 10-90th percentile increase in 24 hour NO2 lagged by one day = 13.2% (95% CI 5.6 to 21.3), with CO = 11.4% (95% CI 3.3 to 20.0), and with SO2 = 9.0% (95% CI 2.2 to 16.2). In adults the only association consistent over different lag periods was with PM10 = 9.2% (3.7 to 15.1). The associations of pollution and consultations for LRD were increased mainly in the winter months: percentage change in consultations by children in winter with NO2 = 7.2% (95% CI 2.8 to 11.6), CO = 6.2% (95% CI 2.3 to 10.2), and SO2 = 5.8% (95% CI 1.6 to 10.2). CONCLUSIONS: There are associations between air pollution and daily consultations for asthma and other lower respiratory disease in London. The most significant associations were observed in children and the most important pollutants were NO2, CO, and SO2. In adults the only consistent association was with PM10.

Global assessment of El Niño's disaster burden.

BACKGROUND: Natural disasters have profound effects on health and require medical intervention as part of relief operations. The world's populations are becoming increasingly vulnerable to extreme weather events, which are responsible for most natural disasters. The El Niño Southern Oscillation (ENSO) is the most prominent global climate system associated with year-to-year weather variability and extreme events. We have estimated the burden on human health of natural disasters associated with ENSO. METHODS: We used time-series regression analysis of the relation between El Niño years and the annual rates of persons affected by natural disasters per 1000 population during 1964-93, globally and also by region and disaster type. Correlations between sea-surface temperature (SST) anomalies (index of ENSO) and the rates of persons affected by natural disasters per 1000 population were determined globally, by region and by disaster type. FINDINGS: The rate of persons affected by natural disasters worldwide is strongly associated with ENSO; rates are greater during the first El Niño year (p = 0.05) and the following year (p = 0.01) than in the pre-Niño year. The correlation between rates of persons affected by natural disasters and SST anomalies in the Eastern Pacific (a key ENSO indicator) is highest in the last quarter of the previous year (r = 0.53, p < 0.01). These associations are strongest in South Asia, the region where more than 50% of all disaster victims live. Worldwide, rates of persons affected by drought/famine (half of all disaster victims) and by volcanic eruptions show significant associations with the ENSO cycle, being highest in the post-Niño year and El Niño year, respectively, and being significantly associated with SST anomalies. INTERPRETATION: The strong relation between ENSO and populations affected by natural disasters can be described as a "natural disaster cycle". Determining the phase in this cycle, using SST from the Eastern Equatorial Pacific, could benefit disaster preparedness on a global scale, for South Asia in particular, and for all populations affected by drought/famine and volcanic disasters.

The relationship of concentrations of insulin and proinsulin-like molecules with coronary heart disease prevalence and incidence. A study of two ethnic groups.

OBJECTIVE: To define the potential role of proinsulin-like molecules as risk factors for cardiovascular disease. RESEARCH DESIGN AND METHODS: Fasting concentrations of proinsulin, des-31,32-proinsulin, and insulin, and of insulin 2 h after a 75-g glucose load, were measured in 1,034 nondiabetic europid subjects and 257 south Asian subjects and related to prevalent coronary heart disease (Minnesota-coded electrocardiographic criteria or ischemic chest pain). In 137 south Asian subjects, the fasting concentrations were related to incident coronary heart disease over a 6.5-year follow-up. RESULTS: The standardized odds ratios for prevalent coronary heart disease were as follows: fasting insulin, 1.29 (1.11-1.49), P = 0.0006; 2-h insulin, 1.25 (1.08-1.45), P = 0.003; proinsulin, 1.23 (0.99-1.53), P = 0.058; and des-31,32-proinsulin, 1.32 (1.03-1.69), P = 0.026. The odds ratios were similar in the two ethnic groups. These relationships became insignificant when controlling for age, sex, and BMI. The standardized odds ratios for incident coronary heart disease were as follows: fasting insulin, 0.99 (0.63-1.55), P = 0.97; proinsulin, 1.13 (0.72-1.78), P = 0.59; and des-31,32-proinsulin, 1.00 (0.61-1.63), P = 1.00. CONCLUSIONS: We have found similar relationships between concentrations of proinsulin-like molecules and prevalent coronary heart disease, as are observed for insulin in these nondiabetic subjects, although these molecules comprise only approximately 10% of all insulin-like molecules. It appears biologically implausible that these relationships represent cause and effect.

Thunderstorm-associated asthma: the effect on GP consultations.

Evidence shows that asthma attacks can be brought on by adverse weather conditions such as those experienced during a thunderstorm; a prime example of such an occasion being a thunderstorm episode on 24 June 1994, which resulted in a well-documented increase in medical attendances made by those suffering with asthma and respiratory disorders. However, most of these studies have concerned admissions to accident and emergency departments. The aim of this paper was to ascertain whether a similar increase in consultations was observed in the primary care setting.

Glucose intolerance in thalassemia major is related to insulin resistance and hepatic dysfunction.

Glucose intolerance is a common consequence of transfusion therapy in patients with thalassemia major (TM), but the relative contribution of pancreatic damage and insulin resistance to glucose intolerance is unclear. We have investigated oral (OGTT) and intravenous (IVGTT) glucose tolerance, insulin sensitivity, and fasting concentrations of insulin, proinsulin, and des 31,32 proinsulin in 12 patients with TM (seven hepatitis C virus [HCV] antibody-negative and five-positive), eight patients with hepatic cirrhosis, and nine healthy controls. Two-hour plasma glucose concentrations were marginally higher in anti-HCV-negative (median, 7.4 mmol/ L; range, 4.0 to 8.2) and significantly so in anti-HCV-positive thalassemics (median, 8.5 mmol/L; range, 6.4 to to 23.0) and cirrhotics (median, 8.0 mmol/L; range, 4.7 to 17.6) than in controls (median, 5.5 mmol/L; range, 3.0 to 6.3). Insulin sensitivity was also reduced in the three patient groups (P < .05). Insulin resistance was the main determinant of oral glucose intolerance in all patient groups (partial r2 = .49, P < .0001, n = 28). In turn, the main determinants of insulin insensitivity in TM patients were liver damage (albumin, r = .67, P = .02) and serum ferritin concentration (r = -.62, P = .03). There was no relationship of either 2-hour or incremental insulin concentrations with ferritin levels or with HCV status in TM subjects. Moreover, these patients showed no elevation of concentrations of proinsulin and des 31,32 proinsulin, markers of pancreatic beta-cell damage, in excess of those observed in cirrhotic patients. In conclusion, the glucose intolerance of TM, like that of cirrhosis, is associated with insulin resistance, not insulin deficiency, and may be a direct or indirect consequence of hepatic damage.

Association of proinsulin-like molecules with lipids and fibrinogen in non-diabetic subjects--evidence against a modulating role for insulin.

Elevated concentrations of proinsulin-like molecules, other than insulin, may be associated with abnormalities of cardiovascular risk factors, promoting atherogenesis and thrombosis. Using specific assays we examined the relationship of levels of insulin, intact proinsulin and des-31,32 proinsulin to blood pressure, lipids, fibrinogen, factor VII and albumin excretion rate in 270 europids with normal glucose tolerance. After correcting for age and body mass index, fasting and 2-h insulin concentrations were significantly associated with those of total and LDL-cholesterol (r = 0.18-0.22), HDL-cholesterol (both r = -0.20) and triglycerides (r = 0.21 and 0.18), but not with blood pressure. Concentrations of intact and des-31,32 proinsulin showed significant associations with those of total and LDL-cholesterol (r = 0.20-0.23), HDL-cholesterol (r = -0.31 and -0.32) and triglycerides (r = 0.22 and 0.26). Fasting insulin and intact proinsulin concentrations were significantly associated with fibrinogen (r = -0.15 and 0.18). Concentrations of proinsulin-like molecules comprised less than 10% of all insulin-like molecules, and so were calculated not to influence previously described relationships between insulin concentrations and cardiovascular risk factors measured using non-specific assays. In multiple regression analyses des-31,32 proinsulin concentration was more strongly associated with those of HDL-cholesterol (negatively), LDL-cholesterol and triglycerides than fasting insulin concentrations, while intact proinsulin replaced insulin concentrations in their relationships with fibrinogen. Our results show correlations between dyslipidaemia and proinsulin-like molecules at concentrations at which biological, insulin-like, activity appears unlikely. We also show relationships between LDL-cholesterol and fibrinogen and the proinsulin-like molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Associations of urinary albumin excretion rate with vascular disease in europid nondiabetic subjects.

Microalbuminuria and its association with vascular disease has previously been reported in nondiabetic individuals. The aims of this study were to determine whether there is a cross-sectional relationship between urinary albumin excretion rate and cardiovascular disease in nondiabetic subjects and to investigate hereditary predisposition to microalbuminuria by studying offspring of the main study population. Europid patients, aged 40-70 years, were randomly selected from a large inner-city general practice; there was a 62.6% attendance rate, and a study population of 959 remained after exclusions. Blood pressure, ankle systolic pressure, height, and weight were measured. Albumin excretion rate was calculated from overnight and morning urine collections. Venous blood was taken for lipids, fibrinogen, and factor VII; and resting electrocardiograms were carried out. Offspring (aged 15-40 years) of those found to be microalbuminuric were invited to attend for the same tests, and controls were selected by age and sex matching the parents. There was no association between parents' albumin excretion rate with that of their offspring, and there were no significant differences in albumin excretion rate between offspring subjects and their controls. There were no statistically significant associations of prevalent coronary heart disease (CHD) with albumin excretion rate or microalbuminuria in either sex [CHD in women: odds ratio (OR) 1.85; 95% confidence interval (CI) 0.19,9.0] [CHD in men: OR 2.13; 95% CI (0.64, 6.59)]. In women, there were significant associations between albumin excretion rate and peripheral vascular disease (positive) and fibrinogen (negative). Because established risk factors may not be as strongly associated with CHD in cross-sectional studies, we intend to follow this group prospectively.

Microalbuminuria: associations with height and sex in non-diabetic subjects.

OBJECTIVES: To study the association(s) between microalbuminuria and cardiovascular risk factors in non-diabetic subjects. DESIGN: Patients aged 40-75 years were randomly selected from a general practice list and invited to participate. SETTING: Health centre in inner city London. SUBJECTS: Of those invited, 1046 out of 1671 (62.6%) attended. Subjects were excluded for the following reasons: not being white (44); urinary albumin excretion rate > 200 micrograms/min (3); having a urinary infection (5); taking penicillamine or angiotensin converting enzyme inhibitors (7); older than 75 (2); having diabetes (25); missing data on glucose concentration (1). MAIN OUTCOME MEASURES: Glucose tolerance test results, albumin excretion rate from overnight and timed morning collections of urine; blood pressure; height. RESULTS: Mean albumin excretion rate was significantly lower in women than men (mean ratio 0.8, 95% confidence interval (0.69 to 0.91)). Mean albumin excretion rate was significantly associated with age, blood pressure, and blood glucose concentration (fasting, 1 hour, and 2 hour) in men and inversely with height. Men who had microalbuminuria in both samples were significantly shorter (by 5 cm (1.3 to 9.3 cm)) than those who had no microalbuminuria in either sample when age was taken into account. In the case of women only systolic pressure was significantly associated with albumin excretion rate. CONCLUSIONS: Microalbuminuria and short stature in men are associated. Cardiovascular risk has been associated with both of these factors and with lower birth weight. The inverse association of microalbuminuria with height is compatible with the suggestion that factors operating in utero or early childhood are implicated in cardiovascular disease. The higher prevalence of microalbuminuria in men compared with women may indicate that sex differences in cardiovascular risk are reflected in differences in albumin excretion rate.