Long term effects of gestational hypertension and pre-eclampsia on kidney function: Record linkage study.

OBJECTIVE: To assess the long term effects of hypertensive disorders of pregnancy on renal function. DESIGN: Cohort study where exposure was gestational hypertension or preeclampsia in the first pregnancy. Normotensive women formed the comparison group. SETTING: Aberdeen, Scotland. PARTICIPANTS: All women with date of birth on or before 30th June 1969 and at least their first singleton delivery recorded in the Aberdeen Maternity and Neonatal Databank. METHODS: Participants were linked to the Renal Biochemistry Register, Scottish Morbidity Records, Scottish Renal Registry and National Register for deaths. MAIN OUTCOME MEASURES: Occurrence of chronic kidney disease (CKD) as identified from renal function tests in later life, hospital admissions or death from kidney disease or recorded as receiving renal replacement therapy. RESULTS: CKD was diagnosed in 7.5% and 5.2% of women who previously had GH and PE respectively compared to 3.9% in normotensive women. The unadjusted odds ratio (95% confidence interval) of having CKD in PE was 2.04 (1.53, 2.71) and that for GH was 1.37 (1.15, 1.65), while the adjusted odds ratio (95% confidence interval) of CKD was 1.93 (1.44, 2.57) and 1.36 (1.13, 1.63) in women with PE and GH respectively. Kaplan-Meier curves of survival time to development of chronic kidney disease revealed that women with preeclampsia were susceptible to kidney function impairment earliest, followed by those with gestational hypertension. CONCLUSIONS: There was an increased subsequent risk of CKD associated with hypertensive disorders of pregnancy. Women with GH and PE were also found to have CKD earlier than normotensive women.

Views of medical students: what, when and how do they want statistics taught?

BACKGROUND: A key skill for a practising clinician is being able to do research, understand the statistical analyses and interpret results in the medical literature. Basic statistics has become essential within medical education, but when, what and in which format is uncertain. METHODS: To inform curriculum design/development we undertook a quantitative survey of fifth year medical students and followed them up with a series of focus groups to obtain their opinions as to what statistics teaching they want, when and how. RESULTS: A total of 145 students undertook the survey and five focus groups were held with between 3 and 9 participants each. Previous statistical training varied and students recognised their knowledge was inadequate and keen to see additional training implemented. Students were aware of the importance of statistics to their future careers, but apprehensive about learning. Face-to-face teaching supported by online resources was popular. Focus groups indicated the need for statistical training early in their degree and highlighted their lack of confidence and inconsistencies in support. CONCLUSION: The study found that the students see the importance of statistics training in the medical curriculum but that timing and mode of delivery are key. The findings have informed the design of a new course to be implemented in the third undergraduate year. Teaching will be based around published studies aiming to equip students with the basics required with additional resources available through a virtual learning environment.

N-terminal pro-B-type natriuretic peptide concentrations and long-term outcome after cardiac surgery: a prospective cohort study.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations predict cardiovascular outcome in many settings. There are very few data assessing the utility of NT-proBNP concentrations in the prediction of long-term outcome after cardiac surgery. We assessed the ability of NT-proBNP to predict 3 yr mortality compared with validated clinical risk prediction tools. METHODS: A secondary analysis of a prospectively recruited patient cohort of 1010 patients undergoing cardiac surgery. Baseline clinical details were obtained including EuroSCORE. Multi-variable modelling, area under the receiver operating characteristic curves (AUCs), and net reclassification improvement were utilized. RESULTS: NT-proBNP was a univariable predictor of 3 yr mortality but was no longer a significant predictor in a multivariable model (hazard ratio 1.00 per 250 ng litre(-1), 95% confidence interval 0.98-1.02, P=0.80). The relative and additive predictive values of the preoperative EuroSCORE (both additive and logistic versions) and NT-proBNP concentrations were compared. All were predictive of 3 yr mortality (P<0.001) with almost identical AUCs (0.71 for EuroSCORE, 0.70 for NT-proBNP). When either the EuroSCORE or NT-proBNP concentrations are known, the addition of the other does not improve the ability to predict 3 yr mortality. CONCLUSIONS: Preoperative NT-proBNP concentrations and the EuroSCORE have equivalent, and moderate, predictive accuracy for mortality 3 yr after cardiac surgery. EuroSCORE uses clinical data but is not routinely used for individual clinical risk prediction. NT-proBNP measurement would incur additional costs but can be measured quickly and objectively. With such similar predictive accuracy, factors such as the ease of calculation and cost will likely determine their use in clinical practice.

Hypertensive disorders of pregnancy and future health and mortality: A record linkage study.

The objective of this register-based cohort study was to examine the relationship between hypertensive disorders of pregnancy and future hospital discharges from specified causes including cardiovascular disease, incident cancer registrations and mortality. From the Aberdeen Maternity and Neonatal Databank we identified 34,854 women who were born on or before 31st December 1967 and who had (i) preeclampsia/eclampsia, (ii) gestational hypertension or (iii) normal blood pressure in their first pregnancy. Hospital discharges from selected causes including cardiovascular disease, cancer registrations and deaths in these women were identified from the Scottish Morbidity Records. There were 2026 women who had preeclampsia, 8891 who had gestational hypertension and 23,937 who were normotensive during their first pregnancy. Compared to normotensive women, women with preeclampsia had a higher mortality from ischaemic heart disease (adj. IRR 1.38, 95% CI 1.03, 1.84) and circulatory disease (adj. IRR 1.30, 95% CI 1.06, 1.60). Similar trends were seen with gestational hypertension. There was no difference in all cause mortality in the three groups. The odds of a hypertensive episode were higher in women with preeclampsia (adj. OR 1.79, 95% CI 1.55, 2.05) and gestational hypertension (adj. OR 1.68, 95% CI 1.55, 1.82) compared to normotensives. Compared to normotensives, women with gestational hypertension (adj. IRR 0.91, 95% CI 0.85, 0.96) or preeclampsia (adj. IRR 0.86, 95% CI 0.77, 0.97) had lower incidences of cancer. Women with pregnancy induced hypertension are at a higher risk of incidence and mortality from ischaemic heart disease and a lower risk of cancer.

The changing pattern of referral in acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is not only managed by nephrologists, but also by several other subspecialists. The referral rate to nephrologists and the factors influencing it are unknown. AIMS: To determine the referral rate, factors affecting referral and outcomes across the spectrum of AKI in a population based study. METHODS: We identified all patients with serum creatinine concentrations ≥150 µmol/l (male) or ≥130 µmol/l (female) over a 6-month period. AKI was defined according to the RIFLE classification (risk, injury, failure, loss, end stage renal disease [ESRD]). Clinical information and outcomes were obtained from each patient's case records. RESULTS: A total of 562 patients were identified as having AKI (incidence 2147 per million population/year [pmp/y]). One hundred and sixty-four patients (29%) were referred to nephrologists-referral rate 627 pmp/y. Forty-nine percent of patients whose serum creatinine rose to >300 µmol/l were referred compared with 22% in our previous study of 1997. Forty-eight patients required renal replacement therapy-incidence 184 pmp/y in comparison to 50 pmp/y in our previous study of 1997. Patients had higher odds of referral if they were male, of younger age and were in the F category of the RIFLE classification. Patients had lower odds of referral if they had multiple co-morbid conditions or if they were managed in a hospital without a nephrology service. CONCLUSION: There has been a significant rise in the referral rate of patients with AKI to nephrologists but even during our period of study only one-third of such patients were being referred. With rising incidence and increased awareness, the referral rate will certainly rise putting a significant burden on the nephrology services.

Recurrence risk of stillbirth in a second pregnancy.

OBJECTIVE: To examine the risk of recurrence of stillbirth in a second pregnancy. DESIGN: Retrospective cohort study. SETTING: Scotland, UK. POPULATION: All women who delivered their first and second pregnancies in Scotland between 1981 and 2005. METHODS: All women delivering for the first time between 1981 and 2000 were linked to records of their second pregnancy using routinely collected data from the Scottish Morbidity Returns. Women who had an intrauterine death in their first pregnancy formed the exposed cohort, whereas those who had a live birth formed the unexposed cohort. MAIN OUTCOME MEASURE: Stillbirth in a second pregnancy. RESULTS: After adjusting for confounding factors, the odds of recurrence of stillbirth in a second pregnancy were found to be 1.94 (99% CI 1.29-2.92) compared with women who had had a live birth in their first pregnancy. Other factors associated with recurrence of stillbirth in a second pregnancy included placental abruption (adjusted OR 1.96; 99% CI 1.60-2.41), preterm delivery (adjusted OR 7.45; 99% CI 5.91-9.39) and low birthweight (adjusted OR 6.69; 99% CI 5.31-8.42). A Bayesian analysis using minimally informative normal priors found the risk of recurrence of stillbirth in a second pregnancy to be 1.59 (99% CI 1.10-2.33). CONCLUSIONS: Women who have stillbirth in their first pregnancy have a higher risk of recurrence in their next pregnancy.

The risk factors for unexplained antepartum stillbirths in Scotland, 1994 to 2003.

OBJECTIVE: To determine the factors contributing to unexplained antepartum stillbirth in Scotland. STUDY DESIGN: A 10-year birth database in Scotland was used to compare the unexplained antepartum stillbirth with other birth outcomes. The sample unit was a pregnant mother with a gestational age of 20 weeks and above and with a fetal birth weight of 200 g and above. RESULT: Maternal age of 35 years and above, lower deprivation category, inaccessible area of residence, maternal smoking, maternal height of <160 cm and gestational age of above 39 weeks were significantly associated with unexplained antepartum stillbirth. In multivariable analysis only maternal age (adjusted odds ratio (OR): 1.8, confidence interval (CI): 1.1 to 3.0, P=0.02), smoking during pregnancy (adjusted OR: 2.0, CI: 1.1 to 3.5, P=0.02), and maternal height (adjusted OR: 1.4, CI: 1.1 to 1.8, P=0.01), remain significant. Screening of pregnancies based on these three risk factors had 4.2% sensitivity and 99.4% specificity. The prevalence of stillbirth for this population was 0.2%. A positive predictive value of only 1.2% implies that only 1 in 83 women with these three risk factors will have antepartum stillbirth. The remaining 82 will suffer needless anxiety and potentially diagnostic procedures. CONCLUSION: Advanced maternal age, maternal smoking, and shorter maternal height were associated risk for unexplained antepartum stillbirth but screening based on these factors would be of limited value.

Costs and consequences of automated algorithms versus manual grading for the detection of referable diabetic retinopathy.

AIMS: To assess the cost-effectiveness of an improved automated grading algorithm for diabetic retinopathy against a previously described algorithm, and in comparison with manual grading. METHODS: Efficacy of the alternative algorithms was assessed using a reference graded set of images from three screening centres in Scotland (1253 cases with observable/referable retinopathy and 6333 individuals with mild or no retinopathy). Screening outcomes and grading and diagnosis costs were modelled for a cohort of 180 000 people, with prevalence of referable retinopathy at 4%. Algorithm (b), which combines image quality assessment with detection algorithms for microaneurysms (MA), blot haemorrhages and exudates, was compared with a simpler algorithm (a) (using image quality assessment and MA/dot haemorrhage (DH) detection), and the current practice of manual grading. RESULTS: Compared with algorithm (a), algorithm (b) would identify an additional 113 cases of referable retinopathy for an incremental cost of pound 68 per additional case. Compared with manual grading, automated grading would be expected to identify between 54 and 123 fewer referable cases, for a grading cost saving between pound 3834 and pound 1727 per case missed. Extrapolation modelling over a 20-year time horizon suggests manual grading would cost between pound 25,676 and pound 267,115 per additional quality adjusted life year gained. CONCLUSIONS: Algorithm (b) is more cost-effective than the algorithm based on quality assessment and MA/DH detection. With respect to the value of introducing automated detection systems into screening programmes, automated grading operates within the recommended national standards in Scotland and is likely to be considered a cost-effective alternative to manual disease/no disease grading.

N-terminal pro-B-type natriuretic peptide levels and early outcome after cardiac surgery: a prospective cohort study.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a powerful predictor of cardiovascular outcome in many circumstances. There are, however, limited data regarding the utility of NT-proBNP or BNP levels in patients undergoing cardiac surgery. The current study assesses the ability of NT-proBNP to predict early outcome in this setting. METHODS: One thousand and ten patients undergoing non-emergent cardiac surgery were recruited prospectively. Baseline clinical details were obtained and the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Parsonnet score were calculated. Preoperative NT-proBNP levels were measured using the Roche Elecsys assay. The primary endpoint was 30 day mortality. RESULTS: Median NT-proBNP levels were 624 ng litre(-1) among patients who died within 30 days of surgery (n=29), compared with 279 ng litre(-1) in survivors [odds ratio (OR) 1.03 per 250 ng litre(-1), 95% confidence interval 1.01-1.05, P=0.001). NT-proBNP levels remained predictors of 30 day mortality in models including either the additive EuroSCORE (OR 1.03 per 250 ng litre(-1), P=0.01), the logistic EuroSCORE (OR 1.03 per 250 ng litre(-1), P=0.004), or the Parsonnet score (OR 1.02 per 250 ng litre(-1), P=0.04). Levels of NT-proBNP were also predictors of prolonged (>1 day) stay in the intensive care unit (OR 1.03 per 250 ng litre(-1), P<0.001) and of a hospital stay >1 week (OR 1.07 per 250 ng litre(-1), P<0.001). They remained predictive of these outcomes in regression models that included either the EuroSCORE or the Parsonnet score and in a model that included all study variables. CONCLUSIONS: NT-proBNP levels predict early outcome after cardiac surgery. Their prognostic utility is modest-but is independent of traditional indicators and conventional risk prediction scores.

Cost-effectiveness of implementing automated grading within the national screening programme for diabetic retinopathy in Scotland.

AIMS: National screening programmes for diabetic retinopathy using digital photography and multi-level manual grading systems are currently being implemented in the UK. Here, we assess the cost-effectiveness of replacing first level manual grading in the National Screening Programme in Scotland with an automated system developed to assess image quality and detect the presence of any retinopathy. METHODS: A decision tree model was developed and populated using sensitivity/specificity and cost data based on a study of 6722 patients in the Grampian region. Costs to the NHS, and the number of appropriate screening outcomes and true referable cases detected in 1 year were assessed. RESULTS: For the diabetic population of Scotland (approximately 160,000), with prevalence of referable retinopathy at 4% (6400 true cases), the automated strategy would be expected to identify 5560 cases (86.9%) and the manual strategy 5610 cases (87.7%). However, the automated system led to savings in grading and quality assurance costs to the NHS of 201,600 pounds per year. The additional cost per additional referable case detected (manual vs automated) totalled 4088 pounds and the additional cost per additional appropriate screening outcome (manual vs automated) was 1990 pounds. CONCLUSIONS: Given that automated grading is less costly and of similar effectiveness, it is likely to be considered a cost-effective alternative to manual grading.

The efficacy of automated "disease/no disease" grading for diabetic retinopathy in a systematic screening programme.

AIM: To assess the efficacy of automated "disease/no disease" grading for diabetic retinopathy within a systematic screening programme. METHODS: Anonymised images were obtained from consecutive patients attending a regional primary care based diabetic retinopathy screening programme. A training set of 1067 images was used to develop automated grading algorithms. The final software was tested using a separate set of 14 406 images from 6722 patients. The sensitivity and specificity of manual and automated systems operating as "disease/no disease" graders (detecting poor quality images and any diabetic retinopathy) were determined relative to a clinical reference standard. RESULTS: The reference standard classified 8.2% of the patients as having ungradeable images (technical failures) and 62.5% as having no retinopathy. Detection of technical failures or any retinopathy was achieved by manual grading with 86.5% sensitivity (95% confidence interval 85.1 to 87.8) and 95.3% specificity (94.6 to 95.9) and by automated grading with 90.5% sensitivity (89.3 to 91.6) and 67.4% specificity (66.0 to 68.8). Manual and automated grading detected 99.1% and 97.9%, respectively, of patients with referable or observable retinopathy/maculopathy. Manual and automated grading detected 95.7% and 99.8%, respectively, of technical failures. CONCLUSION: Automated "disease/no disease" grading of diabetic retinopathy could safely reduce the burden of grading in diabetic retinopathy screening programmes.

Gene-environment interactions in parkinsonism and Parkinson's disease: the Geoparkinson study.

OBJECTIVES: To investigate associations of Parkinson's disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk. METHODS: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders. RESULTS: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only). CONCLUSIONS: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.

Environmental risk factors for Parkinson's disease and parkinsonism: the Geoparkinson study.

OBJECTIVE: To investigate the associations between Parkinson's disease and other degenerative parkinsonian syndromes and environmental factors in five European countries. METHODS: A case-control study of 959 prevalent cases of parkinsonism (767 with Parkinson's disease) and 1989 controls in Scotland, Italy, Sweden, Romania and Malta was carried out. Cases were defined using the United Kingdom Parkinson's Disease Society Brain Bank criteria, and those with drug-induced or vascular parkinsonism or dementia were excluded. Subjects completed an interviewer-administered questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper and manganese. Lifetime and average annual exposures were estimated blind to disease status using a job-exposure matrix modified by subjective exposure modelling. Results were analysed using multiple logistic regression, adjusting for age, sex, country, tobacco use, ever knocked unconscious and family history of Parkinson's disease. RESULTS: Adjusted logistic regression analyses showed significantly increased odds ratios for Parkinson's disease/parkinsonism with an exposure-response relationship for pesticides (low vs no exposure, odds ratio (OR) = 1.13, 95% CI 0.82 to 1.57, high vs no exposure, OR = 1.41, 95% CI 1.06 to 1.88) and ever knocked unconscious (once vs never, OR = 1.35, 95% CI 1.09 to 1.68, more than once vs never, OR = 2.53, 95% CI 1.78 to 3.59). Hypnotic, anxiolytic or antidepressant drug use for more than 1 year and a family history of Parkinson's disease showed significantly increased odds ratios. Tobacco use was protective (OR = 0.50, 95% CI 0.42 to 0.60). Analyses confined to subjects with Parkinson's disease gave similar results. CONCLUSIONS: The association of pesticide exposure with Parkinson's disease suggests a causative role. Repeated traumatic loss of consciousness is associated with increased risk.

A Bayesian approach to prospective binary outcome studies with misclassification in a binary risk factor.

Misclassification in a binary exposure variable within an unmatched prospective study may lead to a biased estimate of the disease-exposure relationship. It usually gives falsely small credible intervals because uncertainty in the recorded exposure is not taken into account. When there are several other perfectly measured covariates, interrelationships may introduce further potential for bias. Bayesian methods are proposed for analysing binary outcome studies in which an exposure variable is sometimes misclassified, but its correct values have been validated for a random subsample of the subjects. This Bayesian approach can model relationships between explanatory variables and between exploratory variables and the probabilities of misclassification. Three logistic regressions are used to relate disease to true exposure, misclassified exposure to true exposure and true exposure to other covariates. Credible intervals may be used to make decisions about whether certain parameters are unnecessary and hence whether the model can be reduced in complexity. In the disease-exposure model, for parameters representing coefficients related to perfectly measured covariates, the precision of posterior estimates is only slightly lower than would be found from data with no misclassification. For the risk factor which has misclassification, the estimates of model coefficients obtained are much less biased than those with misclassification ignored.

Hospitalization in the first year of renal replacement therapy for end-stage renal disease.

BACKGROUND: The requirement for hospitalization of patients on dialysis is likely to be a surrogate marker of age and comorbid diseases. It may also reflect the level of care delivered, and substantially increases the cost of this expensive therapy. AIM: To identify the factors most strongly associated with hospitalization. DESIGN: Prospective population study. METHODS: Data were recorded for all patients starting RRT in Scotland over one year, including the reasons for and duration of, each hospital admission during the first year of RRT. Factors most strongly associated with hospitalization were determined by Poisson regression analysis. RESULTS: Overall, 526 patients were admitted to hospital on 1668 occasions (median 3, IQR 1-4) for 13384 days (median 13, IQR 4-35). Formation of vascular access for haemodialysis (HD) was the most frequent reason for admission, followed by infections. Age, comorbidity, mode of presentation for RRT and primary renal diagnosis were all significantly associated with prolonged hospitalization. Attainment of UK Renal Association standards for urea reduction ratio and serum albumin concentration, and vascular access in the form of arterio-venous fistulae were associated with less hospitalization in patients treated with HD by 90 days. DISCUSSION: Patients in their first year of RRT have a high requirement for in-patient care, 8.6% of patient treatment days being spent in hospital. Vascular access formation, failure and complications account for a large proportion of this. Age and comorbidity prolong the time spent in hospital. As the RRT population continues to increase, with older patients and those with greater comorbidity, in-patient facilities must also expand.

A cohort study of reproductive risk factors, weight and weight change and the development of diabetes mellitus.

AIMS: Reproductive factors (parity, miscarriages, terminations), oral contraceptive use, hormone replacement therapy, body weight at first pregnancy and weight gain following pregnancy may be associated with a long-term risk of diabetes. The aim of this study is to investigate the independent risks of reproductive factors and body weight for diabetes in later life. METHODS: This is a retrospective cohort study of 1257 parous women who had a first pregnancy between 1951 and 1970. Reproductive history, weight and height were measured at the time of first pregnancy, then assessed by questionnaire in 1997 for all women. A clinical examination and an analysis of blood samples were undertaken for 992 women. The main outcome was incidence of diabetes based on medical history, medication and random glucose measurement. RESULTS: Sixty of the 1257 (4.8%) women developed diabetes. Body mass index at index pregnancy and after 28-48 years follow-up were both significantly associated with risk of diabetes, this increased with greater weight gain. There was a non-significant increased risk of diabetes associated with stillbirths and miscarriages after age and BMI adjustment. CONCLUSIONS: In parous women, higher BMI at index pregnancy, weight gain during follow-up and BMI in later life strongly predict diabetes risk.

Acute renal failure requiring renal replacement therapy: incidence and outcome.

BACKGROUND: Renal replacement therapy (RRT) for acute renal failure (ARF) may be provided in many settings within the hospital. Such patients require a high level of care and often have a poor prognosis. No prospective studies have accurately defined this population, making the prediction of necessary resources and the planning of services difficult. AIM: To ascertain the incidence, causes and outcomes of acute renal failure requiring renal replacement therapy in Scotland. DESIGN: A prospective observational census of all clinical areas providing renal replacement therapy in three Scottish health boards (Grampian, Highland, Tayside). METHODS: Patients were identified by liaison with each unit providing RRT. Factors precipitating renal failure and reasons for RRT were recorded at the time of initiation. Comorbid disease burden was scored using the Charlson index. Patient status at 90 days was assessed from case-notes, contacting general practitioners where necessary. RESULTS: 375 patients per million population per year received RRT; 203 per million per year for either ARF or acute-on-chronic renal failure. 73.5% of patients receiving RRT for ARF died within 90 days, 23.5% became independent of RRT. The median duration of hospital admission was 19 days. DISCUSSION: The annual incidence of ARF requiring RRT is just over 200 per million population, almost twice that of end-stage renal disease requiring RRT. Such treatment places high demands upon health care resources.

Coincidence of immune-mediated diseases driven by Th1 and Th2 subsets suggests a common aetiology. A population-based study using computerized general practice data.

BACKGROUND: The recent rise in the prevalence of immune-mediated diseases has been attributed to environmental factors such as a lack of microbial challenge, or dietary change, that deviate the overall balance between mutually antagonistic subsets of T helper (Th) cells. OBJECTIVE: An alternative proposal is that recent environmental changes have resulted in an immune system that is more likely to produce both Th1 and Th2 responses against benign antigens. The prediction of this hypothesis, that Th1 and Th2-mediated diseases are not mutually exclusive, and may be positively associated, is tested here in a whole population. METHODS: Data from General Practices participating in the Scottish Continuous Morbidity Recording (CMR) project were used to determine the coincidence of the major Th2-mediated atopic diseases; asthma, eczema and allergic rhinitis, with the Th1-mediated autoimmune conditions; type I diabetes, rheumatoid arthritis and psoriasis. We also identified the prescription rates of inhaled therapy for asthma in patients with Th1-mediated disease. RESULTS: There was a significant increase in the risk of presenting with a Th1-mediated autoimmune condition in patients with a history of allergic disease (standardized prevalence ratio (95% confidence interval) 1.28 (1.18-1.37)). Likewise, the standardized prevalence ratios of presenting with either eczema (1.67 (1.48-1.87)) or allergic rhinitis (1.22 (1.02-1.44)) were significantly increased in subjects with a history of Th1-mediated disease. There was a particularly strong association between current psoriasis and current eczema (standardized prevalence ratio ofpsoriasis in subjects with eczema 2.88, 95% confidence interval (CI) 2.38-3.45). There was also a significant increase in prescriptions for inhaled asthma therapy in patients with Th1 disease. CONCLUSION: It is concluded that Th1- and Th2-mediated diseases are significantly associated in a large General Practice population. This finding supports the proposal that autoimmune and atopic diseases share risk factors that increase the propensity of the immune system to generate both Th1- and Th2-mediated inappropriate responses to non-pathological antigens.

Asthma admissions and thunderstorms: a study of pollen, fungal spores, rainfall, and ozone.

Asthma admissions have been reported to increase during thunderstorms. In some cases, this has been attributed to rises in pollen or fungal spore counts occurring alone or in combination with rainfall. We tested the hypothesis that thunderstorms in general are associated with asthma admissions, and investigated the possible roles of pollen, fungal spores, ozone, and other meteorological factors. We obtained data on multiple pollen and fungal spore counts, rainfall, temperature, ambient ozone concentrations, and asthma admissions for 32 dates when lightning strikes were recorded in the Cardiff/Newport area, and 64 matched dates in previous and subsequent years. Poisson regression models were used to investigate associations between admissions and proposed causative environmental factors. The number of asthma admissions was greater on days with thunderstorms than on control days (p<0.001). There were no associations or interactions between admissions and any pollen or fungal spore counts or rainfall. After adjusting for thunderstorms, there was an independent association between increasing ozone concentration, when temperature was included in the model, and increasing admissions (p=0.02). Asthma admissions are increased during thunderstorms. The effect is more marked in warmer weather, and is not explained by increases in grass pollen, total pollen or fungal spore counts, nor by an interaction between these and rainfall. There was an independent, positive association between ozone concentrations and asthma admissions.

Continuing medical education by anaesthetists in scotland: activities, motivation and barriers.

A postal questionnaire survey was carried out to determine the activities, motivation and barriers to continuing medical education amongst career grade anaesthetists in Scotland. Four hundred and ten consultants and 49 non-consultant career grade anaesthetists were surveyed with a response rate of 84.5%. All respondents had taken part in some educational activities in the past two years. Over 80% had attended 10 or more departmental meetings and over 90% had attended meetings of a Regional society or National meetings. Less than 50% had attended for clinical experience with a colleague and only 20% had done so in another centre. There were trends of changing educational activity with increasing age. The most common motivation was to keep up to date for current clinical duties with keeping up to date for teaching second, but younger consultants were more likely to undertake continuing medical education activities in case their clinical duties changed. Perceived barriers to continuing medical education were similar for internal and external activities but funding was less of a limitation for those working in district general hospitals. There is scope for encouraging activities such as clinical experience with a colleague and a need to explore in greater detail the perception of barriers to continuing medical education and their influence on participation.