Christopher J. P. Smith

Inhaled corticosteroid use and bone-mineral density in patients with asthma

BACKGROUNDnInhaled corticosteroids are absorbed into the systemic circulation, but the extent to which they have adverse effects on bone is uncertain. The question is important since 3% of the European population take an inhaled corticosteroid regularly and may do so for many years.nnnMETHODSnWe studied the dose-response relation between cumulative inhaled corticosteroid dose and bone-mineral density at the lumbar spine and proximal femur in 196 adults (119 women) with asthma aged 20-40 years. Patients had taken an inhaled corticosteroid regularly for at least 6 months, and had had limited exposure to systemic steroids. Cumulative dose of inhaled corticosteroid was calculated from questionnaires and computerised and written general-practice records, and its effect on bone-mineral density was estimated by multiple regression analysis.nnnFINDINGSnMedian duration of inhaled corticosteroid treatment was 6 years (range 0.5-24), and median cumulative dose was 876 mg (87-4380). There was a negative association between cumulative dose of inhaled corticosteroid and bone-mineral density at the lumbar spine (L2-L4), femoral neck, Wards triangle, and trochanter, both before and after adjustment for the effects of age and sex. A doubling in dose of inhaled corticosteroid was associated with a decrease in bone-mineral density at the lumbar spine of 0.16 SD (95% CI 0.04-0.28). Similar decreases were found at the femoral neck, Wards triangle, and trochanter. Adjustment for potential confounding factors including physical activity and past oral, nasal, dermal, and parenteral corticosteroids did not weaken the associations.nnnINTERPRETATIONnThis study provides evidence of a negative relation between total cumulative dose of inhaled corticosteroid and bone-mineral density in patients with asthma.

Risk of community-acquired pneumonia and the use of statins, ace inhibitors and gastric acid suppressants: a population-based case-control study.

Previous studies have shown that treatment with gastric acid suppressants may be associated with an increased risk of pneumonia whilst the use of statins and ACE inhibitors (ACEI) may decrease the risk of acquiring pneumonia. The evidence is conflicting however. Our aim was to investigate the effect of these drugs on pneumonia using population‐based data from the UK.

Use of Self-controlled Analytical Techniques to Assess the Association Between Use of Prescription Medications and the Risk of Motor Vehicle Crashes

Case-crossover and case-series analyses are 2 epidemiologic approaches that can be used to evaluate the association of exposures with acute events. Using a primary care database from the United Kingdom and these 2 statistical approaches, the authors investigated the impact of using benzodiazepines, nonbenzodiazepine hypnotics, beta-blockers, selective serotonin reuptake inhibitors, tricyclic antidepressants, opioids, and antihistamines on the risk of motor vehicle crashes in 1986-2004. For 49,821 individuals aged 18-74 years, involvement in a motor vehicle crash was documented. The outcome of the case-crossover analyses varied according to the choice of control period, so the case-series approach was preferred. The first 4 weeks of treatment with a combined acetaminophen and opioid preparation was associated with an increased risk of motor vehicle crash (incidence rate ratio = 2.06, 99% confidence interval: 1.84, 2.32), as was use of an opioid alone (incidence rate ratio = 1.70, 99% confidence interval: 1.39, 2.08) and benzodiazepines (incidence rate ratio = 1.94, 99% confidence interval: 1.62, 2.32). Use of selective serotonin reuptake inhibitors, nonbenzodiazepine hypnotics, and antihistamines for more than 4 weeks was associated with motor vehicle crash, but shorter term use was not. The results obtained are broadly consistent with those from well-designed case-control studies and demonstrate how case-only techniques optimize the use of routinely collected data for epidemiologic studies.

Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a UK population-based study.

Background: Clinical advice to pregnant women with asthma is to maintain optimal therapeutic management; however, potential adverse effects of asthma treatments on fetal development remain uncertain. A study was undertaken to assess the association between maternal asthma and gestational exposure to asthma medications with risk of congenital malformation in offspring. Methods: A matched case-control study was performed using The Health Improvement Network primary care database. Children with malformations were matched to control children on birth year, general practice and singleton or twin delivery. Results: 5124 cases of liveborn children with major congenital malformations and 30u2009053 controls were included in the study. The risk of any malformation in children born to women with asthma was marginally higher than that in children born to women without asthma (adjusted OR 1.10, 95% CI 1.01 to 1.20). However, no association was present in children born to mothers receiving asthma treatment in the year before or during pregnancy (OR 1.06, 95% CI 0.94 to 1.20). In assessing teratogenicity of medications, no increased risk of malformation was found with gestational exposures to short- or long-acting β agonists, inhaled corticosteroids, oral corticosteroids, other bronchodilators or cromones. These findings were similar for each of 11 system-specific malformation groups, except for an increase in musculo-skeletal system malformation associated with cromone exposure. Conclusions: Gestational exposure to commonly used asthma medications was found to be safe overall, although a moderate teratogenic risk of cromones cannot be excluded. There was some evidence of a small increased risk of congenital malformation in children born to women with asthma, but this was not explained by gestational exposure to asthma drugs.

Oral and inhaled corticosteroids and adrenal insufficiency: a case-control study

Background: Adrenal insufficiency, a well recognised complication of treatment with oral corticosteroids, has been described in association with inhaled corticosteroid use in over 60 case reports. The risk of adrenal insufficiency in people prescribed an oral or inhaled corticosteroid in the general population is not known. A study was undertaken to quantify the association between adrenal insufficiency and oral and inhaled corticosteroid exposure. Methods: A case-control study was performed using computerised general practice data from The Health Improvement Network. Results: From a cohort of 2.4 million people, 154 cases of adrenal insufficiency and 870 controls were identified. There was a dose related increased risk of adrenal insufficiency in people prescribed an oral corticosteroid with an odds ratio of 2.0 (95% CI 1.6 to 2.5) per course of treatment per year. Adrenal insufficiency was associated with a prescription for an inhaled corticosteroid during the 90 day period before the diagnosis with an odds ratio of 3.4 (95% CI 1.9 to 5.9) and this effect was dose related (p for trend <0.001). After adjusting for oral corticosteroid exposure, this odds ratio was reduced to 1.6 (95% CI 0.8 to 3.2) although the dose relation remained (p for trend 0.036). Conclusion: People prescribed an oral or inhaled corticosteroid are at a dose related increased risk of adrenal insufficiency although the absolute risk is small. This analysis suggests that the increased risk in people prescribed an inhaled corticosteroid is largely due to oral corticosteroid exposure, but inhaled corticosteroids may have an effect when they are taken at higher doses.

The impact of statins, ACE inhibitors and gastric acid suppressants on pneumonia mortality in a UK general practice population cohort.

Pneumonia is a common diagnosis in general practice in the United Kingdom. Previous studies suggest that commonly prescribed drugs in general practice may influence pneumonia mortality.

Using socio-demographic and early clinical features in general practice to identify people with lung cancer earlier.

Introduction In the UK, most people with lung cancer are diagnosed at a late stage when curative treatment is not possible. To aid earlier detection, the socio-demographic and early clinical features predictive of lung cancer need to be identified. Methods We studied 12u2005074 cases of lung cancer and 120u2005731 controls in a large general practice database. Logistic regression analyses were used to identify the socio-demographic and clinical features associated with cancer up to 2u2005years before diagnosis. A risk prediction model was developed using variables that were independently associated with lung cancer up to 4u2005months before diagnosis. The model performance was assessed in an independent dataset of 1u2005826u2005293 patients from the same database. Discrimination was assessed by means of a receiver operating characteristic (ROC) curve. Results Clinical and socio-demographic features that were independently associated with lung cancer were patients’ age, sex, socioeconomic status and smoking history. From 4 to 12u2005months before diagnosis, the frequency of consultations and symptom records of cough, haemoptysis, dyspnoea, weight loss, lower respiratory tract infections, non-specific chest infections, chest pain, hoarseness, upper respiratory tract infections and chronic obstructive pulmonary disease were also independently predictive of lung cancer. On validation, the model performed well with an area under the ROC curve of 0.88. Conclusions This new model performed substantially better than the current National Institute for Health and Clinical Excellence referral guidelines and all comparable models. It has the potential to predict lung cancer cases sufficiently early to make detection at a curable stage more likely by allowing general practitioners to better risk stratify their patients. A clinical trial is needed to quantify the absolute benefits to patients and the cost effectiveness of this model in practice.

The distribution of lung cancer across sectors of society in the United Kingdom: a study using national primary care data.

BackgroundThere is pressing need to diagnose lung cancer earlier in the United Kingdom (UK) and it is likely that research using computerised general practice records will help this process. Linkage of these records to area-level geo-demographic classifications may also facilitate case ascertainment for public health programmes, however, there have as yet been no extensive studies of data validity for such purposes.MethodsTo first address the need for validation, we assessed the completeness and representativeness of lung cancer data from The Health Improvement Network (THIN) national primary care database by comparing incidence and survival between 2000 and 2009 with the UK National Cancer Registry and the National Lung Cancer Audit Database. Secondly, we explored the potential of a geo-demographic social marketing tool to facilitate disease ascertainment by using Experians Mosaic Public Sector ™ classification, to identify detailed profiles of the sectors of society where lung cancer incidence was highest.ResultsOverall incidence of lung cancer (41.4/100, 000 person-years, 95% confidence interval 40.6-42.1) and median survival (232 days) were similar to other national data; The incidence rate in THIN from 2003-2006 was found to be just over 93% of the national cancer registry rate. Incidence increased considerably with area-level deprivation measured by the Townsend Index and was highest in the North-West of England (65.1/100, 000 person-years). Wider variations in incidence were however identified using Mosaic classifications with the highest incidence in Mosaic Public Sector ™types Cared-for pensioners, Old people in flats and Dignified dependency (191.7, 174.2 and 117.1 per 100, 000 person-years respectively).ConclusionsRoutine electronic data in THIN are a valid source of lung cancer information. Mosaic ™ identified greater incidence differentials than standard area-level measures and as such could be used as a tool for public health programmes to ascertain future cases more effectively.

Pneumonia mortality in a UK general practice population cohort

BACKGROUNDnPneumonia is a common diagnosis in general practice in the United Kingdom and yet there is little known about the short- and long-term prognosis of people with a diagnosis of pneumonia in general practice. We investigated the short- and long-term survival of people with pneumonia diagnosed in general practice as compared to the general population for all ages.nnnMETHODSnThis was a general population-based cohort study. Data was obtained from a comprehensive general practice database called The Health Improvement Network (THIN) database which has computerized medical records from 300 general practice surgeries in the United Kingdom. We used Cox regression for our analyses.nnnRESULTSnFor pneumonia cases the 30-day mortality was 18.5% and the 3-year mortality was 30.8%. The equivalent figures for the general population controls were 0.4% and 10.3% respectively. The adjusted hazard ratio (HR) for all-cause mortality (for total follow-up time) in pneumonia cases vs. general population was 4.64 (95% CI 4.35-4.95). For the first 30 days the risk of mortality in cases was 46 times more (adj. HR 45.90, 95% CI 36.80-55.20). Even in the period of follow-up 91 days after diagnosis cases were almost 20% more likely to die compared to general population (adj. HR 1.19, 95% CI 1.08-1.31).nnnCONCLUSIONnPeople in general practice who have a diagnosis of pneumonia have a markedly increased mortality in the short-term but some increase in mortality persists during longer-term follow-up.

Study of lateral epicondylitis (tennis elbow) using the health improvement network database

Background Lateral epicondylitis has been studied mainly in work related and occupational groups, however little is known about the incidence or demographic associations in the general population. We have undertaken a large study using The Health Improvement Network (THIN) database to examine the epidemiology of lateral epicondylitis in the UK general population. Methods Diagnoses of lateral epicondylitis between 1987 and 2006 were used to calculate the incidence stratified by age, gender, deprivation score, UK health authority, and year. The age standardised rates for lateral epicondylitis in the UK were calculated with reference to the European Standard Population. Results The incidence rate of lateral epicondylitis was 2.45 per 1000 person-years. This was more common in males than females (males 2.63, females 2.55 per 1000 person-years, p < 0.001). After direct standardization, the age adjusted rates were 2.38 for males and 2.43 for females. The highest incidence rate of 7.35 per 1000 person-years was found in the age group 45-50 years. Regional distribution of the incidence rates showed a fairly even spread across 13 UK Health Authorities with the exception of London where incidence rates were significantly lower (1.75 per 1000 person-years, p < 0.001). Social deprivation was assessed using the Townsend score. The least deprived areas of the population had the highest incidence rates (2.86 per 1000 person years). Conclusions Our study represents the largest general population study of lateral epicondylitis reported to date. The results obtained provide the clinician with a better understanding of the epidemiology of lateral epicondylitis in the community.