Keele Wurst

First trimester paroxetine use and the prevalence of congenital, specifically cardiac, defects: A meta‐analysis of epidemiological studies

BACKGROUND Several studies have evaluated maternal first trimester paroxetine use and the prevalence of congenital defects, particularly cardiac defects. To synthesize current epidemiologic information, a meta-analysis was conducted. METHODS A systematic literature search was conducted for original research published from January 1, 1992, through September 30, 2008. Results were extracted using predefined criteria, and authors were contacted for additional information when necessary. Compiled results were evaluated for funnel plot asymmetry, heterogeneity, and study characteristic associations. Where appropriate, fixed-effect summary estimates were calculated and sensitivity analyses performed. RESULTS Twenty reports (11 including results for aggregated congenital and combined cardiac defects, six for aggregated congenital defects only, and three for combined cardiac defects only) met prespecified inclusion criteria. There was little evidence of funnel plot asymmetry or overall heterogeneity. Summary estimates were produced for combined cardiac defects (prevalence odds ratio [POR], 1.46; 95% confidence interval [CI], 1.17-1.82) and aggregated congenital defects (POR, 1.24; 95% CI, 1.08-1.43) and first trimester paroxetine use. Some study characteristics may be associated with differential POR estimates for paroxetine and either combined cardiac or aggregated congenital defects. CONCLUSIONS This meta-analysis found little evidence of publication bias or overall statistical heterogeneity and only weak evidence of associations with some study characteristics. Although subject to limitations, the summary estimate indicates an increased prevalence of combined cardiac defects with first trimester paroxetine use. The summary estimate also indicates an increased prevalence of aggregated congenital defects with paroxetine; however, this association may be explained, in part, by the increased prevalence of combined cardiac defects.

Understanding asthma-chronic obstructive pulmonary disease overlap syndrome.

Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is a loosely-defined clinical entity referring to patients who exhibit characteristics of both asthma and chronic obstructive pulmonary disease (COPD). Clinical definitions and classifications for ACOS vary widely, which impacts our understanding of prevalence, diagnosis and treatment of the condition. This literature review was therefore conducted to characterize the prevalence of ACOS and the effect of different disease definitions on these estimates, as this has not previously been explored. From an analysis of English language literature published from 2000 to 2014, the estimated prevalence of ACOS ranges from 12.1% to 55.2% among patients with COPD and 13.3%-61.0% among patients with asthma alone. This variability is linked to differences in COPD and asthma diagnostic criteria, disease ascertainment methods (spirometry-based versus clinical or symptom-based diagnoses and claims data), and population characteristics including age, gender and smoking. Understanding the reasons for differences in prevalence estimates of ACOS across the literature may help guide decision making on the most appropriate criteria for defining ACOS and aid investigators in designing future ACOS clinical studies aimed at effective treatment.

Treatment Evolution after COPD Diagnosis in the UK Primary Care Setting

Rationale To assess the treatment progression during the 24 months following a formal diagnosis of chronic obstructive pulmonary disease (COPD) in the UK primary care setting. Methods A retrospective cohort of newly diagnosed COPD patients was identified in the Clinical Practice Research Datalink (CPRD) from 1/1/2008 until 31/12/2009. Maintenance therapy prescribed within the first 3 months of diagnosis and in the subsequent 3-month intervals for 24 months were analyzed. Treatment classes included long-acting β2-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), inhaled corticosteroids (ICSs), and respective combinations. At each 3-month interval, discontinuation, switching, addition, and stepping down patterns were analyzed cumulatively for the first 12 months and over the 24-month of follow-up. Results A total of 3199 patients with at least one prescription of a maintenance therapy at baseline and during 4th-6th month interval were included in the analysis. At diagnosis (0–3 months), the most frequently prescribed maintenance therapy was LABA+ICS (43%), followed by LAMA (24%) and LABA+LAMA+ICS (23%). Nearly half the patients (LABA-50%, LAMA-43%) starting on a monobronchodilator had additions to their treatment in 24 months. Compared to other medications, patients starting on a LAMA were most likely to escalate to triple therapy in 24 months. Nearly one-fourth of the patients prescribed triple therapy at baseline stepped down to LABA+ICS (25%) or LAMA (31%) within 24 months. Conclusion Disease progression is evident over the 24 months after COPD diagnosis, as more patients were prescribed additional maintenance therapy in the 24-month period compared to baseline. The changes in therapy suggest that it is difficult to achieve a consistently improved COPD disease state.

Respiratory Pharmacotherapy Use in Patients Newly Diagnosed with Chronic Obstructive Pulmonary Disease in a Primary Care Setting in the UK: A Retrospective Cohort Study

Abstract This retrospective cohort study aimed to analyze the prescribing practices of general practitioners treating patients with newly diagnosed chronic obstructive pulmonary disease (COPD), and to assess characteristics associated with initial pharmacotherapy. Patients were identified in the General Practice Research Database, a population-based UK electronic medical record (EMR) with data from January 1, 2008 to December 31, 2009. Patient characteristics, prescribed COPD pharmacotherapies (≤12 months before diagnosis and within 3 months following diagnosis), co-morbidities, hospitalizations, and events indicative of a possible COPD exacerbation (≤12 months before diagnosis) were analyzed in 7881 patients with newly diagnosed COPD. Most patients (64.4%) were prescribed COPD pharmacotherapy in the 12 months before diagnosis. Following diagnosis, COPD pharmacotherapy was prescribed within 3 months in 85.0% of patients. Short-acting bronchodilators alone (22.9%) or inhaled corticosteroids + long-acting beta-2 agonists (ICS+LABA, 22.1%) were prescribed most frequently. Compared with other pharmacotherapies, the prevalence of severe airflow limitation was highest in patients prescribed ICS+LABA+long-acting muscarinic antagonists (LAMA). Moderate-to-severe dyspnea was identified most frequently in patients prescribed a LAMA-containing regimen. Patients prescribed an ICS-containing regimen had a higher prevalence of asthma or possible exacerbations recorded in the EMR than those not prescribed ICS. In conclusion, pharmacotherapy prescribed at initial COPD diagnosis varied by disease severity indicators as assessed by airflow limitation, dyspnea, history of asthma, and possible exacerbations. Frequent prescription of COPD pharmacotherapies before the first-recorded COPD diagnosis indicates a delay between obstructive lung disease presentation in primary care practice and assignment of a medical diagnosis.

A comparison of COPD patients with and without ACOS in the ECLIPSE study

There is growing interest in asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) [1, 2]. Yet, there is no consensus on the best definition of ACOS [1, 2] and, therefore, it is difficult to appropriately characterise these patients. Here, we compare the main clinical characteristics and outcomes of COPD patients with and without ACOS in the ECLIPSE cohort [3] according to six different definitions of ACOS. ECLIPSE offers an opportunity to examine ACOS in a large well-characterised COPD cohort followed over 3 years http://ow.ly/Zcycr

Bupropion therapy in pregnancy and the occurrence of cardiovascular malformations in infants

Bupropion is an aminoketone marketed as an oral antidepressant and non-nicotine smoking cessation aid.1,2 It is listed by the United States Food and Drug Administration as a pregnancy category C medication. A retrospective cohort study of maternal first trimester bupropion use and the occurrence of congenital malformations in infants previously published by Cole et al. (2007)3 showed that the prevalence of all congenital and all cardiovascular malformations among infants born to women exposed to first trimester bupropion therapy, regardless of concurrent exposure to other antidepressants, was comparable with infants born to women exposed to all other antidepressants in the first trimester or to bupropion outside of the first trimester. A subsequent article by Alwan et al. (2010)4 described the association between maternal bupropion treatment in early pregnancy and congenital heart defects in infants from National Birth Defects Prevention Study (NBDPS) data. They reported an approximately two and a half-fold increase in left ventricular outflow tract obstruction (LVOTO) defects with bupropion use in early pregnancy (crude odds ratio [OR]: 2.2, 95% confidence interval [CI]: 1.0–4.8; adjusted OR: 2.6, 95% CI: 1.2–5.7). Alwan et al. (2010)4 also calculated a crude risk ratio (RR) using the Cole et al. (2007)3 published data and found an approximately threefold increase in LVOTO with first trimester bupropion exposure compared with other antidepressant use (RR: 3.2; 95% CI: 1.0–10.6).4 Given the findings of Alwan et al. (2010)4 using both NBDPS and the published Cole et al. (2007)3 data, we refined the original analysis of the Cole et al. (2007)3 data to examine specific cardiovascular malformations, in particular LVOTO. To validate the findings of Alwan et al. (2010)4 using the Cole et al. (2007)3 data, we refined the exposure categories to include monotherapy cohorts and clinically categorized the specific cardiovascular malformations using the same system employed by Alwan et al. (2010)4 and described in detail by Botto et al. (2007).5 This classification system, based on developmental and epidemiologic considerations, is designed to facilitate the assessment of isolated cardiac defects. We utilized the same study population identified from an administrative claims database for the Cole et al. (2007)3 study of bupropion use during pregnancy, which consisted of women aged 12–49 years at the time of delivery with at least one dispensing of bupropion or another antidepressant from pharmacy claims between 1 January 1995 and 30 September 2004. Methods for dataset development are described in detail elsewhere.3 The three following exposure cohorts originally created in Cole et al. (2007)3 included: maternal first trimester exposure to bupropion, regardless of other antidepressant exposure (‘bupropion first trimester monotherapy or polytherapy’), maternal first trimester exposure to antidepressants other than bupropion (‘other antidepressants first trimester monotherapy or polytherapy’), and maternal exposure to bupropion outside the first trimester, regardless of other antidepressant exposure (‘bupropion outside first trimester monotherapy or polytherapy’). For the current analysis, the following monotherapy cohorts were also subsetted from the original cohorts: maternal first trimester exposure to only bupropion (‘bupropion first trimester monotherapy’), maternal first trimester exposure to only one type of antidepressant other than bupropion, (‘other antidepressants first trimester monotherapy’), and maternal exposure to only bupropion outside the first trimester (‘bupropion outside first trimester monotherapy’). For this analysis, a pediatric cardiologist reviewed previously abstracted medical records from Cole et al. (2007)3 for specific cardiovascular malformations. The malformations were classified using the same categorizations used in Alwan et al. (2010)4 and described in detail by Botto et al. (2007).5 To

Resource Use and Costs up to Two Years Post Diagnosis Among Newly Diagnosed COPD Patients in the UK Primary Care Setting: A Retrospective Cohort Study

Abstract The objective of this study was to estimate the annual resource use and costs before and after COPD diagnosis and compare it across stages of airflow obstruction and levels of dyspnoea in the UK primary care setting. A retrospective cohort of newly diagnosed COPD patients (1/1/2008-31/12/2009) was identified in the UK Clinical Practice Research Datalink (CPRD). Resource use did not include medication costs and comprised of exacerbations, all cause GP interactions, and non-COPD hospitalisations, which were estimated for up to 12 months before and 24 months after COPD diagnosis. It was further stratified using baseline characteristics, Medical Research Council (MRC) dyspnoea score, and stages of airflow limitation. COPD costs were estimated using NHS reference costs. The analysis included 7881 newly diagnosed COPD patients (mean age, 67.2 years; 45% females). In the 2 years follow-up, the cohort experienced moderate and severe exacerbations, non-COPD hospitalisations, and GP surgery visits at an annual rate of 0.51, 0.13, 0.47, and 12.85, respectively. All resource components showed an upward trend with increase airflow limitation and dyspnoea. GP interactions accounted for 58.5% of annual per patient COPD management costs, estimated to be £2047 during the observation period. The annual costs doubled from patients with low levels of dyspnoea (MRC = 1; £1473) to those with high levels of dyspnoea (MRC = 5; £3243). COPD management costs in the primary care setting continued to remain high up to 2 years following initial diagnosis. The cost burden increased with high levels of dyspnoea and airflow obstruction, suggesting that both measures can identify patients requiring increased monitoring.

Asthma and Chronic Obstructive Pulmonary Disease Overlap: The Effect of Definitions on Measures of Burden

Background: Although the overlap between asthma and COPD has been recognized for years this overlap has only recently been given a name, asthma-COPD overlap syndrome (ACOS), and better defined. Different definitions of the component diseases can affect prevalence and outcome measures of ACOS. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) from 2007-2012 to determine the population estimates of ACOS in U.S. adults using 2 different definitions of ACOS (ACOS1= self-reported COPD and current asthma; ACOS2 = spirometric-confirmed COPD [pre-bronchodilator FEV1/FVC < 70%] and current asthma) and to describe variation in other factors, such as lung function impairment and health care utilization, by ACOS definitions. Results: Among U.S. adults aged 20 and older, 1.6% had ACOS1, and 1.9% had ACOS2. Both case definitions were similar with regard to symptoms and impairment of lung function. ACOS1 individuals were more likely to have one or more overnight hospital stays relative to those with neither asthma nor COPD, (odds ratio [OR] 3.4, 95% confidence interval [CI] 2.5, 4.6) than ACOS2 (OR 1.6, 95% CI 0.9, 2.9). Conclusions: Different definitions of ACOS in population-based studies affect both estimates of disease prevalence and outcomes related to the disease. These definitions need to be carefully considered in the design of epidemiologic studies and clinical trials.

Chronic airway obstruction in a population-based adult asthma cohort: Prevalence, incidence and prognostic factors

BACKGROUND Asthma and COPD may overlap (ACO) but information about incidence and risk factors are lacking. This study aimed to estimate prevalence, incidence and risk factors of chronic airway obstruction (CAO) in a population-based adult asthma cohort. METHODS During 1986-2001 a large population-based asthma cohort was identified (n = 2055, 19-72y). Subsamples have participated in clinical follow-ups during the subsequent years. The entire cohort was invited to a clinical follow-up including interview, spirometry, and blood sampling in 2012-2014 when n = 983 subjects performed adequate spirometry. CAO was defined as post-bronchodilator FEV1/FVC<0.7. RESULTS At study entry, asthmatics with prevalent CAO (11.4%) reported more respiratory symptoms, asthma medication use, and ischemic heart disease than asthmatics without CAO (asthma only). Subjects who developed CAO during follow-up (17.6%; incidence rate of 16/1000/year) had a more rapid FEV1 decline and higher levels of neutrophils than asthma only. Smoking, older age and male sex were independently associated with increased risk for both prevalent and incident CAO, while obesity had a protective effect. CONCLUSIONS In this prospective adult asthma cohort, the majority did not develop CAO. Smoking, older age and male sex were risk factors for prevalent and incident CAO, similar to risk factors described for COPD in the general population.