Charles E. Wentworth

Comparative Safety of Long-Acting Inhaled Bronchodilators : A Cohort Study Using the UK THIN Primary Care Database

AbstractBackground: Use of a long-acting inhaled bronchodilator, either an anticholinergic or a β-adrenergic receptor agonist (β-agonist), is recommended for maintenance treatment of chronic obstructive pulmonary disease (COPD). In COPD, the organ system most frequently requiring medical care, other than the respiratory system, is the cardiac system. Objectives: To compare the risk of total mortality and certain respiratory and cardiac adverse events among users of the two types of recommended long-acting bronchodilators, we conducted a cohort study. Specifically, the study compared the safety of the only approved long-acting anticholinergic, tiotropium bromide, with the single-ingredient long-acting β-agonists (LABAs) salmeterol or formoterol in a broad population of users. Methods: We used automated general practitioner data from the UK THIN (The Health Information Network) database as the data source for this study. We used Cox proportional hazards models to compute hazard ratio (HR) estimates and 95% CI controlling for propensity scores comprising various baseline demographic variables, medical therapies and illnesses. Results: The 1061 tiotropium users and 1801 LABA users were similar with regard to risk of total mortality (HR 0.93; 95% CI 0.59, 1.44) and most cardiac events, including angina (HR 0.77; 95% CI 0.37, 1.59), atrial fibrillation or flutter (HR 0.60; 95% CI 0.25, 1.42), myocardial infarction (HR 1.29; 95% CI 0.45, 3.66) and tachycardia (HR 0.66; 95% CI 0.29, 1.51). Though imprecise, there was evidence of a decreased risk of heart failure (HR 0.65; 95% CI 0.37, 1.12) in tiotropium users. As regards respiratory endpoints, the risk of COPD exacerbation (HR 1.15; 95% CI 0.79, 1.67) and pneumonia (HR 1.11; 95% CI 0.38, 3.26) were similar among users of each type of drug, although there was a decreased risk of asthma exacerbation (HR 0.41; 95% CI 0.26, 0.64) in tiotropium users compared with LABA users. Conclusions: Users of tiotropium and single-ingredient LABA had similar risk of total mortality and cardiovascular endpoints. The decreased risk of asthma exacerbations with tiotropium may be due to residual confounding by indication. Confidence limits for most events include reduced risks for tiotropium and also small increases in risk. Nevertheless, the point estimates suggest that tiotropium was associated with a lower risk of each cardiac event except myocardial infarction. However, the small number of cases means that further studies are needed to confirm these results.

A new user cohort study comparing the safety of long-acting inhaled bronchodilators in COPD

Objective To investigate a possible increased risk observed in tiotropium clinical trials of stroke and other adverse events. Design New users of long-acting anticholinergic therapy (tiotropium HandiHaler®) were compared with new users of long-acting β-agonist (LABA) monotherapy, and propensity scores were used to control confounding. Setting UK healthcare system general practitioner electronic medical record database. Participants 10 840 patients newly prescribed tiotropium (n=4767) or LABA (n=6073), at least 40 years old, and not having asthma as their only respiratory illness. Primary and secondary outcome measures Incidence rates of total stroke, myocardial infarction, angina and other adverse events. Results Tiotropium was associated with increased rates of stroke (HR=1.49, 95% CI 0.91 to 2.45), angina (HR=1.38, 95% CI 0.88 to 2.16) and myocardial infarction (HR=1.26, 95% CI 0.72 to 2.21). Groups had similar rates of chronic obstructive pulmonary disease exacerbation (HR=0.95, 95% CI 0.80 to 1.12) and pneumonia (HR=0.96, 95% CI 0.58 to 1.58). Tiotropium was associated with a lower rate of total mortality (HR=0.70, 95% CI 0.56 to 0.89) and asthma exacerbations (HR=0.46, 95% CI 0.36 to 0.57) than users of LABA. Conclusion Small increased risks of serious ischaemic cardiovascular events have been reported with inhaled anticholinergic medication from randomised and nonrandomized studies of ipratropium, tiotropium HandiHaler® and tiotropium Respimat®. Additional research is needed to understand the full extent of cardiovascular effects of inhaled anticholinergic medications and the patients who may be most susceptible.

Prescription patterns for asthma medications in children and adolescents with health care insurance in the United States

To cite this article: Arellano FM, Arana A, Wentworth CE, Vidaurre CF, Chipps BE. Prescription patterns for asthma medications in children and adolescents with health care insurance in the United States. Pediatr Allergy Immunol 2011; 22: 469–476.

Impact of health care payer type on HIV stage of illness at time of initiation of antiretroviral therapy in the USA

There is evidence that earlier initiation of HIV antiretroviral therapy (ART) is associated with better outcomes, including lower morbidity and mortality. Based on recent studies indicating that Medicaid enrollees are more likely to have suboptimal access to medical care, we hypothesized that HIV severity at time of ART initiation is worse for Medicaid patients than patients with other health care coverage. We conducted a US retrospective analysis of GE Centricity Outpatient Electronic Medical Records spanning 1 January 1997 through 30 September 2009. Subjects included all adult HIV patients initiating first-line ART who had CD4+ results within 90 days pre-initiation. HIV stage was defined using CD4 ranges: >500 (n=520), 351–500 (n=379), 201–350 (n=580), or ≤200 (n=406) cells/mm3, with lower CD4 count being indicative of increased disease severity. Payer type was defined as the patients primary payer: Medicaid, Medicare, commercial insurance, self-pay or other/unknown. After controlling for demographic and clinical covariates, cumulative logit models assessed the effect of payer type on HIV stage at ART initiation. The study included 1885 subjects with the primary payer being Medicaid (n=218), Medicare (n=330), commercial insurance (n=538), self-pay (n=159) or other/unknown (n=640). Final logit models demonstrated that, compared to patients on Medicaid, the odds of initiating ART at a higher CD4 range were significantly greater for those commercially insured (odds ratio [OR]=1.53; P=0.005), self-paying (OR=1.56; P=0.023) and other/unknown (OR=1.79; P<0.001) and similar for patients enrolled in Medicare (OR=1.11; P=0.521). Medicaid patients initiated ART at a more advanced stage of HIV than patients who were commercially insured, self-paying, or had other/unknown coverage. With HIV treatment guidelines now supporting ART initiation in patients with higher CD4 counts, these findings underscore the need for mitigating barriers, particularly in the Medicaid population, that may delay treatment initiation.

Infliximab paediatric crohn's disease educational plan a European, cross-sectional, multicentre evaluation:

Background: The infliximab (Remicade®; Schering-Plough, Kenilworth, NJ, USA) Risk Management Plan included the development, execution and tracking of an education programme directed towards prescribers of infliximab for patients with paediatric Crohn’s disease (the Infliximab Paediatric Crohn’s Disease Educational Plan). The programme content consisted of educational materials and communications aimed at educating prescribers on the risks associated with infliximab use.Objective: To evaluate the effectiveness of the risk minimization plan.Methods: Evaluation focused on two components: documentation of training of sponsors’ personnel, and evaluation of awareness among prescribing physicians in European countries. Treating physicians, identified both independently of the sponsor (6 countries) and by the sponsor (24 countries), were surveyed using a structured questionnaire.Results: Training of internal staff on the educational programme was performed and completed by every person designated an appropriate candidate for the programme in all European countries. The independent survey conducted in Germany, France, Italy, Spain, Sweden and the UK indicated that around 90% of the physicians were either paediatric gastroenterologists (57%) or paediatricians (33%). The great majority (96%) of the interviewed physicians were currently treating paediatric Crohn’s disease, and most were currently using infliximab in their treatment of the disease. More specifically, 82% of gastroentrologists treating paediatric Crohn’s disease were using infliximab; among paediatricians, the proportion was lower (42%).Ninety-six percent of paediatric gastroenterologists or gastroenterologists declared themselves aware of the benefits and risks of using infliximab for the treatment of paediatric Crohn’s disease; in comparison, fewer paediatricians (82%) declared themselves aware of these benefits and risks. The majority initially gained awareness through congresses and workshops, and at the time of the survey only 25% declared that they were made aware of the benefits and risks through the educational programme. However, the majority of physicians reported that they had been approached by the sponsor’s personnel in France (98%), Italy (100%), Spain (83%) and Sweden (70%). In Germany and the UK this proportion was 42%.Almost all physicians were aware of the need to perform tuberculosis (TB) and cancer screening prior to initiating therapy with infliximab, and to screen for hypersensitivity reactions before, during and after treatment. Ninety percent of the physicians were aware of the need to update immunization therapy before initiating therapy and, except in Italy (92% aware), around 50% of the physicians were aware of the need to provide patients with the infliximab Patient Alert Card.In the other European countries where the survey took place among physicians identified by the sponsor, 99% of paediatric gastroenterologists and 90% of gastroenterologists or paediatricians declared themselves aware of the benefits and risks of using infliximab for the treatment of paediatric Crohn’s disease, and all of them were aware of the risk of TB and opportunistic infections and the need to perform TB and cancer screening prior to initiating therapy with infliximab.Conclusions: Overall, the results of the evaluation of the Infliximab Paediatric Crohn’s Disease Educational Plan were satisfactory. The objective of education of internal personnel of the pharmaceutical companies distributing infliximab was completely achieved; over 90% of physicians reported being aware of the benefits and risks of infliximab for the treatment of paediatric Crohn’s disease. Further work should be carried out across all countries to educate physicians on providing patients with the infliximab Patient Alert Card. In Germany and the UK in particular, where <50% of physicians reported having been approached by the sponsor’s personnel, further work is needed to raise awareness of the educational programme.

a common data model to assess cardiovascular hospitalization and mortality in atrial fibrillation patients using administrative claims and medical records

Purpose Atrial fibrillation/flutter (AF) is frequently associated with cardiovascular comorbidities. Observational health care databases are commonly used for research purposes in studies of quality of care, health economics, outcomes research, drug safety, and epidemiology. This retrospective cohort study applied a common data model to administrative claims data (Truven Health Analytics MarketScan® claims databases [MS-Claims]) and electronic medical records data (Geisinger Health System’s MedMining electronic medical record database [MG-EMR]) to examine the risk of cardiovascular hospitalization and all-cause mortality in relation to clinical risk factors in recent-onset AF and to assess the consistency of analyses for each data source. Methods Cohorts of patients with newly diagnosed AF (n=105,262 [MS-Claims] and n=3,919 [MG-EMR]) and demographically similar patients without AF (n=105,262 [MS-Claims] and n=3,872 [MG-EMR]) were followed from the qualifying AF diagnosis until cardiovascular hospitalization, death, database disenrollment, or study completion. A common data model standardized the data in structure, format, content, and nomenclature to allow for systematic assessment and comparison of outcomes from two disparate data sets. Results In both databases, AF patients had greater overall baseline comorbidity and higher incidence rates of cardiovascular hospitalization (threefold higher) and all-cause mortality (46% higher) than non-AF patients. For AF patients, incidence rates of cardiovascular hospitalization and all-cause mortality were increased by the concomitant presence of coronary disease, chronic obstructive pulmonary disease, and stroke at baseline. Overall, the pattern of cardiovascular hospitalization in the MS-Claims database was similar to that in the MG-EMR database. Compared with the MS-Claims database, the use of cardiovascular medications and the capture of certain comorbidities among AF patients appeared to be higher in the MG-EMR data set. Conclusion Similar standardized analyses across EMR and Claims databases were consistent in the association of AF with acute morbidity and an increased risk of all-cause mortality. Areas of inconsistency were due to differences in underlying population demographics and cardiovascular risks and completeness of certain data fields.