Incidence Rates of Infections, Malignancies, Thromboembolism, and Cardiovascular Events in an Alopecia Areata Cohort from a US Claims Database.

INTRODUCTION: Alopecia areata (AA) is an autoimmune disease with an underlying immuno-inflammatory pathogenesis. Treatments can include systemic corticosteroids and immunomodulators (such as Janus kinase inhibitors); these medications may be associated with a risk of some adverse events. However, large-scale observational studies of baseline incidence rates (IRs) of infection, cardiovascular disease, malignancy, and thromboembolism in US patients with AA, including those with alopecia totalis or alopecia universalis (AT/AU), are limited. This real-world, US claims-based study aimed to estimate the incidence of events in patients with AA compared with matched patients without AA. METHODS: Patients aged ≥ 12 years enrolled in the Optum Clinformatics Data Mart database from 1 October 2016 to 30 September 2020, with ≥ 2 AA diagnosis codes were included in the AA cohort. Patients without AA were age-, sex-, and race-matched 3:1 to patients with AA. Baseline comorbidities were evaluated during the 12-month period pre-index date. Incident cases of serious/herpes infections, malignancies, major adverse cardiovascular events (MACE), and thromboembolic events were evaluated post-index date. Data are presented using descriptive statistics, proportional percentages, frequencies, and IRs (calculated with 95% CI). RESULTS: Overall, 8784 patients with AA, 599 of whom had AT/AU, were matched to 26,352 patients without AA. IRs per 1000 person-years among the AA and non-AA cohorts, respectively, were 18.5 and 20.6 for serious infections, 19.5 and 9.7 for herpes simplex infections, 7.8 and 7.6 for herpes zoster infections, 12.5 and 11.6 for primary malignancies, 16.0 and 18.1 for MACE, and 4.9 and 6.1 for venous thromboembolisms. Compared with patients with non-AT/AU AA, patients with AT/AU largely had higher IRs for most baseline comorbidities and outcome events evaluated. CONCLUSION: Patients with AA had a higher IR of herpes simplex infection than the matched non-AA cohort. Patients with AT/AU generally had higher rates of outcome events than patients without AT/AU.

Prevalence of autoimmune and inflammatory diseases and mental health conditions among an alopecia areata cohort from a US administrative claims database.

Alopecia areata (AA) is associated with an increased burden of autoimmune and inflammatory disease and mental health conditions that may have a negative impact on quality of life. However, the exact burden of comorbidities on US patients with AA and the clinical subtypes alopecia totalis (AT) and alopecia universalis (AU) compared with those without AA is not well understood. This retrospective cohort study aimed to assess the incidence rates and prevalence of AA and its clinical subtypes and examine the autoimmune and inflammatory disease and mental health condition diagnosis burden in US patients with AA and a matched cohort without AA. The Optum Clinformatics Data Mart database was used to select patients aged ≥12 years enrolled between October 1, 2016, and September 30, 2020, who had two or more AA diagnosis codes for the AA cohort. Three patients without AA were age-, sex-, and race-matched to each patient with AA. Autoimmune and inflammatory diseases and mental health conditions were evaluated at baseline and up to 2 years after the index date. In total, 8784 patients with AA (599 with AT/AU) and 26 352 matched patients without AA were included. The incidence rate of AA was 17.5 per 100 000 person-years (PY; AT/AU: 1.1 per 100 000 PY; non-AT/AU: 16.3 per 100 000 PY), and the prevalence was 54.9 per 100 000 persons (AT/AU: 3.8; non-AT/AU: 51.2). Patients with AA had a higher prevalence of autoimmune and inflammatory diseases than the matched non-AA cohort, including allergic rhinitis (24.0% vs 14.5%), asthma (12.8% vs 8.8%), atopic dermatitis (8.3% vs 1.8%), and psoriasis (5.0% vs. 1.6%). The proportions of anxiety (30.7% vs 21.6%) and major depressive disorder (17.5% vs 14.0%) were higher in patients with AA than those without AA. Patients with AT/AU generally had a greater prevalence of autoimmune and inflammatory disease and mental health conditions than patients with non-AT/AU AA.

The incidence of acute myocardial infarction after elective spinal fusions or joint replacement surgery in the United States: a large-scale retrospective observational cohort study in 322,585 patients : Post-surgical myocardial infarction data.

BACKGROUND: Acute myocardial infarction (AMI) is an uncommon but fatal complication among patients undergoing elective spinal fusion surgery (SF), total hip arthroplasty (THA), and total knee arthroplasty (TKA). Our objective was to estimate the incidence of AMI among adults undergoing elective SF, THA, and TKA in different post-operative risk windows and characterize high-risk sub-populations in the United States. METHODS: A retrospective cohort study was conducted using data from a longitudinal electronic healthcare record (EHR) database from January 1, 2007 to June 30, 2018. ICD codes were used to identify SF, THA, TKA, AMI, and selected clinical characteristics. Incidence proportions (IPs) and 95% confidence intervals were estimated in the following risk windows: index hospitalization, ≤ 30, ≤ 90, ≤ 180, and ≤ 365 days post-operation. RESULTS: A total of 67,533 SF patients, 87,572 THA patients, and 167,480 TKA patients were eligible for the study. The IP of AMI after SF, THA, and TKA ranged from 0.36, 0.28, and 0.25% during index hospitalization to 1.05, 0.93, and 0.85% ≤ 365 days post-operation, respectively. The IP of AMI was higher among patients who were older, male, with longer hospital stays, had a history of AMI, and had a history of diabetes. CONCLUSION: The IP of post-operative AMI was generally highest among the SF cohort compared to the THA and TKA cohorts. Additionally, potential high-risk populations were identified. Future studies in this area are warranted to confirm these findings via improved confounder control and to identify effect measure modifiers.

The incidence of stroke among selected patients undergoing elective posterior lumbar fusion: a retrospective cohort study.

BACKGROUND: Although stroke is a rare complication among spinal surgery patients, the recognition of this adverse event is critical given the aging population undergoing surgical procedures. The objective of this study was to estimate the incidence of stroke among selected adults undergoing elective posterior lumbar fusion (PLF) during various post-operative risk windows and among different subgroups. METHODS: A retrospective cohort study using a longitudinal electronic healthcare record (EHR) database was conducted from January 1, 2007 to June 30, 2018. Elective PLF, stroke, and select clinical characteristics were defined based on International Classification of Disease codes. Patients aged 18 to 85 years with ≥183 days of enrollment in the database prior to undergoing elective PLF were followed from the index date until the occurrence of stroke, death, loss to follow-up, or end of study period, whichever occurred first. The incidence of stroke was estimated in the following risk windows: index hospitalization, ≤ 30 days, ≤ 90 days, ≤ 180 days, and ≤ 365 days post-operation. RESULTS: A total of 43,063 patients were eligible for the study. The incidence of stroke following elective PLF was 0.29% (95% confidence interval [CI]: 0.25, 0.35%) during index hospitalization, 0.44% (95% CI: 0.38, 0.50%) ≤ 30 days, 0.59% (95% CI: 0.52, 0.67%) ≤ 90 days, 0.76% (95% CI: 0.68, 0.85%) ≤ 180 days, and 1.12% (95% CI: 1.03, 1.23%) ≤ 365 days post-operation. Stratified analyses revealed that older patients had a higher incidence of stroke. Additionally, black patients had higher stroke incidences. Post-operative stroke incidence was higher among patients with a history of type 2 diabetes than among patients without such history; similarly, stroke incidence was higher among patients with a history of stroke compared to patients without such history. CONCLUSIONS: The incidence of stroke following elective PLF using an EHR database in this study is slightly higher than that reported in the literature. Our results suggest that stroke risk modification prior to PLF may be important for patients who are older, black, type 2 diabetic, and/or have a history of stroke.

Persistence with Newly Initiated Antidepressant Medication in Rhode Island Medicaid: Analysis and Insights for Promoting Patient Adherence.

OBJECTIVE: To describe persistence to newly prescribed antidepressant medications within the Rhode Island Medicaid population. METHODS: This retrospective study analyzed antidepressant medication persistence in a cohort of new users for a period spanning 2013-2014, focusing on the acute treatment phase (first 12 weeks of treatment). Covariates assessed included patient gender, age, comorbidity status, and measures of health system utilization. RESULTS: Only 53.8% of patients persisted with medication for at least 12 weeks. (Figure 1). Persistence was increased with age > 35, and lower among patients lacking a follow-up visit. Multivariable analyses revealed that patients having at least one office visit during the follow-up period were nearly 2.5 times more likely to persist as compared to patients lacking such visits (OR 2.44, 95% CI 1.77-3.35). Persistence was 22% more likely among patients receiving psychiatric services (OR 1.22; 95% CI 1.00-1.48). CONCLUSIONS: Antidepressant treatment persistence within the R.I. Medicaid population is suboptimal, and lowest among patients lacking follow-up care.

Incidence of stroke and seizure in Alzheimer's disease dementia.

BACKGROUND: the objective of the study was to estimate and compare the incidence rates of ischaemic and haemorrhagic stroke and seizure among cohorts with and without Alzheimer's disease (AD) dementia. METHODS: we conducted a retrospective cohort study using electronic medical records (EMRs) from primary care practices that participated in The Health Improvement Network (THIN) in the United Kingdom from 1 January 1990 to 31 July 2009. For each AD-dementia patient, we selected one general population control patient without AD-dementia matched to one AD-dementia patient on year of birth, sex and physician practice. FINDINGS: the AD-dementia cohorts were 68% female and averaged 80 years of age at the start of follow-up. Populations for analysis included 19,902 AD-dementia and matched non-AD-dementia patients with no history of stroke at baseline in which 790 incident cases of stroke occurred, and similarly, 22,084 AD-dementia and matched patients with no history of seizure at baseline in which 286 cases of seizure occurred. After adjusting for risk factors for each outcome, hazard ratios comparing AD-dementia with non-AD-dementia patients indicated higher rates among AD-dementia patients for stroke (HR = 1.29, 95% CI 1.11, 1.50) and seizure (HR = 5.31, 95% CI 3.97, 7.10). For stroke and seizure, the incidence rate ratios comparing AD-dementia patients with non-AD-dementia controls were greatest for the younger age groups. AD-dementia was observed to be a risk factor for both haemorrhagic stroke and seizures. Increasing age was associated with a decrease in relative risk and an increase in absolute risk.

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.

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/mm(3), with lower CD4 count being indicative of increased disease severity. Payer type was defined as the patient's 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.

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 ß-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.

Asthma is the most common chronic condition of childhood, and its prevalence has increased over recent decades. However, many children and adolescents with asthma are not being managed in accordance with guideline recommendations. The objective of this study was to analyze prescribing patterns for asthma medications in 6- to 18-yr-olds, with a focus on those aged 6-11 yr. Data from patients enrolled for ≥6 months in PharMetrics were analyzed between June 1, 1995, and September 30, 2008. PharMetrics contains data from 45 million US patients from 85 health care plans, including standard and mail order prescription records. Prescriptions for asthma medication for each patient were recorded. The overall asthma cohort included 659,169 patients; 34,950 (5%) were classified as having severe asthma. The 6- to 11-yr-old subgroup consisted of 374,068 patients (56.7% of the overall asthma cohort). Almost 40% of the population received no medication (severe asthma 1.0%; non-severe asthma 37.6%), with almost identical findings in the 6- to 11-yr-old subgroup. In patients with non-severe and severe asthma, frequency of medication use was as follows: short-acting ß(2) -agonists (53% and 92%), oral steroids (23% and 64%), leukotriene receptor antagonists (17% and 49%); inhaled corticosteroids alone (15% and 80%) and in combination with long-acting ß(2) -agonists (10% and 22%), respectively. Results for patients in the 6- to 11-yr subgroup were similar to those of the overall cohort. In conclusion, a considerable proportion of children and adolescents with asthma do not receive any asthma medication. Among those who do receive medication, adherence to current guidelines is questionable.

Suicide-related events in patients treated with antiepileptic drugs.

BACKGROUND: A previous meta-analysis of data from clinical trials showed an association between antiepileptic drugs and suicidality (suicidal ideation, behavior, or both). We used observational data to examine the association between the use or nonuse of antiepileptic drugs and suicide-related events (attempted suicides and completed suicides) in patients with epilepsy, depression, or bipolar disorder. METHODS: We used data collected as part of the clinical care of patients who were representative of the general population in the United Kingdom to identify patients with epilepsy, depression, or bipolar disorder and to determine whether they received antiepileptic drugs. We estimated the incidence rate of suicide-related events and used logistic regression to compute odds ratios, controlling for confounding factors. RESULTS: In a cohort of 5,130,795 patients, the incidence of suicide-related events per 100,000 person-years was 15.0 (95% confidence interval [CI], 14.6 to 15.5) among patients without epilepsy, depression, bipolar disorder, or antiepileptic-drug treatment, 38.2 (95% CI, 26.3 to 53.7) among patients with epilepsy who did not receive antiepileptic drugs, and 48.2 (95% CI, 39.4 to 58.5) among patients with epilepsy who received antiepileptic drugs. In adjusted analyses, the use of antiepileptic drugs was not associated with an increased risk of suicide-related events among patients with epilepsy (odds ratio, 0.59; 95% CI, 0.35 to 0.98) or bipolar disorder (1.13; 95% CI, 0.35 to 3.61) but was significantly associated with an increased risk among patients with depression (1.65; 95% CI, 1.24 to 2.19) and those who did not have epilepsy, depression, or bipolar disorder (2.57; 95% CI, 1.78 to 3.71). CONCLUSIONS: The current use of antiepileptic drugs was not associated with an increased risk of suicide-related events among patients with epilepsy, but it was associated with an increased risk of such events among patients with depression and among those who did not have epilepsy, depression, or bipolar disorder.

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.

Lymphoma among patients with atopic dermatitis and/or treated with topical immunosuppressants in the United Kingdom.

BACKGROUND: Atopic dermatitis (AD) has been associated with an increased risk of lymphoma. OBJECTIVES: To assess the risk of lymphoma associated with AD and use of topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) in a database allowing medical record validation. METHODS: We conducted a nested-case control study using the United Kingdom-based The Health Improvement Network (THIN) database. We excluded patients with established risk factors for lymphoma. Cases of lymphoma were identified and classified after review of the medical records and hospital discharge files. RESULTS: In the study population of 3,500,194 individuals, we identified 2738 cases of lymphoma (1722 non-Hodgkin lymphoma [NHL], 466 Hodgkin disease, 550 indeterminate cases; overall, 188 had cutaneous involvement) and 10,949 matched controls. AD was associated with an increased lymphoma risk (odds ratio [OR], 1.83; 95% CI, 1.41-2.36). In patients with AD referred to a dermatologist, the OR further increased (OR, 3.72; 95% CI, 1.40-9.87). We did not find any cases of lymphoma in TCI users; however, the number of patients exposed to TCI was insufficient to study any possible association between lymphoma and these drugs. TCS use was associated with an increased lymphoma risk (OR, 1.46; 95% CI, 1.33-1.61). The risk increase was dependent on TCS potency (OR for high-potency TCS, 1.80; 95% CI, 1.54-2.11). The increased risk involved both Hodgkin disease and NHL, especially NHL with skin involvement (OR for high-potency TCS, 26.24; 95% CI, 13.49-51.07). CONCLUSION: Our results show an association between lymphoma-especially skin lymphoma-and use of TCS. The risk increased with duration of exposure and potency of TCS.

Dosage, titration, and gaps in treatment with extended release niacin in clinical practice.

OBJECTIVE: To examine the dosage, titration patterns, and gaps in treatment of newly-initiated ER niacin in clinical practice. RESEARCH DESIGN AND METHODS: Historical cohort study using the Ingenix Lab/Rx database. Patients were at least 20 years old, received an initial, index ER niacin prescription between January 1, 2001 and June 30, 2003, and had no ER niacin use in the preceding 12 months. Follow-up data were collected for at least 6 months after the index date. MAIN OUTCOME MEASURES: Average daily dosage (ADD) and titration patterns of ER niacin therapy at defined time points after the index prescription, and the incidence and timing of continuous gaps of >/=30 days in ER niacin therapy. RESULTS: A total of 14 386 patients initiating ER niacin were followed for a mean of 6.5 months after the index prescription. The ADD of the initial ER niacin prescription was 750 mg. Forty percent of patients experienced a >/=30-day gap in therapy immediately after the first prescription. Almost 80% had at least one >/=30-day gap in therapy during the post-index period, and the ADD of the last prescription prior to discontinuation was /=1000 mg and only 7.6% reached the dose of 2000 mg. CONCLUSIONS: A considerable proportion of new ER niacin users failed to reach recommended daily maintenance dosages in clinical practice. The main limitations of the study include its reliance on administrative data, inability to capture over-the-counter niacin use, and evaluation of reasons for suboptimal titration. Future research should determine the extent to which gaps in ER niacin therapy and failure to titrate to optimal dosages are due to poor tolerability, physician practice, or other factors.

Comparative safety of long-acting inhaled bronchodilators: a cohort study using the UK THIN primary care database.

BACKGROUND: Use of a long-acting inhaled bronchodilator, either an anticholinergic or a beta-adrenergic receptor agonist (beta-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 beta-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.

The effect of antihypertensive drugs and drug combinations on the incidence of new-onset type-2 diabetes mellitus.

PURPOSE: To evaluate the effect of antihypertensive drugs on new-onset type-2 diabetes. METHODS: This was a cohort study using the UK General Practice Research Database (GPRD). Patients newly diagnosed with hypertension between 1991 and 2001, and treated with antihypertensive drugs, were included. Type-2 diabetes mellitus was identified based on a physician diagnosis or an anti-diabetic drug prescription. Antihypertensive treatments were classified as: ACE inhibitors (ACE-Is), beta blockers, calcium channel blockers (CCB), thiazides, all other drugs, and their combinations. RESULTS: A total of 2706 incident diabetes cases were identified in 98 629 hypertensive patients during 307 356 patient years (8.8/1000 patient years). New-onset diabetes was lower for ACE-I regimens compared with non-ACE inhibitor regimens (HR = 0.90; 95%CI: 0.82-0.99). CCB monotherapy (HR = 1.27; 95%CI: 1.07-1.51) had an increased risk of diabetes compared with ACE-I monotherapy. ACE-I plus thiazide had the lowest risk of diabetes among double combinations, followed by ACE-I plus beta blocker, and ACE-I plus CCB. Double combinations with an ACE-I had 0.79 (95%CI: 0.67-0.92) times the risk compared with non-ACE inhibitor combinations. The risk of new-onset diabetes was significantly higher for beta blocker plus thiazide (HR = 1.37; 1.10-1.70), CCB plus thiazide (HR = 1.44; 95%CI: 1.13-1.83), but not beta blocker plus CCB (HR = 1.30; 95%CI: 0.99-1.70) compared with ACE-I plus thiazide. CONCLUSIONS: Antihypertensive drug combinations including an ACE-I had a significantly lower risk of new-onset diabetes than antihypertensive drug combinations without an ACE-I.

Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis.

Systemic use of immunosuppressant agents increases the risk of lymphoma in transplantation. We performed a nested case-control study in the PharMetrics database to evaluate the association between topical immunosuppressants and lymphoma in a cohort of patients with atopic dermatitis. We identified cases of lymphoma and randomly selected four controls for each case, matched by length of follow-up. We used conditional logistic regression to calculate odds ratio (OR) and 95% confidence intervals (CIs) of the association between topical immunosuppressants and lymphoma. Two hundred and ninety-four cases of lymphoma occurred in 293,253 patients, 81 in patients younger than 20 years. The adjusted analysis yielded the following OR (95%CI) for: severity (OR 2.4; 95% CI 1.5-3.8), oral steroids 1.5 (1.0-2.4), "super potent" topical steroids 1.2 (0.8-1.8) , "low potency" topical steroids OR 1.1 (0.7-1.6); pimecrolimus 0.8(0.4-1.6), tacrolimus OR 0.8 (0.4-1.7), and concomitant topical steroids, pimecrolimus, and tacrolimus 1.0 (0.3-4.1). We did not find an increased risk of lymphoma in patients treated with topical calcineurin inhibitors. It is difficult to disentangle the effects of severity of disease on outcome versus the true effects of drugs. However, in the adjusted analysis, severity of AD was the main factor associated with an increased risk of lymphoma.

Pooled clinical trial analysis of tiotropium safety.

BACKGROUND: Marketing approval of pharmaceutical products is often based on data from several thousand subjects or fewer. Evaluation of safety is greatly enhanced by augmenting the safety database with postapproval studies. METHODS: We conducted a pooled analysis of adverse event data from 19 randomized, double-blind, placebo-controlled trials with tiotropium in patients with obstructive lung disease. We computed incidence rates and rate ratios (RRs) for various reported adverse event end points of interest. Patients contributed person-time to the analysis as long as they were in the study until 30 days after treatment (tiotropium, placebo), or until they had the event of interest, whichever came first. Studies were pooled using the Mantel-Haenszel estimator, and we used 95% confidence intervals (CIs) to assess the precision of effect estimates. RESULTS: The pooled trial population includes 4,435 tiotropium patients and 3,384 placebo patients contributing 2,159 person-years of exposure to tiotropium and 1,662 person-years of exposure to placebo. Dyspnea, dry mouth, COPD exacerbation, and upper respiratory tract infection were the most commonly reported events. There was a higher relative risk of dry mouth in the tiotropium group (RR, 3.60; 95% CI, 2.56 to 5.05). There was a lower risk of dyspnea (RR, 0.64; 95% CI, 0.50 to 0.81) and COPD exacerbation (RR, 0.72; 95% CI, 0.64 to 0.82) in patients receiving tiotropium compared to patients receiving placebo. Other results of interest are as follows: (1) all-cause mortality (RR, 0.76; 95% CI, 0.50 to 1.16); (2) cardiovascular mortality (RR, 0.57; 95% CI, 0.26 to 1.26); and (3) respiratory mortality (RR, 0.71; 95% CI, 0.29 to 1.74). The relative risk of urinary retention was 10.93 (95% CI, 1.26 to 94.88). CONCLUSIONS: Pooling of adverse event data from preapproval and postapproval tiotropium clinical trials increase the precision of effect estimates and supports the present safety profile of tiotropium.

Use of cyclo-oxygenase 2 inhibitors (COX-2) and prescription non-steroidal anti-inflammatory drugs (NSAIDS) in UK and USA populations. Implications for COX-2 cardiovascular profile.

BACKGROUND: COX-2 and NSAIDS differ in their gastrointestinal (GI) and cardiovascular (CV) toxicity from pharmacological, clinical and epidemiologic point of views. OBJECTIVE: Describe the patterns of use of NSAIDS and COX-2 in The Health Improvement Network (THIN) database in UK and the PharMetrics database in USA. METHODS: We examined the experience of 10 distinct cohorts of new users of diclofenac, naproxen, ibuprofen, piroxicam, other NSAIDS, meloxicam, celecoxib, etoricoxib, rofecoxib and valdecoxib. The study period was 1 January 1995 through 2004 (31 March in UK and 28 February in USA). We collected information on covariates including history of upper GI disease, CV disease, hepatic disease, dosage, concomitant medication, and visits to a rheumatologist. RESULTS: We identified 486 076 unique patient-drug pairs in UK and 1 533 239 in USA. In UK population 78 201 (16%) were COX-2 users and in PharMetrics 324 206 (21%) were COX-2 users. Diclofenac and ibuprofen (NSAIDS), and celecoxib and rofecoxib (COX-2) were the agents prescribed most frequently. The duration of therapy was longer among celecoxib and rofecoxib users than among other users. More COX-2 users than NSAIDS users received concomitant gastroprotective agents (GPA), corticosteroids and anti-platelet therapy, and had a history of thromboembolic events and hypertension. PharMetrics patients were prescribed higher doses of NSAIDS and COX-2. The use of any single agent for more than 90 days was uncommon, but more frequent in PharMetrics. Switching was uncommon and was generally to a NSAID. DISCUSSION: Our results confirm some previous findings from other authors such as the presence of both GI and CV channelling to COX-2 agents but refute others, such as the frequency of drug switching between these agents. The typical use of COX-2 agents in practice is for shorter duration, and at lower doses, than was employed in randomized clinical trials. This difference may help clarify the apparent discrepancy with respect to CV toxicity between the results from clinical trials, which showed a higher CV risk with these drugs, and non-experimental epidemiologic studies, which showed lower or no increase in risk.