Multiple sclerosis by phenotype in Germany.

BACKGROUND: A diagnosis of multiple sclerosis (MS) can be categorized based on its disease course into the following phenotypes: relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). With one exception, studies of MS by phenotype either provide only prevalence data or if describing drug utilization, the emphasis is on patients with RRMS; while drug utilization by phenotype tends to be examined over the course of a year. No recent studies have comprehensively evaluated MS phenotypes by prevalence, drug utilization, and comorbidities over time from a population-based perspective, which is essential for understanding the disease burden and identifying unmet needs in MS. Germany is one of the few countries where specific MS phenotypes are commonly recorded in routine clinical practice. The purpose of this study was to compare MS phenotypes with respect to changes in their population-based prevalence rates and the types of MS treatments prescribed over time, as well as the frequency of clinical conditions associated with MS based on data from a German health insurance database. METHODS: This retrospective, observational, cohort study used data from a German health insurance database for the period 2010 to 2017. Patients aged 18+ years with a specified phenotype of MS based on ICD-10 diagnosis coding were included in the analysis. RESULTS: In 2010, RRMS was reported in 73%, PPMS in 8%, and SPMS in 19% of patients with MS with a known phenotype. The mean ages of patients were 41.4, 53.6, and 52.8 years, respectively, and all phenotypes were associated with a female predominance (69%, 63% and 63%, respectively). The prevalence rate of each phenotype markedly increased during the study period (RRMS +113%, PPMS +40%, SPMS +54%; in 2017 the rates were 183, 14, and 34 per 100,000, respectively). The mean age of patients reporting each phenotype also increased (p<0.01), while the female:male proportion remained stable in RRMS and SPMS, the proportion of females significantly declined over time in the PPMS group. The overall percentage of patients prescribed a disease-modifying drug increased across the phenotypes from 51% to 57%. Prescription of interferon-based therapies declined in each phenotype, with the greatest declines observed in RRMS and PPMS. The PPMS and SPMS groups had significantly more prescriptions for symptom management than the RRMS group. Depression was the most prevalent clinical condition associated with each phenotype. There was a significant difference in the percentage of patients with depression across the phenotypes (p = 0.03), with the highest among SPMS (44%) compared with RRMS (35%) or PPMS (37%). Significant differences (p<0.05) across the phenotypes were also observed for the composite prevalence of cardiovascular conditions (highest in PPMS) and cognitive dysfunction (highest in SPMS). CONCLUSION: The increasing numbers of patients across each MS phenotype, aging population in patients with MS regardless of phenotype, gender differences and variations across the types of treatments prescribed, and clinical conditions associated with each MS phenotype present new insight into the disease burden and treatment strategies of MS. These should be considered when developing healthcare strategies and optimizing care for patients with MS.

Design of ideal vibrational signals for stinkbug male attraction through vibrotaxis experiments.

BACKGROUND: Many groups of insects utilize substrate-borne vibrations for intraspecific communication. This characteristic makes them a suitable model for exploring the use of vibrations as a tool for pest control as an alternative to the use of chemicals. Detailed knowledge of species communication is a prerequisite to select the best signals to use. This study explored the use of substrate-borne vibrations for pest control of the brown marmorated stink bug (BMSB), Halyomorpha halys Stål (Heteroptera: Pentatomidae). For this purpose, we first identified the spectral and temporal characteristics that best elicit male responsiveness. Bioassays were conducted with artificial signals that mimicked the natural female calling signal. Second, we used the acquired knowledge to synthesize new signals endowed with different degrees of attractiveness in single- and two-choice bioassays using a wooden custom-made T stand. RESULTS: The results from this study showed that males were attracted to female signals along a high range of amplitudes, especially starting from a threshold of 100 µm s-1 , a high pulse repetition time (1 s) and frequency peak corresponding to the first harmonic (76 Hz). This resulted in an "optimal" signal for use to attract males, while the choice test in the T arena showed that this signal elicits searching behavior and attracts BMSB males towards a stimulation point. CONCLUSION: We confirm the use of vibrational signals as a strong tool for behavioral manipulation of male BMSB and suggest its possible use in the development of field traps and further management of this pest. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Validating an algorithm for multiple myeloma based on administrative data using a SEER tumor registry and medical record review.

PURPOSE: Large numbers of multiple myeloma patients can be studied in real-world clinical settings using administrative databases. The validity of these studies is contingent upon accurate case identification. Our objective was to develop and evaluate algorithms to use with administrative data to identify multiple myeloma cases. METHODS: Patients aged ≥18 years with ≥1 International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code for multiple myeloma (203.0x) were identified at two study sites. At site 1, several algorithms were developed and validated by comparing results to tumor registry cases. An algorithm with a reasonable positive predictive value (PPV) (0.81) and sensitivity (0.73) was selected and then validated at site 2 where results were compared with medical chart data. The algorithm required that ICD-9-CM codes 203.0x occur before and after the diagnostic procedure codes for multiple myeloma. RESULTS: At site 1, we identified 1432 patients. The PPVs of algorithms tested ranged from 0.54 to 0.88. Sensitivities ranged from 0.30 to 0.88. At site 2, a random sample (n = 400) was selected from 3866 patients, and medical charts were reviewed by a clinician for 105 patients. Algorithm PPV was 0.86 (95% CI, 0.79-0.92). CONCLUSIONS: We identified cases of multiple myeloma with adequate validity for claims database analyses. At least two ICD-9-CM diagnosis codes 203.0x preceding diagnostic procedure codes for multiple myeloma followed by ICD-9-CM codes within a specific time window after diagnostic procedure codes were required to achieve reasonable algorithm performance.

Statin use and risk of multiple myeloma: An analysis from the cancer research network.

Animal and human data suggest statins may be protective against developing multiple myeloma; however, findings may be biased by the interrelationship with lipid levels. We investigated the association between statin use and risk of multiple myeloma in a large US population, with an emphasis on accounting for this potential bias. We conducted a case-control study nested within 6 US integrated healthcare systems participating in the National Cancer Institute-funded Cancer Research Network. Adults aged ≥40 years who were diagnosed with multiple myeloma from 1998-2008 were identified through cancer registries (N = 2,532). For each case, five controls were matched on age, sex, health plan, and membership duration prior to diagnosis/index date. Statin prescriptions were ascertained from electronic pharmacy records. To address potential biases related to lipid levels and medication prescribing practices, multivariable marginal structural models were used to model statin use (≥6 cumulative months) and risk of multiple myeloma, with examination of multiple latency periods. Statin use 48-72 months prior to diagnosis/index date was associated with a suggestive 20-28% reduced risk of developing multiple myeloma, compared to non-users. Recent initiation of statins was not associated with myeloma risk (risk ratio range 0.90-0.99 with 0-36 months latency). Older patients had more consistent protective associations across all latency periods (risk ratio range 0.67-0.87). Our results suggest that the association between statin use and multiple myeloma risk may vary by exposure window and age. Future research is warranted to investigate the timing of statin use in relation to myeloma diagnosis.

Predictive Properties of the Asthma Control Test and Its Component Questions for Severe Asthma Exacerbations.

BACKGROUND: Current US guidelines recommend the Asthma Control Test (ACT) for assessing disease control and selecting treatment. OBJECTIVE: The goal of this study was to prospectively assess the ACT and its component questions for their utility in predicting the risk of severe asthma exacerbations. METHODS: Individuals were participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity, and those included in the current analysis had the following characteristics: age 18 years or more, physician-diagnosed asthma, and longitudinal care received at a large health system in southeastern Michigan. Study participants underwent a baseline evaluation, which included answering the ACT. A severe asthma exacerbation was defined as one requiring oral steroids, an emergency department visit, or inpatient admission. Receiver-operator characteristic curves were used to measure and compare the predictive utility of the ACT and its component questions for severe asthma exacerbations. RESULTS: Of 1180 participants, 354 (30.0%) experienced a severe asthma exacerbation within 6 months of their baseline evaluation. When compared with the individual questions that composed the ACT, the composite score was significantly better at predicting severe exacerbations with 1 exception; the composite ACT score and the question assessing rescue medication use were not significantly different (P = .580). Pharmacy-based records of metered-dose inhaler short-acting beta-agonist use and asthma severity were also not significantly different from the composite ACT score. CONCLUSIONS: Our study demonstrates that although the ACT is modestly predictive for exacerbations, the composite score may not be superior to assessing rescue medication use alone for predicting the risk of severe asthma exacerbations.

Assessing differences in inhaled corticosteroid response by self-reported race-ethnicity and genetic ancestry among asthmatic subjects.

BACKGROUND: Inhaled corticosteroids (ICSs) are the preferred treatment for achieving asthma control. However, little is known regarding the factors contributing to treatment response and whether treatment response differs by population group. OBJECTIVE: We sought to assess behavioral, sociodemographic, and genetic factors related to ICS response among African American and European American subjects with asthma. METHODS: Study participants were part of the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). The analytic sample included asthmatic subjects aged 12 to 56 years with greater than 12% bronchodilator reversibility and percent predicted FEV1 of between 40% and 90%. Participants received 6 weeks of inhaled beclomethasone dipropionate. The primary measure of ICS response was a change in Asthma Control Test (ACT) score; the secondary measure was a change in prebronchodilator FEV1. Adherence was measured with electronic monitors. Genetic ancestry was estimated for African American participants by using genome-wide genotype data. RESULTS: There were 339 study participants; 242 self-identified as African American and 97 as European American. Baseline ACT score, percent predicted FEV1, degree of bronchodilator response, and ICS adherence were significantly associated with ICS response. A baseline ACT score of 19 or less was useful in identifying those who would respond, as evidenced by the significant dose-response relationship with ICS adherence. Neither self-reported race-ethnicity among all participants nor proportion of African ancestry among African American participants was associated with ICS responsiveness. CONCLUSIONS: Our findings suggest that baseline lung function measures and self-reported asthma control predict ICS response, whereas self-reported race-ethnicity and genetic ancestry do not.

Incidence of liver injury among cancer patients receiving chemotherapy in an integrated health system.

PURPOSE: Using liver laboratory tests (LLTs), Hy's law is a method used to identify drug-induced liver injury (DILI), after excluding other causes. Elevated LLTs in chemotherapy-exposed patients may result from tumor effects or comorbidities. This study evaluated incidence of Hy's law in chemotherapy-treated cancer patients. METHODS: We identified breast, colorectal, and lung cancer patients diagnosed in 1 January 2000 to 31 December 2007 at a Midwestern health system. Using automated data, potential Hy's law (PHL) cases were defined by patterns of elevated LLTs suggestive of DILI. Among those treated with chemotherapy, we excluded PHL patients with pre-existing conditions that could cause liver injury, producing a cohort meeting Hy's law criteria, according to automated data. Medical record review, conducted among these automated data-derived Hy's law patients, further excluded those with causes of liver injury other than chemotherapy. RESULTS: Using automated data, among chemotherapy-exposed patients (N = 2788), 91 (3.3%) met PHL criteria using LLTs and 64 (2.3%) met Hy's law after excluding underlying liver injury using the International Classification of Diseases, 9th Revision codes. After a medical record review, 62 of 64 patients qualifying as Hy's law through automated data had other potential causes, leaving two patients (0.07%; 95%CI: 0.01-0.24%) with chemotherapy as a likely alternative cause of liver injury. CONCLUSIONS: Abnormal LLTs are common in chemotherapy-treated patients. Medical record review showed that the incidence of Hy's law events is rare. These data provide context for evaluating DILI in clinical trials and postmarketing surveillance of anticancer therapies, understanding that automated data alone may substantially overestimate the number of Hy's law cases.

A randomized controlled trial to provide adherence information and motivational interviewing to improve diabetes and lipid control.

PURPOSE: The purpose of this study was to assess whether providing medication adherence information with or without motivational interviewing improves diabetes and lipid control. METHODS: Study participants were adult members of a health system in southeast Michigan, were using both oral diabetes and lipid-lowering medications, and had glycated hemoglobin (A1C) or low-density lipoprotein cholesterol (LDL-C) levels not at goal. Participants were randomly assigned to receive usual care (UC), n = 567; have medication adherence information (AI) provided to their physician, n = 569; or have AI and receive motivational interviewing (MI) though trained staff (AI + MI), n = 556. Primary outcomes were A1C and LDL-C levels at 18 months post randomization. RESULTS: Primary outcomes were not significantly different between patients in the AI or AI + MI study arms when compared with UC. Similarly, neither oral diabetes nor lipid-lowering medication adherence was significantly different between groups. Patient participation in the AI + MI arm was low and limit the interpretation of the study results, but post hoc analysis of the AI + MI study arm showed that the number of MI sessions received was positively associated with only oral diabetes medication adherence. CONCLUSION: Neither AI nor MI significantly improved diabetes and lipid control when compared with UC. Moreover, patient participation appeared to be a particular barrier for MI.

Nocturnal asthma and the importance of race/ethnicity and genetic ancestry.

RATIONALE: Nocturnal asthma is a common presentation and is associated with a more severe form of the disease. However, there are few epidemiologic studies of nocturnal asthma, particularly in minority populations. OBJECTIVES: To identify factors associated with nocturnal asthma, including the contribution of self-identified race/ethnicity and genetic ancestry. METHODS: The analysis included individuals from the Study for Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) cohort. Nocturnal asthma symptoms were assessed by questionnaire. Genome-wide genotype data were used to estimate genetic ancestry in a subset of African American participants. Logistic regression was used evaluate the association of various factors with nocturnal asthma, such as self-identified race/ethnicity and genetic ancestry. MEASUREMENT AND MAIN RESULTS: The study comprised 3,380 African American and 1,818 European Americans individuals with asthma. After adjusting for other potential explanatory variables, including controller medication use, African Americans were more than twice as likely (odds ratio, 2.56; 95% confidence interval, 2.24-2.93) to report nocturnal asthma when compared with European American individuals. Among the subset of African American participants with genome-wide genotype data (n = 1,040), estimated proportion of African ancestry was also associated with an increased risk of nocturnal asthma (P = 0.007). Differences in lung function explained a small, but statistically significant (P = 0.02), proportion of the relationship between genetic ancestry and nocturnal asthma symptoms. CONCLUSIONS: Both self-identified race/ethnicity and African ancestry appear to be independent predictors of nocturnal asthma. The mechanism by which genetic ancestry contributes to population-level differences in nocturnal asthma appears to be largely independent of lung function.

Differing effects of metformin on glycemic control by race-ethnicity.

CONTEXT: Metformin is considered first-line treatment for type 2 diabetes mellitus. However, little is known about its effects in African American individuals. OBJECTIVE: The objective of the study was to assess whether metformin's effect on glycemic control differs by race-ethnicity Design: Electronic health records were used to identify adults who had a diagnosis of diabetes, two or more fills of metformin, and two or more glycated hemoglobin (HbA1c) measurements. Pharmacy claims were used to estimate metformin exposure based on fill frequency and dose dispensed. Regression analyses modeled the relationship between metformin exposure and HbA1c levels. Analyses were stratified by race-ethnicity and baseline HbA1c values. SETTING: The study was conducted at a large health system in southeast Michigan. MAIN OUTCOME MEASURE: Differences in HbA1c levels while on metformin were measured. RESULTS: We identified 19 672 patients with diabetes taking metformin; 7429 were African American and 8783 were European American. Baseline HbA1c values in these two groups were 7.81% (61.8 mmol/mol) and 7.38% (57.1 mmol/mol), respectively. Compared with no use, metformin was associated with a 0.62% (6.8 mmol/mol) reduction in HbA1c; however, there was a significant difference by race-ethnicity (P < .001). Among African American individuals, metformin use was associated with a 0.90% (9.8 mmol/mol) reduction in HbA1c levels, whereas among European Americans, metformin was associated with a 0.42% (4.6 mmol/mol) reduction. Irrespective of baseline HbA1c, metformin use was associated with lower HbA1c levels in African American individuals. CONCLUSIONS: African American individuals appear to have a better glycemic response to metformin when compared with European Americans. Further studies are needed to determine whether this translates to commensurate reductions in diabetes complications.

Policies and events affecting prescription opioid use for non-cancer pain among an insured patient population.

BACKGROUND: Rising prescription opioid use and abuse have prompted widespread concern. However, to date there have been few rigorous investigations into the policies and events which may have contributed to these trends. OBJECTIVE: This study investigates trends in opioid use and related adverse events among individuals with non-cancer pain before and after implementation of major national policies. STUDY DESIGN: The study used a longitudinal prospective study design. The analysis was limited to adults (age = 18 years) without a recorded cancer diagnosis. Pharmacy claims were used to assess rates of prescription opioid use, the strength of opioids dispensed, the proportion using opioids chronically, and related adverse events. Time trend analysis was used to identify changes in these rates over time. The study was Institutional Review Board approved. SETTING: Study patients were members of a large, health maintenance organization in southeast Michigan, with longitudinal records of prescription opioid use. RESULTS: The analysis comprised 523,623 individuals and 1,066,700 opioid pharmacy fills from January 1, 1997, to December 31, 2011. Contemporaneous with the implementation of health organization accreditation criteria requiring assessment and treatment of pain in all patients beginning January 2001, we observed a consistent and unabated increase in the rate of opioid fills and the proportion of chronic use. A parallel increase in the annual rate of adverse events was also observed. Similarly, we observed a continuous rise in the average strength of opioid fills following January 2001 with the exception of a single drop in December 2010, which was attributable to the withdrawal of propoxyphene from the U.S. market. LIMITATIONS: This was an observational study and not a trial. Other long-term opioid-related benefits or harms, including functional status, quality of life, and substance use disorder, were not assessed. CONCLUSIONS: This study provides temporal evidence for a rise in prescription opioid use after implementation of health organization accreditation criteria requiring standardized management of all individuals with pain.

Real-world effects of once vs greater daily inhaled corticosteroid dosing on medication adherence.

BACKGROUND: Nonadherence to inhaled corticosteroids (ICSs) for asthma maintenance therapy is common and is associated with poor asthma outcomes. Simplifying dosing regimens for some chronic disease conditions has resulted in better adherence; however, little is known regarding the effect of ICS dosing on adherence for the treatment of asthma. OBJECTIVE: To determine whether once daily dosing is associated with higher adherence to ICS therapy when compared with 2 or more times daily dosing among patients with asthma. METHODS: Six years of pharmacy claims data were linked with prescription information to estimate ICS therapy adherence for patients with asthma 12 to 56 years of age who were members of a large health maintenance organization. Patient follow-up continued from the initial ICS fill until one of the following: the last ICS fill in the observation period, a switch of ICS dosing regimen, or the initiation of ICS and long-acting ß-agonist combination therapy. Adherence was estimated by calculating a continuous multiple-interval measure of medication availability. Regression models were used to assess the relationship between adherence in patients treated with once daily vs 2 or more times daily ICS therapy. RESULTS: Among the 1,302 patients who met the inclusion criteria, 17% were prescribed once daily therapy, and 83% were prescribed 2 or more times daily therapy. Models comparing ICS adherence among individuals following once daily and 2 or more times daily ICS regimens suggested that once daily dosing was associated with an approximately 20% increase in adherence. This significant difference persisted among subgroups defined by sex, race/ethnicity, age, and asthma severity. CONCLUSION: Once daily dosing was associated with higher adherence to ICS therapy; this included clinically relevant subgroups.

Examining the relationship between depression and asthma exacerbations in a prospective follow-up study.

BACKGROUND: Although depression has been linked with asthma, its relationship with asthma exacerbations, including emergency department (ED) visits and oral steroid (OS) use, has not been well documented. The aim is to investigate whether depression increases exacerbations among patients with asthma. METHOD: The study included 568 participants with asthma who were between 18 and 56 years old, were taking an inhaled corticosteroid, and participated in baseline and follow-up surveys. Surveys and medical records from a large, health system were collected as part of the Adherence Feedback for Improving Respiratory Medication Use trial. Number of ED visits and OS prescription fills for asthma were calculated for 12-month periods before and after the follow-up survey. Depression was measured using a standardized two-item instrument. Negative binomial regression and modified proportional hazards models were used. RESULTS: Among patients with asthma, those who had depression (n = 187; 32.9%) were at increased risk for an asthma-related ED visit (adjusted relative risk = 1.96, 95% confidence interval [CI] = 1.02-3.75), but not an OS fill (adjusted relative risk = 0.98; 95% CI = 0.72-1.32). Participants with depression and asthma who received psychiatric treatment via antidepressant medication (n = 126; 22.2%) or psychotherapy (n = 39; 6.9%) were more likely to have an ED visit (medication hazard ratio = 2.09, 95% CI = 1.35-3.25; psychotherapy hazard ratio = 2.07, 95% CI = 1.38-3.22). CONCLUSIONS: This study suggests a temporal relationship between depression and asthma-related ED visits. Research and practice must consider the importance of these comorbid conditions. Trial Registration ClinicalTrials.gov identifier: NCT00459368.

Asthma medication adherence: the role of God and other health locus of control factors.

BACKGROUND: Medication adherence is an important determinant of disease outcomes, yet medication use on average tends to be low among patients with chronic conditions, including asthma. Although several predictors of non-adherence have been assessed, more research is needed on patients' beliefs about God and how these relate to medication use. OBJECTIVE: To examine the relationship between perceptions about "God's" role in health and other locus of control factors with inhaled corticosteroid (ICS) adherence among asthma patients. METHODS: Participants were from a clinical trial to improve ICS adherence and were 5-56 years old, had a diagnosis of asthma, and were receiving ICS medication. Baseline adherence was estimated from electronic prescription and pharmacy fill records. Patients were considered to be adherent if ICS use was ≥80% of prescribed. A baseline survey with the Multidimensional Health Locus of Control scale was used to assess five sources (God, doctors, other people, chance, and internal). RESULTS: Medication adherence was low (36%). Patients' who had a stronger belief that God determined asthma control were less likely to be adherent (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70-0.96). This relationship was stronger among African American (OR 0.68, 95% CI0.47-0.99) compared to white patients (OR 0.89, 95% CI 0.75-1.04), and among adults (OR 0.81, 95% CI 0.69-0.96) compared to children (OR 0.84, 95% CI 0.58-1.22). CONCLUSION: Patients' belief in God's control of health appears to be a factor in asthma controller use, and therefore should be considered in physician-patient discussions concerning course of treatment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00459368.

Effect of ezetimibe on major atherosclerotic disease events and all-cause mortality.

Despite ezetimibe's ability to reduce serum cholesterol levels, there are concerns over its vascular effects and whether it prevents or ameliorates atherosclerotic disease (AD). The aims of this study were to estimate the effect of ezetimibe use on major AD events and all-cause mortality and to compare these associations to those observed for hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use. A total of 367 new ezetimibe users were identified from November 1, 2002, to December 31, 2009. These subjects were aged ≥18 years and had no previous statin use. One to 4 statin user matches were identified for each ezetimibe user, resulting in a total of 1,238 closely matched statin users. Pharmacy data and drug dosage information were used to estimate a moving window of ezetimibe and statin exposure for each day of study follow-up. The primary outcome was a composite of major AD events (coronary heart disease, cerebrovascular disease, and peripheral vascular disease events) and all-cause death. Ezetimibe use (odds ratio 0.33, 95% confidence interval 0.13 to 0.86) and statin use (odds ratio 0.61, 95% confidence interval 0.36 to 1.04) were associated with reductions in the likelihood of the composite outcome. These protective associations were most significant for cerebrovascular disease events and all-cause death. Subgroup analyses by gender, race or ethnicity, history of AD, diabetes status, and estimated renal function showed consistent estimates across strata, with no significant differences between ezetimibe and statin use. In conclusion, ezetimibe appeared to have a protective effect on major AD events and all-cause death that was not significantly different from that observed for statin use.

Genetic ancestry and its association with asthma exacerbations among African American subjects with asthma.

BACKGROUND: There are large and persisting disparities in severe asthma exacerbations by race-ethnicity, and African American subjects are among those at greatest risk. It is unclear whether this increased risk solely represents differences in environmental exposures and health care or whether there is a predisposing genetic component. OBJECTIVE: We sought to assess the relationship between genetic ancestry and severe exacerbations among African American subjects with asthma. METHODS: Participants were part of the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). These subjects were 12 to 56 years of age, received care from a single large health system, and had a physician's diagnosis of asthma. Genetic ancestry was estimated by using a set of validated ancestry informative markers. Severe exacerbations (ie, asthma-related emergency department visits, hospitalizations, and burst oral steroid use) were prospectively identified from health care claims. RESULTS: We assessed genetic ancestry in 392 African American subjects with asthma. The average proportion of African ancestry was 76.1%. A significant interaction was identified between ancestry and sex on severe exacerbations, such that the risk was significantly higher with increasing African ancestry among male but not female subjects. The association among male subjects persisted after adjusting for potential confounders (relative rate, 4.30 for every 20% increase in African ancestry; P = .029). CONCLUSIONS: African ancestry was significantly and positively associated with severe exacerbations among male African American subjects. These findings suggest that a portion of the risk of asthma exacerbations in this high-risk group is attributable to a genetic risk factor that partitions with ancestry.

Cardiovascular outcomes in women with advanced breast cancer exposed to chemotherapy.

PURPOSE: To quantify incidence of cardiovascular outcomes in patients with advanced breast cancer receiving cardiotoxic and non-cardiotoxic chemotherapy. METHODS: This study identified all women at a Midwestern health system with initial diagnosis of American Joint Commission on Cancer Stage III/IV breast cancer (1995-2003) and random sample of 50 women initially diagnosed with Stage I/II who progressed to Stage III/IV. The rate of new cardiovascular outcomes (heart failure, dysrhythmia, and ischemia events) for cardiotoxic (anthracycline or trastuzumab) and non-cardiotoxic agents was calculated. RESULTS: Of 315 patients, 90.5% (n = 285) received systemic cancer therapy; 67.7% (n = 193) received cardiotoxic drugs. Older patients were less likely to receive cardiotoxic agents (86.4%, ≤59 years vs. 31.9%, 70+ years). Adjusting for age, race, stage, surgery/radiation, estrogen receptor/progesterone receptor status, and diagnosis year, rate of new cardiac events was higher in patients exposed to cardiotoxic drugs compared with those exposed to non-cardiotoxic drugs (adjusted hazard ratio = 2.5, 95%CI = 0.9-7.2). Patients with cardiac event history (relative risk = 3.2, 95%CI = 2.0-5.1) and those with heart failure history (relative risk = 5.9, 95%CI = 2.4-14.6) were more likely to receive non-cardiotoxic treatment. Heart failure events occurred steadily over time; after 3 years of follow-up, 16% exposed to cardiotoxic drugs experienced an event, and 8% of those exposed to non-cardiotoxic drugs experienced an event. CONCLUSIONS: Patients with cardiac comorbidity are less likely to receive cardiotoxic agents. Use of cardiotoxic agents is common; treatment is related to patient and tumor characteristics and is associated with substantial risk of cardiotoxicity that persists during patients' remaining lifespan.

Association of ß-blocker exposure with outcomes in heart failure differs between African American and white patients.

BACKGROUND: ß-Blockers (BB) are a mainstay of heart failure (HF) treatment, yet there are inconclusive data regarding their efficacy in African American individuals. METHODS AND RESULTS: We performed a retrospective study of insured patients who received care from a large health system who were hospitalized for HF between January 2000 and June 2008 and had a documented ejection fraction <50%. BB exposure was estimated over 6-month rolling windows, using pharmacy claims data. Proportional hazards regression was used to test the association between BB exposure and all-cause hospitalization or death with adjustment for baseline covariates and other HF medication exposure. We performed analyses stratified by race and overall with a BB exposure×race interaction term. A total of 1094 patients met inclusion criteria (476 white and 618 African American individuals). Median follow-up was 2.1 years. In adjusted models, BB exposure was associated with lower risk of death or hospitalization in both groups, but more so in white individuals (hazard ratio, 0.40; 95% confidence interval, 0.27, 0.60; P<0.001) compared with African American individuals (hazard ratio, 0.67; 95% confidence interval, 0.48, 0.94; P=0.024). A formal test for interaction indicated that the protection association for BB exposure differed by race (P=0.098, ß=0.40). Reanalysis restricted to BBs approved for HF or HF-specific hospitalizations did not substantively alter the findings. CONCLUSIONS: BB appears to be 40-50% less effective in preventing death or hospitalization among African American patients with HF as compared with white individuals. Further study is needed to better understand BB effectiveness in African Americans with HF.

The relationship between combination inhaled corticosteroid and long-acting ß-agonist use and severe asthma exacerbations in a diverse population.

BACKGROUND: Safety concerns surround the use of long-acting ß-agonists (LABAs) for the treatment of asthma, even in combination with inhaled corticosteroids (ICSs) and particularly in high-risk subgroups. OBJECTIVE: To estimate the effect of ICS therapy and fixed-dose ICS/LABA combination therapy on severe asthma exacerbations in a racially diverse population. METHODS: ICS and ICS/LABA exposure was estimated from pharmacy data for patients with asthma aged 12 to 56 years who were members of a large health maintenance organization. ICS and ICS/LABA use was estimated for each day of follow-up to create a moving window of exposure. Proportional hazard models were used to assess the relationship between ICS and ICS/LABA combination therapy and severe asthma exacerbations (ie, use of oral corticosteroids, asthma-related emergency department visit, or asthma-related hospitalization). RESULTS: Among the 1828 patients who met the inclusion criteria, 37% were African American, 46% were treated with ICS therapy alone, and 54% were treated with an ICS/LABA combination. Models assessing the risk of severe asthma exacerbations among individuals using ICS treatment alone and ICS/LABA combination therapy suggested that the overall protective effect was as good or better for ICS/LABA combination therapy when compared with ICS treatment alone (hazard ratio, 0.65 vs 0.72, respectively). Analyses in several subgroups, including African American patients, showed a similar statistically significant protective association for combination therapy. CONCLUSION: Treatment with ICS/LABA fixed-dose combination therapy appeared to perform as well as or better than ICS treatment alone in reducing severe asthma exacerbations; this included multiple high-risk subgroups.