Karen Wells

Quantifying the proportion of severe asthma exacerbations attributable to inhaled corticosteroid nonadherence.

BACKGROUND Asthma is an inflammatory condition often punctuated by episodic symptomatic worsening, and accordingly, patients with asthma might have waxing and waning adherence to controller therapy. OBJECTIVE We sought to measure changes in inhaled corticosteroid (ICS) adherence over time and to estimate the effect of this changing pattern of use on asthma exacerbations. METHODS ICS adherence was estimated from electronic prescription and fill information for 298 participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity. For each patient, we calculated a moving average of ICS adherence for each day of follow-up. Asthma exacerbations were defined as the need for oral corticosteroids, an asthma-related emergency department visit, or an asthma-related hospitalization. Proportional hazard models were used to assess the relationship between ICS medication adherence and asthma exacerbations. RESULTS Adherence to ICS medications began to increase before the first asthma exacerbation and continued afterward. Adherence was associated with a reduction in exacerbations but was only statistically significant among patients whose adherence was greater than 75% of the prescribed dose (hazard ratio, 0.61; 95% CI, 0.41-0.90) when compared with patients whose adherence was 25% or less. This pattern was largely confined to patients whose asthma was not well controlled initially. An estimated 24% of asthma exacerbations were attributable to ICS medication nonadherence. CONCLUSIONS ICS adherence varies in the time period leading up to and after an asthma exacerbation, and nonadherence likely contributes to a large number of these exacerbations. High levels of adherence are likely required to prevent these events.

Thiazolidinedione Use and the Longitudinal Risk of Fractures in Patients with Type 2 Diabetes Mellitus

CONTEXT Thiazolidinedione (TZD) use has recently been associated with an increased risk of fractures. OBJECTIVE The aim of this study was to determine the time-dependent relationship between TZD use and fracture risk. DESIGN We conducted a retrospective cohort study in a large health system in southeast Michigan. PATIENTS PATIENTS who received care from the health system were included if they were at least 18 yr of age, had a diagnosis of diabetes, and had at least one prescription for an oral diabetes medication. These criteria identified 19,070 individuals (9,620 women and 9,450 men). INTERVENTION This study compared patients treated with TZDs to patients without TZD treatment. Cox proportional hazard models were used to assess the relationship between exposure and outcomes. MAIN OUTCOME MEASURES The primary outcome was the time to fracture. Secondary analyses examined the risk of fractures in subgroups defined by sex and age. RESULTS TZD use was associated with an increased risk of fracture in the cohort overall [adjusted hazard ratio (aHR), 1.35; 95% confidence interval (CI), 1.05-1.71] and in women (aHR, 1.57; 95% CI, 1.16-2.14), but not in men (aHR, 1.05; 95% CI, 0.70-1.58). Women more than 65 yr of age appeared to be at greatest risk for fracture (aHR, 1.72; 95% CI, 1.17-2.52). Among women, the increased fracture risk was not apparent until after 1 yr of TZD treatment. CONCLUSIONS TZD use was associated with an increased risk for fractures in women, particularly at ages above 65 yr. Clinicians should be aware of this association when considering TZD therapy so as to appropriately manage and counsel their patients.

Incidence of non‐Hodgkin's lymphoma among individuals with chronic hepatitis B virus infection

Although hepatitis C virus (HCV) infection has been shown to be associated with development of non‐Hodgkins lymphoma (NHL), few studies have investigated the association between chronic HBV infection and NHL. The purpose of this study was to compare the incidence of NHL between patients with and without chronic hepatitis B virus (HBV) infection. Using automated laboratory result and clinical data from two United States health systems, we identified individuals with chronic HBV infection from January 1, 1995 through December 31, 2001. Using each health systems population‐based tumor registry, we identified all cases of NHL diagnosed through December 31, 2002. We excluded any individual with a history of NHL or human immunodeficiency virus (HIV). We fit Cox proportional hazards models to calculate hazard ratios comparing the incidence of NHL between chronic HBV‐infected patients (N = 3,888) and patients without HBV (N = 205,203) drawn from the source populations. We identified 8 NHL cases in the chronic HBV infection cohort and 111 cases in the comparison cohort. Patients with chronic HBV infection were 2.8 times more likely to develop NHL than matched comparison patients (adjusted hazard ratio = 2.80, 95% confidence interval = 1.16‐6.75), after controlling for age, race, sex, income, Charlson comorbidity index, study site, and HCV infection. Conclusion: chronic HBV‐infected patients were nearly 3 times more likely to develop NHL than comparison patients. (HEPATOLOGY 2007.)

Race-Ethnic Differences in Factors Associated with Inhaled Steroid Adherence among Adults with Asthma

RATIONALE Adherence to inhaled corticosteroid (ICS) medication is known to be low overall, but tends to be lower among African-American patients when compared with white patients. OBJECTIVES To understand the factors that contribute to ICS adherence among African-American and white adults with asthma. METHODS Eligible individuals had a prior diagnosis of asthma, one or more ICS prescriptions, and were members of a large health maintenance organization in southeast Michigan. Individuals were sent a survey that included questions about internal factors (e.g., patient beliefs, knowledge, and motivation) and external factors (e.g., socioeconomic status, barriers to care, social support, and stressors) potentially related to ICS adherence. Adherence was calculated using electronic prescription and fill data. Stepwise regression was used to identify factors associated with adherence before and after stratifying by race-ethnicity. MEASUREMENTS AND MAIN RESULTS Surveys were returned by 1,006 (56.3%) of 1,787 eligible patients. Adjusting for internal factors, but not external factors, diminished the relationship between race-ethnicity and ICS adherence. Among African-American patients, readiness to take ICS medication was the only internal or external factor significantly associated with ICS adherence; it explained 5.6% of the variance in adherence. Among white patients, perceived ICS necessity, ICS knowledge, doctors being perceived as the source of asthma control, and readiness to take medication were the internal factors associated with ICS adherence; these accounted for 19.8% of the variance in adherence. CONCLUSIONS Factors associated with ICS adherence appear to differ between African-American and white patients, suggesting that group-specific approaches are needed to improve adherence.

A cluster-randomized trial to provide clinicians inhaled corticosteroid adherence information for their patients with asthma

BACKGROUND Inhaled corticosteroid (ICS) nonadherence is common among patients with asthma; however, interventions to improve adherence have often been complex and not easily applied to large patient populations. OBJECTIVE To assess the effect of supplying patient adherence information to primary care providers. METHODS Patients and providers were members of a health system serving southeast Michigan. Providers (88 intervention; 105 control) and patients (1335 intervention; 1363 control) were randomized together by practice. Patients were age 5 to 56 years, had a diagnosis of asthma, and had existing prescriptions for ICS medication. Adherence was estimated by using prescription and fill data. Unlike clinicians in the control arm, intervention arm providers could view updated ICS adherence information on their patients via electronic prescription software, and further details on patient ICS use could be viewed by selecting that option. The primary outcome was ICS adherence in last 3 months of the study period. RESULTS At the study end for the intention-to-treat analysis, ICS adherence was not different among patients in the intervention arm compared with those in the control arm (21.3% vs 23.3%, respectively; P = .553). However, adherence was significantly higher among patients whose clinician elected to view their detailed adherence information (35.7%) compared with both control arm patients (P = .026) and intervention arm patients whose provider did not view adherence data (P = .002). CONCLUSIONS Overall, providing adherence information to clinicians did not improve ICS use among patients with asthma. However, patient use may improve when clinicians are sufficiently interested in adherence to view the details of this medication use.

Relationship between thiazolidinedione use and cardiovascular outcomes and all-cause mortality among patients with diabetes: a time-updated propensity analysis†

To investigate the association of the thiazolidinediones (TZDs), rosiglitazone, and pioglitazone, together and individually on the risk of cardiovascular outcomes and all‐cause mortality, using time‐updated propensity score adjusted analysis.

Barriers to the initiation of, and persistence with, insulin therapy

ABSTRACT Objectives: Many patients with Type 2 diabetes mellitus (DM) delay and/or discontinue the use of insulin. This study determined patient-perceived barriers to the initiation of, and persistence with, insulin therapy. Research design and methods: Patients ≥ 18 years with Type 2 DM and ≥ 1 elevated HbA1c test result (≥ 9%) were identified from computerized laboratory test results within a single healthcare system, a study limitation. Insulin use patterns were characterized by automated pharmacy claims data, and patients were classified into those who discontinued insulin use (discontinuers) or those who did not initiate insulin use (non-initiators). Telephone interviews were conducted to determine the barriers to initiation of, and persistence with, insulin therapy. Results: Response rates were 80.0% (73/91) for discontinuers and 82.0% (129/157) for non-initiators. Pharmacy claims data indicated that discontinuers stopped filling prescriptions for insulin; 46.6% of patients self-reported discontinuing insulin. The average time between first and last prescription for insulin among discontinuers was 4.9 years (SD = 4.4). The most common reasons for discontinuation were related to insulin injection (74.0%) and a doctors advice not to use insulin (47.1%). In the non-initiator group, 86.1% were never advised by a healthcare provider to take insulin. Conclusions: These findings suggest that issues related to insulin injection are the primary reason patients with Type 2 DM discontinue insulin therapy. Understanding these patterns is important to develop interventions to overcome barriers to treatment and improve the medical outcomes of patients with Type 2 DM.

Relationship between recent short-acting β-agonist use and subsequent asthma exacerbations

BACKGROUND US national guidelines recommend assessing short-acting beta-agonist (SABA) medication use as a marker of asthma severity and control. However, the relationship between recent SABA use and asthma exacerbations is not currently known. OBJECTIVE To evaluate the proximal relationship between the type and frequency of SABA use and asthma-related outcomes. METHODS We evaluated SABA use among patients with asthma ages 5 to 56 years who were members of a large health maintenance organization in southeast Michigan. Frequency of use was estimated from pharmacy data assessing the timing and amount of SABA fills. Cox proportional hazards models were used to examine the prospective relationship between average daily SABA use for 3 months and outcomes associated with poor asthma control (ie, oral corticosteroids use, asthma-related emergency department visits, and asthma-related hospitalizations). We separately accounted for SABA metered-dose inhaler (MDI) and SABA nebulizer use. RESULTS Of the 2,056 patients who met study criteria, 1,569 (76.3%) had used a SABA medication in their baseline year. After adjusting for potential confounders, SABA nebulizer use was associated with asthma-related emergency department visits (adjusted hazard ratio [aHR], 6.32; 95% confidence interval [CI], 2.38 to 16.80) and asthma-related hospitalizations (aHR, 21.62; 95% CI, 3.17 to 147.57). In contrast, frequency of SABA MDI use was not associated with these outcomes. CONCLUSIONS Frequency of SABA use during a 3-month period was associated with poor asthma outcomes. The relationship with poor asthma outcomes was strongest for SABA nebulizer use, suggesting that the type of SABA used is also of prognostic importance.

Dual-specificity phosphatase 1 as a pharmacogenetic modifier of inhaled steroid response among asthmatic patients

BACKGROUND Inhaled corticosteroids (ICSs) are considered first-line treatment for persistent asthma, yet there is significant variability in treatment response. Dual-specificity phosphatase 1 (DUSP1) appears to mediate the anti-inflammatory action of corticosteroids. OBJECTIVE We sought to determine whether variants in the DUSP1 gene are associated with clinical response to ICS treatment. METHODS Study participants with asthma were drawn from the following multiethnic cohorts: the Genetics of Asthma in Latino Americans (GALA) study; the Study of African Americans, Asthma, Genes & Environments (SAGE); and the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). We screened GALA study participants for genetic variants that modified the relationship between ICS use and bronchodilator response. We then replicated our findings in SAGE and SAPPHIRE participants. In a group of SAPPHIRE participants treated with ICSs for 6 weeks, we examined whether a DUSP1 polymorphism was associated with changes in FEV(1) and self-reported asthma control. RESULTS The DUSP1 polymorphisms rs881152 and rs34507926 localized to different haplotype blocks and appeared to significantly modify the relationship between ICS use and bronchodilator response among GALA study participants. This interaction was also seen for rs881152 among SAPPHIRE but not SAGE participants. Among the group of SAPPHIRE participants prospectively treated with ICSs for 6 weeks, rs881152 genotype was significantly associated with changes in self-reported asthma control but not FEV(1). CONCLUSION DUSP1 polymorphisms were associated with clinical response to ICS therapy and therefore might be useful in the future to identify asthmatic patients more likely to respond to this controller treatment.

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 metformins 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.