Validity of hospital ICD-10-GM codes to identify acute liver injury in Germany.

PURPOSE: Acute liver injury (ALI) is an important adverse drug reaction. We estimated the positive predictive values (PPVs) of ICD-10-GM codes of ALI used in an international postauthorisation safety study (PASS). METHODS: Analyses used routine data (2007 to 2016, adults) from a German academic hospital in a cross-sectional design. Two algorithms from the PASS were applied to extract potential cases from the hospital information system: specific end point (A) (discharge diagnosis of liver disease-specific codes) and less specific end point (B) (discharge and outpatient-specific and nonspecific codes suggestive of liver injury). ALI cases were confirmed on the basis of plasma liver enzyme activity elevation. Secondary analysis was performed following exclusion of cases with known cancer, chronic liver, biliary and pancreatic disease, heart failure, and alcohol-related disorders, as applied in the PASS. RESULTS: On the basis of ICD codes: outcome A, 154 cases (143 with case notes and lab data for case verification); outcome B, 485 cases (357 with case notes and lab data). ALI was confirmed in 71 outcome A cases, PPV of 49.7% (95% confidence interval [CI], 41.2%-58.1%), and 100 outcome B cases, PPV of 28.0% (95% CI, 23.4%-33.0%). Applying exclusion criteria increased PPV (95% CI) to 62.7% (50.0%-74.2%) for outcome A and 45.7% (37.2%-54.3%) for outcome B. CONCLUSIONS: In safety studies on hepatotoxicity based on routine data using ICD-10-GM discharge codes and when validation of potential cases is not feasible, only the more specific codes should be used to describe ALI, and competing diagnoses for liver injury should be excluded to avoid substantial misclassification.

Validity of ICD-9 and ICD-10 codes used to identify acute liver injury: A study in three European data sources.

PURPOSE: Validating cases of acute liver injury (ALI) in health care data sources is challenging. Previous validation studies reported low positive predictive values (PPVs). METHODS: Case validation was undertaken in a study conducted from 2009 to 2014 assessing the risk of ALI in antidepressants users in databases in Spain (EpiChron and SIDIAP) and the Danish National Health Registers. Three ALI definitions were evaluated: primary (specific hospital discharge codes), secondary (specific and nonspecific hospital discharge codes), and tertiary (specific and nonspecific hospital and outpatient codes). The validation included review of patient profiles (EpiChron and SIDIAP) and of clinical data from medical records (EpiChron and Denmark). ALI cases were confirmed when liver enzyme values met a definition by an international working group. RESULTS: Overall PPVs (95% CIs) for the study ALI definitions were, for the primary ALI definition, 84% (60%-97%) (EpiChron), 60% (26%-88%) (SIDIAP), and 74% (60%-85%) (Denmark); for the secondary ALI definition, 65% (45%-81%) (EpiChron), 40% (19%-64%) (SIDIAP), and 70% (64%-77%) (Denmark); and for the tertiary ALI definition, 25% (18%-34%) (EpiChron), 8% (7%-9%) (SIDIAP), and 47% (42%-52%) (Denmark). The overall PPVs were higher for specific than for nonspecific codes and for hospital discharge than for outpatient codes. The nonspecific code "unspecified jaundice" had high PPVs in Denmark. CONCLUSIONS: PPVs obtained apply to patients using antidepressants without preexisting liver disease or ALI risk factors. To maximize validity, studies on ALI should prioritize hospital specific discharge codes and should include hospital codes for unspecified jaundice. Case validation is required when ALI outpatient cases are considered.

Antidepressant use in Denmark, Germany, Spain, and Sweden between 2009 and 2014: Incidence and comorbidities of antidepressant initiators.

BACKGROUND: We aimed to describe patterns of use and characteristics of 10 commonly used antidepressants for the period 2009-2014 in Denmark, Germany, Spain, and Sweden. METHODS: Adult initiators from 2009 to 2014 of each study antidepressant were identified in four countries using five data sources: the Danish National registers, GePaRD (Germany), EpiChron (Aragon, Spain), SIDIAP (Catalonia, Spain), and the Swedish National Registers. The study included 10 study antidepressants: citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, mirtazapine, and agomelatine. RESULTS: Citalopram was the most prescribed study antidepressant, followed by mirtazapine. Paroxetine and agomelatine were the least prescribed antidepressants. Mirtazapine was widely used among older antidepressant initiators with higher percentages of comorbidities at baseline, and fluoxetine was used among young patients. Citalopram and amitriptyline had the lowest percentage of multiple antidepressant use in the 12 months prior to the current treatment episode, while agomelatine, duloxetine, and venlafaxine had the highest percentage of multiple antidepressant use in the year prior to the current treatment episode. LIMITATIONS: The most important limitations are exposure information based on filled prescriptions, focus on antidepressant initiators only, lack of information on the indication, and heterogeneity of the type of data across data sources. CONCLUSIONS: Results of this study including 4.8 million study antidepressant initiators of study antidepressants suggest that citalopram and mirtazapine are the most commonly prescribed antidepressants. Agomelatine and paroxetine were the least used antidepressants in the participating populations. Mirtazapine was the antidepressant most commonly prescribed among older antidepressant initiators with high percentage of comorbidities at baseline, whereas fluoxetine was commonly used among young patients.

Cardiovascular risk associated with the use of glitazones, metformin and sufonylureas: meta-analysis of published observational studies.

BACKGROUND: The results of observational studies evaluating and comparing the cardiovascular safety of glitazones, metformin and sufonylureas are inconsistent.To conduct and evaluate heterogeneity in a meta-analysis of observational studies on the risk of acute myocardial infarction (AMI) or stroke in patients with type 2 diabetes using non-insulin blood glucose-lowering drugs (NIBGLD). METHODS: We systematically identified and reviewed studies evaluating NIBGLD in patients with type 2 diabetes indexed in Medline, Embase, or the Cochrane Library that met prespecified criteria. The quality of included studies was assessed with the RTI item bank. Results were combined using fixed- and random-effects models, and the Higgins I(2) statistic was used to evaluate heterogeneity. Sensitivity analyses by study quality were conducted. RESULTS: The summary relative risk (sRR) (95% CI) of AMI for rosiglitazone versus pioglitazone was 1.13 (1.04-1.24) [I(2) = 55%]. In the sensitivity analysis, heterogeneity was reduced [I(2) = 16%]. The sRR (95% CI) of stroke for rosiglitazone versus pioglitazone was 1.18 (1.02-1.36) [I(2) = 42%]. There was strong evidence of heterogeneity related to study quality in the comparisons of rosiglitazone versus metformin and rosiglitazone versus sulfonylureas (I (2) ≥ 70%). The sRR (95% CI) of AMI for sulfonylurea versus metformin was 1.24 (1.14-1.34) [I(2) = 41%] and for pioglitazone versus metformin was 1.02 (0.75-1.38) [I(2) = 17%]. Sensitivity analyses decreased heterogeneity in most comparisons. CONCLUSION/INTERPRETATION: Sulfonylureas increased the risk of AMI by 24% compared with metformin; an imprecise point estimate indicated no difference in risk of AMI when comparing pioglitazone with metformin. The presence of heterogeneity precluded any conclusions on the other comparisons. The quality assessment was valuable in identifying methodological problems in the individual studies and for analysing potential sources of heterogeneity.

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.

Quality assessment of observational studies in a drug-safety systematic review, comparison of two tools: the Newcastle-Ottawa Scale and the RTI item bank.

BACKGROUND: The study objective was to compare the Newcastle-Ottawa Scale (NOS) and the RTI item bank (RTI-IB) and estimate interrater agreement using the RTI-IB within a systematic review on the cardiovascular safety of glucose-lowering drugs. METHODS: We tailored both tools and added four questions to the RTI-IB. Two reviewers assessed the quality of the 44 included studies with both tools, (independently for the RTI-IB) and agreed on which responses conveyed low, unclear, or high risk of bias. For each question in the RTI-IB (n=31), the observed interrater agreement was calculated as the percentage of studies given the same bias assessment by both reviewers; chance-adjusted interrater agreement was estimated with the first-order agreement coefficient (AC1) statistic. RESULTS: The NOS required less tailoring and was easier to use than the RTI-IB, but the RTI-IB produced a more thorough assessment. The RTI-IB includes most of the domains measured in the NOS. Median observed interrater agreement for the RTI-IB was 75% (25th percentile [p25] =61%; p75 =89%); median AC1 statistic was 0.64 (p25 =0.51; p75 =0.86). CONCLUSION: The RTI-IB facilitates a more complete quality assessment than the NOS but is more burdensome. The observed agreement and AC1 statistic in this study were higher than those reported by the RTI-IB's developers.

The risk of heart failure associated with the use of noninsulin blood glucose-lowering drugs: systematic review and meta-analysis of published observational studies.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are at high risk of heart failure. A summary of the effects of blood glucose-lowering drugs other than glitazones on the risk of heart failure in routine clinical practice is lacking. The objective of this study was to conduct a systematic review and meta-analysis of observational studies on the risk of heart failure when using blood glucose-lowering drugs. METHODS: We systematically identified and reviewed cohort and case-control studies in which the main exposure of interest was noninsulin blood glucose-lowering medications in patients with T2DM. We searched Medline, Embase, and the Cochrane Library to identify publications meeting prespecified eligibility criteria. The quality of included studies was assessed with the Newcastle-Ottawa Scale and the RTI item bank. Results were combined using fixed and random-effects models when at least 3 independent data points were available for a drug-drug comparison. RESULTS: The summary relative risk of heart failure in rosiglitazone users versus pioglitazone users (95% CI) was 1.16 (1.05-1.28) (5 cohort studies). Heterogeneity was present (I2 = 66%). For new users (n = 4) the summary relative risk was 1.21 (1.14-1.30) and the heterogeneity was reduced (I2 = 31%);. The summary relative risk for rosiglitazone versus metformin was 1.36 (95% CI, 1.17-1.59) (n = 3). The summary relative risk (95% CI) of heart failure in sulfonylureas users versus metformin users was 1.17 (95% CI, 1.06-1.29) (5 cohort studies; I2 = 24%) and 1.22 (1.02-1.46) when restricted to new users (2 studies).Information on other comparisons was very scarce. Information on dose and duration of treatment effects was lacking for most comparisons. Few studies accounted for disease severity; therefore, confounding by indication might be present in the majority of the within-study comparisons of this meta-analysis. CONCLUSIONS: Use of glitazones and sulfonylureas was associated with an increased risk of heart failure compared with metformin use. However, indication bias cannot be ruled out. Ongoing large multidatabase studies will help to evaluate the risk of heart failure in treated patients with diabetes, including those using newer blood glucose-lowering therapies.

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.

Racial disparities in lipid control in patients with diabetes.

OBJECTIVES: To describe lipid management over time in a cohort of insured patients with diabetes and evaluate differences between African American and white patients. STUDY DESIGN: Automated claims data were used to identify a cohort of 11,411 patients with diabetes in 1997 to 1998. Patients were followed through 2007. METHODS: Rates of hypercholesterolemia testing, treatment, and goal attainment were measured annually. Treatment was determined by a claim for lipid-lowering agents, and goal attainment was defined as a low-density lipoprotein cholesterol (LDL-C) level <100 mg/dL. RESULTS: During the study period, LDL-C testing increased from 48% to 70% among African American patients and from 61% to 77% among white patients. Treatment with lipid-lowering drugs increased from 23% to 56% among African American patients and 33% to 61% among white patients. The proportion at goal increased from 35% to 76% and from 24% to 59% among white and African American patients, respectively. African American patients were less likely to be tested for LDL-C (odds ratio [OR] 0.79; 95% confidence interval [CI] 0.73-0.86), treated with lipidlowering agents (OR 0.72; 95% CI 0.65-0.80), have their medication dosage altered (OR 0.65; 95% CI 0.59-0.73), or attain LDL-C goal (OR 0.59; 95% CI 0.56-0.63) compared with white patients. CONCLUSIONS: Although rates of LDL-C testing, treatment, and goal attainment improved over time, racial disparities in dyslipidemia management continued to exist. Further studies to determine the causes of differences in management by race are warranted.

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.

Multicenter cluster-randomized trial of a multifactorial intervention to improve antihypertensive medication adherence and blood pressure control among patients at high cardiovascular risk (the COM99 study).

BACKGROUND: Medication nonadherence is common and results in preventable disease complications. This study assessed the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events. METHODS AND RESULTS: In this multicenter, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥ 50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients' pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end point of all-cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62, 95% confidence interval 0.50 to 0.78) and were more likely to be adherent (odds ratio 1.91, 95% confidence interval 1.19 to 3.05) than control group patients at 6 months. After 5 years, 16% of the patients in the intervention group and 19% in the control group met the composite end point (hazard ratio 0.97, 95% confidence interval 0.67 to 1.39). CONCLUSIONS: A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events.

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.

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.

Reducing the health risks of diabetes: how self-determination theory may help improve medication adherence and quality of life.

PURPOSE: The purpose of this study is to apply the self-determination theory (SDT) model of health behavior to predict medication adherence, quality of life, and physiological outcomes among patients with diabetes. METHODS: Patients with diabetes (N = 2973) receiving care from an integrated health care delivery system in 2003 and 2004 were identified from automated databases and invited to participate in this study. In 2005, patients responded to a mixed telephone-and-mail survey assessing perceived autonomy support from health care providers, autonomous self-regulation for medication use, perceived competence for diabetes self-management, medication adherence, and quality of life. In 2006, pharmacy claims data were used to indicate medication adherence, and patients' non-high-density lipoprotein (HDL) cholesterol, A1C, and glucose levels were assessed. RESULTS: The SDT model of health behavior provided adequate fit to the data. As hypothesized, perceived autonomy support from health care providers related positively to autonomous self-regulation for medication use, which in turn related positively to perceived competence for diabetes self-management. Perceived competence then related positively to quality of life and medication adherence, and the latter construct related negatively to non-HDL cholesterol, A1C, and glucose levels. CONCLUSIONS: Health care providers' support for patients' autonomy and competence around medication use and diabetes self-management related positively to medication adherence, quality of life, and physiological outcomes among patients with diabetes.

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

PURPOSE: 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. METHODS: We conducted a retrospective cohort study in a large vertically integrated health system in southeast Michigan. Cohort inclusion criteria included adult patients with diabetes treated with oral medications and followed longitudinally within the health system between 1 January 2000 and 1 December 2006. The primary outcome was fatal and non-fatal acute myocardial infarction (AMI). Secondary outcomes included hospitalizations for congestive heart failure (CHF), fatal, and non-fatal cerebrovascular accidents (CVA) and transient ischemic attacks (TIA), combined coronary heart disease (CHD) events, and all-cause mortality. RESULTS: 19,171 patients were included in this study. Use of TZDs (adjusted hazard ratio (aHR) with propensity adjustment (PA), 0.92; 95% confidence interval (CI) 0.73-1.17), rosiglitazone (aHR with PA, 1.06; 95%CI 0.66-1.70), and pioglitazone (aHR with PA, 0.91; 95%CI 0.69-1.21) was not associated with a higher risk of AMI. However, pioglitazone use was associated with a reduction in all-cause mortality (aHR with PA, 0.60; 95%CI 0.42-0.96). Compared with rosiglitazone, pioglitazone use was associated with a lower risk of all outcomes assessed, particularly CHF (p = 0.013) and combined CHD events (p = 0.048). CONCLUSIONS: Our findings suggest that pioglitazone may have a more favorable risk profile when compared to rosiglitazone, arguing against a singular effect for TZDs on cardiovascular outcomes.

Relationship between recent short-acting beta-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.

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.

When more is not better: treatment intensification among hypertensive patients with poor medication adherence.

BACKGROUND: Hypertension may be poorly controlled because patients do not take their medications (poor adherence) or because providers do not increase medication when appropriate (lack of medication intensification, or "clinical inertia"). We examined the prevalence of and relationship between patient adherence and provider treatment intensification. METHODS AND RESULTS: We used a retrospective cohort study of hypertensive patients who had filled prescriptions for 1 or more blood pressure (BP) medications at Veterans' Affairs (VA) healthcare facilities in a Midwestern VA administrative region. Our sample included all patients who received at least 2 outpatient BP medication refills during 2004 and had 1 or more outpatient primary care visits with an elevated systolic BP >140 but <200 mm Hg or diastolic BP >90 mm Hg during 2005 (n=38,327). For each episode of elevated BP during 2005 (68,610 events), we used electronic pharmacy refill data to examine patients' BP medication adherence over the prior 12 months and whether providers increased doses or added BP medications ("intensification"). Multivariate analyses accounted for the clustering of elevated BP events within patients and adjusted for patient age, comorbidities, number of BP medications, encounter systolic BP, and average systolic BP over the prior year. Providers intensified medications in 30% of the 68,610 elevated BP events, with almost no variation in intensification regardless of whether patients had good or poor BP medication adherence. After adjustment, intensification rates were 31% among patients who had "gaps" of <20% (days on which patients should have had medication but no medication was available because medications had not been refilled), 34% among patients with refill gaps of 20% to 59%, and 32% among patients with gaps of 60% or more. CONCLUSIONS: Intensification of medications occurred in fewer than one third of visits in which patients had an elevated BP. Patients' prior medication adherence had little impact on providers' decisions about intensifying medications, even at very high levels of poor adherence. Addressing both patient adherence and provider intensification simultaneously would most likely result in better BP control.

Improving asthma care through recertification: a cluster randomized trial.

BACKGROUND: As part of recertification, the American Board of Internal Medicine requires its diplomats to complete at least 1 practice improvement module (PIM). We assessed whether completing an asthma-specific PIM resulted in improved patient outcomes. METHODS: Practices were the unit of randomization in this cluster randomized trial. Physicians in the intervention group were asked to complete the PIM through its planning phase. The primary outcome was the dispensing of an inhaled corticosteroid (ICS) after a postintervention visit for asthma. Secondary outcomes included patient reported processes of care, asthma-related heath care use, and asthma severity. Analyses were adjusted for baseline rates at the cluster-level as well as for individual sociodemographic characteristics. RESULTS: Eight practices (19 internists) were randomized to the intervention group and 8 practices (21 internists) to the control group. For the primary outcome, ICS fill rates, patients seen by intervention group physicians were not more likely to fill an ICS prescription in the postintervention period than patients seen by control group physicians (adjusted odd ratio [AOR], 1.00; 95% confidence interval [CI], 0.64-1.56). Patients seen for asthma by intervention group physicians were less likely to receive a written action plan than patients seen by control group physicians (AOR, 0.67; 95% CI, 0.48-0.93); however, they were more likely to discuss potential asthma triggers (AOR, 1.62; 95% CI, 1.08-2.42) and had lower self-reported asthma severity measures (unadjusted P = .03). Per-protocol analysis supported the latter 2 associations. CONCLUSION: A PIM designed to improve asthma care did not improve filling of ICS prescriptions but may have lessened asthma severity through an increased discussion of asthma triggers.

Patients with asthma who do not fill their inhaled corticosteroids: a study of primary nonadherence.

BACKGROUND: Adherence to inhaled corticosteroids (ICSs) is known to be poor among patients with asthma; however, little is known about patients who do not fill their ICS prescriptions (ie, primary nonadherence). OBJECTIVE: To estimate rates of primary nonadherence and to explore associated factors. METHODS: The study population was members of a large health maintenance organization in southeast Michigan who met the following criteria: age 5 to 56 years; previous diagnosis of asthma; at least 1 electronic prescription for an ICS between February 17, 2005, and June 1, 2006; and at least 3 months follow-up after the ICS prescription. Adherence was estimated by using electronic prescription information and pharmacy claims data. Multivariable stepwise analysis was used to identify factors associated with primary nonadherence compared with adherent patients. RESULTS: One thousand sixty-four patients met the study criteria and had calculable adherence. Of these patients, 82 (8%) never filled their ICS prescription. Stepwise regression identified the following factors to be associated with an increased likelihood of primary nonadherence: younger age, female sex, African American race-ethnicity, and lower rescue medication use. Factors associated with primary nonadherence differed between race-ethnic groups. CONCLUSION: Primary nonadherence was associated with lower baseline rescue medication use, which may reflect lower perceived need for ICS therapy in patients with milder asthma. Rates of primary nonadherence and the factors which influenced this outcome differed by race-ethnicity. CLINICAL IMPLICATIONS: Understanding patient characteristics associated with primary nonadherence may be important for disease management, because many patients with asthma do not fill their ICS prescriptions.