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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Adherence analysis using visual analog scale versus claims-based estimation.

BACKGROUND: Although visual analog scales (VAS) have been used frequently in outcomes research, there is little evidence regarding the validity of this scale for measuring medication adherence. OBJECTIVE: To determine whether a VAS self-report measure of medication adherence is concordant with claims-based measurement of adherence. METHODS: A mail survey was conducted in 2005 of persons with diabetes. Prescription claims were obtained for the 1985 survey respondents who used oral diabetes medications and lipid-modifying drugs. The self-reported measure of adherence was a VAS scored 0-100%, and the claims-based measure was the continuous measure of medication gaps (CMG), reverse-coded to yield a score of 0-100%. Dichotomous measures (highly adherent vs poorly adherent) were also created from the VAS and CMG using a cutoff value of 80%. For diabetes and lipid-modifying drugs, the scores on the VAS and CMG (continuous versions) were compared using a Pearson correlation coefficient, while the concordance of the dichotomous versions of the measures was compared using the kappa coefficient. RESULTS: The mean +/- SD for the VAS and CMG for oral diabetes drugs were 95.9 +/- 9.2 and 84.1 +/- 19.2, respectively, and for lipid-modifying drugs, 95.2 +/- 11.2 and 85.3 +/- 20.0, respectively. The VAS-diabetes and CMG-diabetes scales were moderately correlated (r = 0.22), as were the VAS-lipid and CMG-lipid (r = 0.26). The majority (69.0%) of subjects had consistent adherence classifications across the dichotomous versions of VAS-diabetes and CMG-diabetes (kappa = 0.13), while 73.1% of subjects had consistent classifications for the dichotomous VAS-lipid and CMG-lipid (kappa = 0.19). CONCLUSIONS: The VAS self-reports of adherence to medications had moderate concordance with estimates derived from drug benefit claims. Although the majority of subjects were consistently classified by the VAS and claims, the concordance may not be sufficient for direct comparisons of studies using VAS data with studies using claims-based estimates.

A single factor underlies the metabolic syndrome: a confirmatory factor analysis.

OBJECTIVE: Confirmatory factor analysis (CFA) was used to test the hypothesis that the components of the metabolic syndrome are manifestations of a single common factor. RESEARCH DESIGN AND METHODS: Three different datasets were used to test and validate the model. The Spanish and Mauritian studies included 207 men and 203 women and 1,411 men and 1,650 women, respectively. A third analytical dataset including 847 men was obtained from a previously published CFA of a U.S. population. The one-factor model included the metabolic syndrome core components (central obesity, insulin resistance, blood pressure, and lipid measurements). We also tested an expanded one-factor model that included uric acid and leptin levels. Finally, we used CFA to compare the goodness of fit of one-factor models with the fit of two previously published four-factor models. RESULTS: The simplest one-factor model showed the best goodness-of-fit indexes (comparative fit index 1, root mean-square error of approximation 0.00). Comparisons of one-factor with four-factor models in the three datasets favored the one-factor model structure. The selection of variables to represent the different metabolic syndrome components and model specification explained why previous exploratory and confirmatory factor analysis, respectively, failed to identify a single factor for the metabolic syndrome. CONCLUSIONS: These analyses support the current clinical definition of the metabolic syndrome, as well as the existence of a single factor that links all of the core components.

Time to pharmacotherapy change in response to elevated HbA1c test results.

OBJECTIVE: This study describes the clinical management of type 2 diabetes among a cohort of patients receiving oral antidiabetic monotherapy. STUDY DESIGN AND SETTING: A retrospective study was conducted within an integrated Midwestern health system that included all individuals receiving oral antidiabetic monotherapy during the period June 1, 1999 to November 30, 2002 (n = 9335). Among patients with elevated hemoglobin A(1c) (HbA(1c)) test result(s), Kaplan-Meier estimates of median time until pharmacotherapy change were calculated. RESULTS: Among the 8068 patients who had > or = 1 HbA(1c) measurement during the study period, 21.4% were at goal (i.e. HbA(1c) < 7%). Among patients with at least one elevated test result (> or = 7%), the median time to pharmacotherapy change following an HbA(1c) test result of between 7-10% was just over 1 year (372 days, 95% confidence interval [CI] 358-393 days) and 160 days for patients with HbA(1c) > 10%. Among patients with at least two elevated tests, the median time to pharmacotherapy change was 275 days from the second test result of between 7-10%, and 70 days among patients with a second HbA(1c) > 10%. The median time between HbA(1c) testing was 166 days overall, and 154 days among patients with at least one elevated result. CONCLUSION: Despite the known benefits of glycemic control among patients with diabetes, the time between elevated HbA(1c) results and pharmacotherapy change exceeds 12 months for those with HbA(1c) test results between 7-10% and 9 months for those with results over 10%.

Trends in lipid management among patients with diabetes.

OBJECTIVE: To examine trends in lipid management (cholesterol testing, treatment, and goal attainment) among patients with diabetes and to analyze the factors associated with initiation of lipid-lowering therapy. METHODS: We conducted a longitudinal, retrospective study of patients with diabetes identified during a 24-month baseline period (January 1, 1995, to December 31, 1996) and for whom follow-up was continued for 5 years (1997 to 2001). Generalized estimating equations were used to test for time trend effects in lipid management. We modeled the days from baseline to the first lipid-lowering prescription fill date with a multivariate Cox proportional hazards regression model. RESULTS: Rates of lipid testing, treatment, and goal attainment significantly improved (P<0.001) during the 5-year study period: from 37% to 67% for lipid testing; from 19% to 41% for treatment with a lipid-lowering agent; from 22% to 37% for achievement of low-density lipoprotein cholesterol (LDL-C) levels < 100 mg/dL; and from 54% to 75% for achievement of LDL-C levels < 130 mg/dL. The relative likelihood (hazard rate) of treatment with lipid-lowering agents was greater for patients with LDL-C levels > or = 100 mg/dL relative to patients with LDL-C concentrations < 100 mg/dL. Treatment with lipid-lowering agents of patients with a cardiovascular event during follow-up was approximately 3 times more likely relative to those without such an event. CONCLUSION: We found that rates of lipid testing, treatment, and goal attainment improved significantly between 1997 and 2001. Nevertheless, ample room for improvement of these rates continues to exist. Particular attention may be warranted to ensure that patients with diabetes receive lipid-lowering agents not only after a cardiovascular event but also before such an event occurs.

The impact of diabetes on employment and work productivity.

OBJECTIVE: The purpose of this study was to longitudinally examine the effect of diabetes on labor market outcomes. RESEARCH DESIGN AND METHODS: Using secondary data from the first two waves (1992 and 1994) of the Health and Retirement Study, we identified 7,055 employed respondents (51-61 years of age), 490 of whom reported having diabetes in wave 1. We estimated the effect of diabetes in wave 1 on the probability of working in wave 2 using probit regression. For those working in wave 2, we modeled the relationships between diabetic status in wave 1 and the change in hours worked and work-loss days using ordinary least-squares regressions and modeled the presence of health-related work limitations using probit regression. All models control for health status and job characteristics and are estimated separately by sex. RESULTS: Among individuals with diabetes, the absolute probability of working was 4.4 percentage points less for women and 7.1 percentage points less for men relative to that of their counterparts without diabetes. Change in weekly hours worked was not statistically significantly associated with diabetes. Women with diabetes had 2 more work-loss days per year compared with women without diabetes. Compared with individuals without diabetes, men and women with diabetes were 5.4 and 6 percentage points (absolute increase), respectively, more likely to have work limitations. CONCLUSIONS: This article provides evidence that diabetes affects patients, employers, and society not only by reducing employment but also by contributing to work loss and health-related work limitations for those who remain employed.

Clinical outcomes and adherence to medications measured by claims data in patients with diabetes.

OBJECTIVE: Although poor medication adherence may contribute to inadequate diabetes control, ways to feasibly measure adherence in routine clinical practice have yet to be established. The present study was conducted to determine whether pharmacy claims-based measures of medication adherence are associated with clinical outcomes in patients with diabetes. RESEARCH DESIGN AND METHODS: The study setting was a large, integrated delivery and financial system serving the residents of southeastern Michigan. The study population consisted of 677 randomly selected patients aged > or =18 years with a diagnosis of diabetes, hypercholesterolemia, and hypertension and who filled at least one prescription for either an antidiabetic, lipid-lowering, or antihypertensive drug in each of the 3 study years (1999-2001). The main outcome measures were HbA1c, LDL cholesterol levels, and blood pressure. RESULTS: Nonadherent patients had both statistically and clinically worse outcomes than adherent patients. Even after adjusting for demographic and clinical characteristics, nonadherence was significantly associated with HbA1c and LDL cholesterol levels. A 10% increase in nonadherence to metformin and statins was associated with an increase of 0.14% in HbA1c and an increase of 4.9 mg/dl in LDL cholesterol levels. Nonadherence to ACE inhibitors was not significantly associated with blood pressure. CONCLUSIONS: Claims-based measures of medication adherence are associated with clinical outcomes in patients with diabetes and may therefore prove to be useful in clinical practice. More research is needed on methods to introduce claims-based adherence measurements into routine clinical practice and how to use these measurements to effectively improve adherence and health outcomes in chronic care management.