Manel Pladevall

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.

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.

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.

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.

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.

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

BackgroundPatients 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.MethodsWe 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.ResultsThe 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.ConclusionsUse 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.

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.

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