Faculty Bibliography

BACKGROUND: Clinical prediction rules (CPRs) represent well-validated but underutilized evidence-based medicine tools at the point-of-care. To date, an inability to integrate these rules into an electronic health record (EHR) has been a major limitation and we are not aware of a study demonstrating the use of CPR's in an ambulatory EHR setting. The integrated clinical prediction rule (iCPR) trial integrates two CPR's in an EHR and assesses both the usability and the effect on evidence-based practice in the primary care setting. METHODS: A multi-disciplinary design team was assembled to develop a prototype iCPR for validated streptococcal pharyngitis and bacterial pneumonia CPRs. The iCPR tool was built as an active Clinical Decision Support (CDS) tool that can be triggered by user action during typical workflow. Using the EHR CDS toolkit, the iCPR risk score calculator was linked to tailored ordered sets, documentation, and patient instructions. The team subsequently conducted two levels of 'real world' usability testing with eight providers per group. Usability data were used to refine and create a production tool. Participating primary care providers (n = 149) were randomized and intervention providers were trained in the use of the new iCPR tool. Rates of iCPR tool triggering in the intervention and control (simulated) groups are monitored and subsequent use of the various components of the iCPR tool among intervention encounters is also tracked. The primary outcome is the difference in antibiotic prescribing rates (strep and pneumonia iCPR's encounters) and chest x-rays (pneumonia iCPR only) between intervention and control providers. DISCUSSION: Using iterative usability testing and development paired with provider training, the iCPR CDS tool leverages user-centered design principles to overcome pervasive underutilization of EBM and support evidence-based practice at the point-of-care. The ongoing trial will determine if this collaborative process will lead to higher rates of utilization and EBM guided use of antibiotics and chest x-ray's in primary care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01386047.

Few data are available on factors associated with low adherence or early clopidogrel discontinuation after percutaneous coronary intervention (PCI). Patients (n = 284) were evaluated before hospital discharge after PCI to identify factors associated with low adherence to clopidogrel 30 days later. Adherence to daily medications before PCI was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8) and categorized as low (score <6), medium (score 6 to <8), or high (score 8). Low adherence to clopidogrel was defined as MMAS-8 score <6 (n = 21) or having discontinued clopidogrel (n = 11), which was ascertained during a 30-day interview after PCI. At 30 days after PCI, 11% of patients had low adherence to clopidogrel. Odds ratios (95% confidence intervals [CIs]) for low adherence to clopidogrel were 3.78 (1.09 to 13.1), 3.06 (1.36 to 6.87), 2.46 (0.97 to 6.27), and 3.36 (0.99 to 11.4) for patients who before PCI reported taking smaller doses of medication because of cost, had difficulty filling prescriptions, had difficulty reaching their primary physician, and were not comfortable asking their doctor for instructions, respectively. Odds ratios (95% CIs) for low clopidogrel adherence after PCI in patients with medium and low versus high adherence to daily medications before PCI were 6.13 (1.34 to 28.2) and 10.9 (2.46 to 48.7), respectively. The c-statistic associated with MMAS-8 scores before PCI for discriminating low clopidogrel adherence at 30 days after PCI was 0.733 (95% CI 0.650 to 0.852). In conclusion, adherence to daily medications before PCI may be a useful indicator for identifying patients who will have low clopidogrel adherence after PCI.

BACKGROUND: The prevalence of albuminuria in the general population is high, but awareness of it is low. Therefore, we sought to develop and validate a self-assessment tool that allows individuals to estimate their probability of having albuminuria. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: The population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study for model development and the National Health and Nutrition Examination Survey (NHANES) 1999-2004 for model validation. US adults 45 years or older in the REGARDS Study (n = 19,697) and NHANES 1999-2004 (n = 7,168). PREDICTOR: Candidate items for the self-assessment tool were collected using a combination of interviewer- and self-administered questionnaires. OUTCOME: Albuminuria was defined as a urinary albumin to urinary creatinine ratio >/=30 mg/g in spot samples. RESULTS: 8 items were included in the self-assessment tool (age, race, sex, current smoking, self-rated health, and self-reported history of diabetes, hypertension, and stroke). These items provided a C statistic of 0.709 (95% CI, 0.699-0.720) and good model fit (Hosmer-Lemeshow chi(2)P = 0.49). In the external validation data set, the C statistic for discriminating individuals with and without albuminuria using the self-assessment tool was 0.714. Using a threshold of >/=10% probability of albuminuria from the self-assessment tool, 36% of US adults 45 years or older in NHANES 1999-2004 would test positive and be recommended for screening. Sensitivity, specificity, and positive and negative predictive values for albuminuria associated with a probability >/=10% were 66%, 68%, 23%, and 93%, respectively. LIMITATIONS: Repeated urine samples were not available to assess the persistency of albuminuria. CONCLUSIONS: 8 self-report items provide good discrimination for the probability of having albuminuria. This tool may encourage individuals with a high probability to request albuminuria screening.

BACKGROUND: Observational studies suggest that there are differences in adherence to antihypertensive medications in different classes. Our objective was to quantify the association between antihypertensive drug class and adherence in clinical settings. METHODS AND RESULTS: Studies were identified through a systematic search of English-language articles published from the inception of computerized databases until February 1, 2009. Studies were included if they measured adherence to antihypertensives using medication refill data and contained sufficient data to calculate a measure of relative risk of adherence and its variance. An inverse-variance-weighted random-effects model was used to pool results. Hazard ratios (HRs) and odds ratios were pooled separately, and HRs were selected as the primary outcome. Seventeen studies met inclusion criteria. The pooled mean adherence by drug class ranged from 28% for beta-blockers to 65% for angiotensin II receptor blockers. There was better adherence to angiotensin II receptor blockers compared with angiotensin-converting enzyme inhibitors (HR, 1.33; 95% confidence interval, 1.13 to 1.57), calcium channel blockers (HR, 1.57; 95% confidence interval, 1.38 to 1.79), diuretics (HR, 1.95; 95% confidence interval, 1.73 to 2.20), and beta-blockers (HR, 2.09; 95% confidence interval, 1.14 to 3.85). Conversely, there was lower adherence to diuretics compared with the other drug classes. The same pattern was present when studies that used odds ratios were pooled. After publication bias was accounted for, there were no longer significant differences in adherence between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors or between diuretics and beta-blockers. CONCLUSION: In clinical settings, there are important differences in adherence to antihypertensives in separate classes, with lowest adherence to diuretics and beta-blockers and highest adherence to angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors. However, adherence was suboptimal regardless of drug class.

Increased left ventricular (LV) mass and changes in LV geometry may precede hypertension onset. The authors examined the associations of LV mass and geometry, assessed by cardiac magnetic resonance imaging, with hypertension incidence in 2,567 normotensive participants enrolled in 2000-2002 in the Multi-Ethnic Study of Atherosclerosis, an ethnically diverse, population-based, US study. Over a median follow-up of 4.8 years, 745 (29%) participants developed hypertension. In a fully adjusted model including baseline blood pressure, the relative risks of incident hypertension from the lowest to highest LV mass quartile were 1.00 (referent), 1.13 (95% confidence interval (CI): 0.89, 1.43), 1.28 (95% CI: 1.00, 1.63), and 1.78 (95% CI: 1.38, 2.30) (P < 0.001 for linear trend). Higher levels of LV concentric geometry, defined by higher LV mass to end-diastolic volume quartiles, were associated with higher risk of incident hypertension in a fully adjusted model (P = 0.044 for linear trend). In a final model containing both quartiles of LV mass and LV mass/volume along with all covariates including baseline blood pressure, higher LV mass quartiles were associated with incident hypertension (P < 0.001 for linear trend), whereas higher LV mass/volume quartiles were not (P = 0.643 for linear trend). In this multiethnic cohort, alterations in LV mass preceded hypertension onset among normotensive individuals.

BACKGROUND: Polypills, which include multiple medications for reducing cardiovascular disease (CVD) risk in a single pill, have been proposed for population-wide use. The number of US adults eligible for polypills and potential benefits are unknown. METHODS: The National Health and Nutrition Examination Survey 2003-2004 and 2007-2008 were analyzed to estimate treatment rates for medications proposed for inclusion in polypills (aspirin, statin, an angiotensin-converting enzyme [ACE] inhibitor, and a thiazide-type diuretic for those without and a beta-blocker for those with a history of myocardial infarction) among US adults. The number of coronary heart disease (CHD) and stroke events potentially prevented through polypill use was projected by published meta-analyses and 3 large population-based cohort studies. Two polypill eligibility criteria were analyzed: (1) US adults >/=55 years and (2) US adults with a history of CVD. RESULTS: There are 67.6 million US adults >/=55 years and 15.4 million US adults with a history of CVD and, thus, eligible for polypills using the 2 outlined criteria. In 2007 to 2008, 37.3% of US adults >/=55 years and 57.0% of those with a history of CVD were taking statins. Use of other polypill medications was also low. Polypill use by US adults aged >/=55 years is projected to potentially prevent 3.2 million CHD events and 1.7 million strokes over 10 years. Among those with a history of CVD, the potential to prevent of 0.9 million CHD events and 0.5 million strokes is projected. CONCLUSIONS: Polypills have the potential to lower CVD incidence substantially among US adults.

BACKGROUND: Among individuals without diabetes, elevated hemoglobin A1c (HbA1c) has been associated with increased morbidity and mortality, but the literature is sparse regarding the prognostic importance of low HbA1c. METHODS AND RESULTS: National Health and Nutrition Examination Survey III (NHANES III) participants, 20 years and older, were followed up to 12 years (median follow-up, 8.8 years) for all-cause mortality. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between HbA1c levels and all-cause mortality for 14 099 participants without diabetes. There were 1825 deaths during the follow-up period. Participants with a low HbA1c (<4.0%) had the highest levels of mean red blood cell volume, ferritin, and liver enzymes and the lowest levels of mean total cholesterol and diastolic blood pressure compared with their counterparts with HbA1c levels between 4.0% and 6.4%. An HbA1c <4.0% versus 5.0% to 5.4% was associated with an increased risk of all-cause mortality (HR, 3.73; 95% CI, 1.45 to 9.63) after adjustment for age, race-ethnicity, and sex. This association was attenuated but remained statistically significant after further multivariable adjustment for lifestyle, cardiovascular factors, metabolic factors, red blood cell indices, iron storage indices, and liver function indices (HR, 2.90; 95% CI, 1.25 to 6.76). CONCLUSIONS: In this nationally representative cohort, low HbA1c was associated with increased all-cause mortality among US adults without diabetes. Additional research is needed to confirm these results and identify potential mechanisms that may be underlying this association.