Stephen E Kimmel

Medical University of South Carolina, Charleston, South Carolina, United States

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Publications (177)1237.53 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: PurposePatients starting warfarin often experience lengthy dose-titration periods, when they are at high risk for bleeding and thromboembolism. However, relatively little is known about why some patients take longer than others to reach maintenance dose. Thus, we sought to identify social, clinical, and genetic factors associated with prolonged time to maintenance dose (TTM).Methods We conducted a time-to-event analysis, using a prospective cohort of patients initiating warfarin (N = 390). Additionally, we examined whether changes in post-initiation factors were associated with TTM. Finally, we performed a secondary analysis in a subcohort (N = 156) assessing the effect of adherence on TTM.ResultsNo genetic or post-initiation factors were significantly associated with TTM. However, previous use of warfarin [hazard ratio (HR) = 0.64; 95% confidence interval (CI) 0.46, 0.88], current smoking status (HR = 0.61; 95%CI 0.39, 0.96), fewer than four doctor's visits in the previous year (HR = 0.63 vs 4–12 visits; 95%CI 0.46, 0.88), and worse general health status (HR = 0.63; 95%CI 0.47, 0.84) were significantly associated with longer TTM. Use of illegal injectable drugs (HR = 2.51; 95%CI 1.17, 5.39) was associated with shorter TTM. On secondary analysis, the HR for better adherence and TTM was 1.70 (95%CI 0.88, 3.27).Conclusions Time to maintenance dose was associated with pre-existing behavioral factors, health care utilization, and health quality but not clinical comorbidities or genetic factors in patients initiating warfarin. Future studies are needed to determine whether warfarin patients with prolonged TTM would have better outcomes on alternative agents. Copyright © 2014 John Wiley & Sons, Ltd.
    Pharmacoepidemiology and Drug Safety 12/2014; · 2.90 Impact Factor
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    ABSTRACT: Hypertension is prevalent among patients with psoriasis. The effect of psoriasis and its severity on hypertension control is unknown.
    JAMA Dermatology 10/2014; · 4.30 Impact Factor
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    ABSTRACT: Background The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results. Methods We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy. Results At 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy. Conclusions Genotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657 .).
    New England Journal of Medicine 11/2013; · 54.42 Impact Factor
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    ABSTRACT: -The long-term durability and prognostic significance of improvement in renal function following mechanical circulatory support (MCS) has yet to be characterized in a large multicenter population. The primary goals of this analysis were to describe serial post-MCS changes in estimated glomerular filtration rate (eGFR) and determine their association with all-cause mortality. -Adult patients enrolled in INTERMACS with serial creatinine levels available (n=3,363) were studied. Early post-MCS, eGFR improved substantially (median improvement 48.9%, p<0.001) with 22.3% of the population improving their eGFR by ≥100% within the first few weeks. However, in the majority of patients this improvement was transient, and by one year, eGFR was only 6.7% above the pre-MCS value (p<0.001). This pattern of early improvement followed by deterioration in eGFR was observed with both pulsatile and continuous-flow devices. Interestingly, poor survival was associated with both marked improvement (adjusted HR=1.64, 1.19-2.26, p=0.002) and worsening in eGFR (adjusted HR=1.63, 1.15-2.13, p=0.004). -Post-MCS, early improvement in renal function is common but appears to be largely transient and not necessarily indicative of an improved prognosis. This pattern was observed with both pulsatile and continuous-flow devices. Additional research is necessary to better understand the mechanistic basis for these complex post-MCS changes in renal function and their associated survival disadvantage. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00119834.
    Circulation Heart Failure 11/2013; · 6.68 Impact Factor
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    ABSTRACT: Current dosing practices for warfarin are empiric and result in the need for frequent dose changes as the international normalized ratio gets too high or too low. As a result, patients are put at increased risk for thromboembolism, bleeding, and premature discontinuation of anticoagulation therapy. Prior research has identified clinical and genetic factors that can alter warfarin dose requirements, but few randomized clinical trials have examined the utility of using clinical and genetic information to improve anticoagulation control or clinical outcomes among a large, diverse group of patients initiating warfarin. The COAG trial is a multicenter, double-blind, randomized trial comparing 2 approaches to guiding warfarin therapy initiation: initiation of warfarin therapy based on algorithms using clinical information plus an individual's genotype using genes known to influence warfarin response ("genotype-guided dosing") versus only clinical information ("clinical-guided dosing") (www.clinicaltrials.gov Identifier: NCT00839657). The COAG trial design is described. The study hypothesis is that, among 1,022 enrolled patients, genotype-guided dosing relative to clinical-guided dosing during the initial dosing period will increase the percentage of time that patients spend in the therapeutic international normalized ratio range in the first 4 weeks of therapy. The COAG will determine if genetic information provides added benefit above and beyond clinical information alone.
    American heart journal 09/2013; 166(3):435-441.e2. · 4.65 Impact Factor
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    ABSTRACT: IMPORTANCE Despite the growing literature on comorbidity risks in psoriasis, there remains a critical knowledge gap on the degree to which objectively measured psoriasis severity may affect the prevalence of major medical comorbidity. OBJECTIVE To examine the prevalence of major medical comorbidity in patients with mild, moderate, or severe psoriasis, classified objectively based on body surface area involvement, compared with that in patients without psoriasis. DESIGN, SETTING, AND PARTICIPANTS Population-based cross-sectional study of patient data fromUnited Kingdom-based electronic medical records; analysis included9035 patients aged 25 to 64 years with psoriasis and 90 350 age- and practice-matched patients without psoriasis. MAIN OUTCOMES AND MEASURES Prevalence of major medical comorbidity included in the Charlson comorbidity index. RESULTS Among patients with psoriasis, 51.8%, 35.8%, and 12.4%, respectively, had mild, moderate, or severe disease based on body surface area criteria. The mean Charlson comorbidity index was increasingly higher in patients with mild (0.375 vs 0.347), moderate (0.398 vs 0.342), or severe psoriasis (0.450 vs 0.348) (each P < .05). Psoriasis overall was associated with higher prevalence of chronic pulmonary disease (adjusted odds ratio, 1.08; 95% CI, 1.02-1.15), diabetes mellitus (1.22; 1.11-1.35), diabetes with systemic complications (1.34; 1.11-1.62), mild liver disease (1.41; 1.12-1.76), myocardial infarction (1.34; 1.07-1.69), peptic ulcer disease (1.27; 1.03-1.58), peripheral vascular disease (1.38; 1.07-1.77), renal disease (1.28; 1.11-1.48), and rheumatologic disease (2.04; 1.71-2.42). Trend analysis revealed significant associations between psoriasis severity and each of the above comorbid diseases (each P < .05). CONCLUSIONS AND RELEVANCE The burdens of overall medical comorbidity and of specific comorbid diseases increase with increasing disease severity among patients with psoriasis. Physicians should be aware of these associations in providing comprehensive care to patients with psoriasis, especially those presenting with more severe disease.
    JAMA dermatology (Chicago, Ill.). 08/2013;
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    ABSTRACT: Digitalis glycosides are known to improve the hemodynamic and neurohormonal perturbations that contribute to heart failure (HF)-induced renal dysfunction (RD). The objective of this study was to determine if randomization to digoxin is associated with improvement in renal function (IRF) and to evaluate if patients with digoxin-induced IRF have improved clinical outcomes. Patients in the Digitalis Investigation Group (DIG) dataset with protocol-driven 1-year serum creatinine levels (performed in a central laboratory; n = 980) were studied. IRF was defined as a postrandomization ≥20% increase in estimated glomerular filtration rate (eGFR). IRF occurred in 15.5% of the population (mean improvement in eGFR 34.5 ± 15.4%) and was more common in patients randomized to digoxin (adjusted odds ratio 1.6; P = .02). In patients without IRF, digoxin was not associated with reduced death or hospitalization (adjusted hazard ratio [HR] 0.96, 95% CI 0.8-1.2; P = .67). However, in the group with IRF, digoxin was associated with substantially improved hospitalization-free survival (adjusted HR 0.49, 95% CI 0.3-0.8; P = .006; P interaction = .026). In this subset of the DIG trial, digoxin was associated with long-term improvement in kidney function and, in patients demonstrating this favorable renal response, reduction in death or hospitalization. Additional research is necessary to confirm these hypothesis-generating findings.
    Journal of cardiac failure 05/2013; 19(5):295-302. · 3.25 Impact Factor
  • Thrombosis and Haemostasis 03/2013; 109(6). · 5.76 Impact Factor
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    ABSTRACT: BACKGROUND: -Identifying reversible renal dysfunction (RD) in the setting of heart failure (HF) is challenging. The goal of this study was to evaluate if an elevated admission blood urea nitrogen to creatinine ratio (BUN/Cr) could identify decompensated HF patients likely to experience improvement in renal function (IRF) with treatment. METHODS AND RESULTS: -Consecutive hospitalizations with a discharge diagnosis of HF were reviewed. IRF was defined as ≥20% increase and worsening renal function (WRF) ≥20% decrease in estimated glomerular filtration rate (eGFR). IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with in-hospital IRF (OR=1.5 per 10 increase, 95% CI: 1.3-1.8, p<0.001), an association persisting after adjustment for baseline characteristics (OR=1.4, 95% CI: 1.1-1.8, p=0.004). However, higher admission BUN/Cr was also associated with post-discharge WRF (OR= 1.4, 95% CI: 1.1-1.8, p=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (eGFR<45) was substantial (HR=2.2, 95% CI: 1.6-3.1, p<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (HR=1.2, 95% CI: 0.67-2.0, p=0.59, p interaction= 0.03). CONCLUSIONS: -An elevated admission BUN/Cr identifies decompensated HF patients likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement appears to be largely transient and RD in the setting of an elevated BUN/Cr remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients.
    Circulation Heart Failure 01/2013; · 6.68 Impact Factor
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    ABSTRACT: To compare the incidence rates of serious cardiovascular events in adult initiators of amphetamines or atomoxetine to rates in non-users. This was a retrospective cohort study of new amphetamines (n = 38,586) or atomoxetine (n = 20,995) users. Each medication user was matched to up to four non-users on age, gender, data source, and state (n = 238,183). The following events were primary outcomes of interest 1) sudden death or ventricular arrhythmia, 2) stroke, 3) myocardial infarction, 4) a composite endpoint of stroke or myocardial infarction. Cox proportional hazard regression was used to calculate propensity-adjusted hazard ratios for amphetamines versus matched non-users and atomoxetine versus matched non-users, with intracluster dependence within matched sets accounted for using a robust sandwich estimator. The propensity-score adjusted hazard ratio for amphetamines use versus non-use was 1.18 (95% CI: 0.55-2.54) for sudden death/ventricular arrhythmia, 0.80 (95% CI: 0.44-1.47) for stroke, 0.75 (95% CI: 0.42-1.35) for myocardial infarction, and 0.78 (95% CI: 0.51-1.19) for stroke/myocardial infarction. The propensity-score adjusted hazard ratio for atomoxetine use versus non-use was 0.41 (95% CI: 0.10-1.75) for sudden death/ventricular arrhythmia, 1.30 (95% CI: 0.52-3.29) for stroke, 0.56 (95% CI: 0.16-2.00) for myocardial infarction, and 0.92 (95% CI: 0.44-1.92) for stroke/myocardial infarction. Initiation of amphetamines or atomoxetine was not associated with an elevated risk of serious cardiovascular events. However, some of the confidence intervals do not exclude modest elevated risks, e.g. for sudden death/ventricular arrhythmia.
    PLoS ONE 01/2013; 8(1):e52991. · 3.53 Impact Factor
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    ABSTRACT: Antipsychotic drugs have been linked to QT-interval prolongation, a presumed marker of cardiac risk, and torsade de pointes. To examine the associations between antipsychotics and 1) outpatient-originated sudden cardiac death and ventricular arrhythmia (SD/VA) and 2) all-cause death. Two retrospective cohort studies. Medicaid programs of California, Florida, New York, Ohio and Pennsylvania. Incident antipsychotic users aged 30-75 years. 1) Incident, first-listed emergency department or principal inpatient SD/VA diagnoses; and 2) death reported in the Social Security Administration Death Master File. Among 459,614 incident antipsychotic users, the incidences of SD/VA and death were 3.4 and 35.1 per 1,000 person-years, respectively. Compared to olanzapine as the referent, adjusted hazard ratios (HRs) for SD/VA were 2.06 (95% CI, 1.20-3.53) for chlorpromazine, 1.72 (1.28-2.31) for haloperidol, and 0.73 (0.57-0.93) for quetiapine. Adjusted HRs for perphenazine and risperidone were consistent with unity. In a subanalysis limited to first prescription exposures, HRs for chlorpromazine and haloperidol were further elevated (2.54 [1.07-5.99] and 2.68 [1.59-4.53], respectively), with the latter exhibiting a dose-response relationship. Results for death were similar. Haloperidol and chlorpromazine had less favorable cardiac safety profiles than olanzapine. Among atypical agents, risperidone had a similar cardiac safety profile to olanzapine, whereas quetiapine was associated with 30% and 20% lower risks of SD/VA and death, respectively, compared to olanzapine. These measured risks do not correlate well with average QT prolongation, further supporting the notion that average QT prolongation may be a poor surrogate of antipsychotic arrhythmogenicity.
    Journal of clinical & experimental cardiology. 01/2013; Suppl 10(6):1-9.
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    ABSTRACT: Poor adherence to medications is a major cause of morbidity and inadequate drug effectiveness. Efforts to improve adherence have typically been either ineffective or too complex to implement in clinical practice. Lottery-based incentive interventions could be a scalable approach to improving adherence. This was a randomized, controlled clinical trial of a daily lottery-based incentive in patients on warfarin stratified by baseline international normalized ratio (INR). The trial randomized 100 patients to either a lottery-based incentive or no lottery intervention. Main outcome was out-of-range INRs. Over 6 months, the overall percentage of out-of-range INRs did not differ between the 2 arms (mean 23.0% in lottery arm and 25.9% in control arm, adjusted odds ratio [OR] 0.93, 95% CI 0.62-1.41). However, among the a priori subgroup with a baseline INR below therapeutic range, there was a significant reduction in out-of-range INR in the lottery arm versus the control arm (adjusted OR 0.39, 95% CI 0.25-0.62), whereas there was no such effect among those with therapeutic INRs at baseline (adjusted OR 1.26, 95% CI, 0.76-2.09, P value for interaction = .0016). Among those with low INR at baseline, there was a nonsignificant 49% reduction in the odds of nonadherence with the intervention (OR 0.51, 95% CI 0.23-1.14). Although a lottery-based intervention was not associated with a significant improvement in anticoagulation control among all study participants, it improved control among an a priori group of patients at higher risk for poor adherence.
    American heart journal 08/2012; 164(2):268-74. · 4.65 Impact Factor
  • Stephen E Kimmel, Andrea B Troxel
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    ABSTRACT: BACKGROUND: Adherence to medications for chronic conditions is often very low, limiting the benefit to patients, even when the medications are effective and have favorable side effect profiles. PURPOSE: This article reviews some of the prior work on treatment adherence, introduces novel concepts from behavioral economics that can be used to design interventions to improve adherence, and proposes new approaches for clinical trials. METHODS: Relevant experience of the authors and insights from the literature were combined to identify key issues and propose methodological improvements. Specific examples regarding adherence to warfarin are provided. RESULTS: Several new approaches to trial design can be effectively applied in the context of medication adherence. These include tailored intervention strategies and sequential multiple assignment randomized trial (SMART) designs. LIMITATIONS: While we have proposed to use these new approaches for ongoing studies of adherence in behavioral health, practical experience with their application is still somewhat limited. CONCLUSIONS: Behavioral economics offer a variety of concepts that, when used in the design of interventions to improve adherence, may be more successful than traditional approaches. New clinical trial designs can also be adopted to improve the efficiency of studies that assess these approaches. Clinical Trials 2012; 0: 1-7. http://ctj.sagepub.com.
    Clinical Trials 07/2012; · 2.20 Impact Factor
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    ABSTRACT: PURPOSE: To describe the design and rationale of a series of postmarketing studies to examine the safety of saxagliptin, an oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus, in real-world settings. METHODS: We are conducting a series of retrospective cohort studies using two UK (General Practice Research Database, and The Health Improvement Network) and two US (Medicare, HealthCore Integrated Research Database(SM) ) data sources. The primary outcomes of interest will include (i) hospitalization with acute liver failure, (ii) hospitalization for acute kidney injury, (iii) hospitalization for severe hypersensitivity reactions, (iv) hospitalization for severe infections, (v) hospitalization with infections associated with T-lymphocyte dysfunction (i.e., herpes zoster, tuberculosis, or nontuberculous mycobacteria), and (vi) major cardiovascular events. Diagnosis codes for the outcomes of interest will be validated by medical record review within each data source. Projected use and estimated incidence rates of outcomes of interest suggest there will be at least 80% statistical power to detect a minimum hazard ratio of 1.5 for major cardiovascular events, 2.0 for acute kidney injury and severe infections, 2.4 for acute liver failure, and 4.0 for severe hypersensitivity reactions. RESULTS: Forthcoming. CONCLUSIONS: This postmarketing safety assessment will provide important information regarding the safety of saxagliptin and could potentially identify important dipeptidyl peptidase-4 inhibitor class effects. The methods described may be useful to others planning similar evaluations. Copyright © 2012 John Wiley & Sons, Ltd.
    Pharmacoepidemiology and Drug Safety 07/2012; · 2.90 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis. However, it remains unclear if HCV infection increases the risk of acute myocardial infarction (MI). To determine whether HCV infection is an independent risk factor for acute MI among adults followed in general practices in the United Kingdom (UK), a retrospective cohort study was conducted in The Health Improvement Network, from 1996 through 2008. Patients ≥18 years of age with at least 6 months of follow-up and without a prior history of MI were eligible for study inclusion. HCV-infected individuals, identified with previously validated HCV diagnostic codes (n = 4809), were matched on age, sex and practice with up to 15 randomly selected patients without HCV (n = 71 668). Rates of incident MI among patients with and without a diagnosis of HCV infection were calculated. Adjusted hazard ratios were estimated using Cox proportional hazards regression, controlling for established cardiovascular risk factors. During a median follow-up of 3.2 years, there was no difference in the incidence rates of MI between HCV-infected and -uninfected patients (1.02 vs 0.92 events per 1000 person-years; P = 0.7). HCV infection was not associated with an increased risk of incident MI (adjusted HR, 1.10; 95% confidence interval [CI], 0.67-1.83). Sensitivity analyses including the exploration of a composite outcome of acute MI and coronary interventions yielded similar results (adjusted HR, 1.16; 95% CI, 0.77-1.74). In conclusion, HCV infection was not associated with an increased risk of incident MI.
    Journal of Viral Hepatitis 04/2012; 19(4):271-7. · 3.08 Impact Factor
  • Pharmacoepidemiology and Drug Safety 03/2012; 21(3):331-2. · 2.90 Impact Factor
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    ABSTRACT: The authors sought to determine whether use of methylphenidate in adults is associated with elevated rates of serious cardiovascular events compared with rates in nonusers. This was a cohort study of new users of methylphenidate based on administrative data from a five-state Medicaid database and a 14-state commercial insurance database. All new methylphenidate users with at least 180 days of prior enrollment were identified. Users were matched on data source, state, sex, and age to as many as four comparison subjects who did not use methylphenidate, amphetamines, or atomoxetine. A total of 43,999 new methylphenidate users were identified and matched to 175,955 nonusers. Events of primary interest were 1) sudden death or ventricular arrhythmia, 2) stroke, 3) myocardial infarction, and 4) a composite endpoint of stroke or myocardial infarction. The age-standardized incidence rate per 1,000 person-years of sudden death or ventricular arrhythmia was 2.17 (95% CI=1.63-2.83) in methylphenidate users and 0.98 (95% CI=0.89-1.08) in nonusers, for an adjusted hazard ratio of 1.84 (95% CI=1.33-2.55). Dosage was inversely associated with risk. Adjusted hazard ratios for stroke, myocardial infarction, and the composite endpoint of stroke or myocardial infarction did not differ statistically from 1. Although initiation of methylphenidate was associated with a 1.8-fold increase in risk of sudden death or ventricular arrhythmia, the lack of a dose-response relationship suggests that this association may not be a causal one.
    American Journal of Psychiatry 02/2012; 169(2):178-85. · 14.72 Impact Factor
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    ABSTRACT: Proton pump inhibitors (PPIs) and corticosteroids are commonly prescribed drugs; however, each has been associated with fracture and community-acquired pneumonia. How physicians select patients for co-therapy may have implications for potential additive or synergistic toxicities. We conducted a retrospective cohort study of 13 749 incident corticosteroid users with no prior PPI exposure using the HealthCore Integrated Research Database(SM) . We used logistic regression to evaluate the association between PPI initiation in the first 30 days of steroid therapy and corticosteroid dose, clinical risk factors including comorbid diseases, and medication use including prescription nonsteroidal anti-inflammatory drugs (NSAIDs). A new PPI prescription within 30 days of starting corticosteroids was filled by 1050 patients (7.6%). PPI use was associated with the number of baseline comorbid conditions (OR = 1.21 for each additional condition, 95%CI = 1.13-1.28), recent hospitalization (OR = 4.71, 95%CI = 4.02-5.52), prednisone dose higher than 40 mg/day (OR = 1.87, 95%CI = 1.45-2.41), history of gastroesophageal reflux or gastric ulcer disease (OR = 1.54, 95%CI = 1.24-1.91), renal insufficiency (OR = 2.06, 95%CI = 1.73-2.46), and liver disease (OR = 1.82, 95%CI = 1.45-2.28). The concomitant use of prescription NSAIDs was also associated with PPI use (OR = 1.89, 95%CI = 1.32-2.70); however, the total use of PPIs in this group was low (6.3%, 95%CI = 4.4-8.2%). Overall, PPI therapy among corticosteroid users was uncommon, even among those with risk factors for gastrointestinal toxicity. PPI use was significantly more common among patients who had recently been hospitalized, had a greater burden of comorbid illness, or were receiving high daily doses of corticosteroids.
    Pharmacoepidemiology and Drug Safety 01/2012; 21(4):366-74. · 2.90 Impact Factor
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    ABSTRACT: By guiding initial warfarin dose, pharmacogenetic (PGx) algorithms may improve the safety of warfarin initiation. However, once international normalised ratio (INR) response is known, the contribution of PGx to dose refinements is uncertain. This study sought to develop and validate clinical and PGx dosing algorithms for warfarin dose refinement on days 6-11 after therapy initiation. An international sample of 2,022 patients at 13 medical centres on three continents provided clinical, INR, and genetic data at treatment days 6-11 to predict therapeutic warfarin dose. Independent derivation and retrospective validation samples were composed by randomly dividing the population (80%/20%). Prior warfarin doses were weighted by their expected effect on S-warfarin concentrations using an exponential-decay pharmacokinetic model. The INR divided by that "effective" dose constituted a treatment response index . Treatment response index, age, amiodarone, body surface area, warfarin indication, and target INR were associated with dose in the derivation sample. A clinical algorithm based on these factors was remarkably accurate: in the retrospective validation cohort its R(2) was 61.2% and median absolute error (MAE) was 5.0 mg/week. Accuracy and safety was confirmed in a prospective cohort (N=43). CYP2C9 variants and VKORC1-1639 G→A were significant dose predictors in both the derivation and validation samples. In the retrospective validation cohort, the PGx algorithm had: R(2)= 69.1% (p<0.05 vs. clinical algorithm), MAE= 4.7 mg/week. In conclusion, a pharmacogenetic warfarin dose-refinement algorithm based on clinical, INR, and genetic factors can explain at least 69.1% of therapeutic warfarin dose variability after about one week of therapy.
    Thrombosis and Haemostasis 12/2011; 107(2):232-40. · 5.76 Impact Factor
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    ABSTRACT: Risk biases such as comparative optimism (thinking one is better off than similar others) and risk inaccuracy (misestimating one's risk compared to one's calculated risk) for health outcomes are common. Little research has investigated racial or socioeconomic differences in these risk biases. Results from a survey of individuals with poorly controlled hypertension (N=813) indicated that participants showed (1) comparative optimism for heart attack risk by underestimating their heart attack risk compared to similar others, and (2) risk inaccuracy by overestimating their heart attack risk compared to their calculated heart attack risk. More highly educated participants were more comparatively optimistic because they rated their personal risk as lower; education was not related to risk inaccuracy. Neither race nor the federal poverty level was related to risk biases. Worry partially mediated the relationship between education and personal risk. Results are discussed as they relate to the existing literature on risk perception.
    Psychology & Health 12/2011; 27(6):737-51. · 1.95 Impact Factor

Publication Stats

6k Citations
1,237.53 Total Impact Points

Institutions

  • 2013
    • Medical University of South Carolina
      • Division of Cardiology
      Charleston, South Carolina, United States
  • 1995–2013
    • University of Pennsylvania
      • • Perelman School of Medicine
      • • Center for Health Equity Research
      • • Center for Clinical Epidemiology and Biostatistics
      • • Department of Medicine
      Philadelphia, PA, United States
    • Hospital of the University of Pennsylvania
      • • Department of Medicine
      • • Department of Biostatistics and Epidemiology
      Philadelphia, Pennsylvania, United States
  • 2011
    • London School of Hygiene and Tropical Medicine
      • Faculty of Epidemiology and Population Health
      London, ENG, United Kingdom
    • George Washington University
      • Department of Psychology
      Washington, D. C., DC, United States
  • 2010
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 2003–2010
    • The Children's Hospital of Philadelphia
      • Department of Pediatrics
      Philadelphia, PA, United States
    • Cornell University
      • Department of Medicine
      Ithaca, NY, United States
  • 2009
    • University of Connecticut
      • Department of Psychology
      Storrs, CT, United States
    • Carnegie Mellon University
      • Department of Social and Decision Sciences
      Pittsburgh, Pennsylvania, United States
  • 2002
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 2001
    • Weill Cornell Medical College
      • Division of General Internal Medicine (WCIMA)
      New York City, New York, United States