Cristin P Freeman

Location, Location, Location: Geographic Clustering of Lower-Extremity Amputation Among Medicare Beneficiaries With Diabetes

OBJECTIVE Lower-extremity amputation (LEA) is common among persons with diabetes. The goal of this study was to identify geographic variation and the influence of location on the incidence of LEA among U.S. Medicare beneficiaries with diabetes. RESEARCH DESIGN AND METHODS We conducted a cohort study of beneficiaries of Medicare. The geographic unit of analysis was hospital referral regions (HRRs). Tests of spatial autocorrelation and geographically weighted regression were used to evaluate the incidence of LEA by HRRs as a function of geographic location in the U.S. Evaluated covariates covered sociodemographic factors, risk factors for LEA, diabetes severity, provider access, and cost of care. RESULTS Among persons with diabetes, the annual incidence per 1,000 of LEA was 5.0 in 2006, 4.6 in 2007, and 4.5 in 2008 and varied by the HRR. The incidence of LEA was highly concentrated in neighboring HRRs. High rates of LEA clustered in contiguous portions of Texas, Oklahoma, Louisiana, Arkansas, and Mississippi. Accounting for geographic location greatly improved our ability to understand the variability in LEA. Additionally, covariates associated with LEA per HRR included socioeconomic status, prevalence of African Americans, age, diabetes, and mortality rate associated with having a foot ulcer. CONCLUSIONS There is profound “region-correlated” variation in the rate of LEA among Medicare beneficiaries with diabetes. In other words, location matters and whereas the likelihood of an amputation varies dramatically across the U.S. overall, neighboring locations have unexpectedly similar amputation rates, some being uniformly high and others uniformly low.

Validation of diagnostic codes for outpatient-originating sudden cardiac death and ventricular arrhythmia in Medicaid and Medicare claims data †

Sudden cardiac death (SD) and ventricular arrhythmias (VAs) caused by medications have arisen as an important public health concern in recent years. The validity of diagnostic codes in identifying SD/VA events originating in the ambulatory setting is not well known. This study examined the positive predictive value (PPV) of hospitalization and emergency department encounter diagnoses in identifying SD/VA events originating in the outpatient setting.

Risk of hip fracture associated with hepatitis c virus infection and hepatitis C/human immunodeficiency virus coinfection

Hepatitis C virus (HCV) infection has been associated with reduced bone mineral density, but its association with fracture rates is unknown, particularly in the setting of human immunodeficiency virus (HIV) coinfection. Our aims were to determine whether persons with HCV infection alone are at increased risk for hip fracture, compared to uninfected individuals, and to examine whether the risk of hip fracture is higher among HCV/HIV‐coinfected persons, compared to those with HCV alone, those with HIV alone, and those uninfected with either virus. We conducted a cohort study in 36,950 HCV/HIV‐coinfected, 276,901 HCV‐monoinfected, 95,827 HIV‐monoinfected, and 3,110,904 HCV/HIV‐uninfected persons within the U.S. Medicaid populations of California, Florida, New York, Ohio, and Pennsylvania (1999‐2005). Incidence rates of hip fracture were lowest among uninfected persons (1.29 events/1,000 person‐years), increased with the presence of either HIV infection (1.95 events/1,000 person‐years) or HCV infection (2.69 events/1,000 person‐years), and were highest among HCV/HIV‐coinfected individuals (3.06 events/1,000 person‐years). HCV/HIV coinfection was associated with an increased relative hazard (adjusted hazard ratio [HR] [95% confidence interval; CI]) of hip fracture, compared to HCV‐monoinfected (HR, 1.38; 95% CI: 1.25‐1.53), HIV‐monoinfected (females: HR, 1.76; 95% CI: 1.44‐2.16; males: HR, 1.36; 95% CI: 1.20‐1.55), and HCV/HIV‐uninfected persons (females: HR, 2.65; 95% CI: 2.21‐3.17; males: HR, 2.20; 95% CI: 1.97‐2.47). HCV monoinfection was associated with an increased risk of hip fracture, compared to uninfected individuals, and the relative increase was highest in the youngest age groups (females, 18‐39 years: HR, 3.56; 95% CI: 2.93‐4.32; males, 18‐39 years: HR, 2.40; 95% CI: 2.02‐2.84). Conclusion: Among Medicaid enrollees, HCV/HIV coinfection was associated with increased rates of hip fracture, compared to HCV‐monoinfected, HIV‐monoinfected, and HCV/HIV‐uninfected persons. HCV‐monoinfected patients had an increased risk of hip fracture, compared to uninfected individuals. (HEPATOLOGY 2012;56:1688–1698)

Proton pump inhibitors and traditional nonsteroidal anti-inflammatory drugs and the risk of acute interstitial nephritis and acute kidney injury†‡

This study aims to examine the associations between proton pump inhibitors (PPIs), traditional nonsteroidal anti‐inflammatory drugs (tNSAIDs), PPI + tNSAID co‐exposure, and the development of the following: (i) acute interstitial nephritis (AIN), a specific kidney injury often attributed to these drugs, and (ii) acute kidney injury (AKI), a general kidney injury encompassing AIN.

Antipsychotics and the Risks of Sudden Cardiac Death and All-Cause Death: Cohort Studies in Medicaid and Dually-Eligible Medicaid-Medicare Beneficiaries of Five States.

CONTEXT Antipsychotic drugs have been linked to QT-interval prolongation, a presumed marker of cardiac risk, and torsade de pointes. OBJECTIVE To examine the associations between antipsychotics and 1) outpatient-originated sudden cardiac death and ventricular arrhythmia (SD/VA) and 2) all-cause death. DESIGN Two retrospective cohort studies. SETTING Medicaid programs of California, Florida, New York, Ohio and Pennsylvania. PATIENTS Incident antipsychotic users aged 30-75 years. MAIN OUTCOME MEASURES 1) Incident, first-listed emergency department or principal inpatient SD/VA diagnoses; and 2) death reported in the Social Security Administration Death Master File. RESULTS 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. CONCLUSIONS 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.

A system for de-identifying medical message board text

There are millions of public posts to medical message boards by users seeking support and information on a wide range of medical conditions. It has been shown that these posts can be used to gain a greater understanding of patients’ experiences and concerns. As investigators continue to explore large corpora of medical discussion board data for research purposes, protecting the privacy of the members of these online communities becomes an important challenge that needs to be met. Extant entity recognition methods used for more structured text are not sufficient because message posts present additional challenges: the posts contain many typographical errors, larger variety of possible names, terms and abbreviations specific to Internet posts or a particular message board, and mentions of the authors’ personal lives. The main contribution of this paper is a system to de-identify the authors of message board posts automatically, taking into account the aforementioned challenges. We demonstrate our system on two different message board corpora, one on breast cancer and another on arthritis. We show that our approach significantly outperforms other publicly available named entity recognition and de-identification systems, which have been tuned for more structured text like operative reports, pathology reports, discharge summaries, or newswire.

Safety of saxagliptin: rationale for and design of a series of postmarketing observational studies.

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.

Comparative Risk of Ischemic Stroke Among Users of Clopidogrel Together With Individual Proton Pump Inhibitors

Background and Purpose— There is controversy and little information about whether individual proton pump inhibitors (PPIs) differentially alter the effectiveness of clopidogrel in reducing ischemic stroke risk. We, therefore, aimed to elucidate the risk of ischemic stroke among concomitant users of clopidogrel and individual PPIs. Methods— We conducted a propensity score-adjusted cohort study of adult new users of clopidogrel, using 1999 to 2009 Medicaid claims from 5 large states. Exposures were defined by prescriptions for esomeprazole, lansoprazole, omeprazole, rabeprazole, and pantoprazole—with pantoprazole serving as the referent. The end point was hospitalization for acute ischemic stroke, defined by International Classification of Diseases Ninth Revision Clinical Modification codes in the principal position on inpatient claims, within 180 days of concomitant therapy initiation. Results— Among 325 559 concomitant users of clopidogrel and a PPI, we identified 1667 ischemic strokes for an annual incidence of 2.4% (95% confidence interval, 2.3–2.5). Adjusted hazard ratios for ischemic stroke versus pantoprazole were 0.98 (0.82–1.17) for esomeprazole; 1.06 (0.92–1.21) for lansoprazole; 0.98 (0.85–1.15) for omeprazole; and 0.85 (0.63–1.13) for rabeprazole. Conclusions— PPIs of interest did not increase the rate of ischemic stroke among clopidogrel users when compared with pantoprazole, a PPI thought to be devoid of the potential to interact with clopidogrel.

CYP2C9, CYP2C19, and ABCB1 genotype and hospitalization for phenytoin toxicity.

From the Center for Clinical Epidemiology & Biostatistics and the Department of Biostatistics & Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (Dr Hennessy, Dr Leonard, Ms Freeman, Dr Metlay, Dr Strom, Dr Bilker); the Center for Education and Research on Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (Dr Hennessy, Dr Leonard, Ms Freeman, Dr Metlay, Dr Strom, Dr Bilker); the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (Dr Metlay, Dr Strom); the Center for Health Equity Research and Promotion, Veterans Affairs Medical Center, Philadelphia, Pennsylvania (Dr Metlay); and the Weis Center for Research, Geisinger Clinic Genomics Core, Danville, Pennsylvania (Dr Chu). Submitted for publica-tion April 13, 2009; revised version accepted June 18, 2009. Address for correspondence: Sean Hennessy, PharmD, PhD, 803 Blockley Hall / 423 Guardian Drive, Philadelphia, Pennsylvania 19104.DOI: 10.1177/0091270009343006

Empiric Potassium Supplementation and Increased Survival in Users of Loop Diuretics

Background The effectiveness of the clinical strategy of empiric potassium supplementation in reducing the frequency of adverse clinical outcomes in patients receiving loop diuretics is unknown. We sought to examine the association between empiric potassium supplementation and 1) all-cause death and 2) outpatient-originating sudden cardiac death (SD) and ventricular arrhythmia (VA) among new starters of loop diuretics, stratified on initial loop diuretic dose. Methods We conducted a one-to-one propensity score-matched cohort study using 1999–2007 US Medicaid claims from five states. Empiric potassium supplementation was defined as a potassium prescription on the day of or the day after the initial loop diuretic prescription. Death, the primary outcome, was ascertained from the Social Security Administration Death Master File; SD/VA, the secondary outcome, from incident, first-listed emergency department or principal inpatient SD/VA discharge diagnoses (positive predictive value = 85%). Results We identified 654,060 persons who met eligibility criteria and initiated therapy with a loop diuretic, 27% of whom received empiric potassium supplementation (N = 179,436) and 73% of whom did not (N = 474,624). The matched hazard ratio for empiric potassium supplementation was 0.93 (95% confidence interval, 0.89–0.98, p = 0.003) for all-cause death. Stratifying on initial furosemide dose, hazard ratios for empiric potassium supplementation with furosemide <40 and ≥40 milligrams/day were 0.93 (0.86–1.00, p = 0.050) and 0.84 (0.79–0.89, p<0.0001). The matched hazard ratio for empiric potassium supplementation was 1.02 (0.83–1.24, p = 0.879) for SD/VA. Conclusions Empiric potassium supplementation upon initiation of a loop diuretic appears to be associated with improved survival, with a greater apparent benefit seen with higher diuretic dose. If confirmed, these findings support the use of empiric potassium supplementation upon initiation of a loop diuretic.