Few studies have evaluated the ability of laboratory tests to predict risk of acute liver failure (ALF) among patients with drug-induced liver injury (DILI). We aimed to develop a highly sensitive ...model to identify DILI patients at increased risk of ALF. We compared its performance with that of Hy's Law, which predicts severity of DILI based on levels of alanine aminotransferase or aspartate aminotransferase and total bilirubin, and validated the model in a separate sample.
We conducted a retrospective cohort study of 15,353 Kaiser Permanente Northern California members diagnosed with DILI from 2004 through 2010, liver aminotransferase levels above the upper limit of normal, and no pre-existing liver disease. Thirty ALF events were confirmed by medical record review. Logistic regression was used to develop prognostic models for ALF based on laboratory results measured at DILI diagnosis. External validation was performed in a sample of 76 patients with DILI at the University of Pennsylvania.
Hy's Law identified patients that developed ALF with a high level of specificity (0.92) and negative predictive value (0.99), but low level of sensitivity (0.68) and positive predictive value (0.02). The model we developed, comprising data on platelet count and total bilirubin level, identified patients with ALF with a C statistic of 0.87 (95% confidence interval CI, 0.76-0.96) and enabled calculation of a risk score (Drug-Induced Liver Toxicity ALF Score). We found a cut-off score that identified patients at high risk patients for ALF with a sensitivity value of 0.91 (95% CI, 0.71-0.99) and a specificity value of 0.76 (95% CI, 0.75-0.77). This cut-off score identified patients at high risk for ALF with a high level of sensitivity (0.89; 95% CI, 0.52-1.00) in the validation analysis.
Hy's Law identifies patients with DILI at high risk for ALF with low sensitivity but high specificity. We developed a model (the Drug-Induced Liver Toxicity ALF Score) based on platelet count and total bilirubin level that identifies patients at increased risk for ALF with high sensitivity.
Background. Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is associated with reduced bone mineral density (BMD) and increased fracture rates, particularly in women. ...The structural underpinnings for skeletal fragility in coinfected women have not been characterized. We used tibial peripheral quantitative computed tomography to evaluate skeletal parameters in women, by HIV/HCV status. Methods. We conducted a cross-sectional study among 50 HIV/HCV-coinfected, 51 HCV-monoinfected, and 50 HIV-monoinfected women. Tibial volumetric BMD and cortical dimensions were determined with peripheral quantitative computed tomography. Race-specific z scores for age were generated using 263 female reference participants without HIV infection or liver disease. Results. Coinfected participants had lower mean z scores for trabecular volumetric BMD (-0.85), cortical volumetric BMD (-0.67), cortical area (-0.61), and cortical thickness (-0.77) than reference participants (all P < .001). The smaller cortical dimensions were due to greater mean z scores for endosteal circumference (+0.67; P < .001) and comparable z scores for periosteal circumference (+ 0.04; P = .87). Trabecular volumetric BMD was lower in coinfected than in HCV- or HIV-monoinfected participants. HCV-infected women with stage 3-4 liver fibrosis had lower mean z scores for trabecular volumetric BMD, cortical thickness, and total hip BMD those with stage 0-2 fibrosis. Conclusions. Compared with healthy reference patients, HIV/HCV-coinfected women had decreased tibial trabecular volumetric BMD, diminished cortical dimensions, and significant endocortical bone loss.
Background & Aims Chronic hepatitis B (CHB) infection is associated with reduced bone mineral density, but its association with fractures is unknown. Our objectives were to determine whether ...untreated or treated CHB-infected persons are at increased risk for hip fracture compared to uninfected persons. Methods We conducted a cohort study among 18,796 untreated CHB-infected, 7777 treated CHB-infected, and 979,751 randomly sampled uninfected persons within the U.S. Medicaid populations of California, Florida, New York, Ohio, and Pennsylvania (1999–2007). CHB infection was defined by two CHB diagnoses recorded >6 months apart and was classified as treated if a diagnosis was recorded and antiviral therapy was dispensed. After propensity score matching of CHB-infected and uninfected persons, Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of incident hip fracture in: (1) untreated CHB-infected vs. uninfected, and (2) treated CHB-infected vs. uninfected patients. Results Untreated CHB-infected patients of black race had a higher rate of hip fracture than uninfected black persons (HR, 2.55 95% CI, 1.42–4.58). Compared to uninfected persons, relative hazards of hip fracture were increased for untreated white (HR, 1.26 95% CI, 0.98–1.62) and Hispanic (HR, 1.36 95% CI, 0.77–2.40) CHB-infected patients, and treated black (HR, 3.09 95% CI, 0.59–16.22) and white (HR, 1.90 95% CI, 0.81–4.47) CHB-infected patients, but these associations were not statistically significant. Conclusions Among U.S. Medicaid enrollees, untreated CHB-infected patients of black race had a higher risk of hip fracture than uninfected black persons.
Abstract Purpose Few population-based studies have estimated the number of persons diagnosed with chronic hepatitis B (CHB) infection in the United States. Our objective was to estimate the ...prevalence of diagnosed CHB infection among persons enrolled in the U.S. Medicaid programs of California, Florida, New York, Ohio, and Pennsylvania between 2000 and 2007. As part of our analyses, we confirmed the accuracy of CHB diagnoses within the Medicaid database. Methods CHB infection was defined by the presence of two outpatients CHB diagnoses recorded more than 6 months apart. Two clinicians reviewed the medical records of a random sample of patients who met this definition to confirm the diagnosis, which enabled calculation of the positive predictive value (PPV). The period prevalence of diagnosed CHB infection among Medicaid enrollees with at least 6 months of membership from 2000 to 2007 was then estimated, adjusting for both the PPV and estimated sensitivity of our definition of CHB infection. Results The definition of CHB infection accurately identified clinician-confirmed cases (PPV, 96.3%; 95% confidence interval CI, 87.3–99.5). Using this definition, 31,046 cases of CHB were diagnosed among 31,358,010 eligible Medicaid members from the five states (prevalence, 9.9 95% CI, 9.8–10.0 per 10,000). Adjusting for the PPV and estimated sensitivity of our CHB definition, the prevalence of diagnosed CHB infection was 15.6 (95% CI, 15.4–15.7) per 10,000. Conclusions Two outpatient CHB diagnoses recorded more than 6 months apart validly identified clinician-confirmed CHB. The prevalence of diagnosed CHB infection among U.S. Medicaid enrollees was 15.6 per 10,000.
Summary
HIV and hepatitis B virus (HBV) infections are each associated with reduced bone mineral density, but it is unclear whether HIV/HBV coinfection is associated with an increased risk of ...fracture. We determined whether dually treated HIV/HBV patients had a higher incidence of hip fracture compared to treated HBV‐monoinfected, antiretroviral therapy (ART)‐treated HIV‐monoinfected and HIV/HBV‐uninfected patients. We conducted a cohort study among 4156 dually treated HIV/HBV‐coinfected, 2053 treated HBV‐monoinfected, 96 253 ART‐treated HIV‐monoinfected, and 746 794 randomly sampled uninfected persons within the US Medicaid populations of California, Florida, New York, Ohio and Pennsylvania (1999–2007). Coinfected patients were matched on propensity score to persons in each comparator cohort. Weighted survival models accounting for competing risks were used to estimate cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) of incident hip fracture for dually treated coinfected patients compared to (i) HBV‐monoinfected receiving nucleos(t)ide analogue or interferon alfa therapy, (ii) HIV‐monoinfected on ART and (iii) uninfected persons. Dually treated coinfected patients had a higher cumulative incidence of hip fracture compared to ART‐treated HIV‐monoinfected (at 5 years: 1.70% vs 1.24%; adjusted HR, 1.37 95% CI, 1.03–1.83) and uninfected (at 5 years: 1.64% vs 1.22%; adjusted HR, 1.35 95% CI, 1.03–1.84) persons. The cumulative incidence of hip fracture was higher among coinfected than treated HBV‐monoinfected patients (at 5 years: 0.70% vs 0.27%), but this difference was not statistically significant in competing risk analysis (adjusted HR, 2.62 95% CI, 0.92–7.51). Among Medicaid enrollees, the risk of hip fracture was higher among dually treated HIV/HBV‐coinfected patients than ART‐treated HIV‐monoinfected and uninfected persons.
The patterns and determinants of saxagliptin use among patients with type 2 diabetes mellitus (T2DM) are unknown in real-world settings. We compared the characteristics of T2DM patients who were new ...initiators of saxagliptin to those who were new initiators of non-dipeptidyl peptidase-4 (DPP-4) inhibitor oral anti-diabetic drugs (OADs) and identified factors associated with saxagliptin use.
We conducted a cross-sectional study within the Clinical Practice Research Datalink (CPRD), The Health Improvement Network (THIN), US Medicare, and the HealthCore Integrated Research Database (HIRD(SM)) across the first 36 months of saxagliptin availability (29 months for US Medicare). Patients were included if they were: 1) ≥18 years old, 2) newly prescribed saxagliptin or a non-DPP-4 inhibitor OAD, and 3) enrolled in their respective database for 180 days. For each saxagliptin initiator, we randomly selected up to ten non-DPP-4 inhibitor OAD initiators matched on age, sex, and geographic region. Conditional logistic regression was used to identify determinants of saxagliptin use.
We identified 64,079 saxagliptin initiators (CPRD: 1,962; THIN: 2,084; US Medicare: 51,976; HIRD(SM): 8,057) and 610,660 non-DPP-4 inhibitor OAD initiators (CPRD: 19,484; THIN: 19,936; US Medicare: 493,432; HIRD(SM): 77,808). Across all four data sources, prior OAD use, hypertension, and hyperlipidemia were associated with saxagliptin use. Saxagliptin initiation was also associated with hemoglobin A1c results >8% within the UK data sources, and a greater number of hemoglobin A1c measurements in the US data sources.
In these UK and US data sources, initiation of saxagliptin was associated with prior poor glycemic control, prior OAD use, and diagnoses of hypertension and hyperlipidemia.
ClinicalTrials.gov identifiers NCT01086280 , NCT01086293 , NCT01086319 , NCT01086306 , and NCT01377935.
Rheumatoid arthritis (RA) has been associated with an increased risk of cardiovascular morbidity and mortality but this has not translated to optimal management of traditional cardiovascular risk ...factors such as hyperlipidemia. The objectives of this study were to 1) determine the prevalence of screening for hyperlipidemia in patients with RA followed by primary care practitioners (PCP); 2) examine initiation of lipid-lowering therapy in patients with an indication, and 3) assess whether proposed modifications to cardiovascular risk calculations change the percentage of RA patients with an indication for therapy.
We performed a retrospective cohort study using an academic medical center-based medical record database in the United States. Patients with RA defined by the presence of at least one ICD-9 code between 2005-2010 and followed by a PCP within the health care system were included. The positive predictive value of ICD-9 codes for accurately identifying patients with RA was 96.7%. Descriptive statistics were used to report the prevalence of screening and use of lipid-lowering therapy among those with an indication. Factors associated with not receiving lipid screening were examined using logistic regression models. Indication for and receipt of therapy were then assessed before and after the application of the European Union League Against Rheumatism (EULAR) recommended multiplier to the Framingham risk score.
Among 1,056 patients with RA followed by PCPs and eligible for lipid screening, lipid screening was ordered for 539 (51%) within the 3-year follow-up period. Patients with diabetes, hypertension, chronic kidney disease, obesity or age >50 were more likely to be screened. Of those with lipid results (N = 290), 25 (9%) patients had an indication for lipid-lowering therapy based on Adult Treatment Panel III guidelines. Ten (40%) patients with an indication for lipid-lowering therapy received therapy did not receive therapy. Applying the EULAR multiplier only changed the indication for lipid-lowering therapy in two patients.
Screening and management of traditional cardiovascular risk factors, including hyperlipidemia, need to be optimized.
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