Emily S. Brouwer

Is HIV Infection a Risk Factor for Multi-Drug Resistant Tuberculosis? A Systematic Review

Background Tuberculosis (TB) is an important cause of human suffering and death. Human immunodeficiency virus (HIV), multi-drug resistant TB (MDR-TB), and extensive drug resistant tuberculosis (XDR-TB) have emerged as threats to TB control. The association between MDR-TB and HIV infection has not yet been fully investigated. We conducted a systematic review and meta-analysis to summarize the evidence on the association between HIV infection and MDR-TB. Methods and Results Original studies providing Mycobacterium tuberculosis resistance data stratified by HIV status were identified using MEDLINE and ISI Web of Science. Crude MDR-TB prevalence ratios were calculated and analyzed by type of TB (primary or acquired), region and study period. Heterogeneity across studies was assessed, and pooled prevalence ratios were generated if appropriate. No clear association was found between MDR-TB and HIV infection across time and geographic locations. MDR-TB prevalence ratios in the 32 eligible studies, comparing MDR-TB prevalence by HIV status, ranged from 0.21 to 41.45. Assessment by geographical region or study period did not reveal noticeable patterns. The summary prevalence ratios for acquired and primary MDR-TB were 1.17 (95% CI 0.86, 1.6) and 2.72 (95% CI 2.03, 3.66), respectively. Studies eligible for review were few considering the size of the epidemics. Most studies were not adjusted for confounders and the heterogeneity across studies precluded the calculation of a meaningful overall summary measure. Conclusions We could not demonstrate an overall association between MDR-TB and HIV or acquired MDR-TB and HIV, but our results suggest that HIV infection is associated with primary MDR-TB. Future well-designed studies and surveillance in all regions of the world are needed to better clarify the relationship between HIV infection and MDR-TB.

Communicating quantitative risks and benefits in promotional prescription drug labeling or print advertising

Under the Food, Drug, and Cosmetic Act, all promotional materials for prescription drugs must strike a fair balance in presentation of risks and benefits. How to best present this information is not clear. We sought to determine if the presentation of quantitative risk and benefit information in drug advertising and labeling influences consumers’, patients’, and clinicians’ information processing, knowledge, and behavior by assessing available empirical evidence.

Initial and subsequent therapy for newly diagnosed type 2 diabetes patients treated in primary care using data from a vendor-based electronic health record†

Diabetes is a leading cause of death and disability, and its prevalence is increasing. When diet fails, patients with type 2 diabetes mellitus (T2DM) are prescribed oral hypoglycemics for glycemic control. Few studies have explored initial use or change from initial oral hypoglycemic therapy in the primary care setting. We aimed to describe the utilization of initial oral hypoglycemics among newly diagnosed patients with diabetes from 1998–2009 and changes from initial to subsequent therapy among patients prescribed older oral hypoglycemic agents using electronic health records.

Effects of combination antiretroviral therapies on the risk of myocardial infarction among HIV patients.

Background: Cohort studies have demonstrated greater risk of myocardial infarction (MI) associated with specific antiretroviral use, while meta-analyses of randomized controlled trials (RCTs) have not. These differences may be due to inherent biases in the observational study design or to the limited duration of randomized trials. We conducted a new-user, active-comparator cohort study emulating an RCT comparing the initiation of several antiretrovirals as part of combination antiretroviral therapy (cART) and MI. Methods: We included North Carolina (NC) Medicaid beneficiaries infected with human immunodeficiency virus between 2002 and 2008 who were previously untreated with cART. We compared hazard ratios (HRs) and 95% confidence intervals (CIs) of MI between abacavir and tenofovir recipients, and lopinavir-ritonavir or atazanavir recipients and nonnucleoside reverse transcriptase inhibitor (NNRTI) recipients. We adjusted for confounding through inverse probability weighting methods. Results: There were 3481 NC Medicaid new cART recipients who contributed 6399 person-years and experienced 38 MI events. Receiving abacavir compared with tenofovir as part of cART was associated with an increased rate of MI (unadjusted HR = 2.70 [95% CI = 1.24–5.91]; adjusted HR = 2.05 [0.72–5.86]). Point estimates also suggest a relationship between receipt of atazanavir or lopinavir-ritonavir compared with an NNRTI and MI, although estimates were imprecise. Conclusions: We found an increased rate of MI among patients initiating abacavir compared with tenofovir, although the association was decreased after confounding adjustment. Without a very large prospective comparative clinical trial, a much larger observational study of patients initiating cART would be needed to better define this apparent association.

Comparative effectiveness research using electronic health records: impacts of oral antidiabetic drugs on the development of chronic kidney disease

Little is known about the comparative effects of common oral antidiabetic drugs ([OADs] metformin, sulfonylureas, or thiazolidinediones [THZs]) on chronic kidney disease (CKD) outcomes in patients newly diagnosed with type 2 diabetes (T2DM) and followed in community primary care practices. Electronic health records (EHRs) were used to evaluate the relationships between OAD class use and incident proteinuria and prevention of glomerular filtration rate decline.

Self-report of current and prior antiretroviral drug use in comparison to the medical record among HIV-infected patients receiving primary HIV care.

Patient antiretroviral (ARV) therapy knowledge is essential for regimen adherence, successful therapeutic response, and minimization of resistance evolution. Moreover, a complete and accurate patient ARV history is needed to construct efficacious and tolerable future regimens. In this study we assessed the ability of HIV‐infected patients receiving care in a university infectious diseases clinic to accurately recall current and past ARVs.

Validation of Medicaid Claims-based Diagnosis of Myocardial Infarction Using an Hiv Clinical Cohort

Background:In nonexperimental comparative effectiveness research using health care databases, outcome measurements must be validated to evaluate and potentially adjust for misclassification bias. We aimed to validate claims-based myocardial infarction (MI) algorithms in a Medicaid population using an HIV clinical cohort as the gold standard. Methods:Medicaid administrative data were obtained for the years 2002–2008 and linked to the UNC CFAR HIV Clinical Cohort based on social security number, first name, and last name and MI were adjudicated. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Results:There were 1063 individuals included in the study. Over a median observed time of 2.5 years, 17 had an MI. Specificity ranged from 0.979 to 0.993 with the highest specificity obtained using the ICD-9 code 410.xx in the primary or secondary position and a length of stay >3 days. Sensitivity of MI ascertainment varied from 0.588 to 0.824 depending on algorithm. Conclusions:Specificities of varying claims-based MI ascertainment criteria are high but small changes impact positive predictive value in a cohort with low incidence. Sensitivities vary based on ascertainment criteria. Type of algorithm used should be prioritized based on study question and maximization of specific validation parameters that will minimize bias while also considering precision.

Using administrative data for your research project: 10 considerations before you begin.

With increasing pressure to conduct research during residency training, and given the availability of administrative claims data, pharmacy residents will likely consider using large administrative databases for their research project. With competing time commitments and the short duration of residencies, residents and their preceptors must consider the 10 factors outlined above in order to produce a thoughtful, clinically relevant research project. While this discussion focused on the completion of a residency research project, these topics are also relevant to a broader pharmacy audience. Colleges of pharmacy are increasingly requiring research projects as part of their curriculum, and pharmacy students and practitioners often consider obtaining additional degrees requiring a research component. Both students and practitioners can use the guidance provided herein when planning research projects and investigations to aid in the successful completion of research using administrative claims data.

Sex differences in benzodiazepine use in the HIV-infected population

In the HIV-infected population there is a high prevalence of psychiatric disorders, conditions that often coexist with drug and alcohol dependence. Symptoms associated with psychiatric disorders are frequently managed with benzodiazepines, a class of medication often abused. We examined whether HIV-infected patients were more likely to fill a benzodiazepine prescription than their uninfected counterparts using a privately insured, nationally representative sample receiving clinical care between January 2007 and December 2009. Odds ratios (OR) and 95% confidence intervals (CI) to quantify the likelihood of receiving a benzodiazepine were calculated using multivariate logistic regression models. We examined the presence of interaction between HIV infection and sex using backwards elimination and by comparing stratum-specific OR to identify clinically meaningful differences. Overall, 323,796 beneficiaries were included in the sample, of which 723 were HIV infected. Bivariate analyses showed that compared to the uninfected sample, HIV-infected patients were more likely to have filled a benzodiazepine prescription (24% vs. 19%) during the study period. HIV-infected patients were also more likely to be male (80% vs. 44%), black (21% vs. 7%) and have a diagnosis of depression (12% vs. 8%) or insomnia (6% vs. 3%) than were uninfected patients. Adjusted for other covariates, HIV infection was associated with an increase (OR): 1.68, 95% CI: 1.39, 2.02) in the likelihood of filling a benzodiazepine prescription. When stratified by sex, HIV-infected males were more likely (OR: 1.68, 95% CI: 1.05, 2.67) than uninfected males to fill a benzodiazepine prescription while there was no observed difference in the likelihood of filling a benzodiazepine prescription between HIV-infected and uninfected females (OR: 1.12, 95% CI: 0.73, 1.70). Our findings suggest that HIV-infected patients, particularly HIV-infected males, are more likely to fill benzodiazepine prescriptions than their uninfected counterparts, highlighting the need for further research to investigate reasons for these observed differences.

Evaluating the incident user design in the HIV population: incident use versus naive?

The incident user design is the preferred study design in comparative effectiveness (CER) research. Usually, 180–365 days of exposure free time is adequate to remove biases associated with inclusion of prevalent users. In HIV research, the use of antiretrovirals (ARVs) at any time in the past may influence future treatment choices and CER results; thus, identifying naive as opposed to incident users is of importance. We examined misclassification of antiretroviral naive status based on Medicaid administrative data through linkage to the UNC CFAR HIV Clinical Cohort (UCHCC).