Faculty Bibliography

BACKGROUND: HIV remains a major cause of preventable morbidity and mortality in Kenya. The effects of behaviors that accompany unhealthy alcohol consumption are a pervasive risk factor for HIV transmission and progression. Our objective was to estimate the portion of HIV infections attributable to unhealthy alcohol use and to evaluate the impact of hypothetical interventions directed at unhealthy alcohol use on HIV infections and deaths. METHODS: We estimated outcomes over a time horizon of 20 years using a computer simulation of the Kenyan population. This computer simulation integrates a compartmental model of HIV transmission with a mechanistic model of HIV progression that was previously validated in sub-Saharan Africa. Integration of the transmission and progression models allows simultaneous consideration of alcohol's effects on HIV transmission and progression (e.g., lowering antiretroviral adherence may increase transmission risk by elevating viral load, and may simultaneously increase progression by increasing the likelihood of AIDS). The simulation considers important aspects of heterogeneous sexual mixing patterns, including assortativeness of partners by age and activity level, age-discordant relationships, and high activity subgroups. Outcomes included number of new HIV infections, number of AIDS deaths, and infectivity (number of new infections per infected person per year). RESULTS: Our model estimated that the effects of behaviors accompanying unhealthy alcohol consumption are responsible for 13.0% of new HIV infections in Kenya. An alcohol intervention with effectiveness similar to that observed in a published randomized controlled trial of a cognitive-behavioral therapy-based intervention in Kenya (45% reduction in unhealthy alcohol consumption) could prevent nearly half of these infections, reducing their number by 69,858 and reducing AIDS deaths by 17,824 over 20 years. Estimates were sensitive to assumptions with respect to the magnitude of alcohol's underlying effects on condom use, antiretroviral therapy adherence, and sexually transmitted infection prevalence. CONCLUSIONS: A substantial number of new HIV infections in Kenya are attributable to unhealthy alcohol use. An alcohol intervention with the effectiveness observed in a published randomized controlled trial has the potential to reduce infections over 20 years by nearly 5% and avert nearly 18,000 deaths related to HIV.

Objectives: The objectives of this systematic literature review were to identify all published literature on wearable defibrillators, assess the wearable defibrillator's efficacy and effectiveness in general and among specific patient groups, including post-myocardial infarction, post coronary artery bypass grafting or percutaneous coronary intervention, non-ischemic cardiomyopathy, and ischemic cardiomyopathy, and to evaluate the quality of evidence. Methods: The search and synthesis was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and the quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation and the Newcastle Ottawa Scale. Results: A total of thirty-six articles and conference abstracts from thirty-three studies were included in the review. It appears that wearable defibrillator use compared with no defibrillator use reduces the chance of ventricular tachycardia and ventricular fibrillation (VT/VF) associated deaths by an absolute risk reduction of approximately 1 percent, achieved by averting approximately 4/5th of all VT/VF associated deaths. The quality of evidence was low to very low quality, such that our confidence in the reported estimates is weak. Conclusions: To validate beneficial results, further investigation using robust study designs conducted by independent researchers is warranted.

BACKGROUND: Outbreaks of hepatitis C virus (HCV) infection have been reported in HIV-positive men who have sex with men (MSM) in North America, Europe and Asia. Transmission is believed to be the result of exposure to blood during sexual contact. In those infected with HIV, acute HCV infection is more likely to become chronic, treatment for both HIV and HCV is more complicated and HCV disease progression may be accelerated. There is a need for systematic reviews and meta-analyses to synthesize the epidemiology, prevention and methods to control HCV infection in this population. METHODS/DESIGN: Eligible studies will include quantitative empirical data related to sexual transmission of HCV in HIV-positive MSM, including data describing incidence or prevalence, and associations between risk factors or interventions and the occurrence or progression of HCV disease. Care will be taken to ensure that HCV transmission related to injection drug use is excluded from the incidence estimates. Scientific databases will be searched using a comprehensive search strategy. Proceedings of scientific conferences, reference lists and personal files will also be searched. Quality ratings will be assigned to each eligible report using the Newcastle-Ottawa scale. Pooled estimates of incidence rates and measures of association will be calculated using random effects models. Heterogeneity will be assessed at each stage of data synthesis. DISCUSSION: HIV-positive MSM are a key HCV-affected population in the US and other high-income countries. This review seeks to identify modifiable risk factors and settings that will be the target of interventions, and will consider how to constitute a portfolio of interventions to deliver the greatest health benefit. This question must be considered in relation to the magnitude of HCV infection and its consequences in other key affected populations, namely, young prescription opioid users who have transitioned to illicit opiate injection, and older injection drug users among whom HCV prevalence and incidence are extremely high. This review is part of a series of systematic reviews and meta-analyses that will synthesize the evidence across all these population groups and develop recommendations and decision tools to guide public health resource allocation. TRIAL REGISTRATION: PROSPERO registration number: CRD42013006462.

BACKGROUND: Previous studies have suggested that weekend hospital care is inferior to weekday care and that this difference may be related to diminished care intensity. The purpose of this study was to determine whether a metric for measuring intensity of hospital care based on utilization of the electronic health record (EHR) was associated with patient-level outcomes. METHODS: We performed a cohort study of hospitalizations at an academic medical center. Intensity of care was defined as the hourly number of provider accessions of the electronic health record, termed "EHR interactions." Hospitalizations were categorized based on the mean difference in EHR interactions between the first Friday and Saturday of hospitalization. We used regression models to determine the association of these categories with patient outcomes after adjusting for covariates. RESULTS: EHR interactions decreased from Friday to Saturday in 77% of the 9,051 hospitalizations included in the study. As compared to hospitalizations with no change in Friday to Saturday EHR interactions, the relative lengths of stay for hospitalizations with a small, moderate, and large decrease in EHR interactions were 1.05 (95% CI 1.00-1.10), 1.11 (95% CI 1.05-1.17), and 1.25 (95% CI 1.15-1.35), respectively. Although a large decrease in EHR interactions was associated with in-hospital mortality, these findings were not significant after risk adjustment (odds ratio 1.74, 95% CI 0.93-3.25). CONCLUSIONS: Intensity of inpatient care, measured by EHR interactions, significantly diminished from Friday to Saturday, and this decrease was associated with length of stay. Hospitals should consider monitoring and correcting temporal fluctuations in care intensity.

BACKGROUND:WHO's 2013 revisions to its Consolidated Guidelines on antiretroviral drugs recommend routine viral load monitoring, rather than clinical or immunological monitoring, as the preferred monitoring approach on the basis of clinical evidence. However, HIV programmes in resource-limited settings require guidance on the most cost-effective use of resources in view of other competing priorities such as expansion of antiretroviral therapy coverage. We assessed the cost-effectiveness of alternative patient monitoring strategies. METHODS:We evaluated a range of monitoring strategies, including clinical, CD4 cell count, and viral load monitoring, alone and together, at different frequencies and with different criteria for switching to second-line therapies. We used three independently constructed and validated models simultaneously. We estimated costs on the basis of resource use projected in the models and associated unit costs; we quantified impact as disability-adjusted life years (DALYs) averted. We compared alternatives using incremental cost-effectiveness analysis. FINDINGS/RESULTS:All models show that clinical monitoring delivers significant benefit compared with a hypothetical baseline scenario with no monitoring or switching. Regular CD4 cell count monitoring confers a benefit over clinical monitoring alone, at an incremental cost that makes it affordable in more settings than viral load monitoring, which is currently more expensive. Viral load monitoring without CD4 cell count every 6-12 months provides the greatest reductions in morbidity and mortality, but incurs a high cost per DALY averted, resulting in lost opportunities to generate health gains if implemented instead of increasing antiretroviral therapy coverage or expanding antiretroviral therapy eligibility. INTERPRETATION/CONCLUSIONS:The priority for HIV programmes should be to expand antiretroviral therapy coverage, firstly at CD4 cell count lower than 350 cells per μL, and then at a CD4 cell count lower than 500 cells per μL, using lower-cost clinical or CD4 monitoring. At current costs, viral load monitoring should be considered only after high antiretroviral therapy coverage has been achieved. Point-of-care technologies and other factors reducing costs might make viral load monitoring more affordable in future. FUNDING/BACKGROUND:Bill & Melinda Gates Foundation, WHO.

BACKGROUND: Many analyses of HIV treatment decisions assume a fixed formulary of HIV drugs. However, new drugs are approved nearly twice a year, and the rate of availability of new drugs may affect treatment decisions, particularly when to initiate antiretroviral therapy (ART). OBJECTIVES: To determine the impact of considering the availability of new drugs on the optimal initiation criteria for ART and outcomes in patients with HIV/AIDS. METHODS: We enhanced a previously described simulation model of the optimal time to initiate ART to incorporate the rate of availability of new antiviral drugs. We assumed that the future rate of availability of new drugs would be similar to the past rate of availability of new drugs, and we estimated the past rate by fitting a statistical model to actual HIV drug approval data from 1982-2010. We then tested whether or not the future availability of new drugs affected the model-predicted optimal time to initiate ART based on clinical outcomes, considering treatment initiation thresholds of 200, 350, and 500 cells/mm3. We also quantified the impact of the future availability of new drugs on life expectancy (LE) and quality-adjusted life expectancy (QALE). RESULTS: In base case analysis, considering the availability of new drugs raised the optimal starting CD4 threshold for most patients to 500 cells/mm3. The predicted gains in outcomes due to availability of pipeline drugs were generally small (less than 1%), but for young patients with a high viral load could add as much as a 4.9% (1.73 years) increase in LE and a 8% (2.43 QALY) increase in QALE, because these patients were particularly likely to exhaust currently available ART regimens before they died. In sensitivity analysis, increasing the rate of availability of new drugs did not substantially alter the results. Lowering the toxicity of future ART drugs had greater potential to increase benefit for many patient groups, increasing QALE by as much as 10%. CONCLUSIONS: The future availability of new ART drugs without lower toxicity raises optimal treatment initiation for most patients, and improves clinical outcomes, especially for younger patients with higher viral loads. Reductions in toxicity of future ART drugs could impact optimal treatment initiation and improve clinical outcomes for all HIV patients.

BACKGROUND:Quality reporting is increasingly used as a tool to encourage health systems, hospitals, and their practitioners to deliver the greatest health benefit. However, quality reporting systems may have unintended negative consequences, such as inadvertently encouraging "cherry-picking" by inadequately adjusting for patients who are challenging to take care of, or underpowering to reliably detect meaningful differences in care. There have been no reports seeking to identify a minimum level of accuracy that ought to be viewed as a prerequisite for quality reporting. METHOD/METHODS:Using a decision analytic model, we seek to delineate minimal standards for quality measures to meet, using the simplest assumptions to illustrate what those standards may be. RESULTS:We find that even under assumptions regarding optimal performance of the quality reporting system (sensitivity and specificity of 1), we can identify a minimal level of accuracy required for the quality reporting system to "do no harm": the increase in health-related quality of life from a higher rather than lower quality practitioner must be greater than the number of practitioners per patient divided by the proportion of patients willing to switch from a lower to a higher quality provider. CONCLUSION/CONCLUSIONS:Quality measurement systems that have not been demonstrated to improve health outcomes should be held to a specific standard of measurement accuracy.