Whole-Genome Sequencing Surveillance and Machine Learning of the Electronic Health Record for Enhanced Healthcare Outbreak Detection.

BACKGROUND: Most hospitals use traditional infection prevention (IP) methods for outbreak detection. We developed the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT), which combines whole-genome sequencing (WGS) surveillance and machine learning (ML) of the electronic health record (EHR) to identify undetected outbreaks and the responsible transmission routes, respectively. METHODS: We performed WGS surveillance of healthcare-associated bacterial pathogens from November 2016 to November 2018. EHR ML was used to identify the transmission routes for WGS-detected outbreaks, which were investigated by an IP expert. Potential infections prevented were estimated and compared with traditional IP practice during the same period. RESULTS: Of 3165 isolates, there were 2752 unique patient isolates in 99 clusters involving 297 (10.8%) patient isolates identified by WGS; clusters ranged from 2-14 patients. At least 1 transmission route was detected for 65.7% of clusters. During the same time, traditional IP investigation prompted WGS for 15 suspected outbreaks involving 133 patients, for which transmission events were identified for 5 (3.8%). If EDS-HAT had been running in real time, 25-63 transmissions could have been prevented. EDS-HAT was found to be cost-saving and more effective than traditional IP practice, with overall savings of $192 408-$692 532. CONCLUSIONS: EDS-HAT detected multiple outbreaks not identified using traditional IP methods, correctly identified the transmission routes for most outbreaks, and would save the hospital substantial costs. Traditional IP practice misidentified outbreaks for which transmission did not occur. WGS surveillance combined with EHR ML has the potential to save costs and enhance patient safety.

Method for Economic Evaluation of Bacterial Whole Genome Sequencing Surveillance Compared to Standard of Care in Detecting Hospital Outbreaks.

BACKGROUND: Whole genome sequencing (WGS) surveillance and electronic health record data mining have the potential to greatly enhance the identification and control of hospital outbreaks. The objective was to develop methods for examining economic value of a WGS surveillance-based infection prevention (IP) program compared to standard of care (SoC). METHODS: The economic value of a WGS surveillance-based IP program was assessed from a hospital's perspective using historical outbreaks from 2011-2016. We used transmission network of outbreaks to estimate incremental cost per transmission averted. The number of transmissions averted depended on the effectiveness of intervening against transmission routes, time from transmission to positive culture results and time taken to obtain WGS results and intervene on the transmission route identified. The total cost of an IP program included cost of staffing, WGS, and treating infections. RESULTS: Approximately 41 out of 89 (46%) transmissions could have been averted under the WGS surveillance-based IP program, and it was found to be a less costly and more effective strategy than SoC. The results were most sensitive to the cost of performing WGS and the number of isolates sequenced per year under WGS surveillance. The probability of the WGS surveillance-based IP program being cost-effective was 80% if willingness to pay exceeded $2400 per transmission averted. CONCLUSIONS: The proposed economic analysis is a useful tool to examine economic value of a WGS surveillance-based IP program. These methods will be applied to a prospective evaluation of WGS surveillance compared to SoC.

Economic analysis of screening for subclinical rejection in kidney transplantation using protocol biopsies and noninvasive biomarkers.

Subclinical rejection (SCR) screening in kidney transplantation (KT) using protocol biopsies and noninvasive biomarkers has not been evaluated from an economic perspective. We assessed cost-effectiveness from the health sector perspective of SCR screening in the first year after KT using a Markov model that compared no screening with screening using protocol biopsy or biomarker at 3 months, 12 months, 3 and 12 months, or 3, 6, and 12 months. We used 12% subclinical cellular rejection and 3% subclinical antibody-mediated rejection (SC-ABMR) for the base-case cohort. Results favored 1-time screening at peak SCR incidence rather than repeated screening. Screening 2 or 3 times was favored only with age <35 years and with high SC-ABMR incidence. Compared to biomarkers, protocol biopsy yielded more quality-adjusted life years (QALYs) at lower cost. A 12-month biopsy cost $13 318/QALY for the base-case cohort. Screening for cellular rejection in the absence of SC-ABMR was less cost effective with 12-month biopsy costing $46 370/QALY. Screening was less cost effective in patients >60 years. Using biomarker twice or thrice was cost effective only if biomarker cost was <$700. In conclusion, in KT, screening for SCR more than once during the first year is not economically reasonable. Screening with protocol biopsy was favored over biomarkers.

Criteria and Process for Initiating and Developing an ISPOR Good Practices Task Force Report.

The International Society for Pharmacoeconomics and Outcomes Research (ISPOR)'s "Good Practices Task Force" reports are highly cited, multistakeholder perspective expert guidance reports that reflect international standards for health economics and outcomes research (HEOR) and their use in healthcare decision making. In this report, we discuss the criteria, development, and evaluation/consensus review and approval process for initiating a task force. The rationale for a task force must include a justification, including why this good practice guidance is important and its potential impact on the scientific community. The criteria include: (1) necessity (why is this task force required?); (2) a methodology-oriented focus (focus on research methods, approaches, analysis, interpretation, and dissemination); (3) relevance (to ISPOR's mission and its members); (4) durability over time; (5) broad applicability; and 6) an evidence-based approach. In addition, the proposal must be a priority specifically for ISPOR. These reports are valuable to researchers, academics, students, health technology assessors, medical technology developers and service providers, those working in other commercial entities, regulators, and payers. These stakeholder perspectives are represented in task force membership to ensure the report's overall usefulness and relevance to the global ISPOR membership. We hope that this discussion will bring transparency to the process of initiating, approving, and producing these task force reports and encourage participation from a diverse range of experts within and outside ISPOR.

Cost Effectiveness of Transplanting HCV-Infected Livers Into Uninfected Recipients With Preemptive Antiviral Therapy.

BACKGROUND & AIMS: Guidelines do not recommend transplanting hepatitis C virus (HCV)-infected livers into HCV-uninfected recipients. Direct-acting antivirals (DAAs) can be used to treat donor-derived HCV infection. However, the added cost of DAA therapy is a barrier. We evaluated the cost effectiveness of transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy. METHODS: A previously validated Markov-based mathematical model was adapted to simulate a virtual trial of HCV-negative patients on the liver transplant waitlist. The model compared long-term clinical and economic outcomes in patients willing to accept only HCV-negative livers vs those willing to accept any liver (HCV negative or HCV positive). Recipients of HCV-positive livers received 12 weeks of preemptive DAA therapy. The model incorporated data from the United Network for Organ Sharing and published sources. RESULTS: For patients with a model for end-stage liver disease (MELD) score ≥ 22, accepting any liver vs waiting for only HCV-negative livers was cost effective, with incremental cost-effectiveness ratios ranging from $56,100 to $91,700/quality-adjusted life-year. For patients with a MELD score of 28 (the median MELD score of patients undergoing transplantation in the United States), accepting any liver was cost effective at an incremental cost-effectiveness ratio of $62,600/quality-adjusted life year. In patients with low MELD scores, which may not accurately reflect disease severity, accepting any liver was cost effective, irrespective of MELD score. CONCLUSIONS: Using a Markov-based mathematical model, we found transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy to be a cost-effective strategy that could improve health outcomes.

Transplanting hepatitis C virus-positive livers into hepatitis C virus-negative patients with preemptive antiviral treatment: A modeling study.

Under current guidelines, hepatitis C virus (HCV)-positive livers are not transplanted into HCV-negative recipients because of adverse posttransplant outcomes associated with allograft HCV infection. However, HCV can now be cured post-LT (liver transplant) using direct-acting antivirals (DAAs) with >90% success; therefore, HCV-negative patients on the LT waiting list may benefit from accepting HCV-positive organs with preemptive treatment. Our objective was to evaluate whether and in which HCV-negative patients the potential benefit of accepting an HCV-positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov-based mathematical model that simulated a virtual trial of HCV-negative patients on the LT waiting list to compare long-term outcomes in patients: (1) willing to accept any (HCV-negative or HCV-positive) liver versus (2) those willing to accept only HCV-negative livers. Patients receiving HCV-positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV-negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV-negative livers resulted in an increase in life expectancy when Model for End-Stage Liver Disease (MELD) was ≥20, and the benefit was highest at MELD 28 (0.172 additional life-years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV-positive donor organ rates, that is, Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust. CONCLUSION: Transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. (Hepatology 2018;67:2085-2095).

Cost Effectiveness of Pre- vs Post-Liver Transplant Hepatitis C Treatment With Direct-Acting Antivirals.

BACKGROUND & AIMS: Oral direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment offer new hope to both pre- and post-liver transplant (LT) patients. However, whether to treat HCV patients before vs after LT is not clear because treatment can improve liver function but could reduce the chance of receiving an LT while on the waiting list. Our objective was to evaluate the cost effectiveness of pre-LT vs post-LT HCV treatment with oral DAAs in decompensated cirrhotic patients on the LT waiting list. METHODS: We used a validated mathematical model that simulated a virtual trial comparing long-term clinical and cost outcomes of pre-LT vs post-LT HCV treatment with oral DAAs. Model parameters were estimated from United Network for Organ Sharing data, SOLAR-1 and 2 trials, and published studies. For each strategy, we estimated the quality-adjusted life-year, life expectancy, cost, and the incremental cost-effectiveness ratio. RESULTS: For lower MELD scores, quality-adjusted life-years were higher with pre-LT HCV treatment compared with post-LT treatment. Pre-LT HCV treatment was cost saving in patients with MELD scores of 15 or less, and cost effective in patients with MELD scores of 16 to 21. In contrast, post-LT HCV treatment was cost effective in patients with MELD scores of 22 to 29 and cost saving if MELD scores were 30 or higher. Results varied by drug prices and by United Network for Organ Sharing regions. CONCLUSIONS: For cirrhotic patients awaiting LT, pre-LT HCV treatment with DAAs is cost effective/saving in patients with MELD scores of 21 or lower, whereas post-LT HCV treatment is cost effective/saving in patients with MELD scores of 22 or higher.

Optimal timing of hepatitis C treatment for patients on the liver transplant waiting list.

The availability of oral direct-acting antivirals has altered the hepatitis C virus (HCV) treatment paradigm for both pre-liver transplant (LT) and post-LT patients. There is a perceived trade-off between pre-LT versus post-LT treatment of HCV-treatment may improve liver function but potentially decrease the likelihood of a necessary LT. Our objective was to identify LT-eligible patients with decompensated cirrhosis who would benefit (and not benefit) from pre-LT treatment based on their Model for End-Stage Liver Disease (MELD) scores. We simulated a virtual trial comparing long-term outcomes of pre-LT versus post-LT HCV treatment with oral direct-acting antivirals for patients with MELD scores between 10 and 40. We developed a Markov-based microsimulation model, which simulated the life course of patients on the transplant waiting list and after LT. Simulation of LT integrated data from recent trials of oral direct-acting antivirals (SOLAR 1 and 2), the United Network for Organ Sharing (UNOS), and other studies. The outcomes of the model included life expectancy, 1-year and 5-year patient survival, and mortality. Model-predicted patient survival was validated with UNOS data. We found that, at the national level, treating HCV before LT increased life expectancy if MELD was ≤27 but could decrease life expectancy at higher MELD scores. Depending on the UNOS region, the threshold MELD score to treat HCV pre-LT varied between 23 and 27 and was lower for UNOS regions 3, 10, and 11 and higher for regions 1, 2, 4, 5, 8, and 9. Sensitivity analysis showed that the thresholds were stable. CONCLUSION: Our findings suggest that the optimal MELD threshold below which decompensated cirrhosis patients should receive HCV treatment while awaiting LT is between 23 and 27, depending on the UNOS region. (Hepatology 2017;65:777-788).

Comparison of toxicant load from waterpipe and cigarette tobacco smoking among young adults in the USA.

OBJECTIVES: To form population-level comparisons of total smoke volume, tar, carbon monoxide and nicotine consumed from waterpipe tobacco smoking (WTS) and cigarette smoking using data from a nationally representative sample of smokers and non-smokers aged 18-30 years. METHODS: In March and April 2013, we surveyed a nationally representative sample of 3254 US young adults to assess the frequency and volume of WTS and cigarette smoking. We used Monte Carlo analyses with 5000 repetitions to estimate the proportions of toxicants originating from WTS and cigarette smoking. Analyses incorporated survey weights and used recent meta-analytic data to estimate toxicant exposures associated with WTS and cigarette smoking. RESULTS: Compared with the additive estimates of WTS and cigarette smoking combined, 54.9% (95% CI 37.5% to 72.2%) of smoke volume was attributed to WTS. The proportions of tar attributable to WTS was 20.8% (95% CI 6.5% to 35.2%), carbon monoxide 10.3% (95% CI 3.3% to 17.3%) and nicotine 2.4% (95% CI 0.9% to 3.8%). CONCLUSIONS: WTS accounted for over half of the tobacco smoke volume consumed among young US adult waterpipe and cigarette smokers. Toxicant exposures to tar, carbon monoxide and nicotine were lower, but still substantial, for WTS alone compared with WTS and cigarette smoking. Public health and policy interventions to reduce harm from tobacco smoking in young US adults should explicitly address WTS toxicant exposures.

Hepatitis C Disease Burden in the United States in the era of oral direct-acting antivirals.

Oral direct-acting antivirals (DAAs) represent a major advance in hepatitis C virus (HCV) treatment. Along with recent updates in HCV screening policy and expansions in insurance coverage, treatment demand in the United States is changing rapidly. Our objective was to project the characteristics and number of people needing antiviral treatment and HCV-associated disease burden in the era of oral DAAs. We used a previously developed and validated Hepatitis C Disease Burden Simulation model (HEP-SIM). HEP-SIM simulated the actual clinical management of HCV from 2001 onward, which included antiviral treatment with pegylated interferon (Peg-IFN)-based therapies as well as the recent oral DAAs, risk-based and birth-cohort HCV screening, and the impact of the Affordable Care Act. We also simulated two hypothetical scenarios-no treatment and treatment with Peg-IFN-based therapies only. We estimated that in 2010, 2.5 (95% confidence interval [CI], 1.9-3.1) million noninstitutionalized people were viremic, which dropped to 1.9 (95% CI, 1.4-2.6) million in 2015, and projected to drop below 1 million by 2020. A total of 1.8 million HCV patients will receive HCV treatment from the launch of oral DAAs in 2014 until 2030. Based on current HCV management practices, it will take 4-6 years to treat the majority of patients aware of their disease. However, 560,000 patients would still remain unaware by 2020. Even in the oral DAA era, 320,000 patients will die, 157,000 will develop hepatocellular carcinoma, and 203,000 will develop decompensated cirrhosis in the next 35 years. CONCLUSIONS: HCV-associated disease burden will still remain substantial in the era of oral DAAs. Increasing HCV screening and treatment capacity is essential to further decreasing HCV burden in the United States. (Hepatology 2016;64:1442-1450).

Prevention of Hepatitis C by Screening and Treatment in U.S. Prisons.

BACKGROUND: The prevalence of hepatitis C virus (HCV) in U.S. prisoners is high; however, HCV testing and treatment are rare. Infected inmates released back into society contribute to the spread of HCV in the general population. Routine hepatitis screening of inmates followed by new therapies may reduce ongoing HCV transmission. OBJECTIVE: To evaluate the health and economic effect of HCV screening and treatment in prisons on the HCV epidemic in society. DESIGN: Agent-based microsimulation model of HCV transmission and progression of HCV disease. DATA SOURCES: Published literature. TARGET POPULATION: Population in U.S. prisons and general community. TIME HORIZON: 30 years. PERSPECTIVE: Societal. INTERVENTIONS: Risk-based and universal opt-out hepatitis C screening in prisons, followed by treatment in a portion of patients. OUTCOME MEASURES: Prevention of HCV transmission and associated disease in prisons and society, costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and total prison budget. RESULTS OF BASE-CASE ANALYSIS: Implementing risk-based and opt-out screening could diagnose 41,900 to 122,700 new HCV cases in prisons in the next 30 years. Compared with no screening, these scenarios could prevent 5500 to 12,700 new HCV infections caused by released inmates, wherein about 90% of averted infections would have occurred outside of prisons. Screening could also prevent 4200 to 11,700 liver-related deaths. The ICERs of screening scenarios were $19,600 to $29,200 per QALY, and the respective first-year prison budget was $900 to $1150 million. Prisons would require an additional 12.4% of their current health care budget to implement such interventions. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to the time horizon, and ICERs otherwise remained less than $50,000 per QALY. LIMITATION: Data on transmission network, reinfection rate, and opt-out HCV screening rate are lacking. CONCLUSION: Universal opt-out HCV screening in prisons is highly cost-effective and would reduce HCV transmission and HCV-associated diseases primarily in the outside community. Investing in U.S. prisons to manage hepatitis C is a strategic approach to address the current epidemic. PRIMARY FUNDING SOURCE: National Institutes of Health.

Using Health Information Technology to Foster Engagement: Patients' Experiences with an Active Patient Health Record.

Personal health records (PHRs) typically employ "passive" communication strategies, such as non-personalized medical text, rather than direct patient engagement in care. Currently there is a call for more active PHRs that directly engage patients in an effort to improve their health by offering elements such as personalized medical information, health coaches, and secure messaging with primary care providers. As part of a randomized clinical trial comparing "passive" with "active" PHRs, we explore patients' experiences with using an "active" PHR known as HealthTrak. The "passive" elements of this PHR included problem lists, medication lists, information about patient allergies and immunizations, medical and surgical histories, lab test results, health reminders, and secure messaging. The active arm included all of these elements and added personalized alerts delivered through the secure messaging platform to patients for services coming due based on various demographic features (including age and sex) and chronic medical conditions. Our participants were part of the larger clinical trial and were eligible if they had been randomized to the active PHR arm, one that included regular personalized alerts. We conducted focus group discussions on the benefits of this active PHR for patients who are at risk for cardiovascular disease. Forty-one patients agreed to participate and were organized into five separate focus group sessions. Three main themes emerged from the qualitatively analyzed focus groups: participants reported that the active PHR promoted better communication with providers; enabled them to more effectively partner with their providers; and helped them become more proactive about tracking their health information. In conclusion, patients reported improved communication, partnership with their providers, and a sense of self-management, thus adding insights for PHR designers hoping to address low adoption rates and other patient barriers to the development and use of the technology.

Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States.

BACKGROUND: Sofosbuvir and ledipasvir, which have recently been approved for treatment of chronic hepatitis C virus (HCV) infection, are more efficacious and safer than the old standard of care (oSOC) but are substantially more expensive. Whether and in which patients their improved efficacy justifies their increased cost is unclear. OBJECTIVE: To evaluate the cost-effectiveness and budget impact of sofosbuvir and ledipasvir. DESIGN: Microsimulation model of the natural history of HCV infection. DATA SOURCES: Published literature. TARGET POPULATION: Treatment-naive and treatment-experienced HCV population defined on the basis of HCV genotype, age, and fibrosis distribution in the United States. TIME HORIZON: Lifetime. PERSPECTIVE: Third-party payer. INTERVENTION: Simulation of sofosbuvir-ledipasvir compared with the oSOC (interferon-based therapies). OUTCOME MEASURES: Quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and 5-year spending on antiviral drugs. RESULTS OF BASE-CASE ANALYSIS: Sofosbuvir-based therapies added 0.56 QALY relative to the oSOC at an ICER of $55 400 per additional QALY. The ICERs ranged from $9700 to $284 300 per QALY depending on the patient's status with respect to treatment history, HCV genotype, and presence of cirrhosis. At a willingness-to-pay threshold of $100 000 per QALY, sofosbuvir-based therapies were cost-effective in 83% of treatment-naive and 81% of treatment-experienced patients. Compared with the oSOC, treating eligible HCV-infected persons in the United States with the new drugs would cost an additional $65 billion in the next 5 years, whereas the resulting cost offsets would be $16 billion. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to drug price, drug efficacy, and quality of life after successful treatment. LIMITATION: Data on real-world effectiveness of new antivirals are lacking. CONCLUSION: Treatment of HCV is cost-effective in most patients, but additional resources and value-based patient prioritization are needed to manage patients with HCV. PRIMARY FUNDING SOURCE: National Institutes of Health.

Targeting an alcohol intervention cost-effectively to persons living with HIV/AIDS in East Africa.

BACKGROUND: In the current report, we ask if targeting a cognitive behavioral therapy (CBT)-based intervention aimed at reducing hazardous alcohol consumption to HIV-infected persons in East Africa would have a favorable value at costs that are feasible for scale-up. METHODS: Using a computer simulation to inform HIV prevention decisions in East Africa, we compared 4 different strategies for targeting a CBT intervention-(i) all HIV-infected persons attending clinic; (ii) only those patients in the pre-antiretroviral therapy (ART) stages of care; (iii) only those patients receiving ART; and (iv) only those patients with detectable viral loads (VLs) regardless of disease stage. We define targeting as screening for hazardous alcohol consumption (e.g., using the Alcohol Use Disorders Identification Test and offering the CBT intervention to those who screen positive). We compared these targeting strategies to a null strategy (no intervention) or a hypothetical scenario where an alcohol intervention was delivered to all adults regardless of HIV status. RESULTS: An intervention targeted to HIV-infected patients could prevent 18,000 new infections, add 46,000 quality-adjusted life years (QALYs), and yield an incremental cost-effectiveness ratio of $600/QALY compared to the null scenario. Narrowing the prioritized population to only HIV-infected patients in pre-ART phases of care results in 15,000 infections averted, the addition of 21,000 QALYs and would be cost-saving, while prioritizing based on an unsuppressed HIV-1 VL test results in 8,300 new infections averted, adds 6,000 additional QALYs, and would be cost-saving as well. CONCLUSIONS: Our results suggest that targeting a cognitive-based treatment aimed at reducing hazardous alcohol consumption to subgroups of HIV-infected patients provides favorable value in comparison with other beneficial strategies for HIV prevention and control in this region. It may even be cost-saving under certain circumstances.

HIV Treatment in Resource-Limited Environments: Treatment Coverage and Insights.

BACKGROUND: The effects of antiretroviral treatment on the HIV epidemic are complex. HIV-infected individuals survive longer with treatment, but are less likely to transmit the disease. The standard coverage measure improves with the deaths of untreated individuals and does not consider the fact that some individuals may acquire the disease and die before receiving treatment, making it susceptible to overestimating the long-run performance of antiretroviral treatment programs. OBJECTIVE: The objective was to propose an alternative coverage definition to better measure the long-run performance of HIV treatment programs. METHODS: We introduced cumulative incidence-based coverage as an alternative to measure an HIV treatment program's success. To numerically compare the definitions, we extended a simulation model of HIV disease and treatment to represent a dynamic population that includes uninfected and HIV-infected individuals. Also, we estimated the additional resources required to implement various treatment policies in a resource-limited setting. RESULTS: In a synthetic population of 600,000 people of which 44,000 (7.6%) are infected, and eligible for treatment with a CD4 count of less than 500 cells/mm(3), assuming a World Health Organization (WHO)-defined coverage rate of 50% of eligible people, and treating these individuals with a single treatment regimen, the gap between the current WHO coverage definition and our proposed one is as much as 16% over a 10-year planning horizon. CONCLUSIONS: Cumulative incidence-based definition of coverage yields a more accurate representation of the long-run treatment success and along with the WHO and other definitions of coverage provides a better understanding of the HIV treatment progress.

The PROMIS of QALYs.

Measuring health and health-related quality of life (HRQoL) is important for tracking the health of individuals and populations over time. Generic HRQoL measures allow for comparison across health conditions. One form of generic HRQoL measures are profile measures, which provide a description of health across several different domains (such as physical functioning, depression, and pain). Recent advances in health profile measurement include the development of measures based on item response theory. The Patient-Reported Outcomes Measurement Information System (PROMIS®) has been constructed using this theory. Another form of generic HRQoL measures are utility measures, which assess the value of health states. Multi-attribute utility theory provides a framework for valuing disparate domains of health and aggregating them into a single preference-based score. Such a score provides an overall measure of health outcomes as well as a quality of life weight for use in decision analyses and cost-effectiveness analyses. Developing a utility score for PROMIS® would allow simultaneous estimation of both health profile and utility scores using a single measure. The purpose of this paper is to provide a roadmap of the methodological steps necessary to create such a scoring system.

The changing burden of hepatitis C virus infection in the United States: model-based predictions.

BACKGROUND: Chronic hepatitis C virus (HCV) infection causes a substantial health and economic burden in the United States. With the availability of direct-acting antiviral agents, recently approved therapies and those under development, and 1-time birth-cohort screening, the burden of this disease is expected to decrease. OBJECTIVE: To predict the effect of new therapies and screening on chronic HCV infection and associated disease outcomes. DESIGN: Individual-level state-transition model. SETTING: Existing and anticipated therapies and screening for HCV infection in the United States. PATIENTS: Total HCV-infected population in the United States. MEASUREMENTS: The number of cases of chronic HCV infection and outcomes of advanced-stage HCV infection. RESULTS: The number of cases of chronic HCV infection decreased from 3.2 million in 2001 to 2.3 million in 2013. One-time birth-cohort screening beginning in 2013 is expected to identify 487,000 cases of HCV infection in the next 10 years. In contrast, 1-time universal screening could identify 933,700 cases. With the availability of highly effective therapies, HCV infection could become a rare disease in the next 22 years. Recently approved therapies for HCV infection and 1-time birth-cohort screening could prevent approximately 124,200 cases of decompensated cirrhosis, 78,800 cases of hepatocellular carcinoma, 126,500 liver-related deaths, and 9900 liver transplantations by 2050. Increasing the treatment capacity would further reduce the burden of HCV disease. LIMITATION: Institutionalized patients with HCV infection were excluded, and empirical data on the effectiveness of future therapies and on the future annual incidence and treatment capacity of HCV infection are lacking. CONCLUSION: New therapies for HCV infection and widespread implementation of screening and treatment will play an important role in reducing the burden of HCV disease. More aggressive screening recommendations are needed to identify a large pool of infected patients. PRIMARY FUNDING SOURCE: National Institutes of Health.

Impact of interventions targeting unhealthy alcohol use in Kenya on HIV transmission and AIDS-related deaths.

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.

Patterns of response to patient-centered decision support through a personal health record.

BACKGROUND: Over 140 million people in the United States have at least one chronic medical condition, but they receive fewer than 60% of guideline-recommended services for these conditions. Increasing patients' involvement in their own care may improve the receipt of guideline-recommended services. We evaluated patients' patterns of responses to notifications regarding guideline-recommended services delivered through a personalized health record (PHR). MATERIALS AND METHODS: We enrolled 584 participants with high cardiovascular disease risk from 73 primary care practices into an active PHR in which they received patient-centered decision support-notifications delivered via a PHR regarding prevention gaps (i.e., unmet preventive healthcare or chronic disease monitoring). Participants with prevention gaps received up to three weekly messages regarding all services due within a 2-month time frame. These three-message cycles could repeat up to every 2 months for a new, or continuing, prevention gap. RESULTS: Of the 584 participants, 501 (86%) received at least one reminder. Approximately 61% of these participants accessed the PHR or received the care that triggered the message after the first message and 73% after the first two messages. In subsequent three-message cycles, we observed no change in the number of messages required prior to participants accessing the PHR or receiving recommended care (chi-squared = 12.4, p = 0.3). Of the 2,656 prevention gaps these participants had over 1 year, 1,539 (58%) were closed. CONCLUSIONS: In this low-intensity intervention, participants accessed the PHR and received recommended care. Providing notification through the PHR allows patients to choose when they receive, and take action on, the message. Notifications can be provided to patients through a PHR without alert fatigue and may be an additional tool to help patients achieve better health.