Planning for Mpox on a College Campus: A Model-Based Decision-Support Tool.

BACKGROUND: In spring and summer 2022, an outbreak of mpox occurred worldwide, largely confined to men who have sex with men (MSM). There was concern that mpox could break swiftly into congregate settings and populations with high levels of regular frequent physical contact, like university campus communities. OBJECTIVE: To estimate the likelihood of an mpox outbreak and the potential effect of mitigation measures in a residential college setting. DESIGN: A stochastic dynamic SEIR (susceptible, exposed but not infectious, infectious, or recovered) model of mpox transmission in a study population was developed, composed of: a high-risk group representative of the population of MSM with a basic reproductive number (R 0) of 2.4 and a low-risk group with an R 0 of 0.8. Base input assumptions included an incubation time of 7.6 days and time to recovery of 21 days. SETTING: U.S. residential college campus. PARTICIPANTS: Hypothetical cohort of 6500 students. INTERVENTION: Isolation, quarantine, and vaccination of close contacts. MEASUREMENTS: Proportion of 1000 simulations producing sustained transmission; mean cases given sustained transmission; maximum students isolated, quarantined, and vaccinated. All projections are estimated over a planning horizon of 100 days. RESULTS: Without mitigation measures, the model estimated an 83% likelihood of sustained transmission, leading to an average of 183 cases. With detection and isolation of 20%, 50%, and 80% of cases, the average infections would fall to 117, 37, and 8, respectively. Reactive vaccination of contacts of detected cases (assuming 50% detection and isolation) reduced mean cases from 37 to 17, assuming 20 vaccinated contacts per detected case. Preemptive vaccination of 50% of the high-risk population before outbreak reduced cases from 37 to 14, assuming 50% detection and isolation. LIMITATION: A model is a stylized portrayal of behavior and transmission on a university campus. CONCLUSION: Based on our current understanding of mpox epidemiology among MSM in the United States, this model-based analysis suggests that future outbreaks of mpox on college campuses may be controlled with timely detection and isolation of symptomatic cases. PRIMARY FUNDING SOURCE: National Institutes of Health National Institute on Drug Abuse and National Institute of Allergy and Infectious Diseases.

Population-Level Health Effects of Involuntary Displacement of People Experiencing Unsheltered Homelessness Who Inject Drugs in US Cities.

Importance: At least 500 000 people in the US experience homelessness nightly. More than 30% of people experiencing homelessness also have a substance use disorder. Involuntary displacement is a common practice in responding to unsheltered people experiencing homelessness. Understanding the health implications of displacement (eg, "sweeps," "clearings," "cleanups") is important, especially as they relate to key substance use disorder outcomes. Objective: To estimate the long-term health effects of involuntary displacement of people experiencing homelessness who inject drugs in 23 US cities. Design, Setting, and Participants: A closed cohort microsimulation model that simulates the natural history of injection drug use and health outcomes among people experiencing homelessness who inject drugs in 23 US cities. The model was populated with city-level data from the Centers for Disease Control and Prevention's National HIV Behavioral Surveillance system and published data to make representative cohorts of people experiencing homelessness who inject drugs in those cities. Main Outcomes and Measures: Projected outcomes included overdose mortality, serious injection-related infections and mortality related to serious injection-related infections, hospitalizations, initiations of medications for opioid use disorder, and life-years lived over a 10-year period for 2 scenarios: "no displacement" and "continual involuntary displacement." The population-attributable fraction of continual displacement to mortality was estimated among this population. Results: Models estimated between 974 and 2175 additional overdose deaths per 10 000 people experiencing homelessness at 10 years in scenarios in which people experiencing homelessness who inject drugs were continually involuntarily displaced compared with no displacement. Between 611 and 1360 additional people experiencing homelessness who inject drugs per 10 000 people were estimated to be hospitalized with continual involuntary displacement, and there will be an estimated 3140 to 8812 fewer initiations of medications for opioid use disorder per 10 000 people. Continual involuntary displacement may contribute to between 15.6% and 24.4% of additional deaths among unsheltered people experiencing homelessness who inject drugs over a 10-year period. Conclusion and Relevance: Involuntary displacement of people experiencing homelessness may substantially increase drug-related morbidity and mortality. These findings have implications for the practice of involuntary displacement, as well as policies such as access to housing and supportive services, that could mitigate these harms.

Projected Long-Term Impact of the Coronavirus Disease 2019 (COVID-19) Pandemic on Hepatitis C Outcomes in the United States: A Modeling Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic disrupted access to and uptake of hepatitis C virus (HCV) care services in the United States. It is unknown how substantially the pandemic will impact long-term HCV-related outcomes. METHODS: We used a microsimulation to estimate the 10-year impact of COVID-19 disruptions in healthcare delivery on HCV outcomes including identified infections, linkage to care, treatment initiation and completion, cirrhosis, and liver-related death. We modeled hypothetical scenarios consisting of an 18-month pandemic-related disruption in HCV care starting in March 2020 followed by varying returns to pre-pandemic rates of screening, linkage, and treatment through March 2030 and compared them to a counterfactual scenario in which there was no COVID-19 pandemic or disruptions in care. We also performed alternate scenario analyses in which the pandemic disruption lasted for 12 and 24 months. RESULTS: Compared to the "no pandemic" scenario, in the scenario in which there is no return to pre-pandemic levels of HCV care delivery, we estimate 1060 fewer identified cases, 21 additional cases of cirrhosis, and 16 additional liver-related deaths per 100 000 people. Only 3% of identified cases initiate treatment and <1% achieve sustained virologic response (SVR). Compared to "no pandemic," the best-case scenario in which an 18-month care disruption is followed by a return to pre-pandemic levels, we estimated a smaller proportion of infections identified and achieving SVR. CONCLUSIONS: A recommitment to the HCV epidemic in the United States that involves additional resources coupled with aggressive efforts to screen, link, and treat people with HCV is needed to overcome the COVID-19-related disruptions.

Determining the lower limit of detection required for HCV viral load assay for test of cure following direct-acting antiviral-based treatment regimens: Evidence from a global data set.

Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure.

Long-term Infective Endocarditis Mortality Associated With Injection Opioid Use in the United States: A Modeling Study.

BACKGROUND: The expansion of the US opioid epidemic has led to significant increases in infections, such as infective endocarditis (IE), which is tied to injection behaviors. We aimed to estimate the population-level IE mortality rate among people who inject opioids and compare the risk of IE death against the risks of death from other causes. METHODS: We developed a microsimulation model of the natural history of injection opioid use. We defined injection behavior profiles by both injection frequency and injection techniques. We accounted for competing risks of death and populated the model with primary and published data. We modeled cohorts of 1 million individuals with different injection behavior profiles until age 60 years. We combined model-generated estimates with published data to project the total expected number of IE deaths in the United States by 2030. RESULTS: The probabilities of death from IE by age 60 years for 20-, 30-, and 40-year-old men with high-frequency use with higher infection risk techniques compared to lower risk techniques for IE were 53.8% versus 3.7%, 51.4% versus 3.1%, and 44.5% versus 2.2%, respectively. The predicted population-level attributable fraction of 10-year mortality from IE among all risk groups was 20%. We estimated that approximately 257 800 people are expected to die from IE by 2030. CONCLUSIONS: The expected burden of IE among people who inject opioids in the United States is large. Adopting a harm reduction approach, including through expansion of syringe service programs, to address injection behaviors could have a major impact on decreasing the mortality rate associated with the opioid epidemic.

Supplemental findings of the 2017 National Blood Collection and Utilization Survey.

INTRODUCTION: This report provides supplemental results from the 2017 National Blood Collection and Utilization Survey on characteristics of the donor population, autologous and directed donations and transfusions, platelets, plasma and granulocyte transfusions, pediatric transfusions, severe donor-related adverse events, cost of blood units, hospitals policies and practices, and inventory, dosing, and supply. METHODS: Weighting and imputation were used to generate national estimates including number of donors, donations, donor deferrals, autologous and directed donations and transfusions, severe donor-related adverse events, platelet and plasma collections and transfusions, number of cross-match procedures, irradiation and leukoreduction, and pediatric transfusions. RESULTS: Between 2015 and 2017, successful donations decreased slightly by 2.1% with a 10.3% decrease in donations by persons aged 16-18 years and a 14.4% increase in donations by donors aged >65 years. The median price paid for blood components by hospitals decreased from $211 to $207 for leukoreduced red blood cell units, from $523 to $517 for leukoreduced apheresis platelet units, and from $54 to $51 for fresh frozen plasma units. Plasma transfusions decreased 13.6%, but group AB plasma units transfused increased 24.7%. CONCLUSION: Between 2015 and 2017, blood donations declined slightly because of decreases in donations from younger donors, but the number of donations from older donors increased. The price hospitals pay for blood has continued to decrease. Plasma transfusions have decreased, but the proportion of plasma transfusions involving group AB plasma have increased.

Transfusion-associated adverse events and implementation of blood safety measures - findings from the 2017 National Blood Collection and Utilization Survey.

BACKGROUND: Serious transfusion-associated adverse events are rare in the United States. To enhance blood safety, various measures have been developed. With use of data from the 2017 National Blood Collection and Utilization Survey (NBCUS), we describe the rate of transfusion-associated adverse events and the implementation of specific blood safety measures. STUDY DESIGN AND METHODS: Data from the 2017 NBCUS were used with comparison to already published estimates from 2015. Survey weighting and imputation were used to obtain national estimates of transfusion-associated adverse events, and the number of units treated with pathogen reduction technology (PRT), screened for Babesia, and leukoreduced. RESULTS: The rate of transfusion-associated adverse events requiring any diagnostic or therapeutic interventions was stable (275 reactions per 100,000 transfusions in 2015 and 282 reactions per 100,000 transfusions in 2017). In 2017 among US blood collection centers, 16 of 141 (11.3%) reported screening units for Babesia and 28 of 144 (19.4%) reported PRT implementation; 138 of 2279 (6.1%) hospitals reported transfusing PRT-treated platelets. In 2017, 134 of 2336 (5.7%) hospitals reported performing secondary bacterial testing of platelets (50,922 culture-based and 63,220 rapid immunoassay tests); in 2015, 71 of 1877 (3.8%) hospitals performed secondary testing (87,155 culture-based and 21,779 rapid immunoassay tests). Nearly all whole blood/red blood cell units and platelet units were leukoreduced. CONCLUSIONS: Besides leukoreduction, implementation of most blood safety measures reported in this study remains low. Nationally, hospitals might be shifting from culture-based secondary bacterial testing to rapid immunoassays.

Slowing decline in blood collection and transfusion in the United States - 2017.

INTRODUCTION: The National Blood Collection and Utilization Survey (NBCUS) has demonstrated declines in blood collection and transfusion in the United States since 2008, including declines of 11.6% in red blood cell (RBC) collections and 13.9% in RBC transfusions during 2013-2015. This study described the 2017 NBCUS results. METHODS: The 2017 NBCUS was distributed to all US blood collection centers, all hospitals performing at least 1000 surgeries annually, and a 40% random sample of hospitals performing 100 to 999 surgeries annually. Weighting and imputation were used to generate national estimates for units of blood and components collected, deferred, distributed, transfused, and outdated. RESULTS: Response rates for the 2017 NBCUS were 88% for blood collection centers and 86% for transfusing hospitals. Compared with 2015, the number of RBC units collected during 2017 (12,211,000; 95% confidence interval [CI], 11,680,000-12,742,000) declined by 3.0%, and transfused RBC units (10,654,000, 95% CI, 10,314,000-10,995,000) declined by 6.1%. Distributed platelet (PLT) units (2,560,000; 95% CI, 2,391,000-2,730,000 units) increased by 5.1%, and transfused PLT units (1,937,000, 95% CI, 1,794,000-2,079,000) declined by 2.3%. Distributed plasma units (3,209,000; 95% CI, 2,879,000-3,539,000) declined by 13.6%, and transfused plasma units (2,374,000; 95% CI, 2,262,000-2,487,000) declined by 12.9%. CONCLUSION: The 2017 NBCUS suggests a continued but slowing decline in demand for RBCs. The decline in blood collection and use will likely continue. Despite decreasing demand and increasing manufacturing costs of blood products, the US blood industry has met the regular and emergent needs of the country.

Is surgical volume still the most accurate indicator of blood usage in the United States?

BACKGROUND: Estimates of blood collection and use in the United States derived from the National Blood Collection and Utilization Survey (NBCUS) call for application of robust statistical methods in the analysis of survey data. Since 1993, annual inpatient surgical volume has been used as the main stratification variable for sampling and estimation. However, recent NBCUS results have shown a decrease in blood use in surgical settings, raising the possibility that inpatient surgical volume may no longer be the optimal stratification variable. The objective of this study is to explore factors affecting hospital blood utilization. STUDY DESIGN AND METHODS: A multivariate generalized linear regression with a negative binomial distribution was used to determine which hospital characteristics best explained allogeneic red blood cell (RBC) use, using data from the 2015 NBCUS to determine hospital blood use and the 2013 annual American Hospital Association database to identify hospital characteristics. RESULTS: Annual inpatient surgical volume explained the most variation in allogeneic RBC use among hospitals (pseudo-R2 of 70.8%). Additional variables, such as presence of an oncology service, were also statistically significant in the models but explained little additional variability in blood use. CONCLUSION: These findings suggest that annual inpatient surgical volume is an appropriate indicator for estimating blood utilization in the United States. As trends in blood utilization continue to evolve, ongoing analytic efforts to understand indicators of blood use are necessary.

Evaluation of the National Healthcare Safety Network Hemovigilance Module for transfusion-related adverse reactions in the United States.

INTRODUCTION: The National Healthcare Safety Network (NHSN) Hemovigilance Module (HM) collects data on the frequency, severity, and imputability of transfusion-associated adverse events. These events contribute to significant morbidity and mortality among transfusion patients. We report results from the first systematic assessment of eight attributes of the HM. MATERIALS AND METHODS: Standard methods were used to assess the HM. Evaluation data included training materials, system modification history, and facility survey information. A concordance analysis was performed using data from the Baystate Medical Center's (Springfield, MA) electronic transfusion reporting system. RESULTS: In 2016, system representativeness remained low, with 6% (277 of 4690) of acute care facilities across 43 jurisdictions enrolled in the HM. In 2016, 48% (2147 of 4453) and 89% (3969 of 4,453) of adverse reactions were reported within 30 and 90 days of the reaction date, respectively, compared to 21% (109 of 511) and 56% (284 of 511) in 2010, demonstrating improved reporting timeliness. Data quality from most reactions was adequate, with 10% (45 of 442) misclassified transfusion-associated circulatory overload reactions, and no incomplete transfusion-transmitted infection data reported from 2010 to 2013. When compared to the Baystate system to assess concordance, 43% (24 of 56) of NHSN-reported febrile reactions were captured in both systems (unweighted kappa value, 0.47; confidence interval, 0.33-0.61). CONCLUSION: Since the 2010 HM pilot, improvements have led to enhanced simplicity, timeliness, and strengthened data quality. The HM serves an important and unique role despite incomplete adoption nationwide. Facility efforts to track and prevent transfusion-associated adverse events through systems like the NHSN HM are a key step toward improving transfusion safety in the United States.

Cost projections for implementation of safety interventions to prevent transfusion-transmitted Zika virus infection in the United States.

BACKGROUND: In August 2016, the Food and Drug Administration advised US blood centers to screen all whole blood and apheresis donations for Zika virus (ZIKV) with an individual-donor nucleic acid test (ID-NAT) or to use approved pathogen reduction technology (PRT). The cost of implementing this guidance nationally has not been assessed. STUDY DESIGN AND METHODS: Scenarios were constructed to characterize approaches to ZIKV screening, including universal ID-NAT, risk-based seasonal allowance of minipool (MP) NAT by state, and universal MP-NAT. Data from the 2015 National Blood Collection and Utilization Survey (NBCUS) were used to characterize the number of donations nationally and by state. For each scenario, the estimated cost per donor ($3-$9 for MP-NAT, $7-$13 for ID-NAT) was multiplied by the estimated number of relevant donations from the NBCUS. Cost of PRT was calculated by multiplying the cost per unit ($50-$125) by the number of units approved for PRT. Prediction intervals for costs were generated using Monte Carlo simulation methods. RESULTS: Screening all donations in the 50 states and DC for ZIKV by ID-NAT would cost $137 million (95% confidence interval [CI], $109-$167) annually. Allowing seasonal MP-NAT in states with lower ZIKV risk could reduce NAT screening costs by 18% to 25%. Application of PRT to all platelet (PLT) and plasma units would cost $213 million (95% CI, $156-$304). CONCLUSION: Universal ID-NAT screening for ZIKV will cost US blood centers more than $100 million annually. The high cost of PRT for apheresis PLTs and plasma could be mitigated if, once validated, testing for transfusion transmissible pathogens could be eliminated.

Continued decline in blood collection and transfusion in the United States-2015.

BACKGROUND: In 2011 and 2013, the National Blood Collection and Utilization Survey (NBCUS) revealed declines in blood collection and transfusion in the United States. The objective of this study was to describe blood services in 2015. STUDY DESIGN AND METHODS: The 2015 NBCUS was distributed to all US blood collection centers, all hospitals performing at least 1000 surgeries annually, and a 40% random sample of hospitals performing 100 to 999 surgeries annually. Weighting and imputation were used to generate national estimates for units of blood and components collected, deferred, distributed, transfused, and outdated. RESULTS: Response rates for the 2015 NBCUS were 78.4% for blood collection centers and 73.9% for transfusing hospitals. In 2015, 12,591,000 units of red blood cells (RBCs) (95% confidence interval [CI], 11,985,000-13,197,000 units of RBCs) were collected, and 11,349,000 (95% CI, 10,592,000-11,747,000) were transfused, representing declines since 2013 of 11.6% and 13.9%, respectively. Total platelet units distributed (2,436,000; 95% CI, 2,230,000-2,642,000) and transfused (1,983,000; 95% CI, 1,816,000 = 2,151,000) declined by 0.5% and 13.1%, respectively, since 2013. Plasma distributions (3,714,000; 95% CI, 3,306,000-4,121,000) and transfusions (2,727,000; 95% CI, 2,594,000-2,859,000) in 2015 declined since 2013. The median price paid per unit in 2015-$211 for leukocyte-reduced RBCs, $524 for apheresis platelets, and $54 for fresh frozen plasma-was less for all components than in 2013. CONCLUSIONS: The 2015 NBCUS findings suggest that continued declines in demand for blood products resulted in fewer units collected and distributed Maintaining a blood inventory sufficient to meet routine and emergent demands will require further monitoring and understanding of these trends.

Mortality, incarceration and cost implications of fentanyl felonization laws: A modeling study.

BACKGROUND: Opioid overdose continues to be a major cause of death in the United States. One effort to control opioid use has been to implement policies that enhance criminalization of opioid possession. Laws to further criminalize possession of fentanyl have been enacted or are under consideration across the country, including at the national level. OBJECTIVE: Estimate the long-term effects on opioid death and incarceration resulting from increasingly strict fentanyl possession laws . DESIGN: We built a Markov simulation model to explore the potential outcomes of a 2022 Colorado law which made possession of >1 g of drug with any amount of fentanyl a Level 4 drug felony (and escalation of the previous law, where >4 g of any drug with any amount of fentanyl in possession was considered a felony). The model simulates a cohort of people with fentanyl possession moving through the criminal justice system, exploring the probability of overdose and incarceration under different scenarios, including various fentanyl possession policies and potential interventions. SETTING: Colorado PARTICIPANTS: A simulated cohort of people in possession of fentanyl. MEASUREMENTS: Number of opioid overdose deaths, people incarcerated, and associated costs over 5 years. RESULTS: When >4 g of a drug containing any amount of fentanyl is considered a felony in Colorado, the model predicts 5460 overdose deaths (95% CrI 410-9260) and 2,740 incarcerations for fentanyl possession (95% CrI: 230-10,500) over 5 years. When the policy changes so that >1 g possession of drug with fentanyl is considered a felony, opioid overdose deaths increase by 19% (95% CRI: 16-38%) and incarcerations for possession increase by 98% (CrI: 85-98%). Diversion programs and MOUD in prison help alleviate some of the increases in death and incarceration, but do not completely offset them. LIMITATIONS: The mathematical model is meant to offer broad assessment of the impact of these policies, not forecast specific and exact numerical outcomes. CONCLUSIONS: Our model shows that lowering thresholds for felony possession of fentanyl containing drugs can lead to more opioid overdose deaths and incarceration.

Estimated Clinical Outcomes and Cost-effectiveness Associated With Provision of Addiction Treatment in US Primary Care Clinics.

Importance: US primary care practitioners (PCPs) are the largest clinical workforce, but few provide addiction care. Primary care is a practical place to expand addiction services, including buprenorphine and harm reduction kits, yet the clinical outcomes and health care sector costs are unknown. Objective: To estimate the long-term clinical outcomes, costs, and cost-effectiveness of integrated buprenorphine and harm reduction kits in primary care for people who inject opioids. Design, Setting, and Participants: In this modeling study, the Reducing Infections Related to Drug Use Cost-Effectiveness (REDUCE) microsimulation model, which tracks serious injection-related infections, overdose, hospitalization, and death, was used to examine the following treatment strategies: (1) PCP services with external referral to addiction care (status quo), (2) PCP services plus onsite buprenorphine prescribing with referral to offsite harm reduction kits (BUP), and (3) PCP services plus onsite buprenorphine prescribing and harm reduction kits (BUP plus HR). Model inputs were derived from clinical trials and observational cohorts, and costs were discounted annually at 3%. The cost-effectiveness was evaluated over a lifetime from the modified health care sector perspective, and sensitivity analyses were performed to address uncertainty. Model simulation began January 1, 2021, and ran for the entire lifetime of the cohort. Main Outcomes and Measures: Life-years (LYs), hospitalizations, mortality from sequelae (overdose, severe skin and soft tissue infections, and endocarditis), costs, and incremental cost-effectiveness ratios (ICERs). Results: The simulated cohort included 2.25 million people and reflected the age and gender of US persons who inject opioids. Status quo resulted in 6.56 discounted LYs at a discounted cost of $203 500 per person (95% credible interval, $203 000-$222 000). Each strategy extended discounted life expectancy: BUP by 0.16 years and BUP plus HR by 0.17 years. Compared with status quo, BUP plus HR reduced sequelae-related mortality by 33%. The mean discounted lifetime cost per person of BUP and BUP plus HR were more than that of the status quo strategy. The dominating strategy was BUP plus HR. Compared with status quo, BUP plus HR was cost-effective (ICER, $34 400 per LY). During a 5-year time horizon, BUP plus HR cost an individual PCP practice approximately $13 000. Conclusions and Relevance: This modeling study of integrated addiction service in primary care found improved clinical outcomes and modestly increased costs. The integration of addiction service into primary care practices should be a health care system priority.

Estimated Costs and Outcomes Associated With Use and Nonuse of Medications for Opioid Use Disorder During Incarceration and at Release in Massachusetts.

Importance: Most prisons and jails in the US discontinue medications for opioid use disorder (MOUD) upon incarceration and do not initiate MOUD prior to release. Objective: To model the association of MOUD access during incarceration and at release with population-level overdose mortality and OUD-related treatment costs in Massachusetts. Design, Setting, and Participants: This economic evaluation used simulation modeling and cost-effectiveness with costs and quality-adjusted life-years (QALYs) discounted at 3% to compare MOUD treatment strategies in a corrections cohort and an open cohort representing individuals with OUD in Massachusetts. Data were analyzed between July 1, 2021, and September 30, 2022. Exposures: Three strategies were compared: (1) no MOUD provided during incarceration or at release, (2) extended-release (XR) naltrexone offered only at release from incarceration, and (3) all 3 MOUDs (naltrexone, buprenorphine, and methadone) offered at intake. Main Outcomes and Measures: Treatment starts and retention, fatal overdoses, life-years and QALYs, costs, and incremental cost-effectiveness ratios (ICERs). Results: Among 30 000 simulated incarcerated individuals with OUD, offering no MOUD was associated with 40 927 (95% uncertainty interval [UI], 39 001-42 082) MOUD treatment starts over a 5-year period and 1259 (95% UI, 1130-1323) overdose deaths after 5 years. Over 5 years, offering XR-naltrexone at release led to 10 466 (95% UI, 8515-12 201) additional treatment starts, 40 (95% UI, 16-50) fewer overdose deaths, and 0.08 (95% UI, 0.05-0.11) QALYs gained per person, at an incremental cost of $2723 (95% UI, $141-$5244) per person. In comparison, offering all 3 MOUDs at intake led to 11 923 (95% UI, 10 861-12 911) additional treatment starts, compared with offering no MOUD, 83 (95% UI, 72-91) fewer overdose deaths, and 0.12 (95% UI, 0.10-0.17) QALYs per person gained, at an incremental cost of $852 (95% UI, $14-$1703) per person. Thus, XR-naltrexone only was a dominated strategy (both less effective and more costly) and the ICER of all 3 MOUDs compared with no MOUD was $7252 (95% UI, $140-$10 018) per QALY. Among everyone with OUD in Massachusetts, XR-naltrexone only averted 95 overdose deaths over 5 years (95% UI, 85-169)-a 0.9% decrease in state-level overdose mortality-while the all-MOUD strategy averted 192 overdose deaths (95% UI, 156-200)-a 1.8% decrease. Conclusions and Relevance: The findings of this simulation-modeling economic study suggest that offering any MOUD to incarcerated individuals with OUD would prevent overdose deaths and that offering all 3 MOUDs would prevent more deaths and save money compared with an XR-naltrexone-only strategy.

Keep It Up! 3.0: Study protocol for a type III hybrid implementation-effectiveness cluster-randomized trial.

BACKGROUND: Despite evidence that eHealth approaches can be effective in reducing HIV risk, their implementation requirements for public health scale up are not well established, and effective strategies to bring these programs into practice are still unknown. Keep It Up! (KIU!) is an online program proven to reduce HIV risk among young men who have sex with men (YMSM) and ideal candidate to develop and evaluate novel strategies for implementing eHealth HIV prevention programs. KIU! 3.0 is a Type III Hybrid Effectiveness-Implementation cluster randomized trial designed to 1) compare two strategies for implementing KIU!: community-based organizations (CBO) versus centralized direct-to-consumer (DTC) recruitment; 2) examine the effect of strategies and determinants on variability in implementation success; and 3) develop materials for sustainment of KIU! after the trial concludes. In this article, we describe the approaches used to achieve these aims. METHODS: Using county-level population estimates of YMSM, 66 counties were selected and randomized 2:1 to the CBO and DTC approaches. The RE-AIM model was used to drive outcome measurements, which were collected from CBO staff, YMSM, and technology providers. Mixed-methods research mapped onto the domains of the Consolidated Framework for Implementation Research will examine determinants and their relationship with implementation outcomes. DISCUSSION: In comparing our implementation recruitment models, we are examining two strategies which have shown effectiveness in delivering health technology interventions in the past, yet little is known about their comparative advantages and disadvantages in implementation. The results of the trial will further the understanding of eHealth prevention intervention implementation.

Economic Evaluation of Extended-Release Buprenorphine for Persons With Opioid Use Disorder.

Importance: In 2017, the US Food and Drug Administration (FDA) approved a monthly injectable form of buprenorphine, extended-release buprenorphine; published data show that extended-release buprenorphine is effective compared with no treatment, but its current cost is higher and current retention is lower than that of transmucosal buprenorphine. Preliminary research suggests that extended-release buprenorphine may be an important addition to treatment options, but the cost-effectiveness of extended-release buprenorphine compared with transmucosal buprenorphine remains unclear. Objective: To evaluate the cost-effectiveness of extended-release buprenorphine compared with transmucosal buprenorphine. Design, Setting, and Participants: This economic evaluation used a state transition model starting in 2019 to simulate the lifetime of a closed cohort of individuals with OUD presenting for evaluation for opioid agonist treatment with buprenorphine. The data sources used to estimate model parameters included cohort studies, clinical trials, and administrative data. The model relied on pharmaceutical costs from the Federal Supply Schedule and health care utilization costs from published studies. Data were analyzed from September 2021 to January 2023. Interventions: No treatment, treatment with transmucosal buprenorphine, or treatment with extended-release buprenorphine. Main Outcomes and Measures: Mean lifetime costs per person, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results: The simulated cohort included 100 000 patients with OUD receiving (61% male; mean [SD] age, 38 [11] years) or not receiving medication treatment (58% male, mean [SD] age, 48 [18] years). Compared with no medication treatment, treatment with transmucosal buprenorphine yielded an ICER of $19 740 per QALY. Compared with treatment with transmucosal buprenorphine, treatment with extended-release buprenorphine yielded lower effectiveness by 0.03 QALYs per person at higher cost, suggesting that treatment with extended-release buprenorphine was dominated and not preferred. In probabilistic sensitivity analyses, treatment with transmucosal buprenorphine was the preferred strategy 60% of the time. Treatment with extended-release buprenorphine was cost-effective compared with treatment with transmucosal buprenorphine at a $100 000 per QALY willingness-to-pay threshold only after substantial changes in key parameters. Conclusions and Relevance: In this economic evaluation of extended-release buprenorphine compared with transmucosal buprenorphine for the treatment of OUD, extended-release buprenorphine was not associated with efficient allocation of limited resources when transmucosal buprenorphine was available. Future initiatives should aim to improve retention rates or decrease costs associated with extended-release buprenorphine.

Population-Level Strategies for Nirmatrelvir/Ritonavir Prescribing-A Cost-effectiveness Analysis.

Background: New coronavirus disease 2019 (COVID-19) medications force decision-makers to weigh limited evidence of efficacy and cost in determining which patient populations to target for treatment. A case in point is nirmatrelvir/ritonavir, a drug that has been recommended for elderly, high-risk individuals, regardless of vaccination status, even though clinical trials have only evaluated it in unvaccinated patients. A simple optimization framework might inform a more reasoned approach to the trade-offs implicit in the treatment allocation decision. Methods: We conducted a cost-effectiveness analysis using a decision-analytic model comparing 5 nirmatrelvir/ritonavir prescription policy strategies, stratified by vaccination status and risk for severe disease. We considered treatment effectiveness at preventing hospitalization ranging from 21% to 89%. Sensitivity analyses were performed on major parameters of interest. A web-based tool was developed to permit decision-makers to tailor the analysis to their settings and priorities. Results: Providing nirmatrelvir/ritonavir to unvaccinated patients at high risk for severe disease was cost-saving when effectiveness against hospitalization exceeded 33% and cost-effective under all other data scenarios we considered. The cost-effectiveness of other allocation strategies, including those for vaccinated adults and those at lower risk for severe disease, depended on willingness-to-pay thresholds, treatment cost and effectiveness, and the likelihood of severe disease. Conclusions: Priority for nirmatrelvir/ritonavir treatment should be given to unvaccinated persons at high risk of severe disease from COVID-19. Further priority may be assigned by weighing treatment effectiveness, disease severity, drug cost, and willingness to pay for deaths averted.

Clinical impact, costs, and cost-effectiveness of hospital-based strategies for addressing the US opioid epidemic: a modelling study.

BACKGROUND: The syndemic of injection drug use and serious injection-related infections is leading to increasing mortality in the USA. Although outpatient treatment with medications for opioid use disorder reduces overdose risk and recurrent infections, hospitalisation remains common. We evaluated the clinical impact, costs, and cost-effectiveness of hospital-based strategies to address the US opioid epidemic. METHODS: We developed a microsimulation model to compare the cost-effectiveness of: standard hospital care-detoxification for opioids, no addiction consult service (status quo); expanded inpatient prescribing of medications for opioid use disorder, including bridge prescriptions (ie, medication until they can see an outpatient provider) when possible (medications for opioid use disorder with bridge); implementation of addiction consult services within the hospital (addiction consult services alone); and a combined medication for opioid use disorder with addiction consult services strategy (combined). We used clinical trials and observational cohorts to inform model inputs. Outcomes were life-years, discounted costs, incremental cost-effectiveness ratios, hospitalisations, and deaths. We did deterministic sensitivity analyses on key model inputs related to costs and sequelae of drug use and probabilistic sensitivity analysis to further address uncertainty. FINDINGS: Among people who inject opioids in the USA, we estimated that expanding medications for opioid use disorder with bridge prescriptions would reduce hospitalisations and overdose deaths by 3·2% and 3·6%, respectively, and the combination of expanded medications with opioid use disorder along with addiction consult sevices would reduce hospitalisations and overdoses by 5·2% and 6·6%, respectively, compared with the status quo. Mean lifetime costs ranged from US$731 400 (95% credible interval 447 911-859 189 for the medications for opioid use disorder strategy) to $741 200 (470 930-868 551 for the combined strategy) per person. Assuming a willingness-to-pay threshold of $100 000 per life-year gained, medications for opioid use disorder with bridge and combined strategies were cost-effective ($7600 and $14 300, respectively). A scenario that assumed ideal access to harm reduction services came to the same conclusions as the base case and our results were robust in deterministic and probabilistic sensitivity analyses. INTERPRETATION: The combined interventions of expanding hospital-based prescribing of medications for opioid use disorder and implementing addiction consult services could improve life expectancy, be cost-effective, and could be the basis for a comprehensive hospital-based strategy for addressing the opioid epidemic in the USA and countries with similar opioid epidemics. FUNDING: National Institute on Drug Abuse and National Institute of Allergy and Infectious Diseases.