Comparing frequency of booster vaccination to prevent severe COVID-19 by risk group in the United States.

There is a public health need to understand how different frequencies of COVID-19 booster vaccines may mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age and immune status. By analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively reduce the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit against severe disease. In persons 75+ years, the model estimated that annual boosters would reduce absolute annual risk of severe COVID-19 by 199 (uncertainty interval: 183-232) cases per 100,000 persons, compared to a one-time booster vaccination. In contrast, for persons 18-49 years, the model estimated that annual boosters would reduce this risk by 14 (10-19) cases per 100,000 persons. Those with prior infection had lower benefit of more frequent boosting, and immunocompromised persons had larger benefit. Scenarios with emerging variants with immune evasion increased the benefit of more frequent variant-targeted boosters. This study underscores the benefit of considering key risk factors to inform frequency of COVID-19 booster vaccines in public health guidance and ensuring at least annual boosters in high-risk populations.

Cost-Effectiveness of Community-Based Diet and Exercise for Patients with Knee Osteoarthritis and Obesity or Overweight.

OBJECTIVE: Obesity exacerbates pain and functional limitation in persons with knee osteoarthritis (OA). In the Weight Loss and Exercise for Communities with Arthritis in North Carolina (WE-CAN) study, a community-based diet and exercise (D + E) intervention led to an additional 6 kg weight loss and 20% greater pain relief in persons with knee OA and body mass index (BMI) >27 kg/m2 relative to a group-based health education (HE) intervention. We sought to determine the incremental cost-effectiveness of the usual care (UC), UC + HE, and UC + (D + E) programs, comparing each strategy with the "next-best" strategy ranked by increasing lifetime cost. METHODS: We used the Osteoarthritis Policy Model to project long-term clinical and economic benefits of the WE-CAN interventions. We considered three strategies: UC, UC + HE, and UC + (D + E). We derived cohort characteristics, weight, and pain reduction from the WE-CAN trial. Our outcomes included quality-adjusted life years (QALYs), cost, and incremental cost-effectiveness ratios (ICERs). RESULTS: In a cohort with mean age 65 years, BMI 37 kg/m2, and Western Ontario and McMaster Universities Osteoarthritis Index pain score 38 (scale 0-100, 100 = worst), UC leads to 9.36 QALYs/person, compared with 9.44 QALYs for UC + HE and 9.49 QALYS for UC + (D + E). The corresponding lifetime costs are $147,102, $148,139, and $151,478. From the societal perspective, UC + HE leads to an ICER of $12,700/QALY; adding D + E to UC leads to an ICER of $61,700/QALY. CONCLUSION: The community-based D + E program for persons with knee OA and BMI >27kg/m2 could be cost-effective for willingness-to-pay thresholds greater than $62,000/QALY. These findings suggest that incorporation of community-based D + E programs into OA care may be beneficial for public health.

Daily Oral HIV Pre-exposure Prophylaxis Among Young Men Who Have Sex With Men in the United States: Cost-saving at Generic Drug Price.

BACKGROUND: Adherence and retention concerns raise questions about the effectiveness and cost-effectiveness of oral HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). METHODS: Using an adolescent-focused simulation model, we compared annual HIV screening alone with tenofovir disoproxil fumarate/emtricitabine-based oral PrEP with every 3-month HIV screening in YMSM (aged 15-24) at increased risk of HIV. Data derived from published sources included: age-stratified HIV incidence/100 person-years (PY) on- or off-PrEP (0.6-10.1 or 0.4-6.4), PrEP retention at 6 years (28%), transmissions by HIV RNA level (0.0-78.4/100PY) and annual costs of antiretroviral therapy ($32 000-69 000), HIV care ($3100-34 600), and PrEP program/generic drug ($900/360). Outcomes included transmissions (percent of cohort infected), quality-adjusted life-years (QALYs), costs ($), and incremental cost-effectiveness ratios ($/QALY). We explored the sensitivity of findings to variation in HIV incidence and drug prices. RESULTS: Compared with annual screening alone, PrEP would increase QALYs (9.58 to 9.67), reduce new infections (37% to 30%), and decrease costs (by $5000) over 10 years. PrEP would remain cost-saving for HIV incidence off-PrEP ≥5.1/100PY or annual PrEP price ≤$1200. Over a lifetime horizon, PrEP would be cost-saving for HIV incidence off-PrEP ≥1.0/100PY, across all retention assumptions examined. PrEP would not be cost-effective at HIV incidence ≤0.1/100PY, regardless of drug price, due to programmatic costs. CONCLUSIONS: In US YMSM at increased risk of HIV, generic oral PrEP and every-3-month screening would be cost-saving compared with annual screening alone, even with high discontinuation and low adherence, over a range of HIV incidences.

Optimizing COVID-19 testing strategies on college campuses: Evaluation of the health and economic costs.

Colleges and universities in the US struggled to provide safe in-person education throughout the COVID-19 pandemic. Testing coupled with isolation is a nimble intervention strategy that can be tailored to mitigate the changing health and economic risks associated with SARS-CoV-2. We developed a decision-support tool to aid in the design of university-based screening strategies using a mathematical model of SARS-CoV-2 transmission. Applying this framework to a large public university reopening in the fall of 2021 with a 60% student vaccination rate, we find that the optimal strategy, in terms of health and economic costs, is twice weekly antigen testing of all students. This strategy provides a 95% guarantee that, throughout the fall semester, case counts would not exceed twice the CDC's original high transmission threshold of 100 cases per 100k persons over 7 days. As the virus and our medical armament continue to evolve, testing will remain a flexible tool for managing risks and keeping campuses open. We have implemented this model as an online tool to facilitate the design of testing strategies that adjust for COVID-19 conditions as well as campus-specific populations, resources, and priorities.

The Value-of-Information and Value-of-Implementation from Clinical Trials of Diagnostic Tests for HIV-Associated Tuberculosis: A Modeling Analysis.

Objectives. Conventional value-of-information (VOI) analysis assumes complete uptake of an optimal decision. We employed an extended framework that includes value-of-implementation (VOM)-the benefit of encouraging adoption of an optimal strategy-and estimated how future trials of diagnostic tests for HIV-associated tuberculosis could improve public health decision making and clinical and economic outcomes. Methods. We evaluated the clinical outcomes and costs, given current information, of 3 tuberculosis screening strategies among hospitalized people with HIV in South Africa: sputum Xpert (Xpert), sputum Xpert plus urine AlereLAM (Xpert+AlereLAM), and sputum Xpert plus the newer, more sensitive, and costlier urine FujiLAM (Xpert+FujiLAM). We projected the incremental net monetary benefit (INMB) of decision making based on results of a trial comparing mortality with each strategy, rather than decision making based solely on current knowledge of FujiLAM's improved diagnostic performance. We used a validated microsimulation to estimate VOI (the INMB of reducing parameter uncertainty before decision making) and VOM (the INMB of encouraging adoption of an optimal strategy). Results. With current information, adopting Xpert+FujiLAM yields 0.4 additional life-years/person compared with current practices (assumed 50% Xpert and 50% Xpert+AlereLAM). While the decision to adopt this optimal strategy is unaffected by information from the clinical trial (VOI = $ 0 at $3,000/year-of-life saved willingness-to-pay threshold), there is value in scaling up implementation of Xpert+FujiLAM, which results in an INMB (representing VOM) of $650 million over 5 y. Conclusions. Conventional VOI methods account for the value of switching to a new optimal strategy based on trial data but fail to account for the persuasive value of trials in increasing uptake of the optimal strategy. Evaluation of trials should include a focus on their value in reducing barriers to implementation. Highlights: In conventional VOI analysis, it is assumed that the optimal decision will always be adopted even without a trial. This can potentially lead to an underestimation of the value of trials when adoption requires new clinical trial evidence. To capture the influence that a trial may have on decision makers' willingness to adopt the optimal decision, we also consider value-of-implementation (VOM), a metric quantifying the benefit of new study information in promoting wider adoption of the optimal strategy. The overall value-of-a-trial (VOT) includes both VOI and VOM.Our model-based analysis suggests that the information obtained from a trial of screening strategies for HIV-associated tuberculosis in South Africa would have no value, when measured using traditional methods of VOI assessment. A novel strategy, which includes the urine FujiLAM test, is optimal from a health economic standpoint but is underutilized. A trial would reduce uncertainties around downstream health outcomes but likely would not change the optimal decision. The high VOT (nearly $700 million over 5 y) lies solely in promoting uptake of FujiLAM, represented as VOM.Our results highlight the importance of employing a more comprehensive approach for evaluating prospective trials, as conventional VOI methods can vastly underestimate their value. Trialists and funders can and should assess the VOT metric instead when considering trial designs and costs. If VOI is low, the VOM and cost of a trial can be compared with the benefits and costs of other outreach programs to determine the most cost-effective way to improve uptake.

Increased HIV Transmissions With Reduced Insurance Coverage for HIV Preexposure Prophylaxis: Potential Consequences of Braidwood Management v. Becerra.

A US federal court recently ruled against requiring health insurers to cover human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) under the Affordable Care Act. For every 10% decrease in PrEP coverage resulting from this ruling among US men who have sex with men, we estimate an additional 1140 HIV infections in the following year in that population.

Cost-effectiveness analysis of typhoid conjugate vaccines in an outbreak setting: a modeling study.

BACKGROUND: Several prolonged typhoid fever epidemics have been reported since 2010 throughout eastern and southern Africa, including Malawi, caused by multidrug-resistant Salmonella Typhi. The World Health Organization recommends the use of typhoid conjugate vaccines (TCVs) in outbreak settings; however, current data are limited on how and when TCVs might be introduced in response to outbreaks. METHODOLOGY: We developed a stochastic model of typhoid transmission fitted to data from Queen Elizabeth Central Hospital in Blantyre, Malawi from January 1996 to February 2015. We used the model to evaluate the cost-effectiveness of vaccination strategies over a 10-year time horizon in three scenarios: (1) when an outbreak is likely to occur; (2) when an outbreak is unlikely to occur within the next ten years; and (3) when an outbreak has already occurred and is unlikely to occur again. We considered three vaccination strategies compared to the status quo of no vaccination: (a) preventative routine vaccination at 9 months of age; (b) preventative routine vaccination plus a catch-up campaign to 15 years of age; and (c) reactive vaccination with a catch-up campaign to age 15 (for Scenario 1). We also explored variations in outbreak definitions, delays in implementation of reactive vaccination, and the timing of preventive vaccination relative to the outbreak. RESULTS: Assuming an outbreak occurs within 10 years, we estimated that the various vaccination strategies would prevent a median of 15-60% of disability-adjusted life-years (DALYs). Reactive vaccination was the preferred strategy for WTP values of $0-300 per DALY averted. For WTP values > $300, introduction of preventative routine TCV immunization with a catch-up campaign was the preferred strategy. Routine vaccination with a catch-up campaign was cost-effective for WTP values above $890 per DALY averted if no outbreak occurs and > $140 per DALY averted if implemented after the outbreak has already occurred. CONCLUSIONS: Countries for which the spread of antimicrobial resistance is likely to lead to outbreaks of typhoid fever should consider TCV introduction. Reactive vaccination can be a cost-effective strategy, but only if delays in vaccine deployment are minimal; otherwise, introduction of preventive routine immunization with a catch-up campaign is the preferred strategy.

Patterns of Infectious Disease Associated With Injection Drug Use in Massachusetts.

BACKGROUND: Since 2014, multiple outbreaks of human immunodeficiency virus (HIV) among people who inject drugs have occurred across the United States along with hepatitis C virus (HCV), skin and soft tissue infections (SSTIs), and infective endocarditis (IE), creating a converging public health crisis. METHODS: We analyzed the temporal patterns of infectious disease and overdose using a hierarchical Bayesian distributed lag logistic regression model examining the probability that a given geographic area experienced at least 1 HIV case in a given month as a function of the counts/rates of overdose, HCV, SSTI, and IE and associated medical procedures at different lagged time periods. RESULTS: Current-month HIV is associated with increasing HCV cases, abscess incision and drainage, and SSTI cases, in distinct temporal patterns. For example, 1 additional HCV case occurring 5 and 7 months previously is associated with a 4% increase in the odds of observing at least 1 current-month HIV case in a given locale (odds ratios, 1.04 [90% credible interval {CrI}: 1.01-1.10] and 1.04 [90% CrI: 1.00-1.09]). No such associations were observed for echocardiograms, IE, or overdose. CONCLUSIONS: Lagged associations in other infections preceding rises in current-month HIV counts cannot be described as predictive of HIV outbreaks but may point toward newly discovered epidemics of injection drug use and associated clinical sequalae, prompting clinicians to screen patients more carefully for substance use disorder and associated infections.

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.

Cost-Effectiveness of Weight-Loss Interventions Prior to Total Knee Replacement for Patients With Class III Obesity.

OBJECTIVE: Class III obesity (body mass index >40 kg/m2 ) is associated with higher complications following total knee replacement (TKR), and weight loss is recommended. We aimed to establish the cost-effectiveness of Roux-en-Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG), and lifestyle nonsurgical weight loss (LNSWL) interventions in knee osteoarthritis patients with class III obesity considering TKR. METHODS: Using the Osteoarthritis Policy model and data from published literature to derive model inputs for RYGB, LSG, LNSWL, and TKR, we assessed the long-term clinical benefits, costs, and cost-effectiveness of weight-loss interventions for patients with class III obesity considering TKR. We assessed the following strategies with a health care sector perspective: 1) no weight loss/no TKR, 2) immediate TKR, 3) LNSWL, 4) LSG, and 5) RYGB. Each weight-loss strategy was followed by annual TKR reevaluation. Primary outcomes were cost, quality-adjusted life expectancy (QALE), and incremental cost-effectiveness ratios (ICERs), discounted at 3% per year. We conducted deterministic and probabilistic sensitivity analyses to examine the robustness of conclusions to input uncertainty. RESULTS: LSG increased QALE by 1.64 quality-adjusted life-years (QALYs) and lifetime medical costs by $17,347 compared to no intervention, leading to an ICER of $10,600/QALY. RYGB increased QALE by 0.22 and costs by $4,607 beyond LSG, resulting in an ICER of $20,500/QALY. Relative to immediate TKR, LSG and RYGB delayed and decreased TKR utilization. In the probabilistic sensitivity analysis, RYGB was cost-effective in 67% of iterations at a willingness-to-pay threshold of $50,000/QALY. CONCLUSION: For patients with class III obesity considering TKR, RYGB provides good value while immediate TKR without weight loss is not economically efficient.

Optimizing COVID-19 testing strategies on college campuses: evaluation of the health and economic costs.

Colleges and universities in the US struggled to provide safe in-person education throughout the COVID-19 pandemic. Testing coupled with isolation is a nimble intervention strategy that can be tailored to mitigate health and economic costs, as the virus and our arsenal of medical countermeasures continue to evolve. We developed a decision-support tool to aid in the design of university-based testing strategies using a mathematical model of SARS-CoV-2 transmission. Applying this framework to a large public university reopening in the fall of 2021 with a 60% student vaccination rate, we find that the optimal strategy, in terms of health and economic costs, is twice weekly antigen testing of all students. This strategy provides a 95% guarantee that, throughout the fall semester, case counts would not exceed the CDC's original high transmission threshold of 100 cases per 100k persons over 7 days. As the virus and our medical armament continue to evolve, testing will remain a flexible tool for managing risks and keeping campuses open. We have implemented this model as an online tool to facilitate the design of testing strategies that adjust for COVID-19 conditions, university-specific parameters, and institutional goals.

Cost-effectiveness of hepatitis C virus test-and-treat and risk reduction strategies among men who have sex with men living with HIV in France.

INTRODUCTION: Studies suggest that hepatitis C virus (HCV) micro-elimination is feasible among men who have sex with men (MSM) living with human immunodeficiency virus (HIV), through treatment-as-prevention and interventions aimed at reducing risk behaviours. However, their economic impact is poorly understood. The aim of this study was to assess the cost-effectiveness of HCV screening and risk reduction strategies in France. METHODS: A compartmental deterministic mathematical model was developed to describe HCV disease transmission and progression among MSM living with HIV in France. We evaluated different combinations of HCV screening frequency (every 12, 6 or 3 months) and risk reduction strategies (targeting only high-risk or all MSM) from 2021 onwards. The model simulated the number of HCV infections, life-expectancy (LYs), quality-adjusted life-expectancy (QALYs), lifetime costs and incremental cost-effectiveness ratio (ICER) over a lifetime horizon (leading to an end of the simulation in 2065). RESULTS: All strategies increased QALYs, compared with current practices, that is yearly HCV screening, with no risk reduction. A behavioural intervention resulting in a 20% risk reduction in the high-risk group, together with yearly screening, was the least expensive strategy, and, therefore, cost-saving compared to current practices. The ICER per QALY gained for the strategy combining risk reduction for the high-risk group with 6-month HCV screening, compared to risk reduction with yearly screening, was €61,389. It also prevented 398 new HCV infections between 2021 and 2065, with a cost per infection averted of €37,790. All other strategies were dominated (more expensive and less effective than some other available alternative) or not cost-effective (ICER per QALY gained > €100,000). CONCLUSIONS: In the French context, current HCV screening practices without risk reduction among MSM living with HIV cannot be justified on economic grounds. Risk reduction interventions targeted to high-risk individuals-alongside screening either once or twice a year-could be cost-effective depending on the policymaker's willingness-to-pay.

Estimating deaths averted and cost per life saved by scaling up mRNA COVID-19 vaccination in low-income and lower-middle-income countries in the COVID-19 Omicron variant era: a modelling study.

OBJECTIVES: While almost 60% of the world has received at least one dose of COVID-19 vaccine, the global distribution of vaccination has not been equitable. Only 4% of the population of low-income countries (LICs) has received a full primary vaccine series, compared with over 70% of the population of high-income nations. DESIGN: We used economic and epidemiological models, parameterised with public data on global vaccination and COVID-19 deaths, to estimate the potential benefits of scaling up vaccination programmes in LICs and lower-middle-income countries (LMICs) in 2022 in the context of global spread of the Omicron variant of SARS-CoV2. SETTING: Low-income and lower-middle-income nations. MAIN OUTCOME MEASURES: Outcomes were expressed as number of avertable deaths through vaccination, costs of scale-up and cost per death averted. We conducted sensitivity analyses over a wide range of parameter estimates to account for uncertainty around key inputs. FINDINGS: Globally, universal vaccination in LIC/LMIC with three doses of an mRNA vaccine would result in an estimated 1.5 million COVID-19 deaths averted with a total estimated cost of US$61 billion and an estimated cost-per-COVID-19 death averted of US$40 800 (sensitivity analysis range: US$7400-US$81 500). Lower estimated infection fatality ratios, higher cost-per-dose and lower vaccine effectiveness or uptake lead to higher cost-per-death averted estimates in the analysis. CONCLUSIONS: Scaling up COVID-19 global vaccination would avert millions of COVID-19 deaths and represents a reasonable investment in the context of the value of a statistical life. Given the magnitude of expected mortality facing LIC/LMIC without vaccination, this effort should be an urgent priority.

Cost-Effectiveness of Arthroscopic Partial Meniscectomy and Physical Therapy for Degenerative Meniscal Tear.

OBJECTIVE: We examined the cost-effectiveness of treatment strategies for concomitant meniscal tear and knee osteoarthritis (OA) involving arthroscopic partial meniscectomy surgery and physical therapy (PT). METHODS: We used the Osteoarthritis Policy Model, a validated Monte Carlo microsimulation, to compare three strategies, 1) PT-only, 2) immediate surgery, and 3) PT + optional surgery, for participants whose pain persists following initial PT. We modeled a cohort with baseline meniscal tear, OA, and demographics from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial of arthroscopic partial meniscectomy versus PT. We estimated risks and costs of arthroscopic partial meniscectomy complications and accounted for heightened OA progression post surgery using published data. We estimated surgery use rates and treatment efficacies using MeTeOR data. We considered a 5-year time horizon, discounted costs, and quality-adjusted life-years (QALYs) 3% per year and conducted sensitivity analyses. We report incremental cost-effectiveness ratios. RESULTS: Relative to PT-only, PT + optional surgery added 0.0651 QALY and $2,010 over 5 years (incremental cost-effectiveness ratio = $30,900 per QALY). Relative to PT + optional surgery, immediate surgery added 0.0065 QALY and $3080 (incremental cost-effectiveness ratio = $473,800 per QALY). Incremental cost-effectiveness ratios were sensitive to optional surgery efficacy in the PT + optional surgery strategy. In the probabilistic sensitivity analysis, PT + optional surgery was cost-effective in 51% of simulations at willingness-to-pay thresholds of both $50,000 per QALY and $100,000 per QALY. CONCLUSION: First-line arthroscopic partial meniscectomy has a prohibitively high incremental cost-effectiveness ratio. Under base case assumptions, second-line arthroscopic partial meniscectomy offered to participants with persistent pain following initial PT is cost-effective at willingness-to-pay thresholds between $31,000 and $473,000 per QALY. Our analyses suggest that arthroscopic partial meniscectomy can be a high-value treatment option for patients with meniscal tear and OA when performed following an initial PT course and should remain a covered treatment option.

Reliability of patient self-reports to clinician-assigned functional scores of inclusion body myositis.

BACKGROUND: Sporadic inclusion body myositis (IBM) is a debilitating disease which leads to impaired ambulation and loss of hand function. Yale IBM Registry (IBMR) was launched in November 2016 to address the knowledge gap in IBM natural history data. The registry interface provides an IBM personalized index calculator (IBM-PIC) based on the IBM-functional rating scale (IBM-FRS). While the calculator is based on the IBM-FRS, it has not been directly compared to the IBM-FRS score. Therefore, in this study, we compared the patient-reported IBM-PIC score from this calculator with the physician-obtained IBM-FRS score. METHOD: IBM-FRS was administered over the phone within two weeks of their most recent IBM-PIC entry in the IBMR to 35 participants. To compare the agreement between IBM-FRS and IBM-PIC scores, Interrater Correlation Coefficient (ICC) analysis was performed. For individual questions, Fleiss Kappa statistics was used. RESULTS: Thirty-five active IBM-PIC users participated. Eighty percent of the participants were men, and 91% were White Caucasians. The reported IBM-FRS score of this group was 23.5 ± 7.4 (range 1-38). The Interrater Correlation Coefficient (ICC) between the physician-administered IBM-FRS score and the IBM-PIC was 0.98 (0.96-0.99). There was moderate to substantial agreement on all the questions on IBM-FRS except for handwriting and fine motor skills. DISCUSSION: IBM-PIC is a reliable indicator of the IBM-FRS score obtained by the physician. It is anticipated that this online platform will be a valuable tool for assessing IBM severity and monitoring disease progression remotely both in clinical practice and research studies.

Cost-Effectiveness of Long-Acting Injectable HIV Preexposure Prophylaxis in the United States : A Cost-Effectiveness Analysis.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP). OBJECTIVE: To identify the maximum price premium (that is, greatest possible price differential) that society should be willing to accept for the additional benefits of CAB-LA over tenofovir-based PrEP among men who have sex with men and transgender women (MSM/TGW) in the United States. DESIGN: Simulation, cost-effectiveness analysis. DATA SOURCES: Trial and published data, including estimated HIV incidence (5.32, 1.33, and 0.26 per 100 person-years for off PrEP, generic F/TDF and branded emtricitabine-tenofovir alafenamide (F/TAF), and CAB-LA, respectively); 28% 6-year PrEP retention. Annual base-case drug costs: $360 and $16 800 for generic F/TDF and branded F/TAF. Fewer side effects with branded F/TAF versus generic F/TDF were assumed. TARGET POPULATION: 476 700 MSM/TGW at very high risk for HIV (VHR). TIME HORIZON: 10 years. PERSPECTIVE: Health care system. INTERVENTION: CAB-LA versus generic F/TDF or branded F/TAF for HIV PrEP. OUTCOME MEASURES: Primary transmissions, quality-adjusted life-years (QALYs), costs (2020 U.S. dollars), incremental cost-effectiveness ratios (ICERs; U.S. dollars per QALY), maximum price premium for CAB-LA versus tenofovir-based PrEP. RESULTS OF BASE-CASE ANALYSIS: Compared with generic F/TDF (or branded F/TAF), CAB-LA increased life expectancy by 28 000 QALYs (26 000 QALYs) among those at VHR. Branded F/TAF cost more per QALY gained than generic F/TDF compared with no PrEP. At 10 years, CAB-LA could achieve an ICER of at most $100 000 per QALY compared with generic F/TDF at a maximum price premium of $3700 per year over generic F/TDF (CAB-LA price <$4100 per year). RESULTS OF SENSITIVITY ANALYSIS: In a PrEP-eligible population at high risk for HIV, rather than at VHR (n = 1 906 800; off PrEP incidence: 1.54 per 100 person-years), CAB-LA could achieve an ICER of at most $100 000 per QALY versus generic F/TDF at a maximum price premium of $1100 per year over generic F/TDF (CAB-LA price <$1500 per year). LIMITATION: Uncertain clinical and economic benefits of averting future transmissions. CONCLUSION: Effective oral PrEP limits the additional price society should be willing to pay for CAB-LA. PRIMARY FUNDING SOURCE: FHI 360; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; National Institute on Drug Abuse; the Reich HIV Scholar Award; and the Steve and Deborah Gorlin MGH Research Scholars Award.

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.

Reducing the Prevalence of Alcohol-Exposed Pregnancies in the United States: A Simulation Modeling Study.

BACKGROUND: Public health efforts to prevent alcohol-exposed pregnancies (AEPs) primarily focus on promoting abstinence from alcohol among women if pregnant or seeking pregnancy and using effective contraception to prevent unintended pregnancies if consuming alcohol. Little is known about how programs to improve adherence to these recommendations would affect the prevalence of AEPs. METHODS: We developed an individual-based simulation model of US women of reproductive age to project the prevalence of AEPs under different public health strategies. The model varies each woman's risk of an AEP over time depending on fertility, contraceptive use, awareness of pregnancy, sexual activity, and drinking patterns. We used the 2013-2015 National Survey on Family Growth data set to parameterize the model. RESULTS: We estimate that 54% (95% uncertainty interval: 48%-59%) of pregnancies that result in a live birth in the United States are exposed to alcohol, 12% (10%-15%) are ever exposed to ≥5 alcoholic drinks in a week, and 3.0% (1.3%-4.2%) to ≥9 drinks. Unintended pregnancies (either due to contraceptive failure or sex without contraceptives) account for 80% (75%-87%) of pregnancies unknowingly exposed to alcohol. We project that public health efforts that focus only on promoting alcohol abstinence among women who are aware of their pregnancy or seeking pregnancy could reduce the prevalence of AEPs by at most 42% (36%-48%). Augmenting this strategy with efforts to avert unintended pregnancies could yield an 80% (73%-86%) reduction in the prevalence of AEPs. CONCLUSIONS: Promoting alcohol abstinence among women who are aware of their pregnancy or seeking pregnancy offers limited potential to reduce the prevalence of AEPs. Programs to avert unintended pregnancies are essential to achieve more substantial reductions in AEPs in the United States.

Societal Cost of Opioid Use in Symptomatic Knee Osteoarthritis Patients in the United States.

OBJECTIVE: Symptomatic knee osteoarthritis (SKOA) is a chronic, disabling condition, requiring long-term pain management; over 800,000 SKOA patients in the US use opioids on a prolonged basis. We aimed to characterize the societal economic burden of opioid use in this population. METHODS: We used the Osteoarthritis Policy Model, a validated computer simulation of SKOA, to estimate the opioid-related lifetime and annual cost generated by the US SKOA population. We included direct medical, lost productivity, criminal justice, and diversion costs. We modeled the SKOA cohort with a mean ± SD age of 54 ± 14 years and Western Ontario and McMaster Universities Osteoarthritis Index pain score of 29 ± 17 (0-100, 100 = worst). We estimated annual costs of strong ($1,381) and weak ($671) opioid regimens using Medicare fee schedules, Red Book, the Federal Supply Schedule, and published literature. The annual lost productivity and criminal justice costs of opioid use disorder (OUD), obtained from published literature, were $11,387 and $4,264, per-person, respectively. The 2015-2016 Medicare Current Beneficiary Survey provided OUD prevalence. We conducted sensitivity analyses to examine the robustness of our estimates to uncertainty in input parameters. RESULTS: Assuming 5.1% prevalence of prolonged strong opioid use, the total lifetime opioid-related cost generated by the US SKOA population was estimated at $14.0 billion, of which only $7.45 billion (53%) were direct medical costs. CONCLUSION: Lost productivity, diversion, and criminal justice costs comprise approximately half of opioid-related costs generated by the US SKOA population. Reducing prolonged opioid use may lead to a meaningful reduction in societal costs that can be used for other public health causes.

Adventures in COVID-19 Policy Modeling: Education Edition.

PURPOSE OF REVIEW: To introduce readers to policy modeling, a multidisciplinary field of quantitative analysis, primarily used to help guide decision-making. This review focuses on the choices facing educational administrators, from K-12 to universities in the USA, as they confronted the COVID-19 pandemic. We survey three key model-based approaches to mitigation of SARS-CoV-2 spread in schools and on university campuses. RECENT FINDINGS: Frequent testing, coupled with strict attention to behavioral interventions to prevent further transmission can avoid large outbreaks on college campuses. K-12 administrators can greatly reduce the risks of severe outbreaks of COVID-19 in schools through various mitigation measures including classroom infection control, scheduling and cohorting strategies, staff and teacher vaccination, and asymptomatic screening. Safer re-opening of college and university campuses as well as in-person instruction for K-12 students is possible, under many though not all epidemic scenarios if rigorous disease control and screening programs are in place.