Estimating Transition Probabilities for Modeling Major Depression in Adolescents by Sex and Race or Ethnicity Combinations in the USA.

OBJECTIVE: About one-fifth of US adolescents experienced major depressive symptoms, but few studies have examined longitudinal trends of adolescents developing depression or recovering by demographic factors. We estimated new transition probability inputs, and then used them in a simulation model to project the epidemiologic burden and trajectory of depression of diverse adolescents by sex and race or ethnicity combinations. METHODS: Transition probabilities were first derived using parametric survival analysis of data from the National Longitudinal Study of Adolescent to Adult Health and then calibrated to cross-sectional data from the National Survey on Drug Use and Health. We developed a cohort state-transition model to simulate age-specific depression outcomes of US adolescents. A hypothetical adolescent cohort was modeled from 12-22 years with annual transitions. Model outcomes included proportions of youth experiencing depression, recovery, or depression-free cases and were reported for a US adolescent population by sex, race or ethnicity, and sex and race or ethnicity combinations. RESULTS: At 22 years of age, approximately 16% of adolescents had depression, 12% were in recovery, and 72% had never developed depression. Depression prevalence peaked around 16-17 years-old. Adolescents of multiracial or other race or ethnicity, White, American Indian or Alaska Native, and Hispanic, Latino, or Spanish descent were more likely to experience depression than other racial or ethnic groups. Depression trajectories generated by the model matched well with historical observational studies by sex and race or ethnicity, except for individuals from American Indian or Alaska Native and multiracial or other race or ethnicity backgrounds. CONCLUSIONS: This study validated new transition probabilities for future use in decision models evaluating adolescent depression policies or interventions. Different sets of transition parameters by demographic factors (sex and race or ethnicity combinations) were generated to support future health equity research, including distributional cost-effectiveness analysis. Further data disaggregated with respect to race, ethnicity, religion, income, geography, gender identity, sexual orientation, and disability would be helpful to project accurate estimates for historically minoritized communities.

A mixed methods partner-focused cost and budget impact analysis to deploy implementation strategies for school-based prevention.

BACKGROUND: Obtaining information on implementation strategy costs and local budget impacts from multiple perspectives is essential to data-driven decision-making about resource allocation for successful evidence-based intervention delivery. This mixed methods study determines the costs and priorities of deploying Enhanced Replicating Effective Programs (REP) to implement the Michigan Model for Health™, a universal school-based prevention intervention, from key shareholder perspectives. METHODS: Our study included teachers in 8 high schools across 3 Michigan counties as part of a pilot cluster randomized trial. We used activity-based costing, mapping key Enhanced REP activities across implementation phases. We included multiple perspectives, including state agencies, regional education service agencies, lead organization, and implementers. We also conducted a budget impact analysis (BIA, assessing the potential financial impact of adopting Enhanced REP) and a scenario analysis to estimate replication and account for cost variability. We used an experimental embedded mixed methods approach, conducting semi-structured interviews and collecting field notes during the trial to expand and explain the cost data and the implications of costs across relevant perspectives. RESULTS: Based on trial results, we estimate costs for deploying Enhanced REP are $11,903/school, with an estimated range between $8263/school and $15,201/school. We estimate that adding four additional schools, consistent with the pilot, would cost $8659/school. Qualitative results indicated misalignment in school and teacher priorities in some cases. Implementation activities, including training and implementation facilitation with the health coordinator, were sometimes in addition to regular teaching responsibilities. The extent to which this occurred was partly due to leadership priorities (e.g., sticking to the district PD schedule) and organizational priorities (e.g., budget). CONCLUSIONS: Previous research findings indicate that, from a societal perspective, universal prevention is an excellent return on investment. However, notable misalignment in cost burden and priorities exists across shareholder groups. Our results indicate significant personal time costs by teachers when engaging in implementation strategy activities that impose an opportunity cost. Additional strategies are needed to improve the alignment of costs and benefits to enhance the success and sustainability of implementation. We focus on those perspectives informed by the analysis and discuss opportunities to expand a multi-level focus and create greater alignment across perspectives. TRIAL REGISTRATION: ClinicalTrials.gov NCT04752189. Registered on 12 February 2021.

Preferences and experiences of pediatricians on implementing national guidelines on universal routine screening of adolescents for major depressive disorder: A qualitative study.

BACKGROUND: To explore the preferences of pediatricians for key factors around the implementation of universal routine screening guidelines for major depressive disorder in adolescent patients in a primary care setting. METHOD: Semi-structured qualitative interviews were conducted with U.S. pediatricians. Participants were recruited by convenience sampling and snowball sampling. Qualitive data were summarized using thematic analysis to identify themes relevant to preferences around implementing screening strategies for adolescent patients. Recruitment ended upon reaching thematic saturation when no new themes were revealed. RESULTS: Of the 14 participants, 11 identified as female, 3 male, 10 white, and 4 Asian. Top themes among pediatrician participants were around the screening modality (14/14 participants), screening validity (14/14), time barriers (14/14), and confidentiality barriers (12/14). Less frequently mentioned themes by pediatricians were workplace coordination and logistics (7/14), alternative starting ages for screening (7/14), more frequent screenings than annual screenings (3/14), and additional clinical training regarding depression diagnosis and treatment (2/14). LIMITATIONS: Pool of interviewed participants was limited by diversity in terms of geography, race/ethnicity, or practice settings. CONCLUSIONS: To promote the uptake of universal routine screening of adolescent major depression, pediatricians expressed it was important to address key implementation factors regarding the screening modality, screening validity, time constraints, and confidential care concerns in a primary care delivery context. Findings could be used to inform the development of implementation strategies to facilitate depression screening in primary care. Future research is needed to quantitively assess decisions and tradeoffs that pediatricians make when implementing universal screening to support adolescent mental health.

Cost-effectiveness of surgical treatment of thumb carpometacarpal joint arthritis: a value of information study.

BACKGROUND: Thumb carpometacarpal (CMC) joint arthritis is one of the most prevalent arthritic conditions commonly treated with trapeziectomy alone or trapeziectomy with ligament reconstruction and tendon interposition (LRTI). We evaluate the cost-effectiveness and value of perfect and sample information of trapeziectomy alone, LRTI, and non-operative treatment. METHODS: A societal perspective decision tree was modeled. To understand the value of future research in comparing quality-of-life after trapeziectomy, LRTI, and non-operative management we characterized uncertainty by fitting distributions to EQ-5D utility data published from the United Kingdom hand surgery registry. We used Monte Carlo simulation for the probabilistic sensitivity analysis and to evaluate the value of perfect and sample information. RESULTS: Both trapeziectomy alone and LRTI were cost-effective compared to non-operative management ($2,540 and $3,511/QALY respectively). Trapeziectomy alone (base case total cost $8,251, QALY 14.08) was dominant compared to LRTI (base case total cost $8,798, QALY 13.34). However, probabilistic sensitivity analysis suggested there is a 12.5% chance LRTI may be preferred at a willingness-to-pay of $50,000/QALY. Sensitivity analysis revealed postoperative utilities are the most influential factors in determining cost-effectiveness. The value of perfect information was approximately $1,503/person. A study evaluating the quality-of-life of 1,000 patients in each arm undergoing trapeziectomy alone or LRTI could provide an expected $1,117 of information value. With approximately 40,000 CMC arthroplasties performed each year in the U.S., the annual value is close to $45 million. CONCLUSIONS: Trapeziectomy without LRTI appears to be the most cost-effective procedure in treating late-stage CMC arthritis and should be considered as first-line surgical treatment. There is substantial societal value in conducting additional research to better understand the relative quality-of-life improvements gained from these two common hand surgeries.

Best-worst scaling preferences among patients with well-controlled epilepsy: Pilot results.

Epilepsy is a common, serious condition. Fortunately, seizure risk decreases with increasing seizure-free time on antiseizure medications (ASMs). Eventually, patients may consider whether to stop ASMs, which requires weighing treatment benefit versus burden. We developed a questionnaire to quantify patient preferences relevant to ASM decision-making. Respondents rated how concerning they would finding relevant items (e.g., seizure risks, side effects, cost) on a Visual Analogue Scale (VAS, 0-100) and then repeatedly chose the most and least concerning item from subsets (best-worst scaling, BWS). We pretested with neurologists, then recruited adults with epilepsy who were seizure-free at least one year. Primary outcomes were recruitment rate, and qualitative and Likert-based feedback. Secondary outcomes included VAS ratings and best-minus-worst scores. Thirty-one of 60 (52%) contacted patients completed the study. Most patients felt VAS questions were clear (28; 90%), easy to use (27; 87%), and assessed preferences well (25; 83%). Corresponding results for BWS questions were 27 (87%), 29 (97%), and 23 (77%). Physicians suggested adding a 'warmup' question showing a completed example and simplifying terminology. Patients suggested ways to clarify instructions. Cost, inconvenience of taking medication, and laboratory monitoring were the least concerning items. Cognitive side effects and a 50% seizure risk in the next year were the most concerning items. Twelve (39%) of patients made at least one 'inconsistent choice' for example ranking a higher seizure risk as lower concern compared with a lower seizure risk, though 'inconsistent choices' represented only 3% of all question blocks. Our recruitment rate was favorable, most patients agreed the survey was clear, and we describe areas for improvement. 'Inconsistent' responses may lead us to collapse seizure probability items into a single 'seizure' category. Evidence regarding how patients weigh benefits and harms may inform care and guideline development.

Cost-effectiveness of Aflibercept Monotherapy vs Bevacizumab First Followed by Aflibercept If Needed for Diabetic Macular Edema.

Importance: The DRCR Retina Network Protocol AC showed no significant difference in visual acuity outcomes over 2 years between treatment with aflibercept monotherapy and bevacizumab first with switching to aflibercept for suboptimal response in treating diabetic macular edema (DME). Understanding the estimated cost and cost-effectiveness of these approaches is important. Objective: To evaluate the cost and cost-effectiveness of aflibercept monotherapy vs bevacizumab-first strategies for DME treatment. Design, Setting, and Participants: This economic evaluation was a preplanned secondary analysis of a US randomized clinical trial of participants aged 18 years or older with center-involved DME and best-corrected visual acuity of 20/50 to 20/320 enrolled from December 15, 2017, through November 25, 2019. Interventions: Aflibercept monotherapy or bevacizumab first, switching to aflibercept in eyes with protocol-defined suboptimal response. Main Outcomes and Measures: Between February and July 2022, the incremental cost-effectiveness ratio (ICER) in cost per quality-adjusted life-year (QALY) over 2 years was assessed. Efficacy and resource utilization data from the randomized clinical trial were used with health utility mapping from the literature and Medicare unit costs. Results: This study included 228 participants (median age, 62 [range, 34-91 years; 116 [51%] female and 112 [49%] male; 44 [19%] Black or African American, 60 [26%] Hispanic or Latino, and 117 [51%] White) with 1 study eye. The aflibercept monotherapy group included 116 participants, and the bevacizumab-first group included 112, of whom 62.5% were eventually switched to aflibercept. Over 2 years, the cost of aflibercept monotherapy was $26 504 (95% CI, $24 796-$28 212) vs $13 929 (95% CI, $11 984-$15 874) for the bevacizumab-first group, a difference of $12 575 (95% CI, $9987-$15 163). The aflibercept monotherapy group gained 0.015 (95% CI, -0.011 to 0.041) QALYs using the better-seeing eye and had an ICER of $837 077 per QALY gained compared with the bevacizumab-first group. Aflibercept could be cost-effective with an ICER of $100 000 per QALY if the price per dose were $305 or less or the price of bevacizumab was $1307 per dose or more. Conclusions and Relevance: Variability in individual needs will influence clinician and patient decisions about how to treat specific eyes with DME. While the bevacizumab-first group costs still averaged approximately $14 000 over 2 years, this approach, as used in this study, may confer substantial cost savings on a societal level without sacrificing visual acuity gains over 2 years compared with aflibercept monotherapy.

Cost-effectiveness of Staple Line Reinforcement in Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: To perform a cost-effectiveness analysis of staple-line reinforcement in laparoscopic sleeve gastrectomy. SUMMARY OF BACKGROUND DATA: Exponential increases in surgical costs have underscored the critical need for evidence-based methods to determine the relative value of surgical devices. One such device is staple-line reinforcement, thought to decrease bleeding rates in laparoscopic sleeve gastrectomy. METHODS: Two intervention arms were modeled, staple-line reinforcement and standard nonreinforced stapling. Bleed and leak rates and 30-day treatment costs were obtained from national and state registries. Quality-adjusted life-year (QALY) values were drawn from previous literature. Device prices were drawn from institutional data. A final incremental cost-effectiveness ratio was calculated, and one-way and probabilistic sensitivity analyses were performed. RESULTS: A total of 346,530 patient records from 2012 to 2018 were included. Complication rates for the reinforced and standard cohorts were 0.05% for major bleed in both cohorts ( P = 0.8841); 0.45% compared with 0.59% for minor bleed ( P < 0.0001); and 0.24% compared with 0.26% for leak ( P = 0.4812). Median cost for a major bleed was $5552 ($3287, $16,817) and $2406 ($1861, $3484) for a minor bleed. Median leak cost was $9897 ($4589, $21,619) and median cost for patients who did not experience a bleed, leak, or other serious complication was $1908 ($1712, $2739). Mean incremental cost of reinforced stapling compared with standard was $819.60/surgery. Net QALY gain with reinforced stapling compared with standard was 0.00002. The resultant incremental cost-effectiveness ratio was $40,553,000/QALY. One-way and probabilistic sensitivity analyses failed to produce a value below $150,000/QALY. CONCLUSIONS: Compared with standard stapling, reinforced stapling reduces minor postoperative bleeding but not major bleeding or leaks and is not cost-effective if routinely used in laparoscopic sleeve gastrectomy.

Clinical event reductions in high-risk patients after renal denervation projected from the global SYMPLICITY registry.

AIMS: Renal denervation has been shown to lower blood pressure in sham-controlled trials and represents a device-based treatment option for hypertension. We sought to project clinical event reductions after radiofrequency renal denervation using a novel modelling approach. METHODS AND RESULTS: The Global SYMPLICITY Registry is a global, prospective all-comer registry to evaluate safety and efficacy after renal denervation. For this analysis, change in office systolic blood pressure from baseline was calculated from reported follow-up in the Global SYMPLICITY Registry. Relative risks for death and other cardiovascular events as well as numbers needed to treat for event avoidance were obtained for the respective blood pressure reductions based on previously reported meta-regression analyses for the full cohort and high-risk subgroups including type 2 diabetes, chronic kidney disease, resistant hypertension, and high basal cardiovascular risk. Average baseline office systolic blood pressure and reduction estimates for the full cohort (N = 2651) were 166±25 and -14.8 ± 0.4 mmHg, respectively. Mean reductions in blood pressure ranged from -11.0--21.8 mmHg for the studied high-risk subgroups. Projected relative risks ranged from 0.57 for stroke in the resistant hypertension cohort to 0.92 for death in the diabetes cohort. Significant absolute reductions in major adverse cardiovascular events over 3 years compared with the projected control (8.6 ± 0.7% observed vs. 11.7 ± 0.9% for projected control; P < 0.01) were primarily due to reduced stroke incidence. The robustness of findings was confirmed in sensitivity and scenario analyses. CONCLUSION: Model-based projections suggest radiofrequency renal denervation for patients with uncontrolled hypertension adds considerable clinical benefit across a spectrum of different cohort characteristics.

Impact of the national hepatitis B immunization program in China: a modeling study.

BACKGROUND: Elimination of hepatitis B virus (HBV) is a striking challenge for countries with high or moderate disease burden. Therefore, using China as a practical case to share experiences for similar countries may accelerate the achievement of the WHO 2030 target of 90% reduction in HBV-related incidence. We aim to evaluate the impact of national HBV immunization strategies in China; and the feasibility to achieve WHO 2030 targets under different scenarios. METHODS: We constructed an expanded Susceptible-Exposed-Infectious-Recovered (SEIR) model and decision tree-Markov model to estimate the epidemic of HBV in China, assess the feasibility of 2030 Elimination Goals through the projections and conduct the economic analysis. Least square method was used to calibrate the expanded SEIR model by yearly data of laboratory-confirmed HBV cases from 1990 to 2018. Two models were separately used to evaluate the impact and cost-effectiveness of HBV vaccine by comparing prevalence of chronic HBV infections, quality-adjusted life-years (QALYs), incremental cost effectiveness ratio and benefit-cost ratio (BCR) under various intervention options, providing a basis for exploring new containment strategies. RESULTS: Between 1990 and 2020, the number of chronic HBV infections decreased by 33.9%. The current status quo would lead to 55.73 million infections (3.95% prevalence) in 2030, compared to 90.63 million (6.42% prevalence) of the "Without the NIP" scenario (NIP: National Immunization Program), 114.78 million (8.13% prevalence) without any interventions. The prevention of mother to child transmission (PMTCT) strategy showed a net benefit as 12,283.50 dollars per person, with BCR as 12.66, which is higher than that of universal vaccination at 9.49. Compared with no screening and no vaccination, the PMTCT strategy could save 7726.03 dollars for each QALY increase. CONCLUSIONS: Our findings proved the HBV vaccination has demonstrated a substantial positive impact on controlling the epidemic of HBV in terms of effectiveness and economy after about 30 years of implementation of the national hepatitis B immunization program which also provided containment experience for high or medium burden countries. As for China, the next step should focus on exploring strategies to improve diagnosis and treatment coverage to reduce the burden of HBV-related deaths and ultimately eliminate HBV.

Estimation of Potential Deaths Averted From Hypothetical US Income Support Policies.

Importance: Income has a negative, nonlinear association with all-cause mortality. Income support policies may prevent deaths among low-income populations by raising their incomes. Objective: To estimate the deaths that could be averted among working-age adults age 18 to 64 years with hypothetical income support policies in the US. Design Setting and Population: An open, multicohort life-table model was developed that simulated working-age adults age 18 to 64 years in the US over 5 to 40 years. Publicly available household income data and previous estimates of the income-mortality association were used to generate mortality rates by income group. Deterministic sensitivity analyses were conducted to evaluate the effect of parameter uncertainty and various model assumptions on the findings. Interventions: In addition to a no-intervention scenario, 4 hypothetical income support policies were modeled: universal basic income, modified LIFT Act, poverty alleviation, and negative income tax. Main Outcome and Measures: The main outcome was the number of deaths averted, which was calculated by subtracting the number of deaths experienced in the no-intervention scenario from the number of deaths experienced with the various income support policies. Results: Base-case assumptions used average mortality rates by age, sex, and income group, a 20-year time horizon, and a 3-year lag time. Universal basic income worth $12 000 per year per individual was estimated to avert the most deaths among working-age adults (42 000-104 000 per year), followed by a negative income tax that guaranteed an income of 133% of the federal poverty level (19 000-67 000 per year). A modified LIFT Act that provided $6000 to individuals with annual household incomes less than $100 000 was estimated to avert 17 000 to 52 000 deaths per year. A targeted approach that alleviated poverty was estimated to prevent 12 000 to 32 000 deaths among the lowest-income, working-age adult population. Results were most sensitive to several inputs and assumptions, primarily the income-based mortality rates, analytic time horizon, and assumed time lag between when a policy was implemented and when individuals experienced the mortality benefit of having higher incomes. Conclusions and Relevance: In this modeling study, 4 hypothetical income support policies were estimated to avert thousands of deaths among working-age US adults every year. Additional research is needed to understand the true association of income gains with mortality. Discussions about the costs and benefits of income support policies should include potential gains in health.

Cost-Effectiveness of Hepatitis B Testing and Vaccination of Adults Seeking Care for Sexually Transmitted Infections.

BACKGROUND: The estimated number of people living with hepatitis B virus (HBV) infection acquired through sexual transmission was 103,000 in 2018, with an estimated incidence of 8300 new cases per year. Although hepatitis B (HepB) vaccination is recommended by the Advisory Committee for Immunization Practices for persons seeking evaluation and treatment for sexually transmitted infections (STIs), prevaccination testing is not yet recommended. Screening may link persons with chronic hepatitis B to care and reduce unnecessary vaccination. METHODS: We used a Markov model to calculate the health impact and cost-effectiveness of 1-time HBV testing combined with the first dose of the HepB vaccine for adults seeking care for STI. We ran a lifetime, societal perspective analysis for a hypothetical population of 100,000 aged 18 to 69 years. The disease progression estimates were taken from recent cohort studies and meta-analyses. In the United States, an intervention that costs less than $100,000 per quality-adjusted life-year (QALY) is generally considered cost-effective. The strategies that were compared were as follows: (1) vaccination without HBV screening, (2) vaccination and hepatitis B surface antigen (HBsAg) screening, (3) vaccination and screening with HBsAg and anti-HBs, and (4) vaccination and screening with HBsAg, anti-HBs, and anti-HBc. Data were obtained from Centers for Medicare & Medicaid services reimbursement, the Centers for Disease Control and Prevention vaccine price list, and additional cost-effectiveness literature. RESULTS: Compared with current recommendations, the addition of 1-time HBV testing is cost-saving and would prevent an additional 138 cases of cirrhosis, 47 cases of decompensated cirrhosis, 90 cases of hepatocellular carcinoma, 33 liver transplants, and 163 HBV-related deaths, and gain 2185 QALYs, per 100,000 adults screened. Screening with the 3-test panel would save $41.6 to $42.7 million per 100,000 adults tested compared with $41.5 to $42.5 million for the 2-test panel and $40.2 to $40.3 million for HBsAg alone. CONCLUSIONS: One-time HBV prevaccination testing in addition to HepB vaccination for unvaccinated adults seeking care for STI would save lives and prevent new infections and unnecessary vaccination, and is cost-saving.

An Assessment of Ineligible Donor Use in Solid Organ Transplant.

BACKGROUND: In the United States, the demand for organ transplants far outpaces available organs. The use of Organ Procurement and Transplantation Network-defined ineligible donors is an immediate method for increasing donations. However, the use of ineligible donors varies across organ procurement organizations (OPOs), and its association with recipient survival remains unclear. METHODS: We evaluated ineligible donor use from 2008 to 2020 by OPO and its association with graft and recipient survival across demographics. RESULTS: In this study of 297 223 organ donations, 42 184 (14%) did not meet eligibility criteria as defined by the Organ Procurement and Transplantation Network. Log-rank tests on Kaplan-Meier curves suggested differences in graft and patient survival between eligible and ineligible recipients for kidney and liver transplants ( P ≤ 0.01 for all). Recipients of ineligible kidney and liver donations saw a 2.20% and 9.38% decrease in 10-y graft survival probability, respectively. There were no statistically significant graft and patient survival differences for recipients of ineligible heart, lung, and pancreas donations. Multivariate proportional hazard models showed eligibility was associated with kidney, liver, and lung graft survival ( P ≤ 0.02 for all). However, if OPOs increased ineligible donor use to meet the current 75th percentile use rate, there could be as many as 1000 transplants and 6291 life-years gained annually. CONCLUSIONS: Ineligible donor use can provide significant survival benefit for patients who would otherwise never receive a transplant. Methods to reduce regional heterogeneity in ineligible donor use could increase the number of transplants and improve outcomes for waiting patients.

The Magnitude of the Health and Economic Impact of Increased Organ Donation on Patients With End-Stage Renal Disease.

Objectives. There are several approaches such as presumed consent and compensation for deceased donor organs that could reduce the gap between supply and demand for kidneys. Our objective is to evaluate the magnitude of the economic impact of policies to increase deceased donor organ donation in the United States. Methods. We built a Markov model and simulate an open cohort of end-stage renal disease patients awaiting kidney transplantation in the United States over 20 years. Model inputs were derived from the United States Renal Data System and published literature. We evaluate the magnitude of the health and economic impact of policies to increase deceased donor kidney donation in the United States. Results. Increasing deceased kidney donation by 5% would save $4.7 billion, and gain 30,870 quality-adjusted life years over the lifetime of an open cohort of patients on dialysis on the waitlist for kidney transplantation. With an increase in donations of 25%, the cost saved was $21 billion, and 145,136 quality-adjusted life years were gained. Policies increasing deceased kidney donation by 5% could pay donor estates $8000 or incur a onetime cost of up to $4 billion and still be cost-saving. Conclusions. Increasing deceased kidney donation could significantly impact national spending and health for end-stage renal disease patients.

Assessing patient perception of risk in ocular stem cell therapies.

A wide variety of stem cell-derived therapies are under development for the treatment of retinal degeneration. In order to better understand patient perspectives about these therapies, we assessed risk tolerance using an in-person survey of 178 patients at an academic eye center. Risk of malignancy served as a hypothetical, readily understood, and serious adverse event to be considered in trade for potential visual improvement from a stem cell-derived treatment. The results indicate that patients were willing to trade visual improvement against a risk of malignancy that far exceeds actual risk. Two novel findings were that older patients and those with an intermediate level of visual loss were particularly risk tolerant. The quantitative survey results provide a step toward understanding patient perspectives that will, over the long term, guide the development of ocular stem cell-derived therapies.

A machine learning approach for the prediction of overall deceased donor organ yield.

BACKGROUND: Optimizing organ yield (number of organs transplanted per donor) is a potentially modifiable way to increase the number of organs available for transplant. Models to predict the expected deceased donor organ yield have been developed based on ordinary least squares regression and logistic regression. However, alternative modeling methodologies incorporating machine learning may have superior performance compared with conventional approaches. METHODS: We evaluated the predictive accuracy of 14 machine learning models for predicting overall organ yield in a cross-validation procedure. The models were parameterized using data from the Organ Procurement and Transplantation Network database from 2000 to 2018. The inclusion criteria for the study were adult deceased donors between 18 and 84 years of age that had at least 1 organ procured for transplantation. RESULTS: A total of 89,520 donors met the inclusion criteria. Their mean (standard deviation) age was 44 (15) years, and approximately 58% were male. Our cross-validation analysis showed that a tree-based gradient boosting model outperformed the remaining 13 models. Compared with the currently used prediction models, the gradient boosting model improves prediction accuracy by reducing the mean absolute error between 3 and 11 organs per 100 donors. CONCLUSION: Our analysis demonstrated that the gradient boosting methodology had the best performance in predicting overall deceased donor organ yield and can potentially serve as an aid to assess organ procurement organization performance.

Costs of Managing Diabetic Macular Edema With Good Visual Acuity With Aflibercept, Laser, or Observation: DRCR Retina Network Protocol V.

PURPOSE: Because eyes with center-involved diabetic macular edema (CI-DME) and good baseline visual acuity (VA) showed no difference in VA loss when managed initially with observation, laser, or aflibercept, understanding the estimated costs of these strategies to the US population is relevant for health care planning. DESIGN: Preplanned cost analysis from a randomized controlled trial (DRCR Retina Network Protocol V). METHODS: Total costs for managing participants with CI-DME and good baseline VA assigned to aflibercept (n = 226), laser (n = 240), or observation (n = 236) during the 2-year multicenter trial were calculated. Observation or laser groups initiated aflibercept if VA decreased. The aflibercept group received injections up to every 4 weeks. Using epidemiological data and extrapolating costs, 10-year costs of care for all persons with CI-DME and good baseline VA throughout the United States were caluclated. RESULTS: Assuming that all patients in the United States with CI-DME and good baseline VA received aflibercept initially, 10-year costs were projected to be $28.80 billion compared with $14.42 billion if initially receiving laser treatment or $15.70 billion if initially observed, with aflibercept added if VA worsened in the laser or observation arms. CONCLUSIONS: Similar VA outcomes on average are obtained by initially managing CI-DME and good baseline VA with laser or observation strategies instead of immediately using aflibercept. Although any 1 of these 3 strategies might be warranted depending on an individual's specific circumstances, on a societal level, cost savings might be achieved with these first 2 approaches.

Immunologic and Epidemiologic Drivers of Norovirus Transmission in Daycare and School Outbreaks.

BACKGROUND: Norovirus outbreaks are notoriously explosive, with dramatic symptomology and rapid disease spread. Children are particularly vulnerable to infection and drive norovirus transmission due to their high contact rates with each other and the environment. Despite the explosive nature of norovirus outbreaks, attack rates in schools and daycares remain low with the majority of students not reporting symptoms. METHODS: We explore immunologic and epidemiologic mechanisms that may underlie epidemic norovirus transmission dynamics using a disease transmission model. Towards this end, we compared different model scenarios, including innate resistance and acquired immunity (collectively denoted 'immunity'), stochastic extinction, and an individual exclusion intervention. We calibrated our model to daycare and school outbreaks from national surveillance data. RESULTS: Including immunity in the model led to attack rates that were consistent with the data. However, immunity alone resulted in the majority of outbreak durations being relatively short. The addition of individual exclusion (to the immunity model) extended outbreak durations by reducing the amount of time that symptomatic people contribute to transmission. Including both immunity and individual exclusion mechanisms resulted in simulations where both attack rates and outbreak durations were consistent with surveillance data. CONCLUSIONS: The epidemiology of norovirus outbreaks in daycare and school settings cannot be well described by a simple transmission model in which all individuals start as fully susceptible. More studies on how best to design interventions which leverage population immunity and encourage more rigorous individual exclusion may improve venue-level control measures. See video abstract at http://links.lww.com/EDE/B795.

Cost-effectiveness of pediatric norovirus vaccination in daycare settings.

OBJECTIVE: Noroviruses are the leading cause of acute gastroenteritis in the United States and outbreaks frequently occur in daycare settings. Results of norovirus vaccine trials have been promising, however there are open questions as to whether vaccination of daycare children would be cost-effective. We investigated the incremental cost-effectiveness of a hypothetical norovirus vaccination for children in daycare settings compared to no vaccination. METHODS: We conducted a model-based cost-effectiveness analysis using a disease transmission model of children attending daycare. Vaccination with a 90% coverage rate in addition to the observed standard of care (exclusion of symptomatic children from daycare) was compared to the observed standard of care. The main outcomes measures were infections and deaths averted, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Cost-effectiveness was analyzed from a societal perspective, including medical costs to children as well as productivity losses of parents, over a two-year time horizon. Data sources included outbreak surveillance data and published literature. RESULTS: A 50% efficacious norovirus vaccine averts 571.83 norovirus cases and 0.003 norovirus-related deaths per 10,000 children compared to the observed standard of care. A $200 norovirus vaccine that is 50% efficacious has a net cost increase of $178.10 per child and 0.025 more QALYs, resulting in an ICER of $7,028/QALY. Based on the probabilistic sensitivity analysis, we estimated that a $200 vaccination with 50% efficacy was 94.0% likely to be cost-effective at a willingness-to-pay of $100,000/QALY threshold and 95.3% likely at a $150,000/QALY threshold. CONCLUSION: Due to the large disease burden associated with norovirus, it is likely that vaccinating children in daycares could be cost-effective, even with modest vaccine efficacy and a high per-child cost of vaccination. Norovirus vaccination of children in daycare has a cost-effectiveness ratio similar to other commonly recommended childhood vaccines.

Costs implications of pneumococcal vaccination of adults aged 30-60 with a recent diagnosis of diabetes.

OBJECTIVE: The 23-valent pneumococcal polysaccharide vaccine is routinely recommended for adults with diabetes, but little is known about adherence to this recommendation and how vaccination of these adults affects costs related to pneumococcal disease. RESEARCH DESIGN AND METHODS: We used data from a commercial insurance claims dataset to examine a cohort of non-elderly adults with a new diagnosis of diabetes and adults with no diagnosis of diabetes from 2005 to 2014. We examined rates of pneumococcal polysaccharide vaccination and the relationship between vaccination and pneumococcal disease costs, comparing results for persons with a diagnosis of diabetes and those with no diagnosis of diabetes. RESULTS: Overall rates of pneumococcal polysaccharide vaccination among adults 30-60 years old were <1%/year. Rates of pneumococcal polysaccharide vaccination were higher for adults with diabetes. Pneumococcal polysaccharide vaccination rates more than doubled from 2.9% per year in 2005 to 6.0% per year in 2014 for adults vaccinated during the same year as their diabetes diagnosis. Using a two-part differences-in-differences model on a propensity-score matched dataset, pneumococcal polysaccharide vaccination may reduce average annual per-person pneumococcal disease costs by $90.54 [95% CI: $183.59, -$2.49, (p = 0.056)] in persons with diabetes from two years before to two years after vaccination. CONCLUSIONS: Non-elderly adults with diabetes have low but rising rates of pneumococcal polysaccharide vaccination. Pneumococcal polysaccharide vaccination has a modest impact reducing overall costs of pneumococcal disease in this population.