Personalizing the empiric treatment of gonorrhea using machine learning models.

Despite the emergence of antimicrobial-resistant (AMR) strains of Neisseria gonorrhoeae, the treatment of gonorrhea remains empiric and according to standardized guidelines, which are informed by the national prevalence of resistant strains. Yet, the prevalence of AMR varies substantially across geographic and demographic groups. We investigated whether data from the national surveillance system of AMR gonorrhea in the US could be used to personalize the empiric treatment of gonorrhea. We used data from the Gonococcal Isolate Surveillance Project collected between 2000-2010 to train and validate machine learning models to identify resistance to ciprofloxacin (CIP), one of the recommended first-line antibiotics until 2007. We used these models to personalize empiric treatments based on sexual behavior and geographic location and compared their performance with standardized guidelines, which recommended treatment with CIP, ceftriaxone (CRO), or cefixime (CFX) between 2005-2006, and either CRO or CFX between 2007-2010. Compared with standardized guidelines, the personalized treatments could have replaced 33% of CRO and CFX use with CIP while ensuring that 98% of patients were prescribed effective treatment during 2005-2010. The models maintained their performance over time and across geographic regions. Predictive models trained on data from national surveillance systems of AMR gonorrhea could be used to personalize the empiric treatment of gonorrhea based on patients' basic characteristics at the point of care. This approach could reduce the unnecessary use of newer antibiotics while maintaining the effectiveness of first-line therapy.

Net Monetary Benefit Lines Augmented with Value-of-Information Measures to Present the Results of Economic Evaluations under Uncertainty.

BACKGROUND: Methods to present the result of cost-effectiveness analyses under parameter uncertainty include cost-effectiveness planes (CEPs), cost-effectiveness acceptability curves/frontier (CEACs/CEAF), expected loss curves (ELCs), and net monetary benefit (NMB) lines. We describe how NMB lines can be augmented to present NMB values that could be achieved by reducing or resolving parameter uncertainty. We evaluated the ability of these methods to correctly 1) identify the alternative with the highest expected NMB and 2) communicate the magnitude of parameter and decision uncertainty. METHODS: We considered 4 hypothetical decision problems representing scenarios with high variance or correlated cost and effect estimates and alternatives with similar cost-effectiveness ratios. We used these decision problems to demonstrate the limitations of existing methods and the potential of augmented NMB lines to resolve these issues. RESULTS: CEPs and CEACs/CEAF could falsely imply the lack of sufficient evidence to identify the optimal option if cost and effect estimates have high variance, are correlated across alternatives, or when alternatives have similar cost-effectiveness ratios. The augmented NMB lines and ELCs can correctly identify the option with the highest expected NMB and communicate the potential benefit of resolving uncertainties. Like ELCs, the augmented NMB lines provide information about the value of resolving parameter uncertainties, but augmented NMB lines may be easier to interpret for decision makers. CONCLUSIONS: Our analysis supports recommending the augment NMB lines as an important method to present the results of economic evaluation studies under parameter uncertainty. HIGHLIGHTS: The results of cost-effectiveness analyses (CEAs) when the cost and effect estimates of alternatives are uncertain are commonly presented using cost-effectiveness planes (CEPs), cost-effectiveness acceptability curves/frontier (CEACs/CEAF), and expected loss curves (ELCs).Although currently not often used, net monetary benefit (NMB) lines could present the results of cost-effectiveness to identify the alternative with the highest expected NMB values given the current level of uncertainty. Furthermore, NMB lines can be augmented to 1) show metrics of value of information, which measure the value of additional research to reduce or eliminate the decision uncertainty, and 2) display the confidence intervals along the NMB lines to ensure that NMB values are estimated accurately using a sufficiently large number of parameter samples.Using several decision problems, we demonstrate the limitation of existing methods to present the results of CEAs under parameter uncertainty and how augmented NMB lines could resolve these issues.Our analysis supports recommending augmented NMB lines as an important method to present the results of CEA under uncertainty since they 1) correctly identify the alternative with the highest expected NMB value given the current evidence, 2) provide information about the potential value of additional research to improve the decision by reducing or resolving uncertainty in model parameters, 3) assist the analysis to visually ensure that enough parameter samples are used to estimate the expected NMB of alternatives, and 4) are easier to interpret for decision makers compared with other methods.

Assessing thresholds of resistance prevalence at which empiric treatment of gonorrhea should change among men who have sex with men in the US: A cost-effectiveness analysis.

BACKGROUND: Since common diagnostic tests for gonorrhea do not provide information about susceptibility to antibiotics, treatment of gonorrhea remains empiric. Antibiotics used for empiric therapy are usually changed once resistance prevalence exceeds a certain threshold (e.g., 5%). A low switch threshold is intended to increase the probability that an infection is successfully treated with the first-line antibiotic, but it could also increase the pace at which recommendations are switched to newer antibiotics. Little is known about the impact of changing the switch threshold on the incidence of gonorrhea, the rate of treatment failure, and the overall cost and quality-adjusted life-years (QALYs) associated with gonorrhea. METHODS AND FINDINGS: We developed a transmission model of gonococcal infection with multiple resistant strains to project gonorrhea-associated costs and loss in QALYs under different switch thresholds among men who have sex with men (MSM) in the United States. We accounted for the costs and disutilities associated with symptoms, diagnosis, treatment, and sequelae, and combined costs and QALYs in a measure of net health benefit (NHB). Our results suggest that under a scenario where 3 antibiotics are available over the next 50 years (2 suitable for the first-line therapy of gonorrhea and 1 suitable only for the retreatment of resistant infections), changing the switch threshold between 1% and 10% does not meaningfully impact the annual number of gonorrhea cases, total costs, or total QALY losses associated with gonorrhea. However, if a new antibiotic is to become available in the future, choosing a lower switch threshold could improve the population NHB. If in addition, drug-susceptibility testing (DST) is available to inform retreatment regimens after unsuccessful first-line therapy, setting the switch threshold at 1% to 2% is expected to maximize the population NHB. A limitation of our study is that our analysis only focuses on the MSM population and does not consider the influence of interventions such as vaccine and common use of rapid drugs susceptibility tests to inform first-line therapy. CONCLUSIONS: Changing the switch threshold for first-line antibiotics may not substantially change the health and financial outcomes associated with gonorrhea. However, the switch threshold could be reduced when newer antibiotics are expected to become available soon or when in addition to future novel antibiotics, DST is also available to inform retreatment regimens.

How Many Monte Carlo Samples are Needed for Probabilistic Cost-Effectiveness Analyses?

OBJECTIVES: Probabilistic sensitivity analysis (PSA) is conducted to account for the uncertainty in cost and effect of decision options under consideration. PSA involves obtaining a large sample of input parameter values (N) to estimate the expected cost and effect of each alternative in the presence of parameter uncertainty. When the analysis involves using stochastic models (eg, individual-level models), the model is further replicated P times for each sampled parameter set. We study how N and P should be determined. METHODS: We show that PSA could be structured such that P can be an arbitrary number (say, P=1). To determine N, we derive a formula based on Chebyshev's inequality such that the error in estimating the incremental cost-effectiveness ratio (ICER) of alternatives (or equivalently, the willingness-to-pay value at which the optimal decision option changes) is within a desired level of accuracy. We described 2 methods to confirm, visually and quantitatively, that the N informed by this method results in ICER estimates within the specified level of accuracy. RESULTS: When N is arbitrarily selected, the estimated ICERs could be substantially different from the true ICER (even as P increases), which could lead to misleading conclusions. Using a simple resource allocation model, we demonstrate that the proposed approach can minimize the potential for this error. CONCLUSIONS: The number of parameter samples in probabilistic cost-effectiveness analyses should not be arbitrarily selected. We describe 3 methods to ensure that enough parameter samples are used in probabilistic cost-effectiveness analyses.

Impact and cost-effectiveness of the 6-month BPaLM regimen for rifampicin-resistant tuberculosis in Moldova: A mathematical modeling analysis.

BACKGROUND: Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) was detected on drug susceptibility testing (DST). METHODS AND FINDINGS: The primary objective was to determine whether 6 months of BPaLM is a cost-effective treatment strategy for RR-TB. We used genomic and demographic data to parameterize a mathematical model estimating long-term health outcomes measured in quality-adjusted life years (QALYs) and lifetime costs in 2022 USD ($) for each treatment strategy for patients 15 years and older diagnosed with pulmonary RR-TB in Moldova, a country with a high burden of TB drug resistance. For each individual, we simulated the natural history of TB and associated treatment outcomes, as well as the process of acquiring resistance to each of 12 anti-TB drugs. Compared to the standard of care, 6 months of BPaLM was cost-effective. This strategy was estimated to reduce lifetime costs by $3,366 (95% UI: [1,465, 5,742] p < 0.001) per individual, with a nonsignificant change in QALYs (-0.06; 95% UI: [-0.49, 0.03] p = 0.790). For those stopping moxifloxacin under the BPaLM regimen, continuing with BPaL plus clofazimine (BPaLC) provided more QALYs at lower cost than continuing with BPaL alone. Strategies based on 6 months of BPaLM had at least a 93% chance of being cost-effective, so long as BPaLC was continued in the event of stopping moxifloxacin. BPaLM for 6 months also reduced the average time spent with TB resistant to amikacin, bedaquiline, clofazimine, cycloserine, moxifloxacin, and pyrazinamide, while it increased the average time spent with TB resistant to delamanid and pretomanid. Sensitivity analyses showed 6 months of BPaLM to be cost-effective across a broad range of values for the relative effectiveness of BPaLM, and the proportion of the cohort with FQ-R. Compared to the standard of care, 6 months of BPaLM would be expected to save Moldova's national TB program budget $7.1 million (95% UI: [1.3 million, 15.4 million] p = 0.002) over the 5-year period from implementation. Our analysis did not account for all possible interactions between specific drugs with regard to treatment outcomes, resistance acquisition, or the consequences of specific types of severe adverse events, nor did we model how the intervention may affect TB transmission dynamics. CONCLUSIONS: Compared to standard of care, longer regimens, the implementation of the 6-month BPaLM regimen could improve the cost-effectiveness of care for individuals diagnosed with RR-TB, particularly in settings with a high burden of drug-resistant TB. Further research may be warranted to explore the impact and cost-effectiveness of shorter RR-TB regimens across settings with varied drug-resistant TB burdens and national income levels.

Cost-Effectiveness of CT, CTA, MRI, and Specialized MRI for Evaluation of Patients Presenting to the Emergency Department With Dizziness.

BACKGROUND. Underlying stroke is often misdiagnosed in patients presenting with dizziness. Although such patients are usually ineligible for acute stroke treatment, accurate diagnosis may still improve outcomes through selection of patients for secondary prevention measures. OBJECTIVE. The purpose of our study was to investigate the cost-effectiveness of differing neuroimaging approaches in the evaluation of patients presenting to the emergency department (ED) with dizziness who are not candidates for acute intervention. METHODS. A Markov decision-analytic model was constructed from a health care system perspective for the evaluation of a patient presenting to the ED with dizziness. Four diagnostic strategies were compared: noncontrast head CT, head and neck CTA, conventional brain MRI, and specialized brain MRI (including multiplanar high-resolution DWI). Differing long-term costs and outcomes related to stroke detection and secondary prevention measures were compared. Cost-effectiveness was calculated in terms of lifetime expenditures in 2022 U.S. dollars for each quality-adjusted life year (QALY); deterministic and probabilistic sensitivity analyses were performed. RESULTS. Specialized MRI resulted in the highest QALYs and was the most cost-effective strategy with US$13,477 greater cost and 0.48 greater QALYs compared with noncontrast head CT. Conventional MRI had the next-highest health benefit, although was dominated by extension with incremental cost of US$6757 and 0.25 QALY; CTA was also dominated by extension, with incremental cost of US$3952 for 0.13 QALY. Non-contrast CT alone had the lowest utility among the four imaging choices. In the deterministic sensitivity analyses, specialized MRI remained the most cost-effective strategy. Conventional MRI was more cost-effective than CTA across a wide range of model parameters, with incremental cost-effectiveness remaining less than US$30,000/QALY. Probabilistic sensitivity analysis yielded similar results as found in the base-case analysis, with specialized MRI being more cost-effective than conventional MRI, which in turn was more cost-effective than CTA. CONCLUSION. The use of MRI in patients presenting to the ED with dizziness improves stroke detection and selection for subsequent preventive measures. MRI-based evaluation leads to lower long-term costs and higher cumulative QALYs. CLINICAL IMPACT. MRI, incorporating specialized protocols when available, is the preferred approach for evaluation of patients presenting to the ED with dizziness, to establish a stroke diagnosis and to select patients for secondary prevention measures.

The Impact of Rapid Drug Susceptibility Tests on Gonorrhea Burden and the Life Span of Antibiotic Treatments: A Modeling Study Among Men Who Have Sex With Men in the United States.

Rapid point-of-care tests that diagnose gonococcal infections and identify susceptibility to antibiotics enable individualized treatment. This could improve patient outcomes and slow the emergence and spread of antibiotic resistance. However, little is known about the long-term impact of such diagnostics on the burden of gonorrhea and the effective life span of antibiotics. We used a mathematical model of gonorrhea transmission among men who have sex with men in the United States to project the annual rate of reported gonorrhea cases and the effective life span of ceftriaxone, the recommended antibiotic for first-line treatment of gonorrhea, as well as 2 previously recommended antibiotics, ciprofloxacin and tetracycline, when a rapid drug susceptibility test that estimates susceptibility to ciprofloxacin and tetracycline is available. The use of a rapid drug susceptibility test with ≥50% sensitivity and ≥95% specificity, defined in terms of correct ascertainment of drug susceptibility and nonsusceptibility status, could increase the combined effective life span of ciprofloxacin, tetracycline, and ceftriaxone by at least 2 years over 25 years of simulation. If test specificity is imperfect, however, the increase in the effective life span of antibiotics is accompanied by an increase in the rate of reported gonorrhea cases even under perfect sensitivity.

Resistance-minimising strategies for introducing a novel antibiotic for gonorrhoea treatment: a mathematical modelling study.

BACKGROUND: Gonorrhoea is a highly prevalent sexually transmitted infection and an urgent public health concern because of increasing antibiotic resistance in Neisseria gonorrhoeae. Only ceftriaxone remains as the recommended treatment in the USA. With the prospect of new anti-gonococcal antibiotics being approved, we aimed to evaluate how to deploy a new drug to maximise its clinically useful lifespan. METHODS: We used a compartmental model of gonorrhoea transmission in a US population of men who have sex with men (MSM) to compare strategies for introducing a new antibiotic for gonorrhoea treatment. The MSM population was stratified into three sexual activity groups (low, intermediate, and high) characterised by annual rates of partner change. The four introduction strategies tested were: (1) random 50-50 allocation, where each treatment-seeking infected individual had a 50% probability of receiving either drug A (current drug; a ceftriaxone-like antibiotic) or drug B (a new antibiotic), effective at time 0; (2) combination therapy of both the current drug and the new antibiotic; (3) reserve strategy, by which the new antibiotic was held in reserve until the current therapy reached a 5% threshold prevalence of resistance; and (4) gradual switch, or the gradual introduction of the new drug until random 50-50 allocation was reached. The primary outcome of interest was the time until 5% prevalence of resistance to each of the drugs (the new drug and the current ceftriaxone-like antibiotic); sensitivity of the primary outcome to the properties of the new antibiotic, specifically the probability of resistance emergence after treatment and the fitness costs of resistance, was explored. Secondary outcomes included the time to a 1% resistance threshold for each drug, as well as population-level prevalence, mean and range annual incidence, and the cumulative number of incident gonococcal infections. FINDINGS: Under baseline model conditions, a 5% prevalence of resistance to each of drugs A and B was reached within 13·9 years with the reserve strategy, 18·2 years with the gradual switch strategy, 19·2 years with the random 50-50 allocation strategy, and 19·9 years with the combination therapy strategy. The reserve strategy was consistently inferior for mitigating antibiotic resistance under the parameter space explored and was increasingly outperformed by the other strategies as the probability of de novo resistance emergence decreased and as the fitness costs associated with resistance increased. Combination therapy tended to prolong the development of antibiotic resistance and minimise the number of annual gonococcal infections (under baseline model conditions, mean number of incident infections per year 178 641 [range 177 998-181 731] with combination therapy, 180 084 [178 011-184 405] with the reserve strategy). INTERPRETATION: Our study argues for rapid introduction of new anti-gonococcal antibiotics, recognising that the feasibility of each strategy must incorporate cost, safety, and other practical concerns. The analyses should be revisited once robust estimates of key parameters-ie, the likelihood of emergence of resistance and fitness costs of resistance for the new antibiotic-are available. FUNDING: US Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases.

CT With CTA Versus MRI in Patients Presenting to the Emergency Department With Dizziness: Analysis Using Propensity Score Matching.

BACKGROUND. CT with CTA is widely used to exclude stroke in patients with dizziness, although MRI has higher sensitivity. OBJECTIVE. The purpose of this article was to compare patients presenting to the emergency department (ED) with dizziness who undergo CT with CTA alone versus those who undergo MRI in terms of stroke-related management and outcomes. METHODS. This retrospective study included 1917 patients (mean age, 59.5 years; 776 men, 1141 women) presenting to the ED with dizziness from January 1, 2018, to December 31, 2021. A first propensity score matching analysis incorporated demographic characteristics, medical history, findings from the review of systems, physical examination findings, and symptoms to construct matched groups of patients discharged from the ED after undergoing head CT with head and neck CTA alone and patients who underwent brain MRI (with or without CT and CTA). Outcomes were compared. A second analysis compared matched patients discharged after CT with CTA alone and patients who underwent specialized abbreviated MRI using multiplanar high-resolution DWI for increased sensitivity for posterior circulation stroke. Sensitivity analyses were performed involving MRI examinations performed as the first or only neuroimaging examination and involving alternative matching and imputation techniques. RESULTS. In the first analysis (406 patients per group), patients who underwent MRI, compared with patients who underwent CT with CTA alone, showed greater frequency of critical neuroimaging results (10.1% vs 4.7%, p = .005), change in secondary stroke prevention medication (9.6% vs 3.2%, p = .001), and subsequent echocardiography evaluation (6.4% vs 1.0%, p < .001). In the second analysis (100 patients per group), patients who underwent specialized abbreviated MRI, compared with patients who underwent CT with CTA alone, showed greater frequency of critical neuroimaging results (10.0% vs 2.0%, p = .04), change in secondary stroke prevention medication (14.0% vs 1.0%, p = .001), and subsequent echocardiography evaluation (12.0% vs 2.0%, p = .01) and lower frequency of 90-day ED readmissions (12.0% vs 28.0%, p = .008). Sensitivity analyses showed qualitatively similar findings. CONCLUSION. A proportion of patients discharged after CT with CTA alone may have benefitted from alternative or additional evaluation by MRI (including MRI using a specialized abbreviated protocol). CLINICAL IMPACT. Use of MRI may motivate clinically impactful management changes in patients presenting with dizziness.

Clinical criteria to exclude acute vascular pathology on CT angiogram in patients with dizziness.

BACKGROUND: Patients presenting to the emergency department (ED) with dizziness may be imaged via CTA head and neck to detect acute vascular pathology including large vessel occlusion. We identify commonly documented clinical variables which could delineate dizzy patients with near zero risk of acute vascular abnormality on CTA. METHODS: We performed a cross-sectional analysis of adult ED encounters with chief complaint of dizziness and CTA head and neck imaging at three EDs between 1/1/2014-12/31/2017. A decision rule was derived to exclude acute vascular pathology tested on a separate validation cohort; sensitivity analysis was performed using dizzy "stroke code" presentations. RESULTS: Testing, validation, and sensitivity analysis cohorts were composed of 1072, 357, and 81 cases with 41, 6, and 12 instances of acute vascular pathology respectively. The decision rule had the following features: no past medical history of stroke, arterial dissection, or transient ischemic attack (including unexplained aphasia, incoordination, or ataxia); no history of coronary artery disease, diabetes, migraines, current/long-term smoker, and current/long-term anti-coagulation or anti-platelet medication use. In the derivation phase, the rule had a sensitivity of 100% (95% CI: 0.91-1.00), specificity of 59% (95% CI: 0.56-0.62), and negative predictive value of 100% (95% CI: 0.99-1.00). In the validation phase, the rule had a sensitivity of 100% (95% CI: 0.61-1.00), specificity of 53% (95% CI: 0.48-0.58), and negative predictive value of 100% (95% CI: 0.98-1.00). The rule performed similarly on dizzy stroke codes and was more sensitive/predictive than all NIHSS cut-offs. CTAs for dizziness might be avoidable in 52% (95% CI: 0.47-0.57) of cases. CONCLUSIONS: A collection of clinical factors may be able to "exclude" acute vascular pathology in up to half of patients imaged by CTA for dizziness. These findings require further development and prospective validation, though could improve the evaluation of dizzy patients in the ED.

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.

Cost-Effectiveness and Long-Term Savings of the Bright Bodies Intervention for Childhood Obesity.

OBJECTIVES: To estimate the cost and cost-effectiveness of Bright Bodies, a high-intensity, family-based intervention that has been demonstrated to improve body mass index (BMI) among children with obesity in a randomized controlled trial. METHODS: We developed a microsimulation model to project 10-year BMI trajectories of 8 to 16-year-old children with obesity, using data from the National Longitudinal Surveys and Centers for Disease Control and Prevention growth charts, and we validated the model using data from the Bright Bodies trial and a follow-up study. We used the trial data to estimate the average reduction in BMI per person-year over 10 years and the incremental costs of Bright Bodies, compared with the traditional clinical weight management (control), from a health system's perspective in 2020 US dollars. Using results from studies of Medical Expenditure Panel Survey data, we projected the long-term obesity-related medical expenditure. RESULTS: In the primary analysis, assuming depreciating effects postintervention, Bright Bodies is expected to reduce a participant's BMI by 1.67 kg/m2 (95% uncertainty interval 1.43-1.94) per year over 10 years as compared with control. The incremental intervention cost of Bright Bodies was $360 ($292-$421) per person compared with the clinical control. Nevertheless, savings in obesity-related healthcare expenditure offset these costs and the expected cost-savings of Bright Bodies is $1126 ($689-$1693) per person over 10-years. The projected time to achieve cost-savings compared with clinical control was 3.58 (2.63-5.17) years. CONCLUSIONS: Although resource-intensive, our findings suggest that Bright Bodies is cost-saving compared to the clinical control by averting future obesity-related healthcare costs among children with obesity.

Lifetime quality-adjusted life years lost due to genital herpes acquired in the United States in 2018: a mathematical modeling study.

Background: Genital herpes (GH), caused by herpes simplex virus type 1 and type 2 (HSV-1, HSV-2), is a common sexually transmitted disease associated with adverse health outcomes. Symptoms associated with GH outbreaks can be reduced by antiviral medications, but the infection is incurable and lifelong. In this study, we estimate the long-term health impacts of GH in the United States using quality-adjusted life years (QALYs) lost. Methods: We used probability trees to model the natural history of GH secondary to infection with HSV-1 and HSV-2 among people aged 18-49 years. We modelled the following outcomes to quantify the major causes of health losses following infection: symptomatic herpes outbreaks, psychosocial impacts associated with diagnosis and recurrences, urinary retention caused by sacral radiculitis, aseptic meningitis, Mollaret's meningitis, and neonatal herpes. The model was parameterized based on published literature on the natural history of GH. We summarized losses of health by computing the lifetime number of QALYs lost per genital HSV-1 and HSV-2 infection, and we combined this information with incidence estimates to compute the total lifetime number of QALYs lost due to infections acquired in 2018 in the United States. Findings: We estimated 0.05 (95% uncertainty interval (UI) 0.02-0.08) lifetime QALYs lost per incident GH infection acquired in 2018, equivalent to losing 0.05 years or about 18 days of life for one person with perfect health. The average number of QALYs lost per GH infection due to genital HSV-1 and HSV-2 was 0.01 (95% UI 0.01-0.02) and 0.05 (95% UI 0.02-0.09), respectively. The burden of genital HSV-1 is higher among women, while the burden of HSV-2 is higher among men. QALYs lost per neonatal herpes infection was estimated to be 7.93 (95% UI 6.63-9.19). At the population level, the total estimated lifetime QALYs lost as a result of GH infections acquired in 2018 was 33,100 (95% UI 12,600-67,900) due to GH in adults and 3,140 (95% UI 2,260-4,140) due to neonatal herpes. Results were most sensitive to assumptions on the magnitude of the disutility associated with post-diagnosis psychosocial distress and symptomatic recurrences. Interpretation: GH is associated with substantial health losses in the United States. Results from this study can be used to compare the burden of GH to other diseases, and it provides inputs that may be used in studies on the health impact and cost-effectiveness of interventions that aim to reduce the burden of GH. Funding: The Center for Disease Control and Prevention.

The Estimated Lifetime Quality-Adjusted Life-Years Lost Due to Chlamydia, Gonorrhea, and Trichomoniasis in the United States in 2018.

BACKGROUND: Comprehensive evaluation of the quality-adjusted life-years (QALYs) lost attributable to chlamydia, gonorrhea, andtrichomoniasis in the United States is lacking. METHODS: We adapted a previous probability-tree model to estimate the average number of lifetime QALYs lost due to genital chlamydia, gonorrhea, and trichomoniasis, per incident infection and at the population level, by sex and age group. We conducted multivariate sensitivity analyses to address uncertainty around key parameter values. RESULTS: The estimated total discounted lifetime QALYs lost for men and women, respectively, due to infections acquired in 2018, were 1541 (95% uncertainty interval [UI], 186-6358) and 111 872 (95% UI, 29 777-267 404) for chlamydia, 989 (95% UI, 127-3720) and 12 112 (95% UI, 2 410-33 895) for gonorrhea, and 386 (95% UI, 30-1851) and 4576 (95% UI, 13-30 355) for trichomoniasis. Total QALYs lost were highest among women aged 15-24 years with chlamydia. QALYs lost estimates were highly sensitive to disutilities (health losses) of infections and sequelae, and to duration of infections and chronic sequelae for chlamydia and gonorrhea in women. CONCLUSIONS: The 3 sexually transmitted infections cause substantial health losses in the United States, particularly gonorrhea and chlamydia among women. The estimates of lifetime QALYs lost per infection help to prioritize prevention policies and inform cost-effectiveness analyses of sexually transmitted infection interventions.

Generating simple classification rules to predict local surges in COVID-19 hospitalizations.

Low rates of vaccination, emergence of novel variants of SARS-CoV-2, and increasing transmission relating to seasonal changes and relaxation of mitigation measures leave many US communities at risk for surges of COVID-19 that might strain hospital capacity, as in previous waves. The trajectories of COVID-19 hospitalizations differ across communities depending on their age distributions, vaccination coverage, cumulative incidence, and adoption of risk mitigating behaviors. Yet, existing predictive models of COVID-19 hospitalizations are almost exclusively focused on national- and state-level predictions. This leaves local policymakers in urgent need of tools that can provide early warnings about the possibility that COVID-19 hospitalizations may rise to levels that exceed local capacity. In this work, we develop a framework to generate simple classification rules to predict whether COVID-19 hospitalization will exceed the local hospitalization capacity within a 4- or 8-week period if no additional mitigating strategies are implemented during this time. This framework uses a simulation model of SARS-CoV-2 transmission and COVID-19 hospitalizations in the US to train classification decision trees that are robust to changes in the data-generating process and future uncertainties. These generated classification rules use real-time data related to hospital occupancy and new hospitalizations associated with COVID-19, and when available, genomic surveillance of SARS-CoV-2. We show that these classification rules present reasonable accuracy, sensitivity, and specificity (all ≥ 80%) in predicting local surges in hospitalizations under numerous simulated scenarios, which capture substantial uncertainties over the future trajectories of COVID-19. Our proposed classification rules are simple, visual, and straightforward to use in practice by local decision makers without the need to perform numerical computations.

Estimation of the Lifetime Quality-Adjusted Life Years (QALYs) Lost Due to Syphilis Acquired in the United States in 2018.

BACKGROUND: The purpose of this study was to estimate the health impact of syphilis in the United States in terms of the number of quality-adjusted life years (QALYs) lost attributable to infections in 2018. METHODS: We developed a Markov model that simulates the natural history and management of syphilis. The model was parameterized by sex and sexual orientation (women who have sex with men, men who have sex with women [MSW], and men who have sex with men [MSM]), and by age at primary infection. We developed a separate decision tree model to quantify health losses due to congenital syphilis. We estimated the average lifetime number of QALYs lost per infection, and the total expected lifetime number of QALYs lost due to syphilis acquired in 2018. RESULTS: We estimated the average number of discounted lifetime QALYs lost per infection as 0.09 (95% uncertainty interval [UI] .03-.19). The total expected number of QALYs lost due to syphilis acquired in 2018 was 13 349 (5071-31 360). Although per-case loss was the lowest among MSM (0.06), MSM accounted for 47.7% of the overall burden. For each case of congenital syphilis, we estimated 1.79 (1.43-2.16) and 0.06 (.01-.14) QALYs lost in the child and the mother, respectively. We projected 2332 (1871-28 250) and 79 (17-177) QALYs lost for children and mothers, respectively, due to congenital syphilis in 2018. CONCLUSIONS: Syphilis causes substantial health losses in adults and children. Quantifying these health losses in terms of QALYs can inform cost-effectiveness analyses and can facilitate comparisons of the burden of syphilis to that of other diseases.

Predicting resistance to fluoroquinolones among patients with rifampicin-resistant tuberculosis using machine learning methods.

Background: Limited access to drug-susceptibility tests (DSTs) and delays in receiving DST results are challenges for timely and appropriate treatment of multi-drug resistant tuberculosis (TB) in many low-resource settings. We investigated whether data collected as part of routine, national TB surveillance could be used to develop predictive models to identify additional resistance to fluoroquinolones (FLQs), a critical second-line class of anti-TB agents, at the time of diagnosis with rifampin-resistant TB. Methods and findings: We assessed three machine learning-based models (logistic regression, neural network, and random forest) using information from 540 patients with rifampicin-resistant TB, diagnosed using Xpert MTB/RIF and notified in the Republic of Moldova between January 2018 and December 2019. The models were trained to predict the resistance to FLQs based on demographic and TB clinical information of patients and the estimated district-level prevalence of resistance to FLQs. We compared these models based on the optimism-corrected area under the receiver operating characteristic curve (OC-AUC-ROC). The OC-AUC-ROC of all models were statistically greater than 0.5. The neural network model, which utilizes twelve features, performed best and had an estimated OC-AUC-ROC of 0.87 (0.83,0.91), which suggests reasonable discriminatory power. A limitation of our study is that our models are based only on data from the Republic of Moldova and since not externally validated, the generalizability of these models to other populations remains unknown. Conclusions: Models trained on data from phenotypic surveillance of drug-resistant TB can predict resistance to FLQs based on patient characteristics at the time of diagnosis with rifampin-resistant TB using Xpert MTB/RIF, and information about the local prevalence of resistance to FLQs. These models may be useful for informing the selection of antibiotics while awaiting results of DSTs.

Evaluating spatially adaptive guidelines for the treatment of gonorrhea to reduce the incidence of gonococcal infection and increase the effective lifespan of antibiotics.

In the absence of point-of-care gonorrhea diagnostics that report antibiotic susceptibility, gonorrhea treatment is empiric and determined by standardized guidelines. These guidelines are informed by estimates of resistance prevalence from national surveillance systems. We examined whether guidelines informed by local, rather than national, surveillance data could reduce the incidence of gonorrhea and increase the effective lifespan of antibiotics used in treatment guidelines. We used a transmission dynamic model of gonorrhea among men who have sex with men (MSM) in 16 U.S. metropolitan areas to determine whether spatially adaptive treatment guidelines based on local estimates of resistance prevalence can extend the effective lifespan of hypothetical antibiotics. The rate of gonorrhea cases in these metropolitan areas was 5,548 cases per 100,000 MSM in 2017. Under the current strategy of updating the treatment guideline when the prevalence of resistance exceeds 5%, we showed that spatially adaptive guidelines could reduce the annual rate of gonorrhea cases by 200 cases (95% uncertainty interval: 169, 232) per 100,000 MSM population while extending the use of a first-line antibiotic by 0.75 (0.55, 0.95) years. One potential strategy to reduce the incidence of gonorrhea while extending the effective lifespan of antibiotics is to inform treatment guidelines based on local, rather than national, resistance prevalence.