The Impact of a Place-Tailored Digital Health App Promoting Exercise Classes on African American Women's Physical Activity and Obesity: Simulation Study.

BACKGROUND: The increasing prevalence of smartphone apps to help people find different services raises the question of whether apps to help people find physical activity (PA) locations would help better prevent and control having overweight or obesity. OBJECTIVE: The aim of this paper is to determine and quantify the potential impact of a digital health intervention for African American women prior to allocating financial resources toward implementation. METHODS: We developed our Virtual Population Obesity Prevention, agent-based model of Washington, DC, to simulate the impact of a place-tailored digital health app that provides information about free recreation center classes on PA, BMI, and overweight and obesity prevalence among African American women. RESULTS: When the app is introduced at the beginning of the simulation, with app engagement at 25% (eg, 25% [41,839/167,356] of women aware of the app; 25% [10,460/41,839] of those aware downloading the app; and 25% [2615/10,460] of those who download it receiving regular push notifications), and a 25% (25/100) baseline probability to exercise (eg, without the app), there are no statistically significant increases in PA levels or decreases in BMI or obesity prevalence over 5 years across the population. When 50% (83,678/167,356) of women are aware of the app; 58.23% (48,725/83,678) of those who are aware download it; and 55% (26,799/48,725) of those who download it receive regular push notifications, in line with existing studies on app usage, introducing the app on average increases PA and decreases weight or obesity prevalence, though the changes are not statistically significant. When app engagement increased to 75% (125,517/167,356) of women who were aware, 75% (94,138/125,517) of those who were aware downloading it, and 75% (70,603/94,138) of those who downloaded it opting into the app's push notifications, there were statistically significant changes in PA participation, minutes of PA and obesity prevalence. CONCLUSIONS: Our study shows that a digital health app that helps identify recreation center classes does not result in substantive population-wide health effects at lower levels of app engagement. For the app to result in statistically significant increases in PA and reductions in obesity prevalence over 5 years, there needs to be at least 75% (125,517/167,356) of women aware of the app, 75% (94,138/125,517) of those aware of the app download it, and 75% (70,603/94,138) of those who download it opt into push notifications. Nevertheless, the app cannot fully overcome lack of access to recreation centers; therefore, public health administrators as well as parks and recreation agencies might consider incorporating this type of technology into multilevel interventions that also target the built environment and other social determinants of health.

The Potential Clinical and Economic Value of a Human Papillomavirus Primary Screening Test That Additionally Identifies Genotypes 31, 45, 51, and 52 Individually.

BACKGROUND: Although current human papillomavirus (HPV) genotype screening tests identify genotypes 16 and 18 and do not specifically identify other high-risk types, a new extended genotyping test identifies additional individual (31, 45, 51, and 52) and groups (33/58, 35/39/68, and 56/59/66) of high-risk genotypes. METHODS: We developed a Markov model of the HPV disease course and evaluated the clinical and economic value of HPV primary screening with Onclarity (BD Diagnostics, Franklin Lakes, NJ) capable of extended genotyping in a cohort of women 30 years or older. Women with certain genotypes were later rescreened instead of undergoing immediate colposcopy and varied which genotypes were rescreened, disease progression rate, and test cost. RESULTS: Assuming 100% compliance with screening, HPV primary screening using current tests resulted in 25,194 invasive procedures and 48 invasive cervical cancer (ICC) cases per 100,000 women. Screening with extended genotyping (100% compliance) and later rescreening women with certain genotypes averted 903 to 3163 invasive procedures and resulted in 0 to 3 more ICC cases compared with current HPV primary screening tests. Extended genotyping was cost-effective ($2298-$7236/quality-adjusted life year) when costing $75 and cost saving (median, $0.3-$1.0 million) when costing $43. When the probabilities of disease progression increased (2-4 times), extended genotyping was not cost-effective because it resulted in more ICC cases and accrued fewer quality-adjusted life years. CONCLUSIONS: Our study identified the conditions under which extended genotyping was cost-effective and even cost saving compared with current tests. A key driver of cost-effectiveness is the risk of disease progression, which emphasizes the need to better understand such risks in different populations.

Can following formula-feeding recommendations still result in infants who are overweight or have obesity?

BACKGROUND: Studies show that by 3 months, over half of US infants receive formula, and guidelines play a key role in formula feeding. The question then is, what might happen if caregivers follow guidelines and, more specifically, are there situations where following guidelines can result in infants who are overweight/have obesity? METHODS: We used our "Virtual Infant" agent-based model representing infant-caregiver pairs that allowed caregivers to feed infants each day according to guidelines put forth by Johns Hopkins Medicine (JHM), Children's Hospital of Philadelphia (CHOP), Children's Hospital of the King's Daughters (CHKD), and Women, Infants, and Children (WIC). The model simulated the resulting development of the infants from birth to 6 months. The two sets of guidelines vary in their recommendations, and do not provide studies that support amounts at given ages. RESULTS: Simulations identified several scenarios where caregivers followed JHM/CHOP/CHKD and WIC guidelines, but infants still became overweight/with obesity by 6 months. For JHM/CHOP/CHKD guidelines, this occurred even when caregivers adjusted feeding based on infant's weight. For WIC guidelines, when caregivers adjusted formula amounts, infants maintained healthy weight. CONCLUSIONS: WIC guidelines may be a good starting point for caregivers who adjust as their infant grows, but the minimum amounts for JHM/CHKD/CHOP recommendations may be too high. IMPACT: Our virtual infant simulation study answers the question: can caregivers follow current formula-feeding guidelines and still end up with an infant who is overweight or has obesity? Our study identified several situations in which unhealthy weight gain and/or weight loss could result from following established formula-feeding recommendations. Our study also suggests that the minimum recommended amount of daily formula feeding should be lower for JHM/CHOP/CHKD guidelines to give caregivers more flexibility in adjusting daily feeding levels in response to infant weight. WIC guidelines may be a good starting point for caregivers who adjust as their infant grows. In order to understand how to adjust guidelines, we can use computational simulation models, which serve as "virtual laboratories" to help overcome the logistical and ethical issues of clinical trials.

What Is the Value of Different Zika Vaccination Strategies to Prevent and Mitigate Zika Outbreaks?

BACKGROUND: While the 2015-2016 Zika epidemics prompted accelerated vaccine development, decision makers need to know the potential economic value of vaccination strategies. METHODS: We developed models of Honduras, Brazil, and Puerto Rico, simulated targeting different populations for Zika vaccination (women of childbearing age, school-aged children, young adults, and everyone) and then introduced various Zika outbreaks. Sensitivity analyses varied vaccine characteristics. RESULTS: With a 2% attack rate ($5 vaccination), compared to no vaccination, vaccinating women of childbearing age cost $314-$1664 per case averted ($790-$4221/disability-adjusted life-year [DALY] averted) in Honduras, and saved $847-$1644/case averted in Brazil, and $3648-$4177/case averted in Puerto Rico, varying with vaccination coverage and efficacy (societal perspective). Vaccinating school-aged children cost $718-$1849/case averted (≤$5002/DALY averted) in Honduras, saved $819-$1609/case averted in Brazil, and saved $3823-$4360/case averted in Puerto Rico. Vaccinating young adults cost $310-$1666/case averted ($731-$4017/DALY averted) in Honduras, saved $953-$1703/case averted in Brazil, and saved $3857-$4372/case averted in Puerto Rico. Vaccinating everyone averted more cases but cost more, decreasing cost savings per case averted. Vaccination resulted in more cost savings and better outcomes at higher attack rates. CONCLUSIONS: When considering transmission, while vaccinating everyone naturally averted the most cases, specifically targeting women of childbearing age or young adults was the most cost-effective.

A Decarboxylative Cross-Coupling Platform To Access 2-Heteroaryl Azetidines: Building Blocks with Application in Medicinal Chemistry.

Photoredox-transition metal dual catalysis provides a unique platform for constructing sp3-rich chemical matter. Here, we report a nickel-catalyzed cross-coupling of commercially available or easily prepared redox-active NHP azetidine-2-carboxylates with commercially available heteroaryl iodides to yield 2-heteroaryl azetidines. This "off-the-shelf" approach yielded products amenable to diversification giving access to novel saturated heterocyclic scaffolds useful for medicinal chemistry programs. An alternative mechanism for Hantzsch ester within nickel-catalyzed cross-coupling of heteroaryl halides and α-amino radicals is also presented.

Estimated number of N95 respirators needed for healthcare workers in acute-care hospitals during the coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: Due to shortages of N95 respirators during the coronavirus disease 2019 (COVID-19) pandemic, it is necessary to estimate the number of N95s required for healthcare workers (HCWs) to inform manufacturing targets and resource allocation. METHODS: We developed a model to determine the number of N95 respirators needed for HCWs both in a single acute-care hospital and the United States. RESULTS: For an acute-care hospital with 400 all-cause monthly admissions, the number of N95 respirators needed to manage COVID-19 patients admitted during a month ranges from 113 (95% interpercentile range [IPR], 50-229) if 0.5% of admissions are COVID-19 patients to 22,101 (95% IPR, 5,904-25,881) if 100% of admissions are COVID-19 patients (assuming single use per respirator, and 10 encounters between HCWs and each COVID-19 patient per day). The number of N95s needed decreases to a range of 22 (95% IPR, 10-43) to 4,445 (95% IPR, 1,975-8,684) if each N95 is used for 5 patient encounters. Varying monthly all-cause admissions to 2,000 requires 6,645-13,404 respirators with a 60% COVID-19 admission prevalence, 10 HCW-patient encounters, and reusing N95s 5-10 times. Nationally, the number of N95 respirators needed over the course of the pandemic ranges from 86 million (95% IPR, 37.1-200.6 million) to 1.6 billion (95% IPR, 0.7-3.6 billion) as 5%-90% of the population is exposed (single-use). This number ranges from 17.4 million (95% IPR, 7.3-41 million) to 312.3 million (95% IPR, 131.5-737.3 million) using each respirator for 5 encounters. CONCLUSIONS: We quantified the number of N95 respirators needed for a given acute-care hospital and nationally during the COVID-19 pandemic under varying conditions.

Should countries switch to using five- or ten-dose rotavirus vaccines now that they are available?

INTRODUCTION: Single-dose rotavirus vaccines, which are used by a majority of countries, are some of the largest-sized vaccines in immunization programs, and have been shown to constrain supply chains and cause bottlenecks. Efforts have been made to reduce the size of the single-dose vaccines; however, with two-dose, five-dose and ten-dose options available, the question then is whether using multi-dose instead of single-dose rotavirus vaccines will improve vaccine availability. METHODS: We used HERMES-generated simulation models of the vaccine supply chains of the Republic of Benin, Mozambique, and Bihar, a state in India, to evaluate the operational and economic impact of implementing each of the nine different rotavirus vaccine presentations. RESULTS: Among single-dose rotavirus vaccines, using Rotarix RV1 MMP (multi-monodose presentation) led to the highest rotavirus vaccine availability (49-80%) and total vaccine availability (56-79%), and decreased total costs per dose administered ($0.02-$0.10) compared to using any other single-dose rotavirus vaccine. Using two-dose ROTASIIL decreased rotavirus vaccine availability by 3-6% across each supply chain compared to Rotarix RV1 MMP, the smallest single-dose vaccine. Using a five-dose rotavirus vaccine improved rotavirus vaccine availability (52-92%) and total vaccine availability (60-85%) compared to single-dose and two-dose vaccines. Further, using the ten-dose vaccine led to the highest rotavirus vaccine availability compared to all other rotavirus vaccines in both Benin and Bihar. CONCLUSION: Our results show that countries that implement five-dose or ten-dose rotavirus vaccines consistently reduce cold chain constraints and achieve higher rotavirus and total vaccine availability compared to using either single-dose or two-dose rotavirus vaccines.

The Benefits of Vaccinating With the First Available COVID-19 Coronavirus Vaccine.

INTRODUCTION: During a pandemic, there are many situations in which the first available vaccines may not have as high effectiveness as vaccines that are still under development or vaccines that are not yet ready for distribution, raising the question of whether it is better to go with what is available now or wait. METHODS: In 2020, the team developed a computational model that represents the U.S. population, COVID-19 coronavirus spread, and vaccines with different possible efficacies (to prevent infection or to reduce severe disease) and vaccination timings to estimate the clinical and economic value of vaccination. RESULTS: Except for a limited number of situations, mainly early on in a pandemic and for a vaccine that prevents infection, when an initial vaccine is available, waiting for a vaccine with a higher efficacy results in additional hospitalizations and costs over the course of the pandemic. For example, if a vaccine with a 50% efficacy in preventing infection becomes available when 10% of the population has already been infected, waiting until 40% of the population are infected for a vaccine with 80% efficacy in preventing infection results in 15.6 million additional cases and 1.5 million additional hospitalizations, costing $20.6 billion more in direct medical costs and $12.4 billion more in productivity losses. CONCLUSIONS: This study shows that there are relatively few situations in which it is worth foregoing the first COVID-19 vaccine available in favor of a vaccine that becomes available later on in the pandemic even if the latter vaccine has a substantially higher efficacy.

Using Simulation Modeling to Guide the Design of the Girl Scouts Fierce & Fit Program.

OBJECTIVE: The study aim was to help the Girl Scouts of Central Maryland evaluate, quantify, and potentially modify the Girl Scouts Fierce & Fit program. METHODS: From 2018 to 2019, our Public Health Informatics, Computational, and Operations Research team developed a computational simulation model representing the 250 adolescent girls participating in the Fierce & Fit program and how their diets and physical activity affected their BMI and subsequent outcomes, including costs. RESULTS: Changing the Fierce & Fit program from a 6-week program meeting twice a week, with 5 minutes of physical activity each session, to a 12-week program meeting twice a week with 30 minutes of physical activity saved an additional $84,828 ($80,130-$89,526) in lifetime direct medical costs, $81,365 ($76,528-$86,184) in lifetime productivity losses, and 7.85 (7.38-8.31) quality-adjusted life-years. The cost-benefit of implementing this program was $95,943. Based on these results, the Girl Scouts of Central Maryland then implemented these changes in the program. CONCLUSIONS: This is an example of using computational modeling to help evaluate and revise the design of a program aimed at increasing physical activity among girls.

Economic value of a therapeutic Chagas vaccine for indeterminate and Chagasic cardiomyopathy patients.

BACKGROUND: Therapeutic vaccines to prevent Chagas disease progression to cardiomyopathy are under development because the only available medications (benznidazole and nifurtimox) are limited by their efficacy, long treatment course, and side effects. Better understanding the potential clinical and economic value of such vaccines can help guide development and implementation. METHODS: We developed a computational Chagas Markov model to evaluate the clinical and economic value of a therapeutic vaccine given in conjunction with benznidazole in indeterminate and chronic Chagas patients. Scenarios explored the vaccine's impact on reducing drug treatment dosage, duration, and adverse events, and risk of disease progression. RESULTS: When administering standard-of-care benznidazole to 1000 indeterminate patients, 148 discontinued treatment and 219 progressed to chronic disease, resulting in 119 Chagas-related deaths and 2293 DALYs, costing $18.9 million in lifetime societal costs. Compared to benznidazole-only, therapeutic vaccination administered with benznidazole (25-75% reduction in standard dose and duration), resulted in 37-111 more patients (of 1000) completing treatment, preventing 11-219 patients from progressing, 6-120 deaths, and 108-2229 DALYs (5-100% progression risk reduction), saving ≤$16,171 per patient. When vaccinating determinate Kuschnir class 1 Chagas patients, 10-197 fewer patients further progressed compared to benznidazole-only, averting 11-228 deaths and 144-3037 DALYs (5-100% progression risk reduction), saving ≤$34,059 per person. When vaccinating Kuschnir class 2 patients, 13-279 fewer progressed (279 with benznidazole-only), averting 13-692 deaths and 283-10,785 DALYs (5-100% progression risk reduction), saving ≤$89,759. Therapeutic vaccination was dominant (saved costs and provided health benefits) with ≥ 5% progression risk reduction, except when only reducing drug treatment regimen and adverse events, but remained cost-effective when costing <$200. CONCLUSIONS: Our study helps outline the thresholds at which a therapeutic Chagas vaccine may be cost-effective (e.g., <5% reduction in preventing cardiac progression, 25% reduction in benznidazole treatment doses and duration) and cost-saving (e.g., ≥5% and 25%, respectively).