Clinical Practices for Measles-Mumps-Rubella Vaccination Among US Pediatric International Travelers.

Importance: The US population is experiencing a resurgence of measles, with more than 1000 cases during the first 6 months of 2019. Imported measles cases among returning international travelers are the source of most US measles outbreaks, and these importations can be reduced with pretravel measles-mumps-rubella (MMR) vaccination of pediatric travelers. Although it is estimated that children account for less than 10% of US international travelers, pediatric travelers account for 47% of all known measles importations. Objective: To examine clinical practice regarding MMR vaccination of pediatric international travelers and to identify reasons for nonvaccination of pediatric travelers identified as MMR eligible. Design, Setting, and Participants: This cross-sectional study of pediatric travelers (ages ≥6 months and \u3c18 \u3eyears) attending pretravel consultation at 29 sites associated with Global TravEpiNet (GTEN), a Centers for Disease Control and Prevention-supported consortium of clinical sites that provide pretravel consultations, was performed from January 1, 2009, through December 31, 2018. Main Outcomes and Measures: Measles-mumps-rubella vaccination among MMR vaccination-eligible pediatric travelers. Results: Of 14 602 pretravel consultations for pediatric international travelers, 2864 travelers (19.6%; 1475 [51.5%] males; 1389 [48.5%] females) were eligible to receive pretravel MMR vaccination at the time of the consultation: 365 of 398 infants aged 6 to 12 months (91.7%), 2161 of 3623 preschool-aged travelers aged 1 to 6 years (59.6%), and 338 of 10 581 school-aged travelers aged 6 to 18 years (3.2%). Of 2864 total MMR vaccination-eligible travelers, 1182 (41.3%) received the MMR vaccine and 1682 (58.7%) did not. The MMR vaccination-eligible travelers who did not receive vaccine included 161 of 365 infants (44.1%), 1222 of 2161 preschool-aged travelers (56.5%), and 299 of 338 school-aged travelers (88.5%). We observed a diversity of clinical practice at different GTEN sites. In multivariable analysis, MMR vaccination-eligible pediatric travelers were less likely to be vaccinated at the pretravel consultation if they were school-aged (model 1: odds ratio [OR], 0.32 [95% CI, 0.24-0.42; P \u3c .001]; model 2: OR, 0.26 [95% CI, 0.14-0.47; P \u3c .001]) or evaluated at specific GTEN sites (South: OR, 0.06 [95% CI, 0.01-0.52; P \u3c .001]; West: OR, 0.10 [95% CI, 0.02-0.47; P \u3c .001]). The most common reasons for nonvaccination were clinician decision not to administer MMR vaccine (621 of 1682 travelers [36.9%]) and guardian refusal (612 [36.4%]). Conclusions and Relevance: Although most infant and preschool-aged travelers evaluated at GTEN sites were eligible for pretravel MMR vaccination, only 41.3% were vaccinated during pretravel consultation, mostly because of clinician decision or guardian refusal. Strategies may be needed to improve MMR vaccination among pediatric travelers and to reduce measles importations and outbreaks in the United States

HIV, Tuberculosis, and Non-Communicable Diseases: what is known about the costs, effects, and cost-effectiveness of integrated care?

CAPRISA, 2014.Abstract available in pdf

The Clinical and Economic Impact of Point-of-Care CD4 Testing in Mozambique and Other Resource-Limited Settings: A Cost-Effectiveness Analysis

Background: Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique. Methods and Findings: We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4). Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%), probability of correctly detecting antiretroviral therapy (ART) eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90%) or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%), and test cost (LAB-CD4, US$10; POC-CD4, US$24). In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570) to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9$2,440 (95% CI, US$2,440–US$2,450) and increase with POC-CD4 to 10.3 y (95% CI, 10.3–10.3 y) and US$2,800 (95$2,790–US$2,800); the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS) (95% CI, US$480–US$520/YLS). POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published values. In other resource-limited settings with fewer opportunities to access care, POC-CD4 has a greater impact on clinical outcomes and remains cost-effective compared to LAB-CD4. Limitations of the analysis include the uncertainty around input parameters, which is examined in sensitivity analyses. The potential added benefits due to decreased transmission are excluded; their inclusion would likely further increase the value of POC-CD4 compared to LAB-CD4. Conclusions: POC-CD4 at the time of HIV diagnosis could improve survival and be cost-effective compared to LAB-CD4 in Mozambique, if it improves linkage to care. POC-CD4 could have the greatest impact on mortality in settings where resources for HIV testing and linkage are most limited. Please see later in the article for the Editors' Summar

Clinical Outcomes, Costs, and Cost-effectiveness of Strategies for Adults Experiencing Sheltered Homelessness During the COVID-19 Pandemic

Importance: Approximately 356 000 people stay in homeless shelters nightly in the United States. They have high risk of contracting coronavirus disease 2019 (COVID-19). / Objective: To assess the estimated clinical outcomes, costs, and cost-effectiveness associated with strategies for COVID-19 management among adults experiencing sheltered homelessness. / Design, Setting, and Participants: This decision analytic model used a simulated cohort of 2258 adults residing in homeless shelters in Boston, Massachusetts. Cohort characteristics and costs were adapted from Boston Health Care for the Homeless Program. Disease progression, transmission, and outcomes data were taken from published literature and national databases. Surging, growing, and slowing epidemics (effective reproduction numbers [Re], 2.6, 1.3, and 0.9, respectively) were examined. Costs were from a health care sector perspective, and the time horizon was 4 months, from April to August 2020. / Exposures: Daily symptom screening with polymerase chain reaction (PCR) testing of individuals with positive symptom screening results, universal PCR testing every 2 weeks, hospital-based COVID-19 care, alternative care sites (ACSs) for mild or moderate COVID-19, and temporary housing were each compared with no intervention. / Main Outcomes and Measures: Cumulative infections and hospital-days, costs to the health care sector (US dollars), and cost-effectiveness, as incremental cost per case of COVID-19 prevented. / Results: The simulated population of 2258 sheltered homeless adults had a mean (SD) age of 42.6 (9.04) years. Compared with no intervention, daily symptom screening with ACSs for pending tests or confirmed COVID-19 and mild or moderate disease was associated with 37% fewer infections (1954 vs 1239) and 46% lower costs ($6.10 million vs$3.27 million) at an Re of 2.6, 75% fewer infections (538 vs 137) and 72% lower costs ($1.46 million vs$0.41 million) at an Re of 1.3, and 51% fewer infections (174 vs 85) and 51% lower costs ($0.54 million vs$0.26 million) at an Re of 0.9. Adding PCR testing every 2 weeks was associated with a further decrease in infections; incremental cost per case prevented was $1000 at an Re of 2.6,$27 000 at an Re of 1.3, and $71 000 at an Re of 0.9. Temporary housing with PCR every 2 weeks was most effective but substantially more expensive than other options. Compared with no intervention, temporary housing with PCR every 2 weeks was associated with 81$39.12 million) at an Re of 2.6, 82% fewer infections (95) and 2568% higher costs ($38.97 million) at an Re of 1.3, and 59$38.94 million) at an Re of 0.9. Results were sensitive to cost and sensitivity of PCR and ACS efficacy in preventing transmission. / Conclusions and Relevance: In this modeling study of simulated adults living in homeless shelters, daily symptom screening and ACSs were associated with fewer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decreased costs compared with no intervention. In a modeled surging epidemic, adding universal PCR testing every 2 weeks was associated with further decrease in SARS-CoV-2 infections at modest incremental cost and should be considered during future surges

Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa: a microsimulation modelling study

Background: Health-care resource constraints in low-income and middle-income countries necessitate the identification of cost-effective public health interventions to address COVID-19. We aimed to develop a dynamic COVID-19 microsimulation model to assess clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal province, South Africa. Methods: We compared different combinations of five public health interventions: health-care testing alone, where diagnostic testing is done only for individuals presenting to health-care centres; contact tracing in households of cases; isolation centres, for cases not requiring hospital admission; mass symptom screening and molecular testing for symptomatic individuals by community health-care workers; and quarantine centres, for household contacts who test negative. We calibrated infection transmission rates to match effective reproduction number (Re) estimates reported in South Africa. We assessed two main epidemic scenarios for a period of 360 days, with an Re of 1·5 and 1·2. Strategies with incremental cost-effectiveness ratio (ICER) of less than US$3250 per year of life saved were considered cost-effective. We also did sensitivity analyses by varying key parameters (Re values, molecular testing sensitivity, and efficacies and costs of interventions) to determine the effect on clinical and cost projections. Findings: When Re was 1·5, health-care testing alone resulted in the highest number of COVID-19 deaths during the 360-day period. Compared with health-care testing alone, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres reduced mortality by 94$340 per year of life saved). In settings where quarantine centres were not feasible, a combination of health-care testing, contact tracing, use of isolation centres, and mass symptom screening was cost-effective compared with health-care testing alone (ICER $590 per year of life saved). When Re was 1·2, health-care testing, contact tracing, use of isolation centres, and use of quarantine centres was the least costly strategy, and no other strategies were cost-effective. In sensitivity analyses, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres was generally cost-effective, with the exception of scenarios in which Re was 2·6 and when efficacies of isolation centres and quarantine centres for transmission reduction were reduced. Interpretation: In South Africa, strategies involving household contact tracing, isolation, mass symptom screening, and quarantining household contacts who test negative would substantially reduce COVID-19 mortality and would be cost-effective. The optimal combination of interventions depends on epidemic growth characteristics and practical implementation considerations

Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa

Background Healthcare resource constraints in low and middle-income countries necessitate selection of cost-effective public health interventions to address COVID-19. Methods We developed a dynamic COVID-19 microsimulation model to evaluate clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal, South Africa. Interventions assessed were Healthcare Testing (HT), where diagnostic testing is performed only for those presenting to healthcare centres; Contact Tracing (CT) in households of cases; Isolation Centres (IC), for cases not requiring hospitalisation; community health worker-led Mass Symptom Screening and diagnostic testing for symptomatic individuals (MS); and Quarantine Centres (QC), for contacts who test negative. Given uncertainties about epidemic dynamics in South Africa, we evaluated two main epidemic scenarios over 360 days, with effective reproduction numbers (R e ) of 1.5 and 1.2. We compared HT, HT+CT, HT+CT+IC, HT+CT+IC+MS, HT+CT+IC+QC, and HT+CT+IC+MS+QC, considering strategies with incremental cost-effectiveness ratio (ICER) <US$1,290/year-of-life saved (YLS) to be cost-effective. Findings With R e 1.5, HT resulted in the most COVID-19 deaths and lowest costs over 360 days. Compared with HT, HT+CT+IC+MS reduced mortality by 76$350/YLS). HT+CT+IC+MS+QC provided the greatest reduction in mortality, but increased costs by 95% compared with HT+CT+IC+MS and was not cost-effective (ICER $8,000/YLS). With R e 1.2, HT+CT+IC+MS was the least costly strategy, and HT+CT+IC+MS+QC was not cost-effective (ICER$294,320/YLS). Interpretation In South Africa, a strategy of household contact tracing, isolation, and mass symptom screening would substantially reduce COVID-19 mortality and be cost-effective. Adding quarantine centres for COVID-19 contacts is not cost-effective

The clinical and economic impact of point-of-care CD4 testing in Mozambique and other resource-limited settings: a cost-effectiveness analysis

Emily Hyle and colleagues conduct a cost-effectiveness analysis to estimate the clinical and economic impact of point-of-care CD4 testing compared to laboratory-based tests in Mozambique. Please see later in the article for the Editors' Summar

Transparent nanocrystalline yttria-stabilized-zirconia calvarium prosthesis

UnlabelledLaser-based diagnostics and therapeutics show promise for many neurological disorders. However, the poor transparency of cranial bone (calvaria) limits the spatial resolution and interaction depth that can be achieved, thus constraining opportunity in this regard. Herein, we report preliminary results from efforts seeking to address this limitation through use of novel transparent cranial implants made from nanocrystalline yttria-stabilized zirconia (nc-YSZ). Using optical coherence tomography (OCT) imaging of underlying brain in an acute murine model, we show that signal strength is improved when imaging through nc-YSZ implants relative to native cranium. As such, this provides initial evidence supporting the feasibility of nc-YSZ as a transparent cranial implant material. Furthermore, it represents a crucial first step towards realization of an innovative new concept we are developing, which seeks to eventually provide a clinically-viable means for optically accessing the brain, on-demand, over large areas, and on a chronically-recurring basis, without need for repeated craniectomies.From the clinical editorIn this study, transparent nanocrystalline yttria-stabilized-zirconia is used as an experimental "cranium prosthesis" material, enabling the replacement of segments of cranial bone with a material that allows for optical access to the brain on a recurrent basis using optical imaging methods such as OCT

Cost effectiveness of potential ART adherence monitoring interventions in sub-saharan Africa

Background Interventions based around objective measurement of adherence to antiretroviral drugs for HIV have potential to improve adherence and to enable differentiation of care such that clinical visits are reduced in those with high adherence. It would be useful to understand the approximate upper limit of cost that could be considered for such interventions of a given effectiveness in order to be cost effective. Such information can guide whether to implement an intervention in the light of a trial showing a certain effectiveness and cost. Methods An individual-based model, calibrated to Zimbabwe, which incorporates effects of adherence and resistance to antiretroviral therapy, was used to model the potential impact of adherence monitoring-based interventions on viral suppression, death rates, disability adjusted life years and costs. Potential component effects of the intervention were: enhanced average adherence when on ART, reduced risk of ART discontinuation, and reduced risk of resistance acquisition. We considered a situation in which viral load monitoring is not available and one in which it is. In the former case, it was assumed that care would be differentiated based on the adherence level, with fewer clinic visits in those demonstrated to have high adherence. In the latter case, care was assumed to be primarily differentiated according to viral load level. The maximum intervention cost required to be cost effective was calculated based on a cost effectiveness threshold of $500 per DALY averted. Findings In the absence of viral load monitoring, an adherence monitoring-based intervention which results in a durable 6$50 per person-year on ART, mainly driven by the cost savings of differentiation of care. In the presence of viral load monitoring availability, an intervention with a similar effect on viral load suppression was cost-effective when costing $23-$32 per year, depending on whether the adherence intervention is used to reduce the level of need for viral load measurement. Conclusion The cost thresholds identified suggest that there is clear scope for adherence monitoringbased interventions to provide net population health gain, with potential cost-effective use in situations where viral load monitoring is or is not available. Our results guide the implementation of future adherence monitoring interventions found in randomized trials to have health benefit