Cost-effectiveness of pediatric norovirus vaccination in daycare settings

ObjectiveNoroviruses 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.MethodsWe 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.ResultsA 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.ConclusionDue 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.     

Estimating the number of averted illnesses and deaths as a result of vaccination against an influenza pandemic in nine low- and middle-income countries

BackgroundDuring the 2009 influenza A(H1N1)pdm09 pandemic, 77 countries received donated monovalent A(H1N1)pdm09 vaccine through the WHO Pandemic Influenza A(H1N1) Vaccine Deployment Initiative. However, 47% did not receive their first shipment until after the first wave of virus circulation, and 8% did not receive their first shipment until after the WHO declared the end of the pandemic. Arguably, these shipments were too late into the pandemic to have a substantial effect on virus transmission or disease burden during the first waves of the pandemic.ObjectivesIn order to evaluate the potential benefits of earlier vaccine availability, we estimated the number of illnesses and deaths that could be averted during a 2009-like influenza pandemic under five different vaccine-availability timing scenarios.MethodsWe adapted a model originally developed to estimate annual influenza morbidity and mortality burden averted through US seasonal vaccination and ran it for five vaccine availability timing scenarios in nine low- and middle-income countries that received donated vaccine.ResultsAmong nine study countries, we estimated that the number of averted cases was 61–216,197 for actual vaccine receipt, increasing to 2,914–283,916 had vaccine been available simultaneously with the United States.ConclusionsEarlier delivery of vaccines can reduce influenza case counts during a simulated 2009-like pandemic in some low- and middle-income countries. For others, increasing the number of cases and deaths prevented through vaccination may be dependent on factors other than timely initiation of vaccine administration, such as distribution and administration capacity.     

Cost-effectiveness of seasonal influenza vaccination in pregnant women,healthcare workers and adults >= 60 years of age in Lao People’s Democratic Republic

BackgroundPregnant women, healthcare workers (HW), and adults >= 60 years have shown an increased vulnerability to seasonal influenza virus infections and/or complications. In 2012, the Lao People's Democratic Republic (Lao PDR) initiated a national influenza vaccination program for these target groups. A cost-effectiveness evaluation of this program was undertaken to inform program sustainability.MethodsWe designed a decision-analytical model and collected influenza-related medical resource utilization and cost data, including indirect costs. Model inputs were obtained from medical record abstraction, interviews of patients and staff at hospitals in the national influenza sentinel surveillance system and/or from literature reviews. We compared the annual disease and economic impact of influenza illnesses in each of the target groups in Lao PDR under scenarios of no vaccination and vaccination, and then estimated the cost-effectiveness of the vaccination program. We performed sensitivity analyses to identify influential variables.ResultsOverall, the vaccination of pregnant women, HWs, and adults >= 60 years could annually save 11,474 doctor visits, 1,961 days of hospitalizations, 43,027 days of work, and 1,416 life-years due to laboratory-confirmed influenza illness. After comparing the total vaccination program costs of 23.4 billion Kip, to the 18.4 billion Kip saved through vaccination, we estimated the vaccination program to incur a net cost of five billion Kip (599,391 USD) annually. The incremental cost per life-year saved (ICER) was 44 million Kip (5,295 USD) and 6.9 million Kip (825 USD) for pregnant women and adults >= 60 years, respectively. However, vaccinating HWs provided societal cost-savings, returning 2.88 Kip for every single Kip invested. Influenza vaccine effectiveness, attack rate and illness duration were the most influential variables to the model.ConclusionProviding influenza vaccination to HWs in Lao PDR is cost-saving while vaccinating pregnant women and adults >= 60 is cost-effective and highly cost-effective, respectively, per WHO standards.     

Safety of measles and pertussis-containing vaccines in children with autism spectrum disorders

ObjectivesTo determine whether children aged 4–7 years with a diagnosis of autism spectrum disorders (ASD) were at increased risk of fever, febrile seizures, or emergency department (ED) visits following measles- or pertussis-containing vaccines compared with children without ASD.MethodsThe study included children born between 1995–2012, aged 4–7 years at vaccination, and members of six healthcare delivery systems within Vaccine Safety Datalink. We conducted self-controlled risk interval analyses comparing rates of outcomes in risk and control intervals within each group defined by ASD status, and then compared outcome rates between children with and without ASD, in risk and control intervals, by estimating difference-in-differences using logistic regressions.ResultsThe study included 14,947 children with ASD and 1,650,041 children without ASD. After measles- or pertussis-containing vaccination, there were no differences in association between children with and without ASD for fever (ratio of rate ratio for measles-containing vaccine = 1.07, 95% CI 0.58–1.96; for pertussis-containing vaccine = 1.16, 95% CI 0.63–2.15) or ED visits (ratio of rate ratio for measles-containing vaccine = 1.11, 95% CI 0.80–1.54; for pertussis-containing vaccine = 0.87, 95% CI 0.59–1.28). Febrile seizures were rare. Pertussis-containing vaccines were associated with small increased risk of febrile seizures in children without ASD.ConclusionChildren with ASD were not at increased risk for fever or ED visits compared with children without ASD following measles- or pertussis-containing vaccines. These results may provide further reassurance that these vaccines are safe for all children, including those with ASD.     

Recombinant zoster vaccine (RZV) second-dose series completion in adults aged 50–64 years in the United States

In 2018, CDC recommended a highly efficacious adjuvanted recombinant zoster vaccine (RZV) as a 2-dose series for prevention of herpes zoster (HZ) for immunocompetent persons age ≥ 50 years, with the 2nd dose recommended 2–6 months after the 1st dose. We estimated second-dose RZV series completion in the U.S. among 50–64-year-olds using two administrative databases. Second-dose RZV series completion was ～70% within 6-months and 80% within 12-months of first dose. Among those who received only 1 RZV dose with at least 12 months of follow-up time, 96% had a missed opportunity for a second-dose vaccination, defined as a provider or pharmacy visit, among whom 36% had a visit for influenza or pneumococcal vaccination within 2–12 months of their first-dose of RZV. We found that RZV series completion rates in 50–64-year-olds was high. Availability of RZV at pharmacies has potentially helped increase series completion, but missed opportunities remain.     

miR-146a-5p regulates autophagy and NLRP3 inflammasome activation in epithelial barrier damage in the in vitro cell model of ulcerative colitis through the RNF8/Notch1/mTORC1 pathway

Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon that can be influenced by microRNAs (miRNAs). This study aims to investigate the impact of miR-146a-5p on lipopolysaccharide (LPS)-induced Caco-2/HT-29 cell autophagy and NLRP3 inflammasome activation and the underlying mechanism, with the aim of identifying potential therapeutic targets. We used LPS to establish Caco-2/HT-29 cell models and measured cell viability by CCK-8. The levels of miR-146a-5p, RNF8, markers of NLRP3 inflammasome activation and autophagy, proteins involved in the Notch1/mTORC1 pathway, and inflammatory factors were assessed by RT-qPCR, Western blot, and ELISA. Intestinal epithelial barrier function was evaluated by measuring transepithelial electrical resistance. Autophagic flux was measured using tandem fluorescent-labeled LC3. miR-146a-5p was highly-expressed in LPS-induced Caco-2/HT-29 cells, and autophagy flux was blocked at the autolysosomal stage after LPS induction. Inhibition of miR-146a-5p suppressed NLRP3 inflammasome activation, reduced intestinal epithelial barrier damage, and facilitated autophagy inhibition in LPS-induced Caco-2/HT-29 cells. The autophagy inhibitor NH4Cl partially nullified the inhibitory effects of miR-146a-5p inhibition on NLRP3 inflammation activation. miR-146a-5p targeted RNF8, and silencing RNF8 partly abrogated the action of miR-146a-5p inhibition on promoting autophagy and inhibiting NLRP3 inflammasome activation. miR-146a-5p inhibition suppressed the Notch1/mTORC1 pathway activation by upregulating RNF8. Inhibition of the Notch1/mTORC1 pathway partially nullified the function of silencing RNF8 on inhibiting autophagy and bolstering NLRP3 inflammasome activation. In conclusion, miR-146a-5p inhibition may be a potential therapeutic approach for UC, as it facilitates autophagy of LPS-stimulated Caco-2/HT-29 cells, inhibits NLRP3 inflammasome activation, and reduces intestinal epithelial barrier damage by upregulating RNF8 and suppressing the Notch1/mTORC1 pathway.     

Measuring alcohol use across the transition to adulthood: Racial/ethnic,sexual identity,and educational differences

BackgroundPatterns of alcohol use change from adolescence to adulthood and may differ based on race/ethnicity, sexual identity, and education. If alcohol use measures do not operate consistently across groups and developmental periods, parameter estimates and conclusions may be biased.ObjectivesTo test the measurement invariance of a multi-item alcohol use measure across groups defined by race/ethnicity, sexual identity, and college education during the transition to adulthood.MethodsUsing three waves from the National Longitudinal Study of Adolescent to Adult Health, we tested configural, metric, and scalar invariance of a 3-item alcohol use measure for groups defined by race/ethnicity, sexual identity, and college education at three points during the transition to adulthood. We then assessed longitudinal measurement invariance to test the feasibility of modeling developmental changes in alcohol use within groups defined by these characteristics.ResultsOverall, findings confirm notable variability in the construct reliability of a multi-item alcohol use measure during the transition to adulthood. The alcohol use measure failed tests of metric and scalar invariance, increasingly across ages, both between- and within-groups defined by race/ethnicity, sexual identity, and college education, particularly among females.ConclusionsMeasurement testing is a critical step when utilizing multi-item measures of alcohol use. Studies that do not account for the effects of group or longitudinal measurement non-invariance may be statistically biased, such that recommendations for risk and prevention efforts could be misguided.