Impact of Respiratory Syncytial Virus on Child, Caregiver, and Family Quality of Life in the United States: Systematic Literature Review and Analysis.

BACKGROUND: Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infection in US children, reduces quality of life (QOL) of children, their caregivers, and families. METHODS: We conducted a systematic literature review in PubMed, EconLit, and other databases in the United States of articles published since 2000, derived utility lost per RSV episode from cohort studies, and performed a systematic analysis. RESULTS: From 2262 unique citations, 35 received full-text review and 7 met the inclusion criteria (2 cohort studies, 4 modeling studies, and 1 synthesis). Pooled data from the 2 cohort studies (both containing only hospitalized premature infants) gave quality-adjusted life-year (QALY) losses per episode of 0.0173 at day 38. From the cohort study that also assessed caregivers' QOL, we calculated net QALYs lost directly attributable to RSV per nonfatal episode from onset to 60 days after onset for the child, caregiver, child-and-caregiver dyad of 0.0169 (167% over prematurity alone), 0.0031, and 0.0200, respectively. CONCLUSION: Published data on QOL of children in the United States with RSV are scarce and consider only premature hospitalized infants, whereas most RSV episodes occur in children who were born at term and were otherwise healthy. QOL studies are needed beyond hospitalized premature infants.

Cost of Respiratory Syncytial Virus Infections in US Infants: Systematic Literature Review and Analysis.

BACKGROUND: Limited data are available on the economic costs of respiratory syncytial virus (RSV) infections among infants and young children in the United States. METHODS: We performed a systematic literature review of 10 key databases to identify studies published between 1 January 2014 and 2 August 2021 that reported RSV-related costs in US children aged 0-59 months. Costs were extracted and a systematic analysis was performed. RESULTS: Seventeen studies were included. Although an RSV hospitalization (RSVH) of an extremely premature infant costs 5.6 times that of a full-term infant ($10 214), full-term infants accounted for 82% of RSVHs and 70% of RSVH costs. Medicaid-insured infants were 91% more likely than commercially insured infants to be hospitalized for RSV treatment in their first year of life. Medicaid financed 61% of infant RSVHs. Paying 32% less per hospitalization than commercial insurance, Medicaid paid 51% of infant RSVH costs. Infants' RSV treatment costs $709.6 million annually, representing $187 per overall birth and $227 per publicly funded birth. CONCLUSIONS: Public sources pay for more than half of infants' RSV medical costs, constituting the highest rate of RSVHs and the highest expenditure per birth. Full-term infants are the predominant source of infant RSVHs and costs.

Outcomes for Long-Stay Nursing Facility Residents Following On-Site Acute Care under a CMS Initiative.

OBJECTIVES: The goal of this study was to describe outcomes of long-term nursing facility (NF) residents treated for one of 6 conditions on-site in the NF and to compare outcomes to those treated for the same conditions in the hospital. DESIGN: Cross-sectional retrospective study. SETTINGS AND PARTICIPANTS: The Centers for Medicare & Medicaid Services (CMS) Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents-Payment Reform enabled participating NFs to bill Medicare for providing on-site care to eligible long-stay residents meeting specified severity criteria due to any of 6 medical conditions, as an alternative to hospitalization. For billing purposes, residents were required to meet clinical criteria severe enough to warrant hospitalization. METHODS: We used the Minimum Data Set assessments to identify eligible long-stay NF residents. We used Medicare data to identify residents who were treated, either on-site or in the hospital, for the 6 conditions and measure outcomes including subsequent hospitalization and death. To compare residents treated in the 2 modes, we used logistic regression models and adjusted for demographics, functional and cognitive status, and comorbidities. RESULTS: Among residents treated on-site for the 6 conditions, 13.6% were subsequently hospitalized and 7.8% died, within 30 days, compared to 26.5% and 17.0%, respectively, among those treated in the hospital. Based on multivariate analysis, those treated in the hospital were more likely to be readmitted (OR = 1.666, P < .001) or to die (OR = 2.251, P < .001). CONCLUSIONS AND IMPLICATIONS: Although unable to fully account for differences in unobserved severity of illness between residents treated on-site vs in the hospital, our results do not indicate any harm, but rather a possible benefit, to being treated on-site.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine in Argentinean Adults.

INTRODUCTION: In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23; PCV13 → PPSV23) has been recommended for all adults aged ≥ 65 years and younger adults with chronic medical ("moderate-risk") or immunocompromising ("high-risk") conditions since 2017. With the approval of a 20-valent PCV (PCV20), we evaluated the cost-effectiveness of PCV20 versus current recommendations for moderate-/high-risk adults aged 18-64 years and all adults 65-99 years. METHODS: A probabilistic cohort model was used to project lifetime outcomes and costs associated with invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP), and the expected impact of vaccination. Clinical outcomes were projected annually based on Argentinean data. Economic costs were estimated based on cases and corresponding medical costs (adjusted to 2023 USD) and costs of vaccine and administration. Cost-effectiveness of PCV20 was evaluated versus the current strategy, PCV13 → PPSV23, and alternatively, versus sequentially administered 15-valent PCV and PPSV23 (PCV15 → PPSV23), and presented as cost per quality-adjusted life year gained; a healthcare system perspective was used. Costs and benefits were discounted at 3%/year. RESULTS: PCV20 in lieu of PCV13 → PPSV23 among moderate-/high-risk adults aged 18-64 years and all adults 65-99 years (N = 13.4M) prevented 3838 IPD, 4377 inpatient NBP, and 6003 outpatient NBP cases, and 1865 disease-related deaths; relative to PCV15 → PPSV23 the corresponding reductions were 2775, 3285, 4518, and 1348. PCV20 was projected to be the dominant strategy versus PCV13 → PPSV23 and PCV15 → PPSV23 as overall costs were lower by $87.6M and $80.8M, respectively. In probabilistic sensitivity analyses, PCV20 was dominant (i.e., more effective, less costly) in 100% of 1000 simulations. CONCLUSIONS: Analyses suggest implementing a PCV20 vaccination program in moderate-/high-risk adults aged 18-64 years and all adults ≥ 65 years-in lieu of PCV13 → PPSV23-would yield substantial reductions in pneumococcal disease and would be cost saving to the Argentinean healthcare system.

Pneumococcal pneumonia has a high disease burden in both children and adults. Older adults and those with certain underlying conditions are more susceptible to severe pneumococcal disease resulting in considerable economic burden on the healthcare system. In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) a year later is recommended for all adults aged ≥ 65 years and adults aged 18­64 years with underlying risk conditions. Despite vaccination efforts, prevalence of pneumococcal disease remains high. Two higher-valent PCVs­15-valent PCV (PCV15) and 20-valent PCV (PCV20)­are available for use in adults with PCV20 offering additional serotype coverage. This study assessed the cost-effectiveness of replacing current (PCV13 → PPSV23) and alternative (PCV15 → PPSV23) vaccination strategies with PCV20 alone. The use of PCV20 was evaluated among Argentinean adults aged 18­64 years with underlying risk conditions and all adults aged 65­99 years (N = 13 million). Over a lifetime time horizon, compared to PCV13 → PPSV23, PCV20 use would avert 14,218 cases and 1865 deaths, and increase quality-adjusted life years by 8655. Compared to PCV15 → PPSV23, PCV20 reduced cases and deaths by 10,578 and 1348, respectively, and increased quality-adjusted life years by 6341. In both comparisons, PCV20 use was cost saving with $87.6 million and $80.8 million lower costs compared to PCV13 → PPSV23 and PCV15 → PPSV23, respectively. Results of the cost-effectiveness analyses suggest that the use of PCV20 is a cost-saving strategy, reducing overall costs to the healthcare system and improving public health.

Assessing the impact of the president's emergency plan for AIDS relief on all-cause mortality.

This study estimated the impacts of PEPFAR on all-cause mortality (ACM) rates (deaths per 1,000 population) across PEPFAR recipient countries from 2004-2018. As PEPFAR moves into its 3rd decade, this study supplements the existing literature on PEPFAR 's overall effectiveness in saving lives by focusing impact estimates on the important subgroups of countries that received different intensities of aid, and provides estimates of impact for different phases of this 15-year period study. The study uses a country-level panel data set of 157 low- and middle-income countries (LMICs) from 1990-2018, including 90 PEPFAR recipient countries receiving bilateral aid from the U.S. government, employing difference-in-differences (DID) econometric models with several model specifications, including models with differing baseline covariates, and models with yearly covariates including other donor spending and domestic health spending. Using five different model specifications, a 10-21% decline in ACM rates from 2004 to 2018 is attributed to PEPFAR presence in the group of 90 recipient countries. Declines are somewhat larger (15-25%) in those countries that are subject to PEPFAR's country operational planning (COP) process, and where PEPFAR per capita aid amounts are largest (17-27%). Across the 90 recipient countries we study, the average impact across models is estimated to be a 7.6% reduction in ACM in the first 5-year period (2004-2008), somewhat smaller in the second 5-year period (5.5%) and in the third 5-year period (4.7%). In COP countries the impacts show decreases in ACM of 7.4% in the first period attributed to PEPFAR, 7.7% reductions in the second, and 6.6% reductions in the third. PEPFAR presence is correlated with large declines in the ACM rate, and the overall life-saving results persisted over time. The effects of PEFAR on ACM have been large, suggesting the possibility of spillover life-saving impacts of PEPFAR programming beyond HIV disease alone.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine Among US Children with Underlying Medical Conditions.

INTRODUCTION: A 20-valent pneumococcal conjugate vaccine (PCV20) was recently recommended for use among US children. We evaluated the cost-effectiveness of PCV20 among children aged 6 years with chronic medical conditions (CMC+) and children aged 6 years with immunocompromising conditions (IC) versus one and two doses of 23-valent pneumococcal polysaccharide vaccine (PPSV23), respectively. METHODS: A probabilistic model was employed to depict 10-year risk of clinical outcomes and economic costs of pneumococcal disease, reduction in life years from premature death, and expected impact of vaccination among one cohort of children with CMC+ and IC aged 6 years. Vaccine uptake was assumed to be 20% for both PCV20 and PPSV23. Cost per quality-adjusted life year (QALY) gained was evaluated from the US societal and healthcare system perspectives; deterministic and probabilistic sensitivity analyses (DSA/PSA) were also conducted. RESULTS: Among the 226,817 children with CMC+ aged 6 years in the US, use of PCV20 (in lieu of PPSV23) was projected to reduce the number cases of pneumococcal disease by 5203 cases, medical costs by US$8.7 million, and nonmedical costs by US$6.2 million. PCV20 was the dominant strategy versus PPSV23 from both the healthcare and societal perspectives. In the PSA, 99.9% of the 1000 simulations yielded a finding of dominance for PCV20. Findings in analyses of children with IC aged 6 years in the USA were comparable (i.e., PCV20 was the dominant vaccination strategy). Scenario analyses showed that increasing PCV20 uptake to 100% could potentially prevent > 22,000 additional cases of pneumococcal disease and further reduce medical and nonmedical costs by US$70.0 million among children with CMC+ and IC. CONCLUSIONS: Use of PCV20 among young children with CMC+ and IC in the USA would reduce the clinical burden of pneumococcal disease and yield overall cost savings from both the US healthcare system and societal perspectives. Higher PCV20 uptake could further reduce the number of pneumococcal disease cases in this population.

Analysis of economic and educational spillover effects in PEPFAR countries.

The United States President's Emergency Plan for AIDS Relief (PEPFAR) has been credited with saving millions lives and helping to change the trajectory of the global human immunodeficiency virus (HIV) epidemic. This study assesses whether PEPFAR has had impacts beyond health by examining changes in five economic and educational outcomes in PEPFAR countries: the gross domestic product (GDP) per capita growth rate; the share of girls and share of boys, respectively, who are out of school; and female and male employment rates. We constructed a panel data set for 157 low- and middle-income countries between 1990 and 2018 to estimate the macroeconomic impacts of PEPFAR. Our PEPFAR group included 90 countries that had received PEPFAR support over the period. Our comparison group included 67 low- and middle-income countries that had not received any PEPFAR support or had received minimal PEPFAR support (<$1M or <$.05 per capita) between 2004 and 2018. We used differences in differences (DID) methods to estimate the program impacts on the five economic and educational outcome measures. This study finds that PEPFAR is associated with increases in the GDP per capita growth rate and educational outcomes. In some models, we find that PEPFAR is associated with reductions in male and female employment. However, these effects appear to be due to trends in the comparison group countries rather than programmatic impacts of PEPFAR. We show that these impacts are most pronounced in COP countries receiving the highest levels of PEPFAR investment.

Analysis of maternal and child health spillover effects in PEPFAR countries.

OBJECTIVES: This study examined whether the US President's Emergency Plan for AIDS Relief (PEPFAR) funding had effects beyond HIV, specifically on several measures of maternal and child health in low-income and middle-income countries (LMICs). The results of previous research on the question of PEPFAR health spillovers have been inconsistent. This study, using a large, multicountry panel data set of 157 LMICs including 90 recipient countries, adds to the literature. DESIGN: Seven indicators including child and maternal mortality, several child vaccination rates and anaemia among childbearing-age women are important population health indicators. Panel data and difference-in-differences estimators (DID) were used to estimate the impact of the PEPFAR programme from inception in 2004 to 2018 using a comparison group of 67 LMICs. Several different models of baseline (2004) covariates were used to help balance the comparison and treatment groups. Staggered DID was used to estimate impacts since all countries did not start receiving aid at PEPFAR's inception. SETTING: All 157 LMICs from 1990 to 2018. PARTICIPANTS: 90 LMICs receiving PEPFAR aid and cohorts of those countries, including those required to submit annual country operational plans (COP), other recipient countries (non-COP), and three groupings of countries based on cumulative amount of per capita aid received (high, medium, low). INTERVENTIONS: PEPFAR aid to combat the HIV epidemic. PRIMARY OUTCOME MEASURES: Maternal mortality and child mortality rates, vaccination rates to protect children for diphtheria, whooping cough and tetanus, measles, HepB3, and tetanus, and prevalence of anaemia in women of childbearing age. RESULTS: Across PEPFAR recipient countries, large, favourable PEPFAR health effects were found for rates of childhood immunisation, child mortality and maternal mortality. These beneficial health effects were large and significant in all segments of PEPFAR recipient countries studied. We also found significant and favourable programme effects on the prevalence of anaemia in women of childbearing age in PEPFAR recipient countries receiving the most intensive financial support from the PEPFAR programme. Other recipient countries did not demonstrate significant effects on anaemia. CONCLUSIONS: This study demonstrated that important health indicators, beyond HIV, have been consistently and favourably influenced by PEPFAR presence. Child and maternal mortality have been substantially reduced, and childhood immunisation rates increased. We also found no evidence of 'crowding out' or negative spillovers in these resource-poor countries. These findings add to the body of evidence that PEPFAR has had favourable health effects beyond HIV. The implications of these findings are that foreign aid for health in one area may have favourable health effects in other areas in recipient countries. More research is needed on the influence of the mechanisms at work that create these spillover health effects of PEPFAR.

Quality of life burden on United States infants and caregivers due to lower respiratory tract infection and adjusting for selective testing: Pilot prospective observational study.

Background and Aims: Policymakers need data about the burden of respiratory syncytial virus (RSV) lower respiratory tract infections (LRTI) among infants. This study estimates quality of life (QoL) for otherwise healthy term US infants with RSV-LRTI and their caregivers, previously limited to premature and hospitalized infants, and corrects for selective testing. Methods: The study enrolled infants <1 year with a clinically diagnosed LRTI encounter between January and May 2021. Using an established 0-100 scale, the 36 infants' and caregivers' QoL at enrollment and quality-adjusted life year losses per 1000 LRTI episodes (quality-adjusted life years [QALYs]/1000) were validated and analyzed. Regression analyses examined predictors of RSV-testing and RSV-positivity, creating modeled positives. Results: Mean QoL at enrollment in outpatient (n = 11) LRTI-tested infants (66.4) was lower than that in not-tested LRTI infants (79.6, p = 0.096). For outpatient LRTI infants (n = 23), median QALYs/1000 losses were 9.8 and 0.25 for their caregivers. RSV-positive outpatient LRTI infants (n = 6) had significantly milder QALYs/1000 losses (7.0) than other LRTI-tested infants (n = 5)(21.8, p = 0.030). Visits earlier in the year were more likely to be RSV-positive than later visits (p = 0.023). Modeled RSV-positivity (51.9%) was lower than the observed rate (55.0%). Infants' and caregivers' QALYs/1000 loss were positively correlated (rho = 0.34, p = 0.046), indicating that infants perceived as sicker imposed greater burdens on caregivers. Conclusions: The overall median QALYs/1000 losses for LRTI (9.0) and RSV-LRTI (5.6) in US infants are substantial, with additional losses for their caregivers (0.25 and 0.20, respectively). These losses extend equally to outpatient episodes. This study is the first reporting QALY losses for infants with LRTI born at term or presenting in nonhospitalized settings, and their caregivers.

Between a Rock and a Hard Place: How poverty and lack of agency affect HIV risk behaviors among married women in 25 African countries: A cross-sectional study.

BACKGROUND: Gender inequality and poverty exacerbate the burden of HIV/AIDS among women in Africa. AIDS awareness and educational campaigns have been inadequate in many countries and rates of HIV testing and adherence to condom use remains considerably low, especially among married women. We investigate whether higher HIV knowledge is equally effective in lowering risky behaviors among groups of women with different levels of wealth and agency. METHODS: Pooled data on 113 151 adult married women from Demographic and Health Surveys (DHS) in 25 African countries was used (2010 to 2016). Agency was defined as women's ability to refuse sex and ask her partner to use a condom, plus have a role in decision making in household spending and health-related issues. The lowest tertile of DHS wealth index defined poverty. Questions about HIV prevention and mother-to-child transmission were used to create a scale for knowledge (0-5). Use of condom, HIV testing, absence of sexually transmitted disease (STD), and having one partner were dependent variables. Regression models investigated the effect of agency and knowledge as predictors of behaviors. Separate additional models were run to measure associations of each behavior with knowledge scores on groups of women divided by agency and poverty. Analyses were adjusted for demographic factors, history of pregnancy, wife-beating attitude, and country dummies. RESULTS: Significantly higher risk and lower level of protective factors exist for poor women who lack agency. Knowledge had positive associations with a better score in behavior, higher rate of condom use and testing for HIV both among poor and not poor women. When examining compound effects of agency and poverty, absence of agency reduces the positive effect of knowledge on lowering STD rate and overall behavior score among poor women. It also nullifies the effect of knowledge on condom use in both wealth groups. CONCLUSION: Knowledge of HIV does not exert its potential protective effect when women live in poverty compounded with lack of agency. Success of anti-HIV programs should be tailored to dynamics of risk and sociocultural and economic context of target populations.

Economic burden of dengue illness in India from 2013 to 2016: A systematic analysis.

OBJECTIVES: This paper concerns a systematic analysis of dengue illness and costs in India from 2013 to 2016. A previous study for 2006-2012 found that that projected annual number of dengue cases (5.78 million) was 282 times the officially reported number (20,474), highlighting enormous uncertainty. METHODS: This study updated primary data for India from 2012 to 2014 and synthesized the latest epidemiological and economic literature through 2018 using the country and global estimates. RESULTS: The first empirically-based publication of dengue costs by country (in 2016) estimated India experienced 18,618,706 symptomatic dengue cases and 1602 deaths, and cost $1.51 billion in 2013. With a combination of increased incidence, more refined methods, and better data this 2018 study raised the latest estimates to 53,210,706 cases, 22,527 deaths, and $5.71 billion economic costs for 2016, representing increases over the previous publication of 186%, 1306%, and 278%, respectively. When consistent methods and data were used to compare 2013 to 2016, the corresponding changes were only +29%, -9%, and +12%, respectively over these 3 years. CONCLUSIONS: India's burden of dengue is substantially greater than previously estimated. Although uncertainty intervals remain wide, these latest estimates reinforce the health and economic benefits that India would realize if dengue were substantially controlled.

The Safety and Efficacy of Tranexamic Acid in Adult Spinal Deformity Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVES: Major spinal corrective surgeries can be associated with critical intra-operative blood loss. The objective of this systematic review and meta-analysis was to assess the safety and efficacy of tranexamic acid (TXA), a commonly used antifibrinolytic agent, in adult spinal deformity (ASD) surgery, defined as fusion of five or more levels. METHODS: Articles from PubMed, Embase, Cochrane, and clinicaltrials.gov were screened using PRISMA guidelines through December 2018. Thromboembolic events, blood loss, and transfusion levels were primary outcomes of interest. Randomized controlled trials (RCTs) and observational studies (OBSs) with adult patients (≥ 18 years) were included. Continuous variables were analyzed using mean difference (MD) and categorical variables were analyzed using Peto odds ratio (OR), via random effects models. RESULTS: Of the 604 articles screened, seven studies (two RCTs and five cohort studies) were included. Incidence of thromboembolic events was not statistically significantly different between TXA (1 event/19) and placebo (0 events/13) in the RCT (Peto OR = 1.41, 95% CI 0.05-37.2; 32 patients; 1 study) and in the OBSs (TXA [2 events/135] vs control [0 events/72]; Peto OR = 1.09, 95% CI 0.16-7.61; p-heterogeneity = 0.85; 207 patients; 3 studies). Data from OBSs showed that the pooled MD was statistically significantly lower in the TXA group compared with the control group for intraoperative blood loss (MD: - 620.2 mL, 95% CI - 1066.6 to - 173.7; p-heterogeneity = 0.14; 228 patients; 4 studies) and total transfusion volume (MD: - 958.2 mL, 95% CI - 1867.5 to - 49.0; p-heterogeneity = 0.23; 93 patients; 2 studies). CONCLUSION: In this meta-analysis, TXA was not significantly associated with increased risk of thromboembolic events but was associated with lower intraoperative blood loss and lower total transfusion volumes in ASD surgery.