The economic burden of varicella among children in France: a caregiver survey.

To estimate the economic burden of varicella among children in France from family and societal perspectives. We conducted an online cross-sectional survey of caregivers of 185 French children (≤ 17 years) diagnosed with varicella in the previous six weeks. Data collected included varicella-related healthcare resource use, out-of-pocket costs, missed school days, and workdays missed by either parents or other caregivers. Mean and median direct and indirect costs (2022 Euros) were calculated using survey data and published literature. The annual societal burden of pediatric varicella in France was estimated. Of the 185 children, 95.1% had ≥ 1 outpatient visit, 10.3% had ≥ 1 emergency room visit, and 2.2% were hospitalized. The median [interquartile range, IQR] number of outpatient visits/child was 1.0 [1.0 - 2.0]. The median length of hospital stay among those hospitalized (n = 4) was 5.0 [3.5 - 6.5] days. Caregivers of 185 children missed a median of 2.0 [0 - 5.0] workdays; 113 families (61.1%) had ≥ 1 parent miss work. A median of 5.0 [3.0 - 7.0] school days were missed by 170 children who attended preschool or school. The median direct out-of-pocket cost to the family was €30.0 [€17.0 - €60.0]. The median [IQR] societal costs per varicella case were €455.2 [€70.5 - €1013.5]; the median [IQR] direct and indirect costs per child were €60.8 [€39.0 - €102.7] and €364.7 [€0.0 - €911.7] respectively. The annual societal burden of varicella among children in France was estimated to be €450,427,578 (95% CI: €357,144,618 - €543,710,538), with indirect costs accounting for 85%. CONCLUSIONS: A substantial economic burden is associated with pediatric varicella in France, primarily due to the productivity loss among caregivers. WHAT IS KNOWN: • Although varicella is considered a mild disease, it poses a significant burden on caregivers and society. Our study aimed to estimate the economic burden of varicella among children in France from family and societal perspectives to support policymakers in understanding the value of UVV in France. WHAT IS NEW: • We conducted an online survey of caregivers of 185 French children (≤17 years) diagnosed with varicella and collected data on varicella-related healthcare resource use, missed school days and workdays. Our study estimated annual societal burden of pediatric varicella in France. Out of 185 children with varicella, most (95.1%) had at least one outpatient visit, 10.3% had at least one emergency room visit, and 2.2% were hospitalized. 61.1% of parents with sick child, missed work and median productivity loss was 2.0 workdays. Additionally, 170 children who attended school or preschool missed a median of 5.0 school days. • The societal burden of pediatric varicella in France was estimated to be €450,427,578 (95% CI, €357,144,618 - €543,710,538), with indirect costs accounting for 85%. Pediatric varicella is associated with a substantial economic burden in France, primarily due to high productivity losses among parents and caregivers.

Impact of the COVID-19 Pandemic on Measles Vaccination Coverage and Estimated Catch-up Efforts for Serbia.

BACKGROUND: Measles is highly infectious, requiring ≥95% vaccine coverage rate (VCR) to prevent outbreaks. This study aimed to understand the impact of the COVID-19 pandemic on routine measles-containing vaccine (MCV) VCRs in Serbia and estimate national and regional catch-up vaccination required to prevent outbreaks. METHODS: A multiplier model was used to calculate annual MCV dose 1 (MCV1) and MCV dose 2 (MCV2) VCRs for children 1-6 and 6-12 years of age, respectively, for 2011-2022. Postpandemic (2023-2024) VCRs were modeled. The numbers of administered doses were compared to prepandemic and postpandemic, and monthly catch-up rates were calculated for 12-, 18- and 24-month campaigns. RESULTS: Between prepandemic and pandemic periods, national MCV1 VCR decreased from 88% to 81%, while MCV2 VCR decreased from 92% to 89%, corresponding to 20,856 missed MCV1 and 8760 missed MCV2 doses. Assuming national VCRs returned to prepandemic levels post-2022, 18% of children 1-6 years of age and 11% of children 6-12 years of age would have missed their MCV1 and MCV2 doses, respectively, by 2024. To catch up missed doses under this scenario, most regions would require monthly catch-up rates of 25%, 16% or 12% for MCV1 and 14%, 9% or 7% for MCV2, considering 12-, 18- or 24-month campaigns, respectively. CONCLUSIONS: The pandemic negatively impacted MCV VCRs in Serbia, leaving a sizeable proportion of children with missed doses. Significant catch-up efforts are required to recover VCRs to prepandemic levels and avoid future measles outbreaks, with increased monthly administration rates versus those in prepandemic periods.

Preferences of healthcare providers in Switzerland for attributes of pediatric hexavalent vaccines: a discrete-choice experiment.

OBJECTIVE: To understand the preferences of healthcare providers (HCPs) in Switzerland for pediatric hexavalent vaccine attributes. METHODS: A discrete-choice experiment included a series of choices between 2 hypothetical pediatric hexavalent vaccines with varying attributes: device type (including preparation time and risk of dosage errors), proportion of infants seroprotected against Haemophilus influenzae type b (Hib) at 11-12 months (pre-booster), packaging size, years on the market, and the thermostability at room temperature. Odds ratios (ORs) and conditional relative attribute importance (CRAI) were calculated using random-parameters logit. RESULTS: HCPs (150 pediatricians and 40 nursing staff) in Switzerland were unlikely to choose a vaccine conferring 50% (OR 0.00; 95% CI 0.00-0.00) or 70% (OR 0.01; 95% CI 0.00-0.01) of infants with Hib seroprotection at 11-12 months (pre-booster) compared with a vaccine conferring 90% seroprotection. The odds of choosing a vaccine available on the market for more than 3 years were nearly 5 times the odds of choosing a vaccine available on the market for less than 1 year (OR 4.76; 95% CI 1.87-7.65). The odds of choosing a vaccine in a prefilled syringe were nearly 3 times the odds of choosing a reconstituted vaccine (OR 2.77; 95% CI 1.39-4.15), and the odds of choosing a vaccine with a smaller package size were nearly 2 times the odds of choosing a vaccine with larger package size (OR 1.89; 95% CI 1.23-2.55). HCPs were equally likely to choose vaccines that can stay at room temperature for 6 versus 3 days (OR 1.07; 95% CI 0.73-1.42). According to CRAI, the most important attribute was Hib seroprotection, followed by years on the market, device type, and packaging size. CONCLUSION: Hib seroprotection at 11-12 months was the most important hexavalent vaccine attribute to HCPs in this study.

Modeling the Impact of Exogenous Boosting and Universal Varicella Vaccination on the Clinical and Economic Burden of Varicella and Herpes Zoster in a Dynamic Population for England and Wales.

Universal varicella vaccination (UVV) in England and Wales has been hindered by its potential impact on exogenous boosting and increase in herpes zoster (HZ) incidence. We projected the impact of ten UVV strategies in England and Wales on the incidence of varicella and HZ and evaluated their cost-effectiveness over 50 years. The Maternal-Susceptible-Exposed-Infected-Recovered-Vaccinated transmission model was extended in a dynamically changing, age-structured population. Our model estimated that one- or two-dose UVV strategies significantly reduced varicella incidence (70-92%), hospitalizations (70-90%), and mortality (16-41%) over 50 years. A small rise in HZ cases was projected with UVV, peaking 22 years after introduction at 5.3-7.1% above pre-UVV rates. Subsequently, HZ incidence steadily decreased, falling 12.2-14.1% below pre-UVV rates after 50 years. At a willingness-to-pay threshold of 20,000 GBP/QALY, each UVV strategy was cost-effective versus no UVV. Frontier analysis showed that one-dose UVV with MMRV-MSD administered at 18 months is the only cost-effective strategy compared to other strategies. HZ incidence varied under alternative exogenous boosting assumptions, but most UVV strategies remained cost-effective. HZ vaccination decreased HZ incidence with minimal impact on the cost-effectiveness. Introducing a UVV program would significantly reduce the clinical burden of varicella and be cost-effective versus no UVV after accounting for the impact on HZ incidence.

The Economic Burden of Pneumococcal Disease in Children: A Population-Based Investigation in the Veneto Region of Italy.

Despite widespread childhood immunization programs, pneumococcal disease (PD) continues to be associated with significant clinical and economic burden worldwide. This retrospective study assessed the PD-related economic burden in children from the Veneto region of Italy following the introduction of a 13-valent pneumococcal conjugate vaccine (PCV13) to the Italian immunization schedule in 2010. Between 2010 and 2017, the annual incidences of pneumonia, acute otitis media (AOM), and invasive pneumococcal disease (IPD), as well as syndromic-disease-related episodes, declined. In our analysis of data from regional expenditure and healthcare resource utilization (HCRU) databases related to children < 15 years of age, we found that regional expenditures decreased between 2010 and 2017 for pneumonia (EUR 8.88 to EUR 3.59 million), AOM (EUR 3.78 to EUR 2.76 million), and IPD (EUR 1.40 to EUR 1.00 million). Despite reductions in PD-related expenditure following the introduction of PCV13, there continues to be an economic burden associated with PD in Veneto, Italy.

Timing of Monovalent Vaccine Administration in Infants Receiving DTaP-based Combination Vaccines in the United States.

BACKGROUND: The recommended US infant immunization schedule includes doses of diphtheria, tetanus, acellular pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) and hepatitis B virus (HepB) during the first 6 months of life. Little information is available about the timing of associated, complementary monovalent vaccine administration in infants receiving DTaP-based pentavalent combination vaccines. METHODS: This was a retrospective cohort study of infants born between July 1, 2010, and June 30, 2018, in the US MarketScan commercial claims and encounters database. Descriptive statistics were used to assess vaccine administration patterns. Multivariate logistic regression was performed to explore factors associated with coadministration of DTaP-IPV/Hib and HepB. RESULTS: Among infants who received DTaP-HepB-IPV (n = 129,885), 93.7% had claims for at least 2 Hib doses; most (91.5%-98.3%) of these doses were administered on the same day as DTaP-HepB-IPV doses. Among infants who received DTaP-IPV/Hib (n=214,172), 95.3% had claims for ≥2 doses of HepB. Although coverage was high, 59.2% received the second HepB dose on the same day as the first DTaP-IPV/Hib dose, and 44.6% received the third dose of HepB on the same day as the third DTaP-IPV/Hib dose. Differences in coadministration of the second and third HepB doses with DTaP-IPV/Hib were associated with the region of residence, provider type, health plan type and coadministration of pneumococcal conjugate vaccine and rotavirus vaccine. CONCLUSIONS: Almost all infants received the appropriate, complementary monovalent vaccine series. However, this study found variability in the timing of HepB doses in relation to DTaP-IPV/Hib doses with many infants not completing the HepB series until 9 months of age.

Economic burden of pneumococcal disease in children in Liguria, Italy.

Vaccinations against Streptococcus pneumoniae are included in infant immunization programs globally. However, a substantial burden due to pneumococcal disease (PD) remains. This study aimed to estimate the cost of emergency department (ED) visits and hospitalizations associated with invasive pneumococcal disease, all-cause pneumonia, and acute otitis media in children <15 years of age in the Liguria region of Italy between 2012 and 2018. The retrospective cohort study used data from the Liguria Region Administrative Health Databases and the Ligurian Chronic Condition Data Warehouse, which contain information on hospital stays, outpatient visits, laboratory/imaging techniques, surgical procedures, and pharmaceutical prescriptions. Patients with one or more ED or inpatient claim for PD (based on International Classification of Diseases, Ninth Revision, Clinical Modification codes) were included. Cost of ED visits and hospitalizations were estimated from the diagnosis-related group system and procedures performed in the ED. In Ligurian children <15 years of age during 2012-2018, the median annual number of hospitalizations plus ED visits due to PD was 4,009, and the median estimated annual cost was €3.6 million. All-cause pneumonia accounted for the majority of hospitalization costs during the study period. Number and costs of ED visits and hospitalizations increased from 2012 to 2018. Despite widespread infant immunization in Liguria, economic costs due to PD-associated ED visits and hospitalizations remained high in children 0-14 years of age.

Physician preferences for attributes of pediatric combination vaccines in the United States.

OBJECTIVE: To understand physician preferences for various attributes of pediatric combination vaccines. METHODS: An online survey was completed by 400 US physicians (pediatricians and family physicians) who routinely administer vaccines to infants aged 1-12 months in outpatient settings. Respondents completed a discrete choice experiment (DCE) by selecting their preferred options from different hypothetical vaccine profiles with systematic variation in the levels of five attributes: vaccine presentation, number of injections administered at a single visit, completion rates, timeliness rates (within 30 days of recommended age), and years of availability for routine use, assuming similar cost, safety, and efficacy. Odds ratios and relative attribute importance scores were estimated using a random parameters logit model. RESULTS: Physicians (mean age 50.4 years, 52.5% women) preferred combination vaccines that reduced the number of injections administered at a single visit, facilitated higher completion and timeliness rates for the primary DTaP series, were available as a pre-filled syringe rather than a vial needing reconstitution and had been available for routine use for more than 1 year. All odds ratios were statistically significant. Physicians were twice as likely to prefer administering three injections in a single visit instead of four. The most important attribute was the number of injections administered at a single visit (relative importance 38%), followed by timeliness, completion rates, and vaccine presentation; years a vaccine has been available was the least important attribute. CONCLUSION: US physicians prefer pediatric combination vaccines that enable fewer injections to be administered at a single visit, facilitate higher completion and timeliness rates, are offered as a pre-filled syringe, and have been available for routine use for more than 1 year. The most important attribute of pediatric combination vaccines was a reduction in the number of injections administered at a single visit.

A Retrospective Analysis to Estimate the Burden of Invasive Pneumococcal Disease and Non-Invasive Pneumonia in Children <15 Years of Age in the Veneto Region, Italy

Despite advances in preventative interventions, invasive pneumococcal disease and pneumonia cause significant morbidity and mortality in children. We studied the annual incidence of pneumococcal-specific and syndromic invasive disease and non-invasive pneumonia in children <15 years of age during the early (2010−2013) and late (2014−2017) 13-valent pneumococcal conjugate vaccine (PCV13) periods in Veneto, Italy. In this retrospective observational study, pneumococcal-specific and syndromic invasive disease and non-invasive pneumonia cases were identified from several sources, including the Pedianet database. Interrupted time series analysis and Mann−Kendall tests were conducted to explore trends in incidence rates (IRs). Among 72,570 patients <15 years of age between 2010−2017, 88 episodes of pneumococcal-specific and syndromic invasive disease and 3926 episodes of non-invasive pneumonia were reported. Overall IR of pneumococcal-specific and syndromic invasive disease was 0.4/1000 person-years and did not change significantly (p = 0.46) throughout the study. Overall IR of non-invasive pneumonia was 10/1000 person-years and decreased significantly (−0.64, p = 0.026) over the study period. Following PCV13 introduction, the IRs of non-invasive pneumonia in children <15 years of age declined significantly, with no significant change in the IRs of pneumococcal-specific and syndromic invasive disease. There is a continuing clinical burden associated with pediatric pneumococcal diseases in Veneto, Italy.

Incidence of acute otitis media in children < 16 years old in Germany during 2014-2019.

BACKGROUND: Acute otitis media (AOM) remains a common infection in children despite the introduction of pneumococcal conjugate vaccines. This study estimated AOM incidence rates (IRs) over time in children < 16 years old in Germany following PCV13 introduction. METHODS: AOM episodes were identified in the InGef healthcare claims database from 2014-2019 in children aged < 16 years. Each AOM episode was classified as either simple or recurrent. Recurrent AOM was defined as 3 or more episodes identified within a 6-month period; or 4 or more episodes within a 12-month period with at least one episode in the prior 6 months. AOM-related surgical procedures within 12 months and complications within 21 days of an AOM episode were also identified. Annual IRs were calculated as number of episodes/child-years (CY) at risk. 95% Confidence intervals (95%CI) were calculated using the Wilson method. The Mann-Kendall test was used to assess trends over time. RESULTS: Between 2014 and 2019, the study population comprised 916,805 children with 327,726 AOM episodes, of which 15% (49,011) of all episodes were identified as recurrent AOM and 85% (278,715) as simple AOM. There were significant declines in AOM (p = 0.003) in the study population overall and in all age groups over the study period; from 101 (95%CI 101-102)/1000 CY to 79 (95%CI 78-80)/1000 CY in the total study population, from 209 (95%CI 206-212)/1000 CY to 147 (95%CI 145-150)/1000 CY in < 2-year-olds, from 239 (95%CI 237-242) to 179 (95%CI 177-182)/1000 CY in 2-4-year-olds, and from 50 (95%CI 49-50) to 38 (95%CI 37-39)/1000 CY in 5-15-year-olds. No significant trends were identified for AOM-related surgical procedures over the study period; however, AOM-related complications overall increased (p = 0.003). CONCLUSION: Between 2014 and 2019, AOM incidence overall declined in children aged 0-15 years in Germany. Over the study period, the incidence of complicated AOM cases increased, however the incidence of AOM-related surgical procedures remained constant. Despite the impact of PCV13, the burden associated with AOM in Germany remains substantial.

Incidence of acute otitis media in children in the United States before and after the introduction of 7- and 13-valent pneumococcal conjugate vaccines during 1998-2018.

BACKGROUND: Acute otitis media (AOM) is a leading cause of office visits and antibiotic prescriptions in children. Pneumococcal conjugate vaccines were introduced in the USA in 2000 (7-valent, PCV7) and 2010 (13-valent, PCV13). Expanded valency PCVs are currently under development. To describe the impact of PCVs and quantify the residual burden of AOM, this study estimated annual incidence rates (IRs) of AOM and AOM-related complications and surgical procedures in children < 18 years in the USA before and after the introduction of PCV7 and PCV13. METHODS: AOM episodes were identified in the IBM MarketScan® Commercial and Medicaid databases using diagnosis codes (ICD-9-CM: 382.x; ICD-10-CM: H66.xx and H67.xx). Annual IRs were calculated as the number of episodes per 1000 person-years (PYs) for all children < 18 years and by age group (< 2, 2-4, and 5-17 years). National estimates of annual AOM IRs were extrapolated using Census Bureau data. Interrupted time series analyses were used to assess immediate and gradual changes in monthly AOM IRs, controlling for seasonality. RESULTS: In the commercially insured population, AOM IRs declined between the pre-PCV7 period (1998-1999) and the late PCV13 period (2014-2018) from 1170.1 to 768.8 episodes per 1000 PY for children < 2 years, from 547.4 to 410.3 episodes per 1000 PY in children 2-4 years, and from 115.6 to 91.8 episodes per 1000 PY in children 5-17 years. The interrupted time series analyses indicated significant immediate or gradual decreases in the early PCV7 period (2001-2005), and gradual increases in the late PCV7 period (2006-2009) in children < 2 years; however, crude IRs trended downward in all time periods. In older children, IRs decreased in the early PCV7 and early PCV13 period (2011-2013), but gradually increased in the late PCV7 period. IRs of AOM-related surgical procedures decreased, and IRs of AOM-related complications increased during the study timeframe. CONCLUSIONS: AOM disease burden remains high in children of all ages despite overall reductions in AOM IRs during 1998-2018 following the introduction of PCV7 and PCV13. The impact of investigational PCVs on the disease burden of AOM will likely depend on AOM etiology and circulating pneumococcal serotypes.

A Retrospective Database Analysis to Estimate the Burden of Acute Otitis Media in Children Aged <15 Years in the Veneto Region (Italy)

This study aimed to assess trends in the incidence of acute otitis media (AOM), a common childhood condition, following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in the Veneto region of Italy in 2010. AOM episodes (overall, simple, and recurrent (≥3 or ≥4 episodes in 6 or 12 months, respectively, with ≥1 episode in the preceding 6 months)) in children <15 years of age were identified in Pedianet from 2010−2017. Interrupted time series analyses were conducted to assess changes in the annual incidence rates (IRs) in early (2010−2013) and late (2014−2017) PCV13 periods. In total, 72,570 children (402,868 person-years) were identified; 21,048 had 41,683 AOM episodes. Mean annual AOM IR was 103/1000 person-years (95% confidence interval: 102−104), decreasing from 126 to 79/1000 person-years. AOM IRs were highest in children 2−4 years of age, followed by <2 and 5−14 years of age. Overall and simple AOM IRs decreased among children 0−14 years of age, including 2−4 and 5−14 years of age, while recurrent AOM IRs decreased in children <2 years of age. Following PCV13 introduction, AOM IRs decreased substantially in children <15 years of age, with the greatest benefit observed in older children, driven by a reduction in simple AOM IRs. AOM disease burden remains substantial.

Comprehensive value assessments for new pediatric pneumococcal conjugate vaccines.

Although the incidence of invasive pneumococcal disease (IPD) and acute otitis media (AOM) in young children has decreased since the introduction of pneumococcal conjugate vaccines (PCVs), the subsequent emergence of non-vaccine Streptococcus pneumoniae serotypes and the persistence of certain vaccine serotypes both contribute to substantial residual pneumococcal disease. There is a need for the development of new pneumococcal vaccines to address the clinical and economic burden presented by emerging non-vaccine serotypes, while maintaining suppression of serotypes in existing vaccines. To assess the full value of next-generation vaccines, public health evaluations must consider epidemiological and economic data across all vaccine serotypes, including those included in existing vaccines and those unique to the new product. This is supported by two recent analyses that estimated the health and economic burden of IPD (in the United States and Europe) and AOM (in the United States only) associated with the serotypes in V114, a 15-valent pneumococcal conjugate vaccine (PCV15), which contains all serotypes in the licensed 13-valent pneumococcal conjugate vaccine (PCV13) as well as the unique serotypes 22 F and 33 F and was recently approved for use in adults in the US. The analyses demonstrated considerable health and economic burden associated with PCV13 serotypes, as well as increasing burden associated with serotypes 22 F and 33 F. In addition to addressing the burden of non-vaccine serotypes, ability to maintain or improve protection against disease caused by serotypes in existing vaccines will be an important consideration for decision makers.

Health and economic burden of invasive pneumococcal disease associated with 15-valent pneumococcal conjugate vaccine serotypes in children across eight European countries.

AIMS: V114, a 15-valent pneumococcal conjugate vaccine (PCV15) currently approved in adults in the US, contains the 13 S. pneumoniae serotypes in PCV13 and two additional serotypes, 22 F and 33 F, which are important contributors to residual PD. This study quantified the health and economic burden of pediatric invasive pneumococcal disease (IPD) associated with V114 serotypes in eight countries in Europe. MATERIALS AND METHODS: A Markov model estimated V114-type IPD cases and costs in hypothetical unvaccinated birth cohorts from Denmark, France, Germany, Italy, Norway, Spain, Switzerland, and the UK over 20 years. Inputs were obtained from published literature. IPD cases and costs were calculated for three time periods using time-specific epidemiological data: (a) pre-PCV7; (b) pre-PCV13; and (c) post-PCV13. Costs were estimated from a societal perspective (2018 Euros) and discounted at 3%. RESULTS: The model estimated that 4,649 IPD cases in the pre-PCV7 period, 3,248 cases in the pre-PCV13 period, and 958 cases in the post-PCV13 period were attributable to V114 serotypes. Total discounted costs associated with V114 serotypes were €109.1 million (pre-PCV7 period), €65.7 million (pre-PCV13 period), and €18.7 million (post-PCV13 period). LIMITATIONS: Post-meningitis sequelae, acute otitis media, and non-bacteremic pneumonia were not considered. Direct non-medical costs were not included. Conclusions on effectiveness of V114 or added value over existing infant vaccination programs cannot be drawn. CONCLUSIONS: IPD cases and costs were estimated in hypothetical birth cohorts in eight European countries followed for 20 years during three time periods. Serotypes included in V114 were associated with significant morbidity and costs in pre-PCV7, pre-PCV13, and post-PCV13 periods. Future pediatric pneumococcal vaccines should maintain protection against serotypes in licensed vaccines while extending coverage to additional serotypes to ensure reductions in IPD burden are maintained.

Deep learning for classification of pediatric chest radiographs by WHO's standardized methodology.

BACKGROUND: The World Health Organization (WHO)-defined radiological pneumonia is a preferred endpoint in pneumococcal vaccine efficacy and effectiveness studies in children. Automating the WHO methodology may support more widespread application of this endpoint. METHODS: We trained a deep learning model to classify pneumonia CXRs in children using the World Health Organization (WHO)'s standardized methodology. The model was pretrained on CheXpert, a dataset containing 224,316 adult CXRs, and fine-tuned on PERCH, a pediatric dataset containing 4,172 CXRs. The model was then tested on two pediatric CXR datasets released by WHO. We also compared the model's performance to that of radiologists and pediatricians. RESULTS: The average area under the receiver operating characteristic curve (AUC) for primary endpoint pneumonia (PEP) across 10-fold validation of PERCH images was 0.928; average AUC after testing on WHO images was 0.977. The model's classification performance was better on test images with high inter-observer agreement; however, the model still outperformed human assessments in AUC and precision-recall spaces on low agreement images. CONCLUSION: A deep learning model can classify pneumonia CXR images in children at a performance comparable to human readers. Our method lays a strong foundation for the potential inclusion of computer-aided readings of pediatric CXRs in vaccine trials and epidemiology studies.

Mortality Among US Patients Hospitalized With SARS-CoV-2 Infection in 2020.

Importance: Mortality is an important measure of the severity of a pandemic. This study aimed to understand how mortality by age of hospitalized patients who were tested for SARS-CoV-2 has changed over time. Objective: To evaluate trends in in-hospital mortality among patients who tested positive for SARS-CoV-2. Design, Setting, and Participants: This retrospective cohort study included patients who were hospitalized for at least 1 day at 1 of 209 US acute care hospitals of variable size, in urban and rural areas, between March 1 and November 21, 2020. Eligible patients had a SARS-CoV-2 polymerase chain reaction (PCR) or antigen test within 7 days of admission or during hospitalization, and a record of discharge or in-hospital death. Exposure: SARS-CoV-2 positivity. Main Outcomes and Measures: SARS-CoV-2 infection was defined as a positive SARS-CoV-2 PCR or antigen test within 7 days before admission or during hospitalization. Mortality was extracted from electronically available data. Results: Among 503 409 admitted patients, 42 604 (8.5%) had SARS-CoV-2-positive tests. Of those with SARS-CoV-2-positive tests, 21 592 (50.7%) were male patients. Hospital admissions among patients with SARS-CoV-2-positive tests were highest in the group aged 65 years or older (19 929 [46.8%]), followed by those aged 50 to 64 years (11 602 [27.2%]) and 18 to 49 years (10 619 [24.9%]). Hospital admissions among patients 18 to 49 years of age increased from 1099 of 5319 (20.7%) in April to 1266 of 4184 (30.3%) in June and 2156 of 7280 (29.6%) in July, briefly exceeding those in the group 50 to 64 years of age (June: 1194 of 4184 [28.5%]; 2039 of 7280 [28.0%]). Patients with SARS-CoV-2-positive tests had higher in-hospital mortality than patients with SARS-CoV-2-negative tests (4705 [11.0%] vs 11 707 of 460 805 [2.5%]; P < .001). In-hospital mortality rates increased with increasing age for both patients with SARS-CoV-2-negative tests and SARS-CoV-2-positive tests. In patients with SARS-CoV-2-negative tests, mortality increased from 45 of 11 255 (0.4%) in those younger than 18 years to 4812 of 107 394 (4.5%) in those older than 75 years. In patients with SARS-CoV-2-positive tests, mortality increased from 1 of 454 (0.2%) of those younger than 18 years to 2149 of 10 287 (20.9%) in those older than 75 years. In-hospital mortality rates among patients with SARS-CoV-2-negative tests were similar for male and female patients (6273 of 209 086 [3.0%] vs 5538 of 251 719 [2.2%]) but higher mortality was observed among male patients with SARS-CoV-2-positive tests (2700 of 21 592 [12.5%]) compared with female patients with SARS-CoV-2-positive tests (2016 of 21 012 [9.60%]). Overall, in-hospital mortality increased from March to April (63 of 597 [10.6%] to 1047 of 5319 [19.7%]), then decreased significantly to November (499 of 5350 [9.3%]; P = .04), with significant decreases in the oldest age groups (50-64 years: 197 of 1542 [12.8%] to 73 of 1341 [5.4%]; P = .02; 65-75 years: 269 of 1182 [22.8%] to 137 of 1332 [10.3%]; P = .006; >75 years: 535 of 1479 [36.2%] to 262 of 1505 [17.4%]; P = .03). Conclusions and Relevance: This nationally representative study supported the findings of smaller, regional studies and found that in-hospital mortality declined across all age groups during the period evaluated. Reductions were unlikely because of a higher proportion of younger patients with lower in-hospital mortality in the later period.

Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae associated with invasive pneumococcal disease among adults in Japan.

OBJECTIVES: This study evaluated the serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae isolates from adults (aged ≥20 years) with invasive pneumococcal disease (IPD) in Japan. METHODS: This prospective observational study was conducted in 49 participating Japanese hospitals. S. pneumoniae isolates were serotyped and tested for antimicrobial susceptibility at a central laboratory. Information regarding patient characteristics, underlying disease, IPD clinical syndromes, and treatment was collected through medical chart review. RESULTS: The final analysis included 177 patients enrolled from 45 hospitals between September 2016 and April 2018 (bacteraemic pneumonia, 110; bacteraemia without identified focus, 29; meningitis, 19). Most patients (70.1%) were aged ≥65 years and most had underlying disease (79.1%). The proportion of isolates from serotypes contained in the pneumococcal polysaccharide vaccine (PPV) 23 was 61.0%, while those in the pneumococcal conjugate vaccine (PCV) 7 and PCV13 were 2.8% and 28.2%, respectively. Non-vaccine serotypes accounted for 37.9% of all isolates and 50.8% of isolates from immunosuppressed patients. Serotype 12F was the most common vaccine serotype, followed by serotype 3. CONCLUSIONS: The continued disease burden of IPD in adults in Japan warrants improved vaccination rates and development of next-generation vaccines that include serotypes not currently covered. CLINICAL TRIAL REGISTRATION: Clinical trial summary registration number 160,822,918,146; JapicCTI-163352.

Health and economic burden associated with 15-valent pneumococcal conjugate vaccine serotypes in children in the United States.

AIMS: V114 is an investigational 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 Streptococcus pneumoniae serotypes in 13-valent PCV (PCV13) plus two additional serotypes. This study quantified the health and economic burden of invasive pneumococcal disease (IPD) and acute otitis media (AOM) caused by V114 types among children in the United States. MATERIALS AND METHODS: A Markov model estimated the number of V114-type IPD and AOM cases and costs in a hypothetical, unvaccinated US birth cohort over 20 years. Three time periods were analyzed using time-specific epidemiological data to determine the number of IPD and AOM cases associated with all 15 serotypes in V114. The time periods were: (1) pre-PCV7 (1999); (2) pre-PCV13 (2009); (3) post-PCV13 (2017). Costs were estimated from a societal perspective (2018 US dollars) and discounted at 3%. RESULTS: The model estimated 18,983 IPD cases and 5.4 million AOM cases associated with V114 serotypes pre-PCV7, 4,697 IPD cases and 3.0 million AOM cases pre-PCV13, and 948 IPD cases and 0.2 million AOM cases post-PCV13. Total discounted costs associated with V114 serotypes were $1.7 billion pre-PCV7, $730 million pre-PCV13, and $75 million US dollars post-PCV13. LIMITATIONS: Post-meningitis sequelae, cases of non-bacteremic pneumonia, and direct non-medical costs were not included. CONCLUSIONS: IPD and AOM cases and costs were estimated in a hypothetical US birth cohort followed for 20 years at three time periods. In all three periods, the serotypes targeted by V114 contributed to significant morbidity and costs. New pediatric pneumococcal vaccines must continue to retain serotypes in licensed vaccines to maintain disease reduction while extending coverage to non-vaccine serotypes.

Comparative effectiveness of budesonide inhalation suspension and montelukast in children with mild asthma in Korea.

Objective: The comparative effectiveness of low-dose budesonide inhalation suspension (BIS) versus oral montelukast (MON) in managing asthma control among children with mild asthma was assessed in Korea.Methods: Claims from Korea's national health insurance database for children (2-17 years) with mild asthma (GINA 1 or 2) who initiated BIS or MON during 2015 were retrospectively analyzed. Pre- and post-index windows were 1 year each. Adherence, persistency, asthma control, asthma-related health-care resource utilization, and costs were evaluated using unadjusted descriptive statistics and propensity score-matched regression analyses.Results: The number of children identified was 26,052 for unmatched (n = 1,221 BIS; n = 24,831 MON) and 2,290 for matched populations (n = 1,145 per cohort). Medication adherence, measured by proportion of days covered, was low for both cohorts but significantly higher for MON versus BIS (13.8% vs. 4.5%; p < .001). Time to loss of persistency was longer for MON versus BIS (82.3 vs. 78.4 days, respectively; p < .001). Mean number of post-index asthma-related office visits was 6.6 for BIS versus 8.3 for MON (p < .001). However, a greater proportion of patients in the BIS cohort had an asthma exacerbation-related office visit than the MON cohort (78.3% vs. 56.1%; p < .001). Asthma-related total health-care costs were higher with MON versus BIS (₩ 190,185 vs. ₩ 167,432, respectively; p < .001), likely driven by higher pharmaceutical costs associated with MON (₩ 69,113 vs. ₩ 49,225; p < .001).Conclusions: Montelukast patients had better adherence, a longer time to loss of persistency, and were less likely to experience an exacerbation-related office visit in the post-index period than BIS patients.