Understanding healthcare providers' preferred attributes of pediatric pneumococcal conjugate vaccines in the United States.

As higher-valent pneumococcal conjugate vaccines (PCVs) become available for pediatric populations in the US, it is important to understand healthcare provider (HCP) preferences for and acceptability of PCVs. US HCPs (pediatricians, family medicine physicians and advanced practitioners) completed an online, cross-sectional survey between March and April 2023. HCPs were eligible if they recommended or prescribed vaccines to children age <24 months, spent ≥25% of their time in direct patient care, and had ≥2 y of experience in their profession. The survey included a discrete choice experiment (DCE) in which HCPs selected preferred options from different hypothetical vaccine profiles with systematic variation in the levels of five attributes. Relative attribute importance was quantified. Among 548 HCP respondents, the median age was 43.2 y, and the majority were male (57.9%) and practiced in urban areas (69.7%). DCE results showed that attributes with the greatest impact on HCP decision-making were 1) immune response for the shared serotypes covered by PCV13 (31.4%), 2) percent of invasive pneumococcal disease (IPD) covered by vaccine serotypes (21.3%), 3) acute otitis media (AOM) label indication (20.3%), 4) effectiveness against serotype 3 (17.6%), and 5) number of serotypes in the vaccine (9.5%). Among US HCPs, the most important attribute of PCVs was comparability of immune response for PCV13 shared serotypes, while the number of serotypes was least important. Findings suggest new PCVs eliciting high immune responses for serotypes that contribute substantially to IPD burden and maintaining immunogenicity against serotypes in existing PCVs are preferred by HCPs.

Clinical and economic burden of invasive pneumococcal disease and non-invasive all-cause pneumonia in hospitalized US adults: A multicenter analysis from 2015-2020.

OBJECTIVES: To evaluate the clinical and economic outcomes in adults hospitalized with invasive pneumococcal disease (IPD) and non-invasive all-cause pneumonia (ACP) overall and by antimicrobial resistance (AMR) status. METHODS: Hospitalized adults from the BD Insights Research Database with an ICD10 code for IPD, non-invasive ACP or a positive Streptococcus pneumoniae culture/urine antigen test were included. Descriptive statistics and multivariable analyses were used to evaluate outcomes (in-hospital mortality, length of stay [LOS], cost per admission, and hospital margin [costs - payments]). RESULTS: The study included 88,182 adult patients at 90 US hospitals (October 2015-February 2020). Most (98.6%) had non-invasive ACP and 40.2% were <65 years old. Of 1,450 culture-positive patients, 37.7% had an isolate resistant to ≥1 antibiotic class. Observed mortality, median LOS, cost per admission, and hospital margins were 8.3%, 6 days, $9,791, and $11, respectively. Risk factors for mortality included ≥50 years of age, higher risk of pneumococcal disease (based on chronic or immunocompromising conditions), and intensive care unit admission. Patients with IPD had similar mortality rates and hospital margins compared with non-invasive ACP, but greater costs per admission and LOS. CONCLUSION: IPD and non-invasive ACP are associated with substantial clinical and economic burden across all adult age groups. Expanded pneumococcal vaccination programs may help reduce disease burden and decrease hospital costs.

Incidence of pneumococcal disease in children ≤48 months old in the United States: 1998-2019.

BACKGROUND: Pneumococcal disease (PD) is a major cause of morbidity and mortality among children, particularly in the youngest age groups. This study aimed to assess the incidence of PD over time by age group in young children with commercial or Medicaid coverage in the US. METHODS: Episodes of invasive pneumococcal disease (IPD), all-cause pneumonia (ACP), and acute otitis media (AOM) were identified in the MarketScan® Commercial and Medicaid claims databases using diagnosis codes among children aged ≤ 48 months with confirmed date of birth (DoB), at any time during the study period (1998-2019). DoB was assigned using diagnosis codes for birth or delivery using the child's or mother's medical claims to ensure accurate age determination. Annual incidence rates (IRs) were calculated as number of disease episodes/100,000 person-years (PY) for IPD and ACP and episodes/1,000 PY for AOM, for children aged 0-6, 7-12, 12-24, and 25-48 months. RESULTS: Annual IPD IRs declined from 53 to 7 episodes/100,000 PY between 1998 and 2019 in commercially-insured and 58 to 9 episodes/100,000 PY between 2001 and 2019 in Medicaid-insured children. Annual ACP IRs declined from 5,600 to 3,952 episodes/100,000 PY, and from 6,706 to 4,521 episodes/100,000 PY, respectively, over these periods. In both populations, children aged 0-6 months had the highest incidence of IPD and inpatient ACP. Annual AOM IRs declined from 1,177 to 738 episodes/1,000 PY (commercially-insured) and 633 to 624 episodes/1,000 PY (Medicaid-insured), over these periods. IRs were higher in rural vs. urban areas for all disease manifestations. CONCLUSIONS: Incidence rates of IPD, ACP, and AOM decreased in children with commercial insurance and Medicaid coverage from 1998 to 2019. However, burden of disease remained substantial, with higher annual IRs for IPD and ACP for Medicaid-insured vs. commercially-insured children. IPD and inpatient ACP were most common in the youngest children 0-6 months old, followed by the 7-12-month age group.

Association Between Social Vulnerability and Streptococcus pneumoniae Antimicrobial Resistance in US Adults.

BACKGROUND: Growing evidence indicates antimicrobial resistance disproportionately affects individuals living in socially vulnerable areas. This study evaluated the association between Streptococcus pneumoniae (SP) antimicrobial resistance (AMR) and the CDC/ATSDR Social Vulnerability Index (SVI) in the United States. METHODS: Adult patients ≥ 18 years with 30-day nonduplicate SP isolates from ambulatory/hospital settings from January 2011-December 2022 with zip codes of residence were evaluated across 177 facilities in the BD Insights Research Database. Isolates were identified as SP AMR if they were non-susceptible to ≥ 1 antibiotic class (macrolide, tetracycline, extended-spectrum cephalosporins, or penicillin). Associations between SP AMR and SVI score (overall and themes) were evaluated using generalized estimating equations with repeated measurements within county to account for within-cluster correlations. RESULTS: Of 8,008 unique SP isolates from 574 US counties across 39 states, the overall proportion of AMR was 49.9%. A significant association between socioeconomic status (SES) theme and SP AMR was detected with higher SES theme SVI score (indicating greater social vulnerability) associated with greater risk of AMR. On average, a decile increase of SES, indicating greater vulnerability, was associated with a 1.28% increased risk of AMR (95% confidence interval [CI], 0.61%, 1.95%; P=0.0002). A decile increase of household characteristic score was associated with a 0.81% increased risk in SP AMR (95% CI,0.13%, 1.49%; P=0.0197). There was no association between racial/ethnic minority status, housing type and transportation theme, or overall SVI score and SP AMR. CONCLUSIONS: SES and household characteristics were the SVI themes most associated with SP AMR.

Increased Risk of Long-Term Disabilities Following Childhood Bacterial Meningitis in Sweden.

Importance: Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort. Objective: To describe the long-term risks of disabilities following a childhood diagnosis of bacterial meningitis in Sweden. Design, Setting, and Participants: This nationwide retrospective registry-based cohort study included individuals diagnosed with bacterial meningitis (younger than 18 years) and general population controls matched (1:9) by age, sex, and place of residence. Data were retrieved from the Swedish National Patient Register from January 1, 1987, to December 31, 2021. Data were analyzed from July 13, 2022, to November 30, 2023. Exposure: A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register between 1987 and 2021. Main Outcomes and Measures: Cumulative incidence of 7 disabilities (cognitive disabilities, seizures, hearing loss, motor function disorders, visual disturbances, behavioral and emotional disorders, and intracranial structural injuries) after bacterial meningitis in childhood. Results: The cohort included 3623 individuals diagnosed with bacterial meningitis during childhood and 32 607 controls from the general population (median age at diagnosis, 1.5 [IQR, 0.4-6.2] years; 44.2% female and 55.8% male, median follow-up time, 23.7 [IQR, 12.2-30.4] years). Individuals diagnosed with bacterial meningitis had higher cumulative incidence of all 7 disabilities, and 1052 (29.0%) had at least 1 disability. The highest absolute risk of disabilities was found for behavioral and emotional disorders, hearing loss, and visual disturbances. The estimated adjusted hazard ratios (HRs) showed a significant increased relative risk for cases compared with controls for all 7 disabilities, with the largest adjusted HRs for intracranial structural injuries (26.04 [95% CI, 15.50-43.74]), hearing loss (7.90 [95% CI, 6.68-9.33]), and motor function disorders (4.65 [95% CI, 3.72-5.80]). The adjusted HRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for Streptococcus pneumoniae infection (eg, 7.89 [95% CI, 5.18-12.02] for seizure) compared with Haemophilus influenzae infection (2.46 [95% CI, 1.63-3.70]) or Neisseria meningitidis infection (1.38 [95% CI, 0.65-2.93]). The adjusted HRs for cognitive disabilities, seizures, behavioral and emotional disorders, and intracranial structural injuries were significantly higher for children diagnosed with bacterial meningitis at an age below the median. Conclusions and Relevance: The findings of this cohort study of individuals diagnosed with bacterial meningitis during childhood suggest that exposed individuals may have had an increased risk for long-term disabilities (particularly when diagnosed with pneumococcal meningitis or when diagnosed at a young age), highlighting the need to detect disabilities among surviving children.

Incidence of non-invasive all-cause pneumonia in children in the United States before and after the introduction of pneumococcal conjugate vaccines: a retrospective claims database analysis.

BACKGROUND: Pneumonia is the most serious form of acute respiratory infection and Streptococcus pneumoniae is a leading cause of pediatric bacterial pneumonia. Pneumococcal conjugate vaccines were introduced in the United States (US) in 2000 (7-valent [PCV7]) and 2010 (13-valent [PCV13]). This study estimated annual incidence rates (IRs) of all-cause pneumonia (ACP) among US children aged < 18 years before and after the introduction of PCV7 and PCV13. METHODS: ACP episodes were identified in the IBM MarketScan Commercial and Medicaid Databases using diagnosis codes. Annual IRs were calculated overall and by inpatient and outpatient settings as the number of episodes per 100,000 person-years (PY) for all children aged < 18 years and by age group (< 2, 2-4, and 5-17 years). National estimates of annual pneumonia IRs were extrapolated using Census Bureau data. Interrupted time series (ITS) analyses were used to assess immediate and gradual changes in monthly pneumonia IRs, adjusting for seasonality. RESULTS: In the commercially-insured population, ACP IRs declined between the pre-PCV7 period (1998-1999) and late PCV13 period (2014-2018) from 5,322 to 3,471 episodes per 100,000 PY for children aged < 2 years, from 4,012 to 3,794 episodes per 100,000 PY in children aged 2-4 years but increased slightly from 1,383 to 1,475 episodes per 100,000 PY in children aged 5-17 years. The ITS analyses indicated significant decreases in monthly ACP IRs in the early PCV7 period (2001-2005) among younger children and in the early PCV13 period (2011-2013) among all children. Increases were observed in the late PCV7 period (2006-2009) among all age groups, but were only significant among older children. IRs of inpatient ACP decreased across all age groups, but outpatient pneumonia IRs remained stable during the study timeframe, even increasing slightly in children aged 5-17 years. More prominent declines were observed for Medicaid-insured children across all age groups; however, Medicaid IRs were higher than IRs of commercially-insured children during the entire study timeframe. CONCLUSIONS: ACP disease burden remains high in US children of all ages despite overall reductions in incidence rates during 1998-2018 following the introduction of PCV7 and PCV13.

Healthcare resource utilisation and cost of pneumococcal disease from 2003 to 2019 in children ≤17 years in England.

OBJECTIVE: To estimate healthcare resource utilisation (HCRU) and costs associated with pneumococcal disease (PD) in children aged ≤17 years in England from 2003-2019. METHODS: A retrospective study in children aged ≤17 years was conducted using the Clinical Practice Research Datalink Gold primary care database and Hospital Episodes Statistics Admitted Patient Care database from 2003-2019. Episodes of invasive pneumococcal disease (IPD) were identified in hospital, pneumococcal pneumonia (PP) and all-cause pneumonia (ACP) episodes in primary care and in hospital, and acute otitis media (AOM) episodes in primary care. General practitioner (GP) visits and inpatient admission yearly rates were calculated per 1,000 persons. The average inpatient and primary care cost per episode were calculated. The Mann-Kendall test was used to assess monotonic time trends. RESULTS: 1,500,686 children were followed from 2003-2019. The highest average inpatient cost per episode [£34,255 (95%CI 27,222-41,288)] was in IPD, followed by ACP [£3,549 (95%CI 3,405-3,693)] and PP [£1,498 (95%CI 1,153-1,843)]. The highest primary care costs per episode were in AOM [£48.7 (95%CI 48.7-48.7)], followed by PP [£38.4 (95%CI 37.0-39.7)] and ACP [£28.6 (95%CI 28.2-29.1)]. The highest inpatient admission and GP visits yearly rates were observed in children aged <2 years. Across years, a significant decrease in GP visits yearly rates was observed for PP, ACP and AOM in children overall (p-value<0.001). A decrease in primary care costs was observed for ACP (p-value<0.001). There was an increasing trend in AOM primary care costs (p-value<0.001). No significant trends were observed in inpatient admission yearly rates in PP, ACP or IPD and inpatient costs per episode in PP, ACP and IPD. CONCLUSION: From 2003-2019, primary care HCRU and costs decreased (except for PP cost), but no trends in inpatient HCRU and costs were observed. The economic burden of pneumonia, IPD and AOM remains substantial in children aged ≤17 years in England.

Economic burden of acute otitis media, pneumonia, and invasive pneumococcal disease in children in the United States after the introduction of 13-valent pneumococcal conjugate vaccines during 2014-2018.

BACKGROUND: Streptococcus pneumoniae remains a leading cause of morbidity, mortality, and healthcare resource utilization (HRU) among children. This study quantified HRU and cost of acute otitis media (AOM), pneumonia, and invasive pneumococcal disease (IPD). METHODS: The IBM MarketScan® Commercial Claims and Encounters and Multi-State Medicaid databases from 2014 to 2018 were analyzed. Children with AOM, all-cause pneumonia, or IPD episodes were identified using diagnosis codes in inpatient and outpatient claims. HRU and costs were described for each condition in the commercial and Medicaid-insured populations. National estimates of the number of episodes and total cost ($US 2019 for each condition were extrapolated using data from the US Census Bureau. RESULTS: Approximately 6.2 and 5.6 million AOM episodes were identified in commercial and Medicaid-insured children, respectively, during the study period. Mean cost per AOM episode was $329 (SD $1505) for commercial and $184 (SD $1524) for Medicaid-insured children. A total of 619,876 and 531,095 all-cause pneumonia cases were identified among commercial and Medicaid-insured children, respectively. Mean cost per all-cause pneumonia episode was $2304 (SD $32,309) in the commercial and $1682 (SD $19,282) in the Medicaid-insured population. A total of 858 and 1130 IPD episodes were identified among commercial and Medicaid-insured children, respectively. Mean cost per IPD episode was $53,213 (SD $159,904) for commercial and $23,482 (SD $86,209) for the Medicaid-insured population. Nationally, there were over 15.8 million cases of AOM annually, with total estimated cost of $4.3 billion, over 1.5 million cases of pneumonia annually, with total cost of $3.6 billion, and about 2200 IPD episodes annually, for a cost of $98 million. CONCLUSIONS: The economic burden of AOM, pneumonia, and IPD among US children remains substantial. IPD and its manifestations were associated with higher HRU and costs per episode, compared to AOM and all-cause pneumonia. However, owing to their higher frequencies, AOM and all-cause pneumonia were the main contributors to the economic burden of pneumococcal disease nationally. Additional interventions, such as the development of pneumococcal conjugate vaccinees with sustained protection of existing vaccine type serotypes as well as broader inclusion of additional serotypes, are necessary to further reduce the burden of disease caused by these manifestations.

Trends in Streptococcus pneumoniae Antimicrobial Resistance in US Children: A Multicenter Evaluation.

Background: Antimicrobial resistance (AMR) poses a significant challenge for treating pneumococcal disease. This study assessed AMR trends in Streptococcus pneumoniae from US children. Methods: We evaluated antibiotic resistance, defined as facility antimicrobial susceptibility reports of intermediate/resistant, in 30-day nonduplicate S pneumoniae isolates from children (<18 years of age) with invasive (blood or cerebrospinal fluid/neurological) or noninvasive (respiratory or ear/nose/throat) isolates at 219 US hospital inpatient/outpatient settings in the BD Insights Research Database (January 2011-February 2020). We used descriptive statistics to characterize the percentage of antimicrobial-resistant isolates and generalized estimating equations to assess variations in resistance over time. Results: Of 7605 S pneumoniae isolates analyzed, 6641 (87.3%) were from noninvasive sources. Resistance rates were higher in noninvasive versus invasive isolates. Isolates showed high observed rates of resistance to ≥1 drug class (56.8%), ≥2 drug classes (30.7%), macrolides (39.9%), and penicillin (39.6%) and significant annual increases in resistance to ≥1 drug class (+0.9%), ≥2 drug classes (+1.8%), and macrolides (+5.0%). Conclusions: Among US children over the last decade, S pneumoniae isolates showed persistently high rates of resistance to antibiotics and significant increases in ≥1 drug class, ≥2 drug classes, and macrolide resistance rates. Efforts to address AMR in S pneumoniae may require vaccines targeting resistant serotypes and antimicrobial stewardship efforts.

Incidence of pneumococcal disease from 2003 to 2019 in children ≤17 years in England.

BACKGROUND: Pneumococcal disease is a leading cause of communicable disease morbidity and mortality globally. We aimed to estimate invasive pneumococcal disease (IPD), pneumococcal pneumonia (PP) and all-cause pneumonia (ACP) incidence rates (IRs) in children aged 0-17 years in England from 2003 to 2019. METHODS: A retrospective study in children ≤17 years old from 2003 to 2019 using the Clinical Practice Research Datalink (CPRD) Gold and Hospital Episodes Statistics Admitted Patient Care (HES APC) databases. IPD episodes were identified in hospital records (HES APC). PP (caused by Streptococcus pneumoniae only) and ACP episodes (caused by any pathogen) were identified in primary care (CPRD) and in hospital records (HES APC). Annual IRs by age-group were calculated as the number of episodes/person-years (PY) at risk, with 95% confidence intervals (95% CI). Interrupted time series analyses were conducted to assess changes in IRs across the post-PCV7 (2007-2009), early post-PCV13 (2011-2014) and late post-PCV13 (2015-2019) periods compared to the pre-PCV7 period (2003-2005) using generalized linear models. RESULTS: 170 IPD episodes, 769 PP episodes and 12,142 ACP episodes were identified in 1,500,686 children in 2003-2019. The overall IPD, PP and ACP IRs (per 100,000 PY) were 2.29 (95% CI 1.96-2.66), 10.34 (95% CI 9.62-11.10) and 163.37 (95% CI 160.47-166.30), respectively. The highest IPD, PP and ACP IRs were observed in children aged < 2 years compared to older children (2-4 and 5-17 years). IPD IRs decreased between the pre-PCV7 period and the late post-PCV13 period from 3.28 (95% CI 2.42-4.33) to 1.41 (95% CI 0.80-2.29), IRR 0.28 (95% CI 0.09-0.90), p-value 0.033. PP IRs declined between the pre-PCV7 period and the late post-PCV13 period from 14.65 (95% CI 12.77-16.72) to 3.87 (95% CI 2.81-5.20), IRR 0.19 (95% CI 0.09-0.38), p-value < 0.001. ACP IRs declined between the pre-PCV7 period and the late post-PCV13 period from 167.28 (95% CI 160.78-173.96) to 124.96 (95% CI 118.54-131.63), IRR 0.77 (95% CI 0.66-0.88), p-value < 0.001. CONCLUSIONS: The clinical burden of IPD, PP and ACP declined in children in England aged 0-17 years between 2003 and 2019, especially in the late post-PCV13 period. This study highlights the importance of PCV vaccination in reducing the burden of PD and ACP in children in England.

Incidence of acute otitis media from 2003 to 2019 in children ≤ 17 years in England.

BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2006 and the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 in the UK. PCVs are active immunization for the prevention of invasive disease, pneumonia and acute otitis media (AOM) caused by Streptococcus pneumoniae in children. The aim of this observational study was to estimate incidence rates (IRs) of AOM in children ≤17 years from 2003 to 2019 in England, before and after the introduction of pneumococcal conjugate vaccines (PCVs). METHODS: AOM episodes were identified using Read diagnosis codes in children aged ≤17 years in the Clinical Practice Research Datalink (CPRD) Gold database from 2003 to 2019. Annual IRs with 95% confidence intervals (CI) by age group were calculated as the number of episodes/person-years (PY) at risk. Interrupted time series analyses were conducted to estimate incidence rate ratios (IRR) across post-PCV7 (2007-2009), early post-PCV13 (2011-2014) and late post-PCV13 (2015-2019) periods compared to the pre-PCV7 period (2003-2005) using generalized linear models. RESULTS: From 2003 to 2019, 274,008 all-cause AOM episodes were identified in 1,500,686 children. The overall AOM IR was 3690.9 (95% CI 3677.1-3704.8) per 100,000 PY. AOM IRs were highest in children aged < 5 years and decreased by age; < 2 years: 8286.7 (95% CI 8216.8-8357.1); 2-4 years: 7951.8 (95% CI 7902.5-8001.4); 5-17 years: 2184.4 (95% CI 2172.1-2196.8) (per 100,000 PY). Overall AOM IRs declined by 40.3% between the pre-PCV7 period and the late-PCV13 period from 4451.9 (95% CI 4418.1-4485.9) to 2658.5 (95% CI 2628.6-2688.7) per 100,000 PY, and across all age groups. IRRs indicated a significant decrease in AOM IRs in all the post-vaccination periods, compared to the pre-PCV7 period: post-PCV7 0.87 (95% CI 0.85-0.89), early post-PCV13 0.88 (95% CI 0.86-0.91), and late post-PCV13 0.75 (95% CI 0.73-0.78). CONCLUSIONS: The AOM IRs declined during the 2003-2019 period; however, the clinical burden of AOM remains substantial among children ≤17 years in England.

A Multicenter Evaluation of Trends in Antimicrobial Resistance Among Streptococcus pneumoniae Isolates From Adults in the United States.

Background: Management of pneumococcal disease is complicated by high rates of antimicrobial resistance (AMR). This study assessed AMR trends for Streptococcus pneumoniae isolates from adults with pneumococcal disease. Methods: From January 2011 to February 2020, we evaluated 30-day nonduplicate S. pneumoniae isolates from 290 US hospitals (BD Insights Research Database) from adults (≥18 years) in inpatient and outpatient settings. Isolates were required to have ≥1 AMR result for invasive (blood, cerebrospinal fluid/neurologic) or noninvasive (respiratory or ear/nose/throat) pneumococcal disease samples. Determination of AMR was based on facility reports of intermediate or resistant. Descriptive statistics and generalized estimated equations were used to assess variations over time. Results: Over the study period, 34 039 S. pneumoniae isolates were analyzed (20 749 [61%] from noninvasive sources and 13 290 [39%] from invasive sources). Almost half (46.6%) of the isolates were resistant to ≥1 drug, and noninvasive isolates had higher rates of AMR than invasive isolates. Total S. pneumoniae isolates had high rates of resistance to macrolides (37.7%), penicillin (22.1%), and tetracyclines (16.1%). Multivariate modeling identified a significant increasing trend in resistance to macrolides (+1.8%/year; P < .001). Significant decreasing trends were observed for penicillin (-1.6%/year; P < .001), extended-spectrum cephalosporins (ESCs; -0.35%/year; P < .001), and ≥3 drugs (-0.5%/year; P < .001). Conclusions: Despite decreasing trends for penicillin, ESCs, and resistance to ≥3 drugs, AMR rates are persistently high in S. pneumoniae isolates among US adults. Increasing macrolide resistance suggests that efforts to address AMR in S. pneumoniae may require antimicrobial stewardship efforts and higher-valent pneumococcal conjugate vaccines.

Incidence of Hospitalisation and Emergency Department Visits for Pneumococcal Disease in Children, Adolescents, and Adults in Liguria, Italy: A Retrospective Analysis from 2012-2018.

Streptococcus pneumoniae infection is responsible for significant morbidity and mortality, particularly in young children and older adults. The aim of this study was to investigate the incidence of hospitalisation and emergency department (ED) visits in relation to episodes of pneumococcal disease (PD) following the introduction of pneumococcal conjugate vaccines (PCVs) into the Liguria region of Italy. Between 2012 and 2018, episodes of all-cause pneumonia (80,152), pneumococcal-specific pneumonia (1254), unspecified pneumonia (66,293), acute otitis media (AOM; 17,040), and invasive PD (IPD; 1788) were identified from in-patient claims, ED and hospital discharge records, and the Liguria Chronic Condition Data Warehouse. In children < 15 years of age, pneumococcal pneumonia-related hospitalisations decreased from 35 to 13 per 100,000 person-years during the study period (p < 0.001); this decrease is potentially related to PCV use in children. All-cause pneumonia hospitalisations remained stable, whereas IPD hospitalisations increased and AOM hospitalisations decreased. In adults, hospitalisations for all-cause pneumonia increased from 5.00 to 7.50 per 1000 person-years (+50%; p < 0.001). Pneumococcal and unspecified pneumonia hospital admissions increased significantly during the study period, considerably affecting those ≥ 65 years of age. IPD hospitalisations varied across all age groups, but a significant change was not observed. Despite pneumococcal vaccination, substantial burden remains for PD in children and adults in Liguria, Italy.

Incidence of invasive pneumococcal disease in children with commercial insurance or Medicaid coverage in the United States before and after the introduction of 7- and 13-valent pneumococcal conjugate vaccines during 1998-2018.

BACKGROUND: Invasive pneumococcal disease (IPD) is a major cause of pediatric morbidity and mortality. Pneumococcal conjugate vaccines (PCVs) were introduced in the US in 2000 (PCV7) and 2010 (PCV13). This study estimated the annual incidence rates (IRs) and time trends of IPD to quantify the burden of disease in children before and after the introduction of PCV7 and PCV13 in the US. METHODS: IPD episodes were identified in the IBM MarketScan Commercial and Medicaid Databases using claims with International Classification of Diseases 9/10th Revision, Clinical Modification codes. Annual IRs were calculated as the number of IPD episodes/100,000 person-years (PYs) for children < 18 years and by age group (< 2, 2-4, and 5-17 years). National estimates of annual IPD IRs were extrapolated using Census Bureau data. Interrupted time series (ITS) analyses were conducted to assess immediate and gradual changes in IPD IRs before and after introduction of PCV7 and PCV13. RESULTS: In commercially insured children, IPD IRs decreased from 9.4 to 2.8 episodes/100,000 PY between the pre-PCV7 (1998-1999) and late PCV13 period (2014-2018) overall, and from 65.6 to 11.6 episodes/100,000 PY in children < 2 years. In the Medicaid population, IPD IRs decreased from 11.3 to 4.2 episodes/100,000 PY between the early PCV7 (2001-2005) and late PCV13 period overall, and from 42.6 to 12.8 episodes/100,000 PY in children < 2 years. The trends of IRs for meningitis, bacteremia, and bacteremic pneumonia followed the patterns of overall IPD episodes. The ITS analyses indicated significant decreases in the early PCV7 period, increases in the late PCV7 and decreases in the early PCV13 period in commercially insured children overall. However, increases were also observed in the late PCV13 period in children < 2 years. The percentage of cases with underlying risk factors increased in both populations. CONCLUSIONS: IRs of IPD decreased from 1998 to 2018, following introduction of PCV7 and PCV13, with larger declines during the early PCV7 and early PCV13 periods, and among younger children. However, the residual burden of IPD remains substantial. The impact of future PCVs on IPD IRs will depend on the proportion of vaccine-type serotypes and vaccine effectiveness in children with underlying conditions.

Health and economic burden associated with 15-valent pneumococcal conjugate vaccine serotypes in Korea and Hong Kong.

Use of pneumococcal conjugate vaccines (PCVs) has greatly reduced the incidence of invasive pneumococcal disease (IPD). V114 (VAXNEUVANCE™, Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA) is a 15-valent PCV currently approved in adults in the United States, containing the 13 serotypes in licensed PCV13 and 2 additional serotypes (22F and 33F) which are important contributors to residual pneumococcal disease. This study quantified the health and economic burden of IPD attributable to V114 serotypes in hypothetical birth cohorts from Korea and Hong Kong. A Markov model was used to estimate the case numbers and costs of IPD in unvaccinated birth cohorts over 20 years. The model was applied to 3 scenarios in Korea (pre-PCV7, pre-PCV13, and post-PCV13) and to 2 scenarios in Hong Kong (pre-PCV7 and post-PCV13). For Korea, the model predicted 62, 26, and 8 IPD cases attributable to V114 serotypes in the pre-PCV7, pre-PCV13, and post-PCV13 scenarios, respectively. Costs of V114-type IPD fell from $1.691 million pre-PCV7 to $.212 million post-PCV13. For Hong Kong, the model estimated 62 V114-associated IPD cases in the pre-PCV7 scenario and 46 in the post-PCV13 scenario. Costs attributed to all V114 serotypes were $2.322 million and $1.726 million in the pre-PCV7 and post-PCV13 periods, respectively. Vaccine-type serotypes are predicted to cause continuing morbidity and cost in Korea (19A) and Hong Kong (3 and 19A). New pediatric pneumococcal vaccines must continue to protect against serotypes in licensed vaccines to maintain disease reduction, while extending coverage to non-vaccine serotypes.

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.

Evaluation of Trends in Homeschooling Rates After Elimination of Nonmedical Exemptions to Childhood Immunizations in California, 2012-2020.

Introduction: In 2015, California passed Senate Bill No. 277 (SB 277) and became the first state in more than 30 years to eliminate nonmedical exemptions to mandatory childhood immunizations for school entry. One concern that emerged was that the law created an incentive for parents to remove children from brick-and-mortar schools to bypass the immunization requirements. Objective: To assess the trends in homeschooling rates after the elimination of nonmedical exemptions to the requirement of childhood immunizations for school entry. Design, Setting, and Participants: This preintervention-postintervention cross-sectional study calculated homeschooling rates as the number of students in kindergarten through grade 8 (K-8) enrolled through each of California's 3 homeschooling mechanisms (independent study program, private school affidavit, and private school satellite program) divided by all K-8 students enrolled in the same academic year. Data on homeschooling rates were obtained from the California Department of Education. Interrupted time series analyses were conducted using a linear regression model in which the outcome variable was the percentage of students enrolled in a homeschool program before and after SB 277. Data were collected and analyzed from October 3, 2012, to October 2, 2019. Intervention: Passage of SB 277, which eliminated nonmedical exemptions to childhood immunizations for school entry. Main Outcomes and Measures: Homeschooling rates for K-8 students. Results: Among the students included in the analysis, the homeschooling enrollment for K-8 students in California increased from 35 122 students (0.8%) during the 2012-2013 school year to 86 574 students (1.9%) during the 2019-2020 school year; however, the implementation of SB 277 was not associated with an increase in the percentage of students enrolled in homeschooling programs in California beyond the secular trend. The increase in homeschooling was greatest for the lower grade levels: kindergarten homeschooling enrollment increased from 2068 students (0.4%) in the 2012-2013 school year to 10 553 students (1.9%) in the 2019-2020 school year, whereas the grade 8 homeschool enrollment rate increased from 5146 students (1.0%) in the 2012-2013 school year to 10 485 students (2.0%) in the 2019-2020 school year. Independent study programs accounted for 20 149 students (45.3%) of homeschooling enrollment, private school affidavits accounted for 19 333 students (43.5%), and private school satellite programs accounted for 4935 students (11.1%) during the 2015-2016 school year. Conclusions and Relevance: The findings of this study suggest that legislative action to limit nonmedical exemptions for compulsory vaccination for school entry is not associated with removal of students from classroom-based instruction in brick-and-mortar institutions.

Primary care providers need education and resources to provide optimal care for children and adults with spina bifida.

PURPOSE: The objective of this study was to describe the knowledge, attitudes, and practices related to caring for youth with SB within a statewide pediatric primary care medical home network. METHODS: Health care professionals who were members of the Pennsylvania Medical Home Program (PAMHP) statewide network were surveyed on sociological demographics, confidence in and knowledge of topics that impact the spina bifida (SB) population, education on SB, designating responsibility of care, tasks completed in the office, and transition from pediatric to adult care from October 2016 through November 2016. RESULTS: Among 67 respondents, 78%believed counseling families/caregivers about the impact of SB on everyday life was a shared responsibility between primary care physicians (PCP) and SB clinics. Eighty five percent of participants indicated they had exposure to SB through clinical courses or didactics in training but only 54%of participants felt knowledgeable on the impact of SB on everyday life. CONCLUSION: Findings suggest a need for increased educational efforts, improved awareness of SB, and access to evidence-based guidelines for PCPs to promote accessible and coordinated care to individuals with SB.

Remote Patient Monitoring and Incentives to Support Smoking Cessation Among Pregnant and Postpartum Medicaid Members: Three Randomized Controlled Pilot Studies.

BACKGROUND: Smoking rates among low-income individuals, including those eligible for Medicaid, have not shown the same decrease that is observed among high-income individuals. The rate of smoking among pregnant women enrolled in Medicaid is almost twice that among privately insured women, which leads to significant disparities in birth outcomes and a disproportionate cost burden placed on Medicaid. Several states have identified maternal smoking as a key target for improving birth outcomes and reducing health care expenditures; however, efficacious, cost-effective, and feasible cessation programs have been elusive. OBJECTIVE: This study aims to examine the feasibility, acceptability, and effectiveness of a smartwatch-enabled, incentive-based smoking cessation program for Medicaid-eligible pregnant smokers. METHODS: Pilot 1 included a randomized pilot study of smartwatch-enabled remote monitoring versus no remote monitoring for 12 weeks. Those in the intervention group also received the SmokeBeat program. Pilot 2 included a randomized pilot study of pay-to-wear versus pay-to-quit for 4 weeks. Those in a pay-to-wear program could earn daily incentives for wearing the smartwatch, whereas those in pay-to-quit program could earn daily incentives if they wore the smartwatch and abstained from smoking. Pilot 3, similar to pilot 2, had higher incentives and a duration of 3 weeks. RESULTS: For pilot 1 (N=27), self-reported cigarettes per week among the intervention group declined by 15.1 (SD 27) cigarettes over the study; a similar reduction was observed in the control group with a decrease of 17.2 (SD 19) cigarettes. For pilot 2 (N=8), self-reported cigarettes per week among the pay-to-wear group decreased by 43 cigarettes (SD 12.6); a similar reduction was seen in the pay-to-quit group, with an average of 31 (SD 45.6) fewer cigarettes smoked per week. For pilot 3 (N=4), one participant in the pay-to-quit group abstained from smoking for the full study duration and received full incentives. CONCLUSIONS: Decreases in smoking were observed in both the control and intervention groups during all pilots. The use of the SmokeBeat program did not significantly improve cessation. The SmokeBeat program, remote cotinine testing, and remote delivery of financial incentives were considered feasible and acceptable. Implementation challenges remain for providing evidence-based cessation incentives to low-income pregnant smokers. The feasibility and acceptability of the SmokeBeat program were moderately high. Moreover, the feasibility and acceptability of remote cotinine testing and the remotely delivered contingent financial incentives were successful. TRIAL REGISTRATION: ClinicalTrials.gov NCT03209557; https://clinicaltrials.gov/ct2/show/NCT03209557.

Pneumococcal vaccination coverage among adults aged 19 to 64 years with immuno-compromising conditions, cerebrospinal fluid (CSF) leaks, or cochlear implants in the US.

Background: Adults with immuno-compromising conditions, CSF leaks, or cochlear implants are at increased risk for pneumococcal disease (high-risk patients), yet pneumococcal vaccination rates in the US for this group are low.Methods: A retrospective cohort analysis was conducted from 2010 to 2018 using the Truven Health MarketScan database to estimate pneumococcal vaccination coverage among adults aged 19 to 64 years newly diagnosed with high-risk conditions, and to assess factors associated with receiving the recommended pneumococcal vaccines.Results: The study sample included 2,497,799 adults aged 19 to 64 years old with newly diagnosed high-risk conditions. Most of the study cohort had seven or more annual physician office (52%) and pharmacy (56%) visits. The proportion of high-risk adults who received at least one pneumococcal vaccination increased from 5.4% after 1 year of follow-up to 14.2% after 6 years of follow-up. Compared to those who received no pneumococcal vaccination, high-risk adults who received any pneumococcal vaccination were more likely to be older, female, enrolled in an HMO, had more healthcare encounters, and were treated by a primary care provider.Conclusion: Despite numerous healthcare encounters annually, very few high-risk adults received pneumococcal vaccines, highlighting the need for implementing targeted interventions to increase vaccine uptake in this vulnerable population.