Cost-effectiveness of PCV20 to Prevent Pneumococcal Disease in the Pediatric Population: A German Societal Perspective Analysis.

INTRODUCTION: Since 2009, a pneumococcal conjugate vaccine (PCV) covering 13 serotypes (PCV13) has been included by Germany's Standing Committee on Vaccinations for infants, resulting in major reductions in pneumococcal disease (PD). Higher-valent vaccines may further reduce PD burden. This cost-effectiveness analysis compared 20-valent PCV (PCV20) under a 3+1 schedule with 15-valent PCV (PCV15) and PCV13, both under 2+1 schedule, in Germany's pediatric population. METHODS: A Markov model with annual cycles over a 10-year time horizon was adapted to simulate the clinical and economic impact of pediatric vaccination with PCV20 versus lower-valent PCVs in Germany. The model used PCV13 clinical effectiveness and impact studies as well as PCV7 efficacy studies for vaccine direct and indirect effect estimates. Epidemiologic, utility, and medical cost inputs were obtained from published sources. Benefits and costs were discounted at 3% from a German societal perspective. Outcomes included PD cases, deaths, costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: In the base case, PCV20 provided greater health benefits than PCV13, averting more cases of invasive pneumococcal disease (IPD; 15,301), hospitalized and non-hospitalized pneumonia (460,197 and 472,365, respectively), otitis media (531,634), and 59,265 deaths over 10 years. This resulted in 904,854 additional QALYs and a total cost saving of €2,393,263,611, making PCV20 a dominant strategy compared with PCV13. Compared to PCV15, PCV20 was estimated to avert an additional 11,334 IPD, 704,948 pneumonia, and 441,643 otitis media cases, as well as 41,596 deaths. PCV20 was associated with a higher QALY gain and lower cost (i.e., dominance) compared with PCV15. The robustness of the results was confirmed through scenario analyses as well as deterministic and probabilistic sensitivity analyses. CONCLUSION: PCV20 3+1 dominated both PCV13 2+1 and PCV15 2+1 over 10 years. Replacing lower-valent PCVs with PCV20 would result in greater clinical and economic benefits, given PCV20's broader serotype coverage.

Pneumococcal diseases (e.g., ear infections, pneumonia, bloodstream infections) are among the leading causes of illness and death in children worldwide. The pneumococcal conjugate vaccine protects against pneumococcal diseases and has significantly reduced the number of newly diagnosed cases. Higher-valent vaccines (which provide coverage for a greater number of disease-causing serotypes) have recently received European Commission approval for use in adults and  children. This study examined costs and health benefits associated with the 20-valent pneumococcal conjugate vaccine (PCV20) under a 3+1 (i.e., three primary doses and one booster dose) schedule in Germany's childhood vaccination program compared with 13-valent pneumococcal conjugate vaccine (PCV13) and the 15-valent pneumococcal conjugate vaccine (PCV15), both under a 2+1 (two primary doses, one booster) schedule. PCV20 was estimated to result in greater health benefits from avoiding more cases in pneumococcal diseases and lower costs compared with both PCV13 and PCV15. PCV20, therefore, is considered the best option among the three vaccines for children in Germany.

Did the change of the vaccination schedule effect pneumococcal conjugate vaccination compliance and adherence of premature and mature born infants in Germany? Answers from a claims database analysis.

BACKGROUND: In August 2015, the German Standing Committee on Vaccination (STIKO) changed the pneumococcal conjugate vaccination (PCV) schedule for mature infants from a 3+1 to a 2+1scheme. For premature infants, the 3+1schedule remained unchanged. Aim was to assess vaccination rates, completeness, and timeliness for PCV stratified by premature and mature infants before and after the recommendation change based on real-world data. METHODS: Retrospective claims data analyses were conducted using a comprehensive research database. The study population consisted of all mature and premature infants born in 2013, 2016, or 2018 with an individual follow-up of 24 months using ICD-10-GM codes P07.2 and P07.3 for premature infants. Hexavalent (HEXA) combination vaccination with a consistent 3+1recommendation for premature and mature infants was analyzed as a reference. RESULTS: After follow-up of 24 months, rates of premature and mature infants receiving ≥1PCV and HEXA vaccination steadily increased since the change of STIKO's recommendation. However, in 2018 (2016/2013), only 47 % (41 %/65 %) of premature but 74 % (72 %/68 %) of mature infants obtained the recommended 3+1 respectively 2+1 PCV doses. At the same age, a consistent increase in complete HEXA vaccination with 3+1 doses was observed over time in premature (2013/2016/2018: 66 %/68 %/70 %) and mature (2013/2016/2018: 69 %/72 %/73 %) infants. Timeliness of PCV and HEXA booster administration remained stable with âˆ¼50 % of all premature and mature infants receiving the booster according to recommended timelines. CONCLUSION: There is no proven evidence that the reduced PCV schedule for mature infants induced a higher acceptance of vaccination. The rate of unvaccinated infants remained at a considerable level and vaccinations were often delayed. Although the STIKO still recommends a 3+1 PCV schedule for premature infants in Germany, less than half of children showed a completed vaccination series. To protect these vulnerable groups, efforts are needed to increase adherence to the STIKO recommendation especially for premature infants.

Vaccination rates and adherence in premature infants before and after pneumococcal conjugate vaccine schedule change for term infants - A claims database analysis in Germany.

BACKGROUND: In 2015, the German Standing Committee on Vaccination (STIKO) changed the pneumococcal conjugate vaccination (PCV) schedule for mature infants from a 3+1scheme (2, 3, 4, and 11-14 months of age) to a 2+1scheme (2, 4, and 11-14 months of age). For premature infants, the 3+1scheme remained. The aim of this study was to assess vaccination rates, completeness, and timeliness for PCV in premature infants before and after the modified recommendation. METHODS: A retrospective claims data analysis using the "Institut für angewandte Gesundheitsforschung Berlin" Research Database was conducted. Premature infants born in 2013 and 2016 with an individual follow-up of 24 months were included. Hexavalent combination (HEXA) vaccination with a consistent 3+1recommendation for mature and premature infants was analyzed as reference vaccination. RESULTS: After 24 months, the PCV rate for at least one dose remained stable in premature newborns of 2016 compared to 2013, while the HEXA vaccination rate increased slightly. However, a significant decrease of a completed PCV schedule (4 doses) in premature infants was noted, whereas the completeness of HEXA vaccination did not change. The timeliness of PCV in premature newborns increased for the first and the booster PCV, while the timeliness of HEXA immunization did not change from 2013 to 2016. CONCLUSION: Although STIKO still recommends a 3+1PCV schedule for premature infants in Germany, premature infants were vaccinated according to the changed recommendations for mature born infants. A substantial share of premature infants remained unvaccinated, and their vaccinations were often delayed.

Nasopharyngeal Carriage in Children After the Introduction of Generalized Infant Pneumococcal Conjugate Vaccine Immunization in Germany.

Epidemiological data on nasopharyngeal (NP) bacterial carriage in children in Germany are scarce. We prospectively characterized NP colonization to evaluate the impact of pneumococcal immunization. We longitudinally collected NP swabs from 2-month-old infants (visit 1; V1) at eight representative pediatric offices 10/2008-06/2009. The second swabs were taken at age 9-12 months (V2); the third swab was taken 3-6 months after the booster vaccination at age 17-19 months (V3), and the fourth swab (V4) at age 59-61 months. Samples were broth enriched, cultured for bacteria, and isolates were serotyped. Demographic risk factors for colonization were evaluated. Among 242 vaccinees, bacterial NP carriage increased with age [from 27.2% (V1) to 70.1% (V4)]; leading isolates were S. pneumoniae, H. influenzae, M. catarrhalis, and S. pyogenes. Overall pneumococcal carriage increased [14.7% (V1), 31.5% (V2), 34.8% (V3), 42.2% (V4)], being even greater among day-care attendees. Serotype distribution changed during the study period, with vaccine serotypes declining. At visit 4, 10-valent pneumococcal conjugate vaccine (PCV10) serotypes were no longer among the NP flora, while some serotypes unique to 13-valent pneumococcal conjugate vaccine (PCV13; 3 and 19A) were found. In Germany, universal infant PCV immunization was associated with an almost complete eradication of PCV-serotypes and concomitant increase of non-PCV-serotypes, mainly 11A, 22F, and 23A.

Vaccination rates and adherence in pneumococcal conjugate vaccination in mature born infants before and after vaccination schedule change - A claims database analysis.

BACKGROUND: In August 2015, the German Standing Committee on Vaccination (STIKO) changed the pneumococcal conjugate vaccination (PCV) schedule for mature infants from a 3+1 scheme to a 2+1 scheme. It was expected that a reduction of doses would be associated with a higher acceptance of the vaccination. Aim of this study was to assess vaccination rates and adherence for PCV after the change of recommendation based on real-world data. METHODS: A retrospective claims data analysis using the InGef Research Database was conducted. The study population consisted of all mature infants born in 2013 (last birth cohort completely under 3+1 recommendation) or 2016 (first birth cohort completely under 2+1 recommendation) with an individual follow-up of 24 months. Hexavalent combination vaccination (HEXA) with a consistent 3+1 recommendation was analyzed as reference. RESULTS: After follow-up of 24 months, 90.9% (91.2%) of the 2016 (2013) cohort received at least one dose of PCV. At the same age, 67.7% of the 2013 cohort received a booster dose according to the 3+1 schedule and 75.6% of the 2016 cohort received a booster dose presumably either according to the 2+1 (71.7%) or 3+1 (3.9%) schedule. Of those receiving the booster dose, only 46.3% (2016) and 45.1% (2013) received the booster dose on time as recommended. The HEXA vaccination rate increased from 88.9% (2013) to 91.6% (2016) with a full series completion in 69.1% (2013) vs 72.9% (2016). The proportion of infants receiving the booster vaccination on time rose to 50.0% in 2016 (47.8% in 2013). CONCLUSIONS: Although the rate for the PCV booster dose slightly increased, nearly a quarter of the infants born in 2016 did not receive a booster dose at all. Furthermore, vaccinations were still frequently delayed, and the rate of unvaccinated infants remained constant.

Oral glucose before venepuncture relieves neonates of pain, but stress is still evidenced by increase in oxygen consumption, energy expenditure, and heart rate.

Oral glucose was recommended as pain therapy during venepuncture in neonates. It is unclear whether this intervention reduces excess oxygen consumption (o(2)), energy loss, or cardiovascular destabilization associated with venepuncture, and whether <2 mL glucose solution is effective. We tested the hypothesis that oral glucose solution attenuates the increases in neonatal oxygen consumption, energy expenditure (EE), and heart rate associated with venepuncture for two different volumes of glucose solution (2 and 0.4 mL). In this prospective, randomized, controlled, double-blind trial, 58 neonates (gestational age, 31-42 wk; postnatal age, 1-7 d) were randomized to 2 mL glucose 30%, 0.4 mL glucose 30%, or 2 mL water by mouth before venepuncture. The videotaped behavioral pain reactions were scored with the Premature Infant Pain Profile. Cry duration, o(2), EE (indirect calorimetry), and heart rate were measured. The 2 mL glucose solution reduced pain score and crying after venepuncture compared with controls [median pain score, 5.5 (interquartile range, 4-9) versus 11 (7-12), p = 0.01; median duration of first cry, 0 s (0-43 s) versus 13 s (2-47 s), p < 0.05, respectively]. The 0.4 mL glucose solution had no effect. The 2 mL glucose solution did not attenuate the o(2) increase during venepuncture (1.5 +/- 0.2 mL/kg min (water) versus 1.7 +/- 0.5 (0.4 mL glucose) versus 1.1 +/- 0.2 (2 mL glucose) (mean +/- SEM) nor EE nor heart rate. We conclude that oral administration of 2 mL glucose 30% before venepuncture reduced pain expression and crying, but did not prevent the rise in o(2), EE, or heart rate. Alternative therapies against the stress of nonpainful handling during venepuncture should be explored.

Longitudinal study of energy expenditure in preterm neonates <30 weeks' gestation during the first three postnatal weeks.

OBJECTIVES: The objective of this study was to measure energy expenditure (EE) in a contemporary population of preterm neonates <30 weeks' gestation. STUDY DESIGN: Prospective longitudinal cohort study in 26 consecutive preterm neonates (gestational age, 27 weeks [23-29] [median, range]; birth weight, 980 g [554-1592]). EE was measured by indirect calorimetry on postnatal days 1, 3, 5, 10, and 21. Data on body weight, energy intake, and medical therapy were prospectively collected. RESULTS: EE increased from 121 +/- 25 kJ/kg per day (29 +/- 6 kcal/kg per day) (mean +/- SD) on day 1 to 222 +/- 25 kJ/kg per day (53 +/- 6 kcal/kg per day) on day 21. An energy deficit occurred only on day 1. EE was closely related to energy intake: For each additional kJ given, EE increased by 0.3 kJ (r = 0.789, P <.0001). Neonates with a birth weight <1000 g did not have a more pronounced energy deficit than the heavier neonates. EE during nasal continuous positive airway pressure in the first postnatal week was 25% lower than during spontaneous respiration. CONCLUSIONS: EE could be predicted from energy intake with acceptable accuracy in preterm neonates <30 weeks' gestation during the first 3 postnatal weeks. There was no prolonged energy deficit.