Phase 3 Safety and Immunogenicity Study of a Three-dose Series of Twenty-valent Pneumococcal Conjugate Vaccine in Healthy Infants and Toddlers.

BACKGROUND: Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains. METHODS: This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PCV (PCV13) in healthy infants. Participants received 2 infant doses and a toddler dose of PCV20 or PCV13, with diphtheria-tetanus-acellular pertussis combination vaccine at all doses and measles, mumps, rubella and varicella vaccines at the toddler dose. Primary pneumococcal immunogenicity objectives were to demonstrate noninferiority (NI) of PCV20 to PCV13 for immunoglobulin G geometric mean concentrations after infant and toddler doses and percentages of participants with predefined serotype-specific immunoglobulin G concentrations after infant doses. Safety endpoints included local reactions, systemic events and adverse events. RESULTS: Overall, 1204 participants were vaccinated (PCV20, n = 601; PCV13, n = 603). One month after the toddler dose, 19/20 serotypes met NI for immunoglobulin G geometric mean concentrations; serotype 6B narrowly missed NI [PCV20/PCV13 geometric mean ratio: 0.57 (2-sided 95% confidence interval: 0.48-0.67); NI criterion: lower 2-sided 95% confidence interval >0.5]. Sixteen/twenty serotypes met NI for ≥1 primary objective after 2 infant doses. PCV20 induced robust opsonophagocytic activity, and boosting responses were observed for all vaccine serotypes, including those missing statistical NI. The safety/tolerability profile of PCV20 was like that of PCV13. CONCLUSIONS: PCV20 3-dose series in infants was safe and elicited robust immune responses. Based on these results and PCV13 experience, PCV20 3-dose series is expected to be protective for all 20 vaccine serotypes. NCT04546425.

Immunogenicity and Safety of a Third COVID-19 BNT162b2 mRNA Vaccine Dose in 5- to 11-Year Olds.

In this ongoing study, substantially increased ancestral SARS-CoV-2 neutralizing responses were observed 1 month after a third 10-µg BNT162b2 dose given to 5 to 11-year olds versus neutralizing responses post-dose 2. After dose 3, increased neutralizing responses against Omicron BA.1 and BA.4/BA.5 strains were also observed. The safety/tolerability profile was acceptable. (NCT04816643).

Association of Neutrophil-to-Lymphocyte Ratio and Lymphocyte-to-Monocyte Ratio with Treatment Modalities of Acute Ischaemic Stroke: A Pilot Study.

Background and Objectives: Ischaemic stroke (IS) is the leading cause of death and disability worldwide. All stages of cerebral ischaemia, but especially acute phase, are associated with inflammatory response. Recent studies showed that neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) may be used to assess inflammation in IS. To test whether there is a relationship between these parameters and type of stroke treatment, we analysed NLR and LMR in IS patients treated with three different modalities. Materials and Methods: The study included 58 adults with acute IS. A total of 28 patients received intravenous thrombolysis. In another 10 patients, the thrombolytic therapy was followed by thrombectomy and 20 patients did not undergo causal treatment. Blood samples were obtained within 24 h of the stroke diagnosis to calculate NLR and LMR. Next, NLR and LMR of the study subgroups were compared. Results: Our study revealed that NLR was significantly higher in patients treated with thrombectomy following thrombolysis, compared to no causal treatment. Statistical analysis demonstrated that patients with high National Institutes of Health Stroke Scale (NIHSS) scores presented higher NLR than in those with low NIHSS scores. Additionally, patients with high-sensitivity C-reactive protein (hs-CRP) ≥ 3 mg/L presented with significantly higher NLR and significantly lower LMR than the group of patients with lower hs-CRP (<3 mg/L). Conclusions: The main finding of this pilot study was that NLR in IS patients treated using thrombectomy following thrombolysis was markedly higher than that in other treatment groups, which was associated with increased severity of the disease in these patients. Therefore, patients with higher NLR may be expected to have more severe stroke. The link between stroke severity and NLR deserves further study.

Antenatal corticosteroids and respiratory distress syndrome - the first Polish national survey.

OBJECTIVES: Our retrospective study aimed to evaluate the rate and the appropriate use of antenatal corticosteroid therapy, and their effect on the incidence and treatment of respiratory distress syndrome (RDS) and its complications. MATERIAL AND METHODS: A retrospective analysis of clinical practice in Poland was performed using standard investigating tools: a questionnaire on the frequency of using antennal corticosteroids in the selected centers, as well as neonatal data. A total of 987 newborns at ≤ 32 weeks of gestation, treated in 54 centers (including 42 tertiary and 12 secondary referral centers) over a period of 6 months in 2013, were deemed eligible. The study group consisted of 749 newborns whose mothers received antenatal steroids. The non-steroid group included 238 newborns. RESULTS: Antenatal corticosteroids were administered to 75.89% of the neonates from the study group, with 79% and 21% receiving one and two courses, respectively. Children whose mothers received prenatal steroids presented with less extensive radiographic changes typical of RDS, and less often required surfactant therapy (70% vs. 78%; p = 0.0143). In the group of children undergoing antenatal steroid therapy, the percentage of BPD was lower (13.27% vs. 18.63%) (p = 0.0881). The mortality rates were 20.91% and 10.81% in controls and the study group, respectively (p = 0.0001). CONCLUSIONS: The percentage of antenatal steroid use in secondary and tertiary referral centers in Poland is unsatisfactorily low (76%). Antenatal corticosteroids demonstrated high efficacy in decreasing severe forms of RDS, less need for surfactant therapy, and reduced BPD and mortality rates.

STRATEGIES OF USING SURFACTANT: RESULTS OF THE FIRST POLISH NATIONAL SURVEY OF DAILY PRACTICE.

BACKGROUND: The efficiency of routine practices in the management of neonatal respiratory distress syndrome (RDS) have never been systematically investigated in Poland. OBJECTIVE: To evaluate RDS treatment policies and short-term outcomes in neonatal intensive care units (NICUs). MATERIAL AND METHODS: We retrospectively analyzed medical records of premature neonates ≤ 32 weeks' gestation, diagnosed with RDS in level-2 and level-3 referral centers. Collected data: comprised clinical variables, antenatal corticosteroids, respiratory support, surfactant (SFT) policies and short-term outcomes. RESULTS: Data of 987 infants from 53 NICUs were analyzed. The median gestational age was 29 weeks (range 22-32) and birth weight 1190 g (range 340-2860). Infants requiring SFT had significantly lower exposure to antenatal corticosteroids (75%) vs. those managed without SFT (83%, p = 0.006). SFT was given to 59% infants in level-3 NICUs and 40% in level-2. There was significant variability of SFT use between level 2 and level 3 NICU. (9% to 100%). Poractant alfa was most commonly used (97%) in the median initial dose of 170 mg/kg (IQR 120-200). Single application was most frequent (79.8%). SFT administration methods were endotracheal instillation in babies maintained on mechanical ventilation (68.0%), INSURE (27.6%) and minimally-invasive delivery (MIST) 4.4%. Early rescue treatment remained core SFTstrategy (57.4% cases), while prophylaxis accounted for only 13.3% cases. CONCLUSIONS: There is considerable variation in the frequency of use of surfactant in Polish neonatal centers. Traditional intratracheal instillation with subsequent mechanical ventilation dominates, although newer methods INSURE and MIST are becoming increasingly popular. Early rescue SFT is a predominant strategy, which conforms to current standards. The rate of antenatal corticosteroids remains too low.

Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine manufactured with and without polysorbate 80 given to healthy infants at 2, 3, 4 and 12 months of age.

BACKGROUND: Polysorbate 80 (P80), a nonionic detergent used to solubilize proteins, is used in both oral and injectable medications including vaccines. Development studies with 13-valent pneumococcal conjugate vaccine (PCV13) showed that adding P80 resulted in a more robust manufacturing process. Before adding P80 to the formulation of PCV13, we investigated the immunogenicity and safety of PCV13 with and without P80. METHODS: Phase 3, parallel-group, randomized, active-controlled, double-blind multicenter trial was conducted at 15 sites in Poland. Healthy infants were randomized (1:1) to receive PCV13+P80 or PCV13 without P80 given at ages 2, 3, 4 and 12 months concomitantly with DTaP-IPV-Hib at 2, 3 and 4 months; hepatitis B at 2 months and measles, mumps, and rubella at 12 months. Serotype-specific antipneumococcal immune responses were evaluated using antipolysaccharide capsular immunoglobulin (Ig)G responses and opsonophagocytic activity (OPA) assay. Safety data were also collected. RESULTS: The 2 treatment groups were demographically similar. Following the infant immunization series, anticapsular IgG antibody geometric mean concentrations and OPA geometric mean titers for each serotype were within 2-fold between the 2 groups. Formal noninferiority criteria for comparison of proportion of responders (subjects with IgG titers ≥0.35 µg/mL) were met for 11 of the 13 serotypes. Overall population responses were highly similar. Anticapsular IgG responses were also within 2-fold following the toddler dose. Safety profiles were similar between the 2 groups. CONCLUSIONS: Addition of P80 to PCV13 did not adversely affect PCV13 immunogenicity or safety when compared with vaccine formulated without P80.

The use of cluster and principal component analysis in the estimation of iron status in term newborns.

OBJECTIVE: To assess the relationship between parameters of iron homeostasis in infants and clinical features characterizing newborns and their mothers. METHODS: The goal of the present work was to determine nine iron status parameters, i.e. hepcidin, prohepcidin, soluble transferrin receptor, ferritin, total iron binding capacity, unsaturated iron binding capacity, transferrin saturation, erythropoietin and total iron concentration, in the cord blood of 57 term newborns as well as to determine the complete blood count in their mothers. Moreover, an appraisal of the relationships between all of the iron parameters, the mothers' hematological factors and 12 clinical attributes was carried out using both cluster analysis (CA) and principal component analysis (PCA). RESULTS: We found that hepcidin is not correlated with its precursor, but it is strongly positively correlated with the total iron concentration. The CA divided all of the 24 parameters into three clusters and showed that certain clinical features, e.g. the APGAR score, mother's age or parity are related to the hepcidin and prohepcidin concentration. CONCLUSION: We demonstrated that CA and PCA are efficacious methods for assessing the relationship between iron metabolism parameters in cord blood and large amounts of clinical characteristics.

A multicenter randomized controlled trial comparing effectiveness of two nasal continuous positive airway pressure devices in very-low-birth-weight infants.

OBJECTIVE: Many studies suggest nasal continuous positive airway pressure is an effective and relatively complication-free means of respiratory support in premature infants. However, only limited data exist regarding the practical aspects of nasal continuous positive airway pressure delivery, including the best way to provide the positive airway pressure. DESIGN: Our aim was to compare the results of treatment using two different nasal continuous positive airway pressure devices: variable flow Infant Flow and constant flow nasal continuous positive airway pressure in two different groups of very-low-birth-weight infants in a multicenter randomized controlled trial. The indication groups were elective to avoid intubation and weaning from mechanical ventilation. SETTING: Twelve leading tertiary care neonatal centers in Poland. PATIENTS: Among 276 infants (weighing between 750-1500g, with a gestational age ≤32 wks) enrolled, 51% were randomized to receive Infant Flow and 49% to receive constant flow nasal continuous positive airway pressure. MEASUREMENTS AND MAIN RESULTS: Treatment success (i.e., no need for intubation/reintubation) occurred in 75% of our patients with a nonstatistically significant advantage seen with Infant Flow. The incidence of severe nasal complications and necrotizing enterocolitis were statistically significantly lower in the infants treated with Infant Flow. In our study, factors associated with elective nasal continuous positive airway pressure failure were birth weight ≤1000 g, gestational age ≤28 wks, clinical risk index for babies score >1, and PaO(2)/FIO(2) ratio of <150. Only birth weight ≤1000 g was associated with weaning failure. CONCLUSIONS: We found fewer severe nasal complications but no statistically significant advantage in treatment success in infants assigned to Infant Flow nasal continuous positive airway pressure compared with those assigned to constant flow nasal continuous positive airway pressure treatment. Significant risk factors of treatment failure include small size, maturity, and severity of respiratory distress syndrome.

[Antithrombin and protein C activity in the blood of premature newborns with intrauterine growth retardation]. / Aktywnosc inhibitorów ukladu krzepniecia -- antytrombiny i bialka C we krwi obwodowej noworodków urodzonych przedwczesnie z cechami wewnatrzmacicznego zahamowania wzrastania.

UNLABELLED: Intrauterine growth retardation (IUGR) and prematurity are often correlated with higher mortality and morbidity in the first days of life especially due to complications such as: hypoglycemia, polycythemia, necrotizing enterocolitis, meconium aspiration syndrome. Disturbances in the haemostatic system could be responsible for poor outcome of these complications. AIM: To determine the activity of main inhibitor of coagulation-antithrombin, level of protein C, concentration of thrombin-antithrombin (TAT) complexes and fibrinogen in the blood of premature infants with intrauterine growth retardation (IUGR) in comparison with premature infants without IUGR. MATERIAL: 33 premature infants with symptoms of intrauterine growth retardation (IUGR) and 146 premature infants without IUGR were included in our trial. RESULTS: There were no statistical differences between the analyzed groups in the level of protein C, concentration of TAT and fibrinogen. Activity of antithrombin was higher within 1 hour after birth and lower on the third day of life in the group of children with IUGR. CONCLUSIONS: Higher activity of antithrombin after birth in the group of newborns with IUGR prevents excessive activation of coagulation. On the third or fourth day of life the activity of antithrombin decreases due to its higher consumption in the blood of newborns with IUGR.

[Influence of selected neonatal diseases on the incidence of gastroesophageal reflux in preterm neonates]. / Wplyw wybranych schorzen okresu noworodkowego na wystepowanie refleksu zoladkowo-przelykowego u noworodków urodzonych przedwczesnie.

AIM: To assess the correlation between the incidence of gastroesophageal reflux and chosen neonatal diseases. MATERIAL AND METHODS: Analysis of 106 neonates born before 38 weeks of pregnancy was undertaken. All patients had 24-hour pH-metry and according to the result of this examination we diagnosed or excluded acid gastroesophageal reflux. The correlation between acid gastroesophageal reflux and chosen neonatal diseases, such as congenital infection, intrauterine growth retardation, pneumonia, respiratory distress syndrome, intraventricular hemorrhage, was analyzed. RESULTS: Gastroesophageal reflux was diagnosed in 25 neonates (23.6%). Congenital infection, respiratory distress syndrome, pneumonia and intraventricular hemorrhage showed no influence on the incidence of acid gastroesophageal reflux. Up to 50% of neonates with intrauterine growth retardation had gastroesophageal reflux, whereas in eutrophic neonates it was diagnosed in 16.7% cases. The risk of incidence of gastroesophageal reflux in neonates with intrauterine growth retardation was almost 5 times higher than in eutrophic neonates. CONCLUSIONS: No correlation between gastroesophageal reflux and congenital infection, respiratory distress syndrome, pneumonia, intraventricular hemorrhage has been found. The incidence of gastroesophageal reflux was higher in infants with intrauterine growth retardation.

[Selected ethical problems in neonatology -- opinions of physicians and nurses based on questionnaire study]. / Wybrane problemy etyczne w neonatologii -- poglady lekarzy i pielegniarek na podstawie badan ankietowych.

UNLABELLED: AIM OF THIS PAPER: To present the opinions of doctors and nurses on the limitations of resuscitation and treatment of extremely premature newborns. MATERIAL AND METHODS: Anonymous questionnaire studies were carried out in 342 doctors and 1194 nurses from 6 provinces of Poland. The authors compared the answers of doctors and nurses as well as the answers form different provinces. The results were processed using the Chi2 test, with the significance level p<0.05. RESULTS: The will to resuscitate the neonate, regardless of its birth weight was declared by 29% of the physicians and 49% of the nurses, regardless of the gestational age - by 21% of the physicians and 47% of the nurses. Resuscitation of an extremely immature, asphyctic newborn was declared by 71% of the physicians and 59% of the nurses. Limitation of therapy after diagnosing severe intracranial hemorrhage is declared by 67% of the physicians and 45% of the nurses. 37% of the doctors and 30% of the nurses would comply with parents' will when deciding about resuscitation. 44% of the physicians and 31% of the nurses declare taking parents' decision into account in the matter of abandoning resuscitation. CONCLUSIONS: 1. There is a higher percentage of persons convinced about the necessity of resuscitation of every newborn, regardless of its maturity, among the nurses than among the doctors. 2. Among the nurses there are more persons, who are sceptical about saving the extremely premature newborns born with asphyxia, whereas among the doctors there are more persons inclined to stop therapy in case of a severe intracranial hemorrhage. 3. The most controversial are problems concerning the consideration of parents' will in decision about whether to continue or abandon resuscitation, but physicians are more apt to regard parents' will in resuscitation in some situations. 4. The analysis of the questionnaire points to the need for deeper knowledge of the present mortality rates of the extremely immature newborns and further development of the surviving ones among the physicians and nurses.

[Is antenatal corticosteroid administration associated with increased acid gastroesophageal reflux in preterm neonates?]. / Czy kortykorepia prenatalna zwieksza ryzyko wystapienia kwasnego odplywu zoladkowo-przelykowego u noworodków przedwczesnie urodzonych?

THE AIM OF THE STUDY: Preliminary assessment of the incidence of acid gastroesophageal reflux in preterm neonates with and without antenatal administration of steroids. MATERIAL AND METHODS: Analysis of 96 neonates born before 34 weeks of pregnancy was undertaken. The patients were divided into two groups: I - those who received antenatal corticosteroids n=22; II - those who received no antenatal corticosteroids n=74. All patients had 24-hour pH-metry and basing on the result of this examination we diagnosed or excluded acid gastroesophageal reflux. RESULTS: In group I gastroesophageal reflux was diagnosed in 9/22 neonates (40.9%), in group II in 12/72 (16.2%), odds ratio=3.58. CONCLUSIONS: The frequency of acid gastroesophageal reflux is higher in preterm infants who received antenatal corticosteroids.

[Effectiveness of passive immunisation against respiratory syncytium virus in a group of premature infants with birth weight below 1000 grams]. / Ocena skutecznosci stosowania uodpornienia biernego przeciwko wirusom syncytium nablonka oddechowego (RSV) preparatem Synagis w grupie wczesniakow z masa urodzeniowa ciala ponizej 1000 gramow.

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infection during the child's first year of life. Those who survive neonatal intensive care are commonly rehospitalized. In the absence of vaccine, passive immunoprophylaxis is the preferred approach. Safety and efficacy of Palivizumab (Synagis) was proven in the Impact-RSV Trial, conducted in the USA, Canada and UK. The aim of the study was to determine efficacy of humanized monoclonal RSV antibody in prematures infants born 25-32 week gestation with weight birth below 1000 g with and without broncho-pulmonary dysplasia. We compared the hospitalization rates and morbidity between two groups of children who received palivizumab and without any protection. We confirm the efficacy and safety of Synagis. The outcome of this study supports the use of palivizumab prophylaxis in high-risk children.

[Thyroid dysfunction in pregnant women and correlation with clinical and metabolical status of their newborns]. / Zaburzenia czynnosci tarczycy u ciezarnych i ich wplyw na stan kliniczny i metaboliczny noworodka.

The idea of our work were to estimate the function of thyroid in newborns and their mothers in the group of pregnant women with thyroid disturbances. We examined 38 pregnant women and their newborns. We confirmed that diabetes appeared more frequently in all cases. The mean gestational age of newborns was 39 weeks. The cesarean sections were performed more frequently in the group of mothers with Graves-Basedow disease. The general condition of newborns after delivery were assessed as good acc. Apgar score. The newborns from pregnancies complicated with Graves-Basedow disease in majority cases were dystrophic.

[Economic prerequisites of active influenza prevention]. / Ekonomiczne przeslanki stosowania czynnej profilaktyki grypy.

Influenza and other acute infections of the upper respiratory tract are characterized by a high morbidity and mortality. As a result, they entail not only human but also economic consequences. A typical treatment is nonspecific and conservative. It consists of treatment with nonsteroid antiinflammatory drugs, antitussive drugs, hydratation, etc. Influenza is very often associated with complications especially in high risk groups (children, the elderly, chronically-ill people). The cost of treatment increases because of raising costs of pharmacotherapy and the increased absence from work. Vaccination is a safe and morbidity-diminishing method.

[The examinations of hearing in infants treated in neonatal intensive care units]. / Badania sluchu u niemowlat leczonych na oddziale intensywnej terapii noworodków i niemowlat.

The aim of the study was the estimation of hearing and the analysis of the risk factors for hearing loss in infants treated in neonatal intensive care units. The examinations were performed in 287 infants, who we examined in ENT Department between the ages of three and six months after discharge from neonatal intensive care unit. The infants were investigated with the use of ABR elicited with clicks and tone burst of 500 and 1000 Hz. Elevated auditory thresholds were found in 48 neonates in the first examination and in 27 in the second examination. Among the risk factors we observed the most frequently: gestational age < 33 Hbd, birth weight < 1500 g, respiratory and cardiovascular disorders and intracranial haemorrhages.