A Randomized, Controlled Trial to Investigate the Efficacy of Nebulized Poractant Alfa in Premature Babies with Respiratory Distress Syndrome.

OBJECTIVE: To investigate the efficacy and safety of nebulized poractant alfa (at 200 and 400 mg/kg doses) delivered in combination with nasal continuous positive airway pressure compared with nasal continuous positive airway pressure alone in premature infants with diagnosed respiratory distress syndrome. STUDY DESIGN: This randomized, controlled, multinational study was conducted in infants at 280/7 to 326/7 weeks of gestation. The primary outcome was the incidence of respiratory failure in the first 72 hours of life, defined as needing endotracheal surfactant and/or mechanical ventilation owing to prespecified criteria. Secondary outcomes included the time to respiratory failure in the first 72 hours, duration of ventilation, mortality, incidence of bronchopulmonary dysplasia, and major associated neonatal comorbidities. In addition, the safety and tolerability of the treatments were assessed reporting the number and percentage of infants with treatment-emergent adverse events and adverse drug reactions during nebulization. RESULTS: In total, 129 infants were randomized. No significant differences were observed for the primary outcome: 24 (57%), 20 (49%), and 25 (58%) infants received endotracheal surfactant and/or mechanical ventilation within 72 hours in the poractant alfa 200 mg/kg, poractant alfa 400 mg/kg, and nasal continuous positive airway pressure groups, respectively. Similarly, secondary respiratory outcomes did not differ among groups. Enrollment was halted early owing to a change in the benefit-risk balance of the intervention. Nebulized poractant alfa was well-tolerated and safe, and no serious adverse events were related to the study treatment. CONCLUSIONS: The intervention did not decrease the likelihood of respiratory failure within the first 72 hours of life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03235986.

[Beliefs - Misbeliefs, answering essential questions about hand hygiene from the view of the evidences]. / Hitek és tévhitek, azaz vitatott esszenciális kérdések a kézhigiénérol az evidencia tükrében.

Contaminated hands can play pivotal role in the development and spread of healthcare-associated infections. Consequently hand hygiene practice performed with adequate technique and with adequate timing is an essential implement for patient safety. Inhibition of the practice of high level hand hygiene by the misconceptions or deficient knowledge of healthcare workers may lead to negative influence on the quality of patient care. Erroneous beliefs or "rumourous knowledge" acquired from colleagues can not only influence the attitude of healthcare workers, but can also give rise to insufficient hand hygiene compliance. Finding, interpreting and imparting the related evidence by delivering continuing education and lectures, highlighting the theoretical and practical know-how on hand hygiene could help to understand and imprint the evidence-based practice and adequate technique in the essential issue of hand hygiene. Orv. Hetil., 2017., 158(6), 212-219.

Successful elimination of extended-spectrum beta-lactamase (ESBL)-producing nosocomial bacteria at a neonatal intensive care unit.

BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria are highly dangerous to neonates. At our Neonatal Intensive Care Unit (NICU), the presence of these bacteria became so threatening in 2011 that immediate intervention was required. METHODS: This study was conducted during a nearly two-year period consisting of three phases: retrospective (9 months), educational (3 months) and prospective (9 months). Based on retrospective data analysis, a complex management plan was devised involving the introduction of the INSURE protocol, changes to the antibiotic regimen, microbiological screening at short intervals, progressive feeding, a safer bathing protocol, staff hand hygiene training and continuous monitoring of the number of newly infected and newly colonized patients. During these intervals, a total of 355 patients were monitored. RESULTS: Both ESBL-producing Enterobacter cloaceae and Klebsiella pneumoniae were found (in both patients and environmental samples). In the prospective period a significant reduction could be seen in the average number of both colonized (26/167 patients; P=0.029) and infected (3/167 patients; P=0.033) patients compared to data from the retrospective period regarding colonized (72/188 patients) and infected (9/188 patients) patients. There was a decrease in the average number of patient-days (from 343.72 to 292.44 days per months), though this difference is not significant (P=0.058). During the prospective period, indirect hand hygiene compliance showed a significant increase (from the previous 26.02 to 33.6 hand hygiene procedures per patient per hospital day, P<0.001). CONCLUSION: Colonizations and infections were rolled back successfully in a multi-step effort that required an interdisciplinary approach.

Lesions requiring wound management in a central tertiary neonatal intensive care unit.

BACKGROUND: Most of the skin disorders that occur in neonatal intensive care units are due in part to the immaturity and vulnerability of the neonatal skin. Various iatrogenic diagnostic and therapeutic procedures are also conducive to iatrogenic damage. This study was to review the neonates admitted to our neonatal intensive care unit who needed wound management, and to assess the most common skin injuries and wounds, and their aetiology. METHODS: Data were extracted from medical records of neonates who needed wound management in our Neonatal Intensive Care Unit between January 31, 2012 and January 31, 2013. Information about gestational age, sex, birth weight, area of involvement, wound aetiology, and therapy were collected. RESULTS: Among the 211 neonates observed, wound management was required in 10 cases of diaper dermatitis, 7 epidermal stripping, 6 extravasation injuries, 5 pressure ulcers, 1 surgical wound and infection, 1 thermal burn, and 5 other lesions. CONCLUSIONS: International guidelines in neonatal wound care practice are not available, and further research concerns are clearly needed. Dressings and antiseptic agents should be chosen with great care for application to neonates, with particular attention to the prevention of adverse events in this sensitive population. Team work among dermatologists, neonatologists and nurses is crucial for the successful treatment of neonates.

[After the epidemic - before the epidemic. Incidence of bronchiolitis at the Pediatric ward of the Bács-Kiskun County Hospital]. / Járvány után ­ járvány elott. Bronchiolitis elofordulása a Bács-Kiskun Megyei Kórház Csecsemo- és Gyermekosztályán.

INTRODUCTION: Bronchiolitis may cause severe respiratory insufficiency in infants and toddlers. Respiratory Syncytial Virus (RSV) is its most frequent infective agent. AIM AND METHOD: The authors surveyed the incidence of bronchiolitis during the last 6 seasons, examined the epidemic of the 2014/15 season and compared the groups of RSV positive and negative patients. RSV was tested with a quick essay. Anamnestic data, clinical and laboratory parameters were compared. RESULTS: 72 patients were treated with bronchiolitis. RSV test was performed in 61 cases. There were 36 RSV positive and 25 RSV negative patients. There was a high proportion of prematurely born patients (33% versus 18%, respectively). RSV positive children, who required intensive care therapy, were treated significantly longer at the ICU. No further significant difference was found. CONCLUSIONS: The 2014/15 bronchiolitis season was heavy and may be instructive before the 2016/17 season. Beside supportive care prevention (passive immunization of the risk groups) is important. Orv. Hetil., 2016, 157(51), 2034-2039.

Iatrogenic Skin Disorders and Related Factors in Newborn Infants.

BACKGROUND/OBJECTIVES: Recent technological advances and diagnostic and therapeutic innovations have resulted in an impressive improvement in the survival of newborn infants requiring intensive care. Consequently, with the use of modern invasive diagnostic and therapeutic procedures, the incidence of iatrogenic events has also increased. The aim of this study was to assess various iatrogenic complications in neonates requiring intensive care and determine possible contributing factors to the injuries. METHODS: Our prospective cross-sectional cohort survey was conducted in a central regional level III neonatal intensive care unit (NICU). Correlations between intensive therapeutic interventions, complications, factors influencing attendance and prognosis, and the prevalence of iatrogenic skin injuries (ISIs) were investigated over a 2-year study period. RESULTS: Between January 31, 2012, and January 31, 2014, 460 neonates were admitted to the NICU, 83 of whom exhibited some kind of ISI. The major risk factors for ISIs were low birthweight, young gestational age, long NICU stay, use of the intubation-surfactant-extubation (INSURE) technique, surfactant use, mechanical ventilation, insertion of an umbilical arterial catheter, circulatory and cardiac support with dopamine or dobutamine, pulmonary hemorrhage, intracranial hemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia, and positive microbiology culture results. CONCLUSION: To prevent ISIs, careful consideration of risk factors and the creation of protocols ensuring efficient treatment of injuries are needed.

[Examination of maternal extended spectrum beta-lactamase bacterial colonization and follow-up of newborns requiring Neonatal Intensive Care Unit admission]. / Neonatális Intenzív Centrumban ellátást igénylo betegeink anyai széles spektrumú béta-laktamáz-termelo baktériummal történt kolonizációjának vizsgálata és követése.

INTRODUCTION: The extended beta-lactamase producing Enterobacteriaceae may cause asymptomatic carriage if present in the colon of premature infants or pregnant women. AIM: To assess the incidence of colonization among mothers whose infants were admitted to Neonatal Intensive Center on the day of their delivery for this pathogen. METHOD: From October 1, 2013 until October 31, 2015 the authors screened mothers on the day of their delivery for this pathogen. Nineteen of the 751 anorectal swabs or stool samples were found to be positive. Mothers having positive samples were given personal education for hand hygiene, then they actively participated in the care of their babies. From some premature infants ear swab and stomach washing were taken and sent for culture on the day of their admission. In the course of their hospital stay, anorectal swabs were taken and screened for this bacteria colonization at least once. RESULTS: None of the premature infants of the 19 extended beta-lactamase producing Enterobacteriaceae-positive mothers became positive in the studied period. CONCLUSION: If the mother is colonized, the spreading of pathogen to newborns can be prevented by observing the hygienic rules. Orv. Hetil., 2016. 157(34), 1353-1356.

Overview of dermatologic disorders of neonates in a central regional intensive care unit in Hungary.

The immaturity and vulnerability of the skin and epidermal barrier function and the frequent iatrogenic complications following diagnostic and therapeutic procedures are often associated with skin manifestations in infants in neonatal intensive care units (NICUs). The aim of the current study was to investigate dermatologic disorders in neonates in our NICU. A prospective cohort study was conducted in the NICU at the Department of Pediatrics at the University of Szeged between January 2012 and January 2013. All full- and preterm infants hospitalized in the NICU underwent whole-body skin examinations and all dermatologic disorders and treatment modalities were recorded. Eighty-nine dermatologic conditions were detected in 64 of the 211 neonates admitted to the NICU. A wide variety of clinical symptoms accompanied these conditions in these preterm and severely ill full-term infants. A considerable proportion of the disorders that were seen resulted from the immaturity of the skin and various iatrogenic complications. Dermatologic disorders are frequent in neonates requiring intensive care. Prevention, early detection, and optimal treatment of these disorders with modern, standardized skin care management strategies can result in significant improvements in barrier function and in the integrity of the skin, increasing the overall efficacy of neonatal intensive care.

[Neonatal skin care in tertiary Neonatal Intensive Care Units in Hungary]. / Borápolási gyakorlat a Neonatális Intenzív Centrumokban Magyarországon.

INTRODUCTION: Skin physiology of neonates and preterm infants and evidence-based skin care are not well explored for health care providers. AIM: The aim of our present study was to investigate the skin care methods of the tertiary Neonatal Intensive Care Units in Hungary. METHOD: A standardized questionnaire was distributed among the 22 tertiary Neonatal Intensive Care Units with questions regarding skin care methods, bathing, emollition, skin disinfection, umbilical cord care, treatment of diaper dermatitis, and use of adhesive tapes. RESULTS: The skin care methods of the centres were similar in several aspects, but there were significant differences between the applied skin care and disinfectant products. CONCLUSIONS: The results of this survey facilitate the establishment of a standardized skin care protocol for tertiary Neonatal Intensive Care Units with the cooperation of dermatologists, neonatologists and pharmacists.

Successful postoperative treatment of a lumbosacral ulcer in a neonate after myelomeningocele.

Wound care in neonates demands special awareness of the anatomical and physiological characteristics of their skin, and the danger of adverse mechanical and toxicological events. Here, we present the case of a full-term neonate born with myelomeningocele. Following the closing surgery on the 3rd day of postuterine life, the operated region became inflamed, the sutures opened and a necrotic discharging ulcer developed. Besides parenteral antibiotic treatment based on the microbiological findings, intelligent hydrofiber dressings were applied to the wound with regard to the special characteristics of wound care in neonates. After 72 days, the ulcer had healed with a small residual scar, and the infant is currently demonstrating normal physical and mental development.

Chryseobacterium gleum - a novel bacterium species detected in neonatal respiratory tract infections.

We report three patients with early neonatal infections. All patients had respiratory tract involvement with increased inflammation markers. Chryseobacterium gleum was cultured from the stomach content aspirated on arrival at the Neonatal intensive Care Unit and it was identified with the help of a Microflex™ MALDI Biotyper mass spectrometer (Bruker-Daltonik, Fremont, CA). Recovery could be achieved with ciprofloxacin treatment. We consider our cases a possible new clinical presentation of a rare human pathogen.

The role of complement in Streptococcus pneumoniae-associated haemolytic uraemic syndrome.

BACKGROUND: Atypical forms of haemolytic uraemic syndrome (aHUS) include HUS caused by defects in the regulation of alternative complement pathway and HUS linked to neuraminidase-producing pathogens, such as Streptococcus pneumoniae. Increasing data support a pathogenic role of neuraminidase in the development of S. pneumoniae-associated haemolytic uraemic syndrome (SP-HUS), but the role of complement has never been clarified in detail. Therefore, we aimed to investigate whether the pathologic complement profile and genetic risk factors of aHUS are present in patients with SP-HUS. METHODS: Enrolling five patients with SP-HUS classical and alternative pathway activity, besides C3, C4, factors H, B, I and anti-factor H autoantibody levels were determined. The coding regions of CFH, CFI, CD46 (MCP), THBD, C3 and CFB genes were sequenced and the copy number of CFI, CD46, CFH and related genes were also analyzed. RESULTS: We found that in the acute phase samples of SP-HUS patients, complement components C4, C3 and activity of the classical and alternative pathways were decreased, indicating severe activation and complement consumption, but most of these alterations normalized later in remission. Three of the patients carried mutations and risk haplotypes in complement-mediated aHUS associated genes. The identified mutations include a previously published CFI variant (P50A) and two novel ones in CFH (R1149X) and THBD (T44I) genes. CONCLUSIONS: Our results suggest that severe complement dysregulation and consumption accompany the progress of invasive pneumococcal disease (IPD)-associated SP-HUS and genetic variations of complement genes may contribute to the development of this complication in a proportion of the affected patients.

Measurement of gastric-to-end-tidal carbon dioxide difference in neonates requiring intensive care.

OBJECTIVE: Gastric-arterial partial CO(2) pressure gap (P(g-)(a)CO(2) gap) measured by gastric tonometry may detect the disturbance of splanchnic perfusion. As in the neonatal age it is very difficult to follow up the circulatory condition with frequent acid-base examinations, we wanted to compare the P(g-)(a)CO(2) gap with an alternative gap of P(g)CO(2) - end-tidal carbon dioxide (P(g)(-)(ET)CO(2) gap). METHODS: A prospective study was performed on ventilated neonates requiring intensive therapy (n = 44, weight: 1813 ± 977 g). P(ET)CO(2) and P(g)CO(2) were measured with a side stream capnograph. We applied a newly developed gastric tonometric probe. Patients were divided into two groups: Group 1 of patients in stable condition (n = 35) and Group 2 of patients with severe condition (i.e. Clinical Risk Index for Babies [CRIB] score higher than 10; n = 9). For main statistical analysis a mixed model repeated measurements ANOVA, Bland-Altman analysis were applied. RESULTS: P(g)(-)(ET)CO(2) gap was higher than P(g-)(a)CO(2) gap (11.40 ± 7.79 versus 3.63 ± 7.98 mmHg, p < 0.01). Both gaps were higher in Group 2 (8.71 ± 10.89 and 18.27 ± 10.49 versus 2.53 ± 6.78 and 9.92 ± 6.22 mmHg, p < 0.01 and p < 0.05). Bland-Altman analysis of the two gaps showed an acceptable correspondence. CONCLUSIONS: P(g)(-)(ET)CO(2) gap may be used as a method for continuous estimation of splanchnic perfusion and a prognostic index also in critically ill neonates. However, the P(g-)(a)CO(2) gap should not be abandoned.

Practical experiences and in vitro and in vivo validation studies with a new gastric tonometric probe in human adult patients.

PURPOSE: This study provides practical experiences with a new, simple, balloon-free gastric tonometric probe (probe) and reports the results of simultaneous in vitro and in vivo measurements with a conventional, ballooned gastric air tonometer (catheter) and the new device. MATERIALS AND METHODS: Ten healthy volunteers and 50 anesthetized surgical patients with different American Society of Anesthesiologists (ASA) scores, scheduled for neurologic, orthopedic, trauma, and cardiac operations, were enrolled in the study. The values of 60 in vitro and, in 12 surgical patients, 101 in vivo paired Pco(2) measurements--performed simultaneously with the new tonometric probe and the catheter that was connected to a Tonocap monitor--were compared. The tolerability of the measurement with the new probe was examined, and the results of gastric tonometry and, in surgical cases, the gastric tonometric, end-expiratory, and arterial Pco(2) values were registered. The results were evaluated by analysis of variance test. The data of the in vivo paired measurements were evaluated by Bland-Altman analysis. RESULTS: The use of the probe proved to be well tolerated and easily applicable in the studied cases. The results of 20 measurements obtained in healthy volunteers and those of 520 measurements in the surgical cases correspond to the data obtained with the classical methods published in the medical literature. During in vitro paired measurements, there was a good agreement between the data obtained with the 2 methods; however, in the in vivo studies, the results of measurements performed with the probe were mostly higher. CONCLUSIONS: The differences between the results obtained with the 2 methods might have been caused by the quicker equilibration property of the probe and by the fundamental differences between the 2 methods. The new probe seems to be applicable for routine human measurements.

Minimally invasive genetic screen for GJB2 related deafness using dried blood spots.

OBJECTIVE: Nonsyndromic hearing loss is one of the most abundant human sensory disorders, and can be found in 1 out of 1000 newborns. In 60-70% of the cases this disorder is hereditary. The phenotype varies from moderate hearing loss to almost complete deafness, often only revealed in late childhood. Early detection of hearing related genetic variations in the first few weeks of life would allow planning of the audiological and logopedical procedures to maintain the children's normal audiological and speech development, and if required a cochlear implantation can be planned in time. We wanted to evaluate, whether the blood samples collected from neonates onto Guthrie cards (dried blood spots, or DBS), and blood collected from people of various ages into blood collecting tubes is equally usable for genetic testing. The quality of the samples on DBS's for genetic tests after an extended period of storage was evaluated. The methods for sample preparation and analysis were also evaluated. METHODS: Two DNA extraction methods were compared on the samples. We extracted DNA from whole blood with the Versagene Blood Kit from Gentra, and from DBS's with boiling. Allele-specific PCRs (AS-PCR) were carried out on each sample. Samples were analyzed with AS-PCR and sequencing, for the 35delG mutation in the GJB2 (Cx26) gene. Freshly drawn and dried blood spot samples stored for several years were used in the experiments. RESULTS: An AS-PCR method for detecting 35delG mutation on DNA extracted from Guthrie cards was validated. Blood samples up to 10 years of storage were applicable in the screen. 84 patients were found with 35delG mutations, both heterozygous (with no detected hearing related phenotypical discrepancies), and homozygous (phenotipically with moderate to severe hearing loss) forms. CONCLUSIONS: The dried blood spots on Guthrie cards require only three drops of blood to be collected from children, which causes less stress than taking 3 ml of blood. The blood stored on Guthrie cards can be used to store DNA samples for at least 10 years. Even under suboptimal storage conditions the samples' DNA remains intact for genetic testing. Compared to blood collection tubes Guthrie cards cost less, are easier to transport and store.

Applicability of a new gastric tonometric probe in infants requiring intensive care.

BACKGROUND: Gastric tonometry was developed for measuring the partial pressure of carbon dioxide in the gastrointestinal tract and particularly for monitoring the clinical condition of patients in critical states. The ballooned catheter used in this technique has proved to be a reliable tool in adult patients, but its use in pediatrics is limited because of technical difficulties. The aims of this paper are to describe the technique of application of a recently developed gastric tonometric probe especially suitable for performing measurements on neonates and infants and to present the first human results. MATERIAL/METHODS: Thirty-two neonates and infants requiring intensive care were monitored (age: 2-456 days, weight: 1200-6700 g), of whom 10 died. The pediatric index of mortality, acid-base parameters, PCO2 gap values, and intramucosal pH and pH gap values were measured or calculated. The new gastric tonometric probe, made of silicone rubber tubes, is balloon free. It is introduced into the stomach orally or nasopharyngeally through the use of a guide wire. After equilibration, the PCO2 level of the air inside the probe is measured with a capnograph. RESULTS: Application of the new probe proved simple. The pediatric index of mortality scores (35.1%+/-19.6% vs. 14.6%+/-14.8%), PCO2 gap values (13.48+/-9.30 mmHg vs. 8.43+/-6.54 mmHg), and the systemic-intramucosal pH differences (0.124+/-0.074 vs. 0.079+/-0.054) were significantly higher in the non-surviving patients. CONCLUSIONS: The new probe is well applicable for measurements of gastric PCO2 levels in infants.

Intraoperative gastric tonometric examinations in children and infants with a new probe, combined with measurement of the endtidal PCO2.

BACKGROUND: Important progress relating to the early prediction of postoperative complications was recently achieved through the combined use of endtidal PCO(2) (P(ET)CO(2)) and gastric tonometry. The aim of this article was to present results obtained with a new tonometric instrument, proving its feasibility and extending its use to the control of anesthetized infants and children. METHODS: The new tonometric probe, which is balloon free, consists basically of silicone rubber tubing. The room air initially inside the tubes of the probe equilibrates with the PCO(2) of the body cavity throughout its full length. The PCO(2) content of the gastric cavity (P(g)CO(2)) and simultaneously P(ET)CO(2) were measured with a microcapnograph. A total of 108 measurements were performed intraoperatively on 25 infants and young children operated on at the Surgical Unit of the Department of Pediatrics. The patients were divided into elective surgery cases <2 years of age, group I; elective surgery cases >2 years of age, group II; and acute surgery cases, independently of age, group III. To examine the degree of agreement between the measurements, Pearson's correlation coefficients were determined and Bland-Altman analysis was performed. A mixed model repeated measurements anova was used to compare the differences between the groups. RESULTS: P(ET)CO(2) and P(g)CO(2) for groups I and II were nearly identical, and statistically not significantly different (mean difference 0.10 mmHg and 0.85 mmHg, P = 0.96 and 0.45, respectively), whereas the corresponding data for group III differed significantly from those for groups I and II (P = 0.03 and 0.001, respectively). On Bland-Altman analysis, the bias value for groups proved to be statistically significantly different (P = 0.001). CONCLUSIONS: The tested new probe worked very well in small children. The clinical implications of the large gaps found between P(ET)CO(2) and P(g)CO(2) values in acutely ill children and children undergoing elective operations must be investigated further.

Side-effects of long-term prostaglandin E(1) treatment in neonates.

BACKGROUND: In some neonates suffering from ductus arteriosus dependent congenital heart defect, a Prostaglandin E(1) (PGE1) therapy longer than 2 weeks may be needed. However, PGE1 analogue compounds may produce several adverse effects. METHODS: The authors retrospectively analyzed the data of nine patients who underwent a PGE1 treatment lasting longer than 14 days. RESULTS: The leukocyte count of the patients remained high throughout the treatment period, and the proportion of neutrophils was over 50%. Transient feeding difficulty and abdominal distension, and possible signs of gastric-outlet obstruction, were observed in two cases. In the case of three patients, cortical hyperostosis developed after different cumulative doses (1584, 3384 and 4320 microg). Significant correlations were found between the doses of PGE1 and serum K(+) levels (r=-0.770, P < 0.05) and between the blood standard bicarbonate levels and PGE1 doses (r= 0.889, P < 0.01). Bartter syndrome-like condition developed in those three patients who received the largest cumulative doses. CONCLUSIONS: Fluid-electrolyte parameters must be controlled frequently in the case of each patient treated with PGE1 for longer than 2 weeks. Although the dose, the length of the therapy and individual susceptibility may be equally important, fluid-electrolyte disturbances and the development of pseudo-Bartter syndrome seem to be more dose-dependent than cortical hyperostosis.