The Effectiveness of Different Eradication Schemes for Pediatric Helicobacter pylori Infection-A Single-Center Comparative Study from Romania.

INTRODUCTION: In Romania, studies on the pediatric population regarding H. pylori infection or bacterial resistance to antibiotics are limited. Eradication treatment of this infection still raises important problems in medical practice. This study aims to compare the effectiveness of three eradication therapies used against H. pylori infection in the pediatric population. METHODS: The prospective study enrolled children aged 6-17 years who were first diagnosed with H. pylori infection. Patients received a randomized treatment either the therapy with clarithromycin (CLR), the therapy with metronidazole (MTZ) or sequential therapy. The effectiveness of the eradication treatment was evaluated after 4-8 weeks from the end of the therapy by testing fecal antigen. RESULTS: 149 patients were enrolled over 18 months. The eradication rates were 49.5% for the treatment scheme with proton pump inhibitor (PPI) + amoxicillin (AMO) + MTZ, 26.7% for PPI + AMO + CLR and 23.8% for sequential therapy. MTZ therapy was superior to CLR therapy, but sequential therapy was not. Side effects were recorded for PPI + AMO + CLR with 39.6%, followed by sequential therapy 37.7%, and only 22.6% for PPI + AMO + MTZ. CONCLUSIONS: Therapy with MTZ can achieve a higher eradication rate as a first-line treatment in the case of H. pylori infection. Taking into account that Romania is in an area with increased resistance to CLR, MTZ therapy could be a promising alternative.

Combining Protein Expression and Molecular Data Improves Mutation Characterization of Dystrophinopathies.

Duchenne and Becker muscular dystrophy are X-linked recessive inherited disorders characterized by progressive weakness due to skeletal muscle degeneration. Different mutations in the DMD gene, which encodes for dystrophin protein, are responsible for these disorders. The aim of our study was to investigate the relationship between type, size, and location of the mutation that occurs in the DMD gene and their effect on dystrophin protein expression in a cohort of 40 male dystrophinopathy patients and nine females, possible carriers. We evaluated the expression of dystrophin by immunofluorescence and immunoblotting. The mutational spectrum of the DMD gene was established by MLPA for large copy number variants, followed by HRM analysis for point mutations and sequencing of samples with an abnormal melting profile. MLPA revealed 30 deletions (75%) and three duplications (7.5%). HRM analysis accounted for seven-point mutations (17.5%). We also report four novel small mutations (c. 8507G>T, c.3021delG, c.9563_9563+1insAGCATGTTTATGATACAGCA, c.7661-60T>A) in DMD gene. Our work shows that the DNA translational open reading frame and the location of the mutation both influence the expression of dystrophin and disease severity phenotype. The proposed algorithm used in this study demonstrates its accuracy for the characterization of dystrophinopathy patients.

Review of the measles epidemic in children from Central Eastern Europe in the third millennium.

Measles is an extremely contagious viral disease. Even though a safe vaccine exists for this disease, it remains one of the leading causes of mortality and morbidity in infants and young children. We aimed to create a retrospective descriptive study in which to analyze the evolution of the measles epidemic at the European level. The documentation was carried out using European Centre for Disease Prevention and Control (ECDC) and World Health Organization (WHO) statistics. At the same time, we present the epidemic's evolution in Romania, using data provided by the Romanian National Institute of Public Health and Ministry of Health. European statistical data indicate a high number of patients diagnosed with measles both among children and adults. All European countries benefit from the measles vaccination in the form of the measles-mumps-rubella (MMR) trivaccine included in their National Vaccination Programme. The vaccination schedule varies from country to country. In the vaccination scheme, most European countries include two doses of the MMR vaccine among the pediatric population. Romania registered a limited number of cases of measles between 1980 and 2015 following the introduction of the measles vaccination in the National Vaccination Programme. Since 2005, the Romanian vaccination schedule includes two doses of MMR trivaccine, administered at 12 months and at 6-7 years. After 2015, as a result of a significant decrease in the number of vaccinated children, Romania is facing a major increase in the cases of measles. Consecutively, a measles epidemic was declared in 2016 and an additional dose of mandatory MMR trivaccine was introduced at the age of 9 months. After 4 years of this schedule of administration, starting with August 2020, the additional dose of MMR administered during infancy has been discontinued. We propose an analysis of the factors that influenced the downward evolution of the measles epidemic in Romania at the beginning of the third millennium. Issues related to the limitation of interpersonal contact in the context of the social distancing imposed by the Sars-CoV-2 virus pandemic are discussed. We consider necessary a detailed documentation of the percentage of new disease cases that will appear in the pediatric population in the near future, in the context of the resumption of daily activity after the reopening of nurseries, kindergartens and schools.

Prevention and contrast of child abuse and neglect in the practice of European paediatricians: a multi-national pilot study.

BACKGROUND: Child abuse and neglect, or maltreatment, is a serious public health problem, which may cause long-term effects on children's health and wellbeing and expose them to further adulthood vulnerabilities. Studies on child maltreatment performed in Europe are scarce, and the number of participants enrolled relatively small. The aim of this multi-national European pilot study, was to evaluate the level of understanding and perception of the concepts of child abuse and neglect by European paediatricians working in different medical settings, and the attitude toward these forms of maltreatment in their practice. METHODS: The study was performed by a cross-sectional, descriptive, online survey, made available online to European paediatricians members of 50 national paediatric, who belonged to four different medical settings: hospital, family care, university centres and private practice. The questionnaire, designed as a multiple choice questions survey, with a single answer option consisted of 22 questions/statements. Frequency analyses were applied. Most of the data were described using univariate analysis and Chi-squared tests were used to compare the respondents and answers and a significance level of p ≤ 0.05 applied. RESULTS: Findings show that European paediatricians consider the training on child maltreatment currently provided by medical school curricula and paediatric residency courses to be largely insufficient and continuing education courses were considered of great importance to cover educational gaps. Physical violence was recognized by paediatricians mostly during occasional visits with a significant correlation between detecting abuse during an occasional visit and being a primary care paediatrician. Results also showed a reluctance by paediatricians to report cases of maltreatment to the competent judicial authorities. CONCLUSIONS: Data of this study may provide useful contribution to the current limited knowledge about the familiarity of European paediatricians with child maltreatment and their skills to recognize, manage and contrast abusive childhood experiences in their practice. Finally, they could provide local legislators and health authorities with information useful to further improve public health approaches and rules able to effectively address shared risk and protective factors, which could prevent child abuse and neglect from ever occurring.

Ten-year follow-up on efficacy, immunogenicity and safety of two doses of a combined measles-mumps-rubella-varicella vaccine or one dose of monovalent varicella vaccine: Results from five East European countries.

BACKGROUND: We assessed the 10-year efficacy, immunogenicity and safety of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV) or one dose of a monovalent varicella vaccine (V) in children from Czech Republic, Lithuania, Poland, Romania and Slovakia. METHODS: This was a phase IIIB follow-up of an observer-blind, randomized, controlled trial (NCT00226499). In phase A, healthy children aged 12-22 months from 10 European countries were randomized in a 3:3:1 ratio to receive two doses of MMRV (MMRV group), one dose of MMR followed by one dose of V (MMR + V group), or two doses of MMR (MMR; control group), 42 days apart. Vaccine efficacy (VE) against varicella (confirmed by viral DNA detection or epidemiological link and clinical assessment) was calculated with 95% confidence intervals using Cox proportional hazards regression model. Immunogenicity was assessed as seropositivity rates and geometric mean concentrations (GMCs). Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. RESULTS: A total of 3705 children were vaccinated (1590, MMRV group; 1586, MMR + V group; 529, MMR group). There were 663 confirmed varicella cases (47, MMRV group; 349, MMR + V group; 267, MMR group). VE ranged between 95.4% (Lithuania) and 97.4% (Slovakia) in the MMRV group and between 59.3% (Lithuania) and 74% (Slovakia) in the MMR + V group. At year 10, seropositivity rates were 99.5%-100% in the MMRV group, 98%-100% in the MMR + V group and 50%-100% in the MMR control group, and the anti-VZV antibody GMCs were comparable between MMRV and MMR + V groups. The occurrence of solicited and unsolicited AEs was similar across groups and no SAE was considered as vaccination-related. No new safety concerns were identified. CONCLUSIONS: Our results indicated that two doses of varicella zoster virus-containing vaccine provided better protection than one dose against varicella and induced antibody responses that persisted 10 years post-vaccination.

One or two doses of live varicella virus-containing vaccines: Efficacy, persistence of immune responses, and safety six years after administration in healthy children during their second year of life.

BACKGROUND: This phase III B follow-up of an initial multicenter study (NCT00226499) will evaluate the ten-year efficacy of two doses of the combined measles-mumps-rubella-varicella vaccine (MMRV) and one dose of the live attenuated varicella vaccine (V) versus a measles-mumps-rubella control group (MMR) for the prevention of clinical varicella disease. Here we present efficacy results for six years post-vaccination. METHODS: In phase A of the study, healthy children aged 12-22 months from ten European countries were randomized (3:3:1) and received either two doses of MMRV, or one dose of combined MMR and one dose of monovalent varicella vaccine (MMR+V), or two doses of the MMR vaccine (control), 42 days apart. Vaccine efficacy against all and against moderate or severe varicella (confirmed by detection of viral DNA or epidemiological link) was assessed from six weeks up to six years post-dose 2 for the MMRV and MMR+V groups, and was calculated with 95% confidence intervals (CI). The severity of varicella was calculated using the modified Vázquez scale (mild ≤ 7; moderately severe = 8-15; severe ≥ 16). Herpes zoster cases were also recorded. RESULTS: 5289 children (MMRV = 2279, mean age = 14.2, standard deviation [SD] = 2.5; MMR+V = 2266, mean age = 14.2, SD = 2.4; MMR = 744, mean age = 14.2, SD = 2.5 months) were included in the efficacy cohort. 815 varicella cases were confirmed. Efficacy of two doses of MMRV against all and against moderate or severe varicella was 95.0% (95% CI: 93.6-96.2) and 99.0% (95% CI: 97.7-99.6), respectively. Efficacy of one dose of varicella vaccine against all and against moderate or severe varicella was 67.0% (95% CI: 61.8-71.4) and 90.3% (95% CI: 86.9-92.8), respectively. There were four confirmed herpes zoster cases (MMR+V = 2, MMR = 2), all were mild and three tested positive for the wild-type virus. CONCLUSIONS: Two doses of the MMRV vaccine and one dose of the varicella vaccine remain efficacious through six years post-vaccination.

A systematic review of lung function testing in asthmatic young children.

Asthma diagnosis is difficult in young children being mainly based on clinical signs and parents' history, which is sometimes difficult to obtain. Lung function testing may improve asthma diagnosis by objectively assessing its main features, airway obstruction, spontaneously reversible or after use of a bronchodilator drug, ventilation inhomogeneity during an acute bronchoconstriction and airway hyperresponsiveness. In young children that cannot cope with classical tests, it is important to use and develop simple, short lasting methods, made in spontaneous ventilation without active cooperation. Such techniques are a measurement of respiratory resistance by forced oscillations or the interrupter technique, of specific airway resistance by plethysmography and capnography. All these parameters are sensitive to the presence of an airway obstruction and to a bronchodilator or bronchoconstrictor agent, but their cutoff values in differentiating between asthmatic and healthy children as well as their specific indications in asthma management remain to be established.

Hospital-based surveillance to estimate the burden of rotavirus gastroenteritis in children below five years of age in Romania.

INTRODUCTION: Rotavirus (RV) is a leading cause of acute gastroenteritis (AGE), affecting 95% of children below five years of age. METHODS: In this prospective, multi-center study, children below five years of age who were hospitalized or those who visited the emergency room (ER) due to AGE or who developed AGE at least 48 hours after hospitalization (nosocomial infection) and had a RV-positive stool sample were included (n=1,222). RV-positive samples were genotyped by reverse-transcriptase polymerase chain reaction. RESULTS: RV test results were available for 1,212 children (hospitalizations [n=677], ER visits [n=398] and nosocomial AGE cases [n=137]). Proportions of rotavirus gastroenteritis (RVGE) hospitalizations and ER visits were 51.70% (350/677; 95%CI: 47.86-55.52) and 36.18% (144/398; 95%CI: 31.45-41.12), respectively. Overall, 45.95% (494/1075) of all community-acquired AGE cases were due to RV. High numbers of RVGE cases were recorded between January and March. Most common genotypes were G9P[8] (34.27%) followed by G4P[8] (25.83%) and G1P[8] (23.02%). Of all community-acquired RVGE cases, the highest number of cases was observed in children aged 12-23 months. Median duration of hospitalization among RV-positive subjects was six days (range: 2-31 days). Incidence of nosocomial RVGE was 0.52 (95%CI: 0.45-0.60) cases per 1,000 child-days hospitalization. Median duration for additional hospitalization due to nosocomial RVGE was five days (range: 1-10). The highest burden of nosocomial RVGE was observed in children aged 12-23 months (42.34%, 58/137). Our findings confirm a high burden of acute RVGE disease in Romania and provide useful data to support the implementation of RV vaccination in Romania. TRIAL REGISTRATION: NCT01253967.

Asthma Control Assessment in Children: Correlation between Asthma Control Test and Peak Expiratory Flow.

OBJECTIVES: To assess the correlation between asthma control test and peak expiratory flow measurements in children and the impact of certain factors influencing asthma symptoms perception over their correlation. METHODS: A prospective study including 54 patients aged 5 to 18 years old, who have been diagnosed with asthma in "Victor Gomoiu" Children's Clinical Hospital between May 2012-November 2013, was initiated. For each patient a personalized asthma monitoring plan was designed. This presumes many evaluations assigned to assess the asthma control status. These evaluations consist in counting of asthma symptoms using ACT (Asthma Control Test) and evaluation of pulmonary function using PEF measurement (peak expiratory flow) and spirometry. In each patient factors known to have an influence on asthma symptoms perception (small age, overweighting and allergic rhinitis) were searched. Finally, the correlation between ACT value and PEF variation and how this correlation is influenced by these factors were assessed. RESULTS: From all 54 included patients a total of 113 evaluations moments were recorded. The assessment of correlation between ACT score and PEF variation for all evaluations showed a strong correlation overall (p<0.01). The correlation is stronger in the small age group (5 to 6 years: p<0.01) than in the older age group (6 to 11 years: p=0.014, >12 years: p=0.03). ACT does not correlate with PEF variation in the overweight patients subgroup (p=0.226). We found the percent of overweight equal to 8.57% in the small age subgroup (5 to 6 years), 26.78% in the 6 to 11 years old group and 31.81% in the over 12 years old patient group. ACT is correlated with PEF variation in both the allergic rhinitis and non allergic rhinitis subgroups (p<0.01). CONCLUSIONS: ACT is correlated with PEF variation overall. Their correlation is not influenced by small age and the presence of allergic rhinitis, but is influenced by overweighting.

Postinfectious arthritis in pediatric practice.

ABSTRACT: Postinfectious arthritis is a relatively often encountered in pediatric practice. The authors present the most important data concerneing this pathology, with up to date informations exemplifying with case presentations. Clinical cases bring to attention the most common forms of postinfectious arthritis (reactive arthritis, postinfectious arthritis bacterial, viral, spirochete, and so on). Although highly studied and commonly found in current pediatric practice, arthritis occurring after infections remains controversial entities, especially regarding terminology. While, according to some authors, postinfectious arthritis belongs to the large group of reactive arthritis, by other authors, these joint events are independent entities.

Abnormalities in embryological development in total anomalous pulmonary venous connection. A case report.

Pulmonary venous system development starts early in embryonic life. Abnormalities in the development of pulmonary venous system occur either by the absence of common pulmonary vein communication to the splanchnic plexus or by the absence of its incorporation into the dorsal wall of the left atrium. We present the case of a 10-day-old male newborn, diagnosed with TAPVC, operated, with long recovery and, who died by pneumonia, heart failure, and obstructive pulmonary disease (one pulmonary vein obstructed and another one with severe stenosis). Total anomalous pulmonary venous connection (TAPVC) reflects one of the most severe forms of congenital heart disease, with important clinical consequences.

The role of ¹³C-methacetin breath test for the non-invasive evaluation of nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in many parts of the world. The ¹³C-methacetin breath test (MBT), a microsomal liver function test, enables quantitative evaluation of cytochrome P450-dependent liver function involved in NAFLD pathogenesis. The aim of our study was to evaluate the efficacy of MBT in differentiating patients with non-alcoholic steatohepatitis (NASH) from patients with simple steatosis (SS) and its ability to predict significant fibrosis in NAFLD patients. METHODS: We performed MBT in 64 patients with histologically proven NAFLD (ranging from SS to severe steatohepatitis) and in 20 healthy controls. Brunt scoring system for histological evaluation of NAFLD served as a reference. The correlation between MBT parameters and liver biopsy was tested using Spearman's coefficient. The overall validity was measured using the area under the receiver operating characteristic curve (AUROC) with 95%CI. RESULTS: ¹³C-MBT is a good tool for identifying patients with histologically proven NASH, with an AUROC of 0.824, 95% CI (0.723-0.926), a sensitivity of 95% and a specificity of 74%. The diagnosis accuracy of ¹³C-MBT for significant fibrosis (F ≥2) has a validity of 91% (95% CI, AUROC = 0.830-0.989) with higher sensitivity (90%) and specificity (81%). ¹³C-MBT values predicted better F3 or F4 fibrosis (AUROC were 0.936 and 0.973). CONCLUSION: Due to the impairment of microsomal function which occurs in NAFLD, ¹³C-MBT could be a reliable diagnostic and follow-up test for NAFLD patients.

A randomized, open trial evaluating the effect of Saccharomyces boulardii on the eradication rate of Helicobacter pylori infection in children.

AIM: The failure rate of Helicobacter pylori (H. pylori) eradication imposes the assessment of new options. SUBJECTS AND METHODS: A prospective open study was performed in 90 symptomatic children (range 3-18 years) with H. pylori infection, randomized in two groups: control (42 patients) and intervention group (48 patients). Both groups were treated with the standard triple eradication therapy (omeprazole/esomeprazole, amoxicillin and clarithromycin) for 7-10 days. The intervention group was also treated with Saccharomyces boulardii (S. boulardii), 250 mg b.i.d., for 4 weeks. The eradication rate of H. pylori was assessed by the same methods (urease test and histology) 4-6 weeks after treatment. Adverse events and compliance were evaluated after 7 and 28 days of treatment. The Chi-square test was used for statistical evaluation (p < 0.05). RESULTS: H. pylori infection was identified in 90 of 145 children (62%) and it correlated positively with age (p < 0.002) and inversely with socioeconomic status (p < 0.005). All infected children had chronic gastritis, with antral nodularity in 76.7%. Overall, H. pylori eradication rate was 87.7% (control 80.9%, S. boulardii group 93.3%) (p = 0.750). The incidence of side effects was reduced in the S. boulardii group: 30.9% in the control versus 8.3% in the probiotic group (p = 0.047). CONCLUSION: The addition of S. boulardii to the standard eradication treatment confers a 12% nonsignificant enhanced therapeutic benefit on H. pylori eradication and reduces significantly the incidence of side effects.