Safety and Efficacy of 2.5 mg and 1.25 mg Nebulized Salbutamol Compared with Placebo on Transient Tachypnea of the Newborns: A Triple-Blind Phase II/III Parallel Randomized Controlled Trial.

Background: To evaluate the safety and efficacy of 2.5 and 1.25 mg nebulized salbutamol on Transient Tachypnea of the Newborn (TTN) compared with placebo. Methods: We conducted a triple-blind, phase II/III parallel randomized controlled trial in two university-affiliated hospitals with neonatal intensive care units. Newborns with a confirmed diagnosis of TTN, with gestational age >35 weeks and gestational weight >2 kg were included. Cases of asphyxia, meconium aspiration syndrome, and persistent pulmonary hypertension were excluded. Ninety eligible patients were randomly allocated in three intervention groups (2.5 mg salbutamol, 1.25 mg salbutamol, and placebo), and a single-dose nebulized product was prescribed 6 hours after the birth. Safety outcomes included postintervention tachycardia, hyperglycemia, hypokalemia, and changes in blood pressure. To evaluate the efficacy, the duration of postintervention tachypnea, TTN clinical score, and clinical and paraclinical respiratory indices were assessed. Parents, Outcome assessors, and data analyzer were blind to the intervention. Results: There was no adverse reaction, including tachycardia, hypokalemia, and jitteriness. Both groups of salbutamol recipients showed significant improvement regarding respiratory rate, TTN clinical score, and oxygenation indices compared with the placebo (p-values <0.001). Nonstatistically significant higher hospital stay was observed in the placebo group. Single 2.5 mg salbutamol nebulization showed a little better outcome than the dose of 1.25 mg, although we could not find statistical superiority. Conclusion: The newly applied single high dose of 2.5 mg nebulized salbutamol is safe in treating TTN and leads to notable faster improvement of respiratory status without any considerable adverse reaction. Registry code: IRCT20190328043133N1.

Fulminant coronavirus disease 2019 meningitis in Iranian infants: a case series.

BACKGROUND: Pediatric coronavirus disease 2019 infection usually presents with respiratory and gastrointestinal symptoms. In this report we present fulminant meningitis as the main presentation of coronavirus disease 2019 without major signs and symptoms of other organs' involvement in 3 infants. CASES: The first case was a 4 months Iranian male infant with fulminant meningitis as the main presentation of coronavirus disease 2019 without other organ involvement. He was treated as suspected bacterial meningitis but CSF PCR and CSF culture were negative for common meningeal pathogens. On 3rd day, his coronavirus disease 2019 PCR test became positive, while it was negative on 1st day. The second case was a 13 months Iranian male infant with fever, irritability, and photophobia for 24 h before poorly controlled status epilepticus. CSF coronavirus disease 2019 PCR became positive while CSF PCR and CSF culture were negative for other common meningeal pathogens. Seizures were controlled with multiple anti-seizure medications. The third case was a 14 months Iranian female infant with fever and seizure1 hour before admission, leading to poorly controlled status epilepticus despite anti-epileptic therapy 10 h after admission. CSF coronavirus disease 2019 PCR became positive while CSF PCR and CSF culture were negative for other common meningeal pathogens. He was controlled with multiple anti-seizure medications. CONCLUSION: Meningitis of coronavirus disease 2019 should be considered in severely ill pediatric cases with poorly controlled seizures and RBC in CSF smear. Also, pediatricians can consider corticosteroids, remdesivir, and IVIG therapy in these cases.

Impact of Religiosity on Delirium Severity Among Critically Ill Shi'a Muslims: A Prospective Multi-Center Observational Study.

This study assesses the impact of religiosity on delirium severity and patient outcomes among Shi'a Muslim intensive care unit (ICU) patients. We conducted a prospective observational cohort study in 21 ICUs from 6 Iranian academic medical centers. Delirium was assessed using the Confusion Assessment Method for the ICU (CAM-ICU) tool. Eligible patients were intubated, receiving mechanical ventilation (MV) for ≥ 48 h. Illness severity was assessed using Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. A total of 4200 patients were enrolled. Patient religiosity was categorized as more (40.6%), moderate (42.3%), or less (17.1%) based on responses to patient and surrogate questionnaires. The findings suggest that lower pre-illness religiosity may be associated with greater delirium severity, MV duration, and ICU and hospital LOS. The lower mortality in the less religiosity group may be related in part to a greater proportion of female patients, but it remains unclear whether and to what extent greater religiosity impacted treatment decisions by patients and families. Further investigation is needed to validate and clarify the mechanism of the mortality findings.

A case of classic galactosemia manifesting as neonatal early and profound indirect hyperbilirubinemia.

Galactosemia is a rare autosomal recessive metabolic disorder that has three major types. The most common type is classic galactosemia. These patients have deficient galactose-1-phosphate-urydiltransferase. The enzyme deficiency often results in symptomatic disease if breastfeeding or lactose-containing formulas continue. Neonatal jaundice is among the most prevalent symptoms. Although patients with classic galactosemia mostly demonstrate direct neonatal hyperbilirubinemia (cholestasis), seldom they may initially have indirect hyperbilirubinemia. Herein, we present a newborn with initial neonatal profound indirect hyperbilirubinemia who responded well to intensive phototherapy, then presented with cholestasis and was finally diagnosed as having classic galactosemia. Unfortunately, major textbooks of neonatology and pediatrics are still missing galactosemia as one of the differential diagnoses of neonatal indirect hyperbilirubinemia. It is just mentioned as prolonged or direct neonatal hyperbilirubinemia. We recommend that galactosemia be included in the differential diagnosis of neonatal early indirect hyperbilirubinemia because neonatal screening results may be delayed or missed completely.

Direct drug susceptibility testing of Mycobacterium tuberculosis using the proportional method: A multicenter study.

INTRODUCTION: Conventional indirect drug susceptibility testing (DST) of Mycobacterium tuberculosis with solid media is inexpensive and reliable, but time-consuming. This study aimed to evaluate direct DST for testing sputum samples without culture to significantly reduce the time required to detect multidrug-resistant tuberculosis (MDR-TB). METHODS: Direct and indirect DST of isoniazid (INH), rifampicin (RIF) and ethambutol (EMB) were performed on 334 sputum smear-positive specimens. RESULTS: There was full agreement between the results obtained from direct testing and after isolation of the bacteria by culture. Thus, the sensitivity and specificity were observed to be 100% for all three tested drugs when compared with indirect DST. In comparison with indirect DST, none of the samples with the direct method took >25days to report the DST (between 15-25days with a mean detection time of 20 days). CONCLUSIONS: Direct DST on solid media was shown to give reliable results at a much earlier stage than conventional phenotypic DST. The direct method was found to be more rapid, more accurate and simpler. In addition, it reduced the handling of pathogenic bacteria and thus reduced the bio hazards related to conventional DST.

Neuroprotective Agents in the Intensive Care Unit: -Neuroprotective Agents in ICU.

Neuroprotection or prevention of neuronal loss is a complicated molecular process that is mediated by various cellular pathways. Use of different pharmacological agents as neuroprotectants has been reported especially in the last decades. These neuroprotective agents act through inhibition of inflammatory processes and apoptosis, attenuation of oxidative stress and reduction of free radicals. Control of this injurious molecular process is essential to the reduction of neuronal injuries and is associated with improved functional outcomes and recovery of the patients admitted to the intensive care unit. This study reviews neuroprotective agents and their mechanisms of action against central nervous system damages.

Assessment of Toxoplasma Seropositivity in Children Suffering from Anxiety Disorders.

OBJECTIVE: This study aimed to assess the seroprevalence of Toxoplasma gondii in children with anxiety disorders. MATERIALS & METHODS: This cross-sectional study was conducted between Sep 2012 and May 2013 in Pediatrics Clinic of Baqiyatallah Hospital, Tehran, Iran. Children were assessed clinically. Diagnosis of patients with anxiety disorders was based on DSM-4 system, performed by child psychiatrist. Then their anti-Toxoplasma antibodies were measured. A questionnaire was verbally administered to all individuals' parents including demographic information and questions about life style, family history, medical history, economic situation, residence, nutritional patterns and contact with animals. RESULTS: Ninety-six male and female cases with a mean age of 8.56±2.5 and 8.42±1.9 yr underwent analysis. Anti- T. gondii IgG antibody was found in one case of each group. There was no significant difference between case and control groups for serum Toxoplasma IgG antibody (P=0.14). No case individuals had Anti- T. gondii IgM antibody, while it was found in one control individual. No significant difference was seen between case and control groups for Toxoplasma IgM antibody (P=0.27). CONCLUSION: Toxoplasmosis has no direct effect on the incidence of anxiety disorders. More studies are needed with a larger volume of individuals in future.

Neurobrucellosis Presenting with Unilateral Abducens Nerve Palsy.

One of the rare complications of brucellosis is neurobrucellosis. There have been numerous reports showing clinical forms of brucellosis affecting CNS, such as cranial nerve involvement, myelitis, vascular disease, radiculoneuritis, meningitis, meningoencephalitis, and demyelinating disease. In this case report, we introduce a 2.5 yr old girl with unilateral abducens nerve palsy referred to Baghiyatallah Hospital Outpatient Clinic, Tehran, Iran in June 2015.

The effect of transplanted human Wharton's jelly mesenchymal stem cells treated with IFN-γ on experimental autoimmune encephalomyelitis mice.

Interferon gamma (IFN-γ) increases the immunosuppressive property of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs). In this study, we evaluated the therapeutic effects of IFN-γ primed WJ-MSCs in EAE mice. IFN-γ primed WJ-MSCs were injected on days 3 and 11 after EAE induction. 21 days after EAE induction, splenocytes and cervical lymph node cells were isolated and cell proliferation, secretion of inflammatory cytokines and frequency of regulatory T-cells was measured. On day 50 of the study, cell infiltration and gene expression of inflammatory cytokines in brain of mice were studied. Leukocyte infiltration and symptoms were significantly reduced in IFN-γ primed WJ-MSCs treated group compared to other groups. These cells showed significantly reduced proliferation and increased Treg cells as well as decreased secretion and gene expression of inflammatory cytokines in EAE mice. Our data suggest that IFN-γ may be used to stimulate the immunomodulatory property of WJ-MSCs in clinical situations.

The Main Causes of Bacterial Colonization in Endotracheal Tubes and Tracheal Secretions in Neonates Admitted to the Neonatal Intensive Care Unit.

BACKGROUND: Ventilator-associated pneumonia (VAP) is the second most common nosocomial infection in neonates, admitted to neonatal intensive care units (NICUs). The aim of this study was to identify the main causes of bacterial colonization in endotracheal tubes and tracheal secretions of neonates hospitalized in the NICUs of our university hospitals. MATERIALS AND METHODS: This cross sectional study was conducted during 2015-2016. Thirty-nine neonates, who were under mechanical ventilation in the NICUs of Baqiyatallah and Najmiyeh hospitals of Tehran, Iran, were assessed. The patients were selected using the census sampling method. Gestational age, birth weight, duration of mechanical ventilation, length of hospital stay, tracheal discharge culture, endotracheal tube culture, blood culture, and chest radiography were evaluated. RESULTS: In a total of 39 neonates (50.3% males and 49.7% females) with the mean age of 1.17±1.12 days, bacterial growth was reported in 6 (15.3%) cases. The antibiotic study of tracheal secretion and endotracheal tube cultures showed that 2.6% of patients were resistant to cephalosporins, aminoglycosides, nitrofurantoin, and carbapenem. Moreover, 12.8% were also resistant to fluoroquinolones, besides these antibiotics. CONCLUSION: Tracheal secretion culture is a simple and proper approach for the diagnosis of VAP. Besides reducing the costs, this method can play a significant role in decreasing the incidence of infections.

Comparison of the Vitamin D Status of Children Younger and Older Than 2 Years in Tehran: Are Supplements Really Necessary?

BACKGROUND: Vitamin D is a vital lipid-soluble vitamin in the body, helping the growth and development of bones. Vitamin D deficiency in children has several adverse effects. The most important preventative factor is determining the deficiency at an early stage and prescribing vitamin D-containing supplements. OBJECTIVES: To investigate the vitamin D status of children younger and older than 2 years and determine the utility of prescribing vitamin D supplements. PATIENTS AND METHODS: Three hundred healthy children who attended the pediatric clinic for routine assessments were enrolled in this study. Their parents were asked to complete a questionnaire, which included questions about demographics, nutrition, and supplements. Blood levels of vitamin D, calcium, and phosphorus were then measured. RESULTS: The final study consisted of 286 children, 140 males and 146 females, with a mean age of 4.46 ± 2.82 yr. Of these, 218 (76.22%) children, with a mean age of 5.09 ± 2.82 yr, had vitamin D deficiency, and 76 children (23.78%), with a mean age of 2.58 ± 1.88 yr, had normal vitamin D levels (P = 0.001). The mean level of vitamin D was 29.71 ± 14.42 ng/mL in 88 (30.8%) patients up to 2 years and 17.11 ± 14.02 ng/mL in 198 (69.2%) patients older than 2 years (P = 0.0001). CONCLUSIONS: The vitamin D levels of children aged more than 2 years are lower than those of children aged less than 2 years. Thus, prescribing vitamin D-containing supplements in children older than 2 years may be beneficial.

Low Dose of Octreotide Can be Helpful in the Management of Congenital Chylothorax.

INTRODUCTION: A rare condition in newborns called congenital chylothorax (CC) occurs when lymphatic fluid accumulates within the pleural cavity. Here is a presentation of a birth traumatic case with bilateral pleural effusion successfully treated by octreotide. CASE PRESENTATION: A 3100-g-term male newborn delivered vaginally from a 33-year-old mother was admitted to the neonatal intensive care unit with respiratory distress signs. Early chest x-ray (CXR) showed bilateral pleural effusion. The thoracentesis pleural fluid had been drained with these characteristics: glucose: 1.9425 mmol/l, protein: 11 g/l, cholesterol: 1.295 mmol/l, and triglycerides: 3.39 mmol/l. Counts of red blood cells and white blood cells were 10,000 and 2500 per Cu/mm, respectively; so, congenital chylothorax was diagnosed and total parenteral nutrition (TPN) were initiated. Accumulation of plural fluid was approximately stopped after begging TPN for two weeks. Therefore, we started feeding with a medium chain triglyceride (MCT), but plural effusion was seen once again and we had to restart TPN. We decided to start octreotide subcutaneously (1 µg/kg/day). Finally, the CXR and ultrasound 'did not show any pleural effusion in both sides and the ultrasound done in the third month showed no pleural effusion either. CONCLUSIONS: Octreotide therapy as one of the conservative managements for CC can be considered before surgical methods. This treatment method also had some effects on the feeding initiation time and helped us to start feeding sooner. However, more studies like clinical trials are still necessary to investigate all aspects of octreotide treatment to determine the amount of its dose, initiation time, treatment duration, etc.

Sleep Problems Under-Reported by Parents in Iranian Children.

Sleep problems are common in childhood, but there are limited studies regarding that in Iranian children and awareness of the sleep problems and their complication in Iranian parents. We arranged this study in which parents of children attending for a sick visit or routine growth control to assess whether sleep problems are under-reported at general pediatric visits. In a cross-sectional study from April 2010 to April 2011 in 301 children aged 2-14 years old attending to pediatric clinics were enrolled. To investigate the general orientation of parents about their child sleep problem we asked them a global question at first regarding sleep of their child. After that, the Persian version of BEARS questionnaire was completed by them. Only 30 (9.9%) parents reported sleep problems in their children in response to primary global question but by collecting the data from BEARS questionnaire it was revealed 45.18% (136/301) of children had one or more of sleep disorders at all. As mentioned 136 (45.18%) children had slept problems of which the most frequent complaint (15.28%) was related to bedtime problems. The second complaint (11.96%) was awakening during the night children. A significant association between sleep problems and child gender was not found. Co-sleeping with parents was found in 55.48% of all children in this study. Despite the high prevalence and adverse effects of sleep disorders, the present study suggests that parents underreport sleep problems at consultation. We suggest children should be assessed for sleep disorders in monitoring and health screening visits.

Estimation of Recent Transmission of Mycobacterium Tuberculosis Strains among Iranian and Afghan Immigrants: A Cluster-Based Study.

BACKGROUND: Iran has extended borders with high-TB burden countries (Afghanistan and Pakistan) and immigrations of these populations influences TB distribution in the region and threatens the control strategies. The aim of this study was to evaluate the extent of recent TB transmission among Iranian and Afghan cases. MATERIALS AND METHODS: Spoligotyping and 15-locus variable number tandem repeat (VNTR) typing were applied to genotype 102 MTB isolates (2009 to 2010). Phylogenetic relationships were analysed by two methods: a cluster-graph method and a minimum spanning tree (MST) method. Furthermore, evaluation of recent TB transmission was assessed with three indices including, RTIn, RTIn-1 and TMI. RESULTS: Using molecular typing, 35 different spoligotypes were detected among the studied isolates. Seventy seven cases (75.4%) were distributed into 10 clusters and the remaining 25 (24.5%) isolates had a unique pattern. The cluster sizes also ranged from 2 to 21 isolates. The most frequent spoligotype in our populations belong to Haarlem (n=30, 29.4%) followed by CAS (n= 29, 28.4%) and Beijing (n=16, 15.6%) lineages. The used indices give the following values: RTIn = 0.75, RTIn-1 = 0.65 and TMI = 0.24. CONCLUSION: The low rate of TB transmission in our findings (24%) showed that the mode of TB transmission in Iran is mostly associated with reactivation of a previous TB infection and that recently a transmitted disease has a minor role. However, the increasing incidence of the intra-community transmission in recent years highlights the need for establishing new strategies for control of TB.

The First Macrolide-Resistant Bordetella pertussis Strains Isolated From Iranian Patients.

BACKGROUND: Whooping cough was considered as one of the major causes of childhood morbidity and mortality worldwide. Resistant isolates of Bordetella pertussis to macrolides in some countries have been recently reported. OBJECTIVES: Recent reports on macrolide-resistant B. pertussis isolates and lack of evidence for such resistance in clinical isolates of the Iranian patients led the authors of the current study to study antibiotic susceptibility of the collected isolates in the country. Susceptibility of the B. pertussis isolates to three antibiotics was studied. Relatedness of the strains recovered in this research was also examined. MATERIALS AND METHODS: The antibacterial activities of erythromycin, azithromycin, and clarithromycin antibiotics against the recovered isolates of 779 nasopharyngeal swabs were examined using MIC (Minimum Inhibitory Concentration) method. Relationship of the strains was characterized by Pulsed-field Gel Electrophoresis (PFGE). RESULTS: Among the specimens, 11 cases (1.4%) were culture-positive. Among these isolates, only two isolates had high MIC values for erythromycin and clarithromycin. Pulsed-field gel electrophoresis analysis of the isolates revealed 6 PFGE profiles (A-F) among which three and two isolates had the same patterns in profiles A and B, respectively. CONCLUSIONS: Azithromycin can be a good drug of choice to treat patients infected by B. pertussis in Iran. Clonal relationship of the isolates showed that the same B. pertussis strains were isolated from different patients in Iran.

Thyroid Function Test in Pre-term Neonates During the First Five Weeks of Life.

BACKGROUND: Congenital hypothyroidism (CHT) is one of the most common congenital endocrinal disorders. The prevalence of CHT is estimated about 1 in 3,000 newborns. The prevalence, etiology and associated disorders of abnormal thyroid screening tests are reported in different ranges. In this study, we assessed the pre-term newborns for CHT and associated factors that influence thyroid function. METHODS: One hundred newborns with the gestational age fewer than 35 weeks were investigated. Baseline serum thyroid stimulating hormone (TSH) and free thyroxin (FT4) levels were measured during the first 5 days of life and were repeated during the first 5 weeks. We analyzed the effects of demographic factors and the presence of respiratory distress syndrome on the alteration of thyroid function tests during the first 5 weeks of life. RESULTS: The mean gestational age (GA) at delivery was 32.35í1.97 (range 28 to 35) weeks. CHT was observed in 13(13%) preterm infants. GA was the only factor which affect the FT4 changes over the two weeks follow-up (P < 0.001, b: -2.783, Power: 70.2%) although the differences between baseline and follow-up amount of TSH were not significantly influenced by GA (P = 0.062, power: 46%). However, the adjusted TSH and FT4 serum level changes during follow-up were significantly different between two groups (between CHT and normal, P = 0.006, 0.000, respectively). CONCLUSIONS: It seems that thyroid function tests should be repeated in preterm infants, especially for patients with lower gestational age, to confirm the diagnosis of CHT. Also, CHT should be considered among the newborns that are affected by RDS.

Magnetic resonance imaging findings in epileptic children and its relation to clinical and demographic findings.

Epilepsy is an important disease with a cumulative incidence of 3% all over the life and more than half of them are started from childhood. In this study we surveyed magnetic resonance imaging (MRI) findings in epileptic children and its relation with clinical and demographic findings in order to find better diagnostic and treatment modalities for these children in the future. In this cross sectional study, we investigated consecutively all 1 to 15-year-old epileptic children who referred to the pediatric neurology outpatient clinic from 2004 to 2010. Two hundred children were enrolled for investigation. There were 85 (42.5%) girls and 115 (57.7%) boys, aged 1 to 15-year-old (7.7 ± 4). 196 (98%) of the children had abnormal electroencephalography (EEG). Abnormal MRI was seen in 57 (28.5%) patients and consisted of brain atrophy (10%), increasing white matter signal intensity in T2-weighted images (8%), benign cysts (5%), brain tumors (4%) and vascular abnormalities (1.5%). Abnormal MRI findings had significant relation with abnormal EEG, age, positive family history for epilepsy, dysmorphic appearance, and abnormal physical exam. Considering 98% EEG abnormalities in these epileptic children, benign nature of MRI findings in most of our cases, the high price of MRI and the small minority of patients who benefit from active intervention as a result of MRI, we suggest to use EEG for confirmation of epilepsy and perform MRI for patient with abnormal physical exams, focal neurologic deficits or focal EEG abnormalities.