Israel Medical Association Journal

The discovery of Jewish babies who were born in Nazi concentration camps and survived seems miraculous, but this phenomenon did occur toward the end of World War II. The lives of a small group of mothers and surviving children are of both historical and medical interests. Their survival shows additional support for the hypothesis that maternal nutrition can induce metabolic syndrome and bone demineralization in their offspring. Information obtained through direct contact with some of the surviving children is the basis for this article.

Background: Diabetic ketoacidosis (DKA) as the first presentation of type 1 diabetes mellitus (T1DM) is a serious complication that is preventable.

Objectives: To identify risk factors for DKA at presentation of T1DM to delineate high-risk Israeli populations that could benefit from preventative measures.

Methods: Data for this multicenter retrospective study were collected from the medical files of three pediatric diabetes centers representing three districts in Israel. Inclusion criteria were diagnosis of T1DM, age at diagnosis ≤ 17 years, permanent residency in Israel, and documentation of the presence or absence of DKA at presentation.

Results: The study population included 607 patients of whom 438 met the inclusion criteria. The mean age at diagnosis was 9.1 ± 4.5 years. DKA was present at diagnosis in 156/438 patients (35.6%). The incidence of DKA was different among the three diabetes centers (P = 0.04). The DKA group was significantly younger than the non-DKA group (8.4 ± 4.5 vs. 9.5 ± 4.4, respectively, P = 0.008). DKA was significantly associated with maternal origin (Ashkenazi Jewish origin [lower] vs. non-Ashkenazi, P = 0.04) and with paternal education level (academic [lower] vs. non-academic education, P = 0.04). Stepwise logistic regression showed that maternal Ashkenazi Jewish origin has a protective effect on DKA (odds ratio [OR] 0.4, 95% confidence interval [95%CI] 0.21–0.74, P = 0.004) and that younger age is an independent risk factor (OR 1.06, 95%CI 1.01–1.1, P = 0.02).

Conclusions: A diabetes educational program targeting high-risk population groups may reduce the prevalence of DKA nationwide.

Background: Empiric treatment for Helicobacter pylori is influenced by antibiotic susceptibility of infecting strains. A rise in the resistance rate to clarithromycin and metronidazole has been reported in pediatric populations.

Objectives: To assess the primary and secondary antibiotic resistance of H. pylori isolates in Israeli children and adolescents.

Methods: A retrospective review of H. pylori isolates cultured from antral biopsies of consecutive children aged 1 to 18 years, who were referred to the Pediatric Gastroenterology Unit, Kaplan Medical Center, over a 2.8 year period, was performed. Antibiotic susceptibility to clarithromycin, metronidazole, amoxicillin, tetracycline, and levofloxacin was determined by E-test. Data on the age of the patient, indication for endoscopy, and antibiotic treatment for H. pylori in previously treated children was collected.

Results: Cultures for H. pylori yielded 123 isolates. In children not previously treated (n=95), the primary global resistance was 38% with resistance to clarithromycin 9.5%, metronidazole 32.6 %, and to both 4.2%. Respective rates of resistance in previously treated children (n=28) were 71% (P = 0.002), 29% (P = 0.02), and 61% (P = 0.007). Simultaneous resistance to both drugs was found in 18% (P = 0.02). All H. pylori strains were susceptible to amoxicillin, tetracycline, and levofloxacin. Past eradication treatment was the only independent risk factor for antibiotic resistance in multivariate analysis.

Conclusions: Significantly higher resistance rates were found in previously treated patients, stressing the need to refrain from empiric treatment using the "test and treat strategy." Culture-based treatment strategy should be considered in all previously treated children.

Background: A good physical exam is necessary to help pediatricians make the correct diagnosis and can save unnecessary imaging or invasive procedures. Distraction by medical clowns may create the optimal conditions for a proper physical examination.

Methods: Children aged 2–6 years who required physical examination in the pediatric emergency department were recruited and randomly assigned to one of two groups: physical exam by a pediatrician in the presence of caregivers vs. physical exam with the assistance of a medical clown. Outcome measures consisted of the level of child's discomfort, anxiety, and the quality of the physical examination.

Results: Ninety three children participated. Mean age was 3.3 ± 3.6 years (range 2–6). The duration of the physical exam was similar between the clown and control groups (4.6 ± 1.4 minutes vs. 4.5 ± 1.1 minutes (P = 0.64). The duration of discomfort was shorter in the clown group (0.2 ± 0.6 minutes) than the control group(1.6 ± 2.0 minutes, P = 0.001). In the medical clown group, 94% of pediatricians reported that the medical clown improved their ability to perform a complete physical examination. A trend of less hospitalization in the medical clown group was also noticed (11.3% in the medical clown group vs. 18.3% in the control group, P = 0.1); however, further study is required to verify this observation.

Conclusions: Integration of a medical clown in physical examination improves the overall experience of the child and the caregivers and helps the pediatrician to perform a complete physical examination.

Background: Virtual autopsies by computer tomography (CT) or magnetic resonance imaging can be valuable in cases of unexplained infant death. The radiologist must be familiar with the normal appearance of all the segments of the thoracic aorta in normal and deceased children. A thorough review of the literature revealed no prior articles describing CT changes in the ascending aorta or the aortic arch in pediatric virtual autopsies.

Objectives: To compare the CT appearance of the thoracic aorta in deceased children and in those younger than 3 years of age.

Methods: Hospital registries were searched for cases of unexpected deaths in children younger than 3 years old, with a postmortem CT available, as well as for clinically indicated chest CT in children of the same age during a 5 year period. The ascending aorta (AA), aortic arch (arch), and the descending aorta (DA) diameters were measured. Student's t-tests and Mann–Whitney U-tests were used to compare the two groups.

Results: A total of 64 scans were reviewed: 35 postmortem and 29 performed on living patients. The differences in the diameter and the ratios of the diameter between the AA and the arch, as well as between the arch and the DA in the postmortem and living groups were statistically significant (P < 0.05).

Conclusions: On postmortem CT scans, we found focal tapering of the aortic caliber at the level of the arch between the origin of the brachiocephalic artery and left subclavian artery. This finding should not be misinterpreted as a hypoplastic aortic arch.

Background: Several studies link the pathogenesis of nephrotic syndrome to tumor necrosis factor-alpha (TNFα). However, data on the serum TNFα level in children with nephrotic syndrome are sparse. 

Objective: To investigate serum TNFα levels and the effect of steroid therapy in children with nephrotic syndrome. 

Methods: A prospective cohort pilot study of children with nephrotic syndrome and controls was conducted during a 1 year period. Serum TNFα levels were measured at presentation and at remission, or after a minimum of 80 days if remission was not achieved.

Results: Thirteen patients aged 2–16 years with nephrotic syndrome were compared with 12 control subjects. Seven patients had steroid-sensitive and six had steroid-resistant nephrotic syndrome. Mean baseline serum TNFα level was significantly higher in the steroid-resistant nephrotic syndrome patients than the controls (6.13 pg/ml vs. 4.36 pg/ml, P = 0.0483). Mean post-treatment TNFα level was significantly higher in the steroid-resistant than in the steroid-sensitive nephrotic syndrome patients (5.67 pg/ml vs. 2.14 pg/ml, P = 0.001). In the steroid-resistant nephrotic syndrome patients, mean serum TNFα levels were similar before and after treatment.

Conclusions: Elevated serum TNFα levels are associated with a lack of response to corticosteroids. Further studies are needed to investigate the role of TNFα in the pathogenesis of nephrotic syndrome.

 

Background: Legg-Calvé-Perthes disease (LCPD) is an idiopathic hip osteonecrosis prevalent in children < age 15 years. The etiology remains incompletely understood, partly because of multiple potential environmental risk factors and partly because of lack of genetic markers. It has been hypothesized that hyperactivity may induce mechanical stress and/or vascular damage at a fragile joint. 

Objectives: To assess children with LCPD for markers of attention deficit hyperactivity disorder (ADHD) relative to their unaffected comparably aged siblings to exclude the contribution of hyperactive behavior versus environmental and/or genetic factors in LCPD. 

Methods: All children followed in the Pediatric Orthopedic Clinic, and their comparably aged siblings, were recruited. ADHD was assessed using the TOVA computerized test and DSM-IV criteria. Quality of life and sleep disorders as ancillary tests were assessed using the Child Health Questionnaire (Parent Form 50), Pediatric Outcomes Data Collection Instrument, and Pediatric Daytime Sleepiness Scale.

Results: Sixteen children with LCPD (age 9.1 ± 3.3, 75% males) were compared with their closest-aged siblings (age 9.3 ± 2.6, 30% males). Mean TOVA scores of children with LCPD (-3.79 ± 2.6) and of their non-LCPD siblings (-3.6 ± 4.04) were lower relative to the general population (0 ± 1.8, P < 0.0001). Both group means were in the ADHD range (≤ -1.8) implying that 73% of this LCPD cohort and 53% of their non-LCPD siblings performed in the ADHD range, relative to 3.6% incidence expected in the general population (P < 0.0001). Other test results were similar in both groups. 

Conclusions: Our findings in a small cohort of children with LCPD and their comparably aged siblings do not support an association between LCPD and ADHD. ADHD markers were equally high in the LCPD children and siblings. 

 

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention, impulsivity and hyperactivity. Recently, increases in ADHD prevalence and methylphenidate use have been reported. There is evidence that children and adolescents use ADHD medication only during the school year. 

Objectives: To investigate trends in methylphenidate dispensing over a period of 3 years (2010–2012) at the monthly level and to investigate whether there is any monthly variation, especially during the summer season.

Methods: The database of Clalit Health Services (the largest of the four health funds in Israel) was used to identify (i) patients aged 6–17 years with a diagnosis of ADHD, and (ii) methylpenidate dispensation during the period 2010–2012. 

Results: Among children aged 6–17 years diagnosed with ADHD, 43% were treated with methylphenidate. For the period 2010 to 2012 there was an annual drop in methylphenidate dispensing, beginning in June and continuing through the 2 months of summer vacation, with a 2.5-fold reduction from July as compared to May. This decline was consistently followed by a rise in medications dispensed starting August. A similar small drop was observed during the Passover school vacation. The summer drop decreased over the years.

Conclusions: Our findings showed a decrease in the number of methylphenidate prescriptions dispensed during the summer months and Passover as compared to the rest of the year. However, this phenomenon appears to be decreasing. Given that ADHD is a chronic disease state that can effectively be managed with pharmacotherapy, discontinuation of treatment may be harmful for patients and should be considered only on a patient-by-patient basis.

 

Background: Medical clowns are increasingly used for diminishing pain and anxiety during painful procedures being performed on children in the hospital setting. Cortisol levels rise as a response to emotional distress. 

Objectives: To investigate whether medical clown-assisted interventions to reduce child's distress during venipuncture have an effect on cortisol levels. 

Methods: During a 1 year period, children requiring blood work or intravenous access in the pediatric emergency department were prospectively randomized to either the presence or absence of a medical clown during the procedure. The child's distress was evaluated using the Faces Pain Scale - revised (FPS-R) for the 4–7 year age group and the visual analog scales (VAS) for those aged 8–15 years. Serum cortisol levels were measured in blood samples obtained by venipuncture. 

Results: Fifty-three children aged 2–15 years were randomly assigned to the study group (with medical clown, n=29) or to the control group (without medical clown, n=24). Combined pain scores of the study group and control group were 2.2 and 7.5 respectively (P < 0.001). No difference in mean cortisol levels was found between the study group and the control group at all ages (16.4 µg/dl vs. 18.3 µg/dl, P = 0.65).

Conclusions: In this pilot study, medical clowns reduced the distress from venipuncture in children. No effect on cortisol levels was observed. 

Background: Hypernatremic dehydration is a common and potentially life-threatening condition in children. There is currently no consensus as to the optimal strategy for fluid management. Objectives: To describe the relationship between the type, route and rate of fluids administered and the rate of decline in serum sodium (Na+) concentration. 

Methods: We reviewed the medical records of all children under the age of 2 years who were hospitalized with hypernatremic dehydration (serum Na+ ≥ 155 mEq/L) in Shaare Zedek Medical Center during the period 2001–2010. Collected data of 62 subjects included initial and subsequent serum Na+ levels, and rate and Na+ concentration of all intravenous and oral fluids administered until the serum Na+ reached ≤ 150 mEq/L.

Results: Median initial serum Na+ was 159.5 mEq/L (IQR 157–163, maximal value 170). The median rate of decline in serum Na+ until serum Na+ reached 150 mEq/L was 0.65 mEq/L/hr (IQR 0.45–0.95). Forty-two children received hypotonic oral fluids which accounted for approximately one-quarter of all fluids they received. There was no significant difference in the rate of decline in serum Na+ between those who consumed oral fluids and those who did not. Neither was there a correlation between the rate of IV fluids, receipt of oral fluids or the degree of dehydration, with the rate of decline in serum Na+. No child experienced an apparent short-term adverse outcome. 

Conclusions: A cumulative rate of 5.9 ml/kg/hr of IV fluid administration may reduce the serum Na+ to an acceptable rate (0.65 mEq/L/hr). Fluid therapy comprising up to 25% hypotonic oral fluids and 75% IV fluids high in Na+ concentration was not associated with any short-term adverse outcome in our patient population. 

 

Background: Use of the internet and videogames by children and adolescents has risen dramatically over the last decade. Increasing evidence of internet and videogame addiction among children is causing concern due to its harmful physical, emotional and social consequences. There is also emerging evidence for an association between computer and videogame addiction and attention deficit/hyperactivity disorder (ADHD). 

The major route of hepatitis C virus (HCV) infection in the pediatric age group is vertical, with infection occurring in up to 5% of infants born to mothers positive for HCV-RNA. The natural course of pediatric HCV infection is characterized by a high rate of spontaneous clearance, an asymptomatic clinical course, and normal or mild histologic changes. Cirrhosis is reported in 1–2% of children and progression to severe chronic liver disease and HCC occurs 20–30 years after infection. Treatment with pegylated interferon (Peg-IFN) + ribavirin results in a sustained viral response (SVR) of up to 100% in children with HCV genotypes 2 or 3 but only 45–55% in those infected with genotypes 1 or 4. Treatment is associated with adverse effects ranging from flu-like symptoms, myalgia, anemia and thrombocytopenia, to less commonly observed thyroid-related symptoms, alopecia, neuropsychiatric manifestations and possible long-term effects on growth. Ongoing trials with direct-acting antiviral agents in adults show promising results with treatment regimens of shorter duration and high tolerance. The next few years will likely see these advances introduced to the pediatric population as well. In the meantime, in children with HCV an expectant approach is advocated and treatment should be offered only to those at high risk for more severe, progressive disease. 

Background: Foreign body aspiration (FBA) is common in the pediatric population and if not diagnosed and treated properly can lead to major complications. 

Objectives: To define the clinical and radiological features of aspirated foreign bodies, characterize the incidence of FBA among the Israeli-Arab population, and evaluate flexible bronchoscopy as a diagnostic tool prior to performing rigid bronchoscopy.

Methods: We reviewed the e-files of 115 children who underwent bronchoscopy for suspected FBA between January 2006 and December 2010 in the pediatric department of the St. Vincent French Hospital, Nazareth.

Results: We identified 44 patients (38.3%) who had foreign body aspiration (mean age 31.2 ± 29 months, males 64%). Organic-type foreign body was seen in 70% of cases and location was equally distributed. Statistically significant correlations were found between the presence of a foreign body and a history of choking, abnormal lung auscultation, and abnormal chest X-ray (P < 0.05). The rate of negative finding in rigid bronchoscopy in our study was as low as 15% (in only 8 of 52 rigid bronchoscopies was the finding negative for FBA). Compared with other centers in our region where rigid bronchoscopy was performed without the preceding flexible procedure, we found that our protocol reduced the rate of negative rigid bronchoscopies.

Conclusions: Introducing flexible bronchoscopy initially in FBA management reduced the rate of negative rigid bronchoscopies.