Adherence of caregivers of children to advice provided by a National Poison Information Center.

INTRODUCTION: Most calls to poison information centers are from the public, pertaining to young children, and due to minor or nontoxic exposures. Rational poison center consultations can prevent unnecessary visits to emergency departments (EDs), callers' adherence to such advice is required. OBJECTIVES: Estimate adherence of callers from the public to the poison center concerning exposures of young children to the advice provided by the clinical toxicologist, estimate the number of unnecessary ED visits of these children prevented by poison center consultations. METHODS: Prospective, phone-survey cohort study. Calls from the public concerning children under 6 years old were recorded and collected, telephone follow-up was performed within two weeks. Data collected included: demographics, exposure, severity, triage advised, adherence to the advice, reasons for nonadherence, and what the caller would have done had the poison center been unavailable. The study was conducted over 3 months representing different seasons and holidays times during a 1-year period. RESULTS: 1762 callers completed the telephone follow-up; 1443 (81.9%) cases were asymptomatic at the time of call; 1452 (82.3%) were advised to remain at home, 175 (9.9%) and 137 (7.8%) were referred to community clinics and EDs, respectively; 1648 (93.5%) of callers adhered to the advice provided; highest adherence rate was among callers advised to stay home (98.3%, 1427), and 78.9% (108) and 62.1% (109) among callers referred to EDs and community clinics, respectively. Among callers advised to stay home, 491 stated that they would have referred themselves to the ED had the poison center been unavailable, an annual estimate of 4309 cases. The main parameter predicting nonadherence was calls made during night shift. CONCLUSIONS: The high adherence of callers to the poison center consultation suggests it plays an important role in preventing unnecessary ED visits of young children due to poison exposures, and may substantially reduce ED load and costs.

Poisoning in Israel: Annual Report of the Israel Poison Information Center, 2017.

BACKGROUND: The Israel Poison Information Center (IPIC), Rambam Health Care Campus, provides 24-hour telephone consultations on clinical toxicology and drug and reproductive toxicology. It participates in research, teaching and regulatory activities, and provides laboratory services. In 2014, nurse specialists in poison information joined the IPIC. OBJECTIVES: To report the epidemiology of poison exposures in Israel. METHODS: We present computerized queries and a descriptive analysis of the medical records database of the IPIC for 2017. RESULTS: A total of 39,928 poison exposure cases were recorded, reflecting increases of 226.3% and 26.7% compared with 1995 and 2012, respectively. Children < 6 years of age were involved in 47.0% of cases; 80.4% of calls were made by the public and 17.8% by physicians; 74.2% of exposures were unintentional and 7.3% intentional. Pharmaceuticals were involved in 51.4% of cases, chemicals in 36.9%, bites and stings in 2.2%, and plants and mushrooms in 1.5%. Substances most frequently involved were analgesics, cleaning products, and antimicrobials. Clinical severity was moderate/major in 3.3%, mainly due to insecticides, drugs of abuse, and corrosives. Three fatalities were recorded (due to colchicine, organophosphates, and volatile substance inhalant abuse). CONCLUSIONS: Poison exposures and poisonings have markedly increased in Israel, contributing substantially to morbidity. The IPIC prevented unnecessary referrals to emergency departments. Its database is a valuable national resource for collecting and monitoring poisoning exposure cases. It can be used as a real-time surveillance system for the benefit of public health. It is recommended that reporting to the IPIC become mandatory, and its activities adequately supported by national resources.

Single dose oral midazolam for minor emergency department procedures in children: a retrospective cohort study.

BACKGROUND: In the pediatric emergency department, patients are commonly treated with a single dose of oral midazolam for minor procedures. We sought to evaluate the effect of this treatment on procedure completion rates. METHODS: We conducted a single-center retrospective cohort study of all patients who were treated with pre-procedure oral midazolam between January 2011 and June 2016. The primary outcome was the procedure completion rate. RESULTS: During the study period, 1,504 patients were treated with oral midazolam as per department protocol; 1,467 received midazolam and 37 declined midazolam. Oral midazolam was used in 14 different types of emergency department procedures. The procedure completion rates in the treatment and non-treatment groups were 1,402/1,467 (95.6%) and 24/37 (64.8%), respectively (difference 30.7%; 95% confidence interval [CI] 17.3%-46.8%); p<0.0001. Treatment group patients had procedure completion rates of 25/33 (75.8%), 165/188 (87.8%%), 1,154/1,187 (97.2%), and 58/59 (98.3%), in the less than 0.3 mg/kg group, 0.3 to less than 0.5 mg/kg group, 0.5 to less than 0.7 mg/kg group, and 0.7 to less than 0.9 mg/kg group, respectively. Multivariate regression did not demonstrate an association between sex, ethnicity, dosage of 0.5 mg/kg or greater, type of procedure, and failure to complete procedure. Severe adverse events were not recorded. A dose of less than 0.3 mg/kg was significantly associated with an increased risk of failure to complete a procedure (adjusted odds ratio 8.34, 95% CI 3.32-20.9; p<0.0001). CONCLUSION: The findings suggest that oral midazolam in a single dose of 0.5 mg/kg or greater is associated with successful completion of minor pediatric procedures.

A Randomized Trial to Evaluate the Effect of Two Topical Anesthetics on Pain Response During Frenotomy in Young Infants.

Objective: To examine the comparative effectiveness of two topical anesthetics in controlling the pain associated with tongue-tie release (frenotomy) in young infants. Design: Randomized trial. Setting: A Pediatric Craniofacial Clinic. Subjects: Forty-two infants who were referred for frenotomy were randomly allocated to receive the topical anesthetic gel 2% tetracaine or 20% benzocaine applied prior to frenotomy. Frenotomies were videotaped. The primary outcome measure was the Neonatal Facial Coding System (NFCS) score. Secondary outcome measures included cry duration and a visual analog scale (VAS) assessed by the parents. Results: The two groups were comparable with regard to weight, age, gender, previous painful experience, and last feeding time. Median NFCS scores prior to frenotomy in the tetracaine and the benzocaine groups were 4.5 (IQR: 0.75­10.2) and 3.5 (IQR: 0­9.5), respectively (P = 0.89, 95% CI −3 to 4). During frenotomy, median NFCS score increased to 28 (IQR: 24.5­30.25) in the tetracaine group (P < 0.0001, median difference −22, 95% CI −24.5 to −19), and to 28 (IQR: 26­30) in the benzocaine group (P < 0.0001, median difference −23, 95% CI −27 to −17). Mean cry durations in the tetracaine and the benzocaine groups were 69.4 seconds and 63.9 seconds, respectively (P = 0.32, 95% CI −47 to 15), and mean VAS scores were 57.2 and 58.2, respectively (P = 0.89, 95% CI −15.2 to 13.4). Conclusions: These topical anesthetics seem ineffective in controlling the pain associated with frenotomy. Clinicians should continue to search for an effective treatment for this procedure.

Prediction of Antiphospholipid syndrome using Annexin A5 competition assay in patients with SLE.

A significantly high correlation between reduced activity of Annexin A5 by the flow cytometric assay (FCA) and the diagnosis of antiphospholipid syndrome (APS) has been reported. The aim of this study was to assess the clinical and laboratory significance of the Annexin A5 competition assay among patients with systemic lupus erythematosus (SLE). The FCA competition assay was performed on blood samples from 57 consecutive SLE patients. The FCA was performed according to a previously validated method. Forty-seven patients (82.5 %) had SLE without APS and ten (17.5 %) had SLE with APS. Twenty-four (42 %) of the patients had mean levels of AnxA5 fluorescence below the mean and standard deviation of the controls and were considered positive. SLE patients with a positive FCA were found to have an increased risk for a hypercoagulable or vascular state (86 % of the patients had cerebrovascular disease, 89 % had Raynaud's phenomenon, and 80 % had deep vein thrombosis). The risk for any hypercoagulable or vascular state was significantly increased (P = 0.012, RR-2.3, 95 % CI 1.4-3.8). A positive FCA assay was found in 90 % of the patients with APS (P < 0.001), with a sensitivity of 90 % and a specificity of 68 % for this diagnosis. The positive and negative predictive values were 0.4 and 0.97, respectively. Correlations were found between positive FCA and positive Anti-Cardiolipin antibody (P < 0.001), and Anti-ß2 glycoprotein I levels (P = 0.013). Our findings suggest that the FCA is a practical assay for the detection of clinically relevant APS among patients with SLE.

Ethics of research in pediatric emergency medicine.

Clinical research in the pediatric emergency department (ED) has been rapidly growing in the past decade, and has resulted in some of the most important milestone studies in the pediatric medical literature. However, it presents a unique ethical goal and requires that additional challenges, such as the acute medical condition, fear and anxiety, unfamiliar physician(s), fatigue, and lack of time be addressed in addition to the standard ethical requirements. These may impair several fundamental elements of research, including the patient enrollment process, informed consent/assent, randomization, and others. Every possible attempt must be made to reduce or minimize the risks to which the children are exposed, and one must be cognizant of the special needs of children and their families in the ED. Nevertheless, we are also obliged to find ethical ways to include them in appropriate research endeavors that aim to improve treatments for conditions unique to the ED. This paper explores and overviews the most recent literature in order to characterize the nature of ethical challenges complicating clinical research in pediatric emergency medicine, and then suggests some ethically sound solutions such as deferred/waived consent, designated research staff, and alternative study designs. Finally, a few examples of prospective, blinded randomized trials involving drugs in pediatric emergency medicine are provided, with special emphasis on how the investigators are overcoming the obvious ethical challenges.

Counselling a patient with chronic illness before pregnancy.

As the reproductive age of women increases, women of reproductive age are exposed to more diseases and medications that are potentially related to adverse pregnancy outcomes. The approach to primary prevention of such outcomes is discussed. By minimizing the risks related to the diseases and the medications before conception, the best control of the medical condition and optimized pharmacotherapy is achieved when conception eventually occurs.

Ceftriaxone-induced immune hemolytic anemia.

OBJECTIVES: To describe a case of ceftriaxone-induced immune hemolytic anemia (CIIHA) in a 6 year-old boy with sickle cell disease (SCD) and perform a systematic literature review to delineate the clinical and laboratory features of this condition. DATA SOURCES: EMBASE (1947-January 2014), MEDLINE (1946-January 2014), and databases from the US Food and Drug Administration and Health Canada were searched, using anemia, hemolytic anemia, hemolysis, and ceftriaxone as search terms. Additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: All case reports and observational studies describing clinical and laboratory features of CIIHA were included. DATA SYNTHESIS: A total of 37 eligible reports of CIIHA were identified, including our index case, and 70% were children. Mortality was 30% in all age groups and 64% in children. The majority of patients had underlying conditions (70%), of which SCD was most commonly reported. Previous ceftriaxone exposure was reported in 65%. Common features included elevated lactate dehydrogenase (70%); early, new-onset hemoglobinuria (59%); acute renal failure (46%); positive direct antibody testing (70%); and anticeftriaxone antibodies (68%). Also, 32% had a preceding, unrecognized, hemolytic episode associated with ceftriaxone. SUMMARY: Given the common use of ceftriaxone worldwide, knowledge of CIIHA, which often goes undiagnosed until late in the course, is essential for clinicians. Based on the findings of this review, we suggest obtaining past history of ceftriaxone exposures and screening for new-onset hemoglobinuria during ceftriaxone therapy in selected patients as potential methods for early diagnosis of this rare but potentially fatal condition.

Preconceptional monitoring of mercury levels in hair and blood as a tool for minimizing associated reproductive risks.

We describe the case of a 41-year-old woman, planning a pregnancy, who had a spontaneous abortion and subsequently was found to have high blood mercury levels. The source of high mercury was in her diet that contained fish as her main source of protein. Serial measurements of mercury in hair and blood allowed the team to determine the exact time when safe levels of mercury were reached, to eliminate elevated mercury levels as a potential cause of spontaneous abortion and to use preconception counseling to minimize the risk for adverse pregnancy outcome.

Bupropion and Escitalopram During Lactation.

OBJECTIVE: To report a case of seizure-like symptoms in an infant exposed to bupropion and escitalopram through breastfeeding. CASE SUMMARY: A 6.5-month-old female infant, breastfed by a mother treated with bupropion XL 150 mg/d and escitalopram 10 mg/d for depression, presented to our hospital with severe emesis and tonic seizure-like symptoms. The symptoms resolved with supportive therapy. Urine toxicology screen in the infant revealed bupropion and escitalopram. Bupropion, and its active metabolite, hydroxybupropion, were analyzed and quantified both in the infant's serum and in the breast milk. Diagnostic workup for seizure etiologies was otherwise negative. After being asymptomatic for 48 hours, her discharge diagnosis was adverse events associated with bupropion and escitalopram in lactation. An objective causality assessment (Naranjo assessment) revealed that this adverse effect was probable. DISCUSSION: The adverse events in our case were associated with serum concentrations of bupropion and hydroxybupropion that are lower than the reported therapeutic range, perhaps suggesting that infants, compared with adults, may have a higher susceptibility to the epileptogenic effects of bupropion and/or hydroxybupropion. Furthermore, although we do not have escitalopram serum concentrations, this drug interaction may have had a contributing role in this case, possibly because of cytochrome P4502D6 inhibition by bupropion and metabolites. CONCLUSION: As the number of reproductive-aged women requiring polytherapy to control their depression is increasing, further research is needed to establish the safety of combined antidepressants, such as selective serotonin reuptake inhibitors and bupropion, during lactation.

The differential diagnosis of fetal alcohol spectrum disorder.

Fetal Alcohol Spectrum Disorder (FASD) affects an estimated 1% of all children born in North America. FASD is a chronic disorder impacting many systems of care. Only a minority of these children exhibit the pathognomonic facial features of Fetal alcohol syndrome (FAS) that include short palpebral fissures, smooth philtrum and thin upper lip. Hence, in the majority of affected individuals FASD is a diagnosis of exclusion. The differential diagnosis of both the dysmorphological and neurobehavioral aspects of FASD is wide. This review aims to provide the pediatrician with information concerning the differential diagnosis of FASD and to discuss genetic testing that might be relevant to the assessment.

Implications of serum creatinine measurements on GFR estimation and vancomycin dosing in children.

BACKGROUND: Different serum creatinine (sCr) assays may obtain different values in the same patient, causing discrepancies in estimated glomerular filtration rate (eGFR) and sCr-based vancomycin dosing calculations. OBJECTIVE: To identify potential discrepancies in sCr concentrations obtained by different assays, the compensated Jaffe (sCr-Jaffe) and the enzymatic (sCr-enz), and to compare between the eGFR and vancomycin daily dose, based on these sCr values. METHOD: sCr-Jaffe and, sCr-enz concentrations of 890 healthy children, aged 1-18 years, were available from the Canadian Laboratory Initiative in Pediatric Reference Intervals study in Ontario. For each subject, eGFR (eGFR-Jaffe, eGFR-enz) was calculated using the revised Schwartz equation, and vancomycin daily dose (Vdose-Jaffe, Vdose-enz) was calculated using a sCr-based pharmacokinetic model. RESULT: Significant, age-related differences were found in sCr concentrations, and in subsequent eGFR and Vdose, between the two assays. In children aged 1-5 years, mean sCr-Jaffe was higher than sCr-enz (44.0 ± 5.0 vs. 27.7 ± 7.3 µmol/L, P < 0.001), leading to lower eGFR-Jaffe (83.2 ± 9.0 vs. 137.9 ± 27.1 mL/min/1.73m2, P < 0.001) and lower Vdose-Jaffe (44.7 ± 2.5 vs. 53.5 ± 5.1 mg/kg/24 h, P < 0.001). CONCLUSION: Based on these findings, young children may be at risk for vancomycin under-treatment. Further research is needed to define the more accurate sCr assay in young children treated with renally excreted drugs.

Safety of procedural sedation in pregnancy.

Minor traumatic injuries are common in pregnancy, often subsequently requiring painful diagnostic and therapeutic procedures. Pregnant women who are experiencing significant pain, distress, or fear may benefit from procedural sedation in the emergency department. In this review we examine the fetal safety of specific drugs used for procedural sedation.

Mothersisk update: reproductive outcomes after assisted conception.

QUESTION: Increasingly my patients are undergoing assisted conception. These patients are excitedly anticipating pregnancy, but are there risks to the fetus when using assisted reproductive technology (ART)? ANSWER: The current medical literature suggests only a mild increase in preterm deliveries, low birth weight, birth defects, and genetic imprinting defects. These results might, in part, be related to the indication for ART, rather than the ART itself.

Cross-sectional analysis of cardiovascular risk factors in children with parental history of premature ischemic heart disease.

This study aimed to evaluate the presence of cardiovascular risk factors in children with a parental history of premature ischemic heart disease (two- or three-vessel disease diagnosed before the age of 55 in men and 65 in women). A prospective cross-sectional study was performed on 55 children. The following parameters were assessed: body mass index (BMI), waist and hip circumference, blood pressure, lipids profile, fasting glucose (FG), C-reactive protein (CRP), and carotid intimal-medial thickness (CIMT). Twenty-eight children had hypercholesterolemia, and 11 had other forms of dyslipidemia. Sixteen children had a high BMI; 17 had increased CRP levels; 2 were hypertensive; and 2 had impaired FG. CIMT levels were not correlated with age (Pearson r = -0.486; p = 0.78) and height (Pearson r = -6.31; p = 0.84), but they were correlated with cholesterol levels (Spearman r = 0.375; p < 0.005). Most patients (83%) had ≥ 2 risk factors; half of them had ≥ 3 risk factors. We concluded that these at-risk children should be carefully screened for all known risk factors.

Serum inflammatory markers in overweight children and adolescents with non-alcoholic fatty liver disease.

BACKGROUND: Obesity, a worldwide pandemia, is associated with a large variety of comorbidities, among which is non-alcoholic fatty liver disease. NAFLD is a complex disease that may eventually lead to cirrhosis, posing a high risk for the patient and thus necessitating early diagnosis and treatment. OBJECTIVES: To evaluate the association between ultrasonographically diagnosed non-alcoholic fatty liver disease and the levels of serum inflammatory markers in obese children and adolescents. METHODS: This prospective cohort study was conducted in children and adolescents attending the endocrine obesity clinic in a tertiary care children's hospital in 2001-2003. Blood tests and ultrasound were performed to detect the presence of fatty liver. The severity of fatty liver was determined by measuring the liver/kidney echogenicity ratio (hepatorenal index). Blood tests included complete blood count, liver enzymes, lipid profile, erythrocyte sedimentation rate, high sensitivity C-reactive protein, serum amyloid A, and the degree of erythrocyte adhesiveness/aggregation as measured in peripheral blood slides. RESULTS: The 30 boys and 34 girls, age 9-21 years, who participated in the study were divided into those who evidenced NAFLD on ultrasound (Group 1, n=37) and those whose liver appeared normal on ultrasound (Group 2, n=24). ESR, hs-CRP, SAA and the degree of erythrocyte adhesiveness/aggregation were compared between the groups. There was no significant association between elevated ESR, the levels of CRP, SAA and/or the degree of erythrocyte adhesiveness/aggregation and the hepatorenal index and NAFLD. The degree of erythrocyte adhesiveness/ aggregation correlated with body mass index-standard deviation score in both genders (P < 0.05). CONCLUSIONS: Fatty liver itself may not be a cofactor in stimulating inflammatory markers in obese patients. Obese children diagnosed with NAFLD may have simple steatosis and their increased inflammatory markers are therefore compatible with those expected in obesity.

Unsuccessful suicide attempt of a 15 year old adolescent with ingestion of 5000 mg modafinil.

Modafinil (Provigil) is a wake-promoting drug approved for patients with narcolepsy or other causes of excessive daytime sleepiness. Each pill is 100 to 200 mg; maximal daily dose of modafinil in adults is 400 mg (the medication is not approved by the FDA for children younger than 16 years of age). We report the case of an adolescent who attempted to commit suicide by ingesting 50 pills of modafinil. The medication was prescribed for her mother to treat symptoms associated with multiple sclerosis. Approximately 2 hours following ingestion the patient complained of headache, nausea and abdominal pain. Her ECG demonstrated prolonged QTc interval. Observation for 72 hours revealed 24 hours of inability to sleep, tachycardia, and dyskinesia. There was no deterioration of kidney or liver functions, and no change in complete blood count or blood pressure.