Assessment of Subclinical Atherosclerosis in Children with Atopic Dermatitis.

INTRODUCTION: Data from studies conducted to date have evaluated clinical atherosclerotic conditions in adult patients with atopic dermatitis (AD). Subclinical atherosclerotic changes that are a precursor of atherosclerotic conditions may begin in childhood. The aim of this study was to investigate the presence of subclinical atherosclerosis in pediatric patients with AD and to determine the associated risk factors. METHODS: A total of 59 patients who were referred to our department over a 6-month period and diagnosed with AD, and 53 healthy controls with a similar age and gender were included in the study. Subclinical atherosclerosis markers (carotid intima media thickness [CIMT], distensibility, stiffness, and strain) were measured using conventional echocardiography. The patients' age, SCORAD index, and duration of symptoms were recorded. Serum total immunoglobulin E, C-reactive protein (CRP), blood lipid profile, and complete blood count markers were measured. RESULTS: The median age of the patients was 61 (10-103) months, and 59.3% of them were male. The patients with AD had a higher CIMT (1.60 ± 0.35 vs. 1.30 ± 0.50 mm) and a lower distensibility (0.006 ± 0.009 vs. 0.01 ± 0.008) and strain (0.10 ± 0.14 vs. 0.19 ± 0.14) than the healthy controls (p < 0.01 for all), but there was no significant difference with regard to stiffness (10.16 ± 21.75 vs. 8.99 ± 12.66). Significant correlations between CIMT and disease duration, age, and the SCORAD index were found (p < 0.01, p < 0.01, and p < 0.05, respectively). No correlation between the subclinical atherosclerosis markers and the other laboratory results was found (p > 0.05 for all). CONCLUSION: This study demonstrates that pediatric patients with AD may express subclinical atherosclerosis markers. The evaluation of subclinical atherosclerosis in these patients revealed that CIMT may be the most important marker, as it displayed positive correlations with symptom duration, age, and disease severity.

Factors affecting formula compliance of infants with IgE mediated cow's milk protein allergy during the pandemic.

Introduction: Cow's milk protein allergy (CMPA) is the most commonly encountered food allergy in the world, usually seen in infants under the age of 2 years. This study aims to determine the factors including COVID-19 affecting formula compliance of CMPA patients. Methods: This study is a prospective, observational study based on 10 different Paediatric Allergy-Immunology clinics in Turkey. Patients aged between 6 months and 2 years, who were followed up with IgE-mediated CMPA treatment or newly diagnosed and using breast milk and/or formula were included in the study. The sociodemographic characteristics of the patients, their symptoms, the treatments they received, and the effects of the COVID-19 pandemic on adherence to formula were evaluated with a questionnaire administered to the parents. Results: The compliance rate for formula-based treatment was 30.8% (IQR: 28.3, SD: 21.86). The number of patients with a single and multiple food allergy was 127 (51.6%) and 71 (28.9%), respectively. Breastfeeding duration, daily amount of prescribed formula and addition of sweetener to the formula were found to reduce compliance (p = 0.010, p = 0.003, and p = 0.004, respectively). However, it was determined that the patient's height, weight, age at diagnosis, and age of formula onset did not have a significant effect on compliance. Conclusion: It was found that the duration of breastfeeding, the increase in the daily amount of formula requirement, and the addition of sweeteners had adverse effects on formula compliance. There was no significant correlation between the formula adherence of CMPA patients and the pandemic.

Meningococcemia in a vaccinated child receiving eculizumab and review of the literature.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare and severe disease characterized by uncontrolled activation and dysregulation of the alternative complement pathway and development of thrombotic microangiopathy. Eculizumab, which is used as a first-line therapy in aHUS, blocks the formation of C5 convertase and inhibits the formation of the terminal membrane attack complex. It is known that treatment with eculizumab increases the risk of meningococcal disease by 1000-2000-fold. Meningococcal vaccines should be administered to all eculizumab recipients. CASE: We describe a girl with aHUS who was receiving eculizumab treatment and experienced meningococcemia with non-groupable meningococcal strains which rarely cause disease in healthy people. She recovered with antibiotic treatment and we discontinued eculizumab. CONCLUSIONS: In this case report and review, we discussed similar pediatric case reports in terms of meningococcal serotypes, vaccination history, antibiotic prophylaxis and prognosis of patients who experienced meningococcemia under eculizumab treatment. This case report highlights the importance of a high index of suspicion for invasive meningococcal disease.

NSAID Hypersensitivity in the Pediatric Population: Classification and Diagnostic Strategies.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently administered drugs, mainly for their anti-pyretic, but also for pain-relieving and anti-inflammatory effects in children. NSAIDs are composed of structurally divergent subgroups of drugs with similar pharmacological and adverse effects. Aspirin originates from salicin and was the first synthesized analgesic. As a prototype of NSAIDs; aspirin-induced hypersensitivity reactions were first reported, but subsequently, other phenotypes of hypersensitivity reactions were also described with aspirin and other NSAIDs. There are certain challenging aspects of NSAID-hypersensitivity in the pediatric population that need to be further investigated. These include the effect of age on drug metabolism and the natural history of the various phenotypes of NSAID-hypersensitivity, the effect of certain co-factors (infections, exercise) on NSAID-hypersensitivity, and diagnostic clinical and laboratory biomarkers clarifying the endotypes. In recent years, a non-negligible number of case series, studies and expert panel reports have been published in this field with some novel features and diagnostic modalities in the pediatric population. With the current review; the clinical phenotypes and diagnostic and management modalities of suspected NSAID-induced hypersensitivity reactions in childhood and adolescence were explained and updated by examining past and current publications.

Experiences and attitudes of parents of children with cow's milk and other food-allergy.

INTRODUCTION AND OBJECTIVE: The attitude and behaviors of parents are important in the management of children with food allergy (FA). The aim of this study is to evaluate the experiences and attitudes of parents of children with allergy to cow's milk and other FA. MATERIALS AND METHODS: The parents of children with FA were asked to complete an 18-item questionnaire to evaluate the FA history and experiences during diagnosis, treatment, and follow up. RESULTS: The data from 558 (91.2%) survey questionnaire that were filled completely were analyzed. The mean age of the parents was 33.4+4.9. It was found that most common food allergen was cow's milk (85.3%). The mean time to diagnosis from the onset of symptoms was 10.9±18.4 months. Around 229 parents (41.6%) admitted to at least four different physicians and 68 (12.3%) parents admitted to at least five different physicians before diagnosis. The median time to diagnosis from the onset of symptoms was five (1-108) months in the patients admitted to four or more physicians, but it was one (1-48) month in the patients that admitted to less physicians (p˂0.001). The most common symptoms were dermatitis and mucus-bloody stool, the least common ones were cardiovascular symptoms. Only 21.1% of the patients were able to use hypoallergenic formulas (HAF) in accordance with the recommendation of the physician. CONCLUSIONS: Delayed diagnosis of FA is a major concern, and during this period the patients admit many physicians. A majority of the patients with CMPA experience difficulties while using HAFs, and only one-fifth of them is able to use formula regularly.

COmparisoN of TastES of Available NutriTional integrated or non-integrated formulas for infants older than 1 year of age with cow's milk allergy: A multicenter, prospective, single blind, cross-sectional observational clinical study (CONTEST Study).

Palatability of the infant formulas lacking cow milk protein formulas is reported by parents to be an important drawback. The purpose of this study is to examine decisions made by mothers of infants having cow milk protein allergy, and physicians concerning the palatability of unflavored extensively hydrolyzed formulas and amino acid-based formulas. We conducted a multi-center, randomized, single-blinded, observational taste study involving 149 pediatricians from gastroenterology and allergy subspecialties at 14 tertiary healthcare units from different regions of Turkey and involving 94 mothers of infants with cow milk protein allergy. Blinding was performed for seven formulas available in the market, which were the most commonly prescribed for feeding: four AAFs (Neocate-Numil®, Aptamil Pregomin AS-Numil®, Alfamino-Nestle®, Comidagen-Mamma®), one AAF specifically designed to address the growing nutritional and lifestyle needs of children >1 year (Neocate Junior-Numil®), 2 eHFs (Bebelac Pepti Junior-Numil®, Similac Alimentum-Abott®). Considering all three formula characteristics, Neocate junior-Numil® ranked as the number 1 product among seven products by mothers (63.8%) and physicians (69.8%). The ratings of mothers were significantly higher than the physicians (8.1 points and 6.1 points, respectively; p < 0.001). No difference was found in terms of taste, smell, and appearance for Neocate junior-Numil® between the mothers' and physicians' ratings. Since caregivers have responsibility for careful selection of replacement products for infants with cow milk protein allergy, it is noteworthy that increased awareness and confidence in the palatability characteristics of these products should motivate mothers and physicians to comply with replacement treatment in the long term.

Subclinical cardiovascular dysfunction in children and adolescents with asthma.

BACKGROUND: There is close association between asthma and cardiovascular functions as both diseases share common inflammatory pathways. The current study was aimed at investigating the risk factors, associated with endothelial and cardiac functions in children with newly-diagnosed mild-persistent asthma. METHODS: A total of 33 steroid-naive asthmatic children [median(interquartile-range); 9.1 years(7.8-13.5)] and 16 healthy controls [11.5 years(9.9-13.6)] were included. Their demographic, clinical and laboratory findings were recorded. Carotid Artery intima-media thickness (CIMT), stiffness, distensibility and strain were measured as atheroclerosis markers. Conventional and tissue Doppler imaging was performed to evaluate ventricular function. RESULTS: The patients with asthma had higher CIMT and stiffness and lower strain and distensibility compared to controls (p < 0.001 for all). There was a significant correlation between the duration of asthmatic symptoms and subclinical-atherosclerosis as well as peripheral eosinophil count (p < 0.001, p < 0.05). The patients had lower tricuspid-annular-plane-systolic-excursion (TAPSE), ejection time, and higher isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), and left ventricle myocardial performance index (LVMPI) than the control subjects (p < 0.001 for all). A positive correlation was also observed between the duration of asthmatic-symptoms and cardiac-function parameters. CONCLUSION: Children with mild persistent asthma had subclinical atherosclerosis and ventricular dysfunction even in the early stage of disease. Symptom duration was closely associated with both subclinical atherosclerosis and ventricular dysfunction. Myocardial performance index was abnormal in the asthmatic children when assessed by tissue Doppler Imaging even though they had normal ejection fraction in conventional echocardiography. Future prospective studies with larger sample sizes are needed to confirm these findings and to assess the possible protective effect of ICSs in the prevention of subclinical atherosclerosis.

Food-induced anaphylaxis in early childhood and factors associated with its severity.

Background: Several factors that increase the risk of severe food-induced anaphylaxis have been identified. Objective: We aimed to determine the demographic, etiologic, and clinical features of food-induced anaphylaxis in early childhood and also any other factors associated with severe anaphylaxis. Methods: We carried out a medical chart review of anaphylaxis cases from 16 pediatric allergy and immunology centers in Turkey. Results: The data of 227 patients with 266 food-induced anaphylaxis episodes were included in the study. The median (interquartile range) age of the first anaphylaxis episode was 9 months (6-18 months); 160 of these patients were boys (70.5%). The anaphylaxis episodes were mild in 75 cases (28.2%), moderate in 154 cases (57.9%), and severe in 37 cases (13.9%). The most frequent food allergens involved were cow's milk (47.4%), nuts (16.7%), and hen's egg (15.8%). Epinephrine was administered in only 98 (36.8%) of these anaphylaxis episodes. A logistic regression analysis revealed two statistically significant factors that were independently associated with severe anaphylaxis: the presence of angioedema and hoarseness during the anaphylactic episode. Urticaria was observed less frequently in patients who developed hypotension. In addition, confusion and syncope were associated with 25.9- and 44.6-fold increases, respectively, in the risk of concomitant hypotension. Conclusion: Cow's milk, nuts, and hen's egg caused the majority of mild and moderate-to-severe anaphylaxis episodes. The presence of angioedema and hoarseness in any patient who presents with a history of food-induced anaphylaxis should alert clinicians that the reaction may be severe. In addition, the presence of confusion, syncope, or stridor probably indicates concomitant hypotension.

Healthcare workers` knowledge level regarding anaphylaxis and usage of epinephrine auto-injectors.

BACKGROUND: Inadequate practices in diagnosis and management of anaphylaxis in parallel with an increase in its prevalence may cause serious public health problems today. This is the first study aiming to assess the theoretical knowledge of professional and non-professional healthcare workers from different lines of the healthcare service chain about anaphylaxis management, and their practice approaches for epinephrine autoinjectors (EAIs) together. METHODS: The study included 697 participants comprising physicians, dentists, pharmacists, and school staff. In face-to-face interviews, each participant was asked to fill out the questionnaire forms prepared for assessing their demographic characteristics, experience with a case of anaphylaxis and EAI and theoretical knowledge about the diagnosis and treatment of anaphylaxis, and to demonstrate how to use EAI in practice with trainer device. RESULTS: The rates of 391 physicians, 98 dentists, 102 pharmacists and 105 school staff of knowing the diagnosis criteria of anaphylaxis were 47.6%, 31.6%, 31.1%, 19%, and knowing the first and life-saving treatment of anaphylaxis were 87.2%, 79.6%, 47.6%, 15.2%, respectively. Predictors that affected physicians in knowing the first and life-saving treatment of anaphylaxis were having experience with EAIs [OR:5.5, (%95CI:1.330-23.351, p=0.015)] and a case of anaphylaxis [OR:2.4, (%95CI:1.442-4.020, p=0.001)], and knowing the administration route of epinephrine correctly [OR:1.9, (%95CI:1.191-3.314, p=0.008)]. 31.1% of the participants demonstrated the EAI usage correctly. The EAI usage steps with the most errors were `Place the appropriate injection tip into outer thigh/Press the trigger so it `clicks`` and `Turn the trigger to arrow direction` (60.3% and 34.9%, respectively). CONCLUSIONS: Healthcare workers` knowledge level regarding anaphylaxis management and ability to use EAIs correctly are not adequate. That most errors were made in the same steps of EAI usage indicates that the industry should continue to strive for developing the ideal life-saving device.

Do Pediatric Emergency Physicians Comply With Guideline Recommendations in Management of Patients With Acute Urticaria?

OBJECTIVES: To determine the level of knowledge and practical preferences of pediatricians regarding acute urticaria (AU) management and to assess the effects of training provided in accordance with the current urticaria guideline recommendations on pediatricians who work in the pediatric emergency department (PED). METHODS: A theoretical training was provided to pediatricians regarding the diagnosis and treatment of AU in line with current urticaria guideline recommendations. Before the training, pediatricians completed a 10-item questionnaire. This prospective study assesses their treatment approaches in patients admitted to PED because of AU during the 6-month period before and the 1-year period after training. RESULTS: Four hundred seventeen children in the pretraining and 1085 children in the posttraining periods were treated for AU in PED. Forty-eight pediatricians participated in the training. According to their questionnaire responses, 35% of them used only H1 antihistamine (AH) treatment, 50% used second-generation H1 AH (2nd-GAH) as AHs, 75% preferred the oral route of administration, and 85.4% did not administer systemic corticosteroid (sCS) to all patients. Comparing the practice approaches of the pediatricians in the pretraining and posttraining periods, first-generation H1 antihistamine (1st-GAH) preference rate decreased from 68.4% to 30.3% and the sCS preference rate decreased from 58.5% to 25.7%, while the 2nd-GAH preference rate increased from 31.7% to 69.7% (P < 0.001 for all). No treatments were prescribed for 10.8% of patients before the training and 3% after the training during discharge at home (P < 0.05). Comparing the home treatment choices of the pediatricians in the pretraining and posttraining periods, 1st-GAH preference rate decreased from 11.5% to 5%, while the 2nd-GAH preference rate increased from 78.7% to 91.5% (for both parameters, P < 0.001). CONCLUSIONS: Practical treatment preferences of pediatricians in the treatment of children with AU differ considerably from both current guideline recommendations and their own theoretical knowledge, and training can enhance pediatricians' compliance with current guideline recommendations.

Proven Food-Induced Acute Urticaria and Predictive Factors for Definitive Diagnosis in Childhood.

BACKGROUND: Urticaria can be the only sign of a food allergy or can be seen together with other signs and symptoms of a food allergy. OBJECTIVE: To determine the demographic, etiologic, and clinical features of food-induced acute urticaria in childhood. METHODS: Patients suspected of food-induced acute urticaria were included in this prospective cross-sectional multicenter study. RESULTS: Two hundred twenty-nine urticaria cases were included in this study. Seventeen patients who did not meet the inclusion criteria of the study were excluded. Of the 212 included cases, 179 (84.4%) were diagnosed with definitive food-induced acute urticaria. The most common foods causing acute urticaria were cow's milk, hen's eggs, and nuts in 56.4, 35.2, and 19% of cases, respectively. The positive predictive value of a history of milk-induced acute urticaria together with a milk-specific IgE >5 kU/L for cow's milk-induced acute urticaria was 92% (95% CI: 81-96%). A history of cow's milk-induced and/or hen's egg-induced acute urticaria was consistent with a definitive diagnosis of food-induced urticaria (Chen's kappa: 0.664 and 0.627 for milk and eggs, respectively). Urticaria activity scores were higher in patients with food-induced acute urticaria (p = 0.002). CONCLUSION: Cow's milk, hen's eggs, and nuts were the most common allergens in the etiology of childhood food-induced acute urticaria. Although the urticaria activity score provides guidance for diagnosis, an oral food challenge is often essential for the definitive diagnosis of a patient with a history of food-induced acute urticaria.

The pharmacists' ability to use pressurized metered-dose inhalers with a spacer device and factors affecting it.

Objective: The aim of this study is to evaluate the pharmacists' ability to use pMDIs with a spacer device and the factors that affect this ability.Method: Face to face interviews were conducted with the pharmacists. A nine item questionnaire was completed and the checklist for how to use pMDIs with a spacer device was filled out.Results: A total of 307 pharmacists voluntarily participated in this study. Fifty-six (18.2%) of the pharmacists stated that they did not know how to use pMDIs with a spacer device. These pharmacists were excluded and remaining 251 pharmacists included in the study. Only 100 (39.8%) pharmacists demonstrated all of the inhaler spacer device usage steps correctly. The step in which pharmacists made the most mistakes was "take 5-6 deep and slow breaths, hold for 10 s and slow breaths." Those pharmacists who were more likely to correctly use pMDIs with a spacer device were younger (p = 0.023), had dispensed more asthma medications per day (p < 0.001), had dispensed more asthma medications per day for patients younger than six years of age (p = 0.016), and sold inhaler spacer devices at their pharmacy (p = 0.042).Conclusion: Approximately one third of the pharmacists in the current study were able to correctly demonstrate all of the steps for proper usage of pMDIs with a spacer device, which indicates that pharmacists should be included in the training program and be provided continuous training on the use of pMDIs with a spacer device.

Effects of modifying visual inhaler spacer usage instructions on correct usage rate of untrained users.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) used with spacers are considered the method of choice for delivery of inhaled drugs in preschool-age children. The aim of this study was to determine the effects of modifying the visual inhaler spacer usage guidelines on the correct usage rate. METHODS: The parents and caregivers of patients <6 years old who were prescribed inhalers with spacers for the first time were included in our study. The participants were randomly divided into a modified visual inhaler spacer usage guidelines group and an unmodified visual inhaler spacer usage guidelines group. All study participants underwent face-to-face interviews and completed questionnaires. RESULTS: A total of 510 participants with a median age of 31 (range, 20-46) years were included in this study. The modified visual guidelines group included 254 (49.6%) participants, and the unmodified visual guidelines group included 256 (50.4%) participants. One hundred sixty-five (65.2%) of the 254 participants in the modified visual guidelines group correctly demonstrated the inhaler spacer technique. In contrast, only 21 (8.2%) of the 256 participants in the unmodified visual guidelines group correctly demonstrated the inhaler spacer technique (p < 0.001). When comparing the inhaler spacer usage steps between the 2 groups, the modified visual guidelines group demonstrated the steps more correctly and more quickly (p < 0.001). CONCLUSION: The current visual inhaler spacer usage guidelines are insufficient. We believe that improving the visual inhaler spacer usage guidelines, in particular, will increase the correct usage rate and decrease the number of usage errors.

Independent predictive factors for the persistence and tolerance of cow's milk allergy.

BACKGROUND: Cow's milk protein allergy (CMPA) is usually transient, with most children tolerating ingested cow's milk by 3 years of age. This study aimed to determine factors that promote or hindering the development of tolerance to CMPA. METHODS: A logistic regression model was used to determine independent risk factors associated with tolerance and persistence of CMPA. RESULT: A total of 178 children diagnosed with CMPA were included in the study. The patients' median age was 32 months (minimum-maximum, 14 to 144 months), and their median follow-up period was 30 months (minimum-maximum, 12 to 54 months). In the follow-up, CMPA persisted in 62 (34.8%) patients. The patients were divided into 2 groups according to patient's age. Group I was <3 years old and group II was ≥3 years old. The factors independently associated with the persistence of CMPA for group I were as follows: comorbid food allergies (p = 0.021), the presence of an immunoglobulin E (IgE)-mediated reaction (p = 0.001), and respiratory system symptoms (ie, tachypnea) (p = 0.036). The presence of gastrointestinal-related discomfort (p = 0.001) was an independent risk factor associated with the development of tolerance. The presence of comorbid food allergies (p = 0.03) was the only independent predictive factor for CMPA persistence for group II. CONCLUSION: The prognosis in cases of CMPA, a food allergy, is good, with tolerance developing over time. The presence of IgE-mediated CMPA, respiratory-related symptoms (ie, tachypnea), and the presence of comorbid food allergies have negative effects on tolerance.

Comparison of practical application steps of the previously used adrenaline auto injector in Turkey (EpiPen) and the currently available adrenaline auto injector (Penepin): a multi-center study.

AIM: It has been shown by a great number of studies that the correct use of adrenaline auto injectors prescribed to patients with anaphylaxis is associated with the design of the auto injector, in addition to training. The aim of this study was to compare the skills of adults in using two different auto injectors prescribed to patients with anaphylaxis. MATERIAL AND METHODS: Parents of patients aged between 1 and 18 years who referred to allergy outpatients were included in the study. RESULTS: A total of 630 volunteers from nine centers were included in the study. Four hundred fifty-seven (72.5%) of the participants were females and 235 (37.3%) were undergraduates. The rate of showing all the steps of auto injector trainers correctly by the participants was found as (60.2%) (n=379) for EpiPen and 42.9% (n=270) for Penepin (p<0.001). The most frequent mistake with both auto injector trainers was the step of "place appropriate injection tip into outer thigh/press the trigger so it clicks." When the preferences of the volunteers were asked after training and application, 527 (83.7%) chose EpiPen, stating that it was easier and simpler to use. CONCLUSIONS: Our study showed that the correct usage rates of both adrenaline auto injectors were much lower than expected and there could be mistakes in the application of both. It could be appropriate to make improvements in the design of Penepin, which is still the only available adrenaline auto injector in Turkey, such that its application steps will be simpler and quicker.