Supratherapeutic utilization of paracetamol versus ibuprofen among <12-year-old children in primary care in Istanbul.

BACKGROUND: Paracetamol and ibuprofen are the most preferred analgesics for pain and fever management in children. Prescribing of these drugs in supratherapeutic doses may predispose to their toxicity. We aimed to compare prescribing patterns and potential overdosing of paracetamol and ibuprofen in primary care for <12-year-old children. METHODS: We analysed paracetamol- and ibuprofen-containing prescriptions (PCPs, n = 173,575 and ICPs, n = 145,655) of 1- to 11-year-old children, issued by 3:1 systematically sampled primary care physicians (n = 1,431) in Istanbul during 2016. We compared drug use parameters and prescriptions surpassing daily and single-use dose limits for paracetamol and ibuprofen. RESULTS: We identified that 29.9% of PCPs and 20.8% of ICPs were generated for those aged 1-2 years. Concomitant analgesic use was higher in ICPs than in PCPs (15.1% vs. 12.8%). We found that 4.4% of PCPs and 3.1% of ICPs exceeded maximum daily dose limit of paracetamol and ibuprofen, respectively (P < 0.001). This was more common in girls (5.1% and 3.3%, respectively) and at 1 year of age in both groups (9.2% and 8.5%, respectively). Single-use supratherapeutic dosing was encountered in 16.5% of PCPs and 13.2% of ICPs (P < 0.001, pessimistic model) and in 8.6% of PCPs and 10.6% of ICPs (P < 0.001, optimistic model). CONCLUSIONS: Paracetamol and ibuprofen were generally used in primary care for similar clinical conditions with subtle differences. However, more pronounced in younger children and girls, potential overdosing seems to be more practiced for paracetamol than ibuprofen both in terms of maximal daily and single-use setting.

Utilization of biotechnological drugs in rare diseases requiring the use of off-label drugs in children in Turkey

Background/aim: Pediatric patients, especially those with rare diseases, represent a population that has a high tendency towards off- label drug use (OLDU) and needs a more careful practice of pharmacotherapy than in adults. We aimed to investigate biotechnological drug use in children with rare diseases requiring OLDU. Materials and methods: This retrospective study examined all single-diagnosed OLDU applications (n = 5792) for 4992 children (<18- year) in Turkey. Applications of rare diseases were selected, and their descriptive characteristics were examined, including demographic features of patients, biotechnological drug utilization status, and disease categories. The off-label statuses of the drugs at the end of 2020 were also examined. Results: In total, 77.7% (n = 4501) of OLDU applications were made for rare diseases. Biotechnological drug use was higher in rare disease applications than in nonrare diseases (37.9% vs. 19.2%, respectively; p < 0.0001). Canakinumab was the top applied biotechnological drug (73.2%). Compared to that in small-molecule drugs, the mean age of patients was higher in biotechnological drug-containing applications (8.1 ± 5.3 vs. 9.7 ± 4.9, respectively; p < 0.0001). Biotechnological drug use was higher in nonneoplastic rare diseases (40.3%) than in neoplastic rare diseases (26.4%), (p < 0.0001). At the end of 2020, the approval status of the off-label indications covered in 2016 was significantly higher for rare (24.4%) vs. nonrare (5.2%, p < 0.0001) diseases and for biotechnological (32.3%) vs. small- molecule (13.9%, p < 0.0001) drugs. In total, 87.7% of the drugs would have to be still used in the off-label setting at the end of 2020. Conclusion: It was seen that more than three-quarters of the pediatric OLDU applications are for rare diseases, and the need for biotechnological OLDU in this group is almost 2-fold of small-molecule drug use. While further projected findings imply a higher approval tendency for rare diseases and biotechnological drugs, there seems to be more room for improvement for pediatric drug use.

Evaluation of injectable metamizole utilization in children and adults in primary care.

OBJECTIVE: Use of injectable metamizole in the outpatient setting is controversial due to safety concerns. We aimed to compare injectable metamizole prescribing patterns for children and adults with further evaluation of nationwide metamizole consumption trend. MATERIALS AND METHODS: In this retrospective cross-sectional study, 100 injectable drug-containing prescriptions written in each month of 2010 in 32 provinces of Turkey were selected. Drug utilization patterns on injectable metamizole-containing prescriptions (n = 1,270) were analyzed and compared by "pediatric" and "adult" groups. Additionally, nationwide outpatient consumption data from 2010 to 2018 were obtained, and the utilization trend was examined. RESULTS: Children received 12.4% of injectable metamizole-containing prescriptions. Male predominance was observed in children (62.7%), as opposed to female predominance in adults (55.2%, p < 0.05). The most frequent diagnoses were "acute tonsillopharyngitis" and "acute bronchitis" in both groups. Single-diagnosis prescriptions constituted 79.1% of the pediatric group and 53.1% of the adult group (p < 0.05). Diagnoses, drugs, and injectable analgesics per prescription were significantly higher in adults (1.68 ± 0.86, 3.45 ± 0.90, and 1.06 ± 0.23, respectively) than in children (1.22 ± 0.43, 3.25 ± 0.88, and 1.00, respectively) (p < 0.05). The percentage of prescriptions containing injectable antibiotics was higher in children (83.6%) than in adults (64.9%). Outpatient injectable metamizole consumption showed a decreasing trend in 2010 - 2018. CONCLUSION: Despite recent downward trend, prescribing of injectable metamizole in primary care was considerably prevalent. This study, which highlights fundamental differences among metamizole utilization patterns in children and adults, addresses the inadequacy of rational use of the drug in terms of preferred indications and accompanying drugs.

Pathogens in Pediatric Septic Arthritis: A Multi-Center Study in Turkiye (PEDSART Study).

OBJECTIVES: Septic arthritis (SA) is a serious bacterial infection that must be treated efficiently and timely. The large number of culture-negative cases makes local epidemiological data important. Accordingly, this study aimed to evaluate the etiology, clinical characteristics, and therapeutic approach of SA in children in Turkiye, emphasizing the role of real-time polymerase chain reaction (PCR) techniques in the diagnosis. METHODS: In this multi-center, prospective study, children hospitalized due to SA between February 2018 and July 2020 in 23 hospitals in 14 cities in Turkiye were included. Clinical, demographic, laboratory, and radiological findings were assessed, and real-time PCR was performed using synovial fluid samples. RESULTS: Seventy-five children aged between 3 and 204 months diagnosed with acute SA were enrolled. Joint pain was the main complaint at admission, and the most commonly involved joints were the knees in 58 patients (77.4%). The combination of synovial fluid culture and real-time PCR detected causative bacteria in 33 patients (44%). In 14 (18.7%) patients, the etiological agent was demonstrated using only PCR. The most commonly isolated etiologic agent was Staphylococcus aureus, which was detected in 22 (29.3%) patients, while Streptococcus pyogenes was found in 4 (5.3%) patients and Kingella kingae in 3 (4%) patients. Streptococcus pyogenes and Kingella kingae were detected using only PCR. Most patients (81.3%) received combination therapy with multiple agents, and the most commonly used combination was glycopeptides plus third-generation cephalosporin. CONCLUSIONS: Staphylococcus aureus is the main pathogen in pediatric SA, and with the use of advanced diagnostic approaches, such as real-time PCR, the chance of diagnosis increases, especially in cases due to Kingella kingae and Streptococcus pyogenes.

Comparison of pediatric antibiotic prescribing practice between low and high prescribers for children in primary care.

BACKGROUND: Antibiotic prescribing is more prevalent in children. Many factors influence this practice, including the burden of outpatient visits. We aimed to compare antibiotic prescribing for children by low prescribers (LP) and high prescribers (HP) in primary care. METHODS: We analyzed pediatric prescriptions in primary care in Istanbul. Among the physicians randomly selected by systematic sampling, those generating ≥1 pediatric prescription/day (n=1218) were defined as LP or HP when they belonged to the lowest (n=305) or highest (n=304) quartile of prescribing, respectively. The antibiotic prescribing characteristics of these groups were compared. RESULTS: We identified that 38.5% of the prescriptions written by physicians included antibiotics, significantly higher in HPs (38.8%) than in LPs (37.2%), (p=0.04). Among antibiotic-containing prescriptions, the mean number of drugs and boxes and the percentage of prescriptions containing injectable drugs/antibiotics were significantly higher in HPs compared to that in LPs. We detected that co-amoxiclav was the most frequently prescribed antibiotic in the LP and HP groups (61.1% and 48.3%, respectively). Stratification of antibiotics by their spectra showed that 11.2% were narrow, 79.8% were broad and 0.5% were ultra-broad-spectrum drugs. LPs were significantly more likely to prescribe broad-spectrum antibiotics (82.5%) than do HPs (78.9%,p < 0.001). CONCLUSIONS: Antibiotic prescribing remains excessive in pediatric primary care, slightly more marked in HPs. While HPs also tend to prescribe a higher number of overall and injectable drugs/antibiotics, broad-spectrum anti-biotherapy seems to be more practiced by LPs surprisingly. Both physician groups appeared to prefer either narrow- or broad-spectrum drugs without paying enough attention to their pharmacodynamic properties.

Association of abdominal subcutaneous fat thickness with hepatic steatosis, liver enzymes, and serum lipids in obese children. / Asociación entre el espesor de la grasa subcutánea abdominal y la esteatosis hepática, las enzimas hepáticas y los lípidos séricos en niños obesos.

INTRODUCTION: Childhood obesity can cause hyperlipidemia and hepatic steatosis at early age and chronic disease complications in adult life. We aimed to evaluate the relationship between abdominal subcutaneous fat thickness (ASFT) and hepatic steatosis, serum lipid and transaminase levels in obese children. POPULATION AND METHODS: A retrospective study was conducted with children (aged 4-18 years) who presented to outpatient clinic due to obesity. Associations between ASFT as assessed by ultrasonography (US) and hepatic steatosis, alanine transaminase (ALT), aspartate transaminase (AST) and serum lipid profile were evaluated. RESULTS: We identified 95 children, all of which were diagnosed as having hepatic steatosis; the most common type was grade 1 (73.6 %, n: 70), followed by grade 2 (21.1 %) and grade 3 (5.3 %). The mean values of midline and flank ASFT were measured as 38.48 ± 11.53 mm and 20.91 ± 8.00 mm in grade 1; 41.23 ± 10.03 and 19.84 ± 6.75 in grade 2 and 63.12 ± 12.08 and 23.22 ± 5.92 in grade 3 hepatic steatosis, respectively. Midline and flank ASFT correlated positively with triglycerides in grade 3 steatosis, while midline ASFT correlated with body mass index, total cholesterol, low-density lipoprotein cholesterol, and AST (r: 0.9; p: 0.037; r: 0.648, p: 0.001; r: 0.387, p: 0.001; r: 0.406, p: 0.001, r: 0.463, p: 0.001; respectively) in grade 1 steatosis. CONCLUSION: ASFT as assessed by US may be of predictive value for hyperlipidemia in grade 3 and for hypercholesterolemia in grade 1 hepatic steatosis in obese children.

Introducción. La obesidad infantil puede causar hiperlipidemia y esteatosis hepática y complicaciones crónicas. Nuestro objetivo fue evaluar la relación entre el espesor de la grasa subcutánea abdominal (GSA) y la esteatosis hepática, las transaminasas y los lípidos séricos en niños obesos. Población y métodos. Estudio retrospectivo en niños (4-18 años) que acudieron a los consultorios externos. Se evaluaron las asociaciones entre el espesor de la GSA mediante ecografía y la esteatosis hepática, alanina aminotransferasa (ALT), aspartato aminotransferasa (AST) y el perfil lipídico sérico. Resultados. Se identificaron 95 niños con esteatosis hepática; el grado 1 fue el más frecuente (73,6 %, n: 70), seguido del grado 2 (21,1 %) y del 3 (5,3 %). El espesor medio (en mm) de la GSA de línea media y flancos fue 38,48 ± 11,53 y 20,91 ± 8,00 en grado 1; 41,23 ± 10,03 y 19,84 ± 6,75 en grado 2, y 63,12 ± 12,08 y 23,22 ± 5,92 en grado 3, respectivamente. El espesor de la GSA de línea media y flancos se correlacionó positivamente con triglicéridos en grado 3; el espesor de la GSA de línea media se correlacionó con el índice de masa corporal, colesterol total, colesterol LDL y AST (r: 0,9; p: 0,037; r: 0,648; p: 0,001; r: 0,387; p: 0,001; r: 0,406; p: 0,001; r: 0,463; p: 0,001; respectivamente) en grado 1. Conclusión. El espesor de la GSA mediante ecografía puede predecir hiperlipidemia en niños obesos con esteatosis hepática de grado 3 e hipercolesterolemia en grado 1.

Evaluation of the pregnant women's approaches regarding drug utilization.

OBJECTIVE: Drug utilization habits of the pregnant are a critical aspect of rational use of the medicine (RUM). This study aimed to analyze the RUM related attitudes and the behaviors of women during their pregnancies. METHODS: The data were collected between May 2016-October 2016 by conducting surveys to 71 pregnant women admitted to the private and governmental hospitals in five districts of Northern Cyprus. The sociodemographic characteristics of the pregnant as well as their attitudes and behaviors concerning drug use were evaluated. RESULTS: The mean age and the gestational week of the patients was 29.7±4.3 years and 25.7±11.2 weeks, respectively. Planned pregnancies constituted 71.8% of all. The percentage of patients with an unplanned pregnancies who were using drugs at the time of the survey (25.0%) was lower than that in those with planned pregnancies (49.0%, p<0.05). Almost two-thirds (66.2%) of the women were exposed to a drug during pregnancy, mostly for "vitamin/mineral prophylaxis" (38.3%) and agents controlling nausea/vomiting (19.1%). Two out of eleven women (18.2%) were using folic acid when they learned about their pregnancy. One of the drugs used for the chronic disorder in the third trimester was acetylsalicylic acid (11.1%), a category D drug in this setting. Most of the patients stated that they frequently read the instructions (60.9%), "often" paying attention to side effects (56.5%). Considering some of the habits related to drug use, 8.7% and 10.9% of pregnant women declared that they sometimes "did not follow the instructions" and "dosage/duration of the drug usage", respectively. Seven patients (15.2%) declared that they did not consider side effects on the medication guide while more than half (56.5%) did it "often". Near one in five (19.6%) of the pregnant women stated that they hesitated about the drug usage due to teratogenicity risks. CONCLUSION: Our study highlights the drug utilization attitudes and behaviors of pregnant women during pregnancy in Northern Cyprus, indicating several shortcomings, including insufficient prenatal folic acid use, occasional use of risky drugs, and unsatisfactory medication guide handling. Available findings underline the necessity of education not only for patients but also for healthcare providers to disseminate RUM in pregnancy.

Off-label drug use in pediatric patients: a comparative analysis with nationwide routine prescription data.

BACKGROUND: Children constitute a special population for off-label drug use (OLDU), yet limited drug-focused data exist regarding pediatric OLDU in clinical practice. This study aimed to investigate pediatric OLDU practice and compare it with pediatric drug utilization patterns of routine prescribing data. METHODS: This cross-sectional study examined all approved pediatric OLDU applications, compared with electronic prescription data on national Prescription Information System of Turkish Medicines and Medical Devices Agency in 2015. OLDU applications and prescriptions were analyzed for demographic characteristics, healthcare/socioeconomic indices as well as details of drugs and diagnoses. RESULTS: We found 7,896 OLDU applications and 7,029,512 prescriptions for the pediatric population in 2015. OLDU applications and prescriptions were mostly practiced for `2-11-year-old` children (52.7% vs. 63.4%, respectively; p < 0.01). OLDU applications and prescriptions were detected to have a positive correlation with socio-economic development index (r = 0.45, p < 0.0001 and r: 0.40, p = 0.0002; respectively) and the physician density (r = 0.66, p < 0.0001 and r: 0.43, p < 0.0001; respectively). In addition, OLDU was also positively correlated with the number of hospital beds per province (r = 0.39, p = 0.0003). Antineoplastic/immunomodulating agents were the most commonly applied drug category in OLDU (47.0%), compared with respiratory system drugs (36.6%) in routine prescribing. Eculizumab (6.5%), mycophenolate (5.6%), and canakinumab (4.4%) were the top drugs used as off-label. OLDU applications and routine prescription data revealed the most frequent diagnosis as `I27-other pulmonary heart diseases` (7.4%) and `J06-acute upper respiratory infections` (12.6%), respectively. CONCLUSIONS: This is the first nationwide study to show indication- and drug-centered aspects of pediatric OLDU and prescribing practice. Though OLDU applications is overall consistent with routine clinical practice in terms of demographics and institutional capacity, substantial variations exist regarding main drug classes and diseases. Our findings are expected to shed light on interventions focused on improving `indicated` pediatric use of drugs currently applied as off-label.

Immunomodulator effect of topical zinc oxide application in tuberculin skin test.

OBJECTIVE: We aimed to evaluate the sensitivity of tuberculin skintest (purified protein derivative-PPD) by topical zinc application on test site to improve diagnostic reliability. METHODS: We performed this study in 100 children aged 6-14 years, and plasma zinc levels were analyzed after 10-12 hours fasting. After PPD, we applied 40% zinc oxide cream on one forearm and placebo on the other forearm. PPD indurations were measured 72 hours later. RESULTS: In this study, 26% of the children showed increases in PPD induration following local zinc applications. There was no correlation between indurations size and serum zinc levels. CONCLUSION: We concluded that topical zinc cream application can enhance sensitivity of tuberculin reactivityin the diagnosis of tuberculosis.

Asociación entre el espesor de la grasa subcutánea abdominal y la esteatosis hepática, las enzimas hepáticas y los lípidos séricos en niños obesos / Association of abdominal subcutaneous fat thickness with hepatic steatosis, liver enzymes, and serum lipids in obese children

Introducción. La obesidad infantil puede causar hiperlipidemia y esteatosis hepática y complicaciones crónicas. Nuestro objetivo fue evaluar la relación entre el espesor de la grasa subcutánea abdominal (GSA) y la esteatosis hepática, las transaminasas y los lípidos séricos en niños obesos.Población y métodos. Estudio retrospectivo en niños (4-18 años) que acudieron a los consultorios externos. Se evaluaron las asociaciones entre el espesor de la GSA mediante ecografía y la esteatosis hepática, alanina aminotransferasa (ALT), aspartato aminotransferasa (AST) y el perfil lipídico sérico.Resultados. Se identificaron 95 niños con esteatosis hepática; el grado 1 fue el más frecuente (73,6 %, n: 70), seguido del grado 2 (21,1 %) y del 3 (5,3 %). El espesor medio (en mm) de la GSA de línea media y flancos fue 38,48 ± 11,53 y 20,91 ± 8,00 en grado 1; 41,23 ± 10,03 y 19,84 ± 6,75 en grado 2, y 63,12 ± 12,08 y 23,22 ± 5,92 en grado 3, respectivamente. El espesor de la GSA de línea media y flancos se correlacionó positivamente con triglicéridos en grado 3; el espesor de la GSA de línea media se correlacionó con el índice de masa corporal, colesterol total, colesterol LDL y AST (r: 0,9; p: 0,037; r: 0,648; p: 0,001; r: 0,387; p: 0,001; r: 0,406; p: 0,001; r: 0,463; p: 0,001; respectivamente) en grado 1.Conclusión. El espesor de la GSA mediante ecografía puede predecir hiperlipidemia en niños obesos con esteatosis hepática de grado 3 e hipercolesterolemia en grado 1.

Introduction. Childhood obesity can cause hyperlipidemia and hepatic steatosis at early age and chronic disease complications in adult life. We aimed to evaluate the relationship between abdominal subcutaneous fat thickness (ASFT) and hepatic steatosis, serum lipid and transaminase levels in obese children.Population and methods. A retrospective study was conducted with children (aged 4-18 years) who presented to outpatient clinic due to obesity. Associations between ASFT as assessed by ultrasonography (US) and hepatic steatosis, alanine transaminase (ALT), aspartate transaminase (AST) and serum lipid profile were evaluated.Results. We identified 95 children, all of which were diagnosed as having hepatic steatosis; the most common type was grade 1 (73.6 %, n: 70), followed by grade 2 (21.1 %) and grade 3 (5.3 %). The mean values of midline and flank ASFT were measured as 38.48 ± 11.53 mm and 20.91 ± 8.00 mm in grade 1; 41.23 ± 10.03 and 19.84 ± 6.75 in grade 2 and 63.12 ± 12.08 and 23.22 ± 5.92 in grade 3 hepatic steatosis, respectively. Midline and flank ASFT correlated positively with triglycerides in grade 3 steatosis, while midline ASFT correlated with body mass index, total cholesterol, low-density lipoprotein cholesterol, and AST (r: 0.9; p: 0.037; r: 0.648, p: 0.001; r: 0.387, p: 0.001; r: 0.406, p: 0.001, r: 0.463, p: 0.001; respectively) in grade 1 steatosis.Conclusion. ASFT as assessed by US may be of predictive value for hyperlipidemia in grade 3 and for hypercholesterolemia in grade 1 hepatic steatosis in obese children.

Assessment of DNA damage in children exposed to indoor tobacco smoke.

The present study is aimed to evaluate the possible DNA damage in children who are living with smoker parents. The tests were conducted by using alkaline comet assay, measured as a percentage of DNA damage in tail (%DNA(T)). The children that participated in the study were selected from the pediatric unit of a hospital in Istanbul, Turkey. %DNA(T) was significantly higher (p<0.01) in children who were exposed to indoor tobacco smoke (10.73+/-1.38) compared to the children in the control group (8.16+/-1.29). The number of cigarettes consumed by household members did not seem to affect the severity of the DNA damage. Since children spend most of their time at home and cannot remove themselves from harmful living conditions this important genotoxic finding should be considered by smoker parents for the future health consequences of their children.