Cushing syndrome in paediatric population: who and how to screen.

Cushing's syndrome (CS) is characterised by signs and symptoms resulting from excessive and prolonged exposure to exogenous glucocorticoids or endogenous hypercortisolism. In childhood, exogenous CS represents the main cause of CS due to the widespread therapeutic use of glucocorticoids, while endogenous CS is very rare and accounts for about 10% of CS cases. According to the origin of the hypercortisolism, the ACTH-dependent form due to pituitary ACTH-secreting tumours is the most common form of endogenous CS in paediatric age (about 75-80% of cases), following by adrenal causes (about 15-20% of cases) including adenoma, carcinoma (which has a peak of incidence in the first decade), bilateral adrenal hyperplasia or Carney complex, with a different distribution by age. Ectopic ACTH-secreting CS, genetic forms of pituitary adenomas are more uncommon. The insidious onset of hypercortisolism and the absence of salient early signs make the diagnosis of endogenous CS difficult. Facial changes, weight gain with simultaneous growth failure, prepubertal virilisation, or hypogonadism in adolescence represent some of the key features of CS. The diagnostic workup is essentially aimed at confirming hypercortisolism through screening tests whose diagnostic accuracy is not 100% and therefore the combination of more than two tests is mandatory to confirm the diagnosis of CS.

Perinatal outcomes after a prenatal diagnosis of a fetal copy number variant: a retrospective population-based cohort study.

BACKGROUND: There are no established guidelines for the follow up of infants born after a prenatal diagnosis of a genomic copy number variant (CNV), despite their increased risk of developmental issues. The aims of this study were (i) to determine the perinatal outcomes of fetuses diagnosed with and without a CNV, and (ii) to establish a population-based paediatric cohort for long term developmental follow up. METHODS: An Australian state-wide research database was screened for pregnant individuals who had a prenatal chromosomal microarray (CMA) between 2013-2019 inclusive. Following linkage to laboratory records and clinical referrer details, hospital records were manually reviewed for study eligibility. Eligible participants were mother-child pairs where the pregnancy resulted in a livebirth, the mother was able to provide informed consent in English (did not require a translator) and the mother was the primary caregiver for the child at hospital discharge after birth. Research invitations were sent by registered post at an average of six years after the prenatal diagnostic test. Statistical analysis was performed in Stata17. RESULTS: Of 1832 prenatal records examined, 1364 (74.5%) mother-child pairs were eligible for recruitment into the follow up cohort. Of the 468 ineligible, 282 (60.3%) had 'no live pregnancy outcome' (209 terminations of pregnancy (TOP) and 73 miscarriages, stillbirths, and infant deaths), 157 (33.5%) required a translator, and 29 (6.2%) were excluded for other reasons. TOP rates varied by the type of fetal CNV detected: 49.3% (109/221) for pathogenic CNVs, 18.2% (58/319) for variants of uncertain significance and 3.3% (42/1292) where no clinically significant CNV was reported on CMA. Almost 77% of invitation letters were successfully delivered (1047/1364), and the subsequent participation rate in the follow up cohort was 19.2% (201/1047). CONCLUSIONS: This study provides Australia's first population-based data on perinatal outcomes following prenatal diagnostic testing with CMA. The relatively high rates of pregnancy loss for those with a prenatal diagnosis of a CNV presented a challenge for establishing a paediatric cohort to examine long term outcomes. Recruiting a mother-child cohort via prenatal ascertainment is a complex and resource-intensive process, but an important step in understanding the impact of a CNV diagnosis in pregnancy and beyond. TRIAL REGISTRATION: ACTRN12620000446965p; Registered on April 6, 2020.

Management of paediatric soil-transmitted helminthiasis in a non-endemic area: experience in a reference international health unit.

Soil-transmitted helminth (STH) infections inflict disability worldwide, especially in the poorest communities. Current therapeutic options against STHs show limited efficacy, particularly against Trichuris trichiura. The empirical management of patients coming from high-prevalence areas has been suggested for non-endemic areas. This study aimed to describe the management of STH infections in a non-endemic setting using an individualised approach. We performed a retrospective, descriptive study of all patients up to 16 years of age with STH infections attended at an international health unit in a non-endemic area (2014-2018), including all T. trichiura, Necator americanus, Ancylostoma duodenale, and Ascaris lumbricoides infections diagnosed using a formol-ether concentration technique and direct visualisation. Patients were treated according to current international guidelines. Sixty-one stool samples from 48 patients testing positive for STHs were collected, with 96% (46/48) reporting a previous long-term stay in endemic areas. Cure rates with 3-day benzimidazole regimens were 72% for T. trichiura, 40% for hookworms, and 83% for A. lumbricoides. The results were not influenced by any reinfection risk due to the study being performed in a non-endemic area. Patients coming from STH-endemic areas should be evaluated with appropriate diagnostic tools and followed up until cure control results. Cure rates in our cohort were moderate to low, similar to those published in studies in endemic areas. The efficacy of current treatment options is insufficient to recommend a specific empirical approach in high-income countries' healthcare systems.

Vitamin D deficiency increases with age and adiposity in Emirati children and adolescents irrespective of type 1 diabetes mellitus: a case control study.

BACKGROUND: Association of vitamin D (25(OH)D) deficiency with obesity and diabetes has been well-established in paediatric and adult populations. This study aims to report the association of 25(OH)D deficiency with body composition and prevalence of 25(OH)D deficiency in Emirati children and adolescents, who attended a diabetes centre in the United Arab Emirates. METHODS: Using Abu Dhabi Diabetes and Obesity Study cohort, type 1 diabetes (T1D) and normoglycaemic (NG) participants between 4-19 years of age were selected. WHO criteria were used to define 25(OH)D cut-offs: deficient (< 30 nmol/L), insufficient (30-50 nmol/L) and sufficient (> 50 nmol/L). Based on CDC recommendations, BMI percentile was categorised as underweight, normal weight, overweight and obesity. RESULTS: After age and sex matching, 148 T1D cases and 296 NG controls were identified. 25(OH)D deficiency was observed in 22.3% (n = 33) T1D and 40.5% (n = 120) NG participants. 25(OH)D levels were lower in adolescents (15 - 19 years) than children (4 - 7 years) in both T1D and NG groups (p = 0.018 vs p < 0.001). Females were more likely to be 25(OH)D deficient in both groups. Children and adolescents with BMI ≥ 95th percentile were more likely to be 25(OH)D deficient than those with normal weight (OR: 2.69; 95% CI: 1.56, 4.64). Adiposity measures and 25(OH)D levels correlated negatively in both groups (T1D p < 0.01, NG p < 0.001). CONCLUSION: Vitamin D 25(OH)D deficiency is notably prevalent in Emirati children and adolescents despite adequate sunlight throughout the year. The prevalence was lower in those with T1D which may be indicative of treatment compliance in this population. This study also confirms important negative association of serum 25(OH)D levels with body mass and obesity in this population.

Oral complications in a paediatric graft versus host disease (GVHD) clinic: A retrospective study.

OBJECTIVE: The aim of this study was to investigate the oral health status among allogeneic transplant recipients who were seen in a multidisciplinary graft-versus-host disease paediatric clinic at the University of California, San Francisco (UCSF). METHODS: This was a retrospective cohort study of patients who underwent allogeneic transplants and were seen in the graft-versus-host disease paediatric clinic between January 2010 and September 2021. Demographic, medical and oral health data were recorded and analysed using descriptive statistics. RESULTS: A total of 25 patients were seen in the paediatric graft-versus-host disease clinic (68% males) with a median age of 12 years at the time of transplant were included. Among them, 12 patients (48%) were diagnosed with oral chronic GVHD, 11 (44%) with dry mouth, four (16%) with oral pseudomembranous candidiasis, one (4%) with recrudescent Herpes Simplex Virus (HSV) infection and one (4%) with mammalian target of rapamycin-inhibitor stomatitis and were managed by the oral medicine team, accordingly with medications, such as topical steroids (44%) and anti-fungal (20%). CONCLUSIONS: HSCT recipients may present with a variety of oral complications. Patients may benefit by a multi-disciplinary approach including a dental specialist as part of the cancer care team.

Monochromatic ocular high-order aberrations in children and adolescents.

PURPOSE: To investigate the prevalence and repeatability of high-order aberrations (HOAs) from non-cyclopleged eyes in 1515 children and adolescents 2.5-18 years of age. METHODS: The Leipzig Research Centre for Civilization Diseases (LIFE)-Child study is a population-based, prospective, observational single-centre study that investigates the development of children and adolescents in Germany. Wavefront measurements were repeated three times in each eye of 1515 healthy subjects. Results were described by 36 Zernike coefficients for a 5 mm reference pupil diameter. Short-term repeatability is given for each coefficient. The impact on vision is described by the root mean squared (RMS) value of the HOA Zernike coefficients. RESULTS: High-order aberrations were dominated by five contributions. For 1004 right eyes: spherical aberration (c12 = 0.06 ± 0.07 µm), coma (c7 = 0.03 ± 0.09 µm, c8 = 0.03 ± 0.06 µm) and trefoil (c6 = -0.01 ± 0.07 µm, c9 = 0.008 ± 0.06 µm). The RMS value was 0.18 ± 0.06 µm. Modes higher than fourth order do not contribute clinically to the aberrations. HOAs show no clinically significant dependency with age. Instead, HOA values agree well with previous results on aberrations in adult eyes. Spherical aberration was highly correlated between the two eyes. Repeatability was worst for coma, 0.033 µm, due to variability in the alignment of the pupil centre. The left eye showed, on average, a 0.08 mm larger pupil diameter than the right eye (p < 0.02). CONCLUSIONS: Across the age span from 2.5 to 18 years, we see the same distribution of HOA as for adults. We established that only five Zernike coefficients, spherical aberration, coma and trefoil were of clinical significance in healthy eyes. A high correlation between the two eyes for spherical aberration suggests a common blueprint for each eye in any one subject.

Ability of S100B to predict post-concussion syndrome in paediatric patients who present to the emergency department with mild traumatic brain injury.

INTRODUCTION: Among children who sustain mild traumatic brain injury (mTBI), 10-30% develop a cluster of cognitive, physical, and emotional symptoms commonly referred to as post-concussion syndrome (PCS). Symptoms typically resolve within 7-10 days, but a minority of patients report symptoms that persist for months or even years. The aim of our study was to identify a neurobiochemical marker after mTBI that can predict the presence of post-concussion syndrome three months after head injury in paediatric patients. MATERIALS AND METHODS: Children between 7 and 16 years of age who had head trauma and no other complaints were included. Three months after the initial visit, participants or parents/guardians were interviewed in person about the children's PCS symptoms using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). RESULTS: The mean value of S100B protein in serum in 38 patients without signs of PCS was 0.266 µg L-1, with a 95% confidence interval (CI) of 0.221 - 0.310 µg L-1. Among the 22 patients with signs of PCS, the mean value of S100B protein in serum was 0.845 µg L-1, with a 95% CI of 0.745-0.945 µg L-1. Patients with signs of PCS had higher S100B protein levels than those without signs of PCS (p < 0.0001). CONCLUSIONS: Our prospective study showed that S100B protein is a useful neurobiomarker for detecting paediatric patients at risk for post-concussion syndrome. We found that the biomarker S100B correlated with the severity of traumatic brain injury (number of lesions on CT) and the presence of post-concussion syndrome.

Early childhood caries sequelae and relapse rates in an Australian public dental hospital.

BACKGROUND: Early childhood caries (ECC) remains one of the most prevalent childhood diseases in Australia, disproportionately affecting disadvantaged populations. AIM: To investigate the ECC experience including risk factors, incidence of caries, pain and infection as well as relapse rates of caries and secondary dental general anaesthesia (GA). DESIGN: A retrospective cohort study included dental records of children with ECC, aged <72 months at an Australian public dental hospital paediatric dentistry department from 2013 to 2015 (n = 102). Dental caries, pain, infection, referral patterns, demographic and caries risk factor data were recorded for 24 months. Descriptive statistics were used for patient characteristics and clinical data, and Kaplan-Meier curves and parametric exponential survival models for time-to-event series. RESULTS: The study population demonstrated higher-than-national average dmft and disease progression at baseline. Major risk factors for the development of caries, pain and infection were daily consumption of sweetened beverages, poor oral hygiene, residing in lower socio-economic areas, older age and being male. Rates of caries relapse and new referral for secondary treatment under general anaesthesia were relatively high. CONCLUSION: A high degree of ECC progression and recurrence in this population indicates a need for a more comprehensive approach to ECC addressing multilevel root causes and systemic risk factors.

Conventional fluoroscopy-guided versus zero-fluoroscopy catheter ablation of supraventricular tachycardias.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of zero-fluoroscopy (ZF) catheter ablation (CA) for supraventricular tachycardias (SVT). METHODS: 584 consecutive patients referred to our institution for CA of SVT were analysed. Patients were categorised into two groups; zero-fluoroscopy (ZF) group and conventional fluoroscopy (CF) group. The ZF group was further divided into two subgroups (adults and paediatric). Patient characteristics, procedural information, and follow-up data were compared. RESULTS: The ZF group had a higher proportion of paediatric patients (42.2% vs 0.0%; p < 0.001), resulting in a younger age (30.9 ± 20.3 years vs 52.7 ± 16.5 years; p < 0.001) and lower BMI (22.8 ± 5.7 kg/m2 vs 27.0 ± 5.4 kg/m2; p < 0.001). Procedure time was shorter in the ZF group (94.2 ± 50.4 min vs 104.0 ± 54.0 min; p = 0.002). There were no major complications and the rate of minor complications did not differ between groups (0.0% vs 0.4%; p = 0.304). Acute procedural success as well as the long-term success rate when only the index procedure was considered did not differ between groups (92.5% vs 95.4%; p = 0.155; 87.1% vs 89.2%; p = 0.422). When repeated procedures were included, the long-term success rate was higher in the ZF group (98.3% vs 93.5%; p = 0.004). The difference can be partially explained by the operators' preferences. CONCLUSION: The safety and efficacy of ZF procedures in adult and paediatric populations are comparable to that of CF procedures.

Potential role of salivary cortisol levels to reflect stress response in children undergoing congenital heart surgery.

AIM: This study aimed to provide baseline information on the potential role of salivary cortisol in reflecting the stress response in children undergoing congenital heart surgery. PATIENTS AND METHODS: Children underwent congenital cardiac surgery, aged between one and seventeen years were included. Saliva samples were collected pre- and postoperatively by the health caregiver immediately after the children woke up (07:00-09:00 am) and at 06:00 pm in the evening. Salivary cortisol levels were compared with the reference index values from a large database. RESULTS: Median baseline preoperative morning salivary cortisol levels were significantly lower than the reference values in both < 5-year-old females (p = 0.01) and males (p = 0.04) and in males between 11 and 20 years of age (p = 0.01). Median baseline preoperative evening salivary cortisol levels were significantly higher than the reference value in < 5-year-old females (p = 0.01) and between 5 and 10 years of age (p = 0.04) and in between 11- and20-year-old males (p = 0.01). Median postoperative morning salivary cortisol levels were significantly lower than the reference value in both < 5-year-old females (p = 0.01) and males (p = 0.04) and females between 5 and 10 year of age (p = 0.04). Median postoperative evening salivary cortisol levels were significantly higher than the reference value in < 5-year-old females (p = 0.01) and between 5- and 10-year-old females (p = 0.04). CONCLUSION: Diurnal variability of salivary cortisol levels in children undergoing congenital heart surgery may be different from normal reference values both in preoperative and postoperative periods that can be a predictive indicator of anxiety on pre- and postoperative period for children that undergoing cardiac surgery.

Paediatric vocal fold nodules: management strategies to restore normal phonation-Speech-Language Pathologists perspective: A cross-sectional survey.

Vocal fold nodules are benign vocal cord lesions which develop in voice abusers, including children, though chronic cough, sinusitis, and reflux may also be the causative agents. Since low or no-evidence treatment strategies, like the boone technique, are in use in paediatrics, this study was conducted to determine the treatment strategies used by speech-language pathologists in paediatric vocal fold nodules using a cross-sectional survey at Riphah International University, Lahore, from October 2016 to May 2017. Sixty-five speech-language pathologists working with children in private clinics and multidisciplinary settings were recruited using purposive sampling. A self-structured questionnaire was used for data collection. Analysis using SPSS -18 revealed that a combination of voice therapy and vocal hygiene was the most favoured treatment used by 65 (100%) speech-language pathologists, followed by 58 (89.2%) who also favoured respiratory and relaxation exercises, and 56 (86.2%) who also included parental counselling. Hence, a combination of voice therapy and vocal hygiene is a good therapeutic technique being practiced by speech pathologists for the treatment of vocal nodules among paediatric population.

Formulation and development of paediatric orally disintegrating carbamazepine tablets.

Carbamazepine is a medicine used to manage epilepsy and partial or tonic-clonic seizures. This study aimed at formulating and obtaining carbamazepine orodispersible tablets for paediatric use at a 50 mg dose, with a diameter not greater than 6 mm and a tablet weight of 80 mg, through a direct compression process. The SeDeM pre-formulation/formulation method was used to define the characteristics of both carbamazepine and the selected excipients for direct compression. This study succeeded in formulating and obtaining the proposed tablets. Following the application of the SeDeM method, the tablets met the mass uniformity test and showed appropriate hardness values for orodispersible tablets. The tablets also met the United States Pharmacopeia (USP) test specifications at t = 60 min. The orodispersible tablets obtained may improve compliance with paediatric treatment with carbamazepine, ensuring the safety and effectiveness of the medicine.

Constructing a representative in-silico population for paediatric simulations: Application to HIV-positive African children.

AIMS: Simulations are an essential tool for investigating scenarios in pharmacokinetics-pharmacodynamics. The models used during simulation often include the effect of highly correlated covariates such as weight, height and sex, and for children also age, which complicates the construction of an in silico population. For this reason, a suitable and representative patient population is crucial for the simulations to produce meaningful results. For simulation in paediatric patients, international growth charts from the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) provide a reference, but these may not always be representative for specific populations, such as malnourished children with HIV or acutely unwell children. METHODS: We present a workflow to construct a virtual paediatric patient population using WHO and CDC growth charts, suggest piecewise linear functions to adjust the median of the growth charts by sex and age, and suggest visual diagnostics to compare with the target population. We applied this workflow in a population of 1206 HIV-positive African children, consisting of 19 742 observations with weight ranging from 3.8 to 79.7 kg, height from 55.5 to 180 cm, and an age between 0.40 and 18 years. RESULTS: Before adjustment, the WHO and CDC charts produced weights and heights higher compared to the observed data. After applying our methodology, we could simulate weight, height, sex and age combinations in good agreement with the observed data. CONCLUSION: The methodology presented here is flexible and may be applied to other scenarios where WHO and CDC growth standards might not be appropriate. In addition we provide R scripts and a large ready-to-use paediatric population.

Ocular biometry in children and adolescents from 4 to 17 years: a cross-sectional study in central Germany.

PURPOSE: To evaluate ocular biometry in a large paediatric population as a function of age and sex in children of European descent. METHODS: Children were examined as part of the LIFE Child Study (Leipzig Research Centre for Civilization Disease), a population-based study in Leipzig, Germany. Altogether, 1907 children, aged from 4 to 17 years, were examined with the Lenstar LS 900. Data from the right eye was analysed for axial length, central corneal thickness, flat and steep corneal radii, aqueous depth, lens thickness and vitreous depth. Wavefront-based autorefraction was employed for analysis. RESULTS: Axial length increased in girls from 21.6 mm (4 years) up to 23.4 mm (17 years); this increase (0.174 mm per year) was statistically significant up to age 14 (23.3 mm). Axial length increased in boys from 22.2 mm (4 years) up to 23.9 mm (17 years); this increase (0.178 mm per year) was statistically significant up to age 10 (23.3 mm). No change was observed for central corneal thickness (average: girls 550 µm; boys 554 µm). Corneal curvature in girls was somewhat flatter at age 4 (7.70 mm) compared to age 10 (7.78 mm), whereas it was constant in boys (7.89 mm). Aqueous depth at age 4 was 2.73 mm for girls and 2.86 mm for boys, with the same rate of increase per year (girls: 0.046 mm; boys: 0.047 mm) from age 4 to 10. At age 17, aqueous depth was 3.06 mm in girls and 3.20 mm in boys. Lens thickness was reduced from age 4 (3.75 mm) to age 10 (3.47 mm) in girls and from age 4 (3.73 mm) to age 10 (3.44 mm) in boys, with the same rate of decrease per year of 0.046 and 0.047 mm, respectively. At age 17, lens thickness was 3.52 mm in girls and 3.50 mm in boys. Vitreous depth at age 4 was 14.51 mm for girls and 15.08 mm for boys; with 0.156 mm (girls) or 0.140 mm (boys) increase per year until age 14 (girls: 16.08 mm; boys: 16.48 mm). At age 17, vitreous depth was 16.29 mm in girls and 16.62 mm in boys. CONCLUSIONS: Eye growth (axial length) in girls showed a lag of about four years compared to boys. Aqueous depth increase matches the lens thickness decrease from ages 4 to 10 years in girls and boys. Lens thickness minimum is reached at 11 years in girls and at 12 years in boys. All dimensions of the optical ocular components are closely correlated with axial length. These data may serve as normative values for the assessment of eye growth in central European children and will provide a basis for monitoring refractive error development.

The different surgical impact of the superior cavoatrial incision in children and adults.

INTRODUCTION: The single- and double-patch repairs are undoubtedly the most commonly used techniques for the surgical management of partial anomalous pulmonary venous connection associated with sinus venosus atrial septal defect. The aim of this study was to retrospectively compare early and long-term surgical outcomes in paediatric and adult patients, focusing in particular on the occurrence of ectopic atrial rhythm. MATERIAL AND METHODS: Seventy patients (male: 38, 54.2%) underwent surgical repair for partial anomalous pulmonary venous connection with sinus venosus atrial septal defect. Forty-nine patients (70%) underwent surgical repair in paediatric age (<16 years old), while 21 of (30%) patients were operated in adulthood. Thirty patients (42.8%) underwent single-patch repair and 39 patients (55.7%) underwent double-patch repair. In only one patient, the Warden procedure was performed (1.4%). Median follow-up time was 52 months (IQ 15.1-113). RESULTS: The type of surgical technique didn't affect the incidence of ectopic atrial rhythm (26.6% in single-patch group and 25.6% in double-patch groups, p = 0.9). At long-term follow-up, ectopic atrial rhythm, as an expression of sinoatrial node disturbance, was however significantly more frequent in the paediatric population (28.8% paediatric group and 4.7% adult group, p = 0.02). CONCLUSIONS: The higher incidence of ectopic atrial rhythm in children is probably related to the closer position of the sinus node to the superior cavoatrial incision, which makes irreversible iatrogenic traumatism more likely to occur. Surgical techniques that avoid any manipulation on the superior cavoatrial junction should, therefore, be preferred for children undergoing partial anomalous pulmonary venous connection repair.

Facts and Challenges about Asthma and COVID-19 among the Paediatric Population: A Systematic Literature Review.

A systematic review of the literature was conducted to analyse the factors that affect the probability of the paediatric asthma population suffering from COVID-19 or SARS-CoV-2, such as asthma phenotypes, inhaled corticosteroids, and the effects of lockdown. This systematic review was based on PRISMA guidelines. A bibliographic search was conducted using BNE, BVS (LILAC), CSIC (IME, ISOC), IBECS, Scielo, Scopus, Medline, and PubMed, using the following search profile: (COVID-19 or 2019-NCOV or SARS-CoV-2 or COV-19) AND asthma AND (children or adolescents or youths or children or teenagers). The results were limited to those articles published between December 2019 and December 2020, selecting only articles published in Spanish, English and French that included the study population (children aged 0-18 years). Among the 1066 results of the bibliographic search and seven articles selected from a manual search, only 19 articles were found to fit our eligibility criteria. Most of the articles highlight the effects of lockdown on the paediatric asthma population, increased therapeutic compliance, and the role of inhaled corticosteroids and intrinsic factors such as ACE2 receptors as causes of the decreased prevalence of COVID-19 among the paediatric asthma population. This population has unique characteristics that serve as protective factors against COVID-19. The safety measures implemented during the lockdown period along with inhaled corticosteroid treatment also contributed to this protection.

Parent-related factors influencing antibiotic use in a paediatric population: A qualitative study in Spain.

AIM: To explore the parent-related factors underlying antibiotic misuse/overuse and their implication in the development of resistance in the paediatric population. METHODS: Qualitative study using the focus group (FG) method in Galicia (Spain). FG sessions were conducted with the parents, 27 mothers and three fathers, of children under 12 years old. A discussion topic guide was developed to lead the sessions, which were then transcribed by the researcher and independently interpreted by two researchers working separately. The grounded theory approach was used. RESULTS: Five FG sessions were conducted. The principal factor detected among parents was fear, associated with the perception of poor parent-paediatrician communication. This factor was related to the following behaviours: (a) pressure on physicians; (b) lack of adherence to treatment; and (c) search for other ways of accessing antibiotics. No group highlighted antibiotic resistance as posing a real problem. All groups considered certain external agents to be responsible for such resistance. Four groups also acknowledged that patient behaviour can influence antibiotic resistance. CONCLUSION: Our study points to poor communication between the healthcare system and the population. Identifying the factors underlying the problem enables more efficient, tailor-made interventions to be designed for the purpose of improving antibiotic use and resistance.

Use of Transcription when Assessing Children's Speech: Australian Speech-Language Pathologists' Practices, Challenges, and Facilitators.

OBJECTIVE: There is currently limited knowledge on the useof transcription in the management of children with speech sound disorders (SSD) by speech-language pathologists in Australia. This study explored the use of transcription, the facilitators, and challenges of transcription use, and differences in the use of detailed transcription with various client groups. Method and Participants: Eighty-four participants (speech-language pathologists working in Australia) completed an online exploratory survey which included closed and open-ended questions. RESULTS: 95% of participants reported using transcription. The three most commonly reported strategies/resources were transcription charts (81%), self-practice (68%), and websites (42%). Transcription challenges included the use of two vowel notation systems, reduced proficiency in transcription, service delivery issues, sampling/recording issues, and issues with using transcription to communicate. Finally, results from this survey found that participants use detailed transcription more often when recording the speech of children with childhood apraxia of speech and craniofacial impairment compared to using transcription to document the speech of children who have SSD of unknown origin. Most participants (91%) had not attended transcription professional development. CONCLUSIONS: These findings have implications for the university training of speech-language pathologists and for the establishment of professional development courses for practising speech-language pathologists in Australia.

The Diagnosis of Ceftriaxone Hypersensitivity in a Paediatric Population.

INTRODUCTION: Penicillins and cephalosporins are the most frequent causes of hypersensitivity reactions (HRs) to drugs in children. Among cephalosporins for intravenous use, ceftriaxone (CT) is the most frequently prescribed in Italy. The aims of this study were to evaluate the diagnostic methods for CT hypersensitivity in a population of children with suspected HRs to this drug and their tolerance toward amoxi-cillin/clavulanic acid (AMX/CLV). MATERIALS AND METHODS: From 2012 to 2018, 90 children were investigated for suspected HRs to CT according to the European Academy of Allergy Asthma and Clinical Immunology (EAACI) guidelines. RESULTS: Ninety children had a history of reaction to CT. The majority (79/90; 77.8%) had a history of immediate reactions (IRs). CT hypersensitivity was confirmed in 26/90 patients (28.9%). In case of IRs, skin tests can be useful (24% of positive CT intradermal tests - IDTs) particularly in cases of anaphylaxis (81.8% of positive CT IDTs). Only 5 out of 28 drug provocation tests were positive. Serum-specific IgE (sIgE) determination for CT correlated with positivity upon skin/drug provocation tests (high specificity 95.6%) but had a low sensitivity; sIgE for AMX had a very low positive predictive value (14.3%), advocating against its use. In case of non-IRs, only 7/11 patients reached a confident diagnosis, but the low number of children does not enable proper conclusions. Only 2 children showed cross- and/or co-allergy (2.2%) between CT and AMX/CLV. CONCLUSION: IDTs seem to be useful for diagnosing CT IRs. Hypersensitivity to CT is confirmed in 28.9% of children, although a large fraction of parents refused an intravenous rechallenge (45.6%). It remains unknown whether this is due to the fact this was intravenous rather than a rechallenge with the culprit, but it reflects a clinical reality. Otherwise, cross- and/or co-allergy between CT and AMX/CLV is a rare event.

A review of population pharmacokinetic models of gentamicin in paediatric patients.

WHAT IS KNOWN AND OBJECTIVES: Gentamicin is often used for the treatment of Gram-negative infections. Due to pharmacokinetic variability in paediatric patients, appropriate dosing of gentamicin in the paediatric population is challenging. This article reviews published population pharmacokinetic models of gentamicin in paediatric patients, identifies covariates that significantly influence gentamicin pharmacokinetics, and determines whether there is a consensus on proposed dosing for intravenous gentamicin in this population. METHODS: The PubMed database was searched for articles published until the end of 2017. If the articles described population pharmacokinetic models of gentamicin in the paediatric population (after intravenous administration of gentamicin), the following data were extracted: type of study, year of publication, population characteristics and number of patients, gentamicin dosing, total number of gentamicin (serum and/or plasma) concentrations, type of population modelling approach, developed model with pharmacokinetic parameters and covariates included. RESULTS AND DISCUSSION: In most of the studies, one- or two-compartment modelling was applied. The mean estimated gentamicin clearance for newborns, infants and the complete paediatric population was 0.048, 0.13 and 0.067 L/h/kg, respectively, and the mean predicted volume of distribution was 0.475, 0.35 and 0.33 L/kg, respectively. The values reflect differences in body composition and kidney maturation within the different paediatric populations. Gentamicin pharmacokinetics were most influenced by age, body size and renal function. WHAT IS NEW AND CONCLUSION: Based on our review, the authors agree on a prolonged dosing interval for preterm and term newborns (up to 48 hours). However, there was no agreement on proposed dosing with respect to gestational age. In general, the proposed daily doses were lower compared to those initially applied for preterm newborns and comparable to those for term newborns. For infants and children, the dosing interval remained unchanged (24 hours), but the proposed daily doses were higher than actually applied. When differences in the paediatric population are considered and an appropriate population PK model with applicable covariates is applied, dosing can be individualized. In the future, studies of gentamicin pharmacokinetics in paediatric patients should focus on currently underestimated covariates, such as fat-free mass, concomitantly administered drugs, body temperature and critical illness because these can change gentamicin PK considerably. Consequently, different dosing is required and TDM becomes even more important.