Off-Label Drug Use in Pediatric Out-Patient Care: A Multi-Center Observational Study.

OBJECTIVE: Prescribing a drug for a child is not an easy task and requires using the best available evidence as a guide, especially when a drug is used off-label. The practice of prescribing a drug for off-label use is fairly widespread worldwide. The FDA does not regulate prescribing patterns or practices of individual practitioners and, therefore, allows off-label use. The main objective of this study is to evaluate off-label prescribing among the pediatric population in the Kingdom of Saudi Arabia (KSA). METHOD: This is a retrospective, simple random selection observational study of children (≤15 years) who visited pediatric clinics and had at least 1 drug prescribed over a 12-month period (January to December 2018). RESULTS: A total of 865 drugs (mean 1 and SD 0.24) were prescribed to 326 children. Off-label was identified in 39.4% of the drugs with a frequency of 512 (as 1 drug may belong to more than 1 off-label category). The most common reason for off-label prescribing was related to doses that were "higher or lower than the recommended use" (48.6%), and the most frequently identified drug class prescribed for off-label use was anti-infective drugs for systemic use (39.9%). The percentage of off-label drug use was found to be higher in girls and in the age group of 1 month to 2 years (P = .001) for both variables. In addition, a significant association was found between off label drug use and the total number of drugs prescribed, P < .001. CONCLUSION: The findings of this study showed a high incidence of off-label prescribing mainly related to dosing and indication. The results of this observational study support the need to establish a unified national pediatric dosing formulary guide to ensure safe drug use in pediatrics.

Assessment of COVID-19 Morbidity and Mortality Among Patients With Autoimmune Diseases at King Abdulaziz University Hospital.

Background The coronavirus disease 2019 (COVID-19) pandemic has raised significant concerns about the effects of the virus on patients with autoimmune diseases. Therefore, understanding the COVID-19 outcomes in this population is crucial for effective prevention and management. Objective This study aimed to investigate the association between autoimmune diseases and the severity of COVID-19 in terms of mortality and morbidity. Despite substantial advancements in pandemic-related research concerning COVID-19 and autoimmune diseases, there remain noteworthy gaps in our comprehension of this association, particularly due to limited investigations conducted in Saudi Arabia. Methods This was a retrospective record review of a tertiary center from January 2020 to January 2022. We included 120 patients, among whom 40 were diagnosed with autoimmune diseases, and 80 were age- and sex-matched controls. Afterward, we assessed their demographics, year of admission, intensive care unit (ICU) admission, health status, length of hospitalization, comorbidities, diagnosis of autoimmune diseases, and type of immunosuppressant therapy. Results Most of the included patients (mean age: 45.4 years) were females (65.8%). The ratio of non-autoimmune diseases to autoimmune diseases was 2:1, the mean length of hospitalization was 8.83 ± 8.16 days, and the median was seven days (interquartile range (IQR) = 3 to 11 days). Among them, 17.5% were admitted to the ICU and 10% died. The prevalence of autoimmune diseases was higher in women than in men (77.5%). The most common diseases were systemic lupus erythematosus (40%), rheumatoid arthritis (20%), and ankylosing spondylitis (10%). Regarding COVID-19 outcomes, ICU admissions were higher among patients with autoimmune diseases than those with non-autoimmune diseases (35% vs. 8.8%) (p<0.05). This trend was also observed in mortality, with a higher percentage of deaths among patients with autoimmune diseases (27.5% vs. 1.7%) (p<0.05). In addition, there were no significant differences between genders in terms of ICU admission, health status outcomes, or length of hospitalization among patients with autoimmune diseases (p>0.05). Notably, 25 patients were administered immunosuppressants. Of these, 18 (72%) used steroids only, while seven (28%) used both biological and steroid therapy. However, no significant associations were observed between the type of treatment used and outcomes such as ICU admission, health status at discharge, and length of hospitalization (p>0.05).  Conclusion This study suggests that individuals with autoimmune diseases have more severe COVID-19 outcomes, as shown by ICU admission and mortality rates, than patients with non-autoimmune diseases. Furthermore, we observed that the use of immunosuppressant medications among patients with autoimmune diseases showed no noticeable effect on these outcomes.

Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis.

Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs. -2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man.

Epidemiology and potential associated risk factors of drug-related problems in hospitalised children in the United Kingdom and Saudi Arabia.

AIM: Drug-related problems (DRP) are "an event or circumstance involving drug therapy that actually or potentially interferes with the desired health outcome". The extent and characteristics of DRPs in children in the UK and the Kingdom of Saudi Arabia (KSA) are unknown. Our aim was to determine the epidemiology of and identify risk factors for DRPs in hospitalised children. METHODS: A prospective cohort study was carried out in children aged 0-18 years, admitted to the medical ward, paediatric intensive care unit (PICU) and neonatal intensive care unit (NICU) during a 3-month period in two hospitals. Patients' charts, medical records and laboratory data were reviewed daily to identify DRPs; their preventability and severity were assessed. Logistic regression was used to analyse the potential risk factors associated with DRP incidence. RESULTS: Seven hundred and thirty-seven children (median age 2.3 years, interquartile range 6 months to 8 years, 58.1% male) were included. Three hundred and thirty-three patients suffered from 478 DRPs. Overall DRP incidence was 45.2% (95% CI, 41.5-48.8); KSA (51.1%; 95% CI, 45.8-56.3), UK (39.4%; 95% CI, 34.4-44.6). Incidence was highest in the PICU (59.7%; 95% CI, 47.0-71.5). Dosing problems were the most frequently reported DRPs (n = 258, 54%). 80.3% of DRP (n = 384) cases were preventable; 72.2% (n = 345) of DRPs were assessed as minor; 27% (n = 129) as moderate. Number of prescriptions and type of admission (transferred) were potential risk factors for DRP occurrence in children. CONCLUSIONS: Drug-related problems were common in the hospitalised children in this study; the most frequent were dosing problems and drug choice problems; the majority of them were preventable. Polypharmacy and transferred admission (another hospital or ward) were potential risk factors. To improve prescribing practices and minimise the risk of DRPs in hospitalised children, paediatric pharmacology and pharmacotherapy are important in medical education.

Clinical characterization of pediatric supratentorial tumors and prediction of pituitary insufficiency in two tertiary centers in Saudi Arabia.

Background: Post-operative pituitary insufficiency (PI) occurs in children with supra-tentorial tumors (STT) because of surgery or the mass effect of the tumor. We assessed the prevalence and clinical characteristics of STTs and predicted postoperative PI in our patients. Methods: This retrospective cohort study included children who underwent surgery for STT in two tertiary hospitals in Saudi Arabia (2009-2019). We focused on clinical, radiological, and histopathological features of STTs. We also used a linear regression model to predict post-operative PI. Results: The study included 55 children (1-18 years, mean: 9.5 ± 4.9 years, 32 [54%] females) with an initial presentation of STT that required surgery excluding recurrent episodes. The calculated period prevalence of STT was 18.2%, and the prevalence of postoperative PI was 58.2% (n = 32/55). The most common symptoms were headache and visual disturbances, and 20% patients had preoperative symptoms of PI. Baseline preoperative investigations for PI were performed in 60% of patients, and dynamic tests were conducted in only seven patients. A residual cortisol deficiency was presumed in 24 (43.7%) patients and 18 (32.7%) patients who developed central diabetes insipidus (DI) post-operatively. Overall, the brain imaging correlated well with the histopathological diagnosis (kappa = 0.48; P < .001). Craniopharyngioma (n = 15/55, 27.3%) was the commonest STT. Predictive factors for a postoperative residual PI included age (10.9 ± 4.8 years; p-value = .027), female gender (p-value = .016 [OR = 8.31; 95% CI (1.48-46.71)], presentation with headache (P value = .039 [OR = 9.27; 95% CI (1.12-76.72)]), and visual disturbances (p-value = .044 [OR = 5.07; 95% CI (1.04-24.61)]. Conclusion: STTs commonly occurred in our study population, and females were more prone to develop a residual PI. On-time surveillance of an intact endocrine system during the perioperative period is essential for the prediction and early management of PI.

Drug-related problems found in children attending an emergency department in Saudi Arabia and in the United Kingdom.

BACKGROUND: No published studies investigating drug-related problems (DRPs) in children visiting emergency department (ED) in either the Kingdom of Saudi Arabia (KSA) or the United Kingdom (UK) were identified. OBJECTIVE: To determine the frequency and characteristics of DRPs in paediatric patients attending ED in the KSA and the UK. METHOD: An observational study. DRPs were identified by a researcher, reviewing the medical records of children attending the ED during a three-month period in KSA and a 1 month period in UK; severity and preventability of the DRPs were assessed. Incidence of DRPs overall and in each country was calculated. RESULTS: A total of 253 patients (KSA n = 143, UK n = 110) were included. Fifty-five patients (22%; 55/253), experienced 69 DRPs. 2% (5/253) of the patients attended the ED due to DRPs. Overall incidence was 21.7% (95% CI, 16.8-27.3). 78% (54/69) of the DRPs were assessed as preventable; 33% (23/69) as of moderate severity. CONCLUSION: DRPs were common in paediatric patients attending EDs; the majority were preventable. Further study is needed to investigate the impact of mild and moderate DRPs on paediatric patients' health and also to improve the care provided to minimise the occurrence of preventable DRPs.