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Introduction: Semaglutide, a Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RA), is often prescribed for managing type 2 diabetes, particularly in cases unresponsive to other hypoglycemic agents. Despite its popularity, the real-world efficacy and cost-effectiveness of Semaglutide relative to other treatments remain understudied. Objective: This study aimed to examine the direct medical cost and consequences of adding Semaglutide to the treatment regimen for patients with type 2 diabetes in Saudi Arabia. Methods: We conducted a single-center, retrospective review of Electronic Medical Records (EMRs) for adults with type 2 diabetes. Patients who had been on Semaglutide for at least three months were matched with those receiving alternative hypoglycemic therapies. Exclusions were made for patients with cancer, incomplete EMRs, or lacking prescription data. Investigated outcomes included changes in HbA1C levels and weight, and the direct costs comprised medications, clinic visits, and emergency care. Baseline adjustments were made through inverse probability treatment weighting, and uncertainty was assessed via bootstrapping with 10,000 replications. Results: Out of 350 patients meeting the criteria, 116 were on Semaglutide. Predominantly females (62%), the cohort had an average age of 60 and a disease duration of 22 years. The difference in HbA1C (%) reductions between Semaglutide and non-Semaglutide users over 3,6, and 12 months were 0.154 (95% CI: –0.452-0.483), –0.031(95% CI: –0.754-0.239), –0.16(95% CI: –1.425-0.840), respectively. Semaglutide users did experience modest weight reductions ranging from 0.42 kg to 1.16 kg. The annual additional direct medical cost for Semaglutide was USD 4,086.82 (95% CI: $3,710.85 - $4,294.99). Conclusion: Although Semaglutide induced modest weight reductions, it did not offer significant advantages in lowering HbA1C levels compared to other hypoglycemic treatments. These findings suggest the need for further research involving larger and more diverse cohorts to corroborate these findings.

Aim: We aimed to translate and perform transcultural adaptation of the English version of the Fear of COVID-19 Scale (FCV-19S) to Arabic, and assess predictors of COVID-19 fear. Methods: We translated the original seven-item English FCV-19S to Arabic, then back-translated the scale to English. The scale was evaluated by a group of medical experts and participants from the general population to test for content and face validity. The final version of the scale was assessed in a cross-sectional study that included adults residing in Saudi Arabia, who participated in a study to assess the impact of COVID-19 fear on children's vaccination during the COVID-19 pandemic curfew March 24–July 6, 2020. Results: Overall, 577 participants responded to the survey. The mean age was 32.6 ± 5.7 years, and the majority had bachelor's or postgraduate university degrees. COVID-19 was diagnosed in 1.4% of the participants. The mean total score for the COVID-19 fear scale was 20 ± 5.4. The COVID-19 fear scale had excellent internal consistency and Cronbach's alpha 0.85 (95% confidence interval 0.93–0.96). Conclusions: The modified Arabic version of the FCV-19S is a valid and reliable tool to measure fear levels during the pandemic of COVID-19. Using an appropriate psychometric tool to measure the level of fear can help in monitoring changes in population fear levels, and implementing population-level measures to limit unwarranted fear.

Abstract Background Nephrotic syndrome is the most common kidney disease in children worldwide. Our aim was to critically appraise the quality of recent Clinical Practice Guidelines (CPGs) for idiopathic steroid-sensitive nephrotic syndrome (SSNS) in children in addition to summarize and compare their recommendations. Methods Systematic review of CPGs. We identified clinical questions and eligibility criteria and searched and screened for CPGs using bibliographic and CPG databases. Each included CPG was assessed by four independent appraisers using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE-II) instrument. We summarized the recommendations in a comparison practical table. Results Our search retrieved 282 citations, of which three CPGs were eligible and appraised: Kidney Disease: Improving Global Outcomes (KDIGO) 2012, Japan Society for Pediatric Nephrology (JSPN) 2014, and American Academy of Pediatrics (AAP) 2009. Among these, the overall assessment of two evidence-based CPGs scored > 70% (KDIGO and JSPN), which was consistent with their higher scores in the six domains of the AGREE II Instrument. In domain 3 (rigor of development), KDIGO, JSPN, and AAP scored 84%, 74%, and 41%, respectively. In domain 5 (applicability), they scored 22%, 16%, and 19%, respectively, and in domain 6 (editorial independence), they scored 94%, 65%, and 88%, respectively. Conclusions The methodological quality of the KDIGO CPG was superior, followed by JSPN and AAP CPGs with the relevant recommendations for use in practice. Systematic review registration The protocol was registered in the Center for Open Science (OSF) DOI: 10.17605/OSF.IO/6QTMD and in the International prospective register of systematic reviews PROSPERO 2020 CRD42020197511 .

Background: The coronavirus disease 2019 (COVID-19) pandemic has a significant negative impact on clinical trials. Therefore, maintaining an optimal trial conduct should be considered to minimize risks to trial integrity while ensuring the safety of trial staff and participants. In this study, we aimed to describe the impact of the COVID-19 pandemic on conducting an ongoing clinical trial, along with challenges and solutions encountered and required to continue the trial. Methods: This Phase IV pragmatic randomized superiority controlled open-label trial included children with epilepsy receiving Vitamin D supplementation at King Saud University Medical City, Riyadh, Saudi Arabia (clinicaltrials.gov registration number: NCT03536845). Children with epilepsy receiving chronic antiepileptic medications and with normal baseline 25-hydroxyvitamin D level were randomized to receive cholecalciferol 400 IU/day versus 1000 IU/day for 6 months. The primary outcome was the percentage of children with Vitamin D insufficiency at 6 months. The secondary outcomes included seizure control, bone mineral density, and safety. Results: Under COVID-19 public health emergency measures, exceptional methods were used, such as telemedicine, home visit for blood extractions, shipping of the study medication to the patient's home, using reminder text messages to follow patients' compliance, and using privacy-compliant platforms to connect the research team members. Conclusion: During the widespread pandemic, ethical dilemmas are of major concern, especially when conducting trials on vulnerable age groups. Therefore, actions should be proportionate and based on benefit-risk considerations, affecting the risk of bias from protocol deviation and overall results.

Abstract Central hypothyroidism might be another clinical sign of SSADH deficiency which prompts urinary organic acid screening for GHB in central hypothyroidism patients. Studies on GABA and thyroid hormone interaction might be a concept of a new therapy.

Abstract Objective Vitamin D (vitD) deficiency is a global childhood health problem. Food fortification is a promising strategy to curb vitD deficiency. We aimed to assess the effectiveness of utilizing vitD fortification in staple foods to improve 25hydroxyvitamin D (25(OH)D) concentration and to reduce the prevalence of vitD deficiency among healthy children. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the use of vitD fortified food products compared to no fortification among healthy children aged 1–18 years old. We searched Medline, Embase, Global Health, and Cochrane (CENTRAL) databases from database inception until May 2019. Independently, six reviewers in pairs screened titles and abstracts, assessed the full text for eligibility, and performed data extraction and quality assessment. The primary outcome is the impact of fortification on 25(OH)D concentration. The secondary outcomes included the impact of fortification on the prevalence of vitD deficiency, school performance, cognitive function, school absences, infection rate, hospital admission length, and compliance with fortified food product consumption. Results We identified 2229 articles. After assessing eligibility, 20 RCTs met the inclusion criteria. The eligible RCTs assessed the fortification of milk, cereal, juice, bread, yogurt, and cheese compared with no fortification. All RCTs, except for three, had a low risk of bias. Food fortification improved 25(OH)D concentration by a mean difference (MD) of 15.51 nmol/L (95% confidence interval (CI) 6.28, 24.74; I 2 = 99%), which resulted in a mean increase of 3 nmol/l for every 100 IU of vitD, when adjusted for baseline 25(OH)D concentration and country latitude. Additionally, the prevalence of vitD deficiency decreased by a risk ratio of 0.53 (95% CI 0.41, 0.69; I 2 = 95%), and cognitive function improved by a MD of 1.22 intelligence quotient (IQ) points (95% CI 0.65, 1.79; I 2 = 0%). The overall evidence quality was high. Conclusion VitD food fortification is an effective way to improve 25(OH)D concentration, prevent vitD deficiency, and improve IQ levels. Systematic review registration PROSPERO CRD42017057631

Background: Vitamin D has a role in the pathogenesis of many medical disorders, especially those of the central nervous system. It is essential in maintaining the bone health of children. However, patients with epilepsy are at high risk of developing vitamin D deficiency due to antiseizure medications (ASMs). Therefore, we aimed to assess the prevalence of vitamin D deficiency and related risk factors in children with epilepsy. Methods: This is the baseline report of a pragmatic, randomized, controlled, open-label trial that assessed the impact of vitamin D supplementation in preventing vitamin D deficiency (NCT03536845). We included children with epilepsy aged 2–16 years who were treated with ASMs from December 2017 to March 2021. Children with preexisting vitamin D metabolism problems, vitamin-D-dependent rickets, malabsorption syndromes, renal disease, and hepatic disease were excluded. The baseline demographic data, anthropometric measurements, seizure types, epilepsy syndromes, ASMs, and seizure control measures were recorded. Blood tests for vitamin D (25-hydroxyvitamin D [25(OH)D), serum calcium, serum phosphorus, and parathyroid hormone levels were performed. Based on vitamin D concentration, patients were categorized as deficient (75 nmol/L). Results: Of 159 recruited children, 108 (67.92%) had generalized seizures, 44 (27.67%) had focal seizures, and 7 (4.4%) had unknown onset seizures. The number of children receiving monotherapy was 128 (79.0%) and 31 (19.1%) children were receiving polytherapy. The mean vitamin D concentration was 60.24 ± 32.36 nmol/L; 72 patients (45.28%) had vitamin D deficiency and 45 (28.3%) had vitamin D insufficiency. No significant difference in vitamin D concentration was observed between children receiving monotherapy and those receiving polytherapy. The main risk factors of vitamin D deficiency were obesity and receiving enzyme-inducer ASMs. Conclusions: The prevalence of vitamin D deficiency was high among children with epilepsy. Obese children with epilepsy and those on enzyme-inducer ASMs were at increased risk for vitamin D deficiency. Further studies are needed to establish strategies to prevent vitamin D deficiency.

Background: Routine childhood immunization is the most cost-effective method to prevent infection and decrease childhood morbidity and mortality. The COVID-19 pandemic has affected access to health care in Saudi Arabia, including mandatory vaccinations for young children. We aimed to assess the prevalence of intentionally delayed vaccinations in children aged ≤ 2 years during the COVID-19 pandemic curfew in Saudi Arabia, its relation to the caregivers' fear of infection, and identifying factors affecting the caregivers' decision.Methods: We conducted a cross-sectional study using a self-administered survey that targeted primary caregivers of children aged ≤ 2 years residing in Saudi Arabia during the COVID-19 pandemic curfew (March 4–July 6, 2020).Results: We received responses from 577 caregivers, of whom 90.8% were mothers. The prevalence of intentional vaccination delay was 37%. Upon adjusting the potential confounders, the odds of delaying scheduled childhood vaccination because of COVID-19 pandemic fears were greater among caregivers with higher levels of fear (OR 1.10, 95% CI 1.02–1.11). Common reasons for delaying vaccinations were COVID-19 infection and prevention of exposure to COVID-19 cases.Conclusion: Intentional vaccination delay leaves young children vulnerable to preventable infectious diseases. Identifying these children and offering catch-up vaccinations reduces this risk. Campaigns to increase awareness about the dangers of delaying vaccine-preventable diseases must be promoted to caregivers in addition to the promotion of home vaccination services. In preparation for future pandemics, we recommend countries consider interventions to control the level of fear and anxiety provoked by the pandemics and media, and interventions for improved access to vaccinations.

BackgroundOverburdened healthcare systems during the coronavirus disease (COVID-19) pandemic led to suboptimal chronic disease management, including that of pediatric type 1 diabetes mellitus (T1DM). The pandemic also caused delayed detection of new-onset diabetes in children; this increased the risk and severity of diabetic ketoacidosis (DKA). We therefore investigated the frequency of new-onset pediatric T1DM and DKA in Saudi Arabia during the COVID-19 pandemic and compared it to the same period in 2019.MethodsWe conducted a multicenter retrospective cohort study, including patients aged 1–14 years admitted with new-onset T1DM or DKA during the COVID-19 pandemic (March–June 2020) and the same period in 2019. We assessed factors including age, sex, anthropometric measures, nationality, duration of diabetes, diabetes management, HbA1c levels, glycemic control, cause of admission, blood gas levels, etiology of DKA, DKA complications, length of hospital stay, and COVID-19 test status.ResultDuring the lockdown, 106 children, compared with 154 in 2019, were admitted to 6 pediatric diabetes centers. Among the admissions, DKA was higher in 2020 than in 2019 (83% vs. 73%; P=0.05; risk ratio=1.15; 95% confidence interval, 1.04–1.26), after adjusting for age and sex. DKA frequency among new-onset T1DM and HbA1c levels at diagnosis were higher in 2020 than in 2019 (26% vs. 13.4% [P=

Clonidine is one of the commonly used pharmacological agents for growth hormone stimulation. It is considered generally safe, with only few non-serious reported side effects. Herein, we report a case of an 8 -years-old girl who became unresponsive with poor perfusion and no palpable pulse for 10 seconds, immediately post receiving Arginine for Growth Hormone Stimulation testing, and almost 120 minutes after receiving Clonidine for Growth Hormone Stimulation testing. Serious morbidities that could result in mortality have never been reported as adverse events during Clonidine stimulation. It is important to be aware of this rare complication and closely observe any patients undergoing growth hormone stimulation test with Clonidine. Keywords: Clonidine, Arginine, Growth hormone stimulation test, Adverse effects

Abstract Background Network meta-analysis (NMA) is a powerful analytic tool that allows simultaneous comparison between several management/treatment alternatives even when direct comparisons of the alternatives (such as the case in which treatments are compared against placebo and have not been compared against each other) are unavailable. Though there are still a limited number of pediatric NMAs published, the rapid increase in NMAs in other areas suggests pediatricians will soon be frequently facing this new form of evidence summary. Discussion Evaluating the NMA evidence requires serial judgments on the creditability of the process of NMA conduct, and evidence quality assessment. First clinicians need to evaluate the basic standards applicable to any meta-analysis (e.g. comprehensive search, duplicate assessment of eligibility, risk of bias, and data abstraction). Then evaluate specific issues related to NMA including precision, transitivity, coherence, and rankings. Conclusions In this article we discuss how clinicians can evaluate the credibility of NMA methods, and how they can make judgments regarding the quality (certainty) of the evidence. We illustrate the concepts using recent pediatric NMA publications.

BackgroundMany interventions have shown effectiveness in reducing the duration of acute diarrhea and gastroenteritis (ADG) in children. Yet, there is lack of comparative efficacy of interventions that seem to be better than placebo among which, the clinicians must choose. Our aim was to determine the comparative effectiveness and safety of the pharmacological and nutritional interventions for reducing the duration of ADG in children.MethodsData sources included Medline, Embase, CENTRAL, CINAHL, LILACS, and Global-Health up to May 2017. Eligible trials compared zinc (ZN), vitamin A, micronutrients (MN), probiotics, prebiotics, symbiotics, racecadotril, smectite(SM), loperamide, diluted milk, lactose-free formula(LCF), or their combinations, to placebo or standard treatment (STND), or among them. Two reviewers independently performed screening, review, study selection and extraction. The primary outcome was diarrhea duration. Secondary outcomes were stool frequency at day 2, diarrhea at day 3, vomiting and side effects. We performed a random effects Bayesian network meta-analysis to combine the direct and indirect evidence for each outcome. Mean differences and odds ratio with their credible intervals(CrI) were calculated. Coherence and transitivity assumptions were assessed. Meta-regression, subgroups and sensitivity analyses were conducted to explore the impact of effect modifiers. Summary under the cumulative curve (SUCRA) values with their CrI were calculated. We assessed the evidence quality and classified the best interventions using the Grading of Recommendations, Assessment, Development & Evaluation (GRADE) approach for each paired comparison.ResultsA total of 174 studies (32,430 children) proved eligible. Studies were conducted in 42 countries of which most were low-and middle-income countries (LMIC). Interventions were grouped in 27 categories. Most interventions were better than STND. Reduction of diarrhea varied from 12.5 to 51.1 hours. The combinations Saccharomyces boulardii (SB)+ZN, and SM+ZN were considered the best interventions (i.e., GRADE quality of evidence: moderate to high, substantial superiority to STND, reduction in duration of 35 to 40 hours, and large SUCRA values), while symbiotics (combination of probiotics+prebiotics), ZN, loperamide and combinations ZN+MN and ZN+LCF were considered inferior to the best and better than STND [Quality: moderate to high, superior to STND, and reduction of 17 to 25 hours]. In subgroups analyses, effect of ZN was higher in LMIC and was not present in high-income countries (HIC). Vitamin A, MN, prebiotics, kaolin-pectin, and diluted milk were similar to STND [Quality: moderate to high]. The remainder of the interventions had low to very-low evidence quality. Loperamide was the only intervention with more side effects than STND [Quality: moderate].Discussion/conclusionMost interventions analyzed (except vitamin A, micronutrients, prebiotics, and kaolin-pectin) showed evidence of superiority to placebo in reducing the diarrhea. With moderate-to high-quality of evidence, SB+ZN and SM+ZN, demonstrated the best combination of evidence quality and magnitude of effect while symbiotics, loperamide and zinc proved being the best single interventions, and loperamide was the most unsafe. Nonetheless, the effect of zinc, SB+ZN and SM+ZN might only be applied to children in LMIC. Results suggest no further role for studies comparing interventions against no treatment or placebo, or studies testing loperamide, MN, kaolin-pectin, vitamin A, prebiotics and diluted milk.Prospero registrationCRD42015023778.

Background: Celiac serology can be transiently elevated in patients with type 1 diabetes mellitus (T1DM) and normalized despite gluten consumption. This study aimed to identify the frequency and predictive factors of spontaneous normalization of anti-tissue transglutaminase (anti-TTG-IgA) antibodies in these patients. Methods: The charts of all patients (≤18 years) with T1DM were retrospectively reviewed from 2012 to 2021 at a tertiary care center in Riyadh, Saudi Arabia. The following data were collected: clinical characteristics of the participants, anti-TTG-IgA-immunoglobulin (Ig) A antibody, and histological findings. The outcome of positive anti-TTG-IgA-IgA in patients with T1DM and the predictive factors for spontaneous normalization were investigated. Results: Of the 1,006 patients with T1DM, 138 (13.7%) had elevated anti-TTG-IgA antibodies, celiac disease was diagnosed in 58/138 (42%) patients, spontaneous normalization of anti-TTG-IgA was observed in 65 (47.1%) patients, and fluctuating anti-TTG-IgA antibodies were seen in 15 (10.9%) patients. The patients with anti-TTG-IgA levels at 3–10 times the upper normal limits (UNL), and those with levels ≥10 times UNL were less likely to have spontaneous normalization of anti-TTG-IgA compared to patients with levels at 1–3 times UNL (hazard ratio [HR] = 0.28, 95% confidence interval [Cl] = 0.13–0.61, P = 0.001, and HR = 0.03, 95% Cl = 0.00–0.19, P < 0.001, respectively). Conclusion: Asymptomatic patients with T1DM with mild elevation of anti-TTG-IgA need not be rushed for invasive endoscopy or exposed to an un-needed gluten-free diet but should rather have a regular follow-up of their celiac serology.

BACKGROUND:Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been linked to poor health outcomes, including diminished quality and length of life. This condition is characterized by high phosphate levels and requires phosphate-lowering agents-phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD. METHODS:Data sources included MEDLINE and EMBASE Trials from 1996 to February 2016. We also searched the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD, randomized them to receive calcium (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet, placebo or no treatment, and reported effects on all-cause mortality, cardiovascular mortality or hospitalization at ≥4 weeks follow-up. We performed network meta-analyses (NMA) for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. NCBPBs for all-cause mortality, cardiovascular mortality and hospitalization. In the NMAs, we calculated the effect estimates for direct, indirect and network meta-analysis estimates; for both NMA and conventional meta-analysis, we pooled treatment effects as risk ratios (RR) and calculated 95% confidence intervals (CIs) using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each paired comparison. RESULTS:Our search yielded 1190 citations, of which 71 RCTs were retrieved for full review and 15 proved eligible. With 13 eligible studies from a prior review, we included 28 studies with 8335 participants; 25 trials provided data for our quantitative synthesis. Results suggest higher mortality with calcium than either sevelamer (NMA RR, 1.89 [95% CI, 1.02 to 3.50], moderate quality evidence) or NCBPBs (conventional meta-analysis RR, 1.76 [95% CI, 1.21 to 2.56, moderate quality evidence). Conventional meta-analysis suggested no difference in cardiovascular mortality between calcium and NCBPBs (RR, 2.54 [95% CI, 0.67 to 9.62 low quality evidence). Our results suggest higher hospitalization, although non-significant, with calcium than NCBPBs (RR, 1.293 [95% CI, 0.94 to 1.74, moderate quality evidence). DISCUSSION/CONCLUSIONS:Use of calcium results in higher mortality than either sevelamer in particular and NCBPBs in general (moderate quality evidence). Our results raise questions about whether administration of calcium as an intervention for CKD- MBD remains ethical. Further research is needed to explore the effects of different types of phosphate binders, including novel agents such as iron, on quality and quantity of life. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD-42016032945.