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Leena R Baghdadi,1 Marwah M Hassounah,1 Afnan Younis,1 Hessah I Al Suwaidan,1 Reem Al Khalifah2 1Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, 11362, Saudi Arabia; 2Paediatric Endocrinology Division, Paediatrics Department, College of Medicine, King Saud University, Riyadh, 11362, Saudi ArabiaCorrespondence: Leena R BaghdadiDepartment of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi ArabiaTel/Fax +966 114670836Email lbaghdadi@ksu.edu.saPurpose: This study compared the most used sources of information by caregivers for scheduled childhood vaccination in Saudi Arabia before and during the COVID-19 pandemic and examined the effect of this decision-making.Methods: An electronic survey was administered to 577 caregivers of children aged ≤ 2 years residing in Saudi Arabia during the COVID-19 pandemic curfew. The sources of information on childhood vaccination considered by the caregivers and their influence on the caregivers’ decision to delay scheduled vaccination were assessed and statistically analyzed.Results: Most participants (90.8%) were mothers aged 32.6 ± 5.7 years. Before the pandemic, most caregivers sought information about children’s vaccinations personally from the healthcare workers, or trustworthy sources, including the Ministry of Health (MOH), MOH call center 937, and MOH Sehha app. However, during the pandemic, there was a noticeable decrease in the searches for health information through professional consultations (in person and health websites) and a significant increase in the use of social media platforms. Twitter was the most used platform (29.9%) and the use of Snapchat was significantly higher during the lockdown period compared to its use before the pandemic (21.9% vs 17.2%, P < 0.001). The use of social media not only increased the level of fear among the caregivers but also had a negative effect on their decisions about children’s vaccinations. Searches on YouTube and Facebook particularly increased the odds of delaying vaccinations by 2.63 times (P = 0.008) and 3.66 times (P = 0.025), respectively.Conclusion: During the pandemic, caregivers’ health-information seeking behavior was directed towards social media networking. In Saudi Arabia, YouTube and Facebook, in particular, played an important role in the caregivers’ decision-making about childhood vaccinations. The results of this survey provide valuable information on how to reach the Saudi population and launch an effective awareness campaign using the most commonly accessed and influential sources of information.Keywords: caregivers’ decision, COVID-19, pandemic, immunization, social media, telehealth, health apps

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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., Competing Interests: None

Tendon is similar to rope and consists of strong, flexible, dense connective tissue. Tendon disorder healing is challenging as it is an avascular tissue. The repaired tissue appears scar-like, and its biomechanical properties never ultimately return to their pre-injury state. This study aimed to evaluate the effects of platelet-rich fibrin (PRF) on the hydroxyproline content of the Achilles tendon after injury. For this purpose, 24 adult rabbits weighing 1.5-2 kg were used in this study. The animals were divided into three groups of eight, including the advanced-PRF (A-PRF) group in which the tendon defect was treated with xenogeneic A-PRF, the leukocyte-PRF (L-PRF) group in which xenogeneic L-PRF was used for tendon defect treatment, and a control group which was treated with normal saline. Hydroxyproline concentration was measured 1 and 2 months after the operation. Clinically, lameness was improved in the A-PRF group, compared to the L-PRF and control groups at the end of the third week after the surgery. Hydroxyproline level was significantly increased in the A-PRF group (50.33±1.44), compared to the L-PRF (44.70±1.12) and control (35.97±1.05) groups 2 months after the surgery (P<0.05). Moreover, the L-PRF group showed an increase in hydroxyproline content, compared to the control at the same period. The results of the current study demonstrated that A-PRF could enhance the hydroxyproline content of rabbit Achilles tendon after injury. Xenogenic PRF can be used as an alternative biomaterial to accelerate and regenerate tendon tissue., Competing Interests: The authors declare that they have no conflict of interest.

Background: Acute kidney injury (AKI) is a common complication in patients with diabetic ketoacidosis (DKA) (incidence 35-77%). AKI evolution during DKA treatment/recovery is poorly understood. Our aim was to assess children with DKA for prevalence, short-term kidney outcomes, severity, and predictors of AKI development and resolution., Methods: This retrospective cohort study included children aged 2-14 years admitted with DKA between January 2016 and May 2020 in a Saudi tertiary care hospital. We defined AKI as an increase in serum creatinine of > 1.5 times baseline or > 3 mg/dL (26 mmol/L) within 48 h., Results: Of 213 patients admitted with DKA, 172 (80.75%) developed AKI: stage 1 in 83 (38.96%), stage 2 in 86 (40.37%), and stage 3 in 3 (1.4%). No patient required dialysis. Multivariate analysis showed an increased risk of developing AKI with male gender (OR = 2.85) and lower serum bicarbonate (OR = 0.83) when adjusted for initial heart rate, hematocrit, new onset diabetes, and recurrent AKI. The mean time to AKI resolution was 13.21 ± 6.78 h. Factors leading to prolonged recovery from AKI in linear regression analysis were older age (B coefficient = 0.44, p = 0.01), recurrent DKA episodes (B coefficient = 3.70, p value 0.003), increased acidosis severity (B coefficient =  - 0.44, p = 0.04), increased time to anion gap normalization (B coefficient = 0.44, p = 0.019), and increased initial glucose (B coefficient = 0.01, p = 0.011)., Conclusion: In our cohort, AKI is a common, but mostly transient complication in children presenting with DKA, and its severity is associated with longer intensive care stays and time for acidosis resolution. AKI was associated with male gender, and lower serum bicarbonate. Proper consideration of such risk factors is needed for AKI assessment and management in future DKA clinical practice guidelines. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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 (&lt;50 nmol/L), insufficient (74.9-50 nmol/L), or normal (&gt;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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Baghdadi, Younis, Al Suwaidan, Hassounah and Al Khalifah.)

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 importance of telemedicine in diabetes care became more evident during the coronavirus disease 2019 (COVID-19) pandemic as many people with diabetes, especially those in areas without well-established telemedicine, lost access to their health care providers (HCPs) during this pandemic., Subjects and Methods: We describe a simplified protocol of a Diabetes Telemedicine Clinic that utilizes technological tools readily available to most people with diabetes and clinics around the world. We report the satisfaction of 145 patients and 14 HCPs who participated in the virtual clinic and 210 patients who attended the virtual educational sessions about "Diabetes and Ramadan.", Results: The majority of patients agreed or strongly agreed that the use of telemedicine was essential in maintaining a good glucose control during the pandemic (97%) and they would use the clinic again in the future (86%). A similar high satisfaction was reported by patients who attended the "Diabetes and Ramadan" virtual educational session and 88% of them recommended continuing this activity as a virtual session every year. Majority of the HCPs (93%) thought the clinic protocol was simple and did not require a dedicated orientation session prior to implementing., Conclusions: The simplicity of our Diabetes Telemedicine Clinic protocol and the high satisfaction reported by patients and HCPs make it a suitable model to be adopted by clinics, especially during pandemics or disasters in resource-limited settings. This clinic model can be quickly implemented and does not require technological tools other than those widely available to most people with diabetes, nowadays. We were able to successfully reduce the number of patients, HCPs, and staff physically present in the clinics during the COVID-19 pandemic without negatively impacting the patients' nor the HCPs' satisfaction with the visits.

Aim: We aimed to identify gaps in school care and support required for students with type 1 diabetes mellitus (T1DM) in Saudi Arabia., Methods: We performed a cross-sectional nationwide study using self-administered surveys that targeted teachers and parents of students with T1DM in Saudi Arabia from August to December 2019., Results: We collected surveys from 632 parents and 983 teachers. Responses were received from all 13 regions in Saudi Arabia, with the majority representing governmental schools. Results showed that 172 students (27.3%) had no available help at school to perform blood glucose measurement, 178 students (28.3%) were left with no hypoglycemia treatment, 374 students (59.6%) took their insulin dose for breakfast at home, and 40.0 (6.4%) students omitted insulin. Overall, school admission refusal was reported by 73 students (11.7%). Students with no available help to manage their hypoglycemia or to inject insulin at school had a higher hemoglobin A1c and poorer academic performance., Conclusion: Our study revealed a significant gap between schools' local practices and international recommendations, which impacted students' safety, diabetes control, and school achievement. Our study findings will support the creation of the Saudi T1DM school practice guidelines necessary to improve the care of students with T1DM., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: Automated insulin delivery with predictive low glucose suspend (PLGS) feature has the potential to reduce risk of hypoglycemia in patients with type 1 diabetes mellitus (T1DM). We aim to systematically synthesize the evidence on the efficacy and safety of PLGS in children and adolescents with T1DM., Methods: We performed a systematic search through Ovid/MEDLINE, Ovid/Embase, and other search engines. We included randomized controlled trials (RCTs) evaluating the effect of sensor augmented pump (SAP) with PLGS feature compared to SAP or insulin pump therapy without SAP in decreasing hypoglycemia in children and adolescents aged 2 to 18 years with T1DM, with at least 2 weeks of follow-up. Two reviewers independently selected studies, extracted data, and evaluated the risk of bias (ROB)., Results: Five RCTs with total sample size of 493 children aged 6 to 18 years met the inclusion criteria. The overall ROB of included studies was low. There is high quality evidence that PLGS is superior to SAP in decreasing time spent in hypoglycemia (sensor glucose [SG] <3.9 mmol/L [<70 mg/dL]/24 h) and nocturnal hypoglycemia (SG <3.9 mmol [<70 mg/dL]/L/night) with an absolute mean difference of 17.4 min/d (95% CI: -19.2, -15.5) and 26.3 min/night (95% CI: -35.5, -16.7), respectively, without increasing percentage of time spent in hyperglycemia or episodes of diabetic ketoacidosis (DKA). There was insufficient evidence for the impact of PLGS on health related quality of life (HRQL)., Conclusions: PLGS is superior to SAP in decreasing daytime and nocturnal hypoglycemia without increasing the risk of DKA or hyperglycemia. Future studies should address the impact of PLGS on children younger than 6-years-old and HRQL., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

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: The TBX1 gene encodes the T-box 1 protein that is a transcription factor involved in development. Haploinsufficiency of the TBX1 gene is reported to cause features similar to DiGeorge syndrome. The TBX1 gene is located within the DiGeorge syndrome region, and studies support that the TBX1gene is responsible for most of the features of the phenotype of hemizygous deletion of chromosome 22q11.2. In this study, we report a family of 4 (a father with 3 children) who presented with congenital hypoparathyroidism and hypocalcemia, facial asymmetry, deafness, normal intelligence, and no cardiac involvement., Methods: We performed whole genome sequencing, computational structural analysis of the mutants, and gene expression studies for all affected family members., Results: Whole genome sequencing revealed a paternal inherited novel heterozygous variant, c.1158&#95;1159delinsT p.(Gly387Alafs*73), in the exon 9 isoform C TBX1 gene, causing a loss of nuclear localization sequence (NLS) and transactivation domain (TAD) with no change in gene expression and resulted in a DiGeorge-like phenotype., Conclusion: A pathogenic variant in the TBX1 gene exon 9 C that predicted to cause a loss in the NLS region and most of TAD leads to variable features of hypoparathyroidism, distinctive facial features, deafness, and no cardiac involvement. In addition, our report and previous reports indicate the presence of a wide phenotypic spectrum of TBX1 genetic variants and the consistent absence of cardiac involvement in the case of pathogenic variants on exon 9 isoform C TBX1 gene., (© Endocrine Society 2019.)

Background: Many 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., Methods: Data 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., Results: A 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/conclusion: Most 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 Registration: CRD42015023778., Competing Interests: The authors have declared that no competing interests exist.

Background: To address gaps in knowledge of the longitudinal trajectory of dysglycemia in children with obesity, this study aimed to: (1) describe the changes in glycemic status over 2 years; (2) establish a predictive model for development of prediabetes among children with euglycemia; and (3) evaluate the influence of change in body mass index (BMI) z-score on glycemic status., Methods: Children aged 5 to 17 years entered this prospective, longitudinal study at the time of entry to a weight management program. Measures included a 75-g oral glucose tolerance test (OGTT), fasting blood glucose, hemoglobin A1c (HbA1c), lipid profile, liver enzymes and anthropometric measures at baseline, 1 and 2 years. Cox proportional hazard was used to build a predictive model for prediabetes., Results: The cohort included 270 children, mean age: 11.6 ± 2.7 years and BMI z-score: 3.1. The baseline prevalence of prediabetes, based upon elevated 2-hour glucose in OGTT or HbA1c, was 100/270 (37.0%). Among children with prediabetes at baseline, 53 (53.0%) continued to have prediabetes over the following 2 years, 15 (15.0%) were euglycemic at 1 year and had prediabetes at 2 years, 20 (20.0%) became euglycemic and remained so. Change in BMI z-score predicted dysglycemic status at 2 years. Among those euglycemic at baseline, the incidence of prediabetes was 14 (8.2%) after 1 year, 20 (12.8%) at 2 years. Predictors of incident prediabetes were baseline BMI z-score; hazard ratio (HR): 1.72, 95th confidence interval (CI: 1.08, 2.74) and baseline HbA1c HR: 1.26, 95th CI (1.02-1.56) when controlling for age, family history of diabetes and sex., Conclusion: Prediabetes presents significant morbidity in children with obesity. Family-based lifestyle interventions might delay prediabetes progression., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

Background: Patients with chronic kidney disease mineral and bone disorders (CKD-MBD) suffer high rates of morbidity and mortality, in particular related to bone and cardiovascular outcomes. The management of CKD-MBD remains challenging. The objective of this systematic survey is to critically appraise clinical practice guidelines (CPGs) addressing CKD-MBD., Methods/design: Data sources included MEDLINE, EMBASE, the National Guideline Clearinghouse, Guideline International Network and Turning Research into Practice up to May 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility and subsequently appraised the guidelines using the Advancing Guideline Development, Reporting and Evaluation in Health Care instrument II (AGREE)., Results: Sixteen CPGs published from 2003 to 2015 addressing the diagnosis and management of CKD-MBD in adult patients (11 English, two Spanish, one Italian, one Portuguese and one Slovak) proved eligible. The National Institute for Health and Care Excellence guideline performed best with respect to AGREE II criteria; only three other CPGs warranted high scores on all domains. All other guidelines received scores of under 60% on one or more domains. Major discrepancies in recommendations were not, however, present, and we found no association between quality of CPGs which was not associated with resulting recommendations., Conclusions: Most guidelines assessing CKD-MBD suffer from serious shortcomings using AGREE criteria although limitations with respect to AGREE criteria do not necessarily lead to inappropriate recommendations.

Hyperglycemia is a rare presenting symptom of mitochondrial disorders. We report a case of a young girl who presented shortly after birth with ketoacidosis, hyperlactatemia, hyperammonemia, and insulin-responsive hyperglycemia. Initial metabolic work-up suggested mitochondrial dysfunction. Given our patient's unusual presentation, whole-exome sequencing (WES) was performed on the parent-offspring trio. The patient was homozygous for the c.643C>T (p.Leu215Phe) variant in CYC1, a nuclear gene which encodes cytochrome c 1 , a subunit of respiratory chain complex III. Variants in this gene have only been previously reported in two patients with similar presentation, one of whom carries the same variant as our patient who is also of Sri Lankan origin.Primary complex III deficiencies are rare and its phenotypes can vary significantly, even among patients with the same genotype.

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.

Background: The growth hormone (GH) stimulation protocols for clonidine and arginine tests are non-standardized and can be lengthy. We examined the specificity of both tests using a shorter duration of timed samples: 90 min for clonidine and 60 min for arginine., Methods: We retrospectively studied all children who had GH stimulation with clonidine and arginine to test for GH deficiency (GHD). We compared the diagnostic accuracy of both reference and new shortened test (index)., Results: We reviewed 243 charts (11.4±4.1 years old; 74.5% males). The combined reference test was performed on 159 children, 29 (18.3%) tested positive for GHD on the combined index test, Kappa 0.98, false positive rate 1 (0.8%), specificity 0.99, 95th CI (0.96-1), and p=1.0. The specificity of both the clonidine and arginine single index tests was 0.98%., Conclusions: The shortened clonidine and arginine stimulation index tests have good specificity. This is a viable option for testing children for GHD.

Background: Acute diarrhea and acute gastroenteritis (AD/AGE) are common among children in low- and middle-income countries (LMIC) and high-income countries (HIC). Supportive therapy including maintaining feeding, prevention of dehydration, and use of oral rehydration solution (ORS), is the mainstay of treatment in all children. Several additional treatments aiming to reduce the episode duration have been compared to placebo, but the differences in effectiveness among them are unknown., Methods and Analysis: We will conduct a systematic review of all randomized controlled trials evaluating the use of zinc, vitamin A, probiotics, prebiotics, synbiotics, racecadotril, smectite, and fermented and lactose-free milk/formula for AD/AGE treatment in children. The primary outcomes are diarrhea duration and mortality. Secondary outcomes are diarrhea lasting 3 or 7 days, stool frequency, treatment failure, hospitalizations, and adverse events. We will search MEDLINE, Ovid EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), and LILACS through Ovid, as well as grey literature resources. Two reviewers will independently screen titles and abstracts, review full texts, extract information, and assess the risk of bias (ROB) and the confidence in the estimate (with the grading of recommendations, assessment, development, and evaluation [GRADE] approach). Results will be summarized narratively and statistically. Subgroup analysis according to HIC vs. LMIC, age, nutrition status, and ROB is planned. We will perform a Bayesian network meta-analysis to combine the pooled direct and indirect treatment effect estimates for each outcome, if adequate data is available., Discussion: This is the first systematic review and network meta-analysis that aims to determine the relative effectiveness of pharmacological and nutritional treatments for reducing the duration of AD/AGE in children. The results will help to reduce the uncertainty of the effectiveness of the interventions, find knowledge gaps, and/or encourage further research for other therapeutic options., Systematic Review Registration: PROSPERO registration number: CRD42015023778.

Background: Gestational diabetes mellitus (GDM) affects up to 10% of all pregnancies and results in significant maternal and neonatal morbidities., Objectives: Our main objective was to investigate retrospectively the rate of neonatal intensive care unit (NICU) admissions and significant neonatal complications in pregnant mothers with gestational diabetes., Materials and Methods: A retrospective cohort study was conducted. The medical records of King Khalid University Hospital (KKUH) were reviewed from January till December 2007. All pregnant women with GDM along with their offsprings were included and matched with healthy pregnant women. The primary outcome was the rate of NICU admission, hypoglycemia, birth weight and length of hospital stay., Results: A total of 766 mothers (419 GDM mothers and 347 controls) with their term babies were included. Infants born to GDM mothers had significantly higher risk of NICU admissions [OR 2.7 (95% CI 1.5, 4.9), P value 0.0004], longer hospital stay and higher rates of hypoglycemia. Newborns of GDM mothers had higher rates of perinatal distress and macrosomia; however, the difference did not reach statistical significance., Conclusion: GDM remains a significant morbidity to newborns resulting in increased intensive care admission, prolongation of hospital stay and higher rates of neonatal hypoglycemia. More efforts to assure early recognition and strict sugar control during pregnancy are still needed.