Recombinant PTH Infusion in a Child With Sanjad-Sakati Syndrome Refractory to Conventional Therapy.

Hypoparathyroidism is the most common endocrinological feature in children with Sanjad-Sakati syndrome. Treatment includes active vitamin D and calcium supplementation. Here, we report a case of a newborn with Sanjad-Sakati syndrome who had severe hypocalcemia since birth who responded to PTH subcutaneous pump infusion. The child was born at 35 weeks with hypocalcemia since the first day of life. The standard medical treatment proved ineffective for the newborn, necessitating the administration of unusually high doses of oral and IV calcium and vitamin D analogue for a 2 months. As a result, intermittent subcutaneous injections of PTH were commenced, resulting in an initial improvement in calcium levels, although this proved to be short-lived. Subsequently, a switch to continuous infusion via a Medtronic Vio pump was made, which unfortunately resulted in iatrogenic hypercalcemia, requiring management of hypercalcemia. Later, calcium carbonate and alfacalcidol were resumed at a lower dosage and continued to have average requirements for patients with hypoparathyroidism. PTH subcutaneous infusion can be highly effective in refractory hypocalcemia cases and can significantly impact the treatment course and facilitate hospital discharge as seen in our case. Careful dosage and monitoring are required to avoid iatrogenic hypercalcemia.

Cost consequence analysis of adding semaglutide to treatment regimen for patients with Type II diabetes in Saudi Arabia.

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.

Frequency and predictive factors for spontaneous normalization of anti-tissue transglutaminase-IgA serology among Saudi children with type 1 diabetes mellitus: A cohort study.

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.

Safety and user experience with off-label use of a flash glucose monitor (FreeStyle Libre® 1) among very young children with type 1 diabetes mellitus.

OBJECTIVES: FreeStyle Libre 1 (FGM) has been approved by the FDA for children older than 4 years. It enables noninvasive glucose monitoring without the need for finger pricking. Parents of very young children often use the device off-label. Thus, we aimed to evaluate the safety of and user experience with FreeStyle Libre® 1 and determine its impact on sleep and glycemic control. METHODS: This was an ambi-directional cohort study. We recruited parents of very young children with type 1 diabetes mellitus (T1DM) who were less than 5 years old when they started using FGM at the King Saud University Diabetes Center. The parents filled out a survey evaluating their experience with the system. In addition, the glucose metrics of the children were also obtained from the Libre View system. RESULTS: We included 31 children with mean age of the children when they started using FGM was 3.88 ± 1.10 years (range, 1.46-5.4 years), and the mean sensor use was 2.3 ± 1.3 years. During the use of the device, the parents had increased sleep duration of 0.71 h (p-value=0.04), had earlier bedtime by 2.8 h (p-value=0.04), and were able to sleep in a separate room from their children. In addition, the time in range improved by 9.9%, the time above range decreased by 8.8%, and the HbA1c level reduced by 1.56%. CONCLUSIONS: The safety profile of FGM used for very young children with T1DM is the same for older children, which leads to improved metabolic control and sleep quality of both the parent and the child.

Risk factors, outcomes, and predictors of resolution of acute kidney injury in children with diabetic ketoacidosis.

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.

Prevalence and Related Risk Factors of Vitamin D Deficiency in Saudi Children with Epilepsy.

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.

The long-term growth, cost-effectiveness, and glycemic effects of growth hormone therapy on children born small for gestational age over 10 years: a retrospective cohort study.

OBJECTIVES: We aimed to report our 10-year experience of treating short children born small for gestational age (SGA) by comparing the long-term growth, metabolic safety, and cost-effectiveness of recombinant human growth hormone (rhGH) therapy in short children born SGA with those in rhGH-treated children with growth hormone deficiency (GHD) and Turner syndrome. METHODS: We performed a 10-year retrospective cohort study at King Saud University Medical City. We included children aged 3-16 years who received rhGH for GHD, SGA, or Turner syndrome for >1 year. RESULTS: A total of 166 children received rhGH therapy for GHD, 58 for SGA, and 16 for Turner syndrome. During the last study visit, the average height change was 21 cm for GHD children and 14 cm for children born SGA (p-value <0.001). The height SDS change was 0.84 for GHD children and 0.55 for SGA children (p-value=0.004). The average cost-effectiveness ratios for treating GHD and SGA children were USD 1,717.22 and USD 1,157.19 per centimeter gained, respectively. Moreover, the mean incremental cost-effectiveness ratio for GHD vs. SGA patients was USD 2,820.39 per centimeter gained. Dysglycemia developed in 70 patients: 43 (36.44%), 22 (40.74%), and 5 (13%) in the GHD, SGA, and Turner syndrome groups, respectively. CONCLUSIONS: rhGH is effective in height improvement of short children. However, pursuing rhGH treatment for children born SGA requires a shared decision-making approach to balance the modest benefit of final adult height gain with the long-term metabolic effects, considering the acceptable costs on the Saudi healthcare system.

Estimated Cost-effectiveness of Subcutaneous Insulin Aspart in the Management of Mild Diabetic Ketoacidosis Among Children.

Importance: Intravenous (IV) insulin infusion is the standard of care for treating diabetic ketoacidosis (DKA) worldwide. Subcutaneous (SC) insulin aspart could decrease the use of health care resources. Objective: To compare the cost-effectiveness of mild uncomplicated DKA management with SC insulin aspart vs IV insulin infusion among pediatric patients from the perspective of a public health care payer using clinical data. Design, Setting, and Participants: This economic evaluation included children aged 2 to 14 years presenting to the emergency department of a single academic medical center with mild DKA between January 1, 2015, and March 15, 2020. The medical records for DKA treatment course and its associated hospitalization costs were reviewed. Data were analyzed from January 1, 2015, to March 15, 2020. Exposures: Subcutaneous insulin aspart vs IV regular insulin infusion. Main Outcomes and Measures: The incremental cost-effectiveness ratio (US dollars per hour), duration of DKA treatment, and length of hospital stay. Results: A total of 129 children with mild DKA episodes (mean [SD] age, 9.9 [3.1] years; 72 girls [55.8%]) were enrolled in the study. Seventy children received SC insulin aspart and 59 received IV regular insulin. Overall, the length of hospital stay in the SC insulin group was reduced (mean, 16.9 [95% CI, -31.0 to -2.9] hours) compared with the IV insulin group (P = .005). The mean (SD) cost of hospitalization in the SC insulin group (US $1071.99 [US $523.89]) was less than that in the IV insulin group (US $1648.90 [US $788.03]; P = .001). The incremental cost-effectiveness ratio was -34.08 (95% CI, -25.97 to -129.82) USD/h. The use of SC insulin aspart was associated with a lower likelihood of prolonged hospital stay (ß = -17.22 [95% CI, -32.41 to -2.04]; P = .03) than IV regular insulin when controlling for age and sex. Conclusion and Relevance: Findings of this economic evaluation suggest that SC insulin aspart is dominant vs IV regular insulin in the management of mild uncomplicated DKA in children.

Development and Validation of the Transition Readiness Assessment Instrument in Type 1 Diabetes "On TRAck".

OBJECTIVES: Transition to adult care is challenging for youth with type 1 diabetes (T1D) and their caregivers. We have developed the diabetes-specific "On TRAck" transition readiness scale, and in this study we assess its reliability and validity compared with TRANSITION-Q, a generic transition readiness questionnaire. METHODS: We systematically created 3 versions of On TRAck: adolescent, parent and health-care provider (HCP) versions (for case managers and physicians). Among adolescents 13 to 18 years of age with T1D at a single academic centre, we conducted an exploratory factor analysis and assessed interrater agreement, internal consistency and relationship with age; recent glycated hemoglobin (A1C); and recent diabetic ketoacidosis (DKA) with On TRAck and TRANSITION-Q. RESULTS: One hundred fifteen adolescents (aged 15.8±1.6 years and diabetes duration 6.7±4.1 years), their caregivers and diabetes HCPs participated. The final 24-item adolescent and parent scales (with 3 subscales: "Self-efficacy," "Autonomy" and "Support & maturity") and the 3-item HCP version had a Cronbach's alpha of 0.86 to 0.93. Adolescent scores correlated with parents (r=0.64), case managers (r=0.39) and physicians (r=0.28). Mean adolescent score was 190.3±27.1 points out of 240. Adolescent scores were 3.4 points higher per year of age (p=0.03) and 4.4 points higher for every 1% lower A1C (p=0.01), but were not associated with DKA. TRANSITION-Q was associated with age. On TRAck HCP scores were associated with adolescent's age, A1C and DKA. CONCLUSIONS: On TRAck represents a new psychometrically comprehensive diabetes-specific scale that can be used in adolescent diabetes clinics for measuring transition readiness. It is a multidimensional instrument with ease of use and high reliability scores.

The Arabic Translation and Cross-Cultural Adaptation of the Bristol Activity of Daily Living Scale.

BACKGROUND: There are few Arabic language functional scales for patients with dementia. The Bristol Activity of Daily Living Scale (BADLS) was designed and validated for use in patients with dementia. OBJECTIVE: Our study aimed to translate, cross-culturally adapt, and validate the BADLS to the Arabic language for people with neurocognitive decline and dementia. METHODS: The original BADLS scale was translated to the Arabic language followed by face validity assessment through a pilot testing in five Arabic countries. The Arabic BADLS was assessed in a sample of 139 participants and their caregivers for concurrent and convergent validity. RESULTS: The Arabic BADLS had excellent internal consistency, Cronbach's alpha 0.95 (95% CI 0.93-0.96). Likewise, the Arabic BADLS had strong convergent validity with the Montreal Cognitive Assessment (r = -0.82, p < 0.001). CONCLUSION: The Arabic BADLS is a valid scale that can used to assess the functional performance of people living with dementia.

Caregivers' Sources of Information About Immunization as Predictors of Delayed Childhood Vaccinations in Saudi Arabia During the COVID-19 Pandemic: A Cross-Sectional Questionnaire Study.

PURPOSE: 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.

Impact of the COVID-19 Pandemic Lockdown on Routine Childhood Immunization: A Saudi Nationwide Cross-Sectional Study.

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.

AGREEing on clinical practice guidelines for idiopathic steroid-sensitive nephrotic syndrome in children.

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 .

Succinic semialdehyde dehydrogenase deficiency presenting with central hypothyroidism.

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.

Rapid Implementation of a Diabetes Telemedicine Clinic During the Coronavirus Disease 2019 Outbreak: Our Protocol, Experience, and Satisfaction Reports in Saudi Arabia.

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.

School practice and preparedness in caring for children with type 1 diabetes: A Saudi nationwide cross-sectional study.

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.

Efficacy of Treatments for Polycystic Ovarian Syndrome Management in Adolescents.

Limited evidence on treatment options for polycystic ovarian syndrome (PCOS) has led to considerable variation in health care practices. We aimed to compare the effects of metformin and/or oral contraceptive pills (OCP) in combination with pioglitazone, spironolactone, flutamide, and lifestyle interventions among adolescents aged 11 to 19 years with PCOS. Literature searches were performed in Medline, Embase, and the Cochrane Central Register of Controlled Trials from database inception through December 2018, with no language restriction. Two reviewers screened titles and abstracts, assessed full text eligibility, and extracted information from eligible trials. Evidence was synthesized through network meta-analyses (NMA) using a Bayesian random-effects approach. We identified 37 randomized controlled trials, in which 2400 patients were randomized. NMA showed no statistically important difference among all interventions to improve menstrual regulation or body mass index. Moderate-quality evidence showed hirsutism scores were reduced by multiple interventions that included single and combination medications namely; lifestyle intervention, metformin, OCP, spironolactone, pioglitazone, metformin-OCP, metformin-spironolactone, and metformin-flutamide against placebo. Moderate-quality evidence showed OCP results in more dysglycemia compared to metformin (odds ratio, 2.98; 95% credible interval, 1.02-8.96), no intervention resulted in dysglycemia reduction. In conclusion, metformin and OCP as monotherapy or in combination with other interventions compared with placebo can reduce hirsutism scores, but none of these medications lead to effective menstrual cycle regulation or weight reduction. However, the use of OCP leads to worse cardiometabolic risk factors. Further research into new treatment options is urgently needed. PROSPERO REGISTRATION NUMBER: CRD42015016148.

The efficacy and safety of insulin pump therapy with predictive low glucose suspend feature in decreasing hypoglycemia in children with type 1 diabetes mellitus: A systematic review and meta-analysis.

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.

The impact of vitamin D food fortification and health outcomes in children: a systematic review and meta-regression.

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; I2 = 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; I2 = 95%), and cognitive function improved by a MD of 1.22 intelligence quotient (IQ) points (95% CI 0.65, 1.79; I2 = 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.

A Novel TBX1 Variant Causing Hypoparathyroidism and Deafness.

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_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.