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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.

Objective To systemically review all clinical trials that evaluate the effectiveness of orthodontic intrusion using bone anchorage devices versus using other orthodontic techniques in adult patients. Material and methods All randomized, controlled clinical trials and prospective studies that compare the use of TADs in intrusion versus alternative devices from the year 2000 to 2019 were searched using various electronic databases. Databases used include Pubmed, Cochrane, Scopus, Lilacs, and ScienceDirect. Selection was initially made by reading the titles and abstracts of potential suitable studies. The final selection was made after reading the full retrieved articles. A methodological score developed by Lagravere was used to assess the quality of evidence. The selection process was illustrated using a PRISMA flow chart. Results A total of 3942 articles were retrieved, from which only two randomized clinical trials met the inclusion criteria. This presented a low to medium level of evidence to support the hypothesis that TADs are more effective than other orthodontic intrusion techniques for intruding upper incisors and improving upper incisor to lip relation while eliminating the adverse effect of compromising vertical posterior anchorage. Shorter treatment times and less root resorption were found in the TAD group. Conclusion There is insufficient evidence to state that TADs can be used as orthodontic anchorage to effectively intrude the incisors without the need for patient cooperation. Future high quality prospective randomized clinical trials are required.

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.

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

Aim Type 2 diabetes is a major global epidemic affecting over 400 million people worldwide. The objective of this systematic review was to provide an overview of recommendations from clinical practice guidelines (guidelines) addressing non-insulin based pharmacological management of among non-pregnant adults in an outpatient setting, and critically appraise their methodological development. Methods We systematically searched MEDLINE and Embase databases, for relevant guidelines using the Ovid interface. We scanned the bibliographies of all eligible guidelines for additional relevant citations. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility and appraised the reporting quality of guidelines using the Advancing Guideline Development, Reporting and Evaluation in Health Care instrument II (AGREE II) instrument. Results Our search yielded 11264 unique citations, of which 124 were retrieved for full-text review; 17 guidelines proved eligible. The highest scoring AGREE domain was 'clarity of presentation' (66%; range 7-92%), followed by 'scope and purpose' (58%; range 25-92%), 'editorial independence' (55%; range 0-91%), 'stakeholder involvement' (45%; range 11-90%) and 'rigour of development' (43%; range 4-92%). The poorest domain was 'applicability' (37%; range 6-84%). The guidelines authored by the World Health Organization group achieved the highest AGREE overall score. Conclusions Most of the guidelines provided recommendations with a local jurisdictional focus and showed significant variation in the quality. Nevertheless, only a small number of those scored well overall.

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.

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

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 recommendations in a comparison matrix. 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.

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.

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.

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.

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

Background: Congenital hypopituitarism is a clinical syndrome of deficiency in pituitary hormones production. Panhypopituitarism refers to involvement of more than one pituitary hormone while involvement of one hormone refers to partial hypopituitarism It is an uncommon disorder of the hypophyseal system but could be life threatening, however, it is treatable if the diagnosis is made early. Design and setting: A retrospective hospital based study was conducted at Pediatric endocrine service, King Khalid University Hospital ( KKUH ) Riyadh, Saudi Arabia during the period of January 1990 and December 2017. Material and Methods: The medical records of patients with the diagnosis of hypopituitarism were retrospectively reviewed. Data included age, sex, clinical presentation, and results of relevant laboratory investigations and radiological imaging. Results: During the period under review, a total of 177 patients were diagnosed with possible congenital hypopituitarism. The mean age was 6.5 years range 0-18 years. Seventy-five percent were having isolated hormone deficiency; Growth hormone 117 (87.9%), gonadotrophic hormone 8 (6.0%), central hypothyroidism 5 (3.8%) and adrenocorticotrophic hormone 3 (2.3%). In twenty- five percent of patients the diagnosis was multiple pituitary hormone deficiency (MPHD), in which septo-optic dysplasia and other midline defects, constitute the majority (56.8%). Diabetes Insipidus was found in association in five (2.5%) patients. Conclusion: Congenital hypopituitarism in not that rare in Saudi Arabia. An early diagnosis can be obtained with high accuracy based on a high clinical suspicion index. Imaging abnormalities are frequent and associated with the clinical and biochemical phenotypes. It had variable presentations, such as hypoglycemia, micro phallus in boys and neonatal cholestasis, or in association with midline defects. There is a need to compliment hormonal and radiological investigations with gene study.

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 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: 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.

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.

We aimed to assess the effectiveness of adding metformin to insulin in type 1 diabetes mellitus (T1DM) children for improving metabolic outcomes. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) conducted on children age 6 to 19 years who are diagnosed with T1DM, and examined the effect of adding Metformin to standard insulin therapy. We performed literature searches on Ovid Midline, Ovid Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) from the date of inception of the database to February 15, 2016. Two reviewers screened titles and abstracts independently, assessed full text eligibility, and extracted information from eligible trials. The primary outcome is glycated hemoglobin (HbA1c), and the secondary outcomes are health-related quality of life, body mass index (BMI), lipid profile, total insulin daily dose, hypoglycaemia, and diabetes ketoacidosis. We screened 736 studies, and included 6 RCTs with 325 patients. All RCTs were of low risk of bias, and included adolescents (mean age 15 years). The meta-analysis showed that the addition of Metformin resulted in decreased total insulin daily dose (TIDD) (unit/kg/d) (mean difference [MD] = -0.15, 95%CI, -0.24, -0.06), and reduced BMI kg/m2 (MD -1.46, 95%CI -2.54, 0.38), and BMI z-score (MD= - 0.11, 95%CI -0.21, -0.01), and similar HbA1c (%) (MD= - 0.05, 95%CI, -0.19, 0.29). The overall evidence quality was high to moderate. Current evidence does not support use of Metformin in T1DM adolescents to improve HbA1c. However, Metformin may provide modest reduction in TIDD and BMI.

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: Polycystic ovarian syndrome (PCOS) is a common disease. There is limited evidence to support various treatment choices. This leads to variable treatment practices. OBJECTIVES: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the use of metformin versus oral contraceptive pills (OCPs) for the treatment of PCOS in adolescents aged 11 to 19 years. DATA SOURCES: We performed literature searches through Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials, and gray literature resources, up to January 29, 2015. STUDY SELECTION AND DATA EXTRACTION: Two reviewers screened titles and abstracts of identified citations, assessed full text eligibility, and extracted information from eligible trials. RESULTS: Four RCTs met the inclusion and exclusion criteria. The reviewed evidence came from 170 patients. Overall, OCP treatment resulted in modest improvement in menstrual cycle frequency (weighted mean difference [WMD] = 0.27, P < .01, 95% confidence interval [CI] −0.33 to −0.21) and mild reduction of acne scores (WMD = 0.3, P = .02, 95% CI 0.05 to 0.55). While metformin resulted in greater BMI reduction (WMD = −4.02, P < .01, 95% CI −5.23 to −2.81) it was associated with decreased dysglycemia prevalence (risk ratio: 0.41, P = .02, 95% CI 0.19 to 0.86) and improved total cholesterol and low-density lipoprotein levels. Metformin and OCPs were similar in terms of impact on hirsutism. CONCLUSIONS AND LIMITATIONS: Current evidence is derived from very low to low quality evidence. Therefore, treatment choice should be guided by patient values and preferences while balancing potential side effects. Future high quality RCTs are needed to address several questions for the treatment of adolescents with PCOS.

Background Polycystic ovarian syndrome (PCOS) is a common reproductive endocrine disease that is seen among adolescent women. Currently, there is limited evidence to support treatment options leading to considerable variation in practice among healthcare specialists. The objective of this study is to review and synthesize all the available evidence on treatment options for PCOS among adolescent women. Methods/design We will conduct a systematic review of all randomized controlled trials evaluating the use of metformin, oral contraceptive pills as monotherapy, or as combination with pioglitazone, spironolactone, flutamide, and lifestyle interventions in the treatment of PCOS in adolescent women ages 11 to 19 years. The primary outcome measures are menstrual regulation and change hirsutism scores. The secondary outcome measures include acne scores, prevalence of dysglycaemia, BMI, lipid profile, total testosterone level, and adverse events. We will perform literature searches through Ovid Medline, Ovid Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), and gray literature resources. Two reviewers will independently screen titles and abstracts of identified citations, review the full texts of potentially eligible trials, extract information from eligible trials, and assess the risk of bias and quality of the evidence independently. Results of this review will be summarized narratively and quantitatively as appropriate. We will perform a multiple treatment comparison using network meta-analysis to estimate the pooled direct and indirect effects for all PCOS interventions on outcomes if adequate data is available. Discussion PCOS treatment poses a clinical challenge to the patients and physicians. This is the first systematic review and network meta-analysis for PCOS treatment in adolescents. We expect that our results will help improve patient care, unify the treatment approaches among specialists, and encourage research for other therapeutic options. Systematic review registration PROSPERO CRD42015016148

Objective: Metabolic syndrome in obese teenagers may contribute to future cardiovascular disease (CVD). We designed a pilot study to evaluate the effect on carotid intima media thickness (cIMT) of Atorvastatin treatment over one year in dyslipidemic obese adolescents (DLP) with metabolic syndrome markers. Methods: We conducted a randomized double blinded control study. Adolescents 14-18 years old were recruited; 16 DLP were randomized to either 10 mg Atorvastatin or placebo. Both groups had cIMT measurements on the left and right side before and one year after the intervention. These measurements were compared to those of teenagers with familial hypercholesterolemia (FH). Results: The average left cIMT of the DLP group was 0.582 ± 0.073 mm, and the right, 0.536 ± 0.071 mm, this compared well with measurements from FH individuals, 0.569 ± 0.947 mm and 0.548 ± 0.913 mm (right and left respectively, p=0.49). For the DLP group, the average left cIMT decreased only in the statin group to 0.509 ± 0.041 mm (p=0.04) but not on the right side 0.555 ± 0.062 (p=0.5). On average cIMT decreased by 10% in Atorvastatin treated individuals and increased by 1.6% in placebo treated ones. CIMT correlated best with the diastolic pressure but not with any of the lipid values. Conclusion: To our knowledge this is the first pilot study that showed cIMT regression in dyslipidemic obese teenagers with features of metabolic syndrome after Atorvastatin therapy over one year. However, future long term studies should look at long term CVD risk reduction.

Kevin M Sweet and Ron C Michaelis. Published by Springer Science, 2011, 211 pp., ISBN: 978-94-007-1146-4 As genetic testing increasingly enters into the daily clinic, a short reference text meticulously explaining jargon ought to be a valuable resource for the practitioner. This short volume achieves most of the objectives such a book should aim for, with particularly good coverage of cardiology and oncology. It approaches genetics in focused, well balanced detail for clinicians. Each chapter has an abstract at the beginning and small sections that make it easy to follow through, especially for the busy clinician. The book's first few chapters set a good foundation by going …

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.