Randomized Controlled Trials In Children Research Articles

Physiologic Effects of Isolated or Synthetic Dietary Fiber in Children: A Scoping Review

BackgroundFiber is an integral part of a healthy diet. Studies have shown that the fiber intake in children is below adequate amounts, leading to adverse health outcomes. ObjectivesThis study aimed to perform a scoping review to assess the available evidence for the impact of isolated and synthetic dietary fiber on children’s health outcomes. MethodsA systematic literature search was conducted in Ovid Medline, Ovid Global Health, Embase, and Cochrane Library via Wiley to identify randomized controlled trials (RCTs) in healthy children aged 1–18 y at baseline who consumed added, isolated, or synthetic dietary fiber. The outcomes of interest were categorized based on the Food and Drug Administration’s guidance for industry on nondigestible carbohydrates and the Vahouny Fiber Symposium criteria, which included reduced fasting blood, glucose, total and/or LDL cholesterol concentrations, attenuation of postprandial glycemia/insulinemia, increased fecal bulk/laxation, reduced transit time, weight loss/reduction in adiposity, reduced energy intake from food consumption, increased satiety, bone health/enhanced mineral absorption, and blood pressure. We also cataloged additional reported outcomes. ResultsOf 3837 randomized controlled parallel or crossover trials screened at the abstract level, 160 were eligible for full-text review, and 32 included for data extraction. This scoping review presents analysis of data from 32 RCTs in children who were healthy, overweight/obese or had mild hypercholesterolemia. Inulin-type fructans (41%) and psyllium (22%) were the most frequently administered fiber types, with weight/adiposity, markers of lipid metabolism (41%), and bone-related markers (38%) being the most frequently reported health outcomes. Only a few RCTs have investigated the effects of laxation (9%), and none specifically studied the impact of fiber on reducing postprandial glycemia/insulinemia. ConclusionsThis scoping review demonstrates sufficient evidence for conducting systematic reviews and meta-analyses for several outcomes. Evidence gaps remain on the impact of isolated fibers on outcomes such as laxation, colonic transit time, and postprandial glycemia/insulinemia in children.

Foot orthoses for flexible flatfeet in children and adults: a systematic review and meta-analysis of patient-reported outcomes

BackgroundThis systematic review and meta-analysis examined the effectiveness of orthoses for flexible flatfeet in terms of patient-reported outcomes in children and adults.MethodsEMBASE, Medline (OvidSP), Web-of-Science, Scopus, CINAHL, Cochrane Central Register of Controlled Clinical Trials, i.e., Cochrane Centraland Pubmed were searched to identify relevant studies since their inception up to February 2021. We included randomized controlled trials (RCT) and prospective studies in which patient reported outcomes at baseline and follow-up in an orthoses group were compared with a no orthoses or sham sole group. Methodological quality of the studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I). A meta-analysis was performed where there were multiple studies with the same outcome measures, which was the case for the Visual Analogue Scale (VAS) for pain in adults.ResultsIn total nine studies were included: four RCT in children (N = 353) and four RCT and one prospective study in adults (N = 268) were included. There was considerable heterogeneity between studies. A meta-analysis demonstrated that pain reduction between baseline and follow-up was significantly larger in the orthoses (N = 167) than in the control groups in adults (N = 157; − 4.76, 95% CI [− 9.46, − 0.06], p0.05).ConclusionDue to heterogeneity in study designs, we cannot conclude that foot orthoses are useful for flexible flatfoot in children and adults. However, based on the meta-analysis orthoses might be useful in decreasing pain in adults.The authors did not receive support from any organization for the submitted work.

Sugar-sweetened beverage consumption and weight gain in children and adults: a systematic review and meta-analysis of prospective cohort studies and randomized controlled trials

BackgroundSugar-sweetened beverages (SSBs) have been implicated in fueling the obesity epidemic. ObjectivesThis study aimed to update a synthesis of the evidence on SSBs and weight gain in children and adults. MethodsMEDLINE, Embase, and Cochrane databases were searched through September 8, 2022, for prospective cohort studies and randomized controlled trials (RCTs) that evaluated intake of SSBs in relation to BMI and body weight in children and adults, respectively. Eligible interventions were compared against a noncaloric control. Study-level estimates were pooled using random-effects meta-analysis and presented as β-coefficients with 95% CIs for cohorts and weighted mean differences (MDs) with 95% CIs for RCTs. ResultsWe identified 85 articles including 48 in children (40 cohorts, n = 91,713; 8 RCTs, n = 2783) and 37 in adults (21 cohorts, n = 448,661; 16 RCTs, n = 1343). Among cohort studies, each serving/day increase in SSB intake was associated with a 0.07-kg/m2 (95% CI: 0.04 kg/m2, 0.10 kg/m2) higher BMI in children and a 0.42-kg (95% CI: 0.26 kg, 0.58 kg) higher body weight in adults. RCTs in children indicated less BMI gain with SSB reduction interventions compared with control (MD: −0.21 kg/m2; 95% CI: −0.40 kg/m2, −0.01 kg/m2). In adults, randomization to addition of SSBs to the diet led to greater body weight gain (MD: 0.83 kg; 95% CI: 0.47 kg, 1.19 kg), and subtraction of SSBs led to weight loss (MD: −0.49 kg; 95% CI: −0.66 kg, −0.32 kg) compared with the control groups. A positive linear dose–response association between SSB consumption and weight gain was found in all outcomes assessed. ConclusionsOur updated systematic review and meta-analysis expands on prior evidence to confirm that SSB consumption promotes higher BMI and body weight in both children and adults, underscoring the importance of dietary guidance and public policy strategies to limit intake. This meta-analysis was registered at the International Prospective Register of Systematic Reviews as CRD42020209915.

Sugar-Sweetened Beverage and 100% Fruit Juice Consumption on Body Weight in Children and Adults: A Systematic Review and Meta-Analysis

ObjectivesSugar-sweetened beverages (SSBs) have been increasingly linked to the obesity epidemic, however, the evidence on 100% fruit juice and body weight remains controversial. The objective of this research was to synthesize the available evidence on SSBs and 100% fruit juice on body weight in children and adults.MethodsMEDLINE, EMBASE, and Cochrane were searched through October 11th, 2020 for prospective cohort studies (≥ 6 months) and randomized controlled trials (RCTs) (≥ 2 weeks) assessing the effect of SSBs and 100% fruit juice on BMI and body weight in children and adults. Eligible trials assessed SSBs or 100% fruit juice added to the diet in adults, and reduced from the diet in children against a non-caloric control. Data were pooled using random effects models and presented as b coefficients with 95% CIs for cohort studies and mean differences (MD)s with 95% CIs for RCTs. Results are reported in compliance with the PRISMA guidelines, and the protocol was registered on PROSPERO (ID: CRD42020209915).ResultsSixty-two articles were identified for SSBs: 40 in children (33 cohorts, 7 RCTs) and 22 in adults (14 cohorts, 8 RCTs), and 22 articles were identified for 100% fruit juice: 13 in children (13 cohorts, 0 RCTs), and 9 studies in adults (3 cohorts, 6 RCTs). Among cohort studies, each serving/day increase in SSB was associated with an increase in BMI in children and body weight in adults (0.06 kg/m2; 95% CI: 0.03, 0.10 and 0.47 kg; 95% CI: 0.24, 0.69, respectively). For 100% fruit juice, each serving/day increase was associated with an increase in body weight in adults (0.19 kg; 95% CI: 0.04, 0.34) while no association was found for children (0.02 kg/m2; 95% CI: −0.01, 0.05). RCTs in children indicated a reduction in BMI gain when SSB consumption was reduced (MD = −0.21 kg/m2; 95% CI: −0.42, 0.00). RCTs in adults indicated an increase in body weight when SSBs were added to the diet (MD = 0.76 kg; 95% CI: 0.51, 1.0), however no effect on weight was found for the addition of 100% fruit juice (MD = 0.08 kg; 95% CI: −0.79, 0.96).ConclusionsSSB consumption promotes weight gain in both children and adults. Evidence from cohort studies indicate a positive association between 100% fruit juice and weight gain in adults and a marginal association among children. Findings from RCTs on 100% fruit juice in adults showed no effect, and there is a need for trials among children.Funding SourcesNone.

Multicenter Randomized Trial of Methylprednisolone vs. Intravenous Immunoglobulins to Treat the Pediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS): Protocol of the Swissped RECOVERY Trial.

IntroductionIn 2020, a new disease entitled Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C), emerged, with thousands of children affected globally. There is no available evidence based on randomized controlled trials (RCT) to date on the two most commonly used immunomodulatory treatments, intravenous immunoglobulins (IVIG) and corticosteroids. Therefore, the Swissped RECOVERY trial was conducted to assess whether intravenous (IV) methylprednisolone shortens hospital length of stay compared with IVIG.Methods and AnalysisSwissped RECOVERY is an ongoing investigator-initiated, open-label, multicenter two-arm RCT in children and adolescents <18 years hospitalized with a diagnosis of PIMS-TS. The trial is recruiting at 10 sites across Switzerland. Patients diagnosed with PIMS-TS are randomized 1:1 to methylprednisolone IV (10 mg/kg/day for 3 days) or IVIG (2 g/kg as a single dose). The primary outcome is hospital length of stay censored at day 28, death, or discharge (whichever is first). The target total sample size is ~80 patients 1:1 randomized to each study arm. Ancillary and exploratory studies on inflammation, vaccination acceptance and coverage, long-term outcomes, and healthcare costs are pre-planned.SignificanceCurrently, robust trial evidence for the treatment of PIMS-TS is lacking, with a controversy surrounding the use of corticosteroids vs. IVIG. This trial will provide evidence for the effectiveness and safety of these two treatments.Ethics and DisseminationThe study protocol, which was designed based on the U.K. RECOVERY trial, the patient information and consent forms, and other study-specific study documents were approved by the local ethics committees (Project ID: 2021-00362).Registration DetailsThe study is registered on the Swiss National Clinical Trials Portal (SNCTP000004720) and Clinicaltrials.gov (NCT 04826588).

Effect of Protein-Rich Breakfast on Subsequent Energy Intake and Subjective Appetite in Children and Adolescents: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Breakfast has been labeled “the most important meal of the day”, especially for children and adolescents. Dietary protein intake may benefit and regulate appetite and energy balance. However, few meta–analyses have been conducted to examine the effect of protein–rich (PR) breakfast on both children and adolescents. This meta–analytic study was conducted to examine the effect of consuming a PR breakfast on short–term energy intake and appetite in children and adolescents. PubMed, Embase, Cochrane Central Register of Controlled Trials, China Biology Medicine disc (CBM), and China National Knowledge Infrastructure (CNKI) were searched for randomized controlled trials (RCTs) published in January 1990–January 2021. The inclusion criteria applied were RCTs in children and adolescents (7–19 year) comparing PR breakfast consumption with normal protein (NP)/traditional breakfast consumption. Finally, ten studies were included in the analysis, eight studies examined the effect of consuming PR breakfast on SEI (n = 824), and nine studies examined the effect on appetite (fullness = 736, hunger = 710). Our meta-analysis using the random–effects model shows that participants assigned to consume PR breakfast had lower SEI (MD, −111.2 kcal; 95% CI: −145.4, −76.9), higher fullness (MD, 7.4 mm; 95% CI: 6.0, 8.8), and lower hunger (MD, −8.5 mm; 95% CI: −9. 7, −7.3) than those assigned to consume NP/traditional breakfast. However, there was considerable inconsistency across the trial results. Our review suggests that the consumption of PR breakfast could be an excellent strategy for weight management by declining SEI and suppressing appetite, and provides new evidence of the relationship between energy balance and obesity. However, since most eligible studies were of low quality, the results ought to be interpreted cautiously.

Nasogastric decompression after intestinal surgery in children: a systematic review and meta-analysis

Postoperative nasogastric decompression has been routinely used after intestinal surgery. However, the role of nasogastric decompression in preventing postoperative complications and promoting the recovery of bowel function in children remains controversial. This systematic review aimed to assess whether routine nasogastric decompression is necessary after intestinal surgery in children. A systematic review was conducted following the PRISMA guideline. Literature search was performed in electronic databases including PubMed, Embase, CENTRAL, and Web of science. Studies comparing outcomes between children who underwent intestinal surgery with postoperative nasogastric tube (NGT) placement (NGT group) and without postoperative NGT placement (no NGT group) were included. Six studies were eligible for inclusion criteria including two randomized controlled trials (RCT) and four comparative observational studies. The overall rate of postoperative anastomotic leak was 0.6% (1/179) in NGT group and 0.9% (2/223) in no NGT group. The overall rate of wound dehiscence was 2.4% (4/169) in NGT group and 1.6% (4/245) in no NGT group. Meta-analysis of two RCTs in children undergoing elective intestinal surgery showed significant increase of mild vomiting in no NGT group compared with NGT group (OR 3.54 95% CI 1.04, 11.99) but no significant difference in persistent vomiting requiring NGT reinsertion (OR 3.11 95% CI 0.47, 20.54), abdominal distension (OR 2.36 95% CI 0.34, 16.59), NGT reinsertion (OR 3.11 95% CI 0.47, 20.54), wound infection (OR 1.63 95% CI 0.49, 5.48) and time to return of bowel movement (MD - 0.14 95% CI - 0.45, 0.17). There was no incidence of anastomotic leak in these 2 RCTs. However, there was an incidence of NGT-related discomfort in NGT group, which ranged from 30 to 100% of children studied. Routine postoperative nasogastric decompression can be omitted in children undergoing intestinal surgery due to no benefit in preventing postoperative complications while increasing patient discomfort.

Early versus late parenteral nutrition for critically ill term and late preterm infants.

Recently conducted randomised controlled trials (RCTs) suggest that late commencement of parenteral nutrition (PN) may have clinical benefits in critically ill adults and children. However, there is currently limited evidence regarding the optimal timing of commencement of PN in critically ill term and late preterm infants. To evaluate the benefits and safety of early versus late PN in critically ill term and late preterm infants. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (5 April 2019), MEDLINE Ovid (1966 to 5 April 2019), Embase Ovid (1980 to 5 April 2019), EMCare (1995 to 5 April 2019) and MEDLINE via PubMed (1966 to 5 April 2019). We searched for ongoing or recently completed clinical trials, and also searched the grey literature and reference lists of relevant publications. We included RCTs comparing early versus late initiation of PN in term and late preterm infants. We defined early PN as commencing within 72 hours of admission, and late PN as commencing after 72 hours of admission. Infants born at 37 weeks' gestation or more were defined as term, and infants born between 34 and 36+6 weeks' gestation were defined as late preterm. Two review authors independently selected the trials, extracted the data and assessed the risk of bias. Treatment effects were expressed using risk ratio (RR) and risk difference (RD) for dichotomous outcomes and mean difference (MD) for continuous data. The quality of the evidence was assessed using the GRADE approach. Two RCTs were eligible for inclusion. Data were only available from a subgroup (including 209 term infants) from one RCT in children (aged from birth to 17 years) conducted in Belgium, the Netherlands and Canada. In that RCT, children with medium to high risk of malnutrition were included if a stay of 24 hours or more in the paediatric intensive care unit (PICU) was expected. Early PN and late PN were defined as initiation of PN within 24 hours and after day 7 of admission to PICU, respectively. The risk of bias for the study was considered to be low for five domains and high for two domains. The subgroup of term infants that received late PN had significantly lower risk of in-hospital all-cause mortality (RR 0.35, 95% confidence interval (CI) 0.14 to 0.87; RD -0.10, 95% CI -0.18 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) = 10; 1 trial, 209 participants) and neonatal mortality (death from any cause in the first 28 days since birth) (RR 0.29, 95% CI 0.10 to 0.88; RD -0.09, 95% CI -0.16 to -0.01; NNTB = 11; 1 trial, 209 participants). There were no significant differences in rates of healthcare-associated blood stream infections, growth parameters and duration of hospital stay between the two groups. Neurodevelopmental outcomes were not reported. The quality of evidence was considered to be low for all outcomes, due to imprecision (owing to the small sample size and wide confidence intervals) and high risk of bias in the included studies. Whilst late commencement of PN in term and late preterm infants may have some benefits, the quality of the evidence was low and hence our confidence in the results is limited. Adequately powered RCTs, which evaluate short-term as well as long-term neurodevelopmental outcomes, are needed.

Omega-3 Fatty Acids as a Treatment for Pediatric Depression. A Phase III, 36 Weeks, Multi-Center, Double-Blind, Placebo-Controlled Randomized Superiority Study.

Background: Depressive disorders in childhood and adolescence are a major health problem and often follow a chronic course with severe consequences in later life. Depressive disorders cause the highest burden of disease in this age group across all medical conditions. Treatment adherence is usually very poor, and the use of antidepressant drugs is heavily debated, as suicidal ideations may increase, in particular in the early phase of treatment. Omega-3 fatty acids rich in eicosapentaenoic acid have shown some promising results in over a dozen small scale randomized controlled trials (RCTs) in adult major depressive disorders, with only very few published RCTs in children and adolescents. High-quality phase III RCTs are missing. Methods and Design: The omega-3-pMDD trial is a carefully designed phase III RCT to assess the efficacy and safety of omega-3 fatty acids in the early course of pediatric major depressive disorder (MDD). The study is designed as a multi-center, double-blinded, placebo-controlled, randomized clinical trial enrolling 220 patients aged 8 to 17 years meeting DSM-IV criteria for major depressive disorder of at least moderate symptom severity. After a single-blinded placebo-lead-in phase (7 to 10 days) patients are randomly assigned to omega-3 fatty acids or placebo over 36 weeks. Primary outcomes are changes in depression severity, as well as remission and recovery rates. Secondary outcome measures include the omega-3 index and inflammatory parameters as predictors of response. Data analysis will be performed in the intention-to-treat sample using a (generalized) linear random intercept regression model. Through sampling of blood, hair, saliva, and urine, further putative biological markers for depression and omega-3 fatty response will be investigated. Discussion: This trial addresses if omega-3 fatty acids play a role in the pathogenesis of pediatric MDDs and have antidepressant properties, in particular in clinically depressed children and adolescents with a pre-existing omega-3 fatty acid deficiency, increased markers of oxidative stress, and/or markers of (low grade) inflammation. Ethics and Dissemination: The study was approved by the local ethics committees. The results will be published in peer-reviewed journals irrespective of specific outcomes. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03167307.

Interventions to improve disposal of child faeces for preventing diarrhoea and soil-transmitted helminth infection.

Interventions to improve disposal of child faeces for preventing diarrhoea and soil-transmitted helminth infection.

Carbamazepine versus phenobarbitone monotherapy for epilepsy: an individual participant data review.

Carbamazepine versus phenobarbitone monotherapy for epilepsy: an individual participant data review.

Investigator-initiated randomized controlled trials in children with epilepsy: Mission impossible?

SummaryObjectiveIn children many antiepileptic drugs (AEDs) are prescribed off‐label due to a lack of well‐designed randomized controlled trials (RCTs). We conducted a multicenter RCT in the Netherlands to compare levetiracetam and valproic acid as monotherapy in children with newly diagnosed epilepsy. After 2 years, we had to stop this investigator‐initiated trial prematurely because the inclusion rate was too low. We analyzed the reasons for this failure, assessed the various issues involved in performing RCTs in children, and now give recommendations for future studies.MethodsA questionnaire was completed by all investigators involved in the study. It included questions about the motivation to participate and the perceived reasons for recruitment failure. We also studied literature about financial, logistic, legal, and ethical aspects of RCTs in children.ResultsMain reasons for recruitment failure were overestimation of the number of eligible AED‐naive children referred by general pediatricians; personal preferences of investigators for specific antiepileptic drugs; and the extensive administrative load due to extra regulations and guidelines for children. Fundraising for investigator‐initiated trials is difficult and the majority of RCTs concerning AEDs are sponsored by pharmaceutical companies. Involving children requires balancing between protection and participation; the randomization procedure and obtaining informed consent are complex for both children and parents.SignificancePerforming RCTs with AEDs in children is important but complicated by logistic, regulatory, legal, and ethical restrictions. Based on our recent experience, our advice to colleagues who are planning a similar trial would be to perform a feasibility pilot study; to set up intensive collaboration with referring pediatricians; to arrange support of a clinical trials unit and a local research nurse during the complete trial period; and to incorporate the possibility of extending the recruitment period. Major investments, both financially from governmental organizations and in time, are imperative for independent RCTs in children.

Low bacterial diet versus control diet to prevent infection in cancer patients treated with chemotherapy causing episodes of neutropenia.

Neutropenia is a potentially serious side effect of chemotherapy and a major risk factor for infection, which can be life-threatening. It has been hypothesised that a low bacterial diet (LBD) can prevent infection and (infection-related) mortality in cancer patients receiving chemotherapy that causes episodes of neutropenia, but much remains unclear. This review is an update of a previously published Cochrane review. The primary objective of this review was to determine the efficacy of an LBD versus a control diet in preventing infection and in decreasing (infection-related) mortality in adult and paediatric cancer patients receiving chemotherapy that causes episodes of neutropenia. Secondary objectives were to assess time to first febrile episode, need for empirical antibiotic therapy, diet acceptability and quality of life. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 4), the Database of Abstracts of Reviews of Effects (DARE) (2015, Issue 4), PubMed (from 1946 to 4 May 2015), EMBASE (from 1980 to 4 May 2015) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1981 to 4 May 2015).In addition, we searched the reference lists of relevant articles and conference proceedings of American Society of Hematology (ASH; from 2000 to 2015), European Bone Marrow Transplantation (EBMT; from 2000 to 2015), Oncology Nurses Society (ONS; from 2000 to 2015), International Society for Paediatric Oncology (SIOP; from 2000 to 2014), Multinational Association of Supportive Care in Cancer (MASCC; from 2000 to 2015), American Society of Clinical Oncology (ASCO; from 2000 to 2015), Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC; from 2000 to 2015), European Society for Clinical Nutrition and Metabolism (ESPEN; from 2000 to 2015), American Society for Parenteral and Enteral Nutrition (ASPEN; from 2000 to 2015) and European Hematology Association (EHA; from 2000 to 2015). In May 2015, we scanned the National Institutes of Health Register via clinicaltrials.gov and the International Standard Randomised Controlled Trial Number (ISRCTN) Register (www.controlled-trials.com). Randomised controlled trials (RCTs) comparing use of an LBD versus a control diet with regard to infection rate, (infection-related) mortality, time to first febrile episode, need for empirical antibiotic therapy, diet acceptability and quality of life in adult and paediatric cancer patients receiving chemotherapy causing episodes of neutropenia. Two review authors independently performed study selection, 'Risk of bias' assessment and data extraction. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. In the original version of this review, we identified three RCTs that assessed different intervention and control diets in 192 participants (97 randomised to intervention diet; 95 to control diet) with different types of malignancies. For the update, we identified no eligible new studies. Co-interventions (e.g. protective environment, antimicrobial prophylaxis, central venous catheter care, oral care, hygiene practices, colony-stimulating factors) and outcome definitions also differed between studies. In all included studies, it was standard policy to give empirical antibiotics (and sometimes also antimycotics) to (some of) the participants diagnosed with an infection. Two studies included adults and one study included children. In all studies, only a scant description of treatment regimens was provided. All studies had methodological limitations. Pooling of results of included studies was not possible. In two individual studies, no statistically significant differences in infection rate were identified between intervention and control diets; another study showed no significant differences between treatment groups in the number of chemotherapy cycles with an infection. None of the studies mentioned infection-related mortality, but in one study, no significant difference in overall survival was observed between treatment groups. Time from onset of neutropenia to fever, duration of empirical antibiotics and antimycotics, diet acceptability (i.e. following the diet easily and following the diet throughout all chemotherapy cycles) and quality of life were all evaluated by only one study; for all outcomes, no statistically significant differences between treatment arms were identified. At the moment, no evidence from individual RCTs in children and adults with different malignancies underscores use of an LBD for prevention of infection and related outcomes. All studies differed with regard to co-interventions, outcome definitions and intervention and control diets. As pooling of results was not possible, and as all studies had serious methodological limitations, we could reach no definitive conclusions. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. On the basis of currently available evidence, we are not able to provide recommendations for clinical practice. Additional high-quality research is needed.

Normothermic versus hypothermic cardiopulmonary bypass in children undergoing open heart surgery (thermic-2): study protocol for a randomized controlled trial.

BackgroundDuring open heart surgery, patients are connected to a heart-lung bypass machine that pumps blood around the body (“perfusion”) while the heart is stopped. Typically the blood is cooled during this procedure (“hypothermia”) and warmed to normal body temperature once the operation has been completed. The main rationale for “whole body cooling” is to protect organs such as the brain, kidneys, lungs, and heart from injury during bypass by reducing the body’s metabolic rate and decreasing oxygen consumption. However, hypothermic perfusion also has disadvantages that can contribute toward an extended postoperative hospital stay. Research in adults and small randomized controlled trials in children suggest some benefits to keeping the blood at normal body temperature throughout surgery (“normothermia”). However, the two techniques have not been extensively compared in children.ObjectiveThe Thermic-2 study will test the hypothesis that the whole body inflammatory response to the nonphysiological bypass and its detrimental effects on different organ functions may be attenuated by maintaining the body at 35°C-37°C (normothermic) rather than 28°C (hypothermic) during pediatric complex open heart surgery.MethodsThis is a single-center, randomized controlled trial comparing the effectiveness and acceptability of normothermic versus hypothermic bypass in 141 children with congenital heart disease undergoing open heart surgery. Children having scheduled surgery to repair a heart defect not requiring deep hypothermic circulatory arrest represent the target study population. The co-primary clinical outcomes are duration of inotropic support, intubation time, and postoperative hospital stay. Secondary outcomes are in-hospital mortality and morbidity, blood loss and transfusion requirements, pre- and post-operative echocardiographic findings, routine blood gas and blood test results, renal function, cerebral function, regional oxygen saturation of blood in the cerebral cortex, assessment of genomic expression changes in cardiac tissue biopsies, and neuropsychological development.ResultsA total of 141 patients have been successfully randomized over 2 years and 10 months and are now being followed-up for 1 year. Results will be published in 2015.ConclusionsWe believe this to be the first large pragmatic study comparing clinical outcomes during normothermic versus hypothermic bypass in complex open heart surgery in children. It is expected that this work will provide important information to improve strategies of cardiopulmonary bypass perfusion and therefore decrease the inevitable organ damage that occurs during nonphysiological body perfusion.Trial RegistrationISRCTN Registry: ISRCTN93129502, http://www.isrctn.com/ISRCTN93129502 (Archived by WebCitation at http://www.webcitation.org/6Yf5VSyyG).

Alginiany w leczeniu refluksu żołądkowo-przełykowego u dzieci: przegląd systematyczny badań z randomizacją

BackgroundCurrent therapeutic options for the management of gastroesophageal reflux/reflux disease include dietary measures, reassurance, drugs (mainly proton pump inhibitors) and surgery (usually reserved for complicated cases). The role of alginates remains unclear. ObjectiveTo examine whether alginates are effective in the management of gastroesophageal reflux in children. MethodsThe MEDLINE, EMBASE, and Cochrane Library databases were searched up to August 2014 for published randomized controlled trials (RCTs) that compared the effects of a sodium alginate with placebo, no intervention, or other intervention. ResultsNine RCTs, some with methodological limitations, involving 411 children, aged 0-17 years, were included. There was variability in how outcomes were reported. Four 4 RCTs compared alginates with placebo showing inconsistent results; only 2 RCTs showed clear benefit of the alginates. One RCT found similar effect of alginates as compared with proton pump inhibitors. One RCT in children with gastroesophageal reflux and esophagitis found better efficacy of famitidine as compared with alginates. The efficacy of alginates and prokinetic drugs was similar. One RCT found better efficacy of alginate plus simethicone as compared with than thickened formula and reassurance with lifestyle changes alone. ConclusionThe efficacy of alginates for the management of children with gastroesophageal reflux/reflux disease has not been convincingly documented.

Sugar-sweetened beverages and weight gain in children and adults: a systematic review and meta-analysis

The relation between sugar-sweetened beverages (SSBs) and body weight remains controversial. We conducted a systematic review and meta-analysis to summarize the evidence in children and adults. We searched PubMed, EMBASE, and Cochrane databases through March 2013 for prospective cohort studies and randomized controlled trials (RCTs) that evaluated the SSB-weight relation. Separate meta-analyses were conducted in children and adults and for cohorts and RCTs by using random- and fixed-effects models. Thirty-two original articles were included in our meta-analyses: 20 in children (15 cohort studies, n = 25,745; 5 trials, n = 2772) and 12 in adults (7 cohort studies, n = 174,252; 5 trials, n = 292). In cohort studies, one daily serving increment of SSBs was associated with a 0.06 (95% CI: 0.02, 0.10) and 0.05 (95% CI: 0.03, 0.07)-unit increase in BMI in children and 0.22 kg (95% CI: 0.09, 0.34 kg) and 0.12 kg (95% CI: 0.10, 0.14 kg) weight gain in adults over 1 y in random- and fixed-effects models, respectively. RCTs in children showed reductions in BMI gain when SSBs were reduced [random and fixed effects: -0.17 (95% CI: -0.39, 0.05) and -0.12 (95% CI: -0.22, -0.2)], whereas RCTs in adults showed increases in body weight when SSBs were added (random and fixed effects: 0.85 kg; 95% CI: 0.50, 1.20 kg). Sensitivity analyses of RCTs in children showed more pronounced benefits in preventing weight gain in SSB substitution trials (compared with school-based educational programs) and among overweight children (compared with normal-weight children). Our systematic review and meta-analysis of prospective cohort studies and RCTs provides evidence that SSB consumption promotes weight gain in children and adults.

Blinding in pharmacological trials: the devil is in the details

While the methodological principle of ‘blinding’ for minimising bias in randomised controlled trials (RCT) is widely debated and accepted, rarely is this depth of thinking applied to its correct handling...

The role of milrinone in children with cardiovascular compromise: review of the literature

Cardiovascular instability is a common complication in children after cardiac surgery and in various forms of shock. Systematic literature review. Four randomized controlled trials (RCTs) were included in this systematic literature review. In children after corrective surgery for congenital heart disease milrinone significantly reduced the risk of development of LCOS compared with placebo. In another study in children with high pulmonary vascular resistance and impaired oxygenation after Fontan operation, inhalation of NO with milrinone led to the most significant reduction of pulmonary vascular resistance and improvement of oxygenation. When only milrinone was given these changes were less pronounced. In non-hyperdynamic septic shock, CI, SVI, and DO₂ significantly increased while SVRI significantly decreased after milrinone when compared to placebo. There are a limited number of RCTs in children that suggest a beneficial effect of milrinone in the optimization of cardiovascular function after cardiac surgery and in septic shock.

Cochrane review: Interventions for bone disease in children with chronic kidney disease

AbstractBackgroundBone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates.ObjectivesTo investigate the benefits and harms of interventions for preventing and treating bone disease in children with CKD.Search strategyThe Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists and abstracts were searched without language restriction.Selection criteriaRandomised controlled trials (RCTs) comparing different interventions used to prevent or treat bone disease in children with CKD stages 2‐5D compared with placebo, no treatment or other agents were included. Studies examining different routes or frequency of treatment were also included.Data collection and analysisData were extracted by two authors. The random‐effects model was used and results were reported as risk ratios or risk differences for dichotomous outcomes and mean differences for continuous outcomes with 95% confidence intervals.Main resultsFifteen RCTs (369 children) were identified. Compared with oral calcitriol, intraperitoneal calcitriol significantly reduced the level of serum parathyroid hormone (PTH) but there were no significant differences in bone histology or other biochemical measures (2 RCTs). There were no significant differences detected in growth, PTH, serum calcium or phosphorus between daily versus intermittent calcitriol (3 RCTs). Vitamin D therapy significantly reduced PTH levels compared with placebo or no treatment. The number of children with hypercalcaemia did not differ significantly between groups (4 RCTs). No significant differences were detected in growth rates, bone histology or biochemical parameters between calcitriol and either dihydrotachysterol or ergocalciferol (2 RCTs). Though fewer episodes of hypercalcaemia were reported with sevelamer, no significant differences were detected in serum calcium, phosphorus and PTH levels between calcium‐containing phosphate binders and either aluminium hydroxide or sevelamer (4 RCTs).Authors' conclusionsBone disease, assessed by changes in PTH levels, is improved by all vitamin D preparations. However no consistent differences between routes of administration, frequencies of dosing or vitamin D preparations have been demonstrated. Though fewer episodes of high calcium levels occurred with the non calcium‐containing binder, sevelamer, compared with calcium‐containing binders, there were no differences in serum phosphorus and calcium overall and phosphorus values were reduced to similar extents. All RCTs were small with few data available on patient‐centred outcomes (growth, bone deformities) and limited data on biochemical parameters resulting in considerable imprecision of results thus limiting the applicability to care of children with CKD.Plain Language SummaryInterventions for bone disease in children with chronic kidney diseaseChronic kidney disease (CKD) resulting in reduced kidney function and the need for dialysis and kidney transplant is associated with abnormalities in blood calcium and phosphorus levels leading to high levels of the parathyroid hormone (PTH) and to bone disease. This may result in bone deformities, bone pain, fractures and reduced growth rates. Commonly used treatments (Vitamin D compounds and phosphate binders) aim to prevent or correct these outcomes. However these treatments may raise levels of blood calcium, allow calcium and phosphorus deposition in blood vessels and lead to early cardiovascular disease, which is known to be a problem in adults with CKD. This review identified only 15 small RCTs involving 369 children comparing different vitamin D compounds, different routes and frequencies of administration of vitamin D compounds and different phosphate binders. Only five RCTs reported on growth rates and no differences were detected between treatments. Renal bone disease, as assessed by changes in PTH levels, was improved by all vitamin D preparations regardless of preparation used or the route or frequency of administration. Fewer episodes of high blood calcium levels and lower overall serum calcium levels occurred with the non calcium‐containing binder, sevelamer, compared with calcium‐containing binders. As newer treatments for renal bone disease are developed, comparisons with the current standard therapies will be required in well designed RCTs in children using outcome measures including those of direct clinical relevance to children and their families such as rates of growth, reduction in bone fractures and bone pain and reduction in calcification in blood vessels.

Efficacy and safety of angiotensin II receptor type 1 antagonists in children and adolescents

Our purpose was to evaluate the effects of angiotensin II receptor type 1 antagonists (ARAs) in children and adolescents with hypertension or/and several kinds of nephropathies on blood pressure (BP) and proteinuria and to evaluate related safety issues. Data sources were Medline, Embase, The Cochrane Library, BIOSIS Previews, contact with investigators and manufacturers, personal bibliography of the lead author, and manual searches. We selected randomized controlled trials (RCTs), uncontrolled trials, and case series investigating ARAs in children and adolescents, as well as case reports about adverse events and the embryotoxic effects of ARAs in children. In four RCTs with 698 individuals, mean systolic blood pressure (BP) decreased by 10.5 mmHg [95% confidence interval (CI) 9.8-11.2] and mean diastolic BP by 6.4 mmHg (95% CI 5.8-7.0). Proteinuria decreased by 30-64% (range) in two RCTs and four case series. Safety data were comparable with adult safety data. ARAs can be considered effective and safe in lowering BP and proteinuria in the pediatric age group. The correlation between the surrogate parameters BP and proteinuria with clinical endpoints is documented to a large degree. The evidence is based on RCTs and also on lower evidence levels, such as case series. In some conditions, RCTs in children are not feasible. Registers could provide more evidence in the future.