Effects of prenatal and/or postnatal supplementation with iron, PUFA or folic acid on neurodevelopment: update.

Neurodevelopment has been linked, among other factors, to maternal and early infant diets. The objective of this review, which is part of the NUTRIMENTHE research project 'The effect of diet on the mental performance of children' (www.nutrimenthe.com), was to update current evidence on the effects of nutritional interventions such as iron, folic acid or n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy and/or in early life on the mental performance and psychomotor development of children. In May 2014, we searched MEDLINE and The Cochrane Database of Systematic Reviews for relevant studies published since 2009. The limited updated evidence suggests that iron supplementation of infants may positively influence the psychomotor development of children, although it does not seem to alter their mental development or behaviour. The use of multivitamin-containing folic acid supplements during pregnancy did not benefit the mental performance of the offspring. Evidence from randomised controlled trials (RCT) did not show a clear and consistent benefit of n-3 LCPUFA supplementation during pregnancy and/or lactation on childhood cognitive and visual development. Caution is needed when interpreting current evidence, as many of the included trials had methodological limitations such as small sample sizes, high attrition rates, and no intention-to-treat analyses. Taken together, the evidence is still inconclusive. Large, high-quality RCT to assess the effects of supplementation with iron, LCPUFA or folic acid are still needed to further clarify the effects of these, and other nutrients, on neurodevelopment. Recent recommendations from scientific societies are briefly presented.

Patient groups, clinicians and healthcare professionals agree - all test results need to be seen, understood and followed up.

Background Diagnostic testing provides integral information for the prevention, diagnosis, treatment and management of disease. Inadequate test result reporting and follow-up is a major risk to patient safety. Factors contributing to failure to follow-up test results include unclear delineation of responsibility about who is meant to act on a test result; poor coordination across different levels of care; and the absence of integrated health information systems for the efficient information communication. Methods A 2016 Australian Stakeholder Forum brought together over 30 representatives from 14 different consumer, clinical and management stakeholder organisations to discuss safe and effective test result communication, management and follow-up. Thematic analysis was conducted drawing on multimodal data collected in the form of observational fieldnotes and document artefacts produced by participants. Results The forum identified major challenges which pose immediate risks to patient safety. Participants recommended priorities for addressing issues relating to: (i) the governance of test result management processes; (ii) integration of health care processes through the utilisation of effective digital health solutions; and (iii) involving patients as key partners in the decision-making and care process. Conclusions Stakeholder groups diverged slightly in their priorities. Consumers highlighted the lack of patient involvement in the test result management process but were less concerned about standardisation of reports and critical result thresholds than pathologists. The forum foregrounded the need for a systems approach, capable of identifying and addressing interconnections and multiple factors that contribute to poor test result follow-up, with a strong emphasis on enhancing the contribution of patients.

Current and potential imaging applications of ferumoxytol for magnetic resonance imaging.

Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of i.v. ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent, with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ-specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in magnetic resonance imaging. To more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.

Lactobacillus casei rhamnosus Lcr35 in the Management of Functional Constipation in Children: A Randomized Trial.

OBJECTIVE: To assess the effectiveness of Lactobacillus casei rhamnosus Lcr35 (Lcr35) in the management of functional constipation in children. STUDY DESIGN: A randomized, double-blind, placebo-controlled trial was conducted in 94 children aged <5 years with functional constipation according to the Rome III criteria. Children were assigned to receive Lcr35 (8 × 108 colony-forming units, n = 48) or placebo (n = 46), twice daily, for 4 weeks. The primary outcome measure was treatment success, defined as 3 or more spontaneous stools per week, without episodes of fecal soiling, in the last week of the intervention. Analyses were by intention to treat. RESULTS: Eighty-one (86%) children completed the study. There was no significant difference in treatment success between the placebo and the Lcr35 group (28/40 vs 24/41, respectively; relative risk, 0.6, 95% CI 0.24-1.5, P = .4). There was a significant increase in the frequency of defecation from baseline to week 4 in both the placebo group (median [IQR] 2.0 [1.0, 2.0] to 6.0 [4.0, 9.0], P < .001) and in the Lcr35 group (2.0 [1.0, 2.0] to 4.0 [3.0, 5.0], P < .001), but the defecation frequency in the placebo group was significantly greater than that in the Lcr35 group at weeks 1, 2, 3, and 4. CONCLUSION: Lcr35 as a sole treatment was not more effective than placebo in the management of functional constipation in children <5 years. This study adds to current recommendations that do not support the use of probiotics in the treatment of childhood constipation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01985867.

ω-3 Fatty Acid Supplementation Does Not Affect Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis.

Background: Effective treatments for the core symptoms of autism spectrum disorder (ASD) are still lacking.Objective: We aimed to update the data on the effectiveness of ω-3 (n-3) fatty acid (FA) supplementation as a treatment for ASD.Methods: The Cochrane Library, MEDLINE, and EMBASE databases were systematically searched up until August 2016 with no language restrictions for randomized controlled trials (RCTs) comparing ω-3 FA supplementation with placebo or with no supplementation. Participants were children diagnosed with ASD. All functional outcome measures reported were considered. For dichotomous outcomes, the results for individual studies and pooled statistics were reported as RRs. Mean differences (MDs) were calculated for continuous outcomes.Results: Five RCTs (183 participants) were included. With 4 exceptions, there were no statistically significant differences in ASD symptoms between groups measured by validated scales. Among studies that used the Aberrant Behavior Checklist, parents' ratings indicated significant improvement in lethargy symptoms in the ω-3 FA group compared with the placebo group (2 RCTs) (pooled MD: 1.98; 95% CI: 0.32, 3.63). Among studies that used the Behavioral Assessment System for Children, parents' ratings indicated significant worsening of both externalizing behavior (2 RCTs) (pooled MD: -6.22; 95% CI: -10.9, -1.59) and social skills (1 RCT) (MD: -7; 95% CI: -13.62, -0.38) in the ω-3 FA group compared with the placebo group. One RCT reported a significant improvement in the ω-3 FA group for the daily-living component of the Vineland Adaptive Behavior Scale (MD: 6.2; 95% CI: 0.37, 12.03). Adverse effects were similar in both groups.Conclusions: Because of the limited number of included studies and small sample sizes, no firm conclusions can be drawn. However, the limited data currently available suggest that ω-3 FA supplementation does not enhance the performance of children with ASD.

Quantitative assessment of brain iron by R2* relaxometry in patients with cervical dystonia.

BACKGROUND: The pathophysiology of cervical dystonia is poorly understood. Increased brain iron deposition has been described in different movement disorders. Our aim was to investigate brain iron content in patients with cervical dystonia, using R2* relaxation rate, a validated MRI marker of brain iron level. METHODS: Twelve female patients with primary focal cervical dystonia (mean age: 45.4 ± 8.0 years) and 12 age-matched healthy female subjects (mean age: 45.0 ± 8.0 years) underwent 3T MRI to obtain regional R2* relaxation rates of the thalamus, caudate nucleus, putamen, and globus pallidus (GP). Regions of interest were delineated automatically on T1-weighted MRIs. RESULTS: R2* values in the putamen were positively correlated with age. Patients with cervical dystonia showed elevated R2* values in the GP. CONCLUSIONS: This pilot study provides the first quantitative support for increased brain iron deposition in cervical dystonia. Further studies are needed to explore the implications of this finding.

Enema versus polyethylene glycol for the management of rectal faecal impaction in children with constipation - a systematic review of randomised controlled trials.

INTRODUCTION: Rectal faecal impaction (RFI) from functional constipation is a common problem in children. Maintenance therapy should start after successful disimpaction. However, there is uncertainty with regard to the optimal disimpaction regimen. AIM: We systematically evaluated the effect of polyethylene glycol (PEG) compared to enema for treating RFI. MATERIAL AND METHODS: The MEDLINE, EMBASE, and the Cochrane Library, with no language restrictions, were searched up to July 2014 for randomised controlled trials (RCTs) evaluating the effect of PEG compared with enema for disimpaction in children with functional constipation. The risk of bias was assessed using the Cochrane risk of bias tool. RESULTS: Two RCTs, involving 170 children aged 1 to 17 years, met the inclusion criteria. The studies were generally low in methodological quality. Compared with the enema group, the PEG 3350 group had significantly reduced chance for treatment success, but the difference was of a borderline statistical significance (RR = 0.83, 95% CI: 0.7-0.99). The use of PEG was also more likely to increase defecation frequency, but increased the risk of watery stools and increased faecal incontinence. Other outcomes, in general, were similar in both groups. CONCLUSIONS: Current evidence does not allow us to conclude which intervention is more effective for treating RFI in children with functional constipation. These results should be interpreted with caution due to the limited number of trials and the low quality of reporting in these trials, high or unknown risk of bias, and sparse data. Further high-quality, adequately powered RCTs are needed to determine the optimal management.

Probiotics, prebiotics, and dietary fiber in the management of functional gastrointestinal disorders.

At best, currently available therapies provide symptomatic relief from functional gastrointestinal disorders (FGD). No existing therapy, however, can influence the natural course of any of these disorders, prompting interest in new and safe treatment options. This paper summarizes the clinical evidence from randomized controlled trials (RCTs) and their meta-analyses of the effectiveness of probiotics, prebiotics, and dietary fiber in the treatment of FGD in the pediatric population. While it is too soon to recommend the routine use of any probiotics for treating FGD, some of these therapeutic options can provide a health benefit to patients, and therefore can be discussed with patients and/or caregivers. Lactobacillus reuteri DSM 17938 has consistently improved symptoms of infantile colic. The use of Lactobacillus GG moderately increased treatment success in children with abdominal pain-related FGD, particularly among children with irritable bowel syndrome. Also, data from one trial suggest that VSL#3 seems to be effective in ameliorating symptoms and improving the quality of life of children affected by irritable bowel syndrome. L. reuteri DSM 17938 may help infants with constipation. Limited evidence suggests that administration of a fiber supplement is more effective than placebo for the treatment of childhood constipation.

High- versus low-volume polyethylene glycol plus laxative versus sennosides for colonoscopy preparation in children.

OBJECTIVE: Many protocols of bowel preparation are available for use in children; however, none of them is commonly accepted. The aim of the study was to evaluate the efficacy and acceptability of high-volume polyethylene glycol (PEG) versus low-volume PEG combined with bisacodyl (BPEG) versus sennosides for colonoscopy preparation in children. METHODS: Participants ages 10 to 18 years were randomly assigned to receive either PEG 60 or PEG 30 mL kg⁻¹ day⁻¹ plus oral bisacodyl 10 to 15 mg/day or sennosides 2 mg kg⁻¹ day⁻¹ for 2 days. A blinded assessment of bowel cleansing was made by the endoscopist according to the Aronchick and Ottawa scales. Patient acceptability was evaluated with the visual-analog scale. Analysis was done on an available case analysis basis. RESULTS: Of 240 patients enrolled in the study 234 patients were available for analysis of the efficacy of colon cleansing. There were no significant differences found among the 3 groups for the proportions of participants with excellent/good (PEG: 35/79, BPEG: 26/79, sennosides 25/76) and poor/inadequate (PEG: 20/79, BPEG: 28/79, sennosides 28/76) bowel preparation evaluated with the Aronchick scale and for the mean Ottawa total score (PEG: 5.47 ±â€Š3.63, BPEG: 6.22 ±â€Š3.3, sennosides: 6.18 ±â€Š3.53). Acceptability of bowel cleansing protocol was similar in all of the groups (P = 0.8). CONCLUSIONS: All 3 cleansing methods showed similar efficacy and tolerability; however, none of them was satisfactory.

Systematic review of randomized controlled trials: fiber supplements for abdominal pain-related functional gastrointestinal disorders in childhood.

BACKGROUND: A lack of safe and reliable treatments for abdominal pain-related functional gastrointestinal disorders (FGIDs) has prompted interest in new therapies. AIM: To systematically evaluate the effect of dietary fibers for treating abdominal pain-related FGIDs in children. METHODS: In December 2011, MEDLINE, EMBASE and the Cochrane Library were searched for randomized controlled trials (RCTs) evaluating fiber supplementation in children with FGIDs. RESULTS: Only 3 RCTs were identified, which enrolled a total of 167 children and adolescents (5­17 years old) with recurrent abdominal pain. Only 1 study used the Rome III criteria. Patients were supplemented with different dietary fiber types for 4­6 weeks. The use of dietary fibers did not influence the proportion of responders to treatment, and improvement did not occur in reported clinically relevant outcomes such as no pain or a significant decrease in pain intensity (risk ratio 1.17, 95% confidence interval 0.75­1.81). CONCLUSION: There is no evidence that supplementation with fiber as a dietary manipulation may be useful for treating children with FGIDs. However, one should not overlook the fact that the main limitation for recommendation of the routine fiber use in clinical practice derives from the weak quality and paucity of available studies.

[Controversial issues in colorectal screening in Hungary: conflict of clinical and public health viewpoints]. / A vastag- és végbéldaganatok szurésének vitatott kérdései: klinikai és népegészségügyi nézopontok ütközése.

In Hungary, mortality rates from colorectal cancer are dramatically high, therefore the reduction by population screening as a public health measure is considered as one of the priorities of National Public Health Program. In the beginning, a human-specific immunological test was applied in the "model programs", as a screening tool, to detect the occult blood in the stool; compliance was 32% in average. However, the objectives of the model programs have not been achieved, because, among other reasons, a debate on the method of choice and the strategy to follow have divided the professional public opinion. In this study the debated issues are critically discussed, being convinced that, at present, population screening seems to be the most promising way to alleviate the burden of colorectal cancer.

Effects of n-3 long-chain polyunsaturated fatty acid supplementation during pregnancy and/or lactation on neurodevelopment and visual function in children: a systematic review of randomized controlled trials.

OBJECTIVE: To systematically evaluate the effects of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) supplementation of pregnant and/or lactating women on the neurodevelopment and visual function of their children. METHODS: Systematic review. Randomized controlled trials (RCTs) comparing n-3 LCPUFA maternal supplementation were identified through electronic databases (MEDLINE, EMBASE, the Cochrane Library) and the references of reviewed articles. RESULTS: Overall, 13 publications, some with important methodological limitations, were included. With regard to supplementation during pregnancy, among 3 RCTs that evaluated this intervention, 1 RCT (n = 72) showed significantly better eye and hand coordination assessed with the Griffiths Mental Development Scales at 30 months of age. Another RCT (n = 29) demonstrated an effect of n-3 LCPUFA supplementation on the cloth step of intentional solutions of the 2-step problem-solving test. No other effects were demonstrated. There was no consistent effect of n-3 LCPUFA supplementation during pregnancy on the children's visual acuity. With regard to supplementation during lactation, among 3 RCTs that assessed this intervention, 1 RCT (n =133) showed significant improvement on the Bayley Psychomotor Development Index in 30-month-old children; however, there was no influence of such supplementation on the results of different tests performed in the same group of children or in others. There was no consistent effect of n-3 LCPUFA supplementation during lactation on the children's visual function. Supplementation during pregnancy and lactation (3 RCTs) did not affect child neurodevelopment assessed up to 7 years of age. CONCLUSION: Evidence from RCTs does not demonstrate a clear and consistent benefit of n-3 LCPUFA supplementation during pregnancy and/or lactation on child neurodevelopment and visual acuity. These results should be interpreted with caution due to methodological limitations of the included studies.

Pharmacological interventions for nonalcoholic fatty liver disease in adults and in children: a systematic review.

BACKGROUND: Uncertainty exists regarding the treatment of patients with nonalcoholic fatty liver disease (NAFLD) who are unable to lose weight and/or change lifestyle. The present study assesses the effectiveness and safety of pharmacological and dietary supplement interventions for NAFLD. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched for randomized controlled trials (RCTs) both in adults and in children. RESULTS: Fifteen (2 pediatric patients and 13 adults) RCTs met the inclusion criteria. A significant effect on normalization of alanine transaminase was found in patients treated with metformin compared with vitamin E, and in those treated with high-dose (3 g) carnitine vs diet. In contrast, there was no difference in patients treated with pioglitazone combined with vitamin E versus vitamin E alone, ursodeoxycholic acid (UDCA) combined with vitamin E or alone versus placebo, or UDCA versus combination of vitamin E and vitamin C, and in patients treated with vitamin E, probucol, N-acetylcysteine, low doses of carnitine, or Yo Jyo Shi Ko compared with placebo. Aspartate aminotransferase normalization was significantly higher in those treated with UDCA combined with vitamin E versus UDCA alone or placebo, and in those treated with metformin. Small number of subjects, high drop-out rates, and numerous interventions in 1 study limit the value of many studies. Only 7 RCTs analyzed biopsy specimens, but most of them have significant methodological limitations. Pioglitazone had reduced liver necrosis and inflammation in 1 large study. CONCLUSIONS: Limited data do not allow one to draw firm conclusions on the efficacy of various treatments for NAFLD.

A clinically integrated curriculum in evidence-based medicine for just-in-time learning through on-the-job training: the EU-EBM project.

BACKGROUND: Over the last years key stake holders in the healthcare sector have increasingly recognised evidence based medicine (EBM) as a means to improving the quality of healthcare. However, there is considerable uncertainty about the best way to disseminate basic knowledge of EBM. As a result, huge variation in EBM educational provision, setting, duration, intensity, content, and teaching methodology exists across Europe and worldwide. Most courses for health care professionals are delivered outside the work context ('stand alone') and lack adaptation to the specific needs for EBM at the learners' workplace. Courses with modern 'adaptive' EBM teaching that employ principles of effective continuing education might fill that gap. We aimed to develop a course for post-graduate education which is clinically integrated and allows maximum flexibility for teachers and learners. METHODS: A group of experienced EBM teachers, clinical epidemiologists, clinicians and educationalists from institutions from eight European countries participated. We used an established methodology of curriculum development to design a clinically integrated EBM course with substantial components of e-learning. An independent European steering committee provided input into the process. RESULTS: We defined explicit learning objectives about knowledge, skills, attitudes and behaviour for the five steps of EBM. A handbook guides facilitator and learner through five modules with clinical and e-learning components. Focussed activities and targeted assignments round off the learning process, after which each module is formally assessed. CONCLUSION: The course is learner-centred, problem-based, integrated with activities in the workplace and flexible. When successfully implemented, the course is designed to provide just-in-time learning through on-the-job-training, with the potential for teaching and learning to directly impact on practice.

Effect of supplementation of women in high-risk pregnancies with long-chain polyunsaturated fatty acids on pregnancy outcomes and growth measures at birth: a meta-analysis of randomized controlled trials.

It is hypothesized that the intake of long-chain PUFA (LC-PUFA) throughout pregnancy could protect against pre-eclampsia, pregnancy-induced hypertension or intra-uterine growth retardation, and is essential for optimal neural development. The objective of the present study was to systematically evaluate the effect of LC-PUFA supplementation of high-risk pregnant women's diets on pregnancy outcomes and growth measures at birth. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library through March 2006 and references in reviewed articles for randomized controlled trials (RCT) comparing LC-PUFA supplementation with placebo or no supplementation in women with high-risk pregnancies. We found no evidence that supplementation influenced the duration of pregnancy or the percentage of preterm deliveries < 37 weeks of gestation. However, compared with controls, supplementation was associated with a significantly lower rate of early preterm delivery ( < 34 weeks of gestation) (two RCT; n 291; relative risk 0.39 (95 % CI 0.18, 0.84)). There was no significant difference in the infant birth weight, the rate of low birth weight ( < 2500 g or < 10th percentile) and the recurrence of intra-uterine growth retardation. Other pregnancy outcomes (for example, the rate of pregnancy-induced hypertension, the rate of pre-eclampsia and the rate of Caesarean section) were also similar in both groups. In conclusion, the present data suggest that supplementation with n-3 LC-PUFA in women with high-risk pregnancies reduced the risk of early preterm delivery in the fatty acid-supplemented group compared with the placebo group, while no other effects on pregnancy outcomes were detected.

Effect of n-3 long-chain polyunsaturated fatty acid supplementation of women with low-risk pregnancies on pregnancy outcomes and growth measures at birth: a meta-analysis of randomized controlled trials.

BACKGROUND: It is hypothesized that the intake of long-chain polyunsaturated fatty acids (LC-PUFAs) throughout pregnancy is important to maternal health and fetal and infant development. OBJECTIVE: The objective was to evaluate systematically the effect of LC-PUFA supplementation of pregnant women's diets on pregnancy outcomes and growth measures at birth. DESIGN: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library through August 2005 and also searched the references in reviewed articles for randomized controlled trials (RCTs) comparing LC-PUFA supplementation with placebo or no supplementation. RESULTS: Of 6 included RCTs, only 1 was judged to be at low risk of bias. Supplementation with n-3 LC-PUFAs in these 6 RCTs (1278 infants) was associated with a significantly greater length of pregnancy [weighted mean difference (WMD): 1.57 d; 95% CI: 0.35, 2.78 d; findings stable on sensitivity analysis] than in control subjects. We found no evidence that supplementation influenced the percentage of preterm deliveries, the rate of low-birth-weight infants, or the rate of preeclampsia or eclampsia. We found no significant difference in the 6 RCTs (1278 infants) in birth weight (WMD: 54 g; 95% CI: -3.1, 111 g) and no significant difference in 5 RCTs (1262 infants) in birth length (WMD: 0.23 cm; 95% CI: -0.04, 0.5 cm), but, in 4 RCTs (729 infants), there was a significant increase in head circumference (WMD: 0.26 cm; 95% CI: 0.02, 0.49 cm; significance was lost on sensitivity analysis). CONCLUSIONS: n-3 LC-PUFA supplementation during pregnancy may enhance pregnancy duration and head circumference, but the mean effect size is small. The implications of these findings for later growth and development remain to be elucidated.