Consumption Pattern of Tea Is Associated with Serum Ferritin Levels of Women of Childbearing Age in Nandi County, Kenya: A Cross-Sectional Study.

INTRODUCTION: Tea consumption with meals affects iron absorption, increasing the risk of iron deficiency. Our study investigated the association between tea consumption patterns and serum ferritin levels among women of childbearing age (WCA) in Nandi County, Kenya. METHODS: We conducted a cross-sectional analytical study among 160 WCA selected using a systematic random sampling technique from Kapsabet Ward. Information on tea consumption practices was gathered using a researcher-administered questionnaire, and serum ferritin and C-reactive protein were measured. We assessed associations between tea consumption and iron status of respondents by multivariable regression analysis, adjusting for potential confounders, including parasitic infections and recent severe blood losses. RESULTS: The prevalence of anaemia and iron deficiency among the study participants were 86.2% and 45%, respectively. Majority (90.6%) of the respondents consumed tea or coffee, with an infusion time of more than 5 min (60.0%) and a moderate tea strength (64.1%), within 1 h before or after meals. Iron deficiency was associated the number of teacups consumed (adjusted odds ratio = 7.282, 95% CI = 3.580-14.812). CONCLUSION: High tea consumption is positively associated with iron deficiency among WCA. Lower tea infusion strength, shorter tea infusion duration, and a lower number of teacups overall consumed, as well as consuming tea 1 h before or after meals instead of with meals, may be recommended for better outcomes in iron status among WCA.

Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis.

BACKGROUND: We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS: We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS: We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research.

Effect of chicory-derived inulin-type fructans on abundance of Bifidobacterium and on bowel function: a systematic review with meta-analyses.

Inulin-type fructans are considered to stimulate the growth of beneficial microorganisms, like Bifidobacterium in the gut and support health. However, both the fructan source and chemical structure may modify these effects. A systematic review was conducted to assess the effects of chicory-derived inulin-type fructans consumed either in specific foods or as dietary supplements on abundance of Bifidobacterium in the gut and on health-related outcomes. Three electronic databases and two clinical trial registries were systematically searched until January 2021. Two authors independently selected randomized controlled trials that investigated with a protocol of minimum seven days supplementation the effect of chicory-derived inulin-type fructans on Bifidobacterium abundance in any population. Meta-analyses with random-effects model were conducted on Bifidobacterium abundance and bowel function parameters. We evaluated risk of bias using Cochrane RoB tool. Chicory-derived inulin-type fructans at a dose of 3-20 g/day significantly increased Bifidobacterium abundance in participants with an age range from 0 to 83 years (standardized mean difference: 0.83, 95% CI: 0.58-1.08; p < 0.01; 50 studies; 2525 participants). Significant bifidogenic effects were observed in healthy individuals and in populations with health impairments, except gastrointestinal disorders. Significant beneficial effects on bowel function parameters were observed in healthy subjects. Chicory-derived inulin-type fructans may have significant bifidogenic effects and may beneficially influence bowel function in healthy individuals. PROSPERO registration number CRD42020162892.

A1- and A2 beta-casein on health-related outcomes: a scoping review of animal studies.

PURPOSE: Food-derived bioactive peptides may influence important physiological functions. An important example is beta-casomorphins, which are opioid peptides derived from A1 beta-casein in bovine milk and have been associated to be risk factors for non-communicable diseases in humans. A1 and A2 beta-casein are different with respect to the release of bioactive peptides, in particular BCM-7. However, evidence from human studies is limited and could be complemented with evidence derived from animal studies. We conducted a scoping review to identify animal studies investigating the effects of A1 beta-casein or BCM-7 compared to A2 beta-casein or any other intervention on health-related outcomes. METHODS: We systematically searched for relevant studies in two electronic databases (Medline, Embase; last search performed March 2020). Two reviewers independently undertook study selection and data extraction of included references. Results were summarized tabularly and narratively. RESULTS: We included 42 studies investigating various animal models, including rats, mice, rabbits, and dogs. Six studies investigated health-related outcomes of A1- vs. A2 milk, while most studies (n = 36) reported on physiological properties (e.g., analgesic effect) of BCM-7 as an opioid peptide. Included studies were extremely heterogeneous in terms of the study population, type of intervention and dose, and type of outcome measures. CONCLUSIONS: Only a few studies comparing the effects of A1- and A2 milk were identified. More studies addressing this research question in animal models are needed to provide essential information to inform research gaps. Results from future studies could eventually complement research for humans, particularly when the body of evidence remains uncertain as is the case in the A1- and A2 milk debate.

Effects of a gluten-reduced or gluten-free diet for the primary prevention of cardiovascular disease.

BACKGROUND: Cardiovascular diseases (CVD) are a major cause of disability and the leading cause of death worldwide. To reduce mortality and morbidity, prevention strategies such as following an optimal diet are crucial. In recent years, low-gluten and gluten-free diets have gained strong popularity in the general population. However, study results on the benefits of a gluten-reduced or gluten-free diet are conflicting, and it is unclear whether a gluten-reduced diet has an effect on the primary prevention of CVD. OBJECTIVES: To determine the effects of a gluten-reduced or gluten-free diet for the primary prevention of CVD in the general population. SEARCH METHODS: We systematically searched CENTRAL, MEDLINE, Embase, CINAHL and Web of Science up to June 2021 without language restrictions or restrictions regarding publication status. Additionally, we searched ClinicalTrials.gov for ongoing or unpublished trials and checked reference lists of included studies as well as relevant systematic reviews for additional studies. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs), such as prospective cohort studies, comparing a low-gluten or gluten-free diet or providing advice to decrease gluten consumption with no intervention, diet as usual, or a reference gluten-intake category. The population of interest comprised adults from the general population, including those at increased risk for CVD (primary prevention). We excluded cluster-RCTs, case-control studies, studies focusing on participants with a previous myocardial infarction and/or stroke, participants who have undergone a revascularisation procedure as well as participants with angina or angiographically-defined coronary heart disease, with a confirmed diagnosis of coeliac disease or with type 1 diabetes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility of studies in a two-step procedure following Cochrane methods. Risk of bias (RoB) was assessed using the Cochrane risk of bias tool (RoB2) and the 'Risk Of Bias In Non-randomised Studies - of Interventions' (ROBINS-I) tool, and the certainty of evidence was rated using the GRADE approach. MAIN RESULTS: One RCT and three NRSIs (with an observational design reporting data on four cohorts: Health Professionals Follow-up Study (HPFS), Nurses' Health Study (NHS-I), NHS-II, UK Biobank) met the inclusion criteria. The RCT was conducted in Italy (60 participants, mean age 41 ± 12.1 years), two NRSIs (three cohorts, HPFS, NHS-I, NHS II) were conducted across the USA (269,282 health professionals aged 24 to 75 years) and one NRSI (Biobank cohort) was conducted across the UK (159,265 participants aged 49 to 62 years). Two NRSIs reported that the lowest gluten intake ranged between 0.0 g/day and 3.4 g/day and the highest gluten intake between 6.2 g/day and 38.4 g/day. The NRSI reporting data from the UK Biobank referred to a median gluten intake of 8.5 g/day with an interquartile range from 5.1 g/day to 12.4 g/day without providing low- and high-intake categories. Cardiovascular mortality From a total of 269,282 participants, 3364 (1.3%) died due to cardiovascular events during 26 years of follow-up. Low-certainty evidence may show no association between gluten intake and cardiovascular mortality (adjusted hazard ratio (HR) for low- versus high-gluten intake 1.00, 95% confidence interval (CI) 0.95 to 1.06; 2 NRSIs (3 cohorts)). All-cause mortality From a total of 159,265 participants, 6259 (3.9%) died during 11.1 years of follow-up. Very low-certainty evidence suggested that it is unclear whether gluten intake is associated with all-cause mortality (adjusted HR for low vs high gluten intake 1.00, 95% CI 0.99 to 1.01; 1 NRSI (1 cohort)). Myocardial infarction  From a total of 110,017 participants, 4243 (3.9%) participants developed non-fatal myocardial infarction within 26 years. Low-certainty evidence suggested that gluten intake may not be associated with the development of non-fatal myocardial infarction (adjusted HR for low versus high gluten intake 0.99, 95% CI 0.89 to 1.10; 1 NRSI (2 cohorts)). Lowering gluten intake by 5 g/day also showed no association on the primary prevention of non-fatal and fatal myocardial infarction (composite endpoint) in linear dose-response meta-analyses (adjusted HR 1.02, 95% CI 0.98 to 1.06; 1 NRSI (2 cohorts)). Coronary risk factors  Type 2 diabetes From a total of 202,114 participants, 15,947 (8.0%) developed type 2 diabetes after a follow-up between 22 and 28 years. There was low-certainty evidence that a lower compared with a higher gluten intake may be associated with a slightly increased risk to develop type 2 diabetes (adjusted HR 1.14, 95% CI 1.07 to 1.22; 1 NRSI (3 cohorts)). Furthermore, lowering gluten intake by 5 g/day may be associated with a slightly increased risk to develop type 2 diabetes in linear dose-response meta-analyses (adjusted HR 1.12, 95% CI 1.08 to 1.16; 1 NRSI (3 cohorts)). Blood pressure, low-density lipoprotein level, body mass index (BMI) After six months of follow-up, very low-certainty evidence suggested that it is unclear whether gluten intake affects systolic blood pressure (mean difference (MD) -6.9, 95% CI -17.1 to 3.3 mmHg). There was also no difference between the interventions for diastolic blood pressure (MD -0.8, 95% CI -5.9 to 4.3 mmHg), low-density lipoprotein levels (MD -0.1, 95% CI -0.5 to 0.3 mmol/L) and BMI (MD -0.1, 95% CI -3.3 to 3.1 kg/m²).  No study reported data on adverse events or on other outcomes. Funding sources did not appear to have distorted the results in any of the studies. AUTHORS' CONCLUSIONS: Very low-certainty evidence suggested that it is unclear whether gluten intake is associated with all-cause mortality. Our findings also indicate that low-certainty evidence may show little or no association between gluten intake and cardiovascular mortality and non-fatal myocardial infarction. Low-certainty evidence suggested that a lower compared with a higher gluten intake may be associated with a slightly increased risk to develop type 2 diabetes - a major cardiovascular risk factor. For other cardiovascular risk factors it is unclear whether there is a difference between a gluten-free and normal diet. Given the limited findings from this review predominantly based on observational studies, no recommendations for practice can be made.

A systematic review: the dimensions to evaluate health care performance and an implication during the pandemic.

BACKGROUND: The balanced scorecard (BSC) has been implemented to evaluate the performance of health care organizations (HCOs). BSC proved to be effective in improving financial performance and patient satisfaction. AIM: This systematic review aims to identify all the perspectives, dimensions, and KPIs that are vital and most frequently used by health care managers in BSC implementations. METHODS: This systematic review adheres to PRISMA guidelines. The PubMed, Embase, Cochrane, and Google Scholar databases and Google search engine were inspected to find all implementations of BSC at HCO. The risk of bias was assessed using the nonrandomized intervention studies (ROBINS-I) tool to evaluate the quality of observational and quasi-experimental studies and the Cochrane (RoB 2) tool for randomized controlled trials (RCTs). RESULTS: There were 33 eligible studies, of which we identified 36 BSC implementations. The categorization and regrouping of the 797 KPIs resulted in 45 subdimensions. The reassembly of these subdimensions resulted in 13 major dimensions: financial, efficiency and effectiveness, availability and quality of supplies and services, managerial tasks, health care workers' (HCWs) scientific development error-free and safety, time, HCW-centeredness, patient-centeredness, technology, and information systems, community care and reputation, HCO building, and communication. On the other hand, this review detected that BSC design modification to include external and managerial perspectives was necessary for many BSC implementations. CONCLUSION: This review solves the KPI categorization dilemma. It also guides researchers and health care managers in choosing dimensions for future BSC implementations and performance evaluations in general. Consequently, dimension uniformity will improve the data sharing and comparability among studies. Additionally, despite the pandemic negatively influencing many dimensions, the researchers observed a lack of comprehensive HCO performance evaluations. In the same vein, although some resulting dimensions were assessed separately during the pandemic, other dimensions still lack investigation. Last, BSC dimensions may play an essential role in tackling the COVID-19 pandemic. However, further research is required to investigate the BSC implementation effect in mitigating the pandemic consequences on HCO.

The deployment of balanced scorecard in health care organizations: is it beneficial? A systematic review.

BACKGROUND: Balanced Scorecard (BSC) has been implemented for three decades to evaluate and improve the performance of organizations. To the best of the researchers' knowledge, no previous systematic review has performed a comprehensive and rigorous methodological approach to figure out the impact of BSC implementation in Health Care Organizations (HCO). AIMS: The current work was intended to assess the impact of implementing the BSC on Health Care Workers' (HCW) satisfaction, patient satisfaction, and financial performance. METHODS: The authors prepared the present systematic review according to PRISMA guidelines. Further, the authors customized the search strategy for PubMed, Embase, Cochrane, Google Scholar databases, and Google's search engine. The obtained studies were screened to isolate those measuring scores related to HCW satisfaction, patient satisfaction, and financial performance. The Risk of Bias (RoB) in the non-Randomized Intervention Studies (ROBINS-I) tool was used to assess the quality of observational and quasi-experimental studies. On the other hand, for the Randomized Controlled Trials (RCTs), the Cochrane (RoB 2) tool was used. RESULTS: Out of 4031 studies, the researchers included 20 studies that measured the impact of BSC on one or more of the three entities (HCW satisfaction, patient satisfaction, and financial performance). Throughout these 20 studies, it was found that 17 studies measured the impact of the BSC on patient satisfaction, seven studies measured the impact on HCW satisfaction, and 12 studies measured the impact on financial performance. CONCLUSION: This systematic review provides managers and policymakers with evidence to support utilizing BSC in the health care sector. BSC implementation demonstrated positive outcomes for patient satisfaction and the financial performance of HCOs. However, only a mild impact was demonstrated for effects related to HCW satisfaction. However, it is worth noting that many of the studies reflected a high RoB, which may have affected the impacts on the three primary outcomes measured. As such, this systematic review reflects the necessity for further focus on this area in the future. Moreover, future research is encouraged to measure the real and current impact of implementing BSC in HCO during the pandemic since we did not find any.

Effect of the knee replacement surgery on activity level based on ActivPAL: a systematic review and meta-analysis study.

BACKGROUND: The knee replacement (KR) surgery aims to restore the activity level and reduce the risk of experiencing disabilities. The outcomes of this surgery are evaluated mainly with subjective tools or low validity objective tools. However, the effect of the surgery on activity level using high validity objective accelerometer is still in question. METHODS: A systematic review and meta-analysis were conducted to evaluate the benefit of KR surgery alone to enhance physical activity recommendations based on high validity accelerometer. Two independent reviewers evaluated five electronic databases (Cochrane-Central-Register-of-Controlled Trials, EMBASE, PubMed, Web of Science, and Scopus) to find relative studies between January 2000 and October 2021. The quality assessments and risk of bias assessments were examined. RESULTS: Three articles were included with 202 participants (86 males, 116 females), with an average age of 64 years and an average 32 kg/m2 body mass index. The results found that the number of steps was significantly improved up to 36.35 and 45.5% after 6-months and 1-year of the surgery, respectively. However, these changes did not meet the recommended activity level guideline and could be related to the patients' health status and their activity level before the surgery. No significant changes were seen in sedentary time, standing time, and upright time after 6-months and 1-year follow-ups. Heterogeneity among studies was low to moderate (0-63%). CONCLUSION: Knee replacement surgery is an effective treatment for improving patients' quality of life with severe knee injuries. However, various factors impact the success of surgical and achieving maximum benefit of the surgery. One factor, sedentary time, can be reduced by implementing pre-and post-surgery exercise or physical activity recommendations. Further studies are needed to understand the benefit of surgery with or without rehabilitation assessed using high validity monitors.

Impact of intermittent energy restriction on anthropometric outcomes and intermediate disease markers in patients with overweight and obesity: systematic review and meta-analyses.

This systematic review aims to investigate the effects of intermittent energy restriction (IER) on anthropometric outcomes and intermediate disease markers. A systematic literature search was conducted in three electronic databases. Randomized controlled trials (RCTs) were included if the intervention lasted ≥12 weeks and IER was compared with either continuous energy restriction (CER) or a usual diet. Random-effects meta-analysis was performed for eight outcomes. Certainty of evidence was assessed using GRADE. Seventeen RCTs with 1328 participants were included. IER in comparison to a usual diet may reduce body weight (mean difference [MD]: -4.83 kg, 95%-CI: -5.46, -4.21; n = 6 RCTs), waist circumference (MD: -1.73 cm, 95%-CI: -3.69, 0.24; n = 2), fat mass (MD: -2.54 kg, 95%-CI: -3.78, -1.31; n = 6), triacylglycerols (MD: -0.20 mmol/L, 95%-CI: -0.38, -0.03; n = 5) and systolic blood pressure (MD: -6.11 mmHg, 95%-CI: -9.59, -2.64; n = 5). No effects were observed for LDL-cholesterol, fasting glucose, and glycosylated-hemoglobin. Both, IER and CER have similar effect on body weight (MD: -0.55 kg, 95%-CI: -1.01, -0.09; n = 13), and fat mass (MD: -0.66 kg, 95%-CI: -1.14, -0.19; n = 10), and all other outcomes. In conclusion, IER improves anthropometric outcomes and intermediate disease markers when compared to a usual diet. The effects of IER on weight loss are similar to weight loss achieved by CER.

Investigator initiated trials versus industry sponsored trials - translation of randomized controlled trials into clinical practice (IMPACT).

BACKGROUND: Healthcare decisions are ideally based on clinical trial results, published in study registries, as journal articles or summarized in secondary research articles. In this research project, we investigated the impact of academically and commercially sponsored clinical trials on medical practice by measuring the proportion of trials published and cited by systematic reviews and clinical guidelines. METHODS: We examined 691 multicenter, randomized controlled trials that started in 2005 or later and were completed by the end of 2016. To determine whether sponsorship/funding and place of conduct influence a trial's impact, we created four sub-cohorts of investigator initiated trials (IITs) and industry sponsored trials (ISTs): 120 IITs and 171 ISTs with German contribution compared to 200 IITs and 200 ISTs without German contribution. We balanced the groups for study phase and place of conduct. German IITs were funded by the German Research Foundation (DFG), the Federal Ministry of Education and Research (BMBF), or by another non-commercial research organization. All other trials were drawn from the German Clinical Trials Register or ClinicalTrials.gov. We investigated, to what extent study characteristics were associated with publication and impact using multivariable logistic regressions. RESULTS: For 80% of the 691 trials, results were published as result articles in a medical journal and/or study registry, 52% were cited by a systematic review, and 26% reached impact in a clinical guideline. Drug trials and larger trials were associated with a higher probability to be published and to have an impact than non-drug trials and smaller trials. Results of IITs were more often published as a journal article while results of ISTs were more often published in study registries. International ISTs less often gained impact by inclusion in systematic reviews or guidelines than IITs. CONCLUSION: An encouraging high proportion of the clinical trials were published, and a considerable proportion gained impact on clinical practice. However, there is still room for improvement. For publishing study results, study registries have become an alternative or complement to journal articles, especially for ISTs. IITs funded by governmental bodies in Germany reached an impact that is comparable to international IITs and ISTs.

Effect of using knee valgus brace on pain and activity level over different time intervals among patients with medial knee OA: systematic review.

BACKGROUND: The Knee valgus brace is one of the accepted conservative interventions for patients with medial compartment knee osteoarthritis to correct the knee varus and increase functional activity level. Nevertheless, comprehensive overview of the effects of using this brace on self-reported pain activity level over time is not available. Thus, this study aimed to systematically review the effect of using this brace on pain and activity levels in the last 20 years in patients with medial compartment knee osteoarthritis. METHODS: Five databases were searched to find articles from the year 2000 to the end of November 2020: Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, PubMed, Web of Science, and Scopus. Two reviewers independently evaluated the available articles for eligibility and assessed quality. The risk of bias in each study was assessed by two reviewers independently according to the Strengthening the Reporting of Observational Studies in Epidemiology tool (STROBE) for the non-randomized controlled studies and the Cochrane risk-of-bias tool for the randomized controlled studies. RESULTS: Seven randomized controlled studies and 17 cohort studies (in total 579 participants) were included in the systematic review. Most of these studies found using a knee valgus brace effective in reducing pain and improving activity level over different time intervals. The majority of the included studies (14 studies) evaluated the impact of the brace for a considerably short-term (less than 6 months). Thus, limited evidence is available on the long-term use of the knee valgus brace and its associated complications. CONCLUSION: The knee valgus brace is an effective conservative intervention to improve the quality of life and reduce pain during daily activities for some patients. However, the long term of using this brace is still not very convenient, and the patients who benefit most from using the brace should be identified with high methodological quality studies.

Non-nutritive sweeteners for diabetes mellitus.

BACKGROUND: Products sweetened with non-nutritive sweeteners (NNS) are widely available. Many people with type 1 or type 2 diabetes use NNS as a replacement for nutritive sweeteners to control their carbohydrate and energy intake. Health outcomes associated with NNS use in diabetes are unknown. OBJECTIVES: To assess the effects of non-nutritive sweeteners in people with diabetes mellitus. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Scopus, the WHO ICTRP, and ClinicalTrials.gov. The date of the last search of all databases (except for Scopus) was May 2019. We last searched Scopus in January 2019. We did not apply any language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a duration of four weeks or more comparing any type of NNS with usual diet, no intervention, placebo, water, a different NNS, or a nutritive sweetener in individuals with type 1 or type 2 diabetes. Trials with concomitant behaviour-changing interventions, such as diet, exercise, or both, were eligible for inclusion, given that the concomitant interventions were the same in the intervention and comparator groups. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts, full texts, and records retrieved from trials registries, assessed the certainty of the evidence, and extracted data. We used a random-effects model to perform meta-analysis, and calculated effect estimates as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs). We assessed risk of bias using the Cochrane 'Risk of bias' tool and the certainty of evidence using the GRADE approach. MAIN RESULTS: We included nine RCTs that randomised a total of 979 people with type 1 or type 2 diabetes. The intervention duration ranged from 4 to 10 months. We judged none of these trials as at low risk of bias for all 'Risk of bias' domains; most of the included trials did not report the method of randomisation. Three trials compared the effects of a dietary supplement containing NNS with sugar: glycosylated haemoglobin A1c (HbA1c) was 0.4% higher in the NNS group (95% CI -0.5 to 1.2; P = 0.44; 3 trials; 72 participants; very low-certainty evidence). The MD in weight change was -0.1 kg (95% CI -2.7 to 2.6; P = 0.96; 3 trials; 72 participants; very low-certainty evidence). None of the trials with sugar as comparator reported on adverse events. Five trials compared NNS with placebo. The MD for HbA1c was 0%, 95% CI -0.1 to 0.1; P = 0.99; 4 trials; 360 participants; very low-certainty evidence. The 95% prediction interval ranged between -0.3% and 0.3%. The comparison of NNS versus placebo showed a MD in body weight of -0.2 kg, 95% CI -1 to 0.6; P = 0.64; 2 trials; 184 participants; very low-certainty evidence. Three trials reported the numbers of participants experiencing at least one non-serious adverse event: 36/113 participants (31.9%) in the NNS group versus 42/118 participants (35.6%) in the placebo group (RR 0.78, 95% CI 0.39 to 1.56; P = 0.48; 3 trials; 231 participants; very low-certainty evidence). One trial compared NNS with a nutritive low-calorie sweetener (tagatose). HbA1c was 0.3% higher in the NNS group (95% CI 0.1 to 0.4; P = 0.01; 1 trial; 354 participants; very low-certainty evidence). This trial did not report body weight data and adverse events. The included trials did not report data on health-related quality of life, diabetes complications, all-cause mortality, or socioeconomic effects. AUTHORS' CONCLUSIONS: There is inconclusive evidence of very low certainty regarding the effects of NNS consumption compared with either sugar, placebo, or nutritive low-calorie sweetener consumption on clinically relevant benefit or harm for HbA1c, body weight, and adverse events in people with type 1 or type 2 diabetes. Data on health-related quality of life, diabetes complications, all-cause mortality, and socioeconomic effects are lacking.

Household interventions for secondary prevention of domestic lead exposure in children.

BACKGROUND: Lead exposure is a serious health hazard, especially for children. It is associated with physical, cognitive and neurobehavioural impairment in children. There are many potential sources of lead in the environment, therefore trials have tested many household interventions to prevent or reduce lead exposure. This is an update of a previously published review. OBJECTIVES: To assess the effects of household interventions intended to prevent or reduce further lead exposure in children on improvements in cognitive and neurobehavioural development, reductions in blood lead levels and reductions in household dust lead levels. SEARCH METHODS: In March 2020, we updated our searches of CENTRAL, MEDLINE, Embase, 10 other databases and ClinicalTrials.gov. We also searched Google Scholar, checked the reference lists of relevant studies and contacted experts to identify unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of household educational or environmental interventions, or combinations of interventions to prevent lead exposure in children (from birth to 18 years of age), where investigators reported at least one standardised outcome measure. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed all eligible studies for inclusion, assessed risk of bias and extracted data. We contacted trialists to obtain missing information. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 17 studies (three new to this update), involving 3282 children: 16 RCTs (involving 3204 children) and one quasi-RCT (involving 78 children). Children in all studies were under six years of age. Fifteen studies took place in urban areas of North America, one in Australia and one in China. Most studies were in areas with low socioeconomic status. Girls and boys were equally represented in those studies reporting this information. The duration of the intervention ranged from three months to 24 months in 15 studies, while two studies performed interventions on a single occasion. Follow-up periods ranged from three months to eight years. Three RCTs were at low risk of bias in all assessed domains. The other 14 studies were at unclear or high risk of bias; for example, we considered two RCTs and one quasi-RCT at high risk of selection bias and six RCTs at high risk of attrition bias. National or international research grants or governments funded 15 studies, while the other two did not report their funding sources. Education interventions versus no intervention None of the included studies in this comparison assessed effects on cognitive or neurobehavioural outcomes, or adverse events. All studies reported data on blood lead level outcomes. Educational interventions showed there was probably no evidence of a difference in reducing blood lead levels (continuous: mean difference (MD) -0.03, 95% confidence interval (CI) -0.13 to 0.07; I² = 0%; 5 studies, 815 participants; moderate-certainty evidence; log-transformed data), or in reducing floor dust levels (MD -0.07, 95% CI -0.37 to 0.24; I² = 0%; 2 studies, 318 participants; moderate-certainty evidence). Environmental interventions versus no intervention Dust control: one study in this comparison reported data on cognitive and neurobehavioural outcomes, and on adverse events in children. The study showed numerically there may be better neurobehavioural outcomes in children of the intervention group. However, differences were small and the CI included both a beneficial and non-beneficial effect of the environmental intervention (e.g. mental development (Bayley Scales of Infant Development-II): MD 0.1, 95% CI -2.1 to 2.4; 1 study, 302 participants; low-certainty evidence). The same study did not observe any adverse events related to the intervention during the eight-year follow-up, but observed two children with adverse events in the control group (1 study, 355 participants; very low-certainty evidence). Meta-analysis also found no evidence of effectiveness on blood lead levels (continuous: MD -0.02, 95% CI -0.09 to 0.06; I² = 0%; 4 studies, 565 participants; moderate-certainty evidence; log-transformed data). We could not pool the data regarding floor dust levels, but studies reported that there may be no evidence of a difference between the groups (very low-certainty evidence). Soil abatement: the two studies assessing this environmental intervention only reported on the outcome of 'blood lead level'. One study showed a small effect on blood lead level reduction, while the other study showed no effect. Therefore, we deem the current evidence insufficient to draw conclusions about the effectiveness of soil abatement (very low-certainty evidence). Combination of educational and environmental interventions versus standard education Studies in this comparison only reported on blood lead levels and dust lead levels. We could not pool the studies in a meta-analysis due to substantial differences between the studies. Since the studies reported inconsistent results, the evidence is currently insufficient to clarify whether a combination of interventions reduces blood lead levels and floor dust levels (very low-certainty evidence). AUTHORS' CONCLUSIONS: Based on available evidence, household educational interventions and environmental interventions (namely dust control measures) show no evidence of a difference in reducing blood lead levels in children as a population health measure. The evidence of the effects of environmental interventions on cognitive and neurobehavioural outcomes and adverse events is uncertain too. Further trials are required to establish the most effective intervention for reducing or even preventing further lead exposure. Key elements of these trials should include strategies to reduce multiple sources of lead exposure simultaneously using empirical dust clearance levels. It is also necessary for trials to be carried out in low- and middle-income countries and in differing socioeconomic groups in high-income countries.

A systematic review of the effects of increasing arachidonic acid intake on PUFA status, metabolism and health-related outcomes in humans.

We conducted a systematic review of randomised controlled trials (RCT) of increased intake of arachidonic acid (ARA) on fatty acid status and health outcomes in humans. We identified twenty-two articles from fourteen RCT. Most studies were conducted in adults. These used between 80 and 2000 mg ARA per d and were of 1-12 weeks duration. Supplementation with ARA doses as low as 80 mg/d increased the content of ARA in different blood fractions. Overall there seem to be few marked benefits for adults of increasing ARA intake from the typical usual intake of 100-200 mg/d to as much as 1000 mg/d; the few studies using higher doses (1500 or 2000 mg/d) also report little benefit. However, there may be an impact of ARA on cognitive and muscle function which could be particularly relevant in the ageing population. The studies reviewed here suggest no adverse effects in adults of increased ARA intake up to at least 1000-1500 mg/d on blood lipids, platelet aggregation and blood clotting, immune function, inflammation or urinary excretion of ARA metabolites. However, in many areas there are insufficient studies to make firm conclusions, and higher intakes of ARA are deserving of further study. Based on the RCT reviewed, there are not enough data to make any recommendations for specific health effects of ARA intake.

Inulin-Type Fructan Supplementation of 3- to 6-Year-Old Children Is Associated with Higher Fecal Bifidobacterium Concentrations and Fewer Febrile Episodes Requiring Medical Attention.

Background: Inulin-type fructans used in formula have been shown to promote microbiota composition and stool consistency closer to those of breastfed infants and to have beneficial effects on fever occurrence, diarrhea, and incidence of infections requiring antibiotic treatment in infants. Objectives: The primary study aim was to explore whether prophylactic supplementation with prebiotic fructans is able to influence the frequency of infectious diseases in kindergarten children during a winter period. A secondary objective was to ascertain the effect on the intestinal microbiota. Methods: 142 boys and 128 girls aged 3-6 y were randomly allocated to consume 6 g/d fructans or maltodextrin for 24 wk. At baseline, stool samples were collected for microbiota analysis and anthropometric measurements were made. During the intervention period diagnoses were recorded by physicians, whereas disease symptoms, kindergarten absenteeism, dietary habits, and stool consistency were recorded by parents. Baseline measurements were repeated at wk 24. Results: In total 219 children finished the study. Both the relative abundance of Bifidobacterium (P < 0.001) and that of Lactobacillus (P = 0.014) were 19.9% and 7.8% higher, respectively, post data normalization, in stool samples of children receiving fructans as compared with those of controls at wk 24. This was accompanied by significantly softer stools within the normal range in the prebiotic group from wk 12 onwards. The incidence of febrile episodes requiring medical attention [0.65 ± 1.09 compared with 0.9 ± 1.11 infections/(24 wk × child), P = 0.04] and that of sinusitis (0.01 ± 0.1 compared with 0.06 ± 0.25, P = 0.03) were significantly lower in the prebiotic group. The number of infectious episodes and their duration reported by parents did not differ significantly between the 2 intervention groups. Conclusions: Prebiotic supplementation modified the composition of the intestinal microbiota and resulted in softer stools in kindergarten-aged children. The reduction in febrile episodes requiring medical attention supports the concept of further studies on prebiotics in young children. This trial was registered at clinicaltrials.gov as NCT03241355.

Health outcomes of non-nutritive sweeteners: analysis of the research landscape.

BACKGROUND: Food products containing non-nutritive sweeteners (NNSs) instead of sugar have become increasingly popular in the last decades. Their appeal is obviously related to their calorie-free sweet taste. However, with the dramatic increase in their consumption, it is reasonable and timely to evaluate their potential health benefits and, more importantly, potential adverse effects. The main aim of this scoping review was to map the evidence about health outcomes possibly associated with regular NNS consumption by examining the extent, range, and nature of research activity in this area. METHODS: We systematically searched Ovid MEDLINE, EMBASE and the Cochrane CENTRAL databases for studies on NNSs (artificial sweeteners or natural, non-caloric sweeteners, either used individually or in combination) using text terms with appropriate truncation and relevant indexing terms. All human studies investigating any health outcomes of a NNS intervention or exposure were eligible for inclusion. No studies were excluded based on language, study design or methodological quality. Data for each health outcome were summarized in tabular form and were discussed narratively. RESULTS: Finally, we included 372 studies in our scoping review, comprising 15 systematic reviews, 155 randomized controlled trials (RCTs), 23 non-randomized controlled trials, 57 cohort studies, 52 case-control studies, 28 cross sectional studies and 42 case series/case reports. In healthy subjects, appetite and short term food intake, risk of cancer, risk of diabetes, risk of dental caries, weight gain and risk of obesity are the most investigated health outcomes. Overall there is no conclusive evidence for beneficial and harmful effects on those outcomes. Numerous health outcomes including headaches, depression, behavioral and cognitive effects, neurological effects, risk of preterm delivery, cardiovascular effects or risk of chronic kidney disease were investigated in fewer studies and further research is needed. In subjects with diabetes and hypertension, the evidence regarding health outcomes of NNS use is also inconsistent. CONCLUSIONS: This scoping review identifies the needs for future research to address the numerous evidence gaps related to health effects of NNSs use.It also specifies the research questions and areas where a systematic review with meta-analyses is required for the proper evaluation of health outcomes associated to regular NNSs consumption.

Systematic Review on N-3 and N-6 Polyunsaturated Fatty Acid Intake in European Countries in Light of the Current Recommendations - Focus on Specific Population Groups.

BACKGROUND: Earlier reviews indicated that in many countries adults, children and adolescents consume on an average less polyunsaturated fatty acids (PUFAs) than recommended by the Food and Agriculture Organisation/World Health Organisation. SUMMARY: The intake of total and individual n-3 and n-6 PUFAs in European infants, children, adolescents, elderly and pregnant/lactating women was evaluated systematically. RESULTS: The evaluations were done against recommendations of the European Food Safety Authority. Key Messages: Fifty-three studies from 17 different European countries reported an intake of total n-3 and n-6 PUFAs and/or individual n-3 or n-6 PUFAs in at least one of the specific population groups: 10 in pregnant women, 4 in lactating women, 3 in infants 6-12 months, 6 in children 1-3 years, 11 in children 4-9 years, 8 in adolescents 10-18 years and 11 in elderly >65 years. Mean linoleic acid intake was within the recommendation (4 energy percentage [E%]) in 52% of the countries, with inadequate intakes more likely in lactating women, adolescents and elderly. Mean α-linolenic acid intake was within the recommendation (0.5 E%) in 77% of the countries. In 26% of the countries, mean eicosapentaenoic acid and/or docosahexaenoic acid intake was as recommended. These results indicate that intake of n-3 and n-6 PUFAs may be suboptimal in specific population groups in Europe.

Household interventions for preventing domestic lead exposure in children.

BACKGROUND: Lead poisoning is associated with physical, cognitive and neurobehavioural impairment in children, and trials have tested many household interventions to prevent lead exposure. This is an update of the original review, first published in 2008. OBJECTIVES: To assess the effects of household interventions for preventing or reducing lead exposure in children, as measured by improvements in cognitive and neurobehavioural development, reductions in blood lead levels and reductions in household dust lead levels. SEARCH METHODS: In May 2016 we searched CENTRAL, Ovid MEDLINE, Embase, nine other databases and two trials registers: the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov. We also checked the reference lists of relevant studies and contacted experts to find unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of household educational or environmental interventions, or combinations of interventions to prevent lead exposure in children (from birth to 18 years of age), where investigators reported at least one standardised outcome measure. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed all eligible studies for inclusion, assessed risk of bias and extracted data. We contacted trialists to obtain missing information. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included 14 studies involving 2643 children: 13 RCTs (involving 2565 children) and one quasi-RCT (involving 78 children). Children in all studies were under six years of age. Thirteen studies took place in urban areas of North America, and one was in Australia. Most studies were in areas with low socioeconomic status. Girls and boys were equally represented in all studies. The duration of the intervention ranged from 3 months to 24 months in 12 studies, while 2 studies performed interventions on a single occasion. Follow-up periods ranged from 6 months to 48 months. Three RCTs were at low risk of bias in all assessed domains. We rated two RCTs and one quasi-RCT as being at high risk of selection bias and six RCTs as being at high risk of attrition bias. For educational interventions, we rated the quality of evidence to be high for continuous blood lead levels and moderate for all other outcomes. For environmental interventions, we assessed the quality of evidence as moderate to low. National or international research grants or governments funded 12 studies, while the other 2 did not report their funding sources.No studies reported on cognitive or neurobehavioural outcomes. No studies reported on adverse events in children. All studies reported blood lead level outcomes.We put studies into subgroups according to their intervention type. We performed meta-analyses of both continuous and dichotomous data for subgroups where appropriate. Educational interventions were not effective in reducing blood lead levels (continuous: mean difference (MD) 0.02, 95% confidence interval (CI) -0.09 to 0.12, I² = 0%; 5 studies; N = 815; high quality evidence (log transformed); dichotomous ≥ 10.0 µg/dL (≥ 0.48 µmol/L): risk ratio (RR) 1.02, 95% CI 0.79 to 1.30; I² = 0%; 4 studies; N = 520; moderate quality evidence; dichotomous ≥ 15.0 µg/dL (≥ 0.72 µmol/L): RR 0.60, 95% CI 0.33 to 1.09; I² = 0%; 4 studies; N = 520; moderate quality evidence). Meta-analysis for the dust control subgroup also found no evidence of effectiveness on blood lead levels (continuous: MD -0.15, 95% CI -0.42 to 0.11; I² = 90%; 3 studies; N = 298; low quality evidence (log transformed); dichotomous ≥ 10.0 µg/dL (≥ 0.48 µmol/L): RR 0.93, 95% CI 0.73 to 1.18; I² = 0; 2 studies; N = 210; moderate quality evidence; dichotomous ≥ 15.0 µg/dL (≥ 0.72 µmol/L): RR 0.86, 95% CI 0.35 to 2.07; I² = 56%; 2 studies; N = 210; low quality evidence). After adjusting the dust control subgroup for clustering in meta-analysis, we found no evidence of effectiveness. We could not pool the studies using soil abatement (removal and replacement) and combination intervention groups in a meta-analysis due to substantial differences between studies, and generalisability or reproducibility of the results from these studies is unknown. Therefore, there is currently insufficient evidence to clarify whether soil abatement or a combination of interventions reduces blood lead levels. AUTHORS' CONCLUSIONS: Based on current knowledge, household educational interventions are ineffective in reducing blood lead levels in children as a population health measure. Dust control interventions may lead to little or no difference in blood lead levels (the quality of evidence was moderate to low, meaning that future research is likely to change these results). There is currently insufficient evidence to draw conclusions about the effectiveness of soil abatement or combination interventions. No study reported on cognitive or neurobehavioural outcomes or adverse events. These patient-relevant outcomes would have been of great interest to draw conclusions for practice.Further trials are required to establish the most effective intervention for preventing lead exposure. Key elements of these trials should include strategies to reduce multiple sources of lead exposure simultaneously using empirical dust clearance levels. It is also necessary for trials to be carried out in low- and middle-income countries and in differing socioeconomic groups in high-income countries.