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International Journal of Food Science 2021Infant formulas are an alternative to replace or supplement human milk when breastfeeding is not possible. The knowledge of human milk's bioactive compounds and their... (Review)
Review
Infant formulas are an alternative to replace or supplement human milk when breastfeeding is not possible. The knowledge of human milk's bioactive compounds and their beneficial effects has attracted the interest of researchers in the field of infant nutrition, as well as researchers of technology and food sciences that seek to improve the nutritional characteristics of infant formulas. Several scientific studies evaluate the optimization of infant formula composition. The bioactive compound inclusion has been used to upgrade the quality and nutrition of infant formulas. In this context, the purpose of this systematic literature review is to assess the scientific evidence of bioactive compounds present in infant formulas (-lactalbumin, lactoferrin, taurine, milk fat globule membrane, folates, polyamines, long-chain polyunsaturated fatty acids, prebiotics, and probiotics) and their effects on infant nutrition and health. Through previously determined criteria, studies published in the last fifteen years from five different databases were included to identify the advances in the optimization of infant formula composition. Over the last few years, there has been optimization of the infant formula composition, not only to increase the similarities in their content of macro and micronutrients but also to include novel bioactive ingredients with potential health benefits for infants. Although the infant food industry has advanced in the last years, there is no consensus on whether novel bioactive ingredients added to infant formulas have the same functional effects as the compounds found in human milk. Thus, further studies about the impact of bioactive compounds in infant nutrition are fundamental to infant health.
PubMed: 34095293
DOI: 10.1155/2021/8850080 -
International Braz J Urol : Official... 2022To explore the feasibility of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer. (Meta-Analysis)
Meta-Analysis Review
Performance of 68Ga-labeled prostate-specific membrane antigen ligand positron emission tomography/computed tomography in the diagnosis of primary prostate cancer: a systematic review and meta-analysis.
OBJECTIVE
To explore the feasibility of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer.
MATERIALS AND METHODS
Embase, PubMed and Cochrane Library databases were searched for studies published before July 2020. The studies that used 68Ga-PSMA PET/CT for detecting primary prostate cancer, and pathological biopsy as the reference standard were included. The selecting process used preferred reporting items for systematic reviews and meta-analyses (PRISMA). The quality of enrolled studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.
RESULTS
According to our search strategy, 9 studies were included for analysis. A total of 547 patients with primary prostate cancer and 443 lesion segments that underwent 68Ga-PSMA PET/CT scans were included and their pathological biopsies were compared. The results of these studies showed some differences. For instance, the lowest sensitivity of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer was 67%, while the highest sensitivity recorded was 97%.
CONCLUSIONS
Compared with conventional imaging examinations, 68Ga-PSMA PET/CT had higher sensitivity and specificity in detecting primary prostate cancer. At present, most of the studies that used 68Ga-PSMA PET/CT for detecting prostate cancer are retrospective studies. Based on its advantage of high detection rate, the use of 68Ga-PSMA PET/CT in the detection of primary prostate cancer is worthy of promotion.
Topics: Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Humans; Ligands; Male; Oligopeptides; Positron Emission Tomography Computed Tomography; Prostate; Prostatic Neoplasms; Retrospective Studies
PubMed: 34003611
DOI: 10.1590/S1677-5538.IBJU.2020.0986 -
The British Journal of General Practice... Jul 2021Urinary tract infections (UTIs) are often treated with antibiotics and are a source of antibiotic overuse. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Urinary tract infections (UTIs) are often treated with antibiotics and are a source of antibiotic overuse.
AIM
To systematically review randomised controlled trials (RCTs) of adult women in the community with a history of recurrent UTIs and who use methenamine hippurate prophylactically.
DESIGN AND SETTING
Systematic review of women in the UK, Australia, Norway, and US (aged ≥18 years) with recurrent UTIs receiving methenamine hippurate against placebo or no treatment, and antibiotics.
METHOD
The authors searched three databases, clinical trial registries, and performed forward-backward citation analysis on references of included studies.
RESULTS
Six studies involving 557 participants were included (447 were analysed). Of the six studies, five were published and one was an unpublished trial record with results, three compared methenamine hippurate against placebo or control, and three compared methenamine hippurate with antibiotics. For the number of patients who remained asymptomatic, methenamine hippurate showed a non-statistically significant trend of benefit versus antibiotics over 12 months (risk ratio [RR] 0.65, 95% confidence interval [CI] = 0.40 to 1.07, 49%), versus control over 6 or 12 months (RR 0.56, 95% CI = 0.13 to 2.35, 93%), and a non-statistically significant trend versus any antibiotic for abacteruria (RR 0.80, 95% CI = 0.62 to 1.03, 23%). A similar non-statistically significant trend of benefits for methenamine hippurate for the number of UTI or bacteriuric episodes was found, and a non-statistically significant difference in the number of patients experiencing adverse events between methenamine hippurate and any comparator, with a trend towards benefit for the methenamine hippurate, was identified. Antibiotic use and resistance were not consistently reported.
CONCLUSION
There is insufficient evidence to be certain of the benefits of methenamine hippurate to prevent UTI. Further research is needed to test the drug's effectiveness in preventing UTIs and as an alternative for antibiotic treatment for UTI.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Female; Hippurates; Humans; Methenamine; Pharmaceutical Preparations; Urinary Tract Infections
PubMed: 34001538
DOI: 10.3399/BJGP.2020.0833 -
The Cochrane Database of Systematic... Jan 2021Anaemia is a condition where the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body's physiological needs.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anaemia is a condition where the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body's physiological needs. Fortification of wheat flour is deemed a useful strategy to reduce anaemia in populations.
OBJECTIVES
To determine the benefits and harms of wheat flour fortification with iron alone or with other vitamins and minerals on anaemia, iron status and health-related outcomes in populations over two years of age.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, 21 other databases and two trials registers up to 21 July 2020, together with contacting key organisations to identify additional studies.
SELECTION CRITERIA
We included cluster- or individually-randomised controlled trials (RCTs) carried out among the general population from any country, aged two years and above. The interventions were fortification of wheat flour with iron alone or in combination with other micronutrients. We included trials comparing any type of food item prepared from flour fortified with iron of any variety of wheat DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and assessed the eligibility of studies for inclusion, extracted data from included studies and assessed risks of bias. We followed Cochrane methods in this review.
MAIN RESULTS
Our search identified 3538 records, after removing duplicates. We included 10 trials, involving 3319 participants, carried out in Bangladesh, Brazil, India, Kuwait, Philippines, South Africa and Sri Lanka. We identified two ongoing studies and one study is awaiting classification. The duration of interventions varied from 3 to 24 months. One study was carried out among adult women and one trial among both children and nonpregnant women. Most of the included trials were assessed as low or unclear risk of bias for key elements of selection, performance or reporting bias. Three trials used 41 mg to 60 mg iron/kg flour, three trials used less than 40 mg iron/kg and three trials used more than 60 mg iron/kg flour. One trial used various iron levels based on type of iron used: 80 mg/kg for electrolytic and reduced iron and 40 mg/kg for ferrous fumarate. All included studies contributed data for the meta-analyses. Iron-fortified wheat flour with or without other micronutrients added versus wheat flour (no added iron) with the same other micronutrients added Iron-fortified wheat flour with or without other micronutrients added versus wheat flour (no added iron) with the same other micronutrients added may reduce by 27% the risk of anaemia in populations (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.55 to 0.97; 5 studies, 2315 participants; low-certainty evidence). It is uncertain whether iron-fortified wheat flour with or without other micronutrients reduces iron deficiency (RR 0.46, 95% CI 0.20 to 1.04; 3 studies, 748 participants; very low-certainty evidence) or increases haemoglobin concentrations (in g/L) (mean difference MD 2.75, 95% CI 0.71 to 4.80; 8 studies, 2831 participants; very low-certainty evidence). No trials reported data on adverse effects in children (including constipation, nausea, vomiting, heartburn or diarrhoea), except for risk of infection or inflammation at the individual level. The intervention probably makes little or no difference to the risk of Infection or inflammation at individual level as measured by C-reactive protein (CRP) (mean difference (MD) 0.04, 95% CI -0.02 to 0.11; 2 studies, 558 participants; moderate-certainty evidence). Iron-fortified wheat flour with other micronutrients added versus unfortified wheat flour (nil micronutrients added) It is unclear whether wheat flour fortified with iron, in combination with other micronutrients decreases anaemia (RR 0.77, 95% CI 0.41 to 1.46; 2 studies, 317 participants; very low-certainty evidence). The intervention probably reduces the risk of iron deficiency (RR 0.73, 95% CI 0.54 to 0.99; 3 studies, 382 participants; moderate-certainty evidence) and it is unclear whether it increases average haemoglobin concentrations (MD 2.53, 95% CI -0.39 to 5.45; 4 studies, 532 participants; very low-certainty evidence). No trials reported data on adverse effects in children. Nine out of 10 trials reported sources of funding, with most having multiple sources. Funding source does not appear to have distorted the results in any of the assessed trials.
AUTHORS' CONCLUSIONS
Fortification of wheat flour with iron (in comparison to unfortified flour, or where both groups received the same other micronutrients) may reduce anaemia in the general population above two years of age, but its effects on other outcomes are uncertain. Iron-fortified wheat flour in combination with other micronutrients, in comparison with unfortified flour, probably reduces iron deficiency, but its effects on other outcomes are uncertain. None of the included trials reported data on adverse side effects except for risk of infection or inflammation at the individual level. The effects of this intervention on other health outcomes are unclear. Future studies at low risk of bias should aim to measure all important outcomes, and to further investigate which variants of fortification, including the role of other micronutrients as well as types of iron fortification, are more effective, and for whom.
Topics: Adolescent; Adult; Anemia; Child; Child, Preschool; Edetic Acid; Female; Ferric Compounds; Ferrous Compounds; Flour; Food, Fortified; Fumarates; Hemoglobin A; Humans; Infant; Iron; Iron Deficiencies; Male; Micronutrients; Middle Aged; Randomized Controlled Trials as Topic; Triticum; Young Adult
PubMed: 33461239
DOI: 10.1002/14651858.CD011302.pub3 -
Molecules (Basel, Switzerland) Dec 2020Aging and the emergence of age-associated illnesses are one of the major challenges of our present society. Alzheimer's disease (AD) is closely associated with aging and...
Aging and the emergence of age-associated illnesses are one of the major challenges of our present society. Alzheimer's disease (AD) is closely associated with aging and is defined by increasing memory loss and severe dementia. Currently, there are no therapy options available that halt AD progression. This work investigates three hallmarks of the disease (autophagy, neuroinflammation, and senescence) and systematically analyzes if there is a beneficial effect from three substances derived from food sources, the so called "nutraceuticals" epigallocatechin gallate, fisetin, and spermidine, on these hallmarks. The results imply a positive outlook for the reviewed substances to qualify as a novel treatment option for AD. A combination of nutraceutical substances and other preventive measures could have significant clinical impact in a multi-layered therapy approach to counter AD.
Topics: Alzheimer Disease; Animals; Autophagy; Catechin; Cellular Senescence; Dietary Supplements; Flavonols; Humans; Inflammation; Spermidine
PubMed: 33353228
DOI: 10.3390/molecules25246018 -
NeuroImage. Clinical 2020Cerebrospinal fluid (CSF) enhancement on T2-weighted post-contrast fluid-attenuated inversion recovery (pcT2wFLAIR) images is a relatively unknown neuroradiological... (Review)
Review
Cerebrospinal fluid (CSF) enhancement on T2-weighted post-contrast fluid-attenuated inversion recovery (pcT2wFLAIR) images is a relatively unknown neuroradiological marker for gadolinium-based contrast agent extravasation due to blood-brain barrier (BBB) disruption. We systematically reviewed human studies reporting on CSF enhancement on pcT2wFLAIR images to provide a comprehensive overview of prevalence of this new biomarker in healthy and diseased populations as well as its etiology and optimal detection methodology. We extracted information on the prevalence of CSF enhancement, its vascular risk factor and neuroimaging correlates, and methodological attributes of each study. Forty-four eligible studies were identified. By pooling data, we found that the prevalence of CSF enhancement was 82% (95% confidence interval (CI) 80-89) in meningitis (4 studies, 65 patients), 73% (95%CI 62-81) in cases with (post-) acute intracerebral hemorrhage (2 studies, 77 cases), 64% (95% CI 54-73) in cases who underwent surgery for aneurysm treatment (2 studies, 99 patients), 40% (95% CI 30-51) in cases who underwent surgery for carotid artery disease treatment (3 studies, 76 patients), 27% (95% CI 25-30) in cases with acute ischemic stroke (9 studies, 1148 patients), 21% (95% CI 17-23) in multiple sclerosis (6 studies, 897 patients), and 13% (95% CI 7-21) in adult controls (4 studies, 112 cases). Presence of CSF enhancement was associated with higher age in eleven studies, with lobar cerebral microbleeds in one study, and with cerebral atrophy in four studies. PcT2wFLAIR imaging represents a promising method that can provide novel perspectives on BBB leakage into CSF compartments, with the potential to reveal important new insights into the pathophysiological mechanisms of varying neurological diseases.
Topics: Adult; Brain Ischemia; Contrast Media; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Stroke
PubMed: 33053497
DOI: 10.1016/j.nicl.2020.102456 -
Academic Radiology Feb 2022To perform a systematic review and meta-analysis to determine risk factors for hypervascularization in hepatobiliary phase (HBP) hypointense nodules without arterial... (Meta-Analysis)
Meta-Analysis
RATIONALE AND OBJECTIVES
To perform a systematic review and meta-analysis to determine risk factors for hypervascularization in hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) in patients with hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
Pubmed and EMBASE databases were searched up to May 7, 2020. Studies which evaluated radiologic and clinical risk factors for hypervascularization in HBP hypointense nodules without APHE were included. Hazard ratios were meta-analytically pooled using random-effects model. Methodological quality of included studies was assessed using Quality in Prognostic Studies (QUIPS) tool.
RESULTS
Sixteen studies with 934 patients were included. HBP hypointense nodules without APHE with baseline size greater than 10 mm, T2 hyperintensity, and restricted diffusion showed risk for hypervascularization with pooled HRs of 2.95 (95% confidence interval [CI], 1.94-4.20), 4.21 (95% CI, 1.15-15.40), 5.83 (95% CI, 1.42-23.95), respectively. Previous HCC history contributed to hypervascularization of the nodules with hazard ratio of 2.06 (95% CI, 1.23-3.44). T1 hyperintensity, intralesional fat, Child-Pugh Class B, sex, alfa-fetoprotein, hepatitis B or C infection were not significant risk factors for hypervascularization (p ≥0.05). Study quality was generally moderate.
CONCLUSION
HBP hypointense nodules without APHE on gadoxetic acid-enhanced MRI with baseline size greater than 10 mm, T2 hyperintensity, restricted diffusion and previous hepatocellular carcinoma history pose higher risk for hypervascularization. Proper patient management in patients with HBP hypointense nodules without APHE on gadoxetic acid-enhanced MRI may need to be tailored according to these risk factors.
Topics: Carcinoma, Hepatocellular; Contrast Media; Gadolinium DTPA; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Retrospective Studies; Risk Factors
PubMed: 32962925
DOI: 10.1016/j.acra.2020.08.031 -
The Cochrane Database of Systematic... Aug 2020Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is...
BACKGROUND
Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is characterised by acute or subacute worsening of shortness of breath, cough, wheezing, and chest tightness and may be triggered by viral respiratory infection, poor compliance with usual medication, a change in the weather, or exposure to allergens or irritants. Most children with asthma have mild or moderate exacerbations and respond well to first-line therapy (inhaled short-acting beta-agonists and systemic corticosteroids). However, the best treatment for the small proportion of seriously ill children who do not respond to first-line therapy is not well understood. Currently, a large number of treatment options are available and there is wide variation in management.
OBJECTIVES
Main objective - To summarise Cochrane Reviews with or without meta-analyses of randomised controlled trials on the efficacy and safety of second-line treatment for children with acute exacerbations of asthma (i.e. after first-line treatments, titrated oxygen delivery, and administration of intermittent inhaled short-acting beta-agonists and oral corticosteroids have been tried and have failed) Secondary objectives - To identify gaps in the current evidence base that will inform recommendations for future research and subsequent Cochrane Reviews - To categorise information on reported outcome measures used in trials of escalation of treatment for acute exacerbations of asthma in children, and to make recommendations for development and reporting of standard outcomes in future trials and reviews - To identify relevant randomised controlled trials that have been published since the date of publication of each included review METHODS: We included Cochrane Reviews assessing interventions for children with acute exacerbations of asthma. We searched the Cochrane Database of Systematic Reviews. The search is current to 28 December 2019. We also identified trials that were potentially eligible for, but were not currently included in, published reviews. We assessed the quality of included reviews using the ROBIS criteria (tool used to assess risk of bias in systematic reviews). We presented an evidence synthesis of data from reviews alongside an evidence map of clinical trials. Primary outcomes were length of stay, hospital admission, intensive care unit admission, and adverse effects. We summarised all findings in the text and reported data for each outcome in 'Additional tables'.
MAIN RESULTS
We identified 17 potentially eligible Cochrane Reviews but extracted data from, and rated the quality of, 13 reviews that reported results for children alone. We excluded four reviews as one did not include any randomised controlled trials (RCTs), one did not provide subgroup data for children, and the last two had been updated and replaced by subsequent reviews. The 13 reviews included 67 trials; the number of trials in each review ranged from a single trial up to 27 trials. The vast majority of comparisons included between one and three trials, involving fewer than 100 participants. The total number of participants included in reviews ranged from 40 to 2630. All studies included children; 16 (24%) included children younger than two years of age. Most of the reviews reported search dates older than four years. We have summarised the published evidence as outlined in Cochrane Reviews. Key findings, in terms of our primary outcomes, are that (1) intravenous magnesium sulfate was the only intervention shown to reduce hospital length of stay (high-certainty evidence); (2) no evidence suggested that any intervention reduced the risk of intensive care admission (low- to very low-certainty evidence); (3) the risk of hospital admission was reduced by the addition of inhaled anticholinergic agents to inhaled beta-agonists (moderate-certainty evidence), the use of intravenous magnesium sulfate (high-certainty evidence), and the use of inhaled heliox (low-certainty evidence); (4) the addition of inhaled magnesium sulfate to usual bronchodilator therapy appears to reduce serious adverse events during hospital admission (moderate-certainty evidence); (5) aminophylline increased vomiting compared to placebo (moderate-certainty evidence) and increased nausea and nausea/vomiting compared to intravenous beta-agonists (low-certainty evidence); and (6) the addition of anticholinergic therapy to short-acting beta-agonists appeared to reduce the risk of nausea (high-certainty evidence) and tremor (moderate-certainty evidence) but not vomiting (low-certainty evidence). We considered 4 of the 13 reviews to be at high risk of bias based on the ROBIS framework. In all cases, this was due to concerns regarding identification and selection of studies. The certainty of evidence varied widely (by review and also by outcome) and ranged from very low to high.
AUTHORS' CONCLUSIONS
This overview provides the most up-to-date evidence on interventions for escalation of therapy for acute exacerbations of asthma in children from Cochrane Reviews of randomised controlled trials. A vast majority of comparisons involved between one and three trials and fewer than 100 participants, making it difficult to assess the balance between benefits and potential harms. Due to the lack of comparative studies between various treatment options, we are unable to make firm practice recommendations. Intravenous magnesium sulfate appears to reduce both hospital length of stay and the risk of hospital admission. Hospital admission is also reduced with the addition of inhaled anticholinergic agents to inhaled beta-agonists. However, further research is required to determine which patients are most likely to benefit from these therapies. Due to the relatively rare incidence of acute severe paediatric asthma, multi-centre research will be required to generate high-quality evidence. A number of existing Cochrane Reviews should be updated, and we recommend that a new review be conducted on the use of high-flow nasal oxygen therapy. Important priorities include development of an internationally agreed core outcome set for future trials in acute severe asthma exacerbations and determination of clinically important differences in these outcomes, which can then inform adequately powered future trials.
Topics: Acute Disease; Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aminophylline; Anti-Asthmatic Agents; Anti-Bacterial Agents; Asthma; Bias; Bronchodilator Agents; Child; Child, Preschool; Cholinergic Antagonists; Disease Progression; Helium; Humans; Infant; Length of Stay; Leukotriene Antagonists; Magnesium Sulfate; Nausea; Oxygen; Positive-Pressure Respiration; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Vomiting; Work of Breathing
PubMed: 32767571
DOI: 10.1002/14651858.CD012977.pub2 -
The Cochrane Database of Systematic... Jul 2020Anaemia is a condition where the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body's physiologic needs.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anaemia is a condition where the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body's physiologic needs. Fortification of wheat flour is deemed a useful strategy to reduce anaemia in populations.
OBJECTIVES
To determine the benefits and harms of wheat flour fortification with iron alone or with other vitamins and minerals on anaemia, iron status and health-related outcomes in populations over two years of age.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and other databases up to 4 September 2019.
SELECTION CRITERIA
We included cluster- or individually randomised controlled trials (RCT) carried out among the general population from any country aged two years and above. The interventions were fortification of wheat flour with iron alone or in combination with other micronutrients. Trials comparing any type of food item prepared from flour fortified with iron of any variety of wheat were included.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results and assessed the eligibility of studies for inclusion, extracted data from included studies and assessed risk of bias. We followed Cochrane methods in this review.
MAIN RESULTS
Our search identified 3048 records, after removing duplicates. We included nine trials, involving 3166 participants, carried out in Bangladesh, Brazil, India, Kuwait, Phillipines, Sri Lanka and South Africa. The duration of interventions varied from 3 to 24 months. One study was carried out among adult women and one trial among both children and nonpregnant women. Most of the included trials were assessed as low or unclear risk of bias for key elements of selection, performance or reporting bias. Three trials used 41 mg to 60 mg iron/kg flour, two trials used less than 40 mg iron/kg and three trials used more than 60 mg iron/kg flour. One trial employed various iron levels based on type of iron used: 80 mg/kg for electrolytic and reduced iron and 40 mg/kg for ferrous fumarate. All included studies contributed data for the meta-analyses. Seven studies compared wheat flour fortified with iron alone versus unfortified wheat flour, three studies compared wheat flour fortified with iron in combination with other micronutrients versus unfortified wheat flour and two studies compared wheat flour fortified with iron in combination with other micronutrients versus fortified wheat flour with the same micronutrients (but not iron). No studies included a 'no intervention' comparison arm. None of the included trials reported any other adverse side effects (including constipation, nausea, vomiting, heartburn or diarrhoea). Wheat flour fortified with iron alone versus unfortified wheat flour (no micronutrients added) Wheat flour fortification with iron alone may have little or no effect on anaemia (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.61 to 1.07; 5 studies; 2200 participants; low-certainty evidence). It probably makes little or no difference on iron deficiency (RR 0.43, 95% CI 0.17 to 1.07; 3 studies; 633 participants; moderate-certainty evidence) and we are uncertain about whether wheat flour fortified with iron increases haemoglobin concentrations by an average 3.30 (g/L) (95% CI 0.86 to 5.74; 7 studies; 2355 participants; very low-certainty evidence). No trials reported data on adverse effects in children, except for risk of infection or inflammation at the individual level. The intervention probably makes little or no difference to risk of Infection or inflammation at individual level as measured by C-reactive protein (CRP) (moderate-certainty evidence). Wheat flour fortified with iron in combination with other micronutrients versus unfortified wheat flour (no micronutrients added) Wheat flour fortified with iron, in combination with other micronutrients, may or may not decrease anaemia (RR 0.95, 95% CI 0.69 to 1.31; 2 studies; 322 participants; low-certainty evidence). It makes little or no difference to average risk of iron deficiency (RR 0.74, 95% CI 0.54 to 1.00; 3 studies; 387 participants; moderate-certainty evidence) and may or may not increase average haemoglobin concentrations (mean difference (MD) 3.29, 95% CI -0.78 to 7.36; 3 studies; 384 participants; low-certainty evidence). No trials reported data on adverse effects in children. Wheat flour fortified with iron in combination with other micronutrients versus fortified wheat flour with same micronutrients (but not iron) Given the very low certainty of the evidence, the review authors are uncertain about the effects of wheat flour fortified with iron in combination with other micronutrients versus fortified wheat flour with same micronutrients (but not iron) in reducing anaemia (RR 0.24, 95% CI 0.08 to 0.71; 1 study; 127 participants; very low-certainty evidence) and in reducing iron deficiency (RR 0.42, 95% CI 0.18 to 0.97; 1 study; 127 participants; very low-certainty evidence). The intervention may make little or no difference to the average haemoglobin concentration (MD 0.81, 95% CI -1.28 to 2.89; 2 studies; 488 participants; low-certainty evidence). No trials reported data on the adverse effects in children. Eight out of nine trials reported source of funding with most having multiple sources. Funding source does not appear to have distorted the results in any of the assessed trials.
AUTHORS' CONCLUSIONS
Eating food items containing wheat flour fortified with iron alone may have little or no effect on anaemia and probably makes little or no difference in iron deficiency. We are uncertain on whether the intervention with wheat flour fortified with iron increases haemoglobin concentrations improve blood haemoglobin concentrations. Consuming food items prepared from wheat flour fortified with iron, in combination with other micronutrients, has little or no effect on anaemia, makes little or no difference to iron deficiency and may or may not improve haemoglobin concentrations. In comparison to fortified flour with micronutrients but no iron, wheat flour fortified with iron with other micronutrients, the effects on anaemia and iron deficiency are uncertain as certainty of the evidence has been assessed as very low. The intervention may make little or no difference to the average haemoglobin concentrations in the population. None of the included trials reported any other adverse side effects. The effects of this intervention on other health outcomes are unclear.
Topics: Adolescent; Adult; Anemia; Child; Child, Preschool; Edetic Acid; Female; Ferric Compounds; Ferrous Compounds; Flour; Food, Fortified; Fumarates; Hemoglobin A; Humans; Infant; Iron; Iron Deficiencies; Male; Micronutrients; Middle Aged; Randomized Controlled Trials as Topic; Triticum; Young Adult
PubMed: 32677706
DOI: 10.1002/14651858.CD011302.pub2 -
The Cochrane Database of Systematic... May 2020Chelation therapy is promoted and practiced around the world as a form of alternative medicine in the treatment of atherosclerotic cardiovascular disease. It has been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chelation therapy is promoted and practiced around the world as a form of alternative medicine in the treatment of atherosclerotic cardiovascular disease. It has been suggested as a safe, relatively inexpensive, non-surgical method of restoring blood flow in atherosclerotic vessels. However, there is currently limited high-quality, adequately-powered research informing evidence-based medicine on the topic, specifically regarding clinical outcomes. Due to this limited evidence, the benefit of chelation therapy remains controversial at present. This is an update of a review first published in 2002.
OBJECTIVES
To assess the effects of ethylene diamine tetra-acetic acid (EDTA) chelation therapy versus placebo or no treatment on clinical outcomes among people with atherosclerotic cardiovascular disease.
SEARCH METHODS
For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 6 August 2019. We searched the bibliographies of the studies retrieved by the literature searches for further trials.
SELECTION CRITERIA
We included studies if they were randomised controlled trials of EDTA chelation therapy versus placebo or no treatment in participants with atherosclerotic cardiovascular disease. The main outcome measures we considered include all-cause or cause-specific mortality, non-fatal cardiovascular events, direct or indirect measurement of disease severity, and subjective measures of improvement or adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality using standard Cochrane procedures. A third author considered any unresolved issues, and we discussed any discrepancies until a consensus was reached. We contacted study authors for additional information.
MAIN RESULTS
We included five studies with a total of 1993 randomised participants. Three studies enrolled participants with peripheral vascular disease and two studies included participants with coronary artery disease, one of which specifically recruited people who had had a myocardial infarction. The number of participants in each study varied widely (from 10 to 1708 participants), but all studies compared EDTA chelation to a placebo. Risk of bias for the included studies was generally moderate to low, but one study had high risk of bias because the study investigators broke their randomisation code halfway through the study and rolled the placebo participants over to active treatment. Certainty of the evidence, as assessed by GRADE, was generally low to very low, which was mostly due to a paucity of data in each outcome's meta-analysis. This limited our ability to draw any strong conclusions. We also had concerns about one study's risk of bias regarding blinding and outcome assessment that may have biased the results. Two studies with coronary artery disease participants reported no evidence of a difference in all-cause mortality between chelation therapy and placebo (risk ratio (RR) 0.97, 95% CI 0.73 to 1.28; 1792 participants; low-certainty). One study with coronary artery disease participants reported no evidence of a difference in coronary heart disease deaths between chelation therapy and placebo (RR 1.02, 95% CI 0.70 to 1.48; 1708 participants; very low-certainty). Two studies with coronary artery disease participants reported no evidence of a difference in myocardial infarction (RR 0.81, 95% CI 0.57 to 1.14; 1792 participants; moderate-certainty), angina (RR 0.95, 95% CI 0.55 to 1.67; 1792 participants; very low-certainty), and coronary revascularisation (RR 0.46, 95% CI 0.07 to 3.25; 1792 participants). Two studies (one with coronary artery disease participants and one with peripheral vascular disease participants) reported no evidence of a difference in stroke (RR 0.88, 95% CI 0.40 to 1.92; 1867 participants; low-certainty). Ankle-brachial pressure index (ABPI; also known as ankle brachial index) was measured in three studies, all including participants with peripheral vascular disease; two studies found no evidence of a difference in the treatment groups after three months after treatment (mean difference (MD) 0.02, 95% CI -0.03 to 0.06; 181 participants; low-certainty). A third study reported an improvement in ABPI in the EDTA chelation group, but this study was at high risk of bias. Meta-analysis of maximum and pain-free walking distances three months after treatment included participants with peripheral vascular disease and showed no evidence of a difference between the treatment groups (MD -31.46, 95% CI -87.63 to 24.71; 165 participants; 2 studies; low-certainty). Quality of life outcomes were reported by two studies that included participants with coronary artery disease, but we were unable to pool the data due to different methods of reporting and varied criteria. However, there did not appear to be any major differences between the treatment groups. None of the included studies reported on vascular deaths. Overall, there was no evidence of major or minor adverse events associated with EDTA chelation treatment.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence to determine the effectiveness or ineffectiveness of chelation therapy in improving clinical outcomes of people with atherosclerotic cardiovascular disease. More high-quality, randomised controlled trials are needed that assess the effects of chelation therapy on longevity and quality of life among people with atherosclerotic cardiovascular disease.
Topics: Angina Pectoris; Arteriosclerosis; Cause of Death; Chelating Agents; Chelation Therapy; Coronary Artery Disease; Edetic Acid; Humans; Myocardial Infarction; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Stroke
PubMed: 32367513
DOI: 10.1002/14651858.CD002785.pub2