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Journal of Neuromuscular Diseases 2021Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective...
BACKGROUND
Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and β-oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking.
OBJECTIVE
The objective of this study was to collate all published evidence on pharmacological therapies for the aforementioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the "treatabolome" project.
METHODS
A systematic literature review was conducted to retrieve all levels of evidence examining the therapeutic efficacy of pharmacological treatments on metabolic myopathies related to glycogen storage and lipid metabolism. A key inclusion criterion was the availability of the genetic variant of the treated patients in order to link treatment outcome with the genetic defect.
RESULTS
Of the 1,085 articles initially identified, 268 full-text articles were assessed for eligibility, of which 87 were carried over into the final data extraction. The most studied metabolic myopathies were Pompe disease (45 articles), multiple acyl-CoA dehydrogenase deficiency related to mutations in the ETFDH gene (15 articles) and systemic primary carnitine deficiency (8 articles). The most studied therapeutic management strategies for these diseases were enzyme replacement therapy, riboflavin, and carnitine supplementation, respectively.
CONCLUSIONS
This systematic review provides evidence for treatments of metabolic myopathies linked with the genetic defect in a computationally accessible format suitable for databasing in the treatabolome system, which will enable clinicians to acquire evidence on appropriate therapeutic options for their patient at the time of diagnosis.
Topics: Glycogen; Glycogen Storage Disease Type II; Humans; Lipid Metabolism; Metabolism, Inborn Errors; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Muscle Weakness; Mutation
PubMed: 33720849
DOI: 10.3233/JND-200621 -
Seminars in Ophthalmology Apr 2021: To review the scientific literature on the comparison of the efficacy of different corneal collagen crosslinking (CXL) protocols for the treatment of progressive...
: To review the scientific literature on the comparison of the efficacy of different corneal collagen crosslinking (CXL) protocols for the treatment of progressive keratoconus. Systematic review of randomized clinical trials (RCTs) on CXL outcomes. A search was carried out using the Cochrane Library, PubMed, EMBASE, Web of Science, Ovid MEDLINE, and Scopus databases. Internal validity was analyzed by applying the filter CASPe (Critical Appraisal Skills Program Spain). The search yielded 1151 articles, and among these, 14 articles met the inclusion and exclusion criteria defined. Conventional (S) crosslinking (CXL) provided better topographic outcomes than transepithelial (TE) CXL, and S-CXL had a better therapeutic effect of corneal flattening than accelerated (A) CXL. The corneal thinning after CXL was lower with hypotonic riboflavin than with riboflavin-dextran. While one study demonstrated a better therapeutic effect of corneal flattening with S-CXL than with A-CXL, another study showed similar results between both techniques. No correlation was found between the depth of the demarcation line and topographic changes, which was not a direct measure of treatment effectiveness. Quality analysis of the literature reviewed yielded a mean score of 8.64, indicating that the RCTs evaluated had an overall acceptable quality. Good-quality RCTs comparing CXL techniques have been conducted, and most of them suggest that epi-off CXL can be considered the standard treatment for progressive keratoconus. TE-CXL and iontophoresis-assisted CXL are mainly indicated in patients with a risk of corneal scarring and patients with pain intolerance, respectively.
Topics: Collagen; Cross-Linking Reagents; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents
PubMed: 33617389
DOI: 10.1080/08820538.2021.1890784 -
Neuromuscular Disorders : NMD Mar 2021Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder with a dramatic clinical presentation. It was recently discovered that MADD may...
Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder with a dramatic clinical presentation. It was recently discovered that MADD may present at an advanced age. The clinical and laboratory data of an index patient and patients previously diagnosed at our institution were collected. A systematic review of previous studies retrieved from the PubMed, MEDLINE, and Embase databases published by February 1, 2020 was performed to collect patients with very-late-onset MADD (VLO-MADD, onset age > 60 years) globally and patients with late-onset MADD (LO-MADD, onset age < 60 years) in Taiwan. The clinical characteristics of the VLO-MADD patients were compared to those of LO-MADD patients. We report a patient with VLO-MADD who developed the first symptom at the age of 61 years. The patient presented with a Reye-like syndrome after taking aspirin for coronary artery disease. Repeated bouts of weakness were noted. Two variants of c.250 G > A (;) 419C > T were observed in the ETFDH gene. Another four patients with VLO-MADD were identified globally. Eighteen patients with LO-MADD were collected from our department and previously reported patients in Taiwan. There was no difference in the clinical symptoms (except for the onset age) or laboratory data between these two groups. Homozygous variants were not observed in any patients in the VLO-MADD group but were detected in 12 patients (66.6%) in the LO-MADD group (p = 0.014). Patients with MADD may first show symptoms in their 6th decade or beyond. The disease course may lead to erroneous diagnoses in this age group.
Topics: Acyl-CoA Dehydrogenase; Adult; Age of Onset; Aged; Cohort Studies; Female; Homozygote; Humans; Male; Middle Aged; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Muscle, Skeletal; Mutation; Riboflavin; Taiwan; Young Adult
PubMed: 33589341
DOI: 10.1016/j.nmd.2021.01.006 -
Ophthalmology Aug 2021To evaluate the safety and efficacy of transepithelial corneal cross-linking in comparison with the established epithelium-off technique for corneal ectasia. (Meta-Analysis)
Meta-Analysis
TOPIC
To evaluate the safety and efficacy of transepithelial corneal cross-linking in comparison with the established epithelium-off technique for corneal ectasia.
CLINICAL RELEVANCE
Considerable debate exists regarding whether transepithelial and epithelium-off cross-linking are comparable in their safety and efficacy.
METHODS
We searched 16 electronic databases, including Medline, Embase, Web of Science, and the grey literature, current to July 8, 2020, for randomized controlled trials comparing transepithelial and epithelium-off cross-linking for corneal ectasia. We excluded studies evaluating cross-linking for nonectatic indications, as well as non-randomized controlled trials. Our primary outcome was the change in maximal keratometry (K) at 12 months after cross-linking, and we considered additional topographic, visual, and safety outcomes. We summarized our analyses by calculating weighted mean differences (MDs) with associated 95% confidence intervals (CIs) for continuous outcomes and relative risks (RRs) with corresponding 95% CIs for dichotomous outcomes. We conducted trial sequential analysis to determine whether the required information size was met for each outcome. The quality of individual trials was evaluated using the Cochrane Collaboration's risk of bias assessment tool, and the evidence was assessed at an outcome level using the Grading of Recommendations Assessment, Development, and Evaluation methodology.
RESULTS
Twelve studies totaling 966 eyes were eligible. A significant difference was found between transepithelial and epithelium-off cross-linking groups in the change in K at 12 months (MD, 0.75; 95% CI, 0.23-1.28; P = 0.004; primary outcome) and at longest follow-up (MD, 1.20; 95% CI, 0.62-1.77; P < 0.001; secondary outcome) after treatment. No significant difference was found between the 2 groups when examining uncorrected distance visual acuity (MD, 0.04; 95% CI, -0.06 to 0.14; P = 0.386) or corrected distance visual acuity (MD, 0.01; 95% CI, -0.06 to 0.09; P = 0.732). Transepithelial cross-linking was associated with significantly fewer complications than the epithelium-off approach (RR, 0.22; 95% CI, 0.06-0.79; P = 0.020), although it was associated with an increased rate of disease progression at 12 months after treatment (RR, 4.49; 95% CI, 1.24-16.25; P = 0.022). The required information size was met for our primary outcome and trial sequential analysis supported the conventional meta-analysis. The quality of evidence was rated as moderate using the Grading of Recommendations Assessment, Development, and Evaluation methodology.
DISCUSSION
The efficacy of transepithelial cross-linking remains inferior to the epithelium-off approach, although it is significantly safer.
Topics: Collagen; Corneal Stroma; Cross-Linking Reagents; Debridement; Dilatation, Pathologic; Epithelium, Corneal; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Randomized Controlled Trials as Topic; Riboflavin; Ultraviolet Rays; Visual Acuity
PubMed: 33383093
DOI: 10.1016/j.ophtha.2020.12.023 -
Journal of AAPOS : the Official... Dec 2020Keratoconus is a bilateral progressive noninflammatory degenerative disease of the cornea characterized by corneal thinning, irregular astigmatism, and subsequent visual... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Keratoconus is a bilateral progressive noninflammatory degenerative disease of the cornea characterized by corneal thinning, irregular astigmatism, and subsequent visual impairment. It has an aggressive course in children. This systematic review evaluates the efficacy of available corneal collagen cross-linking (CXL) protocols for stabilizing the cornea in pediatric patients with keratoconus.
METHODS
We searched all peer-reviewed publications from 2000 to 2019 indexed in PubMed, Google Scholars, Web of Science, and Cochrane's Database for the terms keratoconus and cross-linking. The following data were extracted from eligible studies: study design, type of intervention, number of the eyes and mean age of patients for each study, duration of follow-up period, mean pre- and postoperative uncorrected and corrected visual acuity, keratometric and aberrometric indices, were analyzed with RevMan 5.3 software. Intra-and intergroup post hoc analyses of outcome variables were performed using t tests.
RESULTS
A total of 28 studies, including 1,300 eyes, were reviewed. In conventional and accelerated epithelium-off techniques, there was a significant improvement in uncorrected and corrected visual acuities. Similarly, the keratometric indices improved significantly after CXL. Uncorrected visual acuity did not alter after CXL using transepithelial method.
CONCLUSIONS
Both conventional and accelerated collagen CXL of the cornea are effective therapeutic options in management of keratoconus in children.
Topics: Child; Humans; Collagen; Cornea; Corneal Topography; Cross-Linking Reagents; Keratoconus; Photochemotherapy; Photosensitizing Agents; Riboflavin; Ultraviolet Rays
PubMed: 33279597
DOI: 10.1016/j.jaapos.2020.08.013 -
The British Journal of Nutrition Aug 2021Maintaining nutritional adequacy contributes to successful ageing. B vitamins involved in one-carbon metabolism regulation (folate, riboflavin, vitamins B6 and B12) are...
Maintaining nutritional adequacy contributes to successful ageing. B vitamins involved in one-carbon metabolism regulation (folate, riboflavin, vitamins B6 and B12) are critical nutrients contributing to homocysteine and epigenetic regulation. Although cross-sectional B vitamin intake in ageing populations is characterised, longitudinal changes are infrequently reported. This systematic review explores age-related changes in dietary adequacy of folate, riboflavin, vitamins B6 and B12 in community-dwelling older adults (≥65 years at follow-up). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases (MEDLINE, Embase, BIOSIS, CINAHL) were systematically screened, yielding 1579 records; eight studies were included (n 3119 participants, 2–25 years of follow-up). Quality assessment (modified Newcastle–Ottawa quality scale) rated all of moderate–high quality. The estimated average requirement cut-point method estimated the baseline and follow-up population prevalence of dietary inadequacy. Riboflavin (seven studies, n 1953) inadequacy progressively increased with age; the prevalence of inadequacy increased from baseline by up to 22·6 and 9·3 % in males and females, respectively. Dietary folate adequacy (three studies, n 2321) improved in two studies (by up to 22·4 %), but the third showed increasing (8·1 %) inadequacy. Evidence was similarly limited (two studies, respectively) and inconsistent for vitamins B6 (n 559; −9·9 to 47·9 %) and B12 (n 1410; −4·6 to 7·2 %). This review emphasises the scarcity of evidence regarding micronutrient intake changes with age, highlighting the demand for improved reporting of longitudinal changes in nutrient intake that can better direct micronutrient recommendations for older adults. This review was registered with PROSPERO (CRD42018104364).
Topics: Aged; Cross-Sectional Studies; Diet; Female; Folic Acid; Humans; Male; Riboflavin; Vitamin B 12; Vitamin B 6; Vitamin B Complex
PubMed: 33118888
DOI: 10.1017/S0007114520004249 -
Journal of Neuromuscular Diseases 2021Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid...
BACKGROUND
Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking.
OBJECTIVE
We collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies.
METHODS
We searched several databases for randomised controlled trials (RCT), observational studies and case reports of therapies in hereditary peripheral neuropathies. Two investigators extracted and analysed the data independently, assessing study quality using the Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence in conjunction with the Jadad scale.
RESULTS
Of the 2046 studies initially identified, 119 trials met our inclusion criteria, of which only 34 were carried over into our final analysis. Ascorbic acid was shown to have no therapeutic benefit in CMT1A, while a combination of baclofen, naltrexone and sorbitol (PXT3003) demonstrated some efficacy, but phase III data are incomplete. In TTR-related amyloid polyneuropathy tafamidis, patisiran, inotersen and revusiran showed significant benefit in high quality RCTs. Smaller studies showed the efficacy of L-serine for SPTLC1-related hereditary sensory neuropathy, riboflavin for Brown-Vialetto-Van Laere syndrome (SLC52A2/3) and phytanic acid-poor diet in Refsum disease (PHYH).
CONCLUSIONS
The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies.
Topics: Amyloid Neuropathies, Familial; Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy; Humans
PubMed: 32773395
DOI: 10.3233/JND-200546 -
The Cochrane Database of Systematic... Jun 2020Infectious keratitis is an infection of the cornea that can be caused by bacteria, viruses, fungi, protozoa, or parasites. It may be associated with ocular surgery,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Infectious keratitis is an infection of the cornea that can be caused by bacteria, viruses, fungi, protozoa, or parasites. It may be associated with ocular surgery, trauma, contact lens wear, or conditions that cause deficiency or loss of corneal sensation, or suppression of the immune system, such as diabetes, chronic use of topical steroids, or immunomodulatory therapies. Photoactivated chromophore for collagen cross-linking (PACK-CXL) of the cornea is a therapy that has been successful in treating eye conditions such as keratoconus and corneal ectasia. More recently, PACK-CXL has been explored as a treatment option for infectious keratitis.
OBJECTIVES
To determine the comparative effectiveness and safety of PACK-CXL with standard therapy versus standard therapy alone for the treatment of bacterial keratitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 7); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Science Information database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 8 July 2019.
SELECTION CRITERIA
We included randomized controlled trials (RCTs), quasi-RCTs, and controlled clinical trials (CCTs) of PACK-CXL for bacterial keratitis. We included quasi-RCTs and CCTs as we anticipated that there would not be many RCTs eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors working independently selected studies for inclusion in the review, assessed trials for risk of bias, and extracted data. The primary outcome was proportion of participants with complete healing at four to eight weeks. Secondary outcomes included visual acuity, morphology, adverse events, and treatment failure at four to eight weeks.
MAIN RESULTS
We included three trials (two RCTs and one quasi-RCT) in this review for a total of 59 participants (59 eyes) with bacterial keratitis. Trials were all single-center and were conducted in Egypt, Iran, and Thailand between 2010 and 2014. It is very uncertain whether PACK-CXL with standard antibiotic therapy is more effective than standard antibiotic therapy alone for re-epithelialization and complete healing (risk ratio (RR) 1.53, 95% confidence interval (CI) 0.88 to 2.66; participants = 15). We judged the certainty of the evidence to be very low due to the small sample size and high risk of selection and performance bias. The high risk of selection bias reflects the overall review. Masking of participants was not possible for the surgical arm. No participant had a best-corrected visual acuity of 20/100 or better at eight weeks (very low certainty evidence). There is also no evidence that use of PACK-CXL with standard therapy results in fewer instances of treatment failure than standard therapy alone (RR 0.50, 95% CI 0.05 to 4.98; participants = 32). We judged the certainty of evidence to be low due to the small sample size and high risk of selection bias. There were no adverse events reported at 14 days (low certainty evidence). Data on other outcomes, such as visual acuity and morphological characteristics, could not be compared because of variable time points and specific metrics.
AUTHORS' CONCLUSIONS
The current evidence on the effectiveness of PACK-CXL for bacterial keratitis is of low certainty and clinically heterogenous in regard to outcomes. There are five ongoing RCTs enrolling 1136 participants that may provide better answers in the next update of this review. Any future research should include subgroup analyses based on etiology. A core outcomes set would benefit healthcare decision-makers in comparing and understanding study data.
Topics: Anti-Bacterial Agents; Collagen; Eye Infections, Bacterial; Humans; Keratitis; Photosensitizing Agents; Randomized Controlled Trials as Topic; Riboflavin; Ultraviolet Therapy; Visual Acuity
PubMed: 32557558
DOI: 10.1002/14651858.CD013001.pub2 -
The Cochrane Database of Systematic... May 2020Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system. Although the exact pathogenesis remains unknown, the leading theory is that it... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system. Although the exact pathogenesis remains unknown, the leading theory is that it results from immune system dysregulation. Approved disease-modifying therapy appears to modulate the immune system to improve MS-related outcomes. There is substantial interest in the ability of dietary interventions to influence MS-related outcomes. This is an update of the Cochrane Review 'Dietary interventions for multiple sclerosis' (Farinotti 2003; Farinotti 2007; Farinotti 2012).
OBJECTIVES
To assess the effects of dietary interventions (including dietary plans with recommendations for specific whole foods, macronutrients, and natural health products) compared to placebo or another intervention on health outcomes (including MS-related outcomes and serious adverse events) in people with MS.
SEARCH METHODS
On 30 May 2019, we searched CENTRAL, MEDLINE, Embase, and Web of Science. We also searched ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (ICTRP), and Networked Digital Library of Theses and Dissertations (NDLTD). We checked reference lists in identified trials and requested information from trial authors to identify any additional published or unpublished data.
SELECTION CRITERIA
We included any randomized controlled trial (RCT) or controlled clinical trial (CCT) examining the effect of a dietary intervention versus placebo or another intervention among participants with MS on MS-related outcomes, including relapses, disability progression, and magnetic resonance imaging (MRI) measures.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Planned primary outcomes were number of participants experiencing relapse and change in disability progression, according to a validated disability scale at the last reported follow-up. Secondary outcomes included MRI activity, safety, and patient-reported outcomes. We entered and analysed data in Review Manager 5.
MAIN RESULTS
We found 41 full-text articles examining 30 trials following full-text review. Participants were adults with MS, defined by established criteria, presenting to MS clinics in Europe, North America, and the Middle East. Study design varied considerably, although all trials had at least one methodological issue leading to unknown or high risk of bias. Trials examined: supplementation to increase polyunsaturated fatty acids (PUFAs) (11 trials); a variety of antioxidant supplements (10 trials); dietary programmes (3 trials); and other dietary supplements (e.g. acetyl L-carnitine, biotin, creatine, palmitoylethanolamide, probiotic, riboflavin) (6 trials). In three trials comparing PUFAs with monounsaturated fatty acids (MUFAs), the evidence was very uncertain concerning difference in relapses (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.88 to 1.20; 3 studies, 217 participants; 75% in the PUFA group versus 74% in the MUFA group; very low-certainty evidence). Among four trials comparing PUFAs with MUFAs, there may be little to no difference in global impression of deterioration (RR 0.85, 95% CI 0.71 to 1.03; 4 studies, 542 participants; 40% in the PUFA group versus 47% in the MUFA group; low-certainty evidence). In two trials comparing PUFAs with MUFAs (102 participants), there was very low-certainty evidence for change in disability progression. None of the PUFA versus MUFA trials examined MRI outcomes. In one trial comparing PUFAs with MUFAs (40 participants), there were no serious adverse events; based on low-certainty evidence. In two trials comparing different PUFAs (omega-3 versus omega-6), there may be little to no difference in relapses (RR 1.02, 95% CI 0.62 to 1.66; 2 studies, 129 participants; 30% in the omega-3 versus 29% in the omega-6 group; low-certainty evidence). Among three trials comparing omega-3 with omega-6, there may be little to no difference in change in disability progression, measured as mean change in Expanded Disability Status Scale (EDSS) (mean difference (MD) 0.00, 95% CI -0.30 to 0.30; 3 studies, 166 participants; low-certainty evidence). In one trial comparing omega-3 with omega-6, there was likely no difference in global impression of deterioration (RR 0.99, 95% CI 0.51 to 1.91; 1 study, 86 participants; 29% in omega-3 versus 29% in omega-6 group; moderate-certainty evidence). In one trial comparing omega-3 with omega-6 (86 participants), there was likely no difference in number of new T1- weighted gadolinium-enhancing lesions, based on moderate-certainty evidence. In four trials comparing omega-3 with omega-6, there may be little to no difference in serious adverse events (RR 1.12, 95% CI 0.38 to 3.31; 4 studies, 230 participants; 6% in omega-3 versus 5% in omega-6 group; low-certainty evidence). In four trials examining antioxidant supplementation with placebo, there may be little to no difference in relapses (RR 0.98, 95% CI 0.59 to 1.64; 4 studies, 345 participants; 17% in the antioxidant group versus 17% in the placebo group; low-certainty evidence). In six trials examining antioxidant supplementation with placebo, the evidence was very uncertain concerning change in disability progression, measured as mean change of EDSS (MD -0.19, 95% CI -0.49 to 0.11; 6 studies, 490 participants; very low-certainty evidence). In two trials examining antioxidant supplementation with placebo, there may be little to no difference in global impression of deterioration (RR 0.99, 95% 0.50 to 1.93; 2 studies, 190 participants; 15% in the antioxidant group versus 15% in the placebo group; low-certainty evidence). In two trials examining antioxidant supplementation with placebo, the evidence was very uncertain concerning difference in gadolinium-enhancing lesions (RR 0.67, 95% CI 0.09 to 4.88; 2 studies, 131 participants; 11% in the antioxidant group versus 16% in the placebo group; very low-certainty evidence). In three trials examining antioxidant supplementation versus placebo, there may be little to no difference in serious adverse events (RR. 0.72, 95% CI 0.17 to 3.08; 3 studies, 222 participants; 3% in the antioxidant group versus 4% in the placebo group; low-certainty evidence).
AUTHORS' CONCLUSIONS
There are a variety of controlled trials addressing the effects of dietary interventions for MS with substantial variation in active treatment, comparator, and outcomes of interest. PUFA administration may not differ when compared to alternatives with regards to relapse rate, disability worsening, or overall clinical status in people with MS, but evidence is uncertain. Similarly, at present, there is insufficient evidence to determine whether supplementation with antioxidants or other dietary interventions have any impact on MS-related outcomes.
Topics: Adult; Antioxidants; Diet, Fat-Restricted; Diet, Paleolithic; Diet, Vegetarian; Dietary Supplements; Disease Progression; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Humans; Multiple Sclerosis; Randomized Controlled Trials as Topic; Recurrence
PubMed: 32428983
DOI: 10.1002/14651858.CD004192.pub4 -
The Cochrane Database of Systematic... Apr 2020Zinc is a vital micronutrient for humans and is essential for protein synthesis, cell growth, and differentiation. Severe zinc deficiency can lead to slower physical,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Zinc is a vital micronutrient for humans and is essential for protein synthesis, cell growth, and differentiation. Severe zinc deficiency can lead to slower physical, cognitive and sexual growth, cause skin disorders, decrease immunity, increase incidence of acute illnesses in infants and children and contribute to childhood stunting. By estimation, 17.3% of the world population is at risk of inadequate zinc intake. Such nutritional impairment increases the risk of diarrhoea and pneumonia by 20%, as well as leads to a global loss of more than 16 million disability-adjusted life years in children less than five years of age. Not only does zinc deficiency affect lives, it adds to the considerable financial burden on depleted resources in countries that are most affected. By preventing or curing this deficiency, we can improve childhood mortality, morbidity and growth.
OBJECTIVES
To assess the effectiveness of zinc supplementation for the promotion of growth, reduction in mortality, and the prevention of infections in infants less than six months of age.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 4), MEDLINE via PubMed (1966 to 18 May 2018), Embase (1980 to 18 May 2018), and CINAHL (1982 to 18 May 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. An updated search from 1 January 2018 to 29 January 2020 was run in the following databases: CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost.
SELECTION CRITERIA
All randomised controlled (individual and cluster randomised) and quasi-randomised trials of zinc supplementation in healthy, term infants, less than six months of age comparing infant mortality, incidence of diarrhoea or respiratory illnesses, growth and/or serum zinc levels were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors screened search results (title and abstracts) and relevant full texts. Studies fulfilling prespecified inclusion criteria were included with any disagreements resolved by consensus. Extraction and analysis were then conducted. We used the GRADE approach to assess the quality of evidence as indicated by certainty in effect estimates.
MAIN RESULTS
Eight studies (with 85,629 infants) were included and five studies were meta-analysed, out of which four studies compared zinc with placebo, and one compared zinc plus riboflavin versus riboflavin. Certain growth outcomes after six months of intervention (Weight for Age Z-scores (WAZ) (standardised mean difference) (SMD) 0.16, 95% CI 0.03 to 0.29; three studies, n = 955; fixed-effect; heterogeneity Chi² P = 0.96); I² = 0%); change in WAZ (SMD 0.16, 95% CI 0.07 to 0.25; one study, n = 386; fixed-effect); (Weight-for-Length Z-score (WLZ) (SMD 0.15, 95% CI 0.02 to 0.28; three studies, n = 955; fixed-effect; heterogeneity: Chi² P = 0.81); I² = 0%); (change in WLZ (SMD 0.17, 95% CI 0.06 to 0.28; one study, n = 386; fixed-effect)) were positively affected by zinc supplementation compared to placebo. A single study reported no difference in the incidence of diarrhoea and lower respiratory tract infection with zinc supplementation. Zinc had no effect on mortality in children younger than 12 months. When zinc plus riboflavin was compared to riboflavin only, significant improvement was observed in the incidence of wasting at 24 months (risk ratio (RR) 0.59, 95% CI 0.37 to 0.96; one study, n = 296; fixed-effect), but significant worsening of incidence of stunting was present at 21 months (RR 1.53, 95% CI 1.09 to 2.16; one study, n = 298; fixed-effect).
AUTHORS' CONCLUSIONS
There was a significant positive impact of zinc supplementation on WAZ and WLZ after six months of intervention in infants compared to placebo. When a combined supplement of zinc and riboflavin was compared to riboflavin, there was a significant reduction in wasting at 24 months, but stunting at 21 months was negatively affected. Although included trials were of good-to-moderate quality, evidence that could be meta-analysed was based on a few studies which affected the overall quality of results. Regardless, there is a need for strong trials conducted in infants younger than six months before a strong recommendation can be made supporting zinc supplementation in this age group.
Topics: Body Weight; Growth; Humans; Infant; Infant Mortality; Infant, Newborn; Infection Control; Randomized Controlled Trials as Topic; Riboflavin; Trace Elements; Vitamin B Complex; Wasting Syndrome; Zinc
PubMed: 32266964
DOI: 10.1002/14651858.CD010205.pub2