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The Cochrane Database of Systematic... Mar 2021Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many...
BACKGROUND
Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many interventions are used to treat SLE with varying efficacy, risks, and benefits.
OBJECTIVES
To assess the effects of interventions for cutaneous disease in SLE.
SEARCH METHODS
We searched the following databases up to June 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, Wiley Interscience Online Library, and Biblioteca Virtual em Saude (Virtual Health Library). We updated our search in September 2020, but these results have not yet been fully incorporated.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of interventions for cutaneous disease in SLE compared with placebo, another intervention, no treatment, or different doses of the same intervention. We did not evaluate trials of cutaneous lupus in people without a diagnosis of SLE.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes were complete and partial clinical response. Secondary outcomes included reduction (or change) in number of clinical flares; and severe and minor adverse events. We used GRADE to assess the quality of evidence.
MAIN RESULTS
Sixty-one RCTs, involving 11,232 participants, reported 43 different interventions. Trials predominantly included women from outpatient clinics; the mean age range of participants was 20 to 40 years. Twenty-five studies reported baseline severity, and 22 studies included participants with moderate to severe cutaneous lupus erythematosus (CLE); duration of CLE was not well reported. Studies were conducted mainly in multi-centre settings. Most often treatment duration was 12 months. Risk of bias was highest for the domain of reporting bias, followed by performance/detection bias. We identified too few studies for meta-analysis for most comparisons. We limited this abstract to main comparisons (all administered orally) and outcomes. We did not identify clinical trials of other commonly used treatments, such as topical corticosteroids, that reported complete or partial clinical response or numbers of clinical flares. Complete clinical response Studies comparing oral hydroxychloroquine against placebo did not report complete clinical response. Chloroquine may increase complete clinical response at 12 months' follow-up compared with placebo (absence of skin lesions) (risk ratio (RR) 1.57, 95% confidence interval (CI) 0.95 to 2.61; 1 study, 24 participants; low-quality evidence). There may be little to no difference between methotrexate and chloroquine in complete clinical response (skin rash resolution) at 6 months' follow-up (RR 1.13, 95% CI 0.84 to 1.50; 1 study, 25 participants; low-quality evidence). Methotrexate may be superior to placebo with regard to complete clinical response (absence of malar/discoid rash) at 6 months' follow-up (RR 3.57, 95% CI 1.63 to 7.84; 1 study, 41 participants; low-quality evidence). At 12 months' follow-up, there may be little to no difference between azathioprine and ciclosporin in complete clinical response (malar rash resolution) (RR 0.83, 95% CI 0.46 to 1.52; 1 study, 89 participants; low-quality evidence). Partial clinical response Partial clinical response was reported for only one key comparison: hydroxychloroquine may increase partial clinical response at 12 months compared to placebo, but the 95% CI indicates that hydroxychloroquine may make no difference or may decrease response (RR 7.00, 95% CI 0.41 to 120.16; 20 pregnant participants, 1 trial; low-quality evidence). Clinical flares Clinical flares were reported for only two key comparisons: hydroxychloroquine is probably superior to placebo at 6 months' follow-up for reducing clinical flares (RR 0.49, 95% CI 0.28 to 0.89; 1 study, 47 participants; moderate-quality evidence). At 12 months' follow-up, there may be no difference between methotrexate and placebo, but the 95% CI indicates there may be more or fewer flares with methotrexate (RR 0.77, 95% CI 0.32 to 1.83; 1 study, 86 participants; moderate-quality evidence). Adverse events Data for adverse events were limited and were inconsistently reported, but hydroxychloroquine, chloroquine, and methotrexate have well-documented adverse effects including gastrointestinal symptoms, liver problems, and retinopathy for hydroxychloroquine and chloroquine and teratogenicity during pregnancy for methotrexate.
AUTHORS' CONCLUSIONS
Evidence supports the commonly-used treatment hydroxychloroquine, and there is also evidence supporting chloroquine and methotrexate for treating cutaneous disease in SLE. Evidence is limited due to the small number of studies reporting key outcomes. Evidence for most key outcomes was low or moderate quality, meaning findings should be interpreted with caution. Head-to-head intervention trials designed to detect differences in efficacy between treatments for specific CLE subtypes are needed. Thirteen further trials are awaiting classification and have not yet been incorporated in this review; they may alter the review conclusions.
Topics: Age of Onset; Azathioprine; Bias; Biological Factors; Chloroquine; Cosmetic Techniques; Cyclosporine; Dermatologic Agents; Exanthema; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic; Male; Medicine, Chinese Traditional; Methotrexate; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Skin Diseases; Symptom Flare Up
PubMed: 33687069
DOI: 10.1002/14651858.CD007478.pub2 -
The Cochrane Database of Systematic... Dec 2015It has been reported that neural tube defects (NTD) can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It has been reported that neural tube defects (NTD) can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear.
OBJECTIVES
This review aims to examine whether periconceptional folate supplementation reduces the risk of neural tube and other congenital anomalies (including cleft palate) without causing adverse outcomes in mothers or babies. This is an update of a previously published Cochrane review on this topic.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2015). Additionally, we searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (31 August 2015) and contacted relevant organisations to identify ongoing and unpublished studies.
SELECTION CRITERIA
We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, checked data entry for accuracy and assessed the risk of bias of the included studies. We assessed the quality of the body of evidence using the GRADE approach.
MAIN RESULTS
Five trials involving 7391 women (2033 with a history of a pregnancy affected by a NTD and 5358 with no history of NTDs) were included. Four comparisons were made: 1) supplementation with any folate versus no intervention, placebo or other micronutrients without folate (five trials); 2) supplementation with folic acid alone versus no treatment or placebo (one trial); 3) supplementation with folate plus other micronutrients versus other micronutrients without folate (four trials); and 4) supplementation with folate plus other micronutrients versus the same other micronutrients without folate (two trials). The risk of bias of the trials was variable. Only one trial was considered to be at low risk of bias. The remaining studies lacked clarity regarding the randomisation method or whether the allocation to the intervention was concealed. All the participants were blinded to the intervention, though blinding was unclear for outcome assessors in the five trials.The results of the first comparison involving 6708 births with information on NTDs and other infant outcomes, show a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.17 to 0.58); five studies; 6708 births; high quality evidence). Only one study assessed the incidence of NTDs and showed no evidence of an effect (RR 0.07, 95% CI 0.00 to 1.32; 4862 births) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.34, 95% CI 0.18 to 0.64); four studies; 1846 births). Subgroup analyses suggest that the positive effect of folic acid on NTD incidence and recurrence is not affected by the explored daily folic acid dosage (400 µg (0.4 mg) or higher) or whether folic acid is given alone or with other vitamins and minerals. These results are consistent across all four review comparisons.There is no evidence of any preventive or negative effects on cleft palate (RR 0.73, 95% CI 0.05 to 10.89; three studies; 5612 births; low quality evidence), cleft lip ((RR 0.79, 95% CI 0.14 to 4.36; three studies; 5612 births; low quality evidence), congenital cardiovascular defects (RR 0.57, 95% CI 0.24 to 1.33; three studies; 5612 births; low quality evidence), miscarriages (RR 1.10, 95% CI 0.94 to 1.28; five studies; 7391 pregnancies; moderate quality evidence) or any other birth defects (RR 0.94, 95% CI 0.53 to 1.66; three studies; 5612 births; low quality evidence). There were no included trials assessing the effects of this intervention on neonatal death, maternal blood folate or anaemia at term.
AUTHORS' CONCLUSIONS
Folic acid, alone or in combination with vitamins and minerals, prevents NTDs, but does not have a clear effect on other birth defects.
Topics: Dietary Supplements; Female; Folic Acid; Humans; Infant; Neural Tube Defects; Preconception Care; Pregnancy; Randomized Controlled Trials as Topic; Vitamin B Complex
PubMed: 26662928
DOI: 10.1002/14651858.CD007950.pub3 -
Biomedicine & Pharmacotherapy =... Feb 2022To examine the strengths and limitations of existing data to provide guidance for the use of folate supplements as treatment, with or without other psychotropic... (Review)
Review
OBJECTIVES
To examine the strengths and limitations of existing data to provide guidance for the use of folate supplements as treatment, with or without other psychotropic medications, in various psychiatric disorders. To identify area for further research in terms of the biosynthesis of mechanism of folate and genetic variants in metabolic pathway in human.
METHODS
A systematic review of published literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess whether folate supplements are beneficial in certain psychiatric disorders (depression, bipolar disorder, schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder). Methodology of this review is registered with Prospero (Registration number CRD 42021266605).
DATA SOURCES
Eligible studies were identified using a systematic search of four electronic databases: Embase, Pubmed, PsycINFO, and Cochrane. The search strategy covered the time period from 1974 to August 16th, 2021. Therefore, this review examines randomized control trials or open-label trials completed during this period.
RESULTS
We identified 23 studies of folate supplements in various psychiatric disorders for critical review. Of these, 9 studies investigated the efficacy of folate supplements in major depressive disorders, 5 studies in schizophrenia, 6 studies in autism spectrum disorder, 2 studies in bipolar affective disorder and 1 study in attention deficit hyperactive disorder. The most consistent finding association of oral levomefolic acid or 5-methylfolate with improvement in clinical outcomes in mental health conditions as mentioned above, especially in major depressive disorder (including postpartum and post-menopausal depression), schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder and bipolar affective disorder. Folate supplements were well tolerated.
LIMITATION
Our results are not representative of all types of studies such as case reports or case series studies, nor are they representative of the studies conducted in languages that are not in English or not translated in English.
CONCLUSION
Increasing evidence from clinical trials consistently demonstrate folate supplements, especially levomefolic acid or 5-methylfolate, may improve clinical outcomes for certain psychiatric diseases, especially as an adjunct pharmacotherapy with minimal side effects.
Topics: Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Bipolar Disorder; Depressive Disorder, Major; Female; Folic Acid; Humans
PubMed: 34953391
DOI: 10.1016/j.biopha.2021.112541 -
BJOG : An International Journal of... Apr 2023High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically reviewed.
OBJECTIVES
To compile global high-risk GTN (prognostic score ≥7) cohorts to summarise treatments and outcomes by disease characteristics and primary chemotherapy.
SEARCH STRATEGY
MEDLINE, Embase, Scopus, ClinicalTrials.gov and Cochrane were searched through March 2021.
SELECTION CRITERIA
Full-text manuscripts reporting mortality among ≥10 high-risk GTN patients.
DATA COLLECTION AND ANALYSIS
Binomial proportions were summed, and random-effects meta-analyses performed.
MAIN RESULTS
From 1137 records, we included 35 studies, representing 20 countries. Among 2276 unique high-risk GTN patients, 99.7% received chemotherapy, 35.8% surgery and 4.9% radiation. Mortality was 10.9% (243/2236; meta-analysis: 10%, 95% confidence interval [CI] 7-12%) and likelihood of complete response to primary chemotherapy was 79.7% (1506/1890; meta-analysis: 78%, 95% CI: 74-83%). Across 24 reporting studies, modern preferred chemotherapy (EMA/CO or EMA/EP) was associated with lower mortality (overall: 8.8 versus 9.5%; comparative meta-analysis: 8.1 versus 12.4%, OR 0.42, 95% CI: 0.20-0.90%, 14 studies) and higher likelihood of complete response (overall: 76.6 versus 72.8%; comparative meta-analysis: 75.9 versus 60.7%, OR 2.98, 95% CI: 1.06-8.35%, 14 studies), though studies focused on non-preferred regimens reported comparable outcomes. Mortality was increased for ultra-high-risk disease (30 versus 7.5% high-risk; meta-analysis OR 7.44, 95% CI: 4.29-12.9%) and disease following term delivery (20.8 versus 7.3% following molar pregnancy; meta-analysis OR 2.64, 95% CI: 1.10-6.31%). Relapse rate estimates ranged from 3 to 6%.
CONCLUSIONS
High-risk GTN is responsive to several chemotherapy regimens, with EMA/CO or EMA/EP associated with improved outcomes. Mortality is increased in patients with ultra-high-risk, relapsed and post-term pregnancy disease.
Topics: Pregnancy; Female; Humans; Methotrexate; Dactinomycin; Neoplasm Recurrence, Local; Gestational Trophoblastic Disease; Hydatidiform Mole; Retrospective Studies
PubMed: 36648416
DOI: 10.1111/1471-0528.17374 -
Neuroscience and Biobehavioral Reviews Oct 2016Elevated plasma homocysteine (Hcy) levels have been associated with cognitive dysfunction in a wide range of conditions. The aim of this review is to establish... (Review)
Review
BACKGROUND
Elevated plasma homocysteine (Hcy) levels have been associated with cognitive dysfunction in a wide range of conditions. The aim of this review is to establish which cognitive domains and populations are the most affected.
METHODS
We systematically review the literature and consider all articles that showed any relationship between plasma Hcy levels and scores achieved on cognitive performance tests in both, the general population and patients suffering from central nervous system disorders and other diseases. When effect sizes were available and combinable, several meta-analyses were performed.
RESULTS
We found 111 pertinent articles. There were 24 cohort studies, 18 randomized trials, 21 case-control studies, and 48 cross-sectional studies. This review reveals a positive trend between cognitive decline and increased plasma Hcy concentrations in general population and in patients with cognitive impairments. Results from the meta-analyses also confirm this trend. Treatment with vitamin supplementation fails to show a reduction in cognitive decline.
DISCUSSION
Further investigations are warranted to clarify this relationship. Earlier detection of the elevated Hcy levels may be an effective intervention to prevent cognitive impairment and dementia.
Topics: Cognition; Cognition Disorders; Cross-Sectional Studies; Folic Acid; Homocysteine; Humans; Vitamin B 12
PubMed: 27531233
DOI: 10.1016/j.neubiorev.2016.08.014 -
BMC Pulmonary Medicine Jul 2023Acute exacerbation (AE) is a devastating complication of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and leads to high mortality. This study aimed... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Acute exacerbation (AE) is a devastating complication of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and leads to high mortality. This study aimed to investigate the incidence, risk factors, and prognosis of acute exacerbation of rheumatoid arthritis-associated interstitial lung disease (AE-RA-ILD).
METHODS
PubMed, EMBASE, Web of Science, and Medline were searched through 8 February 2023. Two independent researchers selected eligible articles and extracted available data. The Newcastle Ottawa Scale was used to assess the methodological quality of studies used for meta-analysis. The incidence and prognosis of AE-RA-ILD were investigated. Weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) and pooled odds ratios (ORs) with 95% CIs were calculated to explore the risk factors of AE in RA-ILD.
RESULTS
Twenty-one of 1,589 articles were eligible. A total of 385 patients with AE-RA-ILD, of whom 53.5% were male, were included. The frequency of AE in patients with RA-ILD ranged from 6.3 to 55.6%. The 1-year and 5-year AE incidences were 2.6-11.1% and 11-29.4%, respectively. The all-cause mortality rate of AE-RA-ILD was 12.6-27.9% at 30 days and 16.7-48.3% at 90 days. Age at RA diagnosis (WMD: 3.61, 95% CI: 0.22-7.01), male sex (OR: 1.60, 95% CI:1.16-2.21), smoking (OR: 1.50, 95% CI: 1.08-2.08), lower forced vital capacity predicted (FVC%; WMD: -8.63, 95% CI: -14.68 to - 2.58), and definite usual interstitial pneumonia (UIP) pattern (OR: 1.92, 95% CI: 1.15-3.22) were the risk factors of AE-RA-ILD. Moreover, the use of corticosteroids, methotrexate, and biological disease-modifying anti-rheumatic drugs, was not associated with AE-RA-ILD.
CONCLUSION
AE-RA-ILD was not rare and had a poor prognosis. Age at RA diagnosis, male sex, smoking, lower FVC%, and definite UIP pattern increased the risk of AE-RA-ILD. The use of medications, especially methotrexate and biological disease-modifying anti-rheumatic drugs, may not be related to AE-RA-ILD.
REGISTRATION
CRD42023396772.
Topics: Humans; Male; Female; Incidence; Methotrexate; Risk Factors; Arthritis, Rheumatoid; Prognosis; Lung Diseases, Interstitial; Idiopathic Pulmonary Fibrosis; Antirheumatic Agents
PubMed: 37434169
DOI: 10.1186/s12890-023-02532-2 -
Rheumatology International Dec 2022We aimed to summarise effects and use of non-pharmacological and pharmacological treatments for sarcoidosis with musculoskeletal manifestations. We systematically... (Review)
Review
We aimed to summarise effects and use of non-pharmacological and pharmacological treatments for sarcoidosis with musculoskeletal manifestations. We systematically searched the Cochrane Library, Ovid MEDLINE, Embase, CINAHL, AMED, Scopus, clinical.trials.gov, PROSPERO and PEDro for systematic reviews from 2014 to 2022 and for primary studies from date of inception to March 29, 2022, and studies with patients diagnosed with sarcoidosis with musculoskeletal manifestations. Inclusion criteria required that studies reported effects of non-pharmacological and/or pharmacological treatments or number of patients receiving these treatments. Results were reported narratively and in forest plots. Eleven studies were included. No systematic reviews fulfilled our inclusion criteria. None of the included studies had a control group. We found that between 23 and 100% received corticosteroids, 0-100% received NSAIDs, 5-100% received hydroxychloroquine, 12-100% received methotrexate, 0-100% received TNF inhibitors, and 3-4% received azathioprine. Only ten patients in one study had used non-pharmacological treatments, including occupational therapy, chiropractic and acupuncture. There are no controlled studies on treatment effects for patients with sarcoidosis with musculoskeletal manifestations. We found 11 studies reporting use of pharmacological treatments and only one study reporting use of non-pharmacological treatments. Our study identified major research gaps for pharmacological and non-pharmacological treatment in musculoskeletal sarcoidosis and warrant randomised clinical trials for both.
Topics: Humans; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Hydroxychloroquine; Methotrexate; Sarcoidosis; Tumor Necrosis Factor Inhibitors
PubMed: 35943526
DOI: 10.1007/s00296-022-05171-8 -
Acta Obstetricia Et Gynecologica... Sep 2021Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the...
INTRODUCTION
Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the sperm DNA or through fetal exposure caused by a presence in the seminal fluid. This systematic overview summarizes existing literature on the spermatotoxic and genotoxic potentials of methotrexate (MTX), a drug widely used to treat rheumatic and dermatologic diseases, and mycophenolate mofetil (MMF), which alone or supplemented with ganciclovir (GCV) may be crucial for the survival of organ transplants.
MATERIAL AND METHODS
The systematic overview was performed in accordance with the PRISMA guidelines: A systematic literature search of the MEDLINE and Embase databases was done using a combination of relevant terms to search for studies on spermatotoxic or genotoxic changes related to treatment with MTX, GCV or MMF. The search was restricted to English language literature, and to in vivo animal studies (mammalian species) and clinical human studies.
RESULTS
A total of 102 studies were identified, hereof 25 human and 77 animal studies. For MTX, human studies of immunosuppressive dosages show transient effect on sperm quality parameters, which return to reference values within 3 months. No human studies have investigated the sperm DNA damaging effect of MTX, but in other organs the genotoxic effects of immunosuppressive doses of MTX are fluctuating. In animals, immunosuppressive and cytotoxic doses of MTX adversely affect sperm quality parameters and show widespread genotoxic damages in various organs. Cytotoxic doses transiently change the DNA material in all cell stages of spermatogenesis in rodents. For GCV and MMF, data are limited and the results are indeterminate, for which reason spermatotoxic and genotoxic potentials cannot be excluded.
CONCLUSIONS
Data from human and animal studies indicate transient spermatotoxic and genotoxic potentials of immunosuppressive and cytotoxic doses of MTX. There are a limited number of studies investigating GCV and MMF.
Topics: DNA Damage; Ganciclovir; Humans; Immunosuppressive Agents; Male; Methotrexate; Mycophenolic Acid; Spermatozoa
PubMed: 33755191
DOI: 10.1111/aogs.14151 -
The Cochrane Database of Systematic... May 2013Methotrexate (MTX) is a disease modifying antirheumatic drug (DMARD) used as a first line agent for treating rheumatoid arthritis (RA). Pharmacologically, it is... (Review)
Review
BACKGROUND
Methotrexate (MTX) is a disease modifying antirheumatic drug (DMARD) used as a first line agent for treating rheumatoid arthritis (RA). Pharmacologically, it is classified as an antimetabolite due to its antagonistic effect on folic acid metabolism. Many patients treated with MTX experience mucosal, gastrointestinal, hepatic or haematologic side effects. Supplementation with folic or folinic acid during treatment with MTX may ameliorate these side effects.
OBJECTIVES
To identify trials of supplementation with folic acid or folinic acid during MTX therapy for rheumatoid arthritis and to assess the benefits and harms of folic acid and folinic acid (a) in reducing the mucosal, gastrointestinal (GI), hepatic and haematologic side effects of MTX, and (b) whether or not folic or folinic acid supplementation has any effect on MTX benefit.
SEARCH METHODS
We originally performed MEDLINE searches, from January 1966 to June 1999. During the update of this review, we searched additional databases and used a sensitive search strategy designed to retrieve all trials on folic acid or folinic acid for rheumatoid arthritis from 1999 up to 2 March 2012.
SELECTION CRITERIA
We selected all double-blind, randomised, placebo-controlled clinical trials (RCTs) in which adult patients with rheumatoid arthritis were treated with MTX (at a dose equal to or less than 25 mg/week) concurrently with folate supplementation. In this update of the review we only included trials using 'low dose' folic or folinic acid (a starting dose of ≤ 7 mg weekly).
DATA COLLECTION AND ANALYSIS
Data were extracted from the trials, and the trials were independently assessed for risk of bias using a predetermined set of criteria.
MAIN RESULTS
Six trials with 624 patients were eligible for inclusion. Most studies had low or unclear risk of bias for key domains. The quality of the evidence was rated as 'moderate' for each outcome as assessed by GRADE, with the exception of haematologic side effects which were rated as 'low'. There was no significant heterogeneity between trials, including where folic acid and folinic acid studies were pooled.For patients supplemented with any form of exogenous folate (either folic or folinic acid) whilst on MTX therapy for rheumatoid arthritis, a 26% relative (9% absolute) risk reduction was seen for the incidence of GI side effects such as nausea, vomiting or abdominal pain (RR 0.74, 95% CI 0.59 to 0.92; P = 0.008). Folic and folinic acid also appear to be protective against abnormal serum transaminase elevation caused by MTX, with a 76.9% relative (16% absolute) risk reduction (RR 0.23, 95% CI 0.15 to 0.34; P < 0.00001), as well as reducing patient withdrawal from MTX for any reason (60.8% relative (15.2% absolute) risk reduction, RR 0.39, 95% CI 0.28 to 0.53; P < 0.00001).We analysed the effect of folic or folinic acid on the incidence of stomatitis / mouth sores, and whilst showing a trend towards reduction in risk, the results were not statistically significant (RR 0.72, 95% CI 0.49 to 1.06)It was not possible to draw meaningful conclusions on the effect of folic or folinic acid on haematologic side effects of methotrexate due to small numbers of events and poor reporting of this outcome in included trials.It does not appear that supplementation with either folic or folinic acid has a statistically significant effect on the efficacy of MTX in treating RA (as measured by RA disease activity parameters such as tender and swollen joint counts, or physician's global assessment scores).
AUTHORS' CONCLUSIONS
The results support a protective effect of supplementation with either folic or folinic acid for patients with rheumatoid arthritis during treatment with MTX.There was a significant reduction shown in the incidence of GI side effects, hepatic dysfunction (asmeasured by elevated serum transaminase levels) as well as a significant reduction in discontinuation of MTX treatment for any reason. A trend towards a reduction in stomatitis was demonstrated however this did not reach statistical significance.This updated review with its focus on lower doses of folic acid and folinic acid and updated assessment of risk of bias aimed to give a more precise and more clinically relevant estimate of the benefit of folate supplementation for patients with rheumatoid arthritis receiving methotrexate.
Topics: Abdominal Pain; Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Folic Acid; Folic Acid Antagonists; Gastrointestinal Diseases; Hematologic Diseases; Humans; Leucovorin; Methotrexate; Nausea; Vomiting
PubMed: 23728635
DOI: 10.1002/14651858.CD000951.pub2 -
Nutrients Jul 2023Nutritional deficiencies during pregnancy can have serious consequences for the health of the (unborn) child. This systematic review provides an updated overview of the... (Review)
Review
Nutritional deficiencies during pregnancy can have serious consequences for the health of the (unborn) child. This systematic review provides an updated overview of the available food and nutrient intake data for pregnant women in The Netherlands and an evaluation based on the current recommendations. Embase, MEDLINE, and national institute databases were used. Articles were selected if they had been published since 2008 and contained data on food consumption, nutrient intake, or the status of healthy pregnant women. A qualitative comparison was made with the 2021 Dutch Health Council recommendations and reference values. A total of 218 reports were included, representing 54 individual studies. Dietary assessments were primarily performed via food frequency questionnaires. Protein, vitamin A, thiamin, riboflavin, vitamin B, folate, vitamin B, vitamin C, iron, calcium, and magnesium intakes seemed to be adequate. For folate and vitamin D, supplements were needed to reach the recommended intake. The reasons for concern are the low intakes of fruits, vegetables, and (fatty) fish, and the intakes of alcohol, sugary drinks, and salt. For several foods and nutrients, no or limited intake data were found. High-quality, representative, and recent data are needed to evaluate the nutrient intake of pregnant women in order to make accurate assessments and evaluations, supporting scientific-based advice and national nutritional policies.
Topics: Animals; Female; Pregnancy; Humans; Pregnant Women; Netherlands; Energy Intake; Eating; Vitamins; Folic Acid; Diet
PubMed: 37447397
DOI: 10.3390/nu15133071