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BMC Oral Health Mar 2024Recurrent Aphthous Stomatitis (RAS) known as recurrent aphthous ulcer is a common and painful ulcerations in oral cavity. It has been suggested that hematological... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Recurrent Aphthous Stomatitis (RAS) known as recurrent aphthous ulcer is a common and painful ulcerations in oral cavity. It has been suggested that hematological parameters seems to be considered as an etiologic factor. So, this meta-analysis and systematic review was aimed to examine the relationship between RAS and hematological parameters.
METHODS
Relevant studies were found using online international databases including Scopus, Science direct, Web of science (ISI), PubMed, and Google Scholar search engine between 2000 and October 2023. The quality of all papers was determined by NOS checklist. Heterogeneity between the results of primary studies was evaluated with I-square index and publication bias was performed by Egger's test and funnel plots. Also, sensitivity analysis was done to check the effect of each of the primary studies on the overall estimate. Also, the statistical analyses were done using Stata software Ver. 11.
RESULTS
By combining the results of primary studies, the standardized mean difference (SMD) of vitamin B12, ferritin, folic acid, hemoglobin, iron and zinc indices with a 95% confidence interval (CI) between the case (patients with RAS) and control (Healthy) groups were estimated -0.52(-0.89, -0.14), -0.20(-0.51, 0.11), -0.42(-0.95, 0.11), -0.58(-0.90, -0.27), 0.01(-0.12, 0.15), -0.33(-0.81, 0.14) respectively. The patients with vitamin B12, ferritin, folic acid, and iron deficiencies and reduced hemoglobin (Hb) level reported 2.93(2.28, 3.78), 2.50(1.48, 4.22), 1.51(0.53, 4.29), 1.46(0.70, 3.03), and 2.14(1.38, 3.32), times more susceptible to develop RAS than healthy individuals.
CONCLUSION
The results of the meta-analysis indicated that the SMD of vitamin B12 serum and Hb levels in the case group was 52%. Our result have also showed that the odds ratio of vitamin B12, ferritin deficiencies, and decreased Hb level in case group was 2.93, 2.50, and 2.14 times more than healthy group.
Topics: Humans; Stomatitis, Aphthous; Vitamin B 12 Deficiency; Folic Acid Deficiency; Folic Acid; Vitamin B 12; Hemoglobins; Ferritins
PubMed: 38493289
DOI: 10.1186/s12903-024-04072-5 -
Epigenetics Dec 2024Epigenetic modifications, including DNA methylation, are proposed mechanisms explaining the impact of parental exposures to foetal development and lifelong health.... (Review)
Review
Epigenetic modifications, including DNA methylation, are proposed mechanisms explaining the impact of parental exposures to foetal development and lifelong health. Micronutrients including folate, choline, and vitamin B provide methyl groups for the one-carbon metabolism and subsequent DNA methylation processes. Placental DNA methylation changes in response to one-carbon moieties hold potential targets to improve obstetrical care. We conducted a systematic review on the associations between one-carbon metabolism and human placental DNA methylation. We included 22 studies. Findings from clinical studies with minimal ErasmusAGE quality score 5/10 ( = 15) and studies ( = 3) are summarized for different one-carbon moieties. Next, results are discussed per study approach: (1) global DNA methylation ( = 9), (2) genome-wide analyses ( = 4), and (3) gene specific ( = 14). Generally, one-carbon moieties were not associated with global methylation, although conflicting outcomes were reported specifically for choline. Using genome-wide approaches, few differentially methylated sites associated with S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), or dietary patterns. Most studies taking a gene-specific approach indicated site-specific relationships depending on studied moiety and genomic region, specifically in genes involved in growth and development including , , and ; however, overlap between studies was low. Therefore, we recommend to further investigate the impact of an optimized one-carbon metabolism on DNA methylation and lifelong health.
Topics: Female; Humans; Pregnancy; DNA Methylation; Placenta; Genome-Wide Association Study; Folic Acid; S-Adenosylmethionine; Choline; Carbon
PubMed: 38484284
DOI: 10.1080/15592294.2024.2318516 -
European Journal of Medical Research Mar 2024Granulomatous mastitis (GM) is a rare, benign, inflammatory breast disease with an unknown etiology that predominantly affects women of reproductive age. The definitive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Granulomatous mastitis (GM) is a rare, benign, inflammatory breast disease with an unknown etiology that predominantly affects women of reproductive age. The definitive treatment of GM is currently controversial; an appropriate therapeutic strategy has yet to be identified, and the disease's high recurrence rate remains. This study aims to determine the recurrence rate for each GM treatment strategy to identify the most appropriate treatment modality.
METHODS
The search for relevant articles was undertaken using three international databases, including Medline, Scopus, and Web of Science. Articles published in English until the end of 2021 evaluating the recurrence rate of GM were included. Using Stata 13.0, the pooled incidence and 95% confidence interval (CI) for the recurrence rate were determined.
RESULTS
Sixty-five eligible studies were included in our study. The recurrence rates of systemic steroid use, topical steroid use, antibiotic use, methotrexate use, observation, drainage, excision, antibiotic use and surgery, steroid use and surgery, antibiotic and steroid use, methotrexate and steroid use were 24% (95% CI: 21-27%), 11% (95% CI: 6-21%), 18% (95% CI: 14-22%), 13% (95% CI: 7-22%), 11% (95% CI: 7-17%), 65% (95% CI: 50-78%), 13% (95% CI: 10-16%), 23% (95% CI: 14-36%), 7% (95% CI: 5-11%), 11% (95% CI: 6-18%), and 4% (95% CI: 2-8%), respectively. Drainage had the highest recurrence rate, while combined methotrexate and steroid treatment had the lowest rate.
CONCLUSION
The optimal treatment strategy for GM depends on the disease's severity, consequences, and the patient's features. The study results indicate that combination therapy is preferable for minimizing the risk of relapse and reducing treatment complications.
Topics: Female; Humans; Granulomatous Mastitis; Methotrexate; Steroids; Combined Modality Therapy; Anti-Bacterial Agents; Recurrence
PubMed: 38475841
DOI: 10.1186/s40001-024-01761-3 -
Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642 -
RMD Open Jan 2024An important consideration in the treatment of patients with psoriatic arthritis (PsA) is whether the addition of methotrexate (MTX) to biologics has greater efficacy... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
An important consideration in the treatment of patients with psoriatic arthritis (PsA) is whether the addition of methotrexate (MTX) to biologics has greater efficacy than biologic monotherapy with respect to efficacy outcomes in these patients.
OBJECTIVES
To conduct a network meta-analysis (NMA) comparing biologics by treatment class with and without MTX for treatment of adults with active PsA.
METHODS
A systematic literature review (SLR) identified randomised, double-blinded, controlled trials, and a Bayesian NMA compared biologics with and without MTX by treatment class (tumour necrosis factor inhibitors (TNFi), interleukin-23 inhibitors (IL-23i) and IL-17i). Efficacy outcomes included American College of Rheumatology 20%, 50% and 70% (ACR20, ACR50 and ACR70) improvement response.
RESULTS
The SLR initially identified 31 studies, of which 17 met feasibility criteria for the NMA by containing the 'without MTX' subgroup. For ACR20 efficacy (the most robust assessment examined), all active treatments were significantly better than placebo. No statistically significant differences were demonstrated between biologic monotherapy (for all classes examined) and biologics in combination with MTX for ACR20/50. IL-17i were comparable to IL-23i, and IL-17i were significantly better than TNFi for ACR20. Although limited by fewer trials, TNFi, IL-23i and IL-17i were not statistically different for ACR50/70.
CONCLUSIONS
Concomitant use of MTX and biologics did not improve ACR efficacy outcomes versus biologic monotherapy. MTX does not appear to be necessary as a background therapy when biologics are used for the achievement of ACR20/50 responses in patients with PsA.
Topics: Adult; Humans; United States; Methotrexate; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Antibodies, Monoclonal; Network Meta-Analysis; Bayes Theorem; Tumor Necrosis Factor Inhibitors; Biological Products
PubMed: 38296801
DOI: 10.1136/rmdopen-2023-003423 -
BMJ Open Jan 2024The objective of the current study is to compare the treatment effects of different vitamins on essential hypertension to provide an initial basis for developing... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The objective of the current study is to compare the treatment effects of different vitamins on essential hypertension to provide an initial basis for developing evidence-based practices.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Five electronic databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) were searched from their inception to 25 September 2023.
OUTCOMES
The primary outcomes were the difference between the intervention group and the control group in changes in office systolic blood pressure (SBP) and office diastolic blood pressure (DBP) from baseline. The secondary outcomes were the difference between the intervention group and the control group in changes in 24-hour mean ambulatory systolic blood pressure (24 hours SBP), 24-hour mean ambulatory diastolic blood pressure (24 hours DBP) and heart rate (HR) from baseline.
RESULTS
A total of 23 studies comparing five vitamins (vitamin B, vitamin C, vitamin D, vitamin E, folic acid) and involving 2218 participants were included. The included trials were all vitamin versus placebo, so the network was star-shaped. Among the five vitamins, only vitamin E was significantly more effective at reducing SBP (mean difference: -14.14 mm Hg, 95% credible intervals: -27.62 to -0.88) than placebo. In addition, no evidence was found that any of the five vitamins influenced DBP, 24 hours SBP, 24 hours DBP, or HR. The dose of vitamins, geographical region and percentage of males (only SBP) might be sources of heterogeneity. Sensitivity and subgroup analysis revealed that the effect of vitamin intervention on blood pressure varies according to different doses of vitamins.
CONCLUSIONS
According to the results, vitamin E might be an effective measure to reduce SBP, but more research is needed to validate this finding.
PROSPERO REGISTRATION NUMBER
CRD42022352332.
Topics: Adult; Male; Humans; Vitamin D; Ascorbic Acid; Hypertension; Folic Acid; Riboflavin; Vitamin E; Network Meta-Analysis; Vitamins; Essential Hypertension; Blood Pressure; Vitamin A; Vitamin K
PubMed: 38296289
DOI: 10.1136/bmjopen-2023-074511 -
World Journal of Surgical Oncology Jan 2024We aimed to provide a reference based on evidence for an individualized clinical medication of high-dose methotrexate (HD-MTX) in osteosarcoma patients by evaluating the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aimed to provide a reference based on evidence for an individualized clinical medication of high-dose methotrexate (HD-MTX) in osteosarcoma patients by evaluating the effect of gene polymorphism on adverse reactions of HD-MTX usage.
METHODS
Several databases were combed for research on the association between gene polymorphisms and adverse reactions to HD-MTX up to January 2023. A meta-analysis and/or descriptive analysis on the incidence of HD-MTX-related adverse reactions were conducted by using clinical studies meeting inclusion criteria.
RESULTS
Twelve studies involving 889 patients were included. There were 8, 6, 5, and 4 studies related to MTHFR C677T, MTHFR A1298C, RFC1 G80A, and MDR1 C3435T polymorphisms, respectively. The results of the meta-analysis showed that the MTHFR C677T polymorphism was associated with G3-4 hepatotoxicity, G3-4 nephrotoxicity, G3-4 gastrointestinal toxicity, and G3-4 mucositis under the recessive genetic model (MM vs. Mm/mm). Limited research showed that MTHFR C677T was associated with G3-4 nephrotoxicity in the allelic genetic model (M vs. m). MTHFR A1298C polymorphism was associated with a decreased risk of adverse reactions to HD-MTX usage, without statistical significance. This review's descriptive analysis showed no significant correlation between the RFC1 G80A, and MDR1 C3435T polymorphism and adverse reactions of HD-MTX.
CONCLUSION
The MTHFR C677T mutation may enhance the risk of HD-MTX adverse reactions in osteosarcoma patients. Existing studies have not found a significant correlation between the MTHFR A1298C, RFC1 G80A, and MDR1 C3435T polymorphism and adverse reactions caused by HD-MTX. Lastly, this conclusion was limited because of few studies.
Topics: Humans; Methotrexate; Polymorphism, Genetic; Alleles; Methylenetetrahydrofolate Reductase (NADPH2); Osteosarcoma; Polymorphism, Single Nucleotide; Genotype
PubMed: 38212758
DOI: 10.1186/s12957-023-03287-0 -
JAMA Network Open Jan 2024The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and nab-paclitaxel (GEM-NABP) as first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Analyses comparing NALIRIFOX and GEM-NABP with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) have not yet been reported.
OBJECTIVE
To derive survival, response, and toxic effects data from phase 3 clinical trials and compare NALIRIFOX, FOLFIRINOX, and GEM-NABP.
DATA SOURCES
After a systematic search of PubMed, Scopus, Embase, and American Society of Clinical Oncology and European Society for Medical Oncology meetings' libraries, Kaplan-Meier curves were extracted from phase 3 clinical trials conducted from January 1, 2011, until September 12, 2023.
STUDY SELECTION
Phase 3 clinical trials that tested NALIRIFOX, FOLFIRINOX, or GEM-NABP as first-line treatment of metastatic PDAC and reported overall survival (OS) and progression-free survival (PFS) curves were selected. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Individual Participant Data reporting guidelines.
DATA EXTRACTION AND SYNTHESIS
Individual patient OS and PFS data were extracted from Kaplan-Meier plots of original trials via a graphic reconstructive algorithm. Overall response rates (ORRs) and grade 3 or higher toxic effects rates were also collected. A pooled analysis was conducted, and results were validated via a network meta-analysis.
MAIN OUTCOMES AND MEASURES
The primary end point was OS. Secondary outcomes included PFS, ORR, and toxic effects rates.
RESULTS
A total of 7 trials with data on 2581 patients were analyzed, including 383 patients treated with NALIRIFOX, 433 patients treated with FOLFIRINOX, and 1756 patients treated with GEM-NABP. Median PFS was longer in patients treated with NALIRIFOX (7.4 [95% CI, 6.1-7.7] months) or FOLFIRINOX (7.3 [95% CI, 6.5-7.9] months; [HR], 1.21 [95% CI, 0.86-1.70]; P = .28) compared with patients treated with GEM-NABP (5.7 [95% CI, 5.6-6.1] months; HR vs NALIRIFOX, 1.45 [95% CI, 1.22-1.73]; P < .001). Similarly, GEM-NABP was associated with poorer OS (10.4 [95% CI, 9.8-10.8]; months) compared with NALIRIFOX (HR, 1.18 [95% CI, 1.00-1.39]; P = .05], while no difference was observed between FOLFIRINOX (11.7 [95% CI, 10.4-13.0] months) and NALIRIFOX (11.1 [95% CI, 10.1-12.3] months; HR, 1.06 [95% CI, 0.81-1.39]; P = .65). There were no statistically significant differences in ORR among NALIRIFOX (41.8%), FOLFIRINOX (31.6%), and GEM-NABP (35.0%). NALIRIFOX was associated with lower incidence of grade 3 or higher hematological toxic effects (eg, platelet count decreased 1.6% vs 11.8% with FOLFIRINOX and 10.8% with GEM-NABP), but higher rates of severe diarrhea compared with GEM-NABP (20.3% vs 15.7%).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, NALIRIFOX and FOLFIRINOX were associated with similar PFS and OS as first-line treatment of advanced PDAC, although NALIRIFOX was associated with a different toxicity profile. Careful patient selection, financial toxic effects consideration, and direct comparison between FOLFIRINOX and NALIRIFOX are warranted.
Topics: Humans; Pancreatic Neoplasms; Irinotecan; Antineoplastic Combined Chemotherapy Protocols; Leucovorin; Oxaliplatin; Gemcitabine; Fluorouracil; Adenocarcinoma
PubMed: 38190183
DOI: 10.1001/jamanetworkopen.2023.50756 -
Advances in Therapy Feb 2024Immune-mediated inflammatory diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial... (Review)
Review
Safety of Upadacitinib in Immune-Mediated Inflammatory Diseases: Systematic Literature Review of Indirect and Direct Treatment Comparisons of Randomized Controlled Trials.
INTRODUCTION
Immune-mediated inflammatory diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondylarthritis (nr-axSpA), atopic dermatitis (AD), ulcerative colitis (UC), and Crohn's disease (CD) pose a substantial burden on patients and their quality of life. Upadacitinib is an orally administered, selective, and reversible Janus kinase inhibitor indicated for seven conditions, but data on its safety versus other active treatments are limited. A systematic literature review of indirect and direct treatment comparisons of randomized controlled trials (RCTs) was conducted to assess the safety profile of upadacitinib.
METHODS
MEDLINE, Embase, and Cochrane Library databases were searched for indirect and direct treatment comparisons of RCTs that (1) included licensed upadacitinib dosages; (2) studied any of the seven conditions; (3) reported any adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, major adverse cardiovascular event, venous thromboembolism, malignancies, infections or serious infections, and death; and (4) were published between January 2018 and August 2022.
RESULTS
A total of 25 studies were eligible for inclusion. SAEs, AEs leading to discontinuation, and any AEs were commonly studied. RA was the most studied condition, followed by AD and UC. Most studies (16/25, 64%) reported no statistically significant difference in the studied safety outcomes between upadacitinib and other active treatments (e.g., tumor necrosis factor blockers, interleukin receptor antagonists, integrin receptor antagonists, T cell co-stimulation modulator), or placebo (placebo ± methotrexate or topical corticosteroids). Other studies (9/25, 36%) reported mixed results of no statistically significant difference and either statistically higher (8/25, 32%) or lower rates (1/25, 4%) on upadacitinib.
CONCLUSION
Most studies suggested that upadacitinib has no statistically significant difference in the studied safety outcomes compared to active treatments or placebo in patients with RA, PsA, AS, AD, UC, and CD. A few studies reported higher rates, but findings were inconsistent with limited interpretation.
Topics: Humans; Arthritis, Psoriatic; Arthritis, Rheumatoid; Colitis, Ulcerative; Heterocyclic Compounds, 3-Ring; Methotrexate; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing
PubMed: 38169057
DOI: 10.1007/s12325-023-02732-6 -
The Journal of Dermatological Treatment Dec 2024Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing... (Review)
Review
Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing and increased risk of side effects. This systematic review summarizes the available evidence on dosing regimens.A literature search was conducted, screening all randomized controlled trials (RCTs) and guidelines published up to 6 July 2023, in the MEDLINE, Embase, and Cochrane Library databases.Five RCTs and 21 guidelines were included. RCTs compared methotrexate with other treatments rather than different methotrexate dosing regimens. The start and maintenance doses in RCTs varied between 7.5-15 mg/week and 14.5-25 mg/week, respectively. Despite varied dosing, all RCTs demonstrated efficacy in improving atopic dermatitis signs and symptoms. Guidelines exhibited substantial heterogeneity but predominantly proposed starting doses of 5-15 mg/week for adults and 10-15 mg/m/week for children. Maintenance doses suggested were 7.5-25 mg/week for adults and 0.2-0.7 mg/kg/week for children. One guideline suggested a test dose and nearly half advised folic acid supplementation.This systematic review highlights the lack of methotrexate dosing guidelines for atopic dermatitis. It identifies commonly recommended and utilized dosing regimens, serving as a valuable resource for clinicians prescribing methotrexate off-label and providing input for an upcoming consensus study.
Topics: Adult; Child; Humans; Methotrexate; Dermatitis, Atopic
PubMed: 38124505
DOI: 10.1080/09546634.2023.2292962