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Medicine Dec 2021Ectopic pregnancy (EP) is a common cause of acute abdominal pain in the field of gynecology. Because the majority of women with EP are hemodynamically stable,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ectopic pregnancy (EP) is a common cause of acute abdominal pain in the field of gynecology. Because the majority of women with EP are hemodynamically stable, non-surgical therapy is a viable option. The goal of this study was to determine the most effective non-surgical therapy for hemodynamically stable EP.
METHODS
We performed a systematic review and meta-analysis. We searched PubMed, LILACS, SciELO, CINAHL, Embase, and the Cochrane library in May 2020, with no starting date restrictions.Studies were restricted to randomized controlled trials, which were included if the target population contained women with tubal EP and the intervention was non-surgical management. The primary outcome measure was treatment success defined by a decrease in serum hCG to a level ranging from five mIU/mL to 50 mIU/mL. Secondary outcome measures were side effects, time needed to treat, number of injections and operative rate.
RESULTS
We conducted a meta-analysis of 15 studies that included 1573 women who were diagnosed with EP and managed non-surgically. There was no significant difference in treatment success in the matched groups; however, single-dose MTX was associated with fewer side effects than multiple-dose (relative risk 0.48, 95% confidence interval 0.28-0.80, P = .006) and two-dose therapies (relative risk 0.74, 95% confidence interval 0.55-1.00, P = .05).
CONCLUSIONS
We highly recommend that single-dose MTX without mifepristone be used first-line in patients who require conservative therapy due to the inherent negative effects of mifepristone. An EP woman with a low -hCG level that is falling or plateauing should receive expectant treatment to reduce adverse effects.
Topics: Adult; Female; Humans; Methotrexate; Mifepristone; Pregnancy; Pregnancy, Ectopic; Pregnancy, Tubal; Treatment Outcome
PubMed: 34918633
DOI: 10.1097/MD.0000000000027851 -
Ugeskrift For Laeger Nov 2023Juvenile dermatomyositis (JDM) is a rare condition, which causes inflammation in children's skin and musculoskeletal systems. Symptoms include characteristic skin rashes...
Juvenile dermatomyositis (JDM) is a rare condition, which causes inflammation in children's skin and musculoskeletal systems. Symptoms include characteristic skin rashes on the face and extremities, muscle pain and weakness. This is a case report of a ten-year-old boy initially suspected of having lupus erythematosus. He was later diagnosed with JDM by dermatologists. Treatment with methotrexate and prednisolone proved to be effective.
Topics: Male; Child; Humans; Dermatomyositis; Methotrexate; Skin; Inflammation; Prednisolone
PubMed: 37987452
DOI: No ID Found -
Clinical Infectious Diseases : An... Jul 2021
Topics: Humans; Methotrexate
PubMed: 33170206
DOI: 10.1093/cid/ciaa1390 -
Deutsches Arzteblatt International Aug 2022
Topics: Humans; Methotrexate; Radiation Dosage
PubMed: 36422875
DOI: 10.3238/arztebl.m2022.0185 -
Fa Yi Xue Za Zhi Oct 2021
Topics: Female; Humans; Methotrexate; Pregnancy; Pregnancy, Ectopic
PubMed: 35191238
DOI: 10.12116/j.issn.1004-5619.2020.400330 -
Cell Chemical Biology Feb 2024Methotrexate (MTX) is a tight-binding dihydrofolate reductase (DHFR) inhibitor, used as both an antineoplastic and immunosuppressant therapeutic. MTX, like folate...
Methotrexate (MTX) is a tight-binding dihydrofolate reductase (DHFR) inhibitor, used as both an antineoplastic and immunosuppressant therapeutic. MTX, like folate undergoes folylpolyglutamate synthetase-mediated γ-glutamylation, which affects cellular retention and target specificity. Mechanisms of MTX resistance in cancers include a decrease in MTX poly-γ-glutamylation and an upregulation of DHFR. Here, we report a series of potent MTX-based proteolysis targeting chimeras (PROTACs) to investigate DHFR degradation pharmacology and one-carbon biochemistry. These on-target, cell-active PROTACs show proteasome- and E3 ligase-dependent activity, and selective degradation of DHFR in multiple cancer cell lines. By comparison, treatment with MTX increases cellular DHFR protein expression. Importantly, these PROTACs produced distinct, less-lethal phenotypes compared to MTX. The chemical probe set described here should complement conventional DHFR inhibitors and serve as useful tools for studying one-carbon biochemistry and dissecting complex polypharmacology of MTX and related drugs. Such compounds may also serve as leads for potential autoimmune and antineoplastic therapeutics.
Topics: Humans; Antineoplastic Agents; Carbon; Folic Acid Antagonists; Methotrexate; Neoplasms; Proteolysis Targeting Chimera; Tetrahydrofolate Dehydrogenase
PubMed: 37875111
DOI: 10.1016/j.chembiol.2023.09.014 -
The Cochrane Database of Systematic... Jul 2019Morphea (morphoea) is an immune-mediated disease in which excess synthesis and deposition of collagen in the skin and underlying connective tissues results in hardened...
BACKGROUND
Morphea (morphoea) is an immune-mediated disease in which excess synthesis and deposition of collagen in the skin and underlying connective tissues results in hardened cutaneous areas. Morphea has different clinical features according to the subtype and stage of evolution of the disease. There is currently no consensus on optimal interventions for morphea.
OBJECTIVES
To assess the effects of treatments for people with any form of morphea.
SEARCH METHODS
We searched the following databases up to July 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, and five trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials of topical, intralesional, or systemic treatments (isolated or combined) in anyone who has been clinically diagnosed by a medical practitioner with any form of morphea. Eligible controls were placebo, no intervention, any other treatment, or different doses or duration of a treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were global improvement of disease activity or damage assessed by a medical practitioner or by participants, and adverse effects. Secondary outcomes were improvement of disease activity and improvement of disease damage. We used GRADE to assess the quality of the evidence for each outcome.
MAIN RESULTS
We included 14 trials, with a total of 429 randomised participants, aged between 3 and 76 years. There were juvenile and adult participants; over half were female, and the majority had circumscribed morphea, followed by linear scleroderma. The settings of the studies (where described) included a dermatologic centre, a national laboratory centre, paediatric rheumatology and dermatology centres, and a university hospital or medical centre.The studies evaluated heterogenous therapies for different types of morphea, covering a wide range of comparisons. We were unable to conduct any meta-analyses. Seven studies investigated topical medications, two evaluated intralesional medications, and five investigated systemic medications. The study duration ranged from seven weeks to 15 months from baseline.We present here results for our primary outcomes for our four key comparisons. All of these results are based on low-quality evidence.The included studies were at high risk of performance, detection, attrition, and reporting bias.Global improvement of disease activity or damage after treatment may be higher with oral methotrexate (15 mg/m², maximum 20 mg, once a week, for 12 months or until disease flare) plus oral prednisone (1 mg/kg a day, maximum of 50 mg, in a single morning dose, for three months, and one month with gradually decreased dose until discontinuation) than with placebo plus oral prednisone in children and adolescents with active morphea (linear scleroderma, generalised morphea or mixed morphea: linear and circumscribed) (risk ratio (RR) 2.31, 95% confidence interval (CI) 1.20 to 4.45; number needed to treat for an additional beneficial outcome (NNTB) 3; 1 randomised controlled trial (RCT); 70 participants, all juvenile). This outcome was measured 12 months from the start of treatment or until flare of the disease. Data were not available separately for each morphea type. There may be little or no difference in the number of participants experiencing at least one adverse event with oral methotrexate (26/46) or placebo (11/24) (RR 1.23, 95% CI 0.75 to 2.04; 1 RCT; 70 participants assessed during the 12-month follow-up). Adverse events related to methotrexate included alopecia, nausea, headache, fatigue and hepatotoxicity, whilst adverse events related to prednisone (given in both groups) included weight gain (more than 5% of body weight) and striae rubrae.One three-armed RCT compared the following treatments: medium-dose (50 J/cm²) UVA-1; low-dose (20 J/cm²) UVA-1; and narrowband UVB phototherapy. There may be little or no difference between treatments in global improvement of disease activity or damage, as assessed through the modified skin score (where high values represent a worse outcome): medium-dose UVA-1 phototherapy versus low-dose UVA-1 group: MD 1.60, 95% CI -1.70 to 4.90 (44 participants); narrowband UVB phototherapy versus medium-dose UVA-1 group: MD -1.70, 95% CI -5.27 to 1.87 (35 participants); and narrowband UVB versus low-dose UVA-1 group: MD -0.10, 95% CI -2.49 to 2.29 (45 participants). This RCT included children and adults with active morphea (circumscribed morphea, linear scleroderma (with trunk/limb variant and head variant), generalised morphea, or mixed morphea), who received phototherapy five times a week, for eight weeks. Outcomes were measured at eight weeks from the start of treatment.Safety data, measured throughout treatment, from the same RCT (62 participants) showed that treatment with UVA-1 phototherapy may cause mild tanning compared to narrowband UVB: narrowband UVB versus medium-dose UVA-1: RR 0.03, 95% CI 0.00 to 0.42; 35 participants; narrowband UVB versus low-dose UVA-1: RR 0.03, 95% CI 0.00 to 0.41; 45 participants. However, there may be no difference in the number of participants reporting mild tanning when comparing medium and low dose UVA-1 phototherapy (RR 1.00, 95% CI 0.91 to 1.10; 44 participants). Transient erythema was reported in three participants with narrowband UVB and no participants in the low- or medium-dose UVA-1 groups.
AUTHORS' CONCLUSIONS
Compared to placebo plus oral prednisone, oral methotrexate plus oral prednisone may improve disease activity or damage in juvenile active morphea (linear scleroderma, generalised morphea or mixed morphea: linear and circumscribed), but there may be a slightly increased chance of experiencing at least one adverse event.When medium-dose UVA-1 (50 J/cm²), low-dose UVA-1 (20 J/cm²), and narrowband UVB were compared against each other in treating children and adults with active morphea (circumscribed morphea, linear scleroderma, generalised morphea and mixed morphea), there may be little or no difference between these treatments on global improvement of disease activity or damage. UVA-1 phototherapy may cause more mild tanning than narrowband UVB, but there may be no difference between medium- and low-dose UVA-1 phototherapy. These results are based on low-quality evidence.Limitations of data and analyses include risk of bias and imprecision (small number of participants or events and wide confidence intervals). We encourage multicentre RCTs to increase sample size and evaluate, with validated tools, different treatment responses according to the subtypes of morphea and age groups.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Male; Methotrexate; Middle Aged; Phototherapy; Prednisone; Randomized Controlled Trials as Topic; Scleroderma, Localized; Young Adult
PubMed: 31309547
DOI: 10.1002/14651858.CD005027.pub5 -
RMD Open Mar 2023
Topics: Humans; Pregnancy; Female; Methotrexate; Antirheumatic Agents; Arthritis, Rheumatoid
PubMed: 36921981
DOI: 10.1136/rmdopen-2022-002899 -
JAMA Network Open Oct 2023This is the first network meta-analysis to assess outcomes associated with multiple conventional synthetic disease-modifying antirheumatic drugs and glucocorticoid. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
This is the first network meta-analysis to assess outcomes associated with multiple conventional synthetic disease-modifying antirheumatic drugs and glucocorticoid.
OBJECTIVE
To analyze clinical outcomes after treatment with conventional synthetic disease-modifying antirheumatic drugs and glucocorticoid among patients with rheumatoid arthritis.
DATA SOURCES
With no time restraint, English language articles were searched in MEDLINE, Embase, Cochrane Central, ClinicalTrials.gov, and reference lists of relevant meta-analyses until September 15, 2022.
STUDY SELECTION
Four reviewers in pairs of 2 independently included controlled studies randomizing patients with rheumatoid arthritis to mono-conventional synthetic disease-modifying antirheumatic drugs, glucocorticoid, placebo, or nonactive treatment that recorded at least 1 outcome of tender joint count, swollen joint count, erythrocyte sedimentation rate, and C-reactive protein level. Of 1098 assessed articles, 130 articles (132 interventions) were included.
DATA EXTRACTION AND SYNTHESIS
The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline, and data quality was assessed by the Cochrane risk of bias tool RoB 2. Data were extracted by a single author and checked independently by 2 authors. Data were analyzed using a random effect model, and data analysis was conducted from June 2021 to February 2023.
MAIN OUTCOMES AND MEASURES
A protocol with hypothesis and study plan was registered before data recording. The most complete of recorded outcomes (tender joint count) was used as primary outcome, with imputations based on other outcomes to obtain a full analysis of all studies. Absolute change adjusted for baseline disease activity was assessed.
RESULTS
A total of 29 interventions in 275 treatment groups among 132 randomized clinical trials (mean [range], 71.0% [27.0% to 100%] females in studies; mean [range] of ages in studies, 53 [36 to 70] years) were identified, which included 13 260 patients with rheumatoid arthritis. The mean (range) duration of RA was 79 (2 to 243) months, and the mean (range) disease activity score was 6.3 (4.0 to 8.8). Compared with placebo, oral methotrexate was associated with a reduced tender joint count by 5.18 joints (95% credible interval [CrI], 4.07 to 6.28 joints). Compared with methotrexate, glucocorticoid (-2.54 joints; 95% CrI, -5.16 to 0.08 joints) and remaining drugs except cyclophosphamide (6.08 joints; 95% CrI, 0.44 to 11.66 joints) were associated with similar or lower tender joint counts.
CONCLUSIONS AND RELEVANCE
This study's results support the present role of methotrexate as the primary reference conventional synthetic disease-modifying antirheumatic drug.
Topics: Female; Humans; Male; Antirheumatic Agents; Arthritis, Rheumatoid; Glucocorticoids; Methotrexate; Network Meta-Analysis; Adult; Middle Aged; Aged
PubMed: 37801318
DOI: 10.1001/jamanetworkopen.2023.35950 -
The American Journal of Tropical... Jan 2020
Topics: Eye Diseases; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Male; Methotrexate; Middle Aged; Radiotherapy; Retinal Pigment Epithelium; Tomography, Optical Coherence
PubMed: 31971149
DOI: 10.4269/ajtmh.19-0539