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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 -
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 -
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 -
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 -
Clinical Oral Investigations Dec 2023The aim of this scoping review was to evaluate the efficacy and safety of the use of systemic nonsteroidal immunomodulators (SNSI) for oral lichen planus (OLP) treatment. (Review)
Review
OBJECTIVE
The aim of this scoping review was to evaluate the efficacy and safety of the use of systemic nonsteroidal immunomodulators (SNSI) for oral lichen planus (OLP) treatment.
MATERIALS AND METHODS
This review was conducted according to PRISMA-ScR guidelines and registered at PROSPERO (CRD42021243524). Consulted databases were Pubmed, Embase, Scopus, and Web of Science. The inclusion criteria was as follows: clinical trials, case series, prospective, and retrospective studies conducted with participants presenting OLP of any sex and age.
RESULTS
Thirty-two studies were selected, assessing 9 different SNSI: methotrexate, dapsone, levamisole, hydroxychloroquine, thalidomide, metronidazole, azathioprine, mycophenolate mofetil, and colchicine. Methotrexate and dapsone were the drugs with the best evidence among the options included, regarding number and quality of studies. Methotrexate resulted in significant improvement in the clinical condition and remission of symptoms, ranging between 63 and 93% of cases. Dapsone presented a similar effect to the use of topical corticosteroids and tacrolimus CONCLUSION: Among SNSI therapeutic options, methotrexate, and dapsone showed promising efficacy and safety. However, large-scale randomized clinical trials are still needed.
CLINICAL RELEVANCE
SNSI have been used in the treatment of recalcitrant OLP; however, so far, it is not clear which are the best options. This scoping review highlights the potential use of methotrexate and dapsone.
Topics: Humans; Lichen Planus, Oral; Methotrexate; Prospective Studies; Retrospective Studies; Immunologic Factors; Adjuvants, Immunologic; Dapsone
PubMed: 37921879
DOI: 10.1007/s00784-023-05357-9 -
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 -
The Cochrane Database of Systematic... May 2022Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently,... (Review)
Review
BACKGROUND
Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently, synthesis inhibitors of oestrogen (such as letrozole) have also been used to enhance efficacy. The most widely researched drugs are prostaglandins (such as misoprostol, which has a strong uterotonic effect), mifepristone, mifepristone with prostaglandins, and letrozole with prostaglandins. More evidence is needed to identify the best dosage, regimen, and route of administration to optimise patient outcomes. This is an update of a review last published in 2011.
OBJECTIVES
To compare the effectiveness and side effects of different medical methods for first trimester abortion.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Global Health, and LILACs on 28 February 2021. We also searched Clinicaltrials.gov and the World Health Organization's (WHO) International Clinical Trials Registry Platform, and reference lists of retrieved papers.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) that compared different medical methods for abortion before the 12th week of gestation. The primary outcome is failure to achieve complete abortion. Secondary outcomes are mortality, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the method.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected and evaluated studies for inclusion, and assessed the risk of bias. We processed data using Review Manager 5 software. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 99 studies in the review (58 from the original review and 41 new studies). 1. Combined regimen mifepristone/prostaglandin Mifepristone dose: high-dose (600 mg) compared to low-dose (200 mg) mifepristone probably has similar effectiveness in achieving complete abortion (RR 1.07, 95% CI 0.87 to 1.33; I = 0%; 4 RCTs, 3494 women; moderate-certainty evidence). Prostaglandin dose: 800 µg misoprostol probably reduces abortion failure compared to 400 µg (RR 0.63, 95% CI 0.51 to 0.78; I= 0%; 3 RCTs, 4424 women; moderate-certainty evidence). Prostaglandin timing: misoprostol administered on day one probably achieves more success on complete abortion than on day three (RR 1.94, 95% CI 1.05 to 3.58; 1489 women; 1 RCT; moderate-certainty evidence). Administration strategy: there may be no difference in failure of complete abortion with self-administration at home compared with hospital administration (RR 1.63, 95% CI 0.68 to 3.94; I = 84%; 2263 women; 4 RCTs; low-certainty evidence), but failure may be higher when administered by nurses in hospital compared to by doctors in hospital (RR 2.69, 95% CI 1.39 to 5.22; I = 66%; 3 RCTs, 3056 women; low-certainty evidence). Administration route: oral misoprostol probably leads to more failures than the vaginal route (RR 2.38, 95% CI 1.46 to 3.87; I = 39%; 3 RCTs, 1704 women; moderate-certainty evidence) and may be associated with more frequent side effects such as nausea (RR 1.14, 95% CI 1.03 to 1.26; I = 0%; 2 RCTs, 1380 women; low-certainty evidence) and diarrhoea (RR 1.80 95% CI 1.49 to 2.17; I = 0%; 2 RCTs, 1379 women). Compared with the vaginal route, complete abortion failure is probably lower with sublingual (RR 0.68, 95% CI 0.22 to 2.11; I = 59%; 2 RCTs, 3229 women; moderate-certainty evidence) and may be lower with buccal administration (RR 0.71, 95% CI 0.34 to 1.46; I = 0%; 2 RCTs, 479 women; low-certainty evidence), but sublingual or buccal routes may lead to more side effects. Women may experience more vomiting with sublingual compared to buccal administration (RR 1.33, 95% CI 1.01 to 1.77; low-certainty evidence). 2. Mifepristone alone versus combined regimen The efficacy of mifepristone alone in achieving complete abortion compared to combined mifepristone/prostaglandin up to 12 weeks is unclear (RR of failure 3.25, 95% CI 0.81 to 13.09; I = 83%; 3 RCTs, 273 women; very low-certainty evidence). 3. Prostaglandin alone versus combined regimen Nineteen studies compared prostaglandin alone to a combined regimen (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate). Compared to any of the combination regimens, misoprostol alone may increase the risk for failure to achieve complete abortion (RR of failure 2.39, 95% CI 1.89 to 3.02; I = 64%; 18 RCTs, 3471 women; low-certainty evidence), and with more diarrhoea. 4. Prostaglandin alone (route of administration) Oral misoprostol alone may lead to more failures in complete abortion than the vaginal route (RR 3.68, 95% CI 1.56 to 8.71, 2 RCTs, 216 women; low-certainty evidence). Failure to achieve complete abortion may be slightly reduced with sublingual compared with vaginal (RR 0.69, 95% CI 0.37 to 1.28; I = 87%; 5 RCTs, 2705 women; low-certainty evidence) and oral administration (RR 0.58, 95% CI 0.11 to 2.99; I = 66%; 2 RCTs, 173 women). Failure to achieve complete abortion may be similar or slightly higher with sublingual administration compared to buccal administration (RR 1.11, 95% CI 0.71 to 1.74; 1 study, 401 women).
AUTHORS' CONCLUSIONS
Safe and effective medical abortion methods are available. Combined regimens (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate) may be more effective than single agents (prostaglandin alone or mifepristone alone). In the combined regimen, the dose of mifepristone can probably be lowered to 200 mg without significantly decreasing effectiveness. Vaginal misoprostol is probably more effective than oral administration, and may have fewer side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all studies were conducted in settings with good access to emergency services, which may limit the generalisability of these results.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Spontaneous; Diarrhea; Drug Therapy, Combination; Estradiol; Female; Humans; Letrozole; Methotrexate; Mifepristone; Misoprostol; Oxytocics; Pregnancy; Pregnancy Trimester, First; Prostaglandins; Tamoxifen
PubMed: 35608608
DOI: 10.1002/14651858.CD002855.pub5 -
Acta Obstetricia Et Gynecologica... Sep 2023Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment.
MATERIAL AND METHODS
We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times.
TRIAL REGISTRATION NUMBER
PROSPERO: CRD42021214093.
RESULTS
1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95-1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23-1.14). Mean time to success was 19.7 days (95% CI 17.4-22.3) after MTX and 21.2 days (95% CI 17.8-25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group.
CONCLUSIONS
Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.
Topics: Pregnancy; Humans; Female; Methotrexate; Watchful Waiting; Pregnancy, Tubal; Pregnancy, Ectopic; Chorionic Gonadotropin; Abortifacient Agents, Nonsteroidal; Retrospective Studies
PubMed: 37345445
DOI: 10.1111/aogs.14617 -
PloS One 2023Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective treatment for RA, the effects that bDMARDs have on integumentary, cardiac, and immune systems and the high costs associated with these treatments, make that mesenchymal stem cell-based therapies (MSCs) for RA are being considered potential treatment methods. This work analyses the performance in safety and efficacy terms of MSCs techniques.
METHODS AND FINDING
A literature search was performed in PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey databases from inception to October 28, 2022. Three randomized controlled trials (RCTs) and one non-randomized controlled trial (non-RCTs), including 358 patients met our inclusion criteria and were included in qualitative synthesis; only RCTs were eligible for quantitative synthesis (meta-analysis). Meta-analysis of adverse events (AE) in RCTs showed no significant differences in the incidence of AE in the MSCs group compared to the control group (Risk ratio: 2.35; 95% CI, 0.58 to 9.58; I2 = 58.80%). The pooled Risk ratio for non-serious and serious adverse events showed no statistical difference between intervention and control groups concerning the incidence of non-serious and serious adverse events (Risk ratio: 2.35; 95% CI, 0.58 to 9.51; I2 = 58.62%) and (Risk ratio: 1.10; 95% CI, 0.15 to 7.97; I2 = 0.0%) respectively. The Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS28) decreased in agreement with the decreasing values of C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR). Additionally, a trend toward clinical efficacy was observed; however, this improvement was not shown in the studies after 12 months of follow-up without continuous treatment administration.
CONCLUSION
This Systematic review and meta-analysis showed a favorable safety profile, without life-threatening events in subjects with RA, and a trend toward clinical efficacy that must be confirmed through high-quality RCTs, considerable sample size, and extended follow-up in subjects with RA.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Methotrexate; Treatment Outcome; Controlled Clinical Trials as Topic
PubMed: 37498842
DOI: 10.1371/journal.pone.0284828 -
Journal of the American Academy of... Apr 2019This systematic review assesses effects of paternal exposure to dermatologic medications by using the former US Food and Drug Administration (FDA) pregnancy categories...
BACKGROUND
This systematic review assesses effects of paternal exposure to dermatologic medications by using the former US Food and Drug Administration (FDA) pregnancy categories as a benchmark.
OBJECTIVE
To assess whether systemic dermatologic medications can cause infertility and teratogenicity when taken by men.
METHODS
Categories D and X dermatologic medications were identified; a systematic review of the literature and reviews of the FDA Adverse Events Reporting System and prescribing information were performed to identify the effects of these medications on male fertility and teratogenicity. A secondary search was performed to assess for other systemic dermatologic medications causing teratogenicity or infertility following paternal exposure.
RESULTS
A total of 13 medications met the inclusion criteria. Of 1,032 studies identified, 19 were included after a systematic review of the literature. Studies evaluating medication effects with paternal exposure were identified for 10 of the 13 evaluated medications, and evidence of a negative effect was identified for 6 medications.
LIMITATIONS
We did not encounter any studies for 3 medications that met the inclusion criteria. Information submitted to the FDA Adverse Events Reporting System may not reflect the incidence of side effects.
CONCLUSIONS
Many former pregnancy category D and X systemic dermatologic medications also have effects on male fertility. More research and better-quality studies are required in this area, particularly studies assessing potential teratogenicity.
Topics: Acitretin; Adrenal Cortex Hormones; Colchicine; Cyclophosphamide; Dermatologic Agents; Doxycycline; Finasteride; Humans; Infertility, Male; Isotretinoin; Male; Methotrexate; Paternal Exposure; Teratogenesis; Tetracycline; Thalidomide
PubMed: 30287313
DOI: 10.1016/j.jaad.2018.09.031