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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 -
BMC Oral Health Oct 2023Statins are a category of medications widely used to reduce plasma LDL-cholesterol levels, that also possess antibacterial, anti-inflammatory, and immunomodulatory...
OBJECTIVES
Statins are a category of medications widely used to reduce plasma LDL-cholesterol levels, that also possess antibacterial, anti-inflammatory, and immunomodulatory action. The aim of this systematic review was to explore the effects of systemic statins therapy on the development and treatment of apical periodontitis (AP) on humans and animals.
MATERIAL AND METHODS
Three electronic databases (PubMed, Web of Science, and Scopus) and grey literature were searched from their inception until February, 20 2023 (PROSPERO CRD42021246231). For the quality assessment and risk of bias, different guidelines were used according to the typology of the studies considered (Animal Research Reporting of In Vivo Experiments, Newcastle-Ottawa Quality Assessment Form for Cohort Studies, Systematic Review Centre for Laboratory animal Experimentation Risk of Bias tool and Tool to assess risk of bias in cohort studies of CLARITY Group).
RESULTS
Seven hundred eleven records were screened, and six articles were included for this qualitative review. The eligible studies showed a moderate overall quality and risk of bias. Human patients in treatment with statins exhibited a higher healing rate of AP following root canal treatment. In experimental animal models, statins had a beneficial effect on the development of AP.
CONCLUSIONS
Despite the limited number of studies and considering that most of them are on animals, our findings suggest that systemically administered statins make a positive contribution to prevent the development and help healing of AP.
CLINICAL RELEVANCE
There is an increased evidence that a pharmacologic adjunct to endodontic treatment may be considered to enhance healing of AP. Among other medications, statins seem to have a positive impact on the disease.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Periapical Periodontitis; Root Canal Therapy; Anti-Bacterial Agents; Wound Healing
PubMed: 37805447
DOI: 10.1186/s12903-023-03472-3 -
Clinical Neurology and Neurosurgery Aug 2023A variety of dietary adjuncts are known to affect the pathophysiology of glioma, making them a potential therapeutic adjunct to standard of care. We systematically... (Review)
Review
BACKGROUND
A variety of dietary adjuncts are known to affect the pathophysiology of glioma, making them a potential therapeutic adjunct to standard of care. We systematically reviewed clinical outcomes in glioma patients treated with one or more nutritional adjunct and/or an antimetabolite drug.
METHODOLOGY
A systematic review of the literature following PRISMA guidelines was performed using Pubmed from inception till February 2023. In total, 22 manuscripts on nutrition representing 828 patients were included in the review. Statistical analyses were performed to compare the outcomes of various adjuncts.
RESULTS
The median overall survival (OS) increased for newly diagnosed (21 months) and recurrent cases (10 months) when compared to historical data. For newly diagnosed cases, a ketogenic diet had the highest median OS of all the adjuncts (42.6 months) while in recurrent cases, a low copper diet coupled with 1 g penicillamine had the highest median OS (18.5 months). However, no statistically significant difference was observed in OS or progression-free survival (PFS) of newly diagnosed or recurrent gliomas.
CONCLUSION
While nutritional adjuncts may offer a therapeutic benefit in the treatment of glioma, more human subject research is needed to derive meaningful conclusions.
Topics: Humans; Neoplasm Recurrence, Local; Glioma; Progression-Free Survival; Brain Neoplasms
PubMed: 37390567
DOI: 10.1016/j.clineuro.2023.107853 -
Clinics and Research in Hepatology and... Aug 2023Thiopurines are an important therapy for the maintenance of remission in inflammatory bowel disease (IBD). However, the use of thioguanine has been limited by concerns... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Thiopurines are an important therapy for the maintenance of remission in inflammatory bowel disease (IBD). However, the use of thioguanine has been limited by concerns regarding its toxicity. We performed a systematic review to evaluate its effectiveness and safety in IBD.
METHODS
Electronic databases were searched to identify studies reporting clinical responses and/or adverse events of thioguanine therapy in IBD. We calculated the pooled clinical response and clinical remission rates of thioguanine in IBD. Subgroup analyses were done for the dosage of thioguanine and the type of studies (prospective or retrospective). Meta-Regression was used to analyze the impact of dose on clinical efficacy and occurrence of nodular regenerative hyperplasia.
RESULTS
A total of 32 studies were included. The pooled clinical response rate of thioguanine therapy in IBD was 0.66 (95% C.I. 0.62 - 0.70; I = 16%). The pooled clinical response rate with low-dose was similar to high-dose thioguanine therapy [0.65 (95% C.I. 0.59 - 0.70; I = 24%) and 0.68 (95% C.I. 0.61 - 0.75; I = 18%) respectively]. The pooled remission maintenance rate was 0.71 (95% C.I. 0.58 - 0.81; I = 86%). The pooled rates of occurrence of nodular regenerative hyperplasia, liver function tests abnormalities and cytopenia were 0.04 (95% C.I. 0.02 - 0.08; I = 75%), 0.11 (95% C.I. 0.08 - 0.16; I = 72%) and 0.06 (95% C.I. 0.04 - 0.09; I = 62%) respectively. Meta-regression suggested that the risk of nodular regenerative hyperplasia is related to the dose of thioguanine.
CONCLUSION
TG is an efficacious and well-tolerated drug in most patients with IBD. Nodular regenerative hyperplasia, cytopenias, and liver function abnormalities occur in a small subset. Future studies should look into TG as primary therapy in IBD.
Topics: Humans; Thioguanine; Hyperplasia; Retrospective Studies; Prospective Studies; Inflammatory Bowel Diseases
PubMed: 37301255
DOI: 10.1016/j.clinre.2023.102155 -
Archives of Dermatological Research Sep 2023Exaggerated healing and remodeling after skin injury may cause hypertrophic and keloidal scars, which are associated with functional and quality of life impairment.... (Review)
Review
Exaggerated healing and remodeling after skin injury may cause hypertrophic and keloidal scars, which are associated with functional and quality of life impairment. There is limited guidance available regarding the relative effectiveness of therapies for hypertrophic scars and keloids. In this review, we aim to compare the effectiveness of treatments for hypertrophic scars and keloids. MEDLINE, Embase, Scopus, and the Cochrane Collaboration database were searched from inception to March 2019 for randomized control trials of treatments for hypertrophic and keloid scars that included 20 or more patients. Outcomes evaluated included the standardized mean reduction in scarring and adverse events. The type of scar and the demographic features were analyzed for their effect on clinical outcome. Based on 25 included clinical trials, intralesional injection (64.1% [95% CI 60.8-67.5%]) may be more effective than physical (29.9% [95% CI 28.9-30.9%]) or topical treatments (34% [95% CI 31.8-36.8%]). Combination of 5-fluorouracil and triamcinolone (9:1 dilution) appeared superior among intralesional treatments for keloids. Ablative laser and pulsed-dye laser were the most useful laser treatments. Regression modeling showed laser treatment response was linked to Fitzpatrick skin type (p = 0.002). Adverse events were uncommon for all treatments and mostly transient. Intralesional treatments for keloid and hypertrophic scars may be the most reliable treatment option to improve pathologic scars, while laser treatment may have specific benefits for Fitzpatrick skin types I-III over types IV-VI. Management of pathological scars is an area of critical need, where appropriate treatment can have a significant impact on quality of life.
Topics: Humans; Keloid; Cicatrix, Hypertrophic; Quality of Life; Hypertrophy; Fluorouracil; Treatment Outcome; Injections, Intralesional
PubMed: 36781457
DOI: 10.1007/s00403-023-02535-3 -
International Braz J Urol : Official... 2024Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin could cause a reduction in testosterone levels. The objective was to evaluate whether the continued use of statins in patients with hypercholesterolemia causes a deficiency in testosterone and other sex hormones.
MATERIALS AND METHODS
Systematic Review with Meta-analysis, performed in Embase, Medline and Cochrane databases, until May 2023; PROSPERO CRD42021270424protocol. Selection performed by two independent authors with subsequent conference in stages. Methodology based on PRISMA statement. There were selected comparative studies, prospective cohorts (CP), randomized clinical trials (RCT) and cross-sectional studies (CSS) with comparison of testosterone levels before and after statin administration and between groups. Bias analysis were evaluated with Cochrane Tool, The Newcastle-Ottawa Scale (NOS), and using the Assess the Quality of Cross-sectional studies (AXIS) tool.
RESULTS
There were found on MedLine, Embase and Cochrane, after selected comparative studies, 10CP and 6RCT and 6CSS for the meta-analysis. In the Forrest plot with 6CSS, a correlation between patients with continuous use of statins and a reduction in total testosterone was evidenced with a statistically significant reduction of 55.02ng/dL (95%CI=[39.40,70.64],I²=91%,p<0.00001).In the analysis with 5RCT, a reduction in the mean total testosterone in patients who started continuous statin use was evidenced, with a statistical significance of 13.12ng/dL (95%CI=[1.16,25.08],I²=0%,p=0.03). Furthermore, the analysis of all prospective studies with 15 articles showed a statistically significant reduction in the mean total testosterone of 9.11 ng/dL (95%CI=[0.16,18.06],I²=37%,p=0.04). A reduction in total testosterone has been shown in most studies and in its accumulated analysis after statin use. However, this decrease was not enough to reach levels below normal.
CONCLUSION
Statins use causes a decrease in total testosterone, not enough to cause a drop below the normal range and also determines increase in FSH levels. No differences were found in LH, Estradiol, SHBG and Free Testosterone analysis.
Topics: Humans; Male; Databases, Factual; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Reference Values; Testosterone
PubMed: 38386784
DOI: 10.1590/S1677-5538.IBJU.2023.0578 -
Journal of Clinical Pharmacology Mar 2024Several urate-lowering drugs have been linked to muscle injury. This study investigated the association of oral urate-lowering drugs with the risk of muscle injury by... (Meta-Analysis)
Meta-Analysis Review
Several urate-lowering drugs have been linked to muscle injury. This study investigated the association of oral urate-lowering drugs with the risk of muscle injury by performing a network meta-analysis of randomized and non-randomized controlled trials. A systematic search of MEDLINE, via PubMed, the ClinicalTrials.gov website, and the Cochrane Central Register of Controlled Trials was conducted to identify relevant studies with a primary outcome of "all muscle injuries." A random-effects model was used to perform a frequentist network meta-analysis to estimate whether there was significant heterogeneity among the studies. In total, 32 studies including 28,327 participants with 2694 (9.5%) "all muscle injuries" were assessed, and the overall risk of bias was judged to be low to moderate. No statistically significant differences were found between placebo and 6 urate-lowering therapies: allopurinol (risk ratio, RR, 1.05; 95% confidence interval, 95%CI, 0.63-1.73), febuxostat (RR 1.10, 95%CI 0.71-1.70), lesinurad (RR 7.00, 95%CI 0.31-160.36), lesinurad concomitant with allopurinol (RR 0.85, 95%CI 0.34-2.11), lesinurad concomitant with febuxostat (RR 1.97, 95%CI 0.55-7.03), and topiroxostat (RR 0.99, 95%CI 0.37-2.65). The findings suggest that there is little need to consider the risk of muscle injury when using urate-lowering drugs in the clinical setting.
Topics: Humans; Allopurinol; Febuxostat; Muscles; Network Meta-Analysis; Thioglycolates; Triazoles; Uric Acid; Controlled Clinical Trials as Topic
PubMed: 37840156
DOI: 10.1002/jcph.2369 -
Acta Neurologica Belgica Oct 2023Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is... (Review)
Review
Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is low in developing countries. To determine the efficacy and safety of the cheaper methotrexate as an alternative immunosuppressant, Medline/Pubmed, Embase and Cochrane databases and references were searched for clinical trials and observational studies using the search terms: "Myasthenia OR Myasthenia Gravis OR anti AchR antibody positive Myasthenia Gravis OR anti-MuSK antibody Myasthenia Gravis OR MG" AND "Methotrexate". Of 78 possible articles, only 4 were selected using the following eligibility criteria: population: generalized MG patients; intervention: methotrexate; and outcome: effectiveness, steroid sparing efficacy and adverse effects. Two clinical trials and one observational study noted improvement in different MG outcomes in patients given methotrexate. While one randomized controlled clinical trial concluded that methotrexate has no steroid sparing benefit, a single blinded clinical trial established that methotrexate was a better steroid sparing agent than azathioprine starting at 10th month of use. Adverse effects were rare with non-specific pain and elevated transaminases as the most common complaints. Based on available evidence, MTX may be a safe and effective alternative to AZA as steroid sparing agent in developing countries.
Topics: Humans; Methotrexate; Azathioprine; Immunosuppressive Agents; Myasthenia Gravis; Prednisone; Drug-Related Side Effects and Adverse Reactions; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 36967437
DOI: 10.1007/s13760-023-02242-w -
Heart, Lung & Circulation Aug 2023Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting.
METHODS
We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD. The biomarkers included are: cardiac troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), soluble E-selectin (sE-selectin) and endothelin-1 (ET-1). A literature search was performed through Ovid MEDLINE, Embase and CINAHL Plus for randomised controlled trials (RCTs) published up to June 2021.
RESULTS
Overall, 35 RCTs with 26,521 participants were included in our meta-analysis. Data was pooled using random effects models presented as standardised mean differences (SMD) with 95% confidence intervals (CI). Combining 36 effect sizes from 29 RCTs, statin use resulted in a significant reduction in CRP levels (SMD -0.61; 95% CI -0.91, -0.32; P<0.001). This reduction was observed for both hydrophilic (SMD -0.39; 95% CI -0.62, -0.16; P<0.001) and lipophilic statins (SMD -0.65; 95% CI -1.01, -0.29; P<0.001). There were no significant changes in serum concentrations of cardiac troponin, NT-proBNP, TNF-α, IL-6, sVCAM, sICAM, sE-selectin and ET-1.
CONCLUSION
This meta-analysis demonstrates that statin use reduces serum CRP levels in a primary prevention setting for CVD, with no clear effect on the other eight biomarkers studied.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Tumor Necrosis Factor-alpha; Biomarkers; Cardiovascular Diseases; Troponin
PubMed: 37291001
DOI: 10.1016/j.hlc.2023.04.300 -
The Cochrane Database of Systematic... Feb 2024Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Methotrexate has broad immunomodulatory properties and is the most commonly used... (Review)
Review
BACKGROUND
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Methotrexate has broad immunomodulatory properties and is the most commonly used disease-modifying antirheumatic drug (DMARD). This is an update of a 2001 Cochrane review. It supports a living guideline for children and young people with JIA.
OBJECTIVES
To assess the benefits and harms of methotrexate for children and young people with juvenile idiopathic arthritis.
SEARCH METHODS
The Australian JIA Living Guideline Working Group created a registry of all randomised controlled trials (RCTs) of JIA by searching CENTRAL, MEDLINE, Embase, and trials registries. The date of the most recent search of online databases was 1 February 2023.
SELECTION CRITERIA
We searched for RCTs that compared methotrexate with placebo, no treatment, or another DMARD (with or without concomitant therapies) in children and young people (aged up to 18 years) with JIA.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. The main comparison was methotrexate versus placebo. Our outcomes were treatment response, sustained clinically inactive disease, function, pain, participant global assessment of well-being, serious adverse events, and withdrawals due to adverse events. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified three new trials in this update, bringing the total number of included RCTs to five (575 participants). Three trials evaluated oral methotrexate versus placebo, one evaluated methotrexate plus intra-articular glucocorticoid (IAGC) therapy versus IAGC therapy alone, and one evaluated methotrexate versus leflunomide. Doses of methotrexate ranged from 5 mg/m/week to 15 mg/m/week in four trials, and participants in the methotrexate group of the remaining trial received 0.5 mg/kg/week. Trial size varied from 31 to 226 participants. The average age of participants ranged from four to 10 years. Most participants were females and most had nonsystemic JIA. The study that evaluated methotrexate plus IAGC therapy versus IAGC therapy alone recruited children and young people with the oligoarticular disease subtype of JIA. Two placebo-controlled trials and the trial of methotrexate versus leflunomide were adequately randomised and blinded, and likely not susceptible to important biases. One placebo-controlled trial may have been susceptible to selection bias due to lack of adequate reporting of randomisation methods. The trial investigating the addition of methotrexate to IAGC therapy was susceptible to performance and detection biases. Methotrexate versus placebo Methotrexate compared with placebo may increase the number of children and young people who achieve treatment response up to six months (absolute difference of 163 more per 1000 people; risk ratio (RR) 1.67, 95% confidence interval (CI) 1.21 to 2.31; I = 0%; 3 trials, 328 participants; low-certainty evidence). However, methotrexate compared with placebo may have little or no effect on pain as measured on an increasing scale of 0 to 100 (mean difference (MD) -1.10 points, 95% CI -9.09 to 6.88; 1 trial, 114 participants), improvement in participant global assessment of well-being (absolute difference of 92 more per 1000 people; RR 1.23, 95% CI 0.88 to 1.72; 1 trial, 176 participants), occurrence of serious adverse events (absolute difference of 5 fewer per 1000 people; RR 0.63, 95% CI 0.04 to 8.97; 3 trials, 328 participants), and withdrawals due to adverse events (RR 3.46, 95% CI 0.60 to 19.79; 3 trials, 328 participants) up to six months. We could not estimate the absolute difference for withdrawals due to adverse events because there were no withdrawals in the placebo group. All outcomes were reported within six months of randomisation. We downgraded the certainty of the evidence to low for all outcomes due to indirectness (suboptimal dosing of methotrexate and diverse outcome measures) and imprecision (few participants and low event rates). No trials reported function or the number of participants with sustained clinically inactive disease. Serious adverse events included liver derangement, abdominal pain, and inadvertent overdose. Methotrexate plus intra-articular corticosteroid therapy versus intra-articular corticosteroid therapy alone Methotrexate plus IAGC therapy compared with IAGC therapy alone may have little or no effect on the probability of sustained clinically inactive disease or the rate of withdrawals due to adverse events up to 12 months in children and young people with the oligoarticular subtype of JIA (low-certainty evidence). We could not calculate the absolute difference in withdrawals due to adverse events because there were no withdrawals in the control group. We are uncertain if there is any difference between the interventions in the risk of severe adverse events, because none were reported. The study did not report treatment response, function, pain, or participant global assessment of well-being. Methotrexate versus an alternative disease-modifying antirheumatic drug Methotrexate compared with leflunomide may have little or no effect on the probability of treatment response or on function, participant global assessment of well-being, risk of serious adverse events, and rate of withdrawals due to adverse events up to four months. We downgraded the certainty of the evidence for all outcomes to low due to imprecision. The study did not report pain or sustained clinically inactive disease.
AUTHORS' CONCLUSIONS
Oral methotrexate (5 mg/m/week to 15 mg/m/week) compared with placebo may increase the number of children and young people achieving treatment response but may have little or no effect on pain or participant global assessment of well-being. Oral methotrexate plus IAGC injections compared to IAGC injections alone may have little or no effect on the likelihood of sustained clinically inactive disease among children and young people with oligoarticular JIA. Similarly, methotrexate compared with leflunomide may have little or no effect on treatment response, function, and participant global assessment of well-being. Serious adverse events due to methotrexate appear to be rare. We will update this review as new evidence becomes available to inform the living guideline.
Topics: Child; Female; Humans; Adolescent; Aged; Child, Preschool; Male; Methotrexate; Arthritis, Juvenile; Leflunomide; Australia; Antirheumatic Agents; Glucocorticoids; Pain
PubMed: 38334147
DOI: 10.1002/14651858.CD003129.pub2