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JBRA Assisted Reproduction Jun 2024To verify, based on a systematic literature review, the effects of the main analgesics on male fertility. (Review)
Review
OBJECTIVE
To verify, based on a systematic literature review, the effects of the main analgesics on male fertility.
DATA SOURCES
The studies were analyzed from the PubMed, SciELO and LILACS databases.
STUDY SELECTION
The articles selected for the present review included: cohort studies; cross-sectional studies, clinical trials; complete studies; studies with animal models that addressed the proposed theme and that were published within the stipulated period from March 1, 2013, to March 31, 2023, in English, Portuguese and Spanish. These would later have to go through inclusion stages such as framing the type of study and exclusion criteria.
DATA COLLECTION
Author's name, year of publication, study population, number of patients, analgesic, administration time, dose, and effect.
CONCLUSIONS
There are in vitro and in vivo studies that link paracetamol and ibuprofen to endocrine and seminal changes that are harmful to male fertility. However, more clinical research is needed to determine the doses and timing of administration that affect fertility. The effects of aspirin on male fertility are still unclear due to the lack of studies and consistent methodologies. There is not enough research on dipyrone and its relationship with male fertility, requiring more studies in this area.
Topics: Humans; Male; Analgesics; Fertility; Infertility, Male; Ibuprofen; Acetaminophen; Animals; Dipyrone; Aspirin
PubMed: 38546117
DOI: 10.5935/1518-0557.20240020 -
International Journal of Clinical... Jun 2024Zuranolone, an oral version of allopregnanolone and neurosteroid, is a novel drug for the treatment of major depressive disorder (MDD) and postpartum depression (PPD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Zuranolone, an oral version of allopregnanolone and neurosteroid, is a novel drug for the treatment of major depressive disorder (MDD) and postpartum depression (PPD).
AIM
The purpose of this systematic review and meta-analysis was to assess the efficacy of zuranolone in the treatment of MDD and PPD.
METHOD
A systematic search was conducted using EBSCOhost to simultaneously search Academic Search Premier, APA PsycArticles, APA PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL Ultimate, and MEDLINE with Full Text. Two independent reviewers screened the articles and completed a full-text review using Covidence. The quality of each study was assessed using the Cochrane Risk of Bias tool for randomized trials (RoB 2). A meta-analysis was then conducted using Review Manager (RevMan v5.4) software.
RESULTS
The initial search yielded 127 results, with 6 articles fitting our inclusion and exclusion criteria. All 6 studies, comprising 1707 participants, had an overall low risk of bias. There was a significant decrease in HAM-D scores for MDD at 15 days versus placebo (MD - 2.40, 95% CI - 3.07 to - 1.63; p < .001). When pooling data for PDD, there was an overall significant decrease in HAM-D scores at 15 days versus placebo (MD - 4.06, 95% CI - 4.25 to - 3.87; p < .001).
CONCLUSION
The results suggest that zuranolone can improve symptoms of PPD at 15 days; however, results were not clinically significant for MDD. Future research is needed to evaluate the long-term efficacy of zuranolone in PPD and the treatment efficacy in MDD.
Topics: Humans; Depression, Postpartum; Depressive Disorder, Major; Female; Pregnanolone; Antidepressive Agents; Randomized Controlled Trials as Topic; Treatment Outcome; Pyrazoles
PubMed: 38489051
DOI: 10.1007/s11096-024-01714-0 -
Frontiers in Immunology 2024Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined...
BACKGROUND
Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent.
METHODS
Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE).
RESULTS
Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]).
CONCLUSION
Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).
Topics: Humans; Dermatitis, Atopic; Janus Kinase Inhibitors; Nasopharyngitis; Pruritus; Acne Vulgaris; Headache; Herpes Zoster; Immunoglobulin A; Purines; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38464512
DOI: 10.3389/fimmu.2024.1342810 -
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 -
Endocrinology and Metabolism (Seoul,... Feb 2024No recent meta-analysis has holistically analyzed and summarized the efficacy and safety of omarigliptin in type 2 diabetes mellitus (T2DM). We conducted a meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGRUOUND
No recent meta-analysis has holistically analyzed and summarized the efficacy and safety of omarigliptin in type 2 diabetes mellitus (T2DM). We conducted a meta-analysis to address this knowledge gap.
METHODS
Electronic databases were searched to identify randomized controlled trials (RCTs) that included patients with T2DM who received omarigliptin in the intervention arm. The control arm consisted of either a placebo (passive control group [PCG]) or an active comparator (active control group [ACG]). The primary outcome assessed was changes in hemoglobin A1c (HbA1c), while secondary outcomes included variations in glucose levels, achievement of glycemic targets, adverse events (AEs), and hypoglycemic events.
RESULTS
From 332 initially screened articles, data from 16 RCTs involving 8,804 subjects were analyzed. Omarigliptin demonstrated superiority over placebo in reducing HbA1c levels (mean difference, -0.58%; 95% confidence interval, -0.75 to -0.40; P<0.00001; I2=91%). Additionally, omarigliptin outperformed placebo in lowering fasting plasma glucose, 2-hour postprandial glucose, and in the percentage of participants achieving HbA1c levels below 7.0% and 6.5%. The glycemic efficacy of omarigliptin was similar to that of the ACG across all measures. Although the omarigliptin group experienced a higher incidence of hypoglycemic events compared to the PCG, the overall AEs, serious AEs, hypoglycemia, and severe hypoglycemia were comparable between the omarigliptin and control groups (PCG and ACG).
CONCLUSION
Omarigliptin has a favorable glycemic efficacy and safety profile for managing T2DM.
Topics: Humans; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Blood Glucose; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Hypoglycemia; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Heterocyclic Compounds, 2-Ring; Pyrans
PubMed: 38417828
DOI: 10.3803/EnM.2023.1839 -
Bone Marrow Transplantation Jun 2024Steroid-refractory graft-versus-host disease (SR-GvHD) represents a major complication of pediatric allogenic hematopoietic stem cell transplantation. Ruxolitinib, a... (Meta-Analysis)
Meta-Analysis
Steroid-refractory graft-versus-host disease (SR-GvHD) represents a major complication of pediatric allogenic hematopoietic stem cell transplantation. Ruxolitinib, a selective JAK 1-2 inhibitor, showed promising results in the treatment of SR-GvHD in adult trial, including patients >12 years old. This systematic review aims to evaluate ruxolitinib use for SR-GvHD in the pediatric population. Among the 12 studies included, ruxolitinib administration presented slight differences. Overall response rate (ORR) ranged from 45% to 100% in both acute and chronic GvHD. Complete response rates (CR) varied from 9% to 67% and from 0% to 28% in aGvHD and cGvHD, respectively. Individual-patient meta-analysis from 108 children under 12 years showed an ORR and CR for aGvHD of 74% and 56%, respectively, while in cGvHD ORR was 78% but with only 11% achieving CR. Treatment-related toxicities were observed in 20% of patients, including cytopenia, liver toxicity, and infections. Age, weight, graft source, previous lines of therapy, and dose did not significantly predict response, while a higher rate of toxicities was observed in aGvHD patients. In conclusion, ruxolitinib shows promising results in the treatment of SR-GvHD in children, including those under 12 years. Specific pediatric perspective trials are currently ongoing to definitely assess its efficacy and safety.
Topics: Humans; Graft vs Host Disease; Nitriles; Pyrazoles; Pyrimidines; Child; Chronic Disease; Acute Disease; Child, Preschool; Hematopoietic Stem Cell Transplantation; Male; Female; Adolescent; Infant; Bronchiolitis Obliterans Syndrome
PubMed: 38402346
DOI: 10.1038/s41409-024-02252-z -
Medicine Feb 2024To evaluate the efficacy and safety of dorzagliatin for the treatment of type 2 diabetes (T2DM). (Meta-Analysis)
Meta-Analysis
OBJECT
To evaluate the efficacy and safety of dorzagliatin for the treatment of type 2 diabetes (T2DM).
METHODS
Seven databases were systematically searched, spanning the interval from 2016 to August 2023. Randomized controlled trials (RCTS) comparing dorzagliatin with placebo for the treatment of T2DM were applicable for containing this study. The relevant data were extracted, and a meta-analysis was implemented using RevMan 5.4 software.
RESULTS
A total of 3 studies involving 1332 patients were included. We use glycated hemoglobin (HbA1c) levels as the major indicator of efficacy, FBG, 2h postprandial blood glucose, Homa-β and Homa-IR to be Secondary outcome measures. Compared with placebo group, dorzagliatin significantly reduced blood glucose levels as well as enhanced insulin resistance. In terms of safety, no serious adverse events occurred. However, lipid-related indicators, especially triglycerides levels, and the incidence of hypoglycemia were higher in patients in the dorzagliatin group compared with those in the control group, but the increase from baseline was mild.
CONCLUSIONS
Dorzagliatin exerted favorable effects in hypoglycemic control, effectively reduced the HbA1c, FBG, and 2h postprandial blood glucose levels in T2DM patients, stimulated the secretion of insulin during the initial phase, and exerted a consistent hypoglycemic effect. However, the incidence of adverse events such as elevated blood lipids and cardiovascular risk warrants further investigations through long-term clinical trials.
Topics: Humans; Glucokinase; Glycated Hemoglobin; Blood Glucose; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Pyrazoles
PubMed: 38394489
DOI: 10.1097/MD.0000000000036916 -
Frontiers in Immunology 2024Although immune checkpoint inhibitors (ICIs) show a significant overall survival advantage over standard advanced renal cell carcinoma (aRCC) therapies, tumor response... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although immune checkpoint inhibitors (ICIs) show a significant overall survival advantage over standard advanced renal cell carcinoma (aRCC) therapies, tumor response to these agents remains poor. Some studies have shown that combination therapy including an ICI appears to be the best treatment; however, the overall benefit in terms of efficacy and toxicity still needs to be assessed. Thus, we performed a network meta-analysis to evaluate the differences in the efficacy of several combinations that include an ICI to provide a basis for clinical treatment selection.
METHODS
We conducted a thorough search of PubMed, EMBASE, and the Cochrane Library for articles from January 2010 to June 2023. R 4.4.2 and STATA 16.0 were used to analyze data; hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were used to assess the results.
RESULTS
An indirect comparison showed that nivolumab plus cabozantinib and pembrolizumab plus lenvatinib were the most effective treatments for progression-free survival (PFS), with no significant differences between the two interventions (HR, 1.31; 95% CI, 0.96-1.78; P=0.08); rank probability showed that pembrolizumab plus lenvatinib had a 57.1% chance of being the preferred treatment. In the absence of indirect comparisons between pembrolizumab plus axitinib, nivolumab plus ipilimumab, avelumab plus axitinib, nivolumab plus cabozantinib, and pembrolizumab plus lenvatinib, pembrolizumab plus axitinib (40.2%) was the best treatment option for overall survival (OS). Compared to pembrolizumab plus lenvatinib, nivolumab plus ipilimumab (OR, 0.07; 95% CI, 0.01-0.65; P=0.02) and pembrolizumab plus axitinib (OR, 0.05; 95% CI, 0.00-0.78; P<0.001) had a lower incidence of overall adverse events (AEs).
CONCLUSION
Pembrolizumab plus lenvatinib and pembrolizumab plus axitinib resulted in the highest PFS and OS rates, respectively. Pembrolizumab plus axitinib may be the best option when AEs are a concern.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/, identifier INPLASY202410078.
Topics: Humans; Carcinoma, Renal Cell; Axitinib; Nivolumab; Immune Checkpoint Inhibitors; Ipilimumab; Network Meta-Analysis; Kidney Neoplasms; Anilides; Phenylurea Compounds; Pyridines; Quinolines
PubMed: 38390328
DOI: 10.3389/fimmu.2024.1255577 -
Acta Neurologica Belgica Jun 2024The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings.... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings. This study aims to evaluate the effectiveness and long-term efficacy of edaravone.
METHODS
The OVID Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched for articles published between January 1, 2000, and May 1, 2023. Two investigators independently screened the retrieved articles for randomized controlled trials (RCTs), cohort studies, or single-arm trials that evaluated the effect of edaravone on amyotrophic lateral sclerosis (ALS). The risk of bias was evaluated using the revised Cochrane Risk-of-Bias (RoB 2.0) tool for randomized controlled trials (RCTs) and the Risk-of-Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies. The primary outcome was the ALSFRS-R score assessed at month 6, with secondary outcomes including the ALSFRS-R scores evaluated at months 9, 12, and 18, forced vital capacity (FVC), and adverse events. The certainty of evidence was assessed using the GRADE approach.
RESULTS
The analysis included 16 studies with a total of 4828 participants. Among these, four were randomized controlled trials (RCTs) and 12 were observational studies. Of the RCTs, four were rated as having a low risk of bias, while six of the observational studies were rated as having a low risk of bias. Edaravone was associated with slightly slower progression in the reduction of ALSFRS-R score at month 6 compared to placebo (mean difference 1.01, 95%CI -0.87 to 3.09, p = 0.293), as shown by evidence from RCTs. However, observational studies did not show any benefit of adding edaravone to routine practice (mean difference 1.85, 95%CI -2.05 to 5.75, p = 0.352). The change from baseline in ALSFRS-R score was -2.1, -4.04, -7.5, -6.82, and -7.9 at months 3, 6, 9, 12, and 18, respectively. The GRADE assessment indicated moderate certainty for evidence from RCTs, while evidence from observational studies had very low certainty.
CONCLUSION
Due to the limited number of studies and confounding issues in observational studies, further examination of the added benefits of edaravone to routine practice is necessary through RCTs, particularly regarding its long-term efficacy.
Topics: Edaravone; Humans; Amyotrophic Lateral Sclerosis; Free Radical Scavengers; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38347315
DOI: 10.1007/s13760-024-02476-2 -
Health Technology Assessment... Jan 2024Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the age of 5 years, but it can develop at any age. Atopic dermatitis is characterised by dry, inflamed skin accompanied by intense itchiness (pruritus).
OBJECTIVES
To appraise the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib within their marketing authorisations as alternative therapies for treating moderate-to-severe atopic dermatitis compared to systemic immunosuppressants (first-line ciclosporin A or second-line dupilumab and baricitinib).
DATA SOURCES
Studies were identified from an existing systematic review (search date 2019) and update searches of electronic databases (MEDLINE, EMBASE, CENTRAL) to November 2021, from bibliographies of retrieved studies, clinical trial registers and evidence provided by the sponsoring companies of the treatments under review.
METHODS
A systematic review of the clinical effectiveness literature was carried out and a network meta-analysis undertaken for adults and adolescents at different steps of the treatment pathway. The primary outcome of interest was a combined response of Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4; where this was consistently unavailable for a step in the pathway, an analysis of Eczema Area and Severity Index 75 was conducted. A de novo economic model was developed to assess cost effectiveness from the perspective of the National Health Service in England. The model structure was informed through systematic review of the economic literature and by consulting clinical experts. Effectiveness data were obtained from the network meta-analysis. Costs and utilities were obtained from the evidence provided by sponsoring companies and standard UK sources.
RESULTS
Network meta-analyses indicate that abrocitinib 200 mg and upadacitinib 30 mg may be more effective, and tralokinumab may be less effective than dupilumab and baricitinib as second-line systemic therapies. Abrocitinib 100 mg and upadacitinib 15 mg have a more similar effectiveness to dupilumab. Upadacitinib 30 and 15 mg are likely to be more effective than ciclosporin A as a first-line therapy. Upadacitinib 15 mg, abrocitinib 200 and 100 mg may be more effective than dupilumab in adolescents. The cost effectiveness of abrocitinib and upadacitinib for both doses is dependent on the subgroup of interest. Tralokinumab can be considered cost-effective as a second-line systemic therapy owing to greater cost savings per quality-adjusted life-year lost.
CONCLUSIONS
The primary strength of the analysis of the three new drugs compared with current practice for each of the subpopulations is the consistent approach to the assessment of clinical and cost effectiveness. However, the conclusions are limited by the high uncertainty around the clinical effectiveness and lack of data for the primary outcome for comparisons with baricitinib and for the adolescent and adult first-line populations.
FUTURE WORK AND LIMITATIONS
The most significant limitation that Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4 could not be obtained for the adolescent and adult first-line systemic treatment populations is due to a paucity of data for dupilumab and ciclosporin A. A comparison of the new drugs against one another in addition to current practice would be beneficial to provide a robust view on which treatments are the most cost-effective.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42021266219.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: 135138) and is published in full in ; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information.
Topics: Child; Adult; Adolescent; Humans; Child, Preschool; Dermatitis, Atopic; Cyclosporine; State Medicine; Treatment Outcome; Cost-Benefit Analysis; Eczema; Antibodies, Monoclonal; Purines; Heterocyclic Compounds, 3-Ring; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38343072
DOI: 10.3310/LEXB9006