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Cureus Apr 2022A compelling intervention to maintain healthy gut microbiota in graft-versus-host-disease (GVHD) is fecal microbial transplantation (FMT). To examine its role in GVHD,... (Review)
Review
A compelling intervention to maintain healthy gut microbiota in graft-versus-host-disease (GVHD) is fecal microbial transplantation (FMT). To examine its role in GVHD, we conducted a systemic literature search using multiple electronic databases. Upon pooling of data, 79 patients from six studies and five case reports were included. Complete remission (CR) occurred in 55.9% of patients, and partial remission (PR) occurred in 26.5% of patients (82.4% overall response rate). A limited number of patients had treatment-related mortality (TRM), while few showed mild gastrointestinal (GI)-related and non-GI adverse effects. None of the studies directly examined the role of FMT in the prevention of GVHD. In conclusion, FMT seems to be a safe and effective strategy for the management of GVHD based on the current evidence. Due to the small number of patients evaluated and the absence of randomized data, one cannot portray FMT as a standard of care yet; however, the low toxicity along with the clinical improvement justifies this modality to be tested in a randomized fashion.
PubMed: 35530905
DOI: 10.7759/cureus.23873 -
International Journal of Clinical... Jan 2014To describe the efficacy and safety of vortioxetine for the treatment of major depressive disorder (MDD). (Review)
Review
Vortioxetine for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?
OBJECTIVE
To describe the efficacy and safety of vortioxetine for the treatment of major depressive disorder (MDD).
DATA SOURCES
The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/, http://www.clinicaltrialsregister.eu and http://www.clinicaltrials.gov for the search terms 'vortioxetine' and 'Lu AA21004', and by obtaining posters presented at congresses. Product labelling provided additional information.
STUDY SELECTION
All available clinical reports of studies were identified.
DATA EXTRACTION
Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.
DATA SYNTHESIS
Vortioxetine is a multi-modal antidepressant that functions as a human 5-HT3A and 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist, and inhibitor of the serotonin transporter. The recommended dose range is 5-20 mg/day. Approval for the treatment of MDD was based on a clinical development programme that included six positive 6-8 week studies, including one study in elderly people, and one positive maintenance study in adults. In the informative short-term studies in non-elderly patients, NNT for response with vortioxetine vs. placebo was 7 (95% CI 6-9), and NNT for remission vs. placebo was 11 (95% CI 8-17). NNH for discontinuation because of an adverse event (AE) was 36 (95% CI 24-70). The most commonly encountered AEs (incidence ≥ 5% and at least twice the rate of placebo) as identified in product labelling were nausea, constipation and vomiting, with NNH values vs. placebo of 6 (95% CI 6-7), 64 (95% CI 37-240), and 28 (95% CI 23-38), respectively. Changes in weight were not clinically relevant.
CONCLUSIONS
Vortioxetine represents another option for the treatment of MDD. Vortioxetine appears to have a favourable weight-gain profile. Additional information regarding the time course of response/remission and for the commonly occurring AE of nausea would be helpful to better characterise this agent. Pending clinical trials include those examining cognitive dysfunction that can accompany MDD.
Topics: Adult; Aged; Antidepressive Agents; Body Weight; Clinical Trials as Topic; Depressive Disorder, Major; Drug Administration Schedule; Fatigue; Humans; Middle Aged; Numbers Needed To Treat; Patient Harm; Piperazines; Secondary Prevention; Sexual Dysfunction, Physiological; Suicide; Sulfides; Treatment Outcome; Vortioxetine
PubMed: 24165478
DOI: 10.1111/ijcp.12350 -
World Journal of Surgical Oncology Mar 2023Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However,... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However, the superiority of combination therapy to TACE monotherapy remains controversial. Therefore, here we performed a meta-analysis to evaluate the efficacy and safety of TACE plus TKIs in patients with uHCC.
METHODS
We searched four databases for eligible studies. The primary outcome was time to progression (TTP), while the secondary outcomes were overall survival (OS), tumor response rates, and adverse events (AEs). Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were collected for TTP and OS, and the data were analyzed using random-effects meta-analysis models in STATA software. OR and 95% CIs were used to estimate dichotomous variables (complete remission[CR], partial remission[PR], stable disease[SD], progressive disease[PD], objective response rate[ORR], disease control rate[DCR], and AEs) using RStudio's random-effects model. Quality assessments were performed using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane risk of bias tool for randomized controlled trials (RCTs).
RESULTS
The meta-analysis included 30 studies (9 RCTs, 21 observational studies) with 8246 patients. We judged the risk of bias as low in 44.4% (4/9) of the RCTs and high in 55.6% (5/9) of the RCTs. All observational studies were considered of high quality, with a NOS score of at least 6. Compared with TACE alone or TACE plus placebo, TACE combined with TKIs was superior in prolonging TTP (combined HR 0.72, 95% CI 0.65-0.80), OS (combined HR 0.57, 95% CI 0.49-0.67), and objective response rate (OR 2.13, 95% CI 1.23-3.67) in patients with uHCC. However, TACE plus TKIs caused a higher incidence of AEs, especially hand-foot skin reactions (OR 87.17%, 95%CI 42.88-177.23), diarrhea (OR 18.13%, 95%CI 9.32-35.27), and hypertension (OR 12.24%, 95%CI 5.89-25.42).
CONCLUSIONS
Our meta-analysis found that TACE plus TKIs may be beneficial for patients with uHCC in terms of TTP, OS, and tumor response rates. However, combination therapy is also associated with a significantly increased risk of adverse reactions. Therefore, we must evaluate the clinical benefits and risks of combination therapy. Further well-designed RCTs are needed to confirm our findings.
TRIAL REGISTRATION
PROSPERO registration number: CRD42022298003.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Tyrosine Kinase Inhibitors; Chemoembolization, Therapeutic; Combined Modality Therapy; Treatment Outcome
PubMed: 37004052
DOI: 10.1186/s12957-023-02961-7 -
Clinical Journal of the American... May 2013The efficacy and safety of immunosuppression for idiopathic membranous nephropathy (IMN) with nephrotic syndrome are still controversial. A systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
The efficacy and safety of immunosuppression for idiopathic membranous nephropathy (IMN) with nephrotic syndrome are still controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
The Cochrane Library, PUBMED, EMBASE, Chinese Database, and Clinical Trial Registries (June 2012) were searched to identify RCTs investigating the effect of immunosuppression on adults with IMN and nephrotic syndrome.
RESULTS
This review was an update (36 RCTs, 1762 participants) of the 2004 version (18 RCTs, 1025 participants). Immunosuppression significantly reduced all-cause mortality or ESRD (15 RCTs, 791 participants; risk ratio, 0.58 [95% confidence interval, 0.36-0.95]; P=0.03). However, the result was not consistent when prespecified subgroup analyses were undertaken. Immunosuppression increased complete or partial remission (CR + PR) (16 RCTs, 864 participants; 1.31 [1.01-1.70]; P=0.04) but resulted in more withdrawals or hospitalizations (16 RCTs, 880 participants; 5.35 [2.19-13.02]; P=0.002). Corticosteroids combined with alkylating agents significantly reduced all-cause mortality or ESRD (8 RCTs, 448 participants; 0.44 [0.26-0.75]; P=0.002) and increased CR + PR (7 RCTs, 422 participants; 1.46 [1.13-1.89]; P=0.004) but led to more adverse events (4 RCTs, 303 participants; 4.20 [1.15-15.32]; P=0.03). Cyclophosphamide was safer than chlorambucil (3 RCTs, 147 participants; 0.48 [0.26-0.90]; P=0.02). Cyclosporine and mycophenolate mofetil failed to show superiority over alkylating agents. Tacrolimus and adrenocorticotropic hormone significantly reduced proteinuria.
CONCLUSIONS
Alkylating agents plus corticosteroids had long-term and short-term benefits for adult IMN, but resulted in more withdrawals or hospitalizations.
Topics: Chi-Square Distribution; Disease Progression; Drug Therapy, Combination; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Odds Ratio; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome
PubMed: 23449768
DOI: 10.2215/CJN.07570712 -
Immunotherapy Sep 2017Chimeric antigen receptor modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. We conducted a... (Meta-Analysis)
Meta-Analysis Review
Chimeric antigen receptor modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. We conducted a systematic review and meta-analysis of all published clinical trials studying the role of efficacy as well as safety of CD-19 and CD-20 chimeric antigen receptor-T therapy for B-cell hematologic malignancies. A total of 16 studies with 195 patients were identified. The pooled analysis showed an overall response rate of 61% (118/195) with complete response of 42% (81/195) and partial response of 19% (37/195). Major adverse events were cytokine release syndrome 33%, neurotoxicity 33% and B-cell aplasia 54%. Collectively, the results indicate encouraging response in relapsed/refractory B lymphoma and leukemia, especially in acute lymphoblastic leukemia (ALL) patients.
Topics: Animals; Antigens, CD19; Antigens, CD20; B-Lymphocytes; Cell Count; Genetic Therapy; Hematologic Neoplasms; Humans; Immunotherapy, Adoptive; Receptors, Antigen; Recombinant Fusion Proteins; Remission Induction; T-Lymphocytes
PubMed: 28971751
DOI: 10.2217/imt-2017-0062 -
BMC Nephrology Sep 2023Rituximab (RTX) and cyclophosphamide (CYC) based treatments are both recommended as first-line therapies in idiopathic membranous nephropathy (IMN) by KDIGO 2021... (Meta-Analysis)
Meta-Analysis
Rituximab (RTX) and cyclophosphamide (CYC) based treatments are both recommended as first-line therapies in idiopathic membranous nephropathy (IMN) by KDIGO 2021 guideline. However, the efficacy of RTX vs. CYC-based treatments in IMN is still controversial. We performed this systemic review and meta-analysis registered in PROSPERO (CRD 42,022,355,717) by pooling data from randomized controlled trials or cohort studies in IMN patients using the EMBASE, PubMed, and Cochrane libraries (till Orc 1, 2022). The primary outcomes were the complete remission (CR) rate + partial remission (PR) rate. CR rate, immunologic response rate, relapse rate, and the risk of serious adverse events (SAE) were secondary outcomes. Eight studies involving 600 adult patients with IMN were included with a median follow-up duration of 12 to 60 months. RTX induced a similar overall remission rate compared with CYC (RR 0.88, 95% CI: 0.71, 1.09, P = 0.23). At the follow-up time of 6 months, RTX was associated with a lower CR + PR rate compared with CYC (RR 0.67, 95% CI: 0.52, 0.88, P = 0.003). Moreover, RTX might be less effective in inducing CR + PR than CYC treatment in IMN patients with high antiPLA2R antibody levels (RR 0.67, 95% CI: 0.48, 0.94, P = 0.02). The occurrences of CRs, relapse rates, immunologic response rates, and SAE were not significantly different between RTX and CYC, respectively. In conclusion, although the long-term efficacy and safety of CYC compared to RTX were comparable, CYC might respond faster and be more advantageous in IMN patients with high antiPLA2R antibody titers.
Topics: Adult; Humans; Glomerulonephritis, Membranous; Rituximab; Cyclophosphamide; Patients
PubMed: 37740193
DOI: 10.1186/s12882-023-03307-x -
The Journal of Dermatological Treatment Dec 2023The objective of this systematic review was to evaluate the efficacies of different biologic therapies in treating tumor necrosis factor-alpha (TNFα)-induced...
OBJECTIVES
The objective of this systematic review was to evaluate the efficacies of different biologic therapies in treating tumor necrosis factor-alpha (TNFα)-induced paradoxical psoriasis (PXP) and controlling inflammatory bowel disease (IBD) symptoms.
METHODS
We conducted a literature search of the Ovid EMBASE, Ovid Medline, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials databases from their inception to October 3, 2021. We considered all peer-reviewed, randomized controlled trials, chart reviews, and observational studies that discussed the TNFα-induced PXP treatment outcomes in IBD patients of switching to different biologic therapies.
RESULTS
Switching to ustekinumab (UST) resulted in complete or partial resolution of TNFα-induced PXP in 83.1% of patients (74 out of 89 patients), while switching to either vedolizumab (VDZ) or secukinumab led to complete resolution in 100% of patients (eight out of eight patients). Approximately 75.4% of patients who were switched to UST remained in IBD remission, 4.6% in partial remission, and 20.0% in the flare of IBD.
CONCLUSIONS
UST has sufficient data to demonstrate the efficacy in treating TNFα-induced PXP and controlling IBD symptoms concurrently. More data is needed to validate the efficacies of VDZ and SEC in treating TNFα-induced PXP in IBD patients.
Topics: Humans; Tumor Necrosis Factor-alpha; Psoriasis; Ustekinumab; Inflammatory Bowel Diseases; Treatment Outcome
PubMed: 36205507
DOI: 10.1080/09546634.2022.2133533 -
BMC Nephrology Jul 2016Evidence on the role of plasma exchange for treating recurrent post-transplant focal segmental glomerulosclerosis (FSGS) comes largely from individual cases and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evidence on the role of plasma exchange for treating recurrent post-transplant focal segmental glomerulosclerosis (FSGS) comes largely from individual cases and uncontrolled series. We conducted a systematic review and meta-analysis to estimate the remission rate after treatment with plasma exchange, and to determine if remission varied with patient or treatment characteristics.
METHODS
We searched MEDLINE, EMBASE, Science Citation Index Expanded, and the Conference Proceedings Citation Index (Science and BIOSIS) for studies of patients with post-transplant recurrent FSGS who were treated with plasma exchange after recurrence (1950-2012). Of 678 studies screened, 77 met our inclusion criteria: 34 case reports (45 patients) and 43 case series (378 patients). We extracted patient-level data from each study and used random-effects models to calculate remission, defined as proteinuria <3.5 g/day (partial) or <0.5 g/day (complete).
RESULTS
The overall remission rate in 423 patients with outcome data was 71 % (95 % CI: 66 % to 75 %). In 235 patients with data on age, remission was similar for adults and children: 69.1 % (95 % CI: 59.6 % to 77.2 %) and 70.2 % (95 % CI: 61.1 % to 77.9 %). Males were more likely to achieve remission (OR = 2.85; 95 % CI: 1.44 to 5.62) and patients treated within 2 weeks of recurrence showed a trend towards higher likelihood of remission (OR = 2.16; 95 % CI: 0.93 to 5.01). Proteinuria >7 g/day at recurrence was inversely associated with remission (OR = 0.43; 95 % CI: 0.19 to 0.97). Age and type of kidney transplant (living vs. deceased) did not associate with remission.
CONCLUSION
In this systematic review of patients with recurrent post-transplant FSGS, 71 % of patients achieved full or partial remission after treatment with plasma exchange; however, extensive missing data and lack of a control group limit any conclusions on causality.
Topics: Female; Glomerulosclerosis, Focal Segmental; Humans; Kidney Transplantation; Male; Plasma Exchange; Postoperative Period; Proteinuria; Recurrence; Remission Induction; Sex Factors
PubMed: 27473582
DOI: 10.1186/s12882-016-0322-7 -
Cancers Feb 2024This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Bruton tyrosine kinase inhibitors (BTKis) for central nervous system lymphoma... (Review)
Review
BACKGROUND
This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Bruton tyrosine kinase inhibitors (BTKis) for central nervous system lymphoma (CNSL).
METHODS
A systematic review was carried out to identify relevant studies from the PubMed, Embase, Cochrane Library, Web of Science, WanFang, CNKI, and CBM databases. The studies included patients with CNSL who received BTKis and reported the overall response (OR), complete remission (CR), and partial response (PR). An overall effect analysis was performed using STATA 15.0. A random-effects model was utilized to calculate the pooled rates, and 95% confidence intervals (CI) were determined for all outcomes.
RESULTS
A total of 21 studies involving 368 patients were included in the meta-analysis. For newly diagnosed CNSL, due to the small simple size, we conducted a quantitative description, and the ORR could reach up to 100%. For relapsed/refractory patients, the pooled ORR was 72% (95% CI: 64-80%, I = 54.89%, = 0.00), with a pooled CR and PR of 43% (95% CI: 33-54%, I = 65.40%, = 0.00) and 23% (95% CI: 13-35%, I = 78.05%, = 0.00), respectively. Most adverse events were hematology-related and generally manageable.
CONCLUSION
BTKis showed acceptable efficacy and safety in treating patients with CNSL. However, large and well-designed trials are still required to confirm BTKis as a treatment for CNSL.
PubMed: 38473226
DOI: 10.3390/cancers16050860 -
Medicine Jul 2010We performed a systematic review and meta-analysis of randomized controlled trials to compare complete remission and adverse events (that is, infection, leukopenia, and... (Comparative Study)
Comparative Study Meta-Analysis Review
We performed a systematic review and meta-analysis of randomized controlled trials to compare complete remission and adverse events (that is, infection, leukopenia, and gastrointestinal [GI] symptoms) between mycophenolate mofetil (MMF) and cyclophosphamide (CYC) for the treatment of lupus nephritis (LN). We identified trials from MEDLINE using the PubMed and Ovid search engines, and from The Cochrane Central Register of Randomized Controlled Trials. Eligible studies were randomized controlled trials comparing MMF with CYC with 1 of following outcomes: complete remission, complete/partial remission, infection, leukopenia, GI symptoms, serum creatinine, 24-hour urine protein, and urine albumin. Data were independently extracted by 2 reviewers. Five trials with a total of 638 patients were eligible for review. While the MMF group tended to achieve complete remission more frequently than the CYC group, this was not significant (pooled risk ratio [RR], 1.60; 95% confidence interval [CI], 0.87-2.93). Pooling based on the 4 homogeneous trials yielded similar results-that is, no benefit of MMF compared with CYC groups (RR, 1.15; 95% CI, 0.74-1.77). The complete or partial remission rates were also not different (pooled RR, 1.21; 95% CI, 0.97-1.48) among the groups. The adverse events (infection, renal function, and GI symptoms) were not significantly different, except for leukopenia, which was lower in the MMF group. In summary, patients treated with MMF and CYC had similar remission rates, but the MMF group had less frequent leukopenia than the CYC group. Further large-scale trials are needed to confirm these results.
Topics: Cyclophosphamide; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome
PubMed: 20616662
DOI: 10.1097/MD.0b013e3181e93d00