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International Journal of Clinical... Apr 2012To describe the efficacy and safety of vilazodone for the treatment of major depressive disorder (MDD). (Review)
Review
Vilazodone 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 vilazodone 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.fda.gov and http://www.clinicaltrials.gov for the search term 'vilazodone'. Product labeling 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
Vilazodone is a specific serotonin reuptake inhibitor and serotonin 5HT1A receptor partial agonist. In needs to be administered with food to ensure adequate bioavailability. Approval for the treatment of MDD was based on a clinical development programme that included two 8-week placebo-controlled randomised clinical trials in outpatients with MDD where vilazodone was titrated to a target dose of 40 mg/d over the first 2 weeks. Both trials evidenced efficacy for vilazodone as measured by the Montgomery Asberg Depression Rating Scale. NNT for response vs. placebo was 8 (95% CI 6-16) and for remission was 14 (95% CI 8-55). NNH vs. placebo for discontinuation because of an adverse event (AE) was 27 (95% CI 15-104). The most commonly encountered AEs (incidence ≥ 5% and at least twice the rate of placebo) were diarrhoea, nausea, vomiting and insomnia, with NNH values vs. placebo of 6 (95% CI 5-8), 6 (95% CI 5-8), 30 (95% CI 18-82) and 26 (95% CI 16-78), respectively. NNH vs. placebo for any sexual AE was 12 (95% CI 9-18), but systematically collected data using rating scales of sexual function did not reveal treatment associated effects. Vilazodone was not associated with clinically relevant weight change in the short-term trials. In an open-label 1-year study of vilazodone, mean weight increased by 1.7 kg among the observed cases.
CONCLUSIONS
Vilazodone represents another option for the treatment of MDD. Vilazodone appears to have a favourable weight-gain profile based on short-term studies. Sexual side-effects were not consistently demonstrated when assessed using clinical rating scales but spontaneously reported AEs related to sexual functioning were observed. Additional controlled data regarding long-term efficacy and effectiveness will help characterise this new agent when used in maintenance treatment.
Topics: Antidepressive Agents; Benzofurans; Clinical Trials as Topic; Depressive Disorder, Major; Double-Blind Method; Drug Administration Schedule; Drug Labeling; Humans; Indoles; Numbers Needed To Treat; Piperazines; Randomized Controlled Trials as Topic; Treatment Outcome; Vilazodone Hydrochloride
PubMed: 22284853
DOI: 10.1111/j.1742-1241.2011.02885.x -
Translational Cancer Research Apr 2022Autologous hematopoietic stem cell transplantation (AHSCT) is a common method for the clinical treatment of malignant lymphomas that recur after conventional...
Efficacy and safety of autologous hematopoietic stem cell transplantation in the treatment of malignant lymphoma after chemotherapy: a systematic review and meta-analysis.
BACKGROUND
Autologous hematopoietic stem cell transplantation (AHSCT) is a common method for the clinical treatment of malignant lymphomas that recur after conventional chemotherapy. It has been reported that its efficacy is better than conventional chemotherapy, but the efficacy of its first-line treatment is controversial, and the existing clinical randomized controlled trials have not yet reached a unified conclusion. This work intended to use meta-analysis to systematically evaluate the efficacy and safety of AHSCT in the treatment of malignant lymphoma after high-dose chemotherapy, and draw reliable conclusions to provide reference and basis for clinical application.
METHODS
The inclusion and exclusion criteria were formulated based on the PICOIS principle. Relevant articles were retrieved from Medline, Excerpta Medica Database (EMBASE), Elton B. Stephens. Company (EBSCO), Ovid Technologies (OVID), China Biomedical Database, and Wanfang. The search period was limited the study published between January 1, 1980 and November 2021. The search terms included malignant lymphoma, autologous hematopoietic stem cell transplantation, AHSCT, high-dose chemotherapy, etc. The study subjects were diagnosed as malignant lymphoma patients. The experimental group was defined as AHSCT after high-dose chemotherapy, and the control group was defined as conventional chemotherapy (the chemotherapy regimen was not limited). The outcome indicators were overall survival (OS), complete remission rate [complete response (CR) + partial response (PR)], and event-free survival (EFS). RevMan5.3 software provided by the Cochrane Collaboration was used for meta-analysis.
RESULTS
A total of 6 pieces of literature were included, with 264 cases in the experimental group and 389 cases in the control group. There was no risk of bias in the included literature. The intervention method in the control group was conventional chemotherapy (chemotherapy regimen was not limited). The differences in the rates of overall survival and progression-free survival between the groups were compared, and it was found that the overall survival between groups was [odds ratio (OR) =2.88; 95% confidence interval (CI): 1.78-4.66; Z=4.31; P<0.0001] and progression-free survival rate was (OR =2.70; 95% CI: 1.86-3.92, Z=5.21; P<0.00001).
DISCUSSION
AHSCT treatment can significantly prolong the overall survival and progression-free survival rates of patients with malignant lymphoma after chemotherapy.
PubMed: 35571654
DOI: 10.21037/tcr-22-595 -
PloS One 2014Lung cancer, particularly non-small-cell lung cancer (NSCLC) is the leading cause of cancer mortality. Chemotherapy combined dendritic cells co-cultured with... (Meta-Analysis)
Meta-Analysis Review
Effectiveness and safety of chemotherapy combined with dendritic cells co-cultured with cytokine-induced killer cells in the treatment of advanced non-small-cell lung cancer: a systematic review and meta-analysis.
BACKGROUND
Lung cancer, particularly non-small-cell lung cancer (NSCLC) is the leading cause of cancer mortality. Chemotherapy combined dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) immunotherapy has been applied in advanced NSCLC patients' treatment, but couldn't provide consistent beneficial results. Therefore, it is necessary to evaluate the efficiency and safety of combination therapy to promote the application.
METHODS
A literature search for randomized controlled trials of NSCLC was conducted in PubMed database. Before meta-analysis was performed, studies were evaluated heterogeneity. Pooled risk ratios (RRs) were estimated and 95% confidence intervals (CIs) were calculated using a fixed-effect model. Sensitivity analysis was also performed.
RESULTS
Six eligible trials were enrolled. Efficiency and safety of chemotherapy followed by DC-CIK immunotherapy (experimental group) and chemotherapy alone (control group) were compared. 1-year overall survival (OS) (P = 0.02) and progression free survival (PFS) (P = 0.005) in the experimental group were significantly increased compared with the control. Disease control rate (DCR) (P = 0.006) rose significantly in experimental group. However, no significant differences between the two groups were observed in 2-year OS (P = 0.21), 2-year PFS (P = 0.10), overall response rate (ORR) (P = 0.76) and partial response (PR) (P = 0.22). Temporary fever, anemia, leukopenia and nausea were the four major adverse events (AEs) treated by chemotherapy. The incidence of anemia, leukopenia and nausea in the experimental group was obviously lower than the control group. Temporary fever rate was higher in experimental group than that in the control, but could be alleviated by taking sufficient rest.
CONCLUSIONS
Chemotherapy combined with DC-CIK immunotherapy showed superiority in DCR, 1-year OS and PFS, and no more AEs appeared, however, there was no significant improvement in ORR, PR, 2-year OS and PFS. As a whole, the combination therapy is safer but modest in efficacy for advanced NSCLC patients.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Coculture Techniques; Cytokine-Induced Killer Cells; Databases, Factual; Dendritic Cells; Disease-Free Survival; Humans; Immunotherapy; Lung Neoplasms; Remission Induction; Survival Rate
PubMed: 25268709
DOI: 10.1371/journal.pone.0108958 -
Medicine Sep 2022This analysis aimed to assess the effect of decitabine combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treating recurrent and refractory... (Meta-Analysis)
Meta-Analysis
Efficacy of decitabine combined with allogeneic hematopoietic stem cell transplantation in the treatment of recurrent and refractory acute myeloid leukemia (AML): A systematic review and meta-analysis.
BACKGROUND
This analysis aimed to assess the effect of decitabine combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treating recurrent and refractory acute myeloid leukemia.
METHOD
The present analysis was carried out according to the principles of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline statement. Web of Science, Embase, PubMed, The Cochrane Library, CNKI, VIP, and WanFang Data databases were searched for trials published from their corresponding inception to September 13, 2021. Retrospective research or published randomized controlled trials in Chinese or English were ruled out. The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database scale. Mean differences with 95% confidence intervals were used to analyze continuous data. The I2 test was used to determine heterogeneity, and the meta-analysis was conducted using Revman 5.4.
RESULTS
Eight studies including 795 participants in total were identified. Decitabine and allo-HSCT showed significant reductions in recurrence after transplantation (odds ratio [OR] = 0.29, 95% confidence interval [CI] (0.17, 0.50), P < .00001), leukemia-free survival (OR = 2.17, 95% CI (1.47, 3.21), P < .0001), graft related death (OR = 0.50, 95% CI (0.25, 0.98), P = .04), and significant improvements in complete remission (OR = 0.39, 95% CI = 0.23-0.68, P = .0007) and partial remission (OR = 0.46, 95%CI = 0.27-0.78, P = .004). The median follow-up time, acute graft-versus-host disease, and no remission had no significant difference between treatment and control groups (the median follow-up time: OR = -1.76, 95% CI (-6.28, 2.76), P = .45; acute graft-versus-host disease: OR = 0.72, 95% CI (0.50, 1.03), P = .08; no remission: OR = 3.19, 95%CI = 2.06-4.94, P = .05). Overall, the magnitude of the effect was found to be in the small to moderate range.
CONCLUSION
Decitabine combined with allo-HSCT can obtain lower recurrence risk and longer disease-free survival time, and improve the prognosis of patients. The safety is relatively stable. Due to the varying quality level of the included studies, the validation of multiple high-quality studies still needs improvement.
Topics: Decitabine; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Retrospective Studies
PubMed: 36123842
DOI: 10.1097/MD.0000000000030644 -
The Cochrane Database of Systematic... Dec 2016Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy, the majority of which may be able to achieve remission with a single antiepileptic drug (AED).The correct choice of first-line antiepileptic therapy for individuals with newly diagnosed seizures is of great importance. It is important that the choice of AED for an individual is based on the highest-quality evidence available regarding the potential benefits and harms of various treatments. It is also important to compare the efficacy and tolerability of AEDs appropriate to given seizure types.Topiramate and carbamazepine are commonly used AEDs. Performing a synthesis of the evidence from existing trials will increase the precision of results of outcomes relating to efficacy and tolerability, and may help inform a choice between the two drugs.
OBJECTIVES
To assess the effects of topiramate monotherapy versus carbamazepine monotherapy for epilepsy in people with partial-onset seizures (simple or complex partial and secondarily generalised) or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
SEARCH METHODS
We searched the Cochrane Epilepsy Group Specialized Register (14 April 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (14 April 2016) and MEDLINE (Ovid, 1946 to 14 April 2016). We imposed no language restrictions. We also contacted pharmaceutical companies and trial investigators.
SELECTION CRITERIA
Randomised controlled trials in children or adults with partial-onset seizures or generalised-onset tonic-clonic seizures with or without other generalised seizure types with a comparison of monotherapy with either topiramate or carbamazepine.
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) review. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to first seizure post randomisation', 'time to 6-month remission, 'time to 12-month remission' and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs), and used the generic inverse variance method to obtain the overall pooled HRs and 95% CIs.
MAIN RESULTS
IPD were available for 1151 of 1239 eligible individuals from two of three eligible studies (93% of the potential data). A small proportion of individuals recruited into these trials had 'unclassified seizures;' for analysis purposes, these individuals are grouped with those with generalised onset seizures. For remission outcomes, a HR < 1 indicated an advantage for carbamazepine, and for first seizure and withdrawal outcomes, a HR < 1 indicated an advantage for topiramate.The main overall results, given as pooled HR adjusted for seizure type (95% CI) were: for time to withdrawal of allocated treatment 1.16 (0.98 to 1.38); time to first seizure 1.11 (0.96 to 1.29); and time to 6-month remission 0.88 (0.76 to 1.01). There were no statistically significant differences between the drugs. A statistically significant advantage for carbamazepine was shown for time to 12-month remission: 0.84 (0.71 to 1.00).The results of this review are applicable mainly to individuals with partial-onset seizures; 85% of included individuals experienced seizures of this type at baseline. For individuals with partial-onset seizures, a statistically significant advantage for carbamazepine was shown for time to withdrawal of allocated treatment (HR 1.20, 95% CI 1.00 to 1.45) and time to 12-month remission (HR 0.84, 95% CI 0.71 to 1.00). No statistically significant differences were apparent between the drugs for other outcomes and for the limited number of individuals with generalised-onset tonic-clonic seizures with or without other generalised seizure types or unclassified seizures.The most commonly reported adverse events with both drugs were drowsiness or fatigue, 'pins and needles' (tingling sensation), headache, gastrointestinal disturbance and anxiety or depression The rate of adverse events was similar across the two drugs.We judged the methodological quality of the included trials generally to be good; however, there was some evidence that the open-label design of the larger of the two trials may have influenced the withdrawal rate from the trial. Hence, we judged the evidence for the primary outcome of treatment withdrawal to be moderate for individuals with partial-onset seizures and low for individuals with generalised-onset seizures. For efficacy outcomes (first seizure, remission), we judged the evidence from this review to be high for individuals with partial-onset seizures and moderate for individuals with generalised-onset or unclassified seizures.
AUTHORS' CONCLUSIONS
For individuals with partial-onset seizures, there is evidence that carbamazepine is less likely to be withdrawn and that 12-month remission will be achieved earlier than with topiramate. No differences were found between the drugs in terms of the outcomes measured in the review for individuals with generalised tonic-clonic seizures with or without other seizure types or unclassified epilepsy; however, we encourage caution in the interpretation of these results due to the small numbers of participants with these seizure types.We recommend that future trials should be designed to the highest quality possible and take into consideration masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.
Topics: Anticonvulsants; Carbamazepine; Epilepsies, Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Fructose; Humans; Induction Chemotherapy; Topiramate
PubMed: 27922722
DOI: 10.1002/14651858.CD012065.pub2 -
European Journal of Obstetrics,... Aug 2021Increasing incidence of endometrial cancer and late motherhood enhance conservative management in clinical practice. Although different approaches to fertility-sparing...
The results of different fertility-sparing treatment modalities and obstetric outcomes in patients with early endometrial cancer and atypical endometrial hyperplasia: Case series of 30 patients and systematic review.
OBJECTIVE
Increasing incidence of endometrial cancer and late motherhood enhance conservative management in clinical practice. Although different approaches to fertility-sparing treatment are possible, it is still unknown which patients will benefit more from systemic or local treatment. Aim of this paper is to analyze the effectiveness of different methods of conservative management and obstetric outcomes in patients with early endometrial cancer and atypical endometrial hyperplasia.
STUDY DESIGN
30 patients (10 with atypical endometrial hyperplasia, 20 with endometrial cancer) treated conservatively were included to retrospective analysis. 24 patients receiving progestins were divided into 2 groups according to the dose (low and high dose); 6 patients were treated with levonorgestrel releasing intrauterine device. Effectiveness of therapy (complete, partial or absent) and obstetric outcomes (number of pregnancies and live births) were assessed. Electronic databases (MEDLINE, Web of Science, Embase) were searched for articles according to criteria: 1) fertility-sparing treatment of endometrial cancer/atypical endometrial hyperplasia in patients of reproductive age, 2) assessment of pregnancy/obstetric results. The risk of bias was assessed with the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Series.
RESULTS
Complete and partial remission were achieved in 21 and 3 patients, respectively. 6 patients did not respond to treatment. Relapse was diagnosed in 6 patients. Probability of complete remission according to low-, high-dose regimen and levonorgestrel-releasing intrauterine device were 55.6% (46.5%-64.7%), 73.3% (65.2%-81.4%) and 83.3% (76.5%-90.1%) respectively. 4 patients get pregnant and 3 of them born children. 25 studies (21 retrospective, 4 prospective) with 812 participants were included in the systematic review. The most studied was progestin based treatment. Complete and partial response to fertility-sparing management was diagnosed in 634 and 38 patients, respectively. Relapse was diagnosed in 170 patients. Median times of follow-up range from 17 (1-45) to 98 (35-176) months. The total number of pregnancies and live births were 352 and 246, respectively.
CONCLUSIONS
Fertility-sparing treatment is a safe method of management in young women with endometrial cancer/atypical endometrial hyperplasia. While the main goal of conservative management is preserving the possibility of having children, only a small number of women will become pregnant and give birth.
Topics: Child; Child, Preschool; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Neoplasm Recurrence, Local; Pregnancy; Progestins; Prospective Studies; Retrospective Studies; Treatment Outcome
PubMed: 34214800
DOI: 10.1016/j.ejogrb.2021.06.007 -
Annals of Palliative Medicine Jul 2021There has been long-standing controversy regarding the effectiveness and safety of lenalidomide as a maintenance treatment for patients with multiple myeloma (MM) after... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of lenalidomide in the treatment of multiple myeloma patients after allo-hematopoietic stem-cell transplantation: a systematic review and meta-analysis.
BACKGROUND
There has been long-standing controversy regarding the effectiveness and safety of lenalidomide as a maintenance treatment for patients with multiple myeloma (MM) after allogeneic cell transplantation. This meta-analysis aimed to explore the effectiveness and safety of lenalidomide in the maintenance treatment of MM patients after allogeneic cell transplantation based on published data.
METHODS
A systematic review and meta-analysis was conducted in English and Chinese databases, covering all available publications until 1 December 2020. Statistical analysis was performed using the software STATA 14.0, and odds ratios (ORs) combined with 95% confidence intervals (CIs) were calculated to explore the efficacy and safety of lenalidomide in the treatment of MM patients after allogeneic cell transplantation.
RESULTS
A total of 173 MM cases in 8 independent studies from 2007 to 2014 were included. Through a single-arm meta-analysis of the disease status of MM patients after lenalidomide treatment, 3.6% of patients were in minimal response (MR, P=0.006), 39.0% were in complete remission (CR, P=0.169), 20.2% in partial remission (PR, P<0.001), 12.8% in very good partial remission (VGPR, P=0.049), and 9.7% in SD (P=0.023); the PD was 5.6% (P=0.010). Through meta-analysis of adverse reactions after taking lenalidomide, 35.3% (P=0.628) of participants developed acute graft-versus-host disease (GVHD); 22.6% (P=0.049) developed chronic GVHD; 20.3% (P=0.001) developed infection; 22.5% (P=0.352) had thrombocytopenia; 32.5% (P<0.000) had neutropenia; pain occurred in 17.8% (P=0.350) of patients, and peripheral neuropathy occurred in 17.8% (P=0.995) of participants. The overall survival (OS) of ≥2 years and progression-free survival (PFS) of ≥2 years of MM patients after allo-hematopoietic-stem-cell transplantation (HSCT) taking lenalidomide were analyzed, and the results were 64.9% (P=0.049) and 58.4% (P=0.890), respectively.
DISCUSSION
Lenalidomide is effective in the treatment of MM patients after allo-HSCT, and reducing the incidence of infection and peripheral neuropathy, but it is not effective in reducing GVHD and blood system adverse reactions.
Topics: Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Lenalidomide; Multiple Myeloma; Transplantation, Homologous; Treatment Outcome
PubMed: 34353061
DOI: 10.21037/apm-21-1598 -
Diabetologia Apr 2023Sex differences are present in cardiovascular care and in outcomes among adults with type 1 diabetes mellitus, which typically commences in childhood. Whether sex... (Review)
Review
AIMS/HYPOTHESIS
Sex differences are present in cardiovascular care and in outcomes among adults with type 1 diabetes mellitus, which typically commences in childhood. Whether sex influences care and outcomes in childhood is not known. This systematic review provides an overview of sex differences in children with type 1 diabetes, focusing on patient and disease characteristics, treatment, comorbidities and complications.
METHODS
Literature in MEDLINE up to 15 June 2021 was searched, using the terms diabetes mellitus, sex characteristics, sex distribution, children and/or adolescents. All primary outcome studies on children with type 1 diabetes that mentioned a sex difference in outcome were included, with the exception of qualitative studies, case reports or case series. Studies not pertaining to the regular clinical care process and on incidence or prevalence only were excluded. Articles reporting sex differences were identified and assessed on quality and risk of bias using Joanna Briggs Institute critical appraisal tools. Narrative synthesis and an adapted Harvest plot were used to summarise evidence by category.
RESULTS
A total of 8640 articles were identified, rendering 90 studies for review (n=643,217 individuals). Studies were of observational design and comprised cohort, cross-sectional and case-control studies. Most of the included studies showed a higher HbA in young female children both at diagnosis (seven studies, n=22,089) and during treatment (20 out of 21 studies, n=144,613), as well as a steeper HbA increase over time. Many studies observed a higher BMI (all ages, ten studies, n=89,700; adolescence, seven studies, n=33,153), a higher prevalence of being overweight or obese, and a higher prevalence of dyslipidaemia among the female sex. Hypoglycaemia and partial remission occurred more often in male participants, and ketoacidosis (at diagnosis, eight studies, n=3561) and hospitalisation was more often seen in female participants. Most of the findings showed that female participants used pump therapy more frequently (six studies, n=211,324) and needed higher insulin doses than male participants. Several comorbidities, such as thyroid disease and coeliac disease, appeared to be more common in female participants. All studies reported lower quality of life in female participants (15 studies, n=8722). Because the aim of this study was to identify sex differences, studies with neutral outcomes or minor differences may have been under-targeted. The observational designs of the included studies also limit conclusions on the causality between sex and clinical outcomes.
CONCLUSIONS/INTERPRETATION
Sex disparities were observed throughout diabetes care in children with type 1 diabetes. Several outcomes appear worse in young female children, especially during adolescence. Focus on the cause and treatment of these differences may provide opportunities for better outcomes.
REGISTRATION
This systematic review is registered in PROSPERO (CRD42020213640).
Topics: Child; Adult; Adolescent; Humans; Female; Male; Diabetes Mellitus, Type 1; Sex Characteristics; Quality of Life; Cross-Sectional Studies; Insulin
PubMed: 36700969
DOI: 10.1007/s00125-022-05866-4 -
The Cochrane Database of Systematic... Oct 2016The majority of children who present with their first episode of nephrotic syndrome achieve remission with corticosteroid therapy. Children who fail to respond may be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The majority of children who present with their first episode of nephrotic syndrome achieve remission with corticosteroid therapy. Children who fail to respond may be treated with immunosuppressive agents including calcineurin inhibitors (cyclosporin or tacrolimus) and with non-immunosuppressive agents such as angiotensin-converting enzyme inhibitors (ACEi). Optimal combinations of these agents with the least toxicity remain to be determined. This is an update of a review first published in 2004 and updated in 2006 and 2010.
OBJECTIVES
To evaluate the benefits and harms of different interventions used in children with idiopathic nephrotic syndrome, who do not achieve remission following four weeks or more of daily corticosteroid therapy.
SEARCH METHODS
We searched Cochrane Kidney and Transplant's Specialised Register (up to 2 March 2016) through contact with the Information Specialist using search terms relevant to this review.
SELECTION CRITERIA
RCTs and quasi-RCTs were included if they compared different immunosuppressive agents or non-immunosuppressive agents with placebo, prednisone or other agent given orally or parenterally in children aged three months to 18 years with SRNS.
DATA COLLECTION AND ANALYSIS
Two authors independently searched the literature, determined study eligibility, assessed risk of bias and extracted data. For dichotomous outcomes, results were expressed as risk ratios (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model.
MAIN RESULTS
Nineteen RCTs (820 children enrolled; 773 evaluated) were included. Most studies were small. Eleven studies were at low risk of bias for allocation concealment and only four studies were at low risk of performance bias. Fifteen, eight and 10 studies were at low risk of detection bias, attrition bias and reporting bias respectively. Cyclosporin when compared with placebo or no treatment significantly increased the number of children who achieved complete remission. However this was based on only eight children who achieved remission with cyclosporin compared with no children who achieved remission with placebo/no treatment in three small studies (49 children: RR 7.66, 95% CI 1.06 to 55.34). Calcineurin inhibitors significantly increased the number with complete or partial remission compared with IV cyclophosphamide (2 studies, 156 children: RR 1.98, 95% CI 1.25 to 3.13; I = 20%). There was no significant differences in the number who achieved complete remission between tacrolimus versus cyclosporin (1 study, 41 children: RR 0.86, 95% CI 0.44 to 1.66), cyclosporin versus mycophenolate mofetil plus dexamethasone (1 study, 138 children: RR 2.14, 95% CI 0.87 to 5.24), oral cyclophosphamide with prednisone versus prednisone alone (2 studies, 91 children: RR 1.06, 95% CI 0.61 to 1.87), IV versus oral cyclophosphamide (1 study, 11 children: RR 3.13, 95% CI 0.81 to 12.06), IV cyclophosphamide versus oral cyclophosphamide plus IV dexamethasone (1 study, 49 children: RR 1.13, 95% CI 0.65 to 1.96), and azathioprine with prednisone versus prednisone alone (1 study, 31 children: RR 0.94, 95% CI 0.15 to 5.84). One study found no significant differences between three agents (cyclophosphamide, mycophenolate mofetil, leflunomide) used in combination with tacrolimus and prednisone. One study found no significant difference in the percentage reduction in proteinuria (31 children: -12; 95% CI -73 to 110) between rituximab with cyclosporin/prednisolone and cyclosporin/prednisolone alone. Two studies reported ACEi significantly reduced proteinuria.
AUTHORS' CONCLUSIONS
To date RCTs have demonstrated that calcineurin inhibitors increase the likelihood of complete or partial remission compared with placebo/no treatment or cyclophosphamide. For other regimens assessed, it remains uncertain whether the interventions alter outcomes because the certainty of the evidence is low. Further adequately powered, well designed RCTs are needed to evaluate other regimens for children with idiopathic SRNS. Since SRNS represents a spectrum of diseases, future studies should enrol children from better defined groups of patients with SRNS.
Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Azathioprine; Child; Child, Preschool; Cyclophosphamide; Cyclosporine; Dexamethasone; Drug Resistance; Glucocorticoids; Humans; Immunosuppressive Agents; Infant; Isoxazoles; Leflunomide; Mycophenolic Acid; Nephrotic Syndrome; Prednisone; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 27726125
DOI: 10.1002/14651858.CD003594.pub5 -
Frontiers in Pharmacology 2022The (R)-CDOP combination regimen, based on pegylated liposomal doxorubicin, is increasingly used for elderly patients with non-Hodgkin's lymphoma. However, the...
Cardiovascular adverse events associated with cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone with or without rituximab ((R)-CDOP) in non-Hodgkin's lymphoma: A systematic review and meta-analysis.
The (R)-CDOP combination regimen, based on pegylated liposomal doxorubicin, is increasingly used for elderly patients with non-Hodgkin's lymphoma. However, the cardiotoxicity and efficacy of the (R)-CDOP regimen compared with conventional anthracyclines have not been demonstrated in the general population. Therefore, this systematic review and meta-analysis evaluated the risk of cardiotoxicity and efficacy associated with the (R)-CDOP regimen in patients with non-Hodgkin's lymphoma. PubMed, Embase, Cochrane Library, CNKI, WanFang Database, and VIP were searched. The search covered the period from the start of the clinical use of (R)-CDOP to April 2022. We searched the literature for cardiovascular adverse events associated with (R)-CDOP in non-Hodgkin's lymphoma. The data were analyzed using R 4.2.0 and Stata 12.0. From the included studies, the important findings were as follows: total cardiovascular event rate, 7.45% (95% confidence interval [CI] = 4.86%-10.44%); non-serious cardiovascular adverse event rate, 6.48% (95% CI = 3.70%-9.8%); serious cardiovascular adverse event rate, 0.67% (95% CI = 0.00%-2.12%); heart failure rate, 0.55% (95% CI = 0.00%-1.93%); rate of treatment discontinuation attributable to left ventricular dysfunction or heart failure, 0.02% (95% CI = 0.00%-0.57%); and cardiovascular death rate, 0.00% (95% CI = 0.00%-0.37%). Compared with the (R)-CHOP regimen, the (R)-CDOP regimen reduced the risk of cardiovascular events, including total cardiovascular adverse events (odds ratio [OR] = 0.161, 95% CI = 0.103-0.251, < 0.001, and NNT = 3.7), non-serious cardiovascular adverse events (OR = 0.171, 95% CI = 0.093-0.314, < 0.001, and NNT = 3.6), serious cardiovascular adverse events (OR = 0.252, 95% CI = 0.119-0.535, < 0.001, and NNT = 6.8), and heart failure (OR = 0.294, 95% CI = 0.128-0.674, = 0.004, and NNT = 9.5). To evaluate the survival benefits, we compared (R)-CDOP and (R)-CHOP regimens. We found that the (R)-CDOP regimen was no less efficacious, including complete remission (CR) (OR = 1.398, 95% CI = 0.997-1.960, and = 0.052), partial response (PR) (OR = 1.631, 95% CI = 1.162-2.289, and = 0.005), objective response rate (ORR) (OR = 2.236, 95% CI = 1.594-3.135, and < 0.001), stable disease (SD) (OR = 0.526, 95% CI = 0.356-0.776, and = 0.001), and progressive disease (PD) (OR = 0.537, 95% CI = 0.323-0.894, and = 0.017). Our findings suggested that the (R)-CDOP regimen had a lower risk of cardiovascular adverse events in non-Hodgkin's lymphoma than the (R)-CHOP regimen, demonstrating its safety with regard to cardiotoxicity. In addition, this study found the (R)-CDOP regimen was no less efficacious than the (R)-CHOP regimen in the treatment of non-Hodgkin's lymphoma. These findings need to be validated by higher-quality research because of the limited number and quality of included studies.
PubMed: 36532720
DOI: 10.3389/fphar.2022.1060668