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Renal Failure Dec 2021The therapeutic effects of tacrolimus (TAC) versus cyclophosphamide (CTX) were not fully illustrated for patients with idiopathic membranous nephropathy (IMN). (Comparative Study)
Comparative Study Meta-Analysis
Tacrolimus versus cyclophosphamide for patients with idiopathic membranous nephropathy and treated with steroids: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
The therapeutic effects of tacrolimus (TAC) versus cyclophosphamide (CTX) were not fully illustrated for patients with idiopathic membranous nephropathy (IMN).
METHODS
The PubMed, EmBase, Cochrane library, and CNKI were systematically searched throughout March 2020 for randomized controlled trials evaluating the therapeutic effects of TAC versus CTX for IMN patients treated with steroids. The pooled relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using the random-effects model.
RESULTS
Twelve trials recruited a total of 868 IMN patients were identified and contained in final meta-analysis. Patients in TAC group was associated with an increased incidence of overall remission (12 trials: 868 patients; RR: 1.21; 95% CI: 1.11-1.31; < 0.001) and complete remission (12 trials: 868 patients; RR: 1.50; 95% CI: 1.25-1.80; < 0.001). Moreover, we noted TAC therapy significantly reduced urinary protein excretion (9 trials: 567 patients; WMD: -1.06; 95%CI: -1.41 to -0.71; < 0.001), and increased serum albumin (9 trials: 567 patients; WMD: 5.37; 95%CI: 2.97 to 7.77; < 0.001) than CTX therapy. Furthermore, no significant difference between TAC and CTX for serum creatinine was detected (6 trials: 378 patients; WMD: 0.15; 95%CI: -3.46 to 3.75; = 0.936). Finally, the risk of alopecia ( = 0.008), infection ( = 0.045), leukocytosis ( = 0.002), and elevated ALT/AST ( = 0.011) in TAC group was significantly lower than CTX group, whereas TAC was associated with an increased risk of tremor than CTX ( = 0.010).
CONCLUSIONS
This study found IMN patients treated with TAC combined with steroids provides a better therapeutic effect and less adverse events than those treated with CTX combined with steroids, with moderate-certainty evidence.
Topics: Cyclophosphamide; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Randomized Controlled Trials as Topic; Remission Induction; Steroids; Tacrolimus
PubMed: 34016023
DOI: 10.1080/0886022X.2021.1914655 -
BMJ Open Sep 2019This study aimed to compare the effectiveness of 13 types of immunosuppressive agents used to treat idiopathic membranous nephropathy (IMN) in adults with nephrotic... (Comparative Study)
Comparative Study Meta-Analysis
Comparative efficacy of 13 immunosuppressive agents for idiopathic membranous nephropathy in adults with nephrotic syndrome: a systematic review and network meta-analysis.
OBJECTIVES
This study aimed to compare the effectiveness of 13 types of immunosuppressive agents used to treat idiopathic membranous nephropathy (IMN) in adults with nephrotic syndrome.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
PubMed, EMbase, Cochrane Library, Web of Science, Clinical trials, SinoMed, Chinese Biomedicine, CNKI, WanFang and Chongqing VIP Information databases were comprehensively searched until February 2018.
ELIGIBILITY CRITERIA
Randomised clinical trials (RCTs) comparing the effects of different immunosuppressive treatments in adult patients with IMN and nephrotic syndrome were included, and all included RCTs had a study-duration of at least 6 months.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently screened articles, extracted data and assessed study quality. Standard pairwise meta-analysis was performed using DerSimonian-Laird random-effects model.
RESULTS
This study ultimately included 48 RCTs with 2736 patients and 13 immunosuppressive agents. The network meta-analysis results showed that most regimens, except for leflunomide (LEF), mizoribine (MZB) and steroids (STE), showed significantly higher probabilities of total remission (TR) when compared with non-immunosuppressive therapies (the control group),with risk ratios (RRs) of 2.71 (95% CI) 1.81 to 4.06)for tacrolimus+tripterygium wilfordii (TAC+TW), 2.16 (1.27 to 3.69) foradrenocorticotropic hormone, 2.02 (1.64 to 2.49) for TAC, 2.03 (1.13 to3.64) for azathioprine (AZA), 1.91 (1.46 to 2.50) for cyclosporine (CsA), 1.86 (1.44 to2.42) for mycophenolate mofetil (MMF), 1.85 (1.52 to 2.25) for cyclophosphamide (CTX),1.81 (1.10 to 2.98) for rituximab (RIT), 1.80 (1.38 to 2.33) for TW, 1.72 (1.35 to 2.19) for chlorambucil. As for 24 hours UTP, the direct andindirect comparisons showed that AZA (standard mean difference (SMD), -1.02(95% CI -1.90 to -0.15)), CsA (SMD, -0.70 (95% CI -1.33 to -0.08)),CTX (SMD, -1.01 (95% CI -1.44 to -0.58)), MMF (SMD, -0.98 (95% CI -1.64 to -0.32)), MZB (SMD, -0.97 (95% CI -1.90 to-0.04]), TAC (SMD, -1.16 (95% CI -1.72 to -0.60)) and TAC+TW(SMD, -2.03 (95% CI -2.94 to -1.12)) could significantly superior thancontrol, except for chlorambucil, LEF, RIT and STE. Thechanges of serum creatinine (Scr) was not significantly different between eachtreatments of immunosuppressive agents and the control, except for STE whichhas the possibility of increasing Scr (SMD, 1.00 (95% CI 0.36 to 1.64)).Comparisons among all treatments of immunosuppressive agents showed nostatistical significance in the outcome of relapse. A drenocorticotropichormone (85.1%) showed the lowest probability of relapse under the cumulativeranking curve values among all immunosuppressants. Infection,gastrointestinal symptoms, and bone marrow suppression were the common adverseevents associated with most of the immunosuppressive therapies.
CONCLUSIONS
This study demonstrates that TAC+TW, TAC and CTX are superior to other immunosuppressive agents in terms of TR and 24 hours UTP. Moreover, they are all at risk of infection, gastrointestinal symptoms, and myelosuppression. Furthermore, TAC could increase the risk of glucose intolerance or new-onset diabetes mellitus. Conversely, STE alone, LEF and MZB seem to have little advantage in clinical treatment of IMN.
PROSPERO REGISTRATION NUMBER
CRD42018094228.
Topics: Adult; Cyclophosphamide; Drug Therapy, Combination; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Nephrotic Syndrome; Network Meta-Analysis; Randomized Controlled Trials as Topic; Tacrolimus; Tripterygium
PubMed: 31511292
DOI: 10.1136/bmjopen-2019-030919 -
JAMA Oncology Dec 2019Use of haploidentical (HAPLO) stem cell transplantation with posttransplant cyclophosphamide is rapidly increasing in adults with hematologic cancers. However, its... (Comparative Study)
Comparative Study Meta-Analysis
Haploidentical Stem Cell Transplantation With Posttransplant Cyclophosphamide Therapy vs Other Donor Transplantations in Adults With Hematologic Cancers: A Systematic Review and Meta-analysis.
IMPORTANCE
Use of haploidentical (HAPLO) stem cell transplantation with posttransplant cyclophosphamide is rapidly increasing in adults with hematologic cancers. However, its specific role compared with other transplant strategies has yet to be identified.
OBJECTIVE
To synthesize the existing evidence regarding outcomes of stem cell transplantations comparing HAPLO stem cell transplantation and posttransplant cyclophosphamide therapy with transplantations from matched related donors (MRDs), matched unrelated donors (MUDs), or mismatched unrelated donors (MMUDs).
DATA SOURCES
PubMed, Cochrane Library, ClinicalTrials.gov, and meeting abstracts were searched for the key words haploidentical and cyclophosphamide from inception through March 1, 2019.
STUDY SELECTION
Studies comparing HAPLO stem cell transplantation and posttransplant cyclophosphamide therapy with transplantations from other donors in adults with hematologic cancers were eligible for meta-analysis.
DATA EXTRACTION AND SYNTHESIS
Pooled odds ratios (ORs) and 95% CIs were calculated using a random-effects model.
MAIN OUTCOMES AND MEASURES
Main outcomes were all-cause mortality, nonrelapse mortality, and relapse.
RESULTS
A total of 30 studies including 22 974 participants were analyzed. HAPLO stem cell transplantation with posttransplant cyclophosphamide therapy was associated with increased all-cause mortality compared with MRDs (OR, 1.17; 95% CI, 1.05-1.30), similar all-cause mortality compared with MUDs (OR, 1.06; 95% CI, 0.96-1.18), and reduced all-cause mortality compared with MMUDs (OR, 0.75; 95% CI, 0.61-0.92). Regarding nonrelapse mortality, HAPLO stem cell transplantation with posttransplant cyclophosphamide was associated with worse outcomes compared with MRDs (OR, 1.20; 95% CI, 1.04-1.40) but better outcomes compared with MUDs (OR, 0.75; 95% CI, 0.61-0.92) and MMUDs (OR, 0.51; 95% CI, 0.25-1.02). In terms of relapse, HAPLO stem cell transplantation with posttransplant cyclophosphamide was associated with similar outcome compared with MRDs (OR, 1.01; 95% CI, 0.86-1.17) and MMUDs (OR, 1.06; 95% CI, 0.77-1.47) but showed increased relapse compared with MUDs (OR, 1.20; 95% CI, 1.03-1.40).
CONCLUSIONS AND RELEVANCE
Results of this meta-analysis suggest that MRDs, if available, remain the optimal donors regarding mortality and HAPLO stem cell transplantation with posttransplant cyclophosphamide may be preferred over MMUDs. Prospective comparisons with MUDs are needed.
Topics: Adult; Cyclophosphamide; Disease-Free Survival; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Transplantation, Haploidentical; Treatment Outcome; Unrelated Donors
PubMed: 31621796
DOI: 10.1001/jamaoncol.2019.3541 -
The Cochrane Database of Systematic... Dec 2015Oral mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high risk patients. Ulceration can lead to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high risk patients. Ulceration can lead to severe pain and difficulty eating and drinking, which may necessitate opioid analgesics, hospitalisation and nasogastric or intravenous nutrition. These complications may lead to interruptions or alterations to cancer therapy, which may reduce survival. There is also a risk of death from sepsis if pathogens enter the ulcers of immunocompromised patients. Ulcerative oral mucositis can be costly to healthcare systems, yet there are few preventive interventions proven to be beneficial. Oral cryotherapy is a low-cost, simple intervention which is unlikely to cause side-effects. It has shown promise in clinical trials and warrants an up-to-date Cochrane review to assess and summarise the international evidence.
OBJECTIVES
To assess the effects of oral cryotherapy for preventing oral mucositis in patients with cancer who are receiving treatment.
SEARCH METHODS
We searched the following databases: the Cochrane Oral Health Group Trials Register (to 17 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 5), MEDLINE via Ovid (1946 to 17 June 2015), EMBASE via Ovid (1980 to 17 June 2015), CANCERLIT via PubMed (1950 to 17 June 2015) and CINAHL via EBSCO (1937 to 17 June 2015). We searched the US National Institutes of Health Trials Registry, and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching databases.
SELECTION CRITERIA
We included parallel-design randomised controlled trials (RCTs) assessing the effects of oral cryotherapy in patients with cancer receiving treatment. We used outcomes from a published core outcome set registered on the COMET website.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the results of electronic searches, extracted data and assessed risk of bias. We contacted study authors for information where feasible. For dichotomous outcomes, we reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we reported mean differences (MD) and 95% CIs. We pooled similar studies in random-effects meta-analyses. We reported adverse effects in a narrative format.
MAIN RESULTS
We included 14 RCTs analysing 1280 participants. The vast majority of participants did not receive radiotherapy to the head and neck, so this review primarily assesses prevention of chemotherapy-induced oral mucositis. All studies were at high risk of bias. The following results are for the main comparison: oral cryotherapy versus control (standard care or no treatment). Adults receiving fluorouracil-based (5FU) chemotherapy for solid cancersOral cryotherapy probably reduces oral mucositis of any severity (RR 0.61, 95% CI 0.52 to 0.72, 5 studies, 444 analysed, moderate quality evidence). In a population where 728 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 444 (95% CI 379 to 524). The number needed to treat to benefit one additional person (NNTB), i.e. to prevent them from developing oral mucositis, is 4 people (95% CI 3 to 5).The results were similar for moderate to severe oral mucositis (RR 0.52, 95% CI 0.41 to 0.65, 5 studies, 444 analysed, moderate quality evidence). NNTB 4 (95% CI 4 to 6).Severe oral mucositis is probably reduced (RR 0.40, 95% CI 0.27 to 0.61, 5 studies, 444 analysed, moderate quality evidence). Where 300 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 120 (95% CI 81 to 183), NNTB 6 (95% CI 5 to 9). Adults receiving high-dose melphalan-based chemotherapy before haematopoietic stem cell transplantation (HSCT)Oral cryotherapy may reduce oral mucositis of any severity (RR 0.59, 95% CI 0.35 to 1.01, 5 studies, 270 analysed, low quality evidence). Where 824 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 486 (95% CI reduced to 289 to increased to 833). The NNTB is 3, although the uncertainty surrounding the effect estimate means that the 95% CI ranges from 2 NNTB, to 111 NNTH (number needed to treat in order to harm one additional person, i.e. for one additional person to develop oral mucositis).The results were similar for moderate to severe oral mucositis (RR 0.43, 95% CI 0.17 to 1.09, 5 studies, 270 analysed, low quality evidence). NNTB 3 (95% CI 2 NNTB to 17 NNTH).Severe oral mucositis is probably reduced (RR 0.38, 95% CI 0.20 to 0.72, 5 studies, 270 analysed, moderate quality evidence). Where 427 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 162 (95% CI 85 to 308), NNTB 4 (95% CI 3 to 9).Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, numbness/taste disturbance, and tooth pain. This appears to contribute to the high rates of compliance seen in the included studies.There was limited or no evidence on the secondary outcomes of this review, or on patients undergoing other chemotherapies, radiotherapy, targeted therapy, or on comparisons of oral cryotherapy with other interventions or different oral cryotherapy regimens. Therefore no further robust conclusions can be made. There was also no evidence on the effects of oral cryotherapy in children undergoing cancer treatment.
AUTHORS' CONCLUSIONS
We are confident that oral cryotherapy leads to large reductions in oral mucositis of all severities in adults receiving 5FU for solid cancers. We are less confident in the ability of oral cryotherapy to reduce oral mucositis in adults receiving high-dose melphalan before HSCT. Evidence suggests that it does reduce oral mucositis in these adults, but we are less certain about the size of the reduction, which could be large or small. However, we are confident that there is an appreciable reduction in severe oral mucositis in these adults.This Cochrane review includes some very recent and currently unpublished data, and strengthens international guideline statements for adults receiving the above cancer treatments.
Topics: Adult; Antineoplastic Agents; Cryotherapy; Fluorouracil; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Mouth Diseases; Myeloablative Agonists; Neoplasms; Pain; Randomized Controlled Trials as Topic; Stomatitis
PubMed: 26695736
DOI: 10.1002/14651858.CD011552.pub2 -
Medicine Aug 2020Mycophenolate mofetil (MMF) has been recommended for the treatment of lupus nephritis (LN). Although inter-racial differences exist regarding the appropriate dose and... (Meta-Analysis)
Meta-Analysis
BACKGROUD
Mycophenolate mofetil (MMF) has been recommended for the treatment of lupus nephritis (LN). Although inter-racial differences exist regarding the appropriate dose and efficacy of MMF in patients with LN, no definitive meta-analysis has yet been conducted in Chinese patients. This analysis investigated the efficacy and safety of MMF in Chinese patients with proliferative LN.
METHODS
A systematic literature search was conducted to select randomized controlled trials that reported at least one of the following: complete remission (CR), partial remission, total remission (TR; defined as complete remission + partial remission), relapse rate, serum creatinine, creatinine clearance, end-stage renal disease, death, infections, amenorrhea, leukopenia, alopecia, gastrointestinal symptoms, or liver damage.
RESULTS
Eighteen trials (927 patients) were included; 14 (750 patients) reported CR, partial remission, and TR. Two trials (58 patients) reported relapse rates during maintenance treatment. MMF induction significantly improved CR and TR vs cyclophosphamide (relative risk 1.34, 95% confidence interval: 1.13-1.58; P < .001; relative risk 1.16, 95% confidence interval: 1.02-1.33; P = .03), and was associated with significantly lower risks of infection (P < .001), amenorrhea (P < .001), leukopenia, and alopecia. No significant difference in relapse rate was evident between the MMF and azathioprine groups (P = .66).
CONCLUSION
According to this meta-analysis of 18 trials, MMF is significantly more effective than cyclophosphamide induction, and is associated with reduced incidences of infections, amenorrhea, leukopenia, and alopecia in Chinese patients with proliferative LN.
Topics: Asian People; China; Cyclophosphamide; Enzyme Inhibitors; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Randomized Controlled Trials as Topic
PubMed: 32871981
DOI: 10.1097/MD.0000000000021121 -
The Cochrane Database of Systematic... Nov 2019The majority of children who present with their first episode of nephrotic syndrome achieve remission with corticosteroid therapy. Children who fail to respond to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The majority of children who present with their first episode of nephrotic syndrome achieve remission with corticosteroid therapy. Children who fail to respond to corticosteroids in the first episode of nephrotic syndrome (initial resistance) or develop resistance after one or more responses to corticosteroids (delayed resistance) may be treated with immunosuppressive agents including calcineurin inhibitors (CNI) (cyclosporin or tacrolimus) and with non-immunosuppressive agents such as angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). However, response to these agents is limited so newer agents are being assessed for efficacy. This is an update of a review first published in 2004 and updated in 2006, 2010 and 2016.
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 the Cochrane Kidney and Transplant Register of Studies to 17 September 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (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 steroid-resistant nephrotic syndrome (SRNS). Studies, which enrolled children and adults but in which paediatric data could not be separated from adult data, were also included.
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). For continuous outcomes, results were expressed as mean difference (MD) and 95% CI. Data were pooled using the random effects model. The certainty of the evidence was assessed using the GRADE approach.
MAIN RESULTS
Twenty-five studies (1063 participants) were included. Fourteen studies were at low risk of bias for sequence generation and allocation concealment. Five and 19 studies were at low risk of performance and detection bias. Fourteen, 14 and 13 studies were at low risk of attrition bias, reporting bias and other bias respectively. Cyclosporin compared with placebo or no treatment may increase the number of participants who achieve complete remission (4 studies, 74 participants: RR 3.50, 95% CI 1.09 to 11.20) or complete or partial remission (4 studies, 74 children: RR 3.15, 95% CI 1.04 to 9.57) by 6 months (low certainty evidence). It is uncertain whether cyclosporin increases the likelihood of worsening hypertension or reduces the likelihood of end-stage kidney disease (very low certainty evidence). CNI compared with IV cyclophosphamide (CPA) may increase the number of participants with complete or partial remission at 3 to 6 months (2 studies, 156 children: RR 1.98, 95% CI 1.25 to 3.13) (low certainty evidence) and probably reduces the number with treatment failure (non response, serious infection, persistently elevated creatinine (1 study, 124 participants: RR 0.32, 95% CI 0.18 to 0.58) (moderate certainty evidence) with little or no increase in serious infections (1 study, 131 participants: RR 0.49, 95% CI 0.16 to 1.56) (moderate certainty evidence). Tacrolimus compared with cyclosporin may make little or no difference to the number who achieve complete or partial remission (2 studies, 58 participants: RR 1.05, 95% CI 0.87 to 1.25) (low certainty evidence) or in the number with worsening hypertension (2 studies, 58 participants: RR 0.41, 95% CI 0.08 to 2.15) (low certainty evidence). Cyclosporin compared with mycophenolate mofetil (MMF) and dexamethasone probably makes little or no difference to the number who achieve complete or partial remission (1 study, 138 participants: RR 2.14, 95% CI 0.87 to 5.24) (moderate certainty evidence) and makes little or no difference to the number dying (1 study, 138 participants: RR 2.14, 95% CI 0.87 to 5.24) or with 50% reduction in glomerular filtration rate (GFR) (1 study, 138 participants: RR 2.29, 95% CI 0.46 to 11.41) (low certainty evidence). Among children, who have achieved complete remission, tacrolimus compared with MMF may increase the number of children who maintain complete or partial response for 12 months (1 study, 60 children: RR 2.01, 95% CI 1.32 to 3.07) (low certainty evidence). Oral CPA with prednisone compared with prednisone alone may make little or no difference to the number who achieve complete remission (2 studies, 84 children: RR 1.06, 95% CI 0.61 to 1.87) (low certainty evidence). IV CPA compared with oral CPA (2 studies, 61 children: RR 1.58, 95% CI 0.65 to 3.85) and IV compared with oral CPA plus IV dexamethasone (1 study, 49 children: RR 1.13, 95% CI 0.65 to 1.96) may make little or no difference to the number who achieve complete remission (low certainty evidence). It is uncertain whether rituximab and cyclosporin compared with cyclosporin increases the likelihood of remission because the certainty of the evidence is very low. It is uncertain whether adalimumab or galactose compared with conservative therapy increases the likelihood of remission because the certainty of the evidence is very low. Two studies reported that ACEi may reduce proteinuria in children with SRNS. One study reported that the dual angiotensin II and endothelin Type A receptor antagonist, sparsentan, may reduce proteinuria more effectively than the angiotensin receptor blocker, irbesartan.
AUTHORS' CONCLUSIONS
To date RCTs have demonstrated that CNIs may increase the likelihood of complete or partial remission compared with placebo/no treatment or CPA. 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; Drug Resistance; Humans; Immunosuppressive Agents; Infant; Nephrotic Syndrome; Prednisone; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 31749142
DOI: 10.1002/14651858.CD003594.pub6 -
The Cochrane Database of Systematic... Apr 2020About 80% of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. Of these children, half relapse frequently, and are at risk of adverse effects from... (Meta-Analysis)
Meta-Analysis
BACKGROUND
About 80% of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. Of these children, half relapse frequently, and are at risk of adverse effects from corticosteroids. While non-corticosteroid immunosuppressive medications prolong periods of remission, they have significant potential adverse effects. Currently, there is no consensus about the most appropriate second-line agent in children who are steroid sensitive, but who continue to relapse. In addition, these medications could be used with corticosteroids in the initial episode of SSNS to prolong the period of remission. This is the fourth update of a review first published in 2001 and updated in 2005, 2008 and 2013.
OBJECTIVES
To evaluate the benefits and harms of non-corticosteroid immunosuppressive medications in SSNS in children with a relapsing course of SSNS and in children with their first episode of nephrotic syndrome.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 10 March 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs were included if they involved children with SSNS and compared non-corticosteroid immunosuppressive medications with placebo, corticosteroids (prednisone or prednisolone) or no treatment; compared different non-corticosteroid immunosuppressive medications or different doses, durations or routes of administration of the same non-corticosteroid immunosuppressive medication.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study eligibility, risk of bias of the included studies and extracted data. Statistical analyses were performed using a random-effects model and results expressed as risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). The certainty of the evidence was assessed using GRADE.
MAIN RESULTS
We identified 43 studies (91 reports) and included data from 2428 children. Risk of bias assessment indicated that 21 and 24 studies were at low risk of bias for sequence generation and allocation concealment respectively. Nine studies were at low risk of performance bias and 10 were at low risk of detection bias. Thirty-seven and 27 studies were at low risk of incomplete and selective reporting respectively. Rituximab (in combination with calcineurin inhibitors (CNI) and prednisolone) versus CNI and prednisolone probably reduces the number of children who relapse at six months (5 studies, 269 children: RR 0.23, 95% CI 0.12 to 0.43) and 12 months (3 studies, 198 children: RR 0.63, 95% CI 0.42 to 0.93) (moderate certainty evidence). At six months, rituximab resulted in 126 children/1000 relapsing compared with 548 children/1000 treated with conservative treatments. Rituximab may result in infusion reactions (4 studies, 252 children: RR 5.83, 95% CI 1.34 to 25.29). Mycophenolate mofetil (MMF) and levamisole may have similar effects on the number of children who relapse at 12 months (1 study, 149 children: RR 0.90, 95% CI 0.70 to 1.16). MMF may have a similar effect on the number of children relapsing compared to cyclosporin (2 studies, 82 children: RR 1.90, 95% CI 0.66 to 5.46) (low certainty evidence). MMF compared to cyclosporin is probably less likely to result in hypertrichosis (3 studies, 140 children: RR 0.23, 95% CI 0.10 to 0.50) and gum hypertrophy (3 studies, 144 children: RR 0.09, 95% CI 0.07 to 0.42) (low certainty evidence). Levamisole compared with steroids or placebo may reduce the number of children with relapse during treatment (8 studies, 474 children: RR 0.52, 95% CI 0.33 to 0.82) (low certainty evidence). Levamisole compared to cyclophosphamide may make little or no difference to the risk for relapse after 6 to 9 months (2 studies, 97 children: RR 1.17, 95% CI 0.76 to 1.81) (low certainty evidence). Cyclosporin compared with prednisolone may reduce the number of children who relapse (1 study, 104 children: RR 0.33, 95% CI 0.13 to 0.83) (low certainty evidence). Alkylating agents compared with cyclosporin may make little or no difference to the risk of relapse during cyclosporin treatment (2 studies, 95 children: RR 0.91, 95% CI 0.55 to 1.48) (low certainty evidence) but may reduce the risk of relapse at 12 to 24 months (2 studies, 95 children: RR 0.51, 95% CI 0.35 to 0.74), suggesting that the benefit of the alkylating agents may be sustained beyond the on-treatment period (low certainty evidence). Alkylating agents (cyclophosphamide and chlorambucil) compared with prednisone probably reduce the number of children, who experience relapse at six to 12 months (6 studies, 202 children: RR 0.44, 95% CI 0.32 to 0.60) and at 12 to 24 months (4 studies, 59 children: RR 0.20, 95% CI 0.09 to 0.46) (moderate certainty evidence). IV cyclophosphamide may reduce the number of children with relapse compared with oral cyclophosphamide at 6 months (2 studies, 83 children: RR 0.54, 95% CI 0.34 to 0.88), but not at 12 to 24 months (2 studies, 83 children: RR 0.99, 95% CI 0.76 to 1.29) and may result in fewer infections (2 studies, 83 children: RR 0.14, 95% CI 0.03 to 0.72) (low certainty evidence). Cyclophosphamide compared to chlorambucil may make little or no difference in the risk of relapse after 12 months (1 study, 50 children: RR 1.31, 95% CI 0.80 to 2.13) (low certainty evidence).
AUTHORS' CONCLUSIONS
New studies incorporated in this review indicate that rituximab is a valuable additional agent for managing children with steroid-dependent nephrotic syndrome. However, the treatment effect is temporary, and many children will require additional courses of rituximab. The long-term adverse effects of this treatment are not known. Comparative studies of CNIs, MMF, levamisole and alkylating agents have demonstrated little or no differences in efficacy but, because of insufficient power; clinically important differences in treatment effects have not been completely excluded.
Topics: Adolescent; Alkylating Agents; Azathioprine; Child; Child, Preschool; Chlorambucil; Cyclophosphamide; Cyclosporine; Humans; Immunosuppressive Agents; Infant; Levamisole; Mycophenolic Acid; Nephrotic Syndrome; Prednisolone; Prednisone; Randomized Controlled Trials as Topic; Recurrence; Ribonucleosides; Rituximab; Secondary Prevention
PubMed: 32297308
DOI: 10.1002/14651858.CD002290.pub5 -
Asian Pacific Journal of Cancer... 2015To assess the role of two adjuvant chemotherapy regimens, anthracycline-based and CMF on disease free survival and overall survival breast cancer patients by... (Comparative Study)
Comparative Study Meta-Analysis
Comparing Role of Two Chemotherapy Regimens, CMF and Anthracycline-Based, on Breast Cancer Survival in the Eastern Mediterranean Region and Asia by Multivariate Mixed Effects Models: a Meta-Analysis.
PURPOSE
To assess the role of two adjuvant chemotherapy regimens, anthracycline-based and CMF on disease free survival and overall survival breast cancer patients by meta-analysis approach in Eastern Mediterranean and Asian countries to determine which is more effective and evaluate the appropriateness and efficiency of two different proposed statistical models.
MATERIALS AND METHODS
Survival curves were digitized and the survival proportions and times were extracted and modeled to appropriate covariates by two multivariate mixed effects models. Studies which reported disease free survival and overall survival curves for anthracycline-based or CMF as adjuvant chemotherapy that were published in English in the Eastern Mediterranean region and Asia were included in this systematic review. The two transformations of survival probabilities (Ln (-Ln(S)) and Ln(S/ (1-S))) as dependent variables were modeled by a multivariate mixed model to same covariates in order to have precise estimations with high power and appropriate interpretation of covariate effects. The analysis was carried out with SAS Proc MIXED and STATA software.
RESULTS
A total of 32 studies from the published literature were analysed, covering 4,092 patients who received anthracycline-based and 2,501 treated with CMF for the disease free survival and in order to analyze the overall survival, 13 studies reported the overall survival curves in which 2,050 cases were treated with anthracycline-based and 1,282 with CMF regimens.
CONCLUSIONS
The findings illustrated that the model with dependent variable Ln (-Ln(S)) had more precise estimations of the covariate effects and showed significant difference between the effects of two adjuvant chemotherapy regimens. Anthracycline-based treatment gave better disease free survival and overall survival. As an IPD meta-analysis in the Italy the results of Angelo et al in 2011 also confirmed that anthracycline-based regimens were more effective for survival of breast cancer patients. The findings of Zare et al 2012 on disease free survival curves in Asia also provided similar evidence.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Asia; Breast Neoplasms; Cyclophosphamide; Female; Fluorouracil; Humans; Mediterranean Region; Methotrexate; Survival Analysis
PubMed: 26320431
DOI: 10.7314/apjcp.2015.16.14.5655 -
Blood Advances May 2021The dilemma of whether to treat elderly patients with diffuse large B-cell lymphoma (DLBCL) with a full or reduced dose intensity (DI) of R-CHOP (cyclophosphamide,...
The dilemma of whether to treat elderly patients with diffuse large B-cell lymphoma (DLBCL) with a full or reduced dose intensity (DI) of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone+rituximab) is often faced by clinicians. We conducted a systematic review assessing the impact of R-CHOP DI on DLBCL survival outcomes, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (PRISMA-P) guidelines. We searched MEDLINE, EMBASE, and Cochrane CENTRAL for studies with ≥100 patients treated with R-CHOP/R-CHOP-like therapies published from January 2002 through November 2020. Studies were included if they reported the impact of R-CHOP DI on survival outcomes. We screened records, extracted data, and reviewed all the studies for quality and statistical appraisal. Of 380 screened records, 13 studies including 5188 patients were reviewed. DI was often calculated as the ratio of the cumulative delivered dose of prespecified drug(s) to the cumulative planned dose multiplied by a time-correction factor. Lower DI (intended or relative) was associated with inferior survival in 7 of 9 studies reporting crude survival analyses. Multivariable analysis using DI as a covariate was performed in 10 studies. Six showed an association (P < .05) with adjustment for other covariates, and 4 did not. Most studies and those larger studies of higher quality showed poorer outcomes associated with reduced DI. In subgroups aged ≥80 years, survival was not consistently affected by reduced DI. DI-specific randomized trials are warranted, but these data support full-dose R-CHOP in elderly and fit patients aged <80 years with DLBCL, but not in those aged ≥80 years, where dose-reduced R-CHOP does not appear to compromise survival.
Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Rituximab; Vincristine
PubMed: 33961018
DOI: 10.1182/bloodadvances.2021004665 -
The Cochrane Database of Systematic... Mar 2018Occupational exposure to hazardous drugs can decrease fertility and result in miscarriages, stillbirths, and cancers in healthcare staff. Several recommended practices... (Meta-Analysis)
Meta-Analysis Review
Closed-system drug-transfer devices plus safe handling of hazardous drugs versus safe handling alone for reducing exposure to infusional hazardous drugs in healthcare staff.
BACKGROUND
Occupational exposure to hazardous drugs can decrease fertility and result in miscarriages, stillbirths, and cancers in healthcare staff. Several recommended practices aim to reduce this exposure, including protective clothing, gloves, and biological safety cabinets ('safe handling'). There is significant uncertainty as to whether using closed-system drug-transfer devices (CSTD) in addition to safe handling decreases the contamination and risk of staff exposure to infusional hazardous drugs compared to safe handling alone.
OBJECTIVES
To assess the effects of closed-system drug-transfer of infusional hazardous drugs plus safe handling versus safe handling alone for reducing staff exposure to infusional hazardous drugs and risk of staff contamination.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, OSH-UPDATE, CINAHL, Science Citation Index Expanded, economic evaluation databases, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to October 2017.
SELECTION CRITERIA
We included comparative studies of any study design (irrespective of language, blinding, or publication status) that compared CSTD plus safe handling versus safe handling alone for infusional hazardous drugs.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified trials and extracted data. We calculated the risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CI) using both fixed-effect and random-effects models. We assessed risk of bias according to the risk of bias in non-randomised studies of interventions (ROBINS-I) tool, used an intracluster correlation coefficient of 0.10, and we assessed the quality of the evidence using GRADE.
MAIN RESULTS
We included 23 observational cluster studies (358 hospitals) in this review. We did not find any randomised controlled trials or formal economic evaluations. In 21 studies, the people who used the intervention (CSTD plus safe handling) and control (safe handling alone) were pharmacists or pharmacy technicians; in the other two studies, the people who used the intervention and control were nurses, pharmacists, or pharmacy technicians. The CSTD used in the studies were PhaSeal (13 studies), Tevadaptor (1 study), SpikeSwan (1 study), PhaSeal and Tevadaptor (1 study), varied (5 studies), and not stated (2 studies). The studies' descriptions of the control groups were varied. Twenty-one studies provide data on one or more outcomes for this systematic review. All the studies are at serious risk of bias. The quality of evidence is very low for all the outcomes.There is no evidence of differences in the proportion of people with positive urine tests for exposure between the CSTD and control groups for cyclophosphamide alone (RR 0.83, 95% CI 0.46 to 1.52; I² = 12%; 2 studies; 2 hospitals; 20 participants; CSTD: 76.1% versus control: 91.7%); cyclophosphamide or ifosfamide (RR 0.09, 95% CI 0.00 to 2.79; 1 study; 1 hospital; 14 participants; CSTD: 6.4% versus control: 71.4%); and cyclophosphamide, ifosfamide, or gemcitabine (RR not estimable; 1 study; 1 hospital; 36 participants; 0% in both groups).There is no evidence of a difference in the proportion of surface samples contaminated in the pharmacy areas or patient-care areas for any of the drugs except 5-fluorouracil, which was lower in the CSTD group than in the control (RR 0.65, 95% CI 0.43 to 0.97; 3 studies, 106 hospitals, 1008 samples; CSTD: 9% versus control: 13.9%).The amount of cyclophosphamide was lower in pharmacy areas in the CSTD group than in the control group (MD -49.34 pg/cm², 95% CI -84.11 to -14.56, I² = 0%, 7 studies; 282 hospitals, 1793 surface samples). Additionally, one interrupted time-series study (3 hospitals; 342 samples) demonstrated a change in the slope between pre-CSTD and CSTD (3.9439 pg/cm², 95% CI 1.2303 to 6.6576; P = 0.010), but not between CSTD and post-CSTD withdrawal (-1.9331 pg/cm², 95% CI -5.1260 to 1.2598; P = 0.20). There is no evidence of difference in the amount of the other drugs between CSTD and control groups in the pharmacy areas or patient-care areas.None of the studies report on atmospheric contamination, blood tests, or other measures of exposure to infusional hazardous drugs such as urine mutagenicity, chromosomal aberrations, sister chromatid exchanges, or micronuclei induction.None of the studies report short-term health benefits such as reduction in skin rashes, medium-term reproductive health benefits such as fertility and parity, or long-term health benefits related to the development of any type of cancer or adverse events.Five studies (six hospitals) report the potential cost savings through the use of CSTD. The studies used different methods of calculating the costs, and the results were not reported in a format that could be pooled via meta-analysis. There is significant variability between the studies in terms of whether CSTD resulted in cost savings (the point estimates of the average potential cost savings ranged from (2017) USD -642,656 to (2017) USD 221,818).
AUTHORS' CONCLUSIONS
There is currently no evidence to support or refute the routine use of closed-system drug transfer devices in addition to safe handling of infusional hazardous drugs, as there is no evidence of differences in exposure or financial benefits between CSTD plus safe handling versus safe handling alone (very low-quality evidence). None of the studies report health benefits.Well-designed multicentre randomised controlled trials may be feasible depending upon the proportion of people with exposure. The next best study design is interrupted time-series. This design is likely to provide a better estimate than uncontrolled before-after studies or cross-sectional studies. Future studies may involve other alternate ways of reducing exposure in addition to safe handling as one intervention group in a multi-arm parallel design or factorial design trial. Future studies should have designs that decrease the risk of bias and enable measurement of direct health benefits in addition to exposure. Studies using exposure should be tested for a relevant selection of hazardous drugs used in the hospital to provide an estimate of the exposure and health benefits of using CSTD. Steps should be undertaken to ensure that there are no other differences between CSTD and control groups, so that one can obtain a reasonable estimate of the health benefits of using CSTD.
Topics: Adult; Antineoplastic Agents; Chemical Safety; Cyclophosphamide; Deoxycytidine; Endocrine Disruptors; Fluorouracil; Hazardous Substances; Humans; Ifosfamide; Nursing Staff, Hospital; Observational Studies as Topic; Occupational Exposure; Pharmacists; Pharmacy Technicians; Gemcitabine
PubMed: 29582940
DOI: 10.1002/14651858.CD012860.pub2