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The Journal of Evidence-based Dental... Mar 2023To compare the relative efficacy and safety of antiviral agents used in the prevention and management of herpes labialis through a network meta-analysis of clinical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the relative efficacy and safety of antiviral agents used in the prevention and management of herpes labialis through a network meta-analysis of clinical trials.
METHODS
A systematic search was performed in Ovid Medline PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus and Clinicaltrials.gov for randomized controlled trials (RCTs) reporting a comparison of antiviral agents in the management and prevention of herpes labialis in healthy/immunocompetent adults. The data extracted from the selected RCTs were assessed and a network meta-analysis (NMA) was performed. The interventions were ranked according to the surface under the cumulative ranking (SUCRA).
RESULTS
A total of 52 articles were included for qualitative synthesis and for the quantitative part, 26 articles were analyzed for the primary treatment outcome and 7 studies were analyzed for the primary prevention outcome. The combination therapy of oral valacyclovir and topical clobetasol was the best ranked with a mean reduction in healing time of -3.50 (95% CI -5.22 to -1.78) followed by vidarabine monophosphate of -3.22 (95% CI -4.59 to -1.85). No significant inconsistencies, heterogeneity, and publication bias were reported for TTH outcome analysis. For primary prevention outcomes, only 7 RCTs fulfilled the inclusion criteria, and none of the interventions was shown to be superior to each other. The absence of adverse events was reported by 16 studies, whereas other studies reported mild side effects only.
CONCLUSION
NMA highlighted that several agents were effective in the management of herpes labialis among which the combination of oral valacyclovir with topical clobetasol therapy was the most effective in reducing the time to heal. However, further studies are required to determine which intervention is the most effective in preventing the recurrence of herpes labialis.
Topics: Adult; Humans; Antiviral Agents; Clobetasol; Herpes Labialis; Network Meta-Analysis; Valacyclovir
PubMed: 36914303
DOI: 10.1016/j.jebdp.2022.101778 -
Biology of Blood and Marrow... Apr 2019Fludarabine with busulfan (FB) or melphalan (FM) are 2 more commonly used reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (HCT).We... (Meta-Analysis)
Meta-Analysis
Choosing a Reduced-Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation, Fludarabine/Busulfan versus Fludarabine Melphalan: A Systematic Review and Meta-Analysis.
Fludarabine with busulfan (FB) or melphalan (FM) are 2 more commonly used reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (HCT).We present a systematic review and meta-analysis of studies comparing these 2 RIC regimens. We searched electronic databases from inception through November 1, 2017 for literature searches to identify relevant studies. A DerSimonian random effects model was used to measure efficacy outcomes; hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) are reported. Seven studies, including a total of 1955 patients, met criteria for inclusion, of which 6 were included in the overall pooled analysis because of repetition of some patients in 2 studies. Three studies were included in the subgroup analysis of acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS) and 2 in the subgroup analysis of lymphoid malignancies. Overall survival (OS) and progression-free survival were not statistically significantly different between the 2 RIC regimens in analysis of all studies. However, OS was better with FM in subgroup analysis of AML/MDS studies (HR, .83; 95% CI, .73 to .95). Nonrelapse mortality was lower with FB (HR, .64; 95% CI, .46 to .89), whereas relapse was lower with FM (HR, 1.52; 95% CI, 1.13 to 2.06) in the analysis of all studies. This meta-analysis shows that FB and FM are associated with a similar OS in patients undergoing HCT. Relapse rates are lower with FM but at the cost of higher nonrelapse mortality.
Topics: Busulfan; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Melphalan; Transplantation Conditioning; Transplantation, Homologous; Vidarabine
PubMed: 30471339
DOI: 10.1016/j.bbmt.2018.11.016 -
Journal of Comparative Effectiveness... May 2018A systematic literature review and network meta-analysis were conducted to determine the relative efficacy and safety of interventions for treatment-naive chronic... (Meta-Analysis)
Meta-Analysis
AIM
A systematic literature review and network meta-analysis were conducted to determine the relative efficacy and safety of interventions for treatment-naive chronic lymphocytic leukemia patients, as comparative evidence is scarce.
MATERIALS & METHODS
Relative treatment effects of progression-free survival, overall survival and safety outcomes were estimated via network meta-analysis based on data identified via systematic literature review.
RESULTS
Ibrutinib was superior in all pairwise comparisons for progression-free survival (probability to be better [P] range: overall population: 69-100%; fludarabine-ineligible population: 69-100%) and overall survival (P range: overall: 89-100%; fludarabine-ineligible: 91-100%) and had the highest probability of being best for all outcomes.
CONCLUSION
Ibrutinib provides superior benefit in survival and safety compared with other front-line treatments of chronic lymphocytic leukemia.
Topics: Adenine; Antineoplastic Combined Chemotherapy Protocols; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Network Meta-Analysis; Piperidines; Progression-Free Survival; Pyrazoles; Pyrimidines; Vidarabine
PubMed: 29210593
DOI: 10.2217/cer-2017-0086 -
Blood Nov 2017In chronic lymphocytic leukemia (CLL) patients with mutated , 3 recent studies have demonstrated prolonged progression-free survival (PFS) after treatment with... (Review)
Review
In chronic lymphocytic leukemia (CLL) patients with mutated , 3 recent studies have demonstrated prolonged progression-free survival (PFS) after treatment with fludarabine-cyclophosphamide-rituximab (FCR) chemoimmunotherapy. We performed a systematic review to assess the benefit of FCR for patients with CLL and identified 5 randomized trials that met our inclusion criteria. FCR improved complete remission, PFS and overall survival vs the comparator; median PFS was not reached in the subgroup of CLL patients with mutated .
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease-Free Survival; Female; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Variable Region; Immunotherapy; Leukemia, Lymphocytic, Chronic, B-Cell; Middle Aged; Mutation; Remission Induction; Rituximab; Time Factors; Vidarabine
PubMed: 29025740
DOI: 10.1182/blood-2017-07-731588 -
Bone Marrow Transplantation Feb 2016We aimed to evaluate the efficacy and toxicity profile of busulfan-fludarabine (Bu-Flu) compared with busulfan-cyclophosphamide (Bu-Cy) as a preparative regimen for... (Comparative Study)
Comparative Study Meta-Analysis Review
We aimed to evaluate the efficacy and toxicity profile of busulfan-fludarabine (Bu-Flu) compared with busulfan-cyclophosphamide (Bu-Cy) as a preparative regimen for patients undergoing allogeneic hematopoietic cell transplantation. We performed a systematic review and meta-analysis of all comparative trials, both randomized controlled trials (RCTs) and non-randomized. Our search yielded 15 trials recruiting 1830 patients. Four trials were RCTs and 11 were either one-arm intervention trials compared with historical controls or retrospective studies. There was a lower risk for non-relapse mortality (NRM) at 100 days in patients given Bu-Flu regimen compared with those given Bu-Cy regimen (relative risk (RR) 0.56; 95% confidence interval (CI) 0.34-0.92, 8 trials); however, there were no differences in all-cause mortality at 100 days (RR 0.85; 95% CI 0.56-1.30, 9 trials) and at the end of study (RR 0.81; 95% CI 0.64-1.02, 13 trials). The risks of sinusoidal obstruction syndrome (SOS) and microbiologically documented infections were lower in patients given Bu-Flu regimen (RR 0.34; 95% CI 0.19-0.62, 8 trials and RR 0.79; 95% CI 0.64-0.97, 2 trials, respectively); however, risk for SOS was no longer lower when performing sensitivity analysis according to RCTs. Engraftment kinetics, risk of grade 3-4 mucositis, GvHD, relapse and NRM at the end of the study were all similar between the two groups. We conclude that both regimens have similar efficacy profiles, whereas toxicity is lower with the Bu-Flu regimen.
Topics: Allografts; Busulfan; Cyclophosphamide; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Randomized Controlled Trials as Topic; Survival Rate; Transplantation Conditioning; Vidarabine
PubMed: 26457908
DOI: 10.1038/bmt.2015.238 -
Biology of Blood and Marrow... Apr 2016Oral mucositis (OM) is a debilitating early adverse effect of allogeneic hematopoietic stem cell transplantation (HSCT). The intensity of the conditioning regimen... (Review)
Review
Oral mucositis (OM) is a debilitating early adverse effect of allogeneic hematopoietic stem cell transplantation (HSCT). The intensity of the conditioning regimen correlates with the incidence and severity of OM, but no studies have analyzed this relationship among various conditioning regimens. We performed a systematic review on the incidence and outcomes of OM in allogeneic HSCT patients and analyzed this association. A comprehensive search of several databases (Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Cochrane CRCT, Cochrane DSR, Scopus) from 1990 to 2014 for studies of OM in allogeneic HSCT patients was conducted. Professional societies' meeting abstracts were also searched. Grade of OM was analyzed based on the World Health Organization (WHO) or National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events scales. Severe mucositis was defined as either grades 2 to 4 or grades 3 and 4, depending on the studies' definition of severity. Cohorts were analyzed based on regimen intensity; ie, reduced-intensity conditioning (RIC) (including nonmyeloablative) and myeloablative (MA). Random effect (RE) and standard logistic models weighted by the number of patients in each cohort were used for comparisons. A total of 624 studies were generated from the search. Of the 395 patients in 8 eligible MA regimen studies, 73.2% experienced any OM, whereas in 245 patients in the 6 eligible RIC regimen studies, 86.5% experienced any OM (chi-square P < .0001; RE, P = .05). Severe (grades 2 to 4) OM occurred among 79.7% of the WHO/NCI-graded MA patients and 71.5% of RIC patients (chi-square, P = .0421; RE, P < .01). In comparing graft-versus-host disease (GVHD) prophylaxis, only 55.4% of patients receiving nonmethotrexate regimens experienced OM; this was lower (chi-square, P < .0001; RE, P = .06) than that found among patients who received methotrexate (83.4%), either standard or reduced dose. Besides NCI and WHO grading scales, other scales included in the studies were Oral Mucositis Index, the Southwest Oncology Group Criteria, and Eastern Cooperative Oncology Group scale. To our knowledge, this is the first analysis on OM in allogeneic HSCT patients with respect to conditioning regimens, and we observed that RIC regimens led to a high incidence of OM similar to that of MA regimens. Clinical trials on treatment of OM are lacking, emphasizing the essential need for prospective studies in this arena. A significant variance in the criteria for grading OM underscores the importance of establishing a standard grading system for OM measurement in future allogeneic HSCT clinical trials.
Topics: Busulfan; Cyclophosphamide; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Methotrexate; Mouth Mucosa; Myeloablative Agonists; Severity of Illness Index; Stomatitis; Transplantation Conditioning; Transplantation, Homologous; Vidarabine
PubMed: 26409924
DOI: 10.1016/j.bbmt.2015.09.014 -
The Cochrane Database of Systematic... Jan 2015Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis which, though usually self-limiting, may persist or progress without treatment. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis which, though usually self-limiting, may persist or progress without treatment.
OBJECTIVES
To compare the relative effectiveness of antiviral agents, interferon, and corneal debridement in the treatment of HSV epithelial keratitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 12), PubMed (January 1946 to 31 December 2014), EMBASE (January 1980 to 31 December 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to 31 December 2014), System for Information on Grey Literature in Europe (OpenGrey) (January 1995 to 31 December 2014), BIOSIS (January 1926 to 5 May 2014), Scopus (January 1966 to 31 December 2014), Japan Science and Technology Institute (J-Global) (January 1975 to 31 December 2014), China National Knowledge Infrastructure (CNKI) (January 1979 to 31 December 2014), British Library's Electronic Table of Contents (Zetoc) (January 1993 to 7 May 2014). We looked for trials listed on the the metaRegister of Controlled Trials (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en), Chinese Clinical Trial Registry, the U.S. Food and Drug Administration (FDA) (www.fda.gov/), National Institute for Health and Clinical Excellence (NICE) (www.
EVIDENCE
nhs.uk) and the European Medicines Agency (EMA) (www.ema.europa.eu/ema/) as of 31 December 2014. There were no language or date restrictions in the search for trials. We also culled literature digests and conference proceedings as of 15 April 2014. There were no language or date restrictions in the search for trials.
SELECTION CRITERIA
Randomised and quasi-randomised trials of HSV dendritic or geographic epithelial keratitis were included that reported the proportion of eyes healed at one week, two weeks, or both after enrolment.
DATA COLLECTION AND ANALYSIS
We tabulated data on study characteristics, risk of bias, and outcomes and used direct comparisons to estimate a risk ratio (RR) and, when feasible, a hazard ratio (HR) with a 95% confidence interval (CI). Heterogeneity was assessed by an inconsistency index. A multiple treatment comparison meta-analysis consolidated direct and indirect comparisons of relative healing at 14 days.
MAIN RESULTS
One hundred thirty-seven studies involving 8333 eyes met the inclusion criteria. Placebo-controlled studies were heterogeneous in comparison with idoxuridine (RR 1.74; 95% CI 1.03 to 2.91) and few in number for vidarabine (RR 1.81; 95% CI 1.09 to 3.01), interferon (RR 1.32; 95% CI 1.06 to 1.64), and debridement. Vidarabine (RR 1.13; 95% CI 1.02 to 1.25), trifluridine (RR 1.30; 95% CI 1.18 to 1.43), acyclovir (RR 1.23; 95% CI 1.14 to 1.34), and brivudine (RR 1.34; 95% CI 1.18 to 1.51) were more effective than idoxuridine. Trifluridine (RR 1.17; 95% CI 1.03 to 1.32) and acyclovir (RR 1.11; 95% CI 1.03 to 1.19) were more effective than vidarabine. No significant differences in healing emerged among trifluridine, acyclovir, brivudine, and foscarnet although few studies compared brivudine or foscarnet with other antivirals. Any potential advantage of ganciclovir compared to acyclovir was mitigated by study heterogeneity and possible publication bias. Only one study evaluated the joint use of two topical antivirals. In a limited number of studies, oral acyclovir (RR 0.92; 95% CI 0.79 to 1.07) or the combination of oral acyclovir with a topical antiviral (RR 1.36; 95% CI 0.68 to 2.74) appeared as effective as a single topical antiviral agent. Compared to topical antiviral monotherapy, the combination of an antiviral with either interferon or debridement had inconsistent effects on expediting healing and improving outcome.
AUTHORS' CONCLUSIONS
Placebo-controlled studies of HSV epithelial keratitis are limited to superseded interventions. Trifluridine and acyclovir are more effective than idoxuridine or vidarabine and similar in therapeutic effectiveness. Brivudine and foscarnet do not substantially differ in effectiveness from trifluridine or acyclovir. Ganciclovir is at least as effective as acyclovir. The addition of interferon to a nucleoside antiviral agent and the combination of debridement with antiviral treatment need to be further assessed to substantiate any possible advantage in healing.
Topics: Administration, Oral; Administration, Topical; Antiviral Agents; Combined Modality Therapy; Debridement; Humans; Interferons; Keratitis, Herpetic; Randomized Controlled Trials as Topic
PubMed: 25879115
DOI: 10.1002/14651858.CD002898.pub5 -
Critical Reviews in Oncology/hematology Jun 2015Chronic lymphocytic leukemia (CLL) is a disease of the lymphoid system, in which the most common therapy is fludarabine plus cyclophosphamide (FC). The addition of... (Meta-Analysis)
Meta-Analysis Review
Rituximab, fludarabine, and cyclophosphamide versus fludarabine and cyclophosphamide for treatment of chronic lymphocytic leukemia: A systematic review with meta-analysis.
BACKGROUND
Chronic lymphocytic leukemia (CLL) is a disease of the lymphoid system, in which the most common therapy is fludarabine plus cyclophosphamide (FC). The addition of rituximab to FC has been used, a combination known as FCR.
OBJECTIVES
To perform a systematic review with meta-analysis of clinical trials between 2000 and 2012 comparing FC and FCR in patients with CLL.
MATERIAL AND METHODS
Electronic databases were searched using keywords related to the objectives of this review. The outcomes examined were progression-free survival and complete remission.
RESULTS
The progression-free survival and the overall survival showed significant difference between the two regimens, with complete remission being more frequent in FCR-treated patients (odds ratio=2.58; 95% CI: 2.13-3.13). Patients treated with FCR showed significantly higher neutropenia and serious adverse reactions.
CONCLUSION
Despite the favorable results of the FCR regimen on outcomes including complete remission, progression-free survival, and overall survival, there is a lack of methodological rigor and appropriate analyses in many of these studies, and thus, there is a need for further studies examining the effect of rituximab in CLL patients.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Randomized Controlled Trials as Topic; Remission Induction; Rituximab; Treatment Outcome; Vidarabine
PubMed: 25797826
DOI: 10.1016/j.critrevonc.2015.02.013