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Transplantation Oct 2014Rituximab is a B lymphocyte-depleting agent used to treat lymphoma and autoimmune diseases. Recently, it has been used for desensitization therapy in ABO-incompatible... (Review)
Review
BACKGROUND
Rituximab is a B lymphocyte-depleting agent used to treat lymphoma and autoimmune diseases. Recently, it has been used for desensitization therapy in ABO-incompatible and highly sensitized recipients undergoing renal transplantation.
METHODS
A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Four databases and three trial registries were searched for studies comparing rituximab with non-rituximab desensitization protocols. A lack of randomized evidence precluded meta-analysis, and thus a narrative review was conducted.
RESULTS
Forty-five records met the inclusion criteria, relating to 21 individual studies (two randomized controlled trials and 19 retrospective cohort studies). Ten studies investigated the use of rituximab in ABO-incompatible patients; most found no significant differences in patient and graft outcomes when compared most frequently to splenectomy-based protocols. Nine studies of limited quality focused on highly sensitized recipients (positive cross-match, donor-specific antibody, and elevated panel reactive antibody) and demonstrated some benefits in graft survival, acute and chronic rejection, and sensitization levels with rituximab. The remaining two studies combined ABO-incompatible and highly sensitized recipients and found no statistically significant increase in infectious complications with rituximab.
CONCLUSION
Evidence of limited quality was identified to support the use of rituximab desensitization in highly sensitized recipients. Among ABO-incompatible recipients, rituximab was found to be equivalent to splenectomy, indicating that this invasive surgical procedure is not necessary. Further randomized controlled trials are required to better define the efficacy, long-term safety, and optimal dosing regimen of rituximab in this setting.
Topics: ABO Blood-Group System; Antibodies, Monoclonal, Murine-Derived; Blood Group Incompatibility; Desensitization, Immunologic; Histocompatibility Testing; Humans; Isoantibodies; Kidney Transplantation; Randomized Controlled Trials as Topic; Rituximab; Tissue Donors
PubMed: 25321163
DOI: 10.1097/TP.0000000000000362 -
The Journal of Allergy and Clinical... Aug 2023Omalizumab is the only biological agent approved for patients with chronic spontaneous urticaria (CSU), but no biomarker is well established for predicting clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Omalizumab is the only biological agent approved for patients with chronic spontaneous urticaria (CSU), but no biomarker is well established for predicting clinical response to omalizumab.
OBJECTIVE
We aimed to determine the association between baseline total serum IgE levels and the effects of omalizumab in patients with CSU.
METHODS
PubMed, Web of Science, Scopus, and Cochrane Library were systematically searched for relevant studies from inception to August 23, 2022. The research protocol was registered on PROSPERO (CRD42022355592). No language restrictions were applied. A random-effects model was used for meta-analysis.
RESULTS
Ten interventional studies, including 1 randomized controlled trial, were included in the final meta-analysis, and a total of 866 patients with CSU were included. A pooled analysis showed significantly higher serum total IgE levels in complete responders (CRs) than in nonresponders (NRs) (mean difference [MD]: 56.509 IU/mL; 95% confidence interval [CI]: 24.230-88.789) and in partial responders (PRs) than in NRs (MD: 62.688 IU/mL; 95% CI: 32.949-92.427), but no significant difference was detected between CRs and PRs. The mean total IgE levels for CRs, PRs, and NRs were 163.154, 179.926, and 51.535 IU/mL, respectively. Further, the serum total IgE levels in early CRs were significantly higher compared with late CRs (MD: 55.194 IU/mL; 95% CI: 13.402-96.986). The sensitivity analyses with the leave-one-out method validated the robustness of all findings.
CONCLUSIONS
This systematic review and meta-analysis provide convincing evidence that pretreatment total serum IgE levels in patients with CSU are associated with clinical responses to omalizumab.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Urticaria; Immunoglobulin E; Treatment Outcome; Chronic Urticaria; Chronic Disease; Randomized Controlled Trials as Topic
PubMed: 37263348
DOI: 10.1016/j.jaip.2023.05.033 -
Acta Ophthalmologica May 2017Keratoconus can behave more aggressively in pediatric than in adult patients. We systematically reviewed the literature to determine the effectiveness of corneal... (Meta-Analysis)
Meta-Analysis Review
Keratoconus can behave more aggressively in pediatric than in adult patients. We systematically reviewed the literature to determine the effectiveness of corneal collagen cross-linking (CXL) in children. For this study, MEDLINE and Cochrane databases were searched for all studies examining the effects of standard, trans-epithelial or accelerated CXL protocols in patients age 18 years or younger. Primary outcomes were; uncorrected visual acuity (UCVA) and maximum keratometry (Kmax) and secondary outcomes were; best-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), central corneal thickness (CCT) and endothelial cell density (ECD). Standardized mean differences (SMD) and 95% confidence intervals were calculated, comparing baseline values with those at 6, 12 and 24 months. A total of 13 papers, published between May 2011 and December 2014 examining 490 eyes of 401 patients with a mean age of 15.25 (±1.5) years, were included in the qualitative analysis in this review. Nine papers were included in the meta-analysis, showing significant improvement in UCVA and BCVA and stable Kmax at 12 months, and stable UCVA, improved BCVA and improved Kmax at 24 months in the standard protocol group UCVA, BCVA and KMax were stable at 12 months in the trans-epithelial group. Mean refractive spherical equivalent (MRSE), CCT and ECD remained stable in both groups. In conclusion it was found that standard CXL may be effective in halting progression of keratoconus in pediatric patients at 1 year. However, larger, more long-term studies are required to ascertain its effectiveness.
Topics: Collagen; Cornea; Corneal Topography; Cross-Linking Reagents; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Ultraviolet Rays
PubMed: 27678078
DOI: 10.1111/aos.13224 -
Anti-cancer Drugs Nov 2014Raltitrexed is a thymidylate synthase inhibitor belonging to the antimetabolite class of cytotoxic drugs. It is also effective in colorectal cancer (CRC) both as a... (Review)
Review
Raltitrexed is a thymidylate synthase inhibitor belonging to the antimetabolite class of cytotoxic drugs. It is also effective in colorectal cancer (CRC) both as a single agent and in combination with other drugs, in particular in those patients with cardiologic risk factors or previous cardiotoxicity. The efficacy of first-line raltitrexed-based chemotherapy containing oxaliplatin (TOMOX) and irinotecan (TOMIRI) was investigated in this systematic review. Studies that enrolled advanced CRC patients for first-line therapy with TOMOX/TOMIRI combinations were identified using electronic databases (Pubmed, SCOPUS, Web of Science, EMBASE, and the Cochrane Library). A systematic analysis was carried out using Comprehensive Meta Analysis (version 2.2.064) software to calculate the pooled response rate and 95% confidence limits. The median pooled overall survival and progression-free survival were also calculated. Results for TOMOX and TOMIRI studies were compared using the two-sided Student's t-test. We tested for significant heterogeneity using Cochran's χ-test and I index. Twelve studies published between 2001 and 2012 were eligible for this analysis and a total of 735 patients were enrolled in these studies. The overall response rate was 40% (95% confidence interval 34-46%): 43.9% for TOMOX and 34.1% for TOMIRI arms. The weighted median overall survival and progression-free survival times were 14.6 and 6.7 months, respectively. Neutropenia and liver toxicity were more frequent with TOMOX, whereas neutropenia and diarrhea were more frequent with TOMIRI. However, compared with historical FOLFOX and FOLFIRI trials, raltitrexed-based doublets are associated with less neutropenia and gastrointestinal toxicity and uncommon cardiotoxicity. TOMOX and TOMIRI doublets are active as first-line chemotherapy for advanced CRC and seem useful in particular when the use of 5-fluorouracil is contraindicated for cardiac comorbidity.
Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cardiotoxicity; Colorectal Neoplasms; Diarrhea; Humans; Irinotecan; Liver; Neoplasm Metastasis; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Quinazolines; Thiophenes
PubMed: 24869761
DOI: 10.1097/CAD.0000000000000133 -
Cancer Treatment Reviews Feb 2018Despite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy remains poorly defined.
METHODS
We conducted a systematic review and meta-analysis to evaluate benefits and harms of multi-agent chemotherapy in advanced STS. Eligible studies were randomized trials of chemotherapy in advanced STS comparing single agent to multi-agent therapy. Data from studies reporting a hazard ratio (HR) and 95% confidence intervals (CI) for OS and progression-free survival (PFS) were pooled in a meta-analysis. Meta-regression was utilized to explore the association between efficacy (OS and PFS) and both toxicity and dose intensity.
RESULTS
We identified 22 trials published between 1974 and April 2016 and comprising 5044 patients. Overall, multi-agent chemotherapy was associated with improved OS (HR:0.79, p = 0.02), and borderline improvement in PFS (HR:0.86, p = 0.05). While the effect on OS was similar in trials with non-anthracycline controls compared to those with anthracycline controls (HR for OS 0.73 vs. 0.82, p for difference = 0.63) there was a non-significantly greater effect for multi-agent chemotherapy on PFS in non-anthracycline RCT (HR for PFS 0.73 vs. 0.91, p for difference = 0.13). Compared to studies with cytotoxic therapy-based multi-agent therapy, a non-significantly greater magnitude of effect among studies with biological/cytostatic experimental groups was seen (HR for OS 0.64 vs. 0.86, p for difference = 0.37). There was a borderline significant association between dose reductions (which were more common in combination arms) and worse PFS (beta = 0.70, p = 0.053).
CONCLUSION
Multi-agent chemotherapy is associated with a modest, but statistically significant improvement in outcomes in STS. Combining chemotherapy with non-cytotoxic agents might represent a promising strategy.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Doxorubicin; Humans; Randomized Controlled Trials as Topic; Sarcoma
PubMed: 29253836
DOI: 10.1016/j.ctrv.2017.12.003 -
American Journal of Infection Control Sep 2016Several clusters of Carbapenem-resistant Enterobacteriaceae (CRE) infections associated with contaminated endoscopes have recently been reported. Interim guidelines for... (Review)
Review
BACKGROUND
Several clusters of Carbapenem-resistant Enterobacteriaceae (CRE) infections associated with contaminated endoscopes have recently been reported. Interim guidelines for mitigating endoscope-associated transmission have been proposed, but there has not been a systematic appraisal of CRE prevention practices.
METHODS
We conducted a systematic review of endoscope-associated CRE infection episodes, abstracting information on outbreak detection, mitigation, outcomes, and corrective steps taken to prevent recurrence.
RESULTS
Seven distinct outbreaks were identified in the published literature, and 5 of these were associated with duodenal endoscopy, with the remaining 2 associated with cystoscopy and ureteroscopy. Several investigators noted difficulties in cleaning protocols surrounding difficult to access components, such as the elevator on duodenoscopes. The published investigations did not report any failures of sterilization. It is unclear if routine reprocessing was ineffective, or difficult to execute properly.
CONCLUSIONS
Meticulous cleaning protocols and increased surveillance are necessary to prevent and detect future outbreaks of CRE and to determine whether more stringent measures, such as sterilization, are needed for duodenoscopes.
Topics: Anti-Bacterial Agents; Carbapenems; Disease Transmission, Infectious; Endoscopy; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; beta-Lactam Resistance
PubMed: 27179395
DOI: 10.1016/j.ajic.2016.03.029 -
Oncotarget May 2017Although two newly launched monoclonal antibodies (mAbs), elotuzumab and daratumumab, performed well in patients with relapsed or relapsed/refractory multiple myeloma... (Meta-Analysis)
Meta-Analysis Review
Although two newly launched monoclonal antibodies (mAbs), elotuzumab and daratumumab, performed well in patients with relapsed or relapsed/refractory multiple myeloma (RRMM), their efficacy and safety remain uncertain. We therefore performed a systematic review and meta-analysis of the most recent clinical trials that evaluated elotuzumab and/or daratumumab for the treatment of patients with RRMM. Our meta-analysis included 13 clinical trials with 2,402 patients participating. The overall response rate (ORR) was 57% (95% confidence interval [CI]: 38-76%), and the at least very good partial response rate (VGPR) was 32% (95% CI: 19-46%). mAb-based regimens prolonged progression-free survival (PFS, hazard ratio: 0.52, 95% CI: 0.36-0.75) compared to non-mAb-based regimens. Additionally, the efficacy of triplet regimens was superior to that of single or doublet regimens. The same trend was observed in a subgroup analysis of daratumumab and elotuzumab. The most common grade 3/4 adverse events included neutropenia, lymphopenia, thrombocytopenia, anemia, leukopenia, pneumonia, and fatigue. Elotuzumab and daratumumab improved the ORR, at least VGPR, and PFS compared to non-mAb-based regimens. In a pooled analysis, both mAbs had promising efficacy and safety profiles, particularly in triplet regimens. The same trend was observed in daratumumab- and elotuzumab-based regimens. Daratumumab triplet therapy (daratumumab, lenalidomide, and dexamethasone) was superior to other triplet regimens for the treatment of RRMM, and daratumumab monotherapy was more effective than either single agent in heavily pretreated MM patients, suggesting CD38 is an effective target for treatment of RRMM. Additional clinical studies of elotuzumab and daratumumab will be required to validate these results.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drug Resistance, Neoplasm; Humans; Multiple Myeloma; Odds Ratio; Recurrence; Treatment Outcome
PubMed: 28454113
DOI: 10.18632/oncotarget.16987 -
Psychotherapy and Psychosomatics 2017Conditioned pharmacological effects may provide relevant clinical opportunities to improve treatment for patients with a variety of conditions. The aim of this... (Review)
Review
BACKGROUND
Conditioned pharmacological effects may provide relevant clinical opportunities to improve treatment for patients with a variety of conditions. The aim of this systematic review was to create an overview of studies in this field of research and to investigate whether specific characteristics of the study design make for successful conditioning.
METHODS
The protocol of this review was registered in Prospero (PROSPERO 2015: CRD42015024148). A systematic literature search was conducted in the databases PubMed, Embase, and PsychInfo. Studies were included if they were placebo-controlled trials in humans in which the effects of a pharmacological agent on immune or endocrine outcomes (e.g., interleukin-2 and cortisol) were conditioned, using a specific conditioned stimulus. The risk of bias of each study was assessed using the Cochrane risk-of-bias tool.
RESULTS
The final selection included 16 studies. Overall, those studies indicate that conditioning of immunosuppression, conditioning of allergic responses, and conditioning of insulin and glycemic responses is possible. Regarding immunostimulants, antiallergic effects, and cortisol conditioning, the preliminary results are promising, but additional studies are needed.
CONCLUSIONS
This systematic review shows classical conditioning of immune and endocrine responses for various pharmaceutical substances. The studies reviewed here indicate that the number of acquisition and evocation sessions, and characteristics of the unconditioned and conditioned stimuli, are important determinants of the effectiveness of pharmacological conditioning on immune and endocrine parameters. In the future, conditioned pharmacological effects may be used clinically as adjunct therapy in various patient populations.
Topics: Conditioning, Classical; Endocrine System; Humans; Hypersensitivity; Immune System; Placebo Effect
PubMed: 28183096
DOI: 10.1159/000449470 -
Quintessence International (Berlin,... 2017To evaluate the effectiveness of chlorhexidine mouthwashes on the reduction of cariogenic bacteria on patients with moderate to high risk for dental caries. (Review)
Review
OBJECTIVE
To evaluate the effectiveness of chlorhexidine mouthwashes on the reduction of cariogenic bacteria on patients with moderate to high risk for dental caries.
DATA SOURCES
A systematic review of the literature was performed using Cochrane Library, Embase, PubMed, Scopus and Web of Science. The search was limited to articles in English, Spanish, and Portuguese, published until January 2017. The research question was formulated following the PICO strategy. The risk of bias was evaluated using the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.
CONCLUSION
All the authors found statistically significant differences in Streptococcus mutans levels during and after the use of a chlorhexidine mouthwash. Although the results are suggestive, there is a clear need for the development of new studies with higher quality and with longer follow-ups, in order to assess whether the results translate into less development of dental caries and, consequently, whether or not these products should be incorporated into prevention protocols.
Topics: Anti-Infective Agents, Local; Chlorhexidine; Dental Caries; Humans; Mouthwashes
PubMed: 28555200
DOI: 10.3290/j.qi.a38353 -
Expert Opinion on Investigational Drugs Jun 2016Sorafenib is an orally available compound that acts predominantly by targeting the Ras/Raf/MEK/ERK pathway and by inhibiting the vascular endothelial growth factor... (Review)
Review
INTRODUCTION
Sorafenib is an orally available compound that acts predominantly by targeting the Ras/Raf/MEK/ERK pathway and by inhibiting the vascular endothelial growth factor (VEGF). Since the Ras/Raf/MEK/ERK pathway is implicated in the proliferation of multiple myeloma (MM) cells and VEGF in bone marrow neovascularization, sorafenib is a drug offering the potential for targeting two important pathogenetic mechanisms involved in MM. Thus, sorafenib is being proposed for use in MM.
AREAS COVERED
In this review, the authors discuss the rationale for the use of sorafenib in MM. They then summarize the clinical development of sorafenib in MM, from initial Phase I to Phase II studies. A systematic literature review of the trials was performed using PubMed.
EXPERT OPINION
Preliminary data from phase I/II trials showed that sorafenib had a good safety profile but minimal anti-myeloma activity as a single agent in relapsed/refractory patients. Results of phase II trials, evaluating sorafenib combined with new drugs, such as bortezomib and lenalidomide are eagerly awaited.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Cell Proliferation; Humans; Lenalidomide; Multiple Myeloma; Niacinamide; Phenylurea Compounds; Protein Kinase Inhibitors; Sorafenib; Thalidomide
PubMed: 26998658
DOI: 10.1517/13543784.2016.1169272