-
PloS One 2016Sperm DNA fragmentation has been associated with reduced fertilization rates, embryo quality, pregnancy rates and increased miscarriage rates. Various methods exist to... (Meta-Analysis)
Meta-Analysis Review
Sperm DNA fragmentation has been associated with reduced fertilization rates, embryo quality, pregnancy rates and increased miscarriage rates. Various methods exist to test sperm DNA fragmentation such as the sperm chromatin structure assay (SCSA), the sperm chromatin dispersion (SCD) test, the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay and the single cell gel electrophoresis (Comet) assay. We performed a systematic review and meta-analysis to assess the value of measuring sperm DNA fragmentation in predicting chance of ongoing pregnancy with IVF or ICSI. Out of 658 unique studies, 30 had extractable data and were thus included in the meta-analysis. Overall, the sperm DNA fragmentation tests had a reasonable to good sensitivity. A wide variety of other factors may also affect the IVF/ICSI outcome, reflected by limited to very low specificity. The constructed hierarchical summary receiver operating characteristic (HSROC) curve indicated a fair discriminatory capacity of the TUNEL assay (area under the curve (AUC) of 0.71; 95% CI 0.66 to 0.74) and Comet assay (AUC of 0.73; 95% CI 0.19 to 0.97). The SCSA and the SCD test had poor predictive capacity. Importantly, for the TUNEL assay, SCD test and Comet assay, meta-regression showed no differences in predictive value between IVF and ICSI. For the SCSA meta-regression indicated the predictive values for IVF and ICSI were different. The present review suggests that current sperm DNA fragmentation tests have limited capacity to predict the chance of pregnancy in the context of MAR. Furthermore, sperm DNA fragmentation tests have little or no difference in predictive value between IVF and ICSI. At this moment, there is insufficient evidence to recommend the routine use of sperm DNA fragmentation tests in couples undergoing MAR both for the prediction of pregnancy and for the choice of treatment. Given the significant limitations of the evidence and the methodological weakness and design of the included studies, we do urge for further research on the predictive value of sperm DNA fragmentation for the chance of pregnancy after MAR, also in comparison with other predictors of pregnancy after MAR.
Topics: Abortion, Spontaneous; Chromatin; Comet Assay; DNA Fragmentation; Female; Fertilization in Vitro; Humans; In Situ Nick-End Labeling; Male; Pregnancy; Pregnancy Rate; Semen Analysis; Spermatozoa
PubMed: 27832085
DOI: 10.1371/journal.pone.0165125 -
The Cochrane Database of Systematic... Jul 2017Patients prefer oral to intravenous (IV) palliative chemotherapy, provided that oral therapy is not less effective. We compared the efficacy and safety of oral and IV... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients prefer oral to intravenous (IV) palliative chemotherapy, provided that oral therapy is not less effective. We compared the efficacy and safety of oral and IV fluoropyrimidines for treatment of colorectal cancer (CRC).
OBJECTIVES
To compare the effects of oral and IV fluoropyrimidine chemotherapy in patients treated with curative or palliative intent for CRC.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 5), along with OVID MEDLINE, OVID Embase, and Web of Science databases, in June 2016. We also searched five clinical trials registers, several conference proceedings, and reference lists from study reports and systematic reviews. We contacted pharmaceutical companies to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing oral and IV fluoropyrimidine chemotherapy in patients treated with curative or palliative intent for CRC.
DATA COLLECTION AND ANALYSIS
Three review authors extracted data and assessed risk of bias independently. We assessed the seven domains in the Cochrane 'Risk of bias' tool and three additional domains: schedules of outcome assessment and/or follow-up; use of intention-to-treat analysis; and baseline comparability of treatment arms.
MAIN RESULTS
We included nine RCTs (total of 10,918 participants) that examined treatment with curative intent for CRC with neoadjuvant and/or adjuvant chemotherapy. We included 35 RCTs (total of 12,592 participants) that examined treatment with palliative intent for inoperable advanced or metastatic CRC with chemotherapy (31 first-line studies, two second-line studies, and two studies of first- or second-line chemotherapy). All studies included male and female participants, and no studies included participants younger than 18 years of age. Patients treated with curative intent for CRC with neoadjuvant and/or adjuvant chemotherapy • Disease-free survival (DFS): DFS did not differ between participants treated with oral versus IV fluoropyrimidines (hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.87 to 1.00; seven studies, 8903 participants; moderate-quality evidence).• Overall survival (OS): OS did not differ between participants treated with oral versus IV fluoropyrimidines (HR 0.92, 95% CI 0.84 to 1.00; seven studies, 8902 participants analysed; high-quality evidence).• Grade ≥ 3 adverse events (AEs): Participants treated with oral fluoropyrimidines experienced less grade ≥ 3 neutropenia/granulocytopenia (odds ratio (OR) 0.14, 95% CI 0.11 to 0.16; seven studies, 8087 participants; moderate-quality evidence), stomatitis (OR 0.21, 95% CI 0.14 to 0.30; five studies, 4212 participants; low-quality evidence), and any grade ≥ 3 AEs (OR 0.82, 95% CI 0.74 to 0.90; five studies, 7741 participants; low-quality evidence). There was more grade ≥ 3 hand foot syndrome (OR 4.59, 95% CI 2.97 to 7.10; five studies, 5731 participants; low-quality evidence) in patients treated with oral fluoropyrimidines. There were no differences between participants treated with oral versus IV fluoropyrimidines in occurrence of grade ≥ 3 diarrhoea (OR 1.12, 95% CI 0.99 to 1.25; nine studies, 9551 participants; very low-quality evidence), febrile neutropenia (OR 0.59, 95% CI 0.18 to 1.90; four studies, 2925 participants; low-quality evidence), vomiting (OR 1.05, 95% CI 0.83 to 1.34; eight studies, 9385 participants; low-quality evidence), nausea (OR 1.21, 95% CI 0.97 to 1.51; seven studies, 9233 participants; low-quality evidence), mucositis (OR 0.64, 95% CI 0.25 to 1.62; four studies, 2233 participants; very low-quality evidence), and hyperbilirubinaemia (OR 1.67, 95% CI 0.52 to 5.38; three studies, 2757 participants; very low-quality evidence). Patients treated with palliative intent for inoperable advanced or metastatic CRC with chemotherapy • Progression-free survival (PFS): Overall, PFS was inferior in participants treated with oral versus IV fluoropyrimidines (HR 1.06, 95% CI 1.02 to 1.11; 23 studies, 9927 participants; moderate-quality evidence). Whilst PFS was worse in participants treated with oral compared with IV fluoropyrimidines when UFT/Ftorafur or eniluracil with oral 5-fluorouracil (5-FU) was used, PFS did not differ between individuals treated with oral versus IV fluoropyrimidines when capecitabine, doxifluridine, or S-1 was used.• OS: Overall, OS did not differ between participants treated with oral versus IV fluoropyrimidines (HR 1.02, 95% CI 0.99 to 1.05; 29 studies, 12,079 participants; high-quality evidence). OS was inferior in participants treated with oral versus IV fluoropyrimidines when eniluracil with oral 5-fluorouracil (5-FU) was used.• Time to progression (TTP): TTP was inferior in participants treated with oral versus IV fluoropyrimidines (HR 1.07, 95% CI 1.01 to 1.14; six studies, 1970 participants; moderate-quality evidence).• Objective response rate (ORR): ORR did not differ between participants treated with oral versus IV fluoropyrimidines (OR 0.98, 95% CI 0.90 to 1.06; 32 studies, 11,115 participants; moderate-quality evidence).• Grade ≥ 3 AEs: Participants treated with oral fluoropyrimidines experienced less grade ≥ 3 neutropenia/granulocytopenia (OR 0.17, 95% CI 0.15 to 0.18; 29 studies, 11,794 participants; low-quality evidence), febrile neutropenia (OR 0.27, 95% CI 0.21 to 0.36; 19 studies, 9407 participants; moderate-quality evidence), stomatitis (OR 0.26, 95% CI 0.20 to 0.33; 21 studies, 8718 participants; low-quality evidence), mucositis (OR 0.17, 95% CI 0.12 to 0.24; 12 studies, 4962 participants; low-quality evidence), and any grade ≥ 3 AEs (OR 0.83, 95% CI 0.74 to 0.94; 14 studies, 5436 participants; low-quality evidence). There was more grade ≥ 3 diarrhoea (OR 1.66, 95% CI 1.50 to 1.84; 30 studies, 11,997 participants; low-quality evidence) and hand foot syndrome (OR 3.92, 95% CI 2.84 to 5.43; 18 studies, 6481 participants; moderate-quality evidence) in the oral fluoropyrimidine arm. There were no differences between oral and IV fluoropyrimidine arms in terms of grade ≥ 3 vomiting (OR 1.18, 95% CI 1.00 to 1.40; 23 studies, 9528 participants; low-quality evidence), nausea (OR 1.16, 95% CI 0.99 to 1.36; 25 studies, 9796 participants; low-quality evidence), and hyperbilirubinaemia (OR 1.62, 95% CI 0.99 to 2.64; nine studies, 2699 participants; low-quality evidence).
AUTHORS' CONCLUSIONS
Results of this review should provide confidence that treatment for CRC with most of the oral fluoropyrimidines commonly used in current clinical practice is similarly efficacious to treatment with IV fluoropyrimidines. Treatment with eniluracil with oral 5-FU was associated with inferior PFS and OS among participants treated with palliative intent for CRC, and eniluracil is no longer being developed. Oral and IV fluoropyrimidines have different patterns of side effects; future research may focus on determining the basis for these differences.
Topics: Administration, Oral; Adult; Antineoplastic Agents; Camptothecin; Capecitabine; Chemotherapy, Adjuvant; Colorectal Neoplasms; Disease-Free Survival; Female; Floxuridine; Fluorouracil; Humans; Injections, Intravenous; Irinotecan; Male; Neoadjuvant Therapy; Organoplatinum Compounds; Palliative Care; Pyridines; Pyrimidines; Randomized Controlled Trials as Topic; Tegafur; Uracil
PubMed: 28752564
DOI: 10.1002/14651858.CD008398.pub2 -
Annals of Surgical Oncology Sep 2022Patients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor survival. This systematic review describes the survival outcomes of hepatic arterial infusion... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor survival. This systematic review describes the survival outcomes of hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine for patients with unresectable iCCA.
PATIENTS AND METHODS
A literature search was conducted using the electronic databases PubMed, Medline (Ovid), Embase, Web of Science, Google Scholar, and Cochrane to find studies that reported data on the survival of patients with unresectable iCCA treated with HAIP chemotherapy using floxuridine. The quality of the studies was assessed using the Newcastle-Ottawa quality assessment Scale (NOS). Overall survival (OS) was the primary outcome measure, and progression-free survival (PFS), response rates, resection rates, and toxicity were defined as secondary outcome measures.
RESULTS
After removing duplicates, 661 publications were assessed, of which nine studies, representing a total of 478 patients, met the inclusion criteria. Three out of nine studies were phase II clinical trials, one study was a prospective dose-escalation study, and the remaining five studies were retrospective cohort studies. After accounting for overlapping cohorts, 154 unique patients were included for pooled analysis. The weighted median OS of patients with unresectable iCCA treated with HAIP chemotherapy with floxuridine was 29.0 months (range 25.0-39 months). The pooled 1-, 2-, 3-, and 5-year OS were 86.4, 55.5, 39.5, and 9.7%, respectively.
CONCLUSION
HAIP chemotherapy with floxuridine for patients with unresectable iCCA was associated with a 3-year OS of 39.5%, which is favorable compared with systemic chemotherapy for which no 3-year survivors were reported in the Advanced Biliary Cancer (ABC) trials.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Floxuridine; Humans; Infusion Pumps; Infusions, Intra-Arterial; Liver Neoplasms; Prospective Studies; Retrospective Studies; Treatment Outcome
PubMed: 35294656
DOI: 10.1245/s10434-022-11439-x -
BMC Ophthalmology Apr 2015This objective of the review and analysis is to demonstrate that acyclovir (ACV) 3% ophthalmic ointment is superior to idoxuridine (IDU) in treating herpetic keratitis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This objective of the review and analysis is to demonstrate that acyclovir (ACV) 3% ophthalmic ointment is superior to idoxuridine (IDU) in treating herpetic keratitis (HK) presenting as dendritic and geographic ulcer sub-types.
DATA SOURCES
Publications in human subjects were identified by searching the Ovid MEDLINE database through April 2011, combining medical subject headings (MESH) "Keratitis, Herpetic/" AND "Acyclovir/" limiting by the key words "topical" OR "ointment" and also restricted to MESH "Administration, Topical/" OR "Ointments/". The results were cross checked with the references used in the Cochrane Database Syst Rev. 1:1-134, 2009 and GlaxoSmithKline clinical documents related to acyclovir.
STUDY SELECTION
Randomized, double-masked studies in subjects diagnosed with HK with head to head comparator arms of ACV ophthalmic ointment and topical IDU that had actual or calculable healing rates at Day seven.
DATA EXTRACTION
Data independently extracted from identified articles by two authors of this manuscript.
DATA SYNTHESIS
Data from seven randomized, controlled trials (RCT) evaluating 432 subjects that met inclusion criteria (214 were treated with ACV and 218 were treated with IDU) and had Day seven healing rates calculable. All sub-classified lesions were identified as either dendritic ulcers (n = 185) or geographic ulcers (n = 35). The Cochran-Mantel-Haenszel (CMH) method in Biometrics 10:417-51, 1954 and JNCI 22:719-48, 1959, controlling for study, was performed as the primary analysis using SAS v9. Homogeneity was assessed using Breslow-Day-Tarone (BDT) test in IARC 1:1-32, 1980 and Biometrika 72:91-5, 1985. The analysis was performed with outliers removed to assess their impact.
RESULTS
ACV showed statistically significant greater odds of healing HK at Day seven in all subjects (Odds Ratio 3.95, 95% CI2.60, 6.00, p < 0.0001), in dendritic ulcers (Odds Ratio 4.22, 95% CI: 2.14, 8.32; p < 0.0001) and geographic ulcers (Odds Ratio 5.31, 95% CI: 1.09, 25.93; p = 0.0244).
CONCLUSION
ACV 3% ophthalmic ointment is a valuable intervention for dendritic and geographic corneal ulcers. ACV and IDU were generally well tolerated in the studies reviewed.
Topics: Acyclovir; Antiviral Agents; Follow-Up Studies; Humans; Idoxuridine; Keratitis, Herpetic; Ointments; Time Factors; Treatment Outcome
PubMed: 25928630
DOI: 10.1186/s12886-015-0022-2 -
The Journal of Dermatological Treatment Dec 2024Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess the efficacy, safety, incidence of postherpetic neuralgia of brivudine.
METHODS
Data of randomized controlled Trials (RCTS) were obtained from the databases of both English (PubMed, Embase, and Cochrane Library) and Chinese (China National Knowledge Infrastructure, China Science Journal Database, and WanFang Database) literatures from inception to 12 September 2022. Meta-analyses of efficacy and safety of Brivudine for the treatment of herpes zoster for RCTS were conducted.
RESULTS
The analyses included seven RCTS (2095 patients in experimental group and 2076 patients in control group) in the treatment of HZ with brivudine. It suggested that the brivudine group was superior to the control group in terms of efficacy ( = .0002) and incidence of postherpetic neuralgia ( = .04). But the incidence of adverse reactions has no significant difference between the brivudine and the control groups ( = .22). In addition, subgroup analysis of adverse events also showed that brivudine was about the same safety as other modalities in the treatment of HZ ( > .05).
CONCLUSIONS
Brivudine is effective for HZ. However, the evidence on the safety of brivudine is insufficient.
Topics: Humans; Herpes Zoster; Neuralgia, Postherpetic; Antiviral Agents; Randomized Controlled Trials as Topic; Treatment Outcome; Incidence; Bromodeoxyuridine
PubMed: 38811010
DOI: 10.1080/09546634.2024.2355256 -
Arab Journal of Urology Mar 2018To review sperm DNA fragmentation (SDF) testing as an important sperm function test in addition to conventional semen analysis. High SDF is negatively associated with...
OBJECTIVE
To review sperm DNA fragmentation (SDF) testing as an important sperm function test in addition to conventional semen analysis. High SDF is negatively associated with semen quality, the fertilisation process, embryo quality, and pregnancy outcome. Over recent decades, different SDF assays have been developed and reviewed extensively to assess their applicability and accuracy as advanced sperm function tests. Amongst them, the standardisation of the terminal deoxynucleotidyl transferased UTP nick-end labelling (TUNEL) assay with a bench top flow cytometer in clinical practice deserves special mention with a threshold value of 16.8% to differentiate infertile men with DNA damage from fertile men.
MATERIALS AND METHODS
A systematic literature search was performed through the PubMed, Medline, and ScienceDirect databases using the keywords 'sperm DNA fragmentation' and 'laboratory assessment'. Non-English articles were excluded and studies related to humans were only included.
RESULTS
Of the 618 identified, 87 studies (original research and reviews) and in addition eight book chapters meeting the selection criteria were included in this review. In all, 366 articles were rejected in the preliminary screening and a further 165 articles related to non-human subjects were excluded.
CONCLUSION
There are pros and cons to all the available SDF assays. TUNEL is a reliable technique with greater accuracy and as an additional diagnostic test in Andrology laboratories along with basic semen analysis can predict fertility outcome, and thus direct the choice of an assisted reproductive technology procedure for infertile couples. Also, the TUNEL assay can be used as a prognostic test and results are beneficial in deciding personalised treatment for infertile men.
PubMed: 29713537
DOI: 10.1016/j.aju.2017.12.001 -
Journal of Evidence-based Integrative... 2021Moleac (MLC) 901 is a traditional Chinese medication approved by the Sino Food and Drug Administration in 2001 for treating stroke. This study aims to analyze the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Moleac (MLC) 901 is a traditional Chinese medication approved by the Sino Food and Drug Administration in 2001 for treating stroke. This study aims to analyze the efficacy of MLC901 in animal stroke models after medial cerebral artery occlusion (MCAO).
METHODS
Literature selection was performed according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) 2015. Inclusion criteria for the experimental studies were the use of animal models, publication in English between 1990 and 2020, information regarding the intervention technique used, and outcomes regarding the efficacy of MLC901 administration.
RESULTS
MLC901 administration resulted in significantly less infarction volume by a mean difference of 17.17 compared to the control group (p < .00001). The MLC901 group resulted in significant improvement in 5-bromo-20-deoxyuridine (BrdU)-positive cells expression by a mean difference of 662.79 (p < .00001) and neurological function, which was indicated by a mean difference in the Bederson Neurological Outcome Score of 1.40 (p < .00001).
CONCLUSIONS
MLC901 administration in an animal stroke model resulted in a better reduction in infarction volume and improvement in BrdU expression and neurologic function. These data could help in further determining the efficacy of MLC901 for acute ischemic brain injury in humans.
Topics: Animals; Brain Injuries; Disease Models, Animal; Drugs, Chinese Herbal; Ischemic Stroke; Middle Cerebral Artery
PubMed: 34387107
DOI: 10.1177/2515690X211039219 -
Frontiers in Cellular Neuroscience 2020Exosomes, especially stem cell-derived exosomes, have been widely studied in pre-clinical research of ischemic stroke. However, their pooled effects remain...
Exosomes, especially stem cell-derived exosomes, have been widely studied in pre-clinical research of ischemic stroke. However, their pooled effects remain inconclusive. Relevant literature concerning the effects of exosomes on neurological performance in a rodent model of ischemic stroke was identified via searching electronic databases, including PubMed, Embase, and Web of Science. The primary outcomes included neurological function scores (NFS) and infarct volume (IV), and the secondary outcomes were several pro-inflammatory factors and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling-positive cells. Subgroup analyses regarding several factors potentially influencing the effects of exosomes on NFS and IV were also conducted. We identified 21 experiments from 18 studies in the meta-analysis. Pooled analyses showed the positive and significant effects of exosomes on NFS (standardized mean difference -2.79; 95% confidence interval -3.81 to -1.76) and IV (standardized mean difference -3.16; 95% confidence interval -4.18 to -2.15). Our data revealed that the effects of exosomes on neurological outcomes in rodent stroke models might be related to routes of administration and exosomes sources. In addition, there was significant attenuation in pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and interleukin-1β, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling-positive cells when undergoing exosomes treatment. Cell-derived exosomes treatment demonstrated statistically significant improvements in structural and neurological function recovery in animal models of ischemic stroke. Our results also provide relatively robust evidence supporting cell-derived exosomes as a promising therapy to promote neurological recovery in stroke individuals.
PubMed: 33324166
DOI: 10.3389/fncel.2020.593130