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Clinical & Translational Oncology :... Feb 2024The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available.
METHODS
The literature on the efficacy and safety of TAS-102 versus placebo and/or best supportive care (BSC) in mCRC was obtained through a systematic search of PubMed, Embase, and Web of Science databases through January 2023. Identify the included literature and extract pertinent data, such as the overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), disease control rate (DCR), incidence of adverse events (AEs) and serious adverse events (SAEs).
RESULTS
There were eight eligible articles that included 2903 patients (1964 TAS-102 versus 939 Placebo and/or BSC). In this meta-analysis, TAS-102 treatment resulted in longer OS, PFS, TTF, and higher DCR in patients with mCRC versus placebo and/or BSC. TAS-102 improved OS and PFS in subgroup analyses of mCRC patients with KRAS wild-type and KRAS mutant-type. In addition, TAS-102 did not increase the incidence of serious adverse events.
CONCLUSION
TAS-102 can enhance the prognosis of mCRC patients whose standard therapy has failed, regardless of KRAS mutation status, and its safety is acceptable.
Topics: Humans; Trifluridine; Uracil; Colorectal Neoplasms; Proto-Oncogene Proteins p21(ras); Colonic Neoplasms; Rectal Neoplasms; Drug Combinations; Antineoplastic Combined Chemotherapy Protocols; Pyrrolidines; Thymine
PubMed: 37414979
DOI: 10.1007/s12094-023-03268-5 -
Lower Urinary Tract Symptoms Sep 2022Urinary bladder ischemia has been implicated in the pathogenesis of lower urinary tract symptoms (LUTS). However, research regarding urinary molecular markers for... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Urinary bladder ischemia has been implicated in the pathogenesis of lower urinary tract symptoms (LUTS). However, research regarding urinary molecular markers for diagnosis and prognosis of pelvic ischemia is still premature, hindering further implementation in clinical practice. The aim of this study is to systematically appraise biomarkers associated with bladder ischemia detected in urine.
METHODS
We performed a systematic review of PubMed/Medline, Embase, Web of Science, and the Cochrane Library in October 2021 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. A subsequent reference search of retrieved articles was also performed. The identified reports were reviewed according to Systematic Review Center for Laboratory Animal Experimentation's risk-of-bias tool for animal studies.
RESULTS
Eight publications were selected for this analysis. The included reports used 8-hydroxy-2'-deoxyguanosine (8-OHdG) (in eight studies) as urinary marker of bladder ischemia. The pooled mean difference for urinary 8-OHdG levels between study and control groups was 13.73 ng/mg creatinine (95% CI, 9.79-17.67; P < .001; I = 69%) for rat studies and 3.71 ng/mg creatinine (95% CI, 2.91-4.51; P < .001; I = 94%) for rabbit studies. The result remained statistically significant favoring the control group independent of the type of intervention used to achieve bladder ischemia. Regarding secondary outcomes, mean voided volume and micturition interval were significantly lower in the ischemia group.
CONCLUSION
The lack of human randomized controlled trials is a major limitation. 8-OHdG is a urinary biomarker to be investigated in future studies for diagnosis and prognosis of LUTS in patients with vascular injury or bladder outlet obstruction.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers; Creatinine; Humans; Ischemia; Lower Urinary Tract Symptoms; Rabbits; Rats; Urinary Bladder; Urinary Bladder Neck Obstruction
PubMed: 35438247
DOI: 10.1111/luts.12443 -
Environmental Research Nov 2022The present systematic review aimed to evaluate the associations between welding fumes exposure and changes in oxidative stress [superoxide dismutase (SOD) and... (Meta-Analysis)
Meta-Analysis Review
The present systematic review aimed to evaluate the associations between welding fumes exposure and changes in oxidative stress [superoxide dismutase (SOD) and malondialdehyde (MDA)] and DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG) and DNA-protein crosslink (DPC)] markers in professional welders (PROSPERO CRD42022298115). Six electronic bibliographic databases were searched from inception through September 2021 to identify observational epidemiological studies evaluating the association between welding fumes exposures and changes in oxidative stress and DNA damage in professional welders. Two reviewers independently assessed the risk of bias and certainty of the evidence. A narrative synthesis of results was conducted using the Synthesis Without Meta-analysis (SWiM) method. Pooled mean differences with 95% confidence intervals were calculated in a random-effects meta-analysis for the outcomes of interest in the review. From 450 studies identified through the search strategy, 14 observational epidemiological studies were included in the review. Most studies reported significantly higher welding fumes levels in welders than in controls. The narrative synthesis results of SOD showed a significant difference between welders and controls, while the meta-analysis results of MDA did not show a significant difference between the studied groups (MD = 0.26; 95% CI, -0.03, 0.55). The meta-analysis results of 8-OHdG (MD = 9.38; 95% CI, 0.55-18.21) and DPC (MD = 1.07; 95% CI, 0.14-2) revealed significantly differences between the studied groups. The included studies were at high risk of exclusion and confounding bias. The certainty of the evidence for oxidative stress and DNA damage results were very low and moderate, respectively. Exposure to welding fumes and metal particles is associated with DNA damage in professional welders, and 8-OHdG and DPC might be considered reliable markers to assess DNA damage resulting from exposure to welding fumes. We recommend, however, that the evaluation of oxidative stress resulting from welding fumes exposure not be solely based on MDA and SOD.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Air Pollutants, Occupational; Biomarkers; DNA Damage; Gases; Humans; Metal Workers; Occupational Exposure; Oxidative Stress; Superoxide Dismutase; Welding
PubMed: 36041537
DOI: 10.1016/j.envres.2022.114152 -
Nutrients Jan 2022Because pharmacokinetic changes in antiretroviral drugs (ARV), due to their concurrent administration with food or nutritional products, have become a clinical... (Meta-Analysis)
Meta-Analysis Review
Because pharmacokinetic changes in antiretroviral drugs (ARV), due to their concurrent administration with food or nutritional products, have become a clinical challenge, it is necessary to monitor the therapeutic efficacy of ARV in people living with the human immunodeficiency virus (PLWH). A systematic review and meta-analysis were conducted to clarify the pharmacokinetic outcomes of the interaction between supplements such as food, dietary supplements, and nutrients, and ARV. Twenty-four articles in both healthy subjects and PLWH were included in the qualitative analysis, of which five studies were included in the meta-analysis. Food−drug coadministration significantly increased the time to reach maximum concentration (tmax) (p < 0.00001) of ARV including abacavir, amprenavir, darunavir, emtricitabine, lamivudine, zidovudine, ritonavir, and tenofovir alafenamide. In addition, the increased maximum plasma concentration (Cmax) of ARV, such as darunavir, under fed conditions was observed. Area under the curve and terminal half-life were not significantly affected. Evaluating the pharmacokinetic aspects, it is vital to clinically investigate ARV and particular supplement interaction in PLWH. Educating patients about any potential interactions would be one of the effective recommendations during this HIV epidemic.
Topics: Anti-Retroviral Agents; Darunavir; Dietary Supplements; Drug Interactions; Emtricitabine; Humans
PubMed: 35276881
DOI: 10.3390/nu14030520 -
European Journal of Cancer (Oxford,... May 2022S-1 is an oral fluoropyrimidine that is increasingly used in Western countries for the treatment of metastatic colorectal cancer (mCRC). We conducted a non-inferiority... (Meta-Analysis)
Meta-Analysis Review
Systematic review and non-inferiority meta-analysis of randomised phase II/III trials on S-1-based therapy versus 5-fluorouracil- or capecitabine-based therapy in the treatment of patients with metastatic colorectal cancer.
BACKGROUND
S-1 is an oral fluoropyrimidine that is increasingly used in Western countries for the treatment of metastatic colorectal cancer (mCRC). We conducted a non-inferiority meta-analysis on the efficacy of S-1-based therapy versus 5-fluorouracil (5-FU)- or capecitabine-based therapy in the treatment of patients with mCRC.
METHODS
MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Opengrey were searched for randomised clinical trials until May 2021. Data were extracted for progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and adverse events. Pooled effect estimates, stratified by treatment line, with corresponding 99% confidence intervals (CI) were presented. For PFS, a pre-defined non-inferiority margin (ΔNI) of 1.25 was selected.
RESULTS
Ten studies (n = 2117) were included, of which six studies reported PFS and OS data and 10 studies reported ORR data. S-1-based therapy was shown to be non-inferior to 5-FU/capecitabine-based therapy in terms of PFS (HR 0.95, 99% CI 0.83-1.08) with its CI upper limit well below ΔNI, and at least as efficacious in terms of OS (HR 0.93, 99% CI 0.81-1.07), and ORR (RR 1.06, 99% CI 0.90-1.24).
CONCLUSIONS
S-1-based therapy is non-inferior to 5-FU/capecitabine-based therapy in the treatment of mCRC regarding PFS and at least as efficacious as 5-FU/capecitabine-based therapy in terms of ORR and OS. These data support the use of S-1 in mCRC patients who are intolerant to 5-FU/capecitabine-based treatment.
Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Fluorouracil; Humans
PubMed: 35279472
DOI: 10.1016/j.ejca.2022.02.004 -
The Oncologist May 2024We performed a systematic literature review to identify and summarize data from studies reporting clinical efficacy and safety outcomes for trifluridine/tipiracil...
We performed a systematic literature review to identify and summarize data from studies reporting clinical efficacy and safety outcomes for trifluridine/tipiracil (FTD/TPI) combined with other antineoplastic agents in advanced cancers, including metastatic colorectal cancer (mCRC). We conducted a systematic search on May 29, 2021, for studies reporting one or more efficacy or safety outcome with FTD/TPI-containing combinations. Our search yielded 1378 publications, with 38 records meeting selection criteria: 35 studies of FTD/TPI-containing combinations in mCRC (31 studies second line or later) and 3 studies in other tumor types. FTD/TPI plus bevacizumab was extensively studied, including 19 studies in chemorefractory mCRC. Median overall survival ranged 8.6-14.4 months and median progression-free survival 3.7-6.8 months with FTD/TPI plus bevacizumab in refractory mCRC. Based on one randomized and several retrospective studies, FTD/TPI plus bevacizumab was associated with improved outcomes compared with FTD/TPI monotherapy. FTD/TPI combinations with chemotherapy or other targeted agents were reported in small early-phase studies; preliminary data indicated higher antitumor activity for certain combinations. Overall, no safety concerns existed with FTD/TPI combinations; most common grade ≥ 3 adverse event was neutropenia, ranging 5%-100% across all studies. In studies comparing FTD/TPI combinations with monotherapy, grade ≥ 3 neutropenia appeared more frequently with combinations (29%-67%) vs. monotherapy (5%-41%). Discontinuation rates due to adverse events ranged 0%-11% for FTD/TPI plus bevacizumab and 0%-17% with other combinations. This systematic review supports feasibility and safety of FTD/TPI plus bevacizumab in refractory mCRC. Data on non-bevacizumab FTD/TPI combinations remain preliminary and need further validation.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Combinations; Pyrrolidines; Thymine; Trifluridine
PubMed: 38366864
DOI: 10.1093/oncolo/oyae007 -
Journal of Neurology, Neurosurgery, and... Sep 2022Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination... (Meta-Analysis)
Meta-Analysis Review
Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination policies among them. To synthesise the available evidence addressing the effect of MS DMTs on COVID-19 vaccines' immunogenicity and effectiveness, following the Cochrane guidelines, we systematically reviewed all observational studies available in MEDLINE, Scopus, Web of Science, MedRxiv and Google Scholar from January 2021 to January 2022 and extracted their relevant data. Immunogenicity data were then synthesised in a quantitative, and other data in a qualitative manner. Evidence from 28 studies suggests extensively lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM) treated and anti-CD20 (aCD20) treated, and lower T-cell responses in interferon-treated, S1PRM-treated and cladribine-treated pwMS-although most T cell evidence currently comprises of low or very low certainty. With every 10-week increase in aCD20-to-vaccine period, a 1.94-fold (95% CI 1.57 to 2.41, p<0.00001) increase in the odds of seroconversion was observed. Furthermore, the evidence points out that B-cell-depleting therapies may accelerate postvaccination humoral waning, and boosters' immunogenicity is predictable with the same factors affecting the initial vaccination cycle. Four real-world studies further indicate that the comparative incidence/severity of breakthrough COVID-19 has been higher among the pwMS treated with S1PRM and aCD20-unlike the ones treated with other DMTs. S1PRM and aCD20 therapies were the only DMTs reducing the real-world effectiveness of COVID-19 vaccination among pwMS. Hence, it could be concluded that optimisation of humoral immunogenicity and ensuring its durability are the necessities of an effective COVID-19 vaccination policy among pwMS who receive DMTs.
Topics: COVID-19; COVID-19 Vaccines; Cladribine; Humans; Immunologic Factors; Multiple Sclerosis
PubMed: 35688629
DOI: 10.1136/jnnp-2022-329123 -
JAMA Aug 2023A 2019 review for the US Preventive Services Task Force (USPSTF) found oral preexposure prophylaxis (PrEP) associated with decreased HIV infection risk vs placebo or no...
IMPORTANCE
A 2019 review for the US Preventive Services Task Force (USPSTF) found oral preexposure prophylaxis (PrEP) associated with decreased HIV infection risk vs placebo or no PrEP in adults at increased HIV acquisition risk. Newer PrEP regimens are available.
OBJECTIVE
To update the 2019 review on PrEP, to inform the USPSTF.
DATA SOURCES
Ovid MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Embase (January 2018 to May 16, 2022); surveillance through March 24, 2023.
STUDY SELECTION
Randomized clinical trials of PrEP vs placebo or no PrEP or newer vs older PrEP regimens and diagnostic accuracy studies of instruments for predicting incident HIV infection.
DATA EXTRACTION AND SYNTHESIS
Dual review of titles and abstracts, full-text articles, study quality, and data abstraction. Data were pooled using the DerSimonian and Laird random-effects model.
MAIN OUTCOMES AND MEASURES
HIV acquisition, mortality, and harms; and diagnostic test accuracy.
RESULTS
Thirty-two studies were included in the review (20 randomized clinical trials [N = 36 543] and 12 studies of diagnostic accuracy [N = 5 544 500]). Eleven trials in the 2019 review found oral PrEP associated with decreased HIV infection risk vs placebo or no PrEP (n = 18 172; relative risk [RR], 0.46 [95% CI, 0.33-0.66]). Higher adherence was associated with greater efficacy. One new trial (n = 5335) found oral tenofovir alafenamide/emtricitabine (TAF/FTC) to be noninferior to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in men who have sex with men (RR, 0.47 [95% CI, 0.19-1.14]). Two new trials found long-acting injectable cabotegravir associated with decreased risk of HIV infection vs oral TDF/FTC (RR, 0.33 [95% CI, 0.18-0.62] in cisgender men who have sex with men and transgender women [n = 4490] and RR, 0.11 [95% CI, 0.04-0.31] in cisgender women [n = 3178]). Discrimination of instruments for predicting incident HIV infection was moderate in men who have sex with men (5 studies; n = 25 488) and moderate to high in general populations of persons without HIV (2 studies; n = 5 477 291).
CONCLUSIONS AND RELEVANCE
In adults at increased HIV acquisition risk, oral PrEP was associated with decreased risk of acquiring HIV infection compared with placebo or no PrEP. Oral TAF/FTC was noninferior to oral TDF/FTC, and injectable cabotegravir reduced the risk of HIV infection compared with oral TDF/FTC in the populations studied.
Topics: Adult; Female; Humans; Male; Administration, Oral; Anti-HIV Agents; Emtricitabine; HIV Infections; Homosexuality, Male; Injections; Practice Guidelines as Topic; Pre-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Risk; Sexual and Gender Minorities; Tenofovir
PubMed: 37606667
DOI: 10.1001/jama.2023.9865 -
BMC Cancer Jan 2021The role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety.
METHODS
PubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed using I test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs).
RESULTS
A total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65-0.86; P < 0.001) and OS (HR = 0.63; 95% CI, 0.53-0.77; P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53-0.78; P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63-0.85; P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44-0.86; P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23-3.74, P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53-2.64, P < 0.001) and hand-foot syndrome (OR = 8.67, 95% CI 6.70-11.22, P < 0.001).
CONCLUSION
This meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast; Capecitabine; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Mastectomy; Neoadjuvant Therapy; Neoplasm Staging; Proportional Hazards Models; Triple Negative Breast Neoplasms
PubMed: 33468087
DOI: 10.1186/s12885-021-07791-y -
The Lancet. Child & Adolescent Health Oct 2022Abacavir is a nucleoside reverse transcriptase inhibitor recommended in paediatric HIV care. We assessed the safety and efficacy profile of abacavir used in first,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Abacavir is a nucleoside reverse transcriptase inhibitor recommended in paediatric HIV care. We assessed the safety and efficacy profile of abacavir used in first, second, or subsequent lines of treatment for infants, children, and adolescents living with HIV to inform 2021 WHO paediatric ART recommendations.
METHODS
In this systematic review and meta-analysis, we included observational and experimental studies conducted in infants aged 0-1 year, children aged 1-10 years, and adolescents aged 10-19 years living with HIV; with data on safety or efficacy, or both, of abacavir-based antiretroviral therapy (ART); published in English or French between Jan 1, 2009, and Oct 1, 2020, plus an updated search to incorporate studies published between Oct 1, 2020, and May 15, 2022. Studies could be non-randomised or non-comparative and include patients who are treatment-naive or those who previously received abacavir (only if abacavir was combined with other ART). Case studies, studies in adults aged 18 years or older, and those assessing the effect of maternal ART exposure were excluded. We extracted data related to study identifier, study design, study period, setting, population characteristics, ART treatment, and safety (any hypersensitivity reaction, death, grade 3 or 4 adverse events, treatment discontinuation, any other morbidities, and serious adverse events), and efficacy outcomes (HIV viral load and CD4 counts reported at 6 and 12 months after ART initiation). Using random-effect models, we estimated weighted pooled incidence and relative risk (RR) of outcomes. The protocol is published in PROSPERO (CRD42022309230).
FINDINGS
Of 1777 records identified, 1475 (83%) were screened after removing duplicates and a further 1421 (96%) were excluded. Of 54 full-text articles assessed for eligibility, 33 (61%) were excluded. Four records were identified from grey literature plus one duplicate from database searching, resulting in 24 studies included (two randomised controlled trials, one single-arm trial, 12 prospective cohorts, seven retrospective cohorts, and two cross-sectional studies). 19 studies described safety data and 15 described efficacy data. 18 (75%) studies were conducted in ART-naive participants. The risk of bias was considered moderate to high for most studies, and all outcomes had significant between-study heterogeneity. Data from 24 265 participants were included, of whom 7236 (30%) received abacavir. Abacavir hypersensitivity reaction was reported in nine (38%) studies, with an incidence ranging from 0·00% to 8·26% (I=85%; p<0·0001). The incidence of death (reported in seven studies) following abacavir treatment varied from 0·00% to 5·49% (I=58%; p=0·026). Viral suppression (<400 copies per mL) varied from 50% to 70% at 6 months (I=92%, p<0·0001) and from 57% to 78% at 12 months (I=88%, p<0·0001).
INTERPRETATION
Toxic effects due to abacavir use remain rare and manageable. Despite scarce data on efficacy, this meta-analysis supports the use of abacavir as a preferred first-line regimen for infants and children living with HIV.
FUNDING
WHO.
Topics: Adolescent; Adult; Anti-HIV Agents; Child; Cross-Sectional Studies; Cyclopropanes; Dideoxyadenosine; HIV Infections; Humans; Infant; Nucleosides; Observational Studies as Topic; Prospective Studies; Retrospective Studies; Reverse Transcriptase Inhibitors
PubMed: 36058225
DOI: 10.1016/S2352-4642(22)00213-9