-
Journal of Viral Hepatitis Mar 2016Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are frequently used for chronic hepatitis B (CHB) treatment, but are associated with... (Meta-Analysis)
Meta-Analysis Review
Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are frequently used for chronic hepatitis B (CHB) treatment, but are associated with adverse effects and viral resistance. Here we performed a systematic review and meta-analysis evaluating all studies of pegylated interferon alfa (PEG-IFNα) treatment in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB. We searched electronic databases--PubMed, EMBASE, Cochrane Library and LILACS--for randomized controlled trials evaluating PEG-IFNα therapy between 1999 and September 2014. Virological response was the primary outcome. We identified 14 studies involving 2829 patients. Our analysis revealed that PEG-IFNα + lamivudine combination therapy produced better virological and biochemical responses than PEG-IFNα monotherapy in HBeAg-positive and HBeAg-negative patients at the end of treatment. PEG-IFNα + adefovir dipivoxil achieved better seroconversion rate than PEG-IFNα in HBeAg-positive patients at the end of treatment. The present findings demonstrated a beneficial response rate following PEG-IFNα combination therapy with nucelos(t)ides among HBeAg-positive and HBeAg-negative patients with CHB. Further trials are needed to investigate simultaneous and sequential therapy strategies.
Topics: Adenine; Antiviral Agents; Drug Therapy, Combination; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Interferon-alpha; Lamivudine; Organophosphonates; Randomized Controlled Trials as Topic; Treatment Outcome; Viral Load
PubMed: 25967226
DOI: 10.1111/jvh.12418 -
Danish Medical Journal Dec 2016Refractory coeliac disease (RCD) is a rare and severe malabsorptive disease. The condition has two subtypes: RCDI and RCDII. Different treatments have been tested: and... (Review)
Review
INTRODUCTION
Refractory coeliac disease (RCD) is a rare and severe malabsorptive disease. The condition has two subtypes: RCDI and RCDII. Different treatments have been tested: and because RCD has a poor prognosis due to progress to enteropathy-associated T-cell lymphoma, the aim was to review the epidemiologic aspects and the therapeutic options for RCD.
METHODS
A systematic literature search was performed in 18 databases, and 122 records were identified. Incidence, prevalence, treatment methods and their efficacy were evaluated.
RESULTS
Among coeliac disease patients, the cumulative incidence of RCD is 1-4% per ten-year period and the prevalence is 0.31-0.38%. In the general population, the prevalence of RCD is 0.002%. Treatment of RCDI is azathioprine (effect 100%), mesalamine (effect 60%) or tioguanine (effect 83%). Treatment for RCDII is the antimetabolite cladribine (effect 81%) and autologous haematopoetic stem cell transplantation (effect 85%).
CONCLUSION
RCD is a very rare disease. The current evidence for RCDI treatment includes prednisolone in combination with the immunosuppressants azathioprine, mesalamine or tioguanine. The current evidence for RCDII treatment documents use of the antimetabolite cladribine, and if there is no effect, autologous haematopoetic stem cell transplantation may be attempted. In the future, there is a need for more effective treatments which will also prevent further progression to enteropathy-associated T-cell lymphoma.
Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Celiac Disease; Cladribine; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Incidence; Mesalamine; Prednisolone; Prevalence; Thioguanine
PubMed: 27910801
DOI: No ID Found -
Reviews in Medical Virology Jul 2023WHO guidelines recommend daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) of HIV in people at high risk of HIV... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of long-acting cabotegravir versus oral tenofovir disoproxil fumarate-emtricitabine as HIV pre-exposure prophylaxis: A systematic review and meta-analysis.
WHO guidelines recommend daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) of HIV in people at high risk of HIV infection. However, due to social, psychological and other reasons, the compliance with daily oral TDF-FTC in real life is low. Long-acting cabotegravir is currently the only long-acting drug approved by the U.S. Food and Drug Administration (FDA) for HIV PrEP. Due to the long dosing interval (8 weeks), long-acting cabotegravir has low compliance requirements for people at high risk of HIV infection. We aimed to discuss the feasibility of long-acting cabotegravir to replace TDF-FTC as HIV PrEP based on efficacy and safety analyses. Randomized controlled trials were retrieved, and R software was used for meta-analysis after data extraction. and discussion: Results of the meta-analysis showed that compared with TDF-FTC, long-acting cabotegravir was associated with a lower risk of HIV infection (HR = 0.22, 95% CI: 0.08-0.59, p < 0.01), less decreased creatinine clearance (RR = 0.96, 95% CI: 0.93-0.99, p < 0.01), but more tolerated injection sites adverse events (p < 0.01). No statistically significant differences were found between long-acting cabotegravir and oral placebo in non-injection-related adverse events (creatine phosphokinase, headache, nasopharyngitis, upper respiratory tract infection and gastroenteritis) (p > 0.05). Long-acting cabotegravir has a manageable safety profile and is more effective than TDF-FTC in preventing HIV infection. Interestingly, decreased creatinine clearance occurred less frequently with long-acting cabotegravir than with TDF-FTC. Long-acting cabotegravir is very promising to replace TDF-TFC in the future, which requires more large-sample, high-quality RCTs to verify.
Topics: Humans; Tenofovir; Emtricitabine; HIV Infections; Anti-HIV Agents; Creatinine; Pre-Exposure Prophylaxis
PubMed: 37198721
DOI: 10.1002/rmv.2460 -
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 -
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 -
PloS One 2016Gemcitabine and pemetrexed have been used as maintenance therapy. However, few systematic reviews and meta-analyses have assessed their effects in the newest studies.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gemcitabine and pemetrexed have been used as maintenance therapy. However, few systematic reviews and meta-analyses have assessed their effects in the newest studies. This systematic review and meta-analysis were conducted to assess the role of gemcitabine and pemetrexed in the maintenance treatment of non-small-cell lung carcinoma (NSCLC).
METHODS
We performed a literature search using PubMed, EMBASE and Cochrane library databases from their inceptions to September 16, 2015. We also searched the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and National Comprehensive Cancer Network (NCCN) databases from 2008 to 2015. Two authors independently extracted the data. The Cochrane Collaboration's risk of bias graph was used to assess the risk of bias. The GRADE system was used to assess the grading of evidence, and a meta-analysis was conducted using Stata 11.0 software.
RESULTS
Eleven randomized controlled trial (RCT) studies were collected. Ten studies were included in the meta-analysis and divided into the following 4 groups: gemcitabine vs. best supportive care (BSC)/observation, pemetrexed vs. BSC/placebo, pemetrexed + bevacizumab vs. bevacizumab and pemetrexed vs. bevacizumab. Gemcitabine exhibited significantly improved progression-free survival (PFS) compared with BSC (hazard ratio (HR) = 0.62, p = 0.000). Pemetrexed exhibited significantly improved PFS (HR = 0.54, p = 0.000) and OS (HR = 0.75, p = 0.000) compared with BSC. Pemetrexed + bevacizumab almost exhibited significantly improved PFS (HR = 0.71, p = 0.051) compared with bevacizumab. Pemetrexed exhibited no improvement in PFS or overall survival (OS) compared with bevacizumab. Regarding the grade, the GRADE system indicated that the gemcitabine group was "MODERATE", the pemetrexed group was "HIGH", and both the pemetrexed + bevacizumab vs. bevacizumab groups and pemetrexed vs. B groups were "LOW".
CONCLUSIONS
Gemcitabine or pemetrexed compared with BSC/observation/placebo significantly improved PFS or OS. Whether pemetrexed + bevacizumab compared with bevacizumab alone significantly improves PFS requires further investigation.
Topics: Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Pemetrexed; Randomized Controlled Trials as Topic; Survival Rate; Gemcitabine
PubMed: 26954503
DOI: 10.1371/journal.pone.0149247 -
Antioxidants & Redox Signaling Apr 20168-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative... (Meta-Analysis)
Meta-Analysis Review
SIGNIFICANCE
8-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative damage of DNA because guanosine is the most oxidized among the DNA nucleobases. In several pathological conditions, high urinary levels of oxidized DNA-derived metabolites have been reported (e.g., cancer, atherosclerosis, hypertension, and diabetes).
RECENT ADVANCES
Even if published studies have shown that DNA damage is significantly associated with the development of atherosclerosis, the exact role of this damage in the onset and progression of this pathology is not fully understood, and the association of oxidative damage to DNA with cardiovascular disease (CVD) still needs to be more extensively investigated. We performed a meta-analysis of the literature to investigate the association among 8-OHdG levels and CVD.
CRITICAL ISSUES
Fourteen studies (810 CVD patients and 1106 controls) were included in the analysis. We found that CVD patients showed higher 8-OHdG levels than controls (SMD: 1.04, 95%CI: 0.61, 1.47, p < 0.001, I(2) = 94%, p < 0.001). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD: 4.43, 95%CI: 1.71, 7.15, p = 0.001) and in blood samples (MD: 1.42, 95%CI: 0.64, 2.21, p = 0.0004). Meta-regression models showed that age, hypertension, and male gender significantly impacted on the difference in 8-OHdG levels among CVD patients and controls.
FUTURE DIRECTIONS
8-OHdG levels are higher in patients with CVD than in controls. However, larger prospective studies are needed to test 8-OHdG as a predictor of CVD.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Deoxyguanosine; Humans; Oxidation-Reduction; Oxidative Stress; Prognosis; Publication Bias; Regression Analysis
PubMed: 26650622
DOI: 10.1089/ars.2015.6508 -
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 -
Clinical Colorectal Cancer Jun 2017Whether bevacizumab represents a feasible option for the first-line treatment of unfit and elderly patients with metastatic colorectal cancer (mCRC) remains... (Meta-Analysis)
Meta-Analysis Review
Efficacy and Safety of Bevacizumab Combined With Fluoropyrimidine Monotherapy for Unfit or Older Patients With Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.
BACKGROUND
Whether bevacizumab represents a feasible option for the first-line treatment of unfit and elderly patients with metastatic colorectal cancer (mCRC) remains controversial. The present systematic review and meta-analysis evaluated the efficacy and safety data of bevacizumab combined with first-line fluoropyrimidine monochemotherapy for these complex patients.
PATIENTS AND METHODS
A systematic search of the published data was conducted through May 31, 2016. The random-effects model was used to combine the effect estimates and the I index to quantify the between-study heterogeneity unexplained by sampling error.
RESULTS
We included 3 randomized controlled trials, 4 single-arm phase II trials, and 1 prospective cohort study in the present meta-analysis (n = 782). The monochemotherapy administered was capecitabine in 531 patients (67.9%) and 5-fluorouracil in 251 (32.1%); 500 (63.9%) also received bevacizumab. The median age was 75 years, 441 patients (56.4%) were men, and the Eastern Cooperative Oncology Group performance status was 0 to 1 in 684 patients (87.7%). The combination with bevacizumab produced advantages in terms of both progression-free survival (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64; P < .00001; I = 0%) and overall survival (HR, 0.79; 95% CI, 0.64-0.98; P = .03; I = 0%). The pooled effect estimates of the randomized controlled trials have been previously reported. As expected, all-grade hypertension (27% vs. 4.9%), bleeding (24% vs. 6.4%), thromboembolic events (10% vs. 5%), and proteinuria (25.6% vs. 8.2%) were more frequent in the bevacizumab combination group.
CONCLUSION
Adding bevacizumab to first-line fluoropyrimidine monochemotherapy significantly improved progression-free and overall survival in unfit and elderly patients with mCRC, with a manageable safety profile and no unexpected toxicities.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Male; Neoplasm Metastasis; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 27687553
DOI: 10.1016/j.clcc.2016.08.006 -
European Journal of Cancer (Oxford,... Dec 2012Positron emission tomography (PET) imaging using the radiotracer 18F-Fluorothymidine (FLT) has been proposed as an imaging biomarker of tumour proliferation. If FLT-PET... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Positron emission tomography (PET) imaging using the radiotracer 18F-Fluorothymidine (FLT) has been proposed as an imaging biomarker of tumour proliferation. If FLT-PET can be established as such it will provide a non-invasive, quantitative measurement of tumour proliferation across the entire tumour. Results from validation studies have so far been conflicting with some studies confirming a good correlation between FLT uptake and Ki-67 score and others presenting negative results.
METHODS
Firstly we performed a systematic review of published studies between 1998 and 2011 that explored the correlation between FLT uptake and Ki-67 score and examined possible variations in the methods used. Studies were eligible if they: (a) included patients with cancer, (b) investigated the correlation between Ki-67 measured by immunohistochemistry and FLT uptake measured with PET scanning, and (c) were published as a full paper in a peer-reviewed scientific journal. Secondly a meta-analysis of the correlation coefficient values reported from each study was performed. Correlation coefficient (r) values were extracted from each study and 95% confidence intervals (CIs) were calculated after applying Fisher's z transformation. For subgroup analysis, studies were classified by the index used to characterise Ki-67 expression (average or maximum expression), the nature of the sample (whole specimen or biopsy) and the cancer type.
FINDINGS
Twenty-seven studies were identified as eligible for the meta-analysis. In the studies we examined there were variations in aspects of the methods and reporting. The meta-analysis showed that given an appropriate study design the FLT/Ki-67 correlation is significant and independent of cancer type. Specifically subgroup analysis showed that FLT/Ki-67 correlation was high in studies measuring the Ki-67 average expression regardless of use of surgery or biopsy samples (r=0.70, 95% CI=0.43-0.86, p<0.001). Of the studies that measured Ki-67 maximum expression, only those that used the whole surgical specimen provided a significant r value (r=0.72, 95% CI=0.54-0.84, p<0.001). Studies that used biopsy samples for Ki-67 maximum measurements did not produce a significant r value (r=0.04, 95% CI=-0.18-0.26, p=0.71). In terms of the cancer type subgroup analysis there is sufficient data to support a strong FLT/Ki-67 correlation for brain, lung and breast cancer. No publication bias was detected.
INTERPRETATION
This systematic review and meta-analysis highlights the importance of the methods used in validation studies comparing FLT-PET imaging with the biomarker Ki-67. The correlation is significant and independent of cancer type provided a study design that uses Ki-67 average measurements, regardless of nature of sample, or whole surgical samples when measuring Ki-67 maximum expression. Sufficient data to support a strong correlation for brain, lung and breast cancer exist. However, larger, prospective studies with improved study design are warranted to validate these findings for the rest of the cancer types.
Topics: Antigens, Neoplasm; Bias; Biomarkers; Biopsy; Cell Division; Clinical Trials as Topic; Dideoxynucleosides; Female; Fluorine Radioisotopes; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Neoplasms; Positron-Emission Tomography; Radiopharmaceuticals; Research Design; Surveys and Questionnaires; Tissue Distribution
PubMed: 22658807
DOI: 10.1016/j.ejca.2012.05.001