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International Journal of Infectious... Feb 2023Human monkeypox virus (MPXV) infection is a recently declared public health emergency of international concern by the World Health Organization. Besides, there is scant...
OBJECTIVES
Human monkeypox virus (MPXV) infection is a recently declared public health emergency of international concern by the World Health Organization. Besides, there is scant literature available on the use of antivirals in MPXV infection. This systematic review compiles all evidence of various antivirals used on their efficacy and safety and summarizes their mechanisms of action.
METHODS
A review was done of all original studies mentioning individual patient data on the use of antivirals in patients with MPXV infection.
RESULTS
Of the total 487 non-duplicate studies, 18 studies with 71 individuals were included. Tecovirimat was used in 61 individuals, followed by cidofovir in seven and brincidofovir (BCV) in three individuals. Topical trifluridine was used in four ophthalmic cases in addition to tecovirimat. Of the total, 59 (83.1%) were reported to have complete resolution of symptoms; one was experiencing waxing and waning of symptoms, only one (1.8%) had died, and the others were having a resolution of symptoms. The death was thought unrelated to tecovirimat. Elevated hepatic panels were reported among all individuals treated with BCV (leading to treatment discontinuation) and five treated with tecovirimat.
CONCLUSION
Tecovirimat is the most used and has proven beneficial in several aggravating cases. No major safety concerns were detected upon its use. Topical trifluridine was used as an adjuvant treatment option along with tecovirimat. BCV and cidofovir were seldom used, with the latter often being used due to the unavailability of tecovirimat. BCV was associated with treatment discontinuation due to adverse events.
Topics: Humans; Antiviral Agents; Benzamides; Cidofovir; Disease Outbreaks; Isoindoles; Mpox (monkeypox); Monkeypox virus; Trifluridine
PubMed: 36470502
DOI: 10.1016/j.ijid.2022.11.040 -
BMC Cancer Oct 2019High level of reactive oxygen species (ROS) has been detected in almost all cancers, which make it become one of the best-characterized phenotypes in cancers. Though ROS... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High level of reactive oxygen species (ROS) has been detected in almost all cancers, which make it become one of the best-characterized phenotypes in cancers. Though ROS plays an important role in tumors, the degree of oxidative stress can be better evaluated by assessing stable metabolites of oxidative reactions because of its high instability. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a product of oxidative damage to 2'-deoxyguanosine, is known as a useful marker for assessing oxidative DNA damage and has been a feature of carcinogenesis in several researches. But the exact prognostic value of 8-OHdG expression in patients with cancer is still unclear.
METHODS
A comprehensive search was performed in PubMed, Web of Science, EMBASE. Eligible studies were included based on defined exclusion and inclusion criteria to perform a meta-analysis. STATA 14.0 was used to estimate pooled hazard ratios (HRs) with 95% confidence interval (95% CI), the heterogeneity among studies and publication bias to judge the prognostic value.
RESULTS
A total of 2121 patients from 21 eligible studies were included in the meta-analysis. A significant association was found between elevated 8-OHdG expression and poor OS (overall survival) in cancer patients (pooled HR 1.921, 95% CI: 1.437-2.570); In the subgroup analysis, race of sample, cancer types, detection method of 8-OHdG, sample classification, detection location of 8-OHdG and paper quality (score more or less than 7) did not alter the association between 8-OHdG expression and cancer prognosis. Furthermore, 8-OHdG expression was an independent prognostic marker for overall survival in patients with cancer (pooled HR 2.110, 95% CI: 1.482-3.005) using Cox multivariate analyses.
CONCLUSIONS
This meta-analysis found that highly expressed 8-OHdG in tumor tissues may be a predictor of prognosis in most solid tumors. However, especially in breast cancer, low 8-OHdG expression is associated with poor prognosis, which is partly because of the increased antioxidant mechanisms in breast cancer tissues. This study demonstrates for the first time that 8-OHdG expression is associated with the prognosis of cancer patients. In the future, whether the expression level of 8-OHdG can be used as a biomarker for the prognosis of all human cancers requires more research.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers, Tumor; DNA Damage; Disease-Free Survival; Humans; Neoplasms; Oxidative Stress; Prognosis; Proportional Hazards Models; Reactive Oxygen Species
PubMed: 31651287
DOI: 10.1186/s12885-019-6189-9 -
The Oncologist Aug 2021Metastatic urothelial carcinoma (mUC) historically is treated with first-line platinum-based combination chemotherapy, preferably cisplatin plus gemcitabine whenever...
BACKGROUND
Metastatic urothelial carcinoma (mUC) historically is treated with first-line platinum-based combination chemotherapy, preferably cisplatin plus gemcitabine whenever possible. In recent years, multiple classes of targeted therapy have demonstrated benefit, with some receiving approval in mUC. This review will summarize phase III efficacy and safety data for targeted agents, principally immune checkpoint inhibitors (ICIs), as either first-line or first-line switch-maintenance therapy for mUC and interpret these findings in the context of the current treatment landscape.
MATERIALS AND METHODS
Published and presented phase III data on targeted therapy for the first-line or first-line switch-maintenance treatment of mUC were identified using the key search terms "targeted therapy" AND "urothelial carcinoma" AND "advanced" OR respective aliases according to the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
RESULTS
Of the six eligible phase III targeted therapy trials, two assessing ICIs met their primary endpoints in platinum-eligible patients. First-line ICI plus chemotherapy combinations have not improved overall survival (OS), although final OS results of the IMVigor 130 trial are pending. Switch-maintenance using an ICI in patients achieving at least stable disease following platinum-based chemotherapy statistically significantly improved OS (21.4 vs. 14.3 months, hazard ratio, 0.69; 95% confidence interval, 0.56-0.86; p = .001). Current sequencing options for mUC include first-line platinum-based chemotherapy with a switch to ICI either immediately or upon disease progression.
CONCLUSION
Recent targeted therapy trials have expanded ICI sequencing options for mUC. The treatment landscape is likely to evolve rapidly, with results from multiple phase III trials expected in the next 5 years.
IMPLICATIONS FOR PRACTICE
Multiple classes of targeted agents are approved for use in metastatic urothelial carcinoma (mUC). Six phase III trials have recently provided insight on the benefit of these agents in the first-line setting. In platinum-eligible patients, immune checkpoint inhibitors (ICIs) combined with first-line platinum-based chemotherapy failed to demonstrate improved survival, although ICI monotherapy as switch-maintenance significantly improved overall survival in patients with mUC who had achieved at least stable disease following first-line platinum-based chemotherapy. In patients ineligible for any chemotherapy, pembrolizumab, atezolizumab, or pembrolizumab in combination with enfortumab vedotin may be options.
Topics: Antineoplastic Agents; Carcinoma, Transitional Cell; Cisplatin; Deoxycytidine; Humans; Urinary Bladder Neoplasms
PubMed: 34028134
DOI: 10.1002/onco.13827 -
Pharmaceutical Biology Dec 2021Aidi injection is one of the most commonly use antitumor Chinese medicine injections for advanced non-small cell lung cancer (NSCLC). It is made from the extraction of ,... (Comparative Study)
Comparative Study Meta-Analysis
CONTEXT
Aidi injection is one of the most commonly use antitumor Chinese medicine injections for advanced non-small cell lung cancer (NSCLC). It is made from the extraction of , and
OBJECTIVE
To evaluate the efficacy and safety of Aidi injection in combination with gemcitabine-based chemotherapy (GBC) for advanced NSCLC.
MATERIALS AND METHODS
PubMed, Embase, Cochrane Library, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and VIP were searched for relevant randomised controlled trials (RCTs) comparing Aidi injection plus GBC treatment with GBC alone in NSCLC, from inception up to October 2020. The primary outcomes were objective response rate (ORR), and disease control rate (DCR). Secondary outcomes were quality of life (QOL) and adverse drug reactions (ADRs). The quality of evidence was rated using the GRADE approach. This study was registered with PROSPERO: CRD42021221225.
RESULTS
In total, 54 RCTs involving 4318 NSCLC patients were included in this meta-analysis. Compared with GBC alone, Aidi injection plus GBC significantly improve ORR (risk ratios [RR] = 1.38, 95% confidence interval [CI] 1.29-1.48), DCR (RR = 1.15, 95% CI 1.12-1.19), QOL (RR = 1.71, 95% CI 1.54-1.89), and reduced the risk of gastrointestinal toxicity, thrombocytopenia, neutropenia, liver injury, renal injury, and anaemia. The evaluation results of the evidence ranged from moderate to low.
CONCLUSIONS
Current moderate evidence revealed that Aidi injection as an adjunctive treatment to GBC was associated with superior benefits in patients with advanced NSCLC and alleviate toxicities. High-quality RCTs are needed to further confirm the results.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Drugs, Chinese Herbal; Humans; Lung Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome; Gemcitabine
PubMed: 34541998
DOI: 10.1080/13880209.2021.1973038 -
Medicine Apr 2021Uterine leiomyosarcomas are rare malignant mesenchymal tumors. The systemic treatment of these tumors includes chemotherapy and radiotherapy. However, there are still a...
BACKGROUND
Uterine leiomyosarcomas are rare malignant mesenchymal tumors. The systemic treatment of these tumors includes chemotherapy and radiotherapy. However, there are still a lot of unanswered questions regarding the ideal therapeutic approach.
METHODS
We have conducted a systematic review of the treatment strategies of uterine leiomyosarcomas for the last ten years.
RESULTS
Adjuvant chemotherapy is still a matter of dilemma. Doxorubicin based chemotherapy or the combination of Gemcitabine-Docetaxel are the regimens of choice for the first line setting. Beyond the first line, there are several options;, including chemotherapy, targeted therapy, and recently efforts of introducing immunotherapy to the therapeutic armamentarium of clinicians treating uterine leiomyosarcomas.
CONCLUSIONS
Despite the efforts of the clinicians dealing with uterine leiomyosarcomas, the optimal therapeutic algorithm is yet to be described.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Deoxycytidine; Doxorubicin; Female; Humans; Immunotherapy; Leiomyosarcoma; Molecular Targeted Therapy; Treatment Outcome; Uterine Neoplasms; Gemcitabine
PubMed: 33787622
DOI: 10.1097/MD.0000000000025309 -
Cancer May 2020The goal of this study was to characterize the efficacy and safety of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy... (Comparative Study)
Comparative Study Meta-Analysis
Conventionally fractionated radiation therapy versus stereotactic body radiation therapy for locally advanced pancreatic cancer (CRiSP): An international systematic review and meta-analysis.
BACKGROUND
The goal of this study was to characterize the efficacy and safety of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy with concurrent chemotherapy (CFRT) for the definitive treatment of locally advanced pancreatic cancer. The primary outcome measure was efficacy, defined by 2-year overall survival (OS). Secondary outcomes were incidence of any grade 3/4 toxicity and 1-year OS.
METHODS
A PICOS/PRISMA/MOOSE selection protocol was used to identify eligible studies. Inclusion criteria were: 1) patients diagnosed with locally advanced N0-1 M0 pancreatic cancer; 2) CFRT 1.8 to 2.0 Gy/fraction with chemotherapy per protocol or SBRT ≥5 Gy/fraction in ≤5 fractions; 3) either no control group or another definitive chemotherapy or radiation therapy arm; 4) at least 1 of the outcome measures reported; and 5) single or multi-arm phase 2/3 prospective study for CFRT and/or phase 1/2 or retrospective study for SBRT. Neoadjuvant and/or adjuvant chemotherapy was prescribed per protocol specifications. Weighted random effects meta-analyses were conducted using the DerSimonian and Laird method to characterize summary effect sizes for each outcome.
RESULTS
A total of 470 studies were initially screened; of these, 9 studies assessed SBRT and 11 studies assessed CFRT. For SBRT, the median dose was 30 Gy, and the most common regimen was 30 Gy/5 fractions. For CFRT, doses ranged from 45 to 54 Gy in 1.8- to 2.0-Gy fractions, with the majority of studies delivering 50.4 Gy in 28 fractions with concurrent gemcitabine. The random effects estimate for 2-year OS was 26.9% (95% CI, 20.6%-33.6%) for SBRT versus 13.7% (95% CI, 8.9%-19.3%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for 1-year OS was 53.7% (95% CI, 39.3%-67.9%) for SBRT versus 49.3% (95% CI, 39.3%-59.4%) for CFRT, and was not statistically significant. The random effects estimate for acute grade 3/4 toxicity was 5.6% (95% CI, 0.0%-20.0%) for SBRT versus 37.7% (95% CI, 24.0%-52.5%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for late grade 3/4 toxicity was 9.0% for SBRT (95% CI, 3.3%-17.1%) versus 10.1% (95% CI, 1.8%-23.8%) for CFRT, which was not statistically significant.
CONCLUSION
These results suggest that SBRT for LAPC may result in a modest improvement in 2-year OS with decreased rates of acute grade 3/4 toxicity and no change in 1-year-OS or late toxicity. Further study into the use of stereotactic body radiation therapy for these patients is needed.
Topics: Chemoradiotherapy; Deoxycytidine; Dose Fractionation, Radiation; Female; Humans; Kaplan-Meier Estimate; Male; Pancreatic Neoplasms; Prospective Studies; Radiosurgery; Retrospective Studies; Survival Analysis; Treatment Outcome; Gemcitabine
PubMed: 32125712
DOI: 10.1002/cncr.32756 -
BMC Cancer Jun 2024Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy... (Meta-Analysis)
Meta-Analysis
Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included - 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42-0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52-0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51-6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28-2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19-1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44-0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR.
Topics: Humans; Colorectal Neoplasms; Bevacizumab; Trifluridine; Thymine; Antineoplastic Combined Chemotherapy Protocols; Pyrrolidines; Drug Combinations; Neoplasm Metastasis; Progression-Free Survival; Uracil; Drug Resistance, Neoplasm
PubMed: 38825703
DOI: 10.1186/s12885-024-12447-8 -
The Pan African Medical Journal 2021women in sub-Saharan Africa (SSA) are disproportionately affected by the HIV epidemic. In 2019, they constituted 59% of new infections; thus, they remain a key...
INTRODUCTION
women in sub-Saharan Africa (SSA) are disproportionately affected by the HIV epidemic. In 2019, they constituted 59% of new infections; thus, they remain a key population for control. Public health interventions to prevent acquisition of HIV in this high-risk population are urgently needed. Tenofovir-based pre-exposure prophylaxis (TFV-PrEP) has been shown to reduce HIV infections in other key populations. However, comprehensive evidence regarding TFV-PrEP effectiveness in women living in SSA has not been determined. Therefore, we undertook a systematic review to determine the effectiveness of tenofovir-1% (TFV-1%) vaginal gel, oral tenofovir (TFV) and tenofovir-emtricitabine (TDF-FTC) pre-exposure prophylaxis for primary acquisition of HIV in at-risk women living in SSA.
METHODS
OVID Medline, Embase, CENTRAL, Web of Science and Clinical Trials.gov were searched for eligible studies from 1 January 2020 to 31 July 2020. Only randomised controlled trials (RCTs) conducted in women living in SSA were included. Measures of effectiveness (hazard ratios (HR), incidence rate ratios (IRR)) were extracted from individual studies to determine the effectiveness of TFV-PrEP in preventing HIV infection among at-risk women living in SSA.
RESULTS
from 2002 non-duplicate articles, four RCTs evaluating the effectiveness of one or more of the interventions against placebos were included. TFV-1% vaginal gel, oral TDF or TDF-FTC were not effective in preventing the acquisition of HIV infection in women living in SSA. However, poor adherence by study participants could have confounded the true effectiveness of TFV-PrEP in this high risk population. Meta-analysis was not conducted given the limited number of eligible studies identified from the search.
CONCLUSION
the current evidence does not support the effectiveness of TFV-PrEP for HIV in SSA women. More studies aimed at addressing factors driving low adherence to HIV interventions in this high risk population are urgently needed in order to improve the design of future RCTs leading to the determination of more reliable estimates of TFV-1% vaginal gel or oral TDF or TDF-FTC effectiveness. Protocol registration: this systematic review was not registered in PROSPERO.
Topics: Africa South of the Sahara; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Medication Adherence; Pre-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Tenofovir
PubMed: 34178226
DOI: 10.11604/pamj.2021.38.308.26014 -
Clinical Infectious Diseases : An... Feb 2024The HIV Prevention Trials Network (HPTN) 083/084 trials showed up to 88% increased efficacy of long-acting cabotegravir (CAB-LA) versus continuous oral tenofovir...
BACKGROUND
The HIV Prevention Trials Network (HPTN) 083/084 trials showed up to 88% increased efficacy of long-acting cabotegravir (CAB-LA) versus continuous oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). However, CAB-LA's high price limits the number of people who can be treated within fixed prevention budgets. Global human immunodeficiency virus (HIV) prevention budgets are highly limited, with TDF/FTC widely available as a low-cost generic. In randomized clinical trials, event-driven TDF/FTC has shown similar preventive efficacy to continuous TDF/FTC.
METHODS
A systematic review of global HIV incidence studies was conducted. Weighted incidence was calculated in each at-risk population. HIV infection rates were evaluated for 5 prevention strategies, with additional HIV testing, education, and service access costs assumed for each ($18 per person per year). Assumed efficacies were 90% (continuous CAB-LA), 60% (continuous TDF/FTC), and 60% (event-driven TDF/FTC). Using weighted incidence and an assumed 100 000 target population, annual HIV infection rates by population were calculated for each prevention strategy.
RESULTS
Ninety-eight studies in 5 230 189 individuals were included. Incidence per 100 person-years ranged from 0.03 (blood donors) to 3.82 (people who inject drugs). Using the number needed to treat to benefit for each strategy, a mean incidence of 2.6 per 100 person-years in at-risk populations, and a 100 000 target population, current-price continuous CAB-LA cost $949 487 per HIV infection successfully prevented, followed by target-price CAB-LA ($11 453), continuous TDF/FTC ($4231), and event-driven TDF/FTC ($1923).
CONCLUSIONS
High prices of CAB-LA limit numbers treatable within fixed budgets. Low-cost event-driven TDF/FTC consistently prevents the most HIV infections within fixed budgets.
Topics: Humans; HIV Infections; Incidence; Adenine; Organophosphonates; Deoxycytidine; Tenofovir; Emtricitabine; Anti-HIV Agents; HIV-1; Costs and Cost Analysis; Pre-Exposure Prophylaxis; Pyridones; Diketopiperazines
PubMed: 37665213
DOI: 10.1093/cid/ciad537 -
International Journal of Radiation... Nov 2019
Topics: Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Capecitabine; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Consensus; Delphi Technique; ErbB Receptors; Female; Humans; Male; Margins of Excision; Mitomycin; Precision Medicine; Radiotherapy; Salvage Therapy; Sex Factors; Societies, Medical; Treatment Outcome; United States
PubMed: 31288054
DOI: 10.1016/j.ijrobp.2019.06.2544