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Nursing Open Mar 2024To systematically evaluate empirical studies investigating the influences of healthcare workers' behaviours towards infection prevention and control practices in the... (Review)
Review
AIM
To systematically evaluate empirical studies investigating the influences of healthcare workers' behaviours towards infection prevention and control practices in the Coronavirus clinical space, and to appraise and synthesise these findings.
DESIGN
A systematic review of the literature.
METHODS
The review used a five-step framework described by Khan et al. (Journal of the Royal Society of Medicine, 2003, 96 and 118) of Framing questions for a review; Identifying relevant work; Assessing the quality of studies; Summarising the evidence; and Interpreting the findings. Searches were conducted in CINHAL, MEDLINE, PsychINFO, Scopus, and Google Scholar databases to retrieve relevant peer-reviewed literature published in English between 2019 and 2023. Covidence and Joanna Briggs Quality appraisal tools were used for critical assessment. To improve transparent reporting, this review used a Synthesis Without Meta-analysis (SWiM) in systematic review guidelines, as informed by Campbell et al. (BMJ, 2020, 368).
RESULTS
Twenty studies were included in this review, identifying nine themes describing factors influencing HCWs' behaviours towards IPC practices in the coronavirus environment. The overarching influences emerged as knowledge-oriented, person-oriented, and environment-oriented.
CONCLUSION
Healthcare workers' responsibilities at point-of-care involve providing direct care to patients with highly transmissible infections and working in clinical settings that may be ill-designed for IPC practices, increasing the risk of transmission. Given the lack of a definitive solution to eradicate new mutant viruses and that IPC practices are the mainstay of prevention and control of transmissible, measures to improve are imperative. The identified HCWs' domains on behaviours towards IPC are critical in strategies to mitigate risks and further set an opportunity for developing an IPC model congruent with the rapid response required for HCWs during emerging or re-merging mutant virus outbreaks. This is significant, given that HCWs' preparedness with IPC practices at point-of-care is central to patient care, the workforce and community safety.
Topics: Humans; Health Personnel; Coronavirus Infections; Disease Outbreaks
PubMed: 38488425
DOI: 10.1002/nop2.2132 -
Journal of Ovarian Research Feb 2024Ovarian cancer is the eighth leading cause of cancer-related death among women, characterized by late diagnosis and a high relapse rate. In randomized controlled trials,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ovarian cancer is the eighth leading cause of cancer-related death among women, characterized by late diagnosis and a high relapse rate. In randomized controlled trials, we aimed to evaluate the efficacy and safety of PARP inhibitors (PARPi) in treating advanced ovarian cancer.
METHODS
This review was registered on PROSPERO (CRD42021283150), included all phase II and phase III randomized controlled trials (RCTs) assessing the effect of PARPi on ovarian cancer until the 13th of April, 2022. The main outcomes were progression- free survival (PFS), overall survival (OS), and adverse events (AEs). Pooled hazard ratios (HRs), and risk ratios (RRs) were calculated with 95% confidence intervals (95% CI). The random-effects model was applied in all analyses.
RESULTS
In the meta-analysis, 16 eligible RCTs were included, with a total of 5,815 patients. In recurrent ovarian cancer, PARPi maintenance therapy showed a significant PFS benefit over placebo in the total population (HR 0.34, CI 0.29-0.40), BRCA mutant (HR 0.24, CI 0.18-0.31), germline BRCA mutant (HR 0.23, CI 0.18-0.30), and BRCA wild-type cases (HR 0.50, CI 0.39-0.65). PARPi monotherapy also improved PFS (HR 0.62, CI 0.51-0.76) compared with chemotherapy in BRCAm patients with recurrent ovarian cancer. The use of PARPi maintenance therapy resulted in an improvement in PFS over placebo in newly-diagnosed cancers in the overall population (HR 0.46, CI 0.30-0.71) and the BRCAm population (HR 0.36, CI 0.29-0.44). Although the risk of severe AEs was increased by PARPi therapy compared to placebo in most settings investigated, these side effects were controllable with dose modification, and treatment discontinuation was required in the minority of cases.
CONCLUSIONS
PARPis are an effective therapeutic option for newly-diagnosed and recurrent ovarian cancer. Despite a minor increase in the frequency of serious adverse effects, they are generally well tolerated.
Topics: Humans; Female; Poly(ADP-ribose) Polymerase Inhibitors; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Antineoplastic Agents; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
PubMed: 38409030
DOI: 10.1186/s13048-024-01362-y -
Drug Development Research Feb 2024Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have significantly impacted the HIV-1 wild-type due to their high specificity and superior potency. As well as... (Review)
Review
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have significantly impacted the HIV-1 wild-type due to their high specificity and superior potency. As well as different combinations of NNRTIs have been used on clinically approved combining highly active antiretroviral therapy (HAART) to resist the growth of HIV-1 and decrease the mortality rate of HIV/AIDS. Although the feeble strength against the drug-resistant mutant strains and the long-term damaging effects have been reducing the effectiveness of HAART, it could be a crucial challenge to develop novel Anti-HIV leads with a vital mode of action and the least side effects. The extensive chemical reactivity and the diverse chemotherapeutic applications of the 1,3,5-triazine have provided a wide scope of research in medicinal chemistry via a structural modification. In this review, we focused on the Anti-HIV profile of the tri-substituted s-triazine derivatives with structure-based features and also discussed the active mode of action to evaluate the significant findings. The tri-substituted 1,3,5-triazine derivatives have been found more promising to inhibit the growth of the drug-sensitive and drug-resistant variants of HIV-1, especially HIV-1 wild-type, HIV-1 K103N/Y181C, and HIV-1 Tyr181Cys. It has been observed that these derivatives have interacted with the enzyme protein residues via a significant - interaction and hydrogen bonding to resist the proliferation of the viral genomes. Further, the SAR and the active binding modes are critically described and highlight the role of structural variations with functional groups along with the binding affinity of targeted enzymes, which may be beneficial for rational drug discovery to develop highly dynamic Anti-HIV agents.
Topics: Triazines; HIV-1; Reverse Transcriptase Inhibitors; Chemistry, Pharmaceutical; Drug Discovery
PubMed: 38349259
DOI: 10.1002/ddr.22154 -
Molecular Oncology Feb 2024In 2021, Suwala et al. described Primary Mismatch Repair Deficient IDH-mutant Astrocytoma (PMMRDIA) as a distinct group of gliomas. In unsupervised clustering, PMMRDIA... (Review)
Review
In 2021, Suwala et al. described Primary Mismatch Repair Deficient IDH-mutant Astrocytoma (PMMRDIA) as a distinct group of gliomas. In unsupervised clustering, PMMRDIA forms distinct cluster, separate from other IDH-mutant gliomas, including IDH-mutant gliomas with secondary mismatch repair (MMR) deficiency. In the published cohort, three patients received treatment with an immune checkpoint blocker (ICB), yet none exhibited a response, which aligns with existing knowledge about the decreased immunogenicity of IDH-mutant gliomas in comparison to IDH-wildtype. In the case of PMMRDIA, the inherent resistance to the standard-of-care temozolomide caused by MMR deficiency is an additional challenge. It is known that a gain-of-function mutation of IDH1/2 genes produces the oncometabolite R-2-hydroxyglutarate (R-2-HG), which increases DNA and histone methylation contributing to the characteristic glioma-associated CpG island methylator phenotype (G-CIMP). While other factors could be involved in remodeling the tumor microenvironment (TME) of IDH-mutant gliomas, this systematic review emphasizes the role of R-2-HG and the subsequent G-CIMP in immune suppression. This highlights a potential actionable pathway to enhance the response of ICB, which might be relevant for addressing the unmet therapeutic challenge of PMMRDIA.
PubMed: 38339779
DOI: 10.1002/1878-0261.13598 -
Frontiers in Oncology 2023The EGFR gene encodes a protein that stimulates molecular pathways that allow the growth and development of the tumor microenvironment. The current preferred tyrosine...
Effectiveness and safety of the bevacizumab and erlotinib combination erlotinib alone in EGFR mutant metastatic non-small-cell lung cancer: systematic review and meta-analysis.
BACKGROUND
The EGFR gene encodes a protein that stimulates molecular pathways that allow the growth and development of the tumor microenvironment. The current preferred tyrosine kinase inhibitor (TKI) for the first-line treatment of EGFRm metastatic non-small cell lung cancer (NSCLC) is osimertinib. However, the combination of angiogenesis inhibitors and TKI has produced discordant results. We aimed to assess the effects of the bevacizumab and erlotinib combination in EGFRm metastatic NSCLC.
METHODS
Using eligibility criteria focused on patients with EGFRm metastatic NSCLC treated with bevacizumab and erlotinib, we searched databases including clinical trial randomized studies and reviews published until April 15, 2023 in Medline (PubMed), Scopus, and Embase. Eight clinical trials (1,052 patients) were selected from 1,343 articles for quantitative and qualitative assessment. The risk of bias was assessed using the Cochrane Risk of Bias tool. Data were synthesized through random-effects meta-analysis.
RESULTS
The bevacizumab and erlotinib combination significantly improved the progression-free survival (PFS) (log(HR) = 0.63; 95% CI: 0.54-0.73, < 0.001) and overall response ratio (ORR) (RR = 0.79; 95% CI, 0.64-0.97, = 0.03). However, it did not improve the overall survival (log(HR) = 0.93; 95% CI, 0.78-1.10, = 0.38) and was associated with higher serious adverse events (SAEs) (OR = 3.48; 95% CI, 1.76-6.88, = 0.005). A subgroup analysis suggested similar benefits in different mutation subtypes and brain metastasis condition. The evidence is limited by a moderate risk of bias across studies and heterogeneity in the reporting of SAEs.
CONCLUSIONS
The bevacizumab and erlotinib combination significantly improved PFS and ORR in EGFRm metastatic NSCLC but were also associated with higher-grade (≥3) adverse events. These results suggest that while the combination therapy may enhance progression-free survival and overall response, it does not improve the overall survival and is associated with higher toxicity. Thus, the treatment should be personalized based on individual patient comorbidities. Further prospective trials are needed to validate these results.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/#searchadvanced, identifier CDR 42022364692.
PubMed: 38322283
DOI: 10.3389/fonc.2023.1335373 -
Therapeutic Advances in Medical Oncology 2024Frequent failures observed in some trials comparing the efficacy and safety of osimertinib plus bevacizumab to osimertinib monotherapy in advanced non-small-cell lung...
BACKGROUND
Frequent failures observed in some trials comparing the efficacy and safety of osimertinib plus bevacizumab to osimertinib monotherapy in advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) alterations have brought questions.
OBJECTIVES
To evaluate the efficacy and safety of these two treatment regimens in advanced NSCLC patients harboring EGFR mutations.
DESIGN
This study is a systematic review and meta-analysis.
DATA SOURCES AND METHODS
PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases were extensively searched for relevant randomized controlled trials (RCTs) on 14 May 2023. Two researchers independently screened the literature, assessed quality, and extracted data. The primary outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The secondary outcomes were adverse events (AEs) and PFS stratified by patients' characteristics. STATA 17.0 software (StataCorp LLC, USA) was adopted for meta-analysis.
RESULTS
A total of four RCTs involving 390 patients were included. Overall, the risk of bias across the studies was moderate to low. Pooled results showed that compared to osimertinib alone, the addition of bevacizumab to osimertinib failed to show prolongation of PFS [hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.78-1.27], OS (HR = 1.01, 95% CI: 0.73-1.41), or improvement of the ORR (risk ratio = 1.12, 95% CI: 0.90-1.38), while an increased incidence of some AEs was observed, such as nausea, oral mucositis, hypertension, and proteinuria. Notably, combination treatment did significantly prolong the PFS in the subset of smokers (HR = 0.64, 95% CI: 0.44-0.94). A mild trend toward PFS benefit under the combined regimen was also noted in patients with brain metastases and first-line treatment, though not reaching statistical significance.
CONCLUSION
Based on the available evidence, the addition of bevacizumab to osimertinib could not provide additional survival benefits with higher but manageable toxicity for EGFR-mutant NSCLC patients. Osimertinib monotherapy remains the prioritized treatment. Further investigation is warranted.
PubMed: 38304850
DOI: 10.1177/17588359241227677 -
Frontiers in Oncology 2023Mesenchymal-epidermal transition factor gene amplification (amp) is being investigated as a therapeutic target in advanced non-small cell lung cancer (NSCLC). We...
INTRODUCTION
Mesenchymal-epidermal transition factor gene amplification (amp) is being investigated as a therapeutic target in advanced non-small cell lung cancer (NSCLC). We reviewed the epidemiology and disease characteristics associated with primary and secondary amp, as well as the testing procedures used to identify amp, in advanced NSCLC. Economic and humanistic burdens, and the practice patterns and treatments under investigation for amp were also examined.
METHODS
Embase and Medline (via ProQuest), ClinicalTrials.gov, and Cochrane Controlled Register of Trials (2015-2022) were systematically searched. Conference abstracts were searched via Embase and conference proceedings websites (2020-2022). The review focused on evidence from the United States; global evidence was included for identified evidence gaps.
RESULTS
The median rate of primary amp in NSCLC across the references was 4.8% (n=4 studies) and of secondary amp (epidermal growth factor receptor []-mutant NSCLC) was 15% (n=10). Next-generation sequencing (NGS; n=12) and/or fluorescence hybridization (FISH; n=11) were most frequently used in real-world studies and FISH testing most frequently used in clinical trials (n=9/10). amp definitions varied among clinical trials using ISH/FISH testing (MET to chromosome 7 centromere ratio of ≥1.8 to ≥3.0; or gene copy number [GCN] ≥5 to ≥10) and among trials using NGS (tissue testing: GCN ≥6; liquid biopsy: copy number ≥2.1 to >5). Limited to no data were identified on the economic and humanistic burdens, and real-world treatment of amp NSCLC. Promising preliminary results from trials enrolling patients with -mutated, amp advanced NSCLC progressing on an EGFR-tyrosine kinase inhibitor (TKI) were observed with MET-TKIs (i.e., tepotinib, savolitinib, and capmatinib) in combination with EGFR-TKIs (i.e., gefitinib and osimertinib). For metastatic NSCLC and high-level amp, monotherapy with capmatinib, crizotinib, and tepotinib are recommended in the 2022 published NSCLC NCCN Guidelines.
CONCLUSION
Primary amp occurs in approximately 5% of NSCLC cases, and secondary amp in approximately 15% of cases previously treated with an EGFR inhibitor. Variability in testing methods (including ISH/FISH and NGS) and definitions were observed. Several treatments are promising in treating amp NSCLC. Additional studies evaluating the clinical, economic, and humanistic burdens are needed.
PubMed: 38273845
DOI: 10.3389/fonc.2023.1241402 -
Frontiers in Pharmacology 2023The synergistic effects of antiangiogenic inhibitor bevacizumab and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) therapy were encouraging in...
The synergistic effects of antiangiogenic inhibitor bevacizumab and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) therapy were encouraging in patients with EGFR-mutant advanced NSCLC, though some controversy remains. The specific subgroup of patients who might benefit most from the EGFR-TKI and bevacizumab combination therapy is yet to be determined. Randomized clinical trials (RCTs) that had compared the clinical efficacy of EGFR-TKI and bevacizumab combination therapy with EGFR-TKI monotherapy in treating EGFR-mutant advanced NSCLC patients published before 23 December 2022 were searched in the Cochrane, PubMed and Embase. We performed a meta-analysis for the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events with a grade equal or more than 3 (grade≥3 TRAEs). Subgroup analyses of PFS and OS stratified by clinical characteristics and treatment were conducted. We included 10 RCTs involving 1520 patients. Compared with EGFR-TKI monotherapy, addition of bevacizumab to EGFR-TKI resulted in a significantly higher PFS (hazard ratio (HR) = 0.74, 95% confidence interval (95% CI): 0.62-0.87)) and ORR (risk ratio (RR) = 1.07, 95% CI: 1.01-1.13). However, no significant difference in OS (HR = 0.96, 95% CI: 0.83-1.12) was noticed. Patients with EGFR-mutant advanced NSCLC receiving combination therapy showed PFS improvement regardless of gender (male or female), Eastern Cooperative Oncology Group performance status (0 or 1), baseline central nervous system (CNS) metastasis (presence or absence) and EGFR mutation type (19del or 21L858R). Subgroup analyses showed that, with the treatment of bevacizumab and EGFR-TKI, patients who ever smoked achieved significantly better OS and PFS benefits (HR = 0.68, 95% CI: 0.48-0.95; HR = 0.59, 95% CI: 0.46-0.74, respectively), and those aged <75 years and the Asian population had significantly prolonged PFS (HR = 0.69, 95% CI: 0.52-0.91; HR = 0.71, 95% CI: 0.58-0.87; respectively). The superiority of EGFR-TKI and bevacizumab combination therapy against EGFR-TKI monotherapy in improving PFS was more significant in the erlotinib regimen subgroup. The risk of grade≥3 TRAEs was remarkably higher in the combination therapy group (HR = 1.73, 95% CI: 1.39-2.16). Addition of bevacizumab to EGFR-TKI therapy provided significantly better PFS and ORR for EGFR-mutant advanced NSCLC patients, though with higher risk of grade≥3 TRAEs. Patients who ever smoked, aged <75 years, and Asian population might benefit more from the combination regimen. This systematic review and meta-analysis was registered in the PROSPERO database (CRD42023401926).
PubMed: 38269283
DOI: 10.3389/fphar.2023.1238579 -
Cancer Investigation Jan 2024The use of adjuvant first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) in patients with resected EGFR-mutant non-small cell lung... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of adjuvant first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) in patients with resected EGFR-mutant non-small cell lung cancer (NSCLC) remains controversial. Therefore, we performed a systematic review with meta-analysis to investigate the overall survival (OS) in patients with resected NSCLC.
METHODS
Relevant studies were identified from the PubMed and EMBASE databases, and pooled hazard risks were obtained by random-effects models.
RESULTS
Three prospective phase III and one phase II randomized controlled trials were identified, including a total of 839 patients who had undergone resection of EGFR-sensitive mutation in our analysis, 429 of whom received adjuvant first-generation TKIs therapy. For all patients with complete resection, adjuvant first-generation TKIs therapy was associated with improved disease-free survival (DFS) [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.30-0. 82] but not OS (HR: 0.78, 95% CI: 0.48-1.27) compared with adjuvant chemotherapy. In addition, we reconstructed the OS curves of the ADJUVANT and IMPACT studies, and the pooled 3- and 5-year OS rates of stage II-III patients in the TKI group and chemotherapy group were 80% vs. 79% and 66% vs. 64%, respectively. We also reconstructed the DFS curves based on the ADJUVANT, IMPACT, and EVIDENCE studies, and the pooled 1-, 3- and 5-year DFS rates of stage II-III patients in the TKI group and chemotherapy group were 87% vs. 70%, 49% vs. 37% and 28% vs. 29%, respectively.
CONCLUSIONS
In patients with completely resected EGFR-mutant NSCLC, adjuvant first-generation TKIs may delay disease progression but still fail to improve long-term survival compared with conventional chemotherapy.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Prospective Studies; ErbB Receptors; Protein Kinase Inhibitors; Chemotherapy, Adjuvant; Mutation
PubMed: 38224061
DOI: 10.1080/07357907.2024.2303311 -
Frontiers in Medicine 2023The progression of early stage non-small cell lung cancer (NSCLC) is closely related to epidermal growth factor receptor (EGFR) mutation status. The purpose of this...
Distinguishing EGFR mutant subtypes in stage IA non-small cell lung cancer using the presence status of ground glass opacity and final histologic classification: a systematic review and meta-analysis.
BACKGROUND
The progression of early stage non-small cell lung cancer (NSCLC) is closely related to epidermal growth factor receptor (EGFR) mutation status. The purpose of this study was to systematically investigate the relationship between EGFR mutation status and demographic, imaging, and ultimately pathologic features in patients with NSCLC.
METHODS
A complete literature search was conducted using the PubMed, Web of Science, EMBASE, and Cochrane Library databases to discover articles published by May 15, 2023 that were eligible. The relationship between EGFR mutation status and specific demographic, imaging, and ultimately pathologic features in patients with NSCLC was evaluated using pooled odds ratios (ORs) and their 95% confidence intervals (CIs). The standardized mean difference (SMD) with 95% CIs was the appropriate statistic to summarize standard deviations (SDs) means for continuous variables.
RESULTS
A total of 9 studies with 1789 patients were included in this analysis. The final findings suggested that patients with a greater age, female gender, and non-smoking status would have a relatively higher incidence of EGFR mutations. Additionally, the risk of EGFR mutations increased with larger tumor diameter, tumor imaging presentation of mixed ground glass opacity (mGGO), and tumor pathological findings of minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (IAC). Significantly, malignancies presenting as MIA are more likely to contain L858R point mutations (OR = 1.80; 95% CI: 1.04-3.13; = 0.04) rather than exon 19 deletions (OR = 1.81; 95% CI: 0.95-3.44; = 0.07).
CONCLUSION
This meta-analysis showed that imaging parameters and histological classifications of pulmonary nodules may be able to predict stage IA NSCLC genetic changes.
PubMed: 38126071
DOI: 10.3389/fmed.2023.1268846