Identification of cardiotoxicity related to non-small cell lung cancer (NSCLC) treatments: A systematic review

Introduction: In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have decreased. However, it has been reported that cardiovascular disease has become the second leading cause of long-term morbidity and fatality among cancer survivors. Cardiotoxicity from anticancer drugs affects the heart’s function and structure and can occur during any stage of the cancer treatments, which leads to the development of cardiovascular disease.Objectives: To investigate the association between anticancer drugs for non-small cell lung cancer (NSCLC) and cardiotoxicity as to whether: different classes of anticancer drugs demonstrate different cardiotoxicity potentials; different dosages of the same drug in initial treatment affect the degree of cardiotoxicity; and accumulated dosage and/or duration of treatments affect the degree of cardiotoxicity.Methods: This systematic review included studies involving patients over 18 years old with NSCLC and excluded studies in which patients’ treatments involve radiotherapy only. Electronic databases and registers including Cochrane Library, National Cancer Institute (NCI) Database, PubMed, Scopus, Web of Science, ClinicalTrials.gov and the European Union Clinical Trials Register were systematically searched from the earliest available date up until November 2020. A full version protocol of this systematic review (CRD42020191760) had been published on PROSPERO.Results: A total of 1785 records were identified using specific search terms through the databases and registers; 74 eligible studies were included for data extraction. Based on data extracted from the included studies, anticancer drugs for NSCLC that are associated with cardiovascular events include bevacizumab, carboplatin, cisplatin, crizotinib, docetaxel, erlotinib, gemcitabine and paclitaxel. Hypertension was the most reported cardiotoxicity as 30 studies documented this cardiovascular adverse event. Other reported treatment-related cardiotoxicities include arrhythmias, atrial fibrillation, bradycardia, cardiac arrest, cardiac failure, coronary artery disease, heart failure, ischemia, left ventricular dysfunction, myocardial infarction, palpitations, and tachycardia.Conclusion: The findings of this systematic review have provided a better understanding of the possible association between cardiotoxicities and anticancer drugs for NSCLC. Whilst variation is observed across different drug classes, the lack of information available on cardiac monitoring can result in underestimation of this association.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191760, identifier PROSPERO CRD42020191760

Identification of cardiotoxicity related to non-small cell lung cancer (NSCLC) treatments: A systematic review

Introduction In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have decreased. However, it has been reported that cardiovascular disease has become the second leading cause of long-term morbidity and fatality among cancer survivors. Cardiotoxicity from anticancer drugs affects the heart’s function and structure and can occur during any stage of the cancer treatments, which leads to the development of cardiovascular disease. Objectives To investigate the association between anticancer drugs for non-small cell lung cancer (NSCLC) and cardiotoxicity as to whether: different classes of anticancer drugs demonstrate different cardiotoxicity potentials; different dosages of the same drug in initial treatment affect the degree of cardiotoxicity; and accumulated dosage and/or duration of treatments affect the degree of cardiotoxicity Methods This systematic review included studies involving patients over 18 years old with NSCLC and excluded studies in which patients’ treatments involve radiotherapy only. Electronic databases and registers including Cochrane Library, National Cancer Institute (NCI) Database, PubMed, Scopus, Web of Science, ClinicalTrials.gov and the European Union Clinical Trials Register were systematically searched from the earliest available date up until November 2020. A full version protocol of this systematic review (CRD42020191760) had been published on PROSPERO. Results A total of 1785 records were identified using specific search terms through the databases and registers; 74 eligible studies were included for data extraction. Based on data extracted from the included studies, anticancer drugs for NSCLC that are associated with cardiovascular events include bevacizumab, carboplatin, cisplatin, crizotinib, docetaxel, erlotinib, gemcitabine and paclitaxel. Hypertension was the most reported cardiotoxicity as 30 studies documented this cardiovascular adverse event. Other reported treatment-related cardiotoxicities include arrhythmias, atrial fibrillation, bradycardia, cardiac arrest, cardiac failure, coronary artery disease, heart failure, ischemia, left ventricular dysfunction, myocardial infarction, palpitations, and tachycardia. Conclusion The findings of this systematic review have provided a better understanding of the possible association between cardiotoxicities and anticancer drugs for NSCLC. Whilst variation is observed across different drug classes, the lack of information available on cardiac monitoring can result in underestimation of this association. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191760, identifier PROSPERO CRD42020191760

Idaho National Laboratory (INL) Site Greenhouse Gas (GHG) Monitoring Plan - 40 CFR 98

The purpose of this Greenhouse Gas (GHG) Monitoring Plan is to meet the monitoring plan requirements of Title 40 of the Code of Federal Regulations Part 98.3(g)(5). This GHG Monitoring Plan identifies procedures and methodologies used at the Idaho National Laboratory Site (INL Site) to collect data used for GHG emissions calculations and reporting requirements from stationary combustion and other regulated sources in accordance with 40 CFR 98, Subparts A and other applicable subparts. INL Site Contractors determined subpart applicability through the use of a checklist (Appendix A). Each facility/contractor reviews operations to determine which subparts are applicable and the results are compiled to determine which subparts are applicable to the INL Site. This plan is applicable to the 40 CFR 98-regulated activities managed by the INL Site contractors: Idaho National Laboratory (INL), Idaho Cleanup Project (ICP), Advanced Mixed Waste Treatment Project (AMWTP), and Naval Reactors Facilities (NRF)

Identification of cardiotoxicity related to non-small cell lung cancer (NSCLC) treatments: A systematic review

© 2023 Chan, Khatib, Webley, Layton and Salek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/Introduction: In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have decreased. However, it has been reported that cardiovascular disease has become the second leading cause of long-term morbidity and fatality among cancer survivors. Cardiotoxicity from anticancer drugs affects the heart’s function and structure and can occur during any stage of the cancer treatments, which leads to the development of cardiovascular disease. Objectives: To investigate the association between anticancer drugs for non-small cell lung cancer (NSCLC) and cardiotoxicity as to whether: different classes of anticancer drugs demonstrate different cardiotoxicity potentials; different dosages of the same drug in initial treatment affect the degree of cardiotoxicity; and accumulated dosage and/or duration of treatments affect the degree of cardiotoxicity. Methods: This systematic review included studies involving patients over 18 years old with NSCLC and excluded studies in which patients’ treatments involve radiotherapy only. Electronic databases and registers including Cochrane Library, National Cancer Institute (NCI) Database, PubMed, Scopus, Web of Science, ClinicalTrials.gov and the European Union Clinical Trials Register were systematically searched from the earliest available date up until November 2020. A full version protocol of this systematic review (CRD42020191760) had been published on PROSPERO. Results: A total of 1785 records were identified using specific search terms through the databases and registers; 74 eligible studies were included for data extraction. Based on data extracted from the included studies, anticancer drugs for NSCLC that are associated with cardiovascular events include bevacizumab, carboplatin, cisplatin, crizotinib, docetaxel, erlotinib, gemcitabine and paclitaxel. Hypertension was the most reported cardiotoxicity as 30 studies documented this cardiovascular adverse event. Other reported treatment-related cardiotoxicities include arrhythmias, atrial fibrillation, bradycardia, cardiac arrest, cardiac failure, coronary artery disease, heart failure, ischemia, left ventricular dysfunction, myocardial infarction, palpitations, and tachycardia. Conclusion: The findings of this systematic review have provided a better understanding of the possible association between cardiotoxicities and anticancer drugs for NSCLC. Whilst variation is observed across different drug classes, the lack of information available on cardiac monitoring can result in underestimation of this association. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191760, identifier PROSPERO CRD42020191760.Peer reviewe

A Framework for Methodological Choice and Evidence Assessment for Studies Using External Comparators from Real-World Data.

Several approaches have been proposed recently to accelerate the pathway from drug discovery to patient access. These include novel designs such as using controls external to the clinical trial where standard randomised controls are not feasible. In parallel, there has been rapid growth in the application of routinely collected healthcare 'real-world' data for post-market safety and effectiveness studies. Thus, using real-world data to establish an external comparator arm in clinical trials is a natural next step. Regulatory authorities have begun to endorse the use of external comparators in certain circumstances, with some positive outcomes for new drug approvals. Given the potential to introduce bias associated with observational studies, there is a need for recommendations on how external comparators should be best used. In this article, we propose an evaluation framework for real-world data external comparator studies that enables full assessment of available evidence and related bias. We define the principle of exchangeability and discuss the applicability of criteria described by Pocock for consideration of the exchangeability of the external and trial populations. We explore how trial designs using real-world data external comparators fit within the evidence hierarchy and propose a four-step process for good conduct of external comparator studies. This process is intended to maximise the quality of evidence based on careful study design and the combination of covariate balancing, bias analysis and combining outcomes

Safety of Atrovent® CFC-free inhaler:respiratory events reported from an observational cohort study in England

ObjectivesThe aim of the study was to identify any unexpected clinical events associated with starting the new CFC‐free formulation of Atrovent® MDI in general practice in England.MethodsAn active surveillance cohort study was conducted with a focus on selected clinical events, including respiratory symptoms, in past users of Atrovent® CFC MDI (‘switchers’) and Atrovent® naïve users. Incidence density rate ratios (with 99% confidence intervals) for events occurring in the first 3 months of exposure (risk period‐ID1‐3) compared to 3 months prior to starting treatment (reference period‐IDR) were calculated.ResultsThe cohort consisted of 13 211 patients (median age 70 years, 50.1% female; 63.5% prior users of Atrovent® CFC MDI (‘switchers’)). Common respiratory events occurred at higher rates after starting treatment than before for switchers, for example lower respiratory tract infection (LRTI) [ID1/IDR = 1.45 (99% CI: 1.17, 1.81)] and worsening asthma [ID1/IDR = 1.58 (99% CI: 1.00, 2.51)]. Of these events only LRTI was significant for Atrovent® naïve patients [ID1/IDR = 1.42 (99% CI: 1.04, 1.95)].ConclusionsThe results of this study suggest effect modification of risk as a result of prior Atrovent® CFC MDI use. Overall, Atrovent® CFC‐free MDI appeared to be reasonably well tolerated in the immediate postmarketing period and the safety profile appeared similar to that of the CFC formulation

ABSTRACTS OF PRESENTATIONS

Second International Conference on African Digital Libraries and Archives, abstracts of presentation

Narcissism and the strategic pursuit of short-term mating : universal links across 11 world regions of the International Sexuality Description Project-2.

Previous studies have documented links between sub-clinical narcissism and the active pursuit of short-term mating strategies (e.g., unrestricted sociosexuality, marital infidelity, mate poaching). Nearly all of these investigations have relied solely on samples from Western cultures. In the current study, responses from a cross-cultural survey of 30,470 people across 53 nations spanning 11 world regions (North America, Central/South America, Northern Europe, Western Europe, Eastern Europe, Southern Europe, Middle East, Africa, Oceania, Southeast Asia, and East Asia) were used to evaluate whether narcissism (as measured by the Narcissistic Personality Inventory; NPI) was universally associated with short-term mating. Results revealed narcissism scores (including two broad factors and seven traditional facets as measured by the NPI) were functionally equivalent across cultures, reliably associating with key sexual outcomes (e.g., more active pursuit of short-term mating, intimate partner violence, and sexual aggression) and sex-related personality traits (e.g., higher extraversion and openness to experience). Whereas some features of personality (e.g., subjective well-being) were universally associated with socially adaptive facets of Narcissism (e.g., self-sufficiency), most indicators of short-term mating (e.g., unrestricted sociosexuality and marital infidelity) were universally associated with the socially maladaptive facets of narcissism (e.g., exploitativeness). Discussion addresses limitations of these cross-culturally universal findings and presents suggestions for future research into revealing the precise psychological features of narcissism that facilitate the strategic pursuit of short-term mating

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone