27 research outputs found
Prognostic DNA Methylation Biomarkers in High-risk Non–muscle-invasive Bladder Cancer:A Systematic Review to Identify Loci for Prospective Validation
Context: High-risk non–muscle-invasive bladder cancer (HR-NMIBC) represents over 30% of all incident urothelial bladder cancers (BCs); patients are at risk of progression, and 20–30% will die from BC within 5 yr. Current guidelines recommend induction and maintenance of intravesical bacillus Calmette-Guérin (BCG) or upfront radical cystectomy for highest-risk disease, treatments with markedly different morbidity, mortality, and patient burden. There are no validated biomarkers to facilitate such treatment decisions. Alterations in DNA methylation are commonplace in BC; hence, measurable changes in DNA methylation represent an opportunity for the discovery of such biomarkers.Objective: To systematically assess the evidence regarding DNA methylation markers as prognosticators for HR-NMIBC.Evidence acquisition: Standard systematic review methods were employed with searches undertaken in MEDLINE, EMBASE, and PubMed up to January 2019. Studies that included patients with HR-NMIBC and investigated the utility of DNA methylation biomarkers as prognostic tools were included.Evidence synthesis: Of 63 prognostic biomarker studies identified, 21 met the protocol-driven inclusion criteria and were directly relevant to HR-NMIBC patient outcomes: tumour recurrence (TR), tumour progression (TP), disease-specific survival (DSS), and overall survival (OS). These studies described 140 methylation markers; of these, the most promising were cadherin-13 (CDH13; hazard ratios [HRs]: 5.1 for TR, 6.6 for TP, 3.8–8.0 for OS), protocadherins (PCDHs; HRs: 4.7 for TR, 2.5 for TP, 3.0–4.8 for OS), Runt domain transcription factor 3 (RUNX3; HR: 5.1 for TP), Homeobox 9 (HOXA9; HR: 1.9 for TR), Islet-1 (ISL1; HRs: 1.7 for TR, 3.3 for TP), and PAX6 (HR: 2.2 for TR).Conclusions: This systematic review identifies a number of potentially useful prognostic methylation markers for HR-NMIBC. These loci (CDH13, PCDHs, RUNX3, HOXA9, ISL1, and PAX6) should be validated in prospective studies in order to translate benefit to patients.Patient summary: Early bladder cancer represents a more complex spectrum of disease than can be assessed by conventional methods Emerging studies on molecular markers will improve our understanding of this disease, and may enable more precise and personalised treatment.</p
Prognostic DNA Methylation Biomarkers in High-risk Non–muscle-invasive Bladder Cancer:A Systematic Review to Identify Loci for Prospective Validation
Context: High-risk non–muscle-invasive bladder cancer (HR-NMIBC) represents over 30% of all incident urothelial bladder cancers (BCs); patients are at risk of progression, and 20–30% will die from BC within 5 yr. Current guidelines recommend induction and maintenance of intravesical bacillus Calmette-Guérin (BCG) or upfront radical cystectomy for highest-risk disease, treatments with markedly different morbidity, mortality, and patient burden. There are no validated biomarkers to facilitate such treatment decisions. Alterations in DNA methylation are commonplace in BC; hence, measurable changes in DNA methylation represent an opportunity for the discovery of such biomarkers.Objective: To systematically assess the evidence regarding DNA methylation markers as prognosticators for HR-NMIBC.Evidence acquisition: Standard systematic review methods were employed with searches undertaken in MEDLINE, EMBASE, and PubMed up to January 2019. Studies that included patients with HR-NMIBC and investigated the utility of DNA methylation biomarkers as prognostic tools were included.Evidence synthesis: Of 63 prognostic biomarker studies identified, 21 met the protocol-driven inclusion criteria and were directly relevant to HR-NMIBC patient outcomes: tumour recurrence (TR), tumour progression (TP), disease-specific survival (DSS), and overall survival (OS). These studies described 140 methylation markers; of these, the most promising were cadherin-13 (CDH13; hazard ratios [HRs]: 5.1 for TR, 6.6 for TP, 3.8–8.0 for OS), protocadherins (PCDHs; HRs: 4.7 for TR, 2.5 for TP, 3.0–4.8 for OS), Runt domain transcription factor 3 (RUNX3; HR: 5.1 for TP), Homeobox 9 (HOXA9; HR: 1.9 for TR), Islet-1 (ISL1; HRs: 1.7 for TR, 3.3 for TP), and PAX6 (HR: 2.2 for TR).Conclusions: This systematic review identifies a number of potentially useful prognostic methylation markers for HR-NMIBC. These loci (CDH13, PCDHs, RUNX3, HOXA9, ISL1, and PAX6) should be validated in prospective studies in order to translate benefit to patients.Patient summary: Early bladder cancer represents a more complex spectrum of disease than can be assessed by conventional methods Emerging studies on molecular markers will improve our understanding of this disease, and may enable more precise and personalised treatment.</p
National identity predicts public health support during a global pandemic
Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio
The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set
Background
Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables.
Methods
Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set.
Results
Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001).
Conclusions
The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries