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Abstract Background Patients with cancer are at high risk for severe courses of COVID-19. Based on (pre-)clinical data suggesting a potential protective effect due to the immunomodulating properties of azithromycin, we have initiated a prospective randomized trial. Methods This randomized, single-center, single-blinded, placebo-controlled phase 2 trial included adult patients with cancer undergoing systemic treatment. Patients were 1:1 randomized to oral azithromycin (1500 mg once weekly for 8 weeks) or placebo. The primary endpoint was the cumulative number of SARS-CoV-2 infections 12 weeks after treatment initiation. Results In total, 523 patients were screened, 68 patients were randomized, and 63 patients received at least one dose of the study drug. Due to low acceptance and a lack of SARS-CoV-2 infections in the study cohort, the study was prematurely closed. With no reported grade III–IV possibly treatment-related adverse events, azithromycin was generally well tolerated. Overall survival (OS) rates after 12 months were 83.5% and 70.3% in the azithromycin and placebo group, respectively (p = 0.37). Non-SARS-CoV-2 infections occurred in 4/32 (12.5%) in the azithromycin and 3/31 (9.7%) in the placebo group (p = 1). No emergence of azithromycin-resistant S. aureus strains could be observed. According to treatment group, longitudinal alterations in systemic inflammatory parameters were detected for neutrophil/lymphocyte and leukocyte/lymphocyte ratios. Conclusion Although efficacy could not be assessed due to premature closure and low incidence of SARS-CoV-2 infections, azithromycin was associated with a favorable side effect profile in patients with cancer. As other prophylactic treatments are limited, SARS-CoV-2 vaccination remains a high priority in oncological patients. ClinicalTrials.gov registration number and date (dd/mm/yyyy): NCT04369365, 30/04/2020.

Abstract Background Diagnosing ventilator-associated pneumonia (VAP) in an intensive care unit (ICU) is a complex process. Our aim was to collect, evaluate and represent the information relating to current clinical practice for the diagnosis of VAP in UK NHS ICUs, and to explore the potential value and role of a novel diagnostic for VAP, which uses optical molecular alveoscopy to visualise the alveolar space. Methods Qualitative study performing semi-structured interviews with clinical experts. Interviews were recorded, transcribed, and thematically analysed. A flow diagram of the VAP patient pathway was elicited and validated with the expert interviewees. Fourteen clinicians were interviewed from a range of UK NHS hospitals: 12 ICU consultants, 1 professor of respiratory medicine and 1 professor of critical care. Results Five themes were identified, relating to [1] current practice for the diagnosis of VAP, [2] current clinical need in VAP diagnostics, [3] the potential value and role of the technology, [4] the barriers to adoption and [5] the evidence requirements for the technology, to help facilitate a successful adoption. These themes indicated that diagnosis of VAP is extremely difficult, as is the decision to stop antibiotic treatment. The analysis revealed that there is a clinical need for a diagnostic that provides an accurate and timely diagnosis of the causative pathogen, without the long delays associated with return of culture results, and which is not dangerous to the patient. It was determined that the technology would satisfy important aspects of this clinical need for diagnosing VAP (and pneumonia, more generally), but would require further evidence on safety and efficacy in the patient population to facilitate adoption. Conclusions Care pathway analysis performed in this study was deemed accurate and representative of current practice for diagnosing VAP in a UK ICU as determined by relevant clinical experts, and explored the value and role of a novel diagnostic, which uses optical technology, and could streamline the diagnostic pathway for VAP and other pneumonias.

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Radon (Rn) is a naturally occurring radioactive gas that poses a significant lung cancer risk. Subsurface fault zones can act as pathways for fluid and gas migration, potentially amplifying Rn accumulation. This study investigates the impact of fault zones on Rn concentrations within a 25 km 2 area in the Northern Upper Rhine Graben, Germany - a region with available detailed geophysical exploration data and active neotectonic faulting. We conducted 597 Rn soil air measurements along precisely located fault zones, integrating a comprehensive range of environmental parameters. Utilizing the advanced machine learning model eXtreme Gradient Boosting (XGBoost) in conjunction with SHapley Additive exPlanations (SHAP) values, we dissected the influence of soil types, environmental factors, and proximity to fault zones on soil air Rn concentrations at a 1-meter depth. Our results reveal that clay-rich soils and cumulative 30-day precipitation are the primary drivers of elevated Rn levels. Proximity to fault zones also significantly influences Rn concentrations, though its impact is less pronounced than the factors mentioned above. Additionally, environmental factors such as wind speed, air pressure, and temperature exhibited lesser effects on Rn levels. The negligible influence of measuring devices and operating personnel increases confidence in data integrity in extensive environmental studies. This study demonstrates the effectiveness of integrating XGBoost with SHAP values to identify and quantify key factors influencing Rn concentrations. By providing a robust framework for enhancing Rn prediction models through machine learning, our findings contribute to improved risk assessments and mitigation strategies, thereby advancing public health and environmental management., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Conflict of interest: N.L.M. is supported by a Research Excellence Award (RE/24/130012) and a Chair Award (CH/F/21/90010) from the British Heart Foundation and reports research grants awarded to the University of Edinburgh from Abbott Diagnostics, Roche Diagnostics, and Siemens Healthineers outside the submitted work and honoraria from Abbott Diagnostics, Siemens Healthineers, Roche Diagnostics, LumiraDx, and Psyros Diagnostics. J.W.P. has undertaken statistical consulting for Abbott Diagnostics, Siemens Healthineers, Radiometer, and QuidelOrtho and is a shareholder of Wayfind Health. M.P.T. has received research support and honoraria from Abbott Diagnostics, Beckman Coulter, QuidelOrtho, Radiometer, Roche Diagnostics, and Siemens Healthineers.

Introduction: Aging is the strongest risk factor for most chronic diseases. The rising burden of an aging population and non-communicable diseases (NCDs), contributes to escalating costs for society. Several non-pharmaceutical interventions can lower the risk of NCDs, including common mental disorders (CMDs), and may slow down biological aging, as evidenced by outcome markers such as epigenetic clocks. However, a comprehensive overview of whether and which non-pharmaceutical interventions may impact human epigenetic aging is missing. Synthesizing evidence of interventions on epigenetic aging that can be adopted by a wider population is key to guide healthy aging initiatives and to reduce the burden of NCDs and CMDs. This scoping review will identify and assess non-pharmaceutical interventions aimed to slow down epigenetic aging, including their intervention components, and the mode used for intervention delivery., Methods and Analysis: This protocol will include single- and multicomponent intervention studies that target individuals ≥ 18 years of age and use epigenetic clocks as primary or secondary outcomes. Five electronic databases will be searched for studies between July 2011 until December 2023. The final search will include the search terms adults, non-pharmaceutical interventions, epigenetic aging and their respective synonyms. We will include randomized controlled trials, non-randomized controlled studies, cohort studies, and case-control studies. Additionally, the reference list of other reviews will be screened for relevant articles. Study selection is carried out based on the defined eligibility criteria by two authors. Quality and risk of bias for the included studies will be assessed using the Critical Appraisal Skills Programme (CASP) checklist. Data extraction will include generic key information such as the research question and results, the intervention components, and specific epigenetic outcome measures used. Further data regarding the delivery mode of the treatment protocol will be collected., Ethics and Dissemination: This scoping review will summarize the characteristics of non-pharmaceutical intervention studies on epigenetic aging. This review will be the first step to formally identify key intervention components and delivery modes to guide future research on healthy aging interventions. The results will be disseminated through a peer-reviewed publication and presented at relevant conferences. This review will synthesize information from available publications and does not require further ethical approval., Registration Details: Open Science Framework https://doi.org/10.17605/OSF.IO/FEHNB., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AL, JM, MJ, and TK are affiliated with the Centre for Digital Health Interventions, a joint initiative of the Institute for Implementation Science in Health Care, University of Zurich, the Department of Management, Technology, and Economics at ETH Zurich, and the Institute of Technology Man-agement and School of Medicine at the University of St.Gallen. The Centre for Digital Health In-terventions is funded in part by CSS, a Swiss health insurer, MavieNext, an Austrian healthcare provider, and MTIP, a Swiss digital health investor. TK is also a co-founder of Pathmate Technol-ogies, a university spin-off company that creates and delivers digital clinical pathways. However, CSS, MavieNext, MTIP, or Pathmate Technologies were not involved in this protocol. All other authors declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Liebich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Peripherally inserted central catheters are commonly used in cancer patients and provide vascular access for the administration of chemotherapy, antibiotics, or parenteral nutrition. Besides many advantages, they represent a source of possible complications such as catheter related blood stream infection, catheter occlusion, or thrombosis. In this study, the catheter-related complication rate between oncologic and non-oncologic patients was compared., Methods: This retrospective cohort-study included 411 patients who underwent their first catheter placement at the Vienna General Hospital-Medical University of Vienna from January 2013 to June 2018. Patient demographics and catheter-related parameters were collected and statistically analyzed using a competing risk model., Results: Mean catheter dwell time was 27.75 days. The overall complication rate was 7.54% (2.72 per 1000 catheter days). Underlying malignant disease (hazard ratio: 0.351, 95% confidence interval [CI]: 0.133-0.929, P = .035) and chemotherapy administration (hazard ratio: 2.837, 95% CI: 1.088-7.394, P = .033) were significantly associated with the occurrence of any kind of complication. Catheter related blood stream infection was observed among 11 (2.68%) patients and again significantly associated with chemotherapy administration (hazard ratio: 4.545, 95% CI: 1.178-17.539; P = .028). Thrombosis was found in 7 (1.70%) patients and occlusion in 13 (3.16%) cases., Conclusions and Implications for Nursing Practice: Choice of venous access is an interdisciplinary decision with emphasis on patient participation. In oncologic patients, our data suggests that the benefits of peripherally inserted central catheters regarding costs, invasiveness, and accessibility might be outweighed by the higher rate of complications associated with the device. This becomes even more important in a community care setting, where standardized handling procedures and patient education play a pivotal role in device safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Women with a history of gestational diabetes mellitus (GDM) are 12-fold more likely to develop type 2 diabetes (T2D) 4-6 years after delivery than women without GDM. Similarly, GDM is associated with the development of common mental disorders (CMDs) (e.g. anxiety and depression). Evidence shows that holistic lifestyle interventions focusing on physical activity (PA), dietary intake, sleep, and mental well-being strategies can prevent T2D and CMDs. This study aims to assess the effectiveness of a holistic lifestyle mobile health intervention (mHealth) with post-GDM women in preventing T2D and CMDs in a community setting in Singapore., Methods: The study consists of a 1-year randomised controlled trial (RCT) with a 3-year follow-up period. Post-GDM women with no current diabetes diagnosis and not planning to become pregnant will be eligible for the study. In addition, participants will complete mental well-being questionnaires (e.g. depression, anxiety, sleep) and their child's socio-emotional and cognitive development. The participants will be randomised to either Group 1 (Intervention) or Group 2 (comparison). The intervention group will receive the "LVL UP App", a smartphone-based, conversational agent-delivered holistic lifestyle intervention focused on three pillars: Move More (PA), Eat Well (Diet), and Stress Less (mental wellbeing). The intervention consists of health literacy and psychoeducational coaching sessions, daily "Life Hacks" (healthy activity suggestions), slow-paced breathing exercises, a step tracker (including brisk steps), a low-burden food diary, and a journaling tool. Women from both groups will be provided with an Oura ring for tracking physical activity, sleep, and heart rate variability (a proxy for stress), and the "HAPPY App", a mHealth app which provides health promotion information about PA, diet, sleep, and mental wellbeing, as well as display body mass index, blood pressure, and results from the oral glucose tolerance tests. Short-term aggregate effects will be assessed at 26/27 weeks (midpoint) and a 1-year visit, followed by a 2, 3, and 4-year follow-up period., Discussion: High rates of progression of T2D and CMDs in women with post-GDM suggest an urgent need to promote a healthy lifestyle, including diet, PA, sleep, and mental well-being. Preventive interventions through a holistic, healthy lifestyle may be the solution, considering the inextricable relationship between physical and psychological health. We expect that holistic lifestyle mHealth may effectively support behavioural changes among women with a history of GDM to prevent T2D and CMDs., Trial Status: The protocol study was approved by the National Healthcare Group in Singapore, Domain Specific Review Board (DSRB) [2023/00178]; June 2023. Recruitment began on October 18, 2023., Trial Registration: ClinicalTrials.gov NCT05949957. The first submission date is June 08, 2023., (© 2024. The Author(s).)

Competing Interests: Conflict of interest: N.L.M. is supported by a Research Excellence Award (RE/24/130012) and a Chair Award (CH/F/21/90010) from the British Heart Foundation and reports research grants awarded to the University of Edinburgh from Abbott Diagnostics, Roche Diagnostics, and Siemens Healthineers outside the submitted work, and honoraria from Abbott Diagnostics, Siemens Healthineers, Roche Diagnostics, LumiraDx, and Psyros Diagnostics. K.K.L., D.D., and N.L.M. are employed by the University of Edinburgh, who have filed a patent on the CoDE-HF score (patent reference: PCT/GB2021/051470).

Drug-induced liver injury (DILI) is a challenge in clinical medicine and drug development. Highly sensitive novel biomarkers have been identified for detecting DILI following a paracetamol overdose. The study objective was to evaluate biomarker performance in a 14-day trial of therapeutic dose paracetamol. The PATH-BP trial was a double-blind, placebo-controlled, crossover study. Individuals (n = 110) were randomized to receive 1 g paracetamol 4× daily or matched placebo for 2 weeks followed by a 2-week washout before crossing over to the alternate treatment. Blood was collected on days 0 (baseline), 4, 7, and 14 in both arms. Alanine transaminase (ALT) activity was measured in all patients. MicroRNA-122 (miR-122), cytokeratin-18 (K18), and glutamate dehydrogenase (GLDH) were measured in patients who had an elevated ALT on paracetamol treatment (≥50% from baseline). ALT increased in 49 individuals (45%). All 3 biomarkers were increased at the time of peak ALT (K18 paracetamol arm: 18.9 ± 9.7 ng/ml, placebo arm: 11.1 ± 5.4 ng/ml, ROC-AUC = 0.80, 95% CI 0.71-0.89; miR-122: 15.1 ± 12.9fM V 4.9 ± 4.7fM, ROC-AUC = 0.83, 0.75-0.91; and GLDH: 24.6 ± 31.1U/l V 12.0 ± 11.8U/l, ROC-AUC = 0.66, 0.49-0.83). All biomarkers were correlated with ALT (K18 r = 0.68, miR-122 r = 0.67, GLDH r = 0.60). To assess sensitivity, biomarker performance was analyzed on the visit preceding peak ALT (mean 3 days earlier). K18 identified the subsequent ALT increase (K18 ROC-AUC = 0.70, 0.59-0.80; miR-122 ROC-AUC = 0.60, 0.49-0.72, ALT ROC-AUC = 0.59, 0.48-0.70; GLDH ROC-AUC = 0.70, 0.50-0.90). Variability was lowest for ALT and K18. In conclusion, K18 was more sensitive than ALT, miR-122, or GLDH and has potential significant utility in the early identification of DILI in trials and clinical practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology.)

Aims: This study offers an empirical exploration of self-assessed digital competencies of students, most of whom studied in nursing courses, using a discipline-based self-assessment survey tool. A range of digital competencies were explored: information and communication technology proficiency and productivity, information literacy, digital creation, digital research, digital communication, digital learning and development, digital innovation, digital identity management and digital well-being., Design: A cross-sectional empirical study., Methods: Quantitative data were collected from November to December 2021 via a questionnaire survey administered to students. Quantitative results were reported through descriptive statistical analysis. Mann-Whitney (U-test) and Kruskal-Wallis non-parametric statistical tests were used to identify statistically significant differences based on age demographics and pre- or post-registration course. Thematic analysis was utilized for survey open-ended questions data., Results: Students reported low competencies in the following digital literacy dimensions, all of which were imperative for their studies and for their future professional careers: information literacy, digital research, digital innovation. Significant statistical subgroup differences were found between age demographics and pre/post-registration within most of the digital competence dimensions. The survey open-ended comments revealed that students encountered challenges around digital skills they had mostly developed via everyday life experiences and trial-and-error approaches., Conclusion: Increasing awareness of existing digital gaps and offering tailored digital skills enhancement can empower students as future-proof evidence-based practitioners in an evolving digital healthcare landscape., Implications for the Profession And/or Patient Care: Highlights the importance of embedding digital literacy within nursing study programmes, as preparation for comprehensive patient healthcare., Impact: Offers insights into digital competencies gaps of nursing students. Proposes targeted educational digital skills training interventions. Stresses the value of academic staff supporting nursing students to develop digital skills in important areas of professional practice., Reporting Method: JBI critical appraisal checklist. No patient or public contribution., (© 2023 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

We describe the management of two linked severe acute respiratory coronavirus 2 (SARS-CoV-2) outbreaks, predominantly amongst 18-35-year-olds, in a UK county in July-to-September 2021, following the lifting of national coronavirus disease 2019 (COVID-19)-associated social restrictions. One was associated with a nightclub and one with five air force bases. On week beginning 2nd August 2021, air force contact tracing teams detected 68 cases across five bases within one county; 21 (30.9%) were associated with a night-time economy venue, 13 (19.1%) with night-time economy venues in the county's main town and at least one case per base ( n = 6, 8.8%) with a particular nightclub in this town, which itself had been associated with 302 cases in the previous week (coinciding with its reopening following a national lockdown). In response, Public Health England/United Kingdom Health Security Agency, air force and local authority teams collaboratively implemented communication strategies and enhanced access to SARS-CoV-2 testing and vaccination. Key challenges included attempting to encourage behaviours that reduce likelihood of transmission to a population who may have considered themselves at low risk from severe COVID-19. This report may inform future preparation for, and management of, easing of potential future pandemic-related social restrictions, and how an outbreak in this context may be addressed.

Purpose: This review intends to illustrate basic principles on how to apply the Fourth Universal Definition of Myocardial Infarction (UDMI) for the diagnosis of peri-procedural myocardial infarction (MI) after percutaneous coronary interventions (PCI) in clinical practice., Methods and Results: Review of routine case-based events. Increases in cardiac troponin (cTn) concentrations are common after elective PCI in patients with chronic coronary syndrome (CCS). Peri-procedural PCI-related MI (type 4a MI) in CCS patients should be diagnosed in cases of major peri-procedural acute myocardial injury indicated by an increase in cTn concentrations of >5-times the 99th percentile upper reference limit (URL) together with evidence of new peri-procedural myocardial ischaemia as demonstrated by electrocardiography (ECG), imaging, or flow-limiting peri-procedural complications in coronary angiography. Measurement of cTn baseline concentrations before elective PCI is useful. In patients presenting with acute MI undergoing PCI, peri-procedural increases in cTn concentrations are usually due to their index presentation and not PCI-related, apart from obvious major peri-procedural complications, such as persistent occlusion of a large side branch or no-reflow after stent implantation., Conclusion: The distinction between type 4a MI, PCI-related acute myocardial injury, and chronic myocardial injury can be challenging in individuals undergoing PCI. Careful integration of all available clinical data is essential for correct classification.

The number of adults with congenital heart disease (ACHD) already exceeds the number of children with congenital heart disease in the industrialized world. ACHD patients often show complex pathophysiology and anatomy even after reparative cardiac surgery. In case of complications patients may rapidly deteriorate and become unstable, even when they were asymptomatic or had only mild symptoms before the onset of the complication. Compared to all patients seen by emergency physicians, emergencies in ACHD patients are still rare. This review is aimed to guide management in ACHD emergency situations. Approximately two-thirds of all emergency admissions are caused by arrhythmias or acute heart failure. Sustained arrhythmias may rapidly lead to acute cardiac decompensation in ACHD patients. If medical treatment fails or patients present in hemodynamically unstable conditions, prompt electrical cardioversion is mandatory. Symptomatic bradycardia may require urgent pacemaker implantation. Depending on the underlying heart defect, placement of temporary transvenous pacemaker leads may be impossible. Acute heart failure in ACHD patients is often caused by acute right heart failure. Other more frequent emergencies are infections, syncope, thromboembolic events, and aortic dissection. It is highly recommended to contact the tertiary care center that follows the patient regularly early in case of patient presentation to the emergency room., (© 2020. The Author(s).)