A call for action to include psychosocial management into holistic, integrated care for patients with atrial fibrillation.

Contemporary management of atrial fibrillation (AF) has become increasingly complex. Therefore, strong efforts have been made during the past decade to develop models for structured, integrated care for patients with AF. These have also been incorporated in international guidelines for the management of patients with AF. However, implementation of integrated care approaches in daily clinical practice is scarce and far from optimal, and it may require a re-thinking of the structure of the healthcare system. The reasons for the poor implementation are many, from limited time and economic resources to deficits in postgraduate education of healthcare professionals, lack of involvement of patients in how integrated care should be designed, and fragmentation of the healthcare system. Moreover, patients' psychological challenges, which not only impact patients' adherence to treatment but, if untreated, increase their risk of morbidity, mortality, and poor quality of life, are not given sufficient attention. It is time to start a necessary discussion of what integrated care should be, what it should contain, and what is necessary to implement it in daily clinical practice.

Auranofin repurposing for lung and pancreatic cancer: low CA12 expression as a marker of sensitivity in patient-derived organoids, with potentiated efficacy by AKT inhibition.

BACKGROUND: This study explores the repurposing of Auranofin (AF), an anti-rheumatic drug, for treating non-small cell lung cancer (NSCLC) adenocarcinoma and pancreatic ductal adenocarcinoma (PDAC). Drug repurposing in oncology offers a cost-effective and time-efficient approach to developing new cancer therapies. Our research focuses on evaluating AF's selective cytotoxicity against cancer cells, identifying RNAseq-based biomarkers to predict AF response, and finding the most effective co-therapeutic agents for combination with AF. METHODS: Our investigation employed a comprehensive drug screening of AF in combination with eleven anticancer agents in cancerous PDAC and NSCLC patient-derived organoids (n = 7), and non-cancerous pulmonary organoids (n = 2). Additionally, we conducted RNA sequencing to identify potential biomarkers for AF sensitivity and experimented with various drug combinations to optimize AF's therapeutic efficacy. RESULTS: The results revealed that AF demonstrates a preferential cytotoxic effect on NSCLC and PDAC cancer cells at clinically relevant concentrations below 1 µM, sparing normal epithelial cells. We identified Carbonic Anhydrase 12 (CA12) as a significant RNAseq-based biomarker, closely associated with the NF-κB survival signaling pathway, which is crucial in cancer cell response to oxidative stress. Our findings suggest that cancer cells with low CA12 expression are more susceptible to AF treatment. Furthermore, the combination of AF with the AKT inhibitor MK2206 was found to be particularly effective, exhibiting potent and selective cytotoxic synergy, especially in tumor organoid models classified as intermediate responders to AF, without adverse effects on healthy organoids. CONCLUSION: Our research offers valuable insights into the use of AF for treating NSCLC and PDAC. It highlights AF's cancer cell selectivity, establishes CA12 as a predictive biomarker for AF sensitivity, and underscores the enhanced efficacy of AF when combined with MK2206 and other therapeutics. These findings pave the way for further exploration of AF in cancer treatment, particularly in identifying patient populations most likely to benefit from its use and in optimizing combination therapies for improved patient outcomes.

The diagnosis and management of chronic lung allograft dysfunction.

PURPOSE OF REVIEW: Chronic lung allograft dysfunction (CLAD) remains a life-threatening complication following lung transplantation. Different CLAD phenotypes have recently been defined, based on the combination of pulmonary function testing and chest computed tomography (CT) scanning and spurred renewed interests in differential diagnosis, risk factors and management of CLAD. RECENT FINDINGS: Given their crucial importance in the differential diagnosis, we will discuss the latest development in assessing the pulmonary function and chest CT scan, but also their limitations in proper CLAD phenotyping, especially with regards to patients with baseline allograft dysfunction. Since no definitive treatment exists, it remains important to timely identify clinical risk factors, but also to assess the presence of specific patterns or biomarkers in tissue or in broncho alveolar lavage in relation to CLAD (phenotypes). We will provide a comprehensive overview of the latest advances in risk factors and biomarker research in CLAD. Lastly, we will also review novel preventive and curative treatment strategies for CLAD. SUMMARY: Although this knowledge has significantly advanced the field of lung transplantation, more research is warranted because CLAD remains a life-threatening complication for all lung transplant recipients.

Atrial fibrillation: epidemiology, screening and digital health.

Atrial fibrillation (AF) is highly prevalent with a lifetime risk of about 1 in 3-5 individuals after the age of 45 years. Between 2010 and 2019, the global prevalence of AF has risen markedly from 33.5 million to 59 million individuals living with AF. Early detection of AF and implementation of appropriate treatment could reduce the frequency of complications associated with AF. International AF management guidelines recommend opportunistic and systematic screening for AF, but additional data are needed. Digital approaches and pathways have been proposed for early detection and for the transition to early AF management. Mobile health (mHealth) devices provide an opportunity for digital screening and should be part of novel models of care delivery based on integrated AF care pathways. For a broad implementation of mHealth-based, integrated care for patients with chronic diseases as AF, further high quality evidence is necessary. In this review, we present an overview of the present data on epidemiology, screening techniques, and the contribution of digital health solutions to the integrated management of AF. We also provide a systemic review on current data of digital and integrated AF management.

Patient Journey Mapping: emerging methods for understanding and improving patient experiences of health systems and services.

Patient journey mapping is an emerging field of research that uses various methods to map and report evidence relating to patient experiences and interactions with healthcare providers, services and systems. This research often involves the development of visual, narrative, and descriptive maps or tables, which describe patient journeys and transitions into, through and out of health services. This methods corner paper presents an overview of how patient journey mapping has been conducted within the health sector, providing cardiovascular examples. It introduces six key steps for conducting patient journey mapping and describes the opportunities and benefits of using patient journey mapping and future implications of using this approach.

A systematic review of patient-derived tumor organoids generation from malignant effusions.

This review assesses the possibility of utilizing malignant effusions (MEs) for generating patient-derived tumor organoids (PDTOs). Obtained through minimally invasive procedures MEs broaden the spectrum of organoid sources beyond resection specimens and tissue biopsies. A systematic search yielded 11 articles, detailing the successful generation of 190 ME-PDTOs (122 pleural effusions, 54 malignant ascites). Success rates ranged from 33% to 100%, with an average of 84% and median of 92%. A broad and easily applicable array of techniques can be employed, encompassing diverse collection methods, variable centrifugation speeds, and the inclusion of approaches like RBC lysis buffer or centrifuged ME supernatants supplementation, enhancing the versatility and accessibility of the methodology. ME-PDTOs were found to recapitulate primary tumor characteristics and were primarily used for drug screening applications. Thus, MEs are a reliable source for developing PDTOs, emphasizing the need for further research to maximize their potential, validate usage, and refine culturing processes.

Effectiveness of cardiac rehabilitation programs on medication adherence in patients with cardiovascular disease: A systematic review and meta-analysis.

Background: Education to improve medication adherence is one of the core components of cardiac rehabilitation (CR) programs. However, the evidence on the effectiveness of CR programs on medication adherence is conflicting. Therefore, we aimed to summarize the effectiveness of CR programs versus standard care on medication adherence in patients with cardiovascular disease. Methods: A systematic review and meta-analysis was conducted. Seven databases and clinical trial registries were searched for published and unpublished articles from database inception to 09 Feb 2022. Only randomised controlled trials and quasi-experimental studies were included. Two independent reviewers conducted the screening, extraction, and appraisal. The JBI methodology for effectiveness reviews and PRISMA 2020 guidelines were followed. A statistical meta-analysis of included studies was pooled using RevMan version 5.4.1. Results: In total 33 studies were included with 16,677 participants. CR programs increased medication adherence by 14 % (RR = 1.14; 95 % CI: 1.07 to 1.22; p = 0.0002) with low degree of evidence certainty. CR also lowered the risk of dying by 17 % (RR = 0.83; 95 % CI: 0.69 to 1.00; p = 0.05); primary care and emergency department visit by mean difference of 0.19 (SMD = -0.19; 95 % CI: -0.30 to -0.08; p = 0.0008); and improved quality of life by 0.93 (SMD = 0.93; 95 % CI: 0.38 to 1.49; p = 0.0010). But no significant difference was observed in lipid profiles, except with total cholesterol (SMD = -0.26; 95 % CI: -0.44 to -0.07; p = 0.006) and blood pressure levels. Conclusions: CR improves medication adherence with a low degree of evidence certainty and non-significant changes in lipid and blood pressure levels. This result requires further investigation.

Understanding for whom, under what conditions, and how an integrated approach to atrial fibrillation service delivery works: a realist review.

AIMS: To understand for whom, under what conditions, and how an integrated approach to atrial fibrillation (AF) service delivery works (or does not work). METHODS AND RESULTS: A realist review of integrated approaches to AF service delivery for adult populations aged ≥18 years. An expert panel developed an initial programme theory, searched and screened literature from four databases until October 2022, extracted and synthesized data using realist techniques to create context-mechanism-outcome configurations for integrated approaches to AF service, and developed an integrated approach refined programme theory. A total of 5433 documents were screened and 39 included. The refined programme theory included five context-mechanism-outcome configurations for how clinical and system-wide outcomes are affected by the way integrated approaches to AF service delivery are designed and delivered. This review identifies core mechanisms underpinning the already known fundamental components of integrated care. This includes having a central coordinator responsible for service organization to provide continuity of care across primary and secondary care ensuring services are patient centred. Additionally, a fifth pillar, lifestyle and risk factor reduction, should be recognized within an AF care pathway. CONCLUSION: It is evident from our provisional theory that numerous factors need to interlink and interact over time to generate a successfully integrated model of care in AF. Stakeholders should embrace this complexity and acknowledge that the learnings from this review are integral to shaping future service delivery in the face of an aging population and increased prevalence of AF.

Description of self-care behaviours in patients with non-valvular atrial fibrillation on oral anticoagulant therapy: A scoping review.

AIM: The primary aim of this scoping review was to explore and categorise the medication-related self-care behaviours exhibited by patients with non-valvular atrial fibrillation (NVAF) who are on oral anticoagulant (OAC) therapy. METHODS AND RESULTS: A scoping review was performed, and the systematic search of the literature yielded an initial 887 records. After deduplication and screening, 61 studies were included in the analysis, ranging from 2003 to 2023. The studies represented a wide geographical distribution and diverse methodologies. The results identified 16 self-care behaviours: a higher focus of the included literature on self-care monitoring (60.65% of studies), followed by self-care management and self-care maintenance (each 16.39%). These behaviours ranged from regular blood testing to consulting healthcare providers and lifestyle changes. The results also highlighted the relationship between treatment satisfaction, self-efficacy, and adherence. Several studies emphasised the critical role of healthcare providers in influencing medication adherence. Furthermore, patient knowledge, quality of life, and psychological factors were identified as key elements affecting self-care behaviours. CONCLUSION: The review provides a comprehensive landscape of medication-related self-care behaviors among NVAF patients on OAC therapy. It underscores the predominance of self-care monitoring behaviours and the critical roles of healthcare providers, psychological factors, and patient knowledge in influencing these behaviours. The findings also highlight the necessity for an integrated, patient-centred approach to improving self-care and self-management in OAC treatment. Future research should focus on addressing the identified gaps, including the relative lack of studies on lifestyle modification, emotional well-being, and technology-assisted interventions. REGISTRATION: This review is part of a broader project and is documented at ClinicalTrials.gov (NCT05820854).

Effectiveness of nurse-led interventions versus usual care to manage hypertension and lifestyle behaviour: a systematic review and meta-analysis.

AIMS: This review aimed to investigate the effectiveness of nurse-led interventions vs. usual care on hypertension management, lifestyle behaviour, and patients' knowledge of hypertension and associated risk factors. METHODS: A systematic review with meta-analysis was conducted following Joanna Briggs Institute (JBI) guidelines. MEDLINE (Ovid), EmCare (Ovid), CINAHL (EBSCO), Cochrane library, and ProQuest (Ovid) were searched from inception to 15 February 2022. Randomized controlled trials (RCTs) examining the effect of nurse-led interventions on hypertension management were identified. Title and abstract, full text screening, assessment of methodological quality, and data extraction were conducted by two independent reviewers using JBI tools. A statistical meta-analysis was conducted using STATA version 17.0. RESULTS: A total of 37 RCTs and 9731 participants were included. The overall pooled data demonstrated that nurse-led interventions may reduce systolic blood pressure (mean difference -4.66; 95% CI -6.69, -2.64; I2 = 83.32; 31 RCTs; low certainty evidence) and diastolic blood pressure (mean difference -1.91; 95% CI -3.06, -0.76; I2 = 79.35; 29 RCTs; low certainty evidence) compared with usual care. The duration of interventions contributed to the magnitude of blood pressure reduction. Nurse-led interventions had a positive impact on lifestyle behaviour and effectively modified diet and physical activity, but the effect on smoking and alcohol consumption was inconsistent. CONCLUSION: This review revealed the beneficial effects of nurse-led interventions in hypertension management compared with usual care. Integration of nurse-led interventions in routine hypertension treatment and prevention services could play an important role in alleviating the rising global burden of hypertension. REGISTRATION: PROSPERO: CRD42021274900.

Effectiveness of alternative vs traditional exercises on cardiac rehabilitation program utilization in women with or at high risk of cardiovascular disease: a systematic review protocol.

OBJECTIVE: This review will evaluate the effectiveness of alternative vs traditional forms of exercise on cardiac rehabilitation program utilization and other outcomes in women with or at high risk of cardiovascular disease. INTRODUCTION: Exercise-based cardiac rehabilitation programs improve health outcomes in women with or at high risk of cardiovascular disease. However, such programs are underutilized worldwide, particularly among women. Some women perceive traditional gym-based exercise in cardiac rehabilitation programs (eg, typically treadmills, cycle ergometers, traditional resistance training) to be excessively rigorous and unpleasant, resulting in diminished participation and completion. Alternative forms of exercise such as yoga, tai chi, qi gong, or Pilates may be more enjoyable and motivating exercise options for women, enhancing engagement in rehabilitation programs. However, the effectiveness of these alternative exercises in improving program utilization is still inconsistent and needs to be systematically evaluated and synthesized. INCLUSION CRITERIA: This review will focus on randomized controlled trials of studies measuring the effectiveness of alternative vs traditional forms of exercise on cardiac rehabilitation program utilization as well as clinical, physiological, or patient-reported outcomes in women with or at high risk of cardiovascular disease. METHODS: The review will follow the JBI methodology for systematic reviews of effectiveness. Databases including MEDLINE (Ovid), CINAHL (EBSCOhost), Cochrane CENTRAL, Embase (Ovid), Emcare (Ovid), Scopus, Web of Science, LILACS, and PsycINFO (Ovid) will be searched. Two independent reviewers will screen articles and then extract and synthesize data. Methodological quality will be assessed using JBI's standardized instruments. GRADE will be used to determine the certainty of evidence. REVIEW REGISTRATION: PROSPERO CRD42022354996.

Implementation of patient education for patients with atrial fibrillation: nationwide cross-sectional survey and one-year follow-up.

AIMS: Clinical practice guidelines recommend patient education for patients with atrial fibrillation (AF) as a part of holistic care, however, clinical guidelines lack detailed specification on the content, structure, and delivery of AF education programmes. To examine the implementation of education for patients with AF in Denmark in relation to coverage, organization, and content. METHODS AND RESULTS: A cross-sectional survey was conducted from February to May 2021. The survey contained questions on the organization, delivery, and content of education for patients with AF from all 29 AF outpatient hospital sites in Denmark. The survey was conducted by email and telephone. One-year follow-up was done in May 2022 by email. Patient education was provided by healthcare professionals in 16 (55%) hospitals. Nurse workforce issues, management, non-prioritization, and lack of guidance for implementation were reasons for the absence of patient education in 13 (45%) hospitals. The structure of patient education differed in relation to group or individual teaching methods and six different education models were used. Content of the AF disease education was generally similar. At 1-year follow-up, another four hospitals reported offering patient education (69% in total). CONCLUSION: Initially, almost half of the hospitals did not provide patient education, but at 1-year follow-up, 69% of hospitals delivered patient education. Patient education was heterogeneous in relation to delivery, frequency, and duration. Future research should address individualized patient education that may demonstrate superiority in relation to quality of life, less hospital admissions, and increased longevity.

Small Airway Disease in Pre-Chronic Obstructive Pulmonary Disease with Emphysema: A Cross-Sectional Study.

Rationale: Small airway disease is an important pathophysiological feature of chronic obstructive pulmonary disease (COPD). Recently, "pre-COPD" has been put forward as a potential precursor stage of COPD that is defined by abnormal spirometry findings or significant emphysema on computed tomography (CT) in the absence of airflow obstruction. Objective: To determine the degree and nature of (small) airway disease in pre-COPD using microCT in a cohort of explant lobes/lungs. Methods: We collected whole lungs/lung lobes from patients with emphysematous pre-COPD (n = 10); Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I (n = 6), II (n = 6), and III/IV (n = 7) COPD; and controls (n = 10), which were analyzed using CT and microCT. The degree of emphysema and the number and morphology of small airways were compared between groups, and further correlations were investigated with physiologic measures. Airway and parenchymal pathology was also validated with histopathology. Measurements and Main Results: The numbers of transitional bronchioles and terminal bronchioles per milliliter of lung were significantly lower in pre-COPD and GOLD stages I, II, and III/IV COPD compared with controls. In addition, the number of alveolar attachments of the transitional bronchioles and terminal bronchioles was also lower in pre-COPD and all COPD groups compared with controls. We did not find any differences between the pre-COPD and COPD groups in CT or microCT measures. The percentage of emphysema on CT showed the strongest correlation with the number of small airways in the COPD groups. Histopathology showed an increase in the mean chord length and a decrease in alveolar surface density in pre-COPD and all GOLD COPD stages compared with controls. Conclusions: Lungs of patients with emphysematous pre-COPD already show fewer small airways and airway remodeling even in the absence of physiologic airway obstruction.

The impact of diabetes on mortality rates after lower extremity amputation.

OBJECTIVE: To assess the impact of diabetes, amputation level, sex and age on mortality rates after lower extremity amputation (LEA) in Belgium, and to assess temporal trends in one-year survival rates from 2009 to 2018. METHODS: Nationwide data on individuals who underwent minor and major LEA from 2009 to 2018 were collected. Kaplan-Meier survival curves were constructed. A Cox regression model with time-varying coefficients was used to estimate the likelihood of mortality after LEA in individuals with or without diabetes. Matched amputation-free individuals with or without diabetes were used for comparison. Time trends were analysed. RESULTS: Amputations 41,304 were performed: 13,247 major and 28,057 minor. Five-year mortality rates in individuals with diabetes were 52% and 69% after minor and major LEA, respectively (individuals without diabetes: 45% and 63%, respectively). In the first six postoperative months, no differences in mortality rates were found between individuals with or without diabetes. Later, hazard ratios (HRs) for mortality in individuals with diabetes (compared with no diabetes) after minor LEA ranged from 1.38 to 1.52, and after major LEA from 1.35 to 1.46 (all p ≤ 0.005). Among individuals without LEA, HRs for mortality in diabetes (versus no diabetes) were systematically higher compared to the HRs for mortality in diabetes (versus no diabetes) after minor and major LEA. One-year survival rates did not change for individuals with diabetes. CONCLUSIONS: In the first six postoperative months, mortality rates after LEA were not different between individuals with or without diabetes; later, diabetes was significantly associated with increased mortality. However, as HRs for mortality were higher in amputation-free individuals, diabetes impacts mortality less in the minor and major amputation groups relative to the comparison group of individuals without LEA.

Impact of diabetes on medical costs in the pre- and postoperative year of lower extremity amputations in Belgium.

AIMS: To compare the medical costs of individuals undergoing lower extremity amputation (LEA) in Belgium with those of amputation-free individuals. METHODS: Belgian citizens undergoing LEAs in 2014 were identified. The median costs per capita in euros for the 12 months preceding and following minor and major LEAs were compared with those of matched amputation-free individuals. RESULTS: A total of 3324 Belgian citizens underwent LEAs (2295 minor, 1029 major), 2130 of them had diabetes. The comparison group included 31,716 individuals. Amputation was associated with high medical costs (individuals with diabetes: major LEA €49,735, minor LEA €24,243, no LEA €2,877 in the year preceding amputation; €45,740, €21,445 and €2,284, respectively, in the post-amputation year). Significantly higher costs were observed in the individuals with (versus without) diabetes in all groups. This difference diminished with higher amputation levels. Individuals undergoing multiple LEAs generated higher costs (individuals with diabetes: €39,313-€89,563 when LEAs preceded index amputation; €46,629-€92,877 when LEAs followed index amputation). Individuals dying in the year after a major LEA generated remarkably lower costs. CONCLUSIONS: LEA-related medical costs were high. Diabetes significantly impacted costs, but differences in costs diminished with higher amputation levels. Individuals with multiple amputations generated the highest costs.