Advanced Chronic Disease Research Articles

Effectiveness of an in-home healthcare intervention for patients with advanced chronic respiratory disease

Effectiveness of an in-home healthcare intervention for patients with advanced chronic respiratory disease

Nebulized alteplase in coronavirus disease 2019 pneumonia: a case series

BackgroundMany patients with severe coronavirus disease 2019 pneumonia exhibit signs of microthrombosis. Previous studies discussed intravenous fibrinolytic agents as potential add-on therapy in these patients. Therefore, we propose the inhalative administration of fibrinolytics as a possible safer alternative.Case presentationThis case series describes five white male patients, aged 51–78 years, treated with off-label inhalation of alteplase between November and December 2020. All patients suffered from severe severe acute respiratory syndrome coronavirus 2 infection with respiratory failure. Pulmonary embolism was ruled out by pulmonary angiogram in computed tomography scans, and all patients showed signs of coronavirus disease 2019 pneumonia. Four patients improved clinically, while one patient with advanced chronic diseases died due to multiple organ failure. No directly associated adverse effects were observed following inhalation of alteplase.ConclusionThis case series warrants further attention to investigate inhalative alteplase as an additional treatment in patients with severe coronavirus disease 2019 infection.

Factors affecting ageism and depression levels in individuals aged 65 and over living in society

Abstract Background The aging process is perceived negatively by some people. This perception prevents/reduces the happiness that can be gained from the aging process. As a result, depressive symptoms may occur. Therefore, this study aimed to examine the factors affecting ageism and depression levels in individuals aged 65 and over living in society. Methods The sample of the research, which was conducted with a cross-sectional, descriptive design, consisted of 287 individuals aged 65 and over living in a neighborhood on the Anatolian side of Istanbul. Data were collected with socio-demographic form, Ageism Questionnaire and Yesavage Geriatric Depression Scale-15. T test, variance analysis and chi-square test were used to analyze the data. Ethical permissions were obtained. Results Moderate depression was found in 27.5% of individuals with a mean age of 70.80±5.42. Individuals scored below the average (18.48±8.14) on the ageism survey. Ageism scores were higher for men, those aged 85 and over, those with poor economic conditions, those with chronic diseases, those hospitalized in the last year, those with severe and moderate depression, and those who needed help with daily tasks (p < 0.05). A statistically significant difference was found between age groups, chronic disease, continuous medication use, hospitalization in the last year, working status, need for help with daily tasks, economic status and depression levels (p < 0.05). Ageism scores of those with severe and moderate depression were found to be high (F = 3.43;p=0.017). Conclusions Variables that are effective in ageism and depression are being aged 85 and over, having a poor economic situation, having a chronic disease, needing help with daily tasks, and receiving inpatient treatment in the last year. The results of this study show that more efforts and resources are needed within the scope of political and social services to reduce ageism in society and the level of depression in older individuals. Key messages • As the level of depression in elderly individuals increases, ageism increases. • Advanced age, economic status, chronic disease, hospitalization and dependence on daily tasks affect depression and ageism.

High Symptom Burden in Patients With Advanced Chronic or Prolonged Infectious Diseases: Not Only Pain.

The growing evidence of increased life expectancy in the future reveals the high relevance of frailty in patients with chronic-degenerative diseases; identification and management of symptoms may improve significantly their quality of life. The objective of our study was to assess the symptom burden in patients with advanced chronic or prolonged infectious diseases. A cross-sectional study was performed enrolling 88 patients, referred to palliative care consultation for chronic pain, and evaluated using the Edmonton Symptom Assessment System to define Total Symptom Distress Score (TSDS) and high symptom burden (HSB) when more than six symptoms along with Numerical Rating Scale ≥4 were present. All participants reported moderate to severe pain; in addition, 86 (97.7%) experienced a lack of well-being, 81 (92%) tiredness, 67 (76.1%) lack of appetite, 66 (75%) drowsiness, 66 (75%) depression, 56 (63.6%) anxiety, 49 (55.6%) nausea, and 39 (44.3%) shortness of breath. Forty-four patients (50%) had high TSDS, greater than 40.5, and presented lower Karnofsky Performance Scale (KPS) (median 40 vs. 70, p=0.0005), higher comorbidities (median 7 vs. 4, p=0.00001), and higher drug burden (median 9 vs. 6, p=0.0003) than those with low TSDS. Furthermore, considering symptom intensity, 40 patients (45.4%) had HSB and presented lower KPS (median 50 vs. 70, p=0.0005), higher comorbidities (median 7 vs. 4, p=0.00001), and higher drug burden (mean 9 vs. 6, p=0.01) compared to patients without HSB. Our population had an HSB, in addition to pain, revealing high frailty. A correct assessment of symptoms is, therefore, required to manage patients with chronic infectious diseases. In this setting, attention should be given to identifying patients at high risk of HSB through a correct diagnosis and effective management, which should be based on a multi-professional approach.

Experiences of patients with advanced chronic diseases and their associates with a structured palliative care nurse visit followed by an interprofessional case conference in primary care – a deductive-inductive content analysis based on qualitative interviews (KOPAL-Study)

BackgroundChronic, non-malignant diseases (CNMD) like chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) and dementia in advanced stages are very burdensome for patients. Timely palliative care with strong collaboration between general practitioners (GPs) and specialist palliative home care (SPHC) teams can reduce symptom burden, hospitalization rates, hospitalization costs and overall healthcare costs. The KOPAL-study on strengthening interprofessional collaboration for patients with palliative care needs tested the effect of an intervention comprising of a SPHC nurse assessment and an interprofessional case conference. This qualitative evaluative study explores patients’, proxies’ and their associates’ motivation to participate in the KOPAL-study and views on the (benefits of the) intervention.MethodsWe interviewed 13 male and 10 female patients as well as 14 proxies of patients with dementia and six associates of study participants using a semi-structured interview guide. All interviews were digitally recorded, transcribed verbatim and analysed with deductive-inductive qualitative content analysis.ResultsMotivation for participation was driven by curiosity, the aim to please the GP or to support research, respectively to help other patients. Few interviewees pointed out to have expected positive effects for themselves. The nurse visit was evaluated very positively. Positive changes concerning health care or quality of life were reported sparsely. Most study participants did not prepare for the SPHC nurse assessment. They had no expectations concerning potential benefits of such an assessment, the interdisciplinary case conference and an early integration of palliative care. The majority of interviewees reported that they did not talk about the nurse visit and the interprofessional case conference with their GPs.ConclusionOur results lead to the conclusion that SPHC nurses can serve as an advocate for the patient and thereby support the patients’ autonomy. GPs should actively discuss the results of the interdisciplinary case conference with patients and collaboratively decide on further actions. Patient participation in the interdisciplinary case conference could be another way to increase the effects of the intervention by empowering patients to not just passively receive the intervention.Trial registrationDRKS00017795 German Clinical Trials Register, 17Nov2021, version 05.

The experience of hope in dyads living with advanced chronic illness in Portugal: a longitudinal mixed-methods study

BackgroundHope is an important resource that helps patients and families thrive during difficult times. Although several studies have highlighted the importance of hope in different contexts, its specific manifestations in the realm of advanced chronic illness need further exploration. In this study, we sought to elucidate the intricate interplay between the construct of hope and the lived experience of advanced chronic illness within patient-caregiver dyads. Our objectives were (a) to explore the dyadic experience of hope as a changing dynamic over time for patients living with advanced chronic illness and their informal caregivers and (b) to evaluate variations of hope and symptom burden across time.MethodsWe conducted a longitudinal mixed-methods study with a convergent design between December 2020 and April 2021. Patients living with advanced chronic illness and informal caregivers participated as a dyad (n = 8). The Herth Hope Index scale was used to measure dyads' level of hope and the Edmonton Symptom Assessment System was used to measure patients’ symptom burden. Descriptive statistics were undertaken. A thematic analysis as described by Braun and Clarke was conducted to analyze dyadic interview data. Dyads' experience of hope was described by using the six dimensions of hope in the Model of Hope of Dufault and Martocchio.ResultsDyadic scores of hope and patients' symptom burden were stable over time. The constructs of hope in dyads included “Living one day at the time,” “Having inner force/strength,” and “Maintaining good health.” Changes in patterns of hope were captured for each dyad in their transition over time. Data converged for all dyads except one.ConclusionsThe findings of our study show a constant presence of hope even in the face of adversity. Healthcare professionals must find ways to promote hope in dyads of patients living with advanced chronic diseases. Nurses play a pivotal role; dyadic interviews should be promoted to create a safe space for both patients and informal caregivers in order to share experiences. More research is needed to address patients' and informal caregivers' hope in chronic illness because current hope-based interventions primarily target cancer diagnoses.

Risk Factors for Peripheral Vertigo

Background: Several risk factors influence the occurrence of peripheral vertigo, including advanced age, gender, and chronic metabolic diseases. This disease is not widely recorded in primary care due to the need for detection with simple examinations. Research on the association of several risk factors has yet to be reported. Objectives: To examine the relationship between age, gender, type 2 diabetes mellitus (DM2), and hypertension as risk factors for peripheral vertigo. Methods: This study is a case-control study that used consecutive sampling. The study sample consisted of 39 people: 19 in the case group and 20 in the control group. Data were obtained from 2 health centers and Diponegoro National Hospital, Semarang City. The data were obtained from history taking and physical examinations such as the Gans Sensory Organization Performance Test (SOP), past pointing test, and dysdiadokokinesia test. DM2 disease and hypertension were gathered from medical records. Data analysis used univariate analysis, bivariate analysis with chi-square, and logistic regression multivariate analysis. Results: Statistical test results concluded that hypertension is a risk factor for peripheral vertigo (p = 0.008; OR = 6.964; 95%CI = 1.657 - 29.263). Whereas age, gender, and DM2 were not risk factors, with p-values of 0.187, 0.378, and 0.417, respectively. Conclusion: The significant risk factor associated with the occurrence of peripheral vertigo was hypertension by 6.964 times.

Managing Pruritus in Advanced Chronic Disease.

Even though pruritus affects a significant number of people with chronic disease, it is rarely adequately treated. Drug therapies often rely on antihistamines, which have not shown to be beneficial in systemic pruritus. Hydroxyzine is frequently used to treat pruritus associated with kidney failure. Since Canada's sole manufacturer of hydroxyzine is no longer making this product, this is an ideal time to review the mechanisms of itch in advanced organ failure and the specific therapies that give relief. Although there is literature describing itch in patients with cancer, this article is limited to pathogenesis and treatment of systemic itch secondary to chronic, noncancer diseases. We summarize recent systematic reviews, although the studies included in these reviews are often small, and mostly cohort studies.

Implementing digitally enabled integrated healthcare

PurposeThe European funded project ADLIFE focuses on the application of digitally enabled integrated care for people with advanced chronic diseases. The implementation of the ADLIFE intervention required a robust practical tool that would be common to all pilot sites while allowing flexibility for local variations as well as the ability to adapt to unanticipated changes and problems.Design/methodology/approachThe ADLIFE project combined the concepts of implementation research and formative evaluation with the standardized operating procedures (SOP) methodology. The ADLIFE project significantly modified the SOP approach and used it as a means to not only to define and organize the tasks that needed to be performed in preparing and implementing the ADLIFE intervention but also to create a deeper understanding of the unique challenges faced in each site, as well as a method for achieving a consensus.FindingsThe ADLIFE SOPs were developed by a dedicated working group, and they encompassed the preparatory phase leading up to implementation of the intervention. The SOP was also the basis for monitoring the implementation, and this created a structure for the dynamic ongoing tactical and even strategic changes necessitated by local diversity as well as many unanticipated changes.Originality/valueThe SOP methodology was useful in supporting the development of the ADLIFE SOP, which was a consensus-based approach to guide for managing the implementation process, both at project and local levels. It has supported continuous improvement and learning throughout the project. Both the process and the SOP produced by the process can be readily adapted and used in other similar projects.

#1313 Dicumarinics and the direct thrombin or factor Xa inhibitors (NOAs) their usefulness in advanced chronic renal disease

Abstract Background and Aims Our population with advanced chronic kidney disease (ACKD), is more prone to thrombotic and hemorrhagic processes so the indication of anticoagulation before the appearance of atrial fibrillation (AF) is complex. Since AF is the most common cardiac arrhythmia, its main complications are thromboembolism and stroke. New treatments are being developed, such as the new oral anticoagulants (NOAs), but their safety in ACKD is still uncertain. To see anticoagulation needs, safety and major adverse effects (major or minor bleeding) in population with ACKD and taking dicumarinics or NOAs. Method Retrospective study of 234 patients followed in our ACKD practice, at least two revisions, with a mean follow-up 25.5 months, in which we recorded cause of anticoagulation, type and major adverse effects. Results 26% of patients have indication for anticoagulation (66 patients), of which 55 remain anticoagulated during follow-up (45% Dicumarinics, 44% NOAs). The indication for anticoagulation was 23% AF (56 patients) and 3% mechanical prostheses (7 patients). Table 1 shows the characteristics of the overall population and the comparison between anticoagulated patients with different types of anticoagulation and non-anticoagulated patients. Non-anticoagulated patients are younger and have less ischemic heart disease, with no differences in the non-anticoagulated population. Throughout follow-up, we found a higher incidence of bleeding with NOAs (compared to the rest) and higher mortality in patients with dicumarinics (compared to the rest). There were no differences in age, sex and ischemic heart disease between the two anticoagulant treatments. Conclusion Our CKD population has a high need for anticoagulation but also a high risk of bleeding. NOAs can be used in ACKD although they are associated with a higher incidence of bleeding than dicumarinics but lower mortality. More studies are needed to conclude which is the best approach for these patients.

#1591 Analysis of microvesicles and their relationship with oxidative stress as biomarkers of cardiovascular damage in chronic kidney disease

Abstract Background and Aims Chronic kidney disease (CKD) is associated with a higher incidence of cardiovascular diseases. These diseases are preceded by endothelial dysfunction and alterations in coagulation systems. One of the challenges of research in this field is the search for diagnostic and predictive biomarkers of cardiovascular pathology. Our hypothesis is that endothelial dysfunction and cardiovascular risk could be evidenced by the increased release of endothelial microvesicles (EMVs) and platelet microvesicles (PMVs), as well as a greater expression of tissue factor (TF). We also propose a relationship between the release of microvesicles and the oxidative stress observed in these patients. The aim of the study was to analyze the levels of MVEs and MVPs, the expression of FT and its relationship with pro-oxidant and antioxidant parameters as possible early biomarkers of cardiovascular and thrombotic risk in different stages and treatments of CKD. Method It is a cross-sectional study consisted of 116 patients (40 with advanced chronic disease (CKD), 40 undergoing hemodialysis (HD) and 36 undergoing peritoneal dialysis (PD)), as well as 17 healthy subjects (CT). Microvesicle phenotyping was performed by direct immunofluorescence and flow cytometry in plasma isolated by centrifugation from peripheral blood. The analysis of oxidative stress parameters was carried out by spectrophotometry, after isolation of plasma and mononuclear and polymorphonuclear leukocytes by means of a ficoll gradient. Results Patients on PD have higher plasma PMVs levels (p = 0.0005 vs ACKD and p = 0,0002 vs HD), while those on HD and PD have higher levels of EMVs compared to ACKD (p = 0,0001 and p = 0,0125, respectively). FT expression in PMVs is lower in HD (p < 0.0001 vs ACKD) and FT expression in EMVs is lower in HD and PD compared to ACKD (p = 0,0004 and p= 0.0033, respectively) (Fig. 1). Patients with CKD have a higher activity of pro-oxidant enzymes (XO, GPx), as well as high levels of lipid peroxidation by-products (TBARS-MDA) and lower activity of antioxidant enzymes (GSH, CAT, SOD) at the plasma and cellular level. A positive relationship has been observed between pro-oxidant parameters and the release of MVP and MVE, as well as the expression of FT (Table 1). Patients with cardiovascular events during the years of follow-up have higher levels of FT expressed in microvesicles, and long-term survival decreases in patients with elevated FT levels. Conclusion Patients with CKD have higher plasma levels of PMVs and EMVs and higher FT expression, related to a state of oxidative stress. These parameters could be considered as biomarkers for predicting, diagnosing, and prognostic cardiovascular events in CKD.

Exosomes in Atherosclerosis: Role in the Pathogenesis and Targets for Therapy.

Atherosclerotic cardiovascular disease (ASCVD) is an advanced chronic inflammatory disease and the leading cause of death worldwide. The pathological development of ASCVD begins with atherosclerosis, characterised by a pathological remodelling of the arterial wall, lipid accumulation and build-up of atheromatous plaque. As the disease advances, it narrows the vascular lumen and limits the blood, leading to ischaemic necrosis in coronary arteries. Exosomes are nano-sized lipid vesicles of different origins that can carry many bioactive molecules from their parental cells, thus playing an important role in intercellular communication. The roles of exosomes in atherosclerosis have recently been intensively studied, advancing our understanding of the underlying molecular mechanisms. In this review, we briefly introduce exosome biology and then focus on the roles of exosomes of different cellular origins in atherosclerosis development and progression, functional significance of their cargoes and physiological impact on recipient cells. Studies have demonstrated that exosomes originating from endothelial cells, vascular smooth muscle cells, macrophages, dendritic cells, platelets, stem cells, adipose tissue and other sources play an important role in the atherosclerosis development and progression by affecting cholesterol transport, inflammatory, apoptotic and other aspects of the recipient cells' metabolism. MicroRNAs are considered the most significant type of bioactive molecules transported by exosomes and involved in ASCVD development. Finally, we review the current achievements and limitations associated with the use of exosomes for the diagnosis and treatment of ASCVD.

Perspectives from patients with chronic lung disease on a telehealth-facilitated integrated palliative care model: a qualitative content analysis study

BackgroundChronic lung disease affects nearly 37 million Americans and often results in significant quality of life impairment and healthcare burden. Despite guidelines calling for palliative care (PC) integration into pulmonary care as a vital part of chronic lung disease management, existing PC models have limited access and lack scalability. Use of telehealth to provide PC offers a potential solution to these barriers. This study explored perceptions of patients with chronic lung disease regarding a telehealth integrated palliative care (TIPC) model, with plans to use findings to inform development of an intervention protocol for future testing.MethodsFor this qualitative study, we conducted semi-structured interviews between June 2021- December 2021 with patients with advanced chronic lung disease. Interviews explored experiences with chronic lung disease, understanding of PC, and perceived acceptability of the proposed model along with anticipated facilitators and barriers of the TIPC model. We analyzed findings with a content analysis approach.ResultsWe completed 20 interviews, with two that included both a patient and caregiver together due to patient preference. Perceptions were primarily related to three categories: burden of chronic lung disease, pre-conceived understanding of PC, and perspective on the proposed TIPC model. Analysis revealed a high level of disease burden related to chronic lung disease and its impact on day-to-day functioning. Although PC was not well understood, the TIPC model using a shared care planning approach via telehealth was seen by most as an acceptable addition to their chronic lung disease care.ConclusionsThese findings emphasize the need for a patient-centered, shared care planning approach in chronic lung disease. The TIPC model may be one option that may be acceptable to individuals with chronic lung disease. Future work includes using findings to refine our TIPC model and conducting pilot testing to assess acceptability and utility of the model.

Association of serum protein electrophoresis with clinicopathological characteristics and its prognostic relevance in chronic lymphocytic leukaemia patients.

To assess the association of serum protein electrophoresis abnormalities with clinicopathological characteristics, and its impact on overall survival in chronic lymphocytic leukaemia patients. The prospective study was conducted at Haematology and Immunology departments of the University of Health Sciences, Lahore, Pakistan, from 2019 to 2022, and comprised newly diagnosed chronic lymphocytic leukaemia patients. Lactate dehydrogenase and beta-2 microglobulin levels were measured by spectrophotometric principle, whereas serum protein electrophoresis was determined through commercially available capillary electrophoresis systems. Patients were followed up for 2 years post-diagnosis. Data was analysed using SPSS 21. Of the 50 patients, 40(80%) were males and 10(20%) were females. The overall mean age was 60±11 years. Serum protein electrophoresis was available for 40(80%) patients, and, among them, 12(30%) patients had abnormal levels, while 29(72.5%) required treatment. Overall response rate was 25(86.2%), and median two-year overall survival was 16.5 months (95% confidence interval: 10-20 months). Abnormal serum protein electrophoresis was significantly associated with Binet stage C, lower mean haemoglobin levels and higher median levels of lactate dehydrogenase and beta-2 microglobulin (p<0.05)). Regarding overall survival, the survival curves of chronic lymphocytic leukaemia patients with normal and abnormal serum protein electrophoresis status differed significantly (p=0.04). Abnormal serum protein electrophoresis could be considered a surrogate marker for advanced chronic lymphocytic leukaemia disease.

(090) The Relationship Between C-Reactive Protein and Total Testosterone in Aging Men: Findings from the Baltimore Longitudinal Study of Aging

Abstract Introduction Elevated C-Reactive Protein (CRP) and testosterone deficiency are associated with advanced age and chronic inflammatory diseases, such as cancer, diabetes, and cardiovascular disease. Testosterone decreases inflammation through several mechanisms, and testosterone replacement therapy (TRT) has been shown to lower CRP levels in aging, hypogonadal men. While cross-sectional studies have shown an inverse relationship between CRP and total testosterone (TT) levels, mixed findings have been reported when individual components of metabolic syndrome are considered. We hypothesized that men with testosterone deficiency will have high levels of CRP. Objective We evaluated the relationship between CRP and TT levels in men from 2004-2018 using the Baltimore Longitudinal Study of Aging and specifically attempted to determine if low androgen status is associated with a high inflammatory profile independent of comorbidities. Methods Male participants with serum TT level measured during two separate visits &amp;gt;3 years apart were included in our cohort. CRP, High-Density Lipoprotein (HDL) and Triglyceride levels were collected via blood specimens. Comorbidity data were documented at each visit. Panel regression was used to analyze the relationship of a series of independent variables collected in pooled cross-sectional observations over time with a dependent variable for modeling. Results A total of 347 patients were included in this study (mean age = 69 ± 15, average follow up time = 6.7 ± 3.2 years). Participants had a median CRP level of 1.0 mg/dL and a median TT level of 446 ng/dL. On univariable analysis TT and HDL levels were associated with a decline in CRP, while BMI, congestive heart failure (CHF), Diabetes, and Triglycerides were associated with increased CRP. Age was not associated with CRP. On multivariable analysis, we found that increasing TT level was associated with a decline in CRP levels, independent of comorbidities (p = 0.018; Table 1). BMI was associated with a significant increase in CRP (p = 0.001, Table 1). Age, CHF, Diabetes, HDL, and Triglycerides were not significant predictors of CRP on multivariable analysis. Conclusions Lower levels of serum total testosterone are associated with an increased CRP in older men. Given the importance of CRP in pathogenesis of chronic disease, we highlight the potential benefits of restoring testosterone levels in older, hypogonadal men via TRT. Disclosure No.

Evaluation of Sterify Gel as an Adjunctive Treatment to Scaling and Root Planing in Promoting Healing of Periodontal Pockets: A Split-Mouth Randomized Controlled Trial.

Periodontal disease is a common infectious disease that leads to the destruction of tooth-supporting structures. Current treatments, such as scaling and root planing (SRP), have limitations in deep and complex pockets, and antibiotic use carries the risk of resistance. Sterify Gel, a medical device composed of polyvinyl polymers, hydroxytyrosol, nisin, and magnesium ascorbyl phosphate, offers a new approach to periodontal care. This study aims to evaluate the safety and efficacy of Sterify Gel as an adjunctive treatment to SRP in promoting the healing of periodontal pockets. The study includes 34 patients with moderate to advanced chronic periodontal disease. Randomization assigned one site for SRP alone (control) and the other site for SRP with Sterify Gel (treatment). Periodontal parameters were evaluated at baseline, 1, 2, and 3 months after treatment bacterial contamination was assessed through quantitative PCR at baseline and 3 months after treatment. Statistical analysis was conducted using ANOVA and Wilcoxon test. Treatment with Sterify Gel and SRP demonstrated significant improvements in pocket depth, gingival recession, and clinical attachment level compared with SRP alone. Bleeding and plaque indexes, pain perception, tooth mobility, and furcations showed no significant differences between the two groups. The treatment group showed a reduction in bacterial contamination at 3 months. Sterify Gel in combination with SRP shows the potential for improving periodontal health by promoting healing and reducing periodontal pockets. It may offer benefits in preventing bacterial recolonization and reducing reliance on antibiotics.

Study design of the VenaSeal Spectrum Program: Two randomized controlled trials and one single-arm prospective study of a cyanoacrylate closure system to treat early to advanced chronic venous disease

Background/ObjectiveChronic venous disease (CVD) affects >25% of adults in developed countries. It is usually a progressive disease; if left untreated, can lead to advanced disease such as venous ulceration. The VenaSeal Spectrum Program compares the VenaSeal closure system (VenaSeal) to the global standards of care for CVD: endothermal ablation and surgical stripping. It also investigates VenaSeal's usefulness for patients with venous leg ulcers (VLUs). A key component of this clinical program was to measure and quantify patient satisfaction with treatments related to discomfort, healing time, and effectiveness, which often has been overlooked in CVD research. This article describes the rationale and design of the VenaSeal Spectrum Program for patients with CVD. MethodsVenaSeal Spectrum is a prospective, postmarket, clinical trial program reporting outcomes from the periprocedural period through 5 years after treatment with VenaSeal. VenaSeal Spectrum has enrolled 506 participants at 32 sites in 10 countries requiring treatment for symptomatic Clinical, Etiological, Anatomical, and Pathophysiological Classification (CEAP) 2-6 CVD involving the truncal saphenous vein(s). The program is composed of three studies. Two randomized controlled trials compare VenaSeal ablation with either surgical stripping or endovenous thermal ablation in patients with symptomatic CEAP 2-5 disease. A single-arm prospective study investigates participants with active VLUs (CEAP 6) treated with VenaSeal. The unique primary end points for both randomized trials include both periprocedural and postprocedural patient treatment satisfaction measured by a new questionnaire (VenousTSQ) at 30 days post procedure and elimination of clinically relevant superficial truncal reflux in the target vein at index procedure. The primary end point for the VLU study is time to ulcer healing through 12 months. Secondary end points, which are more familiar to clinicians in this disease space, include time to return to work, complication rates, patient-reported outcome measures, and closure rates. ConclusionsVenaSeal Spectrum is a rigorously designed clinical study program with a large study population and unique patient-centric end points after treatment with VenaSeal for early to advanced symptomatic CVD. The studies report on the safety, effectiveness, and patient experience outcomes including two new primary end points assessing the specific needs of patients with venous insufficiency from the periprocedural period through 5-year follow-up.

Long-term culture of patient-derived mammary organoids in non-biogenic electrospun scaffolds for identifying metalloprotein and motor protein activities in aging and senescence.

We recently identified TMEM230 as a master regulator of the endomembrane system of cells. TMEM230 expression is necessary for promoting motor protein dependent intracellular trafficking of metalloproteins for cellular energy production in mitochondria. TMEM230 is also required for transport and secretion of metalloproteinases for autophagy and phagosome dependent clearance of misfolded proteins, defective RNAs and damaged cells, activities that decline with aging. This suggests that aberrant levels of TMEM230 may contribute to aging and regain of proper levels may have therapeutic applications. The components of the endomembrane system include the Golgi complex, other membrane bound organelles, and secreted vesicles and factors. Secreted cellular components modulate immune response and tissue regeneration in aging. Upregulation of intracellular packaging, trafficking and secretion of endosome components while necessary for tissue homeostasis and normal wound healing, also promote secretion of pro-inflammatory and pro-senescence factors. We recently determined that TMEM230 is co-regulated with trafficked cargo of the endomembrane system, including lysosome factors such as RNASET2. Normal tissue regeneration (in aging), repair (following injury) and aberrant destructive tissue remodeling (in cancer or autoimmunity) likely are regulated by TMEM230 activities of the endomembrane system, mitochondria and autophagosomes. The role of TMEM230 in aging is supported by its ability to regulate the pro-inflammatory secretome and senescence-associated secretory phenotypein tissue cells of patients with advanced age and chronic disease. Identifying secreted factors regulated by TMEM230 in young patients and patients of advanced age will facilitate identification of aging associated targets that aberrantly promote, inhibit or reverse aging. Ex situ culture of patient derived cells for identifying secreted factors in tissue regeneration and aging provides opportunities in developing therapeutic and personalized medicine strategies. Identification and validation of human secreted factors in tissue regeneration requires long-term stabile scaffold culture conditions that are different from those previously reported for cell lines used as cell models for aging. We describe a 3 dimensional (3D) platform utilizing non-biogenic and non-labile poly ε-caprolactonescaffolds that supports maintenance of long-term continuous cultures of human stem cells, in vitro generated 3D organoids andpatient derived tissue. Combined with animal component free culture media, non-biogenic scaffolds are suitable for proteomic and glycobiological analyses to identify human factors in aging. Applications of electrospun nanofiber technologies in 3D cell culture allow for ex situ screening and the development of patient personalized therapeutic strategies and predicting their effectiveness in mitigating or promoting aging.

A qualitative analysis of the key contextual factors for the scaling-up of the ADLIFE toolbox in the Basque Health Service

Introduction: The translation of new digital solutions in different settings requires a preliminary analysis of contextual factors. The results might contribute to the development of strategies addressing barriers, for a successful implementation.&#x0D; ADLIFE is an EU funded project to improve the quality of life of older people with advanced chronic diseases by providing integrated personalised care via a toolbox including innovative digital solutions. The contextual factors of the participating organizations were evaluated prior to implementing this toolbox to identify the most relevant ones for the translation of this innovation action into routine practice.&#x0D; To structure this evaluation process, a bespoke framework for implementation assessment was developed, based on the Health Information System evaluation framework HOT-fit and the Consolidated Framework for Implementation Research (CFIR). These frameworks provide a structured and systematic way to identify constructs influencing the implementation of ADLIFE.&#x0D; This work presents the analysis of the contextual factors that would influence the uptake and effectiveness of ADLIFE tools in the Basque Health Service.&#x0D; Methods: Semi-structured interviews were conducted with different stakeholders before the implementation of the ADLIFE toolbox. A standardized set of questions was utilized, based on the main dimensions of the developed framework (human, organization, technology).&#x0D; These interviews were conducted online. They were recorded, transcribed, pseudonymized and subsequently analyzed using qualitative content analysis. These analyses were conducted using the software MAXQDA.&#x0D; Results: A total of 9 interviews were conducted: 2 primary care physicians, 2 specialized care physicians, 2 nurses, 2 IT staff and a manager.&#x0D; Through the implementation of the ADLIFE toolbox, interviewees expect improvements in communication between professionals and with patients, as well as facilitation of patient empowerment.&#x0D; Training about the new systems and time to get used to them were considered essential, which would help to overcome the digital gap that currently influences the lack of adherence to this type of intervention.&#x0D; Finally, direct linkage between the existing and the new systems were considered key to motivate professionals to participate and to facilitate the integration of patient care.&#x0D; Discussion and conclusions: The scaling up of the ADLIFE toolbox in the Basque Health Service requires it to be integrated into the digital systems currently used for the management of the Electronic Health Record. ADLIFE can serve to promote an improvement, not only in quality of life, but also in the quality of care, provided that professionals who care for these patients are involved.&#x0D; This knowledge will help to establish the most effective strategies to facilitate the intervention in the Basque Health Service.&#x0D; Acknowledgements&#x0D; We are grateful for the participation of the professionals who were interviewed.&#x0D; ADLIFE (GA 875209) received funding from the EU Horizon 2020. The authors thank all partners within ADLIFE.&#x0D;

Actioning usability study findings in the development of the ADLIFE integrated care digital tools.

Introduction: The ADLIFE project aims to improve the quality of life of older people with advanced chronic diseases by providing integrated intelligent personalised care via a digitally enabled holistic and integrated supportive care ICT Toolbox. The two interlinked user-facing tools are firstly, a Personalised Care Plan Management Platform (PCPMP) used by healthcare professionals; and secondly, a Patient Empowerment Platform (PEP) that patients and their informal caregivers use to promote patient self-management. &#x0D; The impact of the ADLIFE digital tools will be explored in a 12-month pilot study conducted across 7 clinical sites in 6 countries to evaluate their impact on a range of health-related, implementation and socio-economic outcomes.&#x0D; The development of digital tools needs to be done in continuous collaboration with target end-users. Feedback from prototype testing with typical user scenarios is crucial to identify any remaining issues to resolve ahead of the deployment of such tools. We present the findings from a pre-deployment usability study conducted on the ADLIFE Toolbox.&#x0D; Methods: Pilot sites recruited 3-5 participants for their feedback on the PCPMP and PEP tools. Usability data was collected using a standardised Questionnaire for User Interface Satisfaction (QUIS), administered online, following a training workshop and testing by the participants. One site collected feedback via a Patient and Public Involvement (PPI) approach for the PEP tool as an option for the activity timeline. The questionnaire responses were analysed to identify the key areas of improvement. The analysis includes a standard scoring system giving an indication of users’ satisfaction with each facet of interest. These scores identify specific features of the ADLIFE tools that have lower usability scores, allowing useful improvements to be made before deployment in the main ADLIFE pilot study. Additional free text comments are used to complement the QUIS scores and provide greater depth of understanding around specific usability issues. PPI responses were analysed separately as the group did not test the tool directly.&#x0D; Results: 13 responses were received for PCPMP and 18 for PEP. Overall, the study participants (excluding 10 PPI participants) scored both tools above average, with scores over 66% on average in all questionnaire categories (scores of over 6 out of 9, average score on this scale is 4.5). Some areas of usability scored lower, such as task progression and highlighting where input is required. Together with comments elaborating on scores given, those areas are being assessed further for prioritising updates to the tools and also to be considered in the study planning, such as training materials and communication channels. The PPI feedback provided insight into how ADLIFE tools can fit within the wider context of healthcare and technology. &#x0D; Conclusions: The usability studies have provided an opportunity to get feedback from participants similar to the ADLIFE study participants and make improvements to the ADLIFE tools, training and communication ahead of the pilot study start.&#x0D; Acknowledgements: ADLIFE has received funding from the EU Horizon 2020 research and innovation programme under grant agreement no. 875209. The authors thank all partners within ADLIFE for their cooperation and valuable contribution.