Cost-Effectiveness of a Cardiac Rehabilitation Program Specifically Designed for Patients With Obesity Within the OPTICARE XL Randomized Controlled Trial.

OBJECTIVE: To assess the cost-effectiveness of a cardiac rehabilitation (CR) program specifically designed for cardiac patients with obesity vs standard CR. DESIGN: Cost-effectiveness analysis based on observations in a randomized controlled trial. SETTING: Three regional CR centers in the Netherlands. PARTICIPANTS: Cardiac patients (N=201) with obesity (BMI≥30 kg/m2) referred to CR. INTERVENTIONS: Participants were randomized to a CR program specifically designed for patients with obesity (OPTICARE XL; N=102) or standard CR. OPTICARE XL included aerobic and strength exercise and behavioral coaching on diet and physical activity during 12 weeks, followed by a 9-month after-care program with "booster" educational sessions. Standard CR consisted of a 6- to 12-week aerobic exercise program, supplemented with cardiovascular lifestyle education. MAIN OUTCOME MEASURES: An economic evaluation, with an 18-month time horizon, in terms of quality-adjusted life years (QALYs) and costs from the societal perspective was performed. Costs were reported in 2020 Euros, discounted at a 4% annual rate, and health effects were discounted at a 1.5% annual rate. RESULTS: OPTICARE XL CR and standard CR resulted in comparable health gain per patient (0.958 vs 0.965 QALYs, respectively; P=.96). Overall, OPTICARE XL CR saved costs (-€4542) compared with the standard CR group. The direct costs for OPTICARE XL CR were higher than for standard CR (€10,712 vs €9951), whereas indirect costs were lower (€51,789 vs €57,092), but these differences were not significant. CONCLUSIONS: This economic evaluation showed no differences between OPTICARE XL CR and standard CR in health effects and costs in cardiac patients with obesity.

Novel advances in cardiac rehabilitation : Position paper from the Working Group on Preventive Cardiology and Cardiac Rehabilitation of the Netherlands Society of Cardiology.

Cardiac rehabilitation (CR) has evolved as an important part of the treatment of patients with cardiovascular disease. However, to date, its full potential is fairly underutilised. This review discusses new developments in CR aimed at improving participation rates and long-term effectiveness in the general cardiac population. It consecutively highlights new or challenging target groups, new delivery modes and new care pathways for CR programmes. These new or challenging target groups include patients with atrial fibrillation, obesity and cardiovascular disease, chronic coronary syndromes, (advanced) chronic heart failure with or without intracardiac devices, women and frail elderly patients. Also, the current evidence regarding cardiac telerehabilitation and loyalty programmes is discussed as new delivery modes for CR. Finally, this paper discusses novel care pathways with the integration of CR in residual risk management and transmural care pathways. These new developments can help to make optimal use of the benefits of CR. Therefore we should seize the opportunities to reshape current CR programmes, broaden their applicability and incorporate them into or combine them with other cardiovascular care programmes/pathways.

The scientific basis for secondary prevention of coronary artery disease: recent contributions from the Netherlands.

While the beneficial effects of secondary prevention of cardiovascular disease are undisputed, implementation remains challenging. A gap between guideline-mandated risk factor targets and clinical reality was documented as early as the 1990s. To address this issue, research groups in the Netherlands have performed several major projects. These projects address innovative, multidisciplinary strategies to improve medication adherence and to stimulate healthy lifestyles, both in the setting of cardiac rehabilitation and at dedicated outpatient clinics. The findings of these projects have led to changes in prevention and rehabilitation guidelines.

Recommendations on how to provide cardiac rehabilitation services during the COVID-19 pandemic.

The ongoing coronavirus disease 2019 (COVID-19) crisis is having a large impact on acute and chronic cardiac care. Due to public health measures and the reorganisation of outpatient cardiac care, traditional centre-based cardiac rehabilitation is currently almost impossible. In addition, public health measures are having a potentially negative impact on lifestyle behaviour and general well-being. Therefore, the Working Group of Cardiovascular Prevention and Rehabilitation of the Dutch Society of Cardiology has formulated practical recommendations for the provision of cardiac rehabilitation during the COVID-19 pandemic, by using telerehabilitation programmes without face-to-face contact based on current guidelines supplemented with new insights and experiences.

Cardiac telerehabilitation as an alternative to centre-based cardiac rehabilitation.

Multidisciplinary cardiac rehabilitation (CR) reduces morbidity and mortality and increases quality of life in cardiac patients. However, CR utilisation rates are low, and targets for secondary prevention of cardiovascular disease are not met in the majority of patients, indicating that secondary prevention programmes such as CR leave room for improvement. Cardiac telerehabilitation (CTR) may resolve several barriers that impede CR utilisation and sustainability of its effects. In CTR, one or more modules of CR are delivered outside the environment of the hospital or CR centre, using monitoring devices and remote communication with patients. Multidisciplinary CTR is a safe and at least equally (cost-)effective alternative to centre-based CR, and is therefore recommended in a recent addendum to the Dutch multidisciplinary CR guidelines. In this article, we describe the background and core components of this addendum on CTR, and discuss its implications for clinical practice and future perspectives.

Patients who do not complete cardiac rehabilitation have an increased risk of cardiovascular events during long-term follow-up.

BACKGROUND: Cardiac rehabilitation (CR) has favourable effects on cardiovascular mortality and morbidity. Therefore, it might reasonable to expect that incomplete CR participation will result in suboptimal patient outcomes. METHODS: We studied the 914 post-acute coronary syndrome patients who participated in the OPTImal CArdiac REhabilitation (OPTICARE) trial. They all started a 'standard' CR programme, with physical exercises (group sessions) twice a week for 12 weeks. Incomplete CR was defined as participation in <75% of the scheduled exercise sessions. Patients were followed-up for 2.7 years, and the incidence of cardiac events was recorded. Major adverse cardiac events (MACE) included all-cause mortality, non-fatal myocardial infarction and coronary revascularisation. RESULTS: A total of 142 (16%) patients had incomplete CR. They had a higher incidence of MACE than their counterparts who completed CR (11.3% versus 3.8%, adjusted hazard ratio [aHR] 2.86 and 95% confidence interval [CI] 1.47-5.26). Furthermore, the incidence of any cardiac event, including MACE and coronary revascularisation, was higher (20.4% versus 11.0%, aHR 1.54; 95% CI 0.98-2.44). Patients with incomplete CR were more often persistent smokers than those who completed CR (31.7% versus 11.5%), but clinical characteristics were similar otherwise. CONCLUSION: Post-ACS patients who did not complete a 'standard' 12-week CR programme had a higher incidence of adverse cardiac events during long-term follow-up than those who completed the programme. Since CR is proven beneficial, further research is needed to understand the reasons why patients terminate prematurely.

Modern precipitation of hydrogenetic ferromanganese minerals during on-site 15-year exposure tests.

Redox-sensitive metallic elements, Mn and Fe, are oxidized in deep sea waters and form abundant ferromanganese crusts and nodules on the world's ocean floors at ultraslow rates of growth. This process of oxidation and the mechanism of precipitation are yet unknown. In this paper, the results of the first successful, long-term, on-site experiment of mineral precipitation that ascertains modern, ongoing hydrogenetic deposition of oxide materials from normal seawaters at water depths of 900-4500 m of geologically active and inactive environments are presented. We succeeded in the in-situ precipitation experiment on the sea floor and characterized the precipitates using high-resolution and submicron-scale chemical, mineralogical, and structural analyses. The installed artificial plates of glass, ceramics, and plastic yielded spread-out particles of sizes varying from one to a few micrometers in diameter, of coccoid-like irregular shapes, with a maximum of 1,000-10,000 individual particles/mm2/year after 12-15 years of exposure. The results indicated a continuous substantial growth of the hydrogenetic minerals if both Mn and Fe are supplied to the bottom waters. The mineralogical, chemical, and structural properties of the precipitates are similar to those of the natural precipitates on the seabed that are made up of hydrogenetic ferromanganese crusts and nodules, together with settling sediments, suspended hydrothermal particles, or microbial precipitates from cultivated Mn-oxidizing bacteria. Our work presents new realistic insight into proposed genetic models of marine hydrogenetic ferromanganese deposits in modern diverse ocean environments.

Supraventricular tachycardia and the menstrual cycle.

•the influence of the menstrual cycle on the occurrence of arrhythmia is still understudied.•Episodes of arrhythmia might occur more frequently in the premenstrual phase.•Taking the menstrual cycle into account when scheduling diagnostic tests might lead to more accurate diagnoses.

Cardiac rehabilitation in patients who underwent primary percutaneous coronary intervention for acute myocardial infarction: determinants of programme participation and completion.

BACKGROUND: Hospital length of stay after acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (pPCI) has reduced, resulting in more limited patient education during admission. Therefore, systematic participation in cardiac rehabilitation (CR) has become more essential. We aimed to identify patient-related factors that are associated with participation in and completion of a CR programme. METHODS: We identified 3,871 consecutive AMI patients who underwent pPCI between 2003 and 2011. These patients were linked to the database of Capri CR, which provides dedicated, multi-disciplinary CR. 'Participation' was defined as registration at Capri CR within 6 months after pPCI. CR was 'complete' if a patient undertook the final exercise test. RESULTS: In total, 1,497 patients (39%) were registered at Capri CR. Factors independently associated with CR participation included age (<50 vs. >70 year: odds ratio (OR) 7.0, 95% confidence interval (CI) 5.1-9.6), gender (men vs. women: OR 1.9, 95% CI 1.3-1.8), index diagnosis (ST-elevation myocardial infarction [STEMI] vs. non-ST-elevation myocardial infarction [NSTEMI]: OR 2.4, 95% CI 2.0-2.7) and socio-economic status (high vs. low: OR 2.0, 95% CI 1.6-2.5). The model based on these factors discriminated well (c-index 0.75). CR programme completion was 80% and was inversely related with diabetes, current smoking and previous MI. The discrimination of the model based on these factors was poor (c-index 0.59). CONCLUSIONS: Only a minority of AMI/pPCI patients participated in a CR programme. Completion rates, however, were better. Increased physician and patient awareness of the benefits of CR are still needed, with focus on the elderly, women and patients with low socio-economic status.

OPTImal CArdiac REhabilitation (OPTICARE) following Acute Coronary Syndromes: Rationale and design of a randomised, controlled trial to investigate the benefits of expanded educational and behavioural intervention programs.

The majority of cardiac rehabilitation (CR) referrals consist of patients who have survived an acute coronary syndrome (ACS). Although major changes have been implemented in ACS treatment since the 1980s, which highly influenced mortality and morbidity, CR programs have barely changed and only few data are available on the optimal CR format in these patients. We postulated that standard CR programs followed by relatively brief maintenance programs and booster sessions, including behavioural techniques and focusing on incorporating lifestyle changes into daily life, can improve long-term adherence to lifestyle modifications. These strategies might result in improved (cardiac) mortality and morbidity in a cost-effective fashion. In the OPTImal CArdiac REhabilitation (OPTICARE) trial we will assess the effects of two advanced and extended CR programs that are designed to stimulate permanent adaption of a heart-healthy lifestyle, compared with current standard CR, in ACS patients. We will study the effects in terms of cardiac risk profile, levels of daily physical activity, quality of life and health care consumption.

Flow patterns and preferred sites of intimal thickening in bypass-grafted arteries .

AIM: In bypass-grafted arteries, anastomotic intimal hyperplasia develops more markedly at the distal junction than the proximal one. It is likely that it arises from the difference in flow patterns at these two sites. Therefore we have studied the relationship between the flow patterns and precise locations of wall thickening specific to the particular vessel. METHODS: In total 30 bypass-grafting procedures were carried out on the femoral arteries of dogs with 10 autologous common carotid arteries and 20 saphenous veins. The vessels were harvested at 3 months after operation, and precise locations of intimal thickening and characteristics of the flow such as flow patterns and distributions of fluid velocity and wall shear stress were studied in detail. RESULTS: At the proximal anastomosis, a large recirculation zone was formed only at the inlet of the partially or totally occluded host artery, whereas at the distal anastomosis, it was formed at both the floor of the host artery and the toe of the bypass in most vessels, and the former was connected to the latter, extending the region of disturbed flow to lateral walls of the host artery. Wall thickening was found mainly in these regions occupied with slow secondary and recirculation flows where wall shear stress was very low. CONCLUSION: The flow at the distal anastomosis is more disturbed and complex than that at the proximal anastomosis. This difference in flow pattern that determine the region of low wall shear stress might explain why intimal hyperplasia develop more markedly at the distal junction.

Improving guideline adherence for cardiac rehabilitation in the Netherlands.

BACKGROUND: In 2004, the Netherlands Society of Cardiology released the current guideline on cardiac rehabilitation. Given its complexity and the involvement of various healthcare disciplines, it was supplemented with a clinical algorithm, serving to facilitate its implementation in daily practice. Although the algorithm was shown to be effective for improving guideline adherence, several shortcomings and deficiencies were revealed. Based on these findings, the clinical algorithm has now been updated. This article describes the process and the changes that were made. METHODS: The revision consisted of three phases. First, the reliability of the measurement instruments included in the 2004 Clinical Algorithm was investigated by evaluating between-centre variations of the baseline assessment data. Second, based on the available evidence, a multidisciplinary expert advisory panel selected items needing revision and provided specific recommendations. Third, a guideline development group decided which revisions were finally included, also taking practical considerations into account. RESULTS: A total of nine items were revised: three because of new scientific insights and six because of the need for more objective measurement instruments. In all revised items, subjective assessment methods were replaced by more objective assessment tools (e.g. symptom-limited exercise instead of clinical judgement). In addition, four new key items were added: screening for anxiety/depression, stress, cardiovascular risk profile and alcohol consumption. CONCLUSION: Based on previously determined shortcomings, the Clinical Algorithm for Cardiac Rehabilitation was thoroughly revised mainly by incorporating more objective assessment methods and by adding several new key areas.

Transcriptional silencing of ETS-1 efficiently suppresses angiogenesis of pancreatic cancer.

In this study, we addressed the hypothesis that transcriptional suppression of erythroblastosis virus E26 oncogene homolog 1 (ETS-1) is an efficient therapeutic approach to pancreatic adenocarcinoma by investigating the effect of ETS-1 suppression in human pancreatic cancer cells. We accomplished this by using an adenoviral vector encoding only the DNA-binding domain of wild-type ETS-1 (ETS-1 dominant negative, ETS-1-DN). ETS-1-DN decreases ETS-1-binding by competing for its binding to DNA. Adenoviral-mediated transfer of ETS-1-DN (adenoviral ETS-1-DN construct, AdETS-1-DN) into pancreatic tumor cell lines did not affect their proliferation rate in vitro but did significantly inhibit their in vivo growth in nude mice. Furthermore, to test the efficacy of ETS-1-DN in vivo, we injected the AdETS-1-DN into established human pancreatic adenocarcinomas grown in nude mice. This treatment significantly reduced tumor size as compared to saline injection, without any detectable side effects. Microvessel density in mouse xenografts displayed significantly lower values in tumors in which ETS-1 was downregulated. In addition, expression of the ETS-1-DN in the pancreatic cancer cells resulted in downregulation of urokinase-type plasminogen activator (u-PA) and metalloproteinase-1 (MMP-1) expression. Taken together, these data suggest that transcriptional inactivation of ETS-1 is able to significantly affect angiogenesis and growth of pancreatic cancer. This effect may be due in part to downregulation of MMP-1 and u-PA expression. Our results suggest that ETS-1-DN is a promising candidate for antiangiogenic gene therapy in pancreatic cancer.

Oncolytic replication-competent adenovirus suppresses tumor angiogenesis through preserved E1A region.

An adenovirus (Adv) retaining normal E1A but lacking the 55 kDa E1B protein replicates preferentially in TP53-deficient cancer cells including pancreatic cancer cell lines, resulting in the oncolysis of the tumor. When tumor cells are exposed to hypoxia, hypoxia-inducible factor-1alpha (HIF-1alpha) is stabilized and activated to promote the transcription of several genes such as vascular endothelial growth factor (VEGF), but in the presence of E1A hypoxia-induced VEGF m-RNA synthesis is inhibited by E1A binding to p300. In this study, we demonstrated that the cancer cells infected with a mutant Adv in which the p300 binding site in E1A was partially deleted induced a higher expression level of VEGF as compared to those of Adv with normal E1A. An immunoprecipitation study for E1A confirmed that mutant E1A had a reduced binding capacity for p300. Although the expressions of HIF-1alpha m-RNA were almost the same in both cancer cells infected with the mutant Adv and those with the wild Adv, the amount of HIF-1alpha protein in cancer cells infected with the wild E1A Adv was lower than in those infected with the mutant E1A type Adv. In vivo, in contrast to the angiogenesis treated with mutant E1A, wild-E1A inhibited tumor angiogenesis significantly. These results suggested that E1A suppressed the production of VEGF and inhibited tumor angiogenesis by binding with p300, resulting in the inhibition of the HIF-1alpha-mediated transcription of genes through binding to HRE. This study demonstrates, for the first time, the effect of an oncolytic replication-competent Adv in inhibiting tumor angiogenesis.

Antiangiogenic activity of BAI1 in vivo: implications for gene therapy of human glioblastomas.

Glioblastomas are the most common primary brain tumors in adults. These tumors exhibit a high degree of vascularization, and malignant progression from astrocytoma to glioblastoma is often accompanied by increased angiogenesis and the upregulation of vascular endothelial growth factor and its receptors. In this study, we investigated the in vivo antiangiogenic and antitumor effects of brain-specific angiogenesis inhibitor 1 (BAI1) using human glioblastoma cell lines. Glioblastoma cells were transduced with an adenoviral vector encoding BAI1 (AdBAI1), and Northern and Western blot analyses, respectively, demonstrated BAI1 mRNA and protein expression in the transduced tumor cells. Using an in vivo neovascularization assay, we found that angiogenesis surrounding AdBAI1-transduced glioblastoma cells transplanted into transparent skinfold chambers of SCID mice was significantly impaired compared to control treated cells. Additionally, in vivo inoculation with AdBAI1 of established subcutaneous or intracerebral transplanted tumors significantly impaired tumor growth and promoted increased mouse survival. Morphologically, the tumors exhibited signs of impaired angiogenesis, such as extensive necrosis and reduced intratumoral vascular density. Taken together, these data strongly indicate that BAI1 may be an excellent gene therapy candidate for the treatment of brain tumors, especially human glioblastomas.

New strategy for acute necrotizing pancreatitis: Continuous Regional Arterial Infusion (CRAI) therapy.

Acute pancreatitis is an autodigestive disease, of which protease inhibition has been the focus of experimental and clinical research. Different from Europe and the United States, protease inhibitors are often applied in the treatment of acute pancreatitis in Japan. However, in clinical settings, the effect of protease inhibitors on acute pancreatitis is still controversial. Continuous Regional Arterial Infusion (CRAI) of protease inhibitors and antibiotics therapy were developed in Japan and it has been demonstrated that CRAI therapy has beneficial effects on severe acute necrotizing pancreatitis. In the Japanese clinical guidelines for the treatment of acute pancreatitis, published in 2003, CRAI therapy is still classified as a special therapy. However, a Randomized Controlled Trial for CRAI therapy has started and CRAI therapy is expected to become a new standard therapy for severe acute pancreatitis. CRAI therapy is aimed at preventing the progression of pancreatic inflammation and pancreatic infection. CRAI therapy can decrease the mortality rate and the frequency of pancreatic infection in severe acute pancreatitis, but it should be started as soon as possible after the onset of acute pancreatitis.

Irradiated pancreatic cancer cells undergo both apoptosis and necrosis, and could be phagocytized by dendritic cells.

The interaction of immature dendritic cells (DC) with irradiated pancreatic cancer cells was examined. Flow cytometric analysis using annexin V and propidium iodide revealed that ionizing radiation (25-35 Gy X-ray) induced both apoptosis and necrosis in pancreatic cancer cell lines. After irradiation, PK-1 and Panc-1 cells were likely to undergo necrosis, whereas MIAPaCa-2 cells underwent apoptosis. When DiO-stained immature DCs were co-incubated with DiI-stained irradiated MIAPaCa-2, it was observed under fluorescent microscopy that DCs phagocytized dead tumor cells as early as 4 h after co-incubation. The DCs' phagocytosis of irradiated tumor cells was also confirmed by flow cytometry. These results suggest that irradiated pancreatic cancer cells, which undergo both apoptosis and necrosis, could be a good source of tumor-associated antigens for cross-presentation by DCs.

Dynamics of microbial populations and strong selection for Cycloclasticus pugetii following the Nakhodka oil spill.

Microbial population changes were monitored immediately after the Nakhodka oil spill accident in January 1997 at the heavily oil-contaminated Mikuni coast along the Sea of Japan. The total cell number was almost stable for one year at 2-5 x 10(5) cells mL(-1), while the relative occurrence of culturable heterotrophs and degraders of oil components such as C-heavy oil, kerosene, and n-tetradecane varied, showing a maximum (>50% of the total) immediately following the accident. Gene amplification and phylogenetic analysis of a dilution culture using C-heavy oil as the sole carbon and energy source revealed that one of the predominant oil degraders at the oil-contaminated coast in 2 weeks after the accident closely resembled the aromatic hydrocarbon decomposer Cycloclasticus pugetii. Microbial community composition in oil-contaminated seawater was estimated at the molecular level using newly developed oligonucleotide probes, probe wash-off curve estimation, and quantitative fluorescence dot-blot hybridization techniques. At two different oil-polluted sites, harbor and intertidal regions, the C. pugetii group was estimated to make up 23-25% of the total Bacteria population, followed by the aliphatic hydrocarbon decomposer Alcanivorax borkumensis, which formed 4-7% of the Bacteria. In incubation experiments using floated oil slick and indigenous microbes collected at the harbor, oil degradation activities were enhanced by the addition of both organic and inorganic nutrients. Significant decreases were found in aromatic and aliphatic hydrocarbon fractions: 54-60% and 22-24% in 2 weeks to 68-77% and 23-32% in 2 months, respectively.

Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis.

The brain-specific angiogenesis inhibitor 1 gene has been isolated in an attempt to find fragments with p53 "functional" binding sites. As reported herein and by others, brain-specific angiogenesis inhibitor 1 expression is present in some normal tissues, but is reduced or lost in tumour tissues. Such data and its particular structure prompted the hypothesis that brain-specific angiogenesis inhibitor 1 may act as a mediator in the local angiogenesis balance. We herein demonstrate that brain-specific angiogenesis inhibitor 1 over-expression suppresses tumour angiogenesis, delaying significantly the human tumour growth in immunodeficient mice. The inhibitory effect of brain-specific angiogenesis inhibitor 1 was documented using our intravital microscopy system, strongly implicating brain-specific angiogenesis inhibitor 1 as a mediator in the control of tumour angiogenesis. In contrast, in vitro tumour cell proliferation was not inhibited by brain-specific angiogenesis inhibitor 1 transfection, whereas some level of cytotoxicity was assessed for endothelial cells. Immunohistochemical analysis of tumour samples confirmed a reduction in the microvessel density index in brain-specific angiogenesis inhibitor 1-overexpressing tumours. At messenger level, moderate changes could be detected, involving the down-regulation of vascular endothelial growth factor and collagenase-1 expression. Furthermore, brain-specific angiogenesis inhibitor 1 expression that was lost in a selection of human cancer cell lines could be restored by wild-type p53 adenoviral transfection. Brain-specific angiogenesis inhibitor 1 should be considered for gene therapy and development of efficient drugs based on endogenous antiangiogenic molecules.

Early microcirculatory derangement in mild and severe pancreatitis models in mice.

An in vivo microscopic technique was used to clarify the increase in microvascular permeability and enhanced leukocyte-endothelium interaction of pancreatic microcirculation in experimental pancreatitis of differing severity. Using bovine albumin fluorescein isothiocyanate (FITC) and carboxyfluorescein diacetate succinimidyl ester (CFDASE) as tracers, the change in permeability and the behavior of leukocytes in the acinar microcirculation were quantified during the initial 1, 2, 6, and 12h after the induction of caerulein pancreatitis in mice. Cold stress was added to produce the severe model. It was revealed that the early microcirculatory changes in the pancreas of caerulein pancreatitis included the increased permeability of endothelial lining and an accumulation of extravasated fluid in the perilobular space, which were more severe if cold stress was added. A decrease in flow velocity was also noted 2h after the onset of severe pancreatitis. Leukocyte adherence to the endothelial cells was not observed during the first 12h in either model of severity. In contrast, observation of the hepatic microcirculation revealed a significant number of adherent leukocytes 2h after the induction of severe pancreatitis. These results suggest that during the early course of acute pancreatitis, leukocyte adherence in the pancreatic microcirculation is a secondary event following the increase in pancreatic vascular permeability.