Vascular remodelling is a multifactorial process that involves both adaptive and maladaptive changes of the vessel wall through, among others, cell proliferation and migration, but also apoptosis and ...necrosis of the various cell types in the vessel wall. Vascular remodelling can be beneficial, e.g. during neovascularization after ischaemia, as well as pathological, e.g. during atherosclerosis and aneurysm formation. In recent years, it has become clear that microRNAs are able to target many genes that are involved in vascular remodelling processes and either can promote or inhibit structural changes of the vessel wall. Since many different processes of vascular remodelling are regulated by similar mechanisms and factors, both positive and negative vascular remodelling can be affected by the same microRNAs. A large number of microRNAs has been linked to various aspects of vascular remodelling and indeed, several of these microRNAs regulate multiple vascular remodelling processes, including both the adaptive processes angiogenesis and arteriogenesis as well as maladaptive processes of atherosclerosis, restenosis and aneurysm formation. Here, we discuss the multifactorial role of microRNAs and microRNA clusters that were reported to play a role in multiple forms of vascular remodelling and are clearly linked to cardiovascular disease (CVD). The microRNAs reviewed are miR-126, miR-155 and the microRNA gene clusters 17-92, 23/24/27, 143/145 and 14q32. Understanding the contribution of these microRNAs to the entire spectrum of vascular remodelling processes is important, especially as these microRNAs may have great potential as therapeutic targets for treatment of various CVDs.
The global initiative for chronic obstructive lung disease (GOLD) 2020 emphasizes that there is only a weak correlation between FEV
, symptoms and impairment of the health status of patients with ...chronic obstructive pulmonary disease (COPD). Various studies aimed to identify COPD phenotypes by cluster analyses, but behavioral aspects besides smoking were rarely included.
The aims of the study were to investigate whether (i) clustering analyses are in line with the classification into GOLD ABCD groups; (ii) clustering according to Burgel et al. (Eur Respir J. 36(3):531-9, 2010) can be reproduced in a real-world COPD cohort; and (iii) addition of new behavioral variables alters the clustering outcome. Principal component and hierarchical cluster analyses were applied to real-world clinical data of COPD patients newly referred to secondary care (n = 155). We investigated if the obtained clusters paralleled GOLD ABCD subgroups and determined the impact of adding several variables, including quality of life (QOL), fatigue, satisfaction relationship, air trapping, steps per day and activities of daily living, on clustering.
Using the appropriate corresponding variables, we identified clusters that largely reflected the GOLD ABCD groups, but we could not reproduce Burgel's clinical phenotypes. Adding six new variables resulted in the formation of four new clusters that mainly differed from each other in the following parameters: number of steps per day, activities of daily living and QOL.
We could not reproduce previously identified clinical COPD phenotypes in an independent population of COPD patients. Our findings therefore indicate that COPD phenotypes based on cluster analysis may not be a suitable basis for treatment strategies for individual patients.
To stimulate the integration of chronic care across disciplines, the Netherlands has implemented single-disease management programmes (SDMPs) in primary care since 2010; for example, for COPD, type 2 ...diabetes mellitus, and cardiovascular diseases. These disease-specific chronic care programmes are funded by bundled payments. For chronically ill patients with multimorbidity or with problems in other domains of health, this approach was shown to be less fit for purpose. As a result, we are currently witnessing several initiatives to broaden the scope of these programmes, aiming to provide truly person-centred integrated care (PC-IC). This raises the question if it is possible to design a payment model that would support this transition. We present an alternative payment model that combines a person-centred bundled payment with a shared savings model and pay-for-performance elements. Based on theoretical reasoning and results of previous evaluation studies, we expect the proposed payment model to stimulate integration of person-centred care between primary healthcare providers, secondary healthcare providers, and the social care domain. We also expect it to incentivise cost-conscious provider-behaviour, while safeguarding the quality of care, provided that adequate risk-mitigating actions, such as case-mix adjustment and cost-capping, are taken.
Shared decision making (SDM) is at the core of policy measures for making healthcare person-centred. However, the context-sensitive nature of the challenges in integrated stroke care calls for ...research to facilitate its implementation. This before and after evaluation study identifies factors for implementation and concludes with key recommendations for adoption.
Data were collected at the start and end of an implementation programme in five stroke services (December 2017 to July 2018). The SDM implementation programme consisted of training for healthcare professionals (HCPs), tailored support, development of decision aids and a social map of local stroke care. Participating HCPs were included in the evaluation study: A questionnaire was sent to 25 HCPs at baseline, followed by 11 in-depth interviews. Data analysis was based on theoretical models for implementation and 51 statements were formulated as a result. Finally, all HCPs were asked to validate and to quantify these statements and to formulate recommendations for further adoption.
The majority of respondents said that training of all HCPs is essential. Feedback on consultation and peer observation are considered to help improve performance. In addition, HCPs stated that SDM should also be embedded in multidisciplinary meetings, whereas implementation in the organisation could be facilitated by appointed ambassadors. Time was not seen as an inhibiting factor. According to HCPs, negotiating patients' treatment decisions improves adherence to therapy. Despite possible cognitive or communications issues, all are convinced patients with stroke can be involved in a SDM-process. Relatives play an important role too in the further adoption of SDM. HCPs provided eight recommendations for adoption of SDM in integrated stroke care.
HCPs in our study indicated it is feasible to implement SDM in integrated stroke care and several well-known implementation activities could improve SDM in stroke care. Special attention should be given to the following activities: (1) the appointment of knowledge brokers, (2) agreements between HCPs on roles and responsibilities for specific decision points in the integrated stroke care chain and (3) the timely investigation of patient's preferences in the care process - preferably before starting treatment through discussions in a multidisciplinary meeting.
The 2013 GOLD classification system for COPD distinguishes four stages: A (low symptoms, low exacerbation risk), B (high symptoms, low risk), C (low symptoms, high risk) and D (high symptoms, high ...risk). Assessment of risk is based on exacerbation history and airflow obstruction, whatever results in a higher risk grouping. The previous system was solely based on airflow obstruction. Earlier studies compared the predictive performance of new and old classification systems with regards to mortality and exacerbations. The objective of this study was to compare the ability of both classifications to predict the number of future (total and severe) exacerbations and mortality in a different patient population, and to add an outcome measure to the comparison: lung function decline.
Patient-level data from the UPLIFT trial were used to analyze 4-year survival in a Weibull model, with GOLD stages at baseline as covariates. A generalized linear model was used to compare the numbers of exacerbations (total and severe) per stage. Analyses were repeated with stages C and D divided into substages depending on lung function and exacerbation history. Lung function decline was analysed in a repeated measures model.
Mortality increased from A to D, but there was no difference between B and C. For the previous GOLD stages 2-4, survival curves were clearly separated. Yearly exacerbation rates were: 0.53, 0.72 and 0.80 for stages 2-4; and 0.35, 0.45, 0.58 and 0.74 for A-D. Annual rates of lung function decline were: 47, 38 and 26 ml for stages 2-4 and 44, 48, 38 and 39 for stages A-D. With regards to model fit, the new system performed worse at predicting mortality and lung function decline, and better at predicting exacerbations. Distinguishing between the sub-stages of high-risk led to substantial improvements.
The new classification system is a modest step towards a phenotype approach. It is probably an improvement for the prediction of exacerbations, but a deterioration for predicting mortality and lung function decline.
ClinicalTrials.gov NCT00144339 (September 2, 2005).
Objectives. To evaluate the impact of adding a respiratory dimension (a bolt-on dimension) to the EQ-5D-5L health state valuations. Methods. Based on extensive regression and principal component ...analyses, 2 respiratory bolt-on candidates were formulated: R1, limitations in physical activities due to shortness of breath, and R2, breathing problems. Valuation interviews for the selected bolt-ons were performed with a representative sample from the Dutch general public using the standardized interview protocol and software of the EuroQol group. Hybrid models based on the combined time-tradeoff (TTO) and discrete choice experiment (DCE) data were estimated to assess whether the 5 levels of the respiratory bolt-on led to significant changes in utility values. Results. For each bolt-on candidate, slightly more than 200 valuation interviews were conducted. Mean TTO values and DCE choice probabilities for health states with a level 4 or 5 for the respiratory dimension were significantly lower compared with the same health states in the Dutch EQ-5D-5L valuation study without the respiratory dimension. Results of hybrid models showed that for the bolt-on “limitations in physical activities,” the utility decrements were significant for level 3 (–0.055), level 4 (–0.087), and level 5 (–0.135). For “breathing problems,” the utility decrements for the same levels were greater (–0.086, –0.219, and –0.327, respectively). Conclusions. The addition of each of the 2 respiratory bolt-ons to the EQ-5D-5L had a significant effect on the valuation of health states with severe levels for the bolt-on. The bolt-on dimension “breathing problems” showed the greatest utility decrements and therefore seems the most appropriate respiratory bolt-on dimension.
Cognitive impairment after stroke has a direct impact on daily functioning and quality of life (QoL) of patients and is associated with higher mortality and healthcare costs. The aim of this study ...was to determine the effect of a computer-based brain training programme on cognitive functioning, QoL and self-efficacy compared to a control condition in stroke patients. Stroke patients with self-perceived cognitive impairment were randomly allocated to the intervention or control group. The intervention consisted of an 8-week brain training programme (Lumosity Inc.®). The control group received general information about the brain weekly. Assessments consisted of a set of neuropsychological tests and questionnaires. In addition, adherence with trained computer tasks was recorded. No effect of the training was found on cognitive functioning, QoL or self-efficacy when compared to the control condition, except for very limited effects on working memory and speed. This study found very limited effects on neuropsychological tests that were closely related to trained computer tasks, but no transfers to other tests or self-perceived cognitive failures, QoL or self-efficacy. These findings warrant the need for further research into the value of computer-based brain training to improve cognitive functioning in the chronic phase after stroke.
To describe the illness perceptions (IP) of stroke patients in the first year post stroke; to identify patient clusters with comparable IP trajectories and determine their associations with health.
...This prospective study included consecutive stroke patients after medical rehabilitation. Three and 12 months post stroke they completed the Brief Illness Perception Questionnaire (B-IPQ) and questionnaires on physical and mental health. All eight IP and their changes over time were described. Clusters of patients with comparable IP trajectories were constructed by k-means clustering, with subsequent comparison of patient characteristics. Multivariable logistic regression analyses were conducted to determine the association between IP clusters and 12-month mental health.
Hundred-and-eighty-four patients were included (men n = 107 58.2%; mean age 61.1 SD 12.7 years). At 3 months, the scores of the IP coherence (mean 3.0, SD 2.3) and treatment control (mean 3.2, SD 2.5) were lowest (best), and consequences (mean 6.1, SD 2.8) and anticipated timeline (mean 6.0, SD 2.7) were highest (worst). At 12 months, the timeline and treatment control scores had significantly worsened. Three clusters of the trajectories of IP were identified, and designated as ‘favourable’, ‘average’, and ‘unfavourable’. The unfavourable cluster was significantly associated with worse physical and mental health at 3 months (unadjusted) and depressive symptoms at 12 months.
Stroke patients' IP partly changed between 3 and 12 months post stroke. Patients with an unfavourable IP trajectory had a higher chance of depressive symptoms at 12 months. Illness perceptions could be considered as an additional target of treatment.
•Illness perceptions of stroke patients changed in the first year post stroke.•Both physical and mental health were related to illness perceptions after stroke.•Favourable illness perceptions were associated with lower risk of depressive symptoms.•Illness perceptions may be an additional target of treatment for stroke patients.
Molecular precatalysts complexes (nBuCp)2ZrCl2 (Zr) and (η1:η5‐Me2NCH2CH2C5Me4)CrCl2 (Cr) have been successfully supported on silica nanoparticles, via a single support (SS) or a double support (DS) ...strategy. These catalyst systems have been successfully used to produce bimodal polyethylenes with an ultrahigh molecular weight polyethylene content in a single reactor. The SS and DS catalyst systems have been fully evaluated under an identical polymerization condition to assess the challenges in tailoring the molecular weight distribution. The results show that a detrimental interaction exists between Zr and Cr catalysts, part of the Cr catalyst species is deactivated during polymerization in the both DS and SS systems. The detrimental interaction in the DS system is reduced because the catalysts are supported on separate nanoparticles. But, surprisingly the two catalysts in the DS system are still able to “communicate” to each other via cocatalyst‐induced catalyst leaching or other potential reasons.
Bimodal polyethylenes with ultrahigh molecular weight polyethylene content are produced utilizing a combination of molecular catalysts, via two separate supportation strategies (single support and double support). The polymerization results show that predictive tailoring molecular weight and molecular weight distributions in a single reactor is challenging due to a combination of antagonistic interaction, varying reactivity ratios and kinetic profiles.
Background
Worldwide, chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic lung disease with considerable clinical and socioeconomic impact. Pharmacologic maintenance drugs ...(such as bronchodilators and inhaled corticosteroids) play an important role in the treatment of COPD. The cost effectiveness of these treatments has been frequently assessed, but studies to date have largely neglected the impact of treatment sequence and the exact stage of disease in which the drugs are used in real life.
Objective
We aimed to systematically review recently published articles that reported the cost effectiveness of COPD maintenance treatments, with a focus on key findings, quality and methodological issues.
Methods
We performed a systematic literature search in Embase, PubMed, the UK NHS Economic Evaluation Database (NHS-EED) and EURONHEED (European Network of Health Economics Evaluation Databases) and included all relevant articles published between 2011 and 2015 in either Dutch, English or German. Main study characteristics, methods and outcomes were extracted and critically assessed. The Quality of Health Economic Studies (QHES) instrument was used as basis for quality assessment, but additional items were also addressed.
Results
The search identified 18 recent pharmacoeconomic analyses of COPD maintenance treatments. Papers reported the cost effectiveness of long-acting muscarinic antagonist (LAMA) monotherapy (
n
= 6), phosphodiesterase (PDE)-4 inhibitors (
n
= 4), long-acting beta agonist/inhaled corticosteroid (LABA/ICS) combinations (
n
= 4), LABA monotherapy (
n
= 2) and LABA/LAMA combinations (
n
= 2). All but two studies were funded by the manufacturer, and all studies indicated favourable cost effectiveness; however, the number of quality-adjusted life-years (QALYs) gained was small. Less than half of the studies reported a COPD-specific outcome in addition to a generic outcome (mostly QALYs). Exacerbation and mortality rates were found to be the main drivers of cost effectiveness. According to the QHES, the quality of the studies was generally sufficient, but additional assessment revealed that most studies poorly represented the cost effectiveness of real-life medication use.
Conclusions
The majority of studies showed that pharmacologic COPD maintenance treatment is cost effective, but most studies poorly reflected real-life drug use. Consistent and COPD-specific methodology is recommended.
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