Improvement of shared decision making in integrated stroke care: a before and after evaluation using a questionnaire survey.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Illness perceptions of stroke survivors: Predictors and changes over time - A 1 year follow-up study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Value-Based Stroke Rehabilitation: Feasibility and Results of Patient-Reported Outcome Measures in the First Year After Stroke.

PURPOSE: Structured application of patient-reported outcome measures (PROMs) is a key element in Value Based Healthcare. This study aimed to evaluate the feasibility of a broad set of PROMs reflecting similar patient reported health domains as proposed within the International Standard Set of Patient-Centered Outcome Measures After Stroke within the first year after stroke. METHODS: The study included consecutive stroke patients admitted to inpatient or outpatient specialized rehabilitation. PROMs were administered upon admission, discharge (inpatients only), and at 3, 6, and 12 months. PROMs included: EuroQol 5 Dimensions (EQ-5D), Stroke Impact Scale (SIS), Stroke and Aphasia Quality of Life Scale (SAQOL-39NL), Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P), Hospital Anxiety and Depression Scale (HADS), and Fatigue Severity Scale (FSS). Feasibility was defined as participation, retention, and response rates. Paired t tests were conducted to analyze their changes over time. RESULTS: Of 485 inpatients and 189 outpatients who were invited, 291 (60.0%) and 82 (43.3%) participated, of whom 45 (15.5%) and 7 (8.5%) dropped out before 12 months, respectively. Two hundred seven (71.1%) and 71 (86.6%) of the inpatients and outpatients returned the questionnaires on all or all but one time points, respectively. Between admission and 12 months statistically significant improvements of PROMs addressing general health and quality of life (EQ-5D), psychiatric functioning (HADS), motor functioning (SIS mobility), and social functioning (USER-P, SIS communication) were seen. The SIS memory scale, the SAQOL-39NL and the FSS did not show any changes. CONCLUSIONS: Participation, retention, and response rates for a comprehensive set of PROMS for stroke in patients in rehabilitation were moderate to good, with clinical improvements seen until 1 year post stroke. The SAQOL-39NL and FSS did not demonstrate changes over time and cannot be recommended for repetitive measurements in this setting. By simplifying the set of questionnaires, participation and response rates may be further enhanced.

Attention needed for cognitive problems in patients after out-of-hospital cardiac arrest: an inventory about daily rehabilitation care.

AIM: Recent literature and Dutch guidelines for patients with out-of-hospital cardiac arrest (OHCA) recommend screening for cognitive impairments and referral to cognitive rehabilitation when needed. The aim of this study is to assess the uptake of these recommendations for OHCA patients. METHOD: An internet-based questionnaire was sent to 74 cardiologists and 143 rehabilitation specialists involved in rehabilitation of OHCA patients in the Netherlands. The questionnaire covered: background characteristics, availability and content of cognitive screening and rehabilitation, organisation of care, experienced need for an integrated care pathway including physical and cognitive rehabilitation, barriers and facilitators for an integrated care pathway. RESULTS: Forty-five questionnaires were returned (16 cardiologists and 29 rehabilitation doctors). Thirty-nine percent (n = 17) prescribed cognitive screening. Eighty-nine percent underscores an added value of an integrated care pathway. Barriers for an integrated care pathway included lack of knowledge, logistic obstacles, and poor cooperation between medical specialties. CONCLUSIONS: In the Netherlands, only a minority of cardiologists and rehabilitation specialists routinely prescribe some form of cognitive screening in OHCA patients, although the majority underscores the value of cognitive screening in OHCA patients in an integrated care pathway. The uptake of such a care pathway seems hindered by lack of knowledge and organisational barriers.

Adherence of stroke patients with an online brain training program: the role of health professionals' support.

Background Computer-based cognitive rehabilitation is used to improve cognitive functioning after stroke. However, knowledge on adherence rates of stroke patients is limited. Objective To describe stroke patients' adherence with a brain training program using two frequencies of health professionals' supervision. Methods This study is part of a randomized controlled trial comparing the effect of the brain training program (600 min playtime with weekly supervision) with a passive intervention in patients with self-perceived cognitive impairments after stroke. Patients randomized to the control condition were offered the brain training after the trial and received supervision twice (vs weekly in intervention group). Adherence was determined using data from the study website. Logistic regression analyses were used to examine the impact of supervision on adherence. Results 53 patients allocated to the intervention group (group S8; 64% male, mean age 59) and 52 patients who were offered the intervention after the trial (group S2; 59% male, mean age 59) started the brain training. The median playtime was 562 min (range 63-1264) in group S8 vs. 193 min (range 27-2162) in group S2 (p < 0.001, Mann Whitney U). Conclusions The overall adherence of stroke patients with a brain training was low and there are some implications that systematic, regular interaction with a supervisor can increase training adherence of stroke patients with a restitution-focused intervention performed at home.

The effects of an 8-week computer-based brain training programme on cognitive functioning, QoL and self-efficacy after stroke.

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.

Cognitive problems in patients in a cardiac rehabilitation program after an out-of-hospital cardiac arrest.

OBJECTIVE: Estimate prevalence of cognitive problems due to hypoxic brain injury in out-of-hospital cardiac arrest (OHCA) survivors referred for cardiac rehabilitation and association with quality of life as well as autonomy and participation. DESIGN: Prospective cohort study. METHOD/DESIGN: Consecutive OHCA patients. The Mini-Mental State Examination (MMSE), Cognitive Failures Questionnaire (CFQ) and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were administered 4 weeks after the OHCA. Cognitive problems were defined if MMSE <28, CFQ >32 or IQCODE >3.6. The Impact on Participation and Autonomy Questionnaire (IPAQ) (participation/autonomy), the SF-36 Health Survey (SF-36) (quality of life) and the Hospital Anxiety Depression Scale (HADS) (anxiety/depression) were administered. Correlations between cognitive problems and participation/autonomy and quality of life were calculated. RESULTS: 63 of 77 patients were male (82%), median age 59 years (range 15-84). MMSE median 29 (interquartile range 28-30), CFQ mean 20.9 (SD 9.4) and IQCODE mean 3.1 (SD 0.2). Eighteen patients (23%) scored positive for cognitive problems. Significant correlations were found between MMSE and IPAQ: autonomy inside (r = -0.38), family role (r = -0.26), autonomy outside (r = -0.32), social relations (r = -0.38) and social functioning (r = 0.32). MMSE was related to SF-36: social functioning (r = 0.32). The CFQ was related to IPAQ: autonomy outdoors (r = 0.29) and SF-36: bodily pain (r = -0.37), vitality (r = -0.25), mental health (r = -0.35) and role emotional (r = -0.40). The IQCODE was related to IPAQ: autonomy indoors (r = 0.26) and to SF-36: vitality (r = -0.33) and social functioning (r = -0.41). CONCLUSION: Twenty-three percent of the patients referred for cardiac rehabilitation showed cognitive problems. Associations were found between cognitive problems and several aspects of participation/autonomy and perceived quality of life.

High survival rate of 43% in out-of-hospital cardiac arrest patients in an optimised chain of survival.

AIMS: Survival to hospital discharge after out-of-hospital cardiac arrest (OHCA) varies widely. This study describes short-term survival after OHCA in a region with an extensive care path and a follow-up of 1 year. METHODS: Consecutive patients ≥16 years admitted to the emergency department between April 2011 and December 2012 were included. In July 2014 a follow-up took place. Socio-demographic data, characteristics of the OHCA and interventions were described and associations with survival were determined. RESULTS: Two hundred forty-two patients were included (73 % male, median age 65 years). In 76 % the cardiac arrest was of cardiac origin and 52 % had a shockable rhythm. In 74 % the cardiac arrest was witnessed, 76 % received bystander cardiopulmonary resuscitation and in 39 % an automatic external defibrillator (AED) was used. Of the 168 hospitalised patients, 144 underwent therapeutic procedures. A total of 105 patients survived until hospital discharge. Younger age, cardiac arrest in public area, witnessed cardiac arrest, cardiac origin with a shockable rhythm, the use of an AED, shorter time until return of spontaneous circulation, Glasgow Coma Scale (GCS) ≥13 during transport and longer length of hospital stay were associated with survival. Of the 105 survivors 72 survived for at least 1 year after cardiac arrest and 6 patients died. CONCLUSION: A survival rate of 43 % after OHCA is achievable. Witnessed cardiac arrest, cardiac cause of arrest, initial cardiac rhythm and GCS ≥13 were associated with higher survival.

Pirandello's analogy: a source for a better understanding of the social impact of stroke.

BACKGROUND: Suffering a stroke has major implications for the patient. To understand human suffering, one should understand society. Pirandello described society as a higher entity than the individual, thereby justifying human adaptability to society. We explore a qualitative finding that suggests that social trends may influence how stroke patients prioritize aspects of their rehabilitation. METHODS: We compare a contemporary patient's experience of stroke recovery with that of a fictional character from the works of Luigi Pirandello. Both patients had two main residual symptoms: hemiparesis and aphasia. RESULTS: The rehabilitation priorities of the two patients differed, and appeared to reflect the contemporaneous demands of society. Mobility was prioritized in 1910; communication was prioritized in 2010. However, essential aspects of 'being a stroke patient' remained unchanged; both patients retained a sense of self and both coped emotionally by being hopeful. CONCLUSIONS: We conclude that stroke patients respond to society's contemporaneous demands and expectations. Currently, society demands participation in a large social environment and this is reflected in stroke patients' priorities. This analogy could enable medical professionals to better understand the social impact of stroke, and consequently offer appropriate interventions to improve rehabilitation outcomes for individual patients.

Adenoviral-mediated gene transfer to the synovial tissue.

In various animal models gene transfer to the synovial tissue has been shown after intraarticular injection of adenoviral vectors. Safety of the transfer of therapeutic genes to the synovial tissue depends on multiple factors, including the mode of administration, the vector and the gene used, and the immune system of the host. In this article, data on the biodistribution and induction of inflammation after the intraarticular administration of adenoviral vectors are summarized and discussed. The ultimate goal of gene therapy will be the injection of a vector that has a specific target cell. Such a goal will require major improvements in the currently available delivery systems or the development of novel vectors. In this article new strategies are proposed in which gene transfer efficiency to the synovial tissue increases, whereas simultaneously the effect of neutralization of the adenoviral vector by the synovial fluid is circumvented.

Infection efficiency of type 5 adenoviral vectors in synovial tissue can be enhanced with a type 16 fiber.

OBJECTIVE: To obtain an adenoviral vector with increased infection efficiency in the synovial tissue compared with conventional vectors based on adenovirus serotype 5 (Ad5), without compromising the specificity of infection. METHODS: Coxsackie adenovirus receptor (CAR) expression was assessed in cultured synoviocytes. Chimeric adenoviruses based on Ad5 but carrying the DNA encoding the fiber of adenovirus from subgroup B (Adll, 16, 35) or D (Ad24, 28, 33, 45, or 47) were constructed and produced on PER.C6 cells. The gene transfer efficiency of these chimera was tested on cultured synoviocytes and peripheral blood mononuclear cells (PBMC). RESULTS: No surface expression of CAR protein was observed on synoviocytes. CAR messenger RNA expression of synoviocytes was found to be low. Of all fiber chimeric vectors tested, vectors carrying the fiber of Ad16 (Ad5.fib16) were most potent, yielding approximately150 times increased transgene expression in cultured synoviocytes compared with those of Ad5. Flow cytometry showed that the increase in transgene expression was caused by the transduction of higher percentages of synoviocytes and higher gene expression per synoviocyte. Experiments with 500 virus particles/cell of Ad5.GFP or Ad5.fib16.GFP resulted in an infection efficiency of 0.6% and 1% in PBMC and 43% and 76% in synoviocytes, respectively. CONCLUSION: Synoviocytes hardly express CAR, which hampers Ad5-mediated gene transfer. Ad5.fib16 is superior to Ad5 vectors for transducing synoviocytes, without compromising the specificity of infection. Our data suggest that Ad5.fib16-mediated gene transfer to synovial tissue improves the therapeutic window.

The influence of synovial fluid on adenovirus-mediated gene transfer to the synovial tissue.

OBJECTIVE: To determine the effect of synovial fluid (SF) from rheumatoid arthritis (RA) patients on adenovirus type 5 (Ad5)-mediated gene transfer to synoviocytes, and to explore new strategies for vector development based on the neutralization data obtained. METHODS: SF was derived from 63 randomly selected R4 patients. Ten samples were used to study the effect of SF on Ad5-mediated gene transfer in synoviocytes. IgG and <100-kd fractions were purified from these 10 SF, and their effect on gene transfer was determined. Neutralizing activity against wild-type Ad5 (wt-Ad5), wt-Ad26, wt-Ad34, wt-Ad35, and wt-Ad48 was tested in the SF from the remaining 53 patients. RESULTS: Seven of 10 SF samples inhibited Ad5-mediated gene transfer. Purified antibodies exhibited inhibition patterns similar to those seen with unfractionated SF. In 5 of 10 SF samples, low molecular weight fractions inhibited gene transfer at low dilutions. Neutralization of wt-Ad35 by SF from RA patients was less frequent than neutralization of other wt-Ad tested (4% versus 42-72%; n = 53). CONCLUSION: SF from 70% of the RA patients contained neutralizing antibodies that hamper Ad5-mediated gene transfer to synoviocytes. The activity of neutralizing antibodies may be circumvented in the majority of RA patients when vectors based on an Ad35 backbone are used.

The effect of promoter strength in adenoviral vectors in hyperplastic synovium.

OBJECTIVES: To compare the activity of the CytoMegaloVirus promoter (CMV) and the Major Late promoter (MLP) in synoviocytes in vitro and in vivo. To determine the phenotype of infected cells and the induction of inflammation. To investigate the effects of the cytomegalovirus (CMV) or major late (MLP) promoter on adenovirus-mediated reporter gene transduction of synoviocytes in vitro and in vivo. METHODS: After infection with adenoviral vectors harboring CMV- and MLP-driven luciferase and lacZ genes, gene expression was examined in cultured synoviocytes and in the synovium of rhesus monkeys with collagen-induced arthritis. Immunohistochemical staining for the macrophage-marker CD68 and lacZ expression was performed. Inflammation was scored in the synovial membrane of injected and non-injected joints. RESULTS: CMV-driven reporter gene expression was found to be 6 to 10 times higher than MLP-driven gene expression in both cultured synoviocytes and monkey synovium. Both CD68 positive and CD68 negative cells were lacZ positive. Inflammation in joints injected with CMV-driven adenoviral vectors was not higher than that in MLP-driven adenoviral vectors- or non-injected joints. CONCLUSION: These experiments show that the CMV promoter induces higher gene expression in synoviocytes than the MLP promoter. Both fibroblast-like and macrophage-like synoviocytes can be infected with adenoviral vectors. No deleterious effects of the CMV-promoter driven adenoviral vectors were observed.

Reliability and sensitivity to change of various measures of hand function in relation to treatment of synovitis of the metacarpophalangeal joint in rheumatoid arthritis.

OBJECTIVES: The reliability and discriminative capacity of hand function tests were studied in order to obtain tests suitable for the evaluation of local treatment of an arthritic metacarpophalangeal (MCP) joint. METHODS: To assess reliability, hand function tests were measured twice without local treatment of the MCP in 25 patients with rheumatoid arthritis (RA). The discriminative capacity of the hand function tests with respect to the results of intra-articular corticosteroid injection was assessed in 28 RA patients with synovitis of an MCP joint. Thereafter, a randomized, observer-blind treatment study was performed in 21 RA patients with synovitis of an MCP joint; 10 of the patients were treated. Results/Conclusions. This study showed that the efficacy of treatment of an MCP joint can be measured by several reliable and discriminative parameters: passive flexion, the Ritchie pain score, swelling, the Arthritis Impact Measurements Scales question about buttoning clothes, and visual analogue scale questions about the activity of the disease and swelling of the joint.

Feasibility of adenovirus-mediated nonsurgical synovectomy in collagen-induced arthritis-affected rhesus monkeys.

Gene transfer to synovial tissue by adenoviral vectors (Ad) was studied in vitro in cultured human synoviocytes and in vivo in seven primates with arthritis. Hyperplastic synovium was efficiently transduced with Ad.lacZ in vitro and in vivo in rhesus monkeys with collagen-induced arthritis, whereas chondrocytes were not transduced. Intraarticular injection of recombinant Ad harboring the luciferase gene showed the presence of reporter gene products only in Ad-injected joints. In addition, the feasibility of synovectomy by Ad harboring the herpes simplex virus thymidine kinase gene (tk) was studied. In vitro infection of synovium from rheumatoid arthritis patients with Ad.TK, followed by administration of ganciclovir, resulted in death of >90% of the synoviocytes. By mixing Ad.TK-infected with noninfected cells, it appeared that the presence of 10% infected synoviocytes resulted in the killing of more than 85% of the synoviocytes, demonstrating a substantial bystander effect. Intraarticular injection of Ad.TK in the knees of rhesus monkeys with arthritis, followed by treatment with ganciclovir for 14 days, resulted in increased apoptotic cell death in the synovium of Ad.TK-injected as compared with noninjected joints and ablation of the synovial lining layer. The procedure revealed no toxic side effects. These data suggest that nonsurgical synovectomy by tK gene therapy is feasible.

Stepwise intravenous infusion of apomorphine to determine the therapeutic window in patients with Parkinson's disease.

A new experimental strategy was applied to determine the concentration-effect relation and the therapeutic window of apomorphine in individual patients with Parkinson's disease. Apomorphine was administered by a stepwise intravenous infusion. The infusion rate was increased by 10 micrograms/kg/h every 20 minutes, up to 100 micrograms/kg/h or less when adverse effects occurred. Thereafter, the infusion rate was decreased in a stepwise fashion until zero. Plasma apomorphine concentrations were measured every 20 minutes. Clinical efficacy (tapping score and tremor), dyskinesia, and adverse effects were monitored at the same time. The mean clearance of apomorphine was 4.5 L/min (2.2 to 6.6 L/min). Of the 10 patients, 8 responded to apomorphine. The effects were quantal rather than continuous. Within each patient, the concentrations at onset and offset of effect generally were similar. Significant interpatient variability was observed with respect to minimal concentration for each of the effects. Clinical efficacy occurred at a mean minimal effective concentration (MEC) of 4.7 ng/mL (range 1.4 to 10.7 ng/mL). Dyskinesia was observed at a mean concentration of 8.5 ng/mL (range 2.7 to 20 ng/mL). This value was not significantly different from the MEC. The mean minimal toxic concentration was 16.7 ng/mL (8.5 to 24.5 ng/mL) and was significantly different from the mean MEC. In conclusion, the stepwise increase and decrease of the intravenous infusion rate is a suitable tool for the establishment of the concentration-effect relation of apomorphine in individual patients. The finding of a narrow therapeutic window, in which the onset concentrations vary from patient to patient, underlines the need for accurate and individualized dosing.