Assessment of diagnostic imaging technologies for cardiovascular disease

Cardiovascular disease is the leading cause of death in industrialized countries. In the Netherlands approximately 50,000 patients die each year from cardiovascular disease, which is 35% of all deaths 1. In the United States, this number is over 930,000 patients per year 2. Cardiovascular disease includes all diseases of the heart or blood vessels. This thesis concentrates on arterial stenosis in the cardiovascular system, specifically in the coronary arteries, the carotid arteries, the peripheral arteries, and the renal arteries. Arterial stenosis in these areas may lead to severe morbidity due to, for example, myocardial infarction, stroke, limb amputation, or renal dysfunction, and thus has an enormous impact on the quality of life of the patient and may lead to death3-6. Therefore, it is important to diagnose cardiovascular disease accurately, so that adequate treatment can be initiated

Transcranial direct current stimulation in post-stroke sub-acute aphasia: Study protocol for a randomized controlled trial

Background: Transcranial direct current stimulation (tDCS) is a promising new technique to optimize the effect of regular Speech and Language Therapy (SLT) in the context of aphasia rehabilitation. The present study focuses on the effect of tDCS provided during SLT in the sub-acute stage after stroke. The primary aim is to evaluate the potential effect of tDCS on language functioning, specifically on word-finding, as well as generalization effects to verbal communication. The secondary aim is to evaluate its effect on social participation and quality of life, and its cost-effectiveness. Methods: We strive to include 58 stroke patients with aphasia, enrolled in an inpatient or outpatient stroke rehabilitation program, in a multicenter, double-blind, randomized controlled trial with two parallel groups and 6 months' follow-up. Patients will participate in two separate intervention weeks, with a pause of 2 weeks in between, in the context of their regular aphasia rehabilitation program. The two intervention weeks comprise daily 45-minute sessions of word-finding therapy, combined with either anodal tDCS over the left inferior frontal gyrus (1 mA, 20 minutes; experimental condition) or sham-tDCS over the same region (control condition). The primary outcome measure is word-finding. Secondary outcome measures are verbal communication, social participation, quality of life, and cost-effectiveness of the intervention. Discussion: Our results will contribute to the discussion on whether tDCS should be implemented in regular aphasia rehabilitation programs for the sub-acute post-stroke population in terms of (cost-)effectiveness. Trial registration: Nederlands Trail Register: NTR4364. Registered on 21 February 2014

Accelerometric assessment of different dimensions of natural walking during the first year after stroke

Objectives: To describe the course of walking behaviour over a period of 1 year after stroke, using accelerometry, and to compare 1-year data with those from a healthy group. Design: One-year follow-up cohort study. Subjects: Twenty-three stroke patients and 20 age-matched healthy subjects. Methods: Accelerometer assessments were made in the participants' daily environment for 8 h/day during the 1st (T1), 12th (T2) and 48th (T3) weeks after stroke, and at one timepoint in healthy subjects. Primary outcomes were: percentage of time walking and upright (amount); mean duration and number of walking periods (distribution); step regularity and gait symmetry (quality); and walking speed. Results: Time walking, time upright, and number of walking bouts increased during T1 and T2 (p 0.30). Mean duration of walking periods showed no significant improvements (p > 0.30) during all phases. Step regularity, gait symmetry and gait speed showed a tendency to increase consistently from T1 to T3. At T3, amount and distribution variables reached the level of the healthy group, but significant differences remained (p < 0.02) in step regularity and gait speed. Conclusion: In this cohort, different outcomes of walking behaviour showed different patterns and levels of recovery, which supports the multi-dimensional character of gait

Outcome registry of early intensive neurorehabilitation in patients with disorders of consciousness: study protocol of a prospective cohort study

Background: Prolonged disorders of consciousness (PDOC) may occur after severe brain injury. Two diagnostic entities are distinguished within PDOC: unresponsive wakefulness syndrome (UWS, previously known as vegetative state) and minimally conscious state (MCS). Patients with PDOC may benefit from early intensive neurorehabilitation (EIN). In the Netherlands, the EIN programme is provided by one designated expert rehabilitation centre and forms the starting point of a dedicated chain of specialised rehabilitation and care for this group. This study project, called DOCTOR: Disorders of Consciousness; Treatment and Outcomes Registry, sets up a registry and systematically investigates multiple short- and long-term outcomes of patients with PDOC who receive EIN. Methods: Single-centre prospective cohort study with a 2-year follow-up period. Patients with PDOC due to acute brain injury who receive EIN, aged 16 years and older are included. Measurements will take place at start EIN, in week 5, 10, and at discharge from the EIN programme (duration = max 14 weeks) and at week 28, 40, 52, and 104 after admission to the EIN programme, following patients through the health-care chain. Outcome measures are the changes over time in level of consciousness, using the Coma Recovery Scale-Revised; the frequency and type of medical complications; the mortality rate; level of disability, including the level of motor, cognitive, behavioural and emotional functioning; participation; and quality of life. Secondary outcomes include self-efficacy of caregivers, caregivers’ strain and cost-effectiveness of the programme. Discussion: The DOCTOR study will provide insight in the recovery patterns and predictors of recovery for multiple outcomes in PDOC patients after following EIN. The results of the study will enable us to benchmark and improve EIN and the organisation of the health-care chain, both for patients with PDOC and for their families. Trial registration: Netherlands Trial Register, NL 8138. Retrospectively registered 6 November 2019

A meta-analysis comparing the prognostic accuracy of six diagnostic tests for predicting perioperative cardiac risk in patients undergoing major vascular surgery

OBJECTIVE: To evaluate the discriminatory value and compare the predictive performance of six non-invasive tests used for perioperative cardiac risk stratification in patients undergoing major vascular surgery. DESIGN: Meta-analysis of published reports. METHODS: Eight studies on ambulatory electrocardiography, seven on exercise electrocardiography, eight on radionuclide ventriculography, 23 on myocardial perfusion scintigraphy, eight on dobutamine stress echocardiography, and four on dipyridamole stress echocardiography were selected, using a systematic review of published reports on preoperative non-invasive tests from the Medline database (January 1975 and April 2001). Random effects models were used to calculate weighted sensitivity and specificity from the published results. Summary receiver operating characteristic (SROC) curve analysis was used to evaluate and compare the prognostic accuracy of each test. The relative diagnostic odds ratio was used to study the differences in diagnostic performance of the tests. RESULTS: In all, 8119 patients participated in the studies selected. Dobutamine stress echocardiography had the highest weighted sensitivity of 85% (95% confidence interval (CI) 74% to 97%) and a reasonable specificity of 70% (95% CI 62% to 79%) for predicting perioperative cardiac death and non-fatal myocardial infarction. On SROC analysis, there was a trend for dobutamine stress echocardiography to perform better than the other tests, but this only reached significance against myocardial perfusion scintigraphy (relative diagnostic odds ratio 5.5, 95% CI 2.0 to 14.9). CONCLUSIONS: On meta-analysis of six non-invasive tests, dobutamine stress echocardiography showed a positive trend towards better diagnostic performance than the other tests, but this was only significant in the comparison with myocardial perfusion scintigraphy. However, dobutamine stress echocardiography may be the favoured test in situations where there is valvar or left ventricular dysfunction

Inactive lifestyles and sedentary behavior in persons with chronic aneurysmal subarachnoid hemorrhage: Evidence from accelerometer-based activity monitoring

Background: Aneurysmal subarachnoid hemorrhage (a-SAH) is a potential life-threatening stroke. Because survivors may be at increased risk for inactive and sedentary lifestyles, this study evaluates physical activity (PA) and sedentary behavior (SB) in the chronic phase after a-SAH. Methods: PA and SB were objectively measured at six months post a-SAH with an accelerometer-based activity monitor, with the aim to cover three consecutive weekdays. Total time spent in PA (comprising walking, cycling, running and non-cyclic movement) and SB (comprising sitting and lying) was determined. Also, in-depth analyses were performed to determine the accumulation and distribution of PA and SB throughout the day. Binary time series were created to determine the mean bout length and the fragmentation index. Measures of PA and SB in persons with a-SAH were compared to those in sex- and age-matched healthy controls. Results: The 51 participants comprised 33 persons with a-SAH and 18 controls. None of the participants had signs of paresis or spasticity. Persons with a-SAH spent 105 min/24 h being physically active, which was 35 min/24 h less than healthy controls (p = 0.005). For PA, compared with healthy controls, the mean bout length was shorter in those with a-SAH (12.0 vs. 13.5 s, p = 0.006) and the fragmentation index was higher (0.053 vs. 0.041, p < 0.001). Total sedentary time during waking hours showed no significant difference between groups (514 min vs. 474 min, p = 0.291). For SB, the mean bout length was longer in persons with a-SAH (122.3 vs. 80.5 s, p = 0.024), whereas there was no difference in fragmentation index between groups (0.0032 vs 0.0036, p = 0.396). Conclusions: Persons with a-SAH are less physically active, they break PA time into shorter periods, and SB periods last longer compared to healthy controls. Since inactive lifestyles and prolonged uninterrupted periods of SB are independent risk factors for poor cardiovascular health, interventions seem necessary and should target both PA and SB. Study registration: Dutch registry number: NTR 2085

The six-minute walk test predicts cardiorespiratory fitness in individuals with aneurysmal subarachnoid hemorrhage

Background: Peak oxygen uptake (VO2peak) established during progressive cardiopulmonary exercise testing (CPET) is the “gold-standard” for cardiorespiratory fitness. However, CPET measurements may be limited in patients with aneurysmal subarachnoid hemorrhage (a-SAH) by disease-related complaints, such as cardiovascular health-risks or anxiety. Furthermore, CPET with gas-exchange analyses require specialized knowledge and infrastructure with limited availability in most rehabilitation facilities. Objectives: To determine whether an easy-to-administer six-minute walk test (6MWT) is a valid clinical alternative to progressive CPET in order to predict VO2peak in individuals with a-SAH. Methods: Twenty-seven patients performed the 6MWT and CPET with gas-exchange analyses on a cycle ergometer. Univariate and multivariate regression models were made to investigate the predictability of VO2peak from the six-minute walk distance (6MWD).

Diagnostic value of a ghrelin test for the diagnosis of GH deficiency after subarachnoid hemorrhage

Objective: To determine the diagnostic value of a ghrelin test in the diagnosis of GH deficiency (GHD) shortly after aneurysmal subarachnoid hemorrhage (SAH). Design: Prospective single-center observational cohort study. Methods: A ghrelin test was assessed after the acute phase of SAH and a GH-releasing hormone (GHRH)-arginine test 6 months post SAH. Primary outcome was the diagnostic value of a ghrelin test compared with the GHRH-arginine test in the diagnosis of GHD. The secondary outcome was to assess the safety of the ghrelin test, including patients' comfort, adverse events, and idiosyncratic reactions. Results: Forty-three survivors of SAH were included (15 males, 35%, mean age 56.6G11.7). Six out of 43 (14%) SAH survivors were diagnosed with GHD by GHRH-arginine test. In GHD subjects, median GH peak during ghrelin test was significantly lower than that of non-GHD subjects (5.4 vs 16.6, PZ0.002). Receiver operating characteristics analysis showed an area under the curve of 0.869. A cutoff limit of a GH peak of 15 mg/l corresponded with a sensitivity of 100% and a false-positive rate of 40%. No adverse events or idiosyncratic reactions were observed in subjects undergoing a ghrelin test, except for one subject who reported flushing shortly after ghrelin infusion. Conclusion: Owing to its convenience, validity, and safety, the ghrelin test might be a valuable GH provocative test, especially in the early phase of SAH

Pituitary dysfunction after aneurysmal subarachnoid haemorrhage: Course and clinical predictors-the HIPS study

Objective We describe the occurrence and course of anterior pituitary dysfunction (PD) after aneurysmal subarachnoid haemorrhage (SAH), and identify clinical determinants for PD in patients with recent SAH. Methods We prospectively collected demographic and clinical parameters of consecutive survivors of SAH and measured fasting state endocrine function at baseline, 6 and 14 months. We included dynamic tests for growth-hormone function. We used logistic regression analysis to compare demographic and clinical characteristics of patients with SAH with and without PD. Results 84 patients with a mean age of 55.8 (±11.9) were included. Thirty-three patients (39%) had PD in one or more axes at baseline, 22 (26%) after 6 months and 6 (7%) after 14 months. Gonadotropin deficiency in 29 (34%) patients and growth hormone deficiency (GHD) in 26 (31%) patients were the most common deficiencies. PD persisted until 14 months in 6 (8%) patients: G

Comparative effectiveness of surgery in traumatic acute subdural and intracerebral haematoma: study protocol for a prospective observational study within CENTER-TBI and Net-QuRe

INTRODUCTION: Controversy exists about the optimal treatment for patients with a traumatic acute subdural haematoma (ASDH) and an intracerebral haematoma/contusion (t-ICH). Treatment varies largely between different regions. The effect of this practice variation on patient outcome is unknown. Here, we present the protocol for a prospective multicentre observational study aimed at comparing the effectiveness of different treatment strategies in patients with ASDH and/or t-ICH. Specifically, the aims are to compare (1) an acute surgical approach to an expectant approach and (2) craniotomy to decompressive craniectomy when evacuating the haematoma. METHODS AND ANALYSIS: Patients presenting to the emergency room with an ASDH and/or an t-ICH are eligible for inclusion. Standardised prospective data on patient and injury characteristics, treatment and outcome will be collected on 1000 ASDH and 750 t-ICH patients in 60-70 centres within two multicentre prospective observational cohort studies: the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and Neurotraumatology Quality Registry (Net-QuRe). The interventions of interest are acute surgery, defined as surgery directly after the first CT at presentation versus late or no surgery and craniotomy versus decompressive craniectomy. The primary outcome measure is the Glasgow Outcome Score-Extended at 6 months. Secondary outcome measures include in-hospital mortality, quality of life and neuropsychological tests. In the primary analysis, the effect of treatment preference (eg, proportion of patients in which the intervention under study is preferred) per hospital will be analysed with random effects ordinal regression models, adjusted for casemix and stratified by study. Such a hospital-level approach reduces confounding by the indication. Sensitivity analyses will includ