Amsterdam, NL, Aug. 14, 2018 – Stroke remains a leading cause of adult disability, and the global burden of stroke continues to grow with devastating consequences for patients, families, and caregivers. In this special issue of NeuroRehabilitation leading international experts on stroke rehabilitation provide theoretical and practical insights into the steps necessary to push beyond merely compensatory training and onto a level of recovery that is satisfactory for patients.
“Stroke rehabilitation is at a crossroads,” explains Guest Editor Richard Harvey, MD, Professor, Physical Medicine and Rehabilitation and Physical Therapy and Human Movement Sciences, Northwestern University Feinberg School of Medicine, and Clinical Chair, Brain Innovation Center, Wesley and Suzanne Dixon Stroke Chair, The Shirley Ryan Ability Lab, Chicago, IL, USA. “This issue of NeuroRehabilitation explores novel concepts and approaches to the rehabilitation of stroke that will help point the direction for the next wave of neurorehabilitation research.”
A promising area of research is the use of biomarkers to predict motor recovery and outcomes after stroke. Cathy M. Stinear, PhD, of the Department of Medicine, University of Auckland, Auckland, New Zealand, and colleagues, consider how algorithms to predict motor recovery and outcomes after stroke might be implemented in clinical practice.
“Since 2011 there have been eight large randomized controlled trials of motor rehabilitation that recruited all participants within 30 days of stroke. However, none were able to detect a benefit of the tested intervention,” notes Dr. Stinear. “Using biomarkers to select and stratify patients in rehabilitation trials could increase the sensitivity of trials to intervention effects, which might be particularly important for detecting these effects against the background of recovery experienced by most patients during the initial days and weeks after stroke.”
Biomarkers of the functional and structural integrity of the corticomotor system can predict recovery from motor impairment and motor function outcomes in individual patients. There are two broad categories of motor system biomarkers that have received the most research attention to date: transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI). Dr. Stinear and colleagues describe the accumulating evidence for the use of these motor system biomarkers during the initial days and weeks after stroke and then discusses the potential challenges and benefits of implementing these biomarkers in clinical practice using the PREP2 algorithm as an example.
The PREP2 algorithm combines clinical assessment with biomarkers in an algorithm to predict upper limb functional outcomes for individual patients. It is the first algorithm to be tested in clinical practice. It is the standard of care in two Auckland hospitals and is being rolled out in several other hospitals in New Zealand, North America, Singapore, and Europe. Other biomarker-based algorithms are likely to follow. The researchers describe several potential facilitators and barriers to implementing biomarkers in clinical practice, including characteristics of the algorithm, the clinical setting, and the clinicians themselves.
The researchers conclude that active, theoretically underpinned implementation strategies are needed to ensure that biomarkers are successfully used in clinical practice for predicting motor outcomes after stroke and should be considered in parallel with biomarker development.
“Implementing biomarkers in stroke rehabilitation practice has been shown to help patients leave hospital sooner, with no negative effects on their outcomes or wellbeing,” says Dr. Stinear. “Knowing what to expect for their recovery can also help patients and families adjust more readily to life after stroke. However, principled strategies for implementing biomarkers in clinical practice are needed to produce effective and sustainable improvements in clinical practice.”
Although therapies have improved in recent years, traditional rehabilitation still fails in patients with severe paralysis. Ander Ramos-Murguialday, PhD, MSc, of the Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany, and TECNALIA Research and Innovation, San Sebastián, Spain, and colleagues, review brain-machine interfaces (BMIs) that have emerged as a promising tool to guide motor rehabilitation interventions and promote recovery because they can be applied to patients with no residual movement. A BMI is a system that records, decodes, and ultimately translates brain signals into an effector action or behavior, without necessarily involving the motor system.
The researchers reviewed a total of 13 studies. Following a pilot study in 2008, the first double-blinded controlled clinical trial using a BMI for completely paralyzed stroke patients was published in 2013. The experimental group showed significant motor learning. Subsequent studies confirmed these positive results. The duration of the interventions ranged from one to eight weeks and each session lasted between 30 and 90 minutes. Twelve out of the studies targeted the upper limb, while only one focused on the lower limb. All the studies reported improvements of motor function in the experimental group after the use of the BMI. Six studies demonstrated higher improvements in the intervention group than in the control group. Only two of the studies reported no improvements at all in the control group.
Although significant, Dr. Ramos-Murguialday and colleagues conclude that functional motor recovery achieved with novel BMI technology remains modest. “Motor rehabilitation based on BMIs is still in a preliminary stage, and further improvements are required to boost its efficacy,” comments Dr. Ramos-Murguialday. “Invasive and hybrid approaches are promising and might set the stage for the next generation of stroke rehabilitation therapies.”
“As we stand at this crossroad, the direction we need to take is becoming clearer,” concludes Dr. Harvey. “Be open to new approaches to care beyond task-oriented training. Utilize new technology to extend therapeutic approaches beyond the mat, treadmill, and hi-lo table. Critique new research based on whether it suggests just another form of compensatory training versus expansion of functional capacity. Consider the incorporation of biomarkers into clinical research and bedside care. We know where we need to go. I hope we can successfully negotiate the pathways that push beyond merely 70% recovery.”
Limiting children’s recreational screen time to less than two hours a day linked to better cognition
Only one in 20 US children in the study met the full recommended guidelines on recreational screen time, physical activity and sleep.
Limiting recreational screen time to less than two hours a day, and having sufficient sleep and physical activity is associated with improved cognition, compared with not meeting any recommendations, according to an observational study of more than 4,500 US children aged 8-11 years old published in The Lancet Child & Adolescent Health journal.
Taken individually, limited screen time and improved sleep were associated with the strongest links to improved cognition, while physical activity may be more important for physical health.
However, only one in 20 US children aged between 8-11 years meet the three recommendations advised by the Canadian 24-hour Movement Guidelines to ensure good cognitive development—9-11 hours of sleep, less than two hours of recreational screen time, and at least an hour of physical activity every day.
The study found that US children spend an average of 3.6 hours a day engaged in recreational screen time.
The authors say that their findings indicate that adhering to the guidelines during childhood and adolescence, particularly for screen time, is important for cognitive development.
“Behaviours and day-to-day activities contribute to brain and cognitive development in children, and physical activity, sedentary behaviour, and sleep might independently and collectively affect cognition,” says Dr. Jeremy Walsh, CHEO Research Institute, Ottawa, Canada. “Evidence suggests that good sleep and physical activity are associated with improved academic performance, while physical activity is also linked to better reaction time, attention, memory, and inhibition. The link between sedentary behaviours, like recreational screen time, is unclear as this research is in the early stages and it appears to vary depending on the types of screen-based activity.”
In the study, data was analysed from 4,520 children from 20 sites across the USA. Children and parents completed questionnaires and measures at the outset of the trial to estimate the child’s physical activity, sleep and screen time. Children also completed a cognition test, which assessed language abilities, episodic memory, executive function, attention, working memory and processing speed. The study controlled for household income, parental and child education, ethnicity, pubertal development, body mass index and whether the child had had a traumatic brain injury.
Almost one in three children (29% – 1,330/4,520) met none of the guidelines, 41% (1,845/4,520) met only one, 25% (1,129/4,520) met two, and 5% (216/4,520) met all three recommendations.
Half of the children met the sleep recommendation (51%, 2,303/4,520), 37% (1,655/4,520 children) met the screen time recommendation, and 18% (793/4,520 children) met the physical activity recommendation.
The more individual recommendations the child met, the better their cognition. In addition, meeting only the screen time recommendation or both the screen time and sleep recommendations had the strongest associations with cognitive development.
Although there is substantial evidence for the association between physical activity and cognitive development, in this study meeting the physical activity recommendation alone showed no association with cognition. The authors note this was a surprising finding and may suggest that the measure used may not have been specific enough. They note that physical activity remains the most important behaviour for physical health outcomes, and there is no indication that it negatively affects cognition.
Dr. Walsh concludes: “We found that more than two hours of recreational screen time in children was associated with poorer cognitive development. More research into the links between screen time and cognition is now needed, including studying the effect of different types of screen time, whether content is educational or entertainment, and whether it requires focus or involves multitasking. Based on our findings, paediatricians, parents, educators, and policymakers should promote limiting recreational screen time and prioritising healthy sleep routines throughout childhood and adolescence.”
The authors note some limitations, including that their study is observational so cannot establish the underlying causes or the direction of the association. The data is also self-reported and could be subject to bias. The questionnaires were only used at the outset of the study, and so do not track how behaviours changed over time so future cycles of the study will need to be analysed to understand trends over time.
Writing in a linked Comment, Dr. Eduardo Esteban Bustamante, University of Illinois, USA, says: “Through a stress-adaptation lens, the strong associations between global cognition and meeting the recreational screen time recommendation found by Walsh and colleagues potentially reflect the interruption of the stress-recovery cycle necessary for growth in children who do not meet the recommendation. Each minute spent on screens necessarily displaces a minute from sleep or cognitively challenging activities. In the case of evening screen use, this displacement may also be compounded by impairment of sleep quality. It is tempting to take solace in findings that cognitively challenging screen activities can benefit cognition, but, if given a choice, most children already consistently and predictably choose more stimulating screen activities over less stimulating ones.”
More information: Associations between 24 hour movement behaviours and global cognition in US children: a cross-sectional observational study, doi.org/10.1016/S2352-4642(18)30278-5 , www.thelancet.com/journals/lan … (18)30278-5/fulltext
Aspirin could play valuable role as additional treatment for cancer
Regular use of aspirin could help in the treatment of some cancers, finds a new review of 71 medical studies.
The systematic review, which looked at the survival of 120,000 patients with cancer who took aspirin, compared with 400,000 patients who did not, showed that at any time following the diagnosis of some cancers the proportion of patients who were still alive was 20-30% greater in those taking the drug. The spread of cancer to other parts of the body was also substantially reduced in patients using aspirin.
Peter Elwood, Honorary Professor at Cardiff University, who directed the study said: “The use of low-dose aspirin as a preventive in heart disease, stroke and cancer is well established but evidence is now emerging that the drug may have a valuable role as an additional treatment for cancer too.”
One of the colon cancer studies the researchers looked at suggested that a non-diabetic man of about 65 years who takes aspirin would have a prognosis similar to that of a man five years his junior who takes none. For a woman of similar age with colon cancer the addition of aspirin could lead to a similar prognosis of a woman four years younger.
Almost half the studies included in the review were of patients with bowel cancer, and most of the other studies were of patients with breast or prostate cancer. There were very few studies of patients with other less common cancers, but on the whole the pooled evidence for all the cancers is suggestive of benefit from aspirin.
All this evidence of benefit is however limited. First, it comes from observational studies of patients who took aspirin for reasons other than the treatment of cancer, and not from appropriate randomised trials designed to test aspirin and cancer.
Furthermore, the evidence is not entirely consistent and a few of the studies failed to detect benefit attributable to aspirin. More evidence is therefore urgently needed. A number of new randomised trials have been set up, but these are unlikely to report for quite a few years.
The issue of bleeding was examined carefully in the review. Information on bleeding was requested from an author of each of the 71 reports and replies were received from 31 authors.
Very few patients had serious bleeding. Amongst those who had, the proportion of patients taking aspirin who had a ‘serious’ bleed was no greater than the proportion of patients not taking aspirin who had experienced a ‘spontaneous’ stomach bleed due to causes other than aspirin. In two studies a very small number of fatal stomach bleeds had occurred, but again the proportion was no greater in the patients on aspirin than in those not taking aspirin.
Peter Elwood, Honorary Professor at Cardiff University, who directed the study says: “Patients with cancer should be given the evidence now available and be helped to make their own judgement of the balance between the risks and the benefits of daily low dose. Evidence from further studies is urgently required, and patients should be strongly encouraged to participate in appropriate research studies.
“All patients should consult their GP before starting new medication.”
The research “Systematic review update of observational studies further supports aspirin role in cancer treatment: time to share evidence and decision-making with patients?” is published in Plos One Medicine.
More information: Peter C. Elwood et al. Systematic review update of observational studies further supports aspirin role in cancer treatment: Time to share evidence and decision-making with patients?, PLOS ONE (2018). DOI: 10.1371/journal.pone.0203957
Wearable defibrillator lowers sudden cardiac death, but only when you wear it
An international clinical trial that studied wearable cardioverter defibrillators (WCDs) found that the devices did not significantly reduce sudden cardiac death—the primary goal of the device—among patients assigned to the device in the first 90 days after a heart attack, but did lower mortality among those who wore it as prescribed, according to a study led by researchers at UC San Francisco.
The devices, which consist of highly sensitive vests that can deliver an electric shock when the heart beats out of rhythm, are designed to provide medical intervention around the clock for patients who have had a heart attack and are at further risk of death due to arrhythmia. The study appears Sept. 27, 2018, in the New England Journal of Medicine (NEJM).
“It remains unclear how to reduce the risk of arrhythmic death definitively, beyond what is possible with appropriate medical therapy, in the early period after heart attack before implantable cardioverter defibrillators are suggested,” said UCSF Health cardiologist Jeffrey Olgin, MD, lead author of the paper and chief of the Division of Cardiology at UCSF. “However, given the totality of the data, the WCD may be reasonable in high-risk patients who are likely to wear the WCD based on shared decision-making.”
Patients who are prone to fast heart rhythms that can cause sudden death typically receive a surgically implanted type of cardiac pacemaker known as a cardioverter defibrillator (ICD). However, current medical guidelines recommend waiting at least 40 days after a heart attack before implanting the device, and 90 days if the patient has had a vascular stent implanted or has undergone bypass surgery.
The guidelines recommend considering a wearable device for a wide range of patients at risk of sudden cardiac death, including those who have low ejection fraction—a measure of the heart’s pumping ability—following a heart attack.
“Previous research has shown the risk of mortality in low ejection fraction patients is highest in the first 90 days after a cardiac event, such as a heart attack or a new diagnosis of heart failure,” said UCSF Health cardiologist Byron Lee, MD, MAS, professor of medicine and the Reeves Endowed Chair in Arrhythmia Research at UCSF and study co-principal investigator.
WCDs aim to bridge this sensitive period before a pacemaker can be implanted.
In collaboration with the National Institutes of Health (NIH) and device manufacturer Zoll Medical Corp., the Vest prevention of Early Sudden death Trial (VEST) enrolled 2,302 patients in the United States and Europe from July 2008 to April 2017 who had low ejection fractions within seven days of their hospital discharge for heart attack. Patients were randomly assigned in a 2-to-1 ratio to the LifeVest WCD with guideline-directed therapy (1,524) or directed therapy only (778).
Device participants were fitted, trained and instructed to wear it continuously except while bathing. The WCD group wore the device an average of 14.1 hours daily over the study period, starting at 18 hours and decreasing to 12 hours by day 90, at which point only half of the WCD patients still chose to wear the device.
The study found no statistical difference in sudden cardiac deaths or rehospitalization between the two groups, in part due to the lower-than-expected wear time, said Olgin, the Gallo-Chatterjee Distinguished Professor of Medicine at UCSF. However, death rates dropped significantly during times the WCD was worn compared to times it was not. The study found a 35.5 percent lower risk of overall mortality in the WCD group, at 3.1 percent versus 4.9 percent in the control group.
Twenty (1.3 percent) of the device participants experienced at least one appropriate shock during the study, while nine (0.6 percent) received an inappropriate shock. About 70 percent of participants who had an appropriate shock survived to 90 days. Of the 48 participants who died, only 12 were wearing the WCD at time of death.
“Although this study result is subject to confounding, it suggests a benefit to wearing the device and implies that low adherence to wearing it may be a limiting factor in the potential benefit of a wearable cardioverter-defibrillator,” said Mark J. Pletcher, MD, MPH, a UCSF professor of epidemiology and biostatistics who leads the VEST Data Coordinating Center.
The researchers are exploring new analyses for estimating the true causal effect of wearing the WCD, Pletcher said.
Source: University of California, San Francisco
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