Posts Tagged physical activity
This study aimed to systematically review studies focusing on levels of physical activity (PA) in people with epilepsy (PWE) compared with non-epilepsy controls, and identify factors associated with PA in PWE. Intervention studies were also reviewed to consider the effects of psychological interventions on levels of PA, and the effects of PA-based interventions on seizure activity, psychiatric comorbidity, and health-related quality of life (HRQoL). PRISMA guidelines were followed. Searches were conducted using PubMed, Cochrane Controlled Register of Trials, PsycINFO, and Embase. Forty-six studies met inclusion criteria, including case-control, cross-sectional, and intervention studies. Assessment measures included questionnaires, activity trackers, and measures of physiological fitness. Twelve of 22 (54.5%) case-control studies utilizing self-report questionnaire measures reported that PWE were performing lower levels of PA, less likely to be engaging in PA, or less likely to meet PA guidelines than controls. The remaining studies did not find a difference between PWE and controls. Eight of 12 (67%) case-control studies utilizing exercise/fitness tests reported that PWE performed significantly poorer than controls, whereas in two studies PWE performed better than controls. One of three studies investigating the relationship between PA and seizure frequency found that increased self-reported PA was associated with having fewer seizures, whereas two did not find a significant relationship. All seven cross-sectional studies that included measures of HRQoL and depression/anxiety found a positive relationship between levels of PA and HRQoL/reduced levels of depression and anxiety. All four studies that used PA-based interventions demonstrated improvements in levels of PA and increased HRQoL. Study quality was almost universally low. In conclusion, there is some evidence that PWE engage in less PA than peers, and that interventions can improve PA levels and HRQoL. However, there is a need for more robust study designs to better understand PA in individuals with epilepsy.
Physical activity (PA) is a key health behavior in people with stroke including risk reduction of recurrent stroke. Despite the beneficial effects of PA, many community-dwelling stroke survivors are physically inactive. Information and communication technologies are emerging as a possible method to promote adherence to PA.
The aim of this study is to investigate the effectiveness of a mobile-health (mHealth) App in improving levels of PA.
Forty-one chronic stroke survivors were randomized into an intervention group (IG) n=24 and a control group (CG) n=17. Participants in the IG were engaged in the Multimodal Rehabilitation Program (MMRP) that consisted on supervising adherence to PA through a mHealth app, participating in an 8-week rehabilitation program that included: aerobic, task-oriented, balance and stretching exercises. Participants also performed an ambulation program at home. The CG received a conventional rehabilitation program. Outcome variables were: adherence to PA, (walking and sitting time/day), walking speed (10MWT); walking endurance (6MWT); risk of falling (TUG); ADLs (Barthel); QoL (Eq-5D5L) and participant’s satisfaction.
At the end of the intervention, community ambulation increased more in IG (38.95 min; SD: 20.37) than in the CG (9.47 min; SD: 12.11) (p≤.05). Sitting time was reduced by 2.96 (SD 2.0) hours/day in the IG and by 0.53 (SD 0.24) hours in the CG (p≤.05).
The results suggest that mHealth technology provides a novel way to promote adherence to home exercise programs post stroke. However, frequent support and guidance of caregiver is required to ensure the use of mobile devices.
To systematically evaluate the efficacy of exergames in individuals with major neurocognitive disorder.
Materials and methods
PubMed, EMBASE and PEDro were systematically searched from inception until October 2019 for randomised and clinical controlled trials. Methodological quality of the trials was assessed with the PEDro rating scale or Risk of Bias in Nonrandomised Studies of Interventions-I (ROBINS-I), when appropriate. Grading of Recommendations Assessments, Development and Evaluation (GRADE) was used to assess the overall quality of the evidence.
Eight trials, all of moderate to high methodological quality (i.e., PEDro score of 6 or higher or a Robins-I moderate quality score) were included. The overall quality of evidence was moderate to high according to the GRADE criteria. Improvements in gait, mobility and balance and beneficial effects on activities of daily living performance, cognitive function, fear of falls, quality of life and mood following exergaming were reported. Heterogeneity in outcome measures, intervention characteristics and included participants precluded a meta-analysis.
The current literature is of moderate to high quality and demonstrates that exergames have a wide range of physical and mental benefits in people with major neurocognitive disorder. More controlled trials are however needed to confirm the existing evidence before exergames can be recommended in treatment guidelines for people with major neurocognitive disorder.
Implications for rehabilitation
Exergames have many physical and mental benefits in people with major neurocognitive disorder
Exergaming can enhance gait, mobility and balance in people with major neurocognitive disorder
Evidence for beneficial cognitive effects of exergaming is emerging
We all know that exercise has unparalleled power to improve physical health. But did you know that science is showing that it is one of the best things you can do for your brain? This, in turn, benefits your mental health considerably. Research has confirmed that physical exercise improves memory and thinking skills, mood and creativity, and learning while reducing age-related decline, the risk of dementia and Alzheimer’s, and depression.
It’s that last one we’re going to focus on. You can incorporate regular exercise into your life as an effective preventative and treatment for depression. One Harvard study showed that exercise is every bit as powerful as medication for treating the symptoms and root causes of depression. Another meta-analysis said this:
The mechanisms underlying the antidepressant effects of exercise remain in debate; however, the efficacy of exercise in decreasing symptoms of depression has been well established. Data regarding the positive mood effects of exercise involvement, independent of fitness gains, suggest that the focus should be on frequency of exercise rather than duration or intensity until the behavior has been well established. The addition of self-monitoring techniques may increase awareness of the proximal benefits of exercise involvement, which is generally reinforcing to the patient.”
Why Exercise Helps Your Mood
As stated in the quote above, we don’t really know all the details of exactly why exercise helps depression. There are a couple of possible scientific explanations. Personally, I think it’s most likely to be a combination of these.
The thermogenic hypothesis suggests that the rise in core body temperature during and following physical activity causes the reduction of depression symptoms. Studies show that increases in temperature of specific brain regions, such as the brain stem, can lead to an overall feeling of relaxation and reduction in muscular tension. This produces a kind of “tranquilizer effect”.
The endorphin hypothesis proposes that the positive effects of exercise come from the increased release of endorphins during and following exercise. Endorphins are chemicals produced naturally by your nervous system to cope with pain or stress. They are often called “feel-good” chemicals because of their pain relieving and happiness boosting abilities. They might also be the body’s natural antidepressant. Endorphins correlate with a positive mood and an overall enhanced sense of well-being.
The monoamine hypothesis might be the most promising of the proposed physiologic mechanisms. This theory states that exercise leads to an increase in the availability of brain neurotransmitters, such as serotonin, dopamine, and norepinephrine. These brain chemicals largely determine mood and are often low in depressed people.
As the name suggests, the distraction hypothesis suggests that physical activity serves as a distraction from worries and depressing thoughts. In general, distracting activities have been shown to have more influence on the management and reduction of depression than the use of more self-focused or introspective practices.
The enhancement of self-efficacy through exercise may be another reason for its antidepressant effects. Self-efficacy refers to the belief that a person possesses the skills to complete a task to obtain the desired outcome. Depressed people often feel powerless to bring about any positive outcomes in their lives. This negative feeling perpetuates more negative self-evaluation, rumination, and patterns of thinking. Exercise may provide a depressed individual with a meaningful sense of mastery and control.
What We Do Know About How Exercise Improves Your Brain
In Spark: The Revolutionary New Science of Exercise and the Brain, psychiatrist John Ratey explores the neuroscience behind beneficial effects of aerobic exercise on anxiety, stress, depression, learning, aging, and attention deficit disorder. According to Ratey:
Even people who are overweight and who start exercising see improvements in mood and cognition in as little as 12 weeks.”
Moving your body increases the blood flow to your brain which elevates oxygen levels and triggers biochemical changes and increases in brain-derived neurotrophic factor (BDNF) production. BDNF is a protein produced inside nerve cells. It acts as a fertilizer to help them function optimally, grow, and make more new neurons.
These conditions encourage your brain to form new neural pathways and synaptic connections, a process known as neuroplasticity. Neuroscientists have noted that the hippocampus, which helps regulate mood, is smaller in depressed brains. Exercise supports nerve cell growth in the hippocampus, improving cell connections, which may help counter this and relieve depression.
The Benefits Continue After Physical Activity
While exercise certainly helps your brain while you’re doing it with increased oxygen, blood flow, and neurochemicals. as mentioned above, Ratey explains that it’s what happens AFTER exercising that optimizes the brain in the long run. When you exercise regularly, some of the ongoing effects of exercise include:
- Exercise calms the amygdala, your brain’s fear center, raising the fight-or-flight threshold and decreasing anxiety.
- It kick-starts the cellular recovery process by increasing the efficiency of intercellular energy production. This allows neurons to meet fuel demands without increasing toxic oxidative stress.
- Exercise triggers the production of more receptors for insulin which means better use of blood glucose and stronger cells. It also increases the level of insulin-like growth factor (IGF-1). This helps insulin manage glucose levels and increases synaptic strength (LTP), neuroplasticity, and neurogenesis.
- Exercise elevates brain-derived neurotrophic factor (BDNF) production. BDNF is a protein produced inside nerve cells that acts as a fertilizer to help them function, grow, and make new neurons.
- Exercise relaxes the resting tension in your muscles which breaks the feedback loop to your brain. Your brain figures if your body isn’t stressed, it doesn’t need to be either.
These changes combine to yield a brain that can keep cortisol in check, repair itself, and prevent the damaging effects of stress.
Other Things To Consider
What Exercise Is the Best to Fight Depression?
Some studies show aerobic exercise to be the most beneficial for improving depression with running and walking topping the list. High-intensity exercise releases more endorphins – which is great if you can do it. But it’s good to know that there is also real benefit in low-intensity exercise sustained over time.
Two studies investigated the effects of running vs lifting weights in depressed people. Both experiments had very similar results. In one study, 40 women with depression either ran or lifted weights four times a week for eight weeks. In the second study, 90 depressed people were assigned aerobic exercise (jogging or brisk walking) or non-aerobic exercise (strength-training, stretching, relaxation, coordination and flexibility training) for 60 minutes, three times a week, for eight weeks. Both studies concluded that exercising clearly reduced depressive symptoms, but no significant difference in the activity performed was noted.
Of course, the best exercise for you is the one that you will do consistently and enjoy. It’s that simple.
How Much Exercise Is Enough?
Research has shown that burning 350 calories three times a week through sustained, sweat-inducing activity can reduce symptoms of depression as effectively as antidepressants. One study found that three sessions of yoga per week boosted participants’ levels of the brain chemical GABA, which typically translates into a better mood and decreased anxiety.
Any exercise is better than none and is going to give you some brain benefit. One study noted that a single ten-minute bout of physical activity in an academic setting boosted attention and problem-solving skills in kids. Another study observed mental health benefits after just 20 minutes of physical activity. The results also showed that more exercise and higher intensity correlated with better effects.
Exercise is a safe, effective way to help prevent and manage depression. It allows a person to use the natural processes of their own body to counter depressive symptoms and optimize brain health. Unlike medication, the side effects of exercise are other health benefits. Some side effects are protecting against heart disease and diabetes, improving sleep, and lowering blood pressure.
Exercise as a treatment for depression is a long-term solution, not a quick fix. You will want to pick an activity you can sustain over time. The key is to make it something you like and something that you’ll want to keep doing.
That’s a win/win!
[Abstract] Activity and MObility UsiNg Technology (AMOUNT) rehabilitation trial – description of device use and physiotherapy support in the post-hospital phase
To describe device use and physiotherapy support in the post-hospital phase of the AMOUNT rehabilitation trial.
We performed an evaluation of the support required for device use by participants randomised to the intervention group who received digitally-enabled rehabilitation in the post-hospital phase (n = 144). Intervention, additional to standard rehabilitation, utilised eight digital devices (virtual reality videogames, activity monitors and handheld computer devices) to improve mobility and increase physical activity. Participants were taught to use devices during inpatient rehabilitation and were then discharged home to use the devices for the remainder of the 6-month trial. Physiotherapist-participant contact occurred every 1–2 weeks using a health coaching approach, including technology support when required. Intervention datasheets were audited, and descriptive statistics used to report device use and support required.
Participants (mean (SD) age 70 (18) years; 49% neurological health conditions) used an average of 2 (SD 1) devices (98% used an activity monitor). Eight percent of physiotherapy contact included technology support with 30% provided remotely. Support addressed 845 issues categorised under initial set-up and instruction (27%), education and training (31%), maintenance (23%) and trouble-shooting (19%).
Digital devices can be used for home-based rehabilitation, but ongoing technology support is essential.
IMPLICATIONS FOR REHABILITATION
Digital device use at home to support long-term management of health conditions is likely to become increasingly important as the need for rehabilitation increases and rehabilitation resources become more limited.
Technology support for set-up and ongoing device use is a critical enabler of home-based digital interventions.
Health professionals delivering home-based digital interventions require sufficient training and equipment and may need to vary the mode (e.g., home visit vs. telephone or video conference) depending on the technology support required.
- It is by now well established that exercise has positive effects on the brain, especially as we age.
- Less clear has been why physical activity affects the brain in the first place.
- Key events in the evolutionary history of humans may have forged the link between exercise and brain function.
- Cognitively challenging exercise may benefit the brain more than physical activity that makes fewer cognitive demands.
In the 1990s researchers announced a series of discoveries that would upend a bedrock tenet of neuroscience. For decades the mature brain was understood to be incapable of growing new neurons. Once an individual reached adulthood, the thinking went, the brain began losing neurons rather than gaining them. But evidence was building that the adult brain could, in fact, generate new neurons. In one particularly striking experiment with mice, scientists found that simply running on a wheel led to the birth of new neurons in the hippocampus, a brain structure that is associated with memory. Since then, other studies have established that exercise also has positive effects on the brains of humans, especially as we age, and that it may even help reduce the risk of Alzheimer’s disease and other neurodegenerative conditions. But the research raised a key question: Why does exercise affect the brain at all?
Physical activity improves the function of many organ systems in the body, but the effects are usually linked to better athletic performance. For example, when you walk or run, your muscles demand more oxygen, and over time your cardiovascular system responds by increasing the size of the heart and building new blood vessels. The cardiovascular changes are primarily a response to the physical challenges of exercise, which can enhance endurance. But what challenge elicits a response from the brain?
Answering this question requires that we rethink our views of exercise. People often consider walking and running to be activities that the body is able to perform on autopilot. But research carried out over the past decade by us and others would indicate that this folk wisdom is wrong. Instead exercise seems to be as much a cognitive activity as a physical one. In fact, this link between physical activity and brain health may trace back millions of years to the origin of hallmark traits of humankind. If we can better understand why and how exercise engages the brain, perhaps we can leverage the relevant physiological pathways to design novel exercise routines that will boost people’s cognition as they age—work that we have begun to undertake.
FLEXING THE BRAIN
To explore why exercise benefits the brain, we need to first consider which aspects of brain structure and cognition seem most responsive to it. When researchers at the Salk Institute for Biological Studies in La Jolla, Calif., led by Fred Gage and Henriette Van Praag, showed in the 1990s that running increased the birth of new hippocampal neurons in mice, they noted that this process appeared to be tied to the production of a protein called brain-derived neurotrophic factor (BDNF). BDNF is produced throughout the body and in the brain, and it promotes both the growth and the survival of nascent neurons. The Salk group and others went on to demonstrate that exercise-induced neurogenesis is associated with improved performance on memory-related tasks in rodents. The results of these studies were striking because atrophy of the hippocampus is widely linked to memory difficulties during healthy human aging and occurs to a greater extent in individuals with neurodegenerative diseases such as Alzheimer’s. The findings in rodents provided an initial glimpse of how exercise could counter this decline.
Following up on this work in animals, researchers carried out a series of investigations that determined that in humans, just like in rodents, aerobic exercise leads to the production of BDNF and augments the structure—that is, the size and connectivity—of key areas of the brain, including the hippocampus. In a randomized trial conducted at the University of Illinois at Urbana-Champaign by Kirk Erickson and Arthur Kramer, 12 months of aerobic exercise led to an increase in BDNF levels, an increase in the size of the hippocampus and improvements in memory in older adults.
Other investigators have found associations between exercise and the hippocampus in a variety of observational studies. In our own study of more than 7,000 middle-aged to older adults in the U.K., published in 2019 in Brain Imaging and Behavior, we demonstrated that people who spent more time engaged in moderate to vigorous physical activity had larger hippocampal volumes. Although it is not yet possible to say whether these effects in humans are related to neurogenesis or other forms of brain plasticity, such as increasing connections among existing neurons, together the results clearly indicate that exercise can benefit the brain’s hippocampus and its cognitive functions.
Researchers have also documented clear links between aerobic exercise and benefits to other parts of the brain, including expansion of the prefrontal cortex, which sits just behind the forehead. Such augmentation of this region has been tied to sharper executive cognitive functions, which involve aspects of planning, decision-making and multitasking—abilities that, like memory, tend to decline with healthy aging and are further degraded in the presence of Alzheimer’s. Scientists suspect that increased connections between existing neurons, rather than the birth of new neurons, are responsible for the beneficial effects of exercise on the prefrontal cortex and other brain regions outside the hippocampus.
UPRIGHT AND ACTIVE
With mounting evidence that aerobic exercise can boost brain health, especially in older adults, the next step was to figure out exactly what cognitive challenges physical activity poses that trigger this adaptive response. We began to think that examining the evolutionary relation between the brain and the body might be a good place to start. Hominins (the group that includes modern humans and our close extinct relatives) split from the lineage leading to our closest living relatives, chimpanzees and bonobos, between six million and seven million years ago. In that time, hominins evolved a number of anatomical and behavioral adaptations that distinguish us from other primates. We think two of these evolutionary changes in particular bound exercise to brain function in ways that people can make use of today.
For more, visit —-> Why Your Brain Needs Exercise – Scientific American
Having suffered a car accident, I had some serious injuries. These included my spine, nerves and my brain. I had foot drop, where when you raise your leg, you can not raise your foot from your ankle, leaving it to hang limply. That means you cannot put any weight on it and it will not offer any support or flexibility. On top of this, due tExerciseo a damaged nerve in my neck, and had weakness down my left side. However after 10 days, the hospital team got me walking with crutches, and sent me home.
I knew that I needed to do some exercise to help rebuild some of my strength. But what I didn’t know was how good exercise is for your brain as well.
We all know that the more you practise at something, the better you will get at it. Well, the brain is just the same. Every time you perform an action, you are creating the building blocks for a new pathway in your brain. Let me give you an example. I used to love painting and drawing. But following my brain injury, I could barely write legibly. For me this was depressing, as my art was a part of who I was. My partner James, kept badgering me to keep trying although I felt he just didn’t understand. I couldn’t make my hand follow the instructions I gave it properly, leaving me frustrated.
Exercise doesn’t mean you have to hit the gym. Just practise a physical activity.
So many sheets of paper ended up in the bin. (I would like to apologise to the trees who were sacrificed for my cause.) But in time my writing improved, and I found my artistic flair returning to me. Just by reminding the muscles in my hand and arm how to behave, I had begun to regain my skill. But it wasn’t because the muscles needed to be rebuilt, it was because my brain needed to create new pathways to replace those that were damaged. This is the same process as when you learn a skill for the first time, and why your mother always said “practise makes perfect.” The more we do an action, the more the brain prioritises building pathways which make a shortcut to that action.
Now I know you are saying “but Michelle drawing and writing isn’t exercise.” And yes you are right, but I wanted to share this example with you to help you see that although there is the physical muscles movements, there is much more that needs to happen and I think we can all agree agree creativity is something very much in your brain.
Think about how in sports there is a tactical element, spacial awareness, problem solving… the list goes on.
I’m now 5 years on from my accident, and most people wouldn’t notice my slight limp. For someone who struggled to walk for so long, that’s not bad. I still have nerve damage, and I may do for the rest of my life, but I can deal with it. I’d be frightened to go skiing again, but it doesn’t affect my everyday life much at all. Yes I get pain and tire much easier, but I can cope with that.
My brain is still trying to repair my cognitive skills. Bearing in mind I couldn’t read or write to start with, I think it’s fair to say it’s doing a pretty good job. I even set up this website all by myself even though I had no experience of doing this sort of thing before. (If you are thinking of starting a blog but aren’t sure where to start head over to Starting a blog following a brain injury is difficult, but it is achievable to get some ideas on how to get going.)
No matter what your fitness level, or sporting ability never underestimate the importance of exercise.
You don’t need to run like you’re Mo Farah, just find something you enjoy which you can fit into your busy schedule. Dance, yoga and swimming are all great options. As evidence is growing to show regular exercise can stave off dementia, your brain will thank you for it. We all have days when just getting out of bed is an achievement, so don’t feel any shame in taking it easy. But just remember your efforts will encourage enhancements in much more than just becoming physically stronger. Your mental health and general well being will benefit too. Exercise can help your brain injury recovery process and you might even discover a talent for something new that you never knew you had.
Other articles you may like:
What exercises have you found most beneficial following your brain injury?
[Abstract] A physical activity program is no more effective than standard care at maintaining upper limb activity in community-dwelling people with stroke: secondary outcomes from a randomized trial
To evaluate whether an 18-month, physical activity coaching program is more effective than standard care in terms of upper-limb activity.
The intervention group received follow-up visits and coaching on physical activity and exercise each month for 18 months after inclusion, by a physiotherapist. The control group received standard care.
The primary outcome, in this secondary analysis, was Motor Assessment Scale items 6, 7, and 8. Secondary outcomes were National Institute of Health Stroke Scale item 5, the Stroke Impact Scale domain 7, and the Modified Ashworth Scale in flexion/extension of the elbow.
In total, 380 persons with stroke were recruited, with mean (SD) age 72 (11) years, and baseline scores total National Institute of Health Stroke Scale was 1.4 (2.2)/1.6 (2.4) and Motor Assessment Scale items 6, 7 and 8 in the intervention/control group was 5.5 (1.2)/5.5 (1.2), 5.4 (1.4)/5.4 (1.3), and 3.6 (2)/3.5 (2), respectively. There was no significant difference between groups in terms of upper limb function in any of the Motor Assessment Scale items. In this population with minor stroke, upper-limb activity was good at three months post-stroke (74% of the maximum) and remained good 18 months later (77% of maximum).
via A physical activity program is no more effective than standard care at maintaining upper limb activity in community-dwelling people with stroke: secondary outcomes from a randomized trial – Birgitta Langhammer, Louise Ada, Mari Gunnes, Hege Ihle-Hansen, Bent Indredavik, Torunn Askim, 2019
[NEWS] New Virtual Reality Therapy game could offer relief for patients with chronic pain, mobility issues
A Virtual Reality Therapy game (iVRT) which could introduce relief for patients suffering from chronic pain and mobility issues has been developed by a team of UK researchers.
Dr Andrew Wilson and colleagues from Birmingham City University built the CRPS app in collaboration with clinical staff at Sandwell and West Birmingham Hospitals NHS Trust for a new way to tackle complex regional pain syndrome and to aid people living with musculoskeletal conditions.
Using a head mounted display and controllers, the team created an immersive and interactive game which mimics the processes used in traditional ‘mirror therapy’ treatment. Within the game, players are consciously and subconsciously encouraged to stretch, move and position the limbs that are affected by their conditions.
Mirror therapy is a medical exercise intervention where a mirror is used to create areflective illusion that encourages patient’s brain to move their limb more freely. This intervention is often used by occupational therapists and physiotherapists to treat CRPS patients who have experienced a stroke. This treatment has proven to be successful exercises are often deemed routine and mundane by patients, which contributes to decline in the completion of therapy.
Work around the CRPS project, which could have major implications for other patient rehabilitation programmes worldwide when fully realised, was presented at the 12th European Conference on Game Based Learning (ECGBL) in France late last year.
Dr Wilson, who leads Birmingham City University’s contribution to a European research study into how virtual reality games can encourage more physical activity, and how movement science in virtual worlds can be used for both rehabilitation and treatment adherence, explained, “The first part of the CRPS project was to examine the feasibility of being able to create a game which reflects the rehabilitation exercises that the clinical teams use on the ground to reduce pain and improve mobility in specific patients.”
“By making the game enjoyable and playable we hope family members will play too and in doing so encourage the patient to continue with their rehabilitation. Our early research has shown that in healthy volunteers both regular and casual gamers enjoyed the game which is promising in terms of our theory surrounding how we may support treatment adherence by exploiting involvement of family and friends in the therapy processes.”
The CRPS project was realized through collaborative working between City Hospital, Birmingham, and staff at the School of Computing and Digital Technology, and was developed following research around the provision of a 3D virtual reality ophthalmoscopy trainer.
Andrea Quadling, Senior Occupational Therapist at Sandwell Hospital, said “The concept of using virtual reality to treat complex pain conditions is exciting, appealing and shows a lot of potential. This software has the potential to be very helpful in offering additional treatment options for people who suffer with CRPS.”
[Abstract] Adherence to a Long-Term Physical Activity and Exercise Program After Stroke Applied in a Randomized Controlled Trial