Tai Chi Chuan and Qigong: Physical and Mental Practice to Maintain or Improve Functional Mobility and Health in Elders Author: Bill Gallagher, MSPT, CMT, CYT   Back to Article Index

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Tai Chi Chuan and Qigong: Physical and Mental Practice
to Maintain or Improve Functional Mobility and Health in Elders



Bill Gallagher MSPT, CMT, CYT

EastWestRehab.com

BillGPT@bellatlantic.net





As lifespan increases elders and the rehabilitation professionals who serve them are driven to find ways to prevent or reverse frailty. Frailty includes some combination of slow and unsteady gait, muscle weakness, poor endurance, fear of falling, general anxiety, osteoporosis and incontinence. This pattern of disharmony (to use a concept from traditional Chinese medicine) may have an insidious onset, or may begin precipitously with an event such as myocardial infarction or hip fracture. This pattern often resembles a downward spiral. For example, poor balance can elicit fear of falling, which, in turn leads to decreased physical activity. Diminished activity causes a gradual loss of muscle strength, endurance and motor control, thereby impairing balance further. More fear often follows as a major factor when the individual becomes cognizant of the downhill spiral. Tai Chi Chuan (Taijiquan, T’ai Ch’i Ch’uan) and Qigong (Chi Gung, Chi Gong, Chi Kung) appear to be a potent intervention for elders seeking to prevent or reverse this unpleasant spiral into frailty. Tai Chi Chuan is a Chinese martial art that specializes in maintaining balance (mental and physical) while neutralizing an opponent’s attack by joining with their force to unbalance them in preparation for throws, joint locks, or strikes. Qigong can be thought of as a Chinese system of Yoga encompassing physical, mental and spiritual practice. The Qigong discussed in this paper includes techniques employed to quiet the mind and reduce tension, as well as techniques associated with Tai Chi Chuan and other Chinese internal martial arts including Xingjiquan (Hsing I Chuan, Hsing Yi) and Baguazhang (Pa Kua Chang). This paper will review the direct and indirect evidence that training in this venerable tradition has the potential to prevent and reverse frailty in elders.


Relaxation Response


Stress may play a dominant role in human disease. The effects of mental stress are insidious and affect structure and function of the entire brain and body. As we age, we have a harder time coping with stress. In fact, aging may be defined as the progressive decrease in the ability to adapt to mental and physical stress1.




One part of Taijiquan and Qigong practice is to release unnecessary tension in muscles. Muscles are an excellent mental stress barometer since hyper-arousal consistently leads to amplified muscle tension.2,3 Jacobson4 contends that mental tension is increased by proprioceptive input found in conditions of high musculoskeletal tension, contributing to anxiety. If this is true, learning to release excess muscle tension through Taijiquan and Qigong would have a calming effect on the mind and decrease psychophysiological arousal. Furthermore, the ability to notice that an autonomic excitation has occurred and reverse it, allows the individual to return to homeostasis more quickly, thereby reducing the tendency of mental stress to be a precursor to disease1.


By encouraging diaphragmatic breathing, Taijiquan and Qigong may avoid the sympathetic nervous system stimulation and inefficiency of thoracic respiration. Diaphragmatic respiration is widely acknowledged to be calming mentally and physically.1,5,6,7


Taijiquan and Qigong also have a more direct effect on anxiety. By employing a repetitive focal device, an expansive mode of thinking is facilitated.1 When focusing the mind on the body and breath while scanning for inappropriate muscle tension, troubling thoughts may arise less frequently and may be easier to let go of as they arise. This practice of maintaining focus on the body and motion, and letting go of distracting thoughts is in agreement with the definition of a relaxation technique developed by the U.S. National Institutes of Health8 and other authorities on relaxation techniques.1,6,9


Tai Chi has been shown to elicit key aspects of the relaxation response. Jin10 found decreased salivary cortisol and less anxiety after Tai Chi practice (n=66). In a second study Jin11 tested Tai Chi’s efficacy in post-stressor recovery (n=96). Tai Chi was found to be superior to reading a neutral passage in reducing state anxiety. Brown12 compared the psychological effects of 16 weeks of Tai Chi training to walking and walking plus relaxation technique instruction. While the subjects included men, only women in the Tai Chi group experienced significant reductions in mood disturbance including tension, depression, anger, confusion, total mood disturbance and an improvement in general mood. Wang13 compared 10 regular practitioners of Tai Chi Chuan to 10 sedentary subjects. They performed a graded exercise test on a bicycle ergometer. Measurements of skin blood flow, cutaneous vascular conductance, and skin temperature were taken at rest and during exercise testing. Plasma nitric oxide levels were also analyzed before and after exercise. Blood flow to the skin, cutaneous vascular conductance, skin temperature and plasma nitric oxide levels were higher in the Tai Chi practitioners both at rest and while exercising.


Taijiquan and Qigong could have an agitating effect if taught poorly. If the movements are taught in overwhelming detail, or in an egocentric, competitive atmosphere, any potential for physiological quieting is unrealized1. Conversely, if relaxation of the muscles is overemphasized to the exclusion of postural alignment and movement pattern considerations, the potential for improvement in balance, strength, bone density, arthritis, low back pain, incontinence and functional status may be squandered.


Taijiquan and Qigong are closely associated with Taoism. The happy serenity that characterizes this philosophy may have an impact on elders. By acting in harmony with life’s circumstances, one may transform a negative outlook into a positive sense of optimism. In this view, anxiety is generated by an interfering and unappreciative mind.14 Taoism suggests the possibility of avoiding anxiety and emotions that deplete the body.15 This mindset is in agreement with contemporary cognitive-behavioral therapy approach to treatment of anxiety.


Taoists have a reputation for living long, healthy lives and Taijiquan masters have a reputation for being formidable opponents into old age. Rather than succumbing to frailty, these venerable masters improve in skill as their understanding of the art deepens. This tradition exposes elders to an optimistic view of aging. This exposure may in itself improve functional mobility in elders.16


Finally, Tai Chi Chuan is an excellent choice as an intervention to reduce anxiety and all its potentially ill effects in elders with fear of falling since it directly addresses postural stability. Wolf17 found a significant decrease in the fear of falling after 15 weeks of Tai Chi Chuan. Since excessive fear of falling probably degrades balance18 and gait19, and this degradation may, in turn, cause more fear of falling, an intervention that addresses these two issues can elicit a profoundly synergistic effect on an elder’s mobility, peace of mind and quality of life.




Fall Prevention


A significant, damaging fall can precipitate a steep downward spiral culminating in death.20,21 Tai Chi Chuan appears to prevent falls in elders. Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) was a large scale, (over 2000 elders participated) prospective study to determine the effects of a number of interventions designed to prevent falls22. Seven sites participated, each implementing a different strategy such as traditional physical therapy (individual or group), education/behavior modification, endurance training, flexibility, exercise, home safety evaluations, balance training, resistive training, nutritional supplements and Tai Chi Chuan. Some sites also included control groups. The sites agreed on operational definitions, selection criteria, baseline data collection, and outcome measures. Only two interventions were linked with a statistically significant decrease in the number of falls. A group that engaged in strength and balance training saw a statistically significant decline in falls, while the most potent intervention tested, Tai Chi Chuan, realized a 47.5% decrease in multiple falls.17


Balance


Given Tai Chi’s apparent ability to prevent falls, it is not surprising that literature and clinical experience supports the notion that Tai Chi Chuan can improve balance. Tse23 compared postural control in Tai Chi practitioners (n=9) to non-practitioners (n=9). Practitioners of Tai Chi Chuan were able to perform stork standing and heel to toe walking with eyes open significantly better than control subjects. No difference in performance was found for single leg stance with eyes closed. Hong24 completed another cross-sectional study that included timed single leg stance (with eyes open or closed) in long-time (average 13 years) Tai Chi Chuan practitioners and controls. The average age of the Tai Chi practitioners was 67.5 and the control subjects averaged 66.2 years. The Tai Chi Chuan group held single leg stance longer than controls in both the eyes open and eyes closed condition. Wu25 compared movement of center of pressure in Tai Chi practitioners (n=20) to control subjects (n=19). Results indicated that the Tai Chi group had smaller foot center of pressure excursions for both eyes open and eyes closed conditions than the control group.


Prospective studies have also found improvement in balance tests including Jacobson,26 who trained 24 subjects for 12 weeks in Tai Chi. Significant improvements were found in lateral body stability. Schaller27 found significant improvement in single leg stance with eyes open in elders (over 55) after ten weeks of Tai Chi instruction (n=24) compared to controls (n=22). No improvement was found in single leg stance with the eyes open. Hain28 evaluated the effect of 8 weeks of Tai Chi training on subjects (n=22) with mild balance disorders. Significant improvements were found on both a moving platform posturography test and the Dizziness Handicap Inventory questionnaire scores. Trends toward improvement were noted in Romberg test results and the Medical Outcomes Study survey while the Functional Reach scores did not improve. Shih29 examined the effect of 16 weeks of Tai Chi instruction in 11 subjects. Using an AMTI ® force platform before and after the training period, substantial decreases in velocity of anterior and posterior sway were detected. Over a six month trial, Wolfson30 found Tai Chi to be effective in maintaining balance improvements gained in an orthodox training program. In a prospective case series of 45 patients, Taggart31 found that 25% of participants reported an improvement in balance in response to the open ended question: “Do you feel that you have benefited from the Tai Chi exercise program?”. As previously discussed, a perceived increase in balance will tend to increase confidence in ambulation, which in turn, might lead to a reduced fear of falling, reversing or slowing the spiral into frailty.


Strengthening


While Tai Chi Chuan may appear, at first glance, to have little potential as a strengthening exercise, research has demonstrated the opposite. Lan32 found that subjects (n=32), who were previously sedentary, were able to increase their concentric and eccentric knee extensor peak torque at least 13.5% (max of 23.7%) after a six month training program. Eccentric quadriceps endurance also increased a minimum of 9.6%. Jacobson26 found increased knee extensor strength after 12 weeks of Tai Chi practice compared to controls. Wu25 et al found superior knee extensor strength in 20 longtime practitioners of Tai Chi compared to 19 control subjects. Wolfson30 et al. found that subjects were able to maintain the strength gains made during their traditional physical therapy regimen. Tai Chi Chuan offers an opportunity for patients to continue the pursuit of rehabilitation goals after discharge without a medical professional or special equipment.


Osteoporosis


Osteoporosis can feed the spiral into frailty. The knowledge that ones bones are brittle will likely increase the fear of falling since the chance of fracturing a fragile bone during a fall is higher. Fall prevention becomes critical, since if a fracture occurs, this will typically precipitate a steeper decline. Studies have clearly shown that exercise can help prevent osteoporosis.33 Tai Chi is a weight bearing exercise with a significant muscle strengthening effect in elders. As outlined in the section on arthritis and low back pain, the hip rotators drive all rotation in the transverse plane. This probably selectively strengthens muscles with proximal femoral insertions. These muscles may, following Wolf’s law, focus improvement in bone density at this vulnerable site. In a prospective case control study Qin34 compared longtime practitioners of Tai Chi with an equal number of age matched controls that did not exercise. This study measured bone mineral density of the lumbar spine, proximal femur and distal tibia. They found statistically significant higher bone mineral density of the lumbar spine, proximal femur and distal tibia in the group that practiced Tai Chi than the control group. Then, they followed these groups for twelve months. They found that bone density in the Tai Chi practitioners declined less than in controls. It is difficult to draw conclusions from this study due to a possible selection bias. However, combined with evidence that other weight bearing exercise such as walking helps maintain skeletal integrity and an understanding of the process of bone adaptation it appears that Tai Chi Chuan is helpful to prevent osteoporosis in elders.


Cardiorespiratory Fitness and Rehabilitation


Cardiorespiratory fitness is essential to functional ambulation and health in the elders. Several cross-sectional studies have demonstrated Tai Chi’s effectiveness as a cardiovascular workout. In a case controlled study, Lai35 found that longtime practitioners (11 years) of Tai Chi Chuan were able to raise their heart rate above 70% of the predicted maximum. Compared to controls, the Tai Chi subjects had significantly higher (19% in men, 18% in women) peak oxygen uptake and higher oxygen uptake at ventilatory threshold. Over a two-year period, he found that the rate of decline in VO2max was significantly less in Tai Chi Chuan subjects than sedentary controls. In males who had practiced Tai Chi Chuan VO2max decreased from 1.21 ml/min to 1.19 ml/min whereas controls decreased from 0.96 ml/min to 0.89 ml/min. Similar results were found for women subjects. Brown36 measured ventilatory responses of Tai Chi Chuan practitioners under two conditions. The first was while performing “Wave Hands like Clouds” a Tai Chi Movement. The second condition was while engaged in cycle ergometry at an intensity (VO2) that matched the volume of oxygen uptake in the first condition (performing Tai Chi). Respiratory rate and ratio of dead space to tidal volume were significantly lower while practicing Tai Chi than while biking. Hong24 found that a group of elderly Tai Chi practitioners scored better in resting heart rate and three minute step test heart rate than a sedentary control group. Wang38 compared 10 regular practitioners of Tai Chi Chuan to 10 sedentary subjects. Results confirmed other studies which showed higher VO2 peak compared to controls.


Although the above studies suggest that Tai Chi Chuan has a positive impact on cardiorespiratory function, the cross-sectional nature of these studies introduces a possible selection bias. In a prospective study (n=58), Lan38 measured the effect a twelve-month Tai Chi Chuan training program for elders (age 58-70) compared to a control condition. Although not randomized, baseline characteristics were similar between the intervention and control groups. The experimental group received three months of Tai Chi Chuan training at an intensity of 52-63% of maximal heart rate. The Tai Chi group showed a significant increase in VO2max (males 16.1%, females 21.3%) and maximal work rate, while the control group showed no significant change.


It is clear from the research that Tai Chi Chuan enhances and maintains cardiovascular fitness, so it might have application for cardiac rehabilitation.


Channer39 looked at a cohort of 126 subject post myocardial infarction. Subjects were divided into three groups: Tai Chi Chuan (n=38), Aerobic (n=41), and non-exercise support group (n=47). The control group met for weekly education classes. The Tai Chi Chuan group met several times a week for sessions that included relaxation/breathing training (Qigong) which was followed by a Tai Chi Chuan form practice. The aerobic exercise program consisted of aerobic training, resistance training, stretching and instruction in relaxation techniques. After 11 sessions, similar improvements were found in systolic blood pressure, but only the Tai Chi Chuan group achieved a significant drop in diastolic blood pressure. Lan40 studied the use of a Tai Chi Chuan program for rehabilitation after a coronary artery bypass surgery. This prospective year-long study compared nine subjects who practiced Tai Chi Chuan to 11 controls who were taught a home-based, self-adjusted exercise program. The Tai Chi group increased VO2 Max 10.3% while the controls only increased slightly. As with previously described studies on healthy individuals, these post-surgical patients were able to use Tai Chi Chuan to work at target heart rate sufficient to improve cardiovascular function.


Arthritis


Arthritis pain can have an insidious effect on functional mobility and health in elders. Tai Chi Chuan and Qigong appear to be ideal for elders suffering from arthritic conditions. Tai Chi is very low impact and therefore unlikely to aggravate arthritis symptoms. Kirstiens41 measured the effect of 10 weeks of Tai Chi practice by subjects with rheumatoid arthritis. They found no exacerbation of joint symptoms and reported increases in mobility. Hartman42 conducted a prospective 12 week randomized controlled clinical trial examining the effects of Tai Chi Chuan on osteoarthritis. A total of 33 participants with lower extremity osteoarthritis completed a 12 week training course. They found that compared to controls the Tai Chi group had statistically significant improvement in the following measures: arthritis self-efficacy scale, level of tension, satisfaction and general health status.


It makes sense that Tai Chi and Qigong would be effective in treating or preventing osteoarthritis of the lower extremities, especially when knee valgus pattern is present. This structural malalignment often cause degeneration by increasing compression and degeneration in the lateral tibiofemoral43 and patellofemoral44 joints. Tai Chi and Qigong can reduce or eliminate this skeletal misalignment through engagement of the external hip rotators. These muscles activity opposes the forces that tend to cause valgus and, to some extent, pronation.




Low Back Pain


Tai Chi Chuan and martial Qigong training may be a potent intervention for elders with low back pain syndromes including arthritis7. The posture and body mechanics inherent in this tradition is consistent with current thinking on prevention and treatment of low back pain via therapeutic exercise and neuromuscular reeducation. Likewise, the calming effect attributed to Taijiquan and Qigong is likely to give some relief to elders suffering from low back pain. 8,45,46


Disc degeneration is ubiquitous in elders and this tends to increase weight bearing at the facet joints.47 This facet compression, in turn, may lead to degenerative joint disease. This posterior spinal element (facet) degeneration is particularly evident in the neck and low back. A forward slumped, thoracic kyphosis exacerbates the postural dysfunction to produce the characteristic hyperlordotic, kyphotic, forward head posture often seen in the elderly.


Taijiquan instruction may begin by teaching a static standing exercise such as the Embrace Tree posture (figures 1& 2). By learning to flex the knees and “drop the tailbone”, hyperlordosis and kyphosis are reduced.47 Elongating the back of the neck and gently tucking the chin corrects the forward head postural dysfunction. By lengthening the thorax between the coccyx and the skull, a flexible kyphosis is further addressed. Through learning to avoid lumbar hyperlordosis, elders with spinal stenosis48 and zygapophyseal arthritis49 may experience significant pain relief. A moderately flexed lumbar spine probably protects the disc-vertebral body unit by balancing the distribution of compressive force within the discs50. Also, this flattened lumbar spine stretches the lumbodorsal fascia. Since this fascia acts on a longer lever arm relative to the center of rotation (in the discs) than erector spinae, this posture reduces the compressive force on the spine50.


The body mechanics of this martial art can be used for functional tasks like opening a door, soothing a fussy grandchild, and transferring a bottle of milk from the kitchen counter to the refrigerator. A key component of Taijiquan is to drive all movement in the transverse plane via pelvic axial rotation and translation in the transverse plane. If the pelvis rotates, the thorax rotates in the same direction and at the same time. When the thorax stops rotating, the pelvis stops rotating. The pelvis rotates on the femurs, driven by the hip rotators, including the posterior fibers of gluteus medius. In addition, Taijiquan’s characteristic wide and deep stances afford a large base of support. This stable base of support is consistent with correct lifting, pushing and pulling and these stances will also tend to strengthen the lower extremities,32,26,27 facilitating lumbar stabilization. Furthermore, since maintenance of postural control correlates with good outcome in subjects with low back pain51 the balance improvements expected with Taijiquan training and practice could conceivably have a positive impact on low back pain.


By minimizing segmental spinal rotation, the lumbar spine is maintained in a neutral position in the transverse plane. One advantage of this neutral spine (in all planes) is to balance the forces seen by the spinal elements. By curtailing segmental rotation, the contact stresses in the zygapophysial joints, and thereby the axial torque on the spine are decreased.50 One study that examined lumbopelvic rotation in elite golfers concluded that subjects with low back pain tended to segmentally rotate the lumbar spine while golfers without back pain rotated the lumbar spine as a unit fixated to a rotating pelvis.52


The minimization of segmental spinal rotation is probably facilitated by Tai Chi’s diaphragmatic breath pattern by allowing transversus abdominus, the deepest abdominal muscle, to function in a more ideal length-tension relationship. There is evidence that optimal lumbar stability requires coordination between the diaphragm, pelvic floor, transvesus abdominus and multifidus.53,54 Impaired diaphragmatic excursion found in thoracic respiration may reduce movement in Quadratus Lumborum and Psoas, increasing the tendency of these muscles to shorten.5 Tightness of Quadratus Lumborum and Psoas is implicated in low back pain and postural dysfunction.55,56 Thoracic respiration may also increase sympathetic arousal.57


By eliciting a relaxation response, suboccipital and paraspinal muscles are likely to carry less inappropriate tension, decreasing any tendency for these muscles to spasm while reducing the compressive forces on the spine. A relaxation response may also improve motor control to optimize posture, alignment, breathing patterns, and muscle activity to minimize mechanical stress on the spine. At the very least, the relaxation response from Taijiquan and Qigong practice offers elders with chronic low back and neck pain the possibility of symptomatic pain reduction.6,8,45


Incontinence


Incontinent elders often restrict activity due to shame and embarrassment. By decreasing activity, the pattern of disharmony characterizing frailty is exacerbated. The Chinese have long used pelvic floor awareness and exercise to improve health and vitality58 and Taijiquan and Qigong may be an effective intervention to prevent and treat stress, urge and functional urinary incontinence. The Taijiquan classics instruct the practitioner to lift the anus during practice59 and the diaphragmatic breathing pattern integral to this tradition will tend to provide a dynamic challenge to the pelvic floor, encouraging appropriate tone.54 Furthermore, gentle engagement of the external rotators of the hips (see figure 1) facilitates adequate pelvic floor contraction and lifts the bladder and urethra through the action of Obturator Internus.60,61 This facilitated pelvic floor contraction, in addition to lifting the bladder and flexing the neck of the bladder, thereby addressing the most common cause of stress incontinence in women,61 also tends to relax the detrusor (bladder) muscle via reciprocal inhibition.60 The detrusor muscle may be further inhibited through the relaxation response and decreased sympathetic drive. By relaxing the detrusor muscle, the pelvic floor will have an easier job of preventing self-soiling with urine. Finally, by increasing strength, balance, agility and motor control (as discussed elsewhere in this paper) Taijiquan may improve an elder’s ability to reach the toilet in time.


Self Assessed Physical Functioning and Quality of Life


Does Tai Chi training improve function and quality of life? Kutner62 examined data collected at the end of the FICSIT trials. He compared response to exit interviews in the Tai Chi group versus the individualized balance training group. Only the Tai Chi subjects reported noticeable improvement in quality of life, increased self-confidence, and improved function in activities of daily living. To further examine the effect of Tai Chi practice on physical functioning, Li63 conducted a randomized controlled trial of elderly between the ages of 65 to 96. Ninety four sedentary elders were randomly assigned to either a 6-month, twice a week Tai Chi group or to a wait-list control group. Self reports of physical function and movement efficacy were assessed before, during and after the 6-month training. Improvements (self assessed) in functional activities like walking, climbing, dressing and bathing for the Tai Chi group ranged from 55 percent to 83 percent. For the control group percent improvement ranged from 13 percent to 33 percent. These studies support the clinical observation that Tai Chi Chuan can improve subjective quality of life.


Adherence


Many rehabilitation clinicians find that elders frequently do not perform the home exercise component of therapy. Adherence to medical intervention is rarely more than 60%.64 This is troubling since we know that at least partial adherence to the home exercise program is critical if progress is to be maximized and perpetuated beyond discharge from rehabilitation. Even if a program has no intrinsic benefit, non-adherence may cause or predict a poor outcome.65


Despite the complexity of Tai Chi, the literature and clinical experience indicates that elders are relatively compliant with the home exercise program if it includes Taijiquan or Qigong.63,39 Why might elderly patients and subjects practice Taijiquan and Qigong so reliably? Perhaps practicing this intricate martial art is more interesting than most exercise routinely prescribed by Physical and Occupational therapists as it seeks to engage the client on the physical, mental, social, and spiritual/philosophical levels. A clinician’s enthusiasm while educating the patient regarding potential benefits of Taijiquan and Qigong practice may be contagious. Elders will be more likely to participate in an exercise regime if they expect it to make a significant improvement in function or comfort.66 Likewise, elders may be less resistant to performing these gentle, slow exercises if they perceive them to be non-irritating to joints.41 Henry67 found that elders were more likely to perform two exercises at home than eight exercises. It is possible to develop a Qigong and Taijiquan exercise program that uses one or two postures or movement patterns to effect a change in strength, flexibility, alignment and anxiety. The exotic, unique, cutting edge appeal of Taijiquan and Qigong as a physical exercise and as a mental practice may lead elders to have higher expectations for benefit from this discipline. Along with potentiating a beneficial placebo response,68,69,70 these high expectations would logically encourage practice. Finally, because these movements can be complex, it is difficult for a patient to hide non-adherence to Taijiquan and Qigong. This enhanced ability to assess compliance facilitates a reflective and collaborative relationship with the client that may effect a change in motivation and adherence to the program.


Conclusion


Over the last decade, interest in Tai Chi Chuan and Qigong has grown and evidence is mounting that this system of physical and mental practice deserves to be considered a preventative and restorative therapy for elders seeking avoid a downward spiral into frailty. A multitude of studies with a variety of designs supply direct evidence of its effectiveness to prevent falls, improve balance, build strength, enhance cardiorespiratory fitness, treat arthritis, and to elicit the relaxation response. .By combining knowledge of Chinese internal martial arts with clinical biomechanics and psychophysiology, this paper offers indirect evidence suggesting that Tai Chi and Qigong should be considered an appropriate intervention for some elders with incontinence and low back pain. It is hoped that this combination of direct and indirect evidence will serve as a springboard for further evaluation of potential benefits by researchers and clinicians.




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