Review Article | Open Access
Elderly Stroke Rehabilitation: Overcoming the Complications and Its Associated Challenges
There have been many advances in management of cerebrovascular diseases. However, stroke is still one of the leading causes of disabilities and mortality worldwide with significant socioeconomic burden. This review summarizes the consequences of stroke in the elderly, predictors of stroke rehabilitation outcomes, role of rehabilitation in neuronal recovery, importance of stroke rehabilitation units, and types of rehabilitation resources and services available in Singapore. We also present the challenges faced by the elderly stroke survivors in the local setting and propose strategies to overcome the barriers to rehabilitation in this aging population.
Despite advances in modern medicine, medications, and medical technology, stroke diseases impose a substantial mortality and morbidity risk to the individual with increased economic burden to the society. Globally, stroke is the second leading cause of death after ischemic heart disease, with approximately 6.7 million stroke deaths in 2015 . In Singapore, despite decreasing trend, cerebrovascular diseases are still the fourth leading cause of death, with a prevalence of 6.6% in 2016 . As the population rapidly ages, the burden of stroke is expected to increase significantly, posing challenges to limited healthcare resources.
As such, there is an urgent need to develop an optimal stroke disease management plan, incorporating a comprehensive stroke rehabilitation program.
2. Consequences of Stroke in Elderly Stroke Survivors
The incidence of stroke disease increases with age, in both men and women with approximately 50% of all strokes occurring in people over age 75 and 30% over age 85 [1, 3, 4]. Stroke is among the top leading causes of disability and reduced quality of life . Elderly patients are at higher risk of mortality, poorer functional outcomes, prolonged length of hospital stay, and institutionalization .
Motor impairment is the most common deficit after stroke, which either happens as a direct consequence of the lack of signal transmission from cerebral cortex or as a slowly accumulating process of the cerebral injuries or muscle atrophy due to learned disuse [7, 8]. Divani et al. reported the risk of falling and fall-related injuries were higher in stroke elders . Risk factors associated with increased fall risks in stroke survivors include poor general health, time from first stroke, psychiatric problems, urinary incontinence, pain, motor impairment, and a history of recurrent falls . Risk factors associated with fall-related injuries are female gender, poor general health, past injury from fall, psychiatric problems, urinary incontinence, impaired hearing, pain, motor impairment, and presence of multiple strokes . Motor function deficits, increased fall risks, and fall-related injuries can significantly affect the patients’ mobility, and their daily living activities which limit their participation in social events and other professional activities.
Poststroke cognitive impairment is common and can affect up to one-third of stroke survivors [10, 11]. However, subtle cognitive impairment may not appear apparent, especially when the stroke survivor seems to have recovered functionally in other aspects [10, 11]. In most cases, these deficits are persistent and usually have progressively worsened . Poststroke cognitive impairment is also more common in those with recurrent strokes . It often coexists with other neuropsychological problems including language disorders, fatigue, depression, and apathy . The mechanisms of poststroke cognitive impairment could be either directly due to cerebral vascular injury or indirectly due to an associated asymptomatic Alzheimer pathology or white matter changes from small vessel disease . Factors independently associated with dementia in stroke survivors include atrial fibrillation, previous stroke, myocardial infarction, hypertension, diabetes mellitus, and previous transient ischemic attack . The combined motor and cognitive impairments significantly increase risks of long term functional disability and increase healthcare cost as reflected by an increase in hospital readmission rates and mortality rates .
Bladder and bowel dysfunction are common and cause significant distress to stroke survivors. Poststroke urinary incontinence or retention has been shown to affect about 30% of stroke survivors . Urinary incontinence is an important marker of stroke severity and has been linked with functional dependency, increased risk of institutionalization, and mortality . Risk factors for poststroke urinary retention include cognitive impairment, diabetes mellitus, aphasia, poor functional status on admission, and urinary tract infection . Common gastrointestinal symptoms after stroke include dysphagia, heartburn, abdominal pain, fecal incontinence, bleeding gastrointestinal tract, and constipation . Among these, constipation is the most common bowel dysfunction with the incidence ranging from 29% to 79% in stroke survivors and more prevalent in hemorrhagic stroke patients . Although fecal incontinence is less common with a prevalence of 11% at 1 year after stroke, it is associated with increased risk of nursing home admission and 1-year mortality rate .
Infection is a serious complication after a stroke despite optimal management. The reported prevalence of poststroke infection ranges from 5% to 65%, depending on the study population, study design, and the definition of infection . Mortality rate is higher in stroke patients with any type of infection, particularly higher in patients with pneumonia and patients with urinary tract infection . Among the survivors, stroke-associated infection is also an independent risk factor for poor outcome at discharge and at 1 year . The association between poststroke infection and poor outcome is likely related to a delay in rehabilitation due to prolonged hospital stay and immobilization as well as general frailty . More importantly, evidence from experimental studies suggests that infection also promotes antigen presentation and autoimmunity against the brain which worsens the outcome .
Following a stroke, patients may have impaired mobility which predisposes them to pressure sores and deep vein thrombosis (DVT). Pressure ulcer results from an imbalance between external mechanical forces acting on skin and soft tissue and the internal susceptibility of skin and its underlying soft tissue to injury. Pressure ulcer is associated with increased poststroke mortality in both genders and patients aged 60 years or older . Stroke patients also have an increased risk of developing deep DVT and pulmonary embolism due to immobility and raised prothrombotic activity . The major risk factors of poststroke DVT include advanced age, male gender, congestive heart failure, malignancy, and fluid and electrolyte disorders [27, 28].
Pain is a frequent but often neglected complication of stroke [29, 30]. It can happen immediately, weeks, or months after a stroke event and can span a spectrum from irritating headache to debilitating limb pain secondary to complex regional pain syndrome, spasticity or joint subluxation, and /or contractures . Pain, together with depression and fatigue, is associated with increased risk of cognitive impairment, functional dependence, and reduced quality of life in stroke survivors [30, 31]. Reported risk factors for the development of poststroke pain include female gender, older age at stroke onset, history of alcohol use and depression, anatomical location of stroke and presence of clinical features such as spasticity, reduced upper extremity movement, and sensory deficits .
3. Predictors of Good Rehabilitation Outcome in Elderly Stroke Survivors
Due to the medical complications after stroke, many patients are markedly functionally disabled when they are discharged from acute care. Functional recovery is based on the restitution of brain tissue and on the relearning of and compensation for lost functions . Therefore, understanding and identification of predictors of good rehabilitation outcomes in addition to institution of early rehabilitation are essential in the recovery phase after an acute stroke event.
There are several commonly used tools for measurement of rehabilitation outcomes in stroke patients, including Functional Independence Measure (FIM), Modified Rankin Scale (mRS), and the Barthel Index (BI) . The FIM is the most sensitive and has been widely accepted with good validity and reliability in assessment of the patient’s degree of disability and burden of care . It consists of 18 items, 13 items on motor disability, and 5 items on cognitive disability. The FIM is commonly performed on admission and at discharge, with the score range from 18 to 126. Similarly, the BI is a tool used to measure functional ability, consisting of 10 items on mobility, activity of daily living (ADL), bowel, and bladder function. Its scores range from 0 to 100, with a higher score indicating higher functional ability. On the other hand, the mRS is a scale from 0 to 6 that measures the level of a patient’s disability.
Age has been well established as a strong predictor of functional outcome and discharge destination in stroke patients in multiple studies across the world in both young and elderly stroke survivors [35–39]. A large community-based cohort study in Denmark reported more than 58% of the very elderly (85 years old and above) were discharged to nursing homes or died during hospital stay poststroke . In a multicenter prospective cohort study of over 300 patients of at least 75 years of age with a first stroke, age was both significantly related to low FIM score upon discharge and independently and inversely related to rehabilitation efficacy (Montebello Rehabilitation Factor Score) . Despite the likelihood of higher comorbidities in older patients, a multicenter cohort study showed that rehabilitation outcomes of elderly patients admitted into skilled nursing facilities (SNFs) were not associated with multimorbidity .
Cognitive impairment which occurs either as a prestroke condition or a poststroke is often significantly correlated with reduced functional gains and poor rehabilitation outcomes in elderly patients. A local study by Kong et al. showed that 45% of elderly stroke patients (≥75 years old) admitted to a rehabilitation facility had cognitive impairment and cognition scores strongly predicted functional outcomes . Studies reported evidence of significant impairment of basic and instrumental ADLs in poststroke cognitively impaired elderly survivors [43, 44]. Another study by Pasquini et al. concluded that cognitive impairment (preexisting or new) together with age was the most important predictor of institutionalization 3 years after stroke . Prestroke dementia has been shown to increase risk of 6-month and delayed poststroke mortality . However, elderly stroke patients with cognitive impairments could still benefit from rehabilitation. Rabadi et al. found similar change in total FIM score and FIM efficiency in both cognitively intact and the cognitively impaired groups of stroke patients . Hence, cognitive impairment should be screened for and has to be taken into consideration when rehabilitation goals are formulated and rehabilitation program ought to be individualized according to the stroke survivor’s learning ability .
ADL dependency on admission, defined as either low FIM score or low BI score, significantly predicts functional dependency outcome in stroke survivors [39, 43, 49, 50]. Elderly stroke patients with poorer preadmission functional status also have longer length of stay and are less likely discharged to an independent or assisted living situation [39, 50, 51]. Similarly, stroke severity, measured by National Institute of Health Stroke Scale, is also another important rehabilitation outcome predictor [49–51]. Furthermore, a recent review by Lazar et al. revealed that aphasia arising from stroke was associated with worse outcomes in both the acute and chronic stroke periods with poorer functional recovery and increased length of rehabilitation and mortality risk .
Urinary incontinence is predictive of poor stroke outcome . Mortality at 6 months has been shown to increase in stroke patients with initial urinary incontinence [53, 54]. Ween et al. reported that 64% of incontinent poststroke patients were discharged to nursing homes compared to 18% for continent poststroke patients . The link between urinary incontinence and poor outcomes could be related to incontinence associated with severe hemiparesis, larger stroke lesions, stroke lesion location, and a disruption of the neuromicturition pathways [55–58].
4. Role of Rehabilitation Process in Neuronal Recovery
Rehabilitation aims to enhance and augment natural mechanisms of recovery. At the time of ischemic injury, immediate mechanisms of repair are initiated, which include resolution of poststroke edema, variation of function, and reversal of diaschisis. Vicariation refers to neighboring tissues taking over a function lost by the stroke-affected tissue . Diaschisis is based on the mechanism of reduction in metabolism and blood flow of intact brain regions which are distant away from the ischemic core but are still functionally and structurally connected with the ischemic core. It is thought that at least some of the improvement observed after a stroke could be due to the reversal of diaschisis [60, 61]. Such processes lead to “unmasking” of latent networks which can be as rapid as several hours within ischemic injury .
Evidence suggests that, within days of stroke, the injured brain has the ability for limited neuronal regeneration by angiogenesis and is coupled with neurogenesis. The ability to self-repair has been shown to happen in aged brains . The repair processes are initially intense and then slow down. Most of the spontaneous stroke recovery occurs in the first 3-6 months after the acute neurological event [64–66]. Generally, patients make 70% of their recovery in the first 3 months after a stroke [67–71]. Despite variations in therapy, such observations of proportional recovery have remained consistent which means that a minimum amount of spontaneous activity and therapy is enough for proportional recovery to happen . An exception to this proportional recovery rule includes damage to the corticospinal tract which results in poorer recovery from impairment [69, 73].
In order to achieve a greater proportion of recovery, a much higher intensity of therapy has to be considered . Greater intensity of stroke rehabilitation has been associated with improved outcomes [74–76]. Skill learning and active participation help to promote plasticity and network activation in stroke recovery [77, 78]. Motor retraining not only enables somatotopic reorganization to happen in perilesional areas and in distant areas connected to the infarct site but also negate the inhibitory effects of myelin associated proteins and ephrins which suppress axonal sprouting [79, 80]. An “enriched environment” in addition to motor retraining has been shown to facilitate motor recovery and neural plasticity in animal studies due to the numerous associated cellular and molecular effects [81–84]. Rehabilitation facilities are ideal enriched environments as they are often situated in stimulating and specialized centers managed by a multidisciplinary team of medical professionals.
5. Stroke Rehabilitation Units and Practitioners Involved
Several guidelines recommend all patients admitted with an acute stroke should receive an assessment by a rehabilitation professional [85, 86]. Specialized stroke rehabilitation units have been shown to improve functional outcomes, decrease mortality and reduce length of hospital stay in moderate to severe stroke patients . Combining an enriched environment with skill retraining, stroke rehabilitation units are made up of a multidisciplinary team of medical professionals who offer realistic goal setting and engage in multimodal disability and impairment assessment, medical management, and functional training. The team consists of rehabilitation nurses, occupational therapists, physiotherapists, and speech therapists under the leadership of physicians specialized in rehabilitation medicine. The work of these groups is further supported by dieticians, neuropsychologists, social workers, and recreational therapists such as music therapists. The rehabilitation team addresses the many challenges stroke patients could face such as sensorimotor and balance impairments, dysphagia, cognitive-communication impairments, mood disorders, visual and hearing impairments, and hemispatial neglect. Regular multidisciplinary meetings are conducted to discuss the rehabilitation goals, rehabilitation intervention, functional improvement, discharge planning, and arrangement of outpatient rehabilitation. These structured meetings have been shown to improve functional outcomes [88, 89]. Such collaborative teamwork involves communication among the team members, working towards a common goal and accepting responsibility as a group for the final outcome of the patients [90, 91]. Recommended realistic goals are also planned together with the patients and their caregivers to prepare them for a smooth transition to outpatient rehabilitation and discharge destination with the eventual aim to achieve maximum independence as possible .
The hours of therapy vary across different inpatient rehabilitation settings. Generally, most guidelines advocate minimum 45 minutes of each relevant therapy for at least 5 days a week [85, 86, 93]. In United States, inpatient rehabilitation facilities (IRFs) are mandated to provide at least 3 hours of therapy per day for minimum 5 days in a week. Rehabilitation in an IRF improves functional outcomes, independence, and mortality compared to a SNF (subacute rehabilitation), given the interprofessional team of providers, advanced treatment strategies, and the requirement that patients participate in therapy at least three hours daily . Patient’s ability to tolerate such level of intensity has to be taken into account when considered for an acute intensive inpatient rehabilitation placement. When the stroke patient is admitted to inpatient rehabilitation, the rehabilitation team would assess the patient and determine an individualized rehabilitation program of suitable intensity and duration to suit the needs for favorable stroke recovery .
It is generally recommended to commence stroke rehabilitation as soon as patients are medically stable, to maximize their functional gains and to take advantage of the period of early stroke recovery . However, caution and individualized clinical judgement are indicated especially in older patients and patients with intracerebral hemorrhage . The large multicenter AVERT trial showed that very early, more frequent, and increased dose of mobilization (VEM) intervention reduced the odds of a favorable outcome at 3 months after stroke when compared with usual care (UC) group . However, the median time to first mobilization in both groups was within 24 hours (22.4 hours in UC group versus 18.5 hours in VEM group) . Further analyses from the AVERT study suggested that shorter but more frequent mobilization early after stroke increased the odds of favorable outcome at 3 months when age and stroke severity were controlled . Earlier access to rehabilitation seems to favor better functional outcomes, shorten length of hospital stay, and increase likelihood of discharge to home [97, 98].
6. Transitional Care of Poststroke Survivors
Due to residual functional disability and associated medical complications, poststroke elderly survivors and their caregivers often experience significant physical, mental, and social challenges after being discharged home. In most cases, caregivers are usually poorly understood and ill-prepared for their roles and responsibilities they must face at home . As elderly stroke survivors require substantial care demands at home, their caregivers often feel overwhelmed and exhausted, which eventually lead to depression and deterioration of physical health .
Definition of transitional care (TC) is widely accepted as “a set of actions designed to ensure the coordination and continuity of healthcare as patients transfer between different locations or different levels of care within the same location” . TC can happen within same setting (e.g., primary care to specialty care); between different settings (e.g., hospital to subacute care); across health states (e.g., acute care to palliative care), or between providers (e.g., generalist to specialist). The different types of TC models for poststroke patients include hospital-initiated support; home-visiting programs; structured telephone support; outpatient setting-based support; lastly, primary patient and caregiver education. A recent meta-analysis by Wang Y et al. reported insufficient evidence to support the role of TC interventions in reduction of mortality and functional improvement after stroke . However, among all the TC interventions, home-visiting programs which focus on patients and caregivers’ needs and preferences in addition to well-established rehabilitation goals via multidisciplinary approach seem to be associated with positive outcomes . More research regarding TC interventions needs to be conducted before any further conclusions can be made.
7. Rehabilitation Resources and Services in Singapore in addition to the Challenges Faced
In Singapore, elderly stroke survivors after being medically stabilized at the acute hospitals will be transferred to receive inpatient rehabilitation either at rehabilitation units situated within acute hospitals or in community hospitals which are situated as stand-alone units. When the patients are ready for discharge from inpatient rehabilitation, arrangements are made for them to receive outpatient rehabilitation either at hospital outpatient clinic or at day rehabilitation center. Home therapy can be arranged for patients with difficulties to get out of their house. Government subsidies for day rehabilitation centers are available for patients who satisfy certain financial criteria .
However, the compliance rate of our local stroke survivors attending outpatient day rehabilitation has been dismal. Two local studies showed the attendance rates of outpatient rehabilitation at 1 year after discharge from community hospitals were 28% and 4.3%, respectively [102, 103]. Reasons for noncompliance to outpatient rehabilitation revolved around the patient’s functional, social, financial, medical, and perceptual factors . Firstly, stroke survivors who require ongoing rehabilitation will likely have difficulties in mobility. They also face challenges in stairs and transportation access. Secondly, some elderly live alone and have no caregiver to assist them to the outpatient rehabilitation center [103, 104]. For those with caregivers, the elderly stroke survivors often do not wish to inconvenience them . Thirdly, financial constraint is also commonly cited by the elderly for noncompliance to poststroke medical care and rehabilitation after hospital discharge [103–107]. Although Singaporean residents are eligible for the public healthcare system with significant subsidies from the government, much of the outpatient rehabilitation cannot be paid for with the use of medical savings account (Medicine) or national medical insurance (Medishield) . For those who are qualified for government medical subsidies, the transportation cost and cumulative cost of multiple sessions of outpatient rehabilitation often put them off from continuing rehabilitation . Fourthly, the elderly stroke survivors often suffer from comorbidities which may limit their ability to fully participate in rehabilitation [103, 108]. Cardiovascular and pulmonary diseases such as ischemic heart disease, congestive heart failure, arrhythmias, and chronic obstructive pulmonary disease which are more common in the elderly can result in reduced activity tolerance and restrict them from fully participating in rehabilitation . Vascular-related cognitive impairment which is more common in older stroke survivors could also pose as a barrier to successful rehabilitation . Lastly, although Singapore is one of the most urbanized, modernized, and prosperous countries in Asia, a strong influence of Eastern culture is still present on the local societal perceptions, especially in the elderly. The elderly in the Asian culture are inclined to rely on their children and would perceive rehabilitation as the equivalent of doing exercises at home without the guidance of a therapist and rehabilitation physician. As such, the patients do not see the need to attend outpatient rehabilitation and follow-up .
Home rehabilitation could potentially overcome some of the above challenges associated with outpatient rehabilitation. A local study by Tay et al. found most of the stroke patients in an inpatient rehabilitation unit would consider home rehabilitation program (HRP) . As for the minority who declined HRP, reasons given included financial constraint, unsupportive family members, privacy issues, and preference for a hospital-based rehabilitation . As the cost of each home rehabilitation session in Singapore is at least twice as expensive as each outpatient rehabilitation session, most of the patients would be more inclined to undergo HRP if it is Medisave deductible .
8. Discussion and Conclusions
With the rapidly aging population, several initiatives have been undertaken by the local government to provide better access for the elderly which could overcome the mobility issues faced by elderly stroke survivors. Examples include installation of ramps and additional lifts at local subway stations, introduction of wheelchair-accessible public buses, lift upgrading program to provide lift access on every level of the public housing blocks, and a heavily subsidized public housing home improvement program which includes ramp installation at the entrances of the housing units with steps. As for those elderly stroke survivors who do not have caregivers to assist them to the outpatient rehabilitation center, we propose implementation of an affordable HRP or low cost telerehabilitation. An ongoing local trial looking at telerehabilitation in the first 3 months after stroke perhaps would shed more light on the potential benefit and cost-effectiveness of telerehabilitation in the Singapore poststroke population . The use of home-based robot therapy (HBRT) could also be considered for those who had difficulty in accessing outpatient rehabilitation. Housley et al. found that HBRT reduced costs and increased access of rehabilitation to stroke survivors . In order to rectify the misconception of rehabilitation is the equivalent of doing exercises at home without the guidance of the rehabilitation team, education on stroke rehabilitation should be provided to all stroke patients and caregivers during the acute admission. It has been shown that the use of evidence-based educational guidelines have helped stroke survivors and their families to better understand the importance of stroke rehabilitation, control their comorbidities and cardiovascular risk factors, and reduce their risk of recurrent strokes .
In conclusion, stroke in elderly patients poses a major public health concern, due to its strong association with multiple medical complications, poorer functional outcomes, and substantial healthcare cost. For stroke survivors and their families, a good and comprehensive rehabilitation program is the key to recovery and to enable them to reach their highest level of independence as possible. The success of a stroke rehabilitation unit depends on the effective utilization of its resources and seamless coordination between different healthcare professionals as well as the ongoing support from the caregivers and other community services. Provision of evidence-based and culturally relevant stroke rehabilitation will help to effectively manage limited local healthcare resources and improve quality of life in our aging population.
Conflicts of Interest
The authors declare that there are no conflicts of interest regarding the publication of this article.
- E. J. Benjamin, M. J. Blaha, S. E. Chiuve et al., “Heart Disease and Stroke Statistics'2017 Update: A Report from the American Heart Association,” Circulation, vol. 135, no. 10, pp. e146–e603, 2017.
- Ministry of Health, “Singapore Health Facts,” https://www.moh.gov.sg/content/moh_web/home/statistics/Health_Facts_Singapore.html.
- T. Engstad, T. T. Engstad, M. Viitanen, and H. Ellekjær, “Epidemiology of stroke in the elderly in the Nordic countries. Incidence, survival, prevalence and risk factors,” Norsk epidemiologi, vol. 22, no. 2, pp. 121–126, 2012.
- N. Venketasubramanian, L. C. S. Tan, S. Sahadevan et al., “Prevalence of stroke among Chinese, Malay, and Indian Singaporeans: A community-based tri-racial cross-sectional survey,” Stroke, vol. 36, no. 3, pp. 551–556, 2005.
- Disease GBD, Injury I, and Prevalence C, “Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study,” Lancet, vol. 388, pp. 1545–1602, 2016.
- G. Saposnik, R. Cote, S. Phillips et al., “Stroke outcome in those over 80: A multicenter cohort study across Canada,” Stroke, vol. 39, no. 8, pp. 2310–2317, 2008.
- A. A. Divani, S. Majidi, A. M. Barrett, S. Noorbaloochi, and A. R. Luft, “Consequences of stroke in community-dwelling elderly: The health and retirement study, 1998 to 2008,” Stroke, vol. 42, no. 7, pp. 1821–1825, 2011.
- S. M. Hatem, G. Saussez, M. della Faille et al., “Rehabilitation of motor function after stroke: A multiple systematic review focused on techniques to stimulate upper extremity recovery,” Frontiers in Human Neuroscience, vol. 10, no. 2016, article no. 442, 2016.
- A. A. Divani, G. Vazquez, A. M. Barrett, M. Asadollahi, and A. R. Luft, “Risk factors associated with injury attributable to falling among elderly population with history of stroke,” Stroke, vol. 40, no. 10, pp. 3286–3292, 2009.
- M. Planton, S. Peiffer, J. F. Albucher et al., “Neuropsychological outcome after a first symptomatic ischaemic stroke with 'good recovery',” European Journal of Neurology, vol. 19, no. 2, pp. 212–219, 2012.
- S. M. C. Rasquin, J. Lodder, R. W. H. M. Ponds, I. Winkens, J. Jolles, and F. R. J. Verhey, “Cognitive functioning after stroke: A one-year follow-up study,” Dementia and Geriatric Cognitive Disorders, vol. 18, no. 2, pp. 138–144, 2004.
- M. Leśniak, T. Bak, W. Czepiel, J. Seniów, and A. Członkowska, “Frequency and prognostic value of cognitive disorders in stroke patients,” Dementia and Geriatric Cognitive Disorders, vol. 26, no. 4, pp. 356–363, 2008.
- S. T. Pendlebury and P. M. Rothwell, “Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis,” The Lancet Neurology, vol. 8, no. 11, pp. 1006–1018, 2009.
- F. Pasquier and D. Leys, “Why are stroke patients prone to develop dementia?” Journal of Neurology, vol. 244, no. 3, pp. 135–142, 1997.
- J. Surawan, S. Areemit, S. Tiamkao, T. Sirithanawuthichai, and S. Saensak, “Risk factors associated with post-stroke dementia: A systematic review and meta-analysis,” Neurology International, vol. 9, no. 3, pp. 63–68, 2017.
- D. L. Coco, G. Lopez, and S. Corrao, “Cognitive impairment and stroke in elderly patients,” Vascular Health and Risk Management, vol. 12, pp. 105–116, 2016.
- Z. Mehdi, J. Birns, and A. Bhalla, “Post-stroke urinary incontinence,” International Journal of Clinical Practice, vol. 67, no. 11, pp. 1128–1137, 2013.
- K.-H. Kong and S. Young, “Incidence and outcome of poststroke urinary retention: A prospective study,” Archives of Physical Medicine and Rehabilitation, vol. 81, no. 11, pp. 1464–1467, 2000.
- G. Scivoletto, U. Fuoco, D. Badiali et al., “3-07-43 Gastrointestinal dysfunction following stroke,” Journal of the Neurological Sciences, vol. 150, p. S151, 1997.
- J. Li, M. Yuan, Y. Liu et al., “Incidence of constipation in stroke patients: A systematic review and meta-analysis,” Medicine (United States), vol. 96, no. 25, Article ID e7225, 2017.
- D. Harari, C. Coshall, A. G. Rudd, and C. D. A. Wolfe, “New-onset fecal incontinence after stroke: Prevalence, natural history, risk factors, and impact,” Stroke, vol. 34, no. 1, pp. 144–150, 2003.
- W. F. Westendorp, P. J. Nederkoorn, J.-D. Vermeij, M. G. Dijkgraaf, and D. van de Beek, “Post-stroke infection: A systematic review and meta-analysis,” BMC Neurology, vol. 11, article no. 110, 2011.
- F. H. Vermeij, W. J. M. Scholte Op Reimer, P. De Man et al., “Stroke-associated infection is an independent risk factor for poor outcome after acute ischemic stroke: Data from the netherlands stroke survey,” Cerebrovascular Disease, vol. 27, no. 5, pp. 465–471, 2009.
- C. Iadecola and J. Anrather, “The immunology of stroke: from mechanisms to translation,” Nature Medicine, vol. 17, no. 7, pp. 796–808, 2011.
- S.-Y. Lee, C.-L. Chou, S. P. C. Hsu et al., “Outcomes after Stroke in Patients with Previous Pressure Ulcer: A Nationwide Matched Retrospective Cohort Study,” Journal of Stroke and Cerebrovascular Diseases, vol. 25, no. 1, pp. 220–227, 2016.
- E. Skaf, P. D. Stein, A. Beemath, J. Sanchez, M. A. Bustamante, and R. E. Olson, “Venous thromboembolism in patients with ischemic and hemorrhagic stroke,” American Journal of Cardiology, vol. 96, no. 12, pp. 1731–1733, 2005.
- V. R. Kshettry, B. P. Rosenbaum, A. Seicean, M. L. Kelly, N. K. Schiltz, and R. J. Weil, “Incidence and risk factors associated with in-hospital venous thromboembolism after aneurysmal subarachnoid hemorrhage,” Journal of Clinical Neuroscience, vol. 21, no. 2, pp. 282–286, 2014.
- J. Pongmoragot, A. A. Rabinstein, Y. Nilanont, R. H. Swartz, L. Zhou, and G. Saposnik, “Pulmonary embolism in ischemic stroke: clinical presentation, risk factors, and outcome.,” Journal of the American Heart Association, vol. 2, no. 6, p. e000372, 2013.
- A. Jonsson, I. Lindgren, B. Hallstrom, B. Norrving, and A. Lindgren, “Prevalence and intensity of pain after stroke: a population based study focusing on patients' perspectives,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 77, no. 5, pp. 590–595, 2006.
- H. Naess, L. Lunde, and J. Brogger, “The effects of fatigue, pain, and depression on quality of life in ischemic stroke patients: the Bergen Stroke Study,” Vascular Health and Risk Management, vol. 8, no. 1, pp. 407–413, 2012.
- M. J. O'Donnell, H.-C. Diener, R. L. Sacco, A. A. Panju, R. Vinisko, and S. Yusuf, “Chronic pain syndromes after ischemic stroke: PRoFESS trial,” Stroke, vol. 44, no. 5, pp. 1238–1243, 2013.
- R. A. Harrison and T. S. Field, “Post stroke pain: Identification, assessment, and therapy,” Cerebrovascular Disease, vol. 39, no. 3-4, pp. 190–201, 2015.
- S. C. Cramer and J. D. Riley, “Neuroplasticity and brain repair after stroke,” Current Opinion in Neurology, vol. 21, no. 1, pp. 76–82, 2008.
- A. W. Dromerick, D. F. Edwards, and M. N. Diringer, “Sensitivity to changes in disability after stroke: a comparison of four scales useful in clinical trials,” Journal of Rehabilitation Research and Development , vol. 40, no. 1, pp. 1–8, 2003.
- S. K. Ostwald, P. R. Swank, and M. M. Khan, “Predictors of functional independence and stress level of stroke survivors at discharge from inpatient rehabilitation,” Journal of Cardiovascular Nursing, vol. 23, no. 4, pp. 371–377, 2008.
- L. Denti, M. Agosti, and M. Franceschini, “Outcome predictors of rehabilitation for first stroke in the elderly,” European Journal of Physical and Rehabilitation Medicine, vol. 44, no. 1, pp. 3–11, 2008.
- P. S. Pohl, S. A. Billinger, A. Lentz, and B. Gajewski, “The role of patient demographics and clinical presentation in predicting discharge placement after inpatient stroke rehabilitation: Analysis of a large, US data base,” Disability and Rehabilitation, vol. 35, no. 12, pp. 990–994, 2013.
- P. J. Kelly, K. L. Furie, S. Shafqat, N. Rallis, Y. Chang, and J. Stein, “Functional recovery following rehabilitation after hemorrhagic and ischemic stroke,” Archives of Physical Medicine and Rehabilitation, vol. 84, no. 7, pp. 968–972, 2003.
- H. Mutai, T. Furukawa, K. Araki, K. Misawa, and T. Hanihara, “Factors associated with functional recovery and home discharge in stroke patients admitted to a convalescent rehabilitation ward,” Geriatrics & Gerontology International, vol. 12, no. 2, pp. 215–222, 2012.
- L. P. Kammersgaard, H. S. Jørgensen, J. Reith, H. Nakayama, P. M. Pedersen, and T. S. Olsen, “Short- and long-term prognosis for every old stroke patients. The Copenhagen Stroke Study,” Age and Ageing, vol. 33, no. 2, pp. 149–154, 2004.
- M. Spruit-van Eijk, S. U. Zuidema, B. I. Buijck, R. T. C. M. Koopmans, and A. C. H. Geurts, “Determinants of rehabilitation outcome in geriatric patients admitted to skilled nursing facilities after stroke: A Dutch multi-centre cohort study,” Age and Ageing, vol. 41, no. 6, Article ID afs105, pp. 746–752, 2012.
- K.-H. Kong, K. S. G. Chua, and A. P. Tow, “Clinical characteristics and functional outcome of stroke patients 75 years old and older,” Archives of Physical Medicine and Rehabilitation, vol. 79, no. 12, pp. 1535–1539, 1998.
- S. Stephens, R. A. Kenny, E. Rowan et al., “Association between mild vascular cognitive impairment and impaired activities of daily living in older stroke survivors without dementia,” Journal of the American Geriatrics Society, vol. 53, no. 1, pp. 103–107, 2005.
- S. Zinn, T. K. Dudley, H. B. Bosworth, H. M. Hoenig, P. W. Duncan, and R. D. Horner, “The effect of poststroke cognitive impairment on rehabilitation process and functional outcome,” Archives of Physical Medicine and Rehabilitation, vol. 85, no. 7, pp. 1084–1090, 2004.
- M. Pasquini, D. Leys, M. Rousseaux, F. Pasquier, and H. Hénon, “Influence of cognitive impairment on the institutionalisation rate 3 years after a stroke,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 78, no. 1, pp. 56–59, 2007.
- H. Hénon, I. Durieu, F. Lebert, F. Pasquier, and D. Leys, “Influence of prestroke dementia on early and delayed mortality in stroke patients,” Journal of Neurology, vol. 250, no. 1, pp. 10–16, 2003.
- M. H. Rabadi, F. M. Rabadi, L. Edelstein, and M. Peterson, “Cognitively Impaired Stroke Patients Do Benefit From Admission to an Acute Rehabilitation Unit,” Archives of Physical Medicine and Rehabilitation, vol. 89, no. 3, pp. 441–448, 2008.
- J. S. Luxenberg and L. Z. Feigenbaum, “Cognitive impairment on a rehabilitation service,” Archives of Physical Medicine and Rehabilitation, vol. 67, no. 11, pp. 796–798, 1986.
- B. Gialanella, R. Santoro, and C. Ferlucci, “Predicting outcome after stroke: The role of basic activities of daily living,” European Journal of Physical and Rehabilitation Medicine, vol. 49, no. 5, pp. 629–637, 2013.
- J. M. Veerbeek, G. Kwakkel, E. E. H. Van Wegen, J. C. F. Ket, and M. W. Heymans, “Early prediction of outcome of activities of daily living after stroke: A systematic review,” Stroke, vol. 42, no. 5, pp. 1482–1488, 2011.
- Y. S. Ng, K. H. X. Tan, C. Chen, G. C. Senolos, E. Chew, and G. C. Koh, “Predictors of acute, rehabilitation and total length of stay in acute stroke: A prospective cohort study,” Annals Academy of Medicine, Singapore, vol. 45, no. 9, pp. 394–403, 2016.
- R. M. Lazar and A. K. Boehme, “Aphasia As a Predictor of Stroke Outcome,” Current Neurology and Neuroscience Reports, vol. 17, no. 11, 2017.
- D. H. Barer, “Continence after stroke: Useful predictor or goal of therapy?” Age and Ageing, vol. 18, no. 3, pp. 183–191, 1989.
- D. T. Wade and R. L. Hewer, “Outlook after an acute stroke: Urinary incontinence and loss of consciousness compared in 532 patients,” QJM: An International Journal of Medicine, vol. 56, no. 3-4, pp. 601–608, 1985.
- J. E. Ween, M. P. Alexander, M. D'Esposito, and M. Roberts, “Incontinence after stroke in a rehabilitation setting: Outcome associations and predictive factors,” Neurology, vol. 47, no. 3, pp. 659–663, 1996.
- H. Nakayama, H. S. Jørgensen, P. M. Pedersen, H. O. Raaschou, and T. S. Olsen, “Prevalence and risk factors of incontinence after stroke: The Copenhagen Stroke Study,” Stroke, vol. 28, no. 1, pp. 58–62, 1997.
- M. Patel, C. Coshall, A. G. Rudd, and C. D. A. Wolfe, “Natural history and effects on 2-year outcomes of urinary incontinence after stroke,” Stroke, vol. 32, no. 1, pp. 122–127, 2001.
- B. Thommessen, E. Bautz-Holter, and K. Laake, “Predictors of outcome of rehabilitation of elderly stroke patients in a geriatric ward,” Clinical Rehabilitation, vol. 13, no. 2, pp. 123–128, 1999.
- N. Dancause, “Vicarious function of remote cortex following stroke: recent evidence from human and animal studies,” The Neuroscientist, vol. 12, no. 6, pp. 489–499, 2006.
- R. J. Nudo, “Neural bases of recovery after brain injury,” Journal of Communication Disorders, vol. 44, no. 5, pp. 515–520, 2011.
- E. Carrera and G. Tononi, “Diaschisis: Past, present, future,” Brain, vol. 137, no. 9, pp. 2408–2422, 2014.
- H. Duffau, “Acute functional reorganisation of the human motor cortex during resection of central lesions: a study using intraoperative brain mapping,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 70, no. 4, pp. 506–513, 2001.
- S. Li and S. T. Carmichael, “Growth-associated gene and protein expression in the region of axonal sprouting in the aged brain after stroke,” Neurobiology of Disease, vol. 23, no. 2, pp. 362–373, 2006.
- H. S. Jorgensen, H. Nakayama, H. O. Raaschou, and T. S. Olsen, “Neurologic and functional recovery the Copenhagen Stroke Study,” Physical Medicine & Rehabilitation Clinics of North America, vol. 10, no. 4, pp. 887–906, 1999.
- P. Langhorne, J. Bernhardt, and G. Kwakkel, “Stroke rehabilitation,” The Lancet, vol. 377, no. 9778, pp. 1693–1702, 2011.
- C. E. Skilbeck, D. T. Wade, R. L. Hewer, and V. A. Wood, “Recovery after stroke,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 46, no. 1, pp. 5–8, 1983.
- C. Winters, E. E. H. Van Wegen, A. Daffertshofer, and G. Kwakkel, “Generalizability of the Proportional Recovery Model for the Upper Extremity After an Ischemic Stroke,” Neurorehabilitation and Neural Repair, vol. 29, no. 7, pp. 614–622, 2015.
- E. R. Buch, S. Rizk, P. Nicolo, L. G. Cohen, A. Schnider, and A. G. Guggisberg, “Predicting motor improvement after stroke with clinical assessment and diffusion tensor imaging,” Neurology, vol. 86, no. 20, pp. 1924-1925, 2016.
- W. D. Byblow, C. M. Stinear, P. A. Barber, M. A. Petoe, and S. J. Ackerley, “Proportional recovery after stroke depends on corticomotor integrity,” Annals of Neurology, vol. 78, no. 6, pp. 848–859, 2015.
- W. Feng, J. Wang, P. Y. Chhatbar et al., “Corticospinal tract lesion load: an imaging biomarker for stroke motor outcomes,” Annals of Neurology, vol. 78, no. 6, pp. 860–870, 2015.
- C. M. Stinear, W. D. Byblow, S. J. Ackerley, M.-C. Smith, V. M. Borges, and P. A. Barber, “Proportional Motor Recovery after Stroke: Implications for Trial Design,” Stroke, vol. 48, no. 3, pp. 795–798, 2017.
- J. W. Krakauer, S. T. Carmichael, D. Corbett, and G. F. Wittenberg, “Getting neurorehabilitation right: what can be learned from animal models?” Neurorehabilitation and Neural Repair, vol. 26, no. 8, pp. 923–931, 2012.
- S. Prabhakaran, E. Zarahn, C. Riley et al., “Inter-individual variability in the capacity for motor recovery after ischemic stroke,” Neurorehabilitation and Neural Repair, vol. 22, no. 1, pp. 64–71, 2008.
- R. Teasell, J. Bitensky, K. Salter, and N. A. Bayona, “The role of timing and intensity of rehabilitation therapies,” Topics in Stroke Rehabilitation, vol. 12, no. 3, pp. 46–57, 2005.
- G. Kwakkel, R. C. Wagenaar, T. W. Koelman, G. J. Lankhorst, and J. C. Koetsier, “Effects of intensity of rehabilitation after stroke: A research synthesis,” Stroke, vol. 28, no. 8, pp. 1550–1556, 1997.
- P. Langhorne, R. Wagenaar, and C. Partridge, “Physiotherapy after stroke: more is better?” Physiotherapy Research International: The Journal for Researchers and Clinicians in Physical Therapy, vol. 1, no. 2, pp. 75–88, 1996.
- M. Lotze, C. Braun, N. Birbaumer, S. Anders, and L. G. Cohen, “Motor learning elicited by voluntary drive,” Brain, vol. 126, no. 4, pp. 866–872, 2003.
- P. Zhuang, N. Dang, A. Warzeri, C. Gerloff, L. G. Cohen, and M. Hallett, “Implicit and explicit learning in an auditory serial reaction time task,” Acta Neurologica Scandinavica, vol. 97, no. 2, pp. 131–137, 1998.
- P.-C. Fang, S. Barbay, E. J. Plautz, E. Hoover, S. M. Strittmatter, and R. J. Nudo, “Combination of NEP 1-40 treatment and motor training enhances behavioral recovery after a focal cortical infarct in rats,” Stroke, vol. 41, no. 3, pp. 544–549, 2010.
- L. Zai, C. Ferrari, S. Subbaiah et al., “Inosine alters gene expression and axonal projections in neurons contralateral to a cortical infarct and improves skilled use of the impaired limb,” The Journal of Neuroscience, vol. 29, no. 25, pp. 8187–8197, 2009.
- J. Nithianantharajah and A. J. Hannan, “Enriched environments, experience-dependent plasticity and disorders of the nervous system,” Nature Reviews Neuroscience, vol. 7, no. 9, pp. 697–709, 2006.
- B. B. Johansson and A.-L. Ohlsson, “Environment, social interaction, and physical activity as determinants of functional outcome after cerebral infarction in the rat,” Experimental Neurology, vol. 139, no. 2, pp. 322–327, 1996.
- B. Kolb, M. Forgie, R. Gibb, G. Gorny, and S. Rowntree, “Age, experience and the changing brain,” Neuroscience & Biobehavioral Reviews, vol. 22, no. 2, pp. 143–159, 1998.
- B. Will, R. Galani, C. Kelche, and M. R. Rosenzweig, “Recovery from brain injury in animals: Relative efficacy of environmental enrichment, physical exercise or formal training (1990-2002),” Progress in Neurobiology, vol. 72, no. 3, pp. 167–182, 2004.
- D. Hebert, M. P. Lindsay, A. McIntyre et al., “Canadian stroke best practice recommendations: Stroke rehabilitation practice guidelines, update 2015,” International Journal of Stroke, vol. 11, no. 4, pp. 459–484, 2016.
- C. J. Winstein, J. Stein, R. Arena et al., “Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association,” Stroke, vol. 47, no. 6, pp. e98–e169, 2016.
- Stroke Unit Trialists' Collaboration, “Organised inpatient (stroke unit) care for stroke,” Cochrane Database of Systematic Reviews, vol. 9, Article ID CD000197, 2013.
- D. J. Clarke, “The role of multidisciplinary team care in stroke rehabilitation,” Progress in Neurology and Psychiatry, vol. 17, no. 4, pp. 5–8, 2013.
- S. F. Tyson, L. Burton, and A. McGovern, “The effect of a structured model for stroke rehabilitation multi-disciplinary team meetings on functional recovery and productivity: A Phase I/II proof of concept study,” Clinical Rehabilitation, vol. 29, no. 9, pp. 920–925, 2015.
- P. Mandy, “Interdisciplinary rather than multidisciplinary or generic practice,” International Journal of Therapy and Rehabilitation, vol. 3, no. 2, pp. 110–112, 1996.
- D. J. Clarke, “Achieving teamwork in stroke units: The contribution of opportunistic dialogue,” Journal of Interprofessional Care, vol. 24, no. 3, pp. 285–297, 2010.
- A. L. Conneeley, “Interdisciplinary collaborative goal planning in a post-acute neurological setting: A qualitative study,” The British Journal of Occupational Therapy, vol. 67, no. 6, pp. 248–255, 2004.
- K. Dworzynski, G. Ritchie, and D. Playford, “Stroke rehabilitation: Long-term rehabilitation after stroke,” Clinical Medicine, vol. 15, no. 5, pp. 461–464, 2015.
- P. Langhorne, O. Wu, H. Rodgers, A. Ashburn, and J. Bernhardt, “A very early rehabilitation trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial,” Health Technology Assessment, vol. 21, no. 54, pp. 1–119, 2017.
- “Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial,” The Lancet, vol. 386, no. 9988, pp. 46–55, 2015.
- J. Bernhardt, L. Churilov, F. Ellery et al., “Prespecified dose-response analysis for A Very Early Rehabilitation Trial (AVERT),” Neurology, vol. 86, no. 23, pp. 2138–2145, 2016.
- K. Salter, J. Jutai, M. Hartley et al., “Impact of early vs delayed admission to rehabilitation on functional outcomes in persons with stroke,” Journal of Rehabilitation Medicine, vol. 38, no. 2, pp. 113–117, 2006.
- S. Paolucci, G. Antonucci, M. G. Grasso et al., “Early versus delayed inpatient stroke rehabilitation: A matched comparison conducted in Italy,” Archives of Physical Medicine and Rehabilitation, vol. 81, no. 6, pp. 695–700, 2000.
- B. J. Lutz, M. Young, K. J. Cox, C. Martz, and K. R. Creasy, “The crisis of stroke: Experiences of patients and their family caregivers,” Topics in Stroke Rehabilitation, vol. 18, no. 6, pp. 786–797, 2011.
- E. A. Coleman, “Falling through the cracks: challenges and opportunities for improving transitional care for persons with continuous complex care needs,” Journal of the American Geriatrics Society, vol. 51, no. 4, pp. 549–555, 2003.
- Y. Wang, F. Yang, H. Shi, C. Yang, and H. Hu, “What type of transitional care effectively reduced mortality and improved ADL of stroke patients? A meta-analysis,” International Journal of Environmental Research and Public Health, vol. 14, no. 5, article no. 510, 2017.
- G. C.-H. Koh, S. K. Saxena, T.-P. Ng, D. Yong, and N.-P. Fong, “Effect of duration, participation rate, and supervision during community rehabilitation on functional outcomes in the first poststroke year in Singapore,” Archives of Physical Medicine and Rehabilitation, vol. 93, no. 2, pp. 279–286, 2012.
- A. W. Chen, Y. T. Koh, S. W. Leong, N. g. LW, P. S. Lee, and Koh. G. C., “Post community hospital discharge rehabilitation attendance: Self-perceived barriers and participation over time,” Annals of the Academy of Medicine, Singapore, vol. 43, no. 3, pp. 136–144, 2014.
- K. Wei, C. Barr, and S. George, “Factors influencing post-stroke rehabilitation participation after discharge from hospital,” International Journal of Therapy & Rehabilitation, vol. 21, no. 6, pp. 260–267, 2014.
- A. L. Fitzpatrick, N. R. Powe, L. S. Cooper, D. G. Ives, J. A. Robbins, and E. Enright, “Barriers to health care access among the elderly and who perceives them,” American Journal of Public Health, vol. 94, no. 10, pp. 1788–1794, 2004.
- C. A. Okoro, T. W. Strine, S. L. Young, L. S. Balluz, and A. H. Mokdad, “Access to health care among older adults and receipt of preventive services. Results from the Behavioral Risk Factor Surveillance System, 2002,” Preventive Medicine, vol. 40, no. 3, pp. 337–343, 2005.
- C. A. Okoro, S. L. Young, T. W. Strine, L. S. Balluz, and A. H. Mokdad, “Uninsured adults aged 65 years and older: Is their health at risk?” Journal of Health Care for the Poor and Underserved, vol. 16, no. 3, pp. 453–463, 2005.
- M. Shaughnessy and K. Michael, “Stroke in Older Adults,” in Stroke Recovery and Rehabilitation, J. Stein, R. L. Harvey, C. J. Winstein, R. D. Zorowitz, and G. F. Wittenberg, Eds., pp. 753–766, demosMEDICAL, USA, 2 edition, 2015.
- S. S. Tay, T. C. Wee, S. Mohamed Noor, and N. Hassan, “View towards Rehabilitation in the Home - A Survey of Patient's Mindset towards a Home Rehabilitation Programme,” Annals of the Academy of Medicine, Singapore, vol. 45, no. 12, pp. 560–562, 2016.
- G. C.-H. Koh, S. C. Yen, A. Tay et al., “Singapore Tele-technology Aided Rehabilitation in Stroke (STARS) trial: Protocol of a randomized clinical trial on tele-rehabilitation for stroke patients,” BMC Neurology, vol. 15, no. 1, article no. 161, 2015.
- S. N. Housley, A. R. Garlow, K. Ducote et al., “Increasing Access to Cost Effective Home-Based Rehabilitation for Rural Veteran Stroke Survivors,” Austin Journal of Cerebrovascular Disease & Stroke, vol. 3, no. 2, pp. 1–11, 2016.
- S. K. Ostwald, S. Davis, G. Hersch, C. Kelley, and K. M. Godwin, “Evidence-based educational guidelines for stroke survivors after discharge home,” Journal of Neuroscience Nursing, vol. 40, no. 3, pp. 173–191, 2008.
Copyright © 2018 Siew Kwaon Lui and Minh Ha Nguyen. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.