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1.  Perturbation training to promote safe independent mobility post-stroke: study protocol for a randomized controlled trial 
BMC Neurology  2015;15:87.
Background
Falls are one of the most common medical complications post-stroke. Physical exercise, particularly exercise that challenges balance, reduces the risk of falls among healthy and frail older adults. However, exercise has not proven effective for preventing falls post-stroke. Falls ultimately occur when an individual fails to recover from a loss of balance. Thus, training to specifically improve reactive balance control could prevent falls. Perturbation training aims to improve reactive balance control by repeatedly exposing participants to postural perturbations. There is emerging evidence that perturbation training reduces fall rates among individuals with neurological conditions, such as Parkinson disease. The primary aim of this work is to determine if perturbation-based balance training can reduce occurrence of falls in daily life among individuals with chronic stroke. Secondary objectives are to determine the effect of perturbation training on balance confidence and activity restriction, and functional balance and mobility.
Methods/design
Individuals with chronic stroke will be recruited. Participants will be randomly assigned to one of two groups: 1) perturbation training, or 2) ‘traditional’ balance training. Perturbation training will involve both manual perturbations (e.g., a push or pull from a physiotherapist), and rapid voluntary movements to cause a loss of balance. Training will occur twice per week for 6 weeks. Participants will record falls and activity for 12 months following completion of the training program. Standardized clinical tools will be used to assess functional balance and mobility, and balance confidence before and after training.
Discussion
Falls are a significant problem for those with stroke. Despite the large body of work demonstrating effective interventions, such as exercise, for preventing falls in other populations, there is little evidence for interventions that prevent falls post-stroke. The proposed study will investigate a novel and promising intervention: perturbation training. If effective, this training has the potential to not only prevent falls, but to also improve safe independent mobility and engagement in daily activities for those with stroke.
Trial registration
Current Controlled Trials: ISRCTN05434601.
doi:10.1186/s12883-015-0347-8
PMCID: PMC4456796  PMID: 26048054
Stroke; Rehabilitation; Accidental falls; Postural balance
2.  The effects of augmented visual feedback during balance training in Parkinson’s disease: study design of a randomized clinical trial 
BMC Neurology  2013;13:137.
Background
Patients with Parkinson’s disease often suffer from reduced mobility due to impaired postural control. Balance exercises form an integral part of rehabilitative therapy but the effectiveness of existing interventions is limited. Recent technological advances allow for providing enhanced visual feedback in the context of computer games, which provide an attractive alternative to conventional therapy. The objective of this randomized clinical trial is to investigate whether a training program capitalizing on virtual-reality-based visual feedback is more effective than an equally-dosed conventional training in improving standing balance performance in patients with Parkinson’s disease.
Methods/design
Patients with idiopathic Parkinson’s disease will participate in a five-week balance training program comprising ten treatment sessions of 60 minutes each. Participants will be randomly allocated to (1) an experimental group that will receive balance training using augmented visual feedback, or (2) a control group that will receive balance training in accordance with current physical therapy guidelines for Parkinson’s disease patients. Training sessions consist of task-specific exercises that are organized as a series of workstations. Assessments will take place before training, at six weeks, and at twelve weeks follow-up. The functional reach test will serve as the primary outcome measure supplemented by comprehensive assessments of functional balance, posturography, and electroencephalography.
Discussion
We hypothesize that balance training based on visual feedback will show greater improvements on standing balance performance than conventional balance training. In addition, we expect that learning new control strategies will be visible in the co-registered posturographic recordings but also through changes in functional connectivity.
Trial registration
ISRCTN: ISRCTN47046299
doi:10.1186/1471-2377-13-137
PMCID: PMC3852133  PMID: 24093506
Randomized clinical trial; Parkinson’s disease; Physical therapy; Balance training; Postural control; Virtual reality; Visual feedback; Electroencephalography; Posturography; Force plate
3.  Cueing training in the home improves gait‐related mobility in Parkinson's disease: the RESCUE trial 
Objectives
Gait and mobility problems are difficult to treat in people with Parkinson's disease. The Rehabilitation in Parkinson's Disease: Strategies for Cueing (RESCUE) trial investigated the effects of a home physiotherapy programme based on rhythmical cueing on gait and gait‐related activity.
Methods
A single‐blind randomised crossover trial was set up, including 153 patients with Parkinson's disease aged between 41 and 80 years and in Hoehn and Yahr stage II–IV. Subjects allocated to early intervention (n = 76) received a 3‐week home cueing programme using a prototype cueing device, followed by 3 weeks without training. Patients allocated to late intervention (n = 77) underwent the same intervention and control period in reverse order. After the initial 6 weeks, both groups had a 6‐week follow‐up without training. Posture and gait scores (PG scores) measured at 3, 6 and 12 weeks by blinded testers were the primary outcome measure. Secondary outcomes included specific measures on gait, freezing and balance, functional activities, quality of life and carer strain.
Results
Small but significant improvements were found after intervention of 4.2% on the PG scores (p = 0.005). Severity of freezing was reduced by 5.5% in freezers only (p = 0.007). Gait speed (p = 0.005), step length (p<0.001) and timed balance tests (p = 0.003) improved in the full cohort. Other than a greater confidence to carry out functional activities (Falls Efficacy Scale, p = 0.04), no carry‐over effects were observed in functional and quality of life domains. Effects of intervention had reduced considerably at 6‐week follow‐up.
Conclusions
Cueing training in the home has specific effects on gait, freezing and balance. The decline in effectiveness of intervention effects underscores the need for permanent cueing devices and follow‐up treatment. Cueing training may be a useful therapeutic adjunct to the overall management of gait disturbance in Parkinson's disease.
doi:10.1136/jnnp.200X.097923
PMCID: PMC2077658  PMID: 17229744
4.  V-TIME: a treadmill training program augmented by virtual reality to decrease fall risk in older adults: study design of a randomized controlled trial 
BMC Neurology  2013;13:15.
Background
Recent work has demonstrated that fall risk can be attributed to cognitive as well as motor deficits. Indeed, everyday walking in complex environments utilizes executive function, dual tasking, planning and scanning, all while walking forward. Pilot studies suggest that a multi-modal intervention that combines treadmill training to target motor function and a virtual reality obstacle course to address the cognitive components of fall risk may be used to successfully address the motor-cognitive interactions that are fundamental for fall risk reduction. The proposed randomized controlled trial will evaluate the effects of treadmill training augmented with virtual reality on fall risk.
Methods/Design
Three hundred older adults with a history of falls will be recruited to participate in this study. This will include older adults (n=100), patients with mild cognitive impairment (n=100), and patients with Parkinson’s disease (n=100). These three sub-groups will be recruited in order to evaluate the effects of the intervention in people with a range of motor and cognitive deficits. Subjects will be randomly assigned to the intervention group (treadmill training with virtual reality) or to the active-control group (treadmill training without virtual reality). Each person will participate in a training program set in an outpatient setting 3 times per week for 6 weeks. Assessments will take place before, after, and 1 month and 6 months after the completion of the training. A falls calendar will be kept by each participant for 6 months after completing the training to assess fall incidence (i.e., the number of falls, multiple falls and falls rate). In addition, we will measure gait under usual and dual task conditions, balance, community mobility, health related quality of life, user satisfaction and cognitive function.
Discussion
This randomized controlled trial will demonstrate the extent to which an intervention that combines treadmill training augmented by virtual reality reduces fall risk, improves mobility and enhances cognitive function in a diverse group of older adults. In addition, the comparison to an active control group that undergoes treadmill training without virtual reality will provide evidence as to the added value of addressing motor cognitive interactions as an integrated unit.
Trial Registration
(NIH)–NCT01732653
doi:10.1186/1471-2377-13-15
PMCID: PMC3602099  PMID: 23388087
Falls; Ageing; Gait; Cognitive function; Prevention; Virtual reality
5.  A multi-centre, randomised controlled trial of the effectiveness of PDSAFE to prevent falls among people with Parkinson’s: study protocol 
BMC Neurology  2015;15:81.
Background
Falls amongst people with Parkinson’s (PwP) result in significant disability and reduced quality of life. There is emerging evidence that exercise-based and physiotherapeutic interventions are of benefit for improving fall risk factors, such as balance. However, the benefit, in terms of preventing falls, is mixed. The development of effective interventions has been identified as the highest research priority for this population.
The aim of this trial is to establish the effectiveness and cost-effectiveness of a novel, home-based physiotherapy programme, compared with usual care, on falls amongst PwP.
Methods/Design
A UK multi-centre, community-based, single blind, randomised controlled trial with twelve month follow-up, and nested economic evaluation and qualitative studies will be undertaken. Six hundred PwP who live in their own home, have had one or more falls in the previous year and an MMSE score of ≥24 will be recruited. Those living in care homes and those needing assistance from another person to walk indoors will not be eligible.
The intervention is a physiotherapist delivered, individually tailored and progressive, home-based programme (PDSAFE) comprising task orientated movement strategy training, functional lower limb strengthening and balance training, of six months duration. Unsupervised daily home exercises and strategies will be practised and supported using technology. Control participants will receive usual care.
Data collection will include falls, cognitive state, balance and mobility, fear of falling, freezing of gait, mood, quality of life, carer quality of life and resource use. Data will be collected at baseline, three, six and twelve months. Longitudinal semi-structured interviews will be undertaken with forty participants to explore the expectations and experiences of participants.
The primary outcome is risk of repeat falling at six months post-randomisation.
Discussion
The aims of this trial are to establish the effectiveness and cost-effectiveness of a novel, home-delivered physiotherapy intervention (PDSAFE) compared with usual care on risk of falling for PwP who have a history of falling. PDSAFE is a novel intervention that builds upon the existing literature and targeting known risk factors, being the first study that uses a novel delivery modus (technology) in conjunction with traditional physiotherapeutic approaches.
Trial registration
Current Controlled Trials ISRCTN48152791
doi:10.1186/s12883-015-0332-2
PMCID: PMC4431174  PMID: 25971244
Parkinson’s falls; Randomised; Physiotherapy; Exercise; Strategies
6.  Protocol for a randomized comparison of integrated versus consecutive dual task practice in Parkinson’s disease: the DUALITY trial 
BMC Neurology  2014;14:61.
Background
Multiple tasking is an integral part of daily mobility. Patients with Parkinson’s disease have dual tasking difficulties due to their combined motor and cognitive deficits. Two contrasting physiotherapy interventions have been proposed to alleviate dual tasking difficulties: either to discourage simultaneous execution of dual tasks (consecutive training); or to practice their concurrent use (integrated training). It is currently unclear which of these training methods should be adopted to achieve safe and consolidated dual task performance in daily life. Therefore, the proposed randomized controlled trial will compare the effects of integrated versus consecutive training of dual tasking (tested by combining walking with cognitive exercises).
Methods and design
Hundred and twenty patients with Parkinson’s disease will be recruited to participate in this multi-centered, single blind, randomized controlled trial. Patients in Hoehn & Yahr stage II-III, with or without freezing of gait, and who report dual task difficulties will be included. All patients will undergo a six-week control period without intervention after which they will be randomized to integrated or consecutive task practice. Training will consist of standardized walking and cognitive exercises delivered at home four times a week during six weeks. Treatment is guided by a physiotherapist twice a week and consists of two sessions of self-practice using an MP3 player. Blinded testers will assess patients before and after the control period, after the intervention period and after a 12-week follow-up period. The primary outcome measure is dual task gait velocity, i.e. walking combined with a novel untrained cognitive task to evaluate the consolidation of learning. Secondary outcomes include several single and dual task gait and cognitive measures, functional outcomes and a quality of life scale. Falling will be recorded as a possible adverse event using a weekly phone call for the entire study period.
Discussion
This randomized study will evaluate the effectiveness and safety of integrated versus consecutive task training in patients with Parkinson’s disease. The study will also highlight whether dual task gait training leads to robust motor learning effects, and whether these can be retained and carried-over to untrained dual tasks and functional mobility.
Trial registration
Clinicaltrials.gov NCT01375413.
doi:10.1186/1471-2377-14-61
PMCID: PMC3974198  PMID: 24674594
Parkinson disease; Rehabilitation; Physical therapy; Neurologic gait disorder; Cognition; Dual task
7.  Minimizing the evidence-practice gap – a prospective cohort study incorporating balance training into pulmonary rehabilitation for individuals with chronic obstructive pulmonary disease 
Background
We have recently demonstrated the efficacy of balance training in addition to Pulmonary Rehabilitation (PR) at improving measures of balance associated with an increased risk of falls in individuals with Chronic Obstructive Pulmonary Disease (COPD). Few knowledge translation (KT) projects have been conducted in rehabilitation settings. The goal of this study was to translate lessons learnt from efficacy studies of balance training into a sustainable clinical service.
Methods
Health care professionals (HCPs) responsible for delivering PR were given an hour of instruction on the principles and practical application of balance training and the researchers offered advice regarding; prescription, progression and practical demonstrations during the first week. Balance training was incorporated three times a week into conventional PR programs. Following the program, HCPs participated in a focus group exploring their experiences of delivering balance training alongside PR. Service users completed satisfaction surveys as well as standardized measures of balance control. At six month follow-up, the sustainability of balance training was explored.
Results
HCPs considered the training to be effective at improving balance and the support provided by the researchers was viewed as helpful. HCPs identified a number of strategies to facilitate balance training within PR, including; training twice a week, incorporating an interval training program for everyone enrolled in PR, providing visual aids to training and promoting independence by; providing a set program, considering the environment and initiating a home-based exercise program early. Nineteen service users completed the balance training [ten male mean (SD) age 73 (6) y]. Sixteen patients (84 %) enjoyed balance training and reported that it helped them with everyday activities and 18 (95 %) indicated their wish to continue with it. Scores on balance measures improved following PR that included balance training (all p < 0.05). At six month follow-up balance training is being routinely assessed and delivered as part of standardised PR.
Conclusions
Implementing balance training into PR programs, with support and training for HCPs, is feasible, effective and sustainable.
Trail registration
Clinical Trials ID: NCT02080442 (05/03/2014)
Electronic supplementary material
The online version of this article (doi:10.1186/s12890-015-0067-2) contains supplementary material, which is available to authorized users.
doi:10.1186/s12890-015-0067-2
PMCID: PMC4511452  PMID: 26202647
Knowledge translation; Knowledge to action; COPD; Balance; Falls; Pulmonary rehabilitation; Physiotherapists
8.  Tai Chi and Postural Stability in Patients with Parkinson's Disease 
The New England Journal of Medicine  2012;366(6):511-519.
Background
Patients with Parkinson's disease have substantially impaired balance, leading to diminished functional ability and an increased risk of falling. Although exercise is routinely encouraged by health care providers, few programs have been proven effective.
Methods
We conducted a randomized, controlled trial to determine whether a tailored tai chi program could improve postural control in patients with idiopathic Parkinson's disease. We randomly assigned 195 patients with stage 1 to 4 disease on the Hoehn and Yahr staging scale (which ranges from 1 to 5, with higher stages indicating more severe disease) to one of three groups: tai chi, resistance training, or stretching. The patients participated in 60-minute exercise sessions twice weekly for 24 weeks. The primary outcomes were changes from baseline in the limits-of-stability test (maximum excursion and directional control; range, 0 to 100%). Secondary outcomes included measures of gait and strength, scores on functional-reach and timed up-and-go tests, motor scores on the Unified Parkinson's Disease Rating Scale, and number of falls.
Results
The tai chi group performed consistently better than the resistance-training and stretching groups in maximum excursion (between-group difference in the change from baseline, 5.55 percentage points; 95% confidence interval [CI], 1.12 to 9.97; and 11.98 percentage points; 95% CI, 7.21 to 16.74, respectively) and in directional control (10.45 percentage points; 95% CI, 3.89 to 17.00; and 11.38 percentage points; 95% CI, 5.50 to 17.27, respectively). The tai chi group also performed better than the stretching group in all secondary outcomes and outperformed the resistance-training group in stride length and functional reach. Tai chi lowered the incidence of falls as compared with stretching but not as compared with resistance training. The effects of tai chi training were maintained at 3 months after the intervention. No serious adverse events were observed.
Conclusions
Tai chi training appears to reduce balance impairments in patients with mild-to-moderate Parkinson's disease, with additional benefits of improved functional capacity and reduced falls. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00611481.)
doi:10.1056/NEJMoa1107911
PMCID: PMC3285459  PMID: 22316445
9.  A comparison of Irish set dancing and exercises for people with Parkinson’s disease: A phase II feasibility study 
BMC Geriatrics  2013;13:54.
Background
People with idiopathic Parkinson’s disease (PD) frequently have low activity levels, poor mobility and reduced quality of life. Although increased physical activity may improve mobility, balance and wellbeing, adherence to exercises and activity programs over the longer term can be challenging, particularly for older people with progressive neurological conditions such as PD. Physical activities that are engaging and enjoyable, such as dancing, might enhance adherence over the long term. The objective of this study was to evaluate the feasibility of a randomized controlled trial of Irish set dancing compared with routine physiotherapy for people with mild to moderately severe PD.
Methods
Twenty-four people with idiopathic PD referred for movement rehabilitation were randomized to receive standard physiotherapy exercises or Irish set dancing classes once per week plus a weekly home program for 6 months (12 in each group). The feasibility and safety of the proposed RCT protocol was the main focus of this evaluation. The primary outcome was motor disability measured by the motor component of the UPDRS, which was assessed prior to and after therapy by trained assessors blinded to group assignment. The Timed Up and Go, the Berg Balance Scale and the modified Freezing of Gait Questionnaire were secondary measures. Quality of life of the people with PD was evaluated using the PDQ-39.
Results
Both the Irish set dancing and physiotherapy exercise program were shown to be feasible and safe. There were no differences between groups in the rate of adverse events such as falls, serious injuries, death or rates of admission to hospital. The physiotherapists who provided usual care remained blind to group allocation, with no change in their standard clinical practice. Compliance and adherence to both the exercise and dance programs were very high and attrition rates were low over the 6 months of therapy. Although improvements were made in both groups, the dance group showed superior results to standard physiotherapy in relation to freezing of gait, balance and motor disability.
Conclusions
Irish dancing and physiotherapy were both safe and feasible in this sample from Venice, with good adherence over a comparatively long time period of 6 months. A larger multi-centre trial is now warranted to establish whether Irish set dancing is more effective than routine physiotherapy for enhancing mobility, balance and quality of life in people living with idiopathic PD.
Trial registration
EudraCT number 2012-005769-11
doi:10.1186/1471-2318-13-54
PMCID: PMC3685562  PMID: 23731986
Parkinson’s disease; Dancing; Rehabilitation; Exercise therapy; Balance; Randomized controlled trial; Geriatrics
10.  The ReSPonD trial - rivastigmine to stabilise gait in Parkinson’s disease a phase II, randomised, double blind, placebo controlled trial to evaluate the effect of rivastigmine on gait in patients with Parkinson’s disease who have fallen 
BMC Neurology  2013;13:188.
Background
Gait impairment is common in people with Parkinson’s disease. There is a lack of effective interventions to target this debilitating complication and therefore a need to identify new therapeutic options. An underlying cholinergic deficit contributes to both the gait and cognitive dysfunction seen in Parkinson’s disease. The combined impact of both impairments can be assessed in gait tasks performed with concomitant cognitive tasks. The aim of this trial is to evaluate the impact of a cholinesterase inhibitor on cognitive function and gait performance in people with established Parkinson’s disease.
Methods/design
This is a single centre, double-blind, randomised placebo-controlled trial in 130 people with Hoehn and Yahr stage 2–3 idiopathic Parkinson’s disease who have fallen in the past year. Participants will be randomised to two groups, receiving either rivastigmine capsules or identical placebo capsules for 8 months. Assessment will be undertaken at baseline and at the end of medication prescription (i.e. 8 months) with participants remaining enrolled in the trial for a further 4 months to monitor for falls and adverse events. The primary outcome is step time variability, assessed with and without the addition of concurrent cognitive tasks. Secondary outcomes will include other gait parameters, sensorimotor and balance performances, cognitive indices, falls and fall related injury, fear of falling, Parkinson’s symptoms and data pertaining to possible harms.
Discussion
This randomised controlled trial will examine the effect of cholinesterase inhibitor therapy on gait, balance and falls in Parkinson’s disease. If effective, it would offer a new therapeutic option to ameliorating gait and cognitive deficits in a population at high risk of falls.
Trial registration
ISRCTN19880883, UTN U1111-1124-0244.
doi:10.1186/1471-2377-13-188
PMCID: PMC3880104  PMID: 24299497
Randomised control trial; Parkinson’s disease; Accidental Falls; Freezing of gait; Intervention; Gait analysis; Acetylcholinesterase; Cognitive; Attention; Dual-tasking
11.  Balance circuit classes to improve balance among rehabilitation inpatients: a protocol for a randomised controlled trial 
BMC Geriatrics  2013;13:75.
Background
Impaired balance and mobility are common among rehabilitation inpatients. Poor balance and mobility lead to an increased risk of falling. Specific balance exercise has been shown to improve balance and reduce falls within the community setting. However few studies have measured the effects of balance exercises on balance within the inpatient setting.
The aim of this randomised controlled trial is to investigate whether the addition of circuit classes targeting balance to usual therapy lead to greater improvements in balance among rehabilitation inpatients than usual therapy alone.
Methods/Design
A single centre, randomised controlled trial with concealed allocation, assessor blinding and intention-to-treat analysis. One hundred and sixty two patients admitted to the general rehabilitation ward at Bankstown-Lidcombe Hospital will be recruited. Eligible participants will have no medical contraindications to exercise and will be able to: fully weight bear; stand unaided independently for at least 30 seconds; and participate in group therapy sessions with minimal supervision.
Participants will be randomly allocated to an intervention group or usual-care control group. Both groups will receive standard rehabilitation intervention that includes physiotherapy mobility training and exercise for at least two hours on each week day. The intervention group will also receive six 1-hour circuit classes of supervised balance exercises designed to maximise the ability to make postural adjustments in standing, stepping and walking.
The primary outcome is balance. Balance will be assessed by measuring the total time the participant can stand unsupported in five different positions; feet apart, feet together, semi-tandem, tandem and single-leg-stance. Secondary outcomes include mobility, self reported physical functioning, falls and hospital readmissions. Performance on the outcome measures will be assessed before randomisation and at two-weeks and three-months after randomisation by physiotherapists unaware of intervention group allocation.
Discussion
This study will determine the impact of additional balance circuit classes on balance among rehabilitation inpatients. The results will provide essential information to guide evidence-based physiotherapy at the study site as well as across other rehabilitation inpatient settings.
Trial registration
The protocol for this study is registered with the Australian New Zealand, Clinical Trials Registry: ACTRN=12611000412932
doi:10.1186/1471-2318-13-75
PMCID: PMC3723870  PMID: 23870654
Balance; Rehabilitation; Inpatients; Circuit classes; Physiotherapy; Exercises
12.  Trunk muscle exercises as a means of improving postural stability in people with Parkinson's disease: a protocol for a randomised controlled trial 
BMJ Open  2014;4(12):e006095.
Introduction
Exercise has been shown to improve clinical measures of strength, balance and mobility, and in some cases, has improved symptoms of tremor and rigidity in people with Parkinson's disease (PD). However, to date, no research has examined whether improvements in trunk control can remedy deficits in dynamic postural stability in this population. The proposed randomised controlled trial aims to establish whether a 12-week exercise programme aimed at improving dynamic postural stability in people with PD; (1) is more effective than education; (2) is more effective when training frequency is increased; and (3) provides greater long-term benefits than education.
Methods/design
Forty-five community-dwelling individuals diagnosed with idiopathic PD with a falls history will be recruited. Participants will complete baseline assessments including tests of cognition, vision, disease severity, fear of falling, mobility and quality of life. Additionally, participants will complete a series of standing balance tasks to evaluate static postural stability, while dynamic postural control will be measured during walking using head and trunk-mounted three-dimensional accelerometers. Following baseline testing, participants will be randomly-assigned to one of three intervention groups, who will receive either exercise once per week, exercise 3 days/week, or education. Participants will repeat the same battery of tests conducted at baseline after the 12-week intervention and again following a further 12-week sustainability period.
Discussion
This study has the potential to show that low-intensity and progressive trunk exercises can provide a non-invasive and effective means for maintaining or improving postural stability for people with PD. Importantly, if the programme is noted to be effective, it could be easily performed by patients within their home environment or under the guidance of available allied health professionals.
Trial registration number
The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613001175763).
doi:10.1136/bmjopen-2014-006095
PMCID: PMC4281545  PMID: 25552609
PUBLIC HEALTH
13.  Audio-Biofeedback training for posture and balance in Patients with Parkinson's disease 
Background
Patients with Parkinson's disease (PD) suffer from dysrhythmic and disturbed gait, impaired balance, and decreased postural responses. These alterations lead to falls, especially as the disease progresses. Based on the observation that postural control improved in patients with vestibular dysfunction after audio-biofeedback training, we tested the feasibility and effects of this training modality in patients with PD.
Methods
Seven patients with PD were included in a pilot study comprised of a six weeks intervention program. The training was individualized to each patient's needs and was delivered using an audio-biofeedback (ABF) system with headphones. The training was focused on improving posture, sit-to-stand abilities, and dynamic balance in various positions. Non-parametric statistics were used to evaluate training effects.
Results
The ABF system was well accepted by all participants with no adverse events reported. Patients declared high satisfaction with the training. A significant improvement of balance, as assessed by the Berg Balance Scale, was observed (improvement of 3% p = 0.032), and a trend in the Timed up and go test (improvement of 11%; p = 0.07) was also seen. In addition, the training appeared to have a positive influence on psychosocial aspects of the disease as assessed by the Parkinson's disease quality of life questionnaire (PDQ-39) and the level of depression as assessed by the Geriatric Depression Scale.
Conclusions
This is, to our knowledge, the first report demonstrating that audio-biofeedback training for patients with PD is feasible and is associated with improvements of balance and several psychosocial aspects.
doi:10.1186/1743-0003-8-35
PMCID: PMC3142211  PMID: 21693054
Intervention; mobility; neurodegenerative disease; postural control; posture; Parkinson's disease
14.  Protocol for a randomized controlled clinical trial investigating the effectiveness of Fast muscle Activation and Stepping Training (FAST) for improving balance and mobility in sub-acute stroke 
BMC Neurology  2014;14:187.
Background
Following stroke, many people have difficulty activating their paretic muscles quickly and with sufficient power to regain their balance by taking quick and effective steps. Reduced dynamic balance and mobility following stroke, or ‘walking balance’, is associated with reduced self-efficacy and restrictions in daily living activities, community integration, and quality of life. Targeted training of movement speeds required to effectively regain balance has been largely overlooked in post-stroke rehabilitation. The Fast muscle Activation and Stepping Training (FAST) program incorporates fast functional movements known to produce bursts of muscle activation essential for stepping and regaining standing balance effectively. The purpose of this study is to: 1) compare the effectiveness of an outpatient FAST program to an active control outpatient physiotherapy intervention in improving walking balance following stroke, and 2) explore potential mechanisms associated with improvements in walking balance.
Methods/Design
This will be an assessor-blinded, parallel group randomized controlled trial design. Sixty participants (30 per group) who have sustained a stroke within the previous six months will be randomly assigned with stratification for lower limb motor recovery to receive twelve 45-minute 1:1 physiotherapy intervention sessions over 6 – 10 weeks in an outpatient setting of either: 1) FAST intervention - systematic and progressive practice of fast squatting and stepping exercises, or 2) active control - conventional physiotherapy directed at improving balance and mobility that includes no targeted fast movement training. The same blinded research physiotherapist will assess outcomes at three time points: 1) baseline (prior to intervention), 2) follow up (within one week post-intervention); and 3) retention (one month post-intervention). The primary outcome is dynamic balance assessed using the Community Balance and Mobility Scale. We will also assess fast and self-selected walking speed, balance self-efficacy, and the ability to respond to internal and external perturbations to balance and associated changes in postural muscle activation.
Discussion
The targeted training of fast functional movements in the FAST program is expected to improve walking balance following stroke compared to the active control intervention. Unique to this study is the investigation of potential mechanisms associated with improvements in walking balance.
Trial registration
NCT01573585
Electronic supplementary material
The online version of this article (doi:10.1186/s12883-014-0187-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12883-014-0187-y
PMCID: PMC4207320  PMID: 25300433
Stroke; Postural control; Randomized clinical trial; Rehabilitation; Physiotherapy; Exercise therapy; Treatment outcome; Electromyography; Walking
15.  Effectiveness of balance training exercise in people with mild to moderate severity Alzheimer's disease: protocol for a randomised trial 
BMC Geriatrics  2009;9:29.
Background
Balance dysfunction and falls are common problems in later stages of dementia. Exercise is a well-established intervention to reduce falls in cognitively intact older people, although there is limited randomised trial evidence of outcomes in people with dementia. The primary objective of this study is to evaluate whether a home-based balance exercise programme improves balance performance in people with mild to moderate severity Alzheimer's disease.
Methods/design
Two hundred and fourteen community dwelling participants with mild to moderate severity Alzheimer's disease will be recruited for the randomised controlled trial. A series of laboratory and clinical measures will be used to evaluate balance and mobility performance at baseline. Participants will then be randomized to receive either a balance training home exercise programme (intervention group) from a physiotherapist, or an education, information and support programme from an occupational therapist (control group). Both groups will have six home visits in the six months following baseline assessment, as well as phone support. All participants will be re-assessed at the completion of the programme (after six months), and again in a further six months to evaluate sustainability of outcomes. The primary outcome measures will be the Limits of Stability (a force platform measure of balance) and the Step Test (a clinical measure of balance). Secondary outcomes include other balance and mobility measures, number of falls and falls risk measures, cognitive and behavioural measures, and carer burden and quality of life measures. Assessors will be blind to group allocation.
Longitudinal change in balance performance will be evaluated in a sub-study, in which the first 64 participants of the control group with mild to moderate severity Alzheimer's disease, and 64 age and gender matched healthy participants will be re-assessed on all measures at initial assessment, and then at 6, 12, 18 and 24 months.
Discussion
By introducing a balance programme at an early stage of the dementia pathway, when participants are more likely capable of safe and active participation in balance training, there is potential that balance performance will be improved as dementia progresses, which may reduce the high falls risk at this later stage. If successful, this approach has the potential for widespread application through community based services for people with mild to moderate severity Alzheimer's disease.
Trial registration
The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12608000040369).
doi:10.1186/1471-2318-9-29
PMCID: PMC2722658  PMID: 19607686
16.  Falls and mobility in Parkinson's disease: protocol for a randomised controlled clinical trial 
BMC Neurology  2011;11:93.
Background
Although physical therapy and falls prevention education are argued to reduce falls and disability in people with idiopathic Parkinson's disease, this has not yet been confirmed with a large scale randomised controlled clinical trial. The study will investigate the effects on falls, mobility and quality of life of (i) movement strategy training combined with falls prevention education, (ii) progressive resistance strength training combined with falls prevention education, (iii) a generic life-skills social program (control group).
Methods/Design
People with idiopathic Parkinson's disease who live at home will be recruited and randomly allocated to one of three groups. Each person shall receive therapy in an out-patient setting in groups of 3-4. Each group shall be scheduled to meet once per week for 2 hours for 8 consecutive weeks. All participants will also have a structured 2 hour home practice program for each week during the 8 week intervention phase. Assessments will occur before therapy, after the 8 week therapy program, and at 3 and 12 months after the intervention. A falls calendar will be kept by each participant for 12 months after outpatient therapy.
Consistent with the recommendations of the Prevention of Falls Network Europe group, three falls variables will be used as the primary outcome measures: the number of fallers, the number of multiple fallers and the falls rate. In addition to quantifying falls, we shall measure mobility, activity limitations and quality of life as secondary outcomes.
Discussion
This study has the potential to determine whether outpatient movement strategy training combined with falls prevention education or progressive resistance strength training combined with falls prevention education are effective for reducing falls and improving mobility and life quality in people with Parkinson's disease who live at home.
Trial registration
Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12606000344594
doi:10.1186/1471-2377-11-93
PMCID: PMC3160881  PMID: 21801451
17.  The gait and balance of patients with diabetes can be improved: a randomised controlled trial 
Diabetologia  2009;53(3):458-466.
Aims/hypothesis
Gait characteristics and balance are altered in diabetic patients. Little is known about possible treatment strategies. This study evaluates the effect of a specific training programme on gait and balance of diabetic patients.
Methods
This was a randomised controlled trial (n = 71) with an intervention (n = 35) and control group (n = 36). The intervention consisted of physiotherapeutic group training including gait and balance exercises with function-orientated strengthening (twice weekly over 12 weeks). Controls received no treatment. Individuals were allocated to the groups in a central office. Gait, balance, fear of falls, muscle strength and joint mobility were measured at baseline, after intervention and at 6-month follow-up.
Results
The trial is closed to recruitment and follow-up. After training, the intervention group increased habitual walking speed by 0.149 m/s (p < 0.001) compared with the control group. Patients in the intervention group also significantly improved their balance (time to walk over a beam, balance index recorded on Biodex balance system), their performance-oriented mobility, their degree of concern about falling, their hip and ankle plantar flexor strength, and their hip flexion mobility compared with the control group. After 6 months, all these variables remained significant except for the Biodex sway index and ankle plantar flexor strength. Two patients developed pain in their Achilles tendon: the progression for two related exercises was slowed down.
Conclusions/interpretation
Specific training can improve gait speed, balance, muscle strength and joint mobility in diabetic patients. Further studies are needed to explore the influence of these improvements on the number of reported falls, patients’ physical activity levels and quality of life.
Trial registration:
ClinicalTrials.gov NCT00637546
Funding:
This work was supported by the Swiss National Foundation (SNF): PBSKP-123446/1/
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-009-1592-4) contains supplementary material, which is available to authorised users.
doi:10.1007/s00125-009-1592-4
PMCID: PMC2815802  PMID: 19921145
Balance; Clinical diabetes; Diabetic foot; Exercise; Fear; Gait disorders; Joint mobility; Neuropathy; Muscle strength; Walking
18.  Wearable Sensor Use for Assessing Standing Balance and Walking Stability in People with Parkinson’s Disease: A Systematic Review 
PLoS ONE  2015;10(4):e0123705.
Background
Postural instability and gait disability threaten the independence and well-being of people with Parkinson’s disease and increase the risk of falls and fall-related injuries. Prospective research has shown that commonly-used clinical assessments of balance and walking lack the sensitivity to accurately and consistently identify those people with Parkinson’s disease who are at a higher risk of falling. Wearable sensors provide a portable and affordable alternative for researchers and clinicians who are seeking to objectively assess movements and falls risk in the clinical setting. However, no consensus currently exists on the optimal placements for sensors and the best outcome measures to use for assessing standing balance and walking stability in Parkinson’s disease patients. Hence, this systematic review aimed to examine the available literature to establish the best sensor types, locations and outcomes to assess standing balance and walking stability in this population.
Methods
Papers listed in three electronic databases were searched by title and abstract to identify articles measuring standing balance or walking stability with any kind of wearable sensor among adults diagnosed with PD. To be eligible for inclusion, papers were required to be full-text articles published in English between January 1994 and December 2014 that assessed measures of standing balance or walking stability with wearable sensors in people with PD. Articles were excluded if they; i) did not use any form of wearable sensor to measure variables associated with standing balance or walking stability; ii) did not include a control group or control condition; iii) were an abstract and/or included in the proceedings of a conference; or iv) were a review article or case study. The targeted search of the three electronic databases identified 340 articles that were potentially eligible for inclusion, but following title, abstract and full-text review only 26 articles were deemed to meet the inclusion criteria. Included articles were assessed for methodological quality and relevant data from the papers were extracted and synthesized.
Results
Quality assessment of these included articles indicated that 31% were of low methodological quality, while 58% were of moderate methodological quality and 11% were of high methodological quality. All studies adopted a cross-sectional design and used a variety of sensor types and outcome measures to assess standing balance or walking stability in people with Parkinson’s disease. Despite the typically low to moderate methodological quality, 81% of the studies reported differences in sensor-based measures of standing balance or walking stability between different groups of Parkinson’s disease patients and/or healthy controls.
Conclusion
These data support the use of wearable sensors for detecting differences in standing balance and walking stability between people with PD and controls. Further high-quality research is needed to better understand the utility of wearable sensors for the early identification of Parkinson’s disease symptoms and for assessing falls risk in this population.
PROSPERO Registration
CRD42014010838
doi:10.1371/journal.pone.0123705
PMCID: PMC4403989  PMID: 25894561
19.  Physiotherapy intervention in Parkinson’s disease: systematic review and meta-analysis  
Objective To assess the effectiveness of physiotherapy compared with no intervention in patients with Parkinson’s disease.
Design Systematic review and meta-analysis of randomised controlled trials.
Data sources Literature databases, trial registries, journals, abstract books, and conference proceedings, and reference lists, searched up to the end of January 2012.
Review methods Randomised controlled trials comparing physiotherapy with no intervention in patients with Parkinson’s disease were eligible. Two authors independently abstracted data from each trial. Standard meta-analysis methods were used to assess the effectiveness of physiotherapy compared with no intervention. Tests for heterogeneity were used to assess for differences in treatment effect across different physiotherapy interventions used. Outcome measures were gait, functional mobility and balance, falls, clinician rated impairment and disability measures, patient rated quality of life, adverse events, compliance, and economic analysis outcomes.
Results 39 trials of 1827 participants met the inclusion criteria, of which 29 trials provided data for the meta-analyses. Significant benefit from physiotherapy was reported for nine of 18 outcomes assessed. Outcomes which may be clinically significant were speed (0.04 m/s, 95% confidence interval 0.02 to 0.06, P<0.001), Berg balance scale (3.71 points, 2.30 to 5.11, P<0.001), and scores on the unified Parkinson’s disease rating scale (total score −6.15 points, −8.57 to −3.73, P<0.001; activities of daily living subscore −1.36, −2.41 to −0.30, P=0.01; motor subscore −5.01, −6.30 to −3.72, P<0.001). Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the interventions for any outcomes assessed, apart from motor subscores on the unified Parkinson’s disease rating scale (in which one trial was found to be the cause of the heterogeneity).
Conclusions Physiotherapy has short term benefits in Parkinson’s disease. A wide range of physiotherapy techniques are currently used to treat Parkinson’s disease, with little difference in treatment effects. Large, well designed, randomised controlled trials with improved methodology and reporting are needed to assess the efficacy and cost effectiveness of physiotherapy for treating Parkinson’s disease in the longer term.
doi:10.1136/bmj.e5004
PMCID: PMC3412755  PMID: 22867913
20.  Effects of Single-Task Versus Dual-Task Training on Balance Performance in Older Adults: A Double-Blind, Randomized Controlled Trial 
Objective
To compare the effect of 3 different approaches to balance training on dual-task balance performance in older adults with balance impairment.
Design
A double-blind, randomized controlled trial.
Setting
University research laboratory.
Participants
Older adults (N=23) with balance impairment (mean age, 74.8y). They scored 52 or less on the Berg Balance Scale (BBS), and/or walked with a self-selected gait speed of 1.1m/s or less.
Interventions
Participants were randomly assigned to 1 of 3 interventions: single-task training; dual-task training with fixed-priority instruction; and dual-task training with variable-priority instruction. Participants received 45-minute individualized training sessions, 3 times a week for 4 weeks.
Main Outcome Measures
Gait speed under single-task and dual-task conditions were obtained at baseline, the second week, the end of training, and the twelfth week after the end of training. Other measures, including the BBS and the Activities-specific Balance Confidence (ABC) Scale, were collected at baseline and after training.
Results
Participants in all groups improved on the BBS (P<.001, effect size [ES]=.72), and walked significantly faster after training (P=.02, ES=.27). When a cognitive task was added, however, only participants who received dual-task training with fixed-priority instruction and dual-task training with variable-priority instructions exhibited significant improvements in gait speed (P<.001, ES=.57 and P<.001, ES=.46, respectively). In addition, only the dual-task training with variable-priority instruction group demonstrated a dual-task training effect at the second week of training and maintained the training effect at the 12-week follow-up. Only the single-task training group showed a significant increase on the ABC after training (P<.001, ES=.61).
Conclusions
Dual-task training is effective in improving gait speed under dual-task conditions in elderly with balance impairment. Training balance under single-task conditions may not generalize to balance control during dual-task contexts. Explicit instruction regarding attentional focus is an important factor contributing to the rate of learning and the retention of the dual-task training effect.
doi:10.1016/j.apmr.2008.09.559
PMCID: PMC2768031  PMID: 19254600
Aging; Attention; Rehabilitation
21.  Balance training program is highly effective in improving functional status and reducing the risk of falls in elderly women with osteoporosis: a randomized controlled trial 
Osteoporosis International  2006;18(4):419-425.
Introduction
The purpose of this study was to investigate the effect of a 12-month Balance Training Program on balance, mobility and falling frequency in women with osteoporosis.
Methods
Sixty-six consecutive elderly women were selected from the Osteometabolic Disease Outpatient Clinic and randomized into 2 groups: the ‘Intervention’, submitted for balance training; and the ‘Control’, without intervention. Balance, mobility and falling frequency were evaluated before and at the end of the trial, using the Berg Balance Scale (BBS), the Clinical Test Sensory Interaction Balance (CTSIB) and the Timed “Up & Go” Test (TUGT). Intervention used techniques to improve balance consisting of a 1-hour session each week and a home-based exercise program.
Results
Sixty women completed the study and were analyzed. The BBS difference was significant higher in the Intervention group compared to Control (5.5 ± 5.67 vs −0.5 ± 4.88 score, p < 0.001). Similarly, the number of patients in the Intervention group presented improvement in two conditions of CTSIB compared to Control (eyes closed and unstable surface condition: 13 vs one patient, p < 0.001 and eyes open, visual conflict and unstable surface condition: 12 vs one patient, p < 0.001). Additionally, the differences between the TUGT were reduced in the Intervention group compared to Control (−3.65 ± 3.61 vs 2.27 ± 7.18 seconds, p< 0.001). Notably, this improvement was paralleled by a reduction in the number of falls/patient in the Intervention group compared to Control (−0.77 ± 1.76 vs 0.33 ± 0.96, p = 0.018).
Conclusion
This longitudinal prospective study demonstrated that an intervention using balance training is effective in improving functional and static balance, mobility and falling frequency in elderly women with osteoporosis.
doi:10.1007/s00198-006-0252-5
PMCID: PMC1820755  PMID: 17089080
Balance; Exercise program; Falls; Mobility; Osteoporosis
22.  Exercise therapy for prevention of falls in people with Parkinson's disease: A protocol for a randomised controlled trial and economic evaluation 
BMC Neurology  2009;9:4.
Background
People with Parkinson's disease are twice as likely to be recurrent fallers compared to other older people. As these falls have devastating consequences, there is an urgent need to identify and test innovative interventions with the potential to reduce falls in people with Parkinson's disease. The main objective of this randomised controlled trial is to determine whether fall rates can be reduced in people with Parkinson's disease using exercise targeting three potentially remediable risk factors for falls (reduced balance, reduced leg muscle strength and freezing of gait). In addition we will establish the cost effectiveness of the exercise program from the health provider's perspective.
Methods/Design
230 community-dwelling participants with idiopathic Parkinson's disease will be recruited. Eligible participants will also have a history of falls or be identified as being at risk of falls on assessment. Participants will be randomly allocated to a usual-care control group or an intervention group which will undertake weight-bearing balance and strengthening exercises and use cueing strategies to address freezing of gait. The intervention group will choose between the home-based or support group-based mode of the program. Participants in both groups will receive standardized falls prevention advice. The primary outcome measure will be fall rates. Participants will record falls and medical interventions in a diary for the duration of the 6-month intervention period. Secondary measures include the Parkinson's Disease Falls Risk Score, maximal leg muscle strength, standing balance, the Short Physical Performance Battery, freezing of gait, health and well being, habitual physical activity and positive and negative affect schedule.
Discussion
No adequately powered studies have investigated exercise interventions aimed at reducing falls in people with Parkinson's disease. This trial will determine the effectiveness of the exercise intervention in reducing falls and its cost effectiveness. This pragmatic program, if found to be effective, has the potential to be implemented within existing community services.
Trial registration
The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12608000303347).
doi:10.1186/1471-2377-9-4
PMCID: PMC2637228  PMID: 19161631
23.  The Association of Flexibility, Balance, and Lumbar Strength with Balance Ability: Risk of Falls in Older Adults 
The purpose of the present study was to determine the effects of a proprioceptive training program on older adults, as well as to analyze the association between flexibility, balance and lumbar strength (physical fitness test) with balance ability and fall risk (functional balance tests). This study was a controlled, longitudinal trial with a 12-week follow-up period. Subjects from a population of older adults were allocated to the intervention group (n = 28) or to the usual care (control) group (n = 26). Subjects performed proprioceptive training twice weekly (6 specific exercises with Swiss ball and BOSU). Each session included 50 minutes (10 minutes of warm-up with slow walk, 10 minutes of mobility and stretching exercises, 30 minutes of proprioceptive exercises). The outcome variables were physical fitness (lower-body flexibility, hip-joint mobility, dynamic balance, static balance, and lumbar strength) and functional balance (Berg scale and Tinetti test). The experimental group obtained significantly higher values than the control group in lower-body flexibility, dynamic balance, and lumbar strength (p = 0.019, p < 0.001, and p = 0.034 respectively). Hip-joint mobility, dynamic balance, and lumbar strength were positively associated with balance ability (p < 0.001, p < 0.001, and p = 0.014, respectively) and the prevention of falls (p = 0.001, p < 0.001, and p = 0.017 respectively). These findings suggest that a 12-week proprioception program intervention (twice a week) significantly improves flexibility, balance, and lumbar strength in older adults. Hip-joint mobility, dynamic balance and lumbar strength are positively associated to balance ability and the risk of falls in older adults. This proprioceptive training does not show a significant improvement in hip-joint mobility or static balance.
Key pointsA 12-week proprioceptive intervention program (two times per week) significantly improves flexibility, balance, and lumbar strength in older adults.The risk of falls and balance ability are significantly improved after a training program with Bosu and Swiss ball in older adults.An improvement in joint mobility, dynamic balance and lumbar strength is positively associated with balance ability and improved fall risk in older adults.A 12-week proprioceptive intervention program (two times per week) does not show a significant improvement in hip-joint mobility and static balance.
PMCID: PMC3990889  PMID: 24790489
Proprioception; physical condition; training; physical qualities; swiss ball
24.  Robot-assisted walking training for individuals with Parkinson’s disease: a pilot randomized controlled trial 
BMC Neurology  2013;13:50.
Background
Over the last years, the introduction of robotic technologies into Parkinson’s disease rehabilitation settings has progressed from concept to reality. However, the benefit of robotic training remains elusive. This pilot randomized controlled observer trial is aimed at investigating the feasibility, the effectiveness and the efficacy of new end-effector robot training in people with mild Parkinson’s disease.
Methods
Design. Pilot randomized controlled trial.
Setting. Robot assisted gait training (EG) compared to treadmill training (CG).
Participants. Twenty cognitively intact participants with mild Parkinson’s disease and gait disturbance.
Interventions. The EG underwent a rehabilitation programme of robot assisted walking for 40 minutes, 5 times a week for 4 weeks. The CG received a treadmill training programme for 40 minutes, 5 times a week for 4 weeks.
Main outcome measures. The outcome measure of efficacy was recorded by gait analysis laboratory. The assessments were performed at the beginning (T0) and at the end of the treatment (T1). The main outcome was the change in velocity. The feasibility of the intervention was assessed by recording exercise adherence and acceptability by specific test.
Results
Robot training was feasible, acceptable, safe, and the participants completed 100% of the prescribed training sessions. A statistically significant improvement in gait index was found in favour of the EG (T0 versus T1). In particular, the statistical analysis of primary outcome (gait speed) using the Friedman test showed statistically significant improvements for the EG (p = 0,0195). The statistical analysis performed by Friedman test of Step length left (p = 0,0195) and right (p = 0,0195) and Stride length left (p = 0,0078) and right (p = 0,0195) showed a significant statistical gain. No statistically significant improvements on the CG were found.
Conclusions
Robot training is a feasible and safe form of rehabilitative exercise for cognitively intact people with mild PD. This original approach can contribute to increase a short time lower limb motor recovery in idiopathic PD patients. The focus on the gait recovery is a further characteristic that makes this research relevant to clinical practice. On the whole, the simplicity of treatment, the lack of side effects, and the positive results from patients support the recommendation to extend the use of this treatment. Further investigation regarding the long-time effectiveness of robot training is warranted.
Trial registration
ClinicalTrials.gov NCT01668407
doi:10.1186/1471-2377-13-50
PMCID: PMC3665527  PMID: 23706025
Parkinson’s disease; Gait analysis; Lower limb; Robot
25.  Investigation by Parkinson’s Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson’s disease: further results of randomised trial and confidential inquiry 
BMJ : British Medical Journal  1998;316(7139):1191-1196.
Objective: To determine whether the excess mortality observed in patients who received both levodopa and selegiline in a randomised trial could be explained by revised diagnosis of Parkinson’s disease, autonomic or cardiovascular effects, more rapid disease progression, or drug interactions.
Design: Open randomised trial and blind comparison and reclassification of the cause of death of patients who were recruited from 93 hospitals between 1985 and 1990 and who had died before December 1993 in arms 1 and 2.
Setting: United Kingdom.
Subjects: 624 patients with early Parkinson’s disease who were not receiving dopaminergic treatment and a subgroup of 120 patients who died during the trial.
Interventions: Levodopa and a dopa decarboxylase inhibitor (arm 1), levodopa and a dopa decarboxylase inhibitor in combination with selegiline (arm 2), or bromocriptine alone (arm 3).
Main outcome measures: All cause mortality for 520 subjects in arms 1 and 2 and for 104 subjects who were randomised into these arms from arm 3. Cause specific mortality for people who died in the original arms 1 and 2 on the basis of the opinion of a panel, revised diagnosis and disability ratings, evidence from clinical records of either autonomic or cardiovascular episodes, other clinical features before death, and drug interactions.
Results: After extended follow up (mean 6.8 years) until the end of September 1995, when arm 2 was terminated, the hazard ratio for arm 2 compared with arm 1 was 1.32 (95% confidence interval 0.98 to 1.79). For subjects who were randomised from arm 3 the hazard ratio for arm 2 was 1.54 (0.83 to 2.87). When all subjects were included the hazard ratio was 1.33 (1.02 to 1.74) and after adjustment for other baseline factors it was 1.30 (0.99 to 1.72). The excess mortality seemed to be greatest in the third and fourth year of follow up. Cause specific death rates showed an excess of deaths from Parkinson’s disease only (hazard ratio 2.5 (1.3 to 4.7)). No significant differences were found for revised diagnosis, disability rating scores, autonomic or cardiovascular events, other clinical features, or drug interactions. Patients who died in arm 2 were more likely to have had possible dementia and a history of falls before death compared with those who died in arm 1.
Conclusion: The results consistently show excess mortality in patients treated with combined levodopa and selegiline. Revised diagnosis, autonomic or cardiovascular events, or drug interactions could not explain this finding, but falls and possible dementia were more common in arm 2. The results do not support combined treatment in patients with newly diagnosed Parkinson’s disease. In more advanced disease, combined treatment should perhaps be avoided in patients with postural hypotension, frequent falls, confusion, or dementia.
Key messages New data from the trial of the Parkinson’s Disease Research Group of the United Kingdom still show higher death rates in patients with early, mild Parkinson’s disease treated with combined selegiline and levodopa compared with those treated with levodopa alone No specific cause, other than Parkinson’s disease, could be found for this excess mortality Combined selegiline and levodopa treatment seems to offer no advantage to patients with early, mild Parkinson’s disease In advanced Parkinson’s disease, selegiline may help manage symptoms but is best avoided in patients with postural hypotension, frequent falls, confusion, and dementia
PMCID: PMC28519  PMID: 9583926

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