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A systematic review of the effects of perturbation training on preventing falls.

INTRODUCTION

Approximately one third of older people experience at least one fall per year (Shapiro & Melzer, 2010). Of these, about half will suffer two or more falls annually (Masud & Morris, 2001). Approximately 5% of falls lead to fractures (Masud & Morris, 2001; Rubenstein & Josephson, 2006), 20% of which are hip fractures (Masud & Morris, 2001) that carry a high probability of mortality (Rubenstein & Josephson, 2006).

During the last 30 years, conventional approaches to reducing falls in the healthy but frail older population have involved strength and power training of the lower extremities in combination with balance re-education. Unfortunately, published data have not shown a consistent benefit for such approaches (Orr, Raymond & Fiatarone, 2008). Although such methods may be able to reduce the incidence of falling compared to no treatment, there are still many people who fall despite these measures (Grabiner, Crenshaw, Hurt, Rosenblatt & Troy, 2014).

Part of the reason for the limited efficacy may be that conventional therapy tends to focus on training in a relatively stable standing position. This is at odds with the fact that after a trip or slip, which may be initiating factors in 60% (Blake et al.,1988; Luukinen, Herala, Koski, Honkanen, Laippala & Kivela, 2000) of all accidental falls, the person is rapidly moved into a far less stable posture before there is time for compensatory muscle activity to begin (Grabiner et al., 2014). Conventional methods may also not train the specific muscle synergies at sufficiently high velocities (Pijnappels, Bobbert & Van Dieen, 2005). In addition, the postural responses and recovery strategies triggered by a slip or trip are reflexive, and thus may not be specifically trained by voluntary exercise. Finally, conventional methods may not train 'feedforward' mechanisms of stability control. Theories of feedforward stability control suggest that the central nervous system (CNS) forms representations of stable limits of centre of gravity (COG) excursion relative to the base of support. These allow proactive adjustments to the velocity and trajectory of the COG during movement to decrease the likelihood that these limits will be crossed. This should reduce the probability of balance loss and the need for reactive responses (Pai & Iqbal 1999; Pai, Wening, Runtz, Iqbal & Pavol, 2003). In addition, even if balance loss does occur, such prior COG adjustments may allow successful reactive responses to be more easily achieved (Pai & Bhatt 2007). Only exposure to sudden unexpected shifts in the COG may refine CNS representation of safe COG limits, and thus improve the feedforward mechanism of stability (Pai et al., 2003).

This has led some researchers and clinicians to consider the efficacy of 'perturbation' training, which involves unexpected external perturbations during walking (Shapiro & Melzer, 2010) that mimic environmental slips and trips. Such training should develop feedforward mechanisms of stability control (Pai et al., 2003), as well as specifically training the rapid reactions required after a slip or trip has begun (Bhatt & Pai 2009a; Grabiner, Bareither, Gatts, Marone &Troy, 2012; Lurie, Zagaria, Pidgeon, Forman & Spratt, 2013).

Over the past 10 years much research has been published concerning perturbation training. This can be split into three main categories. The first concerns the effects of perturbation training on the incidence of community falls (those occurring in the natural setting) in older people (Lurie et al., 2013; Maki et al., 2013; Mansfield, Peters, Liu & Maki, 2010; Pai, Bhatt, Yang & Wang, 2014a; Rosenblatt, Marone & Grabiner, 2013).

The second category looks at the effects of perturbation training on the ability of older people to resist a simulated slip or trip in the laboratory (Grabiner et al., 2012; Parijat & Lockhart, 2012; Bhatt, Yang & Pai, 2012). This is clearly different from observing the effects on community falls, as the laboratory participants are 'primed' for the possibility of a fall and more completely focussed on the task, which may reduce the tendency to fall, supported by empirical evidence in older women (Pater, Rosenblatt & Grabiner, 2015). Moreover, the nature of simulated trips and slips in the laboratory may differ from perturbations encountered in the community. Nevertheless, Pai, Wang, Espy & Bhatt (2010a) have shown an association between the propensity to fall in the laboratory and the tendency to fall in the community, and so such studies may provide useful indirect evidence that can support evidence from the first category of research.

The third category concerns the effects of perturbation training on young healthy adults (Bhatt & Pai 2009a; Bhatt & Pai 2009b; Bhatt, Wang, Yang & Pai, 2013; Lee, Bhatt & Pai, 2016; Liu, Bhatt & Pai, 2016; Wang, Bhatt, Yang & Pai, 2011; Yang, Bart & Pai, 2013, Yang, Wang & Pai, 2014). Although the key aim of this review is to inform prevention of falls in older people, for whom falls are both prevalent and dangerous (Rubenstein & Josephson, 2006), data from younger people are also of relevance. Although younger people have greater strength and power, there is evidence that young and older people may respond to perturbation training at a similar rate (Pavol, Runtz, Edwards & Pai, 2002) and in a similar way (Pavol, Runtz & Pai, 2004). Furthermore, studies in younger people tend to experiment with different parameters of training, such as intensity and duration, and so conclusions from these may be used to inform training parameters in older adults. Inclusion of data on young people will therefore be of potential benefit to facilitate development of optimal treatment and research strategies aimed at reducing falls in older people.

Only one relevant systematic review currently exists. Mansfield, Wong, Bryce, Knorr & Patterson (2015) conducted a systematic review of eight randomised controlled trials (RCTs), evaluating the effectiveness of perturbation training in reducing community falls in older people. These authors showed a relative risk of falling of 0.71 (95% CIs: 0.52 to 0.96) if perturbation training was used, in comparison to other approaches. However, four of the RCTs comprised participants with neurological or orthopaedic diagnoses, and meta-analyses were not stratified or sub-grouped for such differing populations. It is possible that the meta-analysis may have overestimated the pooled magnitude of benefit, in relation to what might be expected in healthy frail older people, because the results in those with neurological conditions more strongly favoured perturbation training. Furthermore, an important recent RCT (Pai et al., 2014a) was not included. In contrast, the current review will be limited to healthy older and younger participants without diagnoses (such as stroke or amputation) that could be the cause of falling, because the tendency to respond to perturbation training and the underlying mechanism of postural instability are probably linked. This tallies with the views of Gillespie, Robertson, Gillespie, Sherrington, Gates, Clemson & Lamb (2012), who restricted their Cochrane meta-analysis on conventional fall prevention strategies to healthy frail older adults on the basis that people with neurological or other diagnosed conditions are likely to respond differently from frail healthy older adults.

The current systematic review contains three separate systematic review questions, each conforming to one of the three categories of research described above. These are:

1. Does perturbation training reduce community falls incidence compared to standard falls prevention treatment in healthy older people who are fallers or at risk of falling?

2. Does perturbation training reduce laboratory falls incidence compared to standard falls prevention treatment in healthy older people who are fallers or at risk of falling?

3. Does perturbation training reduce laboratory falls incidence compared to a comparison treatment in young healthy people?

METHODS

Study selection

The three protocols (Table 1) corresponding to the three review questions were developed by the authors through consensus. This was based on an initial survey of the literature, and discussion with clinicians who use perturbation training as part of their clinical practice. The following sections detail the protocol.

The protocols are also located online at: http://wwwcrd.york. ac.uk/PROSPERO/display_record.asp?ID=CRD42016039911 The online protocol was submitted after the initial searches had taken place, as a result of administrative delays.

Types of participants

For the two review questions looking at older people having 1) community falls or 2) laboratory falls, studies comprising adults with a mean age of >65 years were included, on the basis that falls begin to become much more prevalent after this age (Shapiro & Melzer, 2010). If studies comprised adults with a mean age between 55 and 65 years then these were included, but with a reduction in quality rating to reflect the 'indirectness' of such evidence to the specific review questions ('indirectness' refers to any departure in terms of the study PICO to the review protocol, and is explained fully in the 'quality assessment' section). Similarly, at least 50% of participants in a study needed to either have a history of at least one fall in the past year or be deemed at risk of falls by any appropriate criteria provided by study authors. If either of these conditions was not met then the study would again receive a reduction in quality rating. Participants had to be healthy (albeit frail) and studies were excluded if any participants had diagnosed conditions such as stroke or amputation that could cause falling. For the third research question, involving laboratory falls in younger people, any studies comprising healthy adults aged <55 years were included.

Types of intervention

For all three research questions, interventions had to comprise perturbation training, where sudden and unexpected anteroposterior or mediolateral forces were imposed on a treadmill, or on a walkway with moveable plates. Perturbation training could be given alone, or in combination with standard or other treatments.

Types of comparator

The key methodological criterion for inclusion was that studies had to have a comparator group. Any comparator was acceptable, non-active or active, as any comparator would help to eliminate intervening variables such as the placebo effect, practice effects or natural history effects as contributors to changes in the outcome. For the first and second research questions, the comparator would ideally be standard falls prevention treatment (such as lower limb strengthening and dynamic balance training), to permit interpretations of perturbation training efficacy compared to best available practice. If a non-standard treatment was used for the control group then a reduction in quality rating was applied for indirectness. For the third research question the comparator could be any treatment because established falls prevention treatments do not exist in young healthy people.

Types of outcome

For the first review question, the outcome was community falls, defined by the existence or not of at least one fall occurring outside the laboratory setting within a clearly defined time interval. For the second and third questions, the outcome was a laboratory-induced fall 'in harness', defined as a loss of balance during the laboratory falls test that exceeded a study-specified load on the safety harness load cell, or that caused an unambiguously unrecoverable loss of balance.

Types of study

For all three research questions randomised trials were preferred, but non-randomised trials were allowed, even though these would tend to have greater selection bias. Longitudinal observational approaches, such as prospective or retrospective cohort studies, or case-control studies, were not excluded as such studies would still enable some degree of causality to be established between training method and falls incidence. Cross-sectional studies were excluded as they would be unable to provide any evidence of causality.

Search

The search strategy was aimed at all three protocols. This aimed for maximal sensitivity at the expense of specificity by avoiding 'AND' terms. The key words were: trip, trips, tripping, slip, slips, slipping, perturbation, perturbations, "perturbation-based balance training", platform, treadmill, "agility training", "dynamic balance training" all linked by the term 'OR'. The databases used (in order of succession) were PubMed, EBSCOHost CINAHL, and EBSCOHost SportDiscus, and the last search date was 13/11/2016. All searches were limited to peer-reviewed journals and 'English' to facilitate retrieval and extraction of data. For PubMed, the search was also limited to 'controlled clinical trials' and 'humans', whilst for CINAHL the additional limiters were 'clinical trials' and 'humans'. For SportDiscus the limiters were 'academic journals' and 'articles'. The differing limiters used across databases were due to the differing limiters available within each database. No date limits were set as reviewers were uncertain of the time when perturbation training may have begun to be evaluated. Abstract selection was carried out by both authors and decisions on inclusion were based on consensus.

Data extraction and management

Data from the included papers were extracted onto preformatted forms by both authors independently, detailing study design, population, sample characteristics, intervention, comparator, results, conflicts of interest, risk of bias and indirectness. Consensus was used to decide on the final content of forms.

Synthesis of findings

For each of the three separate review questions, findings were synthesised from two or more studies, using fixed effects meta-analysis, when the population, interventions, comparators and outcomes (PICO) of studies were sufficiently similar to enable meaningful and useful pooling of results. If the PICO of different studies was sufficiently dissimilar to allow meta-analysis then a narrative synthesis was carried out. Where available, intention to treat data were used.

Stratification and sub-grouping

Stratification of studies prior to the meta-analysis was carried out as needed, according to the protocols (Table 1), on the grounds that the stratifying variables denoted plausible biological grounds to expect different results within each stratum. After subsequent stratified or non-stratified pooling of studies, further sub-grouping according to a priori strategies outlined in the protocols (Table 1) was carried out if serious heterogeneity was observed, shown by an [I.sup.2]>50%. If more than one sub-grouping strategy was listed in the protocol, then each sub-grouping strategy was used in order of priority, until heterogeneity was resolved, shown by heterogeneity being reduced to [I.sup.2] <50% in all sub-groups. At this point results were reported for each sub-group separately, and the lower priority sub-grouping strategies were not used. If all sub-grouping strategies failed to resolve heterogeneity then no sub-grouping was carried out, and a random effects model was adopted to allow for the likelihood of a distribution of populations. Since the outcome of falling was a binary outcome, risk ratios (RR) were used where possible but Peto odds ratios were used if there was a low event rate in one of the groups. ReviewManager 5.3 [C] was used for meta-analyses.

Quality assessment

Quality assessment was performed according to the GRADE approach (Schunemann et al., 2006), and comprised the following:

1. Risk of bias

Each study was appraised for the risk of selection, performance, detection, attrition and outcome reporting bias for the chosen outcome. Based on these criteria, the overall risk of bias for each study was deemed very serious (score of -2), serious (-1) or not serious (0), based on a reasoned estimation of the overall effects of such bias. This was assessed for each study separately and then a weighted average of bias scores for the chosen outcome across all studies in the meta-analysis was calculated using the meta-analysis weightings (which were based on precision). If a meta-analysis had not been undertaken then a simple average of quality ratings would be given.

2. Indirectness

This concerned any discrepancies between the PICO of the systematic review question (Table 1) and the PICO of each included study. Indirectness was deemed very serious (-2), serious (-1) or not serious (0) for each study separately, depending on the number of discrepancies. An overall score for the outcome across all studies was then calculated (as for risk of bias).

3. Inconsistency

If the outcome meta-analysis [I.sup.2] was <50% then a rating of non-serious inconsistency (score of 0) was given. If the outcome meta-analysis [I.sup.2] was >50% but <75% then a rating of serious inconsistency (score of -1) was given, and if the outcome meta-analysis [I.sup.2] was >75% then a rating of very serious inconsistency (score of -2) was given. Note that if sub-grouping managed to reduce heterogeneity then the results for each sub-group would be appraised as separate outcomes, each rated as having no serious inconsistency. If no meta-analysis had been undertaken then the level of inconsistency was determined based on an estimate of the differing effects.

4. Imprecision

Imprecision was based on the spread of the 95% confidence intervals (CI) of the pooled effect across arbitrary but established thresholds of clinical importance for the outcome. If the confidence intervals crossed the thresholds of a 25% reduction in risk and a 25% increase in risk (risk ratios [RR] of 0.75 and 1.25, and, by default, odds ratios [OR] of the same value) then a rating of very serious imprecision (score of -2) was given. If the confidence intervals crossed just one threshold then a rating of serious imprecision (score of -1) was given. If no thresholds were crossed by the confidence intervals then a rating of no serious imprecision (score of 0) was given. If no meta-analysis had been undertaken then the level of imprecision was determined based on an estimate of the separate effects.

Overall score

Scores from the four quality aspects were summed. If the overall score was -3 or less, then a rating of very low quality was given, if the overall score was -2 a rating of low quality was given, if the overall score was -1 then a moderate quality rating was assigned and if the overall score was 0 then a rating of high quality was given (Schunemann et al., 2006). These gradings were used to guide interpretation of results.

Since only one outcome (incidence of falling) is used in this review, if a study did not include this outcome then it would not be included. However excluded studies were perused to see if any had been excluded solely for the lack of a falls outcome. The plan was to evaluate such studies to assess if the falls outcome had been deliberately left out because it may have contradicted other outcomes or the favoured hypothesis. Assessment of possible publication bias was conducted using a funnel plot where meta-analyses had been undertaken with a minimum of 10 studies (Higgins & Green, 2011).

RESULTS

Included and excluded studies

The PubMed search yielded 5138 articles, from which 42 were obtained for further analysis. Subsequently, the CINAHL search yielded 790 articles, from which 2 previously unseen articles were obtained for further analysis. Finally, the SportDiscus search yielded 13,310 articles, which were deemed too many for preliminary selection. Hence for this search the original search strategy was combined with 'fall or stability or balance' using the AND operator. This reduced the yield to 1935 articles, from which 5 further articles were obtained for further analysis. Perusal of reference lists in retrieved papers yielded four extra articles, and these were also obtained for more detailed reading. Of these 53 articles, 16 met the inclusion criteria of any of the 3 protocols (Table 1) and were included in the review (Figure 1). Reasons for the exclusion of the other 37 articles are given in Table 2.

1. Does perturbation training reduce community falls risk compared to standard falls prevention treatment in healthy older people who are fallers or at risk of falling?

Studies included

Five relevant studies (Lurie et al., 2013; Maki et al., 2013; Mansfield et al., 2010; Pai et al., 2014a; Rosenblatt et al., 2013) comprising 484 participants were found. Mean ages in the studies ranged from 65 to over 80 years, but mean ages were not always documented. Mansfield et al. (2010) contained >50% of fallers in the study, but no other studies were documented to contain >50% of fallers. Lurie et al. (2013) stated that participants were recruited as they were at risk of falling, but criteria were not described, and 'risk of falling' status was unclear in all other papers. These issues contributed to the serious/very serious risks of 'indirectness' described below.

For three studies (Maki et al., 2013; Mansfield et al., 2010; Rosenblatt et al., 2013) data on the numbers falling at follow up were not available in the published papers. However the systematic review by Mansfield et al. (2015) published the numbers falling in these studies, derived from communication with the study authors, and it is these falls data that have been included in the meta-analysis. Detailed study characteristics are given in Table 3.

Effects

The studies were stratified (as per protocol) into two groups according to whether studies had combined the perturbation training with standard training (Figure 2) or not. The study by Lurie et al. (2013), as the only study to have combined perturbation and standard training, was therefore analysed in a separate stratum. No serious heterogeneity was observed in either stratum, so sub-grouping was not carried out. Fixed effects meta-analysis showed uncertain effects for perturbation training in both strata. Relative to the comparator, in the stratum where perturbation training was combined with standard training there was a RR (95% CI) for falls of 0.62 (0.20 to 1.89), and in the stratum where perturbation training was given alone there was a RR (95% CI) for falls of 0.89 (0.70 to 1.12) (Figure 2).

Quality

Quality of the falls outcome in the perturbation-only stratum was deemed very low. This was due to very serious risk of bias, very serious indirectness and very serious imprecision across studies. Quality was also very low in the perturbation and standard training stratum for the same reasons, although indirectness was deemed serious rather than very serious. Details of all these quality issues are provided in Table 3 and the footnotes to Table 7.

2. Does perturbation training reduce laboratory falls risk compared to a comparison treatment in healthy older people who are fallers or at risk of falling?

Studies included

Three relevant studies were found, comprising 145 participants. Two (Grabiner et al., 2012; Parijat et al., 2012) compared the effects of perturbation training to no treatment, and one (Bhatt et al., 2012) compared the effects of perturbation training with a single extra 'top-up' treatment 3 months later to perturbation training without the 'top-up' treatment. Mean ages were above 70 years in both Parijat et al. (2012) and Bhatt et al. (2012), but in Grabiner et al. (2012) the control group had a mean age of <65 years. No study provided any evidence that the participants were fallers or were at risk of falling. Study details are given in Table 4.

Effects

In the meta-analysis comprising the results of Grabiner et al. (2012) and Parijat et al. (2012), the pooled effect favouring perturbation training was statistically and clinically significant, with a Peto OR (95% CI) for falls of 0.18 (0.05 to 0.63) (Figure 3). Bhatt et al. (2012) did not provide clear data on falls rates, and so their data could not be included in the meta-analysis, but the authors stated that the difference in falls rates between groups was non-significant (p=0.5). The different effects may relate to the very active comparator used in Bhatt et al. (2012), which did not differ greatly from the intervention, in contrast to the inactive control treatments in the other two studies. It is worth noting that the risk ratio in both studies in the meta-analysis was similar despite Grabiner et al. (2012) employing trips as the training and testing perturbation, with Parijat et al. (2012) using slips instead.

Quality

Quality of the falls outcomes in the meta-analysis was deemed very low. This was due to very serious risk of bias, and very serious indirectness. Quality was also very low for the single non-meta-analysed study (Bhatt et al., 2012) for the same reasons, as well as very serious imprecision suggested by the p value of 0.5. Details of all these quality issues are provided in Table 4 and the footnotes to Table 7.

3. Does perturbation training reduce laboratory falls risk compared to a comparison treatment in young healthy people?

Included studies

Eight eligible studies were found (Bhatt & Pai, 2009a; Bhatt & Pai, 2009b; Bhatt et al., 2013; Lee et al., 2016; Liu et al., 2016; Wang et al., 2011; Yang et al., 2013; Yang et al., 2014). All studies had ages that complied with the protocol, and all participants were healthy non-fallers. Six compared slip perturbation training to no treatment (Bhatt & Pai, 2009b; Bhatt & Pai, 2013; Lee et al., 2016; Wang et al., 2011; Yang et al., 2013; Yang et al., 2014) (Table 5) and two compared permutations of different intensities and/or frequencies of perturbation training to each other (Bhatt & Pai, 2009b; Liu et al., 2016) (Table 6). These two categories of study are described separately below.

Effects for training versus no training

With the exception of Bhatt et al. (2013) these studies all showed a point estimate indicating a benefit for perturbation training and the pooled effect was statistically significant [RR for laboratory-induced falling for perturbation training versus no training 0.17 (95% CI: 0.06 to 0.49)] (Figure 4). This effect could also be considered to be clinically important.

The pooled effect included summation of intervention falls rates in each of the two studies (Lee at al., 2016; Yang et al., 2014) where two perturbation lengths of 12cm and 18cm were tested against no treatment. Perturbation length did not appear to have a clear effect on falls rates, with the 12cm and 18cm perturbation length intervention groups each having 1/12 falls in the Yang et al. (2014) study, while the Lee et al. (2016) study demonstrated 1/12 falls in the 12cm group and 0/12 falls in the 18cm group.

It is important to note that in the Wang et al. (2011) study, two non-responders (defined by an inability to show any adaptive response during the training slips) in the intervention group were excluded from their analysis, thus increasing the risk of attrition bias. We performed a sensitivity analysis re-including these two participants, and their imputed values are based on the assumption that these would have fallen on the walking slip test. This imputation gave a more conservative pooled effect than otherwise [RR: 0.25 (95% CIs: 0.1 to 0.6)] but did not make an appreciable difference.

The lack of any effect in the Bhatt et al. (2013) study may be partially explained by its use of a simulated trip via the use of a physical obstacle, rather than a trip or slip induced by a treadmill or moving plates. Special glasses were used to prevent participants seeing the obstacle.

Yang et al. (2013) also considered another hypothesis--the effects of treadmill perturbation training versus overground perturbation training. The control group were subsequently given 24 induced slips on an over-ground walkway with moveable plates, and no falls were seen in either the treadmill or overground perturbation groups on a final over-ground slip test, initially suggesting treatment effects were similar. However there was a large difference in baseline falls (treadmill: 8/17; walkway: 4/17) indicating that the improvement might have been better for the treadmill training group.

Effects for intensity and frequency of training

In the study by Bhatt et al. (2009a) there was a significant difference between groups in incidence of backward balance loss at 4 months (p=0.04) with the greatest difference seen between the high intensity/high frequency group (lowest incidence of balance loss) and the low intensity/low frequency group (highest incidence of balance loss). In the Liu et al. (2016) study, 1/9 fell in the low intensity group, but none fell in the other three groups. These results weakly support the hypothesis that more intense training may be more beneficial in reducing falls.

Quality

Results for both the meta-analysis and the narrative analysis were graded as low quality (Tables 5-7). This was due to very serious risk of bias, largely due to selection and performance bias in most included studies.

DISCUSSION

Our two meta-analyses relating to laboratory-induced falls in older and younger people clearly demonstrate that perturbation training has fall-prevention benefits compared to no treatment. The strong effect of perturbation training on falls in a laboratory setting appears to be similar between young and old, with both age groups demonstrating an approximately 6-fold decrease in laboratory falls frequency after perturbation training compared to no training. This is a qualitative impression as no direct age comparisons were conducted, but does agree with a study showing that older participants respond just as well to perturbation training as younger people (Pavol et al., 2002). This suggests that the mechanisms through which perturbation training exerts its benefits are not significantly attenuated by age. In particular the shift in reliance generated by perturbation training from reactive strategies towards a combination of feedforward and reactive strategies may be of particular advantage to older people. This is because feedforward strategies may be less affected by ageing effects on muscle power than the rapid 'emergency' movements involved in feedback responses.

In contrast, our other meta-analysis concerning the effects of perturbation training on community falls in older people suggests a more modest efficacy, with point-estimates of risk reductions of around 30% compared to the comparison treatment. Importantly there is considerable uncertainty about the true effect, indicating the possibility that no benefits may exist at all. The modest effect might relate to training specificity: it is intuitive that perturbation training conducted using laboratory equipment is more likely to promote recovery from falls induced on the same equipment than recovery from falls induced in the community. However some evidence (Bhatt & Pai, 2009a; Grabiner et al., 2012; Wang et al., 2011) suggests that the effects of perturbation training are generalisable to different contexts, and thus specificity may not necessarily be of prime importance. The relatively lower efficacy of perturbation training in the community falls studies might also relate to the fact that participants were generally older and frailer than those in the laboratory studies. For such participants, the low strength and power associated with frailty may be the limiting factor governing the ability to recover from a perturbation, rather than feedforward or reflexive stability control components, which are more amenable to perturbation training. However our inconclusive pooled results do not necessarily indicate that perturbation training is ineffective in preventing community falls. The quality of the meta-analysis for community falls was limited by the methodology and size of included studies, as well as the low number of eligible studies, which prevents a less ambiguous interpretation of findings. Further high quality trials may permit future meta-analyses to provide more certain results.

Only one study (Lurie et al., 2013) has evaluated the effects of perturbation training (combined with standard approaches) on community falls in older people, using standard best-practice falls prevention strategies as the comparator. Use of such a gold standard comparator is essential before it can be suggested that a combined perturbation training strategy is a new best-practice approach. The evidence from that single study was limited by the study not being adequately powered, and also by serious risks of attrition bias and detection bias. However, it weakly suggested that a combined perturbation approach might have some benefits over established methods. This reinforces the need for further work.

If perturbation training does have clinical efficacy, then one of the particular benefits of perturbation training may be its relatively rapid action (Pai et al., 2010b; Pai & Bhatt, 2007). Although limited evidence in younger people (Bhatt & Pai, 2009a; Liu et al., 2016) shows that more intense and frequent training may lead to even greater beneficial effects, the effects from just one session alone seem to be clinically important (Bhatt & Pai, 2009b; Bhatt et al., 2013; Grabiner et al., 2012; Lee et al., 2016; Pai et al., 2014a; Parijat et al. 2012; Wang et al., 2011; Yang et al., 2013; Yang et al., 2014). This rapid effect may be possible because this training may exert effects via immediate changes in CNS representation of the stable limits of the position of the centre of mass (Pai & Bhatt, 2007). It has also been suggested (Pai et al., 2014a) that the speed of such learning may be augmented by the fear induced by a training-induced (though harness-protected) fall, in accordance with animal studies showing that fear accelerates the development of adaptive synaptic pathways (Sacchetti, Scelfo, Tempia & Strata, 2004). In contrast, established approaches, which rely partially on the development of strength and power, may require several weeks of training for the neuromuscular adaptations to occur, and there are consequently likely to be greater problems with patient compliance and higher costs. Even if perturbation training is combined with standard approaches, as it probably should be given that the causes of falls are multifactorial, then the rapid benefits may still be beneficial. This is because any improvements in the proactive and reflexive aspects of postural stability may confer enough overall improvement (and perhaps confidence) to motivate continued standard training.

Another claim of the literature has been that the benefits of a single session of perturbation training may be relatively long-lived. Pai & Bhatt (2007) have discussed how updating of the stable limits of the COG, as part of a feedforward mechanism, may involve cortical and sub-cortical influences which might therefore be associated with longer-term memories. Accordingly, Bhatt et al. (2012) showed that both a single session of training and a single session combined with an ancillary session 3 months later led to continued gains at 6 months in younger people. Pai et al. (2014b) have also shown benefits lasting for up to 12 months in older people. However these results (which are not included in the main body of this systematic review) could be spurious as they were uncontrolled within-group gains, and thus prone to influence by intervening effects. No study has evaluated long-term outcomes using a control group and so it is still unclear if a single session is effective in leading to sustained benefits.

This systematic review has included data from younger people on the grounds that such studies are more likely to experiment with the parameters of training. However, there is currently insufficient evidence to allow definitive guidelines on the optimal parameters. The limited evidence suggests that slip perturbations of 12 cm length are probably sufficient (Lee et al., 2016; Yang et al., 2014), and that more frequent and/or intense sessions may be more effective (Bhatt et al., 2009; Liu et al., 2016). In addition, treadmill-induced perturbations may be slightly more effective than perturbations induced by shifting plates on a walkway (Yang et al., 2013), as well as being more practical, but this is far from clear.

Most of the evidence concerns training in the form of predominantly slip-type perturbations. However, it is known that real-world perturbations can be both slips and trips. So far only two studies (Grabiner et al., 2012; Rosenblatt et al., 2013) have estimated the effects of trip-like perturbation training on falls in older people. It is unknown if slip or trip training is superior and although the laboratory falls evidence in this review suggests each may have similar benefits (Grabiner et al., 2012; Parijat et al., 2012), this evidence is only in terms of how trip training protects against trip-induced falls and how slip-training protects against slip-induced falls. What remains to be seen is how well trip training relates to resistance to slips, and vice versa. Bhatt et al. (2013) attempted to establish the effects of slip training on resistance to trip-induced falls, but no falls were recorded in either intervention or control groups, making conclusions difficult.

It has been theorised that combining slip and trip training may actually be counter-productive because slip and trip training involve opposite stimuli--slip training promoting backward corrections due to the posterior rotation induced by the anterior slip perturbation, and trip training promoting forward corrections due to the anterior rotation induced by the posterior trip perturbation (Bhatt et al., 2013). However, in an extension to their comparative study, Bhatt et al. (2013) also showed that mixing approaches in the perturbation group did not adversely affect measures of stability. The authors concluded that the CNS was able to develop a generalised and adaptable movement strategy. This concurs with other findings. For example, in the Bhatt & Pai (2009b) study the slip perturbations trained on the treadmill transferred to reduced fall rates on a slippery floor. In the Wang et al. (2011) work, perturbations given during a sit-to-stand task transferred to greater falls resistance during walking. Similarly, in the study by Grabiner et al. (2012) perturbations provoked in standing appeared to carry over to protection of falls occurring during walking. Hence it is likely that trip training may carry over to protection from slips and vice versa. This generalisability is important as falls may occur in many different contexts, and perturbation training cannot hope to mimic all of them.

There are two main threats to a review capturing all the available data: 1) actual studies not being found by the search, and 2) failure of researchers to report relevant results or publish their data at all. In terms of the first threat, this systematic review used three databases, alongside cross-referencing, which make us confident that we have surveyed all the relevant literature. In terms of the second threat, we have no evidence to suggest there was any outcome-reporting bias or publication bias, although the latter was not possible to evaluate rigorously due to a small number of studies. One strength of this study was the use of two researchers to sift, extract and appraise all data. For the initial three sifts (Kappa scores: 0.83, 0.67 and 0.57 respectively) any papers selected by either author were automatically sought for further examination for maximum sensitivity. For the final selection of included papers and decisions on GRADE ratings, consensus was used where initial disagreement occurred (Kappa 0.78 and 0.57 respectively), and all were resolved to the satisfaction of both reviewers.

Ultimately, perturbation training is unlikely to be the 'magic bullet'. Even if reflex responses to perturbations are optimised these may not prevent falling in response to trips or slips if failing sensory systems or reduced muscle strength and power are the limiting factor. Furthermore, it has been estimated that 40% of falls are not related to slips or trips (Luukinen et al., 2000), so perturbation training may have limited effects on these. The ideal approach is therefore likely to involve a variety of approaches, based on detailed patient assessment.

CONCLUSION

The evidence that perturbation training has benefits over conventional approaches is unclear. Laboratory studies provide some evidence that perturbation training may have a place in falls prevention and further research is needed to confirm this. Perturbation training may exert effects after one session, but greater frequency and intensity of training may further increase effects.

KEY POINTS

1. Perturbation training is effective in reducing laboratory-induced falls in healthy young and older people,

2. Perturbation training may have rapid effects on reducing laboratory-induced falls, but the duration of effect is unclear.

3. Despite this, the efficacy of perturbation training in reducing community falls in healthy older people is uncertain, and further adequately powered and rigorous research is required before resources should be uncritically devoted to such an approach.

DISCLOSURES

No funding was obtained for this work. The authors state that they have no conflicts of interest.

ADDRESS FOR CORRESPONDENCE

Assistant Professor Mark Perry, Health and Social Sciences Cluster, Singapore Institute of Technology, 10 Dover Drive, Singapore. Telephone: 6592 1348. Email: mark.perry@ singaporetech.edu.sg.

ACKNOWLEDGEMENTS

This article is lovingly dedicated to the memory of Valerie Perry (January 1928-October 2016)

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Angela Papadimitriou d Psych (Clin)

Assistant Professor, Health and Social Sciences Cluster, Singapore Institute of

Technology

Mark Perry PhD

Assistant Professor, Health and Social Sciences Cluster, Singapore Institute of

Technology

Caption: Figure 1: PRISMA Study Flow Diagram
Table 1: Protocol for the 3 research questions

Review          Does               Does               Does
questions       perturbation       perturbation       perturbation
                training reduce    training reduce    training reduce
                community falls    laboratory falls   laboratory falls
                incidence more     incidence more     incidence more
                than standard      than a             than a
                falls prevention   comparison         comparison
                treatment in       treatment in       treatment in
                healthy older      healthy older      young healthy
                people who are     people who are     people?
                fallers or at      fallers or at
                risk of falling?   risk of falling?

Population      * Older people aged 65 years          Young people
                upwards                               (aged <55
                * Healthy--free from or any           years).
                diagnosed condition that could
                lead to falls (e.g. stroke,           These need to be
                amputation, total hip                 healthy and not
                replacement, balance disorders)       frail or
                * Either deemed at risk of            fallers.
                falling (frail) or
                single/frequent fallers.

                Reduce quality rating of studies
                in terms of 'indirectness'
                * If mean age was aged <65 but >
                55 years
                * if >50% of participants were
                not fallers or were not deemed
                at risk of falling

Intervention    * Perturbation (slip/trip) training on treadmill
                or on a walkway with moveable plates Exclude any
                slip/trip training done on slippery surfaces Can
                be combined with or without standard falls
                prevention training

Comparator      * Standard falls prevention           * Any control
                training                              intervention
                * Downgrade for indirectness if
                any other control intervention
                is used

Outcomes        Community falls    "Falls in
                frequency          harness" on
                                   laboratory
                                   walkway or
                                   treadmill
                                   platform.

Study types     Any randomised or non-randomised study which
                uses one or more comparison groups.

Strata */sub-   Stratify by        Sub-group by       Sub-group by
groups **        inclusion of   Comparator type    Comparator type
                standard
                training with
                intervention
                Sub-group by
                * Comparator
                type
                * Single
                fallers/
                frequent fallers
                * Age (<80 vs
                >80)

Analysis plan   Meta-analysis if appropriate.

Search plan     Pubmed, EBSCOHost CINAHL, EBSCOHost SportDiscus;
                key words: trip, trips, tripping, slip, slips,
                slipping, perturbation, perturbations,
                "perturbation-based balance training", platform,
                treadmill, "agility training", "dynamic balance
                training"

* Strata denote categories for separate analyses-synthesis which are
fixed a priori. Strata interact--thus 2 binary strata will lead to 4
sub-strata.

** Sub-groups denote categories for analysis-synthesis that are
conditional upon statistical heterogeneity [[I.sup.2] > 50%] in meta
-analysis. Sub-groups do not interact--each is examined separately

Table 2: Excluded studies list

Study                   Reason for exclusion

Bhatt & Pai, 2008       No control group
Bhatt et al., 2011      No control group
Bieryla et al., 2007    No falls data
Cham & Redfern 2001     Descriptive kinematic study
Dijkstra et al.,2015    No control group
Grabiner et al., 2014   Review
Han & Yang, 2015        Did not relate to perturbation training
Kim & Lockhart, 2010    Did not relate to perturbation training
Kojima et al., 2008     No control group
Kurz et al., 2016       No falls data
Lee et al., 2013        Did not relate to perturbation training
Lesinki et al., 2015    Review with no falls outcomes
Liu & Kim, 2012         No control group
McIlroy & Maki, 1996    No control group
Melzer & Oddison, 2013  No falls data
Oddsson et al., 2004    No control group
Pai et al., 2010b       No control group
Pai & Bhatt, 2007       Review
Pai et al., 2014b       No control group
Parijat et al., 2015a   Virtual reality study
Parijat et al., 2015b   Virtual reality study
Patel & Bhatt, 2015     No control group
Pater et al., 2015      No control group
Pavol et al., 2002      No control group
Pavol et al., 2004      No control group
Rossi et al., 2013      No falls outcomes
Sakai et al., 2008      No falls outcomes or control group
Sessoms et al., 2014    Participants were post amputation
Shapiro & Melzer, 2010  Descriptive account of the
                          perturbation device
Shimada et al., 2004    50% had diagnoses such as
                          Parkinson's disease.
Shirota et al., 2014    Descriptive kinematic study
Sohn & Kim, 2015        Did not relate to perturbation training
Yang et al., 2011       No control group
Yang et al., 2009       No control group
Yang et al., 2012       Descriptive kinematic study
Yang & Pai,2013         No control group
Yang & Pai, 2011        Not evaluating interventions

Table 3: Characteristics of the studies for review question 1.
All participants were protected by a harness during training

Study           Sample              Intervention
name and        characteristics
type

Lurie et al.,   64 healthy          Standard
2013            adults at risk of   physiotherapy (see
                falls.              right) with addition
RCT             Mean age c80        of treadmill
                years. 50%          perturbation
                female in           training. Trips or
                perturbation        slips were applied,
                group and           with magnitude
                67% female          of disturbances
                in standard PT      depending on
                group.              patient ability.
                                    Parameters left to
                                    the discretion of
                                    the PT.

Pai et al.,     212 adults          24 unexpected
2014a           aged 73.6           slip perturbations
                years. Baseline     while walking over
RCT             rates of            a moving platform
                community           in a single session.
                falling (for
                previous 12
                months): 34%
                of intervention
                group; control:
                39%.

Maki et al.,    8 aged 79-89        Perturbation
2013            in perturbation     training, done
                group, and 69-      for 30 minutes,
Pilot RCT       86 in control       3 times per week
                group.              over 6 weeks.

Rosenblatt      170 women           Four one
et al., 2013    of mean age         hour sessions
                65. Baseline        comprising large
Pseudo-         falls history:      trip perturbations
randomised      38.8% in            on a treadmill over
                control group       2 weeks.
                and 37.8% in
                perturbation
                group.

Mansfield et    30 adults (aged     6 week
al., 2010       64-80 years).       perturbation-
                23/30 had           based balance
RCT             experienced at      training program,
                least one fall      conducted on a
                in the past 5       motion platform
                years.              that could move in 4
                                    different
                                    directions. At least
                                    24 perturbations
                                    were related to
                                    stepping and at
                                    least 24 were
                                    related to grasping
                                    tasks.

Study           Comparator            Outcome measure
name and
type

Lurie et al.,   Standard              All-cause community
2013            physiotherapy         falls, evaluated
                comprising            retrospectively by a 3
RCT             patient-specific      month phone call.
                strengthening,
                flexibility and
                dynamic balance
                exercises. Some
                given in clinic
                and some as
                home exercises.
                Parameters left to
                the discretion of
                the PT.

Pai et al.,     One unexpected        All cause community
2014a           slip perturbation     falls at 12 month
                while walking         follow up. Over
RCT             over the moving       the year falls were
                platform.             recorded in a falls
                                      diary, and a researcher
                                      would call each
                                      participant at 6-week
                                      intervals to obtain the
                                      diary details, and if a
                                      fall had occurred the
                                      participant would be
                                      interviewed.

Maki et al.,    Training of rapid     Community falls.
2013            volitional stepping   The data are derived
                and reaching          from Mansfield et al.,
Pilot RCT       movements.            (2015), the authors of
                                      which had contacted Maki
                                      and colleagues for the
                                      falls data.

Rosenblatt      No training           Community falls,
et al., 2013                          collected via postcards
                                      or emails every 2
Pseudo-                               weeks for one year.
randomised                            The data for number
                                      of all-cause fallers per
                                      group was derived
                                      from Mansfield et al.,
                                      (2015).

Mansfield et    6 week control        Community falls. The
al., 2010       program involving     data for number of
                flexibility (2 days   all-cause fallers per
RCT             per week) and         group was derived
                relaxation training   from Mansfield et al.,
                (1 day per week).     (2015).

Study           Risk of bias         Indirectness
name and
type

Lurie et al.,   Very serious.        Serious.
2013            No assessor          No
                blinding,            information
RCT             and possible         on baseline
                attrition and        fallers / risk
                detection            of falling.
                bias.

Pai et al.,     Very serious.        Very serious.
2014a           No allocation        <50%
                concealment,         fallers, no
RCT             and no               information
                assessor             on risk of
                blinding.            falling, and
                                     comparator
                                     not standard
                                     training.

Maki et al.,    Very serious.        Very serious.
2013            No allocation        <50%
                concealment,         fallers, no
Pilot RCT       and no               information
                assessor blinding.   on risk of
                                     falling, and
                                     comparator not
                                     standard
                                     training.

Rosenblatt      Very serious.        Very serious.
et al., 2013    Pseudo               <50%
                random               fallers, no
Pseudo-         alternate            information
randomised      allocation,          on risk of
                no assessor          falling, and
                blinding and         comparator
                likely attrition     not standard
                bias.                training.

Mansfield et    Very serious.        Very serious.
al., 2010       No allocation        <50%
                concealment,         fallers, no
RCT             and no               information
                assessor             on risk of
                blinding.            falling, and
                                     comparator not
                                     standard
                                     training.

Table 4: Characteristics of the studies for review question 2.
All participants were protected by a harness during training

Study             Sample            Intervention
name and          characteristics
type

Parijat et al.,   24 adults aged    Two weeks later,
2012              72.7 years,       the intervention
                  12 of whom        group experienced
RCT               were female.      12 simulated
                  At baseline all   slips on a slippery
                  participants      moving force plate
                  were exposed      embedded on a
                  to a slip on      15m walkway.
                  a slippery        The slip trials
                  surface:          were interspersed
                  5/12 fell in      over 24 trials to
                  intervention      reduce participant
                  group and 6/12    prediction of slips.
                  fell in control
                  group.

Grabiner et       66 women          Mean 142.5
al., 2012         aged 65.9         perturbations in
                  years             total over 4 weeks.
Pseudo-           (intervention)    The perturbations,
randomised        and 58.8 years    made with the
                  (control).        participant in a
                                    standing position,
                                    were exerted by
                                    a treadmill giving
                                    a sudden forward
                                    motion (simulating
                                    a trip). Magnitude
                                    varied according
                                    to participant
                                    performance.

Bhatt et al.,     Forty-eight       24 single session
2012              adults aged       slip perturbations
                  72.3 years.       combined with an
RCT               35% had           ancillary session
                  experienced       of a single slip
                  prior             perturbation 3
                  community         months later. Slips
                  falls.            during ambulation
                                    were induced by 2
                                    moveable platforms
                                    placed on a 7m
                                    walkway.

Study             Comparator            Outcome measure
name and
type

Parijat et al.,   The control group     One day post-training,
2012              had only normal       the single slip test
                  walking trials, but   performed at baseline
RCT               the group were        was repeated.
                  brought to the
                  lab to maintain
                  comparability.

Grabiner et       No treatment          Existence of a fall,
al., 2012                               defined as loss of
                                        stability requiring
Pseudo-                                 'unambiguous'
randomised                              harness protection,
                                        after a single
                                        mechanically induced
                                        trip on a walkway,
                                        undertaken about one
                                        week post training.

Bhatt et al.,     The same 24           At 6 months, the
2012              single session slip   risk of falling was
                  perturbations,        determined by the
RCT               without ancillary     response to a single
                  session.              slip perturbation, with
                                        a fall defined as a slip
                                        where >30% body
                                        weight was detected by
                                        the harness load cell.

Study             Risk of bias      Indirectness
name and
type

Parijat et al.,   Very serious.     Very serious.
2012              No allocation     <50%
                  concealment,      fallers, no
RCT               and no            information
                  assessor          on risk of
                  blinding.         falling, and
                                    comparator
                                    not standard
                                    training.

Grabiner et       Very serious.     Very serious.
al., 2012         Quasi-            <50%
                  randomised        fallers, no
Pseudo-           with              information
randomised        alternate         on risk of
                  allocation,       falling,
                  no assessor       comparator
                  blinding and      not standard
                  probable          training
                  attrition bias.   and control
                                    group aged
                                    55-65 years.

Bhatt et al.,     Very serious.     Very serious.
2012              No allocation     <50%
                  concealment,      fallers, no
RCT               and no            information
                  assessor          on risk of
                  blinding.         falling, and
                                    comparator
                                    not standard
                                    training.

Table 5: Characteristics of studies for review question 3 that
compared perturbation training to no treatment. All participants were
protected by a harness

Study           Sample            Intervention            Comparator
name and        characteristics
type

Bhatt & Pai,    16 young          Repeated-slip           No treatment
2009b           healthy           training on
                subjects aged     a moveable
RCT             26 years.         platform set in
                                  a 7 m walkway.
                                  37 walking trials,
                                  including 24 trials
                                  where a slip was
                                  induced by the
                                  moveable plates.
                                  The participants
                                  were unaware of
                                  when slips would
                                  occur. All slips were
                                  on the right side.

Bhatt et al.,   32 adults (26     Slip training           No treatment
2013            women), aged      including 8 slip
                26 years.         perturbations
RCT                               simulated by a
                                  moveable platform
                                  set in a 7m
                                  walkway.

Yang et al.,    34 adults (16     15-20 forward slip-     No treatment
2013            female), aged     like perturbations
                25.8 years.       during treadmill
Non-                              walking. The
randomised                        intensity of
                                  perturbations
                                  was adjusted to
                                  performance.

Yang et al.,    24 adults aged    Two intervention        No treatment
2014            24.9 years.       groups given
                23/36 female.     perturbation
Non-                              training. 7
randomised                        perturbations were
                                  applied using a 7m
                                  walkway with 2
                                  moveable platforms
                                  over 18 trials. One
                                  group had 12cm slip
                                  perturbations while
                                  the other had 18cm
                                  slip perturbations.

Lee et al.,     24 young          Two groups given        No treatment
2016            adults aged       perturbation
                26.7 years,       training on
Non             18/24 female.     treadmill. 7
randomised                        forward slip-like
                                  perturbations
                                  applied during
                                  treadmill walking
                                  over 12 trials.
                                  One group had
                                  perturbations giving
                                  a slip distance
                                  of 12cm whilst
                                  the other had
                                  perturbations giving
                                  a slip distance of
                                  18cm.

Wang et al.,    43 young          With the participant    No treatment
2011            adults (26        sitting in a custom
                women), aged      built chair a
Non             26 years.         perturbation was
randomised                        applied on moving
                                  from sit to stand, by
                                  a pair of moveable
                                  plates. Participants
                                  performed
                                  28 sit-stands,
                                  containing 14 slip
                                  perturbations.

Study           Outcome measure             Risk of bias
name and
type

Bhatt & Pai,    The ability to retain       Very serious.
2009b           balance was tested          No allocation
                on an oily floor            concealment.
RCT             surface. This occurred      No assessor
                immediately after           blinding.
                training. A single trial
                was used. Falls were
                defined as average
                force on the safety
                harness exceeding
                4.5% body weight over
                any 1 second period
                after the slip onset.

Bhatt et al.,   An in-harness fall          Very serious.
2013            during a single trip        No allocation
                induced during walking      concealment.
RCT             via a physical obstacle     No assessor
                (the participants did not   blinding.
                know when it would
                occur). This occurred
                immediately after
                training.

Yang et al.,    As above                    Very serious.
2013                                        Non random
                                            allocation
Non-                                        with large
randomised                                  baseline
                                            group
                                            discrepancies.
                                            No assessor
                                            blinding.

Yang et al.,    Balance loss was tested     Very serious.
2014            using an overground         Non random
                walking test where a        allocation
Non-            150 cm slip was given       with large
randomised      by moveable plates          baseline
                on a 7m walkway at          group
                a random trial. This        discrepancies.
                occurred immediately        No assessor
                after training.             blinding.

Lee et al.,     As above                    Very serious.
2016                                        Non random
                                            allocation
Non                                         with large
randomised                                  baseline
                                            group
                                            discrepancies.
                                            No assessor
                                            blinding.

Wang et al.,    A fall (defined as >30%     Very serious.
2011            body weight detected        Non-random
                by harness load cell)       allocation
Non             during a novel slip         with large
randomised      during walking on the       baseline
                walkway with two            group
                moveable plates was         discrepancies.
                the outcome.                No assessor
                                            blinding.

Study           Indirectness
name and
type

Bhatt & Pai,    None.
2009b

RCT

Bhatt et al.,   None.
2013

RCT

Yang et al.,    None.
2013

Non-
randomised

Yang et al.,    None.
2014

Non-
randomised

Lee et al.,     None.
2016

Non
randomised

Wang et al.,    None.
2011

Non
randomised

Table 6: Characteristics of studies for review question 3 that
compared different intensities/frequencies of perturbation training.
All participants were protected by a harness

Study          Sample            Interventions
name and       characteristics   to be compared
type

Bhatt & Pai,   49 healthy        Four groups experienced varying
2009a          young subjects    parameters of perturbations induced
               (26 years).       by moveable plates on a walkway.
RCT                              Slips were provided by moveable
                                 plates set in a 7m walkway, and
                                 participants were unaware of when a
                                 slip would occur.

                                 * High intensity, high frequency
                                 perturbation training--24 slips on
                                 an initial session and 3 ancillary
                                 single slip training sessions.

                                 * High intensity, low frequency
                                 perturbation training--24 slips on
                                 an initial session as above, but
                                 with no ancillary single slip
                                 training sessions.

                                 * Low intensity, high frequency
                                 perturbation training--a single slip
                                 on an initial session and 3
                                 ancillary single slip training
                                 sessions.

                                 * Low intensity, low frequency
                                 perturbation training--a single slip
                                 on an initial session as above, but
                                 with no ancillary single slip
                                 training sessions.

Liu et al.,    36 healthy        Four groups experienced varying
2016           young people      parameters of perturbations induced
               of mean age       by a treadmill.
               24.8 years
RCT                              * High intensity group where 24
                                 slips were experienced at an
                                 acceleration of 12 ms2

                                 * Low intensity group where 24 slips
                                 were experienced at an acceleration
                                 of 6 ms 2

                                 * Increasing intensity group where
                                 perturbation accelerations increased
                                 from 6 ms-2 to 12 ms 2 over 18
                                 perturbations and then from 6 ms 2
                                 to 12 ms2 over the final 6
                                 perturbations.

                                 * Decreasing intensity group where
                                 perturbation accelerations decreased
                                 from 12 ms2 to 6 ms 2 over 18
                                 perturbations and then from 12 ms 2
                                 to 6 ms 2 over the final 6
                                 permutations.

Study          Outcome measure        Risk of bias    Indirectness
name and
type

Bhatt & Pai,   Four months after      Very serious.   None.
2009a          the initial session    No allocation
               participants were      concealment.
RCT            tested with a          No assessor
               single slip test on    blinding.
               the walkway. Falls
               were defined by
               'backward balance
               loss' (where the
               contralateral leg
               lands behind the
               slipping heel).

Liu et al.,    In the same session,   Very serious.   None.
2016           all subjects then      No allocation
               walked down a          concealment.
               7m walkway and         No assessor
RCT            were given a single    blinding.
               slip perturbation
               provided by
               moving plates. The
               definition of a fall
               was not provided.

Table 7: Grade table summarising the quality of evidence for all
questions

Number of       Risk of bias   Indirectness    Imprecision
studies
(number of
participants)

Community falls for perturbation combined with standard training vs
standard training in older people

1 (64)          Very           Serious (2)     Very
                serious (1)                    serious (3)

Community falls for perturbation training vs non-standard training in
older people

4 (420)         Very           Very            Very
                serious (4)    serious (5)     serious (3)

Laboratory falls for perturbation training vs no training in older
people

2 (97)          Very           Very            No serious
                serious (6)    serious (7)     imprecision

Laboratory falls for perturbation training vs no training in older
people (not meta-analysed)

1 (48)          Very           Very            Very
                serious (8)    serious (19)    serious (10)

Laboratory falls for perturbation training vs no training in younger
people

6 (199)         Very           1 No serious    No serious
                serious (11)   indirectness    imprecision

Laboratory falls for perturbation training vs no training in younger
people--intensity and frequency effects (not meta-analysed)

2 (85)          Very           2 No serious    No serious
                serious (12)   indirectness    imprecision

Number of       Inconsistency   Outcome
studies                         reporting bias
(number of
participants)

Community falls for perturbation combined with standard training vs
standard training in older people

1 (64)          No serious      None suspected
                inconsistency

Community falls for perturbation training vs non-standard training in
older people

4 (420)         No serious      None suspected
                inconsistency

Laboratory falls for perturbation training vs no training in older
people

2 (97)          No serious      None suspected
                inconsistency

Laboratory falls for perturbation training vs no training in older
people (not meta-analysed)

1 (48)          No serious      None suspected
                inconsistency

Laboratory falls for perturbation training vs no training in younger
people

6 (199)         No serious      None suspected
                inconsistency

Laboratory falls for perturbation training vs no training in younger
people--intensity and frequency effects (not meta-analysed)

2 (85)          No serious      None suspected
                inconsistency

Number of       Publication bias    Grade
studies
(number of
participants)

Community falls for perturbation combined with standard training vs
standard training in older people

1 (64)          Unable to detect    Very low
                as <10 studies

Community falls for perturbation training vs non-standard training in
older people

4 (420)         Unable to detect    Very low
                as <10 studies

Laboratory falls for perturbation training vs no training in older
people

2 (97)          Unable to detect    Very low
                as <10 studies

Laboratory falls for perturbation training vs no training in older
people (not meta-analysed)

1 (48)          Unable to detect    Very low
                as <10 studies

Laboratory falls for perturbation training vs no training in younger
people

6 (199)         Unable to detect    Low
                as <10 studies

Laboratory falls for perturbation training vs no training in younger
people--intensity and frequency effects (not meta-analysed)

2 (85)          Unable to detect    Low
                as <10 studies

1 In the Lurie et al. (2013) study, there was no assessor blinding as
well as likely attrition bias due to the exclusion from follow up and
analysis of 5 subjects in the intervention group who did not attend
for treatment.

2 Less than 50% participants were fallers at baseline in Lurie et al.
(2013). The authors stated that participants were referred because
they were at risk of falling but the criteria are unclear.

3 95% CIs crossed both 0.75 and 1.25 thresholds

4 Rosenblatt et al. (2013) used a pseudo-random alternate allocation
approach, whilst none of the other randomised studies except
Mansfield et al. (2010) used allocation concealment or had assessor
blinding, and most had some degree of attrition bias and performance
bias.

5 No studies used standard physiotherapy approaches as the
comparator. Only Mansfield et al. (2010) had clear documentation that
>50% of participants were fallers, and data concerning the extent to
which participants in the other studies were deemed at risk of
falling was unclear.

6 No reporting of allocation concealment in the Parijat and Lockhart
(2012) study and a pseudo-randomisation procedure in the Grabiner et
al. (2012) study. In addition, neither study ensured assessor
blinding. Attrition bias likely in Grabiner et al. (2012)

7 The outcome also had very serious indirectness as the mean age was
<65 (but >55) in the Grabiner et al. (2012) study, the comparators
were non- standard treatment for both Parijat et al. (2012) and
Grabiner et al. (2012), and there was no documentation in either
study that the participants were fallers or at risk of falling.

8 No reporting of allocation concealment or assessor blinding, and
potential attrition bias.

9 Comparator was no treatment and there was no documentation that the
participants were fallers or at risk of falling.

10 p=0.5 in study

11 In the two randomised studies (Bhatt and Pai 2009b, 2013) neither
reported allocation concealment, whilst in the non-randomised studies
(Yang et al. 2013; Yang et al. 2014; Lee et al., 2016; Wang et al.,
2011) the method of allocation was unclear. Furthermore, assessor
blinding was not reported in any study. In Wang at al. (2011) two
people in the perturbation group were excluded from analysis when it
was likely they would have fallen had they not been excluded.

12 No reports of allocation concealment or assessor blinding in
either study. In the Bhatt et al. (2009a) study attrition rates
differed between groups, but this is unlikely to have related to
outcome (these being a healthy sample) so attrition bias risk was
probably low.

Figure 2: Forest plot for the effects of perturbation training
compared to control on falls risk. The analysis was stratified by
inclusion of standardised training with perturbation training or not.
A generic inverse variance method has been used as the results by
Lurie et al. 2013, adjusted for baseline falls incidence, were only
available as a risk ratio.

Study or Subgroup    log[Risk   SE       Weight   Risk Ratio IV,
                    Ratio]                        Fixed, 95% CI

7.1.2 Perturbation and standard training

Lurie 2013          -0.4762     0.567    100.0%   0.62 [0.20, 1.89]
Subtotal (95% CI)                        100.0%   0.62 [0.20,1.89]

Heterogeneity: Not applicable
Test for overall effect: Z = 0.84 (P = 0.40)

7.1.3 Perturbation alone

Maki 2008           -0.4055     0.5774   4.3%     0.67 [0.21, 2.07]
Mansfield 2010      0.1586      0.5664   4.5%     1.17 [0.39, 3.56]
Pai 2014            -0.6757     0.3017   15.9%    0.51 [0.28, 0.92]
Rosenblatt 2013     -0.0027     0.1388   75.2%    1.00 [0.76, 1.31]

Subtotal (95% CI)                        100.0%   0.89 [0.70,1.12]

Heterogeneity: [Chi square] = 4.59, df = 3 (P = 0.20); [I.sup.2] = 35%

Test for overall effect: Z = 1.00 (P = 0.32)

Test for subgroup differences: [Chi square] = 0.38, df = 1
  (P = 0.54), [I.sup.2] = 0%

Figure 3: Forest plot for the effects of trip perturbation training
compared to no perturbation training on odds of slip-induced
laboratory falls in older participants

Study or            Perturbation          Control
Subgroup         Events   Total      Events   Total

Grabiner 2012    1        22         8        30
Parijat 2012     0        12         3        12

Total (95% CI)            34                  42

Total events     1                   11

Heterogeneity: [Chi square] = 0.23, df = 1 (P = 0.63);[I.sub.2] = 0%

Test for overall effect: Z = 2.70 (P= 0.007)

Study or                  Peto Odds Ratio
Subgroup         Weight   Peto, Fixed,
                          95% CI

Grabiner 2012    73.0%    0.22 [0.05, 0.93]
Parijat 2012     27.0%    0.11 [0.01, 1.19]

Total (95% CI)   100.0%   0.18 [0.05, 0.63]

Total events

Heterogeneity: [Chi square] = 0.23, df = 1 (P = 0.63);[I.sub.2] = 0%

Test for overall effect: Z = 2.70 (P= 0.007)

Figure 4: Forest plot for the effects of perturbation training
compared to no perturbation training on risk of laboratory falls in
young participants. For the trials where two perturbation lengths
were tested, the 12 and 18 cm perturbation length results have been
summated.

Study or           Perturbation       Control
Subgroup         Events   Total   Events   Total

Bhatt 2009b      0        8       3        8
Bhatt 2013       0        16      0        16
Lee 2016         1        24      3        12
Wang 2011        0        20      6        23
Yang 2013        0        17      4        17
Yang 2014        2        24      2        12

Total (95% CI)            109              88

Total events     3                18

Heterogeneity: [Chi square] = 1.64, df = 4 (P = 0.80); [I.sup.2] = 0%

Test for overall effect: Z = 3.28 (P = 0.001)

Study or                  Risk Ratio
Subgroup         Weight   M-H, Fixed, 95% CI

Bhatt 2009b      16.9%    0.14 [0.01, 2.39]
Bhatt 2013                Not estimable
Lee 2016         19.3%    0.17 [0.02, 1.44]
Wang 2011        29.3%    0.09 [0.01, 1.47]
Yang 2013        21.7%    0.11 [0.01, 1.92]
Yang 2014        12.9%    0.50 [0.08, 3.13]

Total (95% CI)   100.0%   0.17 [0.06, 0.49]

Total events

Heterogeneity: [Chi square] = 1.64, df = 4 (P = 0.80); [I.sup.2] = 0%

Test for overall effect: Z = 3.28 (P = 0.001)
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Title Annotation:SYSTEMATIC REVIEW
Author:Papadimitriou, Angela; Perry, Mark
Publication:New Zealand Journal of Physiotherapy
Article Type:Report
Date:Mar 1, 2017
Words:13050
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