Analysis of recurrent events: a systematic review of randomised controlled trials of interventions to prevent falls

Rationale: there are several well-developed statistical methodsfor analysing recurrent events. Although there are guidelinesfor reporting the design and methodology of randomised controlledtrials (RCTs), analysis guidelines do not exist to guide theanalysis for RCTs with recurrent events. Application of statisticalmethods that do not account for recurrent events may provideerroneous results when used to test the efficacy of an intervention.It is unknown what proportion of RCTs of falls prevention studieshave utilised statistical methods that incorporate recurrentevents. Methods: we conducted a systematic review of RCTs of interventionsto prevent falls in community-dwelling older persons. We searchedMedline from 1994 to November 2006. We determined the proportionof studies that reported using three statistical methods appropriatefor the analysis of recurrent events (negative binomial regression,Andersen–Gill extension of the Cox model and the WLW marginalmodel). Results: fewer than one-third of 83 papers that reported fallsas an outcome utilised any appropriate statistical method (negativebinomial regression, Andersen–Gill extension of the Coxmodel and Cox marginal model) to analyse recurrent events andfewer than 15% utilised graphical methods to represent fallsdata. Conclusion: RCTs that have a recurrent event end-point shouldinclude an analysis appropriate for recurrent event data suchas negative binomial regression, Andersen–Gill extensionof the Cox model and/or the WLW marginal model. We recommendthat researchers and clinicians seek consultation with a statisticianwith expertise in recurrent event methodology.     

Effective Exercise for the Prevention of Falls: A Systematic Review and Meta‐Analysis

OBJECTIVES: To determine the effects of exercise on falls prevention in older people and establish whether particular trial characteristics or components of exercise programs are associated with larger reductions in falls. DESIGN: Systematic review with meta‐analysis. Randomized controlled trials that compared fall rates in older people who undertook exercise programs with fall rates in those who did not exercise were included. SETTING: Older people. PARTICIPANTS: General community and residential care. MEASUREMENTS: Fall rates. RESULTS: The pooled estimate of the effect of exercise was that it reduced the rate of falling by 17% (44 trials with 9,603 participants, rate ratio (RR)=0.83, 95% confidence interval (CI)=0.75–0.91, P<.001, I²=62%). The greatest relative effects of exercise on fall rates (RR=0.58, 95% CI=0.48–0.69, 68% of between‐study variability explained) were seen in programs that included a combination of a higher total dose of exercise (>50 hours over the trial period) and challenging balance exercises (exercises conducted while standing in which people aimed to stand with their feet closer together or on one leg, minimize use of their hands to assist, and practice controlled movements of the center of mass) and did not include a walking program. CONCLUSION: Exercise can prevent falls in older people. Greater relative effects are seen in programs that include exercises that challenge balance, use a higher dose of exercise, and do not include a walking program. Service providers can use these findings to design and implement exercise programs for falls prevention.     

Physical activity, falls, and fractures among older adults: a review of the epidemiologic evidence

OBJECTIVES: Assess the relationship between physical activity and risk for falls and osteoporotic fractures among older adults. DESIGN: Review and synthesis of published literature. MEASUREMENTS: We searched the literature using MEDLINE, Current Contents, and the bibliographies of articles identified. We included randomized controlled trials (RCT) of the effects of physical activity on the incidence of falls and case-control and prospective cohort studies of the association of physical activity with osteoporotic fracture risk. We also summarized mechanisms whereby physical activity may influence risk for falls and fractures. RESULTS: Observational epidemiologic studies and randomized clinical trials evaluating the effectiveness of physical activity programs to prevent falls have been inconclusive. However, many studies have lacked adequate statistical power, and recent trials suggest that exercise, particularly involving balance and lower extremity strength training, may reduce risk of falling. There is consistent evidence from prospective and case-control studies that physical activity is associated with a 20-40% reduced risk of hip fracture relative to sedentary individuals. The few studies that have examined the association between physical activity and risk of other common osteoporotic fractures, such as vertebral and wrist fractures, have not found physical activity to be protective. CONCLUSIONS: Epidemiologic studies suggest that higher levels of leisure time physical activity prevent hip fractures and RCTs suggest certain exercise programs may reduce risk of falls. Future research needs to evaluate the types and quantity of physical activity needed for optimal protection from falls and identify which populations will benefit most from exercise.     

Exercise and Fall Prevention: Narrowing the Research‐to‐Practice Gap and Enhancing Integration of Clinical and Community Practice

Falls in older adults are a global public health crisis, but mounting evidence from randomized controlled trials shows that falls can be reduced through exercise. Public health authorities and healthcare professionals endorse the use of evidence‐based, exercise‐focused fall interventions, but there are major obstacles to translating and disseminating research findings into healthcare practice, including lack of evidence of the transferability of efficacy trial results to clinical and community settings, insufficient local expertise to roll out community exercise programs, and inadequate infrastructure to integrate evidence‐based programs into clinical and community practice. The practical solutions highlighted in this article can be used to address these evidence‐to‐practice challenges. Falls and their associated healthcare costs can be reduced by better integrating research on exercise intervention into clinical practice and community programs.     

Prevention of fall and fracture

Many programs to prevent falls were designed for intervention in fall risk factors. Several meta-analyses, based on many randomized, controlled trials and conducted for the purpose of evaluating the efficacy of these interventions, have been published recently. According to these studies, multifactorial fall risk assessment and management, as well as muscle strengthening and balance retraining, succeeded in reducing falls by approximately 10-38%. Only New Zealand trials were found to decrease even injurious falls, with reduction of moderate or serious injuries by 35% using fall prevention. However, there was no significant difference between the two groups when looking at only serious injuries such as fractures. Thus, fall prevention can prevent falls, but not fractures at present.     

Physical exercise in the treatment of Ankylosing Spondylitis: a systematic review

Physical exercise (PE) is a regular component in various disorders management, such as ankylosing spondilitis (AS). AS is a chronic and systematic rheumatic disorder without an effective treatment to restore the health. PE plays an important role on the prevention and management of the deformities related to AS. This review summarizes the randomized controlled trials that have examined the role of PE in AS patients' therapeutic process in order to promote an evidence based practise and to improve the AS patients care. Thirteen randomized controlled trials with a total of 1056 participants were identified in a Cochrane Central, Pubmed/ Medline and PEDro databases computer-based search. The quality assessment of the thirteen randomized controlled trial was 5,62 points in the PEDro scoring scale. Three trials assessed the effects induced by the addition of PE interventions to the medication program, three trials compared individualized home exercise with supervised group exercise, five trials compared alternative exercise programs (hydrotherapy and global posture reeducation) with traditional exercise programs usually recommended to treat AS patients, and two trials investigated the therapy effectiveness. The trials included in this review suggest that PE is a helpful therapy in the management of AS patients; PE should be performed in group under the physiotherapist supervision. New exercise-based approaches, hydrotherapy or global posture reeducation, offers promising results in the management of patients suffering AS.     

Prevention of falls and fall-related fractures in community-dwelling older adults: a meta-analysis of estimates of effectiveness based on recent guidelines

Abstract Background: Two recent falls prevention guidelines have been published but did not include quantitative estimates of effectiveness based on the published reports that were reviewed to support their recommendations. Aim: To produce quantitative estimates of effectiveness of falls prevention programs from the randomised controlled trials cited in the guidelines together with an updated search of the available published reports to August 2002. Methods: A meta‐analysis of randomised controlled trials cited in falls guidelines and studies identified by an updated search of the available published reports was carried out. Randomised controlled trials were identified from the falls guidelines and a search, which met the following criteria: trials in community‐dwelling older people; 1‐year follow up; and outcome measures reported as the number of subjects with at least one fall or the number of subjects with a fracture. Results: The guidelines identified four studies of ‘exercise as a sole intervention’, which when combined with one further study identified in a search of the published reports, gave a fixed effects odds ratio (OR) favouring this strategy of 0.81 (95% confidence interval (CI) 0.58–1.14); the number of patients needed to be treated to prevent one person having a fall was 19.5. The guidelines identified seven studies of a ‘multiple intervention’ strategy that gave a random effects OR favouring this strategy of 0.64 (95% CI 0.47–0.88). Four further studies were identified by the search of the published reports. The updated OR favouring this intervention strategy was 0.65 (95% CI 0.52–0.81); the number of patients needed to be treated to prevent one person having a fall was 9.8. Only two studies had data for fracture and a fixed effects OR favouring falls interventions for fracture prevention was 0.50 (95% CI 0.18–1.40); the number of patients needed to be treated to prevent one person having a fracture was 45.5. Conclusion: Semiquantitative statements of evidence can both understate and overstate the effectiveness of falls prevention strategies. There is moderate evidence of efficacy for falls prevention particularly for multiple intervention strategies. (Intern Med J 2004; 34: 102–108)     

The evidence that exercise during growth or adulthood reduces the risk of fragility fractures is weak

There has never been, and will never be, a randomized double-blind placebo-controlled trial demonstrating that exercise in youth, adulthood or old age reduces fragility or osteoporosis-related fractures in old age. The next level of evidence, a randomized, controlled but unblinded study with fractures as an end-point is feasible but has never been done. The basis for the belief that exercise reduces fractures is derived from lower levels of 'evidence', namely, retrospective and prospective observation cohort studies and case-control studies. These studies are at best hypothesis generating, never hypothesis testing. They are all subject to many systematic biases and should be interpreted with extreme scepticism. Surrogate measures of anti-fracture efficacy are the next level of evidence, such as the demonstration of a reduction in risk factors for falls, a reduction in falls, a reduction in fractures due to falls, an increase in peak bone size and mass, prevention of bone loss in midlife and restoration of bone mass and structure in old age.     

Randomized trials in the treatment of Barrett''s esophagus

Treatment for Barrett's esophagus (BE) has consisted of medical treatment (acid suppression medications), surgery (fundoplication) and endoscopic ablative techniques (photodynamic therapy, argon plasma coagulation and multipolar electrocoagulation). Despite the large number of clinical trials of the efficacy of different therapeutic modalities, there is a paucity of published randomized controlled trials. The aim of this review is to evaluate the published randomized therapeutic trials in patients with BE. A comprehensive MEDLINE search was performed to review randomized clinical trials of different therapeutic modalities in BE. Only eight randomized studies have been published. The eight randomized studies reviewed include: two trials that evaluated medical and surgical therapy; two placebo controlled trials for photodynamic therapy (PDT); one placebo controlled trial comparing argon plasma coagulation (APC) versus surveillance; two trials comparing PDT versus APC; and one trial comparing APC versus multipolar electrocoagulation (MPEC). All the studies are prospective, however only one study is double-blinded. Each study has a small sample size, uses a different population of BE patients (dysplasia versus no dysplasia, short segment BE versus long segment BE), has different defined endpoints (endoscopic ablation of BE, number of treatments required for endoscopic ablation of BE, and elimination of high grade dysplasia) and the methodology for the treatment modalities is different among the studies. Though the data to support the use of endoscopic ablative techniques in the treatment of BE are promising, more rigorous double-blind and larger, well designed randomized studies are required to draw any definitive conclusions.     

Does dance-based training improve balance in adult and young old subjects? A pilot randomized controlled trial

BACKGROUND AND AIMS: Loss of balance is a major risk factor for falls in the elderly, and physical exercise may improve balance in both elderly and middle-aged people. We propose a clinical trial to test the efficacy of an exercise program based on dance in improving balance in adult and young old subjects. METHODS: We carried out a mono-institutional, randomized, controlled clinical trial. 40 subjects (aged 58 to 68 yr) were randomly allocated in two separate groups: the exercise group (n = 20) followed a 3-month exercise program; the control group (n = 20) did not engage in physical activities. Differences in balance between the end of the training period and the baseline were assessed using four different balance tests: Tinetti, Romberg, improved Romberg, Sit up and go. RESULTS: Results showed a significant improvement in balance in the exercise group at the end of the exercise program, whereas the control group did not show any significant changes. The comparison between exercise and control group variations in balance test scores showed a highly significant difference. 17 out of 20 subjects in the exercise group reported great or moderate satisfaction with the dance activity. CONCLUSIONS: Results suggest that physical activity based on dance may improve balance and hence be a useful tool in reducing the risk of falling in the elderly. The exercise program also revealed interesting psychosocial benefits.     

A Small Sample Randomized Clinical Trial Methodology Using N-of-1 Designs and Mixed Model Analysis

Background/Objectives: To date, research on substance abuse prevention relied extensively on large sample randomized clinical trials to evaluate intervention programs. These designs are appropriate for certain types of randomized prevention trials (e.g., efficacy or effectiveness for broad populations) but are unfeasible for other prevention science scenarios (e.g., rare pathologies, pilot studies, or replication tests at specific locales). Methods: An alternative randomized clinical trial is described that relies on much smaller samples, less resources than the large sample designs, randomization, N-of-1 designs for the intervention group, and mixed model analysis. Results: This methodology is illustrated using a small sample prevention study, which demonstrates its statistical power, flexibility, and sophistication for experimental testing of prevention-oriented research questions. Scientific Significance: This methodology can be applied to many existing prevention datasets to facilitate secondary analyses of existing datasets as well as novel studies. It is hoped that such efforts will include further development of the small sample design in substance abuse prevention contexts.     

Exercise leads to faster postural reflexes, improved balance and mobility, and fewer falls in older persons with chronic stroke

OBJECTIVES: To determine the effect of two different community-based group exercise programs on functional balance, mobility, postural reflexes, and falls in older adults with chronic stroke. DESIGN: A randomized, clinical trial. SETTING: Community center. PARTICIPANTS: Sixty-one community-dwelling older adults with chronic stroke. INTERVENTION: Participants were randomly assigned to an agility (n=30) or stretching/weight-shifting (n=31) exercise group. Both groups exercised three times a week for 10 weeks. MEASUREMENTS: Participants were assessed before, immediately after, and 1 month after the intervention for Berg Balance, Timed Up and Go, step reaction time, Activities-specific Balance Confidence, and Nottingham Health Profile. Testing of standing postural reflexes and induced falls evoked by a translating platform was also performed. In addition, falls in the community were tracked for 1 year from the start of the interventions. RESULTS: Although exercise led to improvements in all clinical outcome measures for both groups, the agility group demonstrated greater improvement in step reaction time and paretic rectus femoris postural reflex onset latency than the stretching/weight-shifting group. In addition, the agility group experienced fewer induced falls on the platform. CONCLUSION: Group exercise programs that include agility or stretching/weight shifting exercises improve postural reflexes, functional balance, and mobility and may lead to a reduction of falls in older adults with stroke.     

Twelve month follow up of a falls prevention program in older adults from diverse populations in Australia: A qualitative study

Several randomised trials demonstrate that multi dimensional falls prevention programs are effective in reducing falls in older adults. There is a need to examine the impact of these programs in real life settings where diverse populations exist. The aim of this study was to examine the acceptability and impact on sustained participation in falls prevention activities of a combined exercise and education falls prevention program. A semi structured telephone interview was conducted with 23 participants 12 months following the completion of a 15 week falls prevention program tailored to diverse communities in Victoria, Australia and provided in both a group and home based format. Reported benefits of the falls prevention program included physical improvements in joint flexibility, mobility and balance and enjoyment derived from both the exercises and socialisation. Recall of the educational component was minimal as were ongoing behavioral changes to reduce the risk of falling other than exercise. Participation in sustained exercise for falls prevention following the completion of the program was also inconsistent. Future improvements of such programs could focus upon ensuring the exercises prescribed are sufficiently challenging for each individual in order to be of physical benefit, altering the educational style to be goal directed and more enjoyable, and integrating further strategies to support sustained participation in falls prevention behavioral changes. Linking participants with alternate ongoing exercise opportunities or potential sources of ongoing support may be advantageous in enhancing long term participation in exercise for falls prevention following cessation of the program.     

A randomized trial of exercise programs among older individuals living in two long-term care facilities: the FallsFREE program

OBJECTIVE: To use two different exercise programs over a 2-year period to reduce falls and their sequelae among residents of two long-term care facilities. DESIGN: Randomized, controlled trial. SETTING: The study took place at two long-term care facilities with services ranging from independent living to skilled nursing. PARTICIPANTS: One hundred and ten participants whose average age was 84 and who were capable of ambulating with or without assistive devices and could follow simple directions. INTERVENTION: Participants were randomized to one of two exercise groups (resistance/endurance plus basic enhanced programming or tai chi plus basic enhanced programming) or to a control group (basic enhanced programming only). Exercise classes were held three times per week throughout the study. MEASUREMENTS: Participants were evaluated for cognitive and physical functioning at baseline and 6, 12, and 24 months. Falls were determined from incident reports filed by the nursing staffs at the facilities. RESULTS: Time to first fall, time to death, number of days hospitalized, and incidence of falls did not differ among the treatment and control groups (P>.05). Among all participants, those who fell had significantly lower baseline Folstein Mini-Mental State Examination and instrumental activities of daily living scores and experienced significantly greater declines in these measures over the 2-year program. CONCLUSION: There were no significant differences in falls among the two exercise groups and the control group. Lack of treatment differences and low adherence rates suggest that residents of long-term care facilities may require individualized exercise interventions that can be adapted to their changing needs.     

Effectiveness of a falls-and-fracture nurse coordinator to reduce falls: a randomized, controlled trial of at-risk older adults

OBJECTIVES: To assess the effectiveness of a community‐based falls‐and‐fracture nurse coordinator and multifactorial intervention in reducing falls in older people. DESIGN: Randomized, controlled trial. SETTING: Screening for previous falls in family practice followed by community‐based intervention. PARTICIPANTS: Three hundred twelve community‐living people aged 75 and older who had fallen in the previous year. INTERVENTION: Home‐based nurse assessment of falls‐and‐fracture risk factors and home hazards, referral to appropriate community interventions, and strength and balance exercise program. Control group received usual care and social visits. MEASUREMENTS: Primary outcome was rate of falls over 12 months. Secondary outcomes were muscle strength and balance, falls efficacy, activities of daily living, self‐reported physical activity level, and quality of life (Medical Outcomes Study 36‐item Short Form Questionnaire). RESULTS: Of the 3,434 older adults screened for falls, 312 (9%) from 19 family practices were enrolled and randomized. The average age was 81±5, and 69% (215/312) were women. The incidence rate ratio for falls for the intervention group compared with the control group was 0.96 (95% confidence interval=0.70–1.34). There were no significant differences in secondary outcomes between the two groups. CONCLUSION: This nurse‐led intervention was not effective in reducing falls in older people who had fallen previously. Implementation and adherence to the fall‐prevention measures was dependent on referral to other health professionals working in their usual clinical practice. This may have limited the effectiveness of the interventions.     

Psychotropic medication withdrawal and a home-based exercise program to prevent falls: a randomized, controlled trial.

OBJECTIVE: To assess the effectiveness of psychotropic medication withdrawal and a home-based exercise program in reducing falls in older people. DESIGN: A randomized controlled trial with a two by two factorial design. SETTING: Seventeen general practices in Dunedin, New Zealand. PARTICIPANTS: Women and men aged 65 years registered with a general practitioner and currently taking psychotropic medication (n = 93). INTERVENTIONS: Two interventions: (1) gradual withdrawal of psychotropic medication versus continuing to take psychotropic medication (double blind) and (2) a home-based exercise program versus no exercise program (single blind). MEASUREMENTS: Number of falls and falls risk during 44 weeks of follow-up. Analysis was on an intent to treat basis. RESULTS: After 44 weeks, the relative hazard for falls in the medication withdrawal group compared with the group taking their original medication was .34 (95% CI, .16-.74). The risk of falling for the exercise program group compared with those not receiving the exercise program was not significantly reduced. CONCLUSIONS: Withdrawal of psychotropic medication significantly reduced the risk of falling, but permanent withdrawal is very difficult to achieve.     

Effectiveness of interventions for the treatment of acute and prevention of recurrent gout--a systematic review

OBJECTIVE: To determine the evidence for the effectiveness of treatments for acute gout and the prevention of recurrent gout. METHOD: Seven electronic databases were searched for randomized controlled trials of treatments for gout from their inception to the end of 2004. No language restrictions were applied. All randomized controlled trials of treatments routinely available for the treatment of gout were included. Trials of the prevention of recurrence were included only if patients who had had gout and had at least 6 months of follow-up were studied. RESULTS: We found 13 randomized controlled trials of treatment for acute gout, two of which were placebo controlled. Colchicine was found to be effective in one study; however, the entire colchicine group developed toxicity. The only robust conclusion from studies of non-steroidal anti-inflammatory drugs is that pain relief from indometacin and etoricoxib are equivalent. We found one randomized controlled trial, reported only as a conference abstract, of recurrent gout prevention. CONCLUSION: The shortage of robust data to inform the management of a common problem such as gout is surprising. All of the drugs used to treat gout can have serious side effects. The incidence of gout is highest in the elderly population. It is in this group, who are at a high risk of serious adverse events, that we are using drugs of known toxicity. The balance of risks and benefits for the drug treatment of gout needs to be reassessed.     

Does acetyl salicylic acid (ASA) have a role in the prevention of venous thromboembolism?

Guidelines differ on whether acetyl salicylic acid (ASA, aspirin) should be used for prophylaxis in patients at high-risk of venous thromboembolism (VTE), principally because of differences in perceptions of its efficacy. ASA is an attractive therapeutic option because it is inexpensive, easy to administer and does not require monitoring. We critically reappraised the evidence from randomized controlled trials for the efficacy of ASA in VTE prevention. ASA is clearly efficacious in preventing VTE compared to placebo or no treatment, but appears to be less efficacious than the low molecular weight heparins in small trials. There is little data for ASA in comparison with unfractionated heparin and warfarin. A large randomized controlled trial is required to clarify the role of ASA compared to contemporary anticoagulant strategies for the prevention of VTE.     

Circumcision and HIV transmission

PURPOSE OF REVIEW: To review the recent literature on male circumcision and its effect on HIV acquisition. RECENT FINDINGS: The report from the randomized clinical trial of male circumcision in South Africa demonstrating a 60% protective effect in preventing HIV acquisition provided the first clinical trial evidence of efficacy of male circumcision in protecting men against HIV infection. This protective effect was consistent with both ecological and epidemiologic studies which also show a protective effect of 50-70% in men at high risk for HIV infection. Biological studies also demonstrate an increased number of HIV receptor cells in the mucosa of foreskin providing additional evidence of HIV susceptibility in the uncircumcised male. Male circumcision may also have a beneficial effect in preventing HIV acquisition in women and lowering selected sexually transmitted infections in both sexes. SUMMARY: The results of two ongoing randomized clinical trials of male circumcision in Kenya and Uganda are awaited with interest, however male circumcision should be carefully considered as a potential public health tool in preventing HIV acquisition. If other trials confirm the results of the South African trial, implementation of this surgical procedure will need to be carefully scaled up and integrated into other prevention programs with emphasis on surgical training, aseptic techniques, acceptability, availability and cultural considerations.     

Assessment and management of falls in older people

Falls remain a major cause of mortality and morbidity for older Australians, despite considerable growth in falls prevention activity in recent years. Risk factors for falls are well defined, and there is a growing evidence base from randomized controlled trials in community settings indicating a range of effective individual and multiple strategy interventions to reduce falls and falls injuries. These range from health promotion approaches, such as group exercise programmes, through to multidisciplinary, multifactorial interventions for high-risk populations. Practitioners need to utilize a range of strategies to enhance uptake and sustained participation in falls prevention activities. Future research needs to address important gaps, such as compliance issues, and interventions for people with cognitive impairment, dizziness and vision loss. Further research is also required in residential care and hospital settings, where there is relatively little research evidence to guide practice.