In ten studies21-23,41,43,45,47,50-52 the outcomes of interest were assessed twice, at baseline and at the end of the intervention or study, with measurement intervals varying from eight to 10 weeks21 to 18 months.51 In eight studies32,40,44,46,48,49,54,55 three assessment sessions were conducted. The largest measurement interval between the baseline and the last follow-up assessments was four years,48and the smallest one seven months.49 Finally, three stud- ies29,42,53 provided four assessment sessions. In one of these studies42the outcomes were measured at baseline, after a three-month intervention, and at six and 12 months. The same measurement intervals (at baseline, and three, six and 12 months) were indicated by the authors of another study.53 How- ever in this case the intervention lasted six months so that one of the assessment sessions (at three months) was conducted in the course of the intervention. In
the third study29 the outcomes were measured at baseline and at three, six and twelve months after discharge, with the period of the intervention being unclear (for more detailed information see Table 4).
Methods of economic analysis
The aim of the study developed by Fairhall et al.32 was to compare the costs and cost-effectiveness of a multifactorial interdisciplinary intervention target- ing identified frailty characteristics versus usual care from the community services and general practi-
tioners. The effectiveness outcome measures
included prevalence of frailty (assessed according to CHS criteria) and level of quality of life (assessed based on EuroQol questionnaire including items regarding mobility, self-care, usual activities, pain/ discomfort and anxiety/depression), with data being collected at baseline, and at three and 12 months. In addition, quality adjusted life years (QALYs) were Table 5. (Continued)
Study Experimental condition Control condition Duration of intervention
Vriendt, et al.,
201621 Activity oriented and community based program
The intervention was delivered by occupational therapist according to standardized protocol. It was based on a systematic therapy process and includes 4 phases: (1) client-centered goal-setting (the assessment of functional problems and their impact on health related quality of life plus comprehensive geriatric assessment); (2) negotiating a therapy plan (based on choices and preferences of the participants); (3) the actual intervention (training of functions and skills, education of the primary care giver or professional care giver, advise and instruction in the use of assistive devices or a comprehensive intervention including all aforementioned); (4) an evaluation of the outcome and finally reporting to relevant others (as general practitioner and the community care team).
Community care as usual Support in housekeeping and self-care, healthcare support from a nurse and social sup- port from social worker.
Period of intervention: eight to ten weeks. Frequency: not clear
Wolf et al.,
200355 Tai Chi
Tai Chi classes emphasized all components of movement that typically become limited with aging. Specifically, the progression involved a gradual reduction of the base of standing support until single limb stance was achieved, increased body and trunk rotation, and reciprocal arm movements. Participants were encouraged to home practice, but this practice was not monitored.
Computerized balance training
Training involving use of a Balance System, high technological approach, and being performed individually. During the task, the participant have to move the cursor seen on the screen at eye level into specific targets that can be placed anywhere on the screen. This task is successfully achieved by moving the center of mass with no foot displacement. The goal is to progressively increase sway to the limits of postural stability. Added to this paradigm is the capability of moving the floor upon which the pylons are placed at either linear or angular directions at varying velocities.
The training period consisted of positioning progressively more difficult targets that required increased sway first in the absence of, and then with, concomitant floor movement. For each session, subjects were asked to practice these tasks with eyes open and then with eyes closed, thus demanding more dependence upon vestibular and somatosensory systems to maintain balance.
Education exercise-control condition
Participants met with a geron- tological nurse/researcher to discuss topics of interest, such as pharmacological manage- ment, sleep disorders, cogni- tive deficits coping with bereavement, and other. The participants were also instructed not to change their exercise level.
Period of intervention: 15 weeks.
Tai Chi group: Participants were encouraged to practice at least 15 minutes twice a day.
Computerized Balance Training group: frequency and duration of sessions not clear.
Education group: weekly session with one-hour duration.
calculated based on data obtained from the quality of life measurements. For the calculation of the number of QALYs gained or lost over the 12 months of follow-up, trapezoidal integration (an approach used for measure of the area under a function plotted
on a graph) was used. The study authors32 also
evaluated health and community resource utiliza- tion, that included costs of primary care appoint- ments with general practitioner and nurse or other health professional, costs of hospital-based care, costs of permanent and respite residential care, with high and low care, and costs of home help, transport and meal delivery. The resource use over 12 months was translated into monetary values using local or national prices or unit costs as appropriate. Mone- tary amounts were presented in 2011 Australian dollars. Finally, complete-case cost-utility and cost-effectiveness of multifactorial interdisciplinary intervention versus usual care were carried out, with the adopted perspective of health and community care funder. These economic evaluations included comparison of the difference in cases of transition out of frailty and in total costs between intervention and the control groups, as well as incremental cost- effectiveness ratios (ICERs) determined to assess the additional expenditure required to achieve addi- tional benefits of the intervention.
Cohen et al.44compared the costs of an interven- tion consisting of inpatient and outpatient geriatric evaluation and management versus inpatient and outpatient usual care. The effectiveness of these interventions was measured based on changes in basic and instrumental ADLs, physical performance and quality of life (assessed by Short Form 36 Health Survey). Data about these outcomes was collected at discharge and 12 months. In addition, probability of survival and relative risk of death at one year were calculated. The economic evaluations included utili- zation and costs of health care services, determined using a computer program at each center, centralized Veterans Affairs databases, and patients’ or care- givers’ reports of non-Veterans Affairs nursing home care. The costs considered in the analyses included overall costs of initial hospitalization and overall costs of health care after discharge (that is, costs of inpatient, outpatient, and long-term care provided by Veteran Affairs Medical Centers, as well as care in private nursing homes, without including the costs of inpatient and outpatient care at non-Veterans Affairs facilities). Detailed information about
specific costs was not provided. Monetary amounts were presented in dollars. The authors did not pro- vide information about the adopted perspective.44
Outcomes
The overview of the results on the outcome of frailty, indicated by any validated scale, measurement or index, or assessed by a limited set of indicators, is provided in Table 6. Table 7 summarizes the impact on the secondary outcomes.
Effectiveness of interventions to prevent progression of frailty
Physical exercise programs delivered in class41,42,46,49 or delivered in class and followed by home-based practice53,55were shown to be effective for preventing the progression of pre-frailty and frailty, at least in some of the frailty indicators (sum of indicators,42,53
weakness,41,55 weight loss,49 slowness/gait
speed,41,46,53gait distance,55balance,46exhaustion,49 physical activity,49activities of daily living,46and fear of falls55). These positive effects were observed for different types of exercise programs (including Tai Chi,55 resistance training with42 and without41,53 nutrition consultation, and comprehensive multicom- ponent training46,49) and for different samples (com- munity dwelling older adults,42,49,53,55 older adults aged between 80 years and 90 years contacted through the primary health care center,46institutionalized older adults aged 85 or over41).
On the other hand, home-based exercise pro-
grams43 developed with housebound older adults
showed only a non-significant trend to improve mobility. No effects on the prevention of frailty progression were observed for computerized balance training55performed individually with supervision. Providing nutritional supplements alone, includ- ing milk fat globule membrane (MFGM)49and pro- tein-energy formula,23or increasing protein-calorie and micronutrients intake,53 was also shown to be favorable for prevention of frailty progress. Milk fat globule membrane49provided to frail women from the community improved physical activity immedi- ately after the intervention and reduced long-term exhaustion, but had no significant post-intervention effect on weight. In another study,23 a protein- energy formula provided to community dwelling older adults with low mobility and who were also malnourished (both indicators used for operational definition of frailty), had beneficial effects for energy
intake. However, this improvement in energy intake was not associated with significant change in body weight. An intervention based on increase of protein- calorie and micronutrient intake53provided to pre- frail and frail older adults from the community improved frailty scores from the baseline, with observed change being significant at 12 months, but not at three or six months. The positive effects of this intervention were observed through the increase in long-term physical activity. Regarding body mass index, the highest mean change was observed follow-up at three months; however, this change was not significant.
Hormone replacement with atamestane and/or dehydroepiandrosterone52and conducted with inde- pendently living men without disease or recent hos- pitalization and with low scores on strength tests was shown to have no influence on frailty measurements. Interventions based on individually tailored man- agement of clinical condition by a multi-professional team and according to individual needs21,29,32,44,50 were shown to have inconsistent effects on frailty prevalence. A twelve month multifactorial interdis- ciplinary intervention provided to community dwell- ing older adults meeting with frailty showed a significant impact on frailty prevalence.32Improve- ment in frailty (operationalized in terms of impairment in basic activities of daily living) was also observed in relation to client-centered, individ- ually tailored activity oriented program conducted with community dwelling older adults receiving healthcare support.21 Regarding inpatient care in geriatric evaluation and management units44 that included screening geriatric evaluation and manage- ment according to individual care plan developed by a multi-professional team, positive effects were dem- onstrated on basic ADL and physical performance at discharge, but not at the follow up at 12 months. However, when the same intervention was devel- oped in geriatric clinics with outpatients who had previously received all appropriate hospital ser- vices,44 the positive effects were only observed on physical performance at 12 months. On the other hand, a six month intervention based on screening evaluation results,50 developed with pre-frail and frail community dwelling older adults, as well as continuum care29 provided to older adults with at least one chronic disease and dependent in at least one ADL, discharged from emergency departments, were shown to have no effects on frailty status.
Group sessions focused on the ageing process and health,40conducted with community dwelling older adults resulted in postponing progression in tired- ness in daily activities (measured through Mob-T Scale) for up to one year. When tiredness was not included in the analysis and when the follow-up at
three months was considered,47 group meetings
focused on ageing process and health were shown to have no effect on frailty.
Educational sessions focused on health promo- tion, disease prevention and self-care,51provided in groups for participants who were not at risk of frailty, and individually by a geriatrician for partic- ipants who were at risk of frailty, showed positive impact for a change of frailty status.
Regarding home visits by nurses provided to community dwelling older adults, positive effects were observed in relation to nine months of weekly nurse home visits focused on life-style changes and accompanied by an alert button,45but not in relation to nine months of weekly nurse home visits focused on life-style changes without alert button45 or 18 months of nurse home visits focused on designing of care plan.54 The positive impact of the treatment including alert button was observed on the frailty prevalence, namely on the percentage of older adults who developed frailty during the follow up period. The authors45 suggested that a visiting nurse com- bined with use of technology could produce a sense of security in the patients diminishing the level of risk. They also considered the possibility that the technology could be a tool to make better clinical decisions and to achieve closer patient care.
Favorable effects were also verified for a single preventive home visit by a trained professional40 provided to community dwelling older adults. In this case, the intervention resulted in postponing progression in tiredness in daily activities for up to one year. The authors of the intervention also described the results obtained in the follow–up at three months,47 however the definition of frailty presented in this study did not include tiredness. In this three months follow-up study47 no changes in frailty prevalence were observed.
Cognitive training designed to stimulate short- term memory, and enhance attention, information- processing skills, and reasoning and problem-solving abilities53reduced the frailty score from baseline at 12 months (six months after the intervention).
improvement was observed in knee strength imme- diately after the intervention (at six months) and in follow-up assessment (at 12 months). Other frailty components remained unchanged.
Problem solving therapy42was shown to have no effects on frailty.
Combined multidisciplinary treatment, including nutritional supplementation, physical training and cognitive training53provided to community dwelling older adults, showed a significant positive impact on frailty prevalence in follow up at three-, six- and 12 months. Physical exercise programs with supplemen- tation were also shown to be effective for preventing the progression of frailty in community dwelling older adults, independently of type of supplement used
(protein supplement22or MFGM49). Protein supple- mentation in combination with exercise prevented decrease in maximal walking time, but had no effects on maximal walking distance and physical activity. In addition, for good compliers, a significant increase in walking outcomes was observed.22 Exercise and MFGM supplementation had positive long-term effects on all frailty indicators, with the exception of muscle strength.49Finally, long-term music-based multi task exercise48(also conducted with community dwelling older adults) improved gait speed and hand- grip strength. In addition, pre-frail participants from the continued intervention group were more likely to become robust at four years than participants from the discontinued intervention group.
Table 6: Effectiveness of interventions described in the included studies for outcome of frailty
Study
Intervention/control
condition Primary outcome – frailty Significance
Behm, et al., 201540
Multi-professional senior group meet- ings with one home visit
(n ¼ 171)
At baseline:
- Sum of indicators: 14% non-frail, 70% pre-frail, 16% frail - Tiredness in daily activities: 6%
One year after intervention - Deterioration on frailty: 49% - Frail 3 indicators: 34% - Tiredness in daily activities: 22% Two years after intervention
- Deterioration on frailty: 60% - Frail 3 indicators: 47% - Tiredness in daily activities: 32%
Between group change on frailty status:
Decrease on frailty status measures as tiredness in daily activities was higher in the control group than in the senior meetings group p ¼ .029 or in the preventive visit group p ¼ .006
Single preventive home visit (n ¼ 174)
At baseline:
- Sum of indicators: 13% non-frail, 67% pre-frail, 20% frail - Tiredness in daily activities: 6%
1 year after intervention - Deterioration on frailty: 44% - Frail 3 indicators: 34% - Tiredness in daily activities: 19% 2 years after intervention
- Deterioration on frailty: 58% - Frail 3 indicators: 52% - Tiredness in daily activities: 30% Ordinary range of
community services (n ¼ 114)
At baseline:
- Sum of indicators: 11% non-frail, 70% pre-frail, 19% frail - Tiredness in daily activities: 6%
1 year after intervention - Deterioration on frailty: 38% - Frail 3 indicators: 39% - Tiredness in daily activities: 33% 2 years after intervention
- Deterioration on frailty: 68% - Frail 3 indicators: 59% - Tiredness in daily activities: 39%
Study
Intervention/control
condition Primary outcome – frailty Significance
Bonnefoy, et al., 201222
Home based exercise program with dietary protein supplementa- tion
(n ¼ 53)
At baseline (Median, 1stand 3rdquartiles):
- Maximal walking distance (m): 1000 (450; 1750) - Maximal walking time (mn): 30 (15; 60) - PASE score: 33.6 (30.0; 65.5)
After 4-month intervention (% from baseline, 1stand 3rdquartiles):
- Variation in maximal walking distance (%): 0.00 (55.0; 33.3) - Variation in maximal walking time (%): 0.00 (33.3; 50.0) - Variation in PASE score (%): 0.00 (20.9; 6.0)
Between group change: Maximum walking time kept stable in the interven- tion group and decreased in the control group p ¼ .009 (for age and sex adjusted analysis p ¼ .015) In subgroup of good com- pliers with intervention program (n ¼ 23) also sig- nificant between group dif- ferences on maximum walking distance and max- imum walking time were found ( p ¼ .007; p ¼ .004, respectively)
No intervention (n ¼ 49)
At baseline
- Maximal walking distance (m): 1000 (300; 2000) - Maximal walking time (mn): 30 (15; 60) - PASE score: 33.6 (27.1; 55.0)
After 4-month intervention (% from baseline, 1stand 3rdquartiles):
- Variation in maximal walking distance (%): 16.7 (40.0; 0.0) - Variation in maximal walking time (%): 25.0 (50.0; 0.00) - Variation in PASE score (%): 0.00 (16.7; 31.7)
Cadore et al., 201441 Multicomponent exercise program (n ¼ 11) At baseline (mean SD): - Gait velocity (ms1): 0.76 0.07; - Hand grip (N): 165 63
- Hip flexion strength (N):1.057 262 - Knee extension strength (N): 1.451 441 After 12-week intervention (mean SD):
- Gait velocity (ms1): 0.80 0.08
- Hand grip (N): 183 52
- Hip flexion strength (N): 1.284 203 - Knee extension strength (N): 1.745 460
Group x time interaction: Gait velocity p < .05 Hip flexion strength p < .05 (intervention group >control group) Hand grip p < .01 (inter- vention group > control group)
Knee extension strength p < .01 (intervention group >control group) Within group change in frailty components: In the intervention group improvement on hip flex- ion strength p < .01 and knee extension strength p < .05
In the control group decrease in gait speed p < .05, hand grip p < .05 and knee extension strength p < .05 Mobility exercises (n ¼ 13) At baseline (mean SD): - Gait velocity (ms1): 0.68 0.06 - Hand grip (N): 157 64
- Hip flexion strength (N): 865 268 - Knee extension strength (N): 1.206 336 After 12-week intervention (mean SD):
- Gait velocity (ms1): 0.60 0.07
- Hand grip (N): 130 58
- Hip flexion strength (N): 834 382 - Knee extension strength (N): 1.042 353 Chan et al.,
201242
Exercise and nutri- tion consultation (n ¼ 55)
At baseline:
- Pre-frail: 84%; Frail: 16%
- Weight loss: 33%; Exhaustion: 45%; Low activity level: 5%; Slowness: 18%; Weakness: 60%
After 3-month intervention: - Improvement in frailty: 45%
- Weight loss: 16%; Exhaustion: 29%; Low activity level: 4%; Slowness: 11%; Weakness: 20%
6 months after baseline assessment: - Improvement in frailty: 42%
- Weight loss: 15%; Exhaustion: 31%; Low activity level: 4%; Slowness: 7%; Weakness: 16%
12 months after baseline assessment: - Improvement in frailty: 40%
- Weight loss: 20%; Exhaustion: 35%; Low activity level: 4%; Slowness: 11%; Weakness: 13%
Between group change on frailty status:
At 3 months the improve- ment in frailty status was higher in the exercise and nutrition consultation group than in the respec- tive control group p ¼ .008 Between group change on frailty components: no sig- nificant difference
Table 6. (Continued)
Study
Intervention/control
condition Primary outcome – frailty Significance
Problem solving ther- apy
(n ¼ 57)
At baseline:
- Pre-frail: 84%; Frail: 16%
- Weight loss: 21%; Exhaustion: 39%; Low activity level: 9%; Slowness: 26%; Weakness: 74%
After 3-month intervention: - Improvement in frailty: 44%
- Weight loss: 12%; Exhaustion: 28%; Low activity level: 5%; Slowness: 9%; Weakness: 30%
6 months after baseline assessment: - Improvement in frailty: 35%
- Weight loss: 11%; Exhaustion: 28%; Low activity level: 5%; Slowness: 11%; Weakness: 16%
12 months after baseline assessment: - Improvement in frailty: 35%
- Weight loss: 14%; Exhaustion: 28%; Low activity level: 5%; Slowness: