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EFFECT OF β-HYDROXY-β-METHYLBUTYRATE (HMB) ON MUSCLE STRENGTH IN OLDER ADULTS WITH LOW PHYSICAL FUNCTION

 

K. Kinoshita1, S. Satake1,2, Y. Matsui3, S. Kawashima2, H. Arai1,2,4

 

1. Section of Frailty Prevention, Department of Frailty Research, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Obu, Japan; 2. Department of Geriatric Medicine, Hospital, National Center for Geriatrics and Gerontology, Obu, Japan; 3. Department of Orthopedics, Hospital, National Center for Geriatrics and Gerontology, Obu, Japan; 4. Director, Hospital, National Center for Geriatrics and Gerontology, Obu, Japan

Corresponding Author: Kaori Kinoshita, R.D., M.S. National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, Japan 474-8511, TEL: +81-562-46-2311, FAX: +81-562-44-8518, E-mail address: kino4ta@ncgg.go.jp

J Aging Res Clin Practice 2019;8:1-6
Published online January 2, 2019, http://dx.doi.org/10.14283/jarcp.2019.1

 

 

Abstract

Objectives: To evaluate the effects of β-hydroxy-β-methylbutyrate (HMB) on muscle strength, physical performance, and muscle mass without additional exercise training in older adults with low physical function. Design: Randomized, controlled trial (Open-label study). Setting: Outpatients. Participants: 34 senior outpatients with low physical function who do not exercise regularly. Intervention: 2.4 g of HMB (3.0 g of calcium β-hydroxy-β-methylbutyrate [CaHMB]) per day was given for 60 days, and subjects in the control group were asked to engage in daily activities as normal. Measurements: Weakness or low function was defined by the Asian Working Group for Sarcopenia criteria, then the participants were assigned to the HMB group or the control group. All participants underwent several evaluations such as grip strength, the timed up and go test, the 5-times chair stand test (5CS), and skeletal muscle mass index by the bioimpedance method at baseline and at the end of intervention or control period. Results: An intragroup comparison of pre- to post-treatment values showed significant improvement in grip strength and the 5CS in the HMB group (grip strength: HMB, 16.6±6.1 kg to 18.2±6.4 kg, P=.001; control, 16.5±4.3 kg to 16.7±4.7 kg, P=.729; 5CS: HMB, 11.0 [8.8-13.0] s to 10.1 [8.5-12.6] s, P=.011; control, 11.1 [8.6-13.8] s to 10.0 [8.8-11.3] s, P=.246). Two-way repeated measures analysis of variance (ANOVA) used to compare the HMB and control groups showed a significant improvement in grip strength in the HMB group compared with the control group (P=.029). Conclusion: A supplementation of HMB without additional exercise may improve muscle strength in older patients with low muscle strength.

Key words: Randomized controlled trial, elderly, Asian Working Group for Sarcopenia, dynapenia, low muscle strength.

 

 

Introduction

One of the important cause of disability in the later lives is thought to be frailty. Frailty, characterized primarily by malnutrition and sarcopenia (a condition featuring loss of muscle mass with either muscular weakness or low physical performance) (1), is reversible (2), meaning that proper evaluation and intervention could bring improvement.
Maintaining skeletal muscle mass by consuming sufficient caloric content and protein and maintaining muscle strength through adequate exercise are effective ways to prevent malnutrition and sarcopenia. Food consumption generally induces protein synthesis and reduces protein catabolism in the skeletal muscles (3), but muscle synthesis in the skeletal muscles of older people appears to be less responsive to amino acids (4), which is called as anabolic resistance. To overcome such a condition, enough consumption of protein or essential amino acids is required, with leucine particularly playing a central role in protein synthesis in the body (5, 6).
The β-hydroxy-β-methylbutyrate (HMB) is a natural metabolic product of leucine (7), but only 5% of the leucine consumed is reportedly converted in the body to HMB. The HMB stimulates body protein synthesis (8) with anabolic effects more powerful than those of leucine (9) and may therefore have a potential effect on muscle growth and performance (10). These findings suggest that HMB may be effective in sarcopenia and dynapenia (11), but research in people with sarcopenia or poor physical performance is currently lacking. The findings of systematic reviews suggest that HMB consumption plus exercise may increase muscular strength in older persons, however there are no firm conclusions on the effects of HMB alone (12, 13). No randomized, controlled trial of HMB in sarcopenia or low physical function has been conducted under the Asian Working Group for Sarcopenia (AWGS) criteria (14).
To address this deficit, we decided to evaluate the effects of HMB consumption without additional exercise and within activities of daily living on physical performance of older people with low physical function.

 

Methods

Participants and informed consent

The participants were independent men and women aged 65 years and over who regularly visited the outpatient clinic of the department of geriatrics of the National Center for Geriatrics and Gerontology of Japan on an outpatient basis and were found to have weakness or low physical function according to the criteria of the AWGS (14) (Figure 1). Candidate participants were those who did not regularly exercise or undergo rehabilitation and had to be available for 2 months of the intervention/control period (the study period).

 

Figure 1 A flow chart of participants

Figure 1
A flow chart of participants

 

Candidates were excluded if they had experienced unintentional weight loss of 3 kg or more over the past 3 months, had an acute medical condition, had renal impairment requiring protein restriction, had moderate or greater cognitive impairment as shown by a Mini-Mental State Evaluation (MMSE) score of 18 or less, were certified as requiring assistance under Japan’s Long-term Care Insurance System, had a cardiac pacemaker, or were unsuited to physical performance evaluation because of visual or auditory impairment, quadriplegia, or a similar condition.
This study, which was grounded in the principles of the Declaration of Helsinki, was approved by the Ethics Committee of the National Center for Geriatrics and Gerontology of Japan. All participants were provided information about the purpose and procedures of the study and expected risks and benefits. Those who acknowledged the information and signed the informed consent form were enrolled.

Evaluation of low physical function

Weakness or low physical function was evaluated using the AWGS criteria (14). Grip strength and usual gait speed were first measured, and then muscle mass was evaluated. Men with a grip strength of less than 26 kg and women with a grip strength of less than 18 kg were considered to have muscular weakness. Participants with a gait speed of 0.8 m/s or below in a 5-m usual gait speed test (the middle 5 meters over an 11-meter walk) were considered to have decreased physical performance. A bioimpedance method was used to determine skeletal muscle mass. Men with a skeletal muscle mass index (SMI) of less than 7.0 kg/m² and women with an SMI of less than 5.7 kg/m² were considered to have low skeletal muscle mass. Sarcopenia was defined as low skeletal muscle mass and either muscle weakness or decreased physical performance. The low physical function was defined as either muscular weakness or decreased physical performance.

Randomization and intervention

Candidate participants who satisfied the criteria were examined by a physician and then informed about the study. Nutritional status was assessed with the Mini-Nutritional Assessment-Short Form (MNA®-SF) at the start of study period to confirm that none of the participants was malnourished. Those participants consenting to participate in the study were randomized by lottery to the intervention or control group.
The participants assigned to the interventional group were given 2 packets per day of a supplement containing 1.5 g of calcium HMB (1.2 g of HMB) (7 g of L-glutamine, 7 g of L-arginine, 1.5 g of calcium HMB; Abound™; Abbott Japan Co., Ltd., Tokyo) for 60 days. The participants were instructed to dissolve this powdered supplement in cold water before taking it because dissolving the supplement in hot water could have degraded its ingredients. The participants were given a calendar to use to record the amount consumed each day for 60 days.
The participants assigned to the control group were asked to conduct daily activities as normal for 60 days.
All participants underwent evaluations at baseline and at the end of study period (i.e., after 60 days). These evaluations were performed by a single trained nurse in the present study (Figure 1).
Participants were considered to have dropped out on becoming unable to undergo physical performance evaluations because of an acute illness, hospitalization, or injury during the study or when HMB compliance was less than 60%. This study was conducted in the full analysis set.

Outcome measures

All outcome measures were evaluated at baseline and at the end of study period. Grip strength was measured with a Smedley handgrip dynamometer (Matsumiya Ikaseiki Seisakusho Co., Ltd., Tokyo, Japan) facing outwards and the grip distance adjusted so that the second knuckle of the index finger was bent at a 90° angle. The participants were instructed to stand with their feet normally spaced and squeeze the dynamometer with their arm hanging so that the dynamometer did not touch their body or clothes. The grip strength of each hand was measured twice, with the highest measurement recorded.
The 5-times chair stand test (5CS) was used to evaluate leg strength. The participants, seated in a chair, were asked to stand and sit 5 times as quickly as possible with their arms folded in front of them. The time required was measured.
Skeletal muscle mass was measured with the Inbody 720 precision body composition analyzer (Inbody Japan Inc. Tokyo). Limb skeletal muscle mass (in kilograms) determined using the bioimpedance method was divided by the square of body height (in meters) to determine the SMI.
Functional mobility was evaluated with the timed up and go (TUG) test. The TUG test comprehensively evaluates functional mobility in terms of walking ability, dynamic balance, and agility. The time required for the participants to stand from a seated position, walk around a pylon 3 meters from the chair, return, and touch their pelvis to the chair was measured. The participants walked around the left and right sides of the pylon once. The shorter time was recorded. A time of 10 s or less is considered normal. Those with a time of 20 s or more are considered to require assistance in daily life (15).
Blood samples were taken to measure serum levels of IGF-1, DHEA-S, and 25(OH)D at baseline and at the end of the study period.

Sample size and statistical analyses

The required sample size was determined according to the calculations of a statistician. Based on the results of previous research (16), 2 groups of 17 participants each for a total of 34 participants were found to be necessary for a level of significance of 5% and power of 80% in statistical testing to evaluate the difference in the mean change in the primary outcome measure of grip strength.
SPSS 23.0 (IBM Japan, Tokyo, Japan) was used for all statistical analyses. A paired t-test was used to compare the pre- and post-treatment values in each group. Two-way repeated measures analysis of variance (ANOVA) was used to compare the changes between the groups. A t-test was used to compare mean differences from before to after treatment when a non-normal distribution was present. P-values less than .05 constituted a significant difference.

 

Results

The participants were sequentially randomized to the HMB group (n=19) and the control group (n=17). Two of the 19 participants in the HMB group were considered to have dropped out because they consumed less than the required amount of HMB (participant A: 54.2%, participant B: 50.0%). In the HMB group, 15 participants had sarcopenia. In the control group, 13 participants had sarcopenia.
The baseline characteristics of the participants are shown in Table 1. Their mean age was 80.4±5.9 years. According to the AWGS criteria, 15 participants in the HMB group and 13 participants in the control group had decreased grip strength, and 4 participants in the HMB group and 6 participants in the control group had decreased gait speed. MNA®-SF scores were 11.7±1.3 in the HMB group and 11.4±1.6 in the control group. No participant in either group was malnourished.

Table 1 Baseline characteristics

Table 1
Baseline characteristics

Average intake of HMB in subjects: 2.21 g/day (2.76 g/day CaHMB); GS: grip strength, WS: walking speed, SMI: skeletal muscle mass index, AWGS: Asian Working Group for Sarcopenia, MMSE: Mini Mental State Examination, MNA®-SF: Mini Nutritional Assessment-Short Form

 

Mean HMB consumption was 2.21 g/day (7.6 g/day as CaHMB). Compliance was 92.1%.
Changes in physical performance during the study period in each group are shown in Table 2. The HMB group achieved significant improvements in grip strength (P=.001) and 5CS (P=.011) with 60 days of intervention. SMI, however, did not change from before to after intervention. Gait speed and TUG scores as indicators of leg performance also showed no significant changes. No measure in the control group changed from before to after follow-up.
Intergroup comparisons of the changes using two-way repeated measures ANOVA showed a significant difference only in grip strength (P=.029).
Changes in blood test values during the follow-up period in each group are shown in Table 3. The only significant difference from before to after treatment was seen in serum 25(OH)D levels, which were significantly lower after 60 days in the HMB group.
Any adverse events on HMB supplement intervention were not observed in this study.

Table 2 Changes in physical functions before and after HMB supplementation

Table 2
Changes in physical functions before and after HMB supplementation

Average intake of HMB in subjects: 2.21 g/day (2.76 g/day CaHMB); Difference within group : * Wilcoxon Signed-rank test, otherwise paired t-test; Difference between groups: * t-test, otherwise two-way repeated measures ANOVA; SMI: skeletal muscle mass index, GS: grip strength, WS: walking speed; 5CS: 5 times Chair Stand test, TUG: Timed Up and Go test

 

 

Table 3 Changes in serum biomarkers before and after HMB supplementation

Table 3
Changes in serum biomarkers before and after HMB supplementation

Average intake of HMB in subjects: 2.21 g/day (2.76 g/day CaHMB); Difference within group: Paired t-test; Difference between groups: Two-way repeated measures ANOVA

 

Discussion

This study evaluated the effects of intervention with 60 days of 2.4 g of HMB (3.0 g of CaHMB) consumption without additional exercise in older people with low physical function. Grip strength improved significantly in the HMB group compared with the control group.
This finding supports the findings of a previous study conducted by Flakoll and colleagues (16). In their study, free- and assisted-living older women (mean age: 76.7 years) who were assigned to the intervention group were given 2.0 g of HMB daily for 12 weeks. Grip strength improved significantly in the present study, which featured intervention for 60 days (about 8 weeks). The duration of intervention in the present study, however, may have been too short to capture the effects of intervention on physical performance and muscle mass. Flakoll and colleagues (16) observed significant improvements in grip strength and leg strength, as well as a tendency of improvement in lean mass, after 12 weeks of intervention. Another study of the effects of consuming 2.0 g of CaHMB daily for 1 year found a significant increase in skeletal muscle mass, and in participants whose blood 25(OH)D level was at least 30 ng/mL, a significant improvement was found in leg strength (17). In the present study, 5CS in the HMB group was significantly shorter after 60 days of follow-up, but it did not differ significantly compared with the control group. Physical performance of the legs depends not only on muscular strength, but also pain caused by motor disorders. Such effects were not considered when selecting the participants, which means that the effects of HMB consumption on leg strength may not have been accurately assessed.
Recent studies have found plasma HMB levels in older people to be positively correlated with grip strength and percent appendicular lean mass (18). Although HMB levels in the blood were not measured, increased blood levels of HMB resulting from regular HMB consumption of a certain amount may have contributed to the increase in grip strength that was observed, given that 82.4% of the participants had low skeletal muscle mass (sarcopenia).
Poor grip strength has been associated with negative outcomes in older people. A survey of hospitalized patients found higher hospitalization costs among patients with poor grip strength (19). Separately, grip strength was found to be significantly predictive of quality of life and the condition requiring assistance after 1 year (20). Known to be associated with several measures of muscular strength, grip strength was recently found to be associated with tongue strength, which contributes to chewing and swallowing function (21, 22). Poor chewing and swallowing function contributes to nutritional imbalance and low food consumption, which in turn contribute to sarcopenia and malnutrition. People whose decline in chewing and swallowing function has progressed such that they can no longer eat regular meals require the support of a caregiver to prepare special meals that they can chew and swallow. When further progression of malnutrition and sarcopenia is present, physical performance also decreases to a level at which further assistance is required. Under the assumption that the improvement in grip strength following HMB consumption that was observed is associated with improved tongue strength, consuming HMB may help prevent declines in chewing and swallowing function.
In this study, blood 25(OH)D levels were significantly lower in the HMB group after 60 days than in the control group. Vitamin D, which binds to receptors in the skeletal muscle, may play a central role in regulating the growth, differentiation, and myotube size of skeletal muscle cells (23). Fuller and colleagues (17) observed a significant improvement in leg strength associated with HMB consumption only in participants with a blood 25(OH)D level of 30 ng/mL or greater. This finding, taken together with the findings of the present study, suggests that synergy between HMB and vitamin D may have certain effects on skeletal muscle synthesis and muscular strength enhancement, but further analysis is required because no studies have considered this speculation.
Nevertheless, there is a limitation regarding the blood vitamin D levels measured in this study. Vitamin D is normally synthesized in the body through the action of ultraviolet light, but the effects of ultraviolet light in the present study are unknown, because the participants’ exposure to sunlight was not measured. Other study limitations include the facts that the control group was not given a placebo, leg strength may not have been accurately assessed because the effects of leg pain and other conditions were not considered when selecting the participants, and the 60-day period of intervention was short. Further research that addresses these limitations is needed to better characterize the effects of HMB on low physical function.

 

Conclusions

The findings of the present study suggest that daily consumption of 2.4 g of HMB (3.0 g of CaHMB) for 60 days (about 8 weeks) without additional exercise may improve muscular strength in older people with low physical function. Although the present study identified no gain in skeletal muscle mass or improvement in physical performance, and no association with blood vitamin D levels was found, it indicated that HMB may be a viable treatment for older adults with low physical function.

 

Acknowledgments: Satomi Furuzono and Yayoi Sakuraba kindly assisted with participant measurements and visit scheduling throughout the study, and the authors would like to express their gratitude to them. The authors also deeply appreciate the kind help of our managerial dietician colleagues Noriko Kojima, Kayoko Hattori, and Saki Tomita for working with the participants and supporting this work.

Author Contributions: Study concept and design: Kaori Kinoshita, Shosuke Satake, and Hidenori Arai. Acquisition of data: Kaori Kinoshita, Shosuke Satake, Yasumoto matsui, Shuji Kawashima, and Hidenori Arai. Analysis and interpretation of data: Kaori Kinoshita, Shosuke Satake, and Hidenori Arai. Drafting of the manuscript: Kaori Kinoshita. Critical revision of the manuscript for important intellectual content: Shosuke Satake, Yasumoto Matsui, Shuji Kawashima, and Hidenori Arai.

Conflicts of interest: This work was supported by grants from the Honjo International Scholarship Foundation and the Chukyo Longevity Foundation, and with funds from Abbott Japan Co., Ltd. The funders had no role in study design, data collection, analysis and interpretation, decision to publish, or preparation of the manuscript. Furthermore, none of the authors have any commercial or financial involvement in connection with this study that represent or appear to represent any conflicts of interest.

Ethical standards: This study has been approved by the research ethics committee of National Center for Geriatrics and Gerontology, Japan.

Funding Sources: Abbott Japan, Honjo International Scholarship Foundation, and Chukyo Longevity Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 

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TREATMENT SATISFACTION: A NEGLECTED BUT IMPORTANT OUTCOME MEASURE IN OLDER PEOPLE WITH TYPE 2 DIABETES

 

H. Langerman1,2, R. Gadsby3

 

1. Beds & Herts Postgraduate Medical School, Luton, UK; 2. Merck Sharp and Dohme, UK; 3. University of Warwick Medical School, Coventry, UK.

Corresponding Author: Haya Langerman, Beds & Herts Postgraduate Medical School, Luton, LU2 8LE, UK, E-mail address: haya.langerman@beds.ac.uk.

J Aging Res Clin Practice 2017;6:124-132
Published online June 15, 2017, http://dx.doi.org/10.14283/jarcp.2017.14

 

Abstract

Objective: To investigate the effect of comprehensive geriatric care (CGC) in elderly referred to a rehabilitation unit. This article describes the considerations behind the study. Design: Participants were randomized to either CGC or standard care. Setting: Participants were recruited from two community care rehabilitation units in Aarhus Municipality, Denmark, in the period between 2012 and 2015. Participants: Inclusion:  Elderly patients aged 65 and older admitted from home or hospital. Exclusion: Persons receiving palliative care or assessed by a geriatrician during the past month. Intervention: Medical history, physical examination, blood tests, medication adjustment and follow-up by a geriatrician. The control group received standard care with the general practitioners (GPs) as back-up. Outcomes: Primary outcome: Hospital contacts drawn from national registers. Secondary outcomes: GPs contacts, institutionalization, medication status and mortality collected from national registers and Activities of daily living (ADL), physical and cognitive function and quality of life measures collected by a blinded occupational therapist. All outcomes were assessed at day 10, 30 and 90 after arrival at the rehabilitation unit. Conclusion: A new model of care for elderly referred to community rehabilitation was developed and implemented. The potential benefits of this model were compared with usual care in a community rehabilitation unit in a pragmatic randomized clinical trial. We hypothesized that the geriatrician-performed CGC in elderly referred to a rehabilitation unit will reduce the hospital contacts by 25 % without increase in mortality and in contacts to GPs and home care services. We expect that this model will prevent deterioration in ADL, and physical and cognitive functioning, and reduce the risk of institutionalization. If the results are positive, community rehabilitation services should be encouraged to change their routines for treatment of this population accordingly..

Key words: Randomized controlled trial, Comprehensive geriatric care, rehospitalization, rehabilitation, activity of daily living.

 

Introduction

Older people are the fastest growing segment of the population, responsible for a large portion of the use of health care services, and a large and growing section of the population with diabetes. They are not a uniform group and can be broadly classified into those entering old age (generally 60 years and above), a transitional phase between healthy active life and frailty (the seventh or eighth decade), and frail older people (late old age) (1). Diabetes is up to five times more prevalent in patients aged 65 years or older, compared with patients below the age of 65 (2, 3). Recent estimates suggest that up to 1 in 5 older people have diabetes and that a similar proportion may have undiagnosed diabetes (4).
The management of older people with diabetes presents unique challenges. Observational studies suggest an association between diabetes and the risk of various geriatric conditions (i.e., cognitive impairment, dementia, depression, mobility impairment, disability, and falls) (5, 6). They have an increased rate of diabetes-related complications, are much more likely to present with comorbid conditions, and are more susceptiple to the adverse effects of some . glucose-lowering therapies.
Adherence to treatment is a key factor in achieving therapeutic success. Treatment satisfaction is an important determinant of patients overall health-related decisions such as adherence and willingness to continue treatment (7−9). It is defined as the patient’s evaluation of the process of taking the medication and the outcomes associated with the medication (10). It is an essential measure of treatment effectiveness as some treatments with proven efficacy in clinical trials are less effective when prescribed in routine clinical practice where there is no intensive follow-up to ensure adherence. However, treatment satisfaction is not an easy item to measure as it depends not only on the clinical outcomes achieved such as symptom resolution, control of the disease progression and prevention, but also on factors such as the route and ease of drug administration, and drug tolerability. Overall treatment satisfaction in diabetes consists of the patient’s appraisal of three main treatment-related parameters: efficacy, side effects, and treatment burden or inconvenience. However, in older people with diabetes, outcomes such as hospitalisation rates, quality of life, fall rates, instrumental daily living restrictions and admission rates to care homes assume more importance and should also be considered when assessing treatment satisfaction (11, 12).
Predictors of treatment satisfaction may differ significantly between patients and it cannot be assumed that generic or disease-specific instruments with evidence of good measurement properties in a younger population will perform as well with an older population. For example, older people with type 2 diabetes are more worried about adverse events, have trouble remembering to take their medication or require assistance from another person in order to take their medication (13). In addition, multiple comorbidities, as is commonly found in older populations, are associated with greater decrements in quality-of-life and well-being (14). Consequently, when assessing treatment satisfaction it is important to use a questionnaire that focuses on areas relevant to the target population. For example, older people with type 2 diabetes are particularly at risk of hypoglycaemia and may be less satisfied with treatments that increase this risk. There are several questionnaires that evaluate treatment satisfaction for people with diabetes: Diabetes Treatment Satisfaction Questionnaire (DTSQ) (15), Treatment Satisfaction Questionnaire for Medication (TSQM) (16), Satisfaction with Oral Anti-Diabetic Agent Scale (SOADAS) (17), Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) (18), Diabetes Medication System Rating Questionnaire (DMSRQ) (19), and Oral Hypoglycaemic Agent Questionnaire (OHA-Q) (20). Currently, no treatment satisfaction questionnaires have been designed and validated specifically for older people with type 2 diabetes. This review aims to examine the main validated questionnaires in the area of treatment satisfaction in type 2 diabetes and to assess their applicability to older people.

 

Methods

ProQuest, PubMed, HeinOnline, ScienceDirect, Academic One File, general OneFile and MEDLINE scientific literature databases were searched from 1/1/1980 to 1/4/2014 to identify treatment satisfaction questionnaires validated in diabetes for use in patients receiving oral antidiabetes therapies; insulin-specific questionnaires were not included. Search terms for ProQuest and PubMed included ‘treatment satisfaction, ‘diabetes’,’ older’, ‘elderly’, ‘questionnaires’, ‘assessment’, ‘evaluation’. Seven questionnaires were selected based on their validity in patients with diabetes (Table 1). Data extraction was performed to summarise key components of the studies including study design, demographic characteristics including age, choice of domains and items.

 

Table 1 Study listing

Table 1
Study listing

 

Results

The literature search identified seven questionnaires that had been validated in diabetes. Of these, two were general questionnaires: Treatment Satisfaction Questionnaire for Medication (TSQM) (16) and Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) (18); and five were diabetes-specific: Diabetes Treatment Satisfaction Questionnaire (DTSQ) (15), Diabetes Medication Satisfaction Tool (DMSAT) (21), Diabetes Medication System Rating Questionnaire (DMSRQ) (19), Satisfaction with Oral Anti-Diabetic Agent Scale (SOADAS) (17), and Oral Hypoglycaemic Agent Questionnaire (OHA-Q) (20) (Tables 2 and 3). In addition, the search also identified a quality-of-life questionnaire, the Audit of Diabetes-Dependent Quality of Life (ADDQoL) Senior, which although it looks at quality of life rather than treatment satisfaction is included here as it is the only assessment tool specifically developed for older people with type 2 diabetes (22).

 

General questionnaires

Treatment Satisfaction Questionnaire for Medication (TSQM)

The TSQM is a general tool for assessing patients’ satisfaction with medications designed to treat, control, or prevent a wide variety of conditions. It includes 14 items (Table 2) and has been validated across a wide range of diseases, including type 1 diabetes (16). However, unlike the DTSQ, this measure does not include diabetes-specific items and is therefore unlikely to reliably measure treatment satisfaction with oral antihyperglycaemic agents. In the validation study, respondents’ age ranged from 18 to 88 years, with a mean of 50.5 (16).

 

Table 2 Demographic characteristics of patients included in the studies

Table 2
Demographic characteristics of patients included in the studies

*Oral diabetes medication; **Type 1 and orally treated type 2 diabetes

Table 3 Items included in each questionnaire

Table 3
Items included in each questionnaire

*questionnaire was not available. Information based on validation and might be lacking

 

Although it is a general questionnaire, the TSQM has been used in several studies of people treated with oral antidiabetes agents (23−26). These studies showed that the experience of hypoglycaemia was associated with lower global satisfaction. Marrett et al also found significantly lower scores for the side-effects domain in patients reporting hypoglycaemia compared with those who did not (P ≤ 0.001) (23). Alvarez-Guisasola et al observed that experience of hypoglycaemia was associated with a negative effect on all domains (P < 0.001 for all comparisons) (25). Similar results were found in the Walz et al study, where patients (mean age 69 years) with moderate or worse symptoms of hypoglycaemia indicated several dimensions where they were less satisfied with their antihyperglycaemic medication regimen than patients with no or mild symptoms (26).

Treatment Satisfaction with Medicines Questionnaire (SATMED-Q)

The SATMED-Q is a multidimensional generic questionnaire that was developed to address some of the limitations of the TSQM questionnaire. It explores the same dimensions as the TSQM and two additional dimensions (impact of the treatment on daily life and quality of monitoring by health professionals). These dimensions have been highlighted by patients as important components of medical care. The questionnaire has been designed for use in patients with any chronic illness and undergoing any type of prolonged pharmacological treatment. The questionnaire has been shown to be a reliable and valid measure of treatment satisfaction in a number of chronic diseases including type 2 diabetes (18), and has been shown to be sensitive to changes in patients’ satisfaction with treatment, although this has not been tested in diabetes (27). A search of the literature found no further trials of its use in diabetes.

 

Diabetes-specific questionnaires

Diabetes Treatment Satisfaction Questionnaire (DTSQ)

In its original ‘status’ format, the DTSQ was designed to prospectively measure satisfaction with diabetes treatment regimens among patients with type 1 or type 2 diabetes. The instrument is comprised of eight items, each rated on a 7-point Likert scale ranging from 0 to 6 (15). The questionnaire has been used in a number of clinical trials evaluating new diabetes treatments. However,  the DTSQ measures satisfaction at one point in time, e.g How satisfied are you with your current treatment?  The sensitivity to change of the DTSQ is therefore limited, and ceiling effects are often seen, where maximum or close-to-maximum scores at baseline provide little opportunity for registering improvement in satisfaction with the treatment or strategy being assessed. A ‘change’ format of the DTSQ was designed to overcome the ceiling effects of the ‘status’ version and to measure change in satisfaction (28). This instrument contains the same eight items as the DTSQ-status version, but asks patients to consider their satisfaction with their current treatment compared with their previous treatment. When used together in a clinical trial setting, the status version, used at baseline, permits assessment of absolute levels of satisfaction, while the change version measures relative change, reflecting increased or decreased satisfaction or no change in satisfaction.
Using the DTSQ status version, Biderman et al found that lower treatment satisfaction was related to difficulties in adherence to taking medications (7). The mean age in this study was 67 years. They also found that insulin-treated patients were least satisfied with treatment. This was also the case in the Petterson et al study, which specifically examined treatment satisfaction in older people (≥60 years) with diabetes (mean age 71 years) (29). Aside from the obvious fact that injecting insulin is less comfortable than taking a pill, this outcome may also reflect patients’ perceptions that insulin treatment means that their health status has deteriorated. Another possible explanation is that people with type 2 diabetes who need insulin, have longer disease duration, with more complications. Diabetes complications were also found to be associated with low satisfaction. Furthermore, less satisfaction was associated with having any complication at all, and there was a constant decline in treatment satisfaction with increased number of complications. In contrast to another study, which showed better treatment satisfaction in older patients than younger patients (30), neither the Biderman nor Petterson et al studies found an association between age and treatment satisfaction (7, 29).
Some studies have reported that treatment satisfaction decreases with higher HbA1c levels (30, 31). However, as only a minority of patients may be aware of the term ’HbA1c,’ this could be a possible reason for the lack of correlation between HbA1c levels and treatment satisfaction. In the Biderman and Petterson et al studies, there was no correlation between HbA1c and satisfaction, but lower satisfaction was found at HbA1c >7%(mmol/L) (7, 29).

Diabetes Medication Satisfaction Tool (DMSAT)

The 16-item DMSAT tool measures satisfaction with the patient’s diabetes medication regimens (Table 2) (21). Responses are summed and converted to a score from 0 to 100 for each subscale and overall, with higher scores representing more satisfaction.
The scale has been used to measure treatment satisfaction in a UK survey of patients with type 2 diabetes designed to evaluate associations between hypoglycaemic events and patient-reported outcomes (32). Medication satisfaction was lower among those who experienced ≥1 hypoglycaemic event in the 4 weeks prior to the survey (P<0.0001). People in old age were not recruited, the mean age of participants in the survey was 58.8 ± 10.9 years.

Diabetes Medication System Rating Questionnaire (DMSRQ)

The DMSRQ was developed to assess satisfaction with any diabetes medication, oral or injectable, used to control blood glucose (19). The DMSRQ contains nine scales, scored on a 0-to-100 scale (a higher score indicates greater levels of the construct measured) (Table 2). It is also available in a short form (33). In the validation study patients were aged 40-64 years (19). In contrast to the DTSQ, DMSRQ can distinguish between certain components of the diabetes treatment such as medication, diet, exercise and glucose monitoring. Other than the validation studies a search of the literature found no further trials of its use in diabetes.

Satisfaction with Oral Anti-Diabetic Agent Scale (SOADAS)

SOADAS was the first questionnaire to evaluate people with type 2 diabetes on oral anti-diabetes agents (17). SOADAS has cross-cultural face validity having been translated and validated in 20 languages to ensure that new language versions are sensitive to cultural expressions. Unlike the DTSQ, which was developed based on insulin-treated patients, the six-item SOADAS scale includes items on side effects as well as medication effects on body weight, which may be critical in differentiating treatment satisfaction among patients on different oral anti-diabetes agents (Table 2). The findings from the evaluation study indicate that SOADAS is a valid and reliable measure of patient satisfaction with oral antidiabetes medications, but a limitation of the SOADAS questionnaire is that validation was only carried out on a sample of US patients, with a BMI between 19 and 35. In addition, the questionnaire does not evaluate the impact on daily life, and side effects other than weight gain are reduced to one item (tolerability). A search of the literature did not find any studies that have used SOADAS.

Oral Hypoglycaemic Agent Questionnaire (OHA-Q)

The OHA-Q was developed by Japanese researchers because of a lack of current tools to clarify differences among the oral agents for type 2 diabetes (20). For example, the SOADAS questionnaire oversimplified tolerability aspects as well as lacking evaluation of the impact on daily life. The 20-item OHA-Q provides information useful for the selection of oral agents and unlike SOADAS is also available in Japanese. Subjects in the validation study had type 2 diabetes and had been treated with a single oral antidiabetes agent for the past 1 month or longer. They had to be a least 20 years old, but there was no upper age cut-off.

The Audit of Diabetes-Dependent Quality of Life (ADDQoL)

ADDQoL is a diabetes-specific measure that assesses the impact of diabetes on 18 life domains such as “working life,” “family life,” “freedom to eat as I wish,” and “self-confidence” and has proven to be sensitive to changes in treatment (22, 34).  Individuals with diabetes complications reported a significantly greater negative impact of diabetes on QoL than those without complications (P<0.001). It is of interest to note that the overall impact of diabetes on QoL in the validation study population was profoundly negative, but accompanying DTSQ findings showed a relatively high satisfaction with treatment. Thus, if treatment satisfaction had been used as an indicator of QoL in this study (22), the negative impact of diabetes on QoL would not have been acknowledged, and the high levels of treatment satisfaction may have been misinterpreted to suggest that patients had good QoL. Use of ADDQoL with people with type 1 or type 2 diabetes has shown, on average, a negative impact of diabetes on all domains (22).
In general, these findings indicate that ADDQoL is sensitive to the effects of diabetes (including both its treatment and complications) that cannot be captured by the measurement of treatment satisfaction alone. ADDQoL identifies more negative psychological outcomes than diabetes-specific treatment satisfaction scales such as the DTSQ, and thus it is likely to be even more sensitive to improvements following change to a new treatment that protects aspects of life that are important for QoL. In particular, the DIABQoL+ study has shown that restrictions on dietary freedom have a major negative impact on QoL, suggesting that treatments that increase dietary freedom without loss of metabolic control will improve QoL for many patients (35).

ADDQoL Senior

Quality-of-life questionnaires differ from treatment satisfaction questionnaires and ADDQoL Senior is only mentioned here because it is the only assessment tool that has been specifically developed for assessing quality of life in older people with type 2 diabetes, particularly care-home residents (36). In the validation, ‘independence’ was the aspect of life reported to be most important for quality of life and had the most negative weighted impact score, followed by ‘freedom to eat as I wish’. Thus, further research is required to examine the relationship between ‘independence’ and drug administration related aspects that are likely to be affected by reduced independence and therefore to reduce the level of satisfaction. ADDQoL Senior is being validated in the ongoing MID-Frail study in frail and pre-frail subjects aged ≥70 years with type 2 diabetes (37).

 

Discussion

A review of the literature reveals that a number of treatment satisfaction measures are available, but few have been validated in type 2 diabetes and none appears suited to capturing the satisfaction of older adults with type 2 diabetes. Only SOADAS and OHA-Q are specific to oral antidiabetes therapies. TSQM, and SATMED-Q are general questionnaires designed to assess satisfaction with medication in chronic conditions, and are not specific to type 2 diabetes. Mean age slightly differs between the questionnaires, whilst the patient population in OHA-Q is older compared with the other questionnaires.
The main focus in OHA-Q and TSQM is safety-related items such as adverse events and their implication on physical and mental activities. OHA-Q lists eight different items referring to adverse events such as hypoglycaemia, weight gain and gastrointestinal symptoms. OHA-Q was tested among patients on monotherapy only and therefore may enable comparisons between the different classes of oral therapies to be made. While the mean age in the OHA-Q validation was slightly higher compared with the other questionnaires, none of the questionnaires has been validated in patients >70 years. The choice of items is extremely important especially as there are specific items that are more relevant to older people such as drug administration related aspects as well as adverse events. Both OHA-Q and SOADAS looked at satisfaction with current therapy, weight gain related items and efficacy of the drug. As opposed to SOADAS, OHA-Q includes more items related to safety of the therapy while SOADAS focuses heavily on efficacy-related items. Older people with type 2 diabetes are in many cases frail and suffer from comorbidities. It is therefore important to provide a balance between efficacy- and safety-related items.
Due to the prolonged and progressive nature of chronic diseases such as diabetes, poor adherence can adversely affect the long-term effectiveness of a drug. An assessment of a patient’s treatment satisfaction is therefore useful to help identify those at risk of poor adherence, and enable physicians to target their interventions toward the aspects responsible for this. An important barrier to effective diabetes self-management is hypoglycaemia associated with diabetes medication (38). A number of studies have shown that hypoglycaemia is significantly associated with poorer health-related quality of life and patient outcomes, achievement of treatment goals, and healthcare utilization (25, 32, 39−41). Older people with diabetes are at greater risk for hypoglycaemia; normal aging may contribute to failure in counter regulatory responses (neurohumoral responses, subject awareness) to hypoglycaemia (42), symptoms may be mistaken for other conditions associated more commonly with advanced aged, and several treatments, including the sulphonylureas, other insulin secretagogues, and insulin, may either contribute to or directly cause it (43). In a population-based, retrospective, 4-year cohort study in 19,932 patients, frail older individuals (>80 years) using multiple medications and frequently hospitalised were at greater risk for hypoglycaemia (risk ratio = 1.8; 95% CI, 1.4-2.3; P =0.05) than healthier individuals of the same age (44).
In addition to providing useful insight into the patient’s perspective on their current treatment, treatment satisfaction is a valuable endpoint for clinical studies of treatments for chronic conditions where treatment compliance and adherence are considered issues (45). Thus, when new treatments have comparable efficacy, treatment satisfaction can be used to examine whether drug differences other than clinical efficacy have an impact on outcomes that may be important to patients. However, direct comparisons of satisfaction scores between studies are problematic due to the diversity of assessment instruments used. There is also currently no evidence of reliability or validity of existing instruments in older individuals with type 2 diabetes.
To date, treatment satisfaction has been used in only a limited way to support EMEA drug approvals, which may be due in part to a limited number of appropriate treatment satisfaction measures. Given the high proportion of older individuals with type 2 diabetes (6, 46), there is an urgent need for treatment satisfaction questionnaires to be developed and validated in older populations with type 2 diabetes so that clinical trials can use these measures to differentiate between alternative treatments.

 

Conclusion

Although older people with type 2 diabetes are an important and growing group, no validated treatment satisfaction measure is available to assess satisfaction with oral antidiabetes medication in this population. Future research should focus on developing new measures or adapting existing measures and validating them in a range of older populations with type 2 diabetes to inform treatment decisions on optimal therapy. In addition to medication effectiveness, side effects, and convenience of use, such a questionnaire should include an extended range of concerns, such as dosing schedules, time spent managing diabetes, and integrating medication regimens into ones lifestyle or routine, which may become important as the treatment regimen grows in complexity. Concerns related to older people in particular should also be included such as functional autonomy, independence, fall rates, hospitalization rates, and admission rates to care home. Of the currently available questionnaires, OHA-Q and SOADAS appear best suited to assessing treatment satisfaction in older people with type 2 diabetes, although adjustments may be required to ease reading and completion of the questionnaire.

 

Conflict of interest: The authors declare no conflict of interest. H. Langerman is an employee of Merck Sharp and Dohme, UK. The authors were supported by a medical writer who was funded by Merck Sharp and Dohme. The authors had complete editorial control over the manuscript, which represents the views of the authors.

 

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COMPREHENSIVE GERIATRIC CARE VERSUS STANDARD CARE FOR ELDERLY REFERRED TO A REHABILITATION UNIT – A RANDOMIZED CONTROLLED TRIAL

 

 

D. Zintchouk1, T. Lauritzen2, E.M. Damsgaard1

 

1. Aarhus University Hospital, Department of Geriatrics, Aarhus C, Denmark; 2. Department of Public Health, Section of General Medical Practice, Aarhus University, Aarhus C, Denmark.

Corresponding Author: Dmitri Zintchouk, MD, Aarhus University Hospital, Department of Geriatrics, P.P. Oerumsgade 11, 8000 Aarhus C, Denmark, dmizin@rm.dk, tel. 004526700903, fax 004578461930.

J Aging Res Clin Practice 2017;inpress
Published online December 15, 2016, http://dx.doi.org/10.14283/jarcp.2016.126

 

Abstract

Objective: To investigate the effect of comprehensive geriatric care (CGC) in elderly referred to a rehabilitation unit. This article describes the considerations behind the study. Design: Participants were randomized to either CGC or standard care. Setting: Participants were recruited from two community care rehabilitation units in Aarhus Municipality, Denmark, in the period between 2012 and 2015. Participants: Inclusion: Elderly patients aged 65 and older admitted from home or hospital. Exclusion: Persons receiving palliative care or assessed by a geriatrician during the past month. Intervention: Medical history, physical examination, blood tests, medication adjustment and follow-up by a geriatrician. The control group received standard care with the general practitioners (GPs) as back-up. Outcomes: Primary outcome: Hospital contacts drawn from national registers. Secondary outcomes: GPs contacts, institutionalization, medication status and mortality collected from national registers, activities of daily living (ADL), physical and cognitive function and quality of life measures collected by a blinded occupational therapist. All outcomes were assessed at day 10, 30 and 90 after arrival at the rehabilitation unit. Conclusion: A new model of care for elderly referred to community rehabilitation was developed and implemented. The potential benefits of this model were compared with usual care in a community rehabilitation unit in a pragmatic randomized clinical trial. We hypothesized that the geriatrician-performed CGC in elderly referred to a rehabilitation unit will reduce the hospital contacts by 25 % without increase in mortality and in contacts to GPs and home care services. We expect that this model will prevent deterioration in ADL, physical and cognitive functioning, and reduce the risk of institutionalization. If the results are positive, community rehabilitation services should be encouraged to change their routines for treatment of this population accordingly.

Key words: Randomized controlled trial, comprehensive geriatric care, hospitalization, rehabilitation, activity of daily living.

 

 

Introduction

Older people are the fastest growing sector of the population and they account for the largest increase in hospital admissions (1). More survivors with chronic diseases mean increasing numbers of overlapping comorbidities and increased risk of acute illness (2,3). Admissions to hospital for older people are combined with risk of rapid decline in functional ability, cognitive impairment, and change to residential care (4, 5). Despite a multitude of efforts to reduce hospital attendances and admissions worldwide, the numbers are increasing year after year (6).
To give patients the best life possible and to save health care resources, we intend to evaluate the effect of Comprehensive Geriatric Care performed by a geriatrician in a community operated rehabilitation unit.

Comprehensive geriatric assessment (CGA) and comprehensive geriatric care (CGC)

CGA is defined as a “multidimensional interdisciplinary diagnostic process focusing on a frail older person’s medical, psychological and functional capability”(7). In practice the assessment is followed by an intervention and sometimes by a follow-up based on the assessment. The recently suggested concept of comprehensive geriatric care (CGC) covers the combined assessment and follow-up interventional process more precisely (8).
Several models of CGA and CGC have been proposed. The last meta-analysis from Ellis et al. (9) showed that only inpatient CGA in acute geriatric units is effective and results in an increased likelihood of a patient returning home and avoiding admission to residential care or deterioration and death. Randomized studies of post-hospital discharge CGA found inconsistent benefits in functional status, acute care visits, depression, and patient satisfaction (10, 11). However, post-discharge intervention was associated with reduction in costs and readmission rates (12, 13), and CGC may be beneficial for hip fracture patients by reducing complications, mortality, readmissions, and delirium (8, 14-17).
A few randomized studies on different care models were published in the last five years. Senior and colleagues (18) showed that the model of restorative care services delivered within both residential care and at home by a multi-disciplinary team, included a case manager, nurse, occupational therapist and physiotherapist, tend to reduce the risk of death or permanent residential care. The absolute risk reduction for death or permanent residential care of 14.3% was not significant compared to usual care group at 24 months follow-up. Moreover, the intervention group had more frequent utilization of personal care, home help, career support, respite, day center and day activity centers than the usual care group. The same research group (19) showed that locally based care model managed by experienced nurses working with strong partnerships with family physicians reduces the risk of death and permanent residential care placement in frail older adults by 10.2% compared to usual community care coordinated by a centrally based needs assessor.
A recent Danish study shows that home-visits by a geriatrician and a specialized nurse on the first days after discharge from hospital reduce the readmission rate for acute medical patients by almost 50%, compared to patients accompanied home or subsequently receiving a telephone call. Rehospitalization was reduced, but 30-day mortality did not differ significantly between groups (20).

Geriatrician-performed comprehensive geriatric care in community rehabilitation settings

Physicians alone can perform many aspects of CGA followed by intervention. Often this is not practicable given the limited time available and the workload of instituting a complex care plan (21). We have deliberately chosen to focus on the role of the geriatrician in community rehabilitation. The staff of community rehabilitation units has some expertise in care of elderly with deteriorating function. Involvement of a larger team from the geriatric department may confuse the patients and cause unnecessary expenditure.
To our knowledge, no randomized studies have evaluated the effect of geriatrician-performed CGC comprising CGA and intervention with follow-up in elderly referred to a community rehabilitation unit.

 

Objective

The objective of this study is to investigate the effect of the geriatrician-performed CGC compared to a control group with standard care in elderly referred to a community rehabilitation unit.

 

Methods

The study is a pragmatic open assessor-blinded randomized clinical trial with 90 days’ follow-up.

Participants and settings

The inclusion criteria were: 1) age 65 years or older; 2) referral to a community rehabilitation unit from home or a hospital department. The exclusion criteria were: 1) palliative care; 2) assessment by a geriatrician during the past one month. The participants were all residents of two community rehabilitation units, Vikaergaarden (64 rooms) and Thorsgaarden (24 rooms) in Aarhus Municipality, Denmark. For study flow, see Figure.

Figure 1 Study flow in the Comprehensive Geriatric Care versus Standard Care for Elderly referred to a Rehabilitation Unit – a Randomized Controlled Trial

Figure 1
Study flow in the Comprehensive Geriatric Care versus Standard Care for Elderly referred to a Rehabilitation Unit –
a Randomized Controlled Trial

Recruitment

Participants were consecutively recruited from unit Vikaergaarden in the period January 17, 2012 to May 29, 2015, and from unit Thorsgaarden from October 20, 2014 to May 29, 2015. Eligible elderly and/or their relatives were contacted by the project manager or research nurse, who provided the oral and written information. Participants with cognitive impairment were also included. All had twenty-four hours to consider or discuss with relatives before the written informed consent was obtained.
During the study enrolment the following adjustments were made to accelerate the inclusion of the participants: inclusion age was lowered from 70+ to 65+ from May 14, 2012, previous contact with a geriatrician within three months was reduced to one month from December 2, 2012. All the changes have been submitted to Clinical.Trials.gov (NCT01506219).

Randomization

The random allocation of the participants to the intervention and control groups was done by an independent external organization (“TrialPartner”, Public Health and Quality Improvement, Central Denmark Region). The permuted block sizes stratified the randomization according to sex, age and place of referral. The randomization took place within three days after the participants’ arrival to the rehabilitation unit. In the intervention group the geriatrician informed participants and relatives about the allocation and gave the personal contact information card to participants or relatives.

Blinding

Owing to the nature of this study, it was impossible to blind participants and their relatives to the allocation group. The project manager screened the patients for eligibility, collected data on age, gender, place of referral and comorbidity before randomization, and conducted the intervention. The project manager had no contact with the control participants after randomization. The project manager was blinded to the study outcomes, which were collected from the registers or by the blinded research occupational therapist. Rehabilitation units’ staffs, particularly physiotherapists, were not blinded.

Standard care in the rehabilitation unit

The patients were referred for rehabilitation either from hospital or home by the hospital personnel or by the home care staff. Rehabilitation services are not free of charge, and a moderate fee for the stay is paid by the patients themselves. The typical standard rehabilitation and care program lasts five weeks. The interdisciplinary approach is based on the patient’s whole situation, capability and wishes/needs. On the first day of rehabilitation, the patient’s functional status is observed by the rehabilitation unit’s physiotherapists and occupational therapists, and a nutritional screening is performed by the rehabilitation unit’s nutritionist. The team members discuss the patient’s discharge destination and necessary arrangements with the patient and his/her relatives at the mid-term meeting and before discharge from the rehabilitation unit. Municipality nurse participates in these meeting personally or by telephone. Destination after discharge is based upon the patient’s motivation, functional and medical status.
The patient’s GPs visit the patients during the stay if required or occasionally by own initiative depending on practice routine and geographical distance. GPs mostly visit frail and high-risk elderly patients especially if recently hospitalized. Acute medical aid is called for in case of illness after 4.p.m. and on weekends and public holidays.

Care in the intervention group

Participants randomized to the intervention group underwent the geriatrician-performed CGC during the rehabilitation stay. The intervention was performed by a physician specialized in geriatric medicine. The primary assessments lasted about an hour and included review of diagnoses, organ functional status, medication, and life expectancy evaluation. Individual disease management and coping was provided using the holistic approach during the face-to-face counselling, where the actual problems, expectations and aims were defined in dialogue with the patient and/or relatives. Afterwards, targeted problem solving with focus on the potentially reversible causes of functional deterioration was established. Finally, medication adjustment was carried out with particular attention to drugs which may lead to iatrogenic functional deterioration, delirium, falls, and malnutrition. A simple tool like the STOPP (Screening Tool of Older Person’s Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment) criteria have been used as an evidence-based approach to reduce inappropriate prescribing and to encourage appropriate prescribing in the older adult (22, 23). When no evidence base existed for drug use, the approach was based on clinical judgment only, and the balance of risks and benefits of the drug for the individual was presented to the participants and/or relatives. In collaboration with rehabilitation unit’s staff the geriatrician followed the participants with regard to any change in symptoms, signs, or relevant laboratory and diagnostic test results that might indicate a restart of a specific medication, which had been discontinued.
The geriatrician was present at the rehabilitation unit for about four days a week, and could be contacted on telephone for any reason by participants, their relatives or the unit’s staff on weekdays from 8 a.m. to 3 p.m. In acute situations the geriatrician could also be contacted. The follow-up period by the geriatrician at the rehabilitation units was individualized (generally four weeks). The geriatrician sent the discharge summary for each intervention group participant to the GP. The geriatrician also provided education and support to the staff of the rehabilitation units and informed and advised the GPs and primary care services if needed. After discharge from the rehabilitation units GP are responsible for treatment.
See Table 1 for patient treatment in the intervention versus control group.

Table 1 Patient treatment in the Comprehensive Geriatric Care versus Standard Care for Elderly referred to a Rehabilitation Unit - a Randomized Controlled Trial

Table 1
Patient treatment in the Comprehensive Geriatric Care versus Standard Care for Elderly referred to a Rehabilitation Unit – a Randomized Controlled Trial

* Hemoglobin, Leucocytes, C-reactive protein, P-albumin, P-Potassium, P-Sodium, glomerular filtration rate.

 

Outcomes

Baseline data

Baseline characteristics were registered by the project manager from medical records and/or interview, comprising age, gender, place of referral (own home or hospital), marital status, residential status, diagnoses, comorbidity, and list of medications. The functional tests and quality of life at baseline (day 3) were done by the research occupational therapist after randomization.

Primary outcome

Primary outcome was total number of hospital contacts within 90 days after admission to the rehabilitation units.

Secondary outcomes

Secondary outcomes included all hospital and GPs contacts and number of participants with the hospital and GPs contacts, number of days spent in hospital, use of homecare services, transfer to nursing homes or sheltered housing, changes in medication status and number of deaths within 90 days. Moreover participant’s ADL, cognitive and physical functioning, and quality of life were assessed at day 3, 10, 30 and 90 after admission to the rehabilitation units. Trial outcome follow-up was completed August, 27. 2015.

Measurements

1) Mini-mental state (MMSE) (24). MMSE is a 10-minute bedside measure of impaired thinking. The items of the MMSE include tests of orientation, registration, recall, calculation and attention, naming, repetition, comprehension, reading, writing and drawing (25).
2) The Confusion Assessment Method (CAM) (26).
CAM is a standardized evidence-based tool that enables non-psychiatrically trained clinicians to identify and recognize delirium quickly and accurately in both clinical and research settings. The CAM includes four features found to be most effective in distinguishing delirium from other types of cognitive impairment.
3) Modified Barthel-100 Index (MBI) (27).
MBI is a 10-item instrument that provides a score of basic daily activities (feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfer, mobility, and stair climbing). The scores range from 0-100, with a higher score indicating greater independence.
4) The 30-second chair stand test (28).
The 30-second chair stand test measures body strength, by determining the number of times the participant can stand up fully and sit down in 30 seconds, with the arms crossed over the chest. We have used the modified version of this test, where use of armrest is allowed.
5) Depression List (DL) (29).
DL is a fifteen-item questionnaire, designed to assess quality of life in frail nursing home residents. DL addresses emotional well-being, social relationships, life satisfaction, comfort, functional competence, and autonomy. The scale ranges from 0 (best quality of life) to score 30 (poorest quality of life).
6) Charlson Comorbidity Index (CCI) (30) is used to categorize comorbidity in three levels:
0 = low, 1-2 = moderate, and 3 or more = high.
All the functional measurements, except for the modified version of “The 30-second chair stand test”, are validated for use in an elderly population. All questionnaires were performed as structured interviews. Trial outcome follow-up was completed August, 27. 2015.

Data collection

Data on hospital contacts and GPs contacts and mortality were collected from The National Patient Registry, The National Health Insurance Service Register and Danish Civil Registration System via Researcher Service, Statens Serum Institut, Danish Ministry of Health. Data on causes on hospital contacts were collected by the primary investigator from the Electronic Patient Record. Data on district nurses availability, extent of personal social services, walking aids and residential status were recorded through the Aarhus Community Care Record.
The actual medication usage and the number of Defined Daily Doses (DDD) within the different The Anatomical Therapeutic Chemical (ATC) Classification System were clarified and recorded under the personal medication review and through the Electronic Patient Record and the Aarhus Community Care Record by the primary investigator and the research nurse.
The functional tests and evaluation of the health-related quality of life during the follow-up period were performed by the research occupational therapist.
For data collection details, see Table 2.

 

Table 2 Outcomes in the Comprehensive Geriatric Care versus Standard Care for Elderly referred to a Rehabilitation Unit – a Randomized Controlled Trial

Table 2
Outcomes in the Comprehensive Geriatric Care versus Standard Care for Elderly referred to a Rehabilitation Unit –
a Randomized Controlled Trial

 

Ethics

Written informed consent was obtained from the participants by the project manager or research nurse within two days of arrival at the rehabilitation unit. Under the consent procedure the project manager assessed the elderly’s cognitive capacities. Cognitive impairment was defined by: (1) MMSE score of < 25; (2) CAM indicating delirium; or (3) a clinical cognitive evaluation undertaken by the project manager. Patients who were not cognitively impaired gave their written informed consent. Consent of cognitively impaired patients was given by a relative.
The project manager informed the participant’s GPs by letter about the study participation without information about the allocation. In the intervention group the GPs were shortly informed by the geriatrician about the treatment plan per mail in the Electronic Patient Record.
The CGC contained all known and commonly used and approved testing methods. All data are treated in confidence and participants are assured anonymity. The study is approved by the Danish Data Protection Agency, journal no. 2012-58-006, and the Ethical Committee of Central Denmark Region, journal no. M-20110262.
An interim-analysis was performed on the mortality when 50 % of participants have been randomized and have completed the 90 days’ follow-up. The interim-analysis was performed by an independent statistician, blinded for the treatment allocation. Results were evaluated by an independent researcher in order to stop the study prematurely if significant mortality differences were found.

 

Sample size and data analysis

Power calculation

For power calculation we used data on hospital contacts from The National Patient Registry in persons receiving rehabilitation at the rehabilitation unit Vikaergaarden from 1 April 2009 to 31 March 2010. There were 153 hospital contacts among 550 65+ year old persons within three months after the admission at rehabilitation. An analysis of hospital contacts over 30 days in 68 participants in a pilot project showed 33% fewer hospital contacts in the intervention group (number of persons with hospital contacts=7, total number of contacts=12) compared to the control group (number of persons with hospital contacts=7, total number of contacts=19).
For the sample size calculation we expected a 25% reduction of the hospital contacts, which we regarded as a clinically relevant change. Estimated dropout was set to 20% in both groups, as mortality was expected to be high. To obtain 80% statistical power and a significance level at 0.05 we had to recruit 370 patients.

Data analysis

All data are being entered in a database (Access 2010) by the research nurse. The statistical analyses will be conducted based on a predefined statistical protocol using STATA (version 13, STATA Corporation, Texas). Both descriptive and analytic analysis will be performed. Descriptive data will be calculated in percent, while median, average and minimum and maximum will be used for continuous variables. Continuous variables will be analyzed for normal distribution with the Kolmogorov-Smirnov test. The principle of repeated measurements will be used to analyze continuous variables. Variables with dichotomous outcomes will be analyzed using the logistic regression. Non-normally distributed data will be analyzed with the Mann-Whitney U test/Wilcoxon matched-pair’s test. Mortality will be analyzed with Kaplan-Meier analysis. Survival analysis will be performed with Cox Regression model adjusting for the sex, age, comorbidity and place of referral. In order to ensure the statistical robustness of the intervention outcomes, two different longitudinal imputation methods (last value carried forward and worst value imputation) will be used in case of missing values on sensitive analysis. There will be a bilateral significance level of 5% for evaluation of statistical significance in the primary and secondary endpoints. Intention-to-treat analysis will be performed.

 

Discussion

To our knowledge this is the first randomized controlled study to evaluate the effect of the CGC performed by a geriatrician in elderly citizens referred to community rehabilitation. In a systematic review the authors found that no particular model of geriatric care in community rehabilitation facilities could be recommended (31). In spite of multiple recent advances in providing rehabilitation in community settings, organization of these services, particularly the role of the geriatrician, remains poorly addressed.

Strengths and limitations of the study

Design

The RCT design was chosen to investigate the broad population of elderly with functional loss and multimorbidity, often excluded from RCTs (32-34). This must be considered as a strength. However, it has a price because the heterogeneity of the study population requires a much greater number of participants to demonstrate a possible significant difference.

Study population

The strength of the study population was the broad inclusion criteria, which insured enrolment of participants with a wide range of medical conditions.
We also decided to include elderly with dementia or confusion on arrival at the rehabilitation unit. We expected these persons to benefit most from the geriatrician-performed CGC.
On the other hand the recruitment was expected to be challenged due to difficulties in obtaining written informed consent. In order to detect possible selection bias among participants information about age, gender, place of referral and comorbidity (CCI) was obtained for participants as well as non-participants.

Intervention

The intervention was individualized and holistic based on a dialogue with the patient and/or relatives setting realistic common aims and expectation for treatment. This pragmatic clinical approach attempts to maximize external validity (35). The individual needs of the elderly are complicated by medical, functional, psychological, and social problems (36).This may lead to an atypical clinical presentation requiring flexibility and variation of the treatment.
Yet, the intervention was as systematic as possible in order to be reproducible. However, the medication adjustments by the geriatrician were not standardized. We were not able to use the STOPP-START tool strictly due to a systematic lack of the patient dimension. Medicine adjustments in elderly may conflict with established guidelines not addressing the care of people with multiple conditions (37). Such discrepancies may confuse the participant, the home career or the GP and result in readministration of discontinued drugs.
A specialist physician in geriatric medicine performed the intervention. This has strengths: the rehabilitation units’ staff could easily contact the geriatrician, who was physically available at an office in the rehabilitation units. In the majority of cases the primary investigator/project manager was also the geriatrician who conducted the intervention. It makes continuity possible and optimizes communication with the patients, their relatives and the staff of the rehabilitation units. It may promote the compliance and be more cost effective. On the other hand when the intervention depends on one physician the results are less generalizable and should be confirmed by further studies.
A stronger cooperation was established between the geriatric department and the rehabilitation units, likewise educational courses on common geriatric problems were carried out for the staff during the study period. Both the intervention and the control group were treated by the same personnel, which may have a positive spillover effect reducing a possible difference between the groups.

Blinding

A strength of our study was the systematical efforts tried to minimize information bias. The geriatrician was blinded to the primary endpoint data that were drawn from The National Patient Registry via Researcher Service. The dataset was generated by the Registry’s staff blinded to the patient allocation.
It was a weakness that it was impossible to blind the participants and their relatives or the geriatrician and the rehabilitation units’ staff to the allocation group. The research nurse was not blinded to patient allocation for practical reasons. The research occupational therapist was blinded to treatment allocation, but it could not be ruled out that the participants may have mentioned their allocation during the assessment. Thus, the performance-based measure of physical and cognitive functioning could be biased.

Outcome measures

A strength of this study was the use of functional measurements and questionnaires well validated for elderly. The modified version of the “30-second chair stand test”, in which the use of armrest is allowed, was the only test not validated. However, it is suited for our study population, as the majority of the participants were not able to perform the original version of the test.

 

Conclusion

A new model of care for elderly referred to community rehabilitation was developed and implemented. The potential benefits of this model were compared with usual care in a community rehabilitation unit in a pragmatic randomized clinical trial. This pragmatic approach closely mimics the true clinical situation. We hypothesize that the geriatrician-performed CGC in elderly referred to a rehabilitation unit will reduce the hospital contacts by 25 %. This should be done without increasing mortality, GP contacts or home care services. We expect this model to prevent deterioration in ADL, physical and cognitive functioning, and to reduce the risk of institutionalization. Data collection was recently completed. The results may soon be published.

 

Acknowledgements: This trial is funded by Geriatric Department Aarhus University Hospital and received donations from the Health Insurance Fund (Helsefonden) and Public Health in the Central Region Fund (Folkesundhed i Midten).
Authors’ contributions: DZ in collaboration with EMD and TL designed the study. DZ carried out the interventions. DZ drafted the manuscript. All authors revised the manuscript critically and have given their final approval of this version to be published.

Conflict of Interest: There is no conflict of interest to declare. DZ is a specialist in geriatrics and a member of network of Danish physicians and medical students “Physicians without sponsor”.

 

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