Abstract
Objective: To investigate the association of polypharmacy and physical performance measures in a sample of elderly patients aged ≥65 years admitted to acute care hospitals. Design, setting and participants: Prospective study conducted among 1123 hospitalized older adults participating to the CRiteria to Assess Appropriate Medication Use among Elderly Complex Patients (CRIME) project. Measurements: Physical performance was measured at hospital admission by the 4-meter walking speed (WS) and the grip strength (GS). Polypharmacy was defined as the use of ≥10 drugs during hospital stay. Results: Mean age of 1123 participants was 81.5±7.4 years and 576 (51.3%) were on polypharmacy. Prevalence of polypharmacy was higher in patients with low WS and GS. After adjusting for potential confounders, participants in the highest tertile of WS were less likely to be on polypharmacy as compared with those in the lowest tertile (OR 0.58; 95% CI 0.35–0.96). Similarly, participants in the highest tertile of GS had a significantly lower likelihood of polypharmacy as compared with those in the lowest tertile (OR 0.55; 95% CI 0.36–0.84). When examined as continuous variables, WS and GS were inversely associated with polypharmacy (WS: OR 0.77 per 1 SD increment; 95% CI 0.60–0.98; GS: OR 0.71 per 1 SD increment; 95% CI 0.56–0.90). Conclusion: Among hospitalized older adults WS and GS are inversely related to polypharmacy. These measures should be incorporated in standard assessment of in-hospital patients.
Key words: Polypharmacy, elderly, physical parameters, walking speed, grip strength
Introduction
Hospitalization may represent a relevant event for frail elderly patients because it is associated with an increased rate of morbidity, mortality and hospital readmission (1, 2, 3). Hospitalized older adults are a very heterogeneous and complex population, characterized by the co-occurrence of multiple chronic and acute diseases which may contribute to the development of geriatric syndromes and health adverse events, thus accelerating the rate of functional and cognitive impairment (4, 5, 6). Polypharmacy contributes to this complexity since it has been associated with increased risk of mortality, adverse drug reactions (ADRs), iatrogenic illness, and longer length of stay 7, 8.
Given this level of complexity, the traditional clinical assessment might not provide sufficient information on risk of negative outcomes and a more global evaluation examining domains commonly impaired in advanced age, including functional status, might be necessary to improve quality of care and lead to a better financial resources allocation (9). Physical performance measures were proven to be simple and reliable tools to assess performance abilities along the full spectrum of functioning and they were associated with a number of health outcomes. In particular, among community dwelling older adults, the walking speed and the grip strength tests were shown to correlate with mortality, hospitalization, institutionalization and impaired cognition and they may represent valid and reliable outcome measures for intervention studies (10, 11, 12, 13, 14). Among hospitalized older adults these measures were proven to represent a valid indicator of functional and clinical status and an independent predictor of the length of hospital stay and clinical outcomes after discharge (15, 16, 17). However, the association between physical performance measures and polypharmacy has never been assessed in the hospital setting.
Based on this background, the aim of the present study was to investigate the association of physical performance measures with polypharmacy in a sample of elderly patients aged 65 years or older admitted to acute care hospitals.
Methods
We used data from the CRiteria to Assess Appropriate Medication Use among Elderly Complex Patients (CRIME) project, a study performed in geriatric and internal medicine acute care wards in Italy. Methodology of the CRIME project was described in detail elsewhere (18). Briefly, all patients consecutively admitted to the geriatric and internal medicine acute care wards of participating hospitals between June 2010 and May 2011 were enrolled in the study. The only exclusion criteria were: age < 65 years old and unwillingness to participate to the study. For each participant, a questionnaire, designed following the procedure used for the study of the Gruppo Italiano di Farmacoepidemiologia nell'Anziano (GIFA), was completed at admission and updated daily by study researchers (19).
Drug assessment
Study researchers recorded, on the specific section of the questionnaire, all the drugs taken by the participants before and during the hospitalization and those prescribed at discharge. Particularly they recorded brand name, formulation, daily dose and compliance. Drugs were coded according to the Anatomical Therapeutic and Chemical codes (ATC) (20). Polypharmacy was defined as the use of ≥ 10 drugs during hospital stay. Given the lack of consensus about the optimal cutoff number of drugs for the definition of polypharmacy, the threshold of 10 drugs was chosen based on the median number of drugs used during hospital stay in the CRIME sample. This cutoff was already used in former studies assessing polypharmacy in different settings 21, 22.
Walking Speed
Walking speed was assessed at hospital admission with the participant walking from a standing position at his/her usual pace over a four-meter course. This measure has been shown to be predictive of incident disability, mortality, nursing home and hospital admission and it has shown high test-retest reliability (23). Walking speed was categorized in tertiles based on the following cut-points: low tertile (poor performers) < 0.4866 m/sec; intermediate tertile (intermediate performers) 0.4866-0.718 m/sec; high tertile (good performers) ≥ 0.719 m/sec. Participants unable to perform the test (n=603; 53.7%) were analyzed as a separate group.
Grip strength
Grip strength was assessed by the use of a North Coast Medical hand dynamometer. Patients were seated with the wrist in a neutral position and the elbow flexed 90°. For patients unable to sit grip strength was assessed lying at 30° in bed with elbows supported, as previously described (24). Reliability of grip strength assessed with this methodology in a sample of 20 in-hospital patients was excellent when compared with the one obtained in the seated position with kappa values ranging from 0.92 for the non dominant hand to 0.94 for the dominant hand. Grip strength was measured two times for each hand. The highest value obtained with the dominant hand was used for the present study. Grip strength was categorized in gender specific tertiles based on the following cut-points: low tertile (poor performers) women < 12 kg, men < 20 kg; intermediate tertile (intermediate performers) women 12-17 kg, men 20-27 kg; high tertile (good performers) women ≥ 18 kg, men ≥ 28 kg. Participants unable to perform the test (n=306; 27. 2%) were analyzed as a separate group. Data on grip strength were missing for 37 patients
Covariates
Cognitive Status was examined using Mini Mental State Examination (MMSE) (25). Mood was investigated by the use of the Geriatric Depression Scale (GDS) (26). Dependency in the following Activities of the Daily Living was assessed: transferring, locomotion, dressing, eating, bowel and bladder continence and personal hygiene (27). Diagnoses were assessed gathering information from the patient, the attending physicians and by careful review of charts. Length of hospital stay was defined as the number of days from admission to discharge (or death). Length of stay was categorized according to its median value (10 days).
Analytical approach
To compare characteristics of participants based on polypharmacy we used ANOVA analyses for normally distributed variables, nonparametric Mann–Whitney U test for skewed variables, and chi-square analyses for dichotomous variables. Logistic regression models were used to estimate the association of polypharmacy with walking speed and grip strength. Logistic regression models were adjusted for age, gender, site and variables associated with polypharmacy at p≤0.10 at the univariate analysis. Final logistic regression models were adjusted for age, gender, pain, falls, number of diseases, ischemic heart disease, heart failure, diabetes, length of hospital stay and site.
As the chosen cutoff of 10 drugs to define polypharmacy is not unanimously accepted the association between polypharmacy and physical performance measures was also tested defining polypharmacy as the use of ≥8 drugs. This cutoff was chosen based on a former publication assessing the risk of Adverse Drug Reactions in hospitalized older adults (7). A value of p below 0.05 was considered statistically significant. All analyses were performed using SPSS for Windows version 18.0.
Results
Sample characteristics
A total number of 1123 hospitalized older adults were enrolled in the study, mean (Standard Deviation) age was 81.5 (7.4) years, women were 629 (56.0%) and 572 participants (50.9%) were admitted from Emergency Room (ER). Mean number of drugs used during stay was 10.6 (SD 5.6, median 10) and participants on polypharmacy (≥ 10 drugs during stay) were 576 (51.3%). As shown in table 1, participant on polypharmacy, as compared with those not on polypharmacy, were less likely to be women, had a higher prevalence of pain and falls, presented with a higher number of diseases, including ischemic heart disease, heart failure and diabetes and had a longer length of hospital stay.
Table 1.
Sample characteristics according to polypharmacy status
| All n= 1123 (%) | No polypharmacy (< 10 drugs) n=547 (%) | Polypharmacy (≥ 10 drugs) n= 576 (%) | P | |
|---|---|---|---|---|
| Demographics | ||||
| Age, years (mean±SD) | 81.5 + 7.4 | 81.7 + 7.7 | 81.3 + 7.1 | 0.449 |
| Female gender | 629 (56.0%) | 322 (58.9%) | 307 (53.3%) | 0.060 |
| Functional status and geriatric conditions | ||||
| Number of impaired ADL | 2.5 + 2.5 | 2.4 + 2.5 | 2.5 + 2.4 | 0.629 |
| MMSE score (mean±SD) | 17.2 + 10.8 | 17.5 + 10.7 | 16.9 + 10.7 | 0.390 |
| GDS score (mean±SD) | 5.0 + 3.5 | 4.9 + 3.6 | 5.1 + 3.4 | 0.465 |
| pain | 589 (52.5%) | 272 (49.8%) | 317 (55.1%) | 0.075 |
| Falls | 278 (24.8%) | 120 (21.9%) | 158 (27.4%) | 0.033 |
| poor economical status | 872 (77.6%) | 418 (76.4%) | 454 (78.8%) | 0.334 |
| Comorbidity | ||||
| Number of diseases (mean±SD) | 5.7 + 3.1 | 5.1 + 3.0 | 6.1 + 3.1 | < 0.01 |
| Ischemic heart disease | 356 (31.7%) | 146 (26.7%) | 210 (36.5%) | < 0.01 |
| Heart failure | 307 (27.3%) | 104 (19.2%) | 203 (35.2%) | < 0.01 |
| Parkinson disease | 68 (6.1%) | 31 (5.7%) | 37 (6.4%) | 0.595 |
| Stroke | 151 (13.4%) | 73 (13.3%) | 78 (13.5%) | 0.923 |
| Diabetes | 333 (29.7%) | 125 (22.9%) | 208 (36.1%) | < 0.01 |
| Cancer | 155 (13.8%) | 80 (14.6%) | 75 (13.0%) | 0.436 |
| Dementia | 230 (20.5%) | 109 (19.9%) | 121 (21.0%) | 0.654 |
| Length of stay > 10 days |
577 (51.4%) |
199 (36.4%) |
378 (65.6%) |
< 0.01 |
ADL – Activities of Daily Living; MMSE – Mini Mental State Examination; GDS – Geriatric Depression
Patterns of medication use
Table 2 presents classes of drugs most commonly used in the study sample during the hospital stay, classified by ATC code. The most commonly used drugs were those used for acid related disorders (ATC A02) and antithrombotic agents (ATC B01), followed by agents acting on the renin-angiotensin system (C09), diuretics (C03) and antibacterials for systemic use (J01). Very common was also the use of psycholeptics (N05) and psychoanaleptics (N06).
Table 2.
Classes of drugs more commonly used during hospital stay
| Drugs | ATC codes | Patients on drugs during hospital stay, N(%) |
|---|---|---|
| Drugs for acid related disorders | A02 | 875 (77.9%) |
| Antithrombotic agents | B01 | 862 (76.8%) |
| Agents acting on the renin-angiotensin system | C09 | 651 (58.0%) |
| Diuretics | C03 | 641 (57.1%) |
| Antibacterials for sistemic use | J01 | 513 (45.7%) |
| Psycholeptics | N05 | 385 (34.3%) |
| Beta blocking agents | C07 | 343 (30.6%) |
| Cardiac therapy | C01 | 340 (30.3%) |
| Lipid modifying agents | C10 | 303 (27.0%) |
| Drugs used in diabetes | A10 | 291 (25.9%) |
| Analgesics | N02 | 280 (24.9%) |
| Calcium channel blockers | C08 | 256 (22.8%) |
| Laxatives | A06 | 248 (22.1%) |
| Corticosteroids for | H02 | 251 (22.4%) |
| systemic use | ||
| Psychoanaleptics | N06 | 251 (22.4%) |
| Antiinflammatory and anti | M01 | 52 (4.6%) |
| rheumatic products | ||
| Drugs for treatment of bone diseases |
M05 |
48 (4.3%) |
Physical performance measures and polypharmacy
Overall, 520 participants (46.3% of study sample) were able to perform the walking speed test and 780 participants (69.5%) were able to perform the grip strength test at hospital admission. Patients unable to perform either the walking speed or the grip strength test (n=617) were older (84.0±7.1 vs. 78.5±6.6 years, p<0.001), had a higher number of coexisting conditions (6.1±3.1 vs. 5.1±3.0 diseases, p<0.001), a higher prevalence of dementia (30.6% vs. 8.1%) and lower MMSE score (12.5±11.1 vs. 22.8±7.2 years, p<0.001).
Mean walking speed was 0.64 m/sec, median was 0.57 m/sec (minimum 0.13 m/sec; maximum 1.47 m/sec). Table 3 shows the association between walking speed and polypharmacy. Prevalence of polypharmacy progressively declined as the performance at the walking speed test improved, with participants unable to perform the walking speed test having the highest prevalence of polypharmacy (54.1%) and those in the high tertile the lowest (41.8%). After adjusting for potential confounders, participants in the high tertile had a significantly lower likelihood of polypharmacy as compared with those in the low tertile (OR 0.58; 95% Confidence Interval 0.35 – 0.96). When walking speed was examined as a continuous measure among 520 participants able to perform the test, an inverse association was observed with polypharmacy (OR for 1 SD increment 0.77; 95% CI 0.60 – 0.98).
Table 3.
Association of polypharmacy with walking speed and grip strength measured at hospital admission
| Rate of polypharmacy | Fully adjusted* | |
|---|---|---|
| n (%) | Odds Ratio (95% Confidence Interval) | |
| Walking speed | ||
| Tertiles | ||
| Unable | 326/603 (54.1%) | 1.21 (0.79 – 1.83) |
| Low Tertile (Poor Performers) | 88/171 (51.5%) | 1 |
| Intermediate Tertile (Intermediate Performers) | 88/172 (51.2%) | 0.71 (0.43 – 1.17) |
| High Tertile (Good Performers) | 74/177 (41.8%) | 0.58 (0.35 – 0.96) |
| Continuous measure | ||
| Walking speed per 1 SD increment (0.25 m/sec)† | - | 0.77 (0.60 – 0.98) |
| Grip strength‡ | ||
| Tertiles | ||
| Unable | 137/306 (44.8%) | 0.89 (0.58 – 1.34) |
| Low Tertile (Poor Performers) | 146/250 (58.4%) | 1 |
| Intermediate Tertile | 127/230 (55.2%) | 0.71 (0.46 – 1.10) |
| (Intermediate Performers) | ||
| High Tertile (Good Performers) | 144/300 (48.0%) | 0.55 (0.36 – 0.84) |
| Continuous measure | ||
| Grip strength per 1 SD increment (9.1 kg)¶ |
- |
0.71 (0.56 – 0.90) |
Adjusted for age, gender, pain, falls, number of diseases, ischemic heart disease, heart failure, diabetes, length of hospital stay and site; †Only 520 with valid walking speed data were included in the analysis. Patients unable to perform the test were excluded; ‡ Data on grip strength was missing in 37 patients; ¶ Only 780 patients with valid grip strength data were included in the analysis. Patients unable to perform the test were excluded.
Mean grip strength was 19.1 kg, median was 18 kg (minimum 1 kg, maximum 54 kg). As shown in table 3, participants unable to perform the test had the lowest prevalence of polypharmacy (44.8%). Among participants able to complete the test, prevalence of polypharmacy progressively declined as the performance improved, with 58.4% of participants in the low tertile and 41.8% of those in the high tertile on polypharmacy. After adjusting for potential confounders, participants in the high tertile had a significantly lower likelihood of polypharmacy as compared with those in the low tertile (OR 0.55; 95% CI 0.36 – 0.84). As compared with patients unable to perform (reference category), those in the high tertile had a significantly lower likelihood of polypharmacy (OR 0.62; 95% CI 0.40 – 0.97). When grip strength was examined as a continuous measure among 780 participants able to perform the test, an inverse association was observed with polypharmacy (OR for 1 SD increment 0.71; 95% CI 0.56 – 0.90).
Using a cutoff of ≥ 8 drugs to define polypharmacy, findings described in table 3 were substantially confirmed. In particular, participants in the high tertile of walking speed had a significantly lower OR for polypharmacy as compared with those in the low tertile (OR 0.60; 95% CI 0.40 – 1.00) and those in the high tertile of grip strength had a significantly lower OR for polypharmacy as compared with those in the low tertile (OR 0.52; 95% CI 0.33 – 1.81).
Discussion
The present study showed that, in a sample of older individuals admitted in acute care wards, poor physical performance (as assessed by walking speed and grip strength tests) was associated with higher rate of polypharmacy during hospital stay. Physical performance measures have proven to be valid and reliable and they are now widely used in geriatric research because of their sensitivity to change over time and predictive validity for important health outcomes such as self-rated health, institutionalization, hospitalization, falls, mortality, and onset of disability in several populations (10, 11, 12). However, data about their use in the hospital was limited to few studies. Volpato et al. tested the validity of a summary measure of lower extremity function, the Short Physical Performance Battery (SPPB) in predicting health outcomes in a cohort of elderly patients admitted to an acute care ward. In this sample, lower SPPB scores were associated to higher length of hospital stay, higher severity of diseases, decline in activities of daily living, re-hospitalization and death. This association was even stronger when the decline was detected after discharge 15, 16.
Polypharmacy resulted to be extremely common in the study population, with nearly 50% of older adults receiving ≥10 drugs. This condition is often considered a marker of disease severity, clinical complexity and negative health outcomes, including impaired physical function. Indeed, geriatric syndromes (e.g., falls/fractures, delirium, urinary incontinence) and chronic conditions follow a common pathway ultimately leading to functional status decline, so it is logical that medication use would be considered a factor closely related to functional decline among the elderly.
Former studies have addressed the association between physical performance measures and polypharmacy in the community setting. Pugh et al. in a 7 years prospective study based on data from the Hispanic Established Population for the Epidemiologic Study of the Elderly, showed that polypharmacy was an independent predictor of decline in lower extremity function (assessed with SPPB) among home dwelling people (28). Similarly, Jyrkka et al. reported that in a sample of 294 community dwelling older adults participating to the Geriatric Multidisciplinary Strategy for the Good Care of the Elderly Study, polypharmacy was associated with decline in functional status (measured trough self reporting Instrumental ADL) over a 3 year period (22). These two prospective studies underline the effect of a high number of prescribed drugs on functional status within elderly populations. This association seems to be independent from demographic features, comorbidity and other medical or social condition, suggesting that polypharmacy represent per se an index of complexity and a potential risk factor for adverse events 7, 29.
By showing an association between physical performance measures and polypharmacy, the present study further confirms that these measures may be used to screen not only community dwelling older adults, but also in-hospital patients, to identify patients in need of more intense pharmacological treatment and at risk for adverse outcomes (15, 16, 17). Physical performance measures are likely to capture the integrated and multisystemic effects of aging and chronic diseases on the health status of older persons and they may be considered as a nonspecific but highly sensitive indicator of global health status reflecting several underlying physiological impairments (30). Therefore these measures might provide important additional information not captured by the standard clinical evaluation of older patients and their integration into the traditional geriatric assessment can be helpful to identify patients at risk for negative outcomes.
Overall, about half of participating patients could not complete the walking test. This might be related to the presence of acute conditions which may limit the ability to perform the walking test safely. Indeed, research physicians were instructed to perform the walking test based on their impressions of the general safety of the patient and therefore only the healthiest participants may have completed the test. In our sample participants unable to perform the walking speed test were those with the highest rate of polypharmacy, suggesting that the evaluation of the patient's ability to complete this test may provide important information about the risk of negative health outcomes, including polypharmacy.
Patients unable to perform the grip strength test had the lowest rate of polypharmacy as compared to those able to complete the test. This might be related to the fact that attitudes of prescribing physicians may differ in severely impaired older adults, avoiding the use of multiple drugs in patients severely disabled or with life-limiting chronic conditions 31, 32. This hypothesis is also confirmed by the fact that after adjusting for potential confounders good performers had a significantly lower probability of polypharmacy as compared with patients unable to complete the test.
Median length of stay in our sample was 10 days. This finding underlines the clinical complexity of older adults participating to the CRIME study. In addition, such a length of stay despite substantially different from the one observed in other countries is in line with previous surveys involving elderly patients admitted to acute care wards in Italy (33).
An important limitation of this study relates to generalizability of the results. Our findings, which are based on an old, hospitalized population, may not be directly applicable to different populations and settings. In addition, although we adjusted all analyses for several indicators of health status, it is possible that the association between polypharmacy and physical performance measures is due to residual confounding or lack of adjustment for factors not measured in the study, such as measures of disease severity. From this point of view we cannot exclude that our results may reflect the fact that in some patients, poor physical performance may occur secondary to multiple, potentially disabling illnesses, which may require the use of multiple drugs. Finally, physical performance measures examined were not measurable in a large proportion of study sample (walking speed 53.7%; grip strength 27.2%) and in particular advanced aged, comorbidity and cognitive impairment were associated with reduced likelihood of completing these tests. Therefore the role of these measures in discriminating health status and predicting adverse outcomes (in particular polypharmacy) in the frailest and most cognitively impaired patients may be questionable.
In conclusion, our study demonstrates that physical performance measures are associated with polypharmacy in hospitalized older adults. If incorporated into the routine in-hospital geriatric assessment, these measures could lead to better functional and prognostic evaluation of older acutely ill patients, although they might not be measurable, at least on admission, in several older patients.
Acknowledgments
Acknowledgements: The CRIME project was funded by a grant of the Italian Ministry of Labour, Health and Social Policy (Bando Giovani Ricercatori 2007, convenzione n. 4)
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