J Nutr Health Aging

THE JOURNAL OF NUTRITION, HEALTH & AGING©

PHYSICAL PERFORMANCE MEASURES AND POLYPHARMACY AMONG HOSPITALIZED OLDER ADULTS: RESULTS FROM THE CRIME STUDY F. SGANGA1, D.L. VETRANO1, S. VOLPATO2, A. CHERUBINI3, C. RUGGIERO4, A. CORSONELLO5, P. FABBIETTI6, F. LATTANZIO6, R. BERNABEI1, G. ONDER1 1. Department of Gerontology, Neuroscience and Orthopedics, Università Cattolica Sacro Cuore, Rome, Italy; 2. Section of Internal Medicine and Geriatrics, Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy; 3. Geriatrics, Research Hospital of Ancona, Italian National Research Center on Aging (INRCA), Ancona, Italy; 4. Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia Medical School, Italy; 5. Unit of Geriatric Pharmacoepidemiology, Italian National Research Center on Aging (INRCA), Cosenza, Italy; 6. Biostatistical Center, Italian National Research Centre on Aging (INRCA) , Ancona, Italy. Corresponding author: Federica Sganga, Centro Medicina dell’Invecchiamento, Department of Gerontology, Neuroscience and Orthopedics, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168, Roma, Italy, Tel. +39 06 30154341, Fax +39 06 3051911, E-mail: [email protected]

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.

institutionalization and impaired cognition and they may represent valid and reliable outcome measures for intervention studies (10-14). 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 (15-17). 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.

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 (1-3). 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 (4-6). 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, Received June 20, 2013 Accepted for publication September12, 2013

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 1

J Nutr Health Aging

POLYPHARMACY AND PHYSICAL PERFORMANCE MEASURES 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) 0.48660.718 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 2

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. 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.

J Nutr Health Aging

THE JOURNAL OF NUTRITION, HEALTH & AGING© Table 1 Sample characteristics according to polypharmacy status All n= 1123 (%)

Demographics Age, years (mean±SD) Female gender Functional status and geriatric conditions Number of impaired ADL MMSE score (mean±SD) GDS score (mean±SD) Pain Falls Poor economical status Comorbidity Number of diseases (mean±SD) Ischemic heart disease Heart failure Parkinson disease Stroke Diabetes Cancer Dementia Length of stay > 10 days

No polypharmacy Polypharmacy (< 10 drugs) n= 547 (%) (≥ 10 drugs) n= 576 (%)

P

81.5 + 7.4 629 (56.0%)

81.7 + 7.7 322 (58.9%)

81.3 + 7.1 307 (53.3%)

0.449 0.060

2.5 + 2.5 17.2 + 10.8 5.0 + 3.5 589 (52.5%) 278 (24.8%) 872 (77.6%)

2.4 + 2.5 17.5 + 10.7 4.9 + 3.6 272 (49.8%) 120 (21.9%) 418 (76.4%)

2.5 + 2.4 16.9 + 10.7 5.1 + 3.4 317 (55.1%) 158 (27.4%) 454 (78.8%)

0.629 0.390 0.465 0.075 0.033 0.334

5.7 + 3.1 356 (31.7%) 307 (27.3%) 68 (6.1%) 151 (13.4%) 333 (29.7%) 155 (13.8%) 230 (20.5%) 577 (51.4%)

5.1 + 3.0 146 (26.7%) 104 (19.2%) 31 (5.7%) 73 (13.3%) 125 (22.9%) 80 (14.6%) 109 (19.9%) 199 (36.4%)

6.1 + 3.1 210 (36.5%) 203 (35.2%) 37 (6.4%) 78 (13.5%) 208 (36.1%) 75 (13.0%) 121 (21.0%) 378 (65.6%)

< 0.01 < 0.01 < 0.01 0.595 0.923 < 0.01 0.436 0.654 < 0.01

ADL – Activities of Daily Living; MMSE – Mini Mental State Examination; GDS – Geriatric Depression

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). 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

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). 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

Physical performance measures and polypharmacy among hospitalized older adults: results from the CRIME study.

To investigate the association of polypharmacy and physical performance measures in a sample of elderly patients aged ≥65 years admitted to acute care...
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