Polypharmacy and potentially inappropriate medications in older adults who use long-term care services: A cross-sectional study

Polypharmacy and potentially inappropriate medications in older adults who use long-term care services: A cross-sectional study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Polypharmacy and potentially inappropriate medications in older adults who use long-term care services: A cross-sectional study Shotaro Hagiwara, Jun Komiyama, Masao Iwagami, Shota Hamada, Masato Komuro, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4470744/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Aug, 2024 Read the published version in BMC Geriatrics → Version 1 posted 4 You are reading this latest preprint version Abstract Background: Older adults requiring care often have multiple morbidities that lead to polypharmacy, including the use of potentially inappropriate medications (PIMs), leading to increased medical costs and adverse drug effects. We conducted a cross-sectional study to clarify the actual state of drug prescriptions and the background of polypharmacy and PIMs. Methods: Using long-term care (LTC) and medical insurance claims data in the Ibaraki Prefecture from April 2018 to March 2019, we included individuals aged ≥ 65 who used LTC services. The number of drugs prescribed for ≥ 14 days and the number of PIMs were counted. A generalized linear model was used to analyze the association between the backgrounds of individuals and the number of drugs; logistic regression analysis was used for the presence of PIMs. Results: Herein, 67,531 older adults who received LTC services were included. The median number of total prescribed medications and PIMs was 7(IQR 5–9) and 1(IQR 0–1), respectively. The main PIMs were loop diuretics/aldosterone antagonists, benzodiazepines/similar hypnotics, and nonsteroidal anti-inflammatory drugs. Multivariate analysis revealed that the number of medications and presence of PIMs were significantly higher in patients with comorbidities and in those visiting multiple medical institutions. However, patients requiring care level ≧ 1, nursing home residents, users of short-stay service, and senior daycare were negatively associated with polypharmacy and PIMs. Conclusions: Polypharmacy and PIMs are frequently observed in older adults who require LTC. This was prominent among individuals with comorbidities and at multiple consulting institutions. Therefore, a nationwide cohort study is required. cross-sectional study long-term care older adults potentially inappropriate medication polypharmacy Figures Figure 1 Introduction The number of people requiring care has been on the increase with an increasing aging society. According to the 2020 national census in Japan, individuals aged ≥ 65 years constituted 28.6% of the population (36 million). Among them, 6.68 million individuals require support or care. Older adults requiring long-term care (LTC) often exhibit multiple comorbidities and use multiple medications, as documented in previous studies ( 1 , 2 ). Polypharmacy exerts economic pressure on healthcare and leads to an increased risk of hospitalization due to adverse drug events ( 3 – 6 ). Medications deemed inappropriate for prescription, particularly for elderly individuals with diminished physical and metabolic capacity, are considered potentially inappropriate medications (PIMs) ( 4 ). Exploring the underlying context of these challenges is essential for finding clues to improve polypharmacy and PIMs. Background factors contributing to polypharmacy include age, comorbidities, obesity, and residence in LTC facilities ( 7 – 10 ). Recently, polypharmacy and recent hospitalization, a number of prescriptions, cardiovascular diseases, metabolic disorders, and neurogenic motor functional impairments have been associated ( 11 ). Multimorbidity and polypharmacy are risk factors for PIMs ( 7 , 12 ). However, previous research has focused mainly on residents of care facilities or small cohorts, necessitating larger-scale analyses using data representing the entire older population requiring care. We conducted a cross-sectional study using medical and LTC claims insurance data to examine the prevalence and underlying factors of polypharmacy and PIMs in older adults requiring support or care. Methods Study design and data source This cross-sectional study used medical insurance claims data and LTC insurance claims data from Ibaraki Prefecture, Japan, between April 2018 and March 2019. These medical claims data included information regarding citizen health insurance for municipalities (National Health Insurance) and unions for late elderly health insurance. Data regarding other types of health insurance (e.g., insurance for company employees) were not included. Study population By cross-referencing with medical claims data, we analyzed a population of individuals aged ≥ 65 years who used LTC insurance services in Ibaraki Prefecture, Japan. Among them, “Roken” (Geriatric Health Services Facilities) and “Integrated Facility for Medical and Long-term Care” residents were excluded from the analysis owing to the bundled payment system for medical services. Their medical costs were included in the LTC insurance. Therefore, the drugs prescribed were not recorded in the medical claims data ( 13 , 14 ). Measurements The number of drugs was defined as the number of oral medicines prescribed for ≥ 14 days within three months of the index month. In this study, PIMs, such as sedatives and diuretics, were often prescribed repeatedly for short durations and were focused on orally administered medications prescribed for ≥ 14 days in outpatient settings, excluding those prescribed during hospitalization. The definition of PIMs followed the "Guidelines for medical treatment and its safety in the elderly 2015" by the Japan Geriatrics Society ( 15 ). Medication counts were indexed from October 2018, and the number of medications prescribed for ≥ 14 days over the following three months was tallied. Antipsychotic drugs prescribed concomitantly with anti-dementia medications were considered PIMs in patients with dementia. Covariates As background variables for polypharmacy and PIMs, data on age, sex, level of care needed, number of visiting medical institutions, Charlson comorbidity index (CCI) ( 16 ), physician home-visits, home-visit nursing, and the LTC facility residence excluding Roken and Integrated Facility for Medical and Long-term Care, as well as senior daycare and short stays, were collected in October 2018. The CCI was calculated based on medical claims data using ICD-10 codes from April 2018 to October 2018, as described in our previous study ( 17 ), using the 2011 updated and reweighted version validated in a Japanese national administrative dataset ( 18 ). An overview of the study design is shown in Supplementary Fig. 1. Statistical analysis First, we describe the characteristics of the individuals who require support or LTC. We counted the number of orally administered medications prescribed for ≥ 14 days as well as the number of PIMs. Next, we analyzed the types of frequently prescribed orally administered medications and PIMs. For the relationship between the number of prescribed medications and PIMs and background variables related to LTC services, multivariate analysis was conducted using a generalized linear model with Poisson distribution for the total number of medicines prescribed for ≥ 14 days and a logistic regression analysis for the presence of PIMs. Descriptive statistics for the background variables, medication counts, and multivariate analyses were performed using Stata version 15.0 (Stata Corp LP, College Station, TX, USA). R version 4.2.2 was used to analyze frequently prescribed medication types. Statistical significance was set at p < 0.05. Results Study participants’ characteristics Of the 90351 people identified in the LTC insurance service between April 2018 and March 2019, 9121 were Roken or Integrated Facility for Medical and Long-term Care residents, and 1732 were not certified for requiring LTC; these were excluded from the study population. Among them, 67531 subscribers to the National Health Insurance services or Medical Insurance for the elderly were extracted. The characteristics of the study participants are described in Table 1 . Table 1 Study population’s Characteristics Characteristics ཎ(%) Number of Medicines for 14 days or longer, Median (IQR) Prescription of PIM(s) (%) * Total 67531 (100) 7 ( 5 – 9 ) 66.5 Sex Male Female 20041 (29.7) 47490 (70.3) 7 ( 5 – 9 ) 7 ( 4 – 9 ) 64.9 67.1 Age 65–69 70–74 75–79 80–84 85–89 90–94 95- 1639 (2.4) 3384 (5.0) 5106 (7.6) 13896 (20.6) 21349 (31.6) 16061 (23.8) 6096 (9.0) 7 ( 4 – 10 ) 7 ( 5 – 10 ) 7 ( 5 – 10 ) 7 ( 5 – 10 ) 7 ( 5 – 9 ) 6 ( 4 – 9 ) 6 ( 4 – 8 ) 63.4 65.9 64.8 67.1 67.4 66.5 64.1 Comorbidity Index 0 1 2 3- 14529 (21.5) 5343 (7.9) 20733 (30.7) 26926 (39.9) 6 ( 4 – 8 ) 7 ( 5 – 10 ) 6 ( 4 – 8 ) 8 ( 5 – 10 ) 59.5 67.9 63.5 72.3 Level of Care Support level 1–2 Care level 1–3 4–5 11574 (17.1) 40057 (59.3) 15900 (23.5) 7 ( 5 – 10 ) 7 ( 5 – 9 ) 6 ( 4 – 8 ) 70.2 67.1 62.2 Number of consulting Institutions 1 2 3 4- 32989 (48.9) 21646 (32.0) 8932 (13.2) 3964 (5.9) 6 ( 4 – 8 ) 7 ( 5 – 9 ) 8 ( 6 – 11 ) 9 ( 7 – 12 ) 62.8 67.8 72.5 76.4 Physician home visits No Yes 60052 (88.9) 7479 (11.1) 7 ( 4 – 9 ) 7 ( 4 – 9 ) 66.6 65.8 Home-visit nursing No Yes 63751 (94.4) 3780 (5.6) 7( 4 – 9 ) 7( 5 – 10 ) 66.5 66.1 Nursing home resident No Yes 50709 (75.1) 16822 (24.9) 7 ( 5 – 9 ) 6 ( 4 – 8 ) 67.3 63.8 Senior daycare No Yes 39883 (59.1) 27648 (40.9) 7 ( 4 – 9 ) 7 ( 4 – 9 ) 66.7 66.2 Short stay service Yes No 61235 (90.7) 6296 (9.3) 7 ( 4 – 9 ) 7 ( 4 – 9 ) 66.6 64.8 The median age was 87 (82–91, IQR), the median CCI was 2 (1–4, IQR), and the median number of consulting institutions was 2 (1–2, IQR). Table 1 describes the characteristics of the study population and the number of prescribed medicines and PIMs for ≥ 14 days. The median number of oral medicines prescribed for ≥ 14 days was 7 (4–9, IQR). The number of PIMs was 1 (0–2, IQR), and 66.5% of patients had at least one PIM. The distribution of the number of medicines according to each variable is listed in Supplemental Fig. 2a-k. Frequently prescribed medicines Frequently prescribed medications include antihypertensives, laxatives, gastric acid suppressants, diuretics, anti-platelets, analgesics, anxiolytics/hypnotics, anti-dementia drugs, and anti-hyperlipidemics. The most commonly prescribed PIMs were diuretics (loop-diuretics/spironolactone), followed by benzodiazepines or benzodiazepine-like hypnotics or anxiolytics, nonsteroidal anti-inflammatory drugs (NSAIDs), H2 blockers, and antidiabetics (e.g., sulfonylureas/biguanides/voglibose) (Table 2 ). Table 2 Frequencies of prescribed main drug types and PIMs for 14 days or more Frequency % PIMs (%) Anti-hypertensives 74.2 Alfa1-blockers (2.1) Laxatives 57.4 Gastric acid suppressants 47.6 Proton pump inhibitors 40.2 H 2 blocker 7.4 H 2 blockers (7.4) Diuretics 29.2 Loop diuretics and aldosterone antagonists (23.0) Anti-platelets 28.4 Analgesics 26.1 NSAIDs (10.0) Anxiolytics, Hypnotics 26.0 Benzo-diazepines and similar drugs (18.3) Anti-dementia drugs 25.7 Anti-hyperlipidemics 20.5 Anti-osteoporotics 16.6 Anti-diabetics 13.9 SUs, biguanides, thiazolidinediones, alpha-glucosidase blockers (7.0) Urinary incontinence drugs 11.6 Oxybutynin, muscarinic antagonists (2.5) Gastric mucosal protectives 11.0 Anticoagulants 10.0 Expectorants 9.5 Kampo-medicines 8.6 Gout suppressants 8.4 Vitamin B12 8.2 Peripheral circulation enhancers 7.4 Antipsychotics 6.8 Antipsychotics for patients with dementia (1.0) Probiotics 6.1 Iron supplements 5.3 Multivariate analysis Table 3 lists the background factors associated with the total number of prescribed medications for ≥ 14 days, and the presence of PIMs is shown in Table 4 . Physician home visits and home-visit nursing are associated with an increased number of drugs. Meanwhile, this number decreased for people aged ≥ 85 years. Female sex and ages 90–94 were associated with the presence of PIMs. CCI ≥ 1 and 2 or more consulting institutions were associated with an increased number of drugs and PIMs. Care-level ≥ 1, senior daycare, and short-stay service were associated with a decreased number of medicines and PIMs (Table 4 ). The results of the multivariate analysis are summarized in Fig. 1 . Table 3 The generalized linear model of the number of medicines for ≧ 14 days Coefficient [95% confidence interval] P-value SEX Male Female Reference -0.001 -0.007 0.006 0.856 Age 65–69 70–74 75–79 80–84 85–89 90–94 95- Reference 0.009 0.004 -0.014 -0.028 -0.062 -0.144 -0.013 0.030 -0.017 0.025 -0.032 0.005 -0.047 -0.009 -0.081 -0.043 -0.166 -0.124 0.430 0.706 0.163 0.004 < 0.001 < 0.001 Comorbidity Index 0 1 2 3- Reference 0.207 0.101 0.277 0.195 0.219 0.092 0.109 0.269 0.285 < 0.001 < 0.001 < 0.001 Level of Care Support level 1–2 Care level 1–3 4–5 Reference -0.020 -0.092 -0.028 -0.012 -0.102 -0.081 < 0.001 < 0.001 Number of consulting institutions 1 2 3 4- Reference 0.130 0.246 0.388 0.123 0.136 0.237 0.254 0.377 0.400 < 0.001 < 0.001 < 0.001 Physician home visits No Yes Reference 0.024 0.014 0.033 < 0.001 Home-visit nursing No Yes Reference 0.014 0.001 0.027 0.035 Nursing home resident No Yes Reference -0.084 -0.093 -0.075 < 0.001 Senior daycare No Yes Reference -0.058 -0.064 -0.051 < 0.001 Short stay service No Yes Reference -0.040 -0.050 -0.029 < 0.001 Table 4 The factors associated with PIMs Odds ratio [95% confidence interval] P-value Sex Male Female Reference 1.174 1.131 1.218 < 0.001 Age 65–69 70–74 75–79 80–84 85–89 90–94 95- Reference 1.095 1.003 1.008 1.108 1.117 1.064 0.966 1.240 0.892 1.127 0.969 1.203 0.995 1.233 1.002 1.245 0.947 1.196 0.154 0.963 0.165 0.060 0.046 0.294 Comorbidity Index 0 1 2 3- Reference 1.412 1.226 1.825 1.321 1.510 1.173 1.281 1.747 1.907 < 0.001 < 0.001 < 0.001 Level of Care Support level 1–2 Care level 1–3 4–5 Reference 0.887 0.731 0.845 0.930 0.687 0.777 < 0.001 < 0.001 Number of consulting institutions 1 2 3 4 - Reference 1.199 1.448 1.718 1.155 1.244 1.373 1.528 1.588 1.859 < 0.001 < 0.001 < 0.001 Physician home visits No Yes Reference 1.017 0.963 1.074 0.543 Home-visit nursing No Yes Reference 0.955 0.885 1.030 0.229 Nursing home resident No Yes Reference 0.924 0.879 0.972 0.002 Senior daycare No Yes Reference 0.869 0.836 0.903 < 0.001 Short stay service No Yes Reference 0.925 0.873 0.980 0.008 Discussion The older adults in Ibaraki Prefecture closely mirror the age distribution of the Japanese population; the sample is not precisely representative but is consistent with the situation in Japan. This study is based on LTC claims, and medical insurance claims data, reflecting the reality of medical care for older adults requiring LTC. By analyzing prescription patterns for older adults requiring LTC, the top five categories were anti-hypertensives, laxatives, gastric acid suppressants, diuretics, and antiplatelet agents. While these findings are generally consistent with previous research conducted among individuals aged ≥ 75 years in Tokyo ( 19 ), we found a higher prevalence of laxative and diuretic use in our study population. This may reflect the higher prevalence of constipation and edema due to hypertension and heart failure among older adults who require LTC. Diuretics and anxiolytics/hypnotics are the most common types of PIMs. Diuretics pose the risks of electrolyte imbalance and falls ( 15 , 20 , 21 , 22 ). Similarly, benzodiazepines or similar anxiolytics/hypnotics carry the risks of delirium and falls and should be avoided. We analyzed the background of polypharmacy and PIMs. Multivariate analysis suggested that the total number of medications and PIMs was higher among patients with comorbidities and among those from more than one consulting institution. Total medication prescriptions and PIMs decreased among those with care needs levels 1–5 compared to those with support level 1–2. In older adults certified for long-term care (LTC), polypharmacy and rates of potentially inappropriate medications (PIMs) are significantly elevated compared to those without LTC certification ( 23 ). Polypharmacy reaches its peak at mild care need levels, while the prevalence of PIMs escalates with increasing levels of care needs ( 23 ). While our findings are consistent with those of previous research, our study analyzed a five times larger number of exclusively certified care-needing individuals, which may enhance its reliability. Nursing home residents are at high risk of polypharmacy ( 11 ). However, a narrative review indicated various attempts to rationalize pharmacotherapy in nursing homes, including medication reviews and multidisciplinary and patient-centered interventions that have shown effectiveness ( 24 ). Admission to a nursing home facilitated the rectification of the living environment and nutritional status, and various interventions by the home staff might have contributed to reducing the number of medications. Users of day-care and short-stay services exhibited significantly lower rates of polypharmacy and PIMs. Loneliness and social isolation have been associated with polypharmacy ( 25 ), and homebound older adults are at high risk of polypharmacy ( 26 ). Additionally, Vyas et al. reported that lonely older individuals often use opioids and benzodiazepines daily ( 27 ). Day-care and short-stay services provide opportunities for interaction with other older adults in the community and interventions from healthcare and medical experts, thereby preventing social isolation. Short-stay services have been associated with improvements in cognitive function ( 28 , 29 ) and extended periods of living at home ( 30 ). The use of day-care and short-stay services may contribute to improving polypharmacy and PIMs. Home-visit nursing and physician home visits were associated with polypharmacy but not with PIMs. Home-visit nursing reportedly reduces hospitalizations among older adults ( 31 ). However, compared with nursing homes, home-visit nursing has been associated with increased medication-related issues ( 32 ). Home-visit nursing users often have high care needs, respiratory or circulatory diseases, and long durations of care ( 33 ), rendering them prone to polypharmacy. Home-visiting physicians are responsible for homebound individuals who have difficulty visiting outpatient clinics. Homebound older adults tend to have multiple chronic conditions and require medications ( 7 , 34 ). As a result of addressing the medical needs of patients who had not previously received adequate medical care, home-visit nursing and physician home visits may have contributed to an increase in the number of prescribed medications. This study demonstrated a strong association between CCI, polypharmacy, and PIMs. Komiya et al. reported a significant association between the CCI and polypharmacy in homebound patients and polypharmacy ( 7 ). A systematic review by Jokanovic et al. further reported a substantial correlation between polypharmacy and CCI in LTC facilities ( 11 ). Our results are consistent with those of previous studies. Free access is a characteristic of the healthcare system of Japan. Patients with multiple conditions can visit specialists in different areas, thereby enabling them to receive high-quality medical care. However, this may lead to an increase in the number of prescriptions and complications associated with medication regimens. Few studies have examined the relationship between polypharmacy and the number of consulting institutions. A single-center study reported the relationship between polypharmacy and the department visited by older adult patients at a medium-sized hospital ( 35 ). We previously reported a correlation between the number of medical institutions visited and polypharmacy through questionnaire-based data collection targeting older adults in a single city in Japan ( 36 ). Based on an analysis of medical and care claims data, our study revealed a significant correlation between the number of medical institutions visited and the total number of medications and PIMs. Careful consideration of the advantages and disadvantages of a free-access system and the need for gatekeepers to oversee patient prescriptions may be necessary. Our study has several limitations: The data were limited to the National Health Insurance or Medical Insurance for the elderly in the latter stage of life in Ibaraki Prefecture in the Kanto region of Japan. Employee Health Insurance data are unavailable. This study focused exclusively on orally administered medications and excluded topical and injectable formulations. In addition, medications administered weekly or monthly, such as those prescribed once a week or once a month, were omitted, as only drugs prescribed for ≥ 14 days within three months were counted. Further research using nationwide databases is required to analyze the trends and regional differences across Japan. This study was cross-sectional; therefore, outcomes cannot be evaluated based on the factors extracted from it. Misclassification of the CCI is likely because it is based on the diagnoses recorded in medical claims. In conclusion, most adults aged ≥ 65 years using LTC services were in a state of polypharmacy. Additionally, nearly 70% of the patients had one or more PIMs. High CCI scores and a large number of consulting institutions were associated with a higher risk of polypharmacy and PIMs. Conversely, nursing home residents, senior daycare services, and short-stay services may contribute to reducing polypharmacy and PIMs. Therefore, a nationwide cohort study is warranted. Declarations Author Contributions SH designed the study, performed the data analysis, and wrote the paper. JK supported the research and data analysis design and revised the manuscript. MI, SH, MK, and HK revised the manuscript. NT supervised the study and revised the manuscript. Acknowledgment The authors are grateful to the members of the Health Service Research Department at the University of Tsukuba and to Editage (www.editage.jp) for English language editing. Funding statement This study was supported by the JSPS KAKENHI (grant number: JP23K09521). Data availability The datasets for individual information generated and/or analyzed during the current study, which includes LTC insurance claims data and medical insurance claims data are not publicly available because the local government of Ibaraki Prefecture owns the original data and only approved the secondary use of the data for the current study. Conflict of interest disclosure SHamada is an endowed chair funded by donations from Hakue Technology, PROUMED, Japan BioProducts, Towa Pharmaceutical, Yellow Eight, and Sugi Holdings. SHamada received research funding from SOMPO Care, Inc. outside of this work. 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Effectiveness of home visit nursing on improving mortality, hospitalization, institutionalization, satisfaction, and quality of life among older people: Umbrella review. Geriatr Nurs. 2023 May;51:330–45. Devik SA, Olsen RM, Fiskvik IL, Halbostad T, Lassen T, Kuzina N, Enmarker I. Variations in drug-related problems detected by multidisciplinary teams in Norwegian nursing homes and home nursing care. Scand J Prim Health Care. 2018 Jul;36(3):291–9. Kashiwagi M, Tamiya N, Sato M, Yano E. Factors associated with the use of home-visit nursing services covered by the long-term care insurance in rural Japan: a cross-sectional study. BMC Geriatr. 2013 Dec;13:1. Kojima T, Mizokami F, Akishita M. Geriatric management of older patients with multimorbidity. Geriatr Gerontol Int 2020; Dec 20(12):1105–11. Nomoto S, Nakanishi Y. [Investigation of polypharmacy in late-stage elderly patients visiting a community hospital outpatient unit]. Nihon Ronen Igakkai Zasshi. 2011 Jan;48(3):276–81. Suzuki T, Iwagami M, Hamada S, Matsuda T, Tamiya N. Number of consulting medical institutions and risk of polypharmacy in community-dwelling older people under a healthcare system with free access: a cross-sectional study in Japan. BMC Health Serv Res. 2020 Dec;20(1):359. Additional Declarations No competing interests reported. Supplementary Files SupplementalFigure1Studydesign20240426.pptx Supplemental Figure 1. Study design overview SupplementalFigure2atoK20240426.pptx Supplemental Figure 2 a-k. The distribution of the number of medicines prescribed over 14 days or more Cite Share Download PDF Status: Published Journal Publication published 21 Aug, 2024 Read the published version in BMC Geriatrics → Version 1 posted Editorial decision: Revision requested 17 Jun, 2024 Editor assigned by journal 16 Jun, 2024 Submission checks completed at journal 16 Jun, 2024 First submitted to journal 24 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4470744","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":315536192,"identity":"a793c1b7-d1ab-43c0-a9cc-086b80ec2de2","order_by":0,"name":"Shotaro Hagiwara","email":"data:image/png;base64,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","orcid":"","institution":"Tsukuba University Hospital Mito Clinical Education and Training Center","correspondingAuthor":true,"prefix":"","firstName":"Shotaro","middleName":"","lastName":"Hagiwara","suffix":""},{"id":315536193,"identity":"d19d6c42-7d2b-4a7a-b2ef-ebfe432aed2f","order_by":1,"name":"Jun Komiyama","email":"","orcid":"","institution":"University of Tsukuba","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Komiyama","suffix":""},{"id":315536194,"identity":"f9e00987-20c3-477d-a057-4ac1f019abf2","order_by":2,"name":"Masao Iwagami","email":"","orcid":"","institution":"University of Tsukuba","correspondingAuthor":false,"prefix":"","firstName":"Masao","middleName":"","lastName":"Iwagami","suffix":""},{"id":315536195,"identity":"884a5130-f03c-4874-a62a-707794debe71","order_by":3,"name":"Shota Hamada","email":"","orcid":"","institution":"University of Tsukuba","correspondingAuthor":false,"prefix":"","firstName":"Shota","middleName":"","lastName":"Hamada","suffix":""},{"id":315536196,"identity":"ee11e608-2c86-4be7-8720-715f8c0c56f1","order_by":4,"name":"Masato Komuro","email":"","orcid":"","institution":"Japan Health Research Promotion Bureau","correspondingAuthor":false,"prefix":"","firstName":"Masato","middleName":"","lastName":"Komuro","suffix":""},{"id":315536197,"identity":"efc5cdb1-8426-4efd-b108-9505b68fdbff","order_by":5,"name":"Hiroyuki Kobayashi","email":"","orcid":"","institution":"Tsukuba University Hospital Mito Clinical Education and Training Center","correspondingAuthor":false,"prefix":"","firstName":"Hiroyuki","middleName":"","lastName":"Kobayashi","suffix":""},{"id":315536198,"identity":"bec65ace-f3ed-46db-86c8-18e88e580dbb","order_by":6,"name":"Nanako Tamiya","email":"","orcid":"","institution":"University of Tsukuba","correspondingAuthor":false,"prefix":"","firstName":"Nanako","middleName":"","lastName":"Tamiya","suffix":""}],"badges":[],"createdAt":"2024-05-24 07:32:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4470744/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4470744/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12877-024-05296-4","type":"published","date":"2024-08-21T15:57:47+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60338179,"identity":"d632f796-a7c9-461b-af39-90d985b1c257","added_by":"auto","created_at":"2024-07-15 17:45:05","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36015,"visible":true,"origin":"","legend":"\u003cp\u003eFactors associated with polypharmacy and potentially inappropriate medications (PIMs)\u003c/p\u003e","description":"","filename":"Figure1v20240509.png","url":"https://assets-eu.researchsquare.com/files/rs-4470744/v1/c56619950a429b1c4aba772d.png"},{"id":63300673,"identity":"e3e7e2aa-6fd3-4a23-98ca-89272b339dbb","added_by":"auto","created_at":"2024-08-26 16:16:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":856108,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4470744/v1/78ed2653-9c30-405f-95e0-abc49ebadccd.pdf"},{"id":60338180,"identity":"685ed917-7543-440b-8e5a-a22ca5d67ba4","added_by":"auto","created_at":"2024-07-15 17:45:05","extension":"pptx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":40213,"visible":true,"origin":"","legend":"\u003cp\u003eSupplemental Figure 1. Study design overview\u003c/p\u003e","description":"","filename":"SupplementalFigure1Studydesign20240426.pptx","url":"https://assets-eu.researchsquare.com/files/rs-4470744/v1/3741e997d4c07a8924c272dd.pptx"},{"id":60338182,"identity":"02aa6346-7b0b-456b-8551-e871929e160d","added_by":"auto","created_at":"2024-07-15 17:45:05","extension":"pptx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":35649165,"visible":true,"origin":"","legend":"\u003cp\u003eSupplemental Figure 2 a-k. The distribution of the number of medicines prescribed over 14 days or more\u003c/p\u003e","description":"","filename":"SupplementalFigure2atoK20240426.pptx","url":"https://assets-eu.researchsquare.com/files/rs-4470744/v1/4ff3362de809c60352518737.pptx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Polypharmacy and potentially inappropriate medications in older adults who use long-term care services: A cross-sectional study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe number of people requiring care has been on the increase with an increasing aging society. According to the 2020 national census in Japan, individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years constituted 28.6% of the population (36\u0026nbsp;million). Among them, 6.68\u0026nbsp;million individuals require support or care.\u003c/p\u003e \u003cp\u003eOlder adults requiring long-term care (LTC) often exhibit multiple comorbidities and use multiple medications, as documented in previous studies (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Polypharmacy exerts economic pressure on healthcare and leads to an increased risk of hospitalization due to adverse drug events (\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Medications deemed inappropriate for prescription, particularly for elderly individuals with diminished physical and metabolic capacity, are considered potentially inappropriate medications (PIMs) (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eExploring the underlying context of these challenges is essential for finding clues to improve polypharmacy and PIMs. Background factors contributing to polypharmacy include age, comorbidities, obesity, and residence in LTC facilities (\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Recently, polypharmacy and recent hospitalization, a number of prescriptions, cardiovascular diseases, metabolic disorders, and neurogenic motor functional impairments have been associated (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Multimorbidity and polypharmacy are risk factors for PIMs (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). However, previous research has focused mainly on residents of care facilities or small cohorts, necessitating larger-scale analyses using data representing the entire older population requiring care.\u003c/p\u003e \u003cp\u003e We conducted a cross-sectional study using medical and LTC claims insurance data to examine the prevalence and underlying factors of polypharmacy and PIMs in older adults requiring support or care.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and data source\u003c/h2\u003e \u003cp\u003eThis cross-sectional study used medical insurance claims data and LTC insurance claims data from Ibaraki Prefecture, Japan, between April 2018 and March 2019. These medical claims data included information regarding citizen health insurance for municipalities (National Health Insurance) and unions for late elderly health insurance. Data regarding other types of health insurance (e.g., insurance for company employees) were not included.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eBy cross-referencing with medical claims data, we analyzed a population of individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years who used LTC insurance services in Ibaraki Prefecture, Japan. Among them, \u0026ldquo;Roken\u0026rdquo; (Geriatric Health Services Facilities) and \u0026ldquo;Integrated Facility for Medical and Long-term Care\u0026rdquo; residents were excluded from the analysis owing to the bundled payment system for medical services. Their medical costs were included in the LTC insurance. Therefore, the drugs prescribed were not recorded in the medical claims data (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eMeasurements\u003c/h2\u003e \u003cp\u003eThe number of drugs was defined as the number of oral medicines prescribed for \u0026ge;\u0026thinsp;14 days within three months of the index month. In this study, PIMs, such as sedatives and diuretics, were often prescribed repeatedly for short durations and were focused on orally administered medications prescribed for \u0026ge;\u0026thinsp;14 days in outpatient settings, excluding those prescribed during hospitalization. The definition of PIMs followed the \"Guidelines for medical treatment and its safety in the elderly 2015\" by the Japan Geriatrics Society (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Medication counts were indexed from October 2018, and the number of medications prescribed for \u0026ge;\u0026thinsp;14 days over the following three months was tallied. Antipsychotic drugs prescribed concomitantly with anti-dementia medications were considered PIMs in patients with dementia.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eCovariates\u003c/h2\u003e \u003cp\u003eAs background variables for polypharmacy and PIMs, data on age, sex, level of care needed, number of visiting medical institutions, Charlson comorbidity index (CCI) (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), physician home-visits, home-visit nursing, and the LTC facility residence excluding Roken and Integrated Facility for Medical and Long-term Care, as well as senior daycare and short stays, were collected in October 2018. The CCI was calculated based on medical claims data using ICD-10 codes from April 2018 to October 2018, as described in our previous study (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), using the 2011 updated and reweighted version validated in a Japanese national administrative dataset (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). An overview of the study design is shown in Supplementary Fig.\u0026nbsp;1.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eFirst, we describe the characteristics of the individuals who require support or LTC. We counted the number of orally administered medications prescribed for \u0026ge;\u0026thinsp;14 days as well as the number of PIMs.\u003c/p\u003e \u003cp\u003eNext, we analyzed the types of frequently prescribed orally administered medications and PIMs. For the relationship between the number of prescribed medications and PIMs and background variables related to LTC services, multivariate analysis was conducted using a generalized linear model with Poisson distribution for the total number of medicines prescribed for \u0026ge;\u0026thinsp;14 days and a logistic regression analysis for the presence of PIMs. Descriptive statistics for the background variables, medication counts, and multivariate analyses were performed using Stata version 15.0 (Stata Corp LP, College Station, TX, USA). R version 4.2.2 was used to analyze frequently prescribed medication types. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStudy participants\u0026rsquo; characteristics\u003c/h2\u003e \u003cp\u003eOf the 90351 people identified in the LTC insurance service between April 2018 and March 2019, 9121 were Roken or Integrated Facility for Medical and Long-term Care residents, and 1732 were not certified for requiring LTC; these were excluded from the study population. Among them, 67531 subscribers to the National Health Insurance services or Medical Insurance for the elderly were extracted. The characteristics of the study participants are described in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStudy population\u0026rsquo;s Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eཎ(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber of Medicines for 14 days or longer, Median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePrescription of PIM(s) (%) *\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67531 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e66.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex Male\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20041 (29.7)\u003c/p\u003e \u003cp\u003e47490 (70.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e64.9\u003c/p\u003e \u003cp\u003e67.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge 65\u0026ndash;69\u003c/p\u003e \u003cp\u003e70\u0026ndash;74\u003c/p\u003e \u003cp\u003e75\u0026ndash;79\u003c/p\u003e \u003cp\u003e80\u0026ndash;84\u003c/p\u003e \u003cp\u003e85\u0026ndash;89\u003c/p\u003e \u003cp\u003e90\u0026ndash;94\u003c/p\u003e \u003cp\u003e95-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1639 (2.4)\u003c/p\u003e \u003cp\u003e3384 (5.0)\u003c/p\u003e \u003cp\u003e5106 (7.6)\u003c/p\u003e \u003cp\u003e13896 (20.6)\u003c/p\u003e \u003cp\u003e21349 (31.6)\u003c/p\u003e \u003cp\u003e16061 (23.8)\u003c/p\u003e \u003cp\u003e6096 (9.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e6 (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e6 (\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e63.4\u003c/p\u003e \u003cp\u003e65.9\u003c/p\u003e \u003cp\u003e64.8\u003c/p\u003e \u003cp\u003e67.1\u003c/p\u003e \u003cp\u003e67.4\u003c/p\u003e \u003cp\u003e66.5\u003c/p\u003e \u003cp\u003e64.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidity Index\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14529 (21.5)\u003c/p\u003e \u003cp\u003e5343 (7.9)\u003c/p\u003e \u003cp\u003e20733 (30.7)\u003c/p\u003e \u003cp\u003e26926 (39.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e6 (\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e8 (\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59.5\u003c/p\u003e \u003cp\u003e67.9\u003c/p\u003e \u003cp\u003e63.5\u003c/p\u003e \u003cp\u003e72.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevel of Care\u003c/p\u003e \u003cp\u003eSupport level 1\u0026ndash;2\u003c/p\u003e \u003cp\u003eCare level 1\u0026ndash;3\u003c/p\u003e \u003cp\u003e 4\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11574 (17.1)\u003c/p\u003e \u003cp\u003e40057 (59.3)\u003c/p\u003e \u003cp\u003e15900 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e6 (\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70.2\u003c/p\u003e \u003cp\u003e67.1\u003c/p\u003e \u003cp\u003e62.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of consulting\u003c/p\u003e \u003cp\u003eInstitutions 1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e4-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32989 (48.9)\u003c/p\u003e \u003cp\u003e21646 (32.0)\u003c/p\u003e \u003cp\u003e8932 (13.2)\u003c/p\u003e \u003cp\u003e3964 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e8 (\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e9 (\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62.8\u003c/p\u003e \u003cp\u003e67.8\u003c/p\u003e \u003cp\u003e72.5\u003c/p\u003e \u003cp\u003e76.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysician home visits\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60052 (88.9) 7479 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.6\u003c/p\u003e \u003cp\u003e65.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHome-visit nursing\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63751 (94.4)\u003c/p\u003e \u003cp\u003e3780 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e7(\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.5\u003c/p\u003e \u003cp\u003e66.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNursing home resident\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50709 (75.1)\u003c/p\u003e \u003cp\u003e16822 (24.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e6 (\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67.3\u003c/p\u003e \u003cp\u003e63.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSenior daycare\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39883 (59.1)\u003c/p\u003e \u003cp\u003e27648 (40.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.7\u003c/p\u003e \u003cp\u003e66.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShort stay service\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61235 (90.7)\u003c/p\u003e \u003cp\u003e6296 (9.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e7 (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.6\u003c/p\u003e \u003cp\u003e64.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe median age was 87 (82\u0026ndash;91, IQR), the median CCI was 2 (1\u0026ndash;4, IQR), and the median number of consulting institutions was 2 (1\u0026ndash;2, IQR). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e describes the characteristics of the study population and the number of prescribed medicines and PIMs for \u0026ge;\u0026thinsp;14 days.\u003c/p\u003e \u003cp\u003eThe median number of oral medicines prescribed for \u0026ge;\u0026thinsp;14 days was 7 (4\u0026ndash;9, IQR). The number of PIMs was 1 (0\u0026ndash;2, IQR), and 66.5% of patients had at least one PIM. The distribution of the number of medicines according to each variable is listed in Supplemental Fig.\u0026nbsp;2a-k.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eFrequently prescribed medicines\u003c/h2\u003e \u003cp\u003eFrequently prescribed medications include antihypertensives, laxatives, gastric acid suppressants, diuretics, anti-platelets, analgesics, anxiolytics/hypnotics, anti-dementia drugs, and anti-hyperlipidemics.\u003c/p\u003e \u003cp\u003eThe most commonly prescribed PIMs were diuretics (loop-diuretics/spironolactone), followed by benzodiazepines or benzodiazepine-like hypnotics or anxiolytics, nonsteroidal anti-inflammatory drugs (NSAIDs), H2 blockers, and antidiabetics (e.g., sulfonylureas/biguanides/voglibose) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFrequencies of prescribed main drug types and PIMs for 14 days or more\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency %\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePIMs (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti-hypertensives\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e74.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAlfa1-blockers (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLaxatives\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e57.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGastric acid suppressants\u003c/b\u003e 47.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProton pump inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eH\u003csub\u003e2\u003c/sub\u003e blocker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH\u003csub\u003e2\u003c/sub\u003e blockers (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiuretics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eLoop diuretics and aldosterone antagonists (23.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti-platelets\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnalgesics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNSAIDs (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnxiolytics, Hypnotics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eBenzo-diazepines and similar drugs (18.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti-dementia drugs\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti-hyperlipidemics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti-osteoporotics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti-diabetics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eSUs, biguanides, thiazolidinediones, alpha-glucosidase blockers (7.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrinary incontinence drugs\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eOxybutynin, muscarinic antagonists (2.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGastric mucosal protectives\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnticoagulants\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExpectorants\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKampo-medicines\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGout suppressants\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVitamin B12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePeripheral circulation enhancers\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntipsychotics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eAntipsychotics for patients with dementia (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProbiotics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIron supplements\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eMultivariate analysis\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e lists the background factors associated with the total number of prescribed medications for \u0026ge;\u0026thinsp;14 days, and the presence of PIMs is shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Physician home visits and home-visit nursing are associated with an increased number of drugs. Meanwhile, this number decreased for people aged\u0026thinsp;\u0026ge;\u0026thinsp;85 years. Female sex and ages 90\u0026ndash;94 were associated with the presence of PIMs. CCI\u0026thinsp;\u0026ge;\u0026thinsp;1 and 2 or more consulting institutions were associated with an increased number of drugs and PIMs. Care-level\u0026thinsp;\u0026ge;\u0026thinsp;1, senior daycare, and short-stay service were associated with a decreased number of medicines and PIMs (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The results of the multivariate analysis are summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e The generalized linear model of the number of medicines for ≧\u0026thinsp;14 days\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCoefficient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[95% confidence interval]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSEX Male\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e-0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.007 0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.856\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge 65\u0026ndash;69\u003c/p\u003e \u003cp\u003e 70\u0026ndash;74\u003c/p\u003e \u003cp\u003e 75\u0026ndash;79\u003c/p\u003e \u003cp\u003e 80\u0026ndash;84\u003c/p\u003e \u003cp\u003e 85\u0026ndash;89\u003c/p\u003e \u003cp\u003e 90\u0026ndash;94\u003c/p\u003e \u003cp\u003e 95-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e0.009\u003c/p\u003e \u003cp\u003e0.004\u003c/p\u003e \u003cp\u003e-0.014\u003c/p\u003e \u003cp\u003e-0.028\u003c/p\u003e \u003cp\u003e-0.062\u003c/p\u003e \u003cp\u003e-0.144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.013 0.030\u003c/p\u003e \u003cp\u003e-0.017 0.025\u003c/p\u003e \u003cp\u003e-0.032 0.005\u003c/p\u003e \u003cp\u003e-0.047 -0.009\u003c/p\u003e \u003cp\u003e-0.081 -0.043\u003c/p\u003e \u003cp\u003e-0.166 -0.124\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.430\u003c/p\u003e \u003cp\u003e0.706\u003c/p\u003e \u003cp\u003e0.163\u003c/p\u003e \u003cp\u003e0.004\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidity Index 0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e0.207\u003c/p\u003e \u003cp\u003e0.101\u003c/p\u003e \u003cp\u003e0.277\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.195 0.219\u003c/p\u003e \u003cp\u003e0.092 0.109\u003c/p\u003e \u003cp\u003e0.269 0.285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevel of Care\u003c/p\u003e \u003cp\u003eSupport level 1\u0026ndash;2\u003c/p\u003e \u003cp\u003eCare level 1\u0026ndash;3 4\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e-0.020\u003c/p\u003e \u003cp\u003e-0.092\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.028 -0.012\u003c/p\u003e \u003cp\u003e-0.102 -0.081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of consulting institutions\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2 3\u003c/p\u003e \u003cp\u003e4-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e0.130\u003c/p\u003e \u003cp\u003e0.246\u003c/p\u003e \u003cp\u003e0.388\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.123 0.136\u003c/p\u003e \u003cp\u003e0.237 0.254\u003c/p\u003e \u003cp\u003e0.377 0.400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysician home visits No\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.014 0.033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHome-visit nursing No\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001 0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNursing home resident No\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e-0.084\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.093 -0.075\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSenior daycare No\u003c/p\u003e \u003cp\u003e Yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e-0.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.064 -0.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShort stay service No\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e-0.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.050 -0.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e The factors associated with PIMs\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[95% confidence interval]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex Male\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e1.174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.131 1.218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge 65\u0026ndash;69\u003c/p\u003e \u003cp\u003e70\u0026ndash;74\u003c/p\u003e \u003cp\u003e75\u0026ndash;79\u003c/p\u003e \u003cp\u003e80\u0026ndash;84\u003c/p\u003e \u003cp\u003e85\u0026ndash;89\u003c/p\u003e \u003cp\u003e90\u0026ndash;94\u003c/p\u003e \u003cp\u003e95-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e1.095\u003c/p\u003e \u003cp\u003e1.003\u003c/p\u003e \u003cp\u003e1.008\u003c/p\u003e \u003cp\u003e1.108\u003c/p\u003e \u003cp\u003e1.117\u003c/p\u003e \u003cp\u003e1.064\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.966 1.240\u003c/p\u003e \u003cp\u003e0.892 1.127\u003c/p\u003e \u003cp\u003e0.969 1.203\u003c/p\u003e \u003cp\u003e0.995 1.233\u003c/p\u003e \u003cp\u003e1.002 1.245\u003c/p\u003e \u003cp\u003e0.947 1.196\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.154\u003c/p\u003e \u003cp\u003e0.963\u003c/p\u003e \u003cp\u003e0.165\u003c/p\u003e \u003cp\u003e0.060\u003c/p\u003e \u003cp\u003e0.046\u003c/p\u003e \u003cp\u003e0.294\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidity Index 0\u003c/p\u003e \u003cp\u003e 1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e1.412\u003c/p\u003e \u003cp\u003e1.226\u003c/p\u003e \u003cp\u003e1.825\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.321 1.510\u003c/p\u003e \u003cp\u003e1.173 1.281\u003c/p\u003e \u003cp\u003e1.747 1.907\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevel of Care\u003c/p\u003e \u003cp\u003eSupport level 1\u0026ndash;2\u003c/p\u003e \u003cp\u003eCare level 1\u0026ndash;3\u003c/p\u003e \u003cp\u003e4\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e0.887\u003c/p\u003e \u003cp\u003e0.731\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.845 0.930\u003c/p\u003e \u003cp\u003e0.687 0.777\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of consulting institutions\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e4 -\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e1.199\u003c/p\u003e \u003cp\u003e1.448\u003c/p\u003e \u003cp\u003e1.718\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.155 1.244\u003c/p\u003e \u003cp\u003e1.373 1.528\u003c/p\u003e \u003cp\u003e1.588 1.859\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysician home visits No\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e1.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.963 1.074\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.543\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHome-visit nursing No\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e0.955\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.885 1.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.229\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNursing home resident No\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e0.924\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.879 0.972\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSenior daycare No\u003c/p\u003e \u003cp\u003e Yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e0.869\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.836 0.903\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShort stay service No\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003cp\u003e0.925\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.873 0.980\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe older adults in Ibaraki Prefecture closely mirror the age distribution of the Japanese population; the sample is not precisely representative but is consistent with the situation in Japan. This study is based on LTC claims, and medical insurance claims data, reflecting the reality of medical care for older adults requiring LTC.\u003c/p\u003e \u003cp\u003eBy analyzing prescription patterns for older adults requiring LTC, the top five categories were anti-hypertensives, laxatives, gastric acid suppressants, diuretics, and antiplatelet agents. While these findings are generally consistent with previous research conducted among individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years in Tokyo (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), we found a higher prevalence of laxative and diuretic use in our study population. This may reflect the higher prevalence of constipation and edema due to hypertension and heart failure among older adults who require LTC. Diuretics and anxiolytics/hypnotics are the most common types of PIMs. Diuretics pose the risks of electrolyte imbalance and falls (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Similarly, benzodiazepines or similar anxiolytics/hypnotics carry the risks of delirium and falls and should be avoided.\u003c/p\u003e \u003cp\u003eWe analyzed the background of polypharmacy and PIMs. Multivariate analysis suggested that the total number of medications and PIMs was higher among patients with comorbidities and among those from more than one consulting institution. Total medication prescriptions and PIMs decreased among those with care needs levels 1\u0026ndash;5 compared to those with support level 1\u0026ndash;2. In older adults certified for long-term care (LTC), polypharmacy and rates of potentially inappropriate medications (PIMs) are significantly elevated compared to those without LTC certification (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Polypharmacy reaches its peak at mild care need levels, while the prevalence of PIMs escalates with increasing levels of care needs (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). While our findings are consistent with those of previous research, our study analyzed a five times larger number of exclusively certified care-needing individuals, which may enhance its reliability. Nursing home residents are at high risk of polypharmacy (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, a narrative review indicated various attempts to rationalize pharmacotherapy in nursing homes, including medication reviews and multidisciplinary and patient-centered interventions that have shown effectiveness (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Admission to a nursing home facilitated the rectification of the living environment and nutritional status, and various interventions by the home staff might have contributed to reducing the number of medications.\u003c/p\u003e \u003cp\u003eUsers of day-care and short-stay services exhibited significantly lower rates of polypharmacy and PIMs. Loneliness and social isolation have been associated with polypharmacy (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), and homebound older adults are at high risk of polypharmacy (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Additionally, Vyas et al. reported that lonely older individuals often use opioids and benzodiazepines daily (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Day-care and short-stay services provide opportunities for interaction with other older adults in the community and interventions from healthcare and medical experts, thereby preventing social isolation. Short-stay services have been associated with improvements in cognitive function (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) and extended periods of living at home (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). The use of day-care and short-stay services may contribute to improving polypharmacy and PIMs.\u003c/p\u003e \u003cp\u003eHome-visit nursing and physician home visits were associated with polypharmacy but not with PIMs. Home-visit nursing reportedly reduces hospitalizations among older adults (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). However, compared with nursing homes, home-visit nursing has been associated with increased medication-related issues (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Home-visit nursing users often have high care needs, respiratory or circulatory diseases, and long durations of care (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), rendering them prone to polypharmacy. Home-visiting physicians are responsible for homebound individuals who have difficulty visiting outpatient clinics. Homebound older adults tend to have multiple chronic conditions and require medications (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). As a result of addressing the medical needs of patients who had not previously received adequate medical care, home-visit nursing and physician home visits may have contributed to an increase in the number of prescribed medications.\u003c/p\u003e \u003cp\u003eThis study demonstrated a strong association between CCI, polypharmacy, and PIMs. Komiya et al. reported a significant association between the CCI and polypharmacy in homebound patients and polypharmacy (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). A systematic review by Jokanovic et al. further reported a substantial correlation between polypharmacy and CCI in LTC facilities (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Our results are consistent with those of previous studies.\u003c/p\u003e \u003cp\u003eFree access is a characteristic of the healthcare system of Japan. Patients with multiple conditions can visit specialists in different areas, thereby enabling them to receive high-quality medical care. However, this may lead to an increase in the number of prescriptions and complications associated with medication regimens. Few studies have examined the relationship between polypharmacy and the number of consulting institutions. A single-center study reported the relationship between polypharmacy and the department visited by older adult patients at a medium-sized hospital (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). We previously reported a correlation between the number of medical institutions visited and polypharmacy through questionnaire-based data collection targeting older adults in a single city in Japan (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e Based on an analysis of medical and care claims data, our study revealed a significant correlation between the number of medical institutions visited and the total number of medications and PIMs. Careful consideration of the advantages and disadvantages of a free-access system and the need for gatekeepers to oversee patient prescriptions may be necessary.\u003c/p\u003e \u003cp\u003eOur study has several limitations: The data were limited to the National Health Insurance or Medical Insurance for the elderly in the latter stage of life in Ibaraki Prefecture in the Kanto region of Japan. Employee Health Insurance data are unavailable. This study focused exclusively on orally administered medications and excluded topical and injectable formulations. In addition, medications administered weekly or monthly, such as those prescribed once a week or once a month, were omitted, as only drugs prescribed for \u0026ge;\u0026thinsp;14 days within three months were counted. Further research using nationwide databases is required to analyze the trends and regional differences across Japan. This study was cross-sectional; therefore, outcomes cannot be evaluated based on the factors extracted from it. Misclassification of the CCI is likely because it is based on the diagnoses recorded in medical claims.\u003c/p\u003e \u003cp\u003eIn conclusion, most adults aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years using LTC services were in a state of polypharmacy. Additionally, nearly 70% of the patients had one or more PIMs. High CCI scores and a large number of consulting institutions were associated with a higher risk of polypharmacy and PIMs. Conversely, nursing home residents, senior daycare services, and short-stay services may contribute to reducing polypharmacy and PIMs. Therefore, a nationwide cohort study is warranted.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSH designed the study, performed the data analysis, and wrote the paper. JK supported the research and data analysis design and revised the manuscript. MI, SH, MK, and HK revised the manuscript. NT supervised the study and revised the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are grateful to the members of the Health Service Research Department at the University of Tsukuba and to Editage (www.editage.jp) for English language editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the JSPS KAKENHI (grant number: JP23K09521).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets for individual information generated and/or analyzed during the current study, which includes LTC insurance claims data and medical insurance claims data are not publicly available because the local government of Ibaraki Prefecture owns the original data and only approved the secondary use of the data for the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest disclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSHamada is an endowed chair\u0026nbsp;funded by donations from Hakue Technology, PROUMED, Japan BioProducts, Towa Pharmaceutical, Yellow Eight, and Sugi Holdings. SHamada received research funding from SOMPO Care, Inc. outside of this work.\u003c/p\u003e\n\u003cp\u003eThe other authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Ethics Committee of the Faculty of Medicine, University of Tsukuba (approval no.1595-5) approved this study and waived the requirement for informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient consent statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAndrew MK, Purcell CA, Marshall EG, Varatharasan N, Clarke B, Bowles SK. Polypharmacy and use of potentially inappropriate medications in long-term care facilities: does coordinated primary care make a difference? Int J Pharm Pract 2018 Aug 26(4):318\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHamada S, Iwagami M, Sakata N, Hattori Y, Kidana K, Ishizaki T, et al. Changes in Polypharmacy and Potentially Inappropriate Medications in Homebound Older Adults in Japan, 2015\u0026ndash;2019: a Nationwide Study. J Gen Intern Med. 2023 Dec;38(16):3517\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang YP, Huang SK, Tao P, Chien CW. A population-based study on the association between acute renal failure (ARF) and the duration of polypharmacy. BMC Nephrol 2012 Dec 13:96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBy the American Geriatrics Society Beers Criteria Update Expert P. American Geriatrics. Society 2023 updated AGS Beers Criteria(R) for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023 Apr;71(7):2052\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLalic S, Sluggett JK, Ilomaki J, Wimmer BC, Tan EC, Robson L et al. Polypharmacy and Medication Regimen Complexity as Risk Factors for Hospitalization Among Residents of Long-Term Care Facilities: A Prospective Cohort Study. J Am Med Dir Assoc 2016 Nov 17(11):1067 e1- e6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbe T, Tamiya N, Kitahara T, Tokuda Y. Polypharmacy as a risk factor for hospital admission among ambulance-transported old-old patients. Acute Med Surg. 2016 Apr;3(2):107\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKomiya H, Umegaki H, Asai A, Kanda S, Maeda K, Shimojima T et al. Factors associated with polypharmacy in elderly home-care patients. Geriatr Gerontol Int 2018 Jan 18(1):33\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO'Dwyer M, Peklar J, McCallion P, McCarron M, Henman MC. Factors associated with polypharmacy and excessive polypharmacy in older people with intellectual disability differ from the general population: a cross-sectional observational nationwide study. BMJ Open 2016 Apr 6(4):e010505.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSlater N, White S, Venables R, Frisher M. Factors associated with polypharmacy in primary care: a cross-sectional analysis of data from The English Longitudinal Study of Ageing (ELSA). BMJ Open 2018 Mar 8(3):e020270.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDelara M, Murray L, Jafari B, Bahji A, Goodarzi Z, Kirkham J, et al. Prevalence and factors associated with polypharmacy: a systematic review and Meta-analysis. BMC Geriatr. 2022 Jul;22(1):601.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJokanovic N, Tan EC, Dooley MJ, Kirkpatrick CM, Bell JS. Prevalence and factors associated with polypharmacy in long-term care facilities: a systematic review. J Am Med Dir Assoc. 2015 Jun;16(6):e5351\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLopez-Rodriguez JA, Rogero-Blanco E, Aza-Pascual-Salcedo M, Lopez-Verde F, Pico-Soler V, Leiva-Fernandez F, et al. Potentially inappropriate prescriptions according to explicit and implicit criteria in patients with multimorbidity and polypharmacy. MULTIPAP: A cross-sectional study. PLoS One Aug. 2020;15(8):e0237186.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaruoka H, Hamada S, Hattori Y, Arai K, Arimitsu K, Higashihara K, et al. Changes in chronic disease medications after admission to a Geriatric Health Services Facility: A multi-center prospective cohort study. 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The associations of multimorbidity with the sum of annual medical and long-term care expenditures in Japan. BMC Geriatr. 2019 Dec;19(1):69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQuan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011 Mar;173(6):676\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIshizaki T, Mitsutake S, Hamada S, Teramoto C, Shimizu S, Akishita M, Ito H. Drug prescription patterns and factors associated with polypharmacy in \u0026gt;\u0026thinsp;1 million older adults in Tokyo. Geriatr Gerontol Int. 2020 Apr;20(4):304\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGurwitz JH, Field TS, Judge J, Rochon P, Harrold LR, Cadoret C, et al. The incidence of adverse drug events in two large academic long-term care facilities. Am J Med. 2005;Mar118(3):251\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Vries M, Seppala LJ, Daams JG, van de Glind EMM, Masud T, van der Velde N, et al. Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: I. Cardiovascular Drugs. J Am Med Dir Assoc. 2018 Apr;19(4):371. e1- e9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO'Mahony D, Cherubini A, Guiteras AR, Denkinger M, Beuscart JB, Onder G, et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 3. Eur Geriatr Med. 2023 Aug;14(4):625\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKojima T, Hamaya H, Ishii S, Hattori Y, Akishita M. Association of disability level with polypharmacy and potentially inappropriate medication in community dwelling older people. Arch Gerontol Geriatr. 2023 Mar;106:104873.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpinewine A, Evrard P, Hughes C. Interventions to optimize medication use in nursing homes: a narrative review. Eur Geriatr Med. 2021 Jun;12(3):551\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSvensson M, Ekstrom H, Elmstahl S, Rosso A. Association of polypharmacy with occurrence of loneliness and social isolation among older adults. Arch Gerontol Geriatr. 2024 Jan;116:105158.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCook EA, Duenas M, Harris P. Polypharmacy in the Homebound Population. Clin Geriatr Med. 2022 Nov;38(4):685\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVyas MV, Watt JA, Yu AYX, Straus SE, Kapral MK. The association between loneliness and medication use in older adults. Age Ageing. 2021 Mar;50(2):587\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen AC, Epstein AM, Joynt Maddox KE, Grabowski DC, Orav EJ, Barnett ML. Impact of dementia special care units for short-stay nursing home patients. J Am Geriatr Soc. 2023 Mar;72(3):767\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoomer L, Downer B, Thomas KS. Relationship between Functional Improvement and Cognition in Short-Stay Nursing Home Residents. J Am Geriatr Soc. 2019 Mar;67(3):553\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoriyama Y, Tamiya N, Kawamura A, Mayers TD, Noguchi H, Takahashi H. Effect of short-stay service use on stay-at-home duration for elderly with certified care needs: Analysis of long-term care insurance claims data in Japan. PLoS One 2018 Aug 13(8):e0203112.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEltaybani S, Kawase K, Kato R, Inagaki A, Li CC, Shinohara M, et al. Effectiveness of home visit nursing on improving mortality, hospitalization, institutionalization, satisfaction, and quality of life among older people: Umbrella review. Geriatr Nurs. 2023 May;51:330\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDevik SA, Olsen RM, Fiskvik IL, Halbostad T, Lassen T, Kuzina N, Enmarker I. Variations in drug-related problems detected by multidisciplinary teams in Norwegian nursing homes and home nursing care. Scand J Prim Health Care. 2018 Jul;36(3):291\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKashiwagi M, Tamiya N, Sato M, Yano E. Factors associated with the use of home-visit nursing services covered by the long-term care insurance in rural Japan: a cross-sectional study. BMC Geriatr. 2013 Dec;13:1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKojima T, Mizokami F, Akishita M. Geriatric management of older patients with multimorbidity. Geriatr Gerontol Int 2020; Dec 20(12):1105\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNomoto S, Nakanishi Y. [Investigation of polypharmacy in late-stage elderly patients visiting a community hospital outpatient unit]. Nihon Ronen Igakkai Zasshi. 2011 Jan;48(3):276\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuzuki T, Iwagami M, Hamada S, Matsuda T, Tamiya N. Number of consulting medical institutions and risk of polypharmacy in community-dwelling older people under a healthcare system with free access: a cross-sectional study in Japan. BMC Health Serv Res. 2020 Dec;20(1):359.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"cross-sectional study, long-term care, older adults, potentially inappropriate medication, polypharmacy","lastPublishedDoi":"10.21203/rs.3.rs-4470744/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4470744/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eOlder adults requiring care often have multiple morbidities that lead to polypharmacy, including the use of potentially inappropriate medications (PIMs), leading to increased medical costs and adverse drug effects. We conducted a cross-sectional study to clarify the actual state of drug prescriptions and the background of polypharmacy and PIMs.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eUsing long-term care (LTC) and medical insurance claims data in the Ibaraki Prefecture from April 2018 to March 2019, we included individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;65 who used LTC services. The number of drugs prescribed for \u0026ge;\u0026thinsp;14 days and the number of PIMs were counted. A generalized linear model was used to analyze the association between the backgrounds of individuals and the number of drugs; logistic regression analysis was used for the presence of PIMs.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eHerein, 67,531 older adults who received LTC services were included. The median number of total prescribed medications and PIMs was 7(IQR 5\u0026ndash;9) and 1(IQR 0\u0026ndash;1), respectively. The main PIMs were loop diuretics/aldosterone antagonists, benzodiazepines/similar hypnotics, and nonsteroidal anti-inflammatory drugs. Multivariate analysis revealed that the number of medications and presence of PIMs were significantly higher in patients with comorbidities and in those visiting multiple medical institutions. However, patients requiring care level\u0026thinsp;≧\u0026thinsp;1, nursing home residents, users of short-stay service, and senior daycare were negatively associated with polypharmacy and PIMs.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003ePolypharmacy and PIMs are frequently observed in older adults who require LTC. This was prominent among individuals with comorbidities and at multiple consulting institutions. Therefore, a nationwide cohort study is required.\u003c/p\u003e","manuscriptTitle":"Polypharmacy and potentially inappropriate medications in older adults who use long-term care services: A cross-sectional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-15 17:45:00","doi":"10.21203/rs.3.rs-4470744/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-17T16:53:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-16T14:26:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-16T14:24:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Geriatrics","date":"2024-05-24T07:31:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f30871bc-63f7-487a-94bb-018e0452e91e","owner":[],"postedDate":"July 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-26T16:09:25+00:00","versionOfRecord":{"articleIdentity":"rs-4470744","link":"https://doi.org/10.1186/s12877-024-05296-4","journal":{"identity":"bmc-geriatrics","isVorOnly":false,"title":"BMC Geriatrics"},"publishedOn":"2024-08-21 15:57:47","publishedOnDateReadable":"August 21st, 2024"},"versionCreatedAt":"2024-07-15 17:45:00","video":"","vorDoi":"10.1186/s12877-024-05296-4","vorDoiUrl":"https://doi.org/10.1186/s12877-024-05296-4","workflowStages":[]},"version":"v1","identity":"rs-4470744","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4470744","identity":"rs-4470744","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}