[Polypharmacy in older people].

After the publication of the guidelines about the safe drug therapy for older people in 2015 by the Japan Geriatrics Society, the risk of polypharmacy has become popular. Older people are likely to have multimorbidity, resulting in the use of multiple drugs. This not only increases the frequency of side effects, but also increase confusion and difficulty in medication management and adherence. Polypharmacy is the problem related to these complicated drug therapies and will increase by age. It is necessary to review drugs and resolve polypharmacy without making comorbid conditions worth. To carry out effective medication reviews, the guidance established by the Ministry of Health, Labor and Welfare introduced that geriatric assessment is essential for those with polypharmacy, since not only all medical conditions, but also physical and cognitive functions, medications, living environment, and caregivers should be taken into consideration when discontinuing drugs. When tapering, potentially inappropriate medications (PIMs) should be always the targets, and PIMs drug lists such as the Beers criteria and STOPP/START became very popular in overseas. Even after the reductions, careful attention should be paid to changes in the patient's condition. For drugs that are continued, continuous checks are required to ensure compliance with patients' medication adherence. There are many possible reasons for poor medication adherence, and it will be difficult to improve unless we identify what the cause is in each patient, and making the prescriptions simple may be necessary.

Association of pneumonia admission with polypharmacy and drug use in community-dwelling older people.

AIM: The purpose of the present study was to clarify the association of pneumonia admission with polypharmacy and specific drug use in community-dwelling older people. METHODS: Using health insurance and long-term care insurance data from Kure city in Japan, we retrospectively collected data for older community-dwelling people (aged ≥65 years) from April 2017 to March 2019. The outcome was pneumonia admission. We carried out multivariate logistic regression analysis to identify the association of pneumonia admission with polypharmacy (≥5 drugs), the use of psychotropic drugs or anticholinergics with adjustment for patient backgrounds, such as comorbidity, and the daily life independence level for the older people with disability. RESULTS: Of 59 040 older people, 4017 (6.8%) participants were admitted for pneumonia in 2 years. The ratio of polypharmacy, and the use of psychotropic drugs and anticholinergics in the admission group were significantly higher than the non-admission group. Multivariate logistic regression analysis showed that polypharmacy (odds ratio 1.29, 95% confidence interval 1.18-1.41), and the use of conventional antipsychotic drugs (odds ratio 1.39, 95% confidence interval 1.02-1.90), atypical antipsychotic drugs (odds ratio 1.67, 95% confidence interval 1.37-2.05) and anticholinergics (odds ratio 1.22, 95% confidence interval 1.13-1.33) were significantly associated with pneumonia admission. CONCLUSION: The present results suggest that polypharmacy, and the use of psychotropic drugs and anticholinergics are risk factors for pneumonia admission. Geriatr Gerontol Int 2024; 24: 404-409.

Medication overload: A closer look at polypharmacy and potentially inappropriate medications among older people in Taiwan and Japan.

BACKGROUND: Polypharmacy and potentially inappropriate medications (PIM) are widely recognized as vital quality indicators of pharmacotherapy in older adults. As Taiwan and Japan grapple with the ongoing challenges of population aging, obtaining an accurate understanding of the prevalence of these indicators is crucial for developing effective strategies to optimize pharmacotherapy in older populations. The present study aims to comprehensively evaluate the prevalence of polypharmacy and PIMs in Taiwan and two Japanese cohorts, shedding light on the similarities and differences in prescribing practices across these populations. METHODS: This study employed a cross-sectional design to investigate individuals aged ≥65 years in Taiwan, as well as two Japanese cohorts: Japan Cohort 1 (dispensing data from chain pharmacies; year 2014 and 2019) and Japan Cohort 2 (claims data; year 2017 and 2019). The prescription records of these participants were collected from the national claims database in Taiwan for the years 2014, 2017, and 2019. To identify polypharmacy and hyper-polypharmacy, the study defined the use of 5-9 and 10+ drugs, respectively. Furthermore, the study identified PIMs based on the STOPP-J criteria. Notably, the study further explored the most frequently used PIMs (by categories) in Taiwan. RESULTS: In the year 2019, the prevalence of polypharmacy exhibited similar rates in Taiwan (35.4%) and Japan Cohort 2 (33.1%), while surpassing that of Japan Cohort 1 (25.6%). Nonetheless, the incidence of PIMs in Taiwan was the highest (66.5%), exceeding those of the two Japanese cohorts (Cohort 1: 43.7% and Cohort 2: 40.2%) in the same year. Notably, the top three categories of commonly used PIMs in Taiwan comprised non-steroidal anti-inflammatory drugs (NSAIDs), antithrombotic drugs, and benzodiazepines. CONCLUSIONS: This study highlights the varying prevalence of polypharmacy and PIMs between Taiwan and Japan, but emphasizes the need for collaborative efforts towards optimizing pharmacotherapy in older adults.

Polypharmacy with potentially inappropriate medications as a risk factor of new onset sarcopenia among community-dwelling Japanese older adults: a 9-year Kashiwa cohort study.

BACKGROUND: Clinical evidence demonstrating a longitudinal association between prescribed medications and sarcopenia onset is lacking. We investigated the association of polypharmacy (the use of five or more medications) and potentially inappropriate medications (PIMs) with sarcopenia risk in community-dwelling older adults. METHODS: In this longitudinal population-based cohort study, 2,044 older residents with no long-term care needs were randomly selected from a community in Kashiwa, Japan. Baseline data collection was conducted in 2012, with follow-ups in 2013, 2014, 2016, 2018, and 2021. Prescribed medications and PIMs (drugs listed in the Screening Tool for Older Person's Appropriate Prescriptions for the Japanese or potentially muscle-wasting drugs) were identified through interviews. New-onset sarcopenia was identified according to the 2019 criteria of the Asian Working Group for Sarcopenia over a 9-year period and analyzed. We used Cox proportional hazards models to test the longitudinal association of prescribed medications with sarcopenia onset. RESULTS: Of the 1,549 participants without sarcopenia at baseline (mean age, 72.5 ± 5.5 years; 49.1% women; median and interquartile range, 6.0 [4.0-9.0] years), 230 experienced new-onset sarcopenia during the follow-up. After adjusting for confounders, polypharmacy combined with PIM use was strongly associated with new-onset sarcopenia (adjusted hazard ratio, 2.35; 95% confidence interval, 1.58-3.51; P < 0.001). No significant associations were observed for either PIM use or polypharmacy alone. CONCLUSIONS: Polypharmacy combined with PIM use, but not polypharmacy alone, was associated with an increased risk of new-onset sarcopenia over the 9-year follow-up period among community-dwelling older adults. Limiting polypharmacy and imposing the prescription of appropriate medications may facilitate sarcopenia prevention.

Changes in chronic disease medications after admission to a Geriatric Health Services Facility: A multi-center prospective cohort study.

Older adults often receive polypharmacy, including some medications for chronic diseases. Nutritional management after admission to a nursing home may enable to deprescribe some chronic disease medications. This study aimed to investigate the status of deprescribing of chronic disease medications among nursing home residents, and to assess the appropriateness based on changes of laboratory test values and nutritional status. A multi-center prospective cohort study was conducted in 6 Geriatric Health Services Facilities, a major type of nursing homes in Japan. Newly admitted residents aged ≥ 65 years who took ≥1 medication for hypertension, diabetes, or dyslipidemia at admission were recruited. Participants who stayed for 3 months were included in the analysis. Medications at admission and 3 months after admission and situations for deprescribing were investigated. Changes in body mass index, blood pressure, laboratory tests (e.g., cholesterol and hemoglobin A1c levels), energy intake, and International Classification of Functioning, Disability and Health staging were evaluated. Sixty-nine participants (68% female, 62% aged ≥ 85 years) were included. At admission, 60 participants had medications for hypertension, 29 for dyslipidemia, and 13 for diabetes. Those receiving lipid-modifying drugs (mainly statins) decreased from 29 to 21 (72%; P = .008), since their cholesterol levels was within the normal range or was low at admission, and they had no history of cardiovascular events. However, there were no statistically significant changes in the frequencies of antihypertensive drugs (60 to 55; 92%; P = .063) or antidiabetic drugs (13 to 12; 92%; P = 1.000). During the 3-month observation, body mass index and diastolic blood pressure decreased, while energy intake and serum albumin level increased. Nutritional management after admission to a ROKEN may facilitate appropriate deprescribing of lipid-modifying drugs, by offseting the effects of discontinuation of these drugs.

Association of disability level with polypharmacy and potentially inappropriate medication in community dwelling older people.

AIMS: To investigate the influence of disability severity level on polypharmacy and the prescription of potentially inappropriate medication (PIM) using health insurance and long-term care (LTC) insurance claim data. METHODS: Data were obtained from a health-care insurance and long-term care insurance claims database of citizens of Kure city, Japan, in April 2017. Data including age, sex, and drug profile were obtained, and the level of LTC needs was used to measure disability level. Factors associated with polypharmacy (≥5 prescribed drugs) and PIM prescription (≥1 PIM) defined by STOPP-J were analyzed statistically. RESULTS: Among 67,169 people aged ≥65 (mean age 77.2 ± 7.9, male 40.7%), the frequency of polypharmacy increased with age until 85-89 (male 58.3%, female 57.6%) in both genders, and polypharmacy was most prevalent in those at the mildest LTC level (support level: male 68.9%, female 73.7%). PIM prescriptions was also frequent in those with LTC needs. On multiple logistic regression analysis, polypharmacy was significantly associated with older age and LTC needs, and PIM prescription was associated with older age and higher LTC level, suggesting that there is a large difference in prescription according to the person's age and disability level. CONCLUSION: Polypharmacy was prevalent especially in older persons which peaked at the age of 85-89 or at mild disability level, and PIM prescription was prevalent in those with older age and higher care levels. When optimizing polypharmacy or PIM prescription in older patients, healthcare providers should focus on not only age but also disability level.

Drug prescribing changes in the last year of life among homebound older adults: national retrospective cohort study.

OBJECTIVES: This study aimed to evaluate the prescription patterns of drugs during the last year of life in homebound older adults who received home medical care. METHODS: We used a nationwide claims database in Japan and selected older adults aged ≥75 years who received home medical care services from ≥12 months before their death. We evaluated medications prescribed 12 months before death (month 12), 3 months before death (month 3) and in the last month of life (month 1). We explored the factors associated with the decreased number of cardiovascular preventive drugs from month 12 to both month 3 and month 1. RESULTS: A total of 118 661 participants were included, and the majority were aged ≥90 years and women. The prevalence of cardiovascular preventive drugs decreased but remained common in month 1, which included antihypertensives (34.7%), antiplatelets (15.9%), oral anticoagulants (7.6%), antidiabetic drugs (7.3%) and lipid-lowering drugs (6.1%). The relative decrease from month 12 to month 1 was the largest for lipid-lowering drugs (44.8%) and the smallest for oral anticoagulants (13.6%). Among other drugs, laxatives (enema), antiemetics, oral corticosteroids, analgesics, expectorants, bronchodilators and antibiotics showed a large relative increase. Older age, duration of home medical care services for <1 year and diagnoses of cancer, dementia and Parkinson's disease were associated with a greater likelihood of a decreased number of cardiovascular preventive drugs. CONCLUSIONS: There is room for deprescribing to avoid inappropriate polypharmacy by balancing preventive and symptom management drugs in those receiving home medical care with a limited life expectancy.

Malnutrition and depression as predictors for 30-day unplanned readmission in older patient: a prospective cohort study to develop 7-point scoring system.

BACKGROUND: Readmission is related to high cost, high burden, and high risk for mortality in geriatric patients. A scoring system can be developed to predict the readmission of older inpatients to perform earlier interventions and prevent readmission. METHODS: We followed prospectively inpatients aged 60 years and older for 30 days, with initial comprehensive geriatric assessment (CGA) on admission in a tertiary referral centre. Patients were assessed with CGA tools consisting of FRAIL scale (fatigue, resistance, ambulation, illness, loss of weight), the 15-item Geriatric Depression Scale, Mini Nutritional Assessment short-form (MNA-SF), the Barthel index for activities of daily living (ADL), Charlson Comorbidity Index (CCI), caregiver burden based on 4-item Zarit Burden Index (ZBI), and cognitive problem with Abbreviated Mental Test (AMT). Demographic data, malignancy diagnosis, and number of drugs were also recorded. We excluded data of deceased patients and patients transferred to other hospitals. We conducted stepwise multivariate regression analysis to develop the scoring system. RESULTS: Thirty-day unplanned readmission rate was 37.6 %. Among 266 patients, 64.7 % of them were malnourished, and 46.5 % of them were readmitted. About 24 % were at risk for depression or having depressed mood, and 53.1 % of them were readmitted. In multivariate analysis, nutritional status (OR 2.152, 95 %CI 1.151-4.024), depression status (OR 1.884, 95 %CI 1.071-3.314), malignancy (OR 1.863 95 %CI 1.005-3.451), and functional status (OR 1.584, 95 %CI 0.885-2.835) were included in derivation of 7 score system. The scoring system had maximum score of 7 and incorporated malnutrition (2 points), depression (2 points), malignancy (2 points), and dependent functional status (1 point). A score of 3 or higher suggested 82 % probability of readmission within 30 days following discharge. Area under the curve (AUC) was 0.694 (p = 0.001). CONCLUSIONS: Malnutrition, depression, malignancy and functional problem are predictors for 30-day readmission. A practical CGA-based 7 scoring system had moderate accuracy and strong calibration in predicting 30-day unplanned readmission for older patients.

Screening of Alzheimer's disease by facial complexion using artificial intelligence.

Despite the increasing incidence and high morbidity associated with dementia, a simple, non-invasive, and inexpensive method of screening for dementia is yet to be discovered. This study aimed to examine whether artificial intelligence (AI) could distinguish between the faces of people with cognitive impairment and those without dementia.121 patients with cognitive impairment and 117 cognitively sound participants were recruited for the study. 5 deep learning models with 2 optimizers were tested. The binary differentiation of dementia / non-dementia facial image was expressed as a "Face AI score". Xception with Adam was the model that showed the best performance. Overall sensitivity, specificity, and accuracy by the Xception AI system and AUC of the ROC curve were 87.31%, 94.57%, 92.56%, and 0.9717, respectively. Close and significant correlations were found between Face AI score and MMSE (r = -0.599, p < 0.0001). Significant correlation between Face AI score and chronological age was also found (r = 0.321, p < 0.0001). However, MMSE score showed significantly stronger correlation with Face AI score than chronological age (p < 0.0001). The study showed that deep learning programs such as Xception have the ability to differentiate the faces of patients with mild dementia from that of patients without dementia, paving the way for future studies into the development of a facial biomarker for dementia.

Geriatric management of older patients with multimorbidity.

Older patients tend to have multimorbidity represented by multiple chronic diseases or geriatric conditions due to aging changes of organs, which require a variety of medical management. Currently, there are no sufficient disease treatment guidelines for older people with multimorbidity, therefore physicians have difficulty managing multimorbidity, such as which diseases should be treated intensively or to what extent the conditions should be improved. Furthermore, there are other points to be considered when initiating the treatment of diseases. For example, physicians must assess physical function. Some people have no difficulty with ambulation, but some are bedridden and have difficulty getting up on their own. As there are differences in disease severity, comorbid conditions and life expectancy, there should be differences in deciding treatment and prescribing drugs. It may be necessary to change the option for treatment depending on cognitive function, the living environment and the care environment, using comprehensive geriatric assessments. In addition, when treating multimorbidity, patients tend to have polypharmacy, which is a risk for adverse drug events. Because of this, it is necessary to consider dose reduction and drug discontinuation in patients with polypharmacy. Because of the global increase in older patients with multimorbidity, developing an essential method for managing multimorbidity is an urgent issue. More research and practices are necessary to achieve high-quality care in patients with multimorbidity. Geriatr Gerontol Int 2020; 20: 1105-1111.

Potential prescribing omissions may have no influence on cause of death in care-dependent older adults with percutaneous endoscopic gastrostomy tube.

AIM: Studies of medication use in patients with a percutaneous endoscopic gastrostomy (PEG) tube have not been conducted adequately. The aim of this study was to describe medication use of care-dependent older adults with PEG and evaluate whether potential prescribing omissions (PPO) would affect the cause of death or acute illness. METHODS: In a geriatric long-term care hospital, 116 inpatients aged ≥65 years with insertion of a PEG tube because of dysphagia were enrolled and followed for 2 years: 2016-2018. The patients were divided into two groups, i.e., group A (who died between 2016 and 2018) and group B (who continued to be hospitalized in 2018). Clinical data and prescribed medications were recorded. Logistic regression models were conducted to assess the associations between survival and variables: age, gender, serum albumin level, serum creatinine level, body mass index (BMI), number of drugs and PPO. RESULTS: The patients' mean age was 85.3 ± 10.2 years, 57.8% were women and the mean number of drugs was 6.8 ± 3.5. Medications for managing symptoms, such as constipation and gastrointestinal symptoms, were commonly prescribed. The most common PPO medications were antiplatelet agents and anticoagulants. On logistic regression analysis, PPO had no influence on the cause of death or acute illness. Lower age, higher serum albumin level and body mass index were associated with survival in both univariate and multivariate models. CONCLUSIONS: Polypharmacy was prevalent in patients with PEG. Given the finding that PPO had no influence on health outcome, rational deprescribing could be warranted. Geriatr Gerontol Int 2020; 20: 961-966.

Utilization of drugs for the management of cardiovascular diseases at intermediate care facilities for older adults in Japan.

OBJECTIVES: No established approaches exist for the pharmacological management of cardiovascular diseases (CVDs) in residents of long-term care facilities (LTCFs). This study aimed to evaluate the use of drugs for CVD prevention and treatment (CVD-related drugs) in a major type of LTCF in Japan. METHODS: This study included 1318 randomly selected residents at 349 intermediate care facilities for older adults (called Roken). Prescriptions were investigated at admission and two months after admission according to therapeutic categories. Logistic regression was used to identify residents' characteristics that were associated with prescriptions of CVD-related drugs. RESULTS: Prescriptions of all types of drugs and CVD-related drugs decreased in 36 % and 16 % of residents, respectively. Half of the residents received antihypertensives, a quarter received antiplatelets and diuretics, whereas one-tenth received antidiabetics, oral anticoagulants, and lipid-modifying drugs. The prevalence of most of individual drug categories were similar among residents with different physical or cognitive function, except for fewer antihypertensive and lipid-modifying drugs in those with severe cognitive disability. Adjusted analyses for prescriptions at two months after admission revealed that bedridden residents were more likely to be prescribed diuretics but less likely to be prescribed antihypertensives, antiplatelets, or lipid-modifying drugs. Residents with severe cognitive disability were less likely to be prescribed antihypertensives or lipid-modifying drugs. A known history of cardiovascular events was associated with greater use of CVD-related drugs. CONCLUSION: CVD-related drugs were commonly prescribed for Roken residents, including those with low physical and cognitive functions. Deprescribing may contribute to the optimization of pharmacotherapy in LTCF residents.

Risk factors for adverse drug reactions in older inpatients of geriatric wards at admission: Multicenter study.

AIM: To investigate the characteristics of adverse drug reactions (ADR) and their risk factors among very old patients in five geriatric wards in Japan. METHODS: A retrospective observational multicenter study was carried out to investigate factors related to ADR in older inpatients from geriatric wards of five university hospitals in Japan. Data including drugs profile and short-form comprehensive geriatric assessment were obtained from medical charts. ADR were identified from geriatrician's reports. For each ADR, symptoms and causal drugs were clarified, and factors associated with ADR were analyzed statistically. RESULTS: In 1155 patients (52.5% women, mean age 82.8 ± 7.0 years), the proportion with ADR was 15.4%. There was a great variety of signs and symptoms of ADR, and a great variety of drugs suspected to be the cause of ADR. On multiple logistic regression analysis, ADR was significantly associated with an increase in drugs (odds ratio 1.11, 95% CI 1.07-1.16) and emergency admission (odds ratio 2.76, 95% CI 1.82-4.15). Receiver operating characteristic curve analysis showed that the optimal cut-off number of drugs for predicting ADR was ≥7. CONCLUSIONS: In geriatric inpatients, polypharmacy (especially ≥7 drugs) and emergency admission were associated with ADR. Because there was a great variety of ADR in the study, clinicians must consider reviewing all drugs to prevent adverse drugs reactions during admission in this vulnerable population. Geriatr Gerontol Int 2019; ••: ••-••. Geriatr Gerontol Int 2020; 20: 144-149.

Low-Intensity Exercise Suppresses CCAAT/Enhancer-Binding Protein δ/Myostatin Pathway Through Androgen Receptor in Muscle Cells.

BACKGROUND: Androgen production following exercise has been suggested to contribute anabolic actions of muscle. However, the underlying mechanisms of the androgen receptor (AR) in androgen's action are still unclear. OBJECTIVE: In the present study, we examined androgen/AR-mediated action in exercise, especially for the suppression of myostatin, a potent negative regulator of muscle mass. METHODS: To examine the effects of exercise, we employed low-intensity exercise in mice and electric pulse stimulation (EPS) in C2C12 myotubes. Androgen production by C2C12 myotubes was measured by enzyme-linked immunosorbent assay. To block the action of AR, we pretreated C2C12 myotubes with flutamide. Quantitative real-time polymerase chain reaction was used to determine the expression levels of proteolytic genes including CCAAT/enhancer-binding protein delta (C/EBPδ), myostatin and muscle E3 ubiquitin ligases, as well as myogenic genes such as myogenin and PGC1α. The activation of 5'-adenosine-activated protein kinase and STAT3 was determined by Western blot analysis. RESULTS: Both mRNA and protein levels of AR significantly increased in skeletal muscle of low-intensity exercised mice and C2C12 myotubes exposed to EPS. Production of testosterone and dihydrotestosterone from EPS-treated C2C12 myotubes was markedly increased. Of interest, we found that myostatin was clearly inhibited by EPS, and its inhibition was significantly abrogated when AR was blocked by flutamide. To test how AR suppresses myostatin, we examined the effects of EPS on C/EBPδ because the promoter region of myostatin has several C/EBP recognition sites. C/EBPδ expression was decreased by EPS, and this decrease was negated by flutamide. IL-6 and phospho-STAT3 (pSTAT3) expression, the downstream pathway of myostatin, were decreased by EPS and this was also reversed by flutamide. Similar downregulation of C/EBPδ, myostatin, and IL-6 was seen in skeletal muscle of low-intensity exercised mice. CONCLUSIONS: Muscle AR expression and androgen production were increased by exercise and EPS treatment. As a mechanistical insight, it is suggested that AR inhibited myostatin expression transcriptionally by C/EBPδ suppression, which negatively influences IL-6/pSTAT3 expression and consequently contributes to the prevention of muscle proteolysis during exercise.

Testosterone inhibits aneurysm formation and vascular inflammation in male mice.

Abdominal aortic aneurysm (AAA), one of the pathological phenotypes of vascular aging, is characterized by aortic dilation with impaired arterial wall integrity. Recent epidemiologic studies have shown that men with AAA have lower serum testosterone compared to men without. However, the underlying mechanisms remain unclear. In this study, we investigated the effects of testosterone on AAA formation using a murine AAA model under the conditions of depletion and administration of testosterone. In wild-type male mice (C57BL/6J), AAA was induced by CaCl2 application and angiotensin II infusion at 5 weeks after castration. Exacerbated AAA formation was seen in castrated mice, compared with sham-operated mice. Histological analysis revealed marked infiltration of macrophages in the destroyed aorta and IL-6/pSTAT3 expression was significantly elevated, suggesting that AAA development by castration is attributable to pronounced inflammation. Conversely, both 4-week and 9-week administration of testosterone significantly prevented AAA formation, and improvement of histological findings was confirmed. Aortic F4/80, Il-1b and Il-6 expression were significantly inhibited both by testosterone administration. Indeed, mice with implanted flutamide exhibited exacerbated AAA formation and aortic F4/80, Il-1b and Il-6 expression were significantly increased. Taken together, these results demonstrate that testosterone depletion and AR blockade precede AAA formation, and conversely, testosterone administration could suppress AAA formation by regulating macrophage-mediated inflammatory responses. This anti-inflammatory action of testosterone/AR on AAA formation might provide a mechanistic insight into the vascular protective actions of testosterone and suggest that its proper administration or selective AR modulators might be novel therapeutic strategies for this aortic pathology.

Prevalence of cytochrome P450-mediated potential drug-drug interactions in residents of intermediate care facilities for older adults in Japan.

AIM: Limited information is available on the prevalence of drug-drug interactions (DDI) in residents of long-term care facilities who often receive multiple drugs. This study aimed to evaluate the prevalence of clinically relevant cytochrome P450-mediated potential DDI in residents of intermediate care facilities for older adults (called Roken) in Japan. METHODS: A nationwide drug utilization study was carried out for Roken residents in 2015 (up to five residents per facility). Potential DDI were identified with an explicit list of drugs that can be involved in clinically relevant cytochrome P450-mediated DDI in Japan. Logistic regression was used to evaluate the association of the number of drugs prescribed with the presence of potential DDI, adjusted for age, sex and long-term care needs level. RESULTS: The study included 1222 residents of 348 Roken who were prescribed two or more active drug substances. The participants who received ≥6 and ≥10 drugs represented 49% and 10% of total participants, respectively. In total, 42 two-drug combinations involving potential DDI were identified in 33 participants (2.7%) - benzodiazepines, proton pump inhibitors, calcium channel blockers and anti-epileptic drugs were frequently involved. The adjusted odds ratios for potential DDI were 2.84 (95% confidence interval 1.15-7.02) or 7.82 (95% confidence interval 2.96-20.70) in residents receiving six to nine drugs or ≥10 drugs, compared with those receiving two to five drugs. CONCLUSIONS: Approximately 3% of Roken residents were at risk for clinically relevant DDI. Reducing the number of drugs prescribed through medication reviews would mitigate the potential risk. Geriatr Gerontol Int 2019; 19: 513-517.

Identifying drug substances of screening tool for older persons' appropriate prescriptions for Japanese.

BACKGROUND: In 2015, the Japan Geriatric Society (JGS) updated "the Guidelines for Medical Treatment and its Safety in the elderly," accompanied with the Screening Tool for Older Persons' Appropriate Prescriptions for Japanese (STOPP-J): "drugs to be prescribed with special caution" and "drugs to consider starting." The JGS proposed the STOPP-J to contribute to improving prescribing quality; however, each decision should be carefully based on medical knowledge. The STOPP-J shows examples of commonly prescribed drug substances, but not all relevant drugs. This research aimed to identify substances using such coding, as a standardized classification system would support medication monitoring and pharmacoepidemiologic research using such health-related information. METHODS: A voluntary team of three physicians and two pharmacists identified possible approved medicines based on the STOPP-J, and matched certain drug substances to the Anatomical Therapeutic Chemical Classification (ATC) and the Japanese price list as of 2017 February. Injectables and externally used drugs were excluded, except for self-injecting insulin, since the STOPP-J guidelines are intended to cover medicines used chronically for more than one month. Some vaccines are not available in the Japanese price list since they not reimbursed through the national health insurance. RESULTS: The ATC 5th level was not available for 39 of the 235 identified substances, resulting in their classification at the ATC 4th level. Furthermore, among 26 combinations, 10 products were matched directly to the ATC 5th level of the exact substances, and others were linked to the ATC representing the combination or divided into multiple substances for classification if the combination was not listed in the ATC. CONCLUSION: This initial work demonstrates the challenge of matching ATC codes and the Japan standard commodity classification codes corresponding to STOPP-J substances. Since coding facilitates database analysis, the proposed drug list could be applied to research using large databases to examine prescribing patterns in patients older than 75 years or who are frail. Since ATC is not available for some substances, Japanese medicines need the process to be registered in the ATC for an effective screening tool to be developed for STOPP-J.

The Need for Actions Against Polypharmacy in Older People With Frailty.

Providing safe and effective drug therapy to older patients is challenging for physicians since there is not sufficient evidence to support the efficacy of these drugs and this population is susceptible to adverse drug reactions. Special consideration is needed when treating patients who require nursing care or who are at a stage prior to disability (i.e., frailty) because they may have limited life expectancies, complications, or organ dysfunction. Polypharmacy refers to the condition in which a patient is taking many drugs and, thus, is at an increased risk of adverse events. Although it is difficult to avoid polypharmacy in older people with frailty, the periodic review of drugs and reduction of dose or discontinuation of potentially inappropriate medications are needed to address this problem. This article reviews the association between frailty and polypharmacy and counteractions against polypharmacy in patients with frailty.

Screening Tool for Older Persons' Appropriate Prescriptions for Japanese: Report of the Japan Geriatrics Society Working Group on "Guidelines for medical treatment and its safety in the elderly".

AIM: In 2005, the Japan Geriatrics Society published a list of potentially inappropriate medication that was an extract from the "Guidelines for medical treatment and its safety in the elderly 2005." The 2005 guidelines are due for a revision, and a new comprehensive list of potentially inappropriate medications is required. METHODS: A total of 15 diseases, conditions and special areas related to their clinical care were selected. We originated clinical questions and keywords for these 15 areas, carried out a systematic review using these search criteria, and formulated guidelines applying the Grading of Recommendations Assessment, Development and Evaluation system advocated by Minds2014. If we did not find good evidence despite the drug being clinically important, we looked for evidence of efficacy and for disease-specific guidelines, and incorporated them into our guidelines. RESULTS: We selected 2098 articles (140 articles per area), and extracted another 186 articles through a manual search. We further added guidelines based on disease entity and made two lists, one of "drugs to be prescribed with special caution" and the other of "drugs to consider starting," primarily considering individuals aged 75 years or older or those who are frail or in need of special care. CONCLUSIONS: New lists of potentially inappropriate medications and potential prescribing omissions called "Screening Tool for Older Person's Appropriate Prescriptions for Japanese" were constructed. We anticipate that future studies will highlight more evidence regarding the safety of high-quality drugs, further improving the provision of appropriate medical care for the elderly. Geriatr Gerontol Int 2016: 16: 983-1001.