Latent metabolic bone disease, skeletal dysplasia and other conditions related to low bone formation among 38 patients with subtrochanteric femoral fractures: a retrospective observational study.

Subtrochanteric femoral fracture is rare and intractable due to the possible association with low bone formation. Retrospective analysis of 38 patients with subtrochanteric femoral fractures revealed that four patients suffered from disorders related to low bone formation and there were specific treatments for two of them. PURPOSE: The main aim of this study was to detect latent metabolic bone diseases and skeletal dysplasia associated with low bone formation among patients with morphologic atypical femoral fracture (AFF). A second aim was to evaluate the frequency of recognized risk factors, such as antiresorptive agents, glucocorticoids, and age. METHODS: Clinical information was retrospectively analyzed among 38 Japanese patients who were admitted to the Department of Orthopedic Surgery and Spinal Surgery and the Division of Emergency and Critical Care Medicine at the University of Tokyo Hospital with diagnoses of subtrochanteric fractures between February 2012 and March 2022. RESULTS: Among 38 patients (including 30 females), 21 patients were aged 75 and over. Ten patients had past oral glucocorticoid use, and 18 had past antiresorptive agent use. Two patients were diagnosed with hypophosphatemic osteomalacia after the development of fractures. One patient was suspected to be a carrier of a loss-of-function variant of alkaline phosphatase, biomineralization associated (ALPL), and one other patient had previously been genetically diagnosed with pycnodysostosis. Among four patients with a diagnosis or suspicion of these metabolic bone diseases and skeletal dysplasia, four had past clinical fractures, two had past subtrochanteric femoral fractures, and two had subtrochanteric femoral fractures on both sides. CONCLUSION: If clinicians encounter patients with morphologic AFF, latent diseases related to low bone formation should be carefully differentiated because appropriate treatment may prevent delayed union and recurrent fractures. Additionally, it may be desirable to exclude these bone diseases in advance before initiating long-term use of antiresorptive agents in osteoporotic patients by screening with serum alkaline phosphatase levels to reduce the risk of morphologic AFF.

[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.

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.

Questionnaires for the Assessment of Cognitive Function Secondary to Intake Interviews in In-Hospital Work and Development and Evaluation of a Classification Model Using Acoustic Features.

The number of people with dementia is increasing each year, and early detection allows for early intervention and treatment. Since conventional screening methods are time-consuming and expensive, a simple and inexpensive screening is expected. We created a standardized intake questionnaire with thirty questions in five categories and used machine learning to categorize older adults with moderate and mild dementia and mild cognitive impairment, based on speech patterns. To evaluate the feasibility of the developed interview items and the accuracy of the classification model based on acoustic features, 29 participants (7 males and 22 females) aged 72 to 91 years were recruited with the approval of the University of Tokyo Hospital. The MMSE results showed that 12 participants had moderate dementia with MMSE scores of 20 or less, 8 participants had mild dementia with MMSE scores between 21 and 23, and 9 participants had MCI with MMSE scores between 24 and 27. As a result, Mel-spectrogram generally outperformed MFCC in terms of accuracy, precision, recall, and F1-score in all classification tasks. The multi-classification using Mel-spectrogram achieved the highest accuracy of 0.932, while the binary classification of moderate dementia and MCI group using MFCC achieved the lowest accuracy of 0.502. The FDR was generally low for all classification tasks, indicating a low rate of false positives. However, the FNR was relatively high in some cases, indicating a higher rate of false negatives.

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.

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.

Combination of NMR Methods To Reveal the Interfacial Structure of a Pharmaceutical Nanocrystal and Nanococrystal in the Suspended State.

The detailed structure of a pharmaceutical nanosuspension was investigated using three nuclear magnetic resonance (NMR) methods: solid-state, solution-state, and high resolution-magic angle spinning (HR-MAS) NMR. Carbamazepine (CBZ) and CBZ-saccharin (SAC) cocrystal nanosuspensions were prepared by wet-milling with hydroxypropyl methylcellulose (HPMC) and sodium dodecyl sulfate (SDS) as stabilizing agents. Solid-state 13C NMR indicated the presence of not only the crystalline drug substance but also solid-state HPMC, even though HPMC was used as an aqueous solution to prepare the nanosuspensions. Solution-state 1H NMR of the nanosuspensions with and without ultracentrifugation pretreatment indicated that a fraction of the CBZ, SAC, and SDS formed a solid or semisolid phase on the surface of the nanoparticles and was in equilibrium between the dissolved and undissolved states. 1H HR-MAS NMR was highly effective in detecting and quantifying the semisolid phase on the surface of the nanoparticles. From these comprehensive NMR studies, it was concluded that the nanosuspension was composed of crystalline drug core particles surrounded by a semisolid phase consisting of the drug and stabilizing agents. The semisolid phase on the nanoparticle surface was in equilibrium with the solution phase and contributed to the stabilization of the nanoparticle by steric hindrance and electrostatic repulsion.

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.

Looking back to move forward: a twenty-year audit of herpes zoster in Asia-Pacific.

BACKGROUND: Herpes zoster (HZ) is a prevalent viral disease that inflicts substantial morbidity and associated healthcare and socioeconomic burdens. Current treatments are not fully effective, especially among the most vulnerable patients. Although widely recommended, vaccination against HZ is not routine; barriers in Asia-Pacific include long-standing neglect of adult immunisation and sparse local data. To address knowledge gaps, raise awareness, and disseminate best practice, we reviewed recent data and guidelines on HZ from the Asia-Pacific region. METHODS: We searched PubMed, Scopus, and World Health Organization databases for articles about HZ published from 1994 to 2014 by authors from Australia, China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, New Zealand, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. We selected articles about epidemiology, burden, complications, comorbidities, management, prevention, and recommendations/guidelines. Internet searches retrieved additional HZ immunisation guidelines. RESULTS: From 4007 retrieved articles, we screened-out 1501 duplicates and excluded 1264 extraneous articles, leaving 1242 unique articles. We found guidelines on adult immunisation from Australia, India, Indonesia, Malaysia, New Zealand, the Philippines, South Korea, and Thailand. HZ epidemiology in Asia-Pacific is similar to elsewhere; incidence rises with age and peaks at around 70 years - lifetime risk is approximately one-third. Average incidence of 3-10/1000 person-years is rising at around 5% per year. The principal risk factors are immunosenescence and immunosuppression. HZ almost always causes pain, and post-herpetic neuralgia is its most common complication. Half or more of hospitalised HZ patients have post-herpetic neuralgia, secondary infections, or inflammatory sequelae that are occasionally fatal. These disease burdens severely diminish patients' quality of life and incur heavy healthcare utilisation. CONCLUSIONS: Several countries have abundant data on HZ, but others, especially in South-East Asia, very few. However, Asia-Pacific countries generally lack data on HZ vaccine safety, efficacy and cost-effectiveness. Physicians treating HZ and its complications in Asia-Pacific face familiar challenges but, with a vast aged population, Asia bears a unique and growing burden of disease. Given the strong rationale for prevention, most adult immunisation guidelines include HZ vaccine, yet it remains underused. We urge all stakeholders to give higher priority to adult immunisation in general and HZ in particular.

Physicochemical Evaluation and Developability Assessment of Co-amorphouses of Low Soluble Drugs and Comparison to the Co-crystals.

To judge the developability and analyze functional mechanism of co-amorphouses, we investigated the physicochemical properties of co-amorphouses and compare the properties with the co-crystals having the same drug and counters. Co-amorphous compounds are a novel approach to improve the physicochemical properties of drugs. A co-amorphous is in an amorphous solid state allowing non-ionic interactions between drug molecules and counter molecules. The co-amorphous compounds composed of itraconazole (ITZ) with the organic carboxyl acid, fumaric acid (FA) or L-tartaric acid (TA), were prepared by mechanical grinding. Potential interactions within ITZ-FA co-amorphous were assessed by Raman spectroscopy. ITZ-FA co-amorphous was not crystallized as the co-crystal or as a single ITZ crystal, suggesting that the amorphous state, like the amorphous solid dispersion, was physically stable and that ITZ-FA co-amorphous was also chemically stable. In contrast, no clear interactions were observed within ITZ-TA co-amorphous, and the co-amorphous was physically stable but chemically unstable. The solubility of the co-amorphous state was much higher than those of ITZ crystal and the co-crystals and was almost identical to that of amorphous ITZ. A co-amorphous compound like ITZ-FA co-amorphous might be feasible to implement in the development of solid drug products and bring some merits compared to the co-crystals, and the function is governed by the interaction between a drug and a counter. The co-amorphous approach may be an effective strategy for drug development and can contribute to the production of novel drugs with improved functions.

[Drug-induced dementia].

Many drugs have been reported to induce not only delirium but also cognitive impairment. Some types of drugs are reported to induce dementia, and prolonged hypotension or hypoglycemia induced by overuse of antihypertensive drugs or oral antidiabetic drugs could result in dementia. Recently, taking multiple drugs with anticholinergic activity are reported to cause cognitive decline and anticholinergic burden should be avoided especially in patients with dementia. Drug-induced dementia can be prevented by avoiding polypharmacy and adhering to the saying 'start low and go slow' . Early diagnosis of drug-induced dementia and withdrawal of the offending drug is essential to improve cognitive function.

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.

Medical care priorities of community-dwelling older adults according to three dimensions of quality of life: Quality of daily living, satisfaction and happiness from birth to death, and human vitality.

AIM: Although the maintenance and improvement of quality of life (QoL) through holistic care are important in geriatric medical care, care priorities might differ depending on three essential aspects of QoL: the quality of daily living, satisfaction and happiness from birth to death, and human vitality, which are "Seikatsu," "Jinsei," "Seimei" in Japanese, respectively. We aimed to clarify these priorities in terms of medical care and examined how the definitions of QoL affected these priorities' rankings. METHODS: This cross-sectional study involved community-dwelling older adults aged ≥65 years living in Kashiwa City, Chiba Prefecture, Japan. The number of participants was 1550 (mean age, 76.1 ± 5.8 years; 699 women [45.1%]). A self-administered questionnaire distributed in advance was used to rank 12 items sought in medical care. Participants were randomly assigned to one of three groups and sent the corresponding questionnaire, which differed only in the definition of QoL. RESULTS: The top priorities for medical care were "effective treatment of illness," "improvement of physical function," and "maintaining a high level of activity." When QoL was defined as "the quality of daily living, satisfaction and happiness from birth to death, and human vitality," participants were significantly more likely to rank QoL improvement as one of the top three items (adjusted odds ratio, 1.46; 95% confidence interval, 1.03-2.05). CONCLUSIONS: As a medical care priority, older adults desire improvement of multidimensional elements of life, including human vitality. Health care providers should consider this when making medical care decisions. Geriatr Gerontol Int 2024; 24: 493-498.

Effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor, interleukin-6, and insulin-like growth factor-1 in monocyte in pre-frail older adults: A randomized double-blind placebo-controlled trial.

AIM: To investigate the effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor (VDR), interleukine-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in monocyte in pre-frail older adults. METHODS: We conducted a randomized double-blinded placebo-controlled clinical trial for 12 weeks, involving 120 pre-frail older adults who were randomized to the cholecalciferol group (cholecalciferol 4000 IU/day) or the placebo group. All subjects were given calcium lactate 500 mg/day. Hand grip strength and walking speed, as primary outcomes, were analyzed using intention-to-treat analysis. The expression of VDR, IGF-1 and IL-6 in monocytes, as secondary outcomes, were analyzed using per-protocol analysis. RESULTS: After a 12-week intervention, there was a significant increase in serum 25(OH)D levels in both groups, with the increase being higher in the cholecalciferol group than in the placebo group (49.05 vs. 24.01 ng/mL; P < 0.001). No statistically significant differences were observed in hand grip strength (P = 0.228) and walking speed (P = 0.734) between the groups. There were no differences in the expression of VDR (P = 0.513), IL-6 (P = 0.509), and IGF-1 (P = 0.503) monocytes between the groups. CONCLUSIONS: Cholecalciferol supplementation for 12 weeks increased serum 25(OH)D levels among pre-frail older adults. However, it did not improve hand grip strength and walking speed, and nor did it change the expression of VDR, IL-6, and IGF-1 in monocytes. Geriatr Gerontol Int 2024; 24: 554-562.

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.

Assessment of adjunct cognitive functioning through intake interviews integrated with natural language processing models.

In this article, we developed an interview framework and natural language processing model for estimating cognitive function, based on an intake interview with psychologists in a hospital setting. The questionnaire consisted of 30 questions in five categories. To evaluate the developed interview items and the accuracy of the natural language processing model, we recruited participants with the approval of the University of Tokyo Hospital and obtained the cooperation of 29 participants (7 men and 22 women) aged 72-91 years. Based on the MMSE results, a multilevel classification model was created to classify the three groups, and a binary classification model to sort the two groups. For each of these models, we tested whether the accuracy would improve when text augmentation was performed. The accuracy in the multi-level classification results for the test data was 0.405 without augmentation and 0.991 with augmentation. The accuracy of the test data in the results of the binary classification without augmentation was 0.488 for the moderate dementia and mild dementia groups, 0.767 for the moderate dementia and MCI groups, and 0.700 for the mild dementia and MCI groups. In contrast, the accuracy of the test data in the augmented binary classification results was 0.972 for moderate dementia and mild dementia groups, 0.996 for moderate dementia and MCI groups, and 0.985 for mild dementia and MCI groups.

Polymer-inducing chemical degradation of amorphous solid dispersions driven by drug-polymer interactions for physical stabilization.

Intermolecular interactions between active pharmaceutical ingredients (APIs) and carrier polymers are important for the long-term physical stability of amorphous solid dispersions (ASDs). However, the negative impact of intermolecular interactions on chemical stability has rarely been reported. In this study, the relationship between intermolecular interactions and physical and chemical stability was investigated using two ASDs composed of API and hydroxypropyl methylcellulose acetate succinate (HPMCAS) with different stabilities: ASD1 was physically stable but chemically unstable, whereas ASD2 was physically unstable but chemically stable. Ionic-bonding between the pyridine nitrogen in the API and succinyl group in HPMCAS was found in both ASDs. The additional interaction between the succinyl group in HPMCAS and the hydroxyl group in the API was suggested only in ASD1. It was concluded that the additional interaction contributed to the physical stability of ASD1; however, it accelerated the chemical reaction between the succinyl and hydroxyl groups to generate succinyl ester owing to its close proximity. This study shows that the intermolecular interaction between the API and carrier polymer is not always beneficial for chemical stability. Understanding the molecular states of APIs and polymers in ASDs is important for their successful development.

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.

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.

Incommensurate orbital modulation behind ferroelectricity in CuFeO2.

CuFeO(2) is one of the multiferroic materials and is the first case that the electric polarization is not explained by the magnetostriction model or the spin-current model. We have studied this material using soft x-ray resonant diffraction and found that superlattice reflection 0 1-2q 0 appears in the ferroelectric and incommensurate magnetic ordered phase at the Fe L(2,3) absorption edges and moreover that the rotation of the x-ray polarization such as from σ to π or from π to σ is allowed at this reflection. These findings definitely provide direct evidence that the 3d t(2g↓) orbital state of Fe ions has a long-range order in the ferroelectric state. The spin-orbit interaction in Fe ions plays a crucial role to the ferroelectricity in CuFeO(2), coupling two nontrivial spin and orbital orders, both of which break the crystal symmetry.