[The usefulness of a questionnaire during medical examinations for older subjects in evaluating frailty: Utilization in clinical practice].

AIM: The late-stage medical care system for older people provides medical examinations, including questionnaires for frailty. We examined whether or not this approach is useful in clinical practice. METHODS: We used this questionnaire for the screening of frailty as follows: according to the manual prepared by the Japan Geriatrics Society, each question was classified as concerning oral (Q4, 5), physical (Q6-9), cognitive (Q10, 11), or social (Q13-15) frailty. Each frailty was defined if there was at least one negative answer in each question. The grip power and skeletal muscle index (SMI) according to a bioelectrical impedance analysis were also evaluated. Subjects who showed a reduced grip strength and SMI were defined as having sarcopenia, and those who showed only a reduced grip strength were defined as having possible sarcopenia. RESULTS: One hundred and seventy-one subjects aged 81.0±4.2 years old (63.1% female) were enrolled. A total of 12.3% of subjects showed sarcopenia, and 17.5% showed possible sarcopenia. The prevalence of physical, cognitive, and social frailties was associated with sarcopenia. Oral frailty, defined as having decreased swallowing and mastication functions (Q4 and 5), was significantly related to sarcopenia. Physical frailty was associated with age. In patients with hypertension, a low incidence of cognitive frailty was found. Social frailty was related to a decreased body weight. CONCLUSIONS: A questionnaire during medical examinations for older subjects may be useful for screening various frailties and may lead to promotion of the preventive care activities in the community. Further studies are needed to elucidate the relationship between each type of frailty and background characteristics.

Sex differences in reduction of trunk muscle mass related to falls and cognitive function during the COVID-19 pandemic in older adults.

AIM: This study aimed to examine the influence of the COVID-19 pandemic on physical components and activity, and its relationship to physical performance in older adults. METHODS: Sixty-seven participants aged 75 and older (81 ± 2 years, female: 66%), who underwent medical checkups continuously from 2018 to 2022 in one clinic, were enrolled. Muscle mass was assessed by the biometrical impedance analysis method, which was adjusted by height squared. Physical, oral, and cognitive performance data were obtained from Japanese standard questionnaires at medical checkups. Values obtained in 2018 and 2019 were defined as pre-pandemic, and those in 2021 and 2022 were defined as during the pandemic. RESULTS: Body weight, grip strength, and skeletal mass index did not change from 2018 to 2022, but trunk muscle mass index decreased significantly. A difference in the trunk muscle mass index (TMI) was observed between 2022 and 2018/2019 in men; however, a significant difference was found between 2021 and 2022 in women. Compared with the pre-pandemic period, TMI during the pandemic decreased only in men. The difference in TMI between the pre-pandemic period and during the pandemic (ΔTMI) was significantly decreased in participants with low physical activity and poor oral performance before the pandemic, and in those with falls and poor cognitive function during the pandemic only in men. CONCLUSION: Reduction of trunk muscle mass was related to falls and poor cognitive function during the COVID-19 pandemic in older male adults. These data suggest that the difference in response to the COVID-19 pandemic between men and women necessitates different types of support for older adults. Geriatr Gerontol Int 2024; 24: 1060-1066.

Factors influencing the continuation of home blood pressure measurement in community-dwelling older adults: the NOSE study.

OBJECTIVE: This study aimed to identify the factors influencing home blood pressure measurement (HBPM) continuation in community-dwelling older adults. METHODS: A longitudinal analysis used the NOSE study intervention group datasets. The participants were encouraged HBPM with self-monitoring devices provided to them twice in the morning and twice in the evening. Every 7-day interval from the HBPM start date was defined as 1 week, and the number of HBPMs per week was counted. The first week in which the number of HBPMs was zero was defined as the week in which HBPM was discontinued. Participants who did not experienced discontinuation until the end of the observation period were considered complete survivors in the survival time analysis. RESULTS: Data from 437 participants were included in the analysis. Of these, 120 (27.5%) discontinued HBPM. In univariate analysis, factors significantly associated with HBPM discontinuation included exercise habits [hazard ratio per one unit 0.47; 95% confidence interval (CI) 0.31-0.69], social participation (hazard ratio 0.65; 95% CI 0.42-0.99), MoCA-J score (hazard ratio 0.94; 95% CI 0.90-0.98), and frailty (hazard ratio 5.20; 95% CI 2.87-9.43). In multivariate analysis, factors significantly associated with HBPM discontinuation included sex (hazard ratio 0.55; 95% CI 0.32-0.95; ref. = female individuals), smoking history (hazard ratio 1.69; 95% CI 1.02-2.80), exercise habits (hazard ratio 0.51; 95% CI 0.30-0.85), MoCA-J score (hazard ratio 0.93; 95% CI 0.88-0.98), and frailty (hazard ratio 3.31; 95% CI 1.50-7.29). CONCLUSION: Among community-dwelling older adults, female sex, smoking history, lack of exercise, cognitive decline, and frailty were identified as factors influencing HBPM discontinuation.

Risk factors predicting subtypes of physical frailty incidence stratified by musculoskeletal diseases in community-dwelling older adults: The SONIC study.

AIM: This study aims to identify the key risk factors that lead to subtypes of physical frailty assessed by walking speed and grip strength among community-dwelling Japanese individuals, stratified by the presence of musculoskeletal diseases (MSDs) and age group. METHODS: We included 302 participants aged 70 or 80 years who did not exhibit subtypes of physical frailty at baseline through the Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians (SONIC) study. Our study was a longitudinal study. The outcome was the incidence of subtypes of physical frailty after 3 years. Subtypes of physical frailty were defined as a weak grip strength or slow walking speed, or both, based on the Japanese version of the Cardiovascular Health Study Index. The risk factors for subtypes of physical frailty incidence were examined by age group and MSD, using multivariate logistic regressions. RESULTS: Of the 302 participants, 110 (36.4%) had MSD. Those with MSD were significantly more likely to have subtypes of physical frailty after 3 years compared with those without MSD. Among all participants, older age was a risk factor of subtypes of physical frailty (P < 0.05). Without MSD, older age and dissatisfied financial status were risk factors (P < 0.05). With MSD, older age was a risk factor (P < 0.05). By age group, in individuals aged 70 years old, a dissatisfied financial status was a risk factor for those without MSD (P < 0.05), and a higher BMI was one for those with MSD (P < 0.05). CONCLUSIONS: Older age was a risk factor for subtypes of physical frailty, but other risk factors differed according to the presence of MSD and age. Geriatr Gerontol Int 2024; 24: 797-805.

Optimal treatment schedule of meropenem for adult patients with febrile neutropenia based on pharmacokinetic-pharmacodynamic analysis.

The objectives of this study were to develop a population pharmacokinetic (PK) model of meropenem, to simulate the percent time above minimum inhibitory concentration (%T > MIC) at various MICs, and to estimate effective dosage regimens by calculating the target attainment rates against various strains of bacteria. A total of 209 plasma samples (1-3 concentrations per patient) were obtained from 98 adult Japanese patients with febrile neutropenia in an open-labeled Phase 3 study. The final population PK model was fit to a two-compartment model with zero-order input. Creatinine clearance had a positive significant correlation with CL. Gender had a significant effect on Vc; however, this effect was small, and the PK profile in male patients was similar to that in female patients. The population PK parameters developed in this study are useful in simulating PK profiles of meropenem at various dosage regimens precisely for calculation of %T > MIC. The PK-PD analysis indicated that 0.5 g every 6 h (q6h) was more effective than 1 g q12h, although provided 2 g per day in total. A meropenem dosage regimen of 1 g q8h and/or longer infusion duration was better against a pathogen of comparatively low sensitivity, Pseudomonas aeruginosa (for MIC ≥2 µg/ml). Although causative bacteria were identified in a small number of patients, the target attainment rates at 75%T > MIC (89%) were comparable to microbiological response (89%). The present PK-PD analyses under various conditions are useful in the treatment of febrile neutropenia.

Cerebrospinal pharmacokinetic and pharmacodynamic analysis of efficacy of meropenem in paediatric patients with bacterial meningitis.

BACKGROUND: Meropenem is widely used for the treatment of paediatric patients with bacterial meningitis, but the pharmacodynamic (PD) basis for this has not been fully elucidated. OBJECTIVES: A cerebrospinal pharmacokinetic (PK) and PD analysis was performed to identify the optimal dosage regimen for paediatric patients with inflamed central nervous system disease (bacterial men-ingitis). PATIENTS AND METHODS: Paediatric data from three clinical studies were used to build a novel population PK model with a cerebrospinal fluid (CSF) compartment, assuming CSF clearance of 0.021 L/h from a physical-anatomical perspective. The bactericidal target attainment rates in CSF [50%T>MIC(CSF)], after various dosage regimens, were simulated on the basis of reported or observed minimum inhibitory concentration (MIC) distributions and a newly developed population PK model including CSF concentrations. The effects of increased dose and/or prolonged infusion on target attainment were investigated. RESULTS: Clinical data from 154 patients {mean age 30.6 [standard deviation (SD) 34.4] months, mean body weight 12.4 (SD 7.6) kg} were used for the population PK analysis. The flat profile of the CSF concentration-time curve and attainment of 50%T>MIC(CSF) did not change markedly when the duration of infusion was increased, whereas attainment of 50%T>MIC(CSF) was improved by increasing the dose from 20 to 40 mg/kg q8h for penicillin-resistant Streptococcus pneumoniae and Pseudomonas aeruginosa. Thirty-six patients who achieved satisfactory clinical cure showed at least 75.3%T>MIC(CSF). CONCLUSIONS: A high dose of meropenem (40 mg/kg q8h) is necessary to achieve clinical efficacy in paediatric patients with bacterial meningitis.

Pharmacokinetic evaluation of liposomal amphotericin B (L-AMB) in patients with invasive fungal infection: Population approach in Japanese pediatrics.

The pharmacokinetic characteristics of liposomal amphotericin B (L-AMB; AmBisome(®)) in patients with invasive fungal infection were investigated. A population pharmacokinetic (PK) model in Japanese pediatric patients was developed based on 159 serum amphotericin B (AMPH-B) concentrations obtained in a post-marketing clinical study. The subjects were 39 patients with a mean age of 8.4 years (SD 4.5) and mean body weight of 27.1 kg (SD 14.1). A two-compartment PK model with zero-order input and first-order elimination was fitted to serum AMPH-B concentrations for L-AMB doses of 1.0, 2.5, and 5.0 mg/kg/day. Body weight showed significant correlations with PK parameters, such as clearance (CL) and distribution volume of the central compartment (Vc). The predicted Cmax/dose and AUC0-24/dose in Japanese pediatric patients were similar to those in non-Japanese pediatric patients and Japanese adult patients. Extremely large increases in Ctrough compared with predicted values were observed in some Japanese pediatric patients, but no relationships with demographic characteristics, clinical laboratory test values, or representative adverse drug reaction (decreased potassium) were found. The population PK parameters in this study are useful for simulating PK profiles of L-AMB and will be helpful for PK exposure comparisons among different populations and in investigations of pharmacokinetic-pharmacodynamic characteristics in patients. CHEMICAL COMPOUNDS: Amphotericin B Deoxycholate (PubChem CID:23668620); amphotericin B (PubChem CID:5280965); 3-nitrophenol (PubChem CID:11137); methanol (PubChem CID:887).

Optimal dosage regimen of meropenem for pediatric patients based on pharmacokinetic/pharmacodynamic considerations.

A population pharmacokinetic (PK) model for meropenem in Japanese pediatric patients with various infectious diseases was developed based on 116 plasma concentrations from 50 pediatric patients. The population PK parameters developed in this analysis are useful for calculation of the percent time above minimum inhibitory concentration (%T>MIC) and for optimal dosing of meropenem in pediatric patients. After dosing at 20 mg/kg t.i.d. by 0.5-h infusion (approved standard dose for pediatric patients in Japan), the target value of 50%T>MIC was achieved, indicating that 20 mg/kg t.i.d. by 0.5-h infusion is effective for susceptible bacteria. In contrast, for bacteria with higher MICs such as Pseudomonas aeruginosa (MIC ≥ 2 µg/mL), the probability of target attainment of 50%T>MIC was 60.7% at a dose of 40 mg/kg t.i.d. by 0.5-h infusion (highest dose approved for pediatric patients in Japan). The simulations described in this article indicated that 40 mg/kg t.i.d. with a longer infusion duration (e.g., 4 h) is more effective against bacteria with a MIC higher than 2 µg/mL. The predicted probability of target attainment for 50%T>MIC (97.0%) was well correlated not only to the microbiological efficacy rate (97.0%) but also to the clinical efficacy rate (95.9%) in the present phase 3 study.