Relationship between office blood pressure and actual antihypertensive drug use in patients with hypertension following the promulgation of the guidelines for hypertension (JSH2019).

To achieve appropriate blood pressure control in the treatment of hypertension in Japan, this study examined the relationship between office blood pressure and actual antihypertensive drug use in general hospitals following the promulgation of the guidelines for hypertension (JSH2019). This study focused on blood pressure levels and drug use in outpatients on antihypertensive treatment from June to July 2020. The subjects were 2,537 patients classified into four groups based on their medical history, patients with: hypertension only; hypertension and cardiovascular disease; hypertension and dyslipidaemia; and hypertension and diabetes mellitus. The results showed a significant difference in systolic blood pressure (SBP) between patients with hypertension only and those with hypertension and cardiovascular disease (138.3±17.9 mmHg vs 135.6±19.9 mmHg, p<0.05). Regarding actual drug use, it was found that diuretics were prescribed more frequently in patients with hypertension and cardiovascular disease than in those with hypertension alone (15.5% vs 37.9%, p<0.05), even though the number of drugs for hypertension did not differ significantly. In addition, the dose of diuretics was greater only in patients with cardiovascular disease. These results show the actual drug use and blood pressure for each comorbidity. Furthermore, they suggest that the results of antihypertensive treatment may differ by changing the combination and dosage of antihypertensive drugs without changing the number of antihypertensive drugs used. The study also shows the problem of using less diuretics depending on the risk the patient has, and solving the problem may lead to achieving further antihypertensive goals.

Adverse Drug Event Profile Associated with Anti-dementia Drugs: Analysis of a Spontaneous Reporting Database.

Adverse drug events (ADEs) rates associated with anti-dementia acetylcholinesterase inhibitors are estimated to be 5%-20% and show a wide range of symptoms. No report has examined whether there is a difference in the anti-dementia drugs' ADEs profile. This study aimed to establish whether anti-dementia drugs' ADEs profile differed. Data was based on the Japanese Adverse Drug Event Report (JADER) database. The reporting odds ratios (RORs) was used to analyze data for ADEs from April 2004-October 2021. The target drugs were donepezil, rivastigmine, galantamine, and memantine. The top ten most frequently occurring adverse events were selected. The association between the RORs and antidementia drug ADEs was evaluated, and compared the distribution rate of expression age related to ADEs and each ADEs' timing of onset due to anti-dementia drugs. The primary outcome was RORs. Secondary outcome were expression age and time-to-onset of ADE associated with anti-dementia drugs. A total of 705,294 reports were analyzed. The adverse events incidence differed. Bradycardia, loss of consciousness, falls, and syncope incidence were significantly diverse. The Kaplan-Meier curve results for the cumulative ADEs incidence showed that donepezil had the slowest onset, while galantamine, rivastigmine, and memantine had approximately the same timing of onset.

Association of Pharmacist-led Deprescribing Intervention with the Functional Recovery in Convalescent Setting.

So far, no studies investigated the association between pharmacist intervention and rehabilitation outcomes. The aim of study was to establish whether the pharmacist-led deprescribing intervention affects rehabilitation outcomes. This retrospective, observational, single-center, cohort study included consecutive geriatric patients (n = 448) with pharmacist-led intervention between 2017 and 2019. Participants were divided based on pharmacist-led deprescribing and non deprescribing interventions during hospitalization. Demographic data, laboratory data, the Functional Independence Measure were (FIM) analyzed between the groups. Multiple linear regression analysis was performed to analyze the relationship between pharmacist-led deprescribing and FIM total gain. The primary outcome was FIM total gain. The rate of pharmacist intervention during the study period was 92.4%. A multiple linear regression analysis of FMI-T gain, adjusting for confounding factors, revealed that the pharmacist-led deprescribing intervention was independently correlated with FMI-T gain. Particularly, the use of dyslipidemia drugs, antipsychotic drugs, hypnotics, and nonsteroidal anti-inflammatory drugs significantly decreased during hospitalization. The pharmacist-led deprescribing intervention was independently and significantly associated with FIM-T gain. The pharmacist-led deprescribing intervention improved functional recovery in a rehabilitation setting.

Anticholinergic Load and Nutritional Status in Older Individuals.

OBJECTIVES: The association between anticholinergic load-based Anticholinergic Risk Scale scores and nutritional status is unclear in Japanese patients. The aim of this study was to establish whether anticholinergic load affects the nutritional status of geriatric patients in convalescent stages. DESIGN: Retrospective longitudinal cohort study. SETTING: Convalescent rehabilitation wards. PARTICIPANTS: Of the 1490 patients aged ≥65 years who were discharged from convalescent rehabilitation wards between July 2010 and October 2018, 908 patients met the eligibility criteria. They were categorized according to the presence or absence of increased anticholinergic load from admission to discharge. MEASUREMENTS: Demographic data, laboratory data, the Functional Independence Measure were analyzed between the groups. The primary outcome was Geriatric Nutritional Risk Index (GNRI) at discharge. Multiple linear regression analysis was performed to analyze the relationship between anticholinergic load and GNRI at discharge. RESULTS: Multiple linear regression analysis after adjusting for confounding factors revealed that anticholinergic load was independently and negatively correlated with GNRI at discharge. Particularly, the use of chlorpromazine, hydroxyzine, haloperidol, metoclopramide, risperidone, etc. increased significantly from admission to discharge. CONCLUSION: Increased anticholinergic load during hospitalization may be a predictor of nutritional status in geriatric patients.

Solid dispersion of spironolactone with porous silica prepared by the solvent method.

Solid dispersions of spironolactone (SPI) with porous silica (Sylysia 730 and Sylysia 350) were prepared by the solvent method. The physicochemical properties of the prepared solid dispersions were evaluated by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and atomic force microscopy (AFM). In the SEM study, no differences in the surface condition between Sylysia 350 and the solid dispersion of a Sylysia 350:SPI system in a weight ratio of 1:1 were observed. However, AFM phase images showed that the surface of the solid dispersion of the Sylysia 350:SPI system (weight ratio of 1:1) was rather smooth due to the adsorption of SPI as compared with that of a Sylysia 350 intact. The results of PXRD and DSC data in the solid dispersion of the Sylysia 350:SPI system (weight ratio of 1:1) indicated that the molecular state of the adsorbed SPI changed from crystalline to amorphous. Although the decrease in the SPI concentration increased with the amorphous fraction in the solid dispersion, the diffraction peaks due to SPI crystals still remained in the solid dispersion of a Sylysia 730:SPI system (weight ratio of 1:1), indicating that the mean pore diameter and specific surface area of an additive are some of the important factors for the amorphization of SPI crystals. The dissolution property of the SPI from the solid dispersions was remarkably improved in comparison with that of SPI crystals. The dissolution rate of the SPI from the solid dispersions with Sylysia 350 was faster than that of the SPI from the solid dispersions with Sylysia 730. The difference in the dissolution properties of SPI from both the solid dispersions was attributed to the difference in the molecular state of the SPI in both the solid dispersions. In the stability test, the amorphous state of the SPI in the solid dispersion of the Sylysia 350:SPI system (weight ratio of 1:1) was maintained for 2 weeks at 25 degrees C and 0% RH, while the amorphous SPI without Sylysia 350 crystallized under the same conditions.

Preparation and clinical application of 2% diflunisal oral ointment for painful lesions of the oral mucosa.

We previously reported the development and clinical efficacy of a 2% aspirin oral ointment and 2% ethenzamide oral ointment as hospital preparations for painful lesions of the oral mucosa. This study investigated methods of preparing a more stable oral ointment with a more effective analgesic action, using diflunisal, another salicylic acid derivative, with an analgesic effect stronger than that of aspirin. A two-percent diflunisal oral ointment was prepared similarly to the aspirin ointment using plastibase and CMC-Na as the ointment base. From the results of spreadability measurement, a CMC-Na content of 20% was considered appropriate. The stability of diflunisal in 2% diflunisal oral ointment stored at 5 degrees C, 20 degrees C and 30 degrees C, was determined using HPLC, and a high stability of diflunisal at room temperature for more than 100 days was confirmed. We also investigated its antinociceptive effect using the Randall-Selitto paw pressure test in rats, which showed that 2% diflunisal oral ointment was as effective as 2% aspirin oral ointment. On clinical application of 2% diflunisal oral ointment to 8 patients with painful oral mucous diseases, it was found to be significantly (p = 0.014) more effective than 2% aspirin oral ointment. The results of this study demonstrated that 2% diflunisal oral ointment is a clinically useful analgesic for painful oral lesions.

Development and clinical application of high performance liquid chromatography for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine.

A high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine or caffeine metabolites. The method is simple and of practical use because it is applicable even to plasma samples from patients who take caffeine-containing beverages. The method was also reproducible with a coefficient of variation of less than 5% for each analyte. The levels of theophylline, determined by HPLC, were validated by their high correlation to the levels obtained by fluorescence polarization immunoassay. HPLC was used to determine theophylline levels in patients with bronchial asthma. The data revealed that the ratio of 1,3-dimethyluric acid, the major metabolite of theophylline, to theophylline concentration in the plasma was within a narrow range in most patients (0.055 +/- 0.01, n = 66), regardless of the method of theophylline administration or the time of blood sampling. Conversely, this ratio was as low as 0.027 +/- 0.005 in the patient with a long plasma half-life of theophylline. These results suggest that it may be possible to predict the plasma half-life of theophylline for each patient from a single blood sample. This may be useful when planning theophylline administration, especially in patients with abnormal theophylline metabolism.