[Development and Evaluation of Motivational Interviewing Pulmonary Rehabilitation Program Based on Self-Determination Theory for Patients with Chronic Obstructive Pulmonary Disease].

PURPOSE: This study aimed to develop a motivational interviewing pulmonary rehabilitation program based on self-determination theory to maintain pulmonary rehabilitation-related health behaviors in patients with chronic obstructive pulmonary disease. The program was developed by reviewing the literature on pulmonary rehabilitation guidelines, drawing on the self-determinism theory to establish its contents, recruiting experts to test its validity, and conducting a preliminary survey. METHODS: A quasi-experimental design was used to confirm the effect of the program. The participants were outpatients diagnosed with chronic obstructive pulmonary disease at three general hospitals in Busan. There were 33 subjects: 15 in the experimental group and 18 in the control group. The experimental group performed a motivational interviewing pulmonary rehabilitation program which comprised 11 sessions delivered over 10 weeks. The outcomes were measured using basic psychological needs, dyspnea, 6-minute walking distance, and functional status. Intervention effects were analyzed using repeated-measures ANOVA. RESULTS: The analysis revealed significant differences between the experimental and control groups in competence among the subdomains of basic psychological needs, dyspnea during exercise, and functional status. CONCLUSION: The developed program affects physical conditions and can be applied as an effective clinical nursing intervention to continuously improve the pulmonary rehabilitation behavior of patients with chronic obstructive pulmonary disease.

Tissue pharmacokinetics of DHP107, a novel lipid-based oral formulation of paclitaxel, in mice and patients by positron emission tomography.

DHP107 is a newly developed lipid-based oral formulation of paclitaxel. We evaluated the in vivo tissue pharmacokinetics (PKs) of DHP107 in mice and patients using positron emission tomography (PET). Radioisotope-labeled [3 H]DHP107 and [18 F]DHP107 for oral administration were formulated in the same manner as the manufacturing process of DHP107. In vivo tissue PK were assessed in healthy ICR mice and breast cancer xenografted SCID mice. Two patients with metastatic breast cancer were clinically evaluated for absorption at the target lesion after internal absorbed dose estimation. Whole-body PET/computed tomography data were acquired in healthy and xenografted mice and in patients up to 10-24 h after administration. Tissue [18 F]DHP107 signals were plotted against time and PK parameters were determined. The amounts of radioactivity in various organs and excreta were determined using a beta-counter and are expressed as the percentage of injected dose (ID). Oral [18 F]DHP107 was well-absorbed and reached the target lesion in mice and patients with breast cancer. Significant amounts of radioactivity were found in the stomach, intestine, and liver after oral administration of [3 H]- and [18 F]DHP107 in healthy mice. The [18 F]DHP107 reached a peak distribution of 0.7-0.8%ID in the tumor at 5.6-7.3 h in the xenograft model. The [18 F]DHP107 distribution in patients with metastatic breast cancer was the highest at 3-4 h postadministration. Systemic exposures after administration of a DHP107 therapeutic dose were comparable with those in previous studies. PET using radioisotope-labeled drug candidates is useful for drug development and can provide valuable information that can complement plasma PK data, particularly in early phase clinical trials.

Risk Factors for Frailty in Critical Care Survivors: A secondary analysis.

OBJECTIVES: The purpose of this study was to investigate the prevalence of frailty and its risk factors among critical care survivors who were discharged after receiving treatment in an intensive care unit. METHODS: This was a secondary analysis using data from a methodological study conducted between June and August 2018. The sample included 494 adults who had been admitted to the intensive care unit for more than 48 hours within a year. Only post-intensive care frailty was evaluated using the Kihon Checklist. The sociodemographic and intensive care-related risk factors for frailty were analysed using multivariate logistic regression. RESULTS: The prevalence of frailty in the sample was 65.8%. The risk factors for frailty were female sex (adjusted odds ratio [aOR] = 1.68, 95% CI: 1.02-2.78), aged 70 years or older (aOR = 4.16, 95% CI: 2.00-8.65), unemployment (aOR = 2.41, 95% CI: 1.39-4.17) and longer ICU days (aOR = 2.29, 95% CI: 1.35-3.91). Analysis of differences in risk factors according to sex revealed that risk factors for frailty were unemployment and longer ICU length of stay for male and older age for female. CONCLUSION: Health care providers should be aware of frailty risk factors in female and male patients and provide patient-specific interventions for preventing frailty.

Simultaneous determination of donepezil, 6-O-desmethyl donepezil and spinosin in beagle dog plasma using liquid chromatography‒tandem mass spectrometry and its application to a drug-drug interaction study.

Spinosin, which is traditionally used for sedation and sleep disorders, has recently shown potential effects in alleviating memory loss. As spinosin is the main bioactive component in a standardized dried 50% ethanol extract of the seeds of Zizyphus jujuba var. spinosa, a Phase IIb clinical trial is ongoing, in Korea for the combination of the above extract formulated in a tablet (DHP1401 tablet) with donepezil hydrochloride (Aricept® tablet) in patients with mild to moderate Alzheimer's disease. Therefore, to promote safety and efficacy evaluations, a reliable method for the simultaneous detection and analysis of the two drugs is needed. Toward this end, in this study, we established and validated a rapid and sensitive LC-MS/MS method for the simultaneous determination of donepezil, its pharmacologically active metabolite 6-O-desmethyl donepezil, and spinosin in beagle dog plasma (50 µL). After optimization of the system, we used methanol for simple protein precipitation. Chromatographic separation was performed using a Phenomenex Luna C18 column (100 × 2.0 mm, 3 µm) with a mobile phase consisting of 0.1% formic acid in acetonitrile-0.1% formic acid in distilled water (2:8, v/v) at a flow rate of 0.65 mL/min. All analytes were detected and quantified in selected reaction monitoring mode. All calibration curves showed good linearity (r ≥ 0.9965) over the concentration range of 0.02-20, 0.02-10, and 0.5-250 ng/mL for donepezil, for 6-O-desmethyl donepezil, and spinosin, respectively. This validated method was then successfully applied to a pharmacokinetic study in beagle dogs with no evidence for potential drug-drug interactions between DHP1401 and donepezil hydrochloride. This information and optimized assay can be useful for the anticipated co-administration of these two drugs in clinical settings.

Preparation and evaluation of 2-(allylthio)pyrazine-loaded lipid emulsion with enhanced stability and liver targeting.

To develop 2-(allylthio)pyrazine (2-AP)-loaded lipid emulsion for parenteral administration, various lipid emulsions were prepared with soybean oil, lecithin, and other carriers using homogenization method, and their physical stabilities were investigated by measuring their droplet sizes. The pharmacokinetics and tissue distribution of 2-AP in lipid emulsion after intravenous administration to rats were evaluated compared with 2-AP in solution. 2-AP was lipophilic, sparingly water-soluble, and unstable in aqueous medium. The 2-AP-loaded lipid emulsion composed of 1% of 2-AP, 4% of soybean oil, 4% of lecithin, and 91% of water was physically and chemically stable for at least 8 weeks. It gave significantly faster clearance of 2-AP and higher affinity to the organs, especially the liver, compared with the 2-AP in solution, suggesting that it could selectively deliver 2-AP to the liver. Thus, the lipid emulsion with soybean oil and lecithin could be used as a potential dosage form with the liver-targeting property and enhanced stability of sparingly water-soluble 2-AP.