Characterization of circadian blood pressure patterns using non-linear mixed effects modeling

Characterizing the time course of baseline or pre-drug blood pressure is important in acquiring unbiased estimates of antihypertensive drug effect. In this study, we recruited 23 healthy male volunteers and measured systolic (SBP) and diastolic blood pressure (DBP) over 24 hours on an hourly basis. Using a non-linear mixed effects model, circadian rhythm observed in blood pressure measurements was described by incorporating two cosine functions with periods 24 and 12 hours. A mixture model was applied to identify subgroups exhibiting qualitatively different circadian rhythms. Our results suggested that 78% of the study population, defined as ‘dippers’, demonstrated a typical circadian profile with a morning rise and a nocturnal dip. The remaining 22% of the subjects defined as ‘non-dippers’, however, were not adequately described using the typical profile and demonstrated an elevation of blood pressure during night-time. Covariate search identified weight as being positively correlated with mesor of SBP. Visual predictive checks using 1,000 simulated datasets were performed for model validation. Observations were in agreement with predicted values in ‘dippers’, but deviated slightly in ‘non-dippers’. Our work is expected to serve as a useful reference in assessing systematic intra-day blood pressure fluctuations and antihypertensive effects as well as assessing drug safety of incrementally modified drugs.

A Systematic Review on Nurse-Led Transitional Care Programs for Discharged Patients from Hospital to Home / 임상간호연구

PURPOSE: This study was to systematically review the contents and effects of nurse-led transitional care programs for discharged patients from hospital to home. METHODS: Randomized controlled trials published between 2005 and 2015 were searched in Pubmed, Embase, Cochrane(Central Register of Controlled Trials) and CINAHL. Data were analyzed using Cochrane Review Manager(Revman) software 5.3. RESULTS: Nine studies were selected and analyzed. Patient assessment, education and discharge planning were included in pre-discharge phase. Referring, communication and care planning were performed by nurses in transition phase. Home and phone visits, monitoring and multidisciplinary advices were included in post-discharge phase. Various outcome measures such as hospital utilization(30 days readmission and emergency department visit), quality of life, and cost were used to identify effectiveness of nurse-led transitional care programs. 30 days readmission(OR=.73, 95% CI 0.54, 0.98; p=.03) and emergency department visit(OR=.67, 95% CI 0.50, 0.88; p=.005) were statistically significant in meta-analysis. However, participant blinding was not done in seven studies which put at the risk of performance bias. CONCLUSION: The results indicated that nurse-led transitional care program is effective in reducing unnecessary hospital utilization. Nevertheless, small sample size and risk at performance bias are the limitation of this study. Thus, we suggest that well-designed randomized controlled trials need to be conducted.

Abnormal Urinalysis Results Caused by Interfering Substances

BACKGROUND: To understand causes of abnormal reaction for the urinalysis, we analyze the interfering substances of clinical urine samples. We focused the effect of urinary vitamin C and fluorescein sodium to the urine chemistry especially glucose, hemoglobin, and leukocyte esterase. METHODS: Incidence of urinary vitamin C was determined for patients and people underwent a medical check–up. We decided dipstick results of glucose, hemoglobin, and leukocyte esterase as false negative based on urine sediment and serum glucose results. Dipstick urinalysis was tested by URiSCAN Pro III with URiSCAN 11 strip (YD Diagnostics, Korea). Urine sediments tests were performed by manual microscopic analysis or Sysmex UF–1000i (Sysmex Co., Japan). RESULTS: The incidence of vitamin C was 20.4% for all subjects. The positive rate of the medical check-up group (34.6%) was higher than others. When vitamin C was detected in clinical urine samples, 42.3%, 10.6%, and 8.2% were defined as false negative for glucose, hemoglobin, and leukocyte esterase dipstick tests, respectively. Fluorescein sodium also interfered on the results of hemoglobin and leukocyte esterase of the dipstick reagents. CONCLUSIONS: Vitamin C was frequently found in the clinical urine samples, and its incidence was higher in the people who underwent medical check-up. The urinary vitamin C and fluorescein sodium can cause interferences in urine dipstick results. Thus, it is expected that present study will give useful information to predict false negative rates of urine dipstick tests by vitamin C and fluorescein sodium.

A quantitative approach for cardiovascular safety evaluation of a generic drug

In generic drug development, comparative pharmacokinetic (PK) studies are conducted to assess equivalence in pharmacokinetics and safety profiles between test and reference formulations. However, there is no established quantitative approach available for safety assessment. This study aimed to propose a method for drug safety evaluation in generic drug development, as assessed by drug influence on blood pressure and heart rate change. Data were taken from a randomized, open label, 2-way cross-over comparative PK study for megestrol conducted in 39 healthy male volunteers. Vital signs of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured at 0 (pre-dose), 4, 8, 12, 24, 48, 72, 96 and 120 hours after the dose. Safety parameters used in the analysis were area under vital sign change versus time curve to the last measured time (AUVlast) and maximum vital sign change (Vmax). Considering highly variable nature of vital signs, the scaled bioequivalence approach developed by US FDA was adopted as a decision rule for safety evaluation between formulations. With the FDA scaled approach, 90% confidence intervals of geometric mean ratio for DBP, 0.7969~1.0377 for Vmax and 0.7304~1.0660 for AUVlast, were both included in the equivalence ranges of 0.7694~1.2997 and 0.6815~1.4674, respectively, and similarly, those for HR were included in their respective scaled equivalence limits, while SBP satisfied the conventional equivalence criterion of 0.8-1.25. These results illustrate the feasibility of applying the suggested approach in cardiovascular safety evaluation in a generic drug.

Current Status of Home Visit Programs: Activities and Barriers of Home Care Nursing Services

PURPOSE: The purpose of this study was to examine the current status of home care nursing services provided by community health nurses and to identify barriers to the services. METHODS: A cross-sectional survey was conducted with three types of community health care nurses. Participants were 257 nurses, 46 of whom were hospital based home care nurses, 176 were community based visiting nurses, and 35 were long term care insurance based visiting nurses. A structured questionnaire on 7 domains of home care nursing services with a 4-point Likert scale was used to measure activities and barriers to care. Data were analyzed using SPSS WIN 21.0 program. RESULTS: Hospital based home care nurses showed a high level of service performance activity in the domain of clinical laboratory tests, medications and injections, therapeutic nursing, and education. Community based visiting nurses had a high level of service performance in the reference domain. Long term care insurance based visiting nurses showed a high level of performance in the service domains of fundamental nursing and counseling. CONCLUSION: The results show that although health care service provided by the three types of community health nurse overlapped, the focus of the service is differentiated. Therefore, these results suggest that existing home care services will need to be utilized efficiently in the development of a new nursing care service for patients living in the community after hospital discharge.

Assessment of statistical power for covariate effects in data from phase I clinical trials

One of the important purposes in population pharmacokinetic studies is to investigate the relationships between parameters and covariates to describe parameter variability. The purpose of this study is to evaluate the model's ability to correctly detect the parameter-covariate relationship that can be observed in phase I clinical trials. Data were simulated from a two-compartment model with zero-order absorption and first-order elimination, which was built from valsartan's concentration data collected from a previously conducted study. With creatinine clearance (CLCR) being used as a covariate to be tested, 3 different significance levels of 0.001

Validation of the Korean Version of Liver Disease Quality of Life (LDQOL 1.0) Instrument / 대한간학회지

BACKGROUND/AIMS: Assessment of Health-related quality of life (HRQOL) outcomes in treatment of chronic disease is increasingly important. The objective of this study was to validate a Korean translation of the Liver Disease Quality of Life instrument (LDQOL version 1.0) for use in patients with chronic liver disease. METHODS: Two native Korean speakers with fluent English translated LDQOL including instructions, items, and response choices. This Korean translation of the LDQOL was administered to 121 patients with chronic liver disease. Cronbach's alpha coefficients were applied to test an internal consistency reliability of disease-specific scales of the LDQOL. MELD and modified CTP scores were calculated for all patients. Associations of MELD and modified CTP scores with severity of liver disease were analyzed with LDQOL. RESULTS: Internal consistency reliability was good (Cronbach's Alpha=0.69-0.94) in liver disease specific scales, except for the quality of social interaction scale (Cronbach's Alpha= 0.56). Mean modified CTP score and MELD score were 6.2+/-1.9 and 9.3+/-5.3, respectively. Both MELD score and modified CTP score showed correlations with most of the scores of liver disease specific scales of LDQOL 1.0, except for the quality of social interaction and sleep scale. CONCLUSIONS: The Korean version of the liver disease specific scales of the LDQOL 1.0 is validated and useful for measuring HRQOL in Korean patients with chronic liver disease.