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1.  Population pharmacodynamic analysis of LDL-cholesterol lowering effects by statins and co-medications based on electronic medical records 
HMG-CoA reductase inhibitors are available for use in low density lipoprotein-cholesterol (LDL-C) lowering therapy. The purposes of this study were to develop a population pharmacodynamic (PPD) model to describe the time course for the LDL-C lowering effects of statins and assess the efficacy of combination therapy based on electronic medical records.
Patient backgrounds, laboratory tests and prescribed drugs were collected retrospectively from electronic medical records. Patients who received atorvastatin, pitavastatin or rosuvastatin were enrolled. A physiological indirect response model was used to describe the changes observed in LDL-C concentrations. The PPD analysis was performed using nonmem 7.2.0 with the first order conditional estimation method with interaction (FOCE-INTER).
An indirect response Imax model, based on the 2863 LDL-C concentrations of 378 patients, successfully and quantitatively described the time course for the LDL-C lowering effects of three statins. The combination of ezetimibe, a cholesterol absorption inhibitor, decreased the LDL synthesis rate (Kin) by 10.9%. A simulation indicated that the combined treatment of ezetimibe with rosuvastatin (2.5 mg day−1) led to superior clinical responses than those with high doses of rosuvastatin (5.0 mg day−1) monotherapy, even in patients with higher baseline LDL-C concentrations prior to the treatment.
A newly constructed PPD model supported previous evidence for the beneficial effects of ezetimibe combined with rosuvastatin. In addition, the established framework is expected to be applicable to other drugs without pharmacokinetic data in clinical practice.
PMCID: PMC4239976  PMID: 24734885
electronic medical record; LDL cholesterol; population pharmacodynamics; statins
2.  The longitudinal BMI pattern and body composition of patients with anorexia nervosa who require urgent hospitalization: A case control study 
The prevention of serious physical complications in anorexia nervosa (AN) patients is important. The purpose of this study is to clarify which physical and social factors are related to the necessity for urgent hospitalization of anorexia nervosa (AN) patients in a long-term starvation state. We hypothesized that the change of longitudinal BMI, body composition and social background would be useful as an index of the necessity for urgent hospitalization.
AN patients were classified into; urgent hospitalization, due to disturbance of consciousness or difficulty walking(n = 17); planned admission (n = 96); and outpatient treatment only groups (n = 136). The longitudinal BMI pattern and the clinical features of these groups were examined. In the hospitalization groups, comparison was done of body composition variation and the social background, including the educational level and advice from family members.
After adjusting for age and duration of illness, the BMI of the urgent hospitalization group was lower than that of the other groups at one year before hospitalization (P < 0.01) and decreased more rapidly (P < 0.01). Urgent hospitalization was associated with the fat free mass (FFM) (P < 0.01). Between the groups, no considerable difference in social factors was found.
The longitudinal pattern of BMI and FFM may be useful for understanding the severity in AN from the viewpoint of failure of the homeostasis system.
PMCID: PMC3275451  PMID: 22142436
3.  Relation between psychosocial variables and the glycemic control of patients with type 2 diabetes: A cross-sectional and prospective study 
This cross-sectional and prospective study used a variety of psychological inventories to evaluate the relationship between psychosocial factors and the glycemic control of patients with type 2 diabetes.
Participants were 304 patients with type 2 diabetes who were treated as outpatients at diabetes clinics. All participants were assessed for HbA1c and completed the following self-report psychological inventories: 1) Diabetes Treatment Satisfaction Questionnaire (DTSQ), 2) Problem Areas in Diabetes Survey (PAID), 3) Well-being Questionnaire 12 (W-BQ12), 4) Self-Esteem Scale (SES), 5) Social Support Scale, and 6) Self-Efficacy Scale. HbA1c was again measured one year later. The relationships between the psychosocial variables obtained by analysis of the psychological inventories and baseline or one-year follow-up HbA1c were determined.
Baseline HbA1cwas significantly correlated with age, diet treatment regimen, number of microvascular complication of diabetes, and the total scores of DTSQ, W-BQ12, PAID, SES and the Self-Efficacy Scale. Hierarchical stepwise multiple regression revealed that significant predictors of baseline HbA1c were total DTSQ and PAID scores, along with age, diet treatment regimen, and number of microvascular complication of diabetes after adjustment for demographic, clinical and other psychosocial variables. Two hundred and ninety patients (95.4% of 304) were followed and assessed one year after baseline. Hierarchical stepwise multiple regression analysis showed the significant predictors of follow-up HbA1c to be total DTSQ and PAID scores, along with age and diet treatment regimen. However, the correlation between baseline and follow-up HbA1c was so high that the only other variable to retain significance was diet treatment regimen once baseline HbA1c was included in the regression of follow-up HbA1c.
The DTSQ and the PAID predicted both current and future HbA1c to a similar and significant degree in patients with type 2 diabetes.
PMCID: PMC2667542  PMID: 19298645

Results 1-3 (3)