Factors related to polypharmacy and hyper-polypharmacy for the elderly: A nationwide cohort study using National Health Insurance data in South Korea.

Polypharmacy may cause adverse health outcomes in the elderly. This study examined the prevalence of continuous polypharmacy and hyper-polypharmacy, factors associated with polypharmacy, and the most frequently prescribed medications among older adults in South Korea. This was a retrospective observational study using National Health Insurance claims data. In total, 7,358,953 Korean elderly patients aged 65 years and older were included. Continuous polypharmacy and hyper-polypharmacy were defined as the use of ≥5 and ≥10 medications, respectively, for both ≥90 days and ≥180 days within 1 year. A multivariate logistic regression analysis was conducted with adjustment for general characteristics (sex, age, insurance type), comorbidities (12 diseases, number of comorbidities, and Elixhauser Comorbidity Index [ECI] classification), and healthcare service utilization. Among 7.36 million elderly patients, 47.8% and 36.9% had polypharmacy for ≥90 and ≥180 days, and 11.9% and 7.1% of patients exhibited hyper-polypharmacy for ≥90 and ≥180 days, respectively. Male sex, older age, insurance, comorbidities (cardio-cerebrovascular disease, diabetes mellitus, depressive disorder, dementia, an ECI score of ≥3), and healthcare service utilization were associated with an increased probability of polypharmacy. The therapeutic class with the most prescriptions was drugs for acid-related disorders (ATC A02). The number of outpatient visit days more strongly influenced polypharmacy than hospitalizations and ED visits. This study provides health policymakers with important evidence about the critical need to reduce polypharmacy among older adults.

Aging and the Prevalence of Polypharmacy and Hyper-Polypharmacy Among Older Adults in South Korea: A National Retrospective Study During 2010-2019.

Background: Polypharmacy has become a global health problem and is associated with adverse health outcomes in the elderly. This study evaluated the prevalence of polypharmacy and hyper-polypharmacy in elderly patients in South Korea during 2010-2019. Methods: We analyzed the outpatient care of persons aged ≥65 years covered by National Health Insurance (NHI) using NHI claims data from 2010 to 2019. Polypharmacy was defined as the use of ≥5 medications, and hyper-polypharmacy was defined as the use of ≥10 medications, and we examined them over periods of ≥90 days and ≥180 days. The average annual percent change (AAPC) was calculated using Joinpoint statistical software. Results: The prevalence of polypharmacy among ≥90 days of medication use elderly decreased from 42.5% in 2010 to 41.8% in 2019, and the prevalence of hyper-polypharmacy for ≥90 days increased from 10.4% to 14.4%. The prevalence of polypharmacy for ≥180 days increased from 37.8% in 2010 to 38.1% in 2019, and the prevalence of hyper-polypharmacy for ≥180 days increased from 6.4% to 9.4%. The prevalence of polypharmacy for ≥90 days and ≥180 days steadily increased among elderly patients, with AAPCs of 3.7 and 4.5, respectively. Conclusion: The prevalence of polypharmacy for ≥90 days and ≥180 days remained stably high, with rates of about 42 and 38%, respectively, and hyper-polypharmacy increased over the past 10 years in South Korea. Therefore, strategies to address polypharmacy need to be implemented. Further research is also required to identify the clinical outcomes (including mortality risks) associated with polypharmacy.

Prognostic Value of Metabolic Tumor Volume and Total Lesion Glycolysis on Preoperative 18F-FDG PET/CT in Patients With Very Early and Early Hepatocellular Carcinoma.

PURPOSE: The aim of this article was to evaluate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on preoperative F-FDG PET/CT for predicting intrahepatic recurrence-free survival (IHRFS), extrahepatic metastasis-free survival (EHMFS), and overall survival (OS) in patients with very early/early hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We retrospectively enrolled 132 patients with very early/early HCC who underwent F-FDG PET/CT followed by surgery. The maximum tumor SUV-to-mean normal liver SUV ratio, MTV, and TLG were measured for each patient. Prognostic significances of PET/CT parameters and clinicopathologic factors for IHRFS, EHMFS, and OS were evaluated. Cumulative IHRFS, EHMFS, and OS were calculated using the Kaplan-Meier method. RESULTS: Thirty-three (25%) and 21 (15.9%) of 132 patients experienced intrahepatic and extrahepatic recurrence, respectively, during a median follow-up period of 38.1 months. In multivariate analysis, none of the factors were significant for IHRFS. Metabolic tumor volume and TLG were only significant factors for EHMFS and OS (P < 0.05). The 5-year EHMFS rates were 94.8% in patients with low MTV and TLG, and 62.1% and 63.2% in patients with high MTV and TLG, respectively (P < 0.001). The 5-year OS rates were 92.6% and 92.4% in patients with low MTV and TLG, and 63.3% and 64.3% in patients with high MTV and TLG, respectively (P < 0.001). CONCLUSIONS: Metabolic tumor volume and TLG on preoperative PET/CT were independent prognostic factors for EHMFS and OS but not IHRFS in patients with very early/early HCC. Therefore, patients with high MTV or TLG should be closely observed for extrahepatic metastasis using systemic evaluations.

The Association between Vitamin D and Health-Related Quality of Life in Korean Adults.

BACKGROUND: We examined the relationship between vitamin D status and health-related quality of life, and explored other related factors in the general Korean population. METHODS: We used data from the 2007-2012 Korea National Health and Nutrition Examination Survey on 14,104 adults, aged 20-49 years, who had consented to serum vitamin D measurement and answered health-related quality of life questions. EuroQol-5 was used for measurement. Serum vitamin D levels were measured at intervals of 0-9.99, 10-19.99, 20-29.99, and ≥30 ng/mL. RESULTS: Participants with higher serum vitamin D (serum 25-hydroxyvitamin D) levels were significantly less likely to report problems with depression and anxiety. After adjustment for age, gender, income level, education level, marital status, alcohol consumption, smoking status, and the existence of depressive disorders, the odds ratio for reporting a problem with depression and anxiety was 0.60 (95% confidence interval [CI], 0.39-0.91). The odds ratio for the prevalence of any problem was 0.69 (95% CI, 0.53-0.89) before adjustment, but was not statistically significant after adjustment. No significant associations were observed for problems with mobility, self-care, usual activity, or pain and discomfort. CONCLUSION: This is the first study to examine the associations between vitamin D and health-related quality of life for the general Korean population. Vitamin D status was not significantly associated with the dimensions of EuroQol-5 except for depression and anxiety problems.

A nonparametric spatial scan statistic for continuous data.

BACKGROUND: Spatial scan statistics are widely used for spatial cluster detection, and several parametric models exist. For continuous data, a normal-based scan statistic can be used. However, the performance of the model has not been fully evaluated for non-normal data. METHODS: We propose a nonparametric spatial scan statistic based on the Wilcoxon rank-sum test statistic and compared the performance of the method with parametric models via a simulation study under various scenarios. RESULTS: The nonparametric method outperforms the normal-based scan statistic in terms of power and accuracy in almost all cases under consideration in the simulation study. CONCLUSION: The proposed nonparametric spatial scan statistic is therefore an excellent alternative to the normal model for continuous data and is especially useful for data following skewed or heavy-tailed distributions.

Analysis of 18F-fluorodeoxyglucose positron emission tomography findings in patients with pituitary lesions.

BACKGROUND/AIMS: Although magnetic resonance imaging (MRI) is a good visual modality for the evaluation of pituitary lesions, it has limited value in the diagnosis of mixed nodules and some cystic lesions. We evaluated the usefulness of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) for patients with pituitary lesions. METHODS: (18)F-FDG PET and MRI were performed simultaneously in 32 consecutive patients with pituitary lesions. The relationships between FDG uptake patterns in PET and MRI findings were analyzed. RESULTS: Of 24 patients with piuitary adenomas, 19 (79.2%) showed increased uptake of (18)F-FDG in the pituitary gland on PET scans. All patients with pituitary macroadenomas showed increased (18)F-FDG uptake on PET scans. Meanwhile, only five (50%) of the 10 patients with pituitary microadenomas showed positive PET scans. Interestingly, of two patients with no abnormal MRI findings, one showed increased (18)F-FDG uptake on PET. For positive (18)F-FDG uptake, maximum standardized uptake values (SUV(max)) > 2.4 had 94.7% sensitivity and 100% specificity. In addition, SUV(max) increased in proportion to the size of pituitary adenomas. Most cystic lesions did not show (18)F-FDG uptake on PET scans. CONCLUSIONS: About 80% of pituitary adenomas showed positivity on PET scans, and SUV(max) was related to the size of the adenomas. PET may be used as an ancillary tool for detection and differentiation of pituitary lesions.

PKC phosphorylation regulates mGluR5 trafficking by enhancing binding of Siah-1A.

Glutamate is the major excitatory neurotransmitter in the mammalian CNS and acts on both ionotropic and metabotropic glutamate receptors (mGluRs). The mGluRs are widely distributed in the CNS and modulate a variety of neuronal processes, including neurotransmitter release and ion channel function. In hippocampus and cortex, mGluR5 is highly expressed and plays an important role in the regulation of synaptic plasticity. Calmodulin (CaM) binding dynamically regulates mGluR5 surface expression; however, the mechanisms linking CaM to mGluR5 trafficking are not clear. Recent studies showed that CaM binding to mGluR7 regulates its trafficking in a phosphorylation-dependent manner by disrupting the binding of protein interacting with C kinase 1. The E3 ligase seven in absentia homolog (Siah)-1A binds to mGluR5 and competes with CaM binding, making it an intriguing molecule to regulate phosphorylation-dependent trafficking of mGluR5. In the present study, we find that CaM competes with Siah-1A for mGluR5 binding in a phosphorylation-dependent manner in rat hippocampal neurons. Specifically, phosphorylation of mGluR5 S901 favors Siah-1A binding by displacing CaM. We identified critical residues regulating Siah-1A binding to mGluR5 and showed that binding is essential for the Siah-1A effects on mGluR5 trafficking. Siah-1A binding decreases mGluR5 surface expression and increases endosomal trafficking and lysosomal degradation of mGluR5. Thus CaM-regulated Siah-1A binding to mGluR5 dynamically regulates mGluR5 trafficking. These findings support a conserved role for CaM in regulating mGluR trafficking by PKC-dependent regulation of receptor-binding proteins.

Usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose in predicting treatment response in unresectable hepatocellular carcinoma patients treated with external beam radiotherapy.

PURPOSE: To assess the significance of the ratio between standardized uptake values (SUV) of tumor and normal liver tissue obtained from positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) in predicting the response of hepatocellular carcinoma (HCC) patients treated with external beam radiotherapy (EBRT). METHODS AND MATERIALS: We retrospectively analyzed 35 HCC patients who were treated with EBRT between January 2004 and June 2007. All patients underwent FDG-PET in which SUV values were obtained from tumor and normal liver tissues and were used to calculate the ratios (SUV(Tumor)/SUV(Liver)). After FDG-PET, patients received liver treatment including concurrent chemoradiation, transarterial chemoembolization plus RT, or intraarterial chemotherapy plus RT. Using three-dimensional conformal RT, median dose of 45 Gy was delivered in conventional fractions. Patients underwent abdominal/pelvic CT 1 month after RT, and treatment responses were evaluated according to the Response Evaluation Criteria in Solid Tumors criteria. RESULTS: Patients were divided into high-SUV ratio group (n = 20) and low-SUV ratio group (n = 15) according to SUV ratio at a cutoff value of 2.5. Objective responses consisting of either complete response (CR) or partial response (PR) were observed in 16 and 6 patients (46% vs. 17%, p = 0.015), respectively; median survivals after RT were 8 months and 5 months (p = 0.41) for the high-SUV ratio group and the low-SUV ratio group, respectively. Rates of intrahepatic metastases (9% vs. 11%, p = 0.39) and distant metastases (32% vs. 32%, p = 0.27) showed no significant difference between two groups. CONCLUSIONS: External beam RT for HCC patients with higher SUV ratios resulted in higher response rates than for patients with lower SUV ratios. Treatment of HCC with higher SUV ratios did not result in increased survival; high rates of intrahepatic and distant metastases in both SUV groups may have affected patient survival. SUV ratios from pre-RT FDG-PET may be beneficial for selecting patients who are likely to respond to EBRT for unresectable HCC.

The role of preoperative [18F]fluorodeoxyglucose positron emission tomography in predicting early recurrence after curative resection of hepatocellular carcinomas.

PURPOSE: (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan reflects tumor differentiation and predicts clinical outcome in patients with hepatocellular carcinoma (HCC). We investigated the correlation of PET scans with tumor differentiation and early tumor recurrence (time-to-recurrence <1 year). METHODS: We reviewed the medical records of 93 patients with HCC who underwent curative resection at our hospital from August 2004 through December 2008. PET scans were performed preoperatively, and the maximum standardized uptake value of the tumor (SUV(tumor)) and the tumor-to-non-tumor SUV ratio (TNR) were calculated from FDG uptake. RESULTS: Twenty-six (27.9%) had recurrences and 12 of them (46.2%) had early recurrences. SUV(tumor) and TNR correlated strongly with tumor differentiation (p < 0.001). Early recurrence-free and the overall survival rates in the low TNR group (TNR <2.0) were higher than in the high TNR group (TNR ≥2.0) (p = 0.015, p = 0.013). According to univariate analysis, predictors of early tumor recurrence were large tumor size (≥5 cm), high TNR (≥2), high SUV(tumor) (≥4), and high Edmoson-Steiner grade. However, on multivariate analysis, none of the examined factors were statistically significant independent predictor. CONCLUSION: PET scans reflect tumor differentiation in HCCs. Because high TNR (TNR ≥2) and SUV(tumor) (SUV ≥4) were these cutoff point significant predictors in univariate analysis, future studies with more statistical power are needed to assess the significance.

Usefulness of FDG PET/CT in determining benign from malignant endobronchial obstruction.

OBJECTIVE: To evaluate the usefulness of FDG PET/CT to differentiate malignant endobronchial lesions with distal atelectasis from benign bronchial stenosis. METHODS: This retrospective study reviewed 84 patients who underwent contrast-enhanced chest CT and then PET/CT and had histological (n = 81) or follow-up imaging (n = 3) confirmation. Two chest radiologists reviewed initial chest CT and determined endobronchial lesions to be malignant or benign. Two nuclear medicine physicians reviewed PET/CT for FDG uptake at the obstruction site and measured SUV. Malignancy was considered when increased FDG uptake was seen in the obstruction site, regardless of FDG within the atelectatic lung. RESULTS: The sensitivity, specificity and accuracy of chest CT was 95%, 48% and 84%, compared with 95%, 91% and 94% for PET/CT. Benign obstructive lesions showed statistically lower FDG uptake than malignant obstructions (benign SUV 2.5 ± 0.84; malignant SUV 11.8 ± 5.95, p < 0.001). ROC analysis showed an SUV cut-off value of 3.4 with highest sensitivity of 94% and specificity of 91%. CONCLUSION: Increased FDG PET/CT uptake at the obstruction site indicates a high probability of malignancy, while benign lesions show low FDG uptake. Careful evaluation of FDG uptake pattern at the obstruction site is helpful in the differentiation between benign and malignant endobronchial lesions.