Association between body mass index and fragility fracture in postmenopausal women: a cross-sectional study using Korean National Health and Nutrition Examination Survey 2008-2009 (KNHANES IV).

BACKGROUND: The present study examined the relationship between body mass index (BMI) and the risk for fragility fractures in postmenopausal Korean women. METHODS: Among subjects who participated in the 4th Korea National Health and Nutrition Examination Survey (2008-2009), 2114 women ≥ 40 years of age were included. BMI was based on standards set by the Korean Society for the Study of Obesity, as follows: < 18.5 kg/m2, underweight; 18.5 ≤ to < 25 kg/m2, normal weight; and ≥ 25 kg/m2, obese. Subjects were also divided into three groups according to the location of fragility fracture: spine, hip, or wrist. RESULTS: The mean (± SD) rate of fragility fracture was significantly different among the three groups: 5.9 ± 2.9% (underweight), 1.1 ± 0.3% (normal weight), and 3.0 ± 0.7% (obese) (p = 0.001). After correcting for age, family history, and treatment history of osteoporosis and rheumatoid arthritis, smoking and drinking status, and level of exercise, multivariable regression analysis revealed that the odds ratio for fragility fracture in the underweight group was 5.48 [95% confidence interval (CI) 1.80-16.73] and 3.33 (95% CI 1.61-6.87) in the obese group. After subdividing fragility fractures into vertebral and non-vertebral, the odds ratio for vertebral fracture in the underweight group was 5.49 (95% CI 1.31-23.09) times higher than that in the normal weight group; in the obese group, the non-vertebral fracture odds ratio was 3.87 (95% CI 1.45-10.33) times higher. Analysis of non-vertebral fractures in the obese group revealed an odds ratio for fracture 22.05 (95% CI 1.33-365.31) times higher for hip fracture and 3.85 (95% CI 1.35-10.93) times higher for wrist fracture. CONCLUSIONS: Obesity and underweight increased the risk for fragility fractures in postmenopausal Korean women.

The association between aspirin use and depression: a systematic review and meta-analysis of observational studies.

PURPOSE: Many clinical trials and observational studies have been conducted under the premise that the anti-inflammatory effect of aspirin may prevent depression. These studies, however, showed inconsistent results. To inspect the association between aspirin use and depression, we conducted a meta-analysis of observational studies. METHODS: In August 2019, two authors independently searched PubMed, EMBASE, and PsycINFO to retrieve observational epidemiological studies presenting an association between aspirin use and depression. Case-control and cohort studies were included, and odds ratios (ORs) or relative risks (RRs) with 95% confidence intervals (CIs) for the risk of depression were estimated using a random-effects model. In addition, number needed to harm (NNH) was calculated to measure the rates of depression. RESULTS: In total, 12 observational studies-five case-control studies and seven prospective cohort studies-were included in this meta-analysis. The random-effects model demonstrated a significant association between aspirin use and depression (OR/RR 1.10; 95% CI: 1.05-1.16) with insignificant heterogeneity (I2 = 23.3%). The risk estimates of depression from prospective cohort studies were similar (RR 1.11; 95% CI: 1.08-1.14), and heterogeneity was not observed (I2 = 0.0%). In the subgroup meta-analysis, a duration of aspirin use ≥5 years and a dosage ≥500 mg daily were also associated with depression. The NNH for depression with aspirin use >5 years was 103 (95% CI 91-111) indicating that observed event is rare. CONCLUSIONS: Aspirin use was associated with depression in the present meta-analysis. One of the major limitations is the lack of detail and consistency with respect to exposure verification in the included papers. Another limitation is the lack of randomized controlled studies and prospective cohort studies.

The protective effect of alcohol consumption on the incidence of cardiovascular diseases: is it real? A systematic review and meta-analysis of studies conducted in community settings.

BACKGROUND: This study investigated the dose-response relationship between alcohol consumption and CVD incidence, conducting a meta-analysis of studies focusing on residents from local communities. Further, we examined whether light to moderate alcohol consumption had a protective effect on CVD incidence through a sub-group analysis. METHODS: This study conducted a meta-analysis of the relationship between alcohol consumption and CVD incidence, selecting journals published up to December 2017. The alcohol consumption level was classified into non-consumers, light (0.01-10.0 g/day), light to moderate (10.1-20.0 g/day), moderate (20.1-40.0 g/day), moderate to high (40.1-60.0 g/day), and high (> 60.0 g/day) groups. The sub-group analysis was conducted according to the number of comorbidities and age. RESULTS: Seven articles were selected in total for the meta-analysis. The mean Newcastle-Ottawa scale score was 8.14 points, suggesting studies were of high quality. There was a J-shaped dose-response relationship between alcohol consumption level and CVD incidence only in men. In general, light to moderate and moderate consumption lowered CVD incidence (Relative risk (RR) [95% confidence interval (CI)] was 0.68 [0.57-0.81] and 0.72 [0.58-0.90], respectively). In men with 3-4 comorbidities, there were no protective effects of light to moderate and moderate consumption on CVD incidence. In either groups of only men or men and women there were protective effects of light to moderate and moderate consumption on CVD incidence only in those aged between 41 and 65. DISCUSSION: We found that light to moderate and moderate alcohol consumption had a protective effect on CVD incidence, there was no protective effect either in those with at least three comorbidities or people aged 40 or younger. CONCLUSIONS: We conclude that not all local community residents experience a protective effect of light to moderate consumption on CVD incidence. As such, it is necessary to recommend a moderate amount of drinking or less for each individual.

Dietary intake of calcium and phosphorus and serum concentration in relation to the risk of coronary artery calcification in asymptomatic adults.

OBJECTIVE: The current data regarding the association between calcium and phosphorus and cardiovascular disease are lacking. The aim of this study was to explore whether dietary calcium and phosphorus intake and their serum levels are associated with the prevalence of coronary artery calcification (CAC) using cardiac computed tomography in asymptomatic participants without a history of chronic kidney disease or cardiovascular disease. APPROACH AND RESULTS: A cross-sectional study was performed in 23 652 Korean participants (40.8±7.3 years, male 83.5%) without chronic kidney disease (estimated glomerular filtration rate≥60 mL/min per 1.73 m(2)) or clinically overt cardiovascular disease, who underwent cardiac computed tomographic estimation of CAC scores as part of a general health checkup in addition to completing a self-administered food frequency questionnaire. We assessed the relationship of dietary calcium and phosphorus intake and serum levels with CAC scores using both multivariate-adjusted Tobit models and multinomial logistic regression models. Neither dietary calcium nor phosphorus intake was consistently associated with CAC scores. However, the serum calcium, phosphorus, and calcium-phosphorus product levels were significantly associated with the CAC score ratios. In multivariable-adjusted models, the CAC score ratios (95% confidence intervals) comparing the highest quartiles of serum calcium, phosphorus, and calcium-phosphorus product levels to the lowest quartiles were 1.89 (1.36-2.64), 3.33 (2.55-4.35), and 3.98 (3.00-5.28), respectively (P for trend <0.001). CONCLUSIONS: Elevated serum levels of calcium, phosphorus, and calcium-phosphorus product, but not dietary consumption, are associated with increased CAC scores. Our findings should be explored in further research.

Hypertension associated with alcohol consumption based on the facial flushing reaction to drinking.

BACKGROUND: Alcohol is a risk factor for hypertension. Facial flushing after drinking is a typical symptom of high alcohol sensitivity. This study assessed the role of the facial flushing response in the relationship between alcohol consumption and hypertension. METHODS: The subjects were 1,763 men (288 nondrinkers, 527 flushing drinkers, 948 nonflushing drinkers) who had received a health checkup. Data were collected from the subjects' medical records. The risk of hypertension related to weekly drinking amount in nonflushers and flushers was analyzed and compared with that in nondrinkers. RESULTS: After adjusting for age, body mass index, exercise status, and smoking status, the risk of hypertension was significantly increased when flushers consumed more than 4 drinks per week (more than 4 and up to 8 drinks: odds ratio [OR] = 2.23; above 8 drinks: OR = 2.35). In contrast, in nonflushers, the risk was increased with alcohol consumption of more than 8 drinks (OR = 1.61) per week. The OR (flushers/nonflushers) for hypertension was also increased: more than 4 and up to 8 drinks, 2.27 and above 8 drinks, 1.52. CONCLUSIONS: These findings suggest that hypertension associated with alcohol consumption has a lower threshold value and higher risk in flushers than in nonflushers. Clinicians should consider evaluating patients' flushing response as well as drinking amount in a daily practice for health promotion.

Modifiable factors associated with caregiver burden among family caregivers of terminally ill Korean cancer patients.

PURPOSE: Higher caregiver burden is associated with poor quality of life among family caregivers. However, in Korea, very few studies have examined factors associated with caregiver burden. The present study investigated factors associated with caregiver burden among family caregivers of terminally ill Korean cancer patients, particularly modifiable factors as a potential target of intervention strategies. METHODS: A cross-sectional study using self-administered questionnaires was performed. Sixty-four family caregivers of terminally ill cancer patients who were admitted to the hospice-palliative care unit of a university hospital in South Korea were included. To identify caregiver burden, the Caregiver Reaction Assessment scale (CRA) was used in this study. Time spent in providing care per day, number of visits per week from other family members, family functioning, and a positive subscale, self-esteem, of the CRA were deemed as modifiable factors. Other sociodemographic, caregiving characteristics of the subjects were non-modifiable factors. RESULTS: Longer time spent providing care per day, fewer weekly visits from other family members, poor family functioning, and low self-esteem were considered as modifiable factors associated with caregiver burden. Low monthly income and the spouse being the family caregiver were non-modifiable factors. CONCLUSIONS: Our study has practical significance in that it identifies modifiable factors that can be used to devise intervention strategies. Developing and applying such intervention strategies for alleviating the factors associated with high caregiver burden could be important for improving the quality of life of both patients and their families.

Pharmacokinetic Comparison of a Fixed-Dose Combination of Candesartan Cilexetil/Amlodipine/Atorvastatin Versus Co-administration of Individual Formulations in Healthy Participants.

INTRODUCTION: Fixed-dose combinations (FDCs) of angiotensin II receptor blockers, calcium channel blockers, and statins are conventional therapeutic interventions prescribed for cardiovascular diseases. This study aimed at drawing a comparison between the pharmacokinetics and safety of an FDC and the corresponding individual formulations in healthy subjects. METHODS: A randomized, open-label, single-dose, three-sequence, three-period, partially repeated crossover study was conducted with a cohort of healthy volunteers. A 14-day washout period was maintained between each of the three periods. In this study, candesartan cilexetil, amlodipine, and atorvastatin was administered orally as FDCs of 16/10/40 mg in study 1 and 16/5/20 mg in study 2. The maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of candesartan, amlodipine, and atorvastatin were estimated as the geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the FDC to individual formulations. If the within-subject coefficient of variation (CVwr) of Cmax was greater than 0.3, the bioequivalence (BE) range calculated using the reference-scaled average bioequivalence was used to assess whether the 90% CI was within the BE range. RESULTS: The GMRs (90% CIs) for the AUClast for candesartan and amlodipine were 0.9612 (0.9158-1.0089)/0.9965 (0.9550-1.0397) and 1.0033 (0.9800-1.0271)/1.0067 (0.9798-1.0344), and the GMRs (90% CIs) for Cmax were 0.9600 (0.8953-1.0294)/0.9851 (0.9368-1.0359) and 1.0198 (0.9950-1.0453)/1.0003 (0.9694-1.0321) in studies 1 and 2, respectively. The extended BE ranges calculated from the CVwr of the Cmax of atorvastatin were 0.7814-1.2797 and 0.7415-1.3485, respectively. The GMRs (90% CIs) for the AUClast of atorvastatin were 1.0532 (1.0082-1.1003)/1.0252 (0.9841-1.0680), and the GMRs (90% CIs) for Cmax were 1.0630 (0.9418-1.1997)/0.9888 (0.8792-1.1120) in studies 1 and 2, respectively. CONCLUSION: The Cmax and AUClast values of candesartan cilexetil/amlodipine/atorvastatin 16/10/40 mg and 16/5/20 mg, respectively, were within the BE ranges. There were no clinically significant differences in safety between the two formulations. TRIAL REGISTRATION: ClinicalTrials.gov identifier, study 1: NCT04478097; study 2: NCT04627207.

Association between LEPR Genotype and Gut Microbiome in Healthy Non-Obese Korean Adults.

The LEPR (leptin receptor) genotype is associated with obesity. Gut microbiome composition differs between obese and non-obese adults. However, the impact of LEPR genotype on gut microbiome composition in humans has not yet been studied. In this study, the association between LEPR single nucleotide polymorphism (rs1173100, rs1137101, and rs790419) and the gut microbiome composition in 65 non-obese Korean adults was investigated. Leptin, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels were also measured in all participants. Mean ± SD (standard deviation) of age, body mass index, and leptin hormone levels of participants was 35.2 ± 8.1 years, 21.4 ± 1.8 kg/m2, and 7989.1 ± 6687.4 pg/mL, respectively. Gut microbiome analysis was performed at the phylum level by 16S rRNA sequencing. Among the 11 phyla detected, only one showed significantly different relative abundances between LEPR genotypes. The relative abundance of Candidatus Saccharibacteria was higher in the G/A genotype group than in the G/G genotype group for the rs1137101 single nucleotide polymorphism (p=0.0322). Participant characteristics, including body mass index, leptin levels, and other lipid levels, were similar between the rs1137101 G/G and G/A genotypes. In addition, the relative abundances of Fusobacteria and Tenericutes showed significant positive relationship with plasma leptin concentrations (p=0.0036 and p=0.0000, respectively). In conclusion, LEPR genotype and gut microbiome may be associated even in normal-weight Korean adults. However, further studies with a greater number of obese adults are needed to confirm whether LEPR genotype is related to gut microbiome composition.

A randomized, double-blind, single-dose, phase 1 study comparing the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of denosumab biosimilar CT­P41 and reference denosumab in healthy males.

BACKGROUND: This study's objective was to demonstrate pharmacokinetic (PK) similarity and safety of denosumab biosimilar, CT­P41, and United States-licensed reference denosumab (US-denosumab) in healthy male Asian adults, considering also pharmacodynamic (PD) outcomes. RESEARCH DESIGN AND METHODS: This double-blind, two-arm, parallel-group, Phase 1 study randomized (1:1) healthy males to a single (60-mg) subcutaneous dose of CT­P41 or US-denosumab. Primary endpoints were area under the concentration - time curve (AUC) from time zero to infinity (AUC0-inf), AUC from time zero to the last quantifiable concentration (AUC0-last), and maximum serum concentration (Cmax). PK equivalence was determined if 90% confidence intervals (CIs) for ratios of geometric least-squares means (gLSMs) were within the predefined 80-125% equivalence margin. Secondary PK, PD, safety, and immunogenicity outcomes were also evaluated. RESULTS: Of 154 participants randomized (76 CT­P41; 78 US-denosumab), 151 received study drug (74 CT­P41; 77 US-denosumab). Primary and secondary PK results, PD results, safety, and immunogenicity were comparable between groups. Ninety percent CIs for ratios of gLSMs were within the predefined equivalence margin for AUC0-inf (100.4-114.7), AUC0-last (99.9-114.3), and Cmax (95.2-107.3). CONCLUSIONS: Following a single dose in healthy males, CT­P41 demonstrated PK equivalence with US-denosumab. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06037395.

Pharmacokinetic and Safety Comparison of Fixed-Dose Combination of Cilostazol/Rosuvastatin (200 + 20 mg) Versus Concurrent Administration of the Separate Components in Healthy Adults.

The combined cilostazol and rosuvastatin therapy is frequently used for coronary artery disease treatment. This open-label, 3 × 3 crossover clinical trial evaluated the pharmacokinetics and safety of a fixed-dose combination (FDC) of cilostazol/rosuvastatin (200 + 20 mg) versus a concurrent administration of the separate components (SCs) under both fasted and fed conditions. Among 48 enrolled healthy adults, 38 completed the study. Participants were administered a single oral dose of cilostazol/rosuvastatin (200 + 20 mg), either as an FDC or SCs in a fasted state, or FDC in a fed state, in each period of the trial. Blood samples were taken up to 48 hours after dosing, and plasma concentrations were analyzed using validated liquid chromatography-tandem mass spectrometry. The geometric mean ratios of FDC to SCs for area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUClast ) and maximum plasma concentration (Cmax ) were 0.94/1.05 and 1.06/1.15 for cilostazol and rosuvastatin, respectively (AUClast /Cmax ). Compared with that during fasting, fed-state administration increased the AUClast and Cmax for cilostazol by approximately 72% and 160% and decreased these parameters for rosuvastatin by approximately 39% and 43%, respectively. To conclude, the FDC is bioequivalent to the SCs, with notable differences in pharmacokinetics when administered in a fed state. No significant safety differences were observed between the treatments.

Non-linear relationship between body mass index and self-rated health in older Korean adults: body image and sex considerations.

OBJECTIVES: The purpose of this study was to investigate the association between body mass index (BMI) and self-rated health (SRH) in older adults aged over 65 years while examining the influence of self-perceived body image (SBI) and sex. METHODS: Raw data were obtained from the Korea Community Health Survey, which included BMI measurements of Koreans aged over 65 years (n=59,628). Non-linear relationships between BMI and SRH were analyzed separately for each sex using restricted cubic splines while controlling for SBI and other confounding variables. RESULTS: Men showed a reverse J-shaped association, while women showed a J-shaped association between BMI and poor SRH. However, including SBI in the model changed this association for men to an inverted U-shape showing a negative direction, with the highest risk of poor SRH observed in the underweight to overweight range. For women, a nearly linear positive relationship was observed. Regardless of BMI, those who perceived their weight as not "exactly the right weight" had a higher risk of poor SRH than those who perceived their weight as "exactly the right weight" in both men and women. Older men who thought they were much too fat or too thin had similar highest risks of poor SRH, whereas older women who thought they were too thin had the highest risk of poor SRH. CONCLUSIONS: The findings of this study emphasize the importance of considering sex and body image perceptions when assessing the relationship between BMI and SRH in older adults, especially in men.

Safety and pharmacokinetic comparison between fenofibric acid 135 mg capsule and 110 mg enteric-coated tablet in healthy volunteers.

This study aimed to compare the pharmacokinetic (PK) and safety profiles of 2 fenofibric acid formulations under fasting and fed conditions. The reference was a 135 mg capsule, while the test was a 110 mg enteric-coated tablet. This randomized, open-label, two-sequence, two-period crossover phase 1 clinical trial was conducted in healthy Korean men. Sixty participants were enrolled in each of the fasting and feeding groups. Blood samples were collected 72 hours after drug administration. PK parameters were calculated using a non-compartmental method with Phoenix WinNonlin®. A total of 53 and 51 participants from the fasting and feeding groups, respectively, completed the study. The geometric mean ratio and 90% confidence intervals of the maximum concentration (Cmax) and area under the concentration-time curve to the last measurable plasma concentration were 0.9195 (0.8795-0.9614) and 0.8630 (0.8472-0.8791) in the fasting study and 1.0926 (1.0102-1.1818) and 0.9998 (0.9675-1.0332) in the fed study, respectively. The time to reach Cmax of the enteric-coated tablet compared to that of the capsule was extended by 1 and 3 hours under fasting and fed conditions, respectively. In conclusion, enteric-coated tablets have a higher bioavailability than capsules. In addition, the enteric-coated tablet was smaller than the capsule, making it easier for patients to swallow. Trial Registration: Clinical Research Information Service Identifier: KCT0007177, KCT0003304.

Relationship between Alcohol Consumption and Testosterone Deficiency according to Facial Flushes among Middle-Aged and Older Korean Men.

BACKGROUND: This study examined the relationship between alcohol consumption and total testosterone deficiency based on facial flushing among Korean men. METHODS: A total of 314 men were included in this study and divided into non-drinkers (n=78) and drinkers (n=236). Drinkers were also divided into flushers (n=96) and non-flushers (n=140). Flushers and non-flushers were separated into two groups based on the amount of alcohol consumed: moderate drinkers (≤8 standard drinks per week) and heavy drinkers (>8 standard drinks per week). Total testosterone <3.5 ng/mL was defined as testosterone deficiency. RESULTS: The risk of testosterone deficiency was significantly higher in heavy drinkers who flushed than in nondrinkers (odds ratio, 4.37; 95% confidence interval, 1.20-15.88; P=0.025). However, no significant difference was observed in the risk of testosterone deficiency in non-flushers, regardless of the amount of alcohol consumed. CONCLUSION: This study suggests that the risk of testosterone deficiency increases in heavy drinkers (>8 drinks per week) who flush compared to that in non-drinkers.

Association of High-Sensitivity C-Reactive Protein and Alcohol Consumption on Metabolic Syndrome in Korean Men.

Background: This study aimed to examine the effect of both alcohol consumption and high-sensitivity C-reactive protein (hsCRP) on metabolic syndrome (MetS) in Korean men. Methods: A cohort of 364 men included in this study was divided into four groups according to the amount of alcohol they consumed: the nondrinkers (ND), low moderate drinkers (LM, ≤7 standard drinks per week), high moderate drinkers (HM, 7 to 14 drinks per week), and heavy drinkers (HD, >14 drinks per week). Logistic regression analyses were performed after adjusting for age, exercise, and smoking. Results: The risk of MetS in the LM group with a high hsCRP level (1.0 or more mg/dL) was not significant. However, the risks of MetS were significantly higher in the HM and HD groups with high hsCRP levels than that in the ND group. The odds ratios of MetS in the HM and HD groups with high hsCRP levels were 3.44 (95% confidence interval (CI), 1.25−9.52) and 3.14 (95% CI, 1.07−9.23), respectively. Conclusion: This study suggests that the risk of MetS is higher in men who consume more than seven drinks a week with high hsCRP levels than that in nondrinkers.

Pharmacokinetic Interaction between Atorvastatin and Omega-3 Fatty Acid in Healthy Volunteers.

The interaction between statins and omega-3 fatty acids remains controversial. The aim of this phase 1 trial was to evaluate the pharmacokinetics of drug-drug interaction between atorvastatin and omega-3 fatty acids. Treatments were once-daily oral administrations of omega-3 (4 g), atorvastatin (40 mg), and both for 14 days, 7 days, and 14 days, respectively, with washout periods. The concentrations of atorvastatin, 2-OH-atorvastatin, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were determined with LC-MS/MS. Parameters of DHA and EPA were analyzed after baseline correction. A total of 37 subjects completed the study without any major violations. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the co-administration of a single drug for the area under the concentration-time curve during the dosing interval at steady state of atorvastatin, 2-OH-atorvastatin, DHA, and EPA were 1.042 (0.971-1.118), 1.185 (1.113-1.262), 0.157 (0.091-0.271), and 0.557 (0.396-0.784), respectively. The GMRs (90% Cis) for the co-administration at steady state of atorvastatin, 2-OH-atorvastatin, DHA, and EPA were 1.150 (0.990-1.335), 1.301 (1.2707-1.1401), 0.320 (0.243-0.422), and 0.589 (0.487-0.712), respectively. The 90% CIs for most primary endpoints were outside the range of typical bioequivalence, indicating a pharmacokinetic interaction between atorvastatin and omega-3.

Brief insight-enhancement intervention among patients with alcohol dependence.

Patients' insight has a critical role in the recovery from problematic behavior. The aim of this study was to evaluate the effects of a brief intervention to promote insight among alcohol-dependent patients. A total of 41 alcohol-dependent patients (30 males, 11 females) in an insight-deficient state who had been admitted to a community-based alcohol treatment center, were randomized into two groups based on their admission order: an intervention group (IG) (n = 20) and a control group (CG) (n = 21). Patients in both the IG and CG participated in an identical treatment program with one exception: patients in the IG were required to undergo five sessions of brief individual intervention focusing on insight enhancement. Changes in insight state were assessed after the intervention. The IG exhibited significant (P < 0.05) changes in the distribution of insight level, while the CG did not exhibit any significant changes in the distribution of insight level. The insight score after intervention was significantly (P < 0.05) greater for the IG than the CG with adjustment for the baseline characteristics. The results suggest that a brief individual intervention focused on insight enhancement may be an effective tool to improve insight among alcohol-dependent patients.

Association between Alcohol Consumption and Metabolic Syndrome Determined by Facial Flushing in Korean Women.

BACKGROUND: This study aimed to examine the relationship between alcohol consumption and metabolic syndrome in Korean women as determined by facial flushing. METHODS: Of the female patients aged <65 years who visited the health promotion center at Chungnam National University Hospital from January 2016 to March 2017, 1,344 women were included. After adjusting for confounding factors such as age, body mass index, smoking, exercise, and menopausal status, multiple logistic regression analysis was performed to assess the association between alcohol consumption and the risk of metabolic syndrome in the facial flushing and non-facial flushing groups compared with the non-drinkers. RESULTS: Even after adjusting for confounding factors, the risk of metabolic syndrome was significantly high in all drinking subgroups (≤2 standard drinks: odds ratio [OR], 1.68; 95% confidence interval [CI], 1.10-2.68; 2<, ≤4 standard drinks: OR, 2.48; 95% CI, 1.29-4.74; and >4 standard drinks: OR, 4.16; 95% CI, 2.03-8.30) of the facial flushing group. The risk of metabolic syndrome was significantly high only in the subgroup of weekly alcohol consumption >4 standard drinks (OR, 2.20; 95% CI, 1.07-4.52) in the non-facial flushing group. CONCLUSION: This study suggests that Korean women experiencing facial flushing when drinking have a higher risk of developing metabolic syndrome even with a low weekly drinking amount than those who do not experience face flushing.

Comparison of pharmacokinetics and safety characteristics between two olopatadine hydrochloride 5 mg tablet formulations in healthy Korean subjects.

Histamine acts by binding to four histamine receptors (H1 to H4), of which the H1 is known to participate in dilate blood vessels, bronchoconstriction, and pruritus. Olopatadine hydrochloride blocks the release of histamine from mast cells and it inhibits H1 receptor activation. Olopatadine hydrochloride is anti-allergic agent that is effectively used. The object of this study had conducted to compare the pharmacokinetics (PKs) and safety characteristics between olopatadine hydrochloride 5 mg (test formulation) and olopatadine hydrochloride 5 mg (reference formulation; Alerac ®) in Korean subjects. This study had conducted an open-label, randomized, fasting condition, single-dose, 2-treatment, 2-period, 2-way crossover. Subjects received single-dosing of reference formulation or test formulation in each period and blood samples were collected over 24 hours after administration for PK analysis. A wash-out period of 7 days was placed between the doses. Plasma concentration of olopatadine were determined using liquid chromatography-tandem spectrometry mass (LC-MS/MS). A total of 32 subjects were enrolled and 28 subjects completed. There were not clinical significantly different in the safety between two treatment groups for 32 subjects who administered the study drug more than once. The geometric mean ratio of test formulation to reference formulation and its 90% confidence intervals for The peak plasma concentration (Cmax) and the areas under the plasma concentration-time curve from 0 to the last concentration (AUClast) were 1.0845 (1.0107-1.1637) and 1.0220 (1.0005-1.0439), respectively. Therefore, the test formulation was bioequivalent in PK characteristics and was equally safe as the reference formulation. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0005943.

Validation of the Simplified Palliative Prognostic Index to Predict Survival for Advanced Cancer Patients in Home Hospice Setting.

BACKGROUND: The simplified Palliative Prognostic Index (sPPI) substitutes a single item from the Communication Capacity Scale (CCS) for the delirium item of the original PPI. This study aimed to examine the validity of the sPPI for patients with advanced cancer in a home-based hospice care setting. METHODS: This study included 75 patients with advanced cancer who received home-based hospice care. We used medical records maintained by professional hospice nurses who had visited the patients in their homes. Based on their sPPI score, patients were divided into three groups-A (<4), B (≥4 and <6), and C (≥6)-to compare survival. Further, we investigated the sPPI's accuracy using the area under the receiver operating characteristic curve (AUC) and sensitivity and specificity for 3- and 6-week survival. We used three sPPIs including different substitutions for the delirium item (two methods using the CCS and one using the Korean Nursing Delirium Screening Scale). RESULTS: The median survival was 60-61 days for group A, 27-30 days for group B, and 12-16 days for group C. The difference in survival was significant (P<0.05). The AUC was 0.814-0.867 for 3-week survival and 0.736-0.779 for 6-week survival. For 3- and 6-week survival, prognostic prediction showed sensitivities of 76.2%-90.9% and 76.3%-86.8%, and specificities of 64.2%-88.7% and 51.4%-70.3%, respectively. CONCLUSION: The sPPI, which is measured by professional hospice nurses, has acceptable validity to predict survival for patients with advanced cancer in a home hospice setting in South Korea.

Safety, Virologic Efficacy, and Pharmacokinetics of CT-P59, a Neutralizing Monoclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Protein: Two Randomized, Placebo-Controlled, Phase I Studies in Healthy Individuals and Patients With Mild SARS-CoV-2 Infection.

PURPOSE: Neutralizing antibodies can reduce SARS-CoV-2 cellular entry, viral titers, and pathologic damage. CT-P59 (regdanvimab), a SARS-CoV-2 neutralizing monoclonal antibody, was examined in 2 randomized, double-blind, placebo-controlled, single ascending dose, Phase I studies. METHODS: In study 1.1, healthy adults were sequentially enrolled to receive CT-P59 10, 20, 40, or 80 mg/kg or placebo. In study 1.2, adult patients with mild SARS-CoV-2 infection were enrolled to receive CT-P59 20, 40, or 80 mg/kg or placebo. Primary objectives of both studies were safety and tolerability up to day 14 after infusion. Secondary end points included pharmacokinetic properties. Study 1.2 also measured virology and clinical efficacy. FINDINGS: Thirty-two individuals were randomized to study 1.1 (6 per CT-P59 dose cohort and 8 in the placebo cohort). By day 14 after infusion, adverse events (AEs) were reported in 2 individuals receiving CT-P59 20 mg/kg (headache and elevated C-reactive protein levels) and 1 receiving CT-P59 40 mg/kg (pyrexia) (all Common Terminology Criteria for Adverse Events grade 1). In study 1.2, 18 patients were randomized (5 per dose cohort and 3 in the placebo cohort). Sixteen AEs were reported in 10 patients receiving CT-P59. No AEs in either study led to study discontinuation. Greater reductions in viral titers were reported with CT-P59 than placebo in those with maximum titers >105 copies/mL. Mean time to recovery was 3.39 versus 5.25 days. IMPLICATIONS: CT-P59 exhibited a promising safety profile in healthy individuals and patients with mild SARS-CoV-2 infection, with potential antiviral and clinical efficacy in patients with mild SARS-CoV-2 infection. ClinicalTrials.gov identifier: NCT04525079 (study 1.1) and NCT04593641 (study 1.2).