Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.

Association between lutein intake and lutein concentrations in human milk samples from lactating mothers in South Korea.

This study was performed to investigate the association between maternal lutein intake and lutein concentrations in human milk among exclusive breast-feeding and mixed-feeding groups of lactating mothers in South Korea. From 99 women who were recruited from March to July 2015, dietary data and breast milk samples were obtained. The means of the daily lutein intakes and breast milk lutein concentrations in lactating mothers were 4.04 mg/day and 10.06 µg/dl, respectively, and they did not differ according to the type of breast-feeding. Breast milk lutein concentrations were positively correlated with the dietary lutein intake of lactating mothers after adjustment for the infant's age and supplement use by the lactating women (r=0.3337, P=0.0008). These correlations appeared in both groups. Further research is needed to identify whether breast milk lutein levels influence infant health, especially eye health.European Journal of Clinical Nutrition advance online publication, 25 May 2016; doi:10.1038/ejcn.2016.84.

Bioequivalence study of two imatinib formulations after single-dose administration in healthy Korean male volunteers.

Imatinib mesylate is effective for chronic myeloid leukaemia and gastrointestinal tumours. We aimed to evaluate the pharmacokinetics of a 200-mg imatinib tablet compared to 2×100-mg imatinib tablets in order to meet the regulatory requirements for marketing in Korea.An open-label, randomized, single-dose, 2-period, 2-treatment cross-over study was conducted in 28 healthy Korean male volunteers. Subjects were administered a 200-mg imatinib tablet and 2×100-mg imatinib tablets under a fasting state according to a randomly assigned order with a 2-week wash-out period. Serial blood samples were collected up to 72 h post-dose. The pharmacokinetic parameters were calculated using non-compartmental methods.A total of 28 subjects were enrolled and 23 subjects completed the study. There were no serious adverse events during the study. 23 mild to moderate adverse events were reported (11 events with 200-mg imatinib vs. 12 events with 2×100-mg imatinib) and subjects recovered without sequelae. The Cmax value was 922.8±318.8 µg/L at 3.15 h for 200-mg imatinib tablet, and 986.3±266.0 µg/L at 2.91 h for the 2×100-mg imatinib tablet. The AUClast of 200-mg and 2×100-mg tablets were 13 084.3±39.1 and 14 131.7±3 826.2 h · µg/L, respectively. The geometric mean ratios (90% confidence intervals) for Cmax and AUClast were 0.9121 (0.8188, 1.0161) and 0.9558 (0.8685, 1.0519), respectively.A newly developed 200-mg imatinib tablet was bioequivalent to 2×100-mg imatinib tablets in healthy Korean subjects. A single-dose of either of the 2 formulations was generally well tolerated.

Exploration of optimal dosing regimens of vancomycin in patients infected with methicillin-resistant Staphylococcus aureus by modeling and simulation.

WHAT IS KNOWN AND OBJECTIVE: Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus (MRSA) infection and shows time-dependent bacterial killing. The current study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of vancomycin and explored its optimal dosing regimens by modeling and simulation. METHODS: Pharmacokinetics study was performed for 20 patients who were treated with vancomycin intravenously, 1000 mg, every 12 h, and blood for PK was randomly drawn within prespecified time windows. PD study was in vitro time-kill experiment for vancomycin against 20 MRSA strains independent of the PK study, where bacterial titre was measured at 0, 2, 4, 8, 24 h after the beginning of vancomycin exposure at 0, 1, 2, 4, 8, 16, 32× minimum inhibitory concentrations. PK and PD models were built from each data set, and simulation for MRSA titre changes over time in human body was performed for various vancomycin dosing regimens using NONMEM(®) . RESULTS: Vancomycin followed a two-compartment PK model, and creatinine clearance was the significant covariate affecting the clearance of vancomycin. PD model described the in vitro time-kill data well. The PK/PD model predicted clear dose-response relationships of vancomycin. The therapeutic dosing regimens of vancomycin, suggested by the simulation studies, showed good agreement with the current clinical practice guidance, which indicates that this PK/PD modeling and simulation approach could prove useful for identifying optimal dosing regimens of other antibiotics and expediting novel antibiotic development. Using PD model from in vitro time-kill study and human PK model from phase 1 study, we could predict whether the drug is going to be efficacious or obtain insight into the optimal dosing regimens for a novel antibiotic agent in the early phases of drug development process.

Pharmacokinetics of a new once-daily controlled-release sarpogrelate hydrochloride compared with immediate-release formulation and the effect of food.

WHAT IS KNOWN AND OBJECTIVE: Sarpogrelate is a selective 5-hydroxytryptamine receptor subtype 2A antagonist that inhibits platelet aggregation and vasoconstriction. The aim of this study was to compare the pharmacokinetics of a sarpogrelate controlled-release formulation (CR) with those of the immediate-release formulation (IR). The effect of food on the pharmacokinetics of CR sarpogrelate was also evaluated. METHODS: A randomized, open-label, 3-period, 3-treatment crossover study was conducted in 50 healthy male subjects. Subjects were allocated into one of six sequence groups. In one period, a 100-mg IR formulation was administered three times at 6-h intervals, and in the other two periods, a 300-mg CR formulation was administered once to fasting and once to fed subjects. Each period was separated by a 7-day washout period. Serial blood samples were collected up to 24 h after the first drug administration in each period. The plasma concentrations of sarpogrelate were analysed by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental methods. RESULTS AND DISCUSSION: After the administration of the IR formulation, the plasma concentration reached a peak at 0·48 h and the drug was eliminated with a half-life (t1/2 ) of 0·7 h. After administration of the CR formulation, the plasma concentration reached a peak at 0·5 h and the drug was eliminated with a t1/2 of 3·23 h. The geometric mean ratios (CR/IR) for sarpogrelate area under the plasma concentration-time curve (AUC) and the maximum plasma drug concentration (Cmax) were 1·2040 (90% confidence interval (CI): 1·0992-1·3188) and 0·9462 (90% CI: 0·8504-1·0529). When CR was administered to fed subjects, the time to peak concentration was prolonged to 3·97 h and t1/2 was shortened to 1·45 h. The geometric mean ratios (fasting/fed) for sarpogrelate AUC and Cmax were 0·8573 (90% CI: 0·7687-0·9561) and 0·6452 (90% CI: 0·5671-0·7341). WHAT IS NEW AND CONCLUSION: After the administration of CR and IR formulations of the same daily dose of sarpogrelate hydrochloride, the overall systemic exposure was slightly higher for the CR than for the IR formulation, whereas peak concentration was comparable between the two formulations. Food reduced the bioavailability of sarpogrelate CR.

Asthma and antibodies to pneumococcal virulence proteins.

PURPOSE: We previously reported that asthmatics had lower anti-serotype-specific pneumococcal polysaccharide antibody levels than non-asthmatics, and the T-helper 2 (Th2) immune profile was associated with suboptimal pneumococcal polysaccharide antibody. Our objective was to determine the influence of asthma status on anti-pneumococcal protein antigen antibody levels. METHODS: We conducted a cross-sectional study, which enrolled 16 children and adults with asthma and 14 subjects without asthma. Asthma was ascertained by predetermined criteria. Serum IgG antibody levels to pneumococcal surface protein A (PspA), pneumococcal surface protein C (PspC), pneumococcal choline-binding protein A (PcpA), and pneumolysin (PLY) were measured by enzyme-linked immunosorbent assays (ELISA). These antibody levels were compared between asthmatics and non-asthmatics. The Th2 immune profile was determined by IL-5 secretion from PBMCs cultured with house dust mite (HDM) and staphylococcal enterotoxin B (SEB) at day 7. The correlation between the anti-pneumococcal antibody levels and the Th2-HDM and SEB-responsive immune profile was assessed. RESULTS: Of the 30 subjects, 16 (53%) were male and the median age was 26 years. There were no significant differences in anti-PspA, anti-PspC, anti-PcpA, and anti-PLY antibody levels between asthmatics and non-asthmatics. The Th2 immune profile was inversely correlated with the anti-PspC antibody levels (r = -0.53, p = 0.003). This correlation was significantly modified by asthma status (r = -0.74, p = 0.001 for asthmatics vs. r = -0.06, p = 0.83 for non-asthmatics). Other pneumococcal protein antibodies were not correlated with the Th2 immune profile. CONCLUSION: No significant differences in the anti-pneumococcal protein antigen antibody levels between asthmatics and non-asthmatics were found. Asthma status is an important effect modifier determining the negative influence of the Th2 immune profile on anti-PspC antibody levels.

Housing data-based socioeconomic index and risk of invasive pneumococcal disease: an exploratory study.

We previously developed and validated an index of socioeconomic status (SES) termed HOUSES (housing-based index of socioeconomic status) based on real property data. In this study, we assessed whether HOUSES overcomes the absence of SES measures in medical records and is associated with risk of invasive pneumococcal disease (IPD) in children. We conducted a population-based case-control study of children in Olmsted County, MN, diagnosed with IPD (1995-2005). Each case was age- and gender-matched to two controls. HOUSES was derived using a previously reported algorithm from publicly available housing attributes (the higher HOUSES, the higher the SES). HOUSES was available for 92·3% (n = 97) and maternal education level for 43% (n = 45). HOUSES was inversely associated with risk of IPD in unmatched analysis [odds ratio (OR) 0·22, 95% confidence interval (CI) 0·05-0·89, P = 0·034], whereas maternal education was not (OR 0·77, 95% CI 0·50-1·19, P = 0·24). HOUSES may be useful for overcoming a paucity of conventional SES measures in commonly used datasets in epidemiological research.

Effectiveness, safety, and pharmacokinetic and pharmacodynamic characteristics of microemulsion propofol in patients undergoing elective surgery under total intravenous anaesthesia.

BACKGROUND: The aims of this study were to investigate the effectiveness, safety, pharmacokinetics, and pharmacodynamics of microemulsion propofol, Aquafol (Daewon Pharmaceutical Co., Ltd, Seoul, Republic of Korea). METHODS: In total, 288 patients were randomized to receive 1% Aquafol or 1% Diprivan (AstraZeneca, London, UK) (n=144, respectively). A 30 mg test dose of propofol was administered i.v. over 2 s for assessing injection pain. Subsequently, a bolus of propofol 2 mg kg(-1) (-30 mg) was administered. Anaesthesia was maintained with a variable rate infusion of propofol and a target-controlled infusion of remifentanil. Mean infusion rates of both formulations and times to loss of consciousness (LOC) and recovery of consciousness (ROC) were recorded. Adverse events and pharmacokinetic and pharmacodynamic characteristics were evaluated. RESULTS: Mean infusion rate of Aquafol was not statistically different from that of Diprivan (median: 6.2 vs 6.3 mg kg(-1) h(-1)). Times to LOC and ROC were slightly prolonged in Aquafol (median: 21 vs 18 s, 12.3 vs 10.8 min). Aquafol showed similar incidence of adverse events to Diprivan. Aquafol (vs Diprivan caused more severe (median VAS: 72.0 vs 11.5 mm) and frequent (81.9 vs 29.2%) injection pain. The dose-normalized AUC(last) of Aquafol and Diprivan was 0.71 (0.19) and 0.74 (0.20) min litre(-1). The V(1) of both formulations were proportional to lean body mass. Sex was a significant covariate for k(12) and Ce(50) of Aquafol, and for k(e0) of Diprivan. CONCLUSIONS: Aquafol was as effective and safe as Diprivan, but caused more severe and frequent injection pain. Aquafol demonstrated similar pharmacokinetics to Diprivan.

Ganglioneuroblastoma presenting as dilated cardiomyopathy.

We report an unusual presentation of ganglioneuroblastoma with features of dilated cardiomyopathy in a 22 month old girl. She was admitted with cardiomegaly; during echocardiography a suspicious abdominal mass was detected by chance. Further imaging studies, including abdominal ultrasonography and spiral computed tomography, revealed a solid mass originating in the right adrenal gland. Metabolic studies and pathological findings were compatible with ganglioneuroblastoma. Following tumour removal and supportive therapy for cardiomyopathy, her clinical condition and laboratory findings improved. Although ganglioneuroblastoma with features of dilated cardiomyopathy is rare, because neurogenic tumours may be involved in its development, measurement of catecholamines in children with dilated cardiomyopathy is strongly recommended.

Effect of SKI 306X, a new herbal anti-arthritic agent, in patients with osteoarthritis of the knee: a double-blind placebo controlled study.

SKI 306X is a purified extract from a mixture of three oriental herbal medicines (Clematis mandshurica, Trichosanthes kirilowii and Prunella vulgaris) that have been widely used for the treatment of inflammatory diseases such as lymphadenitis and arthritis in far East Asia. A double-blind, controlled study was performed to evaluate the efficacy and safety of SKI 306X with placebo in 96 patients with classical osteoarthritis of the knee. Patients were randomized to four treatment groups: placebo, 200 mg, 400 mg and 600 mg of SKI 306X t.i.d.. Clinical efficacy and safety were evaluated for 4 weeks continuous treatment. SKI 306X demonstrated its clinical efficacy, as assessed by 100 mm visual analogue scale (VAS), Lequesne index and patients' and investigators opinion of the therapeutic effect compared with placebo (p<0.01). No significant adverse events were observed in patients treated with SKI 306X. This study demonstrated that SKI 306X, a new herbal anti-arthritic agent provided clinical efficacy in patients with osteoarthritis.

Salviae radix root extract inhibits immunoglobulin E-mediated allergic reaction.

We investigated the effects of the aqueous extract of Salviae radix root (SRRAE) on immediate allergic reactions. SRRAE inhibited by 72.7% passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) immunoglobulin E (IgE). SRRAE dose dependently inhibited histamine release and tumor necrosis factor-alpha production from the rat peritoneal mast cells (RPMCs) by anti-DNP IgE. However, SRRAE showed no significant inhibitory effect on compound 48/80-induced systemic allergic reaction and histamine release from RPMCs. The level of cAMP in RPMCs, when SRRAE was added, significantly increased compared with that of a normal control. These results indicate that SRRAE may contain compounds with actions that inhibit anti-DNP IgE-induced mast cell degranulation in rats.

Rapid purification and characterization of nucleoside diphosphate kinase isoforms using ATP-sepharose affinity column chromatography.

Nucleoside diphosphate kinases (NDP kinases), products of the nm23 gene, catalyze the transfer of the terminal phosphate group of the nucleoside triphosphate to the corresponding diphosphate and may be involved in tumor metastasis suppression, development, and signal transduction. NDP kinase from various sources including human erythrocytes, rat brain tissue and E. coli strain BL21 transformed with pET3C expression plasmids containing nm23-H1 or nm23-H2, were purified in one step to homogeneity using ATP-sepharose affinity column chromatography. This method was applicable for the purification of various NDP kinases which show the same enzymatic activity and immunodetection, but have various molecular weight and quaternary structures.