Bench to Bed Evidences for Pharmacokinetic and Pharmacodynamic Interactions Involving Oseltamivir and Chinese Medicine

Oseltamivir (OA), an ethyl ester prodrug of oseltamivir carboxylate (OC), is clinically used as a potent and selective inhibitor of neuraminidase. Chinese medicines have been advocated to combine with conventional drug for avian influenza. The current study aims to investigate the potential pharmacokinetic and pharmacodynamic interactions of a Chinese medicine formula, namely, Yin Qiao San and Sang Ju Yin (CMF1), commonly used for anti-influenza in combination with OA in both rat and human, and to reveal the underlined mechanisms. It was found that although Cmax, AUC and urinary recovery of OC, as well as metabolic ratio (AUCOC/AUCOA), were significantly decreased in a dose-dependent manner following combination use of CMF1 and OA in rat studies (P<0.01), such coadministration in 14 healthy volunteers only resulted in a trend of minor decrease in the related parameters. Further mechanistic studies found that although CMF1 could reduce absorption and metabolism of OA, it appears to enhance viral inhibition of OA (P<0.01). In summary, although there was potential interaction between OA and CMF1 found in rat studies, its clinical impact was expected to be minimal. The coadministration of OA and CMF1 at the clinical recommended dosages is, therefore, considered to be safe

Exhaled air dispersion during coughing with and without wearing a surgical or N95 mask.

OBJECTIVES: We compared the expelled air dispersion distances during coughing from a human patient simulator (HPS) lying at 45° with and without wearing a surgical mask or N95 mask in a negative pressure isolation room. METHODS: Airflow was marked with intrapulmonary smoke. Coughing bouts were generated by short bursts of oxygen flow at 650, 320, and 220L/min to simulate normal, mild and poor coughing efforts, respectively. The coughing jet was revealed by laser light-sheet and images were captured by high definition video. Smoke concentration in the plume was estimated from the light scattered by smoke particles. Significant exposure was arbitrarily defined where there was ≥ 20% of normalized smoke concentration. RESULTS: During normal cough, expelled air dispersion distances were 68, 30 and 15 cm along the median sagittal plane when the HPS wore no mask, a surgical mask and a N95 mask, respectively. In moderate lung injury, the corresponding air dispersion distances for mild coughing efforts were reduced to 55, 27 and 14 cm, respectively, p < 0.001. The distances were reduced to 30, 24 and 12 cm, respectively during poor coughing effort as in severe lung injury. Lateral dispersion distances during normal cough were 0, 28 and 15 cm when the HPS wore no mask, a surgical mask and a N95 mask, respectively. CONCLUSIONS: Normal cough produced a turbulent jet about 0.7 m towards the end of the bed from the recumbent subject. N95 mask was more effective than surgical mask in preventing expelled air leakage during coughing but there was still significant sideway leakage

Speciation pattern of the horned ghost crabOcypode ceratophthalmus(Pallas, 1772): An evaluation of the drivers of Indo-Pacific marine biodiversity using a widely distributed species

Aim The high species richness of the Indo-Australian Archipelago (IAA) marine biodiversity hotspot has been attributed to three competing hypotheses: Centre of Origin/Centre of Overlap/Centre of Accumulation. While most phylogeographic studies testing these hypotheses have focused on marine fishes, we provide a new perspective on this evolutionary important question by examining the population genetics of the horned ghost crab Ocypode ceratophthalmus sensu lato (Ocypodidae) whose distribution spans the entire Indo-Pacific and contains at least two colour morphs. Location Methods Indo-Pacific region, spanning from East Africa, India, East Asia to Central Pacific. Population genetics analyses based on mitochondrial COI and nuclear NaK intron sequences of O. ceratophthalmus from 39 sites throughout the Indo-Pacific. Results Main conclusions We found at least three genetically distinct geographical clades in O. ceratophthalmus, corresponding to the east, west and central region of the species' range. Divergent clades were found to have originated in the peripheral Central Pacific and West Indian Ocean. Populations at the eastern margin of IAA harbour the highest genetic diversity, due to the co-existence of east and central clades in these populations. Peripheral isolation plays an important role in shaping evolutionary history of this species. Particularly, secondary dispersal of divergent lineages from the Central Pacific contributes to the high diversity found in the IAA. Thus, the Centre of Accumulation hypothesis best describes the evolutionary and demographic history of O. ceratophthalmus

Factors Associated with Aspirin Resistance in Hong Kong Chinese Patients with Stable Coronary Heart Disease Using the Multiplate&reg; Analyzer and Serum Thromboxane B2

Introduction: Aspirin resistance may be associated with various conditions. We measured serum thromboxane B2 (TXB2) and platelet function using the Multiplate&reg; Analyzer with arachidonic acid (ASPI) in patients on long term aspirin therapy to identify aspirin resistance and associated factors. Materials and Methods: Chinese patients with stable coronary heart disease had samples for serum TXB2 and ASPI measurement taken before and 1 h after taking a morning dose of 80 mg aspirin. Results: In 266 patients with mean age 66.6 &plusmn; 10.7 years, 17% were female and 55% were current or previous smokers. TXB2 and ASPI measurements were significantly higher before the dose than at 1 h post dose, with 46% of subjects having high ASPI values (AUC &gt; 300 AU*min) pre dose compared with 27% at 1 h post dose. TXB2 and ASPI measures of platelet aggregation showed weak correlations, which were only significant before the dose (r = 0.219, p = 0.001). Increased ASPI measurements were associated with white blood cell (WBC) count, haematocrit, platelet count and heart rate at 24 h post dose but only with WBC count, smoking history and heart rate at 1 h post dose. Diabetes was not associated with reduced platelet response to aspirin. The WBC count associated with aspirin resistance was over 6.55 &times; 109/L by receiver operating characteristic analysis. Conclusions: The antiplatelet response to aspirin was reduced in a large proportion of patients. Patients with higher WBC count within the normal range appear to be at increased risk of aspirin resistance. Higher or more frequent doses of aspirin may be needed in many patients

Exhaled air dispersion distances along the transverse plane during coughing with and without wearing a surgical or N95 mask.

<p>Exhaled air dispersion distances along the transverse plane during coughing with and without wearing a surgical or N95 mask.</p

Room ventilation design and experimental set-up.

<p>The isolation room is fitted with the downward ventilation systems. The design is to supply conditioned and clean air from the ceiling diffuser to sweep away contaminants, which would then be removed via the exhaust outlets at the floor level. The Human Patient Simulator was lying at 45° on the bed. The exhaled air plume was marked with intrapulmonary smoke, and was revealed by the laser light sheet. The images were captured by a high-definition camera positioned to the left side of the simulator when examining the cough propagation distances in the median sagittal plane. Smoke concentration in the plume was estimated from the light scattered by smoke particles.</p

Association of technologically assisted integrated care with clinical outcomes in type 2 diabetes in Hong Kong using the prospective JADE Program: A retrospective cohort analysis.

BackgroundDiabetes outcomes are influenced by host factors, settings, and care processes. We examined the association of data-driven integrated care assisted by information and communications technology (ICT) with clinical outcomes in type 2 diabetes in public and private healthcare settings.Methods and findingsThe web-based Joint Asia Diabetes Evaluation (JADE) platform provides a protocol to guide data collection for issuing a personalized JADE report including risk categories (1-4, low-high), 5-year probabilities of cardiovascular-renal events, and trends and targets of 4 risk factors with tailored decision support. The JADE program is a prospective cohort study implemented in a naturalistic environment where patients underwent nurse-led structured evaluation (blood/urine/eye/feet) in public and private outpatient clinics and diabetes centers in Hong Kong. We retrospectively analyzed the data of 16,624 Han Chinese patients with type 2 diabetes who were enrolled in 2007-2015. In the public setting, the non-JADE group (n = 3,587) underwent structured evaluation for risk factors and complications only, while the JADE (n = 9,601) group received a JADE report with group empowerment by nurses. In a community-based, nurse-led, university-affiliated diabetes center (UDC), the JADE-Personalized (JADE-P) group (n = 3,436) received a JADE report, personalized empowerment, and annual telephone reminder for reevaluation and engagement. The primary composite outcome was time to the first occurrence of cardiovascular-renal diseases, all-site cancer, and/or death, based on hospitalization data censored on 30 June 2017. During 94,311 person-years of follow-up in 2007-2017, 7,779 primary events occurred. Compared with the JADE group (136.22 cases per 1,000 patient-years [95% CI 132.35-140.18]), the non-JADE group had higher (145.32 [95% CI 138.68-152.20]; P = 0.020) while the JADE-P group had lower event rates (70.94 [95% CI 67.12-74.91]; P ConclusionsICT-assisted integrated care was associated with a reduction in clinical events, including death in type 2 diabetes in public and private healthcare settings