Asian Pacific Society of Cardiology Consensus Statements on the Diagnosis and Management of Obstructive Sleep Apnoea in Patients with Cardiovascular Disease

Obstructive sleep apnoea (OSA) is strongly associated with cardiovascular disease (CVD). However, evidence supporting this association in the Asian population is scarce. Given the differences in the epidemiology of CVD and cardiovascular risk factors, as well as differences in the availability of healthcare resources between Asian and Western countries, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the management of OSA in patients with CVD in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of ‘agree’ or ‘neutral.’ The resulting statements provide guidance on the assessment and treatment of OSA in patients with CVD in the Asia-Pacific region. The APSC hopes for these recommendations to pave the way for screening, early diagnosis and treatment of OSA in the Asia-Pacific region

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The effects of gas flow rate and annealing on the morphological properties of zinc oxide nanostructures thin film using chemical vapour deposition process

Zinc Oxide nanostructures thin films have been deposited on glass substrates by using chemical vapour deposition technique at 1000°C assisted by gas blocker. Glass substrates was sputtered by ~5nm of gold to form a catalyst layer on top of glass. Different gas flow rates of 0.05, 0.10, 0.20, 0.40 L/min were used in the deposition. After the deposition, the layer was annealed at temperatures of 500°C for 1 hours under atmospheric pressure. The surface morphologies of ZnO thin film were investigated field emission scanning electron microscope (FESEM). X-ray diffraction (XRD) results confirm the presence of ZnO layer with high peak of (002) crystal orientation and shows improvement after annealing. The mechanism of ZnO nanostructures formation will be discussed in this paper

Electrochemical-Based Biosensors on Different Zinc Oxide Nanostructures: A Review

Electrochemical biosensors have shown great potential in the medical diagnosis field. The performance of electrochemical biosensors depends on the sensing materials used. ZnO nanostructures play important roles as the active sites where biological events occur, subsequently defining the sensitivity and stability of the device. ZnO nanostructures have been synthesized into four different dimensional formations, which are zero dimensional (nanoparticles and quantum dots), one dimensional (nanorods, nanotubes, nanofibers, and nanowires), two dimensional (nanosheets, nanoflakes, nanodiscs, and nanowalls) and three dimensional (hollow spheres and nanoflowers). The zero-dimensional nanostructures could be utilized for creating more active sites with a larger surface area. Meanwhile, one-dimensional nanostructures provide a direct and stable pathway for rapid electron transport. Two-dimensional nanostructures possess a unique polar surface for enhancing the immobilization process. Finally, three-dimensional nanostructures create extra surface area because of their geometric volume. The sensing performance of each of these morphologies toward the bio-analyte level makes ZnO nanostructures a suitable candidate to be applied as active sites in electrochemical biosensors for medical diagnostic purposes. This review highlights recent advances in various dimensions of ZnO nanostructures towards electrochemical biosensor applications

Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients.

UNLABELLED: CELADEN was a randomized placebo-controlled trial of 50 patients with confirmed dengue fever to evaluate the efficacy and safety of celgosivir (A study registered at ClinicalTrials.gov, number NCT01619969). Celgosivir was given as a 400 mg loading dose and 200 mg bid (twice a day) over 5 days. Replication competent virus was measured by plaque assay and compared to reverse transcription quantitative PCR (qPCR) of viral RNA. Pharmacokinetics (PK) correlations with viremia, immunological profiling, next generation sequence (NGS) analysis and hematological data were evaluated as exploratory endpoints here to identify possible signals of pharmacological activity. Viremia by plaque assay strongly correlated with qPCR during the first four days. Immunological profiling demonstrated a qualitative shift in T helper cell profile during the course of infection. NGS analysis did not reveal any prominent signature that could be associated with drug treatment; however the phylogenetic spread of patients' isolates underlines the importance of strain variability that may potentially confound interpretation of dengue drug trials conducted during different outbreaks and in different countries. Celgosivir rapidly converted to castanospermine (Cast) with mean peak and trough concentrations of 5727 ng/mL (30.2 μM) and 430 ng/mL (2.3 μM), respectively and cleared with a half-life of 2.5 (± 0.6) hr. Mean viral log reduction between day 2 and 4 (VLR2-4) was significantly greater in secondary dengue than primary dengue (p = 0.002). VLR2-4 did not correlate with drug AUC but showed a trend of greater response with increasing Cmin. PK modeling identified dosing regimens predicted to achieve 2.4 to 4.5 times higher Cmin. than in the CELADEN trial for only 13% to 33% increase in overall dose. A small, non-statistical trend towards better outcome on platelet nadir and difference between maximum and minimum hematocrit was observed in celgosivir-treated patients with secondary dengue infection. Optimization of the dosing regimen and patient stratification may enhance the ability of a clinical trial to demonstrate celgosivir activity in treating dengue fever based on hematological endpoints. A new clinical trial with a revised dosing regimen is slated to start in 2016 (NCT02569827). Furthermore celgosivir's potential value for treatment of other flaviruses such as Zika virus should be investigated urgently. TRIAL REGISTRATION: ClinicalTrials.gov NCT01619969

Subject disposition for CELADEN study [17].

<p>Subject disposition for CELADEN study [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004851#pntd.0004851.ref017" target="_blank">17</a>].</p

Predicted exposure for different dosing regimens.

<p>The Box-25th to 75^th percentile, whiskers-minimum and maximum values for the various dosing regimens is shown. (A) C_min range for the various dosing regimens shows that 150 mg every 6 hr is predicted to yield a 4.5-fold increase in median Cmin used in CELADEN trial (B) C_max, range do not vary significantly for the various dosing regimens and (C) AUC only shows a modest 1.33-fold increase over the dosing regimen used in the CELADEN trial.</p

Dependence of pharmacokinetic parameters on covariates.

<p>Body Weight (A and B); Age (C and D); Creatinine Clearance (E); and Sex (F). Clearance or volume of distribution were not significantly affected by patients’ body weight, age or sex. Drug clearance was significantly correlated with creatinine clearance, indicating a significant role of the kidneys for elimination of celgosvir. Solid line-linear regression, dashed line- 95% CI. The slope of the linear regression line of creatinine clearance versus drug clearance was 0.86 (95% CI: 0.376, 1.351).</p

Evolutionary relationship of the whole genome of dengue samples isolated from celgosivir treatment and placebo in relation to representative samples collected from Asia.

<p>Maximum likelihood trees were generated using the nucleotide alignment from start to stop codon of the coding region. Tip labels are coloured based on sample type, and genotypes are labelled adjacent to tip labels for DENV 2, and along branches for DENV 1 and 3. Scale bar represents nucleotide substitutions per site.</p