Stanley Sau Ching Wong

Testosterone-augmented contractile responses to α1- and β1-adrenoceptor stimulation are associated with increased activities of RyR, SERCA, and NCX in the heart

We hypothesized that testosterone at physiological levels enhances cardiac contractile responses to stimulation of both alpha(1)- and beta(1)-adrenoceptors by increasing Ca(2+) release from the sarcoplasmic reticulum (SR) and speedier removal of Ca(2+) from cytosol via Ca(2+)-regulatory proteins. We first determined the left ventricular developed pressure, velocity of contraction and relaxation, and heart rate in perfused hearts isolated from control rats, orchiectomized rats, and orchiectomized rats without and with testosterone replacement (200 microg/100 g body wt) in the presence of norepinephrine (10(-7) M), the alpha(1)-adrenoceptor agonist phenylephrine (10(-6) M), or the nonselective beta-adrenoceptor agonist isoprenaline (10(-7) M) in the presence of 5 x 10(-7) M ICI-118,551, a beta(2)-adrenoceptor antagonist. Next, we determined the amplitudes of intracellular Ca(2+) concentration transients induced by electrical stimulation or caffeine, which represent, respectively, Ca(2+) release via the ryanodine receptor (RyR) or releasable Ca(2+) in the SR, in ventricular myocytes isolated from the three groups of rats. We also measured (45)Ca(2+) release via the RyR. We then determined the time to 50% decay of both transients, which represents, respectively, Ca(2+) reuptake by sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and removal via the sarcolemmal Na(+)/Ca(2+) exchanger (NCX). We correlated Ca(2+) removal from the cytosol with activities of SERCA and its regulator phospholamban as well as NCX. The results showed that testosterone at physiological levels enhanced positive inotropic and lusitropic responses to stimulation of alpha(1)- and beta(1)-adrenoceptors via the androgen receptor. The increased contractility and speedier relaxation were associated with increased Ca(2+) release via the RyR and faster Ca(2+) removal out of the cytosol via SERCA and NCX.

Efficacy of Pregabalin in Acute Postoperative Pain Under Different Surgical Categories: A Meta-Analysis

AbstractThe efficacy of pregabalin in acute postsurgical pain has been demonstrated in numerous studies; however, the analgesic efficacy and adverse effects of using pregabalin in various surgical procedures remain uncertain. We aim to assess the postsurgical analgesic efficacy and adverse events after pregabalin administration under different surgical categories using a systematic review and meta-analysis of randomized controlled trials.A search of the literature was performed between August 2014 to April 2015, using PubMed, Ovid via EMBASE, Google Scholar, and ClinicalTrials.gov with no limitation on publication year or language. Studies considered for inclusion were randomized controlled trials, reporting on relevant outcomes (2-, 24-hour pain scores, or 24 hour morphine-equivalent consumption) with treatment with perioperative pregabalin.Seventy-four studies were included. Pregabalin reduced pain scores at 2 hours in all categories: cardiothoracic (Hedges g and 95%CI, −0.442 [−0.752 to −0.132], P = 0.005), ENT (Hedge g and 95%CI, −0.684 [−1.051 to −0.316], P < 0.0001), gynecologic (Hedge g, 95%CI, −0.792 [−1.235 to −0.350], P < 0.0001), laparoscopic cholecystectomy (Hedge g, 95%CI, –0.600 [–0.989 to –0.210], P = 0.003), orthopedic (Hedge g, 95%CI, −0.507 [−0.812 to −0.202], P = 0.001), spine (Hedge g, 95%CI, −0.972 [−1.537 to −0.407], P = 0.001), and miscellaneous procedures (Hedge g, 95%CI, −1.976 [−2.654 to −1.297], P < 0.0001). Pregabalin reduced 24-hour morphine consumption in gynecologic (Hedge g, 95%CI, −1.085 [−1.582 to −0.441], P = 0.001), laparoscopic cholecystectomy (Hedge g, 95%CI, –0.886 [–1.652 to –0.120], P = 0.023), orthopedic (Hedge g, 95%CI, −0.720 [−1.118 to −0.323], P < 0.0001), spine (Hedge g, 95%CI, −1.016 [−1.732 to −0.300], P = 0.005), and miscellaneous procedures (Hedge g, 95%CI, −1.329 [−2.286 to −0.372], P = 0.006). Pregabalin resulted in significant sedation in all surgical categories except ENT, laparoscopic cholecystectomy, and gynecologic procedures. Postoperative nausea and vomiting was only significant after pregabalin in miscellaneous procedures.Analgesic effects and incidence of adverse effects of using pregabalin are not equal in different surgical categories.

Peri‐operative cardiac protection for non‐cardiac surgery

Cardiovascular complications are an important cause of morbidity and mortality after non‐cardiac surgery. Pre‐operative identification of high‐risk individuals and appropriate peri‐operative management can reduce cardiovascular risk. It is important to continue chronic beta‐blocker and statin therapy. Statins are relatively safe and peri‐operative initiation may be beneficial in high‐risk patients and those scheduled for vascular surgery. The pre‐operative introduction of beta‐blockers reduces myocardial injury but increases rates of stroke and mortality, possibly due to hypotension. They should only be considered in high‐risk patients and the dose should be titrated to heart rate. Alpha‐2 agonists may also contribute to hypotension. Aspirin continuation can increase the risk of major bleeding and offset the benefit of reduced myocardial risk. Contrary to the initial ENIGMA study, nitrous oxide does not seem to increase the risk of myocardial injury. Volatile anaesthetic agents and opioids have been shown to be cardioprotective in animal laboratory studies but these effects have, so far, not been conclusively reproduced clinically.

Effects of intra‐operative maintenance of general anaesthesia with propofol on postoperative pain outcomes – a systematic review and meta‐analysis

Propofol is used both for induction and maintenance of anaesthesia. Recent evidence shows that propofol has analgesic properties. This meta‐analysis evaluated differences in postoperative analgesia between general anaesthetic maintenance with intravenous propofol and inhalational anaesthetics. Fourteen trials met inclusion criteria and were included. Our outcomes were pain scores 2 and 24 h after surgery. No significant difference in pain scores was found at 2 h after surgery (Hedges g (95% CI) −0.120 (−0.415–0.175) (p = 0.425). Propofol was associated with a statistically significant, albeit marginal, reduction in pain scores 24 h after surgery (Hedges g (95% CI) −0.134 (−0.248 to −0.021) (p = 0.021). Data were insufficient to allow a meaningful analysis regarding 24‐h morphine‐equivalent consumption. Propofol was associated with reduced postoperative nausea and vomiting (relative risk (95%CI) 0.446 (0.304–0.656) (p < 0.0001). In conclusion, this meta‐analysis suggests that propofol improves postoperative analgesia compared with inhalational anaesthesia 24 h after surgery, with a lower incidence of nausea and vomiting.

Sexually transmitted infection trends among gay or bisexual men from a clinic-based sentinel surveillance system in British Columbia, Canada.

Introduction We described trends for sexually transmitted infections (STI) among gay/bisexual men in British Columbia, Canada, using a sentinel site surveillance approach. Methods Using data from an electronic charting system, we included gay/bisexual men who visited high-volume STI clinics from 2000 to 2013. Diagnosis rates and incidence density were calculated for chlamydia, gonorrhea, syphilis, HIV, hepatitis C, genital herpes, and genital warts. Incidence density was estimated among repeat testers who converted from a negative to positive test result. We also conducted Poisson regression analysis to determine factors that were associated with increased incidence rates. Results A total of 47,170 visits were identified for gay/bisexual men during our time frame. The median age was 34 years (interquartile range, 27–43 years), and most clients were seen in Vancouver. Although trends for most STI were stable, diagnoses of gonorrhea and syphilis have risen steadily in recent years. Coinfection with HIV was associated with higher gonorrhea and syphilis rates in the Poisson regression model. In addition, visiting a Vancouver clinic and younger age were associated with increased incidence. Conclusions Our clinic-based sentinel surveillance system found increasing trends for gonorrhea and syphilis among gay/bisexual men but not for other STI in British Columbia. Further investigation is required to explore the syndemic effects of syphilis, gonorrhea, and HIV. This new platform will be a valuable tool for ongoing monitoring of STI and targeting prevention efforts.

Estimating the Size of the MSM Population in Metro Vancouver, Canada, Using Multiple Methods and Diverse Data Sources

Men who have sex with men (MSM) are disproportionately affected by HIV globally, regionally in Canada, and locally in Vancouver. Lack of reliable population size estimates of MSM impedes effective implementation of health care services and limits our understanding of the HIV epidemic. We estimated the population size of MSM residing in Metro Vancouver drawing on four data sources: the Canadian Community Health Survey (CCHS), a cross-sectional bio-behavioural MSM survey, HIV testing services data from sexually transmitted infection (STI) clinics serving MSM, and online social networking site Facebook. Estimates were calculated using (1) direct estimates from the CCHS, (2) “Wisdom of the Crowds” (WOTC), and (3) the multiplier method using data from a bio-behavioural MSM survey, clinic-based HIV testing, and online social media network site Facebook. Data sources requiring greater public disclosure of sexual orientation resulted in our mid-range population estimates (Facebook 23,760, CCHS 30,605). The WOTC method produced the lowest estimate, 10,000. The multiplier method using STI clinic HIV testing data produced the largest estimate, 41,777. The median of all estimates was 27,183, representing 2.9% of the Metro Vancouver census male adult population, with an interquartile range of 1.1–4.5%. Using multiple data sources, our estimates of the MSM population in Metro Vancouver are similar to population prevalence estimates based on population data from other industrialized nations. These findings will support understanding of the HIV burden among MSM and corresponding public health and health services planning for this key population.

Identifying injection drug use and estimating population size of people who inject drugs using healthcare administrative datasets

BACKGROUND Large linked healthcare administrative datasets could be used to monitor programs providing prevention and treatment services to people who inject drugs (PWID). However, diagnostic codes in administrative datasets do not differentiate non-injection from injection drug use (IDU). We validated algorithms based on diagnostic codes and prescription records representing IDU in administrative datasets against interview-based IDU data. METHODS The British Columbia Hepatitis Testers Cohort (BC-HTC) includes ∼1.7 million individuals tested for HCV/HIV or reported HBV/HCV/HIV/tuberculosis cases in BC from 1990 to 2015, linked to administrative datasets including physician visit, hospitalization and prescription drug records. IDU, assessed through interviews as part of enhanced surveillance at the time of HIV or HCV/HBV diagnosis from a subset of cases included in the BC-HTC (n = 6559), was used as the gold standard. ICD-9/ICD-10 codes for IDU and injecting-related infections (IRI) were grouped with records of opioid substitution therapy (OST) into multiple IDU algorithms in administrative datasets. We assessed the performance of IDU algorithms through calculation of sensitivity, specificity, positive predictive, and negative predictive values. RESULTS Sensitivity was highest (90-94%), and specificity was lowest (42-73%) for algorithms based either on IDU or IRI and drug misuse codes. Algorithms requiring both drug misuse and IRI had lower sensitivity (57-60%) and higher specificity (90-92%). An optimal sensitivity and specificity combination was found with two medical visits or a single hospitalization for injectable drugs with (83%/82%) and without OST (78%/83%), respectively. Based on algorithms that included two medical visits, a single hospitalization or OST records, there were 41,358 (1.2% of 11-65 years individuals in BC) recent PWID in BC based on health encounters during 3- year period (2013-2015). CONCLUSION Algorithms for identifying PWID using diagnostic codes in linked administrative data could be used for tracking the progress of programing aimed at PWID. With population-based datasets, this tool can be used to inform much needed estimates of PWID population size.

Effects of Single Nucleotide Polymorphisms on Surgical and Post-surgical Opioid Requirements - A Systematic Review and Meta-analysis

Objectives: There is great heterogeneity in the way individuals respond to medications. Inherited differences, such as single nucleotide polymorphisms (SNP), can influence the efficacy and toxicity of drugs. This meta-analysis aims to collate data from studies investigating the effect of SNPs on postoperative and/or intraoperative opioid requirements. Materials and Methods: A meta-analysis was conducted following PRISMA guidelines. Eligibility criteria for studies included were reporting amount of postoperative and/or intraoperative opioid used as the primary outcome and genotyping patients for SNPs in one of the following genes; OPRM1, CYP2D6, CYP3A4, CYP3A5, COMT, UGT2B7, or ABCB1. A comprehensive systematic search for articles using keywords “opioid-sensitivity,” “polymorphisms,” “post-operative opioid,” “post-surgical opioid,” “post-operative pain,” and “post-surgical pain” was performed. Results: Fifty-one studies were included. Individuals homozygous for AA at the OPRMI (rs1799971) polymorphisms required less postsurgical opioid compared with those homozygous for GG (Hedges g, −0.270; 95% confidence interval, −0.433 to −0.108; P=0.001). Polymorphisms in CYP2D6, CYP3A4, CYP3A5, COMT, UGT2B7, and ABCB1 did not affect opioid requirements. Discussion: Investigation of single changes in 1 gene can only yield limited information regarding genetic effects on opioid requirements. Rapid development of whole genome sequencing enables information on all genetic modifications that may affect analgesic response to be collected. The information collected must include data on the individual’s metabolic enzymes, as well as information on drug receptors and enzymes responsible for drug degradation, so that a personal profile can be built up which will predict individual response to drugs, and guide clinicians on the type and dosage of drug to use.

Changes in Prevalence, Outcomes, and Help-seeking Behavior of Chronic Pain in an Aging Population Over the Last Decade

Chronic pain is expected to increase as the population ages. This study aimed to investigate the changes in prevalence, patterns, and help‐seeking behavior of chronic pain and prevalence of neuropathic pain of an aging population in Hong Kong.

Effects of Intra-Operative Total Intravenous Anaesthesia with Propofol versus Inhalational Anaesthesia with Sevoflurane on Post-Operative Pain in Liver Surgery: A Retrospective Case-Control Study

Background Patients receiving total intravenous anesthesia (TIVA) with propofol have been shown to experience less postoperative pain. We evaluated the post-operative analgesic effects of propofol compared with sevoflurane maintenance of anesthesia in liver surgery. This study was registered at ClinicalTrials.gov (NCT02179437). Methods In this retrospective study, records of patients who underwent liver surgery between 2010 and 2013 were reviewed. Ninety-five patients anesthetized with propofol TIVA were matched with 95 patients anesthetized with sevoflurane. Numeric pain rating scale (NRS) pain scores, postoperative morphine consumption, side effects and patients’ satisfaction with pain relief were evaluated. Results The TIVA group reported lower NRS pain scores during coughing on postoperative days 1 and 2 but not 3 (p = 0.0127, p = 0.0472, p = 0.4556 respectively). They also consumed significantly less daily (p = 0.001 on day 1, p = 0.0231 on day 2, p = 0.0004 on day 3), accumulative (p = 0.001 on day 1, p<0.0001 on day 2 and p = 0.0064 on day 3) and total morphine (p = 0.03) when compared with the sevoflurane group. There were no differences in total duration of intravenous patient controlled analgesia (PCA) morphine use and patient satisfaction. No difference was found in reported side effects. Conclusion Patients anesthetized with propofol TIVA reported less pain during coughing and consumed less daily, accumulative and total morphine after liver surgery.