Publications by authors named "Stanley Wong"

91 Publications

The impact of current opioid agonist therapy on hepatitis C virus treatment initiation among people who use drugs from in the DAA era: A population-based study.

Clin Infect Dis 2021 Jun 14. Epub 2021 Jun 14.

British Columbia Centre for Disease Control, Vancouver, BC, Canada.

Background: Evidence that opioid agonist therapy (OAT) is associated with increased odds of hepatitis C virus (HCV) treatment initiation among people who use drugs (PWUD) is emerging. The objective of this study was to determine the association between current OAT and HCV treatment initiation among PWUD in a population-level linked administrative dataset.

Methods: The British Columbia (BC) Hepatitis Testers Cohort was used for this study, which includes all people tested for or diagnosed with HCV in BC, linked to medical visits, hospitalizations, laboratory, prescription drug, and mortality data from 1992 until 2019. PWUD with injecting drug use or opioid use disorder and chronic HCV infection were identified for inclusion in this study. HCV treatment initiation was the main outcome, and subdistribution proportional hazards modeling was used to assess the relationship with current OAT.

Results: 13,803 PWUD with chronic HCV were included in this study. Among those currently on OAT at the end of the study period, 47% (2,704/5,770) had started HCV treatment, whereas 22% (1778/8033) of those not currently on OAT has started HCV treatment .. Among PWUD with chronic HCV infection, current OAT was associated with higher likelihood of HCV treatment initiation in time to event analysis (adjusted hazard ratio 1.84 [95%CI, 1.50, 2.26]).

Conclusions: Current OAT was associated with a higher likelihood of HCV treatment initiation. However, many PWUD with HCV currently receiving OAT have yet to receive HCV treatment. Enhanced integration between substance use care and HCV treatment is needed to improve the overall health of PWUD.
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http://dx.doi.org/10.1093/cid/ciab546DOI Listing
June 2021

Impact of HCV infection and ethnicity on incident type 2 diabetes: findings from a large population-based cohort in British Columbia.

BMJ Open Diabetes Res Care 2021 06;9(1)

School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada

Introduction: Increasing evidence indicates that chronic hepatitis C virus (HCV) infection is associated with higher risk of diabetes. Previous studies showed ethnic disparities in the disease burden of diabetes, with increased risk in Asian population. We described the incidence of type 2 diabetes related to HCV infection and assessed the concurrent impact of HCV infection and ethnicity on the risk of diabetes.

Research Design And Methods: In British Columbia Hepatitis Testers Cohort, individuals were followed from HCV diagnosis to the earliest of (1) incident type 2 diabetes, (2) death or (3) end of the study (December 31, 2015). Study population included 847 021 people. Diabetes incidence rates in people with and without HCV were computed. Propensity scores (PS) analysis was used to assess the impact of HCV infection on newly acquired diabetes. PS-matched dataset included 117 184 people. We used Fine and Gray multivariable subdistributional hazards models to assess the effect of HCV and ethnicity on diabetes while adjusting for confounders and competing risks.

Results: Diabetes incidence rates were higher among people with HCV infection than those without. The highest diabetes incidence rate was in South Asians with HCV (14.7/1000 person-years, 95% CI 12.87 to 16.78). Compared with Others, South Asians with and without HCV and East Asians with HCV had a greater risk of diabetes. In the multivariable stratified analysis, HCV infection was associated with increased diabetes risk in all subgroups: East Asians, adjusted HR (aHR) 3.07 (95% CI 2.43 to 3.88); South Asians, aHR 2.62 (95% CI 2.10 to 3.26); and Others, aHR 2.28 (95% CI 2.15 to 2.42).

Conclusions: In a large population-based linked administrative health data, HCV infection was associated with higher diabetes risk, with a greater relative impact in East Asians. South Asians had the highest risk of diabetes. These findings highlight the need for care and screening for HCV-related chronic diseases such as type 2 diabetes among people affected by HCV.
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http://dx.doi.org/10.1136/bmjdrc-2021-002145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186745PMC
June 2021

Impact of direct-acting antivirals for HCV on mortality in a large population-based cohort study.

J Hepatol 2021 Jun 4. Epub 2021 Jun 4.

British Columbia Centre for Disease Control, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.

Background: We evaluated the effect of sustained virologic response(SVR) from direct acting antiviral(DAA) treatments on all-cause, liver- and drug-related mortality in a population-based cohort in British Columbia(BC), Canada.

Methods: We used data from the BC Hepatitis Testers Cohort, which includes people tested for hepatitis C virus(HCV) since 1990, linked with data on medical visits, hospitalizations, prescription drugs and mortality. We followed people who received DAAs and people who did not receive any HCV treatment to death or December 31, 2019. We used inverse probability of treatment weighting(IPTW) to balance the baseline profile of treated and untreated individuals and performed multivariable proportional hazard modeling to assess effect of DAAs on mortality.

Findings: There were 10,855 people treated with DAAs (SVR: 10,426 [96%], no-SVR: 425) and 10,855 untreated individuals. Median follow-up time was 2.2 years (interquartile range: 1.3-3.6; maximum: 6.2). The all-cause mortality rate was 19.5/1000 person-years (PY) among the SVR group(deaths=552), 86.5/1000 PY among the no-SVR group (deaths=96), and 99.2/1000 PY among the untreated group (deaths=2133). In the multivariable model, SVR was associated with significant reduction in all-cause(adjusted hazard ratio[aHR]:0.19, 95%CI:0.17-0.21), liver-(subdistribution HR[asHR]:0.22, 95%CI: 0.18-0.27) and drug-related mortality(asHR: 0.26, 95%CI:0.21-0.32) compared to no-treatment. Older age and cirrhosis were associated with higher risk of liver-related mortality while younger age, injection drug use(IDU), problematic alcohol use and HIV/HBV co-infections were associated with a higher risk of drug-related mortality.

Conclusions: DAA treatment is associated with a substantial reduction in all-cause, liver- and drug-related mortality. The association of IDU and related syndemic factors with a higher risk of drug-related mortality calls for an integrated social support, addiction, and HCV care approach among people with IDU.

Lay Summary: We assessed the effect of treatment of hepatitis C virus infection with direct acting antiviral drugs on deaths from all causes, liver disease and drug use. We found that treatment with direct acting antiviral drugs is associated with substantial lowering in risk of death from all causes, liver disease and drug use among people with hepatitis C virus infection.
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http://dx.doi.org/10.1016/j.jhep.2021.05.028DOI Listing
June 2021

Cohort profile: development and characteristics of a retrospective cohort of individuals dispensed prescription opioids for non-cancer pain in British Columbia, Canada.

BMJ Open 2021 04 13;11(4):e043586. Epub 2021 Apr 13.

BC Centre for Disease Control, Vancouver, British Columbia, Canada.

Purpose: Prescription opioids (POs) are widely prescribed for chronic non-cancer pain but are associated with several risks and limited long-term benefit. Large, linked data sources are needed to monitor their harmful effects. We developed and characterised a retrospective cohort of people dispensed POs.

Participants: We used a large linked administrative database to create the Opioid Prescribing Evaluation and Research Activities cohort of individuals dispensed POs for non-cancer pain in British Columbia (BC), Canada (1996-2015). We created definitions to categorise episodes of PO use based on a review of the literature (acute, episodic, chronic), developed an algorithm for inferring clinical indication and assessed patterns of PO use across a range of characteristics.

Findings To Date: The current cohort includes 1.1 million individuals and 3.4 million PO episodes (estimated to capture 40%-50% of PO use in BC). The majority of episodes were acute (81%), with most prescribed for dental or surgical pain. Chronic use made up 3% of episodes but 88% of morphine equivalents (MEQ). Across the acute to episodic to chronic episode gradient, there was an increasing prevalence of higher potency POs (hydromorphone, oxycodone, fentanyl, morphine), long-acting formulations and chronic pain related indications (eg, back, neck, joint pain). Average daily dose (MEQ) was similar for acute/episodic but higher for chronic episodes. Approximately 7% of the cohort had a chronic episode and chronic pain was the characteristic most strongly associated with chronic PO use. Individuals initiating a chronic episode were also more likely to have higher social/material deprivation and previous experience with a mental health condition or a problem related to alcohol or opioid use. Overall, these findings suggest our episode definitions have face validity and also provide insight into characteristics of people initiating chronic PO therapy.

Future Plans: The cohort will be refreshed every 2 years. Future analyses will explore the association between POs and adverse outcomes.
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http://dx.doi.org/10.1136/bmjopen-2020-043586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051385PMC
April 2021

Differences in risk factors for hepatitis B, hepatitis C, and human immunodeficiency virus infection by ethnicity: A large population-based cohort study in British Columbia, Canada.

Int J Infect Dis 2021 May 23;106:246-253. Epub 2021 Mar 23.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.

Objectives: Addressing the needs of ethnic minorities will be key to finding undiagnosed individuals living with hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV). To inform screening initiatives in British Columbia (BC), Canada, the factors associated with HBV and/or HCV and/or HIV infection among different ethnic groups within a large population-based cohort were assessed.

Methods: Persons diagnosed with HBV, HCV, or HIV in BC between 1990 and 2015 were grouped as East Asian, South Asian, Other Visible Minority (African, Central Asian, Latin American, Pacific Islander, West Asian, unknown ethnicity), and Not a Visible Minority, using a validated name-recognition software. Factors associated with infection within each ethnic group were assessed with multivariable multinomial logistic regression models.

Results: Participants included 202 521 East Asians, 126 070 South Asians, 65 210 Other Visible Minorities, and 1 291 561 people who were Not a Visible Minority, 14.4%, 3.3%, 4.5%, and 6.3% of whom had HBV and/or HCV and/or HIV infections, respectively. Injection drug use was most prevalent among infection-positive people who were Not a Visible Minority (22.1%), and was strongly associated with HCV monoinfection, HBV/HCV coinfection, and HCV/HIV coinfection, but not with HBV monoinfection among visible ethnic minorities. Extreme material deprivation and social deprivation were more prevalent than injection drug use or problematic alcohol use among visible ethnic minorities.

Conclusions: Risk factor distributions varied among persons diagnosed with HBV and/or HCV and/or HIV of differing ethnic backgrounds, with lower substance use prevalence among visible minority populations. This highlights the need for tailored approaches to infection screening among different ethnic groups.
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http://dx.doi.org/10.1016/j.ijid.2021.03.061DOI Listing
May 2021

Characterization of acute pain-induced behavioral passivity in mice: Insights from statistical modeling.

Eur J Neurosci 2021 05 18;53(9):3072-3092. Epub 2021 Mar 18.

Laboratory and Clinical Research Institute for Pain, Department of Anaesthesiology, The University of Hong Kong, Hong Kong, China.

Affective-motivational disturbances are highly inconsistent in animal pain models. The reproducibility of the open-field test in assessing anxiety, malaise or disability remains controversial despite its popularity. While traumatic, persistent or multiregional pain models are commonly considered more effective in inducing negative affect or functional impairment, the early psychobehavioral changes before pain chronification are often underexplored. Here, we aimed to clarify the fundamental relationship between hypernociception and passive distress-like behavior using a model of transient inflammatory pain. To minimize latent confounders and increase data consistency, male C57BL/6N mice were habituated to the open-field arena 6 times before receiving the unilateral intraplantar injection of prostaglandin E2 (PGE2) or vehicle. Open-field (40-min exploration) and nociceptive behavior were evaluated repeatedly along the course of hypernociception in both wild-type and transgenic mice with a known pronociceptive phenotype. To reduce subjectivity, multivariate open-field behavioral outcomes were analyzed by statistical modeling based on exploratory factor analyses, which yielded a 2-factor solution. Within 3 hr after PGE2 injection, mice developed significantly reduced center exploration (factor 1) and a marginally significant increase in their habituation tendency (factor 2), which were not apparent in vehicle-injected mice. The behavioral passivity generally improved as hypernociception subsided. Therefore, transient inflammatory irritation is sufficient to suppress mouse open-field exploratory activity. The apparent absence of late affective-motivational changes in some rodents with prolonged hypernociception may not imply a lack of preceding or underlying neuropsychological alterations. Procedural pain after invasive animal experiments, however small, should be assessed and adequately controlled as a potential research confounder.
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http://dx.doi.org/10.1111/ejn.15174DOI Listing
May 2021

Elevated risk of colorectal, liver, and pancreatic cancers among HCV, HBV and/or HIV (co)infected individuals in a population based cohort in Canada.

Ther Adv Med Oncol 2021 11;13:1758835921992987. Epub 2021 Feb 11.

BC Centre for Disease Control, Vancouver, Canada.

Introduction: Studies of the impact of hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV mono and co-infections on the risk of cancer, particularly extra-hepatic cancer, have been limited and inconsistent in their findings.

Methods: In the British Columbia Hepatitis Testers Cohort, we assessed the risk of colorectal, liver, and pancreatic cancers in association with HCV, HBV and HIV infection status. Using Fine and Gray adjusted proportional subdistribution hazards models, we assessed the impact of infection status on each cancer, accounting for competing mortality risk. Cancer occurrence was ascertained from the BC Cancer Registry.

Results: Among 658,697 individuals tested for the occurrence of all three infections, 1407 colorectal, 1294 liver, and 489 pancreatic cancers were identified. Compared to uninfected individuals, the risk of colorectal cancer was significantly elevated among those with HCV (Hazard ration [HR] 2.99; 95% confidence interval [CI] 2.55-3.51), HBV (HR 2.47; 95% CI 1.85-3.28), and HIV mono-infection (HR 2.30; 95% CI 1.47-3.59), and HCV/HIV co-infection. The risk of liver cancer was significantly elevated among HCV and HBV mono-infected and all co-infected individuals. The risk of pancreatic cancer was significantly elevated among individuals with HCV (HR 2.79; 95% CI 2.01-3.70) and HIV mono-infection (HR 2.82; 95% CI 1.39-5.71), and HCV/HBV co-infection.

Discussion/conclusion: Compared to uninfected individuals, the risk of colorectal, pancreatic and liver cancers was elevated among those with HCV, HBV and/or HIV infection. These findings highlight the need for targeted cancer prevention and diligent clinical monitoring for hepatic and extrahepatic cancers in infected populations.
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http://dx.doi.org/10.1177/1758835921992987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887683PMC
February 2021

Novel approach to reduce SARS-CoV-2 transmission during trans-oral robotic surgery.

J Robot Surg 2021 Feb 6. Epub 2021 Feb 6.

Division of Head and Neck Surgery, Department of Surgery, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, People's Republic of China.

This study describes a novel approach in the reduction of SARS-CoV-2 transmission during trans-oral robotic surgery (TORS). Eight patients underwent TORS between 01 February 2020 and 07 September 2020. A sterile plastic sheet draped over sterile supports with water-tight seal around each cannula was used to create a sterile working space within which the robotic arms could freely move during operation. This set-up acts as an additional physical barrier against droplet and aerosol transmission. Operative diagnosis; droplet count and distribution on plastic sheet and face shields of console and assistant surgeons, and scrub nurse were documented. TORS tumour excision was performed for patients with suspected tonsillar tumour (n = 3) and tongue base tumour (n = 2). TORS tonsillectomy and tongue base mucosectomy was performed for cervical nodal metastatic carcinoma of unknown origin (n = 3). Droplet contamination was noted on all plastic drapes (n = 8). Droplet contamination was most severe over the central surface at 97.2% (91.7-100.0%), with the highest droplet count along the centre-most column where it overlies the site of operation in the oral cavity 33.3% (n = 31). Droplet count decreased towards the periphery. Contamination rate was 2.8% (0.0-8.3%) over the right lateral surface. There was no droplet contamination over the vertex and left lateral surface of plastic drapes. No droplet contamination was noted on face shields of all parties. The use of sterile plastic drapes with water-tight seal around each robotic cannula can help reduce viral transmission to healthcare providers during TORS.
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http://dx.doi.org/10.1007/s11701-021-01200-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866962PMC
February 2021

Central Endothelin-1 Confers Analgesia by Triggering Spinal Neuronal Histone Deacetylase 5 (HDAC5) Nuclear Exclusion in Peripheral Neuropathic Pain in Mice.

J Pain 2021 04 6;22(4):454-471. Epub 2021 Jan 6.

Department of Anaesthesiology, The University of Hong Kong, HKSAR, China; Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, HKSAR, China; Research Centre of Heart, Brain, Hormone & Healthy Aging, The University of Hong Kong, HKSAR, China; Department of Anaesthesiology, The University of Hong Kong-Shenzhen Hospital, Guangdong province, China. Electronic address:

The rationale of spinal administration of endothelin-1(ET-1) mediated anti-nociceptive effect has not been elucidated. ET-1 is reported to promote nuclear effluxion of histone deacetylase 5 (HDAC5) in myocytes, and spinal HDAC5 is implicated in modulation of pain processing. In this study, we aimed to investigate whether central ET-1 plays an anti-nociceptive role by facilitating spinal HDAC5 nuclear shuttling under neuropathic pain. Here, we demonstrate that upregulating spinal ET-1 attenuated the nociception induced by partial sciatic nerve ligation surgery and this analgesic effect mediated by ET-1 was attenuated by intrathecal injection of endothelin A receptor selective inhibitor (BQ123) or by blocking the exportation of nuclear HDAC5 by adeno-associated viruses targeting neuronal HDAC5 (AVV-HDAC5 S259/498A Mutant). Notably, ET-1 administration increased spinal glutamate acid decarboxylases (GAD65/67) expression via initiating HDAC5 nuclear exportation and increased the acetylation of histone 3 at lysine 9 (Acetyl-H3K9) in the promotor regions of spinal Gad1 and Gad2 genes. This was reversed by blocking endothelin A receptor function or by inhibiting the spinal neuronal nuclear exportation of HDAC5. Therefore, inducing spinal GABAergic neuronal HDAC5 nuclear exportation may be a novel therapeutic approach for managing neuropathic pain. PERSPECTIVE: Neuropathic pain is intractable in a clinical setting, and epigenetic regulation is considered to contribute to this processing. Characterizing the anti-nociceptive effect of ET-1 and investigating the associated epigenetic mechanisms in animal models may lead to the development of new therapeutic strategies and targets for treating neuropathic pain.
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http://dx.doi.org/10.1016/j.jpain.2020.12.004DOI Listing
April 2021

HCV reinfection rates after cure or spontaneous clearance among HIV-infected and uninfected men who have sex with men.

Liver Int 2021 03 22;41(3):482-493. Epub 2020 Dec 22.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Background & Aims: Hepatitis C virus (HCV) reinfection among high-risk groups threatens HCV elimination goals. We assessed HCV reinfection rates among men who have sex with men (MSM) in British Columbia (BC), Canada.

Methods: We used data from the BC Hepatitis Testers Cohort, which includes nearly 1.7 million individuals tested for HCV or HIV in BC. MSM who had either achieved sustained virologic response (SVR) after successful HCV treatment, or spontaneous clearance (SC) and had ≥1 subsequent HCV RNA measurement, were followed from the date of SVR or SC until the earliest of reinfection, death, or last HCV RNA measurement. Predictors of reinfection were identified by Cox proportional modelling. The earliest study start date was 6 November 1997 and latest end date was 13 April 2018.

Results: Of 1349 HCV-positive MSM who met the inclusion criteria, 493 had SC while 856 achieved SVR. 349 (25.65%) had HIV coinfection. We identified 98 reinfections during 5203 person-years (PYs) yielding a reinfection rate of 1.88/100PYs. The reinfection rate among SC (2.74/100PYs) was more than twice that of those with SVR (1.03/100 PYs). Problematic alcohol use (aHR 1.73, 95% CI 1.003-2.92), injection drug use (aHR 2.60, 95% CI 1.57-4.29) and HIV coinfection (aHR 2.04, 95% CI 1.29-3.23) were associated with increased risk of HCV reinfection. Mental health counselling history (aHR 0.24, 95% CI 0.13-0.46) was associated with reduced HCV reinfection risk.

Conclusions: There is the need to engage MSM in harm reduction and prevention services following treatment to reduce reinfection risk.
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http://dx.doi.org/10.1111/liv.14762DOI Listing
March 2021

Total Intravenous Anesthesia (TIVA) With Propofol for Acute Postoperative Pain: A Scoping Review of Randomized Controlled Trials.

Asian J Anesthesiol 2020 09 3;58(3):79-93. Epub 2020 Nov 3.

Laboratory and Clinical Research Institute for Pain, Department of Anaesthesiology, The University of Hong Kong, Pokfulam, Hong Kong.

Total intravenous anesthesia (TIVA) with propofol may improve acute postoperative pain control compared to inhalational anesthesia. The objective of this review was to comprehensively update and evaluate the existing literature on the analgesic efficacy of propofol TIVA. A systemized literature search for randomized controlled trials in adult patients was conducted in the PubMed and Cochrane CENTRAL (EMBASE source) databases up to August 2019. Clinical trials included compared propofol TIVA against inhalational isoflurane, sevoflurane, or desflurane. Only clinical trials that studied acute postoperative pain scores or analgesic consumption as a primary outcome were included. Sixteen randomized controlled trials were included. Surgical procedures evaluated included: radical gastrectomy, open vein stripping, breast cancer surgery, laparoscopic cholecystectomy, inguinal herniotomy, abdominoplasty, bariatric surgery, lumbar spine surgery, emergency neurosurgical operations, open and laparoscopic gynecological surgeries, and dental surgery. Propofol TIVA was associated with reduced postoperative pain scores and/or decreased opioid consumption in 9 out of 16 clinical trials. There was no difference in 5 clinical trials, and propofol TIVA was associated with worse analgesic outcomes in 2 trials. Propofol TIVA may improve acute postoperative analgesia after surgery, but different factors such as surgical procedures and anesthetic/analgesic techniques may influence its effectiveness.
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http://dx.doi.org/10.6859/aja.202009_58(3).0001DOI Listing
September 2020

Covalent bonding of aromatic amine daughter products of 2,4-dinitroanisole (DNAN) with model quinone compounds representing humus via nucleophilic addition.

Environ Pollut 2021 Jan 15;268(Pt B):115862. Epub 2020 Oct 15.

Department of Chemical and Environmental Engineering, The University of Arizona, Tucson, AZ, 85721, USA. Electronic address:

2,4-Dinitroanisole (DNAN) is a component of insensitive munitions (IM), which are replacing traditional explosives due to their improved safety. Incomplete IM combustion releases DNAN onto the soil, where it can leach into the subsurface with rainwater, encounter anoxic conditions, and undergo (a)biotic reduction to aromatic amines 2-methoxy-5-nitroaniline (MENA), 4-methoxy-3-nitroaniline (iMENA, isomer of MENA), and 2,4-diaminoanisole (DAAN). We report here studies of nucleophilic addition mechanisms that may account for the sequestration of aromatic amine daughter products of DNAN into soil organic matter (humus), effectively removing these toxic compounds from the aqueous environment. Because quinones are important moieties in humus, we incubated MENA, iMENA, DAAN, and related analogs with model compounds 1,4-benzoquinone and 2,3-dimethyl-1,4-benzoquinone under anoxic conditions. Mass spectrometry and ultra-high performance liquid chromatography revealed that the aromatic amines had covalently bonded to either carbonyl carbons or ring carbons β to carbonyl carbons of the quinones, producing a mixture of imines and Michael adducts, respectively. These products formed rapidly and accumulated in the one-to four-day incubations. Nucleophilic addition reactions, which do not require catalysis or oxic conditions, are proposed as a mechanism resulting in the binding of DNAN to soil observed in previous studies. To remediate sites contaminated with DNAN or other nitroaromatics, reducing conditions and humus amendments may promote their immobilization into the soil matrix.
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http://dx.doi.org/10.1016/j.envpol.2020.115862DOI Listing
January 2021

Preoperative dexamethasone for pain relief after total knee arthroplasty: A randomised controlled trial.

Eur J Anaesthesiol 2020 Dec;37(12):1157-1167

From the Department of Anaesthesiology, Queen Mary Hospital (TCWC, AYFC), Department of Anaesthesiology, University of Hong Kong (CWC, SSCW, MGI), Department of Orthopaedics and Traumatology, Queen Mary Hospital (PKC, HF), Department of Orthopaedics and Traumatology, University of Hong Kong, Hong Kong, China (CHY, KYC).

Background: Corticosteroids can reduce pain but the optimal dose and safety profiles are still uncertain.

Objective: This study aimed to evaluate two different doses of dexamethasone for pain management and their side effects after total knee arthroplasty.

Design: A prospective randomised, controlled trial.

Setting: A tertiary teaching hospital in Hong Kong.

Patients: One hundred and forty-six patients were randomly allocated to one of three study groups.

Interventions: Before operation, patients in group D8, D16 and P received dexamethasone 8 mg, dexamethasone 16 mg and placebo (0.9% saline), respectively.

Main Outcome Measures: The primary outcome was postoperative pain score. Secondary outcomes were opioid consumption, physical parameters of the knees and side effects of dexamethasone.

Results: Compared with placebo, group D16 patients had significantly less pain during maximal active flexion on postoperative day 3 [-1.3 (95% CI, -2.2 to -0.31), P = 0.005]. There was also a significant dose-dependent trend between pain scores and dexamethasone dose (P = 0.002). Compared with placebo, patients in group D16 consumed significantly less opioid [-6.4 mg (95% CI, -11.6 to -1.2), P = 0.025] and had stronger quadriceps power on the first three postoperative days (all P < 0.05). They also had significantly longer walking distance on postoperative day 1 [7.8 m ([95% CI, 0.85 to 14.7), P = 0.023] with less assistance during walking on the first two postoperative days (all P < 0.029) and significantly better quality-of-recovery scores on postoperative day 1 (P = 0.018). There were significant dose-dependent trends between all the above parameters and dexamethasone dose (all P < 0.05). No significant differences were found in the incidence of chronic pain or knee function 3, 6 and 12 months postoperatively.

Conclusion: Dexamethasone 16 mg given before total knee arthroplasty led to a reduction in postoperative pain, less opioid consumption, stronger quadriceps muscle power, better mobilisation and better overall quality-of-recovery after operation. No long-term improvement in reduction in pain and function of the knee was found.

Trial Registration: ClinicalTrials.gov identifier: NCT02767882.
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http://dx.doi.org/10.1097/EJA.0000000000001372DOI Listing
December 2020

Drug-related deaths in a population-level cohort of people living with and without hepatitis C virus in British Columbia, Canada.

Int J Drug Policy 2020 Oct 19;86:102989. Epub 2020 Oct 19.

British Columbia Centre for Disease Control, 655 West 12(th) Avenue, Vancouver, British Columbia, Canada, V5Z 4R4; School of Population and Public Health, University of British Columbia, 2206 E Mall, Vancouver, British Columbia, Canada, V6T 1Z3.

Background: The majority of new HCV infections in Canada occur in people who inject drugs. Thus, while curative direct antiviral agents (DAAs) herald a promising new era in hepatitis C virus (HCV) treatment, improving the lives and wellbeing of people living with HCV (PLHCV) must be considered in the context of reducing overdose-related harms and with a syndemic lens. We measure drug-related deaths (DRDs) among HCV-negative people and PLHCV in British Columbia (BC), Canada, and the impact of potent contaminants like fentanyl on deaths.

Methods: We identified DRDs among PLHCV and HCV-negative individuals from 2010 to 2018 in the BC Hepatitis Testers Cohort, a population-based dataset of ~1.7 million British Columbians comprising comprehensive administrative and clinical data. We estimated annual standardized liver- and drug-related mortality rates per 100,000 person-years (PY) and described the contribution of specific drugs, including fentanyl and its analogues, implicated in DRDs over time.

Results: DRDs constituted 20.1% of deaths among PLHCV and 4.7% of deaths among HCV-negative individuals; a 4.3-fold (95% confidence interval: 4.0-4.5) difference. Drug-related mortality overtook liver-related mortality for PLHCV in 2015 and HCV-negative individuals in 2016 and rose from 241.7 to 436.5 per 100,000 PY from 2010 to 2018 amongPLHCV and from 20.0 to 57.1 per 100,000 PY for HCV-negative individuals over the same period. The proportion of deaths attributable to drugs among PLHCV and HCV-negative individuals increased from 15.1% to 26.1% and 3.1% to 8.0%, in 2010 and 2018, respectively. The proportion of DRDs attributed solely to synthetic opioids such as fentanyl averaged across both groups increased from 2.1% in 2010 to 69.6% in 2017.

Conclusion: Steep drug-related mortality increases among PLHCV and HCV-negative individuals over the last decade highlight the urgent need to address overdose-related drivers and harms in these populations using an integrated care approach.
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http://dx.doi.org/10.1016/j.drugpo.2020.102989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569420PMC
October 2020

Concurrent Hepatitis C and B Virus and Human Immunodeficiency Virus Infections Are Associated With Higher Mortality Risk Illustrating the Impact of Syndemics on Health Outcomes.

Open Forum Infect Dis 2020 Sep 13;7(9):ofaa347. Epub 2020 Aug 13.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Background: Hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) infections are associated with significant mortality globally and in North America. However, data on impact of concurrent multiple infections on mortality risk are limited. We evaluated the effect of HCV, HBV, and HIV infections and coinfections and associated factors on all-cause mortality in British Columbia (BC), Canada.

Methods: The BC Hepatitis Testers Cohort includes ~1.7 million individuals tested for HCV or HIV, or reported as a case of HCV, HIV, or HBV from 1990 to 2015, linked to administrative databases. We followed people with HCV, HBV, or HIV monoinfection, coinfections, and triple infections from their negative status to date of death or December 31, 2016. Extended Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with all-cause mortality.

Results: Of 658 704 individuals tested for HCV, HBV, and HIV, there were 33 804 (5.13%) deaths. In multivariable Cox regression analysis, individuals with HCV/HBV/HIV (HR, 8.9; 95% CI, 8.2-9.7) infections had the highest risk of mortality followed by HCV/HIV (HR, 4.8; 95% CI, 4.4-5.1), HBV/HIV (HR, 4.1; 95% CI, 3.5-4.8), HCV/HBV (HR, 3.9; 95% CI, 3.7-4.2), HCV (HR, 2.6; 95% CI, 2.6-2.7), HBV (HR, 2.2; 95% CI, 2.0-2.3), and HIV (HR, 1.6; 95% CI, 1.5-1.7). Additional factors associated with mortality included injection drug use, problematic alcohol use, material deprivation, diabetes, chronic kidney disease, heart failure, and hypertension.

Conclusions: Concurrent multiple infections are associated with high mortality risk. Substance use, comorbidities, and material disadvantage were significantly associated with mortality independent of coinfection. Preventive interventions, including harm reduction combined with coinfection treatments, can significantly reduce mortality.
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http://dx.doi.org/10.1093/ofid/ofaa347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489531PMC
September 2020

Comparing direct acting antivirals for hepatitis C using observational data - Why and how?

Pharmacol Res Perspect 2020 10;8(5):e00650

Division of Infectious Diseases and Chronic Viral Illness Service, Department of Medicine, Glen Site, McGill University Health Centre, Montreal, QC, Canada.

The World Health Organisation's goal of hepatitis C virus (HCV) elimination by 2030 will require lower drug prices. Estimates of comparative efficacy promote competition between pharmaceutical companies but direct acting antivirals have been approved for the treatment of HCV without comparative trials. We emulated a randomized trial to answer the question of whether easy to treat patients with genotype 1 HCV could be treated with sofosbuvir/ledipasvir (SOF/LDV) rather than sofosbuvir/velpatasvir (SOF/VEL). Patients without comorbidities or end stage liver disease were selected from the British Colombia Hepatitis Testers Cohort. To create a conceptual trial, we matched each patient starting SOF/VEL (a 'case') to the patient starting SOF/LDV with the closest propensity score (a 'control'). We estimated the probability of treatment failure under a Bayesian logistic model with a random effect for each case-control set and used that model to give an estimate of a risk difference for the conceptual trial. Treatment failure was recorded for 27 of 825 (3%) cases and for 29 of 602 (5%) matched controls. Estimates from our model were treatment success rates of 97% (95% credible interval, CrI, 95%-98%) for treatment with SOF/VEL, 95% (95% CrI 93%-97%) for treatment with SOF/LDV and a risk difference between treatments of 2% (95% CrI 0%-4%). This risk difference is evidence that SOF/LDV is not inferior to SOF/VEL for easy to treat patients with genotype 1 HCV. The approach is a template for comparing drugs when there are no data from comparative trials.
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http://dx.doi.org/10.1002/prp2.650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507378PMC
October 2020

Dysregulation of EAAT2 and VGLUT2 Spinal Glutamate Transports via Histone Deacetylase 2 (HDAC2) Contributes to Paclitaxel-induced Painful Neuropathy.

Mol Cancer Ther 2020 10 26;19(10):2196-2209. Epub 2020 Aug 26.

Laboratory and Clinical Research Institute for Pain, Department of Anaesthesiology, The University of Hong Kong, Hong Kong, SAR, China.

Effective treatments for chemotherapy-induced peripheral neuropathy (CIPN) remain unavailable. Given the significance of spinal cord glutamate transporters in neuronal plasticity and central sensitization, this study investigated the role of excitatory amino acid transporter 2 (EAAT2) and vesicular-glutamate transporter 2 (VGLUT2) in the development of paclitaxel-induced painful neuropathy. Paclitaxel (2 mg/kg, i.p., cumulative dose 8 mg/kg) induced long-lasting mechanical allodynia (>28 days) with increased glutamate concentration and decreased EAAT2 expression with no changes in GABA/glycine or VGAT (vesicular GABA transporter) in rat spinal dorsal horn. VGLUT2 expression was upregulated and coexpressed with enhanced synaptophysin, characterizing nociceptive afferent sprouting and new synapse formation of glutamatergic neurons in the spinal cord dorsal horn. HDAC2 and transcription factor YY1 were also upregulated, and their interaction and colocalization were confirmed following paclitaxel treatment using co-immunoprecipitation. Inhibition or knockdown of HDAC2 expression by valproic acid, BRD6688, or HDAC2 siRNA not only attenuated paclitaxel-induced mechanical allodynia but also suppressed HDAC2 upregulation, glutamate accumulation, and the corresponding changes in EAAT2/VGLUT/synaptophysin expression and HDAC2/YY1 interaction. These findings indicate that loss of the balance between glutamate release and reuptake due to dysregulation EAAT2/VGLUT2/synaptophysin cascade in the spinal dorsal horn plays an important role in the development of paclitaxel-induced neuropathic pain. HDAC2/YY1 interaction as a complex appears essential in regulating this pathway, which can potentially be a therapeutic target to relieve CIPN by reversing central sensitization of spinal nociceptive neurons.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0006DOI Listing
October 2020

Syndemic profiles of people living with hepatitis C virus using population-level latent class analysis to optimize health services.

Int J Infect Dis 2020 Nov 15;100:27-33. Epub 2020 Aug 15.

School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; BC Centre for Disease Control, Vancouver, BC, Canada; Centre for Health Evaluation and Outcome Sciences, Vancouver, BC, Canada. Electronic address:

Background: Hepatitis C (HCV) affects diverse populations such as people who inject drugs (PWID), 'baby boomers,' gay/bisexual men who have sex with men (gbMSM), and people from HCV endemic regions. Assessing HCV syndemics (i.e.relationships with mental health/chronic diseases) among subpopulations using Latent Class Analysis (LCA) may facilitate targeted program planning.

Methods: The BC Hepatitis Testers Cohort(BC-HTC) includes all HCV cases identified in BC between 1990 and 2015, integrated with medical administrative data. LCA grouped all BC-HTC HCV diagnosed people(n = 73,665) by socio-demographic/clinical indicators previously determined to be relevant for HCV outcomes. The final model was chosen based on fit statistics, epidemiological meaningfulness, and posterior probability. Classes were named by most defining characteristics.

Results: The six-class model was the best fit and had the following names and characteristics: 'Younger PWID'(n =11,563): recent IDU (67%), people born >1974 (48%), mental illness (62%), material deprivation (59%). 'Older PWID'(n =15,266): past IDU (78%), HIV (17%), HBV (17%) coinfections, alcohol misuse(68%). 'Other Middle-Aged People'(n = 9019): gbMSM (26%), material privilege (31%), people born between 1965-1974 (47%). 'People of Asian backgrounds' (n = 4718): East/South Asians (92%), no alcohol misuse (97%) or mental illness (93%), people born <1945 (26%), social privilege (66%). 'Rural baby boomers' (n = 20,401): rural dwellers (32%), baby boomers (79%), heterosexuals (99%), no HIV (100%). 'Urban socially deprived baby boomers' (n = 12,698): urban dwellers (99%), no IDU (100%), liver disease (22%), social deprivation (94%).

Conclusions: Differences between classes suggest variability in patients' service needs. Further analysis of health service utilization patterns may inform optimal service layout.
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http://dx.doi.org/10.1016/j.ijid.2020.08.035DOI Listing
November 2020

Impacts of Human Papillomavirus Immunization Programs on Rates of Anogenital Warts in British Columbia, Canada, 2000 to 2017.

Sex Transm Dis 2020 10;47(10):691-697

Faculty of Pharmacy, University of British Columbia.

Background: In 2008, British Columbia (BC) implemented a school-based quadrivalent human papillomavirus (HPV-4) immunization program for girls born in 1994 or later. In 2015, an expanded clinic-based program included men who report sex with men (MSM) born in 1989 or later. To evaluate the impacts of HPV-4 programs on anogenital warts (AGWs), diagnosis rates were measured among women who report sex with men (WSM), men who report sex with women (MSW), and MSM.

Methods: Diagnoses of AGW were ascertained from 16 sexually transmitted infection clinics. Rates were calculated as new AGW diagnoses over person-years (py) at risk and stratified by age group, calendar period, and birth cohort. Adjusted relative rates (aRR) were estimated using multivariable Poisson regression.

Results: There were 204,832 clinic visits by 85,158 individuals: 28,366 (33%) WSM, 35,688 (42%) MSW, and 14,534 (17%) MSM. After adjusting for age and period, AGW rates in the 1994-1996 birth cohort decreased by 56% overall (1.21 vs. 2.72 cases/100 py; aRR, 0.44; 95% confidence interval [CI], 0.34-0.59), 65% among WSM (0.97 vs. 2.77 cases/100 py; aRR, 0.35; 95% CI, 0.22-0.57), 58% among MSW (1.60 vs. 3.78 cases/100 py; aRR, 0.42; 95% CI, 0.28-0.65), and 41% among MSM (1.14 vs. 1.19 cases/100 py; aRR, 0.59; 95% CI, 0.38-0.91) versus the 1991-1993 birth cohort.

Conclusions: The HPV-4 programs had significant impacts on lowering AGW rates in BC. The greatest decrease was among WSM eligible for the school-based program, followed by birth cohorts of men who likely have sex with HPV-4 eligible women. The smallest decrease among MSM may reflect the later introduction of the clinic-based program.
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http://dx.doi.org/10.1097/OLQ.0000000000001235DOI Listing
October 2020

Recommendations for surgical management of recurrent nasopharyngeal carcinoma during COVID-19 pandemic.

Laryngoscope Investig Otolaryngol 2020 Jun 13;5(3):468-472. Epub 2020 Jun 13.

Division of Head and Neck Surgery, Department of Surgery University of Hong Kong Li Ka Shing Faculty of Medicine, Queen Mary Hospital Hong Kong SAR China.

Nasopharyngeal carcinoma is endemic in southern parts of China including Hong Kong. Primary treatment entails radiotherapy ± chemotherapy depending on disease stage at presentation. Surgery is offered as a means of salvage for persistent and recurrent disease. Comprehensive preoperative work-up, careful patient selection, attention to details perioperation and multidisciplinary approach is essential in ensuring optimal outcomes after salvage surgery for recurrent nasopharyngeal carcinoma patients. Since the COVID-19 outbreak, we are faced with unprecedented challenges with priorities of care and resources being shifted to combat the virus. These include patient selection and timing of treatment, while preventing disease transmission to heath care providers. Practices and recommendations made in this document are intended to support safe clinical practice and efficient use of resources during this challenging time.
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http://dx.doi.org/10.1002/lio2.417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314480PMC
June 2020

Hospital Costs of Injection Drug Use in Florida.

Clin Infect Dis 2021 02;72(3):499-502

Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.

People who inject drugs (PWID) experience significant injection-related infections (IRIs) at significant healthcare system cost. This study used and validated an algorithm based on the International Classification of Diseases, Tenth Revision, to estimate hospitalized PWID populations, assess the total statewide morbidity for IRIs among PWID, and calculate associated costs of care.
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http://dx.doi.org/10.1093/cid/ciaa823DOI Listing
February 2021

Infraclavicular nerve block reduces postoperative pain after distal radial fracture fixation: a randomized controlled trial.

BMC Anesthesiol 2020 05 28;20(1):130. Epub 2020 May 28.

Laboratory and Clinical Research Institute for Pain, Department of Anaesthesiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Room 424, Block K, 102, Pokfulam Road, Hong Kong SAR, China.

Background: It is unclear whether regional anesthesia with infraclavicular nerve block or general anesthesia provides better postoperative analgesia after distal radial fracture fixation, especially when combined with regular postoperative analgesic medications. The aim of this study was to compare the postoperative analgesic effects of regional versus general anesthesia.

Methods: In this prospective, observer blinded, randomized controlled trial, 52 patients undergoing distal radial fracture fixation received either general anesthesia (n = 26) or regional anesthesia (infraclavicular nerve block, n = 26). Numerical rating scale pain scores, analgesic consumption, patient satisfaction, adverse effects, upper limb functional scores (Patient-Rated Wrist Evaluation, QuickDASH), health related quality of life (SF12v2), and psychological status were evaluated after surgery.

Result: Regional anesthesia was associated with significantly lower pain scores both at rest and with movement on arrival to the post-anesthetic care unit; and at 1, 2, 24 and 48 h after surgery (p ≤ 0.001 at rest and with movement). Morphine consumption in the post-anesthetic care unit was significantly lower in the regional anesthesia group (p<0.001). There were no differences in oral analgesic consumption. Regional anesthesia was associated with lower incidences of nausea (p = 0.004), and vomiting (p = 0.050). Patient satisfaction was higher in the regional anesthesia group (p = 0.003). There were no long-term differences in pain scores and other patient outcomes.

Conclusion: Regional anesthesia with ultrasound guided infraclavicular nerve block was associated with better acute pain relief after distal radial fracture fixation, and may be preferred over general anesthesia.

Trial Registration: Before subject enrollment, the study was registered at ClinicalTrials.gov (NCT03048214) on 9th February 2017.
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http://dx.doi.org/10.1186/s12871-020-01044-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254671PMC
May 2020

Tracheostomy during COVID-19 pandemic-Novel approach.

Head Neck 2020 Jul 6;42(7):1367-1373. Epub 2020 May 6.

Division of Head and Neck Surgery, Department of Surgery, University of Hong Kong Li Ka Shing Faculty of Medicine, Queen Mary Hospital, Hong Kong, China.

Background: This study describes a novel approach in reducing SARS-CoV-2 transmission during tracheostomy.

Methods: Five patients underwent tracheostomy between April 1, 2020 and April 17, 2020. A clear and sterile plastic drape was used as an additional physical barrier against droplets and aerosols. Operative diagnosis; droplet count and distribution on plastic sheet and face shields were documented.

Results: Tracheostomy was performed for patients with carcinoma of tonsil (n = 2) and nasopharynx (n = 1), and aspiration pneumonia (n = 2). Droplet contamination was noted on all plastic sheets (n = 5). Droplet contamination was most severe over the central surface at 91.5% (86.7%-100.0%) followed by the left and right lateral surfaces at 5.2% (6.7%-10.0%) and 3.3% (6.7%-10.0%), respectively. No droplet contamination was noted on all face shields.

Conclusion: Plastic drapes can help reduce viral transmission to health care providers during tracheostomy. Face shields may be spared which in turn helps to conserve resources during the novel coronavirus disease 2019 pandemic.
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http://dx.doi.org/10.1002/hed.26234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267533PMC
July 2020

The Frequency and Healthfulness of Food and Beverage Advertising in Movie Theatres: A Pilot Study Conducted in the United States and Canada.

Nutrients 2020 Apr 28;12(5). Epub 2020 Apr 28.

School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, 600 Peter Morand, Room 301J, Ottawa, ON K1G5Z3, Canada.

The marketing of unhealthy foods and beverages contributes to childhood obesity. In Canada and the United States, these promotions are self-regulated by industry. However, these regulations do not apply to movie theatres, which are frequently visited by children. This pilot study examined the frequency and healthfulness of food advertising in movie theatres in the United States and Canada. A convenience sample of seven movie theatres in both Virginia (US) and Ontario (Canada) were visited once per month for a four-month period. Each month, ads in the movie theatre environment and before the screening of children's movies were assessed. Food ads were categorized as permissible or not permissible for marketing to children using the World Health Organization's European Nutrient Profile Model. There were 1999 food ads in the movie theatre environment in Ontario and 43 food ads identified in the movie theatre environment in Virginia. On average, 8.6 (SD = 3.3) and 2.2 (SD = 0.9) food ads were displayed before children's movies in Ontario and Virginia, respectively. Most or all (97%-100%) food ads identified in Virginia and Ontario were considered not permissible for marketing to children. The results suggest that movie theatre environments should be considered for inclusion in statutory food marketing restrictions in order to protect children's health.
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http://dx.doi.org/10.3390/nu12051253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282003PMC
April 2020

Conservation of personal protective equipment for head and neck cancer surgery during COVID-19 pandemic.

Head Neck 2020 06 29;42(6):1187-1193. Epub 2020 Apr 29.

Division of Head and Neck Surgery, Department of Surgery, University of Hong Kong Li Ka Shing Faculty of Medicine, Queen Mary Hospital, Hong Kong, China.

Background: COVID-19 pandemic has led to a global shortage of personal protective equipment (PPE). This study aims to stratify face shield needs when performing head and neck cancer surgery.

Methods: Fifteen patients underwent surgery between March 1, 2020 and April 9, 2020. Operative diagnosis and procedure; droplet count and distribution on face shields were documented.

Results: Forty-five surgical procedures were performed for neck nodal metastatic carcinoma of unknown origin (n = 3); carcinoma of tonsil (n = 2), tongue (n = 2), nasopharynx (n = 3), maxilla (n = 1), and laryngopharynx (n = 4). Droplet contamination was 57.8%, 59.5%, 8.0%, and 0% for operating, first and second assistant surgeons, and scrub nurse respectively. Droplet count was highest and most widespread during osteotomies. No droplet splash was noted for transoral robotic surgery.

Conclusion: Face shield is not a mandatory adjunctive PPE for all head and neck surgical procedures and health care providers. Judicious use helps to conserve resources during such difficult times.
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http://dx.doi.org/10.1002/hed.26215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267333PMC
June 2020

Optimization of opioid utility in cancer pain populations.

Ann Palliat Med 2020 Mar 17;9(2):558-570. Epub 2020 Mar 17.

Department of Anaesthesiology, Laboratory and Clinical Research Institute for Pain, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.

In this era of crisis and controversy surrounding opioid therapy, we must remember that cancer patients entrust us with supporting them through what might be the most difficult, and oftentimes final, period of their life. The factors that affect the benefits and risks of opioid use in cancer patients and the non-cancer population are quite different. In fact, opioid-associated deaths are 10 times less likely in the former than the latter population, suggesting that a reluctance to initiate opioids in cancer patients can risk under treatment of complex pain. In this review, we outline the considerations and evidence-based practices required to manage the clinical situations that challenge the judicious use of opioids in patients with cancer. A comprehensive review that enable us to better understand and quantify the root causes of variability in pain control, as well as risks of opioid misuse or abuse, would arm healthcare providers with the tools they need to implement multi-modal approaches to treatment planning.
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http://dx.doi.org/10.21037/apm.2020.03.04DOI Listing
March 2020

The impact of SVR from direct-acting antiviral- and interferon-based treatments for HCV on hepatocellular carcinoma risk.

J Viral Hepat 2020 08 17;27(8):781-793. Epub 2020 Apr 17.

British Columbia Centre for Disease Control, Vancouver, BC, Canada.

We evaluated the effect of sustained virologic response (SVR) from direct-acting antiviral (DAA)- and interferon-based treatments on hepatocellular carcinoma (HCC) risk in a large population-based cohort in Canada. We used data from the BC Hepatitis Testers Cohort, which includes ~1.3 million individuals tested for HCV since 1990, linked with healthcare administrative and registry datasets. Patients were followed from the end of HCV treatment to HCC, death or 31 December 2016. We assessed HCC risk among those who did and did not achieve SVR by treatment type using proportional hazard models. Of 12 776 eligible individuals, 3905 received DAAs while 8871 received interferon-based treatments, followed for a median of 1.0 [range: 0.6-2.7] and 7.9 [range: 4.4-17.1] years, respectively. A total of 3613 and 6575 achieved SVR with DAAs- and interferon-based treatments, respectively. Among DAAs-treated patients, HCC incidence rate was 6.9 (95%CI: 4.7-10.1)/1000 person yr (PY) in SVR group (HCC cases: 26) and 38.2 (95%CI: 20.6-71.0) in the no-SVR group (HCC cases: 10, P < .001). Among interferon-treated individuals, HCC incidence rate was 1.8 (95%CI: 1.5-2.2) in the SVR (HCC cases: 99) and 13.9 (95%CI: 12.3-15.8) in the no-SVR group (HCC cases: 239, P < .001). Compared with no-SVR from interferon, SVR from DAA- and interferon-based treatments resulted in significant reduction in HCC risk (adjusted subdistribution hazard ratio (adjSHR) DAA = 0.30, 95%CI: 0.19-0.48 and adjSHR interferon = 0.2, 95%CI: 0.16-0.26). Among those with SVR, treatment with DAAs compared to interferon was not associated with HCC risk (adjSHR = 0.93, 95%CI: 0.51-1.71). In conclusion, similar to interferon era, DAA-related SVR is associated with 70% reduction in HCC risk.
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http://dx.doi.org/10.1111/jvh.13295DOI Listing
August 2020

Analgesic Effects of Cannabinoids for Chronic Non-cancer Pain: a Systematic Review and Meta-Analysis with Meta-Regression.

J Neuroimmune Pharmacol 2020 12 14;15(4):801-829. Epub 2020 Mar 14.

Laboratory and Clinical Research Institute for Pain, Department of Anaesthesiology, The University of Hong Kong, Hong Kong, HKSAR, People's Republic of China.

There is growing interest in using cannabinoids for chronic pain. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the analgesic efficacy and adverse effects of cannabinoids for chronic non-cancer pain. PubMed, EMBASE, Web of Science, Cochrane CENTRAL and clinicaltrials.gov were searched up to December 2018. Information on the type, dosage, route of administration, pain conditions, pain scores, and adverse events were extracted for qualitative analysis. Meta-analysis of analgesic efficacy was performed. Meta-regression was performed to compare the analgesic efficacy for different pain conditions (neuropathic versus non-neuropathic pain). Risk of bias was assessed by The Cochrane Risk of Bias tool, and the strength of the evidence was assessed using the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Forty-three randomized controlled trials were included. Meta-analysis was performed for 33 studies that compared cannabinoids to placebo, and showed a mean pain score (scale 0-10) reduction of -0.70 (p < 0.001, random effect). Meta-regression showed that analgesic efficacy was similar for neuropathic and non-neuropathic pain (Difference = -0.14, p = 0.262). Inhaled, oral, and oromucosal administration all provided statistically significant, but small reduction in mean pain score (-0.97, -0.85, -0.45, all p < 0.001). Incidence of serious adverse events was rare, and non-serious adverse events were usually mild to moderate. Heterogeneity was moderate. The GRADE level of evidence was low to moderate. Pain intensity of chronic non-cancer patients was reduced by cannabinoids consumption, but effect sizes were small. Efficacy for neuropathic and non-neuropathic pain was similar.
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http://dx.doi.org/10.1007/s11481-020-09905-yDOI Listing
December 2020

Real-world Effectiveness of Sofosbuvir/Velpatasvir for Treatment of Chronic Hepatitis C in British Columbia, Canada: A Population-Based Cohort Study.

Open Forum Infect Dis 2020 Mar 29;7(3):ofaa055. Epub 2020 Feb 29.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Background: Clinical trials show high efficacy of sofosbuvir/velpatasvir (SOF/VEL), but there are limited data from "real-world" settings. We aimed to evaluate SOF/VEL effectiveness for all hepatitis C virus (HCV) genotypes (GTs) in British Columbia (BC), Canada.

Methods: We used the BC Hepatitis Testers Cohort, which includes all HCV cases in the province (1990-2015) linked to administrative databases, including prescriptions to end of 2018. We measured sustained virologic response (SVR; negative RNA ≥10 weeks after treatment end) and identified characteristics associated with non-SVR. Conservatively, we excluded individuals with no assessment for SVR if their last RNA test after treatment initiation was negative (but included if positive).

Results: Of 2821 eligible participants, most were infected with GT1 (1076, 38.1%) or GT3 (1072, 38.0%), and a minority (278, 9.9%) were treated with RBV. SVR was 94.6% (2670/2821) overall and 94.5% (1017/1076) for GT1, 96.4% (512/531) for GT2, and 93.7% (1004/1072) for GT3. When disaggregated by GT, treatment regimen, and cirrhosis/treatment experience, SVR was lowest (30/40, 75.0%) among treatment-experienced GT3 individuals treated with RBV. Characteristics associated with non-SVR in multivariable analysis included younger age, RBV addition, and being a person with HIV (PWH) or who injects/injected drugs (PWID). When treatment regimen (±RBV) was removed from multivariable model, treatment experience was associated with non-SVR for GT3. Of 151 non-SVR individuals, 56.3% were nonvirological failures (treatment incomplete/no assessment for SVR) and 43.7% were virological failures (nonresponse/relapse). A disproportionately high percentage of non-SVR among PWID was due to nonvirological failure.

Conclusions: SOF/VEL was highly effective in this "real-world" population-based cohort. Additional support is required for PWID/PWH to reach SVR.
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http://dx.doi.org/10.1093/ofid/ofaa055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052750PMC
March 2020

Loss to follow-up: A significant barrier in the treatment cascade with direct-acting therapies.

J Viral Hepat 2020 03 2;27(3):243-260. Epub 2019 Dec 2.

BC Centre for Disease Control, Vancouver, BC, Canada.

Effectiveness of direct-acting antiviral (DAA) therapies could be influenced by patient characteristics such as comorbid conditions, which could lead to premature treatment discontinuation and/or irregular medical follow-ups. Here, we evaluate loss to follow-up and treatment effectiveness of sofosbuvir/ledipasvir ± ribavirin (SOF/LDV ± RBV), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) for hepatitis C virus (HCV) genotype 1 (GT1) and sofosbuvir + ribavirin (SOF + RBV) for genotype 3 (GT3) in British Columbia Canada: The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV since 1992, integrated with medical visit, hospitalization and prescription drug data. HCV-positive individuals who initiated DAA regimens, irrespective of treatment completion, for GT1 and GT3 until 31 December, 2017 were included. Factors associated with sustained virological response (SVR) and loss to follow-up were assessed by using multivariable logistic regression models. In total 4477 individuals initiated DAAs. The most common prescribed DAA was SOF/LDV ± RBV with SVR of 95%. The highest SVR of 99.5% was observed among OBV/PTV/r + DSV-treated patients. Overall, 453 (10.1%) individuals were lost to follow-up. Higher loss to follow-up was observed among GT1 patients treated with OBV (17.8%) and GT3 patients (15.7%). The loss to follow-up rate was significantly higher among individuals aged <60 years, those with a history of injection drug use (IDU), on opioid substitution therapy and with cirrhosis. Our findings indicate that loss to follow-up exceeds viral failure in HCV DAA therapy and its rate varies significantly by genotype and treatment regimen. Depending on the aetiology of lost to follow-up, personalized case management for those with medical complications and supporting services among IDU are needed to achieve the full benefits of effective treatments.
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http://dx.doi.org/10.1111/jvh.13228DOI Listing
March 2020
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