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Patients with homozygous familial hypercholesterolemia (HoFH) have a high risk for premature death. Supravalvular aortic stenosis (SVAS) is a common and the feature lesion of the aortic root in HoFH. The relation between SVAS and the risk of premature death in patients with HoFH has not been fully investigated. The present study analysis included 97 HoFH patients with mean age of 14.7 (years) from the Genetic and Imaging of Familial Hypercholesterolemia in Han Nationality Study. During the median (±SD) follow-up 4.0 (±4.0) years, 40 (41.2%) participants had SVAS and 17 (17.5%) participants experienced death. The proportion of premature death in the non-SVAS and SVAS group was 7.0% and 32.5%, respectively. Compared with the non-SVAS group, SVAS group cumulative survival was lower in the HoFH (log-rank test, p

Background Visits to the emergency department are critical opportunities to engage individuals after an overdose. We sought to estimate and compare the 12-month mortality between persons with visits to the emergency department related to opioid overdose and those with non-overdose-related visits. Methods We conducted a retrospective cohort study using the Provincial Overdose Cohort, which contains data for patients in British Columbia who had an opioid-related overdose between 2015 and 2017, along with a 20% random sample of BC residents for comparison. We examined all nonfatal visits to the emergency department between Jan. 1, 2015, and Dec. 31, 2016, among persons aged 14 to 74 years and compared the 12-month mortality between those with overdose-related visits and those with non-overdose-related visits. We estimated the hazard ratio for death, with adjustment for age, sex, comorbidity and disposition (discharged or left against medical advice). Results We included 3593 persons with overdose-related visits and 216 453 with non-overdose-related visits to the emergency department. Those with overdose-related visits were younger, were predominantly male and had more mental health conditions. The 12-month crude mortality probability was 5.4% (95% confidence interval [CI] 4.7%-6.2%) in this group and 1.7% (95% CI 1.6%-1.8%) among those with non-overdose-related visits. After adjustment, for persons who were discharged, the 12-month mortality hazard was 3.5 (95% CI 3.0-4.2) times higher among those with overdose-related visits than those with non-overdose-related visits. For persons who left against medical advice, the mortality hazard was 7.1 (95% CI 4.0-12.5) times higher among those with opioid overdose. Interpretation Among persons with overdose-related visits to the emergency department, 12-month mortality was higher than among those with non-overdose-related visits. Overdose-related visits should prompt urgent evidence-based interventions (e.g., take-home naloxone kits, buprenorphine-naloxone induction) to prevent future deaths.

BACKGROUND: Since 2015, illicit drug overdose has been one of British Columbia’s most pressing public health issues. Our objective was to assess prescription history in the context of postmortem toxicology among people who had a fatal illicit drug overdose in BC. METHODS: Toxicology results from drug overdose deaths involving 1 or more illicit drugs, as identified by the BC Coroners Service in 2015–2017, were linked to the prescription drug histories of individuals as recorded in BC’s PharmaNet database for a descriptive analysis. Substances identified in toxicology were considered prescribed if the individual had an active dispensation for a matching medication within 60 days before overdose. RESULTS: There were 2872 deaths from illicit drug toxicity during the study period; 1789 (62.3%) were closed cases with toxicology results available. In 85.5% of cases, 1 or more opioids were found to be relevant to death. Prescribed opioids in the absence of nonprescribed opioids were detected in only 2.0% of cases, and 6.7% had a combination of prescribed and nonprescribed opioids. Among those with 1 or more nonprescribed opioids, 78.5% had fentanyl or fentanyl analogues detected. Medications used in opioid agonist therapy (methadone and buprenorphine) were found to be relevant to death in 7.4% of cases, with methadone (130 cases) much more common than buprenorphine (< 5 cases). Stimulants were detected in 70.6% of cases. INTERPRETATION: Our data show a high prevalence of nonprescribed fentanyl and stimulants, and a low prevalence of prescribed opioids detected on toxicology in people who died from illicit drug overdose. These results suggest that strategies to address the current overdose crisis in Canada must do much more than target deprescribing of opioids.

This study identified factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia. The study used data from the BC COVID-19 Cohort, which integrates data on all COVID-19 cases with data on hospitalizations, medical visits, emergency room visits, prescription drugs, chronic conditions and deaths. The analysis included all laboratory-diagnosed COVID-19 cases in British Columbia to 15 January 2021. We evaluated factors associated with hospital admission using multivariable Poisson regression analysis with robust error variance. Of the 56,874 COVID-19 cases included in the analysis, 2298 were hospitalized. Factors associated with increased hospitalization risk were as follows: male sex (adjusted risk ratio (aRR) = 1.27, 95%CI = 1.17–1.37), older age (p-trend &lt, 0.0001 across age groups increasing hospitalization risk with increasing age [aRR 30–39 years = 3.06, 95%CI = 2.32–4.03, to aRR 80+ years = 43.68, 95%CI = 33.41–57.10 compared to 20–29 years-old]), asthma (aRR = 1.15, 95%CI = 1.04–1.26), cancer (aRR = 1.19, 95%CI = 1.09–1.29), chronic kidney disease (aRR = 1.32, 95%CI = 1.19–1.47), diabetes (treated without insulin aRR = 1.13, 95%CI = 1.03–1.25, requiring insulin aRR = 5.05, 95%CI = 4.43–5.76), hypertension (aRR = 1.19, 95%CI = 1.08–1.31), injection drug use (aRR = 2.51, 95%CI = 2.14–2.95), intellectual and developmental disabilities (aRR = 1.67, 95%CI = 1.05–2.66), problematic alcohol use (aRR = 1.63, 95%CI = 1.43–1.85), immunosuppression (aRR = 1.29, 95%CI = 1.09–1.53), and schizophrenia and psychotic disorders (aRR = 1.49, 95%CI = 1.23–1.82). In an analysis restricted to women of reproductive age, pregnancy (aRR = 2.69, 95%CI = 1.42–5.07) was associated with increased risk of hospital admission. Older age, male sex, substance use, intellectual and developmental disability, chronic comorbidities, and pregnancy increase the risk of COVID-19-related hospitalization.

BackgroundThis study identified factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia.MethodsThis study was performed using the BC COVID-19 Cohort, which integrates data on all COVID-19 cases, hospitalizations, medical visits, emergency room visits, prescription drugs, chronic conditions and deaths. The analysis included all laboratory-diagnosed COVID-19 cases in British Columbia as of January 15th, 2021. We evaluated factors associated with hospital admission using multivariable Poisson regression analysis with robust error variance.FindingsFrom 56,874 COVID-19 cases included in the analyses, 2,298 were hospitalized. Models showed significant association of the following factors with increased hospitalization risk: male sex (adjusted risk ratio (aRR)=1.27; 95%CI=1.17-1.37), older age (p-trend InterpretationOlder age, male sex, substance use, intellectual and developmental disability, chronic comorbidities, and pregnancy increase the risk of COVID-19-related hospitalization.FundingBC Centre for Disease Control, Canadian Institutes of Health Research.Research in contextEvidence before this studyFactors such as older age, social inequities and chronic health conditions have been associated to severe COVID-19 illness. Most of the evidence comes from studies that don’t include all COVID-19 diagnoses in a jurisdiction), focusing on in-hospital mortality. In addition, mental illness and substance use were not evaluated in these studies. This study assessed factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia.Added value of this studyIn this population-based cohort study that included 56,874 laboratory-confirmed COVID-19 cases, older age, male sex, injection drug use, problematic alcohol use, intellectual and developmental disability, schizophrenia and psychotic disorders, chronic comorbidities and pregnancy were associated with the risk of hospitalization. Insulin-dependent diabetes was associated with higher risk of hospitalization, especially in the subpopulation younger than 40 years. To the best of our knowledge this is the first study reporting this finding, (insulin use and increased risk of COVID-19-related death has been described previously).Implications of all the available evidencePrioritization of vaccination in population groups with the above mentioned risk factors could reduce COVID-19 serious outcomes. The findings indicate the presence of the syndemic of substance use, mental illness and COVID-19, which deserve special public health considerations.

We evaluated the effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treating hepatitis C virus (HCV) genotype 1 and SOF/velpatasvir (SOF/VEL) for all genotypes among people who inject drugs (PWID) and those not injecting drugs and who were on or off opioid agonist therapy (OAT). Study participants comprised a population‐based cohort in British Columbia, Canada. The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV from 1990 to 2016 that are integrated with medical visits, hospitalization, and prescription drug data. We classified study participants as off OAT/recent injection drug use (off‐OAT/RIDU), off OAT/past IDU (off‐OAT/PIDU), off OAT/no IDU (off‐OAT/NIDU), on OAT/IDU (on‐OAT/IDU), and on OAT/no IDU (on‐OAT/NIDU). We assessed sustained virologic response (SVR) 10 weeks after HCV treatment among study groups treated with LDV/SOF or SOF/VEL until January 13, 2018. Analysis included 5,283 eligible participants: 390 off‐OAT/RIDU, 598 off‐OAT/PIDU, 3,515 off‐OAT/NIDU, 609 on‐OAT/IDU, and 171 on‐OAT/NIDU. The majority were male patients (64%‐74%) and aged ≥50 years (58%‐85%). The SVRs for off‐OAT/RIDU, off‐OAT/PIDU, off‐OAT/NIDU, on‐OAT/IDU, and on‐OAT/NIDU were 91% (355/390), 95% (570/598), 96% (3,360/3,515), 93% (567/609), and 95% (163/171), respectively. Among those with no SVR, 14 individuals died while on treatment or before SVR assessment, including 4 from illicit drug overdose. In the overall multivariable model, off‐OAT/RIDU, on‐OAT/IDU, male sex, cirrhosis, treatment duration

Background British Columbia is the epicenter of the current fentanyl-related overdose crisis in Canada. Our study characterizes prescribing histories of people who had an opioid-related overdose compared to matched controls. Methods We examined linked administrative data for individuals who overdosed between January 1, 2015 and November 30, 2016. Past prescriptions over five years were assessed for opioids for pain, opioid agonist therapy, benzodiazepines/z-drugs, antidepressants, antipsychotics, gabapentinoids, mood stabilizers and anti-epileptics, muscle relaxants, and other sedating medications. Prescribing history of 9964 cases was compared with that of 49,820 matched controls. Results Overdose cases were more likely to be prescribed opioids for pain and to have used prescription opioids on a long-term basis in the previous five years compared to controls. However, at the time of overdose, 92% of men and 86% of women did not have an active opioid for pain prescription, and approximately half had not filled one in the past five years. Those who overdosed tended to have more prescriptions for psychotropic substances than controls. Fewer than 10% of cases had an active prescription for opioid agonist therapy and most were not on treatment in the past. Conclusions Low prevalence of active prescriptions for opioids for pain at the time of overdose suggests that opioid prescribing plays a limited short-term impact in the current fentanyl-related crisis of overdoses. While liberal opioid prescribing practices may have contributed to the development of the current overdose crisis, regulation and enforcement of clinicians’ prescribing practices will likely have limited impact in reducing overdoses.

Objectives: The objective of study to assess the effect of health education via mobile applications in promoting health-related quality of life among schoolchildren with asthma in urban Malaysia. Methods: A Quasi-experimental with two-group pre- and post-intervention design was used in this study involving a total of 214 students. The students were randomly assigned into two groups (intervention group and control group) in a pre and post intervention approach. The control group received face to face education and the experimental group had health education via mobile apps.Results: The findings showed that the total score of health related quality of life has improvement in the mean total score of health-related quality of life from pre-intervention (5.31±1.27) to post-intervention (5.66±1.28) for the control group, compared with the experimental group with a mean total score of HRQoL at pre-intervention (5.01±1.36) and post-intervention (5.85±1.29). A comparison between the experimental and control groups using an independent t-test showed statistically significant differences in the mean HRQoL scores of asthma between the experimental and control groups. The effect of health education via mobile applications showed statistically significant improvement pre and post intervention in HRQoL score [F (1,288) = 57.46, p = Conclusion: The use of mobile technology in health education improved HRQoL as compared of traditional method of face-to-face lecture or handbooks among school children with asthma. Thus, educational module using mobile apps improves HRQoL. Trial registration: This study was registered under the Medical Research Committee, University Malaya Medical Centre, Malaysia under Trial MRECID. NO: 2016112-4501, Also, this study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) under Trial ID: ACTRN12614300582550

PurposePrescription 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.ParticipantsWe 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 dateThe 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 plansThe cohort will be refreshed every 2 years. Future analyses will explore the association between POs and adverse outcomes.

Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53.6%] women) from 56 countries were included in the study. Of these, 31 798 (75.4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84.2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46.2 years (IQR 34.3-58.0); median age at diagnosis of familial hypercholesterolaemia was 44.4 years (32.5-56.5), with 40.2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17.4% (2.1% for stroke and 5.2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81.1%) were receiving statins and 3691 (21.2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5.43 mmol/L (IQR 4.32-6.72) among patients not taking lipid-lowering medications and 4.23 mmol/L (3.20-5.66) among those taking them. Among patients taking lipid-lowering medications, 2.7% had LDL cholesterol lower than 1.8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1.8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p, Pfizer Independent Grant for Learning Change [16157823]; Amgen; Merck Sharp Dohme; Sanofi-Aventis; Daiichi Sankyo; Regeneron; National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK; NIHR; Czech Ministry of Health [NU20-02-00261]; Canadian Institutes of Health Research; Austrian Heart Foundation; Tyrolean Regional Government; Gulf Heart Association, The EAS FHSC is an academic initiative that has received funding from a Pfizer Independent Grant for Learning & Change 2014 (16157823) and from investigator-initiated research grants to the European Atherosclerosis Society-Imperial College London from Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron. KKR acknowledges support from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK. KID acknowledges support from a PhD Studentship from NIHR under the Applied Health Research programme for Northwest London, UK (the views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health). TF was supported by a grant from the Czech Ministry of Health (NU20-02-00261). JG receives support from the Canadian Institutes of Health Research. The Austrian Familial Hypercholesterolaemia registry has been supported by funds from the Austrian Heart Foundation and the Tyrolean Regional Government. The Gulf Familial Hypercholesterolaemia registry was done under the auspices of the Gulf Heart Association.

Although achieving sustained virological response (SVR) through antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) attributable to hepatitis C virus (HCV) infection, the impact of early viral clearance on HCC is not well defined. In this study, we compared the risk of HCC among individuals who spontaneously cleared HCV (SC), the referent population, with the risk in untreated chronic HCV (UCHC), those achieved SVR, and those who failed interferon-based treatment (TF). The BC Hepatitis Testers Cohort (BC-HTC) includes individuals tested for HCV between 1990-2013, integrated with medical visits, hospitalizations, cancers, prescription drugs and mortality data. This analysis included all HCV-positive patients with at least one valid HCV RNA by PCR on or after HCV diagnosis. Of 46 666 HCV-infected individuals, there were 12 527 (26.8%) SC; 24 794 (53.1%) UCHC; 5355 (11.5%) SVR and 3990 (8.5%) TF. HCC incidence was lowest (0.3/1000 person-years (PY)) in the SC group and highest in the TF group (7.7/1000 PY). In a multivariable model, compared to SC, TF had the highest HCC risk (hazard ratio (HR):14.52, 95% confidence interval (CI): 9.83-21.47), followed by UCHC (HR: 5.85; 95% CI: 4.07-8.41). Earlier treatment-based viral clearance similar to SC could decrease HCC incidence by 69.4% (95% CI: 57.5-78.0), 30% (95% CI: 10.8-45.1) and 77.5% (95% CI: 69.4-83.5) among UCHC, SVR and TF patients, respectively. In conclusion, using SC as a real-world comparator group, it showed that substantial reduction in HCC risk could be achieved with earlier treatment initiation. These analyses should be replicated in patients who have been treated with direct acting antiviral therapies.

AIM To describe the characteristics of people diagnosed with acute and chronic hepatitis B virus (HBV) infection in British Columbia (BC). METHODS We used data from the BC Hepatitis Testers Cohort (BC-HTC), which includes all individuals tested for hepatitis C virus (HCV) or human immunodeficiency virus (HIV) or those diagnosed with HBV or active tuberculosis in BC since 1990. These data were integrated with prescription drug, medical visit, hospitalization and mortality data. HBV cases were classified as acute or chronic according to provincial guidelines. We compared characteristics of individuals by HBV infection group (acute, chronic and negative). Factors associated with acute or chronic HBV infection were assessed with multinomial logistic regression models in comparison to the HBV negative group. RESULTS 46498 of the 1058056 eligible BC-HTC participants were diagnosed with HBV infection. 4.3% of HBV positive individuals were diagnosed with acute HBV infections while 95.7% had chronic infections. Problematic alcohol use, injection drug use, and HIV or HCV co-infection were more common among individuals diagnosed with acute HBV compared to those with chronic infections and HBV negative individuals. In multivariable multinomial logistic regression models, we observed significant associations between acute or chronic HBV diagnosis and being male, age at HBV diagnosis or birth cohort, South and East Asian ethnicity, HCV or HIV infection, and injection drug use. The odds of acute HBV decreased with increasing age among people who inject drugs, while the opposite was true for chronic HBV. Persons with acute HBV were predominantly White (78%) while those with chronic HBV were mostly East Asian (60%). Relative to Whites, East Asians had 12 times greater odds of being diagnosed with chronic HBV infection. These odds increased with increasing socioeconomic deprivation. CONCLUSION Differences in the profiles of people diagnosed with acute and chronic HBV infection necessitate differentiated screening, prevention, care and treatment programs.

Background & Aims The advent of direct-acting antivirals (DAAs) has led to ambitious targets for hepatitis C virus (HCV) elimination. However, in the context of alcohol use disorder the ability of DAAs to achieve these targets may be compromised. The aim of this study was to evaluate the contribution of alcohol use disorder to HCV-related decompensated cirrhosis in three settings. Methods HCV notifications from British Columbia, Canada; New South Wales, Australia, and Scotland (1995–2011/2012/2013, respectively) were linked to hospital admissions (2001–2012/2013/2014, respectively). Alcohol use disorder was defined as non-liver-related hospitalisation due to alcohol use. Age-standardised decompensated cirrhosis incidence rates were plotted, associated factors were assessed using Cox regression, and alcohol use disorder-associated population attributable fractions (PAFs) were computed. Results Among 58,487, 84,529, and 31,924 people with HCV in British Columbia, New South Wales, and Scotland, 2,689 (4.6%), 3,169 (3.7%), and 1,375 (4.3%) had a decompensated cirrhosis diagnosis, and 28%, 32%, and 50% of those with decompensated cirrhosis had an alcohol use disorder, respectively. Age-standardised decompensated cirrhosis incidence rates were considerably higher in people with alcohol use disorder in New South Wales and Scotland. Decompensated cirrhosis was independently associated with alcohol use disorder in British Columbia (aHR 1.92; 95% CI 1.76–2.10), New South Wales (aHR 3.68; 95% CI 3.38–4.00) and Scotland (aHR 3.88; 95% CI 3.42–4.40). The PAFs of decompensated cirrhosis-related to alcohol use disorder were 13%, 25%, and 40% in British Columbia, New South Wales and Scotland, respectively. Conclusions Alcohol use disorder was a major contributor to HCV liver disease burden in all settings, more distinctly in Scotland. The extent to which alcohol use would compromise the individual and population-level benefits of DAA therapy needs to be closely monitored. Countries, where appropriate, must develop strategies combining promotion of DAA treatment uptake with management of alcohol use disorders, if World Health Organization 2030 HCV mortality reduction targets are going to be achieved. Lay summary The burden of liver disease has been rising among people with hepatitis C globally. The recent introduction of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) has brought renewed optimism to the sector. DAA scale-up could eliminate hepatitis C as a public health threat in the coming decades. However, our findings show heavy alcohol use is a major risk factor for liver disease among people with hepatitis C. If continued, heavy alcohol use could compromise the benefits of new antiviral treatments at the individual- and population-level. To tackle hepatitis C as a public health threat, where needed, DAA therapy should be combined with management of heavy alcohol use.

ObjectiveTo assess the association between long term prescription opioid treatment medically dispensed for non-cancer pain and the initiation of injection drug use (IDU) among individuals without a history of substance use.DesignRetrospective cohort study.SettingLarge administrative data source (containing information for about 1.7 million individuals tested for hepatitis C virus or HIV in British Columbia, Canada) with linkage to administrative health databases, including dispensations from community pharmacies.ParticipantsIndividuals age 11-65 years and without a history of substance use (except alcohol) at baseline.Main outcome measuresEpisodes of prescription opioid use for non-cancer pain were identified based on drugs dispensed between 2000 and 2015. Episodes were classified by the increasing length and intensity of opioid use (acute (lasting Results59 804 participants (14 951 people from each opioid use category) were included in the matched cohort, and followed for a median of 5.8 years. 1149 participants initiated IDU. Cumulative probability of IDU initiation at five years was highest for participants with chronic opioid use (4.0%), followed by those with episodic use (1.3%) and acute use (0.7%), and those who were opioid naive (0.4%). In the inverse probability of treatment weighted Cox model, risk of IDU initiation was 8.4 times higher for those with chronic opioid use versus those who were opioid naive (95% confidence interval 6.4 to 10.9). In a sensitivity analysis limited to individuals with a history of chronic pain, cumulative risk for those with chronic use (3.4% within five years) was lower than the primary results, but the relative risk was not (hazard ratio 9.7 (95% confidence interval 6.5 to 14.5)). IDU initiation was more frequent at higher opioid doses and younger ages.ConclusionsThe rate of IDU initiation among individuals who received chronic prescription opioid treatment for non-cancer pain was infrequent overall (3-4% within five years) but about eight times higher than among opioid naive individuals. These findings could have implications for strategies to prevent IDU initiation, but should not be used as a reason to support involuntary tapering or discontinuation of long term prescription opioid treatment.

Background & Aims Evidence is limited on hepatocellular carcinoma (HCC) risk after sustained virological response (SVR) to interferon-based treatment of hepatitis C virus (HCV) infection. We evaluated the effect of SVR on the risk of HCC and estimated its incidence in post-SVR HCV patients from a large population-based Canadian cohort. Methods The British Columbia Hepatitis Testers Cohort includes individuals tested for HCV between 1990–2013 linked with data on their medical visits, hospitalizations, cancers, prescription drugs and mortality. Patients receiving interferon-based HCV treatments were followed from the end of treatment to HCC diagnosis, death or December 31, 2012. We examined HCC risk among those who did and did not achieve SVR using multivariable proportional hazard models with the Fine and Gray modification for competing risks. Results Of 8147 individuals who received HCV treatment and were eligible for analysis, 4663 (57%) achieved SVR and 3484 (43%) did not. Each group was followed for a median of 5.6years (range: 0.5–12.9) for an HCC incidence rate of 1.1/1000 person-years (PY) among the SVR and 7.2/1000 PY among the no SVR group. The HCC incidence rate was higher among those with cirrhosis (SVR: 6.4, no SVR: 21.0/1000 PY). In the multivariable model, SVR was associated with a lower HCC risk (subdistribution hazard ratio [SHR]=0.20, 95% CI: 0.13–0.3), while cirrhosis (SHR=2.61, 95% CI: 1.68–4.04), age ⩾50years, being male and genotype 3 infection were associated with a higher HCC risk. Among those who achieved SVR, cirrhosis, age ⩾50years and being male were associated with a higher HCC risk. Conclusion SVR after interferon-based treatment substantially reduces but does not eliminate HCC risk, which is markedly higher among those with cirrhosis and age ⩾50years at treatment initiation. Treatment of patients at an advanced fibrosis stage with new highly effective drugs will warrant continued surveillance for HCC post-SVR. Lay summary We assessed the effect of successful hepatitis C treatment with older interferon-based treatment on the occurrence of liver cancer (hepatocellular carcinoma) and found that successful treatment prevents liver cancer. However, more people with cirrhosis and older age continued to develop liver cancer after successful treatment. Thus, treatment with new drugs among those with cirrhosis will require continued monitoring for liver cancer.

Sitosterolemia is a rare lipid metabolism disease with heterogeneous manifestations. Atherosclerosis can occur in children, and therefore, early detection, diagnosis, and treatment of this disease are important. We studied 18 pediatric patients with sitosterolemia who showed a significant increase in plasma lipid levels and analyzed their clinical, biochemical, and genetic characteristics. We recorded the initial serum lipid results and clinical manifestations of the patients. Lipid and plant sterol levels were measured after homozygous or compound heterozygous mutations of ABCG5 or ABCG8 were identified by genetic testing. Plasma plant sterol levels were analyzed by gas chromatography. Fourteen cases of sitosterolemia were examined by ultrasound and echocardiography. The initial total cholesterol and low-density lipoprotein levels of the children were significantly increased, but then markedly decreased after diet control or drug treatment, and even reached normal levels. Carotid atherosclerosis and aortic valve regurgitation were present in three of 14 patients. Serum lipid levels of children with sitosterolemia and xanthomas were notably higher than those without xanthomas. There were no significant differences in clinical manifestations between patients with different genotypes. In conclusion, sitosterolemia should be considered in children with hyperlipidemia who do not present with xanthomas, especially with a significant increase in total cholesterol and low-density lipoprotein levels. There does not appear to be a correlation between clinical phenotype and genotype.

Some studies have shown that a higher ideal cardiovascular health score (CVHS) predicts a lower incidence of arterial stiffness. Few studies have used multiple measurements of CVHS to examine the impact of CVHS on arterial stiffness. The current study aimed to identify the long-term patterns in CVHS trajectory and to explore the association between CVHS trajectory and arterial stiffness. The study cohort consisted of 18,854 participants from the Kailuan Study who were followed up for five physical examinations over 8.10 years. Five discrete CVHS trajectories were identified among the participants: low-stable (8.10%), low-moderate (6.84%), moderate-low (23.46%), moderate-stable (39.83%), and elevated-stable (21.77%). After adjustment for confounding factors, generalized linear model analysis showed that CVHS trajectory group correlated negatively with brachial-ankle pulse wave velocity (baPWV). Compared with the low-stable group, the low-moderate group, moderate-low group, moderate-stable group, and elevated-stable group had B values of -41.81, -24.11, -86.79, and -169.54, respectively. We also used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for CVHS trajectory groups and arterial stiffness. In fully adjusted models, ORs were 0.76 (95% CI: 0.62-0.94) for the low-moderate group, 0.80 (95% CI: 0.67-0.97) for the moderate-low group, 0.51 (95% CI: 0.42-0.62) for the moderate-stable group, and 0.23 (95% CI: 0.18-0.29) for the elevated-stable group compared with the low-stable group. The results were consistent across a number of sensitivity analyses. In conclusion, the higher long-term attainment and the improvement of CVHS were negatively associated with baPWV and could reduce the risk of arterial stiffness. Our study emphasizes the importance of optimizing CVH throughout life to prevent the incidence of arterial stiffness.

"Core areas" of transmission for bacterial sexually transmitted infections have been identified. However, it is unclear whether core areas apply to viral infections, such as hepatitis C virus (HCV). We used geographic mapping and spatial analysis to identify distinct core areas of HCV infection in British Columbia (BC) using the BC Hepatitis Testers Cohort (BC-HTC), 1990-2013. The BC-HTC includes all BC residents tested for HCV (~1.5 million; 1990-2013). Core HCV infection areas were identified spatially and temporally for five time periods (1990-1993, 1994-1998, 1999-2003, 2004-2008 and 2009-2013) through thematic mapping, Kernel Density Estimation, Hotspot analysis and cluster analysis at the Census dissemination area level in ArcGIS and SatScan. HCV infection core areas were consistently identified. HCV core areas expanded from the downtown of major cities in different regions of BC (Metro Vancouver, Vancouver Island, and Northern BC; 1990-1998), to smaller cities in Metro Vancouver and Interior BC (2000 onwards). Statistically significant clusters, or hotspots, were also observed for downtown Vancouver, Northern BC (Prince George) and Vancouver Island from 1990 to 2008 with expansion to other urban areas in Metro Vancouver from 1990-2013. Statistically significant clusters persisted after adjustment for injection drug use, number of HCV tests, age, sex, material and social deprivation. Persistence of areas with high HCV diagnoses rates in Vancouver and Prince George supports the theory of core areas of HCV transmission. Identification of core areas can inform prevention, care and treatment programme interventions and evaluate their impact over time.

Summary T-cell host immune response against hepatitis C virus (HCV) has been suggested to play an important role in determining HCV infection outcome. However, data from human studies are not available. This study examined the effect of primary T-cell deficiency along with other factors on the spontaneous clearance of HCV in a large population-based cohort in British Columbia, Canada. The BC Hepatitis Testers Cohort includes all individuals tested for HCV in BC in 1990-2013 linked with data on their medical visits, hospitalizations and prescription drugs. HCV-positive individuals with at least one valid HCV PCR test on/after HCV diagnosis (n=46 783) were included in this study. To examine factors associated with the spontaneous clearance of HCV, multivariable logistic regression was fitted on the full sample, and Cox proportional hazards model on the HCV seroconverters. Spontaneous clearance was observed in 25.1% (n=11 737) of those tested for HCV. After adjusting for potential confounders, the odds of spontaneous clearance of HCV was lower in people with primary T-cell immunodeficiency (adjusted odds ratio [aOR]: 0.55, 95% CI: 0.32-0.94), and higher in females (aOR: 1.61, 95% CI: 1.54-1.68) and in those coinfected with HBV (aOR: 2.31, 95% CI: 1.93-2.77). Similar results were observed in HCV seroconverters except HBV coinfection was not significant. In conclusion, primary T-cell immunodeficiency is associated with a lower spontaneous clearance of HCV while female sex and coinfection with HBV are associated with a higher spontaneous clearance.

Background Thrombocytopenia-associated multi-organ failure (TAMOF) in children is a well-described factor for increased hospital mortality. Low cardiac output syndrome (LCOS) and the effects of cardiopulmonary bypass may manifest with several adverse physiologic and immunologic effects, with varying degrees of thrombocytopenia and multi-organ dysfunction, sometimes very similar to TAMOF. LCOS is a common occurrence in children with critical heart disease, presenting in as much as 23.8% of infants postoperative of congenital heart surgery. Therapeutic plasma exchange (TPE) has been offered as a promising therapy for TAMOF; however, the therapeutic implications of this modality in children with critical heart disease and a clinical diagnosis of TAMOF are unknown. Objectives We describe our institutional experience with TPE as an adjuvant rescue therapy for children with critical heart disease and a clinical diagnosis of TAMOF, while supported by extracorporeal membrane oxygenation (ECMO). Methods Single-center retrospective analysis of children with critical heart disease admitted to the CICU and supported by ECMO, undergoing TPE for a clinical diagnosis of TAMOF between January 2006 and June 2015. Results Forty-one patients were included for analysis. Median age and weight of patients was 0.6 years (range 0.0–17.2) and 8.5 kg (range 1.5–80.0). TPE was initiated at a median of 1 day (0–13) after initiation of ECMO. Modified organ failure index (MOFI) and platelet count improved after TPE start (p

This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct-acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada, New South Wales (NSW), Australia, and Scotland (1995-2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001-2012/2013/2014, respectively), and mortality (1995-2013/2014/2015, respectively). Age-standardised HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58,487, 84,529, and 31,924 people with HCV in BC, NSW, and Scotland, 734 (1.3%), 1,045 (1.2%), and 345 (1.1%) had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all jurisdictions. Age-standardised HCC incidence rates remained stable in BC and Scotland, and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth

The aim of this study was to evaluate the results following surgeries for the treatment of coarctation of the aorta in Chinese paediatric patients and to compare the surgery outcomes between simple and complex coarctation procedures.Between January 2006 and December 2011, 107 consecutive paediatric patients with coarctation of the aorta underwent surgery. Forty-four patients (41.12%) were classified as having simple coarctations (group A), and 54 patients (50.47%) were classified as having complex coarctations (group B). Echocardiography and the resting systolic blood pressure were evaluated prior to the operation, at one month following the operation, and then once annually.Follow-up was 93.5% complete (100 patients), without significant differences between the two groups. Arch hypoplasias and bicuspid aortic valves were initially present in 10 (9.35%) and 11 (10.28%) of 107 patients, respectively. There were no deaths among the group A patients and three (5.56%) early deaths among the group B patients. There was a significant difference in the restenosis incidence rate between the two groups during the most recent follow-up consultations (p0.05). Additionally, only 10 of 43 group A and 10 of 51 group B patients had persistently abnormal blood pressures during the annual follow-up consultations.The postoperative restenosis ratio was increased in the complex coarctation group compared with the simple coarctation group. Additionally, the complex coarctation patients who did not have restenosis at follow-up had a lower proportion of hypertension.

Background: We and others have identified the aldo-keto reductase AKR1C3 as a potential drug target in prostate cancer, breast cancer and leukaemia. As a consequence, significant effort is being invested in the development of AKR1C3-selective inhibitors. Methods: We report the screening of an in-house drug library to identify known drugs that selectively inhibit AKR1C3 over the closely related isoforms AKR1C1, 1C2 and 1C4. This screen initially identified tetracycline as a potential AKR1C3-selective inhibitor. However, mass spectrometry and nuclear magnetic resonance studies identified that the active agent was a novel breakdown product (4-methyl(de-dimethylamine)-tetracycline (4-MDDT)). Results: We demonstrate that, although 4-MDDT enters AML cells and inhibits their AKR1C3 activity, it does not recapitulate the anti-leukaemic actions of the pan-AKR1C inhibitor medroxyprogesterone acetate (MPA). Screens of the NCI diversity set and an independently curated small-molecule library identified several additional AKR1C3-selective inhibitors, none of which had the expected anti-leukaemic activity. However, a pan AKR1C, also identified in the NCI diversity set faithfully recapitulated the actions of MPA. Conclusions: In summary, we have identified a novel tetracycline-derived product that provides an excellent lead structure with proven drug-like qualities for the development of AKR1C3 inhibitors. However, our findings suggest that, at least in leukaemia, selective inhibition of AKR1C3 is insufficient to elicit an anticancer effect and that multiple AKR1C inhibition may be required.

IntroductionBritish Columbia (BC), Canada declared a public health emergency in April 2016 for opioid overdose. Comprehensive data was needed to identify risk factors, inform interventions, and evaluate response actions. We describe the development of an overdose cohort, including linkage strategy, case definitions, and data governance model, and present the resulting characteristics, including data linkage yields and case overlap among data sources.MethodsOverdose events from hospital admissions, physician visits, poison centre and ambulance calls, emergency department visits, and coroner's data were grouped into episodes if records were present in multiple sources. A minimum of five years of universal health care records (all prescription dispensations, fee-for-service physician billings, emergency department visits and hospitalizations) were appended for each individual. A 20% random sample of BC residents and a 1:5 matched case-control set were generated. Consultation and prioritization ensured analysts worked to address questions to directly inform public health actions.Results10,456 individuals suffered 14,292 overdoses from January 1, 2015 to Nov 30, 2016. Only 28% of overdose events were found in more than one dataset with the unique contribution of cases highest from ambulance records (32%). Compared with fatal overdoses, non-fatal events more often involved females, younger individuals (20 to 29 years) and those 60 or older. In 78% of illegal drug deaths, there was no associated ambulance response. In the year prior to first recorded overdose, 60% of individuals had at least one ED visit, 31% at least one hospital admission, 80% at least one physician visit, and 87% had filled at least one prescription in a community pharmacy.ConclusionWhile resource-intensive to establish, a linked cohort is useful for characterizing the full extent of the epidemic, defining sub-populations at risk, and patterns of contact with the health system. Overdose studies in other jurisdictions should consider the inclusion of multiple data sources.

Objective: This study aimed to investigate the risk of birth weights over 4000 g (macrosomia) in association with following the 2009 American Institute of Medicine (AIOM) recommendations. Materials and Methods: Seventy-six nondiabetic women who delivered a singleton, term macrosomic fetus and 82 women who delivered a singleton, term fetus weighing 1000 mL at delivery (35.5% vs. 6.1%, p 11.5 kg, the risk of macrosomia increased nine-fold (OR = 9.63; 95% CI 1.76–52.74). Conclusion: Macrosomia resulted in more cesarean deliveries and greater maternal blood loss at birth. In Taiwan, to prevent macrosomia, we suggest that the total gestational weight gain should be

We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.

Background Recent studies have shown an increasing incidence of herpes zoster (HZ) infection, which may be related to the introduction of varicella vaccination programs in children. We examined the epidemiology and treatment costs of HZ and post-herpetic neuralgia (PHN) over time in British Columbia, Canada. Methods The cohort consisted of all cases with HZ infection from January 1, 1997 and December 31, 2012. Incident zoster was defined as a case (ICD-9 053 or ICD-10 B02) without a previous episode of HZ or PHN in the previous 12 months. We determined the incidence for HZ and PHN and the age-sex standardized rate for the overall population. We determined the association between the varicella vaccination program and increased HZ rates by evaluating the rate ratios in the publicly-funded varicella vaccine period compared to the non-publicly funded period in a regression model. We evaluated the hospitalization rates, treatment by GPs and their associated yearly costs for HZ and PHN. Results HZ incidence increased for the entire study period from 3.2 per 1000 population in 1997 to 4.5 in 2012. HZ rates were higher for females than males and all age groups had an increased incidence rate, except the 0–9 year olds, where the rate decreased. Crude and age-sex standardized incidence rates of PHN demonstrated very similar patterns to HZ incidence. Based on the regression model, rates of HZ were higher in the older individuals. No significant increase with HZ incidence was seen during the publically funded varicella vaccination program compared to the non-publicly funded period. From 1997 to 2012, the annual HZ-related costs associated with hospitalizations and GP visits were over $CDN4.9 million and $CDN537,286, respectively; treatment costs for hospitalizations have increased significantly over time. Majority of PHN-related cases are managed by GPs, with a steady increase over time in number of cases and associated annual costs. Conclusions The incidence of zoster and PHN is increasing with time, particularly in the elderly population and the risk is greater in the over 65 year olds. Treatment costs for both HZ and PHN represent a significant burden on the Canadian healthcare system. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1898-z) contains supplementary material, which is available to authorized users.

Background The British Columbia (BC) Hepatitis Testers Cohort (BC-HTC) was established to assess and monitor hepatitis C (HCV) epidemiology, cost of illness and treatment effectiveness in BC, Canada. In this paper, we describe the cohort construction, data linkage process, linkage yields, and comparison of the characteristics of linked and unlinked individuals. Methods The BC-HTC includes all individuals tested for HCV and/or HIV or reported as a case of HCV, hepatitis B (HBV), HIV or active tuberculosis (TB) in BC linked with the provincial health insurance client roster, medical visits, hospitalizations, drug prescriptions, the cancer registry and mortality data using unique personal health numbers. The cohort includes data since inception (1990/1992) of each database until 2012/2013 with plans for annual updates. We computed linkage rates by year and compared the characteristics of linked and unlinked individuals. Results Of 2,656,323 unique individuals available in the laboratory and surveillance data, 1,427,917(54%) were included in the final linked cohort, including about 1.15 million tested for HCV and about 1.02 million tested for HIV. The linkage rate was 86% for HCV tests, 89% for HCV cases, 95% for active TB cases, 48% for HIV tests and 36% for HIV cases. Linkage rates increased from 40% for HCV negatives and 70% for HCV positives in 1992 to ~90% after 2005. Linkage rates were lower for males, younger age at testing, and those with unknown residence location. Linkage rates for HCV testers co-infected with HIV, HBV or TB were very high (90–100%). Conclusion Linkage rates increased over time related to improvements in completeness of identifiers in laboratory, surveillance, and registry databases. Linkage rates were higher for HCV than HIV testers, those testing positive, older individuals, and females. Data from the cohort provide essential information to support the development of prevention, care and treatment initiatives for those infected with HCV.

Cervical cerclage is widely used to prevent preterm birth in women at moderate or high risk of prematurity due to a history of preterm birth in the second trimester. Several studies reported, however, that cerclage is not effective; one study found no difference in the risk of preterm birth between cerclage and bed rest alone. Many of these studies, however, can be criticized because of deficiencies in design. A number of authors believe that placement of the suture close to the internal os may improve perinatal outcomes. Most studies investigating cerclage have used a single purse-string cerclage suture. The investigators in the present study suggest that use of a single suture is inadequate, no matter where it is placed in the cervix. This prospective randomized controlled pilot study compared the effect of double cervical cerclage with traditional single cervical cerclage on the frequency of preterm birth, perinatal outcomes, and maternal side effects in 51 singleton women with a history of pregnancy loss in the second trimester and suspected cervical incompetence. The participants were randomized into 2 groups: double cervical cerclage (n = 17) and traditional single cervical cerclage (n = 34). The effect of using double or single cervical sutures on a number of outcomes was compared. Outcomes examined included the duration of pregnancy, perinatal outcomes, maternal hospital stay, neonatal death, and neonatal admission to the intensive care unit. At less than 34 weeks of gestation, there was a nonsignificant difference in the rate of preterm delivery between the 2 groups favoring double cerclage, 12% versus 41%. At less than 28 weeks of gestation, the incidence of preterm delivery was lower (but not significantly) in the double cervical cerclage group compared to the single cerclage group, 6% versus 29%. The mean birth weight in the double cerclage group was higher (double suture: 2696 ± 911 vs. single suture: 2242 ± 1119 g, P = 0.048). The rates of neonatal survival and admission to the intensive care unit were not significantly different in the 2 groups. Few neonatal complications and no intraoperative maternal complications were associated with use of double cervical cerclage. The findings of this pilot study suggest that double cervical cerclage is effective and may be more effective than traditional single cervical cerclage in preventing preterm delivery and improving perinatal outcome among women with a prior history of premature delivery in the second trimester.

To analyze the role of different measures in the treatment of acute moderate or severe symptomatic hydronephrosis in pregnancy.Of the 18,130 women delivering at our institution between January 2000 and December 2004, 93 patients were admitted due to symptomatic hydronephrosis. Among these, 50 patients were diagnosed with moderate or severe hydronephrosis, and were randomly treated with conservative measures (25 patients) or double pigtail stent insertion (25 patients). Renal sonography, urinalysis, serum creatinine levels, white blood cell counts, and urine culture were done in all patients at first visit. The clinical and perinatal outcomes of the two groups were compared.The incidence of symptomatic hydronephrosis in pregnancy was 0.5% in our institution (93/18,130). The majority of the moderate or severe hydronephrosis (88%) cases were diagnosed after the first trimester. There were no statistically significant differences in the fetal body weight, Apgar score, preterm labor, and hospitalization day between the two groups. Among those receiving conservative treatment, five patients (5/25, 20%) failed to respond and were subsequently treated by double pigtail stent insertion successfully, compared with the surgical group, in which all patients were successfully relieved by double pigtail stent (p=0.018). Four patients receiving double pigtail stent insertion complained of stent discomfort and flank pain after the procedure (16%).Double pigtail stent insertion is effective for the treatment of moderate or severe symptomatic hydronephrosis in pregnancy, and showed a lower failure rate than the conservative treatment. However, due to the complications and discomfort with surgical treatment, conservative treatment should still be the first choice.

Delta-sarcoglycan, one member of the sarcoglycan complex, is a very conservative muscle-specific protein exclusively expressed in the skeletal and cardiac muscles of vertebrates. Mutations in sarcoglycans are known to be involved in limb-girdle muscular dystrophy (LGMD) and dilated cardiomyopathy (DCM) in humans. To address the role of delta-sarcoglycan gene in zebrafish development, we have studied expression pattern of delta-sarcoglycan in zebrafish embryos and examined the role of delta-sarcoglycan in zebrafish embryonic development by morpholino. Strong expression of delta-sarcoglycan was observed in various muscles including those of the segment, heart, eye, jaw, pectoral fin, branchial arches, and swim bladder in zebrafish embryo. Delta-sarcoglycan was also expressed in midbrain and retina. Knockdown of delta-sarcoglycan resulted in severe abnormality in both the cardiac and skeletal muscles. Some severe ones displayed serious morphological abnormality such as hypoplastic head, linear heart, very weak heartbeats, and runtish trunk, all dead within 5 dpf. Whole-mount in situ hybridization analysis showed that adaxial cells and muscle pioneers were affected in delta-sarcoglycan knockdown embryos. In addition, absence of delta-sarcoglycan protein severely delayed the cardiac development and influenced the differentiation of cardiac muscle, and the cardiac left-right asymmetry was dramatically changed in morpholino-treated embryos. These data together suggest that delta-sarcoglycan plays an important role in early heart and muscle development.

Summary Objective Primitive neuroectodermal tumors (PNETs) are a group of unusual malignancies arising in the bone and soft tissue. Pure uterine neuroectodermal tumors are rare. We report the first case of PNET arising from the uterus in our hospital. Case Report A 52-year-old perimenopausal woman had multiple myoma and was regularly followed-up in our hospital. She suddenly developed lower abdominal pain without vaginal bleeding. Sonography revealed a pelvic mass measuring 10.7 × 6.8 cm with multiple myoma. The patient underwent tumor resection. There were multiple necrotic tumors on the uterus, bladder, broad ligaments, cardinal ligaments, and cul-de-sac. Final pathology revealed PNET because tumor cells were CD99 positive. Conclusion PNETs belong to the Ewing's sarcoma family. They are closely related to malignant, small round-cell tumors of soft tissue and bones. They strongly express the glycoprotein p30/32 (CD99) on the cell membrane, which is encoded by the MIC2 gene. A translocation at t(11;22)(q24;q12) has been identified. PNETs are mostly recognized by the histologic characteristics of neural differentiation and immunohistochemical expression of at least two different neural markers. Uterine PNETs have a poor prognosis and, to date, there is no standard treatment. Total abdominal hysterectomy and bilateral salpingo-oophorectomy plus adjuvant chemotherapy or radiotherapy are recommended.

Basiliximab is a high-affinity chimeric monoclonal antibody directed against the alpha-chain of the interleukin (IL)-2 receptor. Individual studies have shown that it is highly effective in preventing acute rejection and causes no measurable incremental toxicity. However, incorporation of basiliximab immunoprophylaxis into routine practice depends upon the demonstration of benefit across treatment regimens and quantitation of the treatment effect.This study employed a meta-analysis to examine the clinical benefit of basiliximab. Parameter estimates were derived from four randomised prospective double-blind studies conducted in 93 renal transplant centres in 18 countries. A total of 1185 adult primary allograft recipients were randomised within the centres to receive either basiliximab 20mg intravenously on days 0 and 4 or placebo, in addition to double or triple immunosuppression consisting of cyclosporin-microemulsion (Neoral((R))The use of tradenames is for product identification purposes only and does not imply endorsement.), corticosteroids, and azathioprine or mycophenolate mofetil. Key clinical events included patient and graft survival, graft rejection and complications. Analysis was performed using a variable model; odds ratios and the numbers needed to treat (NNT) to benefit or to harm one patient were calculated for each principal outcome at 6 or 12 months post-transplant.Basiliximab reduced the relative risk (RR) and absolute risk (AR) of clinical and biopsy-proven acute graft rejection across all treatment regimens. The overall RR of clinical acute graft rejection was decreased by 35% in patients receiving basiliximab. AR was reduced by 15.6% (pooled incidence: 28.8% vs 44.4%, p0.0001), and the NNT for efficacy was six. The reduction in RR of biopsy-proven rejection was similar (32%) with an absolute risk reduction (ARR) of 11.7% (pooled incidence: 25.1% vs 36.8%, p0.0001) and NNT of nine over 6 months. There was a concomitant reduction in the risk of graft loss which did not reach statistical significance (p = 0.14). The RR of graft loss was reduced by 26% with an AR reduction of 2.3% (pooled incidence: 6.4% vs 8.7%) and an NNT of 42 over 6 months. The risk of death was unchanged.Immunoprophylaxis with basiliximab produces a significant reduction in the RR and AR of clinical and biopsy-proven acute graft rejection with a trend towards a concomitant reduction in the risk of graft loss. The magnitude of protection provided by basiliximab, the fact that it is observed across treatment regimens and the safety of this therapy are arguments for its routine use in renal transplantation.

Summary Objective Ovarian hyperstimulation syndrome (OHSS) is more severe when pregnancy occurs, as the developing pregnancy produces human chorionic gonadotropin, which stimulates the ovary's persistent growth. If no pregnancy occurs, the syndrome will typically resolve within 1 week. In a maintained pregnancy, slow resolution of symptoms usually occurs over 1-2 months. Case Report A 31-year-old woman, gravida 2, para 1, aborta 1, with polycystic ovary syndrome underwent in vitro fertilization (IVF) with clomiphene citrate and follicle-stimulating hormone/gonadotropin releasing hormone-antagonist stimulation. During transvaginal oocyte retrieval, enlarged bilateral ovaries were noted. She had an episode of OHSS after IVF/embryo transfer, for which paracentesis was performed three times. Pregnancy was achieved. Throughout antenatal examinations, bilateral ovaries were enlarged. She delivered a healthy baby by cesarean section at term. However, 1 month after delivery, the bilateral ovary had not shrunk, and levels of tumor markers CA125 and CA199 were 50.84 and 41.34 U/mL, respectively. At laparotomy for suspected malignancy, both adnexae formed "kissing ovaries", which were multinodulated with yellow serous fluid. Specimens from wedge resection submitted for frozen section showed a benign ovarian cyst. The final pathology report showed bilateral follicle cysts. Conclusion With the increasing use of gonadotropins in the management of infertility, ovarian enlargement secondary to hyperstimulation is common. Generally, symptoms appear between the 6 th and 13 th weeks of pregnancy and disappear thereafter. The hyperstimulated ovary often subsides after the first trimester. This case is unusual as the megalocystic ovary persisted after delivery. To the best of our knowledge, we report the first case of enlarged bilateral ovaries persisting 2 months after delivery.

Paraurethral leiomyoma is rare. This is the first reported case of a woman with a 6 × 7 × 5 cm urethral leiomyoma with profuse vaginal bleeding. The site of bleeding was identified as the anterior vaginal mucosal vein, which we subsequently electrocauterized. Enucleation of the mass was performed smoothly with a Foley catheter to avoid damage to the urethra. Profuse bleeding from a paraurethral myoma is possibly due to increased vascularity and the prolapsed nature of the tumor in this area.

Background RNA-Seq is a powerful means of identifying changes in gene expression in cancerous tissue. Widespread adoption of RNA-Seq is hampered by lack of familiarity with the appropriate analysis tools and excessive turn around time. Maverix Biomics, Inc offers a scalable, reliable, validated, and easily accessible differential expression pipeline for translational and clinical researchers to analyze and explore RNA-Seq data. Here we describe the pipeline, demonstrate the available tools and visualizations, and provide benchmarks for completion time from lung adenocarcinoma. Results Lung adenocarcinoma samples appear very different compared to their normal counterparts in terms of overall gene expression and exhibit many differentially expressed genes. For analysis completion time, parallelization is far superior than the theoretical curve without parallelization. It took 7.9 hours to analyze two samples, but took only 13.1 hours to analyze 25 samples. We found 2246 significant genes common to three different differential expression tools: DESeq, edgeR, and cuffdiff. Conclusions The Maverix RNA-Seq pipeline is demonstrated here to be highly scalable, easy to use, and includes a range of tools and visualizations for understanding differential expressions results. This pipeline is a great analytic option to accelerate translational and clinical research in the field of oncology. Citation Format: Michael S. Fitzsimons, Mei-Chong Wendy Lee, Byung-In Lee, Lenin Subramanian. Lung adenocarcinoma differential expression analysis using the Maverix RNA-Seq pipeline. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1518.

Objective Quantify and describe Acanthamoeba keratitis (AK) cases in British Columbia (BC). Design A comparison of annual incidence rates confirms the presence of an outbreak. A case series describes characteristics of the outbreak. Participants All laboratory-confirmed AK cases (persons) in BC (1988–2011; n=68) were included in the incidence rate comparison. Of the 42 cases (persons) between 2003 and 2007, 32 were selected to interview (laboratory confirmed, 2005–2007), and the 23 who completed interviews form the case series. Methods A comparison of standardized annual incidence rates in historic to outbreak periods is performed by z -score test. A telephone interview and descriptive analysis detailing demographics, risk factors, and contact lens (CL) wearing habits was completed for 23 cases. Main Outcome Measures We measure number of laboratory confirmed cases in BC. In addition, risk factors and potential exposures of these cases are reported. Results The annual incidence of AK increased significantly from 0.029 to 0.200 per 100 000 population between historic years (1988–2002) and outbreak years (2003–2007; P = 0.022). The annual incidence of AK has since returned to near historic levels (0.056/100 000 population). The case series identified multiple risk factors, including the use of a specific recalled solution (60.9%), daily soft CL wear (95.7%), all-in-one solutions (95.7%), showering while wearing CL (65.2%), and generally poor CL hygiene. Conclusions A significant increase in annual AK incidence occurred between 2003 and 2007 in BC. After 2007, the incidence of AK returned to near historic levels. The recalled solution was associated with many cases; however, other risk factors were also identified, including being unaware of the recall and poor CL hygiene practices, highlighting the need for improved education about the severity of AK and consequences of improper CL hygiene. Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

BACKGROUND: A possible breach of the transducer protector in specific dialysis machines was reported in June 2004 in British Columbia (BC), which led to testing of hemodialysis patients for hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV. This testing provided an opportunity to examine HCV incidence, prevalence and coinfection with HBV and HIV, and to compare anti-HCV and HCV polymerase chain reaction (PCR).METHODS: The results of hemodialysis patients who were dialyzed on the implicated machines (65% of BC dialysis patients), and tested for HCV, HBV and HIV, between June 1, 2004, and December 31, 2004, were reviewed and compared with available previous results.RESULTS: Of 1286 hemodialysis patients with anti-HCV and/or HCV-PCR testing, 69 (5.4%) tested positive. Two HCV genotype 4 seroconversions were identified. HCV incidence rate on dialysis was 78.8 cases per 100,000 person-years. Younger age, history of renal transplant and past HBV infection were associated with HCV infection. No occult infection was identified using HCV-PCR.INTERPRETATION: Hemodialysis patients had three times the HCV prevalence rate of the general BC population, and more than 20 times the incident rate of the general Canadian population. One of the two seroconversions occurred before the testing campaign; the patient was likely infected during hemodialysis in South Asia. The other was plausibly a late seroconversion following renal transplant in South Asia. Nosocomial transmission cannot be ruled out because both patients were dialyzed in the same centre. Baseline and annual anti-HCV testing is recommended. HCV-PCR should be considered at baseline for persons with HCV risk factors, and for returning travellers who received dialysis in HCV-endemic countries to identify HCV infection occurring outside the hemodialysis unit.

The influenza immunization program in North America has been primarily designed to provide direct benefit to vaccinated individuals at highest risk of serious influenza outcomes. Some evidence suggests that immunization of certain age groups may also extend indirect protective benefit to vulnerable populations. Our goal was to identify age groups associated earliest with seasonal influenza activity and who may have the greatest indirect impact at the population level. We examined age-based associations between influenza medical visits and population-wide hospitalization/mortality due to pneumonia & influenza (P&I) using administrative datasets in British Columbia, Canada. A peak week was identified for each age group based on the highest rates observed in a given week for that study year. Mean rates at the peak week were averaged over the study years per age group. Timeliness (T) was defined as the mean difference in days between the first peak in influenza medical visits and population-wide P&I hospitalizations/deaths. Poisson regression was applied to calculate prediction (Pr) as the average proportion of deviance in P&I explained by influenza medical visits. T and Pr were derived by age group, and the product (T x Pr) was used as a summary measure to rank potential indirect effects of influenza by age group. Young children (0-23 months) and the elderly (> or = 65 years) had the highest peak rates of P&I hospitalization. Children < 6m and the elderly had the highest peak rates of P&I mortality. We found no significant differences by age for influenza medical visits in predicting population-wide P&I hospitalizations or deaths. School-aged children (5-19 years) showed the best relative combination of T x Pr, followed by preschool-aged children (2-4 years). We conclude that the very young and old suffer the greatest morbidity due to P&I, and an indirect role for school-aged children in anticipating the risk to others warrants further evaluation.

BACKGROUND: In North America use of second-generation macrolides such as clarithromycin and azithromycin is popular due to favourable dosing and adverse event profiles. However, studies have also shown that use of second-generation macrolides promotes carriage of macrolide-resistant nasopharyngeal and oral streptococci. The present study was undertaken to characterize overall antibiotic use including macrolide antibiotics among children in British Columbia. METHODS: Population-based data from British Columbia were analysed to determine antibiotic prescribing patterns for outpatient prescriptions from 1996 to 2003. Antibiotic prescription rates per 1000 children per year were evaluated by age (0-4, 5-9, 10-14

BACKGROUND: A relationship betweenChlamydia pneumoniae infection and acute coronary syndromes has not been consistently found in published studies. It has been hypothesized that a bacteriophage-infected subset ofC pneumoniaemay be uniquely equipped to promote atherosclerosis and acute coronary syndromes through the expression of phage genes. METHODS: The authors performed a pilot case-control study of acute coronary events. Case and control subjects were characterized demographically and according to recognized coronary risk factors. These subjects also provided serum for the detection of antibody to the elementary bodies ofC pneumoniaeand antibody to the Vp1 protein coded by the phage. Bivariate and multivariate comparisons were performed using statistics appropriate for paired analyses. RESULTS: Antibodies toC pneumoniae, Vp1 protein or both were not associated with acute coronary events by bivariate or multivariate analysis. As expected, case subjects were significantly more likely to have hypertension, hypercholesterolemia or diabetes mellitus. CONCLUSION: The present study adds to a growing body of literature that does not support the hypothesized relationship betweenC pneumoniae(or a phage-infected subset ofC pneumoniae) and acute coronary syndromes.

Summary Objective Pyomyoma is an uncommon complication of benign leiomyoma. Here, we report a rare case of a perforated pyomyoma with purulent peritonitis. Case Report A 53-year-old postmenopausal woman presented with impending septic shock on arrival at our emergency department. Physical examination and imaging studies revealed a pelvic mass with peritonitis. Emergency exploratory laparotomy due to suspicion of a ruptured pyomyoma or malignancy revealed a spontaneously perforated large pyomyoma leaking copious purulent material directly into the peritoneal cavity. Total hysterectomy and bilateral salpingo-oophorectomy were performed. Histopathology revealed no malignancy. The patient recovered smoothly after combined antibiotic therapy. Conclusion Gynecologists should be aware of this rare emergency condition, especially when handling a patient with a history of leiomyoma uteri and if signs of infection or even sepsis are present.

Objective The recommendations of the American Institute of Medicine (IOM) were revised recently in order to enhance maternal and neonatal health. The aim of our study was to investigate the risk of low birth weight (LBW) among women who follow the IOM recommendations. Materials and methods Gestational weight gain (GWG) and rate of weight gain (RWG) across the different periods of pregnancy among women who delivered LBW fetuses were analyzed retrospectively. The logistic regression was used to analyze the risk of LBW and to identify recommendations. Results From January 2008 to December 2009, 117 out of 4924 (2.4%) women delivered term LBW fetuses. After exclusions, 88 LBW and 91 control subjects were enrolled into the study. There was increased risk of cesarean delivery [odds ratio (OR) with 95% confidence interval (CI): 2.53 (1.33–4.83)] and neonatal asphyxia within 7 days of birth [OR 95% CI: 5.71 (1.21–26.83)] for the LBW group compared with the control group. Normal weight women [body mass index (BMI): 18.5–24.9 kg/m 2 ] who followed the GWG and RWG recommendations of the IOM had no increased risk of LBW. However, there was a two-to three-fold increased LBW risk among normal weight women who followed the IOM guidelines when, during the 2 nd trimester, their GWG was ≤7 kg [OR 95% CI: 2.21 (1.28–6.49)] or their RWG was ≤0.45 kg/week [OR 95% CI: 3.14 (1.32–7.47)]. Among underweight women (BMI 2 ), if, during the 2 nd and 3 rd trimesters, they followed the lower range of the GWG and RWG recommendations of the IOM there was a five-fold increased risk of LBW if the GWG was ≤13 kg [OR 95% CI: 5.29 (1.61–25.51)]; or the RWG was ≤0.45 kg/week [OR 95% CI: 5.35 (1.61–24.66)]. Conclusion For underweight women, it is suggested that they follow the upper range of the IOM recommendation in order to avoid LBW. For normal weight women, although the IOM guidelines provide a good basis, it is suggested that they carefully follow the recommended GWG and the RWG values during the 2 nd trimester, which is a very important period for fetal growth.

Background: Iron deficiency and its consequent anemia constitute the commonest micronutrient deficiency in the world. Objective: We investigated whether long-term, weekly iron-folate supplements administered at school would improve hemoglobin and ferritin concentrations in adolescent girls, including those with mild-to-moderate anemia and hemoglobin concentrations indicating borderline anemia. Design: Subjects were 266 girls with hemoglobin concentrations of 80-119.9 g/L (group A) and 358 girls with hemoglobin concentrations of 120-130 g/L (group B) who were otherwise healthy. Two hundred sixty-six girls in group A and 268 girls in group B were randomly assigned to receive either 60 or 120 mg Fe plus 3.5 mg folic acid weekly for 22 wk. Ninety of the girls in group B wi:re randomly assigned to receive only 5 mg folic acid weekly. Capillary hemoglobin and plasma ferritin were measured at baseline and after 12 and 22 wk of supplementation. Results: By the end of the study, 2% of the girls had dropped out and >96% hart taken greater than or equal to 20 of the 22 tablets; side effects were minimal. Mean plasma ferritin increased significantly in all iron-supplemented groups, independently of initial hemoglobin values and iron doses. Ferritin concentrations decreased in the girls supplemented with folic acid only. As expected, hemoglobin responses to iron were higher in group A than in group B and increases were positively correlated with initial plasma ferritin. Hemoglobin failed to respond to folate supplementation if initial plasma ferritin concentrations were low. Mean hemoglobin increased significantly and consistently in relation to the length of treatment. Conclusion: Long-term, weekly iron-folate supplementation was found to be a practical, safe, effective, and inexpensive method for improving iron nutrition in adolescent schoolgirls.

OBJECTIVES: Antimicrobial resistance in Streptococcus pneumoniae has increased in recent decades. We linked two surveillance programs to evaluate trends in incidence, serotype distribution, and antimicrobial resistance in invasive pneumococcal disease (IPD) since the heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in BC in 2003. METHODS: IPD case reports for BC from 2002–2005 from the BC Centre for Disease Control were linked to serotype and antimicrobial susceptibility results from the National Centre for Streptococcus (NCS). RESULTS: There was a significant decrease in IPD incidence in children

Summary Objective Pyogenic granuloma is a relatively common skin growth. The skin of the head, neck, upper trunk, and hands and feet and the oral mucosa and gingiva are the most common sites, but it seldom appears on the female genitalia. Case Report A 52-year-old woman presented with a lobulated lesion on the right labia majora. The surface of the lesion was reddish and bled occasionally. The lesion was excised and histopathology revealed features suggestive of lobular capillary hemangioma (pyogenic granuloma). Conclusion Pyogenic granuloma is considered a reactive hyperproliferative vascular response to trauma or other stimuli. The name “pyogenic granuloma” is a misnomer since the condition is not associated with pus and does not represent a granuloma histologically. There are a few cases of lobular capillary hemangioma of the glans penis but it is rare on the female genitalia. We present this case to help physicians become aware that lobular capillary hemangiomas may occur at this site.