bluuebunny/crossref_metadata_2025 huggingface dataset:
Benchmarking Pain Outcomes for Children with Sickle Cell Disease Hospitalized in a Tertiary Referral Pediatric Hospital
Authors: Vijenthira Abi , Stinson Jennifer , Friedman Jeremy , Palozzi Lori , Taddio Anna , Scolnik Dennis , Victor Charles , Kirby-Allen Melanie , Campbell Fiona
Published: March 2016

BACKGROUND: Painful vaso‐occlusive crisis (VOC) is the most common reason for hospitalization in children with sickle cell disease.

OBJECTIVE: To benchmark pain outcomes in sickle cell disease, including process outcomes (eg, pain assessment and documentation practices, pain management interventions) and clinical outcomes (eg, pain intensity over hospital stay), to identify areas for improvement.

METHODS: A retrospective study was conducted on electronic charts of children hospitalized with a primary diagnosis of VOC between July 2007 and August 2008.

RESULTS: A convenience sample of 50 admissions was used. In terms of clinical outcomes, patients presented to the emergency department with an initial median pain intensity of 9/10 (interquartile range 8/10 to 10/10). Forty‐three per cent had not used opioids for pain relief at home. The mean (± SD) length of stay was 4.0±2.3 days. For most patients, median scores for highest daily pain intensity remained moderate to high throughout hospitalization, although scores did decrease significantly per day of hospitalization. In terms of process outcomes, pain intensity was assessed according to hospital standards on 25% of days in both the emergency department and the ward. There was no discrepancy between prescribed and administered opioid doses and medication use. In 95% of cases, strong opioid use was in a subtherapeutic or low therapeutic dosage range.

CONCLUSIONS: The results showed three areas to target for improvement: improved pain assessment and documentation using valid pain tools; more aggressive multimodal management for peak VOC pain; and better education and support for pain management at home. Further studies are required to evaluate optimal pain treatment practices.
Influence of Stimulation Location and Posture on the Reliability and Comfort of the Nociceptive Flexion Reflex
Authors: Lewis Gwyn N , Rice David A , Jourdain Kathryn , McNair Peter J
Published: March 2016

BACKGROUND: The lower limb nociceptive flexion reflex (NFR) is commonly used to assess the function of the nociceptive system. Currently, there is a lack of standardized stimulation procedures to determine the NFR threshold, making comparisons of thresholds across studies difficult.

OBJECTIVES: To assess and compare the within‐ and between‐session reliability of NFR threshold when elicited from two common stimulation locations: the medial arch of the foot (while standing) and the sural nerve (while seated).

METHODS: A staircase procedure was used to determine NFR threshold in 20 healthy participants twice within one session and once more in a separate session approximately four days later. At both sessions, NFR threshold was determined from both medial arch and sural nerve stimulation. Comparisons of NFR threshold, reliability and participant discomfort ratings were made between the two stimulation locations.

RESULTS: NFR thresholds were statistically equivalent at the two stimulation locations, but there were more nonresponders and ratings of participant discomfort were significantly higher during stimulation over the sural nerve. Within‐session reliability measures were superior for stimulation over the sural nerve; however, between‐session measures were more reliable using stimulation over the medial arch of the foot.

CONCLUSIONS: The authors recommend stimulation over the medial arch of the foot while standing as the preferred location for eliciting the lower limb NFR, particularly if measurements are to be compared across multiple sessions.
Blood Cytokine, Chemokine and Gene Expression in Cholestasis Patients with Intractable Pruritus Treated with a Molecular Adsorbent Recirculating System: A Case Series
Authors: Lisboa Luiz F , Asthana Sonal , Kremer Andreas E , Swain Mark , Bagshaw Sean M , Gibney Noel , Karvellas Constantine J
Published: March 2016

BACKGROUND: The molecular adsorbent recirculating system (MARS) is an albumin-dialysis modality that has been investigated predominantly in patients with acute and acute-on-chronic liver failure.

OBJECTIVES: To report the clinical efficacy and safety of MARS therapy for intractable pruritus in cholestasis patients with stable chronic liver disease, characterizing the impact of MARS on cytokine levels and on the transcriptome in the blood compartment.

METHODS: MARS therapy was performed on three patients with cholestatic liver disease using 8 h runs for two consecutive days. The expression levels of 65 cytokines/chemokines and 24,000 genes were profiled by Luminex (Luminex Corporation, USA) and microarray, respectively.

RESULTS: A quality-of-life assessment demonstrated a marked improvement during therapy, which was sustained in two of three patients. No bleeding or infectious complications were observed. Bile acid levels were markedly reduced following MARS (mean [± SD] pretreatment 478.9±112.2 μmol/L versus post-treatment 89.7±68.8 μmol/L). Concordant decreases in cytokine/chemokine levels were noted for interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-12 (p40), RANTES, tranforming growth factor-alpha, tumour necrosis factor-alpha and thrombopoietin following MARS. On microarray profiling, biologically relevant concordant changes among all patients were evident for 20 different genes (10 upregulated and 10 downregulated). The upregulation of several potentially immune suppressive/regulatory genes (eg, early growth response 3 [EGR-3], ephrin-A2 [EFNA2] and serum amyloid A1 [SAA1]), concurrent with downregulation of genes involved in innate immunity (eg, toll-like receptor 4 interactor with leucine-rich repeats [TRIL]) and inflammation (eg, ephrin receptor B1 [EPHB1]), was observed.

CONCLUSIONS: This investigative approach offers new insights into intractable pruritus and suggests future therapeutic targets. The clinical benefit of MARS in cholestasis patients with intractable pruritus may not exclusively result from filtration of pruritogens, but also from systemic changes in cytokine/chemokine levels and changes in gene expression of blood cells.
Canadian Thoracic Society 2012 Guideline Update: Diagnosis and Management of Asthma in Preschoolers, Children and Adults
Authors: Lougheed M Diane , Lemiere Catherine , Ducharme Francine M , Licskai Chris , Dell Sharon D , Rowe Brian H , FitzGerald Mark , Leigh Richard , Watson Wade , Boulet Louis-Philippe ,   Canadian Thoracic Society Asthma Clinical Assembly
Published: March 2016

BACKGROUND: In 2010, the Canadian Thoracic Society (CTS) published a Consensus Summary for the diagnosis and management of asthma in children six years of age and older, and adults, including an updated Asthma Management Continuum. The CTS Asthma Clinical Assembly subsequently began a formal clinical practice guideline update process, focusing, in this first iteration, on topics of controversy and/or gaps in the previous guidelines.

METHODS: Four clinical questions were identified as a focus for the updated guideline: the role of noninvasive measurements of airway inflammation for the adjustment of anti-inflammatory therapy; the initiation of adjunct therapy to inhaled corticosteroids (ICS) for uncontrolled asthma; the role of a single inhaler of an ICS/long-acting beta2-agonist combination as a reliever, and as a reliever and a controller; and the escalation of controller medication for acute loss of asthma control as part of a self-management action plan. The expert panel followed an adaptation process to identify and appraise existing guidelines on the specified topics. In addition, literature searches were performed to identify relevant systematic reviews and randomized controlled trials. The panel formally assessed and graded the evidence, and made 34 recommendations.

RESULTS: The updated guideline recommendations outline a role for inclusion of assessment of sputum eosinophils, in addition to standard measures of asthma control, to guide adjustment of controller therapy in adults with moderate to severe asthma. Appraisal of the evidence regarding which adjunct controller therapy to add to ICS and at what ICS dose to begin adjunct therapy in children and adults with poor asthma control supported the 2010 CTS Consensus Summary recommendations. New recommendations for the adjustment of controller medication within written action plans are provided. Finally, priority areas for future research were identified.

CONCLUSIONS: The present clinical practice guideline is the first update of the CTS Asthma Guidelines following the Canadian Respiratory Guidelines Committee’s new guideline development process. Tools and strategies to support guideline implementation will be developed and the CTS will continue to regularly provide updates reflecting new evidence.
The Pain and Sleep Questionnaire Three‐Item Index (PSQ‐3): A Reliable and Valid Measure of The Impact of Pain on Sleep in Chronic Nonmalignant Pain of Various Etiologies
Authors: Ayearst Lindsay E , Harsanyi Zoltan , Michalko Kenneth J
Published: March 2016

BACKGROUND: Sleep disturbance is among the more common complaints reported by chronic pain patients. Because pain‐related sleep disturbance may serve as a marker for the assessment of responses to treatment for chronic pain, inclusion of a measure designed to assess the impact of pain on sleep in clinical trial protocols is important, if not necessary. Measures typically used for this purpose lack scales specifically designed for the assessment of the impact of pain on sleep or are based on a single item. Single‐item scales lack reliability and, therefore, validity.

OBJECTIVES: To investigate the psychometric properties of the five‐item Pain and Sleep Questionnaire (PSQ) Index, which is embedded in the eight‐item inventory, by applying an accepted methodology using retrospective analyses in controlled clinical trials in which the measure had been administered among patients with chronic nonmalignant pain.

METHODS: Data were pooled from nine independent, single‐site, double‐blind, randomized placebo‐controlled clinical trials conducted over a period of approximately 10 years, the majority of which were cross‐over designs. A cross‐validation approach was adopted with exploratory and confirmatory factor analyses conducted to evaluate the underlying structure and dimensionality of the measure. Internal consistency reliability was evaluated using Cronbach’s alpha coefficient. Mean score differences were used to assess the ability of the index to detect important treatment changes. Correlation coefficients were calculated between index scores and scores from other health‐related outcome measures to evaluate the criterion validity of the index. Finally, predictive validity was assessed using multiple regression analyses.

RESULTS: Pooling the data resulted in a sample of 605 patients (65.5% female; mean age 55.7 years). Findings suggested a revised three‐item PSQ Index (PSQ‐3). The PSQ‐3 demonstrated high internal consistency across samples (ranging from 0.82 to 0.93) and was sensitive to detecting meaningful treatment effects within different chronic pain categories. Moderate to strong correlations (r>0.40) between the PSQ‐3 and other health‐related outcome measures provided preliminary evidence for criterion‐related validity. Results of multiple regression analyses demonstrated that the PSQ‐3 accounted for between 29% and 40% of the variance in scores from other health‐related outcome measures.

CONCLUSIONS: Results support the scoring of a revised three‐item index for the assessment of the impact of pain on sleep. The revised index demonstrated acceptable levels of internal consistency and preliminary support for the structural, criterion‐related and predictive validity of the index was achieved.
Detection of Clostridium difficile in Retail Ground Meat Products in Manitoba
Authors: Visser Monique , Sepehrim Shadi , Olson Nancy , Du Tim , Mulvey Michael R , Alfa Michelle J
Published: March 2016

The aim of the present study was to determine whether Clostridium difficile was present in uncooked retail ground beef and ground pork products sold in Winnipeg, Manitoba. Using an alcohol treatment protocol and inoculation of cultures on C difficile Moxalactam Norfloxacin (CDMN), toxigenic C difficile was found in 6.3% of 48 meat samples. The C difficile isolates belonged to different pulsotypes, all of which had been previously isolated from the stool of Manitoba patients with C difficile disease. Because cooking of meat will not eradicate C difficile spores, this raises a concern regarding potential foodborne transmissibility of this organism.
Spirometry in Primary Care: An Analysis of Spirometry Test Quality in a Regional Primary Care Asthma Program
Authors: Licskai Christopher J , Sands Todd W , Paolatto Lisa , Nicoletti Ivan , Ferrone Madonna
Published: March 2016

BACKGROUND: Primary care office spirometry can improve access to testing and concordance between clinical practice and asthma guidelines. Compliance with test quality standards is essential to implementation.

OBJECTIVE: To evaluate the quality of spirometry performed onsite in a regional primary care asthma program (RAP) by health care professionals with limited training.

METHODS: Asthma educators were trained to perform spirometry during two 2 h workshops and supervised during up to six patient encounters. Quality was analyzed using American Thoracic Society (ATS) 1994 and ATS/European Respiratory Society (ERS) 2003 (ATS/ERS) standards. These results were compared with two regional reference sites: a primary care group practice (Family Medical Centre [FMC], Windsor, Ontario) and a teaching hospital pulmonary function laboratory (London Health Sciences Centre [LHSC], London, Ontario).

RESULTS: A total of 12,815 flow‐volume loops (FVL) were evaluated: RAP – 1606 FVL in 472 patient sessions; reference sites – FMC 4013 FVL in 573 sessions; and LHSC – 7196 in 1151 sessions. RAP: There were three acceptable FVL in 392 of 472 (83%) sessions, two reproducible FVL according to ATS criteria in 428 of 469 (91%) sessions, and 395 of 469 (84%) according to ATS/ERS criteria. All quality criteria – minimum of three acceptable and two reproducible FVL according to ATS criteria in 361 of 472 (77%) sessions and according to ATS/ERS criteria in 337 of 472 (71%) sessions. RAP met ATS criteria more often than the FMC (388 of 573 [68%]); however, less often than LHSC (1050 of 1151 [91%]; P<0.001).

CONCLUSIONS: Health care providers with limited training and experience operating within a simple quality program achieved ATS/ERS quality spirometry in the majority of sessions in a primary care setting. The quality performance approached pulmonary function laboratory standards.
Dietary Iron Intake and Serum Ferritin Concentration in 213 Patients Homozygous for theHFEC282YHemochromatosis Mutation
Authors: Gordeuk Victor R , Lovato Laura , Barton James C , Vitolins Mara , McLaren Gordon , Acton Ronald T , McLaren Christine , Harris Emily L , Speechley Mark , Eckfeldt John H , Diaz Sharmin , Sholinsky Phyliss , Adams Paul
Published: March 2016

BACKGROUND:HFEC282Yhomozygotes have an increased risk for developing increased iron stores and related disorders. It is controversial whether dietary iron restrictions should be recommended to such individuals.

OBJECTIVE: To determine whether dietary iron content influences iron stores inHFEC282Yhomozygotes as assessed by serum ferritin concentration.

DESIGN: Serum ferritin concentration was measured and a dietary iron questionnaire was completed as part of the evaluation of 213HFEC282Yhomozygotes who were identified through screening of >100,000 primary care patients at five HEmochromatosis and IRon Overload Screening (HEIRS) Study Field Centers in the United States and Canada.

RESULTS: No significant relationships between serum ferritin concentration and dietary heme iron content, dietary nonheme iron content or reports of supplemental iron use were found.

CONCLUSION: These results do not support recommending dietary heme or nonheme iron restrictions forHFEC282Yhomozygotes diagnosed through screening in North America.
Hyperamylasemia and pancreatitis following spiral enteroscopy
Authors: Teshima Christopher W , Aktas Huseyin , Kuipers Ernst J , Mensink Peter B
Published: March 2016

BACKGROUND: Acute pancreatitis is a significant potential complication with double-balloon enteroscopy. Hyperamylasemia is frequently observed after both double-balloon enteroscopy and single-balloon enteroscopy but often without associated pancreatitis. Whether the same phenomenon occurs with spiral enteroscopy is currently unknown.

AIMS: To determine the incidence of pancreatitis and hyperamylasemia following spiral enteroscopy.

METHODS: A prospective cohort study of consecutive patients undergoing proximal spiral enteroscopy was conducted. Serum amylase levels were measured immediately before and following the procedure, combined with observation for clinical signs of pancreatitis.

RESULTS: A total of 32 patients underwent proximal spiral enteroscopy, with a mean total procedure time of 51 min (range 30 min to 100 min) and mean depth of insertion of 240 cm (range 50 cm to 350 cm). The diagnostic yield was 50%, with 31% of all procedures being therapeutic. While no patients exhibited signs that raised suspicion of pancreatitis, hyperamylasemia was common (20%). Hyperamylasemia was not significantly associated with procedure duration or depth of insertion but was linked to patients with Peutz-Jeghers syndrome and with the use of propofol sedation, suggesting that it may be more common in difficult cases.

CONCLUSIONS: Postprocedural hyperamylasemia occurred frequently with proximal spiral enteroscopy, while no associated pancreatitis was observed. This finding suggests that hyperamylasemia may not necessarily reflect pancreatic injury nor portend a risk for pancreatitis.
The Impact Of Hepatitis B Knowledge and Stigma on Screening in Canadian Chinese Persons
Authors: Li Dorothy , Tang Taryn , Patterson Matt , Ho Michael , Heathcote Jenny , Shah Hemant
Published: March 2016

BACKGROUND: Chronic hepatitis B (CHB) infection is endemic in East Asia, and those who emigrate to North America have higher rates of CHB infection when compared with the general population. To date, Chinese persons residing in Canada have not been mandated to be screened for CHB infection.

OBJECTIVE: To understand factors that influence hepatitis B screening behaviour among the Chinese community in Toronto, Ontario, and to determine whether stigma acts as a barrier to screening.

METHODS: Self-identified Chinese individuals at a family physician’s office and at English as a second language (ESL) classes in Toronto completed a questionnaire with demographic questions, a hepatitis B virus (HBV) stigma scale and an HBV knowledge scale. Pearson product moment correlation and multiple regression techniques were used to analyze the data.

RESULTS: The study group included 343 individuals. Their mean (± SD) age was 48.76±17.49 years and the majority were born in China (n=229 [68%]). The mean score on the HBV knowledge scale was 10.13±1.76 (range 0 to 15), with higher scores indicating greater HBV knowledge. The mean score on the stigma scale was 54.60±14.18 (range 20 to 100), with higher scores indicating more stigma. Being an immigrant, having a family physician and having greater knowledge of HBV were associated with increased rates of screening for this infection. In contrast, greater levels of HBV stigma were associated with decreased likelihood of screening for HBV infection.

CONCLUSIONS: HBV stigma is associated with reduced rates of screening for this infection.
Integrated Approach to Diagnosis of Associated Occupational Asthma and Rhinitis
Authors: Nguyen Sébastien , Castano Roberto , Labrecque Manon
Published: March 2016

Patients with coexisting work-related rhinitis and asthma would benefit from an adequate and simultaneous recognition of both diseases. The present case illustrates the advantages and importance of using an integrated approach to confirm a diagnosis of occupational rhinitis (OR) and occupational asthma (OA).

A 38-year-old woman, who worked as an animal laboratory technician since 2004, first noticed the appearance of rhinitis and conjunctivitis symptoms in 2007 when she was exposed to rats. A skin-prick test with rat extract was strongly positive. A specific inhalation challenge with parallel assessment of nasal and bronchial responses was conducted. After 10 min of exposure, she developed rhinitis and conjunctivitis symptoms, her forced expiratory volume in 1 s dropped by 27.5% and her nasal volume, measured by acoustic rhinometry, decreased by 80% from baseline values. After allergen exposure, induced sputum and nasal lavage examination demonstrated an increase in eosinophils (11% and 20%, respectively). A diagnosis of associated allergic OA and OR was confirmed and she was advised to stop working with rats.

A systematic and parallel diagnostic approach enables confirmation of a diagnosis of OA and OR in patients complaining of work-related rhinitis and asthma symptoms.
First Canadian Outbreak of Enterobacteriaceae‐Expressing Klebsiella pneumoniae Carbapenemase Type 3
Authors: Leung Victor , Loo Vivian G , Frenette Charles , Domingo Marc-Christian , Bourgault Anne-Marie , Mulvey Michael R , Robson Hugh G
Published: March 2016

BACKGROUND: Organisms expressing Klebsiella pneumoniae carbapenemase (KPC) are found in several regions worldwide but are rarely detected in Canada. The first outbreak of KPC‐expressing strains of Enterobacteriaceae clinical isolates in a university‐affiliated hospital intensive care unit (ICU) in Canada is described.

METHODS: Enterobacteriaceae isolates that were flagged by the Vitek 2 (bioMérieux, France) system as possible carbapenemase producers were subjected to the modified Hodge test. Modified Hodge test‐positive organisms were analyzed by pulsed‐field gel electrophoresis, tested for KPC and other beta‐lactamase genes by polymerase chain reaction analysis and underwent subsequent nucleic acid sequencing. Antimicrobial susceptibility profiles were determined by Vitek 2 and Etest (bioMérieux, France). A chart review was conducted to establish epidemiological links.

RESULTS: During the study period, 10 unique Enterobacteriaceae isolates expressing KPC were detected from nine ICU patients. Five patients had infections (three pneumonias, one surgical site infection, one urinary tract infection). Isolates included Escherichia coli (5), Klebsiella oxytoca (2), Serratia marcescens (2) and Citrobacter freundii (1). Polymerase chain reaction analysis and sequencing confirmed the presence of KPC‐3 in all isolates; four also carried TEM, two CTX‐M and one CMY‐2. The imipenem minimum inhibitory concentrations as determined by Etest ranged from 0.75 μg/mL to ≥32 μg/mL. Pulsed field gel electrophoresis clonal patterns and patient location in the ICU revealed presumptive horizontal transmission events.

CONCLUSIONS: In the present study, Enterobacteriaceae isolates with KPC are emerging and can result in serious infections. The KPC gene can spread via plasmids to different genera of the Enterobacteriaceae family. The dissemination of KPC in Enterobacteriaceae and the consequences for treatment and infection control measures warrant a high degree of vigilance among clinicians and microbiologists.
Prevalence, Risk Factors, Activity Limitation and Health Care Utilization of an Obese Population‐Based Sample with Chronic Obstructive Pulmonary Disease
Authors: Vozoris Nicholas T , O’Donnell Denis E
Published: March 2016

OBJECTIVE: To estimate the prevalence and determine the risk factors and health associations among individuals with combined chronic obstructive pulmonary disease and obesity.

METHODS: Canadian national health survey data from 1994 to 2007 (n=650,000) were used. The presence of COPD was based on health professional‐diagnosed self‐report. The presence of obesity, defined by body mass index ≥30 kg/m2, was identified using self‐reported and measured height and weight. Hospitalization, homecare use, physical activity assessments and socioeconomic data were all self‐reported.

RESULTS: In 2005, the prevalence of obesity in COPD (n=3470) and non‐COPD (n=92,237) individuals was 24.6% and 17.1%, respectively (P<0.0001). In contrast to the non‐COPD group, in which obesity prevalence increased by 38% over 14 years, obesity prevalence increased by only 5% in people with COPD over this same time period. Female sex was the only independent risk factor for obesity in COPD. Previous smoking, residing in Atlantic Canada and the Territories, and low education level were independent risk factors for obesity in the non‐COPD group, but not in the COPD group. The odds of physical activity limitation and health care utilization were significantly higher among obese individuals with COPD compared with nonobese COPD and obese non‐COPD groups.

CONCLUSIONS: The prevalence of obesity was higher in COPD, and exceeded that of the larger non‐COPD group throughout the 13‐year observation period. The presence of obesity in COPD was associated with significantly higher risk of severe activity limitation and increased health care utilization. The combination of obesity and COPD has major implications for health care delivery that has not been previously appreciated.
Health State Utilities and Quality of Life in Patients with Hepatitis B
Authors: Woo Gloria , Tomlinson George , Yim Colina , Lilly Les , Therapondos George , Wong David KH , Ungar Wendy , Einarson Thomas R , Sherman Morris , Heathcote E Jenny , Krahn Murray
Published: March 2016

BACKGROUND: The effect of chronic hepatitis B (CHB) infection on health-related quality of life (HRQoL) and health state utilities has not been well characterized.

OBJECTIVE: To measure utility scores and HRQoL across disease states associated with CHB infection.

METHODS: Patients attending four tertiary care clinics for CHB were approached between July 2007 and March 2009. Respondents completed version 2 of the Short-Form 36 Health Survey, the EQ5D, a visual analogue scale, the Health Utilities Index Mark 3, standard gamble, and demographics and risk factor surveys in English, Cantonese or Mandarin. Charts were reviewed to determine disease stage and comorbidities.

RESULTS: A total of 433 patients were studied: 294 had no cirrhosis; 79 had compensated cirrhosis; seven had decompensated cirrhosis; 23 had hepatocellular carcinoma; and 30 had received a liver transplant. The mean standard gamble utilities for these disease states were 0.89, 0.87, 0.82, 0.84 and 0.86, respectively. HRQoL scores in noncirrhotic patients were similar to those of the general population. Scores of patients with compensated cirrhosis were not significantly lower; however, patients with decompensated cirrhosis and hepatocellular carcinoma had significantly lower HRQoL scores compared with noncirrhotic patients (P<0.05). Similar scores were observed among patients on and off oral antiviral treatment. Post-liver transplant patients had a higher HRQoL than patients with decompensated cirrhosis. Age, number of comorbidities and relationship status were significantly associated with HRQoL scores.

CONCLUSIONS: HRQoL in CHB patients is only impaired in the later stages of liver disease. Neither CHB infection nor antiviral treatment is associated with a lower quality of life.
Review of Boceprevir and Telaprevir for the Treatment of Chronic Hepatitis C
Authors: Wilby Kyle J , Partovi Nilufar , Ford Jo-Ann E , Greanya Erica D , Yoshida Eric M
Published: March 2016

OBJECTIVE: To summarize and evaluate the published literature pertaining to boceprevir and telaprevir, and to provide clinicians with suggestions for use in patients with chronic hepatitis C infection.

METHODS: A standardized search strategy was performed using the MEDLINE, EMBASE, Google Scholar and International Pharmaceuticals Abstracts databases using the search terms “boceprevir”, “telaprevir”, “boceprevir and hepatitis C” and “telaprevir and hepatitis C”. A manual search of references was performed to identify articles missed by the electronic search. Studies were included in the review if they assessed either boceprevir or telaprevir in comparison with standard of care in chronic hepatitis C patients.

RESULTS: The studies identified assessed boceprevir and telaprevir in genotype-1 hepatitis C patients. In both treatment-naive and treatment-experienced patients, sustained virological response rates were achieved more often with boceprevir or telaprevir in combination with pegylated interferon and ribavirin compared with pegylated interferon and ribavirin alone. Both medications were well tolerated, with anemia presenting as the most treatment-limiting adverse effect.

CONCLUSIONS: Boceprevir and telaprevir will revolutionize the management of hepatitis C genotype 1 patients and will most likely decrease the burden of end-stage disease worldwide. However, current clinical limitations include establishing appropriate and cost-effective treatment durations, and use in special populations such as transplant patients and patients coinfected with HIV. Future research will need to clarify these clinical obstacles to clearly define the role of these agents in hepatitis C management.
Origins of the Canadian Association for the Study of the Liver: A Personal Memoir
Authors: Simon Jerome B
Published: March 2016

The Canadian Association for the Study of the Liver (CASL) (Association Canadienne Pour L’Étude Du Foie) is a thriving organization. Although it was established more than a quarter of a century ago and has been successful since the beginning, most members are unaware of how CASL came into being or of its humble origins as a precursor club in the 1970s. The present article reviews those early days. It is written as a memoir because of the author’s personal involvement and is based on detailed records, correspondence and handwritten notes from that era.
Evidence‐Based Guideline for Neuropathic Pain Interventional Treatments: Spinal Cord Stimulation, Intravenous Infusions, Epidural Injections and Nerve Blocks
Authors: Mailis Angela , Taenzer Paul
Published: March 2016

BACKGROUND: The Special Interest Group of the Canadian Pain Society has produced consensus‐based guidelines for the pharmacological management of neuropathic pain. The society aimed to generate an additional guideline for other forms of neuropathic pain treatments.

OBJECTIVE: To develop evidence‐based recommendations for neuropathic pain interventional treatments.

METHODS: A task force was created and engaged the Institute of Health Economics in Edmonton, Alberta, to survey the literature pertaining to multiple treatments. Sufficient literature existed on four interventions only: spinal cord stimulation; epidural injections; intravenous infusions; and nerve blocks. A comprehensive search was conducted for systematic reviews, randomized controlled trials and evidence‐based clinical practice guidelines; a critical review was generated on each topic. A modified United States Preventive Services Task Force tool was used for quality rating and grading of recommendations.

RESULTS: Investigators reviewed four studies of spinal cord stimulation, 19 studies of intravenous infusions, 14 studies of epidural injections and 16 studies of nerve blocks that met the inclusion criteria. The task force chairs rated the quality of evidence and graded the recommendations. Feedback was solicited from the members of the task force.

CONCLUSION: There is sufficient evidence to support recommendations for some of these interventions for selected neuropathic pain conditions. This evidence is, at best, moderate and is often limited or conflicting. Pain practitioners are encouraged to explore evidence‐based treatment options before considering unproven treatments. Full disclosure of risks and benefits of the available options is necessary for shared decision making and informed consent.
Racial Differences in Pain Treatment and Empathy in a Canadian Sample
Authors: Kaseweter Kimberley A , Drwecki Brian B , Prkachin Kenneth M
Published: March 2016

BACKGROUND: Evidence of inadequate pain treatment as a result of patient race has been extensively documented, yet remains poorly understood. Previous research has indicated that nonwhite patients are significantly more likely to be undertreated for pain.

OBJECTIVE: To determine whether previous findings of racial biases in pain treatment recommendations and empathy are generalizable to a sample of Canadian observers and, if so, to determine whether empathy biases mediate the pain treatment disparity.

METHODS: Fifty Canadian undergraduate students (24 men and 26 women) watched videos of black and white patients exhibiting facial expressions of pain. Participants provided pain treatment decisions and reported their feelings of empathy for each patient.

RESULTS: Participants demonstrated both a prowhite treatment bias and a prowhite empathy bias, reporting more empathy for white patients than black patients and prescribing more pain treatment for white patients than black patients. Empathy was found to mediate the effect of race on pain treatment.

CONCLUSIONS: The results of the present study closely replicate those from a previous study of American observers, providing evidence that a prowhite bias is not a peculiar feature of the American population. These results also add support to the claim that empathy plays a crucial role in racial pain treatment disparity.
Interleukin-4 receptor −3223C→T Polymorphism is Associated with Increased Gastric Adenocarcinoma Risk
Authors: Burada Florin , Angelescu Cristina , Mitrut Paul , Ciurea Tudorel , Cruce Mihai , Saftoiu Adrian , Ioana Mihai
Published: March 2016

BACKGROUND: Gastric cancer remains one of the most common types of cancer worldwide, with a large geographical variation in incidence and mortality rates. Cytokine polymorphisms are the most studied host polymorphisms and are associated with an increased risk of stomach cancer in many regions, but have not been studied extensively in Eastern European populations.

OBJECTIVE: To investigate the potential association between five cytokine promoter polymorphisms (interleukin [IL] 1β −511C→T [rs16944], IL-4 receptor [IL-4R] −3223C→T [rs2057768], IL-8 −251T→A [rs4073], IL-10 −1082A→G [rs1800896] and tumour necrosis factor-alpha −308G→A [rs1800629]) and susceptibility to gastric adenocarcinoma in a Romanian population.

METHODS: A total of 347 subjects, consisting of 105 patients with gastric adenocarcinoma and 242 controls, were included. All cytokine polymorphisms were genotyped using allele-specific, commercially available probes. Hardy-Weinberg equilibrium in both groups was analyzed using the χ2test, and the relationship between targeted polymorphisms and the risk of gastric cancer was estimated using OR and 95% CI.

RESULTS: A significant association between the IL-4R −3223C→T polymorphism and risk of gastric cancer was found. Carriers of the IL-4R −3223TT genotype were at a 2.5-fold increased risk for gastric cancer (OR 2.51 [95% CI 1.08 to 5.84]; P=0.041). Moreover, the presence of the IL-4R −3223TT genotype was associated with an increased risk of noncardia gastric adenocarcinoma (OR 3.08 [95% CI 1.25 to 7.58]; P=0.023). No associations were found among the other polymorphisms.

CONCLUSION: The results suggest that the IL-4R −3223C→T polymorphism may increase the risk of gastric adenocarcinoma, mainly for the noncardia type, in the Romanian population.
Prevalence of Asthma and Chronic Obstructive Pulmonary Disease in Aboriginal and Non-Aboriginal Populations: A Systematic Review and Meta-Analysis of Epidemiological Studies
Authors: Ospina Maria B , Voaklander Donald C , Stickland Michael K , King Malcolm , Senthilselvan Ambikaipakan , Rowe Brian H
Published: March 2016

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) have considerable potential for inequities in diagnosis and treatment, thereby affecting vulnerable groups.

OBJECTIVE: To evaluate differences in asthma and COPD prevalence between adult Aboriginal and non-Aboriginal populations.

METHODS: MEDLINE, EMBASE, specialized databases and the grey literature up to October 2011 were searched to identify epidemiological studies comparing asthma and COPD prevalence between Aboriginal and non-Aboriginal adult populations. Prevalence ORs (PORs) and 95% CIs were calculated in a random-effects meta-analysis.

RESULTS: Of 132 studies, eight contained relevant data. Aboriginal populations included Native Americans, Canadian Aboriginals, Australian Aboriginals and New Zealand Maori. Overall, Aboriginals were more likely to report having asthma than non-Aboriginals (POR 1.41 [95% CI 1.23 to 1.60]), particularly among Canadian Aboriginals (POR 1.80 [95% CI 1.68 to 1.93]), Native Americans (POR 1.41 [95% CI 1.13 to 1.76]) and Maori (POR 1.64 [95% CI 1.40 to 1.91]). Australian Aboriginals were less likely to report asthma (POR 0.49 [95% CI 0.28 to 0.86]). Sex differences in asthma prevalence between Aboriginals and their non-Aboriginal counterparts were not identified. One study compared COPD prevalence between Native and non-Native Americans, with similar rates in both groups (POR 1.08 [95% CI 0.81 to 1.44]).

CONCLUSIONS: Differences in asthma prevalence between Aboriginal and non-Aboriginal populations exist in a variety of countries. Studies comparing COPD prevalence between Aboriginal and non-Aboriginal populations are scarce. Further investigation is needed to identify and account for factors associated with respiratory health inequalities among Aboriginal peoples.
New‐Onset Neonatal Pulmonary Hypertension Associated with a Rhinovirus Infection
Authors: Patel Nishit , The Tiong G
Published: March 2016

A 3.5‐week‐old male neonate who developed an upper and lower respiratory tract rhinovirus infection that was temporally associated with the development of severe pulmonary hypertension is described. Rhinovirus has not previously been associated with pulmonary hypertension. This child developed severe pulmonary hypertension with right ventricular failure, requiring mechanical ventilation, nitric oxide inhalation and, eventually, extracorporeal membrane oxygenation.
Application and Interpretation of an Interferon‐Gamma Release Assay: Results of an Audit in a Canadian Centre
Authors: Vat Sopharat , Ghannoum Marc , Laflamme Pierre , Dugas Mario , Labrecque Manon , Lavergne Valéry
Published: March 2016

BACKGROUND: Interferon‐gamma release assays (IGRAs) are newly approved for diagnosing latent tuberculosis infection (LTBI). An internal audit was conducted to review the use of a newly implemented IGRA at the Hôpital du Sacré-Coeur de Montréal (Montréal, Québec) to evaluate its concordance with Canadian recommendations and its implication on diagnosis.

METHODS: From April 2007 to January 2009, all Quantiferon TB Gold In‐Tube (QFT, Cellestis inc, USA) tests performed in at the Hôpital du Sacré-Coeur de Montréal were retrieved. Strategies used to investigate LTBI and clinical interpretation of test results were compared with the local algorithm, which is derived from the current national guidelines.

RESULTS: A total of 200 patients tested with QFT were included in the analysis. LTBI investigation and QFT testing were considered to be appropriate in 87.5% and 66.5% of patients, respectively. Overall, 67 QFT tests were performed inappropriately; 25 were performed when a LTBI investigation was not indicated and 42 were performed whe LTBI interpretation was possible with the result of the tuberculin skin test alone. Among the 175 patients investigated appropriately for LTBI, 49 QFT tests (28%) were interpreted incorrectly; 32 patients (at high risk of developing active tuberculosis) had a positive tuberculin skin test and a negative QFT result wrongly interpreted as being negative for LTBI and 13 patients should have undergone further LTBI investigations.

CONCLUSION: Globally, the present study revealed that there are discrepancies on how the IGRA was employed and interpreted in a Montreal hospital and that strict compliance to the guidelines could significantly reduce errors in interpretation.
Cardiac Work-Up Protocol for Liver Transplant Candidates: Experience from a Single Liver Transplant Centre
Authors: Ye Carrie , Saincher Meghana , Tandon Puneeta , Meeberg Glenda , Williams Randy , Burak Kelly W , Bain Vincent G
Published: March 2016

BACKGROUND: Ischemic cardiac events can cause significant morbidity and mortality postliver transplantation; however, no validated protocols to screen patients before transplantation exist.

OBJECTIVES: To report the introduction of a noninvasive cardiac screening protocol used at the Liver Unit, University of Calgary (Calgary, Alberta); to determine whether the protocol decreases use of coronary angiograms; and to compare cardiac outcomes using the new protocol with an appropriately matched historical control group.

METHODS: A new cardiac screening protocol was introduced into the program in 2005, which uses perfusion scintigraphy to screen high-risk cardiac patients, reserving coronary angiograms for abnormal results. Transplanted patients screened using this protocol were compared with matched historical controls. Electronic charts were reviewed for cardiac outcomes intra- and postliver transplantation.

RESULTS: A total of 396 patients were screened between April 2005 and February 2009. Eighty-two were transplanted by February 2009 and included in the study. Eighty-one patients were successfully matched according to age, sex, cardiac history and presence of diabetes. Twelve of 82 (14.6%) and 11 of 81 (13.6%) in the study and control groups, respectively, underwent coronary angiograms (P=0.85). Coronary artery disease was found in six of 12 (50.0%) study patients and three of 11 (27.3%) control patients who underwent coronary angiography (P=0.27). The mean (± SD) length of the follow-up period was 1.87±0.91 years and 4.45±1.89 years in the study and control groups, respectively. One of 81 in the control group and zero of 82 in the study group experienced an acute coronary syndrome event postoperatively.

CONCLUSIONS: Coronary events are infrequent in liver transplant recipients. The described protocol is an effective method of coronary artery disease screening before liver transplant but does not reduce the number of cardiac investigations performed.
Mucosal Airway Laceration Secondary To Endobronchial Ultrasonography
Authors: Sandhu Amarinder , Rubio Edmundo , Ie Susanti , Boyd Michael
Published: March 2016

Endobronchial ultrasound‐guided transbronchial needle aspiration is becoming the standard of care for mediastinal sampling to diagnose and stage lung cancer. It is considered to be safe and rivals the gold standard, mediastinoscopy, in safety and accuracy. The present article describes a mucosal airway laceration and pneumothorax associated with the procedure.
Why Do Mortality Rates for Nonvariceal Upper Gastrointestinal Bleeding Differ around the World? A Systematic Review of Cohort Studies
Authors: Jairath Vipul , Martel Myriam , Logan Richard FA , Barkun Alan N
Published: March 2016

BACKGROUND: Discrepancies exist in reported mortality rates of nonvariceal upper gastrointestinal bleeding (NVUGIB).

OBJECTIVE: To perform a systematic review assessing possible reasons for these disparate findings and to more reliably compare them.

METHODS: The MEDLINE, EMBASE and ISI Web of Knowledge databases were searched for studies reporting mortality rates in NVUGIB involving adults and published in English. To ensure robust and contemporary estimates, studies spanning 1996 to January 2011 that included more than 1000 patients were selected.

RESULTS: Eighteen of 3077 studies were selected. Ten studies used administrative databases and the remaining eight used registries. The mortality rates reported in these studies ranged from 1.1% in Japan to 11% in Denmark. There were variations in reported mortality rates among countries and also within countries. Reasons for these disparities included a spectrum of quality in reporting as well as heterogeneous definitions of case ascertainment, differing patient populations with regard to severity of presentation and associated comorbidities, varying durations of follow-up and different health care system-related practices.

CONCLUSIONS: Wide differences in reported NVUGIB mortality rates are attributable to differences in adopted methodologies and populations studied. More uniform standards in reporting are needed; only then can true observed variations enable a better understanding of causes of death and pave the way to improved patient outcomes.
A Cross-Sectional Study of the Association between Overnight Call and Irritable Bowel Syndrome in Medical Students
Authors: Wells Malcolm , Roth Lee , McWilliam Morgan , Thompson Kim , Chande Nilesh
Published: March 2016

BACKGROUND: Shift work has been associated with irritable bowel syndrome (IBS), which includes gastrointestinal symptoms such as abdominal pain, constipation and diarrhea. Overnight call shifts also lead to a disruption of the endogenous circadian rhythm.

HYPOTHESIS: Medical students who perform intermittent overnight call shifts will demonstrate a higher prevalence of IBS symptoms when compared with medical students who perform no overnight call shifts.

METHODS: First- and second-year (preclinical) medical students have no overnight call requirements, whereas third- and fourth-year medical (clerkship) students do have overnight call requirements. All medical students at the Schulich School of Medicine and Dentistry (London, Ontario) were invited to complete an anonymous, web-based survey or an identical paper copy that included demographic data, the Rome III questionnaire and the IBS-Quality of Life measure (IBS-QOL). The prevalence of IBS symptoms and quality of life secondary to those symptoms were determined.

RESULTS: Data were available for 247 medical students (110 pre-clinical students, 118 clerkship students and 19 excluded surveys). There was no significant difference in the presence of IBS between preclinical and clerkship students (21 of 110 [19.1%] versus 26 of 118 [22.0%]; P=0.58). The were no significant differences in mean (± SD) IBS-QOL score of those with IBS between preclinical (43.5±8.3) and clerkship students (45.7±13.8) (P=0.53).

CONCLUSIONS: Participation in overnight call was not associated with the development of IBS or a lower quality of life secondary to IBS in medical students.