bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity and Chronic Obstructive Pulmonary Disease: Is Fatter Really Better?
Authors: Galesanu Roxana G , Bernard Sarah , Marquis Karine , Lacasse Yves , Poirier Paul , Bourbeau Jean , Maltais François
Published: March 2016

BACKGROUND: Overweight/obesity is associated with longer survival in chronically ill patients, a phenomenon referred to as the ‘obesity paradox’.

OBJECTIVE: To investigate whether the obesity paradox in patients with chronic obstructive pulmonary disease (COPD) is due to fat accumulation or confounding factors.

METHODS: A total of 190 patients with stable COPD who underwent a mean (± SD) follow‐up period of 72±34 months were enrolled. Anthropometry, pulmonary function tests, midthigh muscle cross‐sectional area obtained using computed tomography (MTCSACT), arterial blood gas and exercise testing data were measured at baseline. Patients were categorized into two subgroups according to body mass index (BMI) <25 kg/m2 or ≥25 kg/m2 (normal and overweight/obese, respectively).

RESULTS: Seventy‐two patients (38%) died during the follow‐up period. Survival tended to be better in the overweight/obese patients but this difference did not reach statistical significance. Overweight/obese patients had better lung function and a larger MTCSACT than those with normal BMI (P<0.001). Overweight/obese patients also had a significantly higher peak work rate than patients with normal BMI (P<0.001). PaO2 and PaCO2 were not significantly different in the two groups. When adjusted for PaCO2, peak work rate and MTCSACT, the tendency for improved survival in overweight/obese patients disappeared. In fact, when these variables were considered in the survival analysis, patients with lower BMI tended to have better survival.

CONCLUSION: These results suggest that important confounders, such as hypercapnia, exercise capacity and muscle mass, should be considered when interpreting the association between increased BMI and survival in patients with COPD.
Screening, Detecting and Enhancing the Yield of Previously Undiagnosed Hepatitis B and C In Patients with Acute Medical Admissions to Hospital: A Pilot Project Undertaken at the Vancouver General Hospital
Authors: Kapeluto Jordanna E , Kadatz Matthew , Wormsbecker Andrew , Sidhu Kiran , Yoshida Eric M
Published: March 2016

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) represent an increasing health burden and morbidity in Canada. Viral hepatitis, specifically HCV, has high prevalence among persons born between 1945 and 1965, with 45% to 85% of infected adults asymptomatic and unaware of their infection. Screening has been shown to be cost effective in the detection and treatment of viral hepatitis.

OBJECTIVE: To quantify incidence and identify undocumented HBV and HCV infection in hospitalized patients at a single centre with secondary analysis of risk factors as part of a quality improvement initiative.

METHODS: A one-time antibody test was conducted in patients admitted to the acute medicine and gastroenterology services.

RESULTS: Over a 12-week period, hospital screening for HBV and HCV was performed in 37.3% of 995 admitted patients. There was identification of 15 previously undiagnosed cases of HCV (4%) and 36 undocumented cases of occult (ie, antihepatitis B core antigen seropositive) or active (ie, hepatitis B surface antigen seropositive) HBV (9.7%). Among patients with positive screens, 60% of seropositive HCV patients had no identifiable risk factors.

CONCLUSIONS: The prevalence of HBV and HCV infection among hospitalized patients in Vancouver was higher than that of the general population. Risk factors for contraction are often not identified. These results can be used as part of an ongoing discussion regarding a ‘seek and treat’ approach to the detection and treatment of chronic blood-borne viral illnesses.
The Influence of Communicative Relations on Facial Responses to Pain: Does It Matter Who Is Watching?
Authors: Karmann Anna J , Lautenbacher Stefan , Bauer Florian , Kunz Miriam
Published: March 2016

BACKGROUND: Facial responses to pain are believed to be an act of communication and, as such, are likely to be affected by the relationship between sender and receiver.

OBJECTIVES: To investigate this effect by examining the impact that variations in communicative relations (from being alone to being with an intimate other) have on the elements of the facial language used to communicate pain (types of facial responses), and on the degree of facial expressiveness.

METHODS: Facial responses of 126 healthy participants to phasic heat pain were assessed in three different social situations: alone, but aware of video recording; in the presence of an experimenter; and in the presence of an intimate other. Furthermore, pain catastrophizing and sex (of participant and experimenter) were considered as additional influences.

RESULTS: Whereas similar types of facial responses were elicited independent of the relationship between sender and observer, the degree of facial expressiveness varied significantly, with increased expressiveness occurring in the presence of the partner. Interestingly, being with an experimenter decreased facial expressiveness only in women. Pain catastrophizing and the sex of the experimenter exhibited no substantial influence on facial responses.

CONCLUSION: Variations in communicative relations had no effect on the elements of the facial pain language. The degree of facial expressiveness, however, was adapted to the relationship between sender and observer. Individuals suppressed their facial communication of pain toward unfamiliar persons, whereas they overtly displayed it in the presence of an intimate other. Furthermore, when confronted with an unfamiliar person, different situational demands appeared to apply for both sexes.
Clinical Features and Outcomes of Serotype 19A Invasive Pneumococcal Disease in Calgary, Alberta
Authors: Ricketson Leah J , Vanderkooi Otto G , Wood Melissa L , Leal Jenine , Kellner James D
Published: March 2016

BACKGROUND: Streptoccocus pneumoniae serotype 19A (ST19A) became an important cause of invasive pneumococcal disease (IPD) after the introduction of the conjugate vaccine.

OBJECTIVE: To examine the severity and outcome of ST19A IPD compared with non‐ST19A IPD.

METHODS: The Calgary Area Streptococcus pneumoniae Epidemiology Research (CASPER) study collects clinical and laboratory data on all IPD cases in Calgary, Alberta. Analysis was performed on data from 2000 to 2010 comparing ST19A and non‐ST19A IPD cases. Adjusted linear and logistic regression models were used to examine outcomes of duration of appropriate intravenous antibiotic therapy and intensive care unit admission, respectively.

RESULTS: ST19A tended to cause disease in younger patients. ST19A isolates were more often multidrug resistant (19% versus 0.3%; P<0.001). Adjusted logistic regression showed no difference in intensive care unit admission between ST19A and non‐ST19A IPD cases (OR 1.4 [95% CI 0.8 to 2.7]). An adjusted linear regression model showed patients <18 years of age with a diagnosis of bacteremia and no risk factors infected with ST19A were, on average, treated with antibiotics 1.4 times (95% CI 1.1 to 1.9) as long as patients with non‐19A IPD and the same baseline characteristics.

DISCUSSION: ST19A IPD was associated with an increase in average time on antibiotics. Although many of the infecting strains of ST19A were within the threshold for susceptibility, they may be sufficiently resilient to require a longer duration of antibiotic therapy or higher dose to clear the infection.

CONCLUSIONS: ST19A is more common in younger individuals, is more antibiotic resistant and may require longer average treatment duration.
Development, Implementation and Evaluation of A Pain Management and Palliative Care Educational Seminar for Medical Students
Authors: Paneduro Denise , Pink Leah R , Smith Andrew J , Chakraborty Anita , Kirshen Albert J , Backstein David , Woods Nicole N , Gordon Allan S
Published: March 2016

BACKGROUND: Despite calls for the development and evaluation of pain education programs during early medical student training, little research has been dedicated to this initiative.

OBJECTIVES: To develop a pain management and palliative care seminar for medical students during their surgical clerkship and evaluate its impact on knowledge over time.

METHODS: A multidisciplinary team of palliative care and pain experts worked collaboratively and developed the seminar over one year. Teaching methods included didactic and case‐based instruction, as well as small and large group discussions. A total of 292 medical students attended a seminar during their third‐ or fourth‐year surgical rotation. A 10‐item test on knowledge regarding pain and palliative care topics was administered before the seminar, immediately following the seminar and up to one year following the seminar. Ninety‐five percent (n=277) of students completed the post‐test and 31% (n=90) completed the follow‐up test.

RESULTS: The mean pretest, post‐test and one‐year follow‐up test scores were 51%, 75% and 73%, respectively. Mean test scores at post‐test and follow‐up were significantly higher than pretest scores (all P<0.001). No significant difference was observed in mean test scores between follow‐up and post‐test (P=0.559), indicating that students retained knowledge gained from the seminar.

CONCLUSIONS: A high‐quality educational seminar using interactive and case‐based instruction can enhance students’ knowledge of pain management and palliative care. These findings highlight the feasibility of developing and implementing pain education material for medical students during their training.
Increased Moxifloxacin Utilization Associated with an Unrestricted Addition to a Drug Reimbursement Formulary: A Population‐Based Analysis
Authors: Wright Alissa Jade , Marra Fawziah , Chong Mei , Chambers Catharine , Bowie William R , Patrick David M
Published: March 2016

OBJECTIVES:To determine whether utilization of moxifloxacin, a broad‐spectrum fluoroquinolone antibiotic, has changed since its addition to the British Columbia provincial formulary in 2009 and to determine whether utilization was guideline concordant.

METHODS: BC PharmaNet prescriptions for moxifloxacin from 2001 to 2010 were anonymously linked to associated Medical Services Plan fee‐for‐service practitioner claims for indication‐specific analysis. Prescribing trends for adults ≥18 years of age were described using defined daily dose (DDD) per 1000 person‐years. Monthly utilization rates were fit to a linear regression model that controlled for seasonal variation to examine the effect of the formulary addition.

RESULTS: Utilization rose more than sevenfold throughout the study period, from 21.3 DDD per 1000 person‐years in 2001 to 163.3 DDD per 1000 person‐years in 2010. Although the formulary addition was not associated with an immediate increase in utilization (7.5% [95% CI −4.4% to 20.9%]; P=0.226), it was associated with an overall increase in utilization of 2.1% (95% CI 1.3% to 3.0%; P<0.001) for every month after 2009. Overall, only 29% of moxifloxacin prescriptions could be linked to a diagnostic code that was considered to be guideline concordant. In more than one‐half of moxifloxacin prescriptions, the patient had not used another antibiotic in the previous 90 days. Among moxifloxacin prescriptions in which another antibiotic had been used in the previous 90 days, 41.5% were prescriptions for an alternative fluoroquinolone.

CONCLUSIONS: The formulary addition was associated with a sustained increase in moxifloxacin utilization over time. Moxifloxacin is often prescribed to patients for indications that are not guideline concordant or to patients who have not previously received first‐line antibiotics.
Can the Presence of Endoscopic High-Risk Stigmata be Bredicted before Endoscopy? A Multivariable Analysis Using the RUGBE Database
Authors: Chen Yen-I , Wyse Jonathan , Barkun Alan , Bardou Marc , Gralnek Ian M , Martel Myriam
Published: March 2016

BACKGROUND: Many aspects in the management of acute upper gastrointestinal bleeding rely on pre-esophagogastroduodenoscopy (EGD) stratification of patients likely to exhibit high-risk stigmata (HRS); however, data predicting the presence of HRS are lacking.

OBJECTIVE: To determine clinical and laboratory predictors of HRS at the index EGD in patients presenting with acute upper gastrointestinal bleeding using retrospective data from a validated national database – the Canadian Registry in Upper Gastrointestinal Bleeding and Endoscopy registry.

METHODS: Relevant clinical and laboratory parameters were evaluated. HRS was defined as spurting, oozing, nonbleeding visible vessel or adherent clot after vigorous irrigation. Multivariable modelling was used to identify predictors of HRS including age, sex, hematemesis, use of antiplatelet agents, American Society of Anesthesiologists (ASA) classification, nasogastric tube aspirate, hemoglobin level and elapsed time from the onset of bleeding to EGD.

RESULTS: Of the 1677 patients (mean [± SD] age 66.2±16.8 years; 38.3% female), 28.7% had hematemesis, 57.8% had an ASA score of 3 to 5, and the mean hemoglobin level was 96.8±27.3 g/L. The mean time from presentation to endoscopy was 22.2±37.5 h. The best fitting multivariable model included the following significant predictors: ASA score 3 to 5 (OR 2.16 [95% CI 1.71 to 2.74]), a shorter time to endoscopy (OR 0.99 [95% CI 0.98 to 0.99]) and a lower initial hemoglobin level (OR 0.99 [95% CI 0.99 to 0.99]).

CONCLUSION: A higher ASA score, a shorter time to endoscopy and lower initial hemoglobin level all significantly predicted the presence of endoscopic HRS. These criteria could be used to improve the optimal selection of patients requiring more urgent endoscopy.
CIHR Canadian HIV Trials Network Co‐Infection and Concurrent Diseases Core: Updated Canadian Guidelines for the Treatment of Hepatitis C Infection in HIV‐hepatitis C Coinfected Adults
Authors: Hull Mark , Shafran Stephen , Tseng Alice , Giguère Pierre , Klein Marina B , Cooper Curtis
Published: March 2016

BACKGROUND: Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Management of HIV‐HCV coinfection is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug‐drug interactions between new HCV direct‐acting antiviral therapies and antiretroviral regimens.

OBJECTIVE: To update national standards for the management of HCV‐HIV coinfected adults in the Canadian context.

METHODS: A standing working group with specific clinical expertise in HIV‐HCV coinfection was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published data regarding HCV antiviral treatments and to update the Canadian HIV‐HCV coinfection guidelines.

RESULTS: Recent data suggest that the gap in sustained virological response rates between HCV monoinfection and HIV‐HCV coinfection has been eliminated with newer HCV antiviral regimens. All HIV‐HCV coinfected individuals should be assessed for HCV therapy. First‐line treatment for genotypes 1 through 6 includes pegylated interferon and weight‐based ribavirin dosing plus the nucleotide sofosbuvir for 12 weeks. Sofosbuvir in combination with the protease inhibitor simeprevir is another first‐line consideration for genotype 1 infection. Sofosbuvir with ribavirin for 12 weeks (genotype 2) and 24 weeks (genotype 3) is also recommended as first‐line treatment.

DISCUSSION: Recommendations may not supersede individual clinical judgement.
Adherence to Guidelines: A National Audit of the Management of Acute upper Gastrointestinal Bleeding. The REASON Registry
Authors: Lu Yidan , Barkun Alan N , Martel Myriam
Published: March 2016

OBJECTIVES: To assess process of care in nonvariceal upper gastrointestinal bleeding (NVUGIB) using a national cohort, and to identify predictors of adherence to ‘best practice’ standards.

METHODS: Consecutive charts of patients hospitalized for acute upper gastrointestinal bleeding across 21 Canadian hospitals were reviewed. Data regarding initial presentation, endoscopic management and outcomes were collected. Results were compared with ‘best practice’ using established guidelines on NVUGIB. Adherence was quantified and independent predictors were evaluated using multivariable analysis.

RESULTS: Overall, 2020 patients (89.4% NVUGIB, variceal in 10.6%) were included (mean [± SD] age 66.3±16.4 years; 38.4% female). Endoscopy was performed in 1612 patients: 1533 with NVUGIB had endoscopic lesions (63.1% ulcers; high-risk stigmata in 47.8%). Early endoscopy was performed in 65.6% and an assistant was present in 83.5%. Only 64.5% of patients with high-risk stigmata received endoscopic hemostasis; 9.8% of patients exhibiting low-risk stigmata also did. Intravenous proton pump inhibitor was administered after endoscopic hemostasis in 95.7%. Rebleeding and mortality rates were 10.5% and 9.4%, respectively. Multivariable analysis revealed that low American Society of Anesthesiologists score patients had fewer assistants present during endoscopy (OR 0.63 [95% CI 0.48 to 0.83), a hemoglobin level <70 g/L predicted inappropriate high-dose intravenous proton pump inhibitor use in patients with low-risk stigmata, and endoscopies performed during regular hours were associated with longer delays from presentation (OR 0.33 [95% CI 0.24 to 0.47]).

CONCLUSION: There was variability between the process of care and ‘best practice’ in NVUGIB. Certain patient and situational characteristics may influence guideline adherence. Dissemination initiatives must identify and focus on such considerations to improve quality of care.
Community‐Associated Methicillin‐Resistant Staphylococcus aureus in a Pediatric Emergency Department in Newfoundland and Labrador
Authors: Peebles Erin , Morris Robert , Chafe Roger
Published: March 2016

BACKGROUND: First‐generation cephalosporins and antistaphylococcal penicillins are typically the first choice for treating skin and soft tissue infections (SSTI), but are not effective for infections caused by methicillin‐resistant Staphylococcus aureus (MRSA). It is currently unclear what percentage of SSTIs is caused by community‐associated MRSA in different regions in Canada.

OBJECTIVES:To determine the incidence of MRSA in children presenting to a pediatric emergency department with SSTI, and to determine which antibiotics were used to treat these infections.

METHODS: All visits to a pediatric emergency department were reviewed from April 15, 2010 to April 14, 2011. Diagnoses of cellulitis, abscess, impetigo, folliculitis and skin infection (not otherwise specified) were reviewed in detail to determine whether a culture was taken and which antibiotic was prescribed.

RESULTS: There were 367 cases of SSTI diagnosed over the study period. Forty‐five (12.3%) patients had lesions that were swabbed for culture and sensitivity. S aureus was the most common organism found, with 14 (66%) methicillin‐sensitive cases and seven (33%) methicillin‐resistant cases. Of the seven cases of MRSA identified, only one patient had clear risk factors for hospital‐acquired MRSA. First‐generation cephalosporins were initially prescribed for 280 (76%) patients.

CONCLUSIONS: The overall incidence of MRSA in the population presenting to a pediatric emergency department in Newfoundland and Labrador appeared to be low, although only a small percentage of infections were cultured. At this time, there appears to be no need to change empirical antibiotic coverage, which remains a first‐generation cephalosporin.
Music as a Sleep Aid in Fibromyalgia
Authors: Picard Larry M , Bartel Lee R , Gordon Allan S , Cepo Davor , Wu Qi , Pink Leah R
Published: March 2016

BACKGROUND: Interventions to improve sleep in fibromyalgia may generalize to improvements in multiple symptom domains. Delta‐embedded music, pulsating regularly within the 0.25 Hz to 4 Hz frequency band of brain wave activity, has the potential to induce sleep.

OBJECTIVES: To assess the effects of a delta‐embedded music program over four weeks for sleep induction in patients with fibromyalgia.

METHODS: The present unblinded, investigator‐led pilot study used a within‐subject design. Analysis was based on 20 individuals with fibromyalgia who completed the study, of the 24 recruited into the study. The primary outcome variables were the change from baseline in Fibromyalgia Impact Questionnaire (FIQ) and Jenkins Sleep Scale scores. A patient global impression of change was measured on a seven‐point Likert scale. Secondary outcome measures, comprised of items 5, 6 and 7 of the FIQ, were used as indicators of pain, tiredness and being tired on awakening.

RESULTS: The FIQ median score of 76.4 (95% CI 61.3 to 82.1) at baseline improved to 60.3 (95% CI 53.1 to 72.0; P=0.004). The Jenkins Sleep Scale median value of 17.5 (95% CI 15.5 to 18.5) at baseline fell to 12.5 (95% CI 8.5 to 14.5; P=0.001) at study completion. The outcomes of the patient global impression of change ratings were mostly positive (P=0.001). Being tired on awakening declined significantly from a median of 9.0 (95% CI 8.0 to 10.0) to 8.0 (95% CI 5.5 to 9.0; P=0.021). However, there was no significant improvement in pain level (baseline median 7.5 [95% CI 7.0 to 8.5] versus study completion median 7.0 [95% CI 6.5 to 8.0]; P=0.335) or tiredness (baseline median 9.0 [95% CI 8.0 to 9.5] versus study completion median 8.0 [95% CI 6.0 to 8.5]; P=0.061). There were no serious adverse events.

CONCLUSIONS: Delta‐embedded music is a potential alternative therapy for fibromyalgia.
Factors Predicting Adverse Events Associated with Pregabalin Administered for Neuropathic Pain Relief
Authors: Kanbayashi Yuko , Onishi Keiko , Hosokawa Toyoshi
Published: March 2016

BACKGROUND:Pregabalin administration is occasionally abandoned due to adverse events such as somnolence, dizziness, unsteadiness, weight gain and edema. However, the exact causes of these differences in adverse events associated with pregabalin have not been elucidated.

OBJECTIVE: To identify factors predicting adverse events associated with pregabalin administered for neuropathic pain.

METHODS: The present study was a retrospective analysis involving 208 patients with neuropathic pain who had been treated with pregabalin in the pain clinic at the authors’ hospital between July 2010 and September 2011. Variables were extracted from the clinical records for regression analysis of factors related to the occurrence of adverse events associated with pregabalin administration. Multivariate logistic regression analysis was used to examine the relationship between various predictive factors and the adverse events.

RESULTS: Predictive factors were: duration of therapy (OR 1.684 [95% CI 1.179 to 2.406]; P=0.0042) for somnolence; nonsteroidal anti‐inflammatory drugs (OR 0.132 [95% CI 0.030 to 0.578]; P=0.0072), age (OR 3.137 [95% CI 1.220 to 8.066]; P=0.0177) and maintenance dose (OR 0.437 [95% CI 0.217 to 0.880]; P=0.0205) for unsteadiness; serum creatinine (OR 6.439 [95% CI 1.541 to 26.902]; P=0.0107) for body weight gain; and neurotropin (OR 8.538 [95% CI 1.159 to 62.901]; P=0.0353) and serum creatinine (OR 6.912 [95% CI 1.118 to 42.726]; P=0.0375) for edema.

CONCLUSIONS: The results of the present study indicate that care is warranted regarding long durations of therapy for somnolence, advanced age rather than dose‐dependent adverse events for unsteadiness, elevated serum creatinine level for weight gain, and elevated serum creatinine level and combination use of neurotropin for edema. The safety of the combined use of pregabalin and nonsteroidal anti‐inflammatory drugs were also suggested.
Longitudinal Surveillance of Outpatient Quinolone Antimicrobial Use in Canada
Authors: Glass-Kaastra Shiona K , Finley Rita , Hutchinson Jim , Patrick David M , Weiss Karl , Conly John
Published: March 2016

INTRODUCTION: Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is important.

OBJECTIVE: To assess the use of quinolone antimicrobials within Canadian provinces over time.

METHODS: Antimicrobial prescribing data collected by IMS Health Canada were acquired from the Canadian Integrated Program for Antimicrobial Resistance Surveillance and the Canadian Committee for Antimicrobial Resistance, and were used to calculate two yearly metrics: prescriptions per 1000 inhabitant‐days and the mean defined daily doses (DDDs) per prescription. These measures were used to produce linear mixed models to assess differences among provinces and over time, while accounting for repeated measurements.

RESULTS: The quinolone class of antimicrobials is used similarly among Canadian provinces. Year‐to‐year increases in quinolone prescribing occurred from 1995 to 2010, with a levelling off in the latter years. Year‐to‐year decreases in the DDDs per prescription were found to be significant from 2000 to 2010.

DISCUSSION: Although the overall use of antimicrobials differs significantly among Canadian provinces, the use of the quinolone class does not vary at the provincial level. Results suggest that prescribing of ciprofloxacin may be a potential target for antimicrobial stewardship programs; however, decreases in the average DDDs per prescription suggest continued uptake of appropriate treatment guidelines.
Prevalence of Plasmid‐Mediated Quinolone Resistance Genes among Ciprofloxacin‐Nonsusceptible Escherichia coli and Klebsiella pneumoniae Isolated from Blood Cultures in Korea
Authors: Yang Hee Young , Nam You Sun , Lee Hee Joo
Published: March 2016

OBJECTIVES:To analyze the prevalence of plasmid‐mediated quinolone resistance (PMQR) determinants in ciprofloxacin‐nonsusceptible Escherichia coli and Klebsiella pneumoniae isolated from patients at a tertiary care hospital in Korea.

METHODS: A total of 102 nonduplicate isolates of ciprofloxacin‐intermediate or ciprofloxacin‐resistant E coli (n=80) and K pneumoniae (n=22) from blood cultures were obtained. The qnr (qnrA, qnrB, qnrS), aac(6′)-Ib-cr, qepA and oqxAB genes were detected using polymerase chain reaction (PCR) and confirmed using direct sequencing. To determine whether the PMQR‐positive plasmid was horizontally transferable, conjugation experiments were performed.

RESULTS: Of the 102 isolates, 81 (79.4%) had one or more PMQR genes; these consisted of 59 (73.8%) E coli and 22 (100%) K pneumoniae isolates. The qnr genes were present in 15 isolates (14.7%): qnrB4 was detected in 10.8% and qnrS1 was detected in 3.9%. The aac(6′)-Ib-cr, qepA and oqxAB genes were detected in 77.5%, 3.9% and 10.8%, respectively. In conjugation experiments, PMQR genes were successfully transferred from seven (8.6%) isolates. The range of minimum inhibitory concentrations of ciprofloxacin for these seven transconjugants increased to 0.5 mg/L to 1 mg/L, which was 16‐ to 33‐fold that of the recipient E coli J53 bacteria.

CONCLUSIONS: PMQR genes were highly prevalent among ciprofloxacin‐nonsusceptible E coli and K pneumoniae from blood cultures in the authors’ hospital. Therefore, it is necessary to monitor for the spread of PMQR genes of clinical isolates and to ensure careful antibiotic use in a hospital setting.
Therapeutic drug monitoring for triazoles: A needs assessment review and recommendations from a Canadian perspective
Authors: Laverdiere Michel , Bow Eric J , Rotstein Coleman , Autmizguine Julie , Broady Raewyn , Garber Gary , Haider Shariq , Hussaini Trana , Husain Shahid , Ovetchkine Philippe , Seki Jack T , Théorêt Yves
Published: March 2016

Invasive fungal infections cause significant morbidity and mortality in patients with concomitant underlying immunosuppressive diseases. The recent addition of new triazoles to the antifungal armamentarium has allowed for extended‐spectrum activity and flexibility of administration. Over the years, clinical use has raised concerns about the degree of drug exposure following standard approved drug dosing, questioning the need for therapeutic drug monitoring (TDM). Accordingly, the present guidelines focus on TDM of triazole antifungal agents. A review of the rationale for triazole TDM, the targeted patient populations and available laboratory methods, as well as practical recommendations based on current evidence from an extended literature review are provided in the present document.
Dual Effects of Rho‐Kinase Inhibitors on a Rat Model of Inflammatory Pain
Authors: Paiva-Lima Patricia , Bakhle YS , Francischi Janetti N
Published: March 2016

BACKGROUND: Rho‐kinases (ROCKs), a family of small GTP‐dependent enzymes, are involved in a range of pain models, and their inhibition typically leads to antinociceptive effects.

OBJECTIVES: To study the effects of inhibiting ROCKs using two known inhibitors, Y27632 and HA1077 (fasudil), administered locally, on nociception and paw edema in rats.

METHODS: A range of doses of Y27632 or HA1077 (2.5 μg to 1000 μg) were injected locally into rat paws alone or in combination with carrageenan, a known proinflammatory stimulus. Nociceptive responses to mechanical stimuli and increased paw volume, reflecting edema formation, were measured at 2 h and 3 h, using a Randall‐Selitto apparatus and a hydroplethysmometer, respectively.

RESULTS: Animals treated with either ROCK inhibitor showed biphasic nociceptive effects, with lower doses being associated with pronociceptive, and higher doses with antinociceptive responses. In contrast, a monophasic dose‐dependent increase in edema was observed in the same animals. Local injection of 8‐bromo‐cyclic (c)GMP, an activator of the nitric oxide/cGMP/protein kinase G pathway, also produced biphasic effects on nociceptive responses in rat paws; however, low doses were antinociceptive and high doses were pronociceptive. Local administration of cytochalasin B, an inhibitor of actin polymerization and a downstream mediator of ROCK activity, reversed the antinociceptive effect of Y27632.

CONCLUSIONS: The results of the present study suggest that ROCKs participate in the local mechanisms associated with nociception/antinociception and inflammation, with a possible involvement of the nitric oxide/cGMP/protein kinase G pathway. Also, drug effects following local administration may differ markedly from the effects following systemic administration. Finally, separate treatment of pain and edema may be needed to maximize clinical benefit in inflammatory pain.
Single-Dose Infliximab in Hepatitis C Genotype 1 Treatmentnaive Patients with High Serum Levels of Tumour Necrosis Factor-Alpha Does Not Influence the Efficacy of Pegylated Interferon Alpha-2B/Ribavirin Therapy
Authors: Cooper Curtis , Shafran Stephen , Greenbloom Susan , Enns Robert , Farley John , Hilzenrat Nir , Williams Kurt , Elkashab Magdy , Abadir Nabil , Neuman Manuela
Published: March 2016

BACKGROUND: Serum tumour necrosis factor-alpha (TNF-α) levels correlate negatively with hepatitis C virus (HCV) antiviral response.

OBJECTIVES: To test the hypothesis that a single infliximab induction dose would positively influence on-treatment virological response and sustained virological response (SVR).

METHODS: The present study was a phase IIIB, randomized, prospective, open-label pilot trial conducted at eight Canadian sites. Treatment-naive HCV genotype 1-infected patients 18 to 65 years of age with high serum TNF-α values (>300 pg/mL) were randomly assigned to receive a single pretreatment induction infliximab infusion (5 mg/kg) seven days before antiviral therapy (arm A) or no pretreatment (arm B). All patients received pegylated interferon α2b (1.5 μg/kg/week) plus weight-based ribavirin (800 mg/day to 1400 mg/day) for up to 48 weeks.

RESULTS: Eighty-five patients (arm A [n=41], arm B [n=44]; 70% male) received pegylated interferon α2b. The mean age (48.1 years), race (81% white) and METAVIR fibrosis stage (F0–2 = 79%, F3–4 = 21%) were similar between groups. Infliximab was well tolerated without attributable severe adverse events; 56.5% completed the study (arm A [n=21], arm B [n=27]). Most discontinuations were due to virological failure at weeks 12 (n=20 [23.5%]) and 24 (n=7 [8.2%]) and did not differ according to group. Numerically lower proportions of infliximab recipients achieved rapid virological response (19.5% versus 36.4%), complete early virological response (43.9% versus 59.1%) and SVR (34.1% versus 52.3%). However, between-group differences did not reach statistical significance. No differences in adverse event profile or laboratory measures were noted.

CONCLUSION: A single infliximab dose before pegylated-interferon α2b and ribavirin therapy did not result in greater viral decline during the first 12 weeks of HCV therapy or improved SVR.
Susceptibility of Clinical Moraxella catarrhalis Isolates in British Columbia to Six Empirically Prescribed Antibiotic Agents
Authors: Bandet Tamara , Whitehead Sue , Blondel-Hill Edith , Wagner Ken , Cheeptham Naowarat
Published: March 2016

BACKGROUND: Moraxella catarrhalis is a commensal organism of the respiratory tract that has emerged as an important pathogen for a variety of upper and lower respiratory tract infections including otitis media and acute exacerbations of chronic bronchitis. Susceptibility testing of M catarrhalis is not routinely performed in most diagnostic laboratories; rather, a comment predicting susceptibility based on the literature is attached to the report. The most recent Canadian report on M catarrhalis antimicrobial susceptibility was published in 2003; therefore, a new study at this time was of interest and importance.

OBJECTIVE: To determine the susceptibility of M catarrhalis isolates from British Columbia to amoxicillin‐clavulanate, doxycycline, clarithromycin, cefuroxime, levofloxacin and trimethoprimsulfamethoxazole.

METHODS: A total of 117 clinical M catarrhalis isolates were isolated and tested from five Interior hospitals and two private laboratory centres in British Columbia between January and December 2012. Antibiotic susceptibility of M catarrhalis isolates was characterized using the Etest (E‐strip; bioMérieux, USA) according to Clinical Laboratory Standards Institute guidelines.

RESULTS: All isolates were sensitive to amoxicillin‐clavulanate, doxycycline, clarithromycin, levofloxacin and trimethoprimsulfamethoxazole. One isolate was intermediately resistant to cefuroxime, representing a 99.15% sensitivity rate to the cephem agent. Cefuroxime minimum inhibitory concentrations (MICs) inhibiting 50% and 90% of organisms (MIC50 and MIC90) were highest among the antibiotics tested, and the MIC90 (3 μg/mL) of cefuroxime reached the Clinical Laboratory Standards Institute breakpoint of susceptibility.

DISCUSSION: The antibiotic susceptibility of M catarrhalis isolates evaluated in the present study largely confirms the findings of previous surveillance studies performed in Canada. Cefuroxime MICs are in the high end of the sensitive range and the MIC50 and MIC90 observed in the present study are the highest ever reported in Canada.

CONCLUSION: Although cefuroxime MICs in M catarrhalis are high, all agents tested showed antimicrobial activity, supporting their continued therapeutic and empirical use.
HIV and Liver transplantation: The British Columbia Experience, 2004 to 2013
Authors: Tan-Tam Clara , Liao Pamela , Montaner Julio S , Hull Mark W , Scudamore Charles H , Erb Siegfried R , Yoshida Eric M
Published: March 2016

BACKGROUND: The demand for definitive management of end‐stage organ disease in HIV‐infected Canadians is growing. Until recently, despite international evidence of good clinical outcomes, HIV‐infected Canadians with end‐stage liver disease were ineligible for transplantation, except in British Columbia (BC), where the liver transplant program of BC Transplant has accepted these patients for referral, assessment, listing and provision of liver allograft. There is a need to evaluate the experience in BC to determine the issues surrounding liver transplantation in HIV‐infected patients.

METHODS: The present study was a chart review of 28 HIV‐infected patients who were referred to BC Transplant for liver transplantation between 2004 and 2013. Data regarding HIV and liver disease status, initial transplant assessment and clinical outcomes were collected.

RESULTS: Most patients were BC residents and were assessed by the multidisciplinary team at the BC clinic. The majority had undetectable HIV viral loads, were receiving antiretroviral treatments and were infected with hepatitis C virus (n=16). The most common comorbidities were anxiety and mood disorders (n=4), and hemophilia (n=4). Of the patients eligible for transplantation, four were transplanted for autoimmune hepatitis (5.67 years post‐transplant), nonalcoholic steatohepatitis (2.33 years), hepatitis C virus (2.25 years) and hepatitis B‐delta virus coinfection (recent transplant). One patient died from acute renal failure while waiting for transplantation. Ten patients died during preassessment and 10 were unsuitable transplant candidates. The most common reason for unsuitability was stable disease not requiring transplantation (n=4).

CONCLUSIONS: To date, interdisciplinary care and careful selection of patients have resulted in successful outcomes including the longest living HIV‐infected post‐liver transplant recipient in Canada.
An Unusual Case of Vaccine‐Associated Paralytic Poliomyelitis
Authors: Desai S , Diener T , Tan BJ-K , Lowry NJ , Talukdar C , Chrusch WM , Wiebe S
Published: March 2016

The present article reports a case involving an immunocompetent, previously well child who, despite two previous doses of inactivated poliovirus vaccine, developed severe flaccid paralysis consistent with polio after receiving oral polio vaccine.
Raoultella Planticola Bacteremia Following Consumption of Seafood
Authors: Lam Philip W , Salit Irving E
Published: March 2016

Raoultella planticola is a Gram‐negative bacillus commonly found in water, soil and aquatic environments. There have only been 16 cases of R planticola infection documented in the literature to date. R planticola possesses the ability to convert histidine to histamine and can produce symptoms of scombroid poisoning when poorly prepared seafood is consumed in large amounts. The present report describes a case involving a 56‐year‐old woman who presented with R planticola bacteremia and symptoms consistent with cholangitis four days after consuming a seafood salad containing squid and octopus. She was successfully treated with intravenous ceftriaxone followed by oral ciprofloxacin. Recent chemotherapy, proton pump inhibitor use and altered biliary flow secondary to hepatic metastases may have been contributing factors to the pathogenesis of disease.
Triage and Protocol Recommendations for the Parasitology Laboratory Based on an Epidemiological Investigation of Parasite Diagnostics in Ontario Laboratories
Authors: Maier Allison , Krolik Julia , Majury Anna
Published: March 2016

OBJECTIVES:A study was performed using a subset of Ontario laboratory parasitology data, with three objectives: to describe parasitic infections in Ontario; to identify risk factors for acquiring a parasitic infection using routinely collected information; and to use this information to assess current protocols for parasite testing in laboratories and, in turn, to propose alternatives to optimize the allocation of laboratory resources.

METHODS: All parasitology records from January 4, 2010 to September 14, 2010 were reviewed descriptively and risk factor analyses were performed using information collected from requisitions. These results were used to develop preliminary alternative protocols, which considered high‐throughput screening tests and inclusion/exclusion criteria for ova and parasite testing; these were then retrospectively analyzed with the dataset to determine appropriateness.

RESULTS: Of the 29,260 records analyzed, 10% were multiple samples from single patients submitted on the same day, of which 98% had the same result. Three percent of all parasite tests were positive, with the most prevalent parasites being (in ascending order) Dientamoeba fragilis, Giardia lamblia, Cryptosporidium species and Entamoeba histolytica/dispar. Age and sex were found to be weak risk factors, while rural living was found to be a moderate risk factor for D fragilis, G lamblia and Cryptosporidium infections. The strongest risk factor was travel history, especially for nonendemic parasites. The retrospective analysis of six alternative protocols identified four that may be more efficient than current procedures.

CONCLUSIONS: The present study demonstrated that current protocols may be redundant and can be optimized to target prevalent parasites and populations with high risk factors.
Follow-up of Participants in the Canadian Association of Gastroenterology Scholars’ Program, 2006 to 2012
Authors: Lam Mindy CW , Sey Michael SL , Gregor Jamie , Wong Clarence
Published: March 2016

The Canadian Association of Gastroenterology (CAG) Scholars’ Program (previously known as the Bright Lights Course) is designed to encourage trainees to consider a subspecialty career in gastroenterology. A formal analysis of the Scholars’ Program performed in 2007 revealed that 82% of participants invited to the program pursued or were planning to pursue a career in gastroenterology. The positive results are consistent with the CAG’s strategic plan of developing “the next generation of gastroenterology clinical practitioners, researchers, educators, and leaders” and to “attract, train, and retain the best and the brightest to gastroenterology”. The present study was a follow-up analysis of participants in the Scholars’ Program between 2006 and 2012. Although 93.1% of participants had an interest in gastroenterology before attending the Scholars’ Program, the majority (68.7%) reported a greater interest in gastroenterology after the program. Similar to the study from 2007, the present study again illustrates the importance and success of the Scholars’ Program in generating interest and retaining candidates in gastroenterology.
Does Prone Positioning Improve Oxygenation and Reduce Mortality in Patients with Acute Respiratory Distress Syndrome?
Authors: Henderson William R , Griesdale Donald EG , Dominelli Paolo , Ronco Juan J
Published: March 2016

The emergence of computed tomography imaging more than 25 years ago led to characterization of acute respiratory distress syndrome (ARDS) as areas of relatively normal lung parenchyma juxtaposed with areas of dense consolidation and atelectasis. Given that this heterogeneity is often dorsally distributed, investigators questioned whether care for ARDS patients in the prone position would lead to improved mortality outcomes. This clinical review discusses the physiological rationale and clinical evidence supporting prone positioning in treating ARDS, in addition to its complications and contraindications.
One‐Year Results of an Algorithmic Approach to Managing Failed Back Surgery Syndrome
Authors: Avellanal Martín , Diaz-Reganon Gonzalo , Orts Alejandro , Soto Silvia
Published: March 2016

BACKGROUND: Failed back surgery syndrome (FBSS) is a major clinical problem. Different etiologies with different incidence rates have been proposed. There are currently no standards regarding the management of these patients. Epiduroscopy is an endoscopic technique that may play a role in the management of FBSS.

OBJECTIVE: To evaluate an algorithm for management of severe FBSS including epiduroscopy as a diagnostic and therapeutic tool.

METHODS: A total of 133 patients with severe symptoms of FBSS (visual analogue scale score ≥7) and no response to pharmacological treatment and physical therapy were included. A six‐step management algorithm was applied. Data, including patient demographics, pain and surgical procedure, were analyzed. In all cases, one or more objective causes of pain were established. Treatment success was defined as ≥50% long‐term pain relief maintained during the first year of follow‐up. Final allocation of patients was registered: good outcome with conservative treatment, surgical reintervention and palliative treatment with implantable devices.

RESULTS: Of 122 patients enrolled, 59.84% underwent instrumented surgery and 40.16% a noninstrumented procedure. Most (64.75%) experienced significant pain relief with conventional pain clinic treatments; 15.57% required surgical treatment. Palliative spinal cord stimulation and spinal analgesia were applied in 9.84% and 2.46% of the cases, respectively. The most common diagnosis was epidural fibrosis, followed by disc herniation, global or lateral stenosis, and foraminal stenosis.

CONCLUSIONS: A new six‐step ladder approach to severe FBSS management that includes epiduroscopy was analyzed. Etiologies are accurately described and a useful role of epiduroscopy was confirmed.
Autonomic Arousal And Experimentally Induced Pain: A Critical Review of the Literature
Authors: Kyle Brandon N , McNeil Daniel W
Published: March 2016

BACKGROUND: Autonomic arousal frequently is assumed to be a component of the pain response, perhaps because physiological mechanisms connecting pain and autonomic reactivity can be easily conceptualized. The evidence clarifying autonomic responses specific to painful stimulation, however, has been rather sporadic and lacks coherence; thus, a summary and critical review is needed in this area.

OBJECTIVES: To summarize and integrate findings from 39 experimental investigations from 1970 to 2012 of pain‐induced autonomic arousal in humans.

METHODS: Medline and PsycINFO databases were searched for relevant articles. References from these articles were also considered for review.

RESULTS: Painful stimuli increase respiration rate, induce muscle tension, intensify electrodermal activity and dilate the pupils. Cardiovascular activity also increases, but the pattern displayed in response to pain is complex; peripheral vasoconstriction and sympathetically mediated cardiac responses are most typical. Additionally, autonomic expression of pain shows inconsistent relations with verbal and overt motor responses.

CONCLUSIONS: Autonomic arousal can be legitimately measured and modified as one facet of the pain response. Future research should particularly focus on increasing sample size and broadening the diversity of participants. To improve the ability to compare and contrast findings across studies, as well as to increase the applicability of laboratory findings to naturalistic pain, investigators also must enhance experimental design by increasing uniformity or accounting for differences in methodology. Finally, further work remains to utilize more specific assessments of autonomic response and to assess relationships of autonomic reactivity with other cognitive (eg, attention) and affective (eg, anxiety) variables.