bluuebunny/crossref_metadata_2025 huggingface dataset:
Fecal Occult Blood Testing as a Diagnostic Test in Symptomatic Patients is not Useful: A Retrospective Chart Review
Authors: Narula Neeraj , Ulic Diana , Al-Dabbagh Raed , Ibrahim Ali , Mansour Maged , Balion Cynthia , Marshall John K
Published: March 2016

BACKGROUND: The fecal occult blood test (FOBT) is a screening tool designed for the early detection of colorectal cancer in primary care. Although not validated for use in hospitalized patients, it is often used by hospital physicians for reasons other than asymptomatic screening.

OBJECTIVE: To profile the in-hospital use of the FOBT and assess its impact on patient care.

METHODS: Patient charts were retrospectively reviewed for all FOBTs conducted over a three-month period in 2011 by the central laboratory supporting the three acute care campuses of Hamilton Health Sciences (Hamilton, Ontario).

RESULTS: A total of 229 patients underwent 351 tests; 52% were female and the mean age was 49 years (range one to 104 years). A total of 80 (34.9%) patients had at least one positive test. The most common indications for testing were anemia (51.0%) and overt gastrointestinal bleeding (19.2%). Only one patient had testing performed for asymptomatic colorectal cancer screening. In only 20 (8.7%) cases medications were modified before testing and diet was modified in only 21 (9.2%) cases. Most patients (85.2%) were taking one or more medications that could result in a false-positive result. Only 18 (7.9%) patients had a digital rectal examinations documented, of which seven were positive. All patients with a positive digital rectal examination underwent endoscopic procedures that revealed a source of bleeding. Among 44 patients with overt gastrointestinal bleeding, 12 (27.3%) had endoscopic investigations delayed to await results of the FOBT. Four patients were referred despite a negative FOBT due to a high degree of suspicion of gastrointestinal bleeding.

CONCLUSIONS: The FOBT is often used inappropriately in the hospital setting. Confounding factors, such as diet and medication use, which may lead to false positives, are often ignored. Use of the FOBT in-hospital may lead to inappropriate management of patients, increased length of stay and increased direct medical costs. Use of the FOBT should be limited to validated indications only.
Laboratory Personnel Gender and Cold Pressor Apparatus Affect Subjective Pain Reports
Authors: Vigil Jacob M , Rowell Lauren N , Alcock Joe , Maestes Randy
Published: March 2016

BACKGROUND: There is no standardized method for cold pressor pain tasks across experiments. Temperature, apparatus and aspects of experimenters vary widely among studies. It is well known that experimental pain tolerance is influenced by setting as well as the sex of the experimenter. It is not known whether other contextual factors influence experimental pain reporting.

OBJECTIVES: The present two‐part experiment examines whether minimizing and standardizing interactions with laboratory personnel (eg, limiting interaction with participants to consenting and questions and not during the actual pain task) eliminates the influence of examiner characteristics on subjective pain reports and whether using different cold pain apparatus (cooler versus machine) influences reports.

METHODS:The present experiment manipulated the gender of the experimenter (male, female and transgender) and the type of cold pressor task (CPT) apparatus (ice cooler versus refrigerated bath circulator). Participants conducted the CPT at one of two pain levels (5°C or 16°C) without an experimenter present.

RESULTS:Men and women showed lower pain sensitivity when they were processed by biological male personnel than by biological female personnel before the CPT. Women who interacted with a transgendered researcher likewise reported higher pain sensitivity than women processed by biological male or female researchers. The type of CPT apparatus, despite operating at equivalent temperatures, also influenced subjective pain reports.

DISCUSSION: The findings show that even minimal interactions with laboratory personnel who differ in gender, and differences in laboratory materials impact the reliable measurement of pain.

CONCLUSION: More standardized protocols for measuring pain across varying research and clinical settings should be developed.
Serum Voriconazole Level Variability in Patients with Hematological Malignancies Receiving Voriconazole Therapy
Authors: Saini Lalit , Seki Jack T , Kumar Deepali , Atenafu Eshetu G , Cole David EC , Wong Betty YL , Božović Andrea , Brandwein Joseph M
Published: March 2016

INTRODUCTION: Voriconazole plasma concentrations have been correlated with oral dosing in healthy subjects, but have been poorly characterized in ill patients with hematological malignancies receiving intensive chemotherapy.

METHODS: The relationship between orally administered voriconazole, plasma concentrations and liver toxicity was examined in a cohort of 69 primarily acute leukemia patients undergoing intensive chemotherapy.

RESULTS: Oral administration of voriconazole was associated with significant interpatient variability, with voriconazole steady‐state concentrations ranging from 0 μg/mL to 16.6 μg/mL. Approximately 20% of patients achieved steady‐state concentrations <1 μg/mL. When adjusted for weight, patients receiving higher voriconazole doses tended toward higher plasma concentrations; however, there was no significant relationship between the plasma concentration and genotype, age, sex or use of concomitant proton pump inhibitors. Voriconazole concentrations were correlated with higher serum alkaline phosphatase levels at day 6 to 8, and with higher bilirubin and aspartate aminotransferase levels at day 14 to 16, but not with other liver enzyme levels.

CONCLUSION: In ill patients with acute leukemia and related disorders undergoing treatment with oral voriconazole, there is a poor correlation between the voriconazole dose and plasma concentrations, and many patients achieve levels that are considered to be subtherapeutic. The findings support the routine use of therapeutic drug monitoring in these patients.
Use of a Level 3 Portable Monitor for The Diagnosis and Management of Sleep-Disordered Breathing in an Inpatient Tertiary Care Setting
Authors: Povitz Marcus , Kimoff R John
Published: March 2016

BACKGROUND: Sleep-disordered breathing (SDB) may impact the course of medical illness among hospitalized patients. Access to testing during hospitalization to assess this may be limited by wait times for laboratory polysomnography. Level 3 portable monitoring (PM) may provide an alternative.

OBJECTIVE: To assess the rate of technically adequate studies, diagnostic information obtained and impact on patient management of inpatient PM studies performed for SDB.

METHODS: A retrospective review of 114 PM (Embletta, Natus Inc, Canada) records from the past two years was performed. Studies were ordered by pulmonologists, initiated by respiratory therapists and performed unattended on inpatient units. Admitting diagnoses, indication for sleep study, diagnostic information obtained from recordings and change in clinical management subsequent to PM were determined from medical charts.

RESULTS: Of 114 studies reviewed, 99 (87%) met predetermined criteria for adequate signal quality and duration. Five studies could not be interpreted due to inadequate data, yielding an overall success rate of 83% (94 of 114). Of 86 studies performed for diagnosis, clinical and PM data supported a new diagnosis of SDB in 55 patients, of which 23 (42%) were started on positive pressure therapy. Thirteen PM studies were performed during SDB treatment. All were technically adequate and six of 13 demonstrated new or persistent SDB. Results from PM testing informed clinical management during hospitalization in 70 (61%) cases.

CONCLUSION: Unattended level 3 PM studies are technically feasible in hospitalized patients and may provide information that influences clinical management.
The Utility of a Portable Sleep Monitor to Diagnose Sleep‐Disordered Breathing in a Pediatric Population
Authors: Massicotte Colin , Al-Saleh Suhail , Witmans Manisha , Narang Indra
Published: March 2016

BACKGROUND: Central and/or obstructive sleep‐disordered breathing (SDB) in children represents a spectrum of abnormal breathing during sleep. SDB is diagnosed using the gold standard, overnight polysomnography (PSG). The limited availability and access to PSG prevents its widespread use, resulting in significant delays in diagnosis and treatment of SDB. As such, portable sleep monitors are urgently needed.

OBJECTIVE: To evaluate the utility of a commercially available portable sleep study monitor (PSS‐AL) (ApneaLink, ResMed, USA) to diagnose SDB in children.

METHODS: Children referred to a pediatric sleep facility were simultaneously monitored using the PSS‐AL monitor and overnight PSG. The apnea‐hypopnea index (AHI) was calculated using the manual and autoscoring function of the PSS‐AL, and PSG. Sensitivity and specificity were compared with the manually scored PSS‐AL and PSG. Pearson correlations and Bland‐Altman plots were constructed.

RESULTS: Thirty‐five children (13 female) completed the study. The median age was 11.0 years and the median body mass index z‐score was 0.67 (range −2.3 to 3.8). SDB was diagnosed in 17 of 35 (49%) subjects using PSG. The AHI obtained by manually scored PSS‐AL strongly correlated with the AHI obtained using PSG (r=0.89; P<0.001). Using the manually scored PSS‐AL, a cut‐off of AHI of >5 events/h had a sensitivity of 94% and a specificity of 61% to detect any SDB diagnosed by PSG.

CONCLUSIONS: Although PSG is still recommended for the diagnosis of SDB, the ApneaLink sleep monitor has a role for triaging children referred for evaluation of SDB, but has limited ability to determine the nature of the SDB.
Regional Differences in Outcomes of Nonvariceal upper Gastrointestinal Bleeding in Saskatchewan
Authors: O’Byrne Michael , Smith-Windsor Erin L , Kenyon Chris R , Bhasin Sanchit , Jones Jennifer L
Published: March 2016

BACKGROUND: Nonvariceal upper gastrointestinal bleeding (NVUGIB) is associated with significant mortality.

OBJECTIVE: To examine several factors that may impact the mortality and 30-day rebleed rates of patients presenting with NVUGIB.

METHODS: A retrospective study of the charts of patients admitted to hospital in either the Saskatoon Health Region (SHR) or Regina Qu’Appelle Health Region (RQHR) (Saskatchewan) in 2008 and 2009 was performed. Mortality and 30-day rebleed end points were stratified according to age, sex, day of admission, patient status, health region, specialty of the endoscopist and time to endoscopy. Logistic regression modelling was performed, controlling for the Charlson comorbidity index, age and sex as covariates.

RESULTS: The overall mortality rate observed was 12.2% (n=44), while the overall 30-day rebleed rate was 20.3% (n=80). Inpatient status at the time of the rebleeding event was associated with a significantly increased risk of both mortality and rebleed, while having endoscopy performed in the RQHR versus SHR was associated with a significantly decreased risk of rebleed. A larger proportion of endoscopies were performed both within 24 h and by a gastroenterologist in the RQHR.

CONCLUSION: Saskatchewan has relatively high rates of mortality and 30-day rebleeding among patients with NVUGIB compared with published rates. The improved outcomes observed in the RQHR, when compared with the SHR, may be related to the employ of a formal call-back endoscopy team for the treatment of NVUGIB.
Prediction Scores Do Not Correlate with Clinically Adjudicated Categories of Pulmonary Embolism in Critically Ill Patients
Authors: Katsios CM , Donadini M , Meade M , Mehta S , Hall R , Granton J , Kutsiogiannis J , Dodek P , Heels-Ansdell D , McIntyre L , Vlahakis N , Muscedere J , Friedrich J , Fowler R , Skrobik Y , Albert M , Cox M , Klinger J , Nates J , Bersten A , Doig C , Zytaruk N , Crowther M , Cook DJ
Published: March 2016

BACKGROUND: Prediction scores for pretest probability of pulmonary embolism (PE) validated in outpatient settings are occasionally used in the intensive care unit (ICU).

OBJECTIVE: To evaluate the correlation of Geneva and Wells scores with adjudicated categories of PE in ICU patients.

METHODS: In a randomized trial of thromboprophylaxis, patients with suspected PE were adjudicated as possible, probable or definite PE. Data were then retrospectively abstracted for the Geneva Diagnostic PE score, Wells, Modified Wells and Simplified Wells Diagnostic scores. The chance‐corrected agreement between adjudicated categories and each score was calculated. ANOVA was used to compare values across the three adjudicated PE categories.

RESULTS: Among 70 patients with suspected PE, agreement was poor between adjudicated categories and Geneva pretest probabilities (kappa 0.01 [95% CI −0.0643 to 0.0941]) or Wells pretest probabilities (kappa −0.03 [95% CI −0.1462 to 0.0914]). Among four possible, 16 probable and 50 definite PEs, there were no significant differences in Geneva scores (possible = 4.0, probable = 4.7, definite = 4.5; P=0.90), Wells scores (possible = 2.8, probable = 4.9, definite = 4.1; P=0.37), Modified Wells (possible = 2.0, probable = 3.4, definite = 2.9; P=0.34) or Simplified Wells (possible = 1.8, probable = 2.8, definite = 2.4; P=0.30).

CONCLUSIONS: Pretest probability scores developed outside the ICU do not correlate with adjudicated PE categories in critically ill patients. Research is needed to develop prediction scores for this population.
Gender Expression, Sexual Orientation and Pain Sensitivity in Women
Authors: Vigil Jacob M , Rowell Lauren N , Lutz Charlotte
Published: March 2016

BACKGROUND: Despite a growing body of literature investigating sex differences with regard to pain, surprisingly little research has been conducted on the influence of various aspects of self‐identity, including gender expression and sexual orientation, on pain sensitivity within each sex, particularly among women. In men, dispositional femininity is linked to greater clinical pain and trait masculinity is associated with higher pain thresholds.

OBJECTIVES: To examine whether gender expression and sexual orientation are associated with within‐sex differences in ischemic pain sensitivity in healthy young women.

METHODS: A convenience sample of 172 females (mean age 21.4 years; range 18 to 30 years of age; 56.0% white, 89% heterosexual) performed an ischemic pain task in counterbalanced order. Desired levels of dispositional femininity for a preferred romantic partner and self‐described levels of personal dispositional femininity were measured.

RESULTS: Compared with heterosexual women, lesbian and bisexual women reported lower pain intensity ratings early in the discomfort task. Irrespective of sexual orientation, attraction to more feminine romantic partners and dispositional masculinity were correlated with lower pain intensity, and with higher pain thresholds and tolerance levels.

DISCUSSION: These preliminary findings suggest that within‐sex differences in sexual orientation and other aspects of identity, irrespective of biological sex, may be important to consider when examining experimental pain performance and clinical pain experiences.

CONCLUSION: Larger investigations of the psychophysiological relationships among sexual orientation, gender expression and pain sensitivity are warranted. These findings may have implications for differences in clinical pain sensitivity of lesbian and bisexual women compared with heterosexual women.
Patterns and Correlates of Cannabis Use among Individuals with HIV/AIDS in Maritime Canada
Authors: Harris Gregory E , Dupuis Lise , Mugford Gerald J , Johnston Lynn , Haase David , Page Ginny , Haldane Heather , Harris Nicholas , Midodzi William K , Dow Gordon
Published: March 2016

BACKGROUND: The prevalence of cannabis use in HIV‐infected individuals is high and its long‐term effects are unclear.

METHODS: The prevalence, perceived benefits and consequences, and predictors of cannabis use were studied using a cross‐sectional survey in two immunodeficiency clinics in Maritime Canada.

RESULTS: Current cannabis use was identified in 38.5% (87 of 226) of participants. Almost all cannabis users (85 of 87 [97.7%]) acknowledged its use for recreational purposes, with 21.8% (19 of 87) reporting medicinal cannabis use. The majority of patients enrolled in the present study reported mild or no symptoms related to HIV (n=179). Overall, 80.5% (70 of 87) of the cannabis‐using participants reported a symptom‐relieving benefit, mostly for relief of stress, anorexia or pain. Participants consumed a mean (± SD) of 18.3±21.1 g of cannabis per month and spent an average of $105.15±109.87 on cannabis per month. Cannabis use was associated with rural residence, lower income level, driving under the influence of a substance, and consumption of ecstasy and tobacco. Income level, ecstasy use and tobacco use were retained as significant predictors in regression modelling. Cannabis use was not associated with adverse psychological outcomes.

DISCUSSION: Prolonged previous cannabis consumption and the substantial overlap between recreational and medicinal cannabis use highlight the challenges in obtaining a tenable definition of medicinal cannabis therapy.
Burden of Disease and Cost of Chronic Hepatitis C Virus Infection in Canada
Authors: Myers Robert P , Krajden Mel , Bilodeau Marc , Kaita Kelly , Marotta Paul , Peltekian Kevork , Ramji Alnoor , Estes Chris , Razavi Homie , Sherman Morris
Published: March 2016

BACKGROUND: Chronic infection with hepatitis C virus (HCV) is a major cause of cirrhosis, hepatocellular carcinoma and liver transplantation.

OBJECTIVE: To estimate the burden of HCV-related disease and costs from a Canadian perspective.

METHODS: Using a system dynamic framework, the authors quantified the HCV-infected population, disease progression and costs in Canada between 1950 and 2035. Specifically, 36 hypothetical, ageand sex-defined cohorts were tracked to define HCV prevalence, complications and direct medical costs (excluding the cost of antivirals). Model assumptions and costs were extracted from the literature with an emphasis on Canadian data. No incremental increase in antiviral treatment over current levels was assumed, despite the future availability of potent antivirals.

RESULTS: The estimated prevalence of viremic hepatitis C cases peaked in 2003 at 260,000 individuals (uncertainty interval 192,460 to 319,880), reached 251,990 (uncertainty interval 177,890 to 314,800) by 2013 and is expected to decline to 188,190 (uncertainty interval 124,330 to 247,200) in 2035. However, the prevalence of advanced liver disease is increasing. The peak annual number of patients with compensated cirrhosis (n=36,210), decompensated cirrhosis (n=3380), hepatocellular carcinoma (n=2220) and liver-related deaths (n=1880) are expected to occur between 2031 and 2035. During this interval, an estimated 32,460 HCV-infected individuals will die of liver-related causes. Total health care costs associated with HCV (excluding treatment) are expected to increase by 60% from 2013 until the peak in 2032, with the majority attributable to cirrhosis and its complications (81% in 2032 versus 56% in 2013). The lifetime cost for an individual with HCV infection in 2013 was estimated to be $64,694.

CONCLUSIONS: Although the prevalence of HCV in Canada is decreasing, cases of advanced liver disease and health care costs continue to rise. These results will facilitate disease forecasting, resource planning and the development of rational management strategies for HCV in Canada.
Timing of Rebleeding in High-Risk Peptic Ulcer Bleeding after Successful Hemostasis: A Systematic Review
Authors: Ouali Sara El , Barkun Alan N , Martel Myriam , Maggio Davide
Published: March 2016

BACKGROUND: Peptic ulcer rebleeding (PUR) usually occurs within three days following endoscopic hemostasis. However, recent data have increasingly suggested delayed rebleeding.

OBJECTIVE: To better characterize the timing of PUR (Forrest Ia to IIb) following initially successful endoscopic hemostasis.

METHODS: An exhaustive literature search (1989 to 2013), with cross-referencing, was performed to identify pertinent randomized controlled trial (RCT) arms. Patients receiving high-dose proton pump inhibitor (PPI) infusion following successful modern-day endoscopic hemostasis were included. A sensitivity analysis included any patients receiving PPI doses >40 mg daily. The main outcome measure was 30-day rebleeding, while weighted mean averages at t = three, seven, 14 and 28 to 30 days are also reported.

RESULTS: Of 756 citations, six RCTs were included (561 patients; 58.5% to 89.5% male; 55.3 to 67.5 years of age). Among patients receiving high-dose PPI (five RCTs [393 patients]), 11.5% (95% CI 8.4% to 14.7%) experienced rebleeding, 55.6% (95% CI 41.1% to 70.1%) rebled within three days, 20% (95% CI 8.3% to 31.7%) between four and seven days, 17.8% (95% CI 6.6% to 28.9%) at eight to 14 days, and 6.7% (95% CI 0% to 14%) at 15 to 28 to 30 days. Using the relaxed lower PPI dosing threshold, similar respective rates were 14.4% (95% CI 11.5% to 17.3%) overall, with interval rates of 39.5% (95% CI 28.9% to 50.15%), 34.6% (95% CI 24.2% to 44.9%), 19.7% (95% CI 11% to 28.4%) and 6.2% (95% CI 0.95% to 11.5%). Qualitative review of patient characteristics, limited by small sample size, possible bias and study heterogeneity, suggested increased patient comorbidity and postendoscopic use of lower PPI dosing may predict delayed rebleeding.

CONCLUSION: In patients with high-risk PUR undergoing successful endoscopic hemostasis, most rebled within three days, with many experiencing later rebleeding. Additional research is needed to better predict such an outcome.
Serrated Adenoma Prevalence in Inflammatory Bowel Disease Surveillance Colonoscopy, And Characteristics Revealed by Chromoendoscopy and Virtual Chromoendoscopy
Authors: Iacucci Marietta , Hassan Cesare , Gasia Miriam Fort , Urbanski Stefan , Gui Xianyong , Eksteen Bertus , Eustace Gregory , Kaplan Gilaad G , Panaccione Remo
Published: March 2016

BACKGROUND: Sessile or nonpolypoid neoplastic lesions, including sessile serrated adenomas (SSAs), are difficult to detect in patients with inflammatory bowel disease (IBD).

OBJECTIVES: To assess the prevalence and endoscopic features of SSA in IBD patients undergoing surveillance colonoscopy using novel endoscopic techniques.

METHODS: Histology results of biopsies from a cohort of 87 patients (47 men; median age 51.4 years; median duration of disease 16.9 years; ulcerative colitis [n=40], Crohn disease [n=43], ischemic colitis [n=4]) with longstanding colonic IBD undergoing surveillance colonoscopy were reviewed. Lesions of dysplasia (adenoma-like mass, or dysplasia-associated lesion or mass), SSAs, adenoma-like polyps, hyperplastic polyps and inflammatory polyps were identified. Surveillance colonoscopy using high-definition alone, or with iScan (Pentax, USA) dye-sprayed or virtual chromoendoscopy was performed. Lesion characteristics were described before histological diagnosis.

RESULTS: Fourteen SSAs were detected in 87 (11%) IBD patients. The endoscopic characteristics of SSA lesions were: nonpolypoid appearance (86%), predominant localization in the proximal colon (79%), >6 mm in size (79%), cloudy cover (64%), Kudo pit pattern modified type IIO (86%) and irregular spiral vascular pattern (79%). Among the 44 SSAs and hyperplastic polyps found in the present study, the above characteristics of SSA at colonoscopy had a sensitivity of 92.86% (95% CI 66.06% to 98.8%) and specificity of 93.33% (95% CI 77.89% to 98.99%) in predicting a histological diagnosis of SSA (positive predictive value 86.67%, negative predictive value 96.55%).

CONCLUSION: SSAs are a common finding at surveillance colonoscopy in IBD and have several characteristic features. Further studies are needed to evaluate the natural history of these lesions in IBD patients.
Dyspnea due to Pulmonary Vessel Arteritis
Authors: Gilmour Suzana M , Dominelli Giulio S , Leipsic Jonathon A , Levy Robert D
Published: March 2016

Pulmonary arteritis is a rare cause of pulmonary hypertension. Causes of pulmonary arteritis can be divided into primary and secondary, as well as classified according to vessel size. Only large vessel vasculitis is associated with pulmonary hypertension; primary forms include Takayasu arteritis and giant cell arteritis. The diagnosis of pulmonary arteritis can be challenging and the associated morbidity is serious without prompt, directed treatment. The authors present a case involving a 48‐year‐old First Nations man presenting with a six‐month history of exertional dyspnea and severe stenosis of the left pulmonary artery, who was ultimately diagnosed with pulmonary arteritis related to large vessel vasculitis.
Physician Attitudes toward the Use of Fecal Microbiota Transplantation for the Treatment of RecurrentClostridium difficileInfection
Authors: Zipursky Jonathan S , Sidorsky Tivon I , Freedman Carolyn A , Sidorsky Misha N , Kirkland Kathryn B
Published: March 2016

BACKGROUND: Fecal microbiota transplantation (FMT) is a safe and effective, yet infrequently used therapy for recurrentClostridium difficileinfection (CDI).

OBJECTIVE: To characterize barriers to FMT adoption by surveying physicians about their experiences and attitudes toward the use of FMT.

METHODS: An electronic survey was distributed to physicians to assess their experience with CDI and attitudes toward FMT.

RESULTS: A total of 139 surveys were sent and 135 were completed, yielding a response rate of 97%. Twenty-five (20%) physicians had treated a patient with FMT, 10 (8%) offered to treat with FMT, nine (7%) referred a patient to receive FMT, and 83 (65%) had neither offered nor referred a patient for FMT. Physicians who had experience with FMT (performed, offered or referred) were more likely to be male, an infectious diseases specialist, >40 years of age, fellowship trained and practicing in an urban setting. The most common reasons for not offering or referring a patient for FMT were: not having ‘the right clinical situation’ (33%); the belief that patients would find it too unappealing (24%); and institutional or logistical barriers (23%). Only 8% of physicians predicted that the majority of patients would opt for FMT if given the option. Physicians predicted that patients would find all aspects of the FMT process more unappealing than they would as providers.

CONCLUSIONS: Physicians have limited experience with FMT despite having treated patients with multiple recurrent CDIs. There is a clear discordance between physician beliefs about FMT and patient willingness to accept FMT as a treatment for recurrent CDI.
Determination of Real‐Time Polymerase Chain Reaction Uncertainty of Measurement Using Replicate Analysis and a Graphical User Interface with Fieller’s Theorem
Authors: Stuart James Ian , Delport Johan , Lannigan Robert , Zahariadis George
Published: March 2016

BACKGROUND: Disease monitoring of viruses using real‐time polymerase chain reaction (PCR) requires knowledge of the precision of the test to determine what constitutes a significant change. Calculation of quantitative PCR confidence limits requires bivariate statistical methods.

OBJECTIVE: To develop a simple‐to‐use graphical user interface to determine the uncertainty of measurement (UOM) of BK virus, cytomegalovirus (CMV) and Epstein‐Barr virus (EBV) real‐time PCR assays.

METHODS: Thirty positive clinical samples for each of the three viral assays were repeated once. A graphical user interface was developed using a spreadsheet (Excel, Microsoft Corporation, USA) to enable data entry and calculation of the UOM (according to Fieller’s theorem) and PCR efficiency.

RESULTS: The confidence limits for the BK virus, CMV and EBV tests were ∼0.5 log, 0.5 log to 1.0 log, and 0.5 log to 1.0 log, respectively. The efficiencies of these assays, in the same order were 105%, 119% and 90%. The confidence limits remained stable over the linear range of all three tests.

DISCUSSION: A >5 fold (0.7 log) and a >3‐fold (0.5 log) change in viral load were significant for CMV and EBV when the results were ≤1000 copies/mL and >1000 copies/mL, respectively. A >3‐fold (0.5 log) change in viral load was significant for BK virus over its entire linear range. PCR efficiency was ideal for BK virus and EBV but not CMV. Standardized international reference materials and shared reporting of UOM among laboratories are required for the development of treatment guidelines for BK virus, CMV and EBV in the context of changes in viral load.
Pain‐Related and Negative Semantic Priming Enhances Perceived Pain Intensity
Authors: Richter Maria , Schroeter Christoph , Puensch Theresa , Straube Thomas , Hecht Holger , Ritter Alexander , Miltner Wolfgang HR , Weiss Thomas
Published: March 2016

BACKGROUND: Negative affective and pain‐related cues, such as pictures or words, have been shown to act as primes and enhance the perceived intensity of subsequent painful events. For pain‐related semantic primes, it remains unclear whether this effect depends on negative valence itself or, specifically, on the pain‐relatedness of the words.

OBJECTIVES: To investigate the effect of pain‐related, negative affective (pain‐unrelated) and neutral semantic primes on the perception of subsequent noxious target stimuli.

METHODS: Pain ratings in response to noxious electrical stimulation of light and moderate intensity were examined in 39 healthy subjects after subjects were exposed to semantic primes of different meaning and valence (pain‐related, negative, positive and neutral adjectives) presented with different interstimulus intervals (0 ms, 500 ms and 1500 ms).

RESULTS: Increased pain ratings of noxious stimuli were observed following pain‐related and negative compared with neutral primes.

DISCUSSION: The results support the motivational priming theory for semantic stimuli, indicating that affectively negative semantic primes increase subjective pain intensity. However, a specific pain‐related priming effect was not reliably demonstrated. Additionally, it is shown that experimental parameters (ie, stimulus intensity and interstimulus interval) modify the extent of negative and pain‐related semantic priming.

CONCLUSIONS: Verbal priming plays a role for the perception of noxious stimuli in a time‐dependent manner.
When in Doubt, Ask the Audience: Potential Users′ Perceptions of Internet‐Delivered Cognitive Behavioural Therapy for Chronic Pain
Authors: Schneider Luke H , Hadjistavropoulos Heather D
Published: March 2016

BACKGROUND: Although research has demonstrated that Internet‐delivered cognitive behavioural therapy (ICBT) for chronic pain helps with adjustment to pain, it remains unclear how this treatment option would initially be perceived by individuals with chronic pain.

OBJECTIVES: To explore initial perceptions of ICBT and to examine variables that correlate with an expressed interest in ICBT as a treatment option among individuals with chronic pain.

METHODS: A total of 129 individuals with chronic pain completed a survey assessing perceptions of ICBT and individual difference variables that could be correlated with expressed interest in ICBT (eg, demographic characteristics, pain, computer self‐efficacy).

RESULTS: Results showed that most participants perceived ICBT as a potentially valuable service with multiple benefits. Being female, having greater pain severity and interference, and having greater computer self‐efficacy and lower computer anxiety were positively correlated with interest in receiving ICBT.

CONCLUSIONS: Combined with previous research on treatment efficacy of ICBT for chronic pain, the results should serve to stimulate further research on integrating ICBT within existing health care services.
Care of the Liver Transplant Patient
Authors: Bhat Mamatha , Al-Busafi Said A , Deschênes Marc , Ghali Peter
Published: March 2016

OBJECTIVE: To provide an approach to the care of liver transplant (LT) patients, a growing patient population with unique needs.

METHODS: A literature search of PubMed for guidelines and review articles using the keywords “liver transplantation”, “long term complications” and “medical management” was conducted, resulting in 77 articles.

RESULTS: As a result of being on immunosuppression, LT recipients are at increased risk of infections and must be screened regularly for metabolic complications and malignancies.

DISCUSSION: Although immunosuppression is key to maintaining allograft health after transplantation, it comes with its own set of medical issues to follow. Physicians following LT recipients must be aware of the greater risk for hypertension, diabetes, dyslipidemia, renal failure, metabolic bone disease and malignancies in these patients, all of whom require regular monitoring and screening. Vaccination, quality of life, sexual function and pregnancy must be specifically addressed in transplant patients.
Trends in Canadian Respiratory Clinical Trials from 2001 to 2011
Authors: Tacon Claire Elizabeth , Abbas Hina , Zhang Shiyuan , Nicholls Barbara , Crater Glenn , Su Zhen
Published: March 2016

Clinical research bridges patients’ unmet medical need with innovative medicines, increases knowledge acquisition by clinicians, and creates solutions to improve the sustainability and quality of the Canadian health care system and economy. The Canadian Institutes of Health Research and the Canadian Lung Association have recently raised concerns over declining research activities within the Canadian respiratory community. While there are currently >3000 ongoing clinical trials in Canada, the number of trials investigating common respiratory diseases is unknown. The objective of the present study was to monitor the trends in industry‐ and non‐industry‐sponsored respiratory clinical trials in Canada from 2001 to 2011. Trialtrove 2012 (Citeline, an Informa UK business), a database containing summarized clinical trial information regarding pharmaceutical products, was searched using common chronic respiratory disease terms: “allergic rhinitis”, “asthma”, “chronic obstructive pulmonary disease (COPD)”, “cystic fibrosis”, “respiratory infections”, “pulmonary fibrosis” and “smoking cessation”. Over the past 10 years, the number of respiratory clinical trials conducted in Canada has increased (4.49 per year; P=0.004). From 2001 to 2011, the majority of trials were performed in asthma, followed closely by respiratory infections and COPD. Over the past decade, the number of trials investigating COPD and respiratory infections increased (P<0.05), while asthma trials showed a declining trend since 2007. Of the clinical trials performed during this 10‐year period, the majority were in phase III, with a significant increase in the number of phase II trials (2.49 per year; P=0.008). However, certain trends observed are concerning and warrant further monitoring in the coming years.
How Many Individuals with Asthma Need to Be Vaccinated to Prevent One Case of Invasive Pneumococcal Disease?
Authors: Okapuu Julie M , Chétrit Estelle , Lefebvre Brigitte , Quach Caroline
Published: March 2016

BACKGROUND: The American Advisory Committee on Immunization Practices recommended the inclusion of adults with asthma in the high‐risk category for pneumococcal vaccination based on a twofold increase in risk of invasive pneumococcal disease (IPD).

OBJECTIVE: To determine whether, among individuals with asthma, the number needed to vaccinate (NNV) using pneumococcal conjugate vaccine (PCV)‐13 or 23‐valent pneumococcal polysaccharide vaccine (PPV‐23) warrants its addition to the high‐risk category for pneumococcal vaccination in Canada.

METHODS: Using IPD incidence (per 10,000 individuals) figures from published articles (4.2 in high‐risk asthmatics, 2.3 in low‐risk asthmatics and 1.2 in healthy individuals), the NNV to prevent one case of IPD in asthmatics five to 17 years of age and 18 to 50 years of age was calculated, factoring in the proportion of pneumococcal serotypes included in vaccines (based on data from Quebec) and accounting for the possibility of waning vaccine efficacy (VE) using four scenarios.

RESULTS: Assuming a VE of 65% for PCV‐13 in asthmatics, the NNV would be 704 to 820 in low‐risk and 386 to 449 in high‐risk children; and 355 to 1532 in low‐risk and 195 to 839 in high‐risk adults (range depends on waning scenario). Assuming a VE of 65% for PPV‐23 in asthmatics, the NNV would be 581 to 677 in low‐risk and 318 to 371 in high‐risk children; and 246 to 1059 in low‐risk and 135 to 580 in high‐risk adults.

CONCLUSION: The NNV with both PCV‐13 and PPV‐23 in asthmatic children and adults is comparable with that of other high‐risk conditions such as age ≥65 years. Therefore, the addition of asthma to the list of high‐risk conditions for pneumococcal vaccination is warranted.
Correlates of Illness Severity in Infectious Mononucleosis
Authors: Odame John , Robinson Joan , Khodai-Booran Nasser , Yeung Simon , Mazzulli Tony , Stephens Derek , Allen Upton D
Published: March 2016

INTRODUCTION: Understanding the spectrum and frequencies of Epstein‐Barr virus (EBV) complications and markers of illness severity in immunocompetent patients with primary EBV infection will inform management of patients with EBV‐related illnesses.

OBJECTIVES:To determine the clinical and laboratory correlates of illness severity among infants, children and youth with infectious mononucleosis (IM).

METHODS: Study subjects with confirmed IM were prospectively enrolled. Illness severity was assessed at baseline and at six weeks using a scoring tool. Peripheral blood viral loads served as a measure of viral burden.

RESULTS: Among 32 children and young adults with IM, the median age was 16 years (range two to 24 years). The predominant clinical findings were lymphadenopathy (23 of 32 [72%]), pharyngitis (16 of 32 [50%]), fever (nine of 32 [28%]) and splenomegaly (six of 32 [19%]). With respect to symptoms or signs that persisted to at least six weeks after illness onset, the predominant complaint was lymphadenopathy in 35% of subjects available for reassessment. Deranged liver function tests were present at presentation in up to 44% of subjects. Patients with the highest viral loads at presentation had significantly higher illness severity scores associated with fatigue (P=0.02). Other than the scores associated with fatigue, viral load values were not significantly correlated with the illness severity scores at baseline and at six weeks.

CONCLUSION: In IM, viral loads are not necessarily correlated with illness severity, with the exception of fatigue. EBV‐related hepatitis is common in IM, confirming the status of this virus as a relatively common cause of transient hepatitis in children and youth. This entity is not necessarily a marker of disease severity.
Tough Guys or Sensitive Guys? Disentangling the Role of Examiner Sex on Patient Pain Reports
Authors: Vigil Jacob M , Alcock Joe
Published: March 2016

BACKGROUND: Experimental and clinical pain studies are conflicting regarding whether individuals report heightened or dampened pain sensitivity in the presence of other men or women.

OBJECTIVES: In the present preliminary study, two small medical record reviews of patients admitted for emergency care were conducted to examine the possibility that patients may report differential pain intensity to male and female health care examiners. The study also sought to determine whether these effects are moderated by and, thus, only detectable by examining patients at different pain (debilitation) levels.

METHODS: Pain intensity scores were extracted from two medical record reviews of patients admitted for emergency care (n=64 and n=135, respectively). Pain intensity was measured using an 11‐point numerical scale during standard triage assessments and the sex of the examiner was recorded.

RESULTS: Mean pain scores reported to male and female emergency staff did not differ in either set of medical records. However, when patients were split between low and high pain levels, male patients reported higher pain scores to male practitioners when experiencing relatively low pain levels, and both male and female patients reported higher pain scores to female practitioners when experiencing relatively high pain levels.

DISCUSSION: The statistical magnitudes of these effects were large, suggesting that this phenomenon may be a pervasive feature in clinical settings and experimental pain studies.

CONCLUSION: These preliminary findings warrant larger‐scale investigations of social contextual influences on patient pain reports, which are necessary for creating more standardized protocols for reliably assessing and treating patient pain experiences.
Longitudinal surveillance of outpatient β‐lactam antimicrobial use in Canada, 1995 to 2010
Authors: Glass-Kaastra Shiona K , Finley Rita , Hutchinson Jim , Patrick David M , Weiss Karl , Conly John
Published: March 2016

INTRODUCTION: β‐lactam antimicrobials are the most commonly prescribed group of antimicrobials in Canada, and are categorized by the WHO as critically and highly important antimicrobials for human medicine. Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is highly important.

OBJECTIVE: To assess the use of penicillin and cephalosporin antimicrobials within Canadian provinces over the 1995 to 2010 time frame according to two metrics: prescriptions per 1000 inhabitant‐days and the average defined daily doses dispensed per prescription.

METHODS: Antimicrobial prescribing data were acquired from the Canadian Integrated Program for Antimicrobial Resistance Surveillance and the Canadian Committee for Antimicrobial Resistance, and population data were obtained from Statistics Canada. The two measures developed were used to produce linear mixed models to assess differences among provinces and over time for the broad‐spectrum penicillin and cephalosporin groups, while accounting for repeated measurements at the provincial level.

RESULTS: Significant differences among provinces were found, as well as significant changes in use over time. A >28% reduction in broad‐spectrum penicillin prescribing occurred in each province from 1995 to 2010, and a >18% reduction in cephalosporin prescribing occurred in all provinces from 1995 to 2010, with the exception of Manitoba, where cephalosporin prescribing increased by 18%.

DISCUSSION: Significant reductions in the use of these important drugs were observed across Canada from 1995 to 2010. Newfoundland and Labrador and Quebec emerged as divergent from the remaining provinces, with high and low use, respectively.
Anxiety, Depression and School Absenteeism in Youth With Chronic or Episodic Headache
Authors: Rousseau-Salvador Céline , Amouroux Rémy , Annequin Daniel , Salvador Alexandre , Tourniaire Barbara , Rusinek Stéphane
Published: March 2016

BACKGROUND: Chronic daily headache (CDH) in children has been documented in general and clinical populations. Comorbid psychological conditions, risk factors and functional outcomes of CDH in children are not well understood.

OBJECTIVES: To examine anxiety and depression, associated risk factors and school outcomes in a clinical population of youth with CDH compared with youth with episodic headache (EH).

METHODS: Data regarding headache characteristics, anxiety, depression and missed school days were collected from 368 consecutive patients eight to 17 years of age, who presented with primary headache at a specialized pediatric headache centre.

RESULTS: A total of 297 patients (81%) were diagnosed with EH and 71 were diagnosed with CDH. Among those with CDH, 78.9% presented with chronic tension‐type headache and 21.1% with chronic migraine (CM). Children with CDH had a higher depression score than the standardized reference population. No difference was observed for anxiety or depression scores between children with CDH and those with EH. However, children with CM were more anxious and more depressed than those with chronic tension‐type headache. Youth experiencing migraine with aura were three times as likely to have clinically significant anxiety scores. Headache frequency and history were not associated with psychopathological symptoms. Children with CDH missed school more often and for longer periods of time.

CONCLUSIONS: These findings document the prevalence of anxiety, depression and school absenteeism in youth with CDH or EH. The present research also extends recent studies examining the impact of aura on psychiatric comorbidity and the debate on CM criteria.
Registered Nurse-Performed Flexible Sigmoidoscopy in Ontario: Development and Implementation of the Curriculum and Program
Authors: Cooper Mary Anne , Tinmouth Jill Margaret , Rabeneck Linda
Published: March 2016

Although colorectal cancer is a leading cause of death in Canada, it is curable if detected in the early stages. Flexible sigmoidoscopy has been shown to reduce the incidence and mortality of colorectal cancer in patients who are at average risk for this disease and, therefore, is an appropriate screening intervention. Moreover, it may be performed by nonphysicians. A program to enable registered nurses to perform flexible sigmoidoscopy to increase colorectal cancer screening capacity in Ontario was developed. This program incorporated practical elements learned from other jurisdictions as well as specific regional considerations to fit within the health care system of Ontario. The nurses received structured didactic and simulation training before performing sigmoidoscopies on patients under physician supervision. After training, nurses were evaluated by two assessors for their ability to perform complete sigmoidoscopies safely and independently. To date, 17 nurses have achieved independence in performing flexible sigmoidoscopy at 14 sites. In total, nurses have screened >7000 Ontarians, with a cancer detection rate of 5.1 per 1000 screened, which is comparable with rates in other jurisdictions and with sigmoidoscopy performed by gastroenterologists, surgeons and other trained nonphysicians. We have shown, therefore, that with proper training and program structure, registered nurses are able to perform flexible sigmoidoscopy in a safe and thorough manner resulting in a significant increase in access to colorectal cancer screening.
Bacterial Meningitis in the Absence of Cerebrospinal Fluid Pleocytosis: A Case Report and Review of the Literature
Authors: Hase Ryota , Hosokawa Naoto , Yaegashi Makito , Muranaka Kiyoharu
Published: March 2016

Elevation of cerebrospinal fluid (CSF) cell count is a key sign in the diagnosis of bacterial meningitis. However, there have been reports of bacterial meningitis with no abnormalities in initial CSF testing. This type of presentation is extremely rare in adult patients. Here, a case involving an 83‐year‐old woman who was later diagnosed with bacterial meningitis caused by Neisseria meningitidis is described, in whom CSF at initial and second lumbar puncture did not show elevation of cell counts. Twenty‐six non‐neutropenic adult cases of bacterial meningitis in the absence of CSF pleocytosis were reviewed. The frequent causative organisms were Streptococcus pneumoniae and N meningitidis. Nineteen cases had bacteremia and seven died. The authors conclude that normal CSF at lumbar puncture at an early stage cannot rule out bacterial meningitis. Therefore, repeat CSF analysis should be considered, and antimicrobial therapy must be started immediately if there are any signs of sepsis or meningitis.