bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed-Release Oral Mesalamine 4.8 g/day (800 mg tablets) Compared with 2.4 g/day (400 mg tablets) for the Treatment of Mildly to Moderately Active Ulcerative Colitis: The ASCEND I Trial
Authors: Hanauer Stephen B , Sandborn William J , Dallaire Christian , Archambault André , Yacyshyn Bruce , Yeh Chyon , Smith-Hall Nancy
Published: March 2016

BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC), but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease.

PATIENTS AND METHODS: A six-week, multicentre, randomized, double-blind, controlled trial assessing the safety and clinical efficacy of a new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was overall improvement (ie, treatment success), defined as complete remission or response to therapy from baseline to week 6. Primary safety end points were adverse events and laboratory evaluations. Data were also analyzed separately for the prespecified subgroup of patients with moderate UC at baseline.

RESULTS: Treatment success was not statistically different between the treatment groups at week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine 2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the efficacy end point (P=0.441). Among the moderate disease subgroup, however, the higher initial dose was more effective; 57% of patients (53 of 93) given delayed-release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day achieved treatment success (P=0.0384). Both regimens were well tolerated.

CONCLUSIONS: Delayed-release oral mesalamine is an effective and well-tolerated initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day.
The Effect of Sham Feeding on Neurocardiac Regulation in Healthy Human Volunteers
Authors: Kamath Markad V , Spaziani Robert , Ullal Sangeeta , Tougas Gervais , Guzman Juan C , Morillo Carlos , Capogna Joshua , Al-Bayati Mohammed , Armstrong David
Published: March 2016

BACKGROUND: Distension and electrical stimuli in the esophagus alter heart rate variability (HRV) consistent with activation of vagal afferent and efferent pathways. Sham feeding stimulates gastric acid secretion by means of vagal efferent pathways. It is not known, however, whether activation of vagal efferent pathways is organ- or stimulus-specific.

OBJECTIVE: To test the hypothesis that sham feeding increases the high frequency (HF) component of HRV, indicating increased neurocardiac vagal activity in association with the known, vagally mediated, increase in gastric acid secretion.

METHODS: Continuous electrocardiography recordings were obtained in 12 healthy, semirecumbent subjects during consecutive 45 min baseline, 20 min sham feeding (standard hamburger meal) and 45 min recovery periods. The R-R intervals and beat-to-beat heart rate signal were determined from digitized electrocardiography recordings; power spectra were computed from the heart rate signal to determine sympathetic (low frequency [LF]) and vagal (HF) components of HRV.

RESULTS: Heart rate increased during sham feeding (median 70.8 beats/min, 95% CI 66.0 to 77.6; P<0.001), compared with baseline (63.6, 95% CI 60.8 to 70.0) and returned to baseline levels within 45 min. Sham feeding increased the LF to HF area ratio (median: 1.55, 95% C.I 1.28 to 1.77; P<0.021, compared with baseline (1.29, 95% CI 1.05 to 1.46); this increase in LF to HF area ratio was associated with a decrease in the HF component of HRV.

CONCLUSIONS: Sham feeding produces a reversible increase in heart rate that is attributable to a decrease in neurocardiac parasympathetic activity despite its known ability to increase vagally mediated gastric acid secretion. These findings suggest that concurrent changes in cardiac and gastric function are modulated independently by vagal efferent fibres and that vagally mediated changes in organ function are stimulus- and organ-specific.
Anxiety Sensitivity, Fear of Pain and Pain‐Related Disability in Children and Adolescents with Chronic Pain
Authors: Martin Andrea L , McGrath Patricia A , Brown Stephen C , Katz Joel
Published: March 2016

BACKGROUND: Converging lines of evidence suggest that anxiety sensitivity and fear of pain may be important vulnerability factors in the development of avoidance behaviours and disability in adults with chronic pain. However, these factors have not been evaluated in children with chronic pain.

OBJECTIVES: To examine the relationships among anxiety sensitivity, fear of pain and pain‐related disability in children and adolescents with chronic pain.

METHODS: An interview and five questionnaires (Childhood Anxiety Sensitivity Index, Pain Anxiety Symptoms Scale, Functional Disability Inventory, Multidimensional Anxiety Scale for Children, and Reynolds Child or Adolescent Depression Scale) were administered to 21 children and adolescents eight to 17 years of age (mean ± SD 14.24±2.21 years) who continued to experience pain an average of three years after discharge from a specialized pain clinic for children.

RESULTS: Anxiety sensitivity accounted for 38.6% of the variance in fear of pain (F[1,20]=11.30; P=0.003) and fear of pain accounted for 39.9% of the variance in pain‐related disability (F[1,20]=11.95; P=0.003), but anxiety sensitivity was not significantly related to pain disability (R2=0.09; P>0.05).

CONCLUSIONS: These findings indicate that children with high levels of anxiety sensitivity had a higher fear of pain, which, in turn, was linked to increased pain disability. The results of this study suggest that anxiety sensitivity and fear of pain may play important and distinct roles in the processes that maintain chronic pain and pain‐related disability in children.
Patient Care and Support Measures Overcome Reluctance to Initiate New Regimen Containing Enfuvirtide
Authors: Trottier Benoit
Published: March 2016

Patients can be resistant to initiation of enfuvirtide therapy because of concerns about self‐injection and related issues. Because the introduction of a new drug class can substantially enhance the efficacy of an antiretroviral regimen, supporting the patient in the introduction of enfuvirtide, a safe and efficacious agent in a new class, offers therapeutic benefits. In the present patient, who showed resistance to all three of the major antiretroviral drug classes, enfuvirtide was successfully introduced with clinic and peer support group assistance. The patient’s acceptance was enhanced by the use of a needle‐free injection system (Biojector), with minimal side effects and significantly improved virological and immunological control.
Colonic Squamous Cell Carcinoma in Ulcerative Colitis: Report of a Case and Review of the Literature
Authors: Cheng Huilan , Sitrin Michael D , Satchidanand Sateesh K , Novak Jan M
Published: March 2016

Squamous cell carcinoma (SCC) is a rare neoplasm in the colorectum. A case of SCC rising from an area of squamous metaplasia in the rectum is presented in a patient with long-standing ulcerative colitis and perianal warts. This is the first report in the literature describing the evolution of squamous metaplasia in the colonic mucosa into invasive carcinoma over time. Related literature on colorectal SCC and squamous metaplasia, and their relationships with inflammatory bowel disease and human papilloma virus, is reviewed.
N-acetyltransferase 2 Slow Acetylator Genotype Associated with Adverse Effects of Sulfasalazine in the Treatment of Inflammatory Bowel Disease
Authors: Chen Min , Xia Bing , Chen Bixiao , Guo Qiusha , Li Jin , Ye Mei , Hu Zhengguo
Published: March 2016

AIM:N-acetyltransferase 2 (NAT2) is an important enzyme catalyzingN-acetylation of sulfasalazine (SASP). The aim of the present study was to investigate associations of the genotypes ofNAT2with inflammatory bowel disease (IBD), and with adverse effects of SASP, which is used as the first-line treatment of IBD.

PATIENTS AND METHODS: The wildtype allele (NAT2*4) and three variant alleles (NAT2*5B, NAT2*6AandNAT*7B) of theNAT2gene were determined in 101 patients with IBD (84 patients with ulcerative colitis and 17 patients with Crohn’s disease) and 109 healthy controls by the polymerase chain reaction-restriction fragment length polymorphism method. Sixty-eight patients with IBD treated with SASP were followed, and their adverse reactions were recorded.

RESULTS: Eleven patients (16%) experienced adverse effects from SASP, including nine cases of sulfapyridine (SP) dose-related adverse effects and two cases of hypersensitivity (skin rash). Patients with the slow acetylator genotypes without theNAT2*4allele experienced adverse effects more frequently (36%) than those with the fast acetylator genotypes with at least oneNAT2*4allele (11%), but the results were not significantly different (OR of 0.26, 95% CI 0.065 to 1.004; P=0.051). However, those with the slow acetylator genotypes experienced more SP dose-related adverse effects than those with the fast acetylator genotypes (36% versus 8%, OR of 0.17, 95% CI 0.039 to 0.749; P=0.019).

CONCLUSIONS: TheNAT2gene polymorphism was not associated with susceptibility to IBD in Chinese populations, but theNAT2slow acetylator genotypes were significantly associated with SP dose-related adverse effects of SASP in the treatment of IBD.
Airflow Obstruction in Young Adults in Canada
Authors: Al-Hazmi Manal , Wooldrage Kate , Anthonisen Nicholas R , Becklake Margaret R , Bowie Dennis , Chan-Yeung Moira , Dimich-Ward Helen , Ernst Pierre , Manfreda Jure , Sears Malcolm R , Siersted Hans C , Sweet Lamont , Van Til Linda
Published: March 2016

OBJECTIVE: Airflow obstruction is relatively uncommon in young adults, and may indicate potential for the development of progressive disease. The objective of the present study was to enumerate and characterize airflow obstruction in a random sample of Canadians aged 20 to 44 years.

SETTING: The sample (n=2962) was drawn from six Canadian sites.

DESIGN: A prevalence study using the European Community Respiratory Health Survey protocol was conducted. Airflow obstruction was assessed by spirometry. Bronchial responsiveness, skin reactivity to allergens and total serum immunoglobulin E were also measured. Logistic regression was used for analysis.

RESULTS: Airflow obstruction was observed in 6.4% of the sample, not associated with sex or age. The risk of airflow obstruction increased in patients who had smoked and in patients who had lung trouble during childhood. Adjusted for smoking, the risk of airflow obstruction was elevated for subjects with past and current asthma, skin reactivity to allergens, elevated levels of total immunoglobulin E and bronchial hyper‐responsiveness. Of the subjects with airflow obstruction, 21% were smokers with a history of asthma, 50% were smokers without asthma, 12% were nonsmokers with asthma and 17% were nonsmokers with no history of asthma. Bronchial hyper‐responsiveness increased the prevalence of airflow obstruction in each of these groups.

CONCLUSION: Smoking and asthma, jointly and individually, are major determinants of obstructive disorders in young adults. Bronchial hyper‐responsiveness contributes to obstruction in both groups.
Endoscopic Ultrasound-Guided Intratumoural Therapy for Pancreatic Cancer
Authors: Yan Brian M , Van Dam Jacques
Published: March 2016

Pancreatic cancer is the second most frequent gastrointestinal malignancy and carries a dismal prognosis. The current standard of care includes resection, if possible, as well as systemic chemoradiation therapy. Endoscopic ultrasound (EUS) is an established technique for the diagnosis and staging of pancreatic adenocarcinoma. Interventional EUS via fine needle injection (FNI) for the treatment of pancreatic cancer is a rapidly expanding field. The present article reviews the up-to-date developments in EUS FNI for intratumoural pancreatic cancer therapy, including antitumoural agents, immunotherapy, ablative techniques and new delivery systems. The therapeutic modalities discussed are currently under development and will hopefully reach clinical practice if benefit is demonstrated through clinical trials. EUS FNI may be an exciting new technique for the delivery of desperately needed novel therapies for pancreatic cancer.
Acceptance of Colonoscopy Requires more than Test Tolerance
Authors: Condon Amanda , Graff Lesley , Elliot Lawrence , Ilnyckyj Alexandra
Published: March 2016

BACKGROUND: Colon cancer screening, including colonoscopy, lags behind other forms of cancer screening for participation rates. The intrinsic nature of the endoscopic procedure may be an important barrier that limits patients from finding this test acceptable and affects willingness to undergo screening. With colon cancer screening programs emerging in Canada, test characteristics and their impact on acceptance warrant consideration.

OBJECTIVES: To measure the acceptability of colonoscopy and define factors that contribute to procedural acceptability, in relation to another invasive gastrointestinal scope procedure, gastroscopy.

PATIENTS AND METHODS: Consecutive patients undergoing a colonoscopy (n=55) or a gastroscopy (n=33) were recruited. Their procedural experience was evaluated and compared pre-endoscopy, immediately before testing and postendoscopy. Questionnaires were used to capture multiple domains of the endoscopy experience and patient characteristics.

RESULTS: Patient scope groups did not differ preprocedurally for general or procedure-specific anxiety. However, the colonoscopy group did anticipate more pain. Those who had a gastroscopy demonstrated higher preprocedural acceptance than those who had a colonoscopy. The colonoscopy group had a significant decrease in scope concerns and anxiety postprocedurally. As well, they reported less pain than they anticipated. Regardless, postprocedurally, the colonoscopy group’s acceptance did not increase significantly, whereas the gastroscopy group was almost unanimous in their test acceptance. The best predictor of pretest acceptability of colonoscopy was anticipated pain.

CONCLUSIONS: The findings indicate that concerns that relate specifically to colonoscopy, including anticipated pain, influence acceptability of the procedure. However, the experience of a colonoscopy does not lead to improved test acceptance, despite decreases in procedural anxiety and pain. Patients’ preprocedural views of the test are most important and should be addressed directly to potentially improve participation in colonoscopy.
A Comparison of Self-Perceived Health Status in Inflammatory Bowel Disease and Irritable Bowel Syndrome Patients from a Canadian National Population Survey
Authors: Tang Linda YL , Nabalamba Alice , Graff Leslie A , Bernstein Charles N
Published: March 2016

OBJECTIVE: To determine whether differences exist in perceptions of physical health, mental health and stress levels between patients with inflammatory bowel disease (IBD) and patients with irritable bowel syndrome (IBS).

METHODS: Data were obtained from the 2005 Canadian Community Health Survey, which had a sample size of 132,947 Canadians. Information on 4441 participants aged 19 years or older who reported that they had been diagnosed with Crohn’s disease (n=474), ulcerative colitis (n=637) or IBS (n=3330) was analyzed regarding perceptions of their physical health, mental health, stress levels and activity levels.

RESULTS: Overall, IBD patients reported being in fair to poor health (P<0.01) more often than IBS patients. In addition, IBS patients were more likely than IBD patients to report poor mental health status (P<0.01) and greater stress levels (P<0.01). In multivariate analyses, having IBS or IBD along with another chronic disease significantly increased the odds of reporting poorer health status.

CONCLUSIONS: People with IBD were more likely to experience fair or poor general health. IBS patients reported higher levels of stress and poorer mental health than IBD patients. When IBS or IBD coexisted with another chronic condition, activity participation at home and at work was significantly more likely to be impaired.
Effect of Maintenance Azithromycin on Established Bronchiolitis Obliterans Syndrome in Lung Transplant Patients
Authors: Porhownik Nancy R , Batobara Wael , Kepron Wayne , Unruh Helmut W , Bshouty Zoheir
Published: March 2016

BACKGROUND: Bronchiolitis obliterans syndrome (BOS), the main cause of late mortality following lung transplantation, is defined as an irreversible decline in forced expiratory volume in 1 s (FEV1).Previous studies using azithromycin for BOS in lung transplant patients have demonstrated a potential reversibility of the decline in FEV1.

OBJECTIVES: To examine whether initiating azithromycin reverses decline in FEV1 in lung transplant recipients with established BOS of at least three months.

METHODS: Pulmonary function tests were performed every three months in seven lung transplant recipients with established BOS of at least three months. FEV1 was recorded at six and three months before initiation, at time of initiation, and three, six, nine and 12 months postazithromycin initiation. The primary end point was change in FEV1. During the study, no immunosuppressive medication changes or acute rejection episodes occurred.

RESULTS: Mean time from transplant to azithromycin initiation was 64 months (range 17 to 117 months). Mean time from BOS diagnosis to azithromycin initiation was 22 months (range three to 67 months). Rate of FEV1 decline from six months before azithromycin initiation, and rates of FEV1 increase from initiation to three and 12 months post‐treatment initiation, were not statistically significant (P=0.32, P=0.16 and P=0.18, respectively). Following a trend toward improvement in the first three months after treatment initiation, FEV1 tended to stabilize.

DISCUSSION: Although several studies address the possible benefit of maintenance azithromycin in lung transplant patients with BOS, the role of the drug remains unproven in these patients, and would best be addressed by a large randomized controlled trial.
Economic Evaluation of Voriconazole for the Treatment of Candidemia in Canadian Adults
Authors: Rotstein Coleman , Cragin Lael , Laverdière Michel , Garber Gary , Bow Eric J , Scalera Alissa , Roberts Craig , Sorenson Sonja V , the Canadian Expert Panel
Published: March 2016

BACKGROUND: Candidemia is a common cause of nosocomial bloodstream infection. When selecting therapeutic treatments for candidemia, cost‐effectiveness is an important consideration. The present study assessed the cost‐effectiveness of voriconazole for the treatment of candidemia.

METHODS: A decision‐analytical model was used for evaluating the cost‐effectiveness of voriconazole compared with a regimen of conventional amphotericin B (CAB) followed by fluconazole (FLU) in the treatment of non‐neutropenic patients diagnosed with candidemia in the Canadian setting, based on the Global Candidemia Study. The time frame of the model was 98 days (14 weeks). Model parameters were based primarily on clinical outcome, and resource use data collected from the clinical trial were used. Supplemental data were obtained from an independent panel of 12 Canadian experts for parameters not available from the clinical trial. Unit costs were collected from Canadian sources. The outcome variables selected in the study were the number of patients cured within 98 days, the number of patients surviving at 98 days and the number of patients avoiding toxicity. Incremental costs per outcome were calculated to compare the cost‐effectiveness analyses (both probabilistic and one‐way sensitivity analyses were performed).

RESULTS: The cost‐effectiveness analysis demonstrated a difference of $1,121 in the total average cost of treatment with voriconazole ($70,489) versus CAB/FLU ($69,368). While the costs of voriconazole exceeded the costs of CAB/FLU, these costs were almost completely offset by lower hospitalization costs. While patients in both treatment arms experienced cure rates of 41%, both the percentage of patients surviving at day 98 (64.5% versus 58.2%) and the percentage of patients avoiding toxicity (64.5% versus 52.5%) were higher in the voriconazole arm. Accounting for differences in total costs and clinical outcomes, this analysis estimated an incremental cost per patient surviving at day 98 of $17,739, and an incremental cost per patient avoiding toxicity of $9,298. In the case of cost per patient cured, voriconazole had a higher cost ($1,121) than CAB/FLU. The results of the deterministic and probabilistic sensitivity analyses indicated that the model was robust.

CONCLUSIONS: Results of the decision‐analytical model provided evidence to support the cost‐effectiveness of voriconazole relative to a regimen of CAB/FLU in the treatment of non‐neutropenic patients diagnosed with candidemia in the Canadian setting.
A Randomized, Double‐Blind, Crossover Comparison of the Efficacy and Safety of Oral Controlled‐Release Tramadol and Placebo in Patients with Painful Osteoarthritis
Authors: Thorne Carter , Beaulieu André D , Callaghan Denis J , O’Mahony William F , Bartlett John M , Knight Richard , Kraag Gunnar R , Akhras Ronald , Piraino Paula S , Eisenhoffer John , Harsanyi Zoltan , Darke Andrew C
Published: March 2016

OBJECTIVE: To compare the efficacy and safety of controlled‐release (CR) tramadol (Zytram XL, Purdue Pharma, Canada) and placebo in patients with painful osteoarthritis.

METHODS: Patients underwent analgesic washout for two to seven days before random assignment to 150 mg daily of CR tramadol or placebo, and were titrated weekly to 200 mg, 300 mg or a maximum of 400 mg once daily. After four weeks, patients crossed over to the alternate treatment for another four weeks. Plain acetaminophen was provided as a rescue analgesic. All patients who completed the crossover study were eligible to receive open label CR tramadol for six months.

RESULTS: Seventy‐seven of 100 randomly assigned patients were evaluable for efficacy. CR tramadol resulted in significantly lower visual analogue scale pain intensity scores (37.4±23.9 versus 45.1±24.3, P=0.0009). Western Ontario and McMaster Universities osteoarthritis index subscale scores for pain (189.0±105.0 versus 230.0±115.4; P=0.0001) and physical function (632.4±361.3 versus 727.4±383.4; P=0.0205) were significantly better with CR tramadol. Total pain and disability (22.8±14.5 versus 27.2±14.8; P=0.0004), and overall pain and sleep (104.7±98.0 versus 141.0±108.2; P=0.0005) scores in the Pain and Sleep Questionnaire were significantly lower for CR tramadol. Short‐form 36 Health Survey scores were significantly better during CR tramadol treatment for the pain index (38.8±10.8 versus 35.6±9.0; P=0.0100), general health perception (46.5±11.2 versus 44.4±11.6; P=0.0262), vitality (43.1±13.2 versus 40.2±13.7; P=0.0255) and overall physical components (40.8±8.9 versus 37.8±7.7; P=0.0002). CR tramadol treatment was preferred by 55.8% of patients (P=0.0005) versus 20.8% and 23.4% of patients who chose placebo or had no preference, respectively. These improvements were sustained for up to six months, and 86.5% of patients reported at least moderate benefit from CR tramadol during long‐term treatment.

CONCLUSION: CR tramadol is effective for the management of painful osteoarthritis.
Does Blood Urea Nitrogen Level Predict Severity and High-Risk Endoscopic Lesions in Patients with Nonvariceal Upper Gastrointestinal Bleeding?
Authors: Al-Naamani Khalid , Alzadjali Nabil , Barkun Alan N , Fallone Carlo A
Published: March 2016

BACKGROUND: Nonvariceal upper gastrointestinal bleeding (UGIB) is a serious medical condition requiring prompt resuscitation and early endoscopic therapy in those with high-risk endoscopic lesions (HRLs). There are little or no data correlating sole blood urea nitrogen (BUN) level with the severity of nonvariceal UGIB or the presence of HRLs in the adult population.

OBJECTIVES: To determine if the BUN level on presentation correlates with parameters of severity of UGIB (need for blood transfusion or intensive care unit [ICU] admission) or to the subsequent finding of HRL, and in so doing identify patients who will require early endoscopic intervention.

METHODS: The Canadian Registry of patients with Upper Gastrointestinal Bleeding undergoing Endoscopy was used to identify patients enrolled from the McGill University Health Centre (Montreal, Quebec) who presented with or developed acute nonvariceal UGIB while admitted. All comparisons were performed using Student’sttest or Wilcoxon’s signed rank test, as appropriate. Logistic regression modelling using a stepwise method was performed to identify independent predictors of severe nonvariceal UGIB and HRL.

RESULTS: Two hundred nine patients were enrolled in the study. The mean age was 67±18 years and 59.8% were male. The mean BUN level was 13.4±9.4 mmol/L. Univariate analysis demonstrated that the BUN level was a significant predictor of ICU admission (BUN 14.7±10.4 mmol/L versus 12.0±8.0 mmol/L, P=0.035). However, when adjusted for systolic blood pressure, BUN level became a weaker predictor of ICU admission, just failing to achieve statistical significance (OR 1.03, 95% CI 1.00 to 1.06; P=0.08). Univariate analysis also demonstrated that BUN level was not a statistically significant predictor of blood transfusion requirement (BUN 14.1±10.6 mmol/L versus 13.6±8.6 mmol/L, P=0.508), nor of HRL (BUN 14.2±10.7 mmol/L versus 12.9±8.6 mmol/L, P=0.605).

CONCLUSION: In patients with nonvariceal UGIB, the BUN level at initial presentation is a weak predictor of the severity of UGIB as defined by ICU admission, but is not helpful in identifying patients with a HRL.
Community‐Acquired Serratia Marcescens Spinal Epidural Abscess in a Patient Without Risk Factors: Case Report and Review
Authors: Parkins Michael D , Gregson Daniel B
Published: March 2016

Serratia marcescens has rarely been reported as an agent of invasive disease in patients presenting from the community. Furthermore, S marcescens is frequently opportunistic, affecting individuals with serious medical comorbidities including immune suppression and diabetes. A case of a community‐acquired S marcescens spontaneous lumbar epidural abscess presenting as cauda equina syndrome is reported in a previously well 36‐year‐old man with no identifiable risk factors. To the authors’ knowledge, this is the first report of invasive S marcescens causing disease in a patient with no medical comorbidities.
Long-Term Survivorship of Esophageal Cancer Patients Treated with Radical Intent
Authors: Agranovich Alex , McGahan Colleen E , Gurjal Anagha
Published: March 2016

To investigate the recent trends in definitive management of esophageal cancer, the records of 138 consecutive patients treated with radical intent in a single institution between 1995 and 2003 were reviewed and analyzed. The median follow-up period was 5.7 years (range 1.1 to 10.4 years). Seventy-seven patients were treated with radiation therapy (RT) only and 61 with combined regimens (CRT), in which RT was combined with either radical surgery or chemotherapy, or both. The overall survival of the entire cohort was 32% over two years and 20% over five years. The survivorship in the RT group was 17% over two years and 5% over five years. In the CRT group, 51% and 35% survived over two and five years, respectively. From all the potential prognostic factors examined by univariate and multivariate analyses, only male sex and use of CRT were strongly associated with better survivorship. There was no significant difference in the outcomes among the different regimens of CRT. Survivorship was not affected by the location or histology of the tumour, clinical stage, dose of RT or use of endoluminal brachytherapy in addition to external beam RT. There was a greater tendency to use RT only more often in older patients, but patient age did not affect survivorship. The proportion of patients treated with CRT did not change significantly over the last versus the first four years of the observed period. Combined regimens are undoubtedly superior to RT as a single modality. The long-term survivorship of patients in a subgroup of our patients treated with combined modality protocols compared favourably with the previously reported results in the literature and specifically in prospective randomized trials. However, the optimal combined modality regimen is yet to be defined.
Attachment Dimensions and Young Children’s Response to Pain
Authors: Walsh Trudi M , McGrath Patrick J , Symons Douglas K
Published: March 2016

BACKGROUND/OBJECTIVE: The present study examined the relationship between attachment dimensions and child pain behaviour following both an everyday pain incident (eg, bumps and scrapes) and acute pain incident (eg, immunization) in 66 five‐year‐old children.

METHODS: Secure, avoidant, ambivalent and controlling attachment dimensions were assessed using aggregates of laboratory‐based reunion behaviour, performance on representational measures of attachment and the measure of emotion regulation. Child pain behaviour, during immunization and everyday pain incidents, was rated in terms of reactivity, anger and calming time.

RESULTS: The ambivalence and controlling attachment dimensions were differentially related to child pain behaviour. Specifically, children with either more ambivalent or controlling attachment had a relatively greater reaction to both the immunization procedure and everyday pain incident. Children with more controlling attachment also took more time to calm down following the immunization and displayed greater anger. Security and avoidance, however, were not systematically related to child pain behaviour.

CONCLUSIONS: Results are discussed in terms of Bowlby’s theory of attachment relationships and pain as an important distress signal to children.
Effects of Smoke Exposure and Other Lifestyle Factors on Pain Response to Electrical Stimulation in Women
Authors: May Wee Joy Yenn , Hopman Wilma M
Published: March 2016

BACKGROUND: A relationship between smoking and development of pain syndromes has been suggested in the literature. The present study examined associations between smoke exposure and other related variables, and pain response to suprathreshold electrical stimulation.

METHODS: Subjects were prospectively recruited from a population referred to an electrodiagnostic clinic. Information about age, smoke exposure, caffeine and alcohol consumption was obtained, as well as documented objective signs of stress through physical assessment. One investigator applied two standardized 0.1 ms electrical stimulations (50 mA followed by 100 mA) to asymptomatic extremities at the beginning of each electrodiagnostic session, using consistent technique. Subjects used a visual analogue scale to indicate the level of pain felt after each stimulation.

RESULTS: Two hundred fifteen women were included. Current smokers and those currently exposed to second‐hand smoke had significantly higher pain ratings (P=0.003 for 50 mA, P=0.005 for 100 mA) than those not currently exposed to smoke. Time since exposure was negatively associated with pain ratings. Those with objective signs of stress reported higher levels of pain, which was significant for the 100 mA stimulation (P=0.046). Linear regression modelling indicated that current smoke exposure and alcohol use were associated with higher pain ratings at both 50 mA and 100 mA, while stress was associated with higher pain ratings and older age was associated with lower pain ratings at 100 mA only.

INTERPRETATION: Exposure to cigarette smoke is significantly related to higher reported levels of pain experienced in response to electrical stimulation in this study population. Exposure to smoke can add 10 points to the 100‐point visual analogue scale compared with subjects without exposure, with alcohol use adding another eight points. Reported pain decreases as length of time since previous exposure to smoke increases.
Barrett’s Esophagus and Cardiac Intestinal Metaplasia: Two Conditions within the Same Spectrum
Authors: White Nicole , Gabril Manal , Ejeckam Gershon , Mathews Maria , Fardy John , Kamel Fady , Doré Jules , Yousef George M
Published: March 2016

BACKGROUND: Immunostaining for cytokeratin 7 (CK7) and cytokeratin 20 (CK20) has a characteristic pattern in Barrett’s esophagus (BE), but reports regarding its sensitivity and specificity are inconsistent. Intestinal metaplasia of the gastric cardia (CIM) is histologically similar to BE, but with no abnormal endoscopic findings.

OBJECTIVES: To evaluate the sensitivity and specificity of a semi-quantitative CK7/CK20 immunostaining pattern for the diagnosis of BE, and to further elucidate the pathogenesis of CIM.

METHODS: Tissues were examined by hematoxylin and eosin and periodic acid schiff/alcian blue stains, and then were immunostained with CK7 and CK20 antibodies. Correlations with other clinical parameters were statistically analyzed.

RESULTS: When values were revised based on follow-up data and auxiliary testing, all BE cases (100%) displayed the characteristic BE CK7/CK20 immunostaining pattern, compared with 66% of CIM cases. In the subgroup of patients who were endoscopically and immunohistochemistry-positive but histologically negative, all patients except for one had documented BE when clinical history, auxiliary testing and follow-up were evaluated. There were no statistically significant differences between BE and CIM regardingHelicobacter pyloriinfection or the type of metaplasia (complete versus incomplete). The sensitivity of the CK7/CK20 pattern reached 100% in the subgroup of CIM patients with a history of acid reflux. Of 26 cases of CIM where follow-up was available, four cases (15%) progressed to BE, and one developed dysplasia. All four cases showed the BE pattern of CK7/CK20 staining and were negative forH pyloriinfection.

CONCLUSIONS: A semiquantitative CK7/CK20 pattern can be used to confirm BE even in the absence of histological evidence. The subgroup of CIM with acid reflux may develop into BE and may need closer follow-up.
The Meaning and Process of Pain Acceptance. Perceptions of Women Living with Arthritis and Fibromyalgia
Authors: LaChapelle Diane L , Lavoie Susan , Boudreau Ainsley
Published: March 2016

BACKGROUND: Within the past 10 years, cognitive‐behavioural pain management models have moved beyond the traditional focus on coping strategies and perceived control over pain, to incorporate mindfulness‐and acceptance‐based approaches. Pain acceptance is the process of giving up the struggle with pain and learning to live life despite pain. Acceptance is associated with lower levels of pain, disability and psychological distress. Relatively little is known, however, about how patients arrive at a state of acceptance without the aid of therapy.

OBJECTIVES: To explore personal definitions of acceptance and the factors that facilitate or hinder acceptance.

METHODS: Eleven focus groups, involving a total of 45 women with arthritis and fibromyalgia, were conducted.

RESULTS: The qualitative analysis revealed that, while the women rejected the word ‘acceptance’, they did agree with the main components of existing research definitions. The women’s responses revealed that acceptance was a process of realizations and acknowledgements, including realizing that the pain was not normal and help was needed, receiving a diagnosis, acknowledging that there was no cure and realizing that they needed to redefine ‘normal’. Diagnosis, social support, educating self and others, and self‐care were factors that promoted acceptance. Struggling to retain a prepain identity, negative impacts on relationships, others not accepting their pain and the unspoken message that the pain was ‘all in their head’ were barriers to acceptance.

CONCLUSION: The implications of these findings, distinctions between the diagnostic groups and recommendations regarding how health professionals can facilitate the process of acceptance are discussed.
Requiem for the Term ‘Carcinoid Tumour’ in the Gastrointestinal Tract?
Authors: Chetty Runjan
Published: March 2016

Use of the term ‘carcinoid tumour’ to describe a unique type of tumour in the gastroenteropancreatic system is endemic in the medical literature and in daily clinical and pathological parlance. However, it is a somewhat misleading moniker because a spectrum of histopathological changes and hence, biological outcomes may occur in these tumours. The World Health Organization classification scheme recommends the use of the terms neuroendocrine tumours or carcinomas, which may be stratified as well-differentiated neuroendocrine tumours with benign or uncertain behaviour, well-differentiated tumours with low-grade neuroendocrine carcinoma behaviour and high-grade neuroendocrine carcinomas. These categories may be applied within different sites in the gastrointestinal tract and pancreas, and convey a sense of biological behaviour. In addition, a recently suggested tumour-node-metastasis scheme has been proposed and awaits clinical validation and acceptance. Thus, the term ‘carcinoid’ has served its purpose well, but its use should be phased out in favour of ‘neuroendocrine tumour’ or ‘neuroendocrine carcinoma’.
Does Subclinical Malabsorption of Carbohydrates Prevent Colorectal Cancer? A Hypothesis
Authors: Bolin Terry Dorcen
Published: March 2016

The incidence of colorectal cancer (CRC) is high in the western world and low in Asia and Africa. Fibre and starch are thought to be important protective factors, with a strong inverse relationship between starch consumption and CRC incidence. Whether this is true in Asia, particularly, and Africa is debatable. Because rice is the most easily absorbed of carbohydrates, a mechanism whereby there is an increased starch load in the colon in the Asian population needs to be identified. One possible cause is subclinical malabsorption. This is linked to increased mucosal permeability and low gross domestic product (GDP) per capita, which reflects poor sanitation and water supplies with increased risk for small bowel bacterial overgrowth leading to mucosal cell damage. A potential cause of the dramatic rise in CRC incidence in Japan may relate to its equally dramatic increase in GDP per capita of 600% over 50 years. This correlation appears to be stronger than with other dietary factors including fruit, vegetables and meat. Worldwide, a close correlation exists among low GDP per capita, low CRC incidence and presumed subclinical malabsorption. All these factors combine to maintain a low incidence of CRC in poorly developed countries.
Methicillin‐Resistant Staphylococcus aureus Colonization in Schoolteachers in Ontario
Authors: Hanselman Beth A , Kruth Steven A , Rousseau Joyce , Weese J Scott
Published: March 2016

A prospective study of methicillin‐resistant Staphylococcus aureus (MRSA) colonization was performed involving teachers at a science teachers’ conference in Toronto, Ontario. Nasal swabs and questionnaire data were collected from consenting individuals. MRSA colonization was identified in seven of 220 (3.2%) participants. No colonized individuals reported recent contact with the health care system, antimicrobial therapy, residence with health care workers or previous MRSA infections. Methicillin‐susceptible S aureus colonization was identified in 72 of 220 (33%) individuals. The prevalence of MRSA colonization was higher than expected for a purportedly low‐risk population.
Comparison of Liver Biopsy and Transient Elastography based on Clinical Relevance
Authors: Masuzaki Ryota , Tateishi Ryosuke , Yoshida Haruhiko , Goto Eriko , Sato Takahisa , Ohki Takamasa , Goto Tadashi , Yoshida Hideo , Kanai Fumihiko , Sugioka Yosuke , Ikeda Hitoshi , Shiina Shuichiro , Kawabe Takao , Omata Masao
Published: March 2016

BACKGROUND: Liver stiffness measurement (LSM) by transient elastography has recently been validated for the evaluation of liver fibrosis in chronic liver diseases. The present study focused on cases in which liver biopsy and LSM were discordant.

METHODS: Three hundred eighty-six patients with chronic hepatitis C who underwent a liver biopsy between December 2004 and April 2007 were studied. First, the optimal cut-off value of LSM was selected for the determination of cirrhosis based on the receiver operating characteristic curve. Then, the cases in which liver histology and evaluation by LSM were discordant were selected. Laboratory test results such as serum total bilirubin concentration, prothrombin activity, albumin concentration, platelet count and the aspartate aminotransferase to platelet ratio index, together with the presence of esophageal varices, were analyzed.

RESULTS: The optimal cut-off value was chosen to be 15.9 kPa for cirrhosis (fibrosis stage [F] 4) determination to maximize the sum of sensitivity (78.9%) and specificity (81.0%). There were 78 discordant cases: 51 patients showed an LSM of 15.9 kPa or higher and a fibrosis stage of F1 to F3 (high LSM group), and 27 patients had an LSM lower than 15.9 kPa and a fibrosis stage of F4 (low LSM group). Esophageal varices were seen in 11 patients in the high LSM group (n=51) and in no patients in the low LSM group (n=27) (P=0.0012). The aspartate aminotransferase to platelet ratio index was significantly higher in the high LSM group (1.49 versus 0.89, P=0.019). Other parameters did not differ significantly. However, platelet count, prothrombin activity and albumin concentration tended to be lower in the high LSM group.

CONCLUSIONS: Patients with a high LSM need proper attention for cirrhosis, even if liver biopsy does not reveal cirrhosis.
Outcomes of Peginterferon Alpha-2a and Ribavirin Hepatitis C therapy in Aboriginal Canadians
Authors: Cooper Curtis L , Bailey Robert J , Bain Vince G , Anderson Frank , Yoshida Eric M , Krajden Mel , Marotta Paul , for the Canadian Pegasys Study Group
Published: March 2016

BACKGROUND: There is little published information on baseline characteristics and therapeutic outcomes in hepatitis C virus (HCV)-infected Aboriginal Canadians. It is unclear what proportion of HCV-infected Aboriginal people receive therapy relative to other populations.

METHODS: Adults with chronic HCV infection, quantifiable serum HCV-RNA levels and compensated liver disease were assigned, at the physician’s discretion, to either 24 or 48 weeks of treatment with peginterferon alpha-2a 180 μg/week plus ribavirin at a dose of 800 mg/day, or 1000 mg/day or 1200 mg/day in an open-label, expanded access program. The primary outcome was sustained virological response, defined as undetectable HCV-RNA by qualitative polymerase chain reaction (less than 50 IU/mL) at the end of 24 weeks of untreated follow-up. Baseline characteristics and outcomes in Aboriginal and non-Aboriginal patients were compared.

RESULTS: A total of 2614 patients were eligible for the analysis; 44 individuals (1.7%) self-identified as being of Aboriginal heritage. The baseline characteristics of these two groups were similar. An overall sustained virological response was achieved in 47.7% and 46.5% of Aboriginal and non-Aboriginal patients, respectively. The overall frequencies of adverse events and laboratory abnormalities were similar between the two groups, although cytopenias occurred less frequently in Aboriginal patients.

INTERPRETATION: Aboriginal patients were greatly under-represented in the present ‘community’-based treatment program, yet viral responses were similar to those of a non-Aboriginal cohort. To increase the uptake of HCV therapy in the Aboriginal population, clarification of the obstacles to treatment is warranted.
The Need for Knowledge Translation in Chronic Pain
Authors: Henry James L
Published: March 2016

One in five Canadians suffers from some form of persistent or chronic pain. The impact on individual lives, families and friends, the health services sector and the economy is huge. Reliable evidence is available that the burden of persistent pain can be markedly reduced when available knowledge is applied. Bridging the quality chasm between chronic pain and the care process will require a unique confluence of opinion from all stakeholders committed within a focused community of practice to address the impact of pain. Various levels of success in this regard have been demonstrated when there is exchange, synthesis and ethically sound application of research findings within a complex set of interactions among researchers and knowledge users. It is now critical to accelerate the capture of the benefits of research for Canadians through improved health, more effective and responsive services and products, and a strengthened health care system to bring about health reform and health care reform across Canada as it pertains to the one in five Canadians living with chronic, disabling pain. The overarching outcome of such an initiative needs to be promoted to sustain a balanced portfolio of curiosity‐and needs‐based research, which along with existing knowledge, can be mobilized and applied for the benefit of Canadians, the health care system and the economy.
Working Out the Kinks: Testing the Feasibility of an Electronic Pain Diary for Adolescents with Arthritis
Authors: Stinson Jennifer N , Petroz Guy C , Stevens Bonnie J , Feldman Brian M , Streiner David , McGrath Patrick J , Gill Navreet
Published: March 2016

BACKGROUND: Current approaches to evaluating pain in children with chronic arthritis suffer from methodological problems. A real‐time data capture approach using electronic diaries has been proposed as a new standard for pain measurement. However, there is limited information available regarding the development and feasibility of this approach in children.

OBJECTIVES: The aim of the present study was to pilot test the e‐Ouch electronic pain diary in terms of compliance and acceptability in adolescents with arthritis to further refine the prototype.

METHODS: A descriptive study design – with two iterative phases of testing, modifying the prototype and retesting – was used. A purposive sample of 13 adolescents with mild to severe pain and disability was drawn from a large rheumatology clinic in a university‐affiliated pediatric tertiary care centre in Canada over a four‐week period in December 2004. Participants were signalled with an alarm to use the diary three times per day for a two‐week period. Adolescents completed an electronic diary acceptability questionnaire.

RESULTS: Overall mean compliance rates for phases 1 and 2 were 72.9% and 70.5%, respectively. Compliance was affected by the timing of data collection and technical difficulties. Children rated the diary as highly acceptable and easy to use. Phase 1 testing revealed aspects of the software program that affected compliance, which were subsequently altered and tested in phase 2. No further technical difficulties arose in phase 2 testing.

CONCLUSIONS: Feasibility testing is a crucial first step in the development of electronic pain measures before use in clinical and research practice.