bluuebunny/crossref_metadata_2025 huggingface dataset:
The Hot Foot Syndrome: Evans’ Sign and the Old Way
Authors: Evans RJ , Watson C Peter N
Published: March 2016

BACKGROUND: Pelvic cancers such as cancer of the cervix can spread locally to involve adjacent structures such as the lumbosacral plexus and the sympathetic chain. When this happens the prognosis is usually poor. An early suspicion of recurrence may result in investigation leading to earlier and better treatment. A physical sign that may be an early and only sign of recurrence is described.

OBJECTIVE: To report the late Dr Ramon Evans’ unpublished case series of the hot foot syndrome due to (mostly malignant) retroperitoneal disease. This unique contribution is an opportunity to pay tribute to a man who was a meticulous recorder of the patient narrative and practitioner of a detailed and comprehensive physical examination.

METHODS: A longitudinal, observational, retrospective, descriptive study is reported. Data were collected from a convenience sample of 86 patients, 75 of whom had retroperitoneal cancer and 11 of whom were diagnosed with other conditions in that area. Patients referred to the Smythe Pain Clinic were seen at both the Princess Margaret Hospital and Toronto General Hospital in Toronto, Ontario, in the 1970s. They were referred with intractable pain in the leg or back and often a history of a treated abdominal or pelvic cancer in the previous months or years. Baseline demographic data were collected including age, sex, diagnosis, pain location, characteristics and severity, physical findings, investigations and mortality.

RESULTS: The 86 subjects comprised 27 men and 59 women. Carcinoma of the cervix was the most common tumour. Most had a presenting complaint of leg pain. Neurological physical signs were demonstrated in the lower extremities in 44%; however, 56% (48 patients) had only an ipsilateral, warm, dry ‘hot foot’ due to sympathetic deafferentation. The prognosis for the underlying illness was poor for the malignant group.

DISCUSSION: Sympathetic interruption by cancer is well known in apical lung cancer as the tumour spreads upwards to involve the inferior brachial plexus. An analogous situation occurs as cancers, such as that of the cervix, spread laterally to invade the lumbosacral plexus and sympathetic chain. Signs of sympathetic deafferentation (the ‘hot foot’) may be the earliest and only sign in this situation. This sign may be missed unless it is anticipated and a thorough physical examination carried out.

CONCLUSION: Evans’ sign is important because it may be an early and solitary sign of retroperitoneal recurrence of pelvic (cervix, rectum, bladder, ovary and prostate) cancers. Recognition of this finding when intractable pain in the back and leg occurs with a history of this type of cancer could lead to earlier and more successful treatment.
Long‐Acting Morphine Following Hip or Knee Replacement: A Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Musclow Shirley L , Bowers Tabatha , Vo Hanna , Glube Mark , Nguyen Thong
Published: March 2016

BACKGROUND: Patients undergoing total hip or knee replacement surgery experience unmanaged pain during postoperative physiotherapy sessions. It was theorized that a baseline opioid would improve pain management.

OBJECTIVES: To examine the effectiveness of adding long‐acting oral morphine to a routine postoperative regimen for total hip or knee replacement surgery.

METHODS: The present study was a double‐blind, randomized, placebo‐controlled trial for patients undergoing total hip or knee replacement surgery. All patients received routine postoperative analgesia; in addition, the treatment group received long‐acting oral morphine 30 mg orally twice daily for three days, while the control group received placebo capsules. The primary end point was a decrease in pain scores by two points on a 0‐ to 10‐point pain rating scale. Secondary end points included adverse effects, acute confusion, pain‐related interferences in function and sleep, length of stay and patient satisfaction.

RESULTS: Two hundred patients were enrolled in the present study (March 2004 to March 2006). Although the groups were large enough to yield statistical significance, most pain scores did not reach the predetermined improvement for clinical significance. Additionally, there was an increase in opioid usage (P<0.0001), vomiting (P=0.0148) and oversedation (P=0.08). There were no statistically significant changes in function or sleep. Improved satisfaction with pain management was minimal (P=0.052).

DISCUSSION: The present study was undertaken to determine the value of adding a long‐acting opioid (morphine) to the usual care of patients undergoing total hip or total knee replacement surgery. The results yielded minimally improved pain scores and additional adverse effects (vomiting and oversedation). Published research in which long‐acting opioids (oxycodone) were used for similar postoperative procedures did not robustly report improved pain scores. In addition, patients using a long‐acting opioid (oxycodone) during the postoperative period reported somnolence, dizziness and confusion. Statistically, the patients in the present study showed higher confusion scores and no improvement for pain‐related interferences with activity or walking. The treatment group did report increased satisfaction; however, the significance was weak.

CONCLUSIONS: Thirty milligrams twice per day of long‐acting morphine from days 1 to 3 following total hip and total knee replacement surgery provided minimal improvements in pain scores, and more adverse effects in the treatment group. The overall strength of evidence for improved outcomes is minimal and thus not supported.
Current Treatment Options for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis
Authors: Beaton Melanie D
Published: March 2016

Nonalcoholic fatty liver disease is the leading cause of liver disease in western society. It is a cause of end-stage liver disease, with increased mortality secondary to cirrhosis and its complications. It is also recognized that cardiovascular disease is a significant cause of death in these patients. Significant work evaluating various treatments has been performed in recent years; however, to date, no ideal therapy exists. Lifestyle modification remains the cornerstone of management. The present article reviews the current status of various treatment modalities evaluated in nonalcoholic fatty liver disease.
Canadian Digestive Health Foundation Public Impact Series 5: Pancreatitis in Canada. Incidence, Prevalence, and Direct and Indirect Economic Impact
Authors: Teshima Christopher W , Bridges Ronald J , Fedorak Richard N
Published: March 2016

The Canadian Digestive Health Foundation initiated a scientific program to assess the incidence, prevalence, mortality and economic impact of digestive disorders across Canada in 2009. The current article presents the updated findings from the study concerning pancreatitis.
Evaluation and Management of Skeletal Health in Celiac Disease: Position Statement
Authors: Fouda Mona A , Khan Aliya A , Sultan Muhammad , Rios Lorena P , McAssey Karen , Armstrong David
Published: March 2016

OBJECTIVE: To review the evaluation and management of skeletal health in patients with celiac disease (CD), and to make recommendations on screening, diagnosis, treatment and follow-up of low bone mineral density (BMD) in CD patients.

METHODS: A multidisciplinary team developed clinically relevant questions for review. An electronic search of the literature was conducted using the MEDLINE and EMBASE databases from 1996 to 2010. All original studies, reviews and guidelines, both pediatric and adult, were included. A document summarizing the results of the review and proposed recommendations was prepared and underwent multiple revisions until consensus was reached.

RESULTS: At diagnosis, approximately one-third of adult CD patients have osteoporosis, one-third have osteopenia and one-third have normal BMD. Children with CD have low bone mass at diagnosis. Adult and pediatric CD patients are at increased risk of fractures.

DISCUSSION: For adults, serum calcium, albumin, 25(OH) vitamin D3, parathyroid hormone and 24 h urine calcium testing should be performed at diagnosis; patients with ‘classic’ CD and those at risk for osteoporosis should undergo a dual x-ray absorptiometry scan. An abnormal baseline dual x-ray absorptiometry scan should be repeated one to two years after initiation of a gluten-free diet (GFD). For children, BMD should be assessed one year after diagnosis if GFD adherence is not strict. A GFD is the most important treatment for bone loss. Supplemental antiresorptives may be justified in those who remain at high fracture risk (eg, postmenopausal women, older men) after implementation of a GFD.

CONCLUSION: Current evidence does not support the screening of all CD patients for low BMD at diagnosis. Follow-up BMD assessment should be performed one to two years after initiation of a GFD.
Safety of Esophagogastroduodenoscopy within 30 Days of Myocardial Infarction: A Retrospective Cohort Study from a Canadian Tertiary Centre
Authors: Al-Ebrahim Fahad , Khan Khurram J , Alhazzani Waleed , Alnemer Ahmed , Alzahrani Abdullah , Marshall John , Armstrong David
Published: March 2016

Patients who experience gastrointestinal bleeding after myocardial infarction (MI) often have comorbidities that could place them at increased risk of complications if evaluative endoscopy were to be performed. Although esophagogastroduodenoscopy is considered to be generally safe in high-risk individuals, some post-MI patients may be more susceptible to a variety of cardiopulmonary complications. This cohort study examined cardiopulmonary safety in post-MI patients and evaluated specific predictors of complications of post-MI endoscopy.

BACKGROUND: Patients who experience myocardial infarction (MI) are at risk of gastrointestinal (GI) bleeding complications. Endoscopic evaluation may lead to cardiopulmonary complications. Guidelines and studies regarding the safety of endoscopy in this population are limited.

OBJECTIVE: To evaluate the safety of endoscopy in a retrospective cohort of post-MI patients at a Canadian tertiary centre.

METHODS: Using hospital diagnostic/procedure codes, the charts of patients meeting the inclusion criteria of having ST elevation MI or non-ST elevation MI, and GI bleeding detected at endoscopy were reviewed. The information retrieved included demographics, medical history, medications, endoscopy details and cardiopulmonary/GI events.

RESULTS: A total of 121 patients experienced an MI and underwent endoscopy within 30 days. However, only 44 met the inclusion criteria and were reviewed. The mean age of the patients was 75 years, and 55% were female. The mean hemoglobin level was 86 g/L, and 38 of 44 patients required a transfusion. Comorbidities included hypertension (82%), diabetes (46%), heart failure (55%), stroke (21%), lung disease (27%), previous MI (46%), cardiac bypass surgery (30%), history of GI bleed (25%), history of ulcer (18%) and ejection fraction <50% (48%). The median number of days to endoscopy after MI was three. Complications included seven patients with acute coronary syndrome, one with arrhythmia, one with respiratory failure, one with aspiration pneumonia and two with perforation. Age, hemoglobin level or timing of endoscopy did not significantly predict a complication.

CONCLUSIONS: Patients with GI bleeding after MI often have comorbidities and are on antiplatelet agents. Endoscopy is a valuable tool in the diagnosis and management of bleeding complications, but must be weighed against the potential risk of other complications, which in the present study occurred in more than 25% of procedures.
Complex Regional Pain Syndrome in Children: Asking the Right Questions
Authors: Goldschneider Kenneth R
Published: March 2016

BACKGROUND: Complex regional pain syndrome (CRPS) is a painful disorder without a known unifying mechanism. There are little data on which to base evaluation and treatment decisions, and what data are available come from studies involving adults; however, even that literature is relatively sparse. Developing robust research for CRPS in children is essential for the progress toward optimal treatment.

OBJECTIVES: To determine potential avenues of research in pediatric CRPS based on a review of the literature. Areas of concern include diagnostic criteria, peripheral mechanisms, central nervous system mechanisms, the role of the autonomic nervous system, possible risk factors, options for prevention and potential avenues of treatment.

METHODS: A literature review was performed and the results applied to form the hypotheses posited in the form of research questions.

RESULTS AND CONCLUSIONS: CRPS is a complicated entity that is more than a painful sensory condition. There is evidence for peripheral inflammatory and neurological changes, and reorganization in both sensory and motor cortexes. In addition, a significant motor component is frequently observed and there appear to be tangible risk factors. Many of these pieces of evidence suggest options for prevention, treatment and monitoring progress and outcome. Most of the data are derived from adult studies and need to be replicated in children. Furthermore, there may be factors unique to pediatrics due to developmental changes in neuroplasticity as well as somatic, endocrinological and emotional growth. Some of these developmental factors may shed light on the adult condition.
Canadian Digestive Health Foundation Public Impact Series 3: Irritable Bowel Syndrome in Canada. Incidence, Prevalence, and Direct and Indirect Economic Impact
Authors: Fedorak Richard N , Vanner Stephen J , Paterson William G , Bridges Ron J
Published: March 2016

The Canadian Digestive Health Foundation initiated a scientific program to assess the incidence, prevalence, mortality and economic impact of digestive disorders across Canada in 2009. The current article presents the updated findings from the study concerning irritable bowel syndrome.
Point Prevalence Study of Antibiotic Susceptibility of Genital Group B Streptococcus Isolated from Near‐Term Pregnant Women in Calgary, Alberta
Authors: Church Deirdre , Carson Julie , Gregson Dan
Published: March 2016

BACKGROUND: Genital group B streptococcus (GBS) may be transmitted from a colonized mother to her infant if appropriate intrapartum antibiotic prophylaxis is not given. A recent case of GBS neonatal sepsis occurred due to an erythromycin‐intermediate strain after empirical use of this drug as intrapartum prophylaxis.

OBJECTIVE: To determine the regional antibiotic resistance rates of genital GBS isolates to penicillin, erythromycin and clindamycin.

METHODS: A total of 309 genital GBS strains cultured from vaginal/rectal swabs were prospectively isolated and randomly selected between March and May 2011. Etest strips (bioMèrieux, France) were used to determine the minimum inhibitory concentrations to penicillin, erythromycin and clindamycin according to standard methods. All isolates that either demonstrated intermediate or full resistance to erythromycin had a D‐test performed to detect inducible resistance to clindamycin. The resistance mechanism for each isolate was inferred from its antibiogram phenotype.

RESULTS: All genital GBS isolates were susceptible to penicillin, but high rates of resistance were found to both erythromycin (25%) and clindamycin (22%), mainly due to acquisition of erythromycin ribosomal methylation genes (erm) that result in the MLSB resistance phenotype. Most often the MLSB resistance phenotype was constitutive (MLSB‐C; 14.2%) rather than inducible (MLSB‐I; 8.1%), and an efflux mechanism (msrA; 3%) was much less common.

DISCUSSION: The present article is the first point prevalence study of genital GBS antibiogram profile that has been reported from a Canadian health care region. The high rates of resistance of genital GBS to both erythromycin and clindamycin is mainly due to the acquisition and spread of erm genes conveying the MSLB phenotype.

CONCLUSION: Changes to clinical and laboratory practice in the Calgary, Alberta, region were made to prevent additional cases of neonatal GBS sepsis due to inappropriate intrapartum antibiotic prescription.
Clinical Significance of Autoantibodies to P53 Protein in Patients with Autoimmune Liver Diseases
Authors: Himoto Takashi , Yoneyama Hirohito , Kurokohchi Kazutaka , Inukai Michio , Masugata Hisashi , Goda Fuminori , Haba Reiji , Watanabe Seishiro , Senda Shoichi , Masaki Tsutomu
Published: March 2016

Mutations in thep53gene leading to conformational changes in the p53 protein have been well established in many human cancers. Conformational changes and/or cellular accumulation of the protein may induce an immune response, resulting in circulating autoantibodies to p53, which have been documented in several types of cancers. Although rarely associated with autoimmune disease, a few reports have documented titres of anti-p53 autoantibodies in patients with autoimmune hepatitis and primary biliary cirrhosis. The clinical relevance of circulating autoantibodies to p53, therefore, remains unclear. Accordingly, this study aimed to examine the prevalence and clinical relevance of anti-p53 autoantibodies in patients with selected autoimmune liver diseases.

BACKGROUND: Autoantibodies to p53 (anti-p53) are rarely present in the sera of patients with autoimmune diseases or the sera of patients with malignancies.

OBJECTIVE: To examine the prevalence of anti-p53 in patients with autoimmune liver disease including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), AIH/PBC overlap syndrome (AIH/PBC OS) and primary sclerosing cholangitis (PSC), and to determine the clinical significance of anti-p53 in autoimmune liver diseases.

METHODS: Forty patients with AIH, 41 patients with PBC, eight patients with AIH/PBC OS and five patients with PSC were enrolled. Anti-p53 and antibodies to double-stranded DNA (anti-ds-DNA) were analyzed using commercially available ELISA kits. Demographic, laboratory and histological data were compared between the AIH groups seropositive and seronegative for anti-p53.

RESULTS: Six of 40 (15.0%) patients with AIH and four of eight (50.0%) patients with AIH/PBC OS were positive for anti-p53. One of 41 (2.4%) patients with PBC was also positive for anti-p53, but all five patients with PSC were negative, indicating a significantly higher prevalence of anti-p53 in patients with AIH or AIH/PBC OS compared with patients with PBC. None of the AIH patients positive for anti-p53 progressed to hepatic failure or relapsed after immunosuppressive treatment. Titres of anti-ds-DNA in patients with AIH and AIH/PBC OS significantly correlated with titres of anti-p53 (r=0.511; P=0.0213).

CONCLUSION: The emergence of anti-p53 is likely to be useful for discriminating AIH or AIH/PBC OS from PBC and helpful for predicting favourable prognoses in patients with AIH. DNA damage may trigger the production of anti-p53 in patients with AIH or AIH/PBC OS.
Predictive Factors of Lamivudine Treatment Success in a Hepatitis B Virus-Infected Pediatric Cohort: A 10-Year Study
Authors: Yousef Yasmine , Béland Kathie , Mas Emmanuel , Lapierre Pascal , Bouron Dal Soglio Dorothée , Alvarez Fernando
Published: March 2016

BACKGROUND: Hepatitis B virus (HBV) infections are responsible for the development of chronic hepatitis in 400 million people worldwide. Currently, no consensus exists as to when treatment should be initiated for pediatric patients.

OBJECTIVES: To evaluate the risks and predictive factors of success of lamivudine treatment in children with chronic, active HBV infection.

METHODS: Forty-three children (22 male, median age 9.6 years) chronically infected with HBV and treated between 1998 and 2008 at CHU Ste-Justine (Montreal, Quebec) were included in the present chart review study. Inclusion criteria were detectable hepatitis B surface antigen and hepatitis B e antigen (HBeAg), minimum serum alanine aminotransferase (ALT) level of two times the upper limit of normal and detectable serum HBV DNA for at least three months. Patients received lamivudine for a minimum of six months (median 14 months). Genotyping was performed.

RESULTS: Lamivudine treatment was effective in 35% of cases (15 of 43) and overall virological response (during or after treatment) was achieved in 51% of patients. Three patients harboured suspected lamivudine-resistant mutations and five progressed to HBeAg-chronic HBV. Predictive factors for success of treatment were: younger age at beginning of treatment (P=0.05), elevated ALT levels throughout treatment duration (P=0.003) and loss of HBeAg during treatment (P=0.016). Asian origin did not affect treatment success or spontaneous viral control during follow-up. HBV genotype did not influence treatment success.

CONCLUSIONS: Lamivudine treatment in a carefully selected cohort of HBV patients demonstrated a good rate of success and low incidence of mutation. Younger age at the beginning of treatment and high ALT levels during treatment predicted a positive outcome.
A Survey of the Practice of After-Hours and Emergency Endoscopy in Canada
Authors: Muthiah Karuppan Chetty , Enns Robert , Armstrong David , Noble Angela , Gray James , Sinclair Paul , Colacino Palma , Singh Harminder
Published: March 2016

OBJECTIVE: To determine staffing and practice patterns for after-hours endoscopy service in Canada

METHODS: A link to a web-based survey was sent by e-mail to all clinical members of the Canadian Association of Gastroenterology in February 2011. A priori, it was planned to compare variations in practice among gastroenterologists (GIs) performing endoscopy in different regions of Canada, between pediatric and adult GIs, and between university and community hospitals.

RESULTS: Of 422 potential respondents, 168 (40%) responded. Of the 139 adult GIs, 61% performed after-hours endoscopy in the endoscopy suite where daytime procedures were performed, 62% had a trained endoscopy nurse available for all procedures, 38% had access to propofol sedation, 12% reprocessed the endoscopes themselves or with the help of a resident, 4% had out-of-hospital patients come directly to their endoscopy suite and 53% were highly satisfied. The adult endoscopists practising at community hospitals were more likely to have an anesthetist attend the procedure. Regional differences were noted, with more involvement of anesthetists (13%) and availability of propofol (50%) in Ontario, more frequent reprocessing of endoscopes in the central reprocessing units in British Columbia (78%) and almost universal availability of a trained endoscopy nurse (96%) with concomitant higher endoscopist satisfaction (84% highly satisfied) in Alberta.

CONCLUSIONS: More than one-third of surveyed endoscopists across the country do not have a trained endoscopy nurse to assist in after-hours endoscopy – the time period when urgent patients often present and typically require therapeutic endoscopic interventions. There are significant regional differences in the practice of after-hours endoscopy in Canada.
Breakthrough Filamentous Fungal Infections in Pediatric Hematopoetic Stem Cell Transplant and Oncology Patients Receiving Caspofungin
Authors: Morris Shaun K , Allen Upton D , Gupta Sumit , Richardson Susan E
Published: March 2016

BACKGROUND: Caspofungin is an echinocandin class antifungal medication that is commonly used empirically in immunocompromised patients at high risk for invasive fungal disease.

OBJECTIVE: To describe the clinical characteristics of breakthrough fungal infections in pediatric hematopoetic stem cell transplant recipients, and oncology and hematology patients receiving caspofungin.

METHODS: A five‐year retrospective review, from 2004 through 2008, of all cases of proven invasive filamentous fungal infection of children admitted to The Hospital for Sick Children (Toronto, Ontario) was conducted. A breakthrough infection was defined as new onset of symptoms that were later proven to be due to an invasive mold infection on day 3 or later after initiation of caspofungin therapy.

RESULTS: Six confirmed positive cultures (Aspergillus fumigatus [two cases], Aspergillus niger, Fusarium oxysporum, Alternaria infectoria and Rhizomucor pusillus) met the criteria for breakthrough filamentous mold infection while on caspofungin therapy. Underlying immunocompromising conditions included acute lymphoblastic leukemia (two cases), acute myeloid leukemia (two cases), Burkitt’s lymphoma and aplastic anemia. Four of the patients underwent a hematopoetic stem cell transplant. All patients received a lipid amphotericin B product as part of their treatment for breakthrough infection. Five patients also received voriconazole and one received posaconazole. Four of the six patients died and two responded with a clinical and microbiological cure.

DISCUSSION: There are few descriptions of breakthrough fungal infections in pediatric patients receiving caspofungin. The six cases presented here, all microbiologically proven, are likely only a fraction of the total number of possible breakthrough invasive fungal infections that occured over the study period.

CONCLUSION: Clinicians must remain aware that breakthrough fungal infections by species not covered by particular antifungals, including caspofungin, do occur and may have poor outcomes.
Primary Endobronchial Plasmacytoma Involving Local Lymph Nodes and Presenting with Rare Immunoglobulin G Lambda Monoclonal Gammopathy
Authors: Wei Sen , Li Xin , Song Zuoqing , Zhao Honglin , Qiu Xiaomin , Gong Lei , Chen Jun , Zhou Qinghua
Published: March 2016

Extramedullary plasmacytoma occurring as a primary pulmonary lesion is rare. The present report describes a 42‐year‐old Chinese man diagnosed with primary pulmonary plasmacytoma following left lower lobectomy. Of note, an extremely rare immunoglobulin G lambda paraprotein was documented in the patient’s serum by immunofixation electrophoresis. The patient has been well, showing no local recurrence or multifocal disease during a 15‐month follow‐up.
Supra‐Additive Expression of Interleukin‐6, Interleukin‐8 and Basic Fibroblast Growth Factor in Vascular Smooth Muscle Cells Following Coinfection with Chlamydia pneumoniae and Cytomegalovirus as a Novel Link between Infection and Atherosclerosis
Authors: Prochnau Dirk , Straube Eberhard , Figulla Hans-Reiner , Rödel Jürgen
Published: March 2016

BACKGROUND: Chlamydia pneumoniae and human cytomegalovirus (HCMV) may be involved in the pathogenesis of atherosclerosis. Prospective studies indicate an increased risk for cardiovascular events in patients with evidence of multiple infections.

OBJECTIVE: To determine whether there is a synergistic effect of coinfection with C pneumoniae and HCMV on expression of selected growth factors and cytokines.

METHODS: The production of interleukin (IL)‐6, IL‐8, basic fibroblast growth factor (bFGF), platelet‐derived growth factor (PDGF), and ‘regulated on activation normal T‐cell expressed and secreted’ (RANTES) was measured in coinfected aortic smooth muscle cells (AoSMC).

RESULTS: Using reverse transcription polymerase chain reaction and immunoassays, it was demonstrated that the expression of IL‐6, IL‐8, RANTES and bFGF was stimulated in a dose‐ and time‐dependent fashion in C pneumoniae and also in HCMV‐infected cultures. In contrast, the expression of PDGF‐AA was only stimulated following HCMV infection. Coinfection with C pneumoniae and HCMV resulted in a supra‐additive stimulation of IL‐6 (30% increased expression, P≤0.05) at 48 h, IL‐8 (137% increased expression, P≤0.001) at 24 h and bFGF (209% increased expression, P≤0.01) at 48 h following infection.

CONCLUSIONS: The findings of the present study show that C pneumoniae and HCMV are able to act in synergy in coinfected AoSMC. The supra‐additive induction of AoSMC growth factors and cytokines indicates a novel molecular link between infection and vascular disease development.
Living with Difference: Exploring the Social Self of Adolescents with Chronic Pain
Authors: Forgeron Paula A , Evans Joan , McGrath Patrick J , Stevens Bonnie , Finley G Allen
Published: March 2016

BACKGROUND: Chronic pain negatively affects an adolescent’s life; however, little is known about the social impact of chronic pain for adolescents. More is known about the general peer relationships of adolescents with chronic pain than their close friendships. Close friendships begin to take on more importance during adolescence as these relationships facilitate the development of an adolescent’s sense of personal identity and increasing independence from family influences. Thus, chronic pain may create friendship challenges for adolescents beyond those typically experienced during this developmental trajectory, which may negatively impact their abilities to secure social support.

OBJECTIVES: To better understand the challenges adolescents with chronic pain face with regard to their friendships.

METHODS: An interpretative phenomenological study using individual interviews was conducted.

RESULTS: Two themes emerged. ‘Rethinking the self with pain’ describes the intrusive nature of chronic pain, challenging the participants to rethink the way they view themselves and their place within their social network. ‘Rethinking friendships’ describes the interpretation of their friends’ reactions to their chronic pain condition, which led to these adolescents spending more time by themselves, and feeling misunderstood and unsupported.

CONCLUSIONS: The impact of chronic pain on the adolescent as an individual as well as the responses of close friends and others within their social network resulted in the development of new friendship needs. However, the adolescents were not always able to secure these new friendship needs. Their experiences suggest factors within friendships that may be ameliorated by interventions, thus maintaining and strengthening their close friendships.
A Systematic Review of the Effectiveness of Knowledge Translation Interventions for Chronic Noncancer Pain Management
Authors: Ospina Maria B , Taenzer Paul , Rashiq Saifee , MacDermid Joy C , Carr Eloise , Chojecki Dagmara , Harstall Christa , Henry James L
Published: March 2016

BACKGROUND: Reliable evidence detailing effective treatments and management practices for chronic noncancer pain exists. However, little is known about which knowledge translation (KT) interventions lead to the uptake of this evidence in practice.

OBJECTIVES: To conduct a systematic review of the effectiveness of KT interventions for chronic noncancer pain management.

METHODS: Comprehensive searches of electronic databases, the gray literature and manual searches of journals were undertaken. Randomized controlled trials, controlled clinical trials and controlled before‐and‐after studies of KT interventions were included. Data regarding interventions and primary outcomes were categorized using a standard taxonomy; a risk‐of‐bias approach was adopted for study quality. A narrative synthesis of study results was conducted.

RESULTS: More than 8500 titles and abstracts were screened, with 230 full‐text articles reviewed for eligibility. Nineteen studies were included, of which only a small proportion were judged to be at low risk of bias. Interactive KT education for health care providers has a positive effect on patients’ function, but its benefits for other health provider‐ and patient‐related outcomes are inconsistent. Interactive education for patients leads to improvements in knowledge and function. Little research evidence supports the effectiveness of structural changes in health systems and quality improvement processes or coordination of care.

CONCLUSIONS: KT interventions incorporating interactive education in chronic noncancer pain led to positive effects on patients’ function and knowledge about pain. Future studies should provide implementation details and use consistent theoretical frameworks to better estimate the effectiveness of such interventions.
Predictors of Early Rebleeding after Endoscopic Therapy in Patients with Nonvariceal Upper Gastrointestinal Bleeding Secondary to High-Risk Lesions
Authors: Maggio Davide , Barkun Alan N , Martel Myriam , Elouali Sara , Gralnek Ian M , the REASON investigators
Published: March 2016

BACKGROUND: In an era of increasingly shortened admissions, data regarding predictors of early rebleeding among patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) exhibiting high-risk stigmata (HRS) having undergone endoscopic hemostasis are lacking.

OBJECTIVES: To determine predictors of early rebleeding, defined as rebleeding before completion of recommended 72 h intravenous proton pump inhibitor infusion postendoscopic hemostasis.

METHODS: Data from a national registry of patients with upper gastrointestinal bleeding (the REASON registry) were accessed. Univariable and multivariable analyses were sequentially performed to identify significant independent predictors among a comprehensive list of clinical and laboratory characteristics.

RESULTS: Overall, 393 patients underwent endoscopic hemostasis for NVUGIB with HRS. Forty patients rebled ≤72 h thereafter (32.5% female, mean [± SD] age 70.2±11.8 years, 2.88±2.11 comorbidities), while 21 rebled later (38.1% female, mean 70.5±14.1 years of age, 2.62±2.06 comorbidities). Hematemesis or bright red blood per nasogastric tube aspirate was identified as the sole independent significant predictor of early rebleeding versus later among both NVUGIB and, more specifically, patients with peptic ulcer bleeding (OR 7.94 [95% CI 1.80 to 35.01]; P<0.01, and OR 8.41 [95% CI 1.54 to 46.10]; P=0.014, respectively).

CONCLUSIONS: When attempting to determine the optimal duration of pharmacotherapy and timing of discharge for patients following endoscopic hemostasis for NVUGIB with HRS, it is noteworthy that individuals who present with hematemesis or bright red blood per nasogastric tube aspirate are at particularly high risk for rebleeding within the first 72 h.
Duration of Antibiotic Therapy for Critically Ill Patients with Bloodstream Infections: A Retrospective Cohort Study
Authors: Havey Thomas C , Fowler Robert A , Pinto Ruxandra , Elligsen Marion , Daneman Nick
Published: March 2016

BACKGROUND: The optimal duration of antibiotic treatment for bloodstream infections is unknown and understudied.

METHODS: A retrospective cohort study of critically ill patients with bloodstream infections diagnosed in a tertiary care hospital between March 1, 2010 and March 31, 2011 was undertaken. The impact of patient, pathogen and infectious syndrome characteristics on selection of shorter (≤10 days) or longer (>10 days) treatment duration, and on the number of antibiotic‐free days, was examined. The time profile of clinical response was evaluated over the first 14 days of treatment. Relapse, secondary infection and mortality rates were compared between those receiving shorter or longer treatment.

RESULTS: Among 100 critically ill patients with bloodstream infection, the median duration of antibiotic treatment was 11 days, but was highly variable (interquartile range 4.5 to 17 days). Predictors of longer treatment (fewer antibiotic‐free days) included foci with established requirements for prolonged treatment, underlying respiratory tract focus, and infection with Staphylococcus aureus or Pseudomonas species. Predictors of shorter treatment (more antibiotic‐free days) included vascular catheter source and bacteremia with coagulase‐negative staphylococci. Temperature improvements plateaued after the first week; white blood cell counts, multiple organ dysfunction scores and vasopressor dependence continued to decline into the second week. Among 72 patients who survived to 10 days, clinical outcomes were similar between those receiving shorter and longer treatment.

CONCLUSION: Antibiotic treatment durations for patients with bloodstream infection are highly variable and often prolonged. A randomized trial is needed to determine the duration of treatment that will maximize cure while minimizing adverse consequences of antibiotics.
The 2012 Sage Wait Times Program: Survey of Access to Gastroenterology in Canada
Authors: Leddin Desmond , Armstrong David , Borgaonkar Mark , Bridges Ronald J , Fallone Carlo A , Telford Jennifer J , Chen Ying , Colacino Palma , Sinclair Paul
Published: March 2016

BACKGROUND: Periodically surveying wait times for specialist health services in Canada captures current data and enables comparisons with previous surveys to identify changes over time.

METHODS: During one week in April 2012, Canadian gastroenterologists were asked to complete a questionnaire (online or by fax) recording demographics, reason for referral, and dates of referral and specialist visits for at least 10 consecutive new patients (five consultations and five procedures) who had not been seen previously for the same indication. Wait times were determined for 18 indications and compared with those from similar surveys conducted in 2008 and 2005.

RESULTS: Data regarding adult patients were provided by 173 gastroenterologists for 1374 consultations, 540 procedures and 293 same-day consultations and procedures. Nationally, the median wait times were 92 days (95% CI 85 days to 100 days) from referral to consultation, 55 days (95% CI 50 days to 61 days) from consultation to procedure and 155 days (95% CI 142 days to 175 days) (total) from referral to procedure. Overall, wait times were longer in 2012 than in 2005 (P<0.05); the wait time to same-day consultation and procedure was shorter in 2012 than in 2008 (78 days versus 101 days; P<0.05), but continued to be longer than in 2005 (P<0.05). The total wait time remained longest for screening colonoscopy, increasing from 201 days in 2008 to 279 days in 2012 (P<0.05).

DISCUSSION: Wait times for gastroenterology services continue to exceed recommended targets, remain unchanged since 2008 and exceed wait times reported in 2005.
Effects of Hyperbaric Oxygen on Pain‐Related Behaviours and Nitric Oxide Synthase Expression in a Rat Model of Neuropathic Pain
Authors: Han Guang , Li Lu , Meng Ling-xin
Published: March 2016

BACKGROUND: Neuropathic pain is complex, and a satisfactory therapeutic method of treatment has yet to be developed; therefore, finding a new and effective therapeutic method is an important issue in the field of neuropathic pain.

OBJECTIVE: To determine the effects of hyperbaric oxygen (HBO) on pain‐related behaviours and nitric oxide synthase (NOS) expression in a rat model of neuropathic pain.

METHODS: Forty male Sprague Dawley rats were randomly divided into five groups (eight rats per group) including control, sham operation, sciatic nerve with chronic constriction injury (CCI), HBO pretreatment (pre‐HBO) and HBO post‐treatment (post‐HBO) groups. Pain‐related behaviours and NOS expression in the spinal cord were compared among the five groups.

RESULTS: Compared with the CCI group, the mechanical withdrawal threshold was significantly increased and thermal withdrawal latency was significantly extended in the pre‐HBO and post‐HBO groups (all P<0.05). After CCI, expression of spinal neuronal NOS and inducible NOS were increased. Expression of spinal neuronal NOS and inducible NOS were significantly decreased in the pre‐HBO and post‐HBO groups compared with the CCI group (all P<0.05). Spinal eNOS expression changed very little.

DISCUSSION: HBO has been used as an effective and noninvasive method for the treatment of spinal cord injuries and high‐altitude sickness, and in immunosuppression and stem‐cell research; however, it has yet to be applied to the treatment of neuropathic pain. The present study indicated that HBO effectively increased mechanical withdrawal threshold and thermal withdrawal latency, demonstrating that HBO has therapeutic effects on neuropathic pain.

CONCLUSION: HBO inhibits pain in rats with CCI through the regulation of spinal NOS expression.
Risk of Cytomegalovirus Infection and Disease after Umbilical Cord Blood Transplantation in Children
Authors: Crisinel Pierre Alex , Duval Michel , Crisinel Delphine Thuillard , Mallette Brigitte , Bellier Nathalie , Vachon Marie-France , Dedeken Laurence , Rousseau Céline , Tapiero Bruce , Ovetchkine Philippe
Published: March 2016

BACKGROUND: Pediatric data regarding cytomegalovirus (CMV) infections in pediatric patients receiving umbilical cord blood (UCB) transplantation are sparse.

OBJECTIVE: To determine whether UCB transplantation increases the risk of CMV infection and disease compared with other graft sources.

METHODS: The medical files of patients who underwent allogeneic hematopoietic stem cell transplantation at CHU Ste‐Justine (Montreal, Quebec) from April 2000 to December 2006 were retrospectively reviewed. A Cox proportional hazard model was used to assess the effect of potential predictors of outcomes.

RESULTS: A total of 176 patients with a median age of nine years (range 0.1 to 18 years) underwent hematopoietic stem cell transplantation. The source of stem cells were UCB, bone marrow and peripheral blood stem cells in 86, 86 and four of the cases, respectively. CMV infection occurred in 29 patients (16%). At day 100 post‐transplantation, the rate of CMV infection was 13% in UCB transplant recipients (11 of 86) versus 20% in those with other sources of graft (18 of 90) (P=0.19). Positive CMV serology of the recipient and leukocyte depletion were two independent variables associated with an increased risk of CMV infection. Among infected patients, six developed CMV disease (20.7%). The rate of CMV disease one year after infection was 49% in patients who received UCB (five of 11) and 6% in others (one of 18). This difference was significant by univariate (P=0.01) but not by multivariate analysis.

CONCLUSION: In the setting of the current study, with a moderate CMV infection rate (16.5%), UCB transplantation did not appear to increase the risk of CMV infection and disease.
Controlled‐Release Oxycodone and Naloxone in the Treatment of Chronic Low Back Pain: A Placebo‐Controlled, Randomized Study
Authors: Cloutier C , Taliano J , O’Mahony W , Csanadi M , Cohen G , Sutton I , Sinclair D , Awde M , Henein S , Robinson L , Eisenhoffer J , Piraino PS , Harsanyi Z , Michalko KJ
Published: March 2016

BACKGROUND: For Canadian regulatory purposes, an analgesic study was required to complement previously completed, pivotal studies on bowel effects and analgesia associated with controlled‐release (CR) oxycodone/CR naloxone.

OBJECTIVES: To compare the analgesic efficacy and safety of CR oxycodone/CR naloxone versus placebo in patients with chronic low back pain.

METHODS: Patients requiring opioid therapy underwent a two‐ to seven‐day opioid washout before being randomly assigned to receive either 10 mg/5 mg CR oxycodone/CR naloxone or placebo every 12 h, titrated weekly according to efficacy and tolerability to 20 mg/10 mg, 30 mg/15 mg or 40 mg/20 mg every 12 h. After four weeks, patients crossed over to the alternative treatment for an additional four weeks. Acetaminophen/codeine (300 mg/30 mg every 4 h to 6 h as needed) was provided as rescue medication.

RESULTS: Of the 83 randomized patients, 54 (65%) comprised the per‐protocol population. According to per‐protocol analysis, CR oxycodone/CR naloxone resulted in significantly lower mean (± SD) pain scores measured on a visual analogue scale (48.6±23.1 mm versus 55.9±25.4 mm; P=0.0296) and five‐point ordinal pain intensity scores (2.1±0.8 versus 2.4±0.9; P=0.0415) compared with placebo. After the double‐blinded phase, patients and investigators both preferred CR oxycodone/CR naloxone over placebo. These outcomes continued in the 79% of patients who chose to continue receiving CR oxycodone/CR naloxone in a six‐month, open‐label evaluation.

CONCLUSIONS: In patients complying with treatment as per protocol, CR oxycodone/CR naloxone was effective for the management of chronic low back pain of moderate or severe intensity.

Erratum to “Controlled-Release Oxycodone and Naloxone in the Treatment of Chronic Low Back Pain: A Placebo-Controlled, Randomized Study”dx.doi.org/10.1155/2013/407817
The Endoscopy Global Rating Scale – Canada: Development And Implementation of a Quality Improvement Tool
Authors: MacIntosh Donald , Dubé Catherine , Hollingworth Roger , van Zanten Sander Veldhuyzen , Daniels Sandra , Ghattas George
Published: March 2016

BACKGROUND: Increasing use of gastrointestinal endoscopy, particularly for colorectal cancer screening, and increasing emphasis on health care quality highlight the need for endoscopy facilities to review the quality of the service they offer.

OBJECTIVE: To adapt the United Kingdom Global Rating Scale (UK-GRS) to develop a web-based and patient-centred tool to assess and improve the quality of endoscopy services provided.

METHODS: Based on feedback from 22 sites across Canada that completed the UK endoscopy GRS, and integrating results of the Canadian consensus on safety and quality indicators in endoscopy and other Canadian consensus reports, a working group of endoscopists experienced with the GRS developed the GRS-Canada (GRS-C).

RESULTS: The GRS-C mirrors the two dimensions (clinical quality and quality of the patient experience) and 12 patient-centred items of the UK-GRS, but was modified to apply to Canadian health care infrastructure, language and current practice. Each item is assessed by a yes/no response to eight to 12 statements that are divided into levels graded D (basic) through A (advanced). A core team consisting of a booking clerk, charge nurse and the physician responsible for the unit is recommended to complete the GRS-C twice yearly.

CONCLUSION: The GRS-C is intended to improve endoscopic services in Canada by providing endoscopy units with a straightforward process to review the quality of the service they provide.
Role of Monoclonal Antibodies in the Treatment of Asthma
Authors: O’Byrne Paul M
Published: March 2016

BACKGROUND: Patients with severe refractory asthma represent a small subset of the asthmatic population (between 5% and 10% of all patients) but are the greatest burden to the health care system. New treatment approaches developed to manage some of the phenotypes of severe refractory asthma have included humanized monoclonal antibodies (hMabs).

OBJECTIVE: To review the evidence and ascertain whether hMabs provide clinical benefit to patients with severe refractory asthma.

METHODS: Studies that examined the efficacy of hMabs against immunoglobulin (Ig) E, tumour necrosis factor-alpha, interleukin (IL)-5, and IL-4/IL-13 in patients with severe refractory asthma were reviewed and summarized.

RESULTS: Treatment with anti-IgE improved asthma control and reduced severe exacerbations in patients with severe asthma and elevated serum IgE levels. Treatments with hMabs that block tumour necrosis factor-alpha are unlikely to be useful in asthma treatment. In contrast, hMabs that block IL-5 have consistently shown benefit in reducing severe exacerbations in patients with severe refractory asthma with persistent eosinophilia. Finally, hMabs that block IL-13 may provide benefit in patients with elevated blood periostin levels.

DISCUSSION: hMabs that block IgE are approved for the treatment of allergic asthma. It is likely that blocking IL-5 will also provide benefit in patients with severe asthma with persistent eosinophilia. These studies have emphasized the importance of careful phenotyping of patients with severe refractory asthma before embarking on treatment with hMabs.