bluuebunny/crossref_metadata_2025 huggingface dataset:
Blastomycosis Presenting as Multiple Splenic Abscesses: Case Report and Review of the Literature
Authors: Al-Nassar Sami , MacNair Tracy , Lipschitz Jeremy , Greenberg Howard , Trepman Elly , Hamza Sate , Embil John M
Published: March 2016

A 31‐year‐old Canadian Aboriginal man from northwestern Ontario presented with left upper quadrant pain and a tender left upper quadrant mass. Evaluation with a computed tomography scan showed multiple lesions within the spleen, a collection between the splenic tip and splenic flexure of the colon, and several small adrenal lesions. Computed tomographic‐guided needle biopsy showed necrotizing granulomatous inflammation and multinucleated giant cells. Gomori’s methenamine silver stain showed broad‐based budding yeast consistent with Blastomyces dermatitidis. Abdominal symptoms resolved after two months of oral itraconazole. Multiple splenic abscesses are a rare presentation of blastomycosis and should be considered in the differential diagnosis of left upper quadrant abdominal pain in a patient with a history of travel or residence in a region endemic for B dermatitidis.
Strategies for the Use of Oseltamivir and Zanamivir during Pandemic Outbreaks
Authors: Hansen Elsa , Day Troy , Arino Julien , Wu Jianhong , Moghadas Seyed M
Published: March 2016

BACKGROUND: The use of neuraminidase inhibitors (oseltamivir and zanamivir) for the treatment of ill individuals has been an important intervention during the 2009 H1N1 pandemic. However, the emergence and spread of drug resistance remains a major concern and, therefore, optimizing antiviral strategies is crucial to retain the long‐term effectiveness of these pharmaceutical interventions.

METHODS: A dynamic model of disease transmission was developed to investigate optimal scenarios for the use of a secondary drug (eg, zanamivir). Considering both small and large stockpiles, attack rates were projected by simulating the model to identify ‘tipping points’ for switching to zanamivir as resistance to oseltamivir develops.

RESULTS: The use of a limited stockpile of zanamivir can substantially reduce the overall attack rate during pandemic outbreaks. For a reasonably large stockpile of zanamivir, it is optimal to delay the use of this drug for a certain amount of time during which oseltamivir is used as the primary drug. For smaller stockpiles, however, earlier use of zanamivir will be most effective in reducing the overall attack rate. Given a limited stockpile of zanamivir (1.8% in the Canadian plan) without replenishment, and assuming that the fraction of ill individuals being treated is maintained below 60%, the results suggest that zanamivir should be dispensed as the primary drug for thresholds of the cumulative number of oseltamivir resistance below 20%.

INTERPRETATION: Strategic use of a secondary drug becomes crucial for pandemic mitigation if vaccination and other interventions fail to sufficiently reduce disease transmission in the community. These findings highlight the importance of enhanced surveillance and clinical monitoring for rapid identification of resistance emergence and its population incidence, so that optimal timing for adaptation to the use of drugs can be achieved.
Mycobacterium Avium Paratuberculosisand the Etiology of Crohn’s Disease: A Review of the Controversy from the Clinician’s Perspective
Authors: Rosenfeld Greg , Bressler Brian
Published: March 2016

Mycobacterium avium paratuberculosis(MAP) is an obligate intracellular organism that has frequently been associated with Crohn’s disease (CD). Because CD is a chronic inflammatory condition, many researchers have speculated that an infectious agent must be the cause of CD. MAP has often been proposed to be one such agent; however, despite considerable research, the evidence remains inconclusive. Higher levels of MAP have been found in the tissues and blood of CD patients than in controls, forming the foundation for much of the research into the role of MAP in CD and the primary argument in support of a causative role for MAP in CD. MAP is a slow-growing and fastidious organism that is difficult to grow in culture and, therefore, challenging to detect in patients. As a result, there has been variability in the results of studies attempting to detect the presence of MAP in CD patients, and considerable controversy over whether this organism has a causative role in the etiology of CD. Two main hypotheses exist with respect to the role of MAP in CD. The first is that MAP is a principal cause of CD, while the second is that MAP is more prevalent because of the immune dysfunction seen in CD but does not play a causative role. Clinicians are often faced with questions regarding the role of this organism and the need to treat it. The present article attempts to provide an overview of the controversy including the nature of the mycobacterium, the difficulty in detecting it, the use of antimycobacterial agents to treat it and the effect of immunosuppressive agents – all from a clinician’s perspective. Although the role of MAP in CD remains controversial and an area of considerable research, it is currently only of academic interest because there is no clinically useful test to identify the presence of the organism, and no evidence to support the use of antibiotics to eradicate it for the treatment of CD.
Diagnostic Evaluation and Management of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Practice Guideline
Authors: Mehta Sanjay , Helmersen Doug , Provencher Steeve , Hirani Naushad , Rubens Fraser D , De Perrot Marc , Blostein Mark , Boutet Kim , Chandy George , Dennie Carole , Granton John , Hernandez Paul , Hirsch Andrew M , Laframboise Karen , Levy Robert D , Lien Dale , Martel Simon , Shoemaker Gerard , Swiston John , Weinkauf Justin
Published: March 2016

BACKGROUND: Pulmonary embolism is a common condition. Some patients subsequently develop chronic thromboembolic pulmonary hypertension (CTEPH). Many care gaps exist in the diagnosis and management of CTEPH patients including lack of awareness, incomplete diagnostic assessment, and inconsistent use of surgical and medical therapies.

METHODS: A representative interdisciplinary panel of medical experts undertook a formal clinical practice guideline development process. A total of 20 key clinical issues were defined according to the patient population, intervention, comparator, outcome (PICO) approach. The panel performed an evidence-based, systematic, literature review, assessed and graded the relevant evidence, and made 26 recommendations.

RESULTS: Asymptomatic patients postpulmonary embolism should not be screened for CTEPH. In patients with pulmonary hypertension, the possibility of CTEPH should be routinely evaluated with initial ventilation/ perfusion lung scanning, not computed tomography angiography. Pulmonary endarterectomy surgery is the treatment of choice in patients with surgically accessible CTEPH, and may also be effective in CTEPH patients with disease in more ‘distal’ pulmonary arteries. The anatomical extent of CTEPH for surgical pulmonary endarterectomy is best assessed by contrast pulmonary angiography, although positive computed tomography angiography may be acceptable. Novel medications indicated for the treatment of pulmonary hypertension may be effective for selected CTEPH patients.

CONCLUSIONS: The present guideline requires formal dissemination to relevant target user groups, the development of tools for implementation into routine clinical practice and formal evaluation of the impact of the guideline on the quality of care of CTEPH patients. Moreover, the guideline will be updated periodically to reflect new evidence or clinical approaches.
The Ontario Universal Typing of Tuberculosis (OUT‐TB) Surveillance Program – What It Means to You
Authors: Bolotin Shelly , Alexander David C , Guthrie Jennifer L , Drews Steven J , Jamieson Frances
Published: March 2016

BACKGROUND: Tuberculosis (TB) is a serious disease that is transmitted primarily by the airborne route. Effective disease control and outbreak management requires the timely diagnosis, isolation and treatment of infected individuals with active disease; contact tracing to identify secondary cases likely to benefit from treatment of latent infection; and laboratory identification or confirmation of epidemiologically linked cases. TB genotyping enables the comparison of Mycobacterium tuberculosis complex (MTBC) strains and the identification of cases that may or may not be linked. The increased availability of molecular methods for genotyping has allowed for greater discrimination of MTBC strains and greatly enhanced understanding of TB transmission patterns.

OBJECTIVE: To improve TB surveillance and control in Ontario, the Public Health Laboratories of the Ontario Agency for Health Protection and Promotion has introduced the Ontario Universal Typing of Tuberculosis (OUT‐TB) Surveillance Program.

METHODS: The first isolate from every new TB case will be genotyped with two rapid molecular methods: spoligotyping and mycobacterial interspersed repetitive unit‐variable‐number tandem repeat typing. MTBC isolates with nonunique genotypes and, thus, potentially linked to other TB cases, will also be genotyped by IS6110 restriction fragment length polymorphism analysis.

CONCLUSION: By providing TB control programs using these new genotyping tools, and using traditional and new case investigation methods (eg, social network analysis), this new program will provide a clearer picture of TB in Ontario, and permit more effective use of public health resources and improve disease control.
Parenteral Nutrition-Associated Hyperglycemia in Noncritically Ill Inpatients Is Associated with Higher Mortality
Authors: Sarkisian Sofia , Fenton Tanis R , Shaheen Abdel Aziz , Raman Maitreyi
Published: March 2016

BACKGROUND: Hyperglycemia is a marker of poor clinical outcomes in studies evaluating hospitalized critically ill patients.

OBJECTIVES: To identify whether glycemic control is associated with health outcomes including acute coronary events, renal failure, infection, hospital length of stay, intensive care unit (ICU) admission, sepsis and mortality in noncritically ill patients administered parenteral nutrition (PN), and to compare the current standard of care for glucose monitoring at the Foothills Medical Centre (Calgary, Alberta) with the 2009 American Society of Parenteral and Enteral Nutrition guidelines.

METHODS: A retrospective chart review of 100 adult (18 years of age or older) non-ICU inpatients who received PN for seven days or longer at the Foothills Medical Centre was conducted.

RESULTS: Seventeen patients (17%) had a mean blood glucose level of 10.0 mmol/L or greater. PN patients with a mean blood glucose level of 10 mmol/L or greater had a higher rate of mortality than patients with a mean blood glucose level of less than 10 mmol/L (OR 7.22; 95% CI 1.08 to 48.29; P=0.042). Hyperglycemia was independently and significantly associated with mortality when adjusted for age and sex. Acute coronary events, renal failure, infection, hospital length of stay, ventilator use and ICU admissions were not associated with hyperglycemia. Only one-half of those with hyperglycemia, and none of the patients in the euglycemic group, received adequate glucose monitoring during the first two days of PN.

CONCLUSION: Hyperglycemia in noncritically ill inpatients receiving PN was found to be a risk factor for increased mortality.
Analysis of Complaints to a Tertiary Care Pain Clinic Over a Nine‐Year Period
Authors: Mailis-Gagnon Angela , Nicholson Keith , Chaparro Luis
Published: March 2016

BACKGROUND: The present study is the result of an internal audit and examines the profiles of complainants and the sources and nature of complaints toward the staff in a tertiary care pain clinic, the Comprehensive Pain Program of the Toronto Western Hospital in Toronto, Ontario.

METHODS: All sources of complaints over a nine‐year period were reviewed, which included the following: Toronto Western Hospital Patient Relations (PR) records, with a subset of the files qualitatively analyzed in depth regarding the nature of complaints and complainants; complaints that bypassed PR and were addressed directly to the program director against members of the staff; complaints to the College of Physicians and Surgeons of Ontario; and complaints recorded anonymously at rateMDs.com.

RESULTS: Although the prevalence of PR complaints was very low (1.73 complaints per 1000 visits), several other sources of complaints were identified. The typical complainant was a Canadian‐born woman acting on her behalf or on behalf of a family member. More than one‐half of the complaints were directed against the physicians regarding their opinion of psychological factors augmenting the patient’s presentation and/or inappropriate use of opioids. Defensive techniques instituted by the Comprehensive Pain Program staff in reaction to the complaints are discussed, and pertinent literature is reviewed.

CONCLUSION: The present study is the first to examine the nature of complaints and complainants from a Canadian pain clinic. Further studies are needed to explore the complex issues of patient and staff interactions, and complaints in the era of ‘patient‐centred care’.
Antifungal Agents for the Treatment of Systemic Fungal Infections in Children
Authors: Allen UD
Published: March 2016

Traditionally, the mainstay of systemic antifungal therapy has been amphotericin B deoxycholate (conventional amphotericin B). Newer agents have been developed to fulfill special niches and to compete with conventional amphotericin B by virtue of having more favourable toxicity profiles. Some agents have displaced conventional amphotericin B for the treatment of specific fungal diseases. For example, voriconazole has emerged as the preferred treatment for invasive pulmonary aspergillosis. This notwithstanding, conventional amphotericin B remains a useful agent for the treatment of paediatric fungal infections. Knowledge of the characteristics of the newer agents is important, given the increasing numbers of patients who are being treated with these drugs. Efforts need to be directed at research aimed at generating paediatric data where these are lacking. The antifungal agents herein described are most often used as monotherapy regimens because there is no uniform consensus on the value of combination therapy, except for specific scenarios.
IBD 2009: Emerging Research Frontiers on the Path to a Cure
Authors: Steinhart A Hillary , Tolomiczenko G
Published: March 2016

The Crohn’s and Colitis Foundation of Canada (CCFC) hosted a research symposium in April 2009. The current article presents short synopses of the presentations given at that symposium. Invitees included CCFC‐funded clinician‐scientists and researchers, research administrators and international leaders in inflammatory bowel disease research. Research challenges were outlined while acknowledging advances made in several domains relevant to informing the search for cures. Following the scientific presentations, discussions endorsed current activities of the CCFC and supported the creation of a new pediatric inflammatory bowel disease initiative.
Canadian Thoracic Society Asthma Management Continuum – 2010 Consensus Summary for Children Six Years of Age and Over, and Adults
Authors: Lougheed M Diane , Lemière Catherine , Dell Sharon D , Ducharme Francine M , FitzGerald J Mark , Leigh Richard , Licskai Chris , Rowe Brian H , Bowie Dennis , Becker Allan , Boulet Louis-Philippe
Published: March 2016

BACKGROUND/OBJECTIVE: To integrate new evidence into the Canadian Asthma Management Continuum diagram, encompassing both pediatric and adult asthma.

METHODS: The Canadian Thoracic Society Asthma Committee members, comprised of experts in pediatric and adult respirology, allergy and immunology, emergency medicine, general pediatrics, family medicine, pharmacoepidemiology and evidence‐based medicine, updated the continuum diagram, based primarily on the 2008 Global Initiative for Asthma guidelines, and performed a focused review of literature pertaining to key aspects of asthma diagnosis and management in children six years of age and over, and adults.

RESULTS: In patients six years of age and over, management of asthma begins with establishing an accurate diagnosis, typically by supplementing medical history with objective measures of lung function. All patients and caregivers should receive self‐management education, including a written action plan. Inhaled corticosteroids (ICS) remain the first‐line controller therapy for all ages. When asthma is not controlled with a low dose of ICS, the literature supports the addition of long‐acting beta2‐agonists in adults, while the preferred approach in children is to increase the dose of ICS. Leukotriene receptor antagonists are acceptable as second‐line monotherapy and as an alternative add‐on therapy in both age groups. Anti‐immunoglobulin E therapy may be of benefit in adults, and in children 12 years of age and over with difficult to control allergic asthma, despite high‐dose ICS and at least one other controller.

CONCLUSIONS: The foundation of asthma management is establishing an accurate diagnosis based on objective measures (eg, spirometry) in individuals six years of age and over. Emphasis is placed on the similarities and differences between pediatric and adult asthma management approaches to achieve asthma control.
The Natural History of Inflammatory Bowel Disease and Primary Sclerosing Cholangitis after Liver Transplantation – a Single-Centre Experience
Authors: Moncrief Karli J , Savu Anamaria , Ma Mang M , Bain Vince G , Wong Winnie W , Tandon Puneeta
Published: March 2016

OBJECTIVE: To describe the natural history of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) after liver transplant, the predictors of PSC and IBD recurrence, and the interaction of these disease processes.

METHODS: Data regarding patients who received liver transplants for PSC at the University of Alberta Hospital (Edmonton, Alberta) from 1989 to 2006 were retrospectively reviewed. Recurrent PSC (rPSC) was defined by the Mayo Clinic criteria. Cox proportional hazards modelling and Kaplan-Meier statistics were used.

RESULTS: Fifty-nine patients were studied, with a median follow-up of 68 months. A total of 71.2% of patients were diagnosed with IBD pre-transplant. Clinical IBD severity post-transplant compared with severity pretransplant was unchanged in 67%, worse in 26.5% and improved in 6.1% of patients. Twenty-five per cent of patients developed rPSC post-transplant. The occurrence of at least one episode of acute cellular rejection (hazard ratio 5.7; 95% CI 1.3 to 25.8) and cytomegalovirus mismatch (hazard ratio 4.2; 95% CI 1.1 to 15.4) were found to be significant predictors of rPSC. Although not statistically significant, there was no rPSC in patients without pre- or post-transplant IBD, and in only one patient with a colectomy. Actuarial patient survival rates at one, five and 10 years post-transplant were 97%, 86% and 79%, respectively. Although a significant proportion of patients experienced worsening IBD post-transplantation, the presence or severity of IBD did not influence rPSC or patient survival.

CONCLUSION: Acute cellular rejection and cytomegalovirus mismatch were both identified as independent predictors of rPSC. The impact of steroids and the ideal immunosuppressive regimen for the control of both IBD and PSC post-transplant requires further examination in prospective studies.
Challenges in Initiating Antiretroviral Therapy in 2010
Authors: Tremblay Cécile L , Baril Jean-Guy , Fletcher David , Kilby Donald , MacPherson Paul , Shafran Stephen D , Tyndall Mark W
Published: March 2016

Many clinical trials have shown that initiating antiretroviral therapy (ART) at higher rather than lower CD4 T cell‐positive counts results in survival benefit. Early treatment can help prevent end‐organ damage associated with HIV replication and can decrease infectivity. The mainstay of treatment is either a non‐nucleoside reverse transcriptase inhibitor or a ritonavir‐boosted protease inhibitor in combination with two nucleoside reverse transcriptase inhibitors. While effective at combating HIV, ART can produce adverse alterations of lipid parameters, with some studies suggesting a relationship between some anti‐retroviral agents and cardiovascular disease. As the HIV‐positive population ages, issues such as hypertension and diabetes must be taken into account when initiating ART. Adhering to ART can be difficult; however, nonoptimal adherence to ART can result in the development of resistance; thus, drug characteristics and the patient’s preparedness to begin therapy must be considered. Reducing the pill burden through the use of fixed‐dose antiretroviral drug combinations can facilitate adherence.
Mycophenolate Mofetil for the Treatment of Autoimmune Hepatitis in Patients Refractory or Intolerant to Conventional Therapy
Authors: Sharzehi Kaveh , Huang Mary Ann , Schreibman Ian R , Brown Kimberly A
Published: March 2016

BACKGROUND: Autoimmune hepatitis is characterized by hepatocellular inflammation often progressing to cirrhosis. Standard treatment consists of corticosteroids and azathioprine. For the 20% of patients with refractory disease or those who are intolerant to medication, there is no standardized treatment.

OBJECTIVE: To evaluate mycophenolate mofetil (MMF) as an alternative therapy for autoimmune hepatitis.

METHODS: The present retrospective study identified all patients with autoimmune hepatitis who were treated with MMF over a 10-year period at the Henry Ford Hospital (Michigan, USA). These patients were evaluated for tolerance and response.

RESULTS: Of the 90 patients participating in the study, 48% had a complete response, 32% experienced relapses and 21% were refractory. MMF was initiated in 21 patients – 12 (57%) for refractory disease and nine (43%) for medication intolerance. Of the 12 patients converted for refractory disease, all showed biochemical improvement but none had a complete response. Of the patients converted due to intolerance, 88% maintained complete remission. For all patients converted to MMF, there was a mean decrease in steroid dose from 18.9 mg/day to 7.8 mg/day (P=0.01).

CONCLUSIONS: In patients with autoimmune hepatitis who were intolerant to conventional therapy, MMF was well tolerated, with 88% of patients maintained in remission. MMF did not induce remission in those refractory to conventional therapy; however, it resulted in a significant decrease in steroid use. Prospective studies are needed to better assess the role of MMF as an alternative therapy.
Ankaferd Blood Stopper for Controlling Gastrointestinal Bleeding due to Distinct Benign Lesions Refractory to Conventional Antihemorrhagic Measures
Authors: Kurt Mevlut , Onal Ibrahim Koral , Akdogan Meral , Kekilli Murat , Arhan Mehmet , Sayilir Abdurrahim , Oztas Erkin , Haznedaroglu Ibrahim Celalettin
Published: March 2016

OBJECTIVE: To assess the hemostatic efficacy of the Ankaferd Blood Stopper (ABS, Ankaferd Health Products Ltd, Turkey) hemostatic agent for controlling gastrointestinal bleeding associated with various benign lesions refractory to conventional antihemorrhagic measures.

METHODS: The records of all patients who underwent upper and lower endoscopy procedures at the Turkiye Yuksek Ihtisas Teaching and Research Hospital (Ankara, Turkey) between April 2008 and June 2009 were reviewed. Patients in whom ABS was used as a primary or adjuvant hemostatic agent were included in the study. Rates of bleeding control and postprocedural complications were documented.

RESULTS: Hemostasis with no immediate complications was achieved in all patients within seconds of endoscopic application of ABS.

CONCLUSIONS: ABS may have a role as a primary treatment or as an adjuvant to conventional modalities used to control gastrointestinal bleeding. Prospective controlled studies are needed to help establish its efficacy and, perhaps, offer a comparison with conventional hemostatic interventions.
Endoscopic Alcohol Injection Therapy of Giant Gastric Leiomyomas: An Alternative Method to Surgery
Authors: Ozdil Burhan , Akkiz Hikmet , Kece Can , Sandikci Macit
Published: March 2016

Leiomyomas are the most common benign mesenchymal tumours of the upper gastrointestinal tract. They rarely cause symptoms when they are smaller than 5 cm in diameter. Observation with repeated endoscopies is recommended in asymptomatic patients with small lesions. Surgical resection remains the main therapy option for symptomatic and complicated patients. The treatment of esophageal leiomyoma has been enhanced by improvements in diagnostic and therapeutic endoscopic techniques; however, the same cannot be said for gastric leiomyoma management. The present article describes the management of two cases involving giant gastric leiomyomas that were successfully treated using endoscopic injection of alcohol. To the authors’ knowledge, the present study is the first report of the treatment of such hemorrhagic gastric tumours using this alternative and low‐cost technique. Endoscopic local ethanol injection may be the treatment of choice in carefully selected patients with hemorrhagic leiomyomas of the upper gastrointestinal tract.
How Well Does the Internet Answer Patients’ Questions about Inflammatory Bowel Disease?
Authors: Promislow Steven , Walker John R , Taheri Mohammad , Bernstein Charles N
Published: March 2016

BACKGROUND: The Internet is an increasingly important source of health information.

OBJECTIVE: To assess how well common websites answered patients’ questions regarding inflammatory bowel disease (IBD).

METHODS: Thirty websites were identified and evaluated. Based on a previous survey of patient information needs, a comprehensive question list was developed in the three following areas: medical information (seven items), medical treatment (six items) and self‐management (eight items). The websites were evaluated for the amount of information they provided to answer each question using two standard measures of information quality – the DISCERN and the Ensuring Quality Information for Patients scales.

RESULTS: Four particularly strong websites, scoring highest (on a scale from 1 to 5) in terms of IBD information, were the Crohn’s and Colitis Foundation of America (mean information score 4.3), About.com (4.2), HealthCentral (3.8) and WebMD (3.8). These websites also scored well on the DISCERN and the Ensuring Quality Information for Patients quality scales. Most websites provided at least adequate information on common symptoms, complications, treatments and what is known (or not known) about the causes of IBD. However, many web‐sites did not provide adequate information about prognosis, possible side effects of treatment and risks of developing cancer. Information regarding self‐management was covered to a very limited extent.

CONCLUSION: Websites could be strengthened by providing more of the information patients deem to be important, and by more clearly identifying sources of information and the date the information was updated. Most websites would benefit from more attention given to reducing the reading level and improving the organization of material.
A 10‐Year Retrospective Review of Salmonella Infections at the Children’s Hospital in London, Ontario
Authors: Cellucci Tania , Seabrook Jamie A , Chagla Yasmine , Bannister Susan L , Salvadori Marina I
Published: March 2016

OBJECTIVES: To describe Salmonella infections in children presenting to the Children’s Hospital (London Health Sciences Centre, London, Ontario), to assess risk factors for infection and to examine whether younger children, particularly infants younger than 12 weeks of age, experience higher morbidity than older children.

METHODS: A 10‐year retrospective review of children with Salmonella infections at the Children’s Hospital was conducted. Patient demographics, risk factors for infection, clinical characteristics, bacteriology and outcome were collected from the hospital charts and laboratory records. Data were separated into groups based on age and recent use of antibiotics to analyze differences in outcomes.

RESULTS: Sixty‐six children with Salmonella infections presented to the Children’s Hospital over a 10‐year period. Common risk factors for Salmonella infection included having sick contacts, living in a rural area, recent travel, contact with pets (especially reptiles) and exposure to local water. Younger age was associated with an increased likelihood of admission to hospital, treatment with antibiotics and a longer course of antibiotic therapy. This was true when comparing older infants with those younger than 12 weeks of age. Patients recently treated with antibiotics and those with significant underlying medical conditions were more likely to be admitted.

CONCLUSIONS: A wider knowledge of the epidemiological risk factors for Salmonella infection may improve diagnosis. Higher admission rates were expected in children younger than 12 weeks of age, those recently treated with antibiotics and those who had a significant underlying medical condition. A prospective, multicentre study is needed to further address questions regarding increased illness severity and appropriate management of Salmonella infections in children younger than 12 weeks of age.
Bacterial Infections Complicating Tongue Piercing
Authors: Yu Catherine HY , Minnema Brian J , Gold Wayne L
Published: March 2016

Tongue piercing has become an increasingly popular form of body art. However, this procedure can occasionally be complicated by serious bacterial infections. The present article reports a case of prosthetic valve endocarditis caused by a Gemella species in a patient with a pierced tongue, and reviews 18 additional cases of local and systemic bacterial infections associated with tongue piercing. Infections localized to the oral cavity and head and neck region included molar abscess, glossal abscess, glossitis, submandibular lymphadenitis, submandibular sialadenitis, Ludwig’s angina and cephalic tetanus. Infections distal to the piercing site included eight cases of infective endocarditis, one case of chorioamnionitis and one case of cerebellar abscess. Oropharyngeal flora were isolated from all cases. While bacterial infections following tongue piercing are rare, there are reports of potentially life‐threatening infections associated with the procedure. Both piercers and their clients should be aware of these potential complications, and standardized infection prevention and control practices should be adopted by piercers to reduce the risk.
Transition from Intravenous Epoprostenol to Oral or Subcutaneous Therapy in Pulmonary Arterial Hypertension: A Retrospective Case Series and Systematic Literature Review
Authors: Park Kirily , Ostrow David , Levy Robert D , Swiston John
Published: March 2016

BACKGROUND: Intravenous epoprostenol, a prostaglandin analogue, has been a mainstay of therapy for patients with advanced pulmonary arterial hypertension (PAH) since the early 1990s. This medication has multiple side effects, and sudden discontinuation is potentially associated with severe sequelae. Several recent case series have described the transition from intravenous to newer oral or subcutaneous therapies. A case series detailing the authors’ experience with such transitions, and a systematic lierature review is presented.

METHODS: All consecutive PAH patients seen at the Vancouver Pulmonary Hypertension Clinic (Vancouver, British Columbia) between June 1995 and July 2009 were reviewed for cases in which weaning or transition from intravenous epoprostenol was attempted. The Cochrane Collaboration, Cochrane Register of Controlled Trials, Journals@Ovid, MEDLINE, EMBASE and Papers First were searched using predefined key words for publications describing transition of PAH patients from parenteral prostanoids to oral or subcutaneous agents.

RESULTS: Of the six patients who attempted, all transitioned successfully to oral or subcutaneous agents, having been on intravenous epoprostenol for a mean of 3.8 years (range 1.8 to 9.75 years). Five are living, surviving a mean of 5.5 years after transition. The literature search yielded nine studies and, of 127 patients described, 82 transitioned successfully. The length of pretransition prostanoid treatment (range 1.7 to 7.6 years) and the post‐transition follow‐up period (range two months to 70 months) were shorter than for patients described in the present study.

CONCLUSIONS: Given the rarity of PAH, the absolute numbers of patients transitioned from intravenous epoprostenol are still low. With the advent of new therapies, these numbers will hopefully increase; continued study is necessary to identify factors that are predictive of success.
Health‐Related Quality of Life and 6 Min Walk Distance in Patients with Idiopathic Pulmonary Fibrosis
Authors: Verma Geetika , Marras Theodore , Chowdhury Noori , Singer Lianne
Published: March 2016

BACKGROUND: Few studies have investigated the relationship between physiological outcomes and quality of life in patients with idiopathic pulmonary fibrosis (IPF). Health‐related quality of life (HRQL) data may provide a valuable patient‐centred outcome for the evaluation of interventions. Determination of which physiological and functional variables are associated with HRQL may facilitate interpretation of disease progression and impacts of therapy.

OBJECTIVES: To determine whether an association between Medical Outcomes Short‐Form 36 and St George’s Respiratory Questionnaire scores and other markers of disease severity exist, and to identify which physiological and functional variables are independently associated with HRQL.

METHODS: In a cross‐sectional study, 137 patients with IPF completed HRQL surveys and underwent clinical assessment. Multiple linear regression analysis was used to determine the relationship between age, forced vital capacity, diffusing capacity of carbon monoxide, 6 min walk distance (6MWD) and oxygen requirement, and HRQL scores.

RESULTS: 6MWD was the only functional measure of disease severity significantly associated with all domain scores of the St George’s Respiratory Questionnaire and the Medical Outcomes Short‐Form 36 physical component summary score.

CONCLUSIONS: 6MWD was associated with HRQL among patients with IPF. This highlights the importance of 6MWD not only as a prognostic indicator in IPF, but also a predictor of HRQL and a meaningful outcome for patients.
Azathioprine Metabolite Measurements Are not Useful for Following Treatment of Autoimmune Hepatitis in Alaska Native and other Non-Caucasian People
Authors: Ferucci Elizabeth D , Hurlburt Kathy J , Mayo Marlyn J , Livingston Stephen , Deubner Heike , Gove James , Plotnik Julia , McMahon Brian J
Published: March 2016

BACKGROUND: In autoimmune hepatitis (AIH) patients treated with azathioprine, the utility of measuring thiopurine methyltransferase (TPMT) and azathioprine metabolites has been limited.

OBJECTIVE: To evaluate the association between TPMT genotype and enzyme activity, and the impact of TPMT enzyme activity on levels of azathioprine metabolites and leukopenia to assess the clinical utility of monitoring azathioprine metabolites in Alaska Native and other non-Caucasian AIH patients.

METHODS: Individuals with AIH were recruited at the Alaska Native Medical Center (Alaska, USA) and the University of Texas Southwestern Medical Center (Texas, USA). Identification of TPMT genotype and measurement of enzyme activity were performed. The metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) were measured in participants who were on azathioprine, and the associations with disease remission and leukopenia were assessed.

RESULTS: Seventy-one patients with AIH were included. The distribution of TPMT genotypes was similar to that reported in other population-based studies. TPMT genotype and phenotype were strongly associated (P<0.0001). Levels of 6-TGN and 6-MMP correlated with azathioprine dose only in individuals with normal TPMT enzyme activity. Patients with leukopenia due to azathioprine were no more likely to have abnormal TPMT enzyme levels than those without leukopenia (P=1.0). No specific level of 6-TGN metabolites was associated with remission or leukopenia.

DISCUSSION: Results of the present study were consistent with previous studies in Caucasian populations. TPMT genotype and phenotype correlated well, and levels of 6-TGN and 6-MMP metabolites were not associated with remission of AIH or toxicity of azathioprine.

CONCLUSIONS: The present study confirmed the limited utility of monitoring levels of azathioprine metabolites in AIH patients.
Health Care Resource Use and Costs for Crohn’s Disease before and after Infliximab Therapy
Authors: Loomes Dustin E , Teshima Christopher , Jacobs Philip , Fedorak Richard
Published: March 2016

BACKGROUND: Infliximab therapy in patients with Crohn’s disease decreases resource use; however, the overall impact on health-related expenditures is unclear, especially beyond one year of study.

METHODS: A retrospective analysis of economic data one and two years before and after infliximab therapy was performed using patients who served as their own controls. Total health care resource use and direct health care costs were compared for patients with or without fistulae.

RESULTS: Patients with one (n=66) and two (n=39) years of economic data before and after infliximab treatment had their resource use and direct health care costs estimated. In the year following initiation of infliximab therapy, there were significant decreases in health care use, reflected in total hospital days (495 to 155 [P<0.05]), inpatient colonoscopies (46 to 24 [P<0.05]), outpatient colonoscopies (58 to 33 [P<0.05]) and major surgeries (10 to 2 [P<0.05]). Direct health care costs of inpatient costs for luminal (−$1,747 [P<0.05]) and fistulizing disease (−$2,530 [P<0.05]), major surgeries (−$1240 [P<0.05]) and outpatient colonoscopies (−$184 [P<0.05]) were also significantly reduced before and after infliximab therapy. Total direct health care costs, including the drug cost of infliximab, increased ($21,416 [P<0.05]). In general, the trends in health care costs analyzed over four consecutive years paralleled the two consecutive-year analysis.

CONCLUSIONS: Infliximab therapy in patients with Crohn’s disease resulted in a significant decrease in both resource use and health care costs, but an increase in total direct health care costs once the cost of infliximab was added.
The Pathophysiology of Chronic Constipation
Authors: Andrews Christopher N , Storr Martin
Published: March 2016

Constipation is broadly defined as an unsatisfactory defecation characterized by infrequent stools, difficult stool passage or both. The common approach to the pathophysiology of constipation groups the disorder into primary and secondary causes. Primary causes are intrinsic problems of colonic or anorectal function, whereas secondary causes are related to organic disease, systemic disease or medications. The normal process of colonic transit and defecation is discussed, and the etiology of constipation is reviewed.
Examining Nurse Empathy for Infant Procedural Pain: Testing a New Video Measure
Authors: Latimer Margot , Jackson Philip , Johnston Celeste , Vine Jocelyn
Published: March 2016

BACKGROUND: Research reporting effective pain care strategies exists, yet it is not translated to care. Little is known about how repeated pain exposure has affected nurses’ ability to be empathetic and use their knowledge to provide evidence‐based care. Concerns have been raised regarding the validity of self‐report empathy instruments; therefore, a novel video program was developed for testing. It was hypothesized that those who viewed infants in painful and nonpainful states would have a measureable empathy (pain rating) response correlating to the level of pain expressed by the infants.

OBJECTIVE: To validate the newly developed Empathy for Infant Pain video program (EIPvp) by determining whether nurse and non‐nurse control groups’ pain scores of 24 video clips showing infants undergoing real medical procedures were equal.

DESIGN: A descriptive cross‐sectional video judgement study.

METHODS: Fifty female participants (25 nurses and 25 allied health controls) were asked to score the infant procedural pain level displayed in the EIPvp using a visual analogue scale and a composite score of known infant pain cues. Participants also scored their own sensitivity to painful events.

RESULTS: Participants rated the videos contained in the EIPvp similarly in three categories (no, low or high pain); however, there were consistent differences between groups within the categories. Nurses scored facial cues for all categories higher than the control group. Nurses scored their own pain in hypothetical situations and that of the infants consistently higher than the control group.

CONCLUSION: The EIPvp yielded predictable responses from both the nurse and non‐nurse control groups when scoring the pain expressed in the video clips. Nurses’ detection of pain more often than controls may have been an indication that they have greater knowledge of pain cues, or their empathy levels may have been different as a result of their exposure to, or their perceived relationship with, patients. The EIPvp was validated and has promising potential for training and research purposes.
Evaluation of Influenza‐Specific Humoral Response by Microbead Array Analysis
Authors: Keynan Yoav , Bodnarchuk Tavis , Wayne Stephen , Li Yan , Fowke Keith R.
Published: March 2016

RATIONALE: Quantitation and determination of antigen specificity of systemic and mucosal immune responses to influenza vaccination is beneficial for future vaccine development. Previous methods to acquire this information were costly, time consuming and sample exhaustive. The benefits of suspension microbead array (MBA) analysis are numerous. The multiplex capabilities of the system conserve time, money and sample, while generating statistically powerful data.

OBJECTIVE: To demonstrate the use of the assay by comparing the humoral influenza‐specific responses of two cohorts from two countries that differed in circulating influenza strains and rates of influenza vaccination.

METHODS: Influenza hemagglutinin (HA) from different strains were coated on microbeads and incubated with serum samples to capture immunoglobulin (Ig) A1 and IgG1 host antibodies.

RESULTS: Statistically significant differences in IgA1 and IgG1 exist between the serum samples from Winnipeg (Manitoba) donors and those from Kenyan (Africa) donors. Data were compared using Mann‐Whitney nonparametric tests. The Winnipeg donors had higher mean fluorescence intensity values, with significant P values for anti‐HA IgA1 to A/Wyoming/3/2003 (P=0.044), A/Vietnam/1203/2004 (P=0.0179), A/New Caledonia/20/99 (P<0.0001) and B/Tokyo/53/99 (P=0.0002). No differences were seen between the groups in their response to B/Jilin/20/2003. The Winnipeg donors had higher mean fluorescence intensity values, with significant P values for anti‐HA IgG1 to A/Wyoming/3/2003 (P=0.0135), B/Tokyo/53/99 (P=0.006) and B/Jilin20/2003 (P=0.026).

CONCLUSION: Influenza‐specific IgA1 and IgG1 antibodies were successfully detected using MBA technology. A significant difference in antibody response was observed between Winnipeg and Kenyan donor serums. MBA analysis is a relatively quick and cost‐effective method for serum antibody analysis. The potential to simultaneously assay small sample volumes for a multitude of antigens makes this method invaluable for future vaccine response monitoring.
Antimicrobial Resistance Surveillance Systems: Are Potential Biases Taken into Account?
Authors: Rempel Olivia , Pitout Johann DD. , Laupland Kevin B.
Published: March 2016

The objective of this study was to assess potential biases that may influence the validity of contemporary antimicrobial‐resistant (AMR) pathogen surveillance systems. Although surveillance data have been widely published and used by researchers and decision makers, little attention has been devoted to the assessment of their validity. A Medline search was used to identify reports, in 2008, of laboratory‐based AMR surveillance systems. Identified surveillance systems were appraised for six different types of bias. Scores were assigned as ‘2’ (good), ‘1’ (fair) and ‘0’ (poor) for each bias. The results of this assessment indicate that there are several potential biases that can influence the validity of AMR surveillance information and, therefore, the potential for bias should be considered in the interpretation and use of AMR surveillance data.

BACKGROUND: The validity of surveillance systems has rarely been a topic of investigation.

OBJECTIVE: To assess potential biases that may influence the validity of contemporary antimicrobial‐resistant (AMR) pathogen surveillance systems.

METHODS: In 2008, reports of laboratory‐based AMR surveillance systems were identified by searching Medline. Surveillance systems were appraised for six different types of bias. Scores were assigned as ‘2’ (good), ‘1’ (fair) and ‘0’ (poor) for each bias.

RESULTS: A total of 22 surveillance systems were included. All studies used appropriate denominator data and case definitions (score of 2). Most (n=18) studies adequately protected against case ascertainment bias (score = 2), with three studies and one study scoring 1 and 0, respectively. Only four studies were deemed to be free of significant sampling bias (score = 2), with 17 studies classified as fair, and one as poor. Eight studies had explicitly removed duplicates (score = 2). Seven studies removed duplicates, but lacked adequate definitions (score = 1). Seven studies did not report duplicate removal (score = 0). Eighteen of the studies were considered to have good laboratory methodology, three had some concerns (score = 1), and one was considered to be poor (score = 0).

CONCLUSION: Contemporary AMR surveillance systems commonly have methodological limitations with respect to sampling and multiple counting and, to a lesser degree, case ascertainment and laboratory practices. The potential for bias should be considered in the interpretation of surveillance data.