bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Preoperative Oral Pregabalin and Perioperative Intravenous Lidocaine Infusion on Postoperative Morphine Requirement in Patients Undergoing Laparatomy
Authors: Zengin Senniye Ulgen , Saracoglu Ayten , Eti Zeynep , Umuroglu Tumay , Gogus Fevzi Yilmaz
Published: March 2016

OBJECTIVES: To evaluate and compare the effects of preoperative oral pregabalin and perioperative intravenous lidocaine infusion on postoperative morphine requirement, adverse effects, patients’ satisfaction, mobilization, time to first defecation and time to discharge in patients undergoing laparotomy.

METHODS: Eighty patients (18 to 65 years of age) undergoing elective laparotomy were randomly divided into four groups (n=20 in each group): group C, placebo capsules and normal saline infusion perioperatively (control); group L, placebo capsules and lidocaine 1 mg/kg intravenous bolus dose followed by 2 mg/kg/h infusion until skin closure; group P, 150 mg oral pregabalin and normal saline infusion perioperatively; and group PL, 150 mg oral pregabalin and lidocaine 2 mg/kg/h infusion until skin closure. Hemodynamic parameters, visual analogue scale (VAS) scores, analgesic consumption, side effects, time to mobilization, time to first defecation, time to discharge and patients’ satisfaction were recorded.

RESULTS: VAS scores of group L, group P and group PL were lower than group C (P<0.05). Morphine consumption of group P and group PL was lower than group C (P<0.05). Incidence of nausea in group C was higher than group L and group PL. Time to first defecation and mobilization were shorter in group L and group PL compared with group C (P<0.05).

CONCLUSION: Preoperative oral pregabalin and perioperative intravenous lidocaine infusion decreased postoperative VAS scores. Preoperative oral pregabalin decreased morphine requirement and perioperative intravenous lidocaine infusion hastened gastrointestinal motility and mobilization, and decreased the incidence of nausea in patients undergoing laparotomy. Therefore, preoperative pregabalin with or without lidocaine provides superior pain relief in patients undergoing laparatomy.
Turn‐Amplitude Analysis as a Diagnostic Test for Myofascial Syndrome in Patients with Chronic Pelvic Pain
Authors: Itza Fernando , Zarza Daniel , Salinas Jesus , Teba Fernando , Ximenez Carmen
Published: March 2016

BACKGROUND: Myofascial pain syndrome of the pelvic floor (MPSPF) is a common disease in the context of chronic pelvic pain (CPP); however, there is currently no gold‐standard test to diagnose it.

OBJECTIVE: To validate the turns‐amplitude analysis (TAA) as a diagnostic test for MPSPF in patients with CPP.

METHODS: A case‐control study was performed, and patients were consecutively sampled within a specified period of time. A total of 128 patients were included: 64 patients with CPP (32 men and 32 women) and 64 control patients (32 men and 32 women). The same operator conducted all tests. Electromyography of the TAA is based on the collection of motor unit potentials that measure the number of changes in the signal and the mean amplitude of the changes. The electromyogram transfers the data to a graphical point cloud, which enables the patient’s results to be compared with the results of the healthy subjects.

RESULTS: In patients and control subjects, the sensitivity and specificity of the proposed diagnostic test showed a marked clinical significance: the sensitivity was 83%, and the specificity was 100%. A positive predictive value of 1 (95% CI 1 to 1) and a negative predictive value of 0.85 (95% CI 0.77 to 0.93) were observed.

CONCLUSION: TAA is a reliable diagnostic test to detect MPSPF. Further studies are needed to reproduce these results.
The Effectiveness of Ultrasound Surveillance for Hepatocellular Carcinoma in a Canadian Centre and Determinants of Its Success
Authors: Khalili Korosh , Menezes Ravi , Kim Tae Kyoung , Yazdi Leyla Kochak , Jang Hyun-Jung , Sharma Suraj , Feld Jordan , Sherman Morris
Published: March 2016

BACKGROUND: The effectiveness of surveillance for hepatocellular carcinoma (HCC) using ultrasound (US) in North America has been questioned due to the predominance of patients of Caucasian ethnicity and larger body habitus.

OBJECTIVE: To determine the effectiveness of US surveillance for HCC in a Canadian hepatobiliary centre and to identify independent variables associated with early detection of tumour(s).

METHODS: A retrospective review of patients with first HCC in a US surveillance population at the authors’ hospital yielded 201 patients (over a 10.5-year period). Patients were categorized into three groups: regular surveillance (frequency of surveillance ≤12 months [n=109]); irregular surveillance (frequency of surveillance >12 months [n=38]); or first surveillance (tumour detected on first scan [n=54]). The Milan criteria for transplantation and Barcelona Clinic Liver Cancer (BCLC) staging system were used as outcome measures. Effective surveillance was defined as tumour detection within Milan criteria or curative BCLC stages 0 and A; its association with multiple patient- and disease-related variables was tested.

RESULTS: When using the Milan criteria as outcome, 84 of 109 (77%) regular surveillance patients, 23 of 38 (61%) irregular surveillance patients and 40 of 54 (74%) first surveillance patients had tumours meeting the transplantation criteria. The difference between regular and irregular surveillance was statistically significant (P=0.03). When using the BCLC staging system, 87 of 109 (80%) regular surveillance patients, 26 of 38 (68%) irregular surveillance patients and 41 of 54 (76%) first surveillance patients had their tumours detected in BCLC curative stages (0 and A; P=0.11). Regular surveillance was the only variable significantly associated with detection of tumour(s) within the Milan criteria (OR 2.76 [95% CI 1.10 to 6.88]). Tumours detected more recently were more likely to be <2 cm in size (BCLC stage 0; OR 2.38 [95% CI 1.07 to 5.31]).

CONCLUSION: A high rate of HCC surveillance success was achieved using US alone when performed regularly in a specialized hepatobiliary centre.
Atypical Nummular Headache or Circumscribed Migraine: The Utility of Pressure Algometry
Authors: Barón Johanna , Rodríguez Cristina , Ruiz Marina , Pedraza María Isabel , Guerrero Ángel Luis , Madeleine Pascal , Cuadrado María Luz , Fernández-de-las-Peñas César
Published: March 2016

A peripheral mechanism has been proposed for nummular headache; however, there have been descriptions of atypical features resembling migraine. The authors describe a case in which algometry assessment facilitated the discrimination between atypical nummular headache and circumscribed migraine. A 21‐year‐old woman presented with a history of focal episodic pain in a circumscribed area on the left frontal region. The algometry study showed a unilateral and diffuse decrease of the pain pressure thresholds with frontal predominance, as has been proposed for migraine patients. This result led the authors to introduce a more specific preventive therapy with topiramate, with significant relief. In conclusion, cartographic investigation of pressure pain sensitivity is a simple tool that can help to differentiate between nummular headache and migraine. Further confirmatory investigations are needed.
Use of Electronic Data and Existing Screening Tools to Identify Clinically Significant Obstructive Sleep Apnea
Authors: Severson Carl A , Pendharkar Sachin R , Ronksley Paul E , Tsai Willis H
Published: March 2016

OBJECTIVES: To assess the ability of electronic health data and existing screening tools to identify clinically significant obstructive sleep apnea (OSA), as defined by symptomatic or severe OSA.

METHODS: The present retrospective cohort study of 1041 patients referred for sleep diagnostic testing was undertaken at a tertiary sleep centre in Calgary, Alberta. A diagnosis of clinically significant OSA or an alternative sleep diagnosis was assigned to each patient through blinded independent chart review by two sleep physicians. Predictive variables were identified from online questionnaire data, and diagnostic algorithms were developed. The performance of electronically derived algorithms for identifying patients with clinically significant OSA was determined. Diagnostic performance of these algorithms was compared with versions of the STOP‐Bang questionnaire and adjusted neck circumference score (ANC) derived from electronic data.

RESULTS: Electronic questionnaire data were highly sensitive (>95%) at identifying clinically significant OSA, but not specific. Sleep diagnostic testing‐determined respiratory disturbance index was very specific (specificity ≥95%) for clinically relevant disease, but not sensitive (<35%). Derived algorithms had similar accuracy to the STOP‐Bang or ANC, but required fewer questions and calculations.

CONCLUSIONS: These data suggest that a two‐step process using a small number of clinical variables (maximizing sensitivity) and objective diagnostic testing (maximizing specificity) is required to identify clinically significant OSA. When used in an online setting, simple algorithms can identify clinically relevant OSA with similar performance to existing decision rules such as the STOP‐Bang or ANC.
Increased Eligibility for Treatment of Chronic Hepatitis C Infection with Shortened Duration of Therapy: Implications for Access to Care and Elimination Strategies in Canada
Authors: Borgia Sergio M , Rowaiye Adenike
Published: March 2016

BACKGROUND: All oral, highly effective direct-acting antiviral combinations, such as sofosbuvir-ledipasvir, have recently been licensed in Canada but cost as much as $67,000 for a 12-week course of therapy, representing a major economic barrier to predominately single-payer health care systems such as that found in Ontario. In hepatitis C virus (HCV) genotype 1 noncirrhotic patients with a baseline viral load of <6×106IU/mL, treatment with sofosbuvir-ledipasvir can be shortened to eight weeks without compromising ≥95% efficacy. The number of HCV-infected patients in Ontario eligible for shortened therapy, and the associated cost savings, are unknown. The authors propose that treating every patient with shortened therapy, regardless of baseline viral load, would lead to significant public cost savings and collateral efficiencies, enabling increased HCV treatment capacity and cure.

METHODS: The present study designed a three-part model to investigate the cost of cure per patient and cost savings per patient under three eligibility pathways: conservative, permissive and ideal. In the conservative model, every patient is treated for 12 weeks regardless of baseline viral load, whereas in the permissive model, patients with a baseline viral load <6×106IU/mL are treated for eight weeks. In the ideal model, every patient receives eight weeks of therapy regardless of baseline viral load. Relapsed patients are retreated for 12 weeks. Data obtained from the Ontario Public Health Laboratory were used to validate the model and generate the outcomes.

RESULTS: In Ontario, 75.34% of HCV genotype 1 patients had a baseline viral load of <6×106IU/mL and were eligible for shortened therapy. The cost of cure per patient in the ideal model was $47,328.44, representing a 29% reduction in the cost of curative therapy and 3.5 weeks of shortened treatment duration compared with the conservative model. The ideal model generated a cost savings per patient of $3,855.17 (8% reduction in treatment cost) and 0.7 weeks of shorter therapy compared with the permissive model, and was the shortest and most efficient while maintaining a cure rate ≥95%.

CONCLUSIONS: These results demonstrate that recommendations for a shortened treatment course of eight weeks using all-oral direct-acting antivirals in HCV genotype 1 noncirrhotic patients, regardless of baseline viral load, affords significant public cost savings and, on a population level, offers opportunities for expanded HCV treatment and cure.
Ulcerative Colitis-Associated Hospitalization Costs: A Population-Based Study
Authors: Coward Stephanie , Heitman Steven J , Clement Fiona , Hubbard James , Proulx Marie-Claude , Zimmer Scott , Panaccione Remo , Seow Cynthia , Leung Yvette , Datta Neel , Ghosh Subrata , Myers Robert P , Swain Mark , Kaplan Gilaad G
Published: March 2016

BACKGROUND: Hospitalization costs for ulcerative colitis (UC) following the introduction of infliximab have not been evaluated.

OBJECTIVE: To study predictors of costs for UC patients who were hospitalized for a flare or colectomy.

METHODS: Population-based surveillance identified adults (≥18 years of age) admitted to hospital for UC flare or colectomy between 2001 and 2009 in the Calgary Health Zone (Alberta). Medical charts were reviewed and patients stratified into three admission types: responsive to inpatient medical therapy (n=307); emergent colectomy (n=227); and elective colectomy (n=208). The annual median cost with interquartile range (IQR) was calculated. Linear regression determined the effect of admission type on hospital charges after adjusting for age, sex, smoking, comorbidities, disease extent, medication use (eg, infliximab) and year. The adjusted cost increase was presented as the percent increase with 95% CIs. Joinpoint analysis assessed for an inflection point in hospital cost after the introduction of infliximab.

RESULTS: Median hospitalization cost for UC flare, emergent colectomy and elective colectomy, respectively, were: $5,499 (IQR $3,374 to $8,904), $23,698 (IQR $17,981 to $32,385) and $14,316 (IQR $11,932 to $18,331). Adjusted hospitalization costs increased approximately 6.0% annually (95% CI 4.5% to 7.5%). Adjusted costs were higher for patients who underwent an elective colectomy (percent increase cost 179.8% [95% CI 151.6% to 211.1%]) or an emergent colectomy (percent increase cost 211.1% [95% CI 183.2% to 241.6%]) than medically responsive patients. Infliximab in hospital was an independent predictor of increased costs (percent increase cost 69.5% [95% CI 49.2% to 92.5%]). No inflection points were identified.

CONCLUSION: Hospitalization costs for UC increased due to colectomy and infliximab.
A Family Cluster of Chagas Disease Detected through Selective Screening of Blood Donors: A Case Report and Brief Review
Authors: Mongeau-Martin Guillaume , Ndao Momar , Libman Michael , Delage Gilles , Ward Brian J
Published: March 2016

Chagas disease (CD) is a protozoan infection caused by Trypanosoma cruzi, which is transmitted by triatomine insect vectors in parts of Latin America. In a nonendemic country, such as Canada, spread can still occur via vertical transmission, and infected blood or organ donations. The Canadian Blood Services and Héma‐Québec have both implemented selective screening of blood donors for CD based on risk factors. In 2011, Héma‐Québec identified two seropositive ‘at‐risk’ Chilean siblings who had donated blood in Montreal, Quebec. They were referred to the JD MacLean Centre for Tropical Diseases (Montreal, Quebec) for confirmatory testing (T cruzi excreted‐secreted antigen ELISA, polymerase chain reaction and/or radioimmunoprecipitation assay) and follow‐up. Screening of the rest of the family revealed two other seropositive family members (the mother and sister). While their geographical history in Chile suggests vectorial transmission, this family cluster of CD raises the possibility of vertical transmission. Congenital infection should always be considered among CD‐positive mothers and pregnant women. With blood donor screening, Canadian physicians will increasingly see patients with CD and should know how to manage them appropriately. In addition to the case presentation, the authors review the transmission, screening and clinical management of CD in a nonendemic context.
Is Intra‐Articular Magnesium Effective for Postoperative Analgesia in Arthroscopic Shoulder Surgery?
Authors: Saritas Tuba Berra , Borazan Hale , Okesli Selmin , Yel Mustafa , Otelcioglu Seref
Published: March 2016

BACKGROUND: Various medications are used intra‐articularly for postoperative pain reduction after arthroscopic shoulder surgery. Magnesium, a N‐methyl‐D‐aspartate receptor antagonist, may be effective for reduction of both postoperative pain scores and analgesic requirements.

METHODS: A total of 67 patients undergoing arthroscopic shoulder surgery were divided randomly into two groups to receive intra‐articular injections of either 10 mL magnesium sulphate (100 mg/mL; group M, n=34) or 10 mL of normal saline (group C, n=33). The analgesic effect was estimated using a visual analogue scale 1 h, 2 h, 6 h, 8 h, 12 h, 18 h and 24 h after operation. Postoperative analgesia was maintained by intra‐articular morphine (0.01%, 10 mg) + bupivacaine (0.5%, 100 mL) patient‐controlled analgesia device as a 1 mL infusion with a 1 mL bolus dose and 15 min lock‐out time; for visual analogue scale scores >5, intramuscular diclofenac sodium 75 mg was administered as needed during the study period (maximum two times).

RESULTS: Intra‐articular magnesium resulted in a significant reduction in pain scores in group M compared with group C 1 h, 2 h, 6 h, 8 h and 12 h after the end of surgery, respectively, at rest and with passive motion. Total diclofenac consumption and intra‐articular morphine + bupivacaine consumption were significantly lower in group M. Postoperative serum magnesium levels were significantly higher in group M, but were within the normal range.

CONCLUSIONS: Magnesium causes a reduction in postoperative pain in comparison to saline when administered intra‐articularly after arthroscopic shoulder surgery, and has no serious side effects.
Partially Covered Self-Expandable Metal Stents versus Polyethylene Stents for Malignant Biliary Obstruction: A Cost-Effectiveness Analysis
Authors: Barkun Alan N , Adam Viviane , Martel Myriam , AlNaamani Khalid , Moses Peter L
Published: March 2016

BACKGROUND/OBJECTIVE: Partially covered self-expandable metal stents (SEMS) and polyethylene stents (PES) are both commonly used in the palliation of malignant biliary obstruction. Although SEMS are significantly more expensive, they are more efficacious than PES. Accordingly, a cost-effectiveness analysis was performed.

METHODS: A cost-effectiveness analysis compared the approach of initial placement of PES versus SEMS for the study population. Patients with malignant biliary obstruction underwent an endoscopic retrograde cholangiopancreatography to insert the initial stent. If the insertion failed, a percutaneous transhepatic cholangiogram was performed. If stent occlusion occurred, a PES was inserted at repeat endoscopic retrograde cholangiopancreatography, either in an outpatient setting or after admission to hospital if cholangitis was present. A third-party payer perspective was adopted. Effectiveness was expressed as the likelihood of no occlusion over the one-year adopted time horizon. Probabilities were based on a contemporary randomized clinical trial, and costs were issued from national references. Deterministic and probabilistic sensitivity analyses were performed.

RESULTS: A PES-first strategy was both more expensive and less efficacious than an SEMS-first approach. The mean per-patient costs were US$6,701 for initial SEMS and US$20,671 for initial PES, which were associated with effectiveness probabilities of 65.6% and 13.9%, respectively. Sensitivity analyses confirmed the robustness of these results.

CONCLUSION: At the time of initial endoscopic drainage for patients with malignant biliary obstruction undergoing palliative stenting, an initial SEMS insertion approach was both more effective and less costly than a PES-first strategy.
Use of Calcitonin in Recalcitrant Phantom Limb Pain Complicated by Heterotopic Ossification
Authors: Viana Ricardo , Payne Michael WC
Published: March 2016

A common complication following amputation is phantom sensation, which may include experiencing pain in the phantom limb. This study details the management of phantom limb pain in a 72‐year‐old man, in whom comorbid heterotopic ossification was present. In addition, the authors provide a review of the literature regarding phantom limb pain management, and summarize the current understanding of heterotopic ossification and its possible link to peripheral nerve injury.

BACKGROUND: Phantom limb pain (PLP) is a common complication after amputation, affecting up to 80% of the amputee population. However, only 5% to 10% of amputees have severe PLP impacting daily function. The present report details the management of severe, treatment‐resistant PLP in a 72‐year‐old man with a traumatic left transradial amputation and a comorbid complication of heterotopic ossification (HO).

OBJECTIVE: To describe a case of PLP with HO and the possible role of calcitonin in the treatment of both conditions.

METHODS: A systematic review of the literature regarding the management of PLP.

RESULTS: Seventeen articles that directly addressed PLP were identified; 11 were randomized controlled trials. All involved small samples and follow‐up ranged from 6 h to one year, with the majority limited to six weeks.

DISCUSSION: In the present case, medication management was limited by side effects, lack of response and the patient’s desire to avoid long‐term medication. Investigations revealed HO, which was suspected to envelop the median nerve in the proximal forearm. After several unsuccessful medication trials, the literature was reviewed in search of common variables between HO formation and persistent PLP. Ultimately, the biochemical effects associated with nerve injury were identified to be a possible factor in both HO and PLP development. Calcitonin’s proposed mechanisms of action may help to manage HO and PLP at multiple stages of disease development and maintenance. In the present case, a four‐week trial of intranasal calcitonin was successful, with pain control lasting at least 18 months.

CONCLUSION: The present case report provided a review of the current literature in PLP pharmacological management and the current understanding of the etiology of PLP and HO, as well as how the two may coexist. It also provided an opportunity to discuss the proposed mechanisms of action of calcitonin in the management of PLP and HO.
Exogenous Endophthalmitis Caused by Enterococcus casseliflavus: A Case Report and Discussion Regarding Treatment of Intraocular Infection with Vancomycin‐Resistant Enterococci
Authors: Berenger Byron M , Kulkarni Shobhana , Hinz Brad J , MD Sarah E Forgie
Published: March 2016

BACKGROUND: Endophthalmitis caused by enterococci is rare, and cases involving vancomycin‐resistant enterococci are even more so. Due to the poor bioavailability of many antibiotics in the vitreous chamber, special considerations are required when choosing antibiotics to treat these infections. The authors report the first case of exogenous endophthalmitis caused by Enterococcus casseliflavus via the unique mechanism of high‐velocity water stream trauma from a toy water gun.

A previously healthy four‐year old boy presented with endophthalmitis of the left eye after injury from a water gun. Empirical treatment for endophthalmitis was started on presentation to the ophthalmologist. After the identification of the pathogen and a review of the literature, the antibiotic regimen was changed to include intravitreal ampicillin and amikacin with systemic linezolid.

Endophthalmitis caused by E casseliflavus and other vancomycin‐resistant enterococci are challenging to treat. Rapid identification of vancomycin‐resistant enterococcal endophthalmitis is important to guide appropriate antibiotic therapy. Systemic linezolid achieves excellent intravitreal concentrations, and should be used in combination with intravitreal and topical antibiotics.
Risk Factors for Mortality in Patients with Alcoholic Hepatitis and Assessment of Prognostic Models: A Population-Based Study
Authors: Pang Jack XQ , Ross Erin , Borman Meredith A , Zimmer Scott , Kaplan Gilaad G , Heitman Steven J , Swain Mark G , Burak Kelly , Quan Hude , Myers Robert P
Published: March 2016

BACKGROUND: Severe alcoholic hepatitis (AH) is associated with a substantial risk for short-term mortality.

OBJECTIVES: To identify prognostic factors and validate well-known prognostic models in a Canadian population of patients hospitalized for AH.

METHODS: In the present retrospective study, patients hospitalized for AH in Calgary, Alberta, between January 2008 and August 2012 were included. Stepwise logistic regression models identified independent risk factors for 90-day mortality, and the discrimination of prognostic models (Model for End-stage Liver Disease [MELD] and Maddrey discriminant function [DF]) were examined using areas under the ROC curves.

RESULTS: A total of 122 patients with AH were hospitalized during the study period; the median age was 49 years (interquartile range [IQR] 42 to 55 years) and 60% were men. Median MELD score and Maddrey DF on admission were 21 (IQR 18 to 24) and 45 (IQR 26 to 62), respectively. Seventy-three percent of patients received corticosteroids and/or pentoxifylline, and the 90-day mortality was 17%. Independent predictors of mortality included older age, female sex, international normalized ratio, MELD score and Maddrey DF (all P<0.05). For discrimination of 90-day mortality, the areas under the ROC curves of the prognostic models (MELD 0.64; Maddrey DF 0.68) were similar (P>0.05). At optimal cut-offs of ≥22 for MELD score and ≥37 for Maddrey DF, both models excluded death with high certainty (negative predictive values 90% and 96%, respectively).

CONCLUSIONS: In patients hospitalized for AH, well-known prognostic models can be used to predict 90-day mortality, particularly to identify patients with a low risk for death.
Yield of Screening Colonoscopy in Renal Transplant Candidates
Authors: AlAmeel Turki , Bseiso Bahaa , AlBugami Meteb M , AlMomen Sami , Roth Lee Stuart
Published: March 2016

BACKGROUND: Cardiovascular disease is the most common cause of death among patients with end-stage renal disease undergoing maintenance dialysis. Renal transplantation offers a survival advantage to patients with end-stage renal disease; it is also associated with a three- to fivefold increase in the risk of developing a neoplasm.

OBJECTIVE: To determine the yield of screening colonoscopy among patients with chronic kidney disease who were considered for renal transplantation.

METHODS: Patients were included if they were ≥50 years of age, had chronic kidney disease and were being considered for renal transplantation. They underwent a screening colonoscopy that was performed as part of their pretransplant workup. Data from December 2008 to May 2014 were collected retrospectively for all eligible patients.

RESULTS: During the study period, 433 patients were considered for renal transplantation. Of these, 170 underwent colonoscopies as part of their pretransplant workup. One was excluded because of previous history of colon cancer. Of the 169 procedures performed, ≥1 polyp(s) was diagnosed in 24%. The most common pathological diagnoses were hyperplastic polyp or normal colonic tissue. Fifteen (37%) patients had tubular adenomas and one patient had a sessile serrated adenoma. Advanced adenomas, defined as villous, tubulovillous or high-grade dysplasia, were found in four patients. Adenocarcinoma was diagnosed in one patient.

CONCLUSION: In a population of asymptomatic potential kidney transplant recipients ≥50 years of age, the prevalence of colorectal adenomatous polyps was 24%. Colonoscopy appeared to be useful as a screening tool in potential transplant recipients.
Hepatocellular Carcinoma: Consensus, Controversies and Future Directions: A Report from the Canadian Association for the Study of the Liver Hepatocellular Carcinoma Meeting
Authors: Burak Kelly Warren , Sherman Morris
Published: March 2016

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and its incidence has rapidly increased in North America in recent years. Although there are many published guidelines to assist the clinician, there remain gaps in knowledge and areas of controversy surrounding the diagnosis and management of HCC. In February 2014, the Canadian Association for the Study of the Liver organized a one-day single-topic consensus conference on HCC. Herein, the authors present a summary of the topics covered and the result of voting on consensus statements presented at this meeting.
Association among Fraction of Exhaled Nitrous Oxide, Bronchodilator Response and Inhaled Corticosteroid Type
Authors: Smith Ryan W , Downey Kim , Snow Nadia , Dell Sharon , Smith W Gary
Published: March 2016

BACKGROUND: Fraction of exhaled nitrous oxide (FeNO) is a known marker of airway inflammation and a topic of recent investigation for asthma control in children.

OBJECTIVE: To investigate the relationship among FeNO and bronchodilator response measured by spirometry and types of inhaled corticosteroids (ICS).

METHODS: A one-year review of children tested with spirometry and FeNO in a regional pediatric asthma centre was conducted.

RESULTS: A total of 183 children were included (mean [± SD] age 12.8±2.8 years). Fluticasone was used most commonly (n=66 [36.1%]), followed by ciclesonide (n=50 [27.3%]). Most children (n=73 [39.9%]) had moderate persistent asthma. Increased FeNO was associated with percent change in forced expiratory volume in 1 s (FEV1) after bronchodilator adjusted for allergic rhinitis, parental smoking and ICS type (B=0.08 [95% CI 0.04 to 0.12]; P<0.001). Similarly, FeNO was associated with percent change in forced expiratory flow at 25% to 75% of the pulmonary volume (FEF25–75) after bronchodilator adjusted for parental smoking and ICS type (B=0.13 [95% CI 0.01 to 0.24]; P=0.03). FeNO accounted for only 16% and 9% of the variability in FEV1and FEF25–75, respectively. Mean-adjusted FeNO was lowest in fluticasone users compared with no ICS (mean difference 18.6 parts per billion [ppb] [95% CI 1.0 to 36.2]) and there was no difference in adjusted FeNO level between ciclesonide and no ICS (5.9 ppb [95% CI −9.0 to 20.8]).

CONCLUSION: FeNO levels correlated with bronchodilator response in a regional pediatric asthma centre. However, FeNO accounted for only 16% and 9% of the variability in FEV1and FEF25–75, respectively. Mean adjusted FeNO varied according to ICS type, suggesting a difference in relative efficacy between ICS beyond their dose equivalents.
Clinicians’ Guide to the Use of Fecal Calprotectin to Identify and Monitor Disease Activity in Inflammatory Bowel Disease
Authors: Bressler Brian , Panaccione Remo , Fedorak Richard N , Seidman Ernest G
Published: March 2016

BACKGROUND: Objective monitoring of the severity of inflammation in patients with inflammatory bowel disease (IBD) is an essential part of disease management. However, repeat endoscopy to define extent and severity of inflammation is not practical. Fecal calprotectin (FC) is a biomarker that can be used as a surrogate test to distinguish inflammatory from noninflammatory gastrointestinal disease.

METHODS: A targeted search of the literature regarding FC, focusing primarily on the past three years, was conducted to develop practical clinical guidance on the current utility of FC in the routine management of IBD patients.

RESULTS: It is recommended that samples for FC testing be obtained from the first bowel excretion of the day. FC testing should be used as standard of care to accurately confirm inflammation and ‘real-time’ disease activity when a clinician suspects an IBD flare. Although FC is a reliable marker of inflammation, its role in routine monitoring in improving long-term outcomes has not yet been fully assessed. Based on available evidence, the authors suggest the following cut-off values and management strategies: when FC levels are <50 μg/g to 100 μg/g, quiescent disease is likely and therapy should be continued; when FC levels are >100 μg/g to 250 μg/g, inflammation is possible and further testing (eg, colonoscopy) is required to confirm inflammation; and when FC levels are >250 μg/g, active inflammation is likely and strategies to control inflammation should be initiated (eg, optimizing current therapies or switching to an alternative therapy).

DISCUSSION: FC is a useful biomarker to accurately assess the degree of inflammation and should be incorporated into the management of patients with IBD.
Antimicrobial Susceptibility of Canadian Isolates of Helicobacter pylori in Northeastern Ontario
Authors: Eng Nelson F , Ybazeta Gustavo , Chapman Katrina , Fraleigh Nya L , Letto Rebecca , Altman Eleonora , Diaz-Mitoma Francisco
Published: March 2016

BACKGROUND: Helicobacter pylori plays a significant role in gastritis and ulcers. It is a carcinogen as defined by the WHO, and infection can result in adenocarcinomas and mucosa‐associated lymphoid tissue lymphomas. In Canada, rates of antimicrobial resistance are relatively unknown, with very few studies conducted in the past 15 years.

OBJECTIVE: To examine rates of resistance in Sudbury, Ontario, compare antimicrobial susceptibility methods and attempt to determine the molecular basis of antibiotic resistance.

METHODS: Patients attending scheduled visits at Health Sciences North (Sudbury, Ontario) provided gastric biopsy samples on a volunteer basis. In total, 20 H pylori isolates were collected, and antimicrobial susceptibility testing (on amoxicillin, tetracycline, metronidazole, ciprofloxacin, levofloxacin and clarithromycin) was conducted using disk diffusion and E‐test methods. Subsequently, genomic DNA from these isolates was sequenced to detect mutations associated with antimicrobial resistance.

RESULTS: Sixty‐five percent of the isolates were found to be resistant to at least one of the listed antibiotics according to E‐test. Three isolates were found to be resistant to ≥3 of the above‐mentioned antibiotics. Notably, 25% of the isolates were found to be resistant to both metronidazole and clarithromycin, two antibiotics that are normally prescribed as part of first‐line regimens in the treatment of H pylori infections in Canada and most of the world. Among the resistant strains, the sequences of 23S ribosomal RNA and gyrA, which are linked to clarithromycin and ciprofloxacin/levofloxacin resistance, respectively, revealed the presence of known point mutations associated with antimicrobial resistance.

CONCLUSIONS: In general, resistance to metronidazole, ciprofloxacin/levofloxacin and clarithromycin has increased since the studies in the early 2000s. These results suggest that surveillance programs of H pylori antibiotic resistance may need to be revisited or improved to prevent antimicrobial therapy failure.
Use of Electronic Health Records for Early Detection of High‐Cost, Low Back Pain Patients
Authors: Maeng Daniel D , Stewart Walter F , Yan Xiaowei , Boscarino Joseph A , Mardekian Jack , Harnett James , Von Korff Michael R
Published: March 2016

BACKGROUND: Low back pain (LBP) is a debilitating condition that is complex to manage. One reason is that clinicians lack means to identify early on patients who are likely to become high care utilizers.

OBJECTIVE: To explore the feasibility of developing a ‘dynamic’ predictive model using electronic health record data to identify costly LBP patients within the first year after their initial LBP encounter with a primary care provider. Dynamic, in this context, indicates a process in which the decision on how to manage patients is dependent on whether they are at their first, second or third LBP visit with the provider.

METHODS: A series of logistic regression models was developed to predict who will be a high‐cost patient (defined as top 30% of the cost distribution) at each of the first three LBP visits.

RESULTS: The c‐statistics of the three logistic regression models corresponding to each of the first three visits were 0.683, 0.795 and 0.741, respectively. The overall sensitivity of the model was 42%, the specificity was 86% and the positive predictive value was 48%. Men were more likely to become expensive than women, while patients who had workers’ compensation as their primary payer type had higher use of prescription opioid drugs or were smokers before the first LBP visit were also more likely to become expensive.

CONCLUSION: The results suggest that it is feasible to develop a dynamic, primary care provider visit‐based predictive model for LBP care based on longitudinal data obtained via electronic health records.
A new Era of Personalized Medicine for Cystic Fibrosis – at Last!
Authors: Quon Bradley S , Wilcox Pearce G
Published: March 2016

The gene responsible for cystic fibrosis (CF) was discovered 25 years ago. This breakthrough has enabled a sophisticated understanding of how various mutations lead to specific alterations in the structure and function of the CF transmembrane regulator (CFTR) protein. Until recently, all therapies in CF were focused on ameliorating the downstream consequences of CFTR dysfunction. High‐throughput drug screening approaches have yielded compounds that can modify CFTR structure and function, thus targeting the basic defect in CF. The present article describes the CFTR mutational classes, reviews mutation‐specific therapies currently in late‐phase clinical development, and highlights research opportunities and challenges with personalized medicine in CF.
Prevalence of Celiac Disease and Celiac Autoimmunity in the Toba Native Amerindian Community of Argentina
Authors: Vázquez Horacio , de la Paz Temprano María , Sugai Emilia , Scacchi Stella M , Souza Cecilia , Cisterna Daniel , Smecuol Edgardo , Moreno María Laura , Longarini Gabriela , Mazure Roberto , Bartellini María A , Verdú Elena F , González Andrea , Mauriño Eduardo , Bai Julio C
Published: March 2016

BACKGROUND: Celiac disease (CD) is mostly recognized among subjects with a Caucasian ethnic ancestry. No studies have explored conditions predisposing Amerindians to CD.

OBJECTIVE: To prospectively assess environmental, genetic and serological conditions associated with CD among members of the Toba native population attending a multidisciplinary sanitary mission.

METHODS: An expert nutritionist determined daily gluten intake using an established questionnaire. Gene typing for the human leukocyte antigen (HLA) class II alleles was performed on DNA extracted from peripheral blood (HLA DQ2/DQ8 haplotype). Serum antibodies were immunoglobulin (Ig) A tissue transglutaminase (tTG) and the composite deamidated gliadin peptides/tTG Screen test. Positive cases were tested for IgA endomysial antibodies.

RESULTS: A total of 144 subjects (55% female) were screened. The estimated mean gluten consumption was 43 g/day (range 3 g/day to 185 g/day). Genetic typing showed that 73 of 144 (50.7%) subjects had alleles associated with CD; 69 (94.5%) of these subjects had alleles for HLA DQ8 and four had DQ2 (5.5%). Four and six subjects had antibody concentrations above the cut-off established by the authors’ laboratory (>3 times the upper limit of normal) for IgA tTG and deamidated gliadin peptides/tTG screen, respectively. Four of these had concomitant positivity for both assays and endomysial antibodies were positive in three subjects who also presented a predisposing haplotype.

CONCLUSION: The present study was the first to detect CD in Amerindians. The native Toba ethnic population has very high daily gluten consumption and a predisposing genetic background. We detected subjects with persistent CD autoimmunity and, at least, three of them fulfilled serological criteria for CD diagnosis.
Bacteremia Due to Pasteurella dagmatisAcquired from a Dog Bite, with a Review of Systemic Infections and Challenges in Laboratory Identification
Authors: Xiong Jianhui , Krajden Sigmund , Kus Julianne V , Rawte Prasad , Blondal John , Downing Mark , Zurawska Urszula , Chapman William
Published: March 2016

A case of bacteremia in a 74‐year‐old man, which was caused by Pasteurella dagmatis and complicated by thrombocytopenia, is presented. Microorganism identification was performed by the provincial reference laboratory using traditional biochemical profiling, completmented with both the sequencing of the 16S ribosomal RNA gene and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry; antibiotic‐susceptibility testing was also performed. After treatment with the appropriate antibiotics, the patient fully recovered. Systemic infections attributed to this organism are rarely reported in the literature. Other reported cases of bacteremia due to P dagmatis are reviewed and compared with the present case. The challenges of relying on standard automatic identification are discussed, with alternative methodologies provided.
Fecal Calprotectin Use in Inflammatory Bowel Disease and Beyond: A Mini-Review
Authors: Alibrahim Bashaar , Aljasser Mohammed I , Salh Baljinder
Published: March 2016

Given the number of inflammatory disorders affecting the gastrointestinal tract directly and indirectly, coupled with the considerable overlap with functional disorders, it is evident that more useful noninvasive diagnostic tests are required to aid with diagnosis. If these tests can also have some utility for individual patient follow-up in terms of disease activity and response to treatment, as well as providing forewarning of disease relapse, it would be extremely useful information for the clinician. One recently described test that may fulfill several of these attributes is based on leakage of a mononuclear cell cytoplasmic protein, calprotectin, along the intestinal tract, which can then be quantified in feces. This has been used to distinguish patients exhibiting symptoms of irritable bowel syndrome from patients with inflammatory bowel disease, with a measure of success greater than with currently used techniques. The present article summarizes the experience with this test used in inflammatory bowel disease, as well as a variety of gastrointestinal disorders.
Neutrophil Infiltration and the Distribution of Intestinal Metaplasia Is Associated with Metachronous Gastric Cancer following Endoscopic Submucosal Dissection
Authors: Sugimoto Takafumi , Yamaji Yutaka , Sakitani Kosuke , Isomura Yoshihiro , Yoshida Shuntaro , Yamada Atsuo , Hirata Yoshihiro , Ogura Keiji , Okamoto Makoto , Koike Kazuhiko
Published: March 2016

BACKGROUND: Endoscopic submucosal dissection (ESD) of early gastric cancer is a minimally invasive procedure. However, the risk for metachronous cancers after successful cancer treatment remains high and the risk factors for metachronous cancers have not been elucidated.

OBJECTIVE: To evaluate the risk factors for metachronous gastric cancers after ESD with a long-term follow-up.

METHODS: A total of 155 consecutive patients (119 men, 36 women, mean age 68.9 years) were treated with ESD between September 2000 and September 2009. Biopsy specimens were obtained from the greater curvature of the antrum and middle corpus to evaluate gastric mucosal status, includingHelicobacter pylori, intestinal metaplasia (IM) and neutrophil infiltration (NI) before ESD. Follow-up endoscopy after ESD was scheduled at two and six months, one year and annually thereafter.H pylorieradication was recommended when possible.

RESULTS: The median follow-up period was 4.2 years. Metachronous gastric cancers were found in 23 of 155 patients (3.5% per year). No local recurrences were observed. The cumulative incidence of metachronous gastric cancer was significantly high in IM and NI in the corpus (P=0.0093 and P=0.0025, respectively [log-rank test]). The ORs for IM and NI in the corpus were 2.65 and 3.06, respectively, according to the Cox proportional hazards model (P=0.024 and P=0.0091, respectively).

CONCLUSIONS: The presence of IM and NI in the corpus was closely related to the development of metachronous gastric cancer after ESD.
Hospital Volume and Other Risk Factors for In-Hospital Mortality among Diverticulitis Patients: A Nationwide Analysis
Authors: Diamant Michael J , Coward Stephanie , Buie W Donald , MacLean Anthony , Dixon Elijah , Ball Chad G , Schaffer Samuel , Kaplan Gilaad G
Published: March 2016

BACKGROUND: Previous studies have found that a higher volume of colorectal surgery was associated with lower mortality rates. While diverticulitis is an increasingly common condition, the effect of hospital volume on outcomes among diverticulitis patients is unknown.

OBJECTIVE: To evaluate the relationship between hospital volume and other factors on in-hospital mortality among patients admitted for diverticulitis.

METHODS: Data from the Nationwide Inpatient Sample (years 1993 to 2008) were analyzed to identify 822,865 patients representing 4,108,726 admissions for diverticulitis. Hospitals were divided into quartiles based on the volume of diverticulitis cases admitted over the study period, adjusted for years contributed to the dataset. Mortality according to hospital volume was modelled using logistic regression adjusting for age, sex, race, comorbidities, health care insurance, admission type, calendar year, colectomy, disease severity and clustering. Risk estimates were expressed as adjusted ORs with 95% CIs.

RESULTS: Patients at high-volume hospitals were more likely to be admitted emergently, undergo surgical treatment and have more severe disease. In-hospital mortality was higher among the lowest quartile of hospital volume compared with the highest volume (OR 1.13 [95% CI 1.05 to 1.21]). In-hospital mortality was increased among patients admitted emergently (OR 2.58 [95% CI 2.40 to 2.78]) as well as those receiving surgical treatment (OR 3.60 [95% CI 3.42 to 3.78]).

CONCLUSIONS: Diverticulitis patients admitted to hospitals with a low volume of diverticulitis cases had an increased risk for death compared with those admitted to high-volume centres.
Renal Impairment in Cirrhosis Unrelated to Hepatorenal Syndrome
Authors: Low Gavin , Alexander Graeme JM , Lomas David J
Published: March 2016

Renal impairment is common in liver disease and may occur as a consequence of the pathophysiological changes that underpin cirrhosis or secondary to a pre-existing unrelated insult. Nevertheless, the onset of renal impairment often portends a worsening prognosis. Hepatorenal syndrome remains one of the most recognized and reported causes of renal impairment in cirrhosis. However, other causes of renal impairment occur and can be classified into prerenal, intrinsic or postrenal, which are the subjects of the present review.
The Influence of Probiotic Lactobacillus casei in Combination with Prebiotic Inulin on the Antioxidant Capacity of Human Plasma
Authors: Kleniewska Paulina , Hoffmann Arkadiusz , Pniewska Ewa , Pawliczak Rafał
Published: March 2016

The aim of the present study was to assess whether probiotic bacteria Lactobacillus casei (4 × 108 CFU) influences the antioxidant properties of human plasma when combined with prebiotic Inulin (400 mg). Experiments were carried out on healthy volunteers (n = 32). Volunteers were divided according to sex (16 male and 16 female) and randomly assigned to synbiotic and control groups. Blood samples were collected before synbiotic supplementation and after 7 weeks, at the end of the study. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, and the ferric reducing ability of plasma (FRAP) in human plasma were examined. The administration of synbiotics containing L. casei plus Inulin resulted in a significant increase in FRAP values (p = 0.00008) and CAT activity (p = 0.02) and an insignificant increase in SOD and GPx activity compared to controls. Synbiotics containing L. casei (4 × 108 CFU) with prebiotic Inulin (400 mg) may have a positive influence on human plasma antioxidant capacity and the activity of selected antioxidant enzymes.