bluuebunny/crossref_metadata_2025 huggingface dataset:
EHDViz: clinical dashboard development using open-source technologies
Authors: Badgeley Marcus A , Shameer Khader , Glicksberg Benjamin S , Tomlinson Max S , Levin Matthew A , McCormick Patrick J , Kasarskis Andrew , Reich David L , Dudley Joel T
Published: March 2016

Objective

To design, develop and prototype clinical dashboards to integrate high-frequency health and wellness data streams using interactive and real-time data visualisation and analytics modalities.

Materials and methods

We developed a clinical dashboard development framework called electronic healthcare data visualization (EHDViz) toolkit for generating web-based, real-time clinical dashboards for visualising heterogeneous biomedical, healthcare and wellness data. The EHDViz is an extensible toolkit that usesRpackages for data management, normalisation and producing high-quality visualisations over the web usingR/Shinyweb server architecture. We have developed use cases to illustrate utility of EHDViz in different scenarios of clinical and wellness setting as a visualisation aid for improving healthcare delivery.

Results

Using EHDViz, we prototyped clinical dashboards to demonstrate the contextual versatility of EHDViz toolkit. An outpatient cohort was used to visualise population health management tasks (n=14 221), and an inpatient cohort was used to visualise real-time acuity risk in a clinical unit (n=445), and a quantified-self example using wellness data from a fitness activity monitor worn by a single individual was also discussed (n-of-1). The back-end system retrieves relevant data from data source, populates the main panel of the application and integrates user-defined data features in real-time and renders output using modern web browsers. The visualisation elements can be customised using health features, disease names, procedure names or medical codes to populate the visualisations. The source code of EHDViz and various prototypes developed using EHDViz are available in the public domain athttp://ehdviz.dudleylab.org.

Conclusions

Collaborative data visualisations, wellness trend predictions, risk estimation, proactive acuity status monitoring and knowledge of complex disease indicators are essential components of implementing data-driven precision medicine. As an open-source visualisation framework capable of integrating health assessment, EHDViz aims to be a valuable toolkit for rapid design, development and implementation of scalable clinical data visualisation dashboards.
Towards optimising local reviews of severe incidents in maternity care: messages from a comparison of local and external reviews
Authors: Shah Anjali , Kemp Bryn , Sellers Susan , Hinton Lisa , O'Connor Melanie , Brocklehurst Peter , Kurinczuk Jenny , Knight Marian
Published: March 2016

Background

Detailed local case review is commonly used as a strategy to improve care. However, recent reports have highlighted concerns over quality of local reviews in maternity care. The aim of this project was to describe the methods used for conducting local reviews of care of women with severe maternal morbidity, and to compare lessons identified for future care through external and local reviews.

Methods

Thirty-three anonymised clinical records from women with severe maternal morbidities were obtained, together with the report of the local review of their care. The methodology used for the local reviews was described, including specific tools used, team members involved, their disciplines, report format and whether an action plan with recommendations for audit was produced. Multidisciplinary external reviewers considered the records using a standard confidential enquiry approach. A thematic analysis of lessons learned from the two approaches was undertaken.

Results

A formal report of the local review was produced for 11/33 cases; 4 of these used root cause analysis. A further 12 local reviews consisted of a group discussion with output noted in a spreadsheet; 5 consisted of a timeline with good practice points and 5 had no formal review. Patients were involved in five local reviews; only one was multidisciplinary. Action plans were recorded in 14 local reviews; 3 of these included a recommendation to audit the proposed changes. External reviews identified additional messages for care and highlighted aspects of good care in every case, whereas only 55% (n=18) of local reviews identified good care (p<0.0005).

Conclusions

The quality of local reviews can clearly be improved. Very few of the reviews involved patients. Local reviews should be multidisciplinary, generate an action plan, and the implementation of recommendations should be audited. Improvements in local reviews may be achieved by standardised training or development of national protocols.
‘Managing My Patellofemoral Pain’: the creation of an education leaflet for patients
Authors: Barton Christian J , Rathleff Michael S
Published: March 2016

Study design

Qualitative, including consultation with international experts and patients.

Purpose

Develop a brief yet comprehensive evidence-based education leaflet to be used as an adjunct in the management of patellofemoral pain (PFP) through consultation with both experts (clinical academics) and individuals with PFP.

Background

Appropriate patient education is an essential component of effective PFP management. However, there are currently no published educational resources for clinicians and researchers treating individuals with PFP to help translate current evidence into clinical practice.

Methods

A preliminary education leaflet titled ‘Managing My Patellofemoral Pain’ was created using information from the ‘Best Practice Guide to Conservative Management of Patellofemoral Pain’ and educational content used in published research. Feedback was sought from 21 experts (clinical academics) for accuracy, adequacy and clarity of the information in the leaflet using a semistructured questionnaire, and a number of suggested modifications were made as a result. Further feedback was sought from 20 patients diagnosed with PFP regarding the clarity and adequacy of information contained in the leaflet, and to determine additional educational resource needs.

Results

The leaflet created is titled ‘Managing My Patellofemoral Pain’ and the main topics of the leaflet are ‘What might cause my knee pain?’ and ‘Treatment options’, which are divided into exercise and additional treatments. Patient feedback was positive, and included a number of considerations for further education resource development.

Conclusions

The ‘Managing My Patellofemoral Pain’ education leaflet may provide a valuable resource for patients, clinicians and researchers to assist the provision of education and translation of the current evidence.
Pharmacological macrophage inhibition decreases metastasis formation in a genetic model of pancreatic cancer
Authors: Griesmann Heidi , Drexel Christof , Milosevic Nada , Sipos Bence , Rosendahl Jonas , Gress Thomas M , Michl Patrick
Published: March 2016

Objectives

Tumour-associated macrophages play an important role in mediating tumour progression. In pancreatic cancer, infiltrating macrophages are known to mediate tumour progression and have been identified in invasive tumours and in early preinvasive pancreatic intraepithelial precursor lesions. We aimed to study the impact of pharmacological macrophage depletion by liposomal clodronate in a genetic mouse model of pancreatic cancer.

Methods

KPC mice (LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre) were treated for 12 weeks with liposomal clodronate or control liposomes. Tumour and metastasis formation as well as alterations in local and circulating immune cells and cytokines were analysed.

Results

Treatment with liposomal clodronate effectively reduced CD11b-positive macrophages both in the pancreas and other organs such as liver, lung and spleen. While tumour incidence and growth were only slightly reduced, metastasis formation in the liver and lungs was significantly diminished after macrophage depletion. This antimetastatic effect was independent of the presence of an endogenous primary tumour, since reduced pulmonary colonisation was also detected in clodronate-pretreated mice after tail vein injection of syngeneic pancreatic cancer cell lines. Macrophage inhibition by liposomal clodronate was associated with significantly impaired angiogenesis, reduced circulating vascular endothelial growth factor levels and decreased circulating CD4+CD25+ T cells. These alterations could be confirmed in an independent macrophage depletion model using CD11b-diphtheria toxin receptor mice.

Conclusions

Pharmacological depletion of macrophages in a genetic mouse model of pancreatic cancer markedly reduced metastasis formation and is associated with impaired angiogenesis and reduced CD4+CD25+ T cell levels. Pharmacological targeting of infiltrating macrophages represents a promising novel tool for antimetastatic therapeutic approaches.
Overdose of oral contraceptive pills as a means of intentional self-poisoning amongst young women in Sri Lanka: considerations for family planning
Authors: Weerasinghe Manjula , Konradsen Flemming , Eddleston Michael , Pearson Melissa , Agampodi Thilini , Storm Frederikke , Agampodi Suneth
Published: March 2016

Objective

Oral contraceptive pills (OCPs) are one of the most popular family planning methods in Sri Lanka. As part of two hospital-based studies on self-harm, the use of OCPs was identified, from yet unpublished results, as a means of intentional self-poisoning. To inform future guidelines for better OCP promotion, this article aims to describe the extent, patient characteristics and outcomes of OCP self-poisoning in the North Central Province of Sri Lanka.

Methods

A secondary analysis was carried out on two hospital-based self-harm case series, from January 2011 to June 2014.

Results

Fifty-four patients (52 women and two men) with an overdose of OCP as a means of intentional self-poisoning were admitted to one of the surveyed hospitals. The median age of the patients was 19 (interquartile range, 5) years. None of the patients were severely sick from their overdose and two-thirds of the patients were discharged within a day of admission. Intentional self-poisoning with OCPs represented less than 5% of all types of intentional medicine self-poisonings recorded at the hospitals. Information available for a subset of female patients indicates that many cases (13/23, 56.5%) were in their first year of marriage.

Conclusions

More research is required to understand why young women in rural Sri Lanka overdose with OCPs as a means of intentional self-poisoning. Although the toxicity of OCPs is low and the public health significance of OCP poisoning remains minor, reproductive health service providers should be attentive to OCP overdose, monitor the development of this problem, and ensure appropriate information to OCP users.
Medicare expenditures for elderly patients undergoing surgical clipping or endovascular intervention for unruptured cerebral aneurysms
Authors: Bekelis Kimon , Gottlieb Dan , Su Yin , Labropoulos Nicos , Bovis George , Lawton Michael T , MacKenzie Todd A
Published: March 2016

Background

The cost difference between the two treatment options (surgical clipping and endovascular therapy) for unruptured cerebral aneurysms remains an issue of debate. We investigated the association between treatment method for unruptured cerebral aneurysms and Medicare expenditures in elderly patients.

Methods

We performed a cohort study of 100% Medicare fee-for-service claims data for elderly patients who underwent treatment for unruptured cerebral aneurysms from 2007 to 2012. In order to control for measured confounding we used multivariable regression analysis with mixed effects to account for clustering at the Hospital Referral Region (HRR) level. An instrumental variable (regional rates of endovascular treatment) analysis was used to control for unmeasured confounding by creating pseudo-randomization on the treatment method.

Results

During the study period 8705 patients underwent treatment for unruptured cerebral aneurysms and met the inclusion criteria. Of these, 2585 (29.7%) had surgical clipping and 6120 (70.3%) had endovascular treatment. The median total Medicare expenditures in the first year after the admission for the procedure were $46 800 (IQR $31 000–$74 400) for surgical clipping and $48 100 (IQR $34 500–$73 900) for endovascular therapy. When we adjusted for unmeasured confounders, using an instrumental variable analysis, clipping was associated with increased 7-day Medicare expenditures by $3527 (95% CI $972 to $5736) and increased 1-year Medicare expenditures by $15 984 (95% CI $9017 to $22 951).

Conclusions

In a cohort of Medicare patients, after controlling for unmeasured confounding, we demonstrated that surgical clipping of unruptured cerebral aneurysms was associated with increased 1-year expenditures compared with endovascular treatment.
Minimal loss of genetic diversity and no inbreeding depression in blueflag iris (Iris versicolor) on islands in the Bay of Fundy
Authors: Wheelwright Nathaniel T. , Begin Elise , Ellwanger Claire , Taylor Samuel H. , Stone Judy L.
Published: March 2016

Isolated island plant populations founded by few individuals are often characterized by decreased genetic variation and increased inbreeding. Our aim was to measure population genetic diversity and inbreeding depression in blueflag iris (Iris versicolor L., Iridaceae), a native allotetraploid, on islands in the Bay of Fundy, Canada. Hand-pollination experiments (inbreeding, within-site outbreeding, between-island outbreeding) on Kent Island, New Brunswick, revealed no evidence for inbreeding depression across a broad array of morphological, physiological, and life-history traits. Leaf tissue samples collected from three mainland sites and 10 islands in the Bay of Fundy and genotyped using three microsatellite primer pairs showed that island populations were less genetically diverse than mainland populations. Island populations were genetically distinct from each other, indicating a bottleneck effect associated with colonization and continued isolation. Nonetheless, substantial genetic variation was maintained at the population level. Polyploidy and a history of self-fertilization may allow Iris versicolor to avoid inbreeding depression in isolated populations. Our study supports Anderson’s (1936) original hypothesis that substantial genetic diversity can be preserved within polyploid species, even with extensive inbreeding.
Stanniocalcin 2 induces oxaliplatin resistance in colorectal cancer cells by upregulating P-glycoprotein
Authors: Yuan Qiong , Zhan Lin , Zhang Li-Li , Wang Qiang , Liu Juan , Jiang Zhen-Yu , Hu Xia-Min , Yuan Xin-Chu
Published: March 2016

Multidrug resistance (MDR) limits the anticancer effects of chemotherapy in patients with metastatic colorectal cancer (CRC). Oxaliplatin is a common component of combinational therapeutic regimens administered to patients with metastatic CRC; however, it is also used as a constituent of adjuvant therapy for patients at a risk of recurrent disease. In the present study, we investigated the role of stanniocalcin 2 (STC2) in chemoresistance. STC2 knockdown sensitized chemoresistant CRC cells to oxaliplatin. Moreover, the expression of exogenous STC2 in chemonaïve CRC cells induced oxaliplatin resistance. We confirmed that STC2 upregulated P-glycoprotein (P-gp) expression in CRC cells. Furthermore, shRNA against phosphoinositide 3-kinase (PI3K) or Akt inhibited the action of STC2 on P-gp upregulation and MDR in CRC. To our knowledge, this is the first report to demonstrate the induction of oxaliplatin resistance in CRC cells in response to STC2 stimulation of P-gp via the PI3K/Akt signaling pathway.
Influence of interface on the formation process of polymer coatings on metal
Authors: Maksimova O. G. , Maksimov A. V. , Moiseeva A. I.
Published: March 2016

The purpose of this work is in development of the model that allows to investigate the conformations of macromolecules near the interface “dielectric-metal” depending on the conditions of formation of the polymer coating. In the modified model of “sticky tape”, one part of macromolecule is anchored to the metal surface while the other can be elongated due to effective mean (molecular) field of dipolar type formed by free ends of other chains. The dynamic Monte-Carlo method for Langmuir’s model is used for calculation of adhesion force taking into account the interaction energy of monomers with the metal surface. It is shown that conformation of polymer chain is defined by temperature conditions of its formation. The obtained results are confirmed by the data of production tests on polymer coatings in JSC “Severstal”.
Dynamic fluid recycling at Laguna Caliente (Poás, Costa Rica) before and during the 2006–ongoing phreatic eruption cycle (2005–10)
Authors: Rouwet Dmitri , Mora-Amador Raúl , Ramírez-Umaña Carlos J. , González Gino , Inguaggiato Salvatore
Published: March 2016

Poás Volcano (Costa Rica) resumed phreatic activity on 24 March 2006 after twelve years of quiescence. From March 2006 to June 2010, the initial phase of the ongoing eruption cycle, 110 phreatic eruptions were reported. This study presents the temporal variations in the chemical and isotopic (δD and δ
18
O) compositions of Laguna Caliente crater lake for the period prior to the eruption until June 2010. No systematic relationship with the phreatic eruptive activity exists. A combined mass and Cl budget analysis enables quantification of the seepage rate (7 kg s
−1
), the input rate of the ‘volcanic fluid’ (
Q
f
), and the Cl concentration (Cl
e
) in the evaporation plume (13 300 mg l
−1
). A modelling procedure for variable seepage rates leads to more realistic estimates of 50–100 kg s
−1
, which better represent the observed lake water chemistry, hence suggesting dynamic fluid recycling between the lake and the underlying magmatic–hydrothermal system. The high Cl concentration in the evaporation plume and the dynamic fluid recycling at the lake bottom characterize Laguna Caliente as an ‘open-air’ fumarole, discrediting water chemistry as an efficient monitoring tool at the classic monitoring frequency. A conceptual model of phreatic eruptions is linked to our observations.
Sampling bias in CS education, and where's the cyber strategy?
Authors: Guzdial Mark , Arquilla John
Published: March 2016

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

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Follow us on Twitter at http://twitter.com/blogCACM

http://cacm.acm.org/blogs/blog-cacm

Mark Guzdial examines a logical fallacy in consumer science education; John Arquilla sees an absence of discussion about the use of information technologies in future conflicts.
p38 MAPK α and β isoforms differentially regulate plasma membrane localization of MRP2
Authors: Schonhoff Christopher M. , Park Se Won , Webster Cynthia R.L. , Anwer M. Sawkat
Published: March 2016

In hepatocytes, cAMP both activates p38 mitogen-activated protein kinase (MAPK) and increases the amount of multidrug resistance-associated protein-2 (MRP2) in the plasma membrane (PM-MRP2). Paradoxically, taurolithocholate (TLC) activates p38 MAPK but decreases PM-MRP2 in hepatocytes. These opposing effects of cAMP and TLC could be mediated via different p38 MAPK isoforms (α and β) that are activated differentially by upstream kinases (MKK3, MKK4, and MKK6). Thus we tested the hypothesis that p38α MAPK and p38β MAPK mediate increases and decreases in PM-MRP2 by cAMP and TLC, respectively. Studies were conducted in hepatocytes isolated from C57BL/6 wild-type (WT) and MKK3-knockout (MKK3−/−) mice and in a hepatoma cell line (HuH7) that overexpresses sodium-taurocholate cotransporting polypeptide (NTCP) (HuH-NTCP). Cyclic AMP activated MKK3, p38 MAPK, and p38α MAPK and increased PM-MRP2 in WT hepatocytes, but failed to activate p38α MAPK or increase PM-MRP2 in MKK3−/−hepatocytes. In contrast to cAMP, TLC activated total p38 MAPK but decreased PM-MRP2, and did not activate MKK3 or p38α MAPK in WT hepatocytes. In MKK3−/−hepatocytes, TLC still decreased PM-MRP2 and activated p38 MAPK, indicating that these effects are not MKK3-dependent. Additionally, TLC activated MKK6 in MKK3−/−hepatocytes, and small interfering RNA knockdown of p38β MAPK abrogated TLC-mediated decreases in PM-MRP2 in HuH-NTCP cells. Taken together, these results suggest that p38α MAPK facilitates plasma membrane insertion of MRP2 by cAMP, whereas p38β MAPK mediates retrieval of PM-MRP2 by TLC.
Butyrate enhances antibacterial effects while suppressing other features of alternative activation in IL-4-induced macrophages
Authors: Fernando Maria R. , Saxena Alpana , Reyes José-Luis , McKay Derek M.
Published: March 2016

The short-chain fatty acid butyrate is produced by fermentation of dietary fiber by the intestinal microbiota; butyrate is the primary energy source of colonocytes and has immunomodulatory effects. Having shown that macrophages differentiated with IL-4 [M(IL-4)s] can suppress colitis, we hypothesized that butyrate would reinforce an M(IL-4) phenotype. Here, we show that in the presence of butyrate M(IL-4)s display reduced expression of their hallmark markers Arg1 and Ym1 and significantly suppressed LPS-induced nitric oxide, IL-12p40, and IL-10 production. Butyrate treatment likely altered the M(IL-4) phenotype via inhibition of histone deacetylation. Functionally, M(IL-4)s treated with butyrate showed increased phagocytosis and killing of bacteria, compared with M(IL-4) and this was not accompanied by enhanced proinflammatory cytokine production. Culture of regulatory T cells with M(IL-4)s and M(IL-4 + butyrate)s revealed that both macrophage subsets suppressed expression of the regulatory T-cell marker Foxp3. However, Tregs cocultured with M(IL-4 + butyrate) produced less IL-17A than Tregs cocultured with M(IL-4). These data illustrate the importance of butyrate, a microbial-derived metabolite, in the regulation of gut immunity: the demonstration that butyrate promotes phagocytosis in M(IL-4)s that can limit T-cell production of IL-17A reveals novel aspects of bacterial-host interaction in the regulation of intestinal homeostasis.
Sucrose ingestion after exhaustive exercise accelerates liver, but not muscle glycogen repletion compared with glucose ingestion in trained athletes
Authors: Fuchs Cas J. , Gonzalez Javier T. , Beelen Milou , Cermak Naomi M. , Smith Fiona E. , Thelwall Pete E. , Taylor Roy , Trenell Michael I. , Stevenson Emma J. , van Loon Luc J. C.
Published: March 2016

The purpose of this study was to assess the effects of sucrose vs. glucose ingestion on postexercise liver and muscle glycogen repletion. Fifteen well-trained male cyclists completed two test days. Each test day started with glycogen-depleting exercise, followed by 5 h of recovery, during which subjects ingested 1.5 g·kg−1·h−1sucrose or glucose. Blood was sampled frequently and13C magnetic resonance spectroscopy and imaging were employed 0, 120, and 300 min postexercise to determine liver and muscle glycogen concentrations and liver volume. Results were as follows: Postexercise muscle glycogen concentrations increased significantly from 85 ± 27 (SD) vs. 86 ± 35 mmol/l to 140 ± 23 vs. 136 ± 26 mmol/l following sucrose and glucose ingestion, respectively (no differences between treatments: P = 0.673). Postexercise liver glycogen concentrations increased significantly from 183 ± 47 vs. 167 ± 65 mmol/l to 280 ± 72 vs. 234 ± 81 mmol/l following sucrose and glucose ingestion, respectively (time × treatment, P = 0.051). Liver volume increased significantly over the 300-min period after sucrose ingestion only (time × treatment, P = 0.001). As a result, total liver glycogen content increased during postexercise recovery to a greater extent in the sucrose treatment (from 53.6 ± 16.2 to 86.8 ± 29.0 g) compared with the glucose treatment (49.3 ± 25.5 to 65.7 ± 27.1 g; time × treatment, P < 0.001), equating to a 3.4 g/h (95% confidence interval: 1.6-5.1 g/h) greater repletion rate with sucrose vs. glucose ingestion. In conclusion, sucrose ingestion (1.5 g·kg−1·h−1) further accelerates postexercise liver, but not muscle glycogen repletion compared with glucose ingestion in trained athletes.
Long-Term Prognosis of Early-Onset Chrohn's Disease Diagnosed in Childhood or Adolescence
Authors: Freeman Hugh J
Published: March 2016

Long-term follow-up data on Crohn's disease diagnosed before 20 years of age is limited. Mortality, intestinal malignancy and the need for resection were assessed in 224 patients with early-onset disease (96 males, 42.9%; 128 females, 57.1%). Mean follow-up was 12.2 years; more than 50% of patients were seen for over 10 years (almost 10% for over 25 years). Most patients were diagnosed from ages 13 to 19 years, rather than in childhood. Ileocolonic disease was most common (128 of 224; 57.1%), while upper tract involvement (42 of 224; 18.8%) was frequent. Complex disease with strictures (28.6%) or penetrating complications (46.4%) was common. To date, one patient with early-onset disease died from a drug overdose and one developed rectal cancer, but epithelial dysplasia has not been reported in endoscopic biopsies or resected intestine. One or more intestinal resections were required in 126 patients (56.3%; 58 males and 68 females). More than one resection was needed in 52 patients (23.2%). The mean time from diagnosis to first resection was 4.2 years and from first to second resection was 6.6 years, with most resections required in the first two years. Most patients who needed one or more resections had ileocolonic disease and had complex stricturing or penetrating disease. Information on long-term follow-up of early-onset Crohn's disease is crucial to avoid the direct extrapolation of adult data to children and adolescents.
The Management of Chronic Viral Hepatitis: A Canadian Consensus Conference 2004
Authors: Sherman Morris , Bain Vincent , Villeneuve Jean-Pierre , Myers Robert P , Cooper Curtis , Martin Steven , Lowe Catherine
Published: March 2016

Several government and nongovernment organizations held a consensus conference on the management of acute and chronic viral hepatitis to update previous management recommendations. The conference became necessary because of the introduction of new forms of therapy for both hepatitis B and hepatitis C. The conference issued recommendations on the investigation and management of chronic hepatitis B, including the use of lamivudine, adefovir and interferon. The treatment of hepatitis B in several special situations was also discussed. There were also recommendations on the investigation and treatment of chronic hepatitis C and hepatitis C-HIV coinfection. In addition, the document makes some recommendations about the provision of services by provincial governments to facilitate the delivery of care to patients with hepatitis virus infection. The present document is meant to be used by practitioners and other health care providers, including public health staff and others not directly involved in patient care.
Description of Prescribing Practices in Patients with Upper Gastrointestinal Bleeding Receiving Intravenous Proton-Pump Inhibitors: A Multicentre Evaluation
Authors: Enns Robert , Andrews Christopher N , Fishman Martin , Hahn Michael , Atkinson Kenneth , Kwan Peter , Levy Adrian
Published: March 2016

BACKGROUND:Intravenous forms of proton pump inhibitors (IV PPI) are routinely used for patients with acute upper gastrointestinal bleeding, but a significant concern for their inappropriate use has been suggested.

PATIENTS and METHODS:All consecutive patients who received IV PPI (pantoprazole) over 20 months in six Canadian hospitals were reviewed. Prescribing practices, endoscopic findings and outcomes were recorded.

RESULTS:A total of 854 patients received IV PPI. Over 90% of patients were given IV PPI for treatment of known or suspected active upper gastrointestinal bleeding. Most patients (69%) underwent upper endoscopy, and 58% of these patients had peptic ulcer disease (PUD). The majority of patients who had endoscopy (57%) had IV PPI administered in advance of the procedure. Of the 334 patients who had IV PPI given in advance, 46 (13.8%) were found to have high risk bleeding PUD stigmata at endoscopy. The remaining 288 patients (86.2%) with advance IV PPI had low-risk PUD lesions or non-PUD lesions; IV PPI was continued after endoscopy in 164 (56.9%) of these patients.

CONCLUSIONS:IV PPI is often used before endoscopy in suspected upper gastrointestinal bleed and maintained, regardless of endoscopic findings, after the endoscopy in many Canadian centres. Further study is required to support these clinical practices.
Wireless Capsule Endoscopy for Obscure Gastrointestinal Bleeding: Single Center, One Year Experience
Authors: Tang Shou-jiang , Christodoulo Dimitrios , Zanati Simon , Dubcenco Elena , Petroniene Rima , Cirocco Maria , Kandel Gabor , Haber Gregory B , Kortan Paul , Marcon Norman E
Published: March 2016

BACKGROUND:Wireless capsule endoscopy (CE) is increasingly being used in the investigation of obscure gastrointestinal (GI) bleeding, but some studies have found that many of the bleeding lesions recognized by this technique are within the reach of conventional endoscopy.

METHODS:The results of CE performed in the authors' centre in a 12 month period for obscure GI bleeding were retrospectively reviewed.

RESULTS:Of the 46 patients with obscure GI bleeding, CE found a definite or probable cause in 19 (41%) and a possible cause in another 10 (22%), with an overall diagnostic yield of 63%. One of these lesions was found to be within reach of conventional gastroscopy, two were within reach of push enteroscopy, four were within reach of colonoscopy and one was within reach of retrograde enteroscopy through a stoma. The percentage of patients with a bleeding source within reach of routine endoscopy but missed during pre-CE endoscopy was significantly higher for those patients having endoscopy only in the community (30% [eight of 27]) versus in the authors' centre (0% [zero of 19]).

CONCLUSIONS:CE was valuable for diagnosing bleeding lesions not only within the small bowel, but also in the stomach and colon. However, 'second-look' endoscopy may be considered before ordering CE for obscure GI bleeding when local expertise is available.
D(—)–Lactic Acid Producing Probiotics, D(—)–Lactic Acidosis and Infants
Authors: Mack David R
Published: March 2016

There is mounting evidence that ingestion of selected probiotics can modify disease morbidity for specific conditions affecting humans, and there is growing interest in the amelioration or prevention of disease with probiotics. Modulation in gene expression of the cellular elements of the intestinal mucosa and interbacterial interactions are leading theories as to the mechanism whereby probiotics can effect benefit for the host. Furthermore, gene-environmental interactions are considered to be important in the development of disease in those at genetic risk. With the intestinal tract harbouring large numbers of bacteria, alteration of the microbial environment with probiotic microbes is being considered as a controllable factor that may limit disease expression for those at genetic risk. This reasoning has led to interest in the administration of probiotics to infants. However, there are significant developmental changes occurring in many organ systems from the time of parturition and during the first months of life. Because there is little in the published scientific medical literature regarding the effects of long-term administration of probiotics to infants, potential problems must be considered; one such issue is that of administration of D(-)-lactate-producing probiotics. An appraisal of the current knowledge of this potential adverse effect is the subject of this communication.
The Economic Impact of Inflammatory Bowel Disease in Canada
Authors: Hilsden Robert
Published: March 2016

Longobardi and colleagues examined the effect of inflammatory bowel disease (IBD) on employment, using data from 10,891 respondents aged 20 to 64 years from the 1998 cycle of the Canadian National Population Health Survey (NPHS) (1). This sample included 187 (1.7%) subjects who self‐reported IBD or a similar bowel disorder. A significantly greater proportion of IBD than non‐IBD respondents reported that they were not in the labour force (28.9% versus 18.5%). Even after adjusting for other factors (age group, level of pain, etc), subjects with IBD had a 2.9% higher nonparticipation rate (21.4%). For example, among people not hospitalized within the past year and with no limitation of activities due to pain, IBD subjects were 1.2 times more likely to be unemployed than those without IBD. Subjects who reported high levels of pain had a very high probability of being out of the labour force. Based on Canadian annual compensation data for all employed persons in Canada, and age‐ and sex‐specific prevalence, and incidence rates for IBD, the authors estimated that there are 119,980 IBD patients between the ages of 20 and 64 years in Canada and that this group includes 3479 people who are not in the labour force. This translates into lost wages of $104.2 million, or $868 per IBD patient
The Perfect Way to Predict the Severity of Acute Pancreatitis: The Search Continues
Authors: Sadowski Daniel C
Published: March 2016

This study was designed to determine the clinical utility of three rating scales (Ranson's, Acute Physiology And Chronic Health Evaluation [APACHE] II and Glasgow) in predicting the severity of acute pancreatitis experienced by patients known to have human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). A retrospective analysis identified 73 patients with both acute pancreatitis and HIV who had been admitted to two Canadian hospitals between 1989 and 1999. Of those 73, 11 (15%) went on to have a clinical course consistent with a diagnosis of severe pancreatitis. For the purposes of the study, severe pancreatitis was defined by the occurrence of death, intensive care unit admission, surgical intervention or significant symptomatic local complications (necrosis, abscess or pseudocyst). The authors found that the APACHE II and Ranson's scores had a sensitivity of 100% and specificities of 70% and 33% for severe pancreatitis, respectively. The Glasgow score had a statistically poorer diagnostic performance.
Cytokines as Therapeutic Targets for the Gastrointestinal Manifestations of Scleroderma
Authors: Raoul Jennifer M , Verma Monica , Tan Ernest , Peterson Theresa C
Published: March 2016

Systemic sclerosis (SSc), or scleroderma, is a connective tissue disorder characterized by progressive fibrosis of the skin and internal organs. It has significance for gastroenterologists because the gastrointestinal tract is involved in 90% of SSc patients, who often present with esophageal dysfunction. Though the exact pathogenesis of SSc is unknown, there is increasing evidence supporting an immune mechanism. Cytokines are the soluble mediators of immune activation, altered fibroblast proliferation and extracellular matrix accumulation in SSc and thereby provide important therapeutic targets. In the present review, the involvement of cytokines in SSc is discussed with particular emphasis on cytokines and growth factors that have been implicated in the disease process and likely play an important role in the gastrointestinal manifestations of scleroderma. The role of cytokines as therapeutic targets in scleroderma forms the basis of this timely review
The Ultimate Therapeutic Goal: Establishing and Maintaining Quality of Life
Authors: Panaccione Remo
Published: March 2016

Outcomes in Crohn's disease clinical trials are traditionally reported in terms of remission and response rates according to the Crohn's Disease Activity Index (CDAI), which was developed as part of the National Cooperative Crohn's Disease Study (1). However, it has been argued that the CDAI does not measure the overall burden of the illness experienced by patients. An alternative is to assess the impact of a particular therapy on health-related quality of life (HRQL). HRQL not only measures the benefits of the therapy on disease symptoms but also is probably better at evaluating the trade-off between therapeutic efficacy and potential adverse effects.
Think Stop before Going 'Off-Label'
Authors: Minuk Gerald Y
Published: March 2016

Only after careful and extensive review of all available safety and efficacy data derived from preclinical and clinical trials will a regulatory body approve the licensing of a drug for a specific medical condition ('indication'). Experience with thalidomide, fialuridine and troglitazone, to name a few, reveal that despite these efforts, the process is not infallible. What then can we expect when a drug is used for a medical condition in which no such review process has been undertaken ('offlabel' use of the drug)?
Endoscopic Ultrasound Findings in Duodenal Gangliocytic Paraganglioma
Authors: Sheen-Chen Shyr-Ming , Tsai Tung-Lung , Eng Hock-Liew
Published: March 2016

Gangliocytic paraganglioma is an uncommon benign neurogenic tumour of the digestive tract that is usually located in the descending duodenum. Due to the unusual location, such lesions are frequently overlooked on routine radiological examinations and initial endoscopy. With the recent development of endoscopic ultrasound, lesions in this location can be more easily detected and better viewed. A case of a duodenal gangliocytic paraglioma detected by endoscopic ultrasound is presented; this is possibly only the second such case to be reported in the literature.
Patient Non-Adherence to Medication in Inflammatory Bowel Disease
Authors: Thomson Alan BR
Published: March 2016

Dr Sewitch and colleagues at the University of Montreal and McGill University undertook a prospective study that provided evidence for the important relationship between patient-physician discordance and patient nonadherence with medication for inflammatory bowel disease (IBD).
The Hereditary Spectrum of Pancreatic Cancer: The Edmonton Experience
Authors: Lilley Margaret , Gilchrist Dawna
Published: March 2016

OBJECTIVE:Pancreatic cancer is known to aggregate in some families and has been associated with a wide variety of cancer syndromes. The authors describe their experience with pancreatic cancer and the range of associated cancer syndromes.

METHODS:The charts of all patients seen for concern of a hereditary cancer syndrome in the Cancer Genetics Clinic at the University of Alberta between 1995 and 2002 were reviewed.

RESULTS:Forty families reported a personal or family history of pancreatic cancer in the context of a possible hereditary cancer syndrome. Three additional families reported a history of pancreatitis. Twenty-four (56%) of those families were suspected of having a hereditary breast and ovarian cancer syndrome. A further seven (16%) were suspected of having hereditary nonpolyposis colon cancer. Only three (7%) were believed to be at risk for a site-specific pancreatic cancer syndrome. Another three (7%) were suspicious for hereditary pancreatitis. The remaining family histories were suggestive of Li-Fraumeni syndrome, von Hippel-Lindau syndrome or a nonspecific cancer predisposition.

CONCLUSIONS:With such a wide variety of hereditary cancer syndromes associated with pancreatic cancer, an accurate assessment of the family history is essential to determine the most appropriate cancer screening for at-risk family members and to guide any molecular testing that may be offered.
Functional Development of the Human Gastrointestinal Tract: Hormone- and Growth Factor-Mediated Regulatory Mechanisms
Authors: Ménard Daniel
Published: March 2016

The present review focuses on the control of gastrointestinal (GI) tract development. The first section addresses the differences in general mechanisms of GI development in humans versus rodents, highlighting that morphogenesis of specific digestive organs and the differentiation of digestive epithelia occur not only at different stages of ontogeny but also at different rates. The second section provides an overview of studies from the author's laboratory at the Université de Sherbrooke pertaining to the development of the human fetal small intestine and colon. While both segments share similar morphological and functional characteristics, they are nevertheless modulated by distinct regulatory mechanisms. Using the organ culture approach, the author and colleagues were able to establish that hormones and growth factors, such as glucocorticoids, epidermal growth factor, insulin and keratinocyte growth factor, not only exert differential effects within these two segments, they can also trigger opposite responses in comparison with animal models. In the third section, emphasis is placed on the functional development of human fetal stomach and its various epithelial cell types; in particular, the glandular chief cells responsible for the synthesis and secretion of gastric enzymes such as pepsinogen-5 and gastric lipase. Bearing in mind that limitations of available cell models have, until now, greatly impeded the comprehension of molecular mechanisms regulating human gastric epithelial cell functions, the last section focuses on new human gastric epithelial cell models recently developed in the author's laboratory. These models comprise a novel primary culture system of human fetal gastric epithelium including, for the first time, functional chief cells, and human gastric epithelium cell lines cloned from the parental NCI-N87 strain. These new cells lines could serve important applications in the study of pathogenic action and epithelial regeneration.
Capsule endoscopy: New Technology That is Here to Stay
Authors: Enns Robert
Published: March 2016

Capsule endoscopy (CE) has recently been approved as a new technique for the examination of the small intestine. Following approval by the Food and Drug Administration of the United States in August 2001, CE has quickly gained widespread acceptance as the new 'gold standard' for visualization of the small intestine. Food and Drug Administration approval was based on two clinical studies (1,2). The first (1) compared CE with push enteroscopy (PE) (the previous gold standard) in dogs who had nine to 13 beads (3 mm to 6 mm each) sewn into the small intestine. CE identified more beads (median of six) than PE (median of three), with 64% sensitivity compared with 37% sensitivity for PE. The authors concluded that this new method of assessing the small intestine was superior to PE.
Cost-Effectiveness of Intravenous Proton Pump Inhibitors in High-Risk Bleeders
Authors: van Zanten Sander Veldhuyzen
Published: March 2016

There is unequivocal evidence that proton pump inhibitors (PPIs) are currently the most effective acid suppressive agents available. Intravenous (IV) formulations have been developed, although only IV pantoprazole is available in Canada. In patients presenting with serious upper gastrointestinal (GI) bleeding due to duodenal or gastric ulcers, it has always been believed that IV administration of acid-lowering agents would improve clinical outcomes. The reason behind this thinking is twofold. First, there is in vitro evidence that formed clots are more stable at or near neutral pH (1). Second, by administering the agent intravenously, suppression of acid production is achieved much more quickly, thereby promoting more rapid healing of the ulcer and reducing the risk of persistent or recurrent bleeding. Interestingly and surprisingly, however, the data for intravenous H2-blockers have been disappointing (2). This failure to demonstrate clinical benefit has never been fully explained.
Finally... Real Utility Scores for Hepatitis C Patients!
Authors: Peltekian Kevork M
Published: March 2016

Chong and colleagues (1) used gold-standard methods to assess health-state utilities in 193 outpatients at various stages of liver disease due to chronic hepatitis C (HCV) infection. They showed worsening of health-state utility scores with progression of disease from mild to moderate chronic hepatitis, to compensated cirrhosis, to decompensated cirrhosis and to hepatocellular carcinoma. They also confirmed improvement in health-state utility scores after liver transplantation and with sustained virological response (SVR) to treatment of HCV infection. Patients with HCV infection had lower health-state utility scores than the general Canadian population (PÃ0.001) and significantly poorer quality of life compared with population norms in the United States (PÃ0.005).
There May Be a Way to Say 'NO' to Gastric Injury Associated with the Combined Use of Aspirin and Cyclooxygenase-2 Inhibitors
Authors: Williams Jennifer J , Beck Paul L
Published: March 2016

Due to evidence that it reduces the frequency of cardiac events and stroke, the use of daily low-dose aspirin has dramatically increased over the past 20 years (1). The use of other nonsteroidal anti-inflammatory drugs (NSAIDs) for the relief of pain and inflammation has also increased (2). Unfortunately, aspirin and conventional NSAIDs such as diclofenac are notorious for causing significant damage to the upper gastrointestinal tract because they suppress prostaglandin (PG) synthesis (3).
Complete Histological Resolution of Collagenous Sprue
Authors: Freeman Hugh J , Davis Jennifer E , Myers Danny M
Published: March 2016

A 65-year-old woman developed a watery diarrhea syndrome with collagenous colitis. Later, weight loss and hypoalbuminemia were documented. This prompted small bowel biopsies that showed pathological changes of collagenous sprue. An apparent treatment response to a gluten-free diet and prednisone resulted in reduced diarrhea, weight gain and normalization of serum albumin. Later repeated biopsies from multiple small and large bowel sites over a period of over three years, however, showed reversion to normal small intestinal mucosa but persistent collagenous colitis. These results indicate that collagenous inflammatory disease may be a far more extensive process in the gastrointestinal tract than is currently appreciated. Moreover, collagenous colitis may be a clinical signal that occult small intestinal disease is present. Finally, collagenous sprue may, in some instances, be a completely reversible small intestinal disorder.
Primary Multidrug Resistant Tuberculosis and Utility of Line Probe Assay for Its Detection in Smear-Positive Sputum Samples in a Tertiary Care Hospital in South India
Authors: Yacoob Fahmiya Leena , Philomina Jose Beena , Karunakaran Lelitha Sarada Devi , Sreenivasan Sreelatha
Published: March 2016

In a high tuberculosis burdened country like India, rapid, cost-effective, and reliable diagnostic tools for tuberculosis are an urgent need of the hour to prevent inappropriate treatment strategies and further spread of resistance. This study aimed to estimate the proportion of new smear-positive tuberculosis cases with primary resistance to rifampicin and/or isoniazid as well as identify the common mutations associated with it. Sputum of 200 newly diagnosed smear-positive cases of 1+ score and above was directly subjected to Line Probe Assay using the GenoType MTBDRplusassay kit. All samples were inoculated onto solid media and 61 samples were inoculated in automated liquid culture also. The Line Probe Assay gave hundred percent interpretable results with 2.5% of the study population showing resistant pattern. Only 1% of the cases were primary multidrug resistant tuberculosis and 1.5% showed isoniazid monoresistance. S531L and C15T were the most common genetic mutations seen for rifampicin and isoniazid resistance, respectively. 40% had absentrpoBwild type 8 band indicating probable silent mutation after clinical correlation. The average turnaround time for Line Probe Assay was far less (3.8 days) as compared to solid and liquid cultures (35.6 days and 13.5 days, resp.).