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1.  Evaluation of funding gastroenterology research in Canada illustrates the beneficial role of partnerships 
BACKGROUND:
Funders of health research in Canada seek to determine how their funding programs impact research capacity and knowledge creation.
OBJECTIVE:
To evaluate the impact of a focused grants and award program that was cofunded by the Canadian Institutes of Health Research Institute of Nutrition, Metabolism and Diabetes, and the Canadian Association of Gastroenterology; and to measure the impact of the Program on the career paths of funded researchers and assess the outcomes of research supported through the Program.
METHODS:
A survey of the recipients of grants and awards from 2000 to 2008 was conducted in 2012. The CIHR Funding Decisions database was searched to determine subsequent funding; a bibliometric citation analysis of publications arising from the Program was performed.
RESULTS:
Of 160 grant and award recipients, 147 (92%) completed the survey. With >$17.4 million in research funding, support was provided for 131 fellowship awards, seven career transition awards, and 22 operating grants. More than three-quarters of grant and award recipients continue to work or train in a research-related position. Combined research outputs included 545 research articles, 130 review articles, 33 book chapters and 11 patents. Comparative analyses indicate that publications supported by the funding program had a greater impact than other Canadian and international comparators.
CONCLUSIONS:
Continuity in support of a long-term health research funding partnership strengthened the career development of gastroenterology researchers in Canada, and enhanced the creation and dissemination of new knowledge in the discipline.
PMCID: PMC3915015  PMID: 24340317
CAG; CIHR; Gastroenterology; Inflammatory bowel disease; Research capacity
2.  Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia 
Nature  2014;508(7494):98-102.
Changes in gene dosage are a major driver of cancer, engineered from a finite, but increasingly well annotated, repertoire of mutational mechanisms1. This can potentially generate correlated copy number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21)2,3. We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. We find that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have ~2700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimised for leukemic potential, showing constrained copy number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can co-ordinate to fashion copy number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes.
doi:10.1038/nature13115
PMCID: PMC3976272  PMID: 24670643
3.  The 2012 SAGE wait times program: Survey of Access to GastroEnterology in Canada 
BACKGROUND:
Periodically surveying wait times for specialist health services in Canada captures current data and enables comparisons with previous surveys to identify changes over time.
METHODS:
During one week in April 2012, Canadian gastroenterologists were asked to complete a questionnaire (online or by fax) recording demographics, reason for referral, and dates of referral and specialist visits for at least 10 consecutive new patients (five consultations and five procedures) who had not been seen previously for the same indication. Wait times were determined for 18 indications and compared with those from similar surveys conducted in 2008 and 2005.
RESULTS:
Data regarding adult patients were provided by 173 gastroenterologists for 1374 consultations, 540 procedures and 293 same-day consultations and procedures. Nationally, the median wait times were 92 days (95% CI 85 days to 100 days) from referral to consultation, 55 days (95% CI 50 days to 61 days) from consultation to procedure and 155 days (95% CI 142 days to 175 days) (total) from referral to procedure. Overall, wait times were longer in 2012 than in 2005 (P<0.05); the wait time to same-day consultation and procedure was shorter in 2012 than in 2008 (78 days versus 101 days; P<0.05), but continued to be longer than in 2005 (P<0.05). The total wait time remained longest for screening colonoscopy, increasing from 201 days in 2008 to 279 days in 2012 (P<0.05).
DISCUSSION:
Wait times for gastroenterology services continue to exceed recommended targets, remain unchanged since 2008 and exceed wait times reported in 2005.
PMCID: PMC3731118  PMID: 23472243
Access; Audit; Canada; Endoscopy; Gastroenterology; Wait time
4.  A survey of the practice of after-hours and emergency endoscopy in Canada 
OBJECTIVE:
To determine staffing and practice patterns for after-hours endoscopy service in Canada
METHODS:
A link to a web-based survey was sent by e-mail to all clinical members of the Canadian Association of Gastroenterology in February 2011. A priori, it was planned to compare variations in practice among gastroenterologists (GIs) performing endoscopy in different regions of Canada, between pediatric and adult GIs, and between university and community hospitals.
RESULTS:
Of 422 potential respondents, 168 (40%) responded. Of the 139 adult GIs, 61% performed after-hours endoscopy in the endoscopy suite where daytime procedures were performed, 62% had a trained endoscopy nurse available for all procedures, 38% had access to propofol sedation, 12% reprocessed the endoscopes themselves or with the help of a resident, 4% had out-of-hospital patients come directly to their endoscopy suite and 53% were highly satisfied. The adult endoscopists practising at community hospitals were more likely to have an anesthetist attend the procedure. Regional differences were noted, with more involvement of anesthetists (13%) and availability of propofol (50%) in Ontario, more frequent reprocessing of endoscopes in the central reprocessing units in British Columbia (78%) and almost universal availability of a trained endoscopy nurse (96%) with concomitant higher endoscopist satisfaction (84% highly satisfied) in Alberta.
CONCLUSIONS:
More than one-third of surveyed endoscopists across the country do not have a trained endoscopy nurse to assist in after-hours endoscopy – the time period when urgent patients often present and typically require therapeutic endoscopic interventions. There are significant regional differences in the practice of after-hours endoscopy in Canada.
PMCID: PMC3551559  PMID: 23248785
Emergency care; Endoscopy; Staffing; Standards
6.  Planetary Stewardship in an Urbanizing World: Beyond City Limits 
Ambio  2012;41(8):787-794.
Cities are rapidly increasing in importance as a major factor shaping the Earth system, and therefore, must take corresponding responsibility. With currently over half the world’s population, cities are supported by resources originating from primarily rural regions often located around the world far distant from the urban loci of use. The sustainability of a city can no longer be considered in isolation from the sustainability of human and natural resources it uses from proximal or distant regions, or the combined resource use and impacts of cities globally. The world’s multiple and complex environmental and social challenges require interconnected solutions and coordinated governance approaches to planetary stewardship. We suggest that a key component of planetary stewardship is a global system of cities that develop sustainable processes and policies in concert with its non-urban areas. The potential for cities to cooperate as a system and with rural connectivity could increase their capacity to effect change and foster stewardship at the planetary scale and also increase their resource security.
doi:10.1007/s13280-012-0353-7
PMCID: PMC3492563  PMID: 23076974
Urban; Rural; Resources; Sustainability; Planetary stewardship; Global; Governance
7.  Insights into interphase large-scale chromatin structure from analysis of engineered chromosome regions 
How chromatin folds into mitotic and interphase chromosomes has remained a difficult question for many years. We have used three generations of engineered chromosome regions as a means of visualizing specific chromosome regions in live cells and cells fixed under conditions which preserve large-scale chromatin structure. Our results confirm the existence of large-scale chromatin domains and fibers formed by the folding of 10 and 30 nm chromatin fibers into larger, spatially distinct domains. Transcription at levels within several fold of the levels measured for endogenous loci occur within these large-scale chromatin structures on a condensed template linearly compacted several hundred fold to one thousand fold relative to B-form DNA. However, transcriptional induction is accompanied by a several fold decondensation of this large-scale chromatin structure that propagates hundreds of kb beyond the induced gene. Examination of engineered chromosome regions in mouse ES and differentiated cells suggests a surprising degree of plasticity in this large-scale chromatin structure, allowing long-range DNA interactions within the context of large-scale chromatin fibers. Recapitulation of gene specific differences in large-scale chromatin conformation and nuclear positioning using these engineered chromosome regions will facilitate identification of cis and trans determinants of interphase chromosome architecture.
doi:10.1101/sqb.2010.75.050
PMCID: PMC3370657  PMID: 21467143
9.  Point-of-care, peer-comparator colonoscopy practice audit: The Canadian Association of Gastroenterology Quality Program – Endoscopy 
BACKGROUND
Point-of-care practice audits allow documentation of procedural outcomes to support quality improvement in endoscopic practice.
OBJECTIVE
To evaluate a colonoscopists’ practice audit tool that provides point-of-care data collection and peer-comparator feedback.
METHODS
A prospective, observational colonoscopy practice audit was conducted in academic and community endoscopy units for unselected patients undergoing colonoscopy. Anonymized colonoscopist, patient and practice data were collected using touchscreen smart-phones with automated data upload for data analysis and review by participants. The main outcome measures were the following colonoscopy quality indicators: colonoscope insertion and withdrawal times, bowel preparation quality, sedation, immediate complications and polypectomy, and biopsy rates.
RESULTS
Over a span of 16 months, 62 endoscopists reported on 1279 colonoscopy procedures. The mean cecal intubation rate was 94.9% (10th centile 84.2%). The mean withdrawal time was 8.8 min and, for nonpolypectomy colonoscopies, 41.9% of colonoscopists reported a mean withdrawal time of less than 6 min. Polypectomy was performed in 37% of colonoscopies. Independent predictors of polypectomy included the following: endoscopy unit type, patient age, interval since previous colonoscopy, bowel preparation quality, stable inflammatory bowel disease, previous colon polyps and withdrawal time. Withdrawal times of less than 6 min were associated with lower polyp removal rates (mean difference −11.3% [95% CI −2.8% to −19.9%]; P=0.01).
DISCUSSION
Cecal intubation rates exceeded 90% and polypectomy rates exceeded 30%, but withdrawal times were frequently shorter than recommended. There are marked practice variations consistent with previous observations.
CONCLUSION
Real-time, point-of-care practice audits with prompt, confidential access to outcome data provide a basis for targeted educational programs to improve quality in colonoscopy practice.
PMCID: PMC3027329  PMID: 21258663
Colonoscopy; Health care; Practice audit; Quality assurance; Quality indicators
10.  A one-year economic evaluation of six alternative strategies for the management of uninvestigated upper gastrointestinal symptoms in Canadian primary care 
BACKGROUND:
The cost-effectiveness of initial strategies in managing Canadian patients with uninvestigated upper gastrointestinal symptoms remains controversial.
OBJECTIVE:
To assess the cost-effectiveness of six management approaches to uninvestigated upper gastrointestinal symptoms in the Canadian setting.
METHODS:
The present study analyzed data from four randomized trials assessing homogeneous and complementary populations of Canadian patients with uninvestigated upper gastrointestinal symptoms with comparable outcomes. Symptom-free months, quality-adjusted life-years (QALYs) and direct costs in Canadian dollars of two management approaches based on the Canadian Dyspepsia Working Group (CanDys) Clinical Management Tool, and four additional strategies (two empirical antisecretory agents, and two prompt endoscopy) were examined and compared. Prevalence data, probabilities, utilities and costs were included in a Markov model, while sensitivity analysis used Monte Carlo simulations. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were determined.
RESULTS:
Empirical omeprazole cost $226 per QALY ($49 per symptom-free month) per patient. CanDys omeprazole and endoscopy approaches were more effective than empirical omeprazole, but more costly. Alternatives using H2-receptor antagonists were less effective than those using a proton pump inhibitor. No significant differences were found for most incremental cost-effectiveness ratios. As willingness to pay (WTP) thresholds rose from $226 to $24,000 per QALY, empirical antisecretory approaches were less likely to be the most cost-effective choice, with CanDys omeprazole progressively becoming a more likely option. For WTP values ranging from $24,000 to $70,000 per QALY, the most clinically relevant range, CanDys omeprazole was the most cost-effective strategy (32% to 46% of the time), with prompt endoscopy-proton pump inhibitor favoured at higher WTP values.
CONCLUSIONS:
Although no strategy was the indisputable cost-effective option, CanDys omeprazole may be the strategy of choice over a clinically relevant range of WTP assumptions in the initial management of Canadian patients with uninvestigated dyspepsia.
PMCID: PMC2947002  PMID: 20711528
Antisecretory therapy; Cost-effectiveness; Dyspepsia; Economic modelling; Endoscopy; Helicobacter pylori
11.  Dynamic plasticity of large-scale chromatin structure revealed by self-assembly of engineered chromosome regions 
The Journal of Cell Biology  2010;190(5):761-776.
Folding of gene loci organized in tandem arrays reveals variation of chromatin structure as a function of cell differentiation.
Interphase chromatin compaction well above the 30-nm fiber is well documented, but the structural motifs underlying this level of chromatin folding remain unknown. Taking a reductionist approach, we analyzed in mouse embryonic stem (ES) cells and ES-derived fibroblasts and erythroblasts the folding of 10–160-megabase pair engineered chromosome regions consisting of tandem repeats of bacterial artificial chromosomes (BACs) containing ∼200 kilobases of mammalian genomic DNA tagged with lac operator (LacO) arrays. Unexpectedly, linear mitotic and interphase chromatid regions formed from noncontiguously folded DNA topologies. Particularly, in ES cells, these model chromosome regions self-organized with distant sequences segregating into functionally distinct, compact domains. Transcriptionally active and histone H3K27me3-modified regions positioned toward the engineered chromosome subterritory exterior, with LacO repeats and the BAC vector backbone localizing within an H3K9me3, HP1-enriched core. Differential compaction of Dhfr and α- and β-globin transgenes was superimposed on dramatic, lineage-specific reorganization of large-scale chromatin folding, demonstrating a surprising plasticity of large-scale chromatin organization.
doi:10.1083/jcb.200912167
PMCID: PMC2935575  PMID: 20819934
14.  Survey of Access to GastroEnterology in Canada: The SAGE wait times program 
BACKGROUND:
Assessment of current wait times for specialist health services in Canada is a key method that can assist government and health care providers to plan wisely for future health needs. These data are not readily available. A method to capture wait time data at the time of consultation or procedure has been developed, which should be applicable to other specialist groups and also allows for assessment of wait time trends over intervals of years.
METHODS:
In November 2008, gastroenterologists across Canada were asked to complete a questionnaire (online or by fax) that included personal demographics and data from one week on at least five consecutive new consultations and five consecutive procedure patients who had not previously undergone a procedure for the same indication. Wait times were collected for 18 primary indications and results were then compared with similar survey data collected in 2005.
RESULTS:
The longest wait times observed were for screening colonoscopy (201 days) and surveillance of previous colon cancer or polyps (272 days). The shortest wait times were for cancer-likely based on imaging or physical examination (82 days), severe or rapidly progressing dysphagia or odynophagia (83 days), documented iron-deficiency anemia (90 days) and dyspepsia with alarm symptoms (99 days). Compared with 2005 data, total wait times in 2008 were lengthened overall (127 days versus 155 days; P<0.05) and for most of the seven individual indications that permitted data comparison.
CONCLUSION:
Median wait times for gastroenterology services continue to exceed consensus conference recommended targets and have significantly worsened since 2005.
PMCID: PMC2830635  PMID: 20186352
Access; Audit; Diagnosis; Endoscopy; Gastroenterology; Wait time
21.  Treating Helicobacter pylori infection in primary care patients with uninvestigated dyspepsia: the Canadian adult dyspepsia empiric treatment—Helicobacter pylori positive (CADET-Hp) randomised controlled trial 
BMJ : British Medical Journal  2002;324(7344):1012.
Objective
To determine whether a “test for Helicobacter pylori and treat” strategy improves symptoms in patients with uninvestigated dyspepsia in primary care.
Design
Randomised placebo controlled trial.
Setting
36 family practices in Canada.
Participants
294 patients positive for H pylori (13C- urea breath test) with symptoms of dyspepsia of at least moderate severity in the preceding month.
Intervention
Participants were randomised to twice daily treatment for 7 days with omeprazole 20 mg, metronidazole 500 mg, and clarithromycin 250 mg or omeprazole 20 mg, placebo metronidazole, and placebo clarithromycin. Patients were then managed by their family physicians according to their usual care.
Main outcome measures
Treatment success defined as no symptoms or minimal symptoms of dyspepsia at the end of one year. Societal healthcare costs collected prospectively for a secondary evaluation of actual mean costs.
Results
In the intention to treat population (n=294), eradication treatment was significantly more effective than placebo in achieving treatment success (50% v 36%; P=0.02; absolute risk reduction=14%; number needed to treat=7, 95% confidence interval 4 to 63). Eradication treatment cured H pylori infection in 80% of evaluable patients. Treatment success at one year was greater in patients negative for H pylori than in those positive for H pylori (54% v 39%; P=0.02). Eradication treatment reduced mean annual cost by $C53 (−86 to 180) per patient.
Conclusions
A “test for H pylori with 13C-urea breath test and eradicate” strategy shows significant symptomatic benefit at 12 months in the management of primary care patients with uninvestigated dyspepsia.
What is already known on this topicDyspepsia is a common problem in primary health care, although controversy exists about its definitionStudies of H pylori eradication in patients with uninvestigated dyspepsia have shown reduced need for endoscopy and thus significant cost savings compared with a strategy of prompt endoscopyThe “test for H pylori and treat” strategy has been recommended for uninvestigated dyspepsia, but there have been no randomised controlled trials showing improvement in symptomsWhat this study addsWhen given eradication treatment in primary care, H pylori positive patients with uninvestigated dyspepsia show improvement in overall dyspepsia symptoms at 12 monthsThis supports the “test for H pylori and treat” strategy
PMCID: PMC102778  PMID: 11976244

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