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1.  A survey of the management of newborns with severe hemophilia in Canada 
Paediatrics & Child Health  2013;18(4):189-193.
To determine the practice patterns of Canadian hematologists and neonatologists/paediatricians who care for newborns with hemophilia, with regard to vitamin K administration, use of empirical clotting factor replacement therapy, neuroimaging and timing of hematology consultation.
Hematologists and neonatologists/paediatricians, identified from membership lists of Canadian professional organizations, were provided electronic and/or paper versions of the survey instrument. Questions were posed in the context of specific clinical scenarios. Differences in response proportions between groups were compared for selected questions.
There were 171 respondents among 616 eligible persons who were sent the survey; 58 respondents had recent experience managing a newborn with hemophilia. There was a consensus not to provide empirical treatment to well newborns after uncomplicated deliveries, to provide empirical treatment to symptomatic newborns and to obtain neuroimaging for symptomatic newborns. Systematic differences between hematologists and neonatologists/paediatricians existed with regard to the timing of hematology consultation when the diagnosis of hemophilia had not been confirmed antenatally, the route of vitamin K administration for newborns with hemophilia and the choice of product to use for empirical treatment of a symptomatic newborn.
The observed lack of consensus regarding important management decisions indicates a need for ongoing research in the care of newborns with hemophilia. Systematic differences between hematologists and neonatologists/paediatricians suggest a role for improved communication and collaboration between these two groups of practitioners.
PMCID: PMC3805619  PMID: 24421686
Hemophilia A; Hemophilia B; Intracranial hemorrhages; Neuroimaging; Newborn
2.  Nanolitre real-time PCR detection of bacterial, parasitic, and viral agents from patients with diarrhoea in Nunavut, Canada 
International Journal of Circumpolar Health  2013;72:10.3402/ijch.v72i0.19903.
Little is known about the microbiology of diarrhoeal disease in Canada's Arctic regions. There are a number of limitations of conventional microbiology testing techniques for diarrhoeal pathogens, and these may be further compromised in the Arctic, given the often long distances for specimen transport.
To develop a novel multiple-target nanolitre real-time reverse transcriptase (RT)-PCR platform to simultaneously test diarrhoeal specimens collected from residents of the Qikiqtani (Baffin Island) Region of Nunavut, Canada, for a wide range of bacterial, parasitic and viral agents.
Study design/methods
Diarrhoeal stool samples submitted for bacterial culture to Qikiqtani General Hospital in Nunavut over an 18-month period were tested with a multiple-target nanolitre real-time PCR panel for major diarrhoeal pathogens including 8 bacterial, 6 viral and 2 parasitic targets.
Among 86 stool specimens tested by PCR, a total of 50 pathogens were detected with 1 or more pathogens found in 40 (46.5%) stool specimens. The organisms detected comprised 17 Cryptosporidium spp., 5 Clostridium difficile with toxin B, 6 Campylobacter spp., 6 Salmonella spp., 4 astroviruses, 3 noroviruses, 1 rotavirus, 1 Shigella spp. and 1 Giardia spp. The frequency of detection by PCR and bacterial culture was similar for Salmonella spp., but discrepant for Campylobacter spp., as Campylobacter was detected by culture from only 1/86 specimens. Similarly, Cryptosporidium spp. was detected in multiple samples by PCR but was not detected by microscopy or enzyme immunoassay.
Cryptosporidium spp., Campylobacter spp. and Clostridium difficile may be relatively common but possibly under-recognised pathogens in this region. Further study is needed to determine the regional epidemiology and clinical significance of these organisms. This method appears to be a useful tool for gastrointestinal pathogen research and may also be helpful for clinical diagnostics and outbreak investigation in remote regions where the yield of routine testing may be compromised.
PMCID: PMC3619031  PMID: 23570023
multiplex real-time PCR; detection; pathogens; Campylobacter spp.; Cryptosporidium spp.; Clostridium difficile; viral agents; diarrhoea; gastroenteritis; Nunavut; Arctic
3.  Community-acquired lobar pneumonia in children in the era of universal 7-valent pneumococcal vaccination: a review of clinical presentations and antimicrobial treatment from a Canadian pediatric hospital 
BMC Pediatrics  2012;12:133.
Community-acquired pneumonia (CAP) is a common cause of pediatric admission to hospital. The objectives of this study were twofold: 1) to describe the clinical characteristics of CAP in children admitted to a tertiary care pediatric hospital in the pneumococcal vaccination era and, 2) to examine the antimicrobial selection in hospital and on discharge.
A retrospective review of healthy immunocompetent children admitted to a tertiary pediatric hospital from January 2007 to December 2008 with clinical features consistent with pneumonia and a radiographically-confirmed consolidation was performed. Clinical, microbiological and antimicrobial data were collected.
One hundred and thirty-five hospitalized children with pneumonia were evaluated. Mean age at admission was 4.8 years (range 0–17 years). Two thirds of patients had been seen by a physician in the 24 hours prior to presentation; 56 (41.5%) were on antimicrobials at admission. 52 (38.5%) of patients developed an effusion, and 22/52 (42.3%) had pleural fluid sampled. Of 117 children who had specimens (blood/pleural fluid) cultured, 9 (7.7%) had pathogens identified (7 Streptococcus pneumoniae, 1 Group A Streptococcus, and 1 Rhodococcus). 55% of patients received 2 or more antimicrobials in hospital. Cephalosporins were given to 130 patients (96.1%) in hospital. Only 21/126 patients (16.7%) were discharged on amoxicillin. The median length of stay was 3 days (IQR 2–4) for those without effusion and 9 (IQR 5–13) for those with effusion. No deaths were related to pneumonia.
This study provides comprehensive data on the clinical characteristics of hospitalized children with CAP in the pneumococcal 7-valent vaccine era. Empiric antimicrobial choice at our institution is variable, highlighting a need for heightened antimicrobial stewardship.
PMCID: PMC3477073  PMID: 22928588
4.  Attitudes and practice of Children’s Hospital of Eastern Ontario (Ottawa, Ontario) paediatricians and residents toward literacy promotion in Canada 
Paediatrics & Child Health  2011;16(5):e38-e42.
Literacy is a critical health issue in Canada. Paediatricians play an important role in improving literacy skills; however, formal training in literacy education and promotion is not currently part of most Canadian paediatric residency programs.
To examine the attitudes and practice of paediatricians and residents at the Children’s Hospital of Eastern Ontario (CHEO [Ottawa, Ontario]) toward literacy promotion.
A descriptive, cross-sectional survey of CHEO-affiliated paediatricians, residents and fellows was performed. Survey items addressed demographics, attitudes toward literacy, current practice and previous education/training in literacy education through self-reporting.
One hundred ninety-seven surveys were distributed, with a response rate of 82%. Ninety-one per cent of respondents reported never having formal training in literacy development and promotion. Seventy-four per cent of respondents believed that low literacy is a significant health issue in Canada; however, only 16% of respondents reported regularly discussing literacy with patients and their families. Thirty-nine per cent of general paediatricians reported discussing literacy with patients and families regularly, compared with 10% of paediatric subspecialists (P<0.01). Seventy-one per cent of respondents believed that literacy education should be a standard part of residency education.
While most respondents identified literacy as an important paediatric issue, most paediatricians did not regularly discuss the importance of literacy with their patients. General paediatricians are most likely to discuss literacy. There is a lack of formal education among paediatricians in literacy development and promotion, and the majority of respondents believe that this should be a standard part of paediatric residency training.
PMCID: PMC3115000  PMID: 22547952
Advocacy; Literacy; Medical education; Reading
5.  Comparing multiple competing interventions in the absence of randomized trials using clinical risk-benefit analysis 
To demonstrate the use of risk-benefit analysis for comparing multiple competing interventions in the absence of randomized trials, we applied this approach to the evaluation of five anticoagulants to prevent thrombosis in patients undergoing orthopedic surgery.
Using a cost-effectiveness approach from a clinical perspective (i.e. risk benefit analysis) we compared thromboprophylaxis with warfarin, low molecular weight heparin, unfractionated heparin, fondaparinux or ximelagatran in patients undergoing major orthopedic surgery, with sub-analyses according to surgery type. Proportions and variances of events defining risk (major bleeding) and benefit (thrombosis averted) were obtained through a meta-analysis and used to define beta distributions. Monte Carlo simulations were conducted and used to calculate incremental risks, benefits, and risk-benefit ratios. Finally, net clinical benefit was calculated for all replications across a range of risk-benefit acceptability thresholds, with a reference range obtained by estimating the case fatality rate - ratio of thrombosis to bleeding.
The analysis showed that compared to placebo ximelagatran was superior to other options but final results were influenced by type of surgery, since ximelagatran was superior in total knee replacement but not in total hip replacement.
Using simulation and economic techniques we demonstrate a method that allows comparing multiple competing interventions in the absence of randomized trials with multiple arms by determining the option with the best risk-benefit profile. It can be helpful in clinical decision making since it incorporates risk, benefit, and personal risk acceptance.
PMCID: PMC3292458  PMID: 22233221
Risk-Benefit Analysis; Decision Making; Meta-Analysis; Methods; Monte Carlo Method; Risk; indirect comparison
6.  Rapid PCR detection of group a streptococcus from flocked throat swabs: A retrospective clinical study 
Rapid diagnosis of GAS pharyngitis may improve patient care by ensuring that patients with GAS pharyngitis are treated quickly and also avoiding unnecessary use of antibiotics in those without GAS infection. Very few molecular methods for detection of GAS in clinical throat swab specimens have been described.
We performed a study of a laboratory-developed internally-controlled rapid Group A streptococcus (GAS) PCR assay using flocked swab throat specimens. We compared the GAS PCR assay to GAS culture results using a collection of archived throat swab samples obtained during a study comparing the performance of conventional and flocked throat swabs.
The sensitivity of the GAS PCR assay as compared to the reference standard was 96.0% (95% CI 90.1% to 98.4%), specificity 98.6% (95% CI 95.8% to 99.5%), positive predictive value (PPV) 96.9% (95% CI 91.4% to 99.0%) and negative predictive value (NPV) of 98.1% (95% CI 95.2% to 99.2%). For conventional swab cultures, sensitivity was 96.0% (95% CI 90.1% to 98.4%), specificity 100% (95% CI 98.2% to 100%), PPV 100%, (95% CI 96.1% to 100%) and NPV 98.1% (95% CI 95.2% to 99.3%)
In this retrospective study, the GAS PCR assay appeared to perform as well as conventional throat swab culture, the current standard of practice. Since the GAS PCR assay, including DNA extraction, can be performed in approximately 1 hour, prospective studies of this assay are warranted to evaluate the clinical impact of the assay on management of patients with pharyngitis.
PMCID: PMC3179694  PMID: 21888649
PCR; rapid; internally-controlled; LCGreen; Group A Streptococcus; pharyngitis; flocked swab
PMCID: PMC2802109  PMID: 20034094
translocation 11;22; breast cancer; melanoma; esophageal cancer
8.  Assessment of Flocked Swabs for Use in Identification of Streptococcal Pharyngitis▿  
Journal of Clinical Microbiology  2009;47(9):3029-3030.
We compared the performance of flocked swabs to that of traditional swabs for culture of beta-hemolytic streptococci in children with pharyngitis. Sensitivity was higher for flocked swabs, but this did not reach statistical significance. We conclude that flocked swabs can be used in place of traditional swabs for diagnosis of streptococcal pharyngitis.
PMCID: PMC2738109  PMID: 19605581
9.  Comparing Administration of Questionnaires via the Internet to Pen-and-Paper in Patients with Heart Failure: Randomized Controlled Trial 
The use of the Internet to administer questionnaires has many potential advantages over the use of pen-and-paper administration. Yet it is important to validate Internet administration, as most questionnaires were initially developed and validated for pen-and-paper delivery. While some have been validated for use over the Internet, these questionnaires have predominately been used amongst the healthy general population. To date, information is lacking on the validity of questionnaires administered over the Internet in patients with chronic diseases such as heart failure.
To determine the validity of three heart failure questionnaires administered over the Internet compared to pen-and-paper administration in patients with heart failure.
We conducted a prospective randomized study using test-retest design comparing administration via the Internet to pen-and-paper administration for three heart failure questionnaires provided to patients recruited from a heart failure clinic in Toronto, Ontario, Canada: the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and the Self-Care Heart Failure Index (SCHFI).
Of the 58 subjects enrolled, 34 completed all three questionnaires. The mean difference and confidence intervals for the summary scores of the KCCQ, MLHFQ, and SCHFI were 1.2 (CI -1.5 to 4.0, scale from 0 to 100), 4.0 (CI -1.98 to 10.04, scale from 0 to 105), and 10.1 (CI 1.18 to 19.07, scale from 66.7 to 300), respectively.
Internet administration of the KCCQ appears to be equivalent to pen-and-paper administration. For the MLHFQ and SCHFI, we were unable to demonstrate equivalence. Further research is necessary to determine if the administration methods are equivalent for these instruments.
PMCID: PMC2762767  PMID: 19275979
Heart failure; Internet; questionnaires; validation
10.  An alternative to the hand searching gold standard: validating methodological search filters using relative recall 
Search filters or hedges play an important role in evidence-based medicine but their development depends on the availability of a "gold standard" – a reference standard against which to establish the performance of the filter. We demonstrate the feasibility of using relative recall of included studies from multiple systematic reviews to validate methodological search filters as an alternative to validation against a gold standard formed through hand searching.
We identified 105 Cochrane reviews that used the Highly Sensitive Search Strategy (HSSS), included randomized or quasi-randomized controlled trials, and reported their included studies. We measured the ability of two published and one novel variant of the HSSS to retrieve the MEDLINE-index studies included in these reviews.
The systematic reviews were comprehensive in their searches. 72% of included primary studies were indexed in MEDLINE. Relative recall of the three strategies ranged from .98 to .91 across all reviews and more comprehensive strategies showed higher recall.
An approach using relative recall instead of a hand searching gold standard proved feasible and produced recall figures that were congruent with previously published figures for the HSSS. This technique would permit validation of a methodological filter using a collection of approximately 100 studies of the chosen design drawn from the included studies of multiple systematic reviews that used comprehensive search strategies.
PMCID: PMC1557524  PMID: 16848895
11.  Can electronic search engines optimize screening of search results in systematic reviews: an empirical study 
Most electronic search efforts directed at identifying primary studies for inclusion in systematic reviews rely on the optimal Boolean search features of search interfaces such as DIALOG® and Ovid™. Our objective is to test the ability of an Ultraseek® search engine to rank MEDLINE® records of the included studies of Cochrane reviews within the top half of all the records retrieved by the Boolean MEDLINE search used by the reviewers.
Collections were created using the MEDLINE bibliographic records of included and excluded studies listed in the review and all records retrieved by the MEDLINE search. Records were converted to individual HTML files. Collections of records were indexed and searched through a statistical search engine, Ultraseek, using review-specific search terms. Our data sources, systematic reviews published in the Cochrane library, were included if they reported using at least one phase of the Cochrane Highly Sensitive Search Strategy (HSSS), provided citations for both included and excluded studies and conducted a meta-analysis using a binary outcome measure. Reviews were selected if they yielded between 1000–6000 records when the MEDLINE search strategy was replicated.
Nine Cochrane reviews were included. Included studies within the Cochrane reviews were found within the first 500 retrieved studies more often than would be expected by chance. Across all reviews, recall of included studies into the top 500 was 0.70. There was no statistically significant difference in ranking when comparing included studies with just the subset of excluded studies listed as excluded in the published review.
The relevance ranking provided by the search engine was better than expected by chance and shows promise for the preliminary evaluation of large results from Boolean searches. A statistical search engine does not appear to be able to make fine discriminations concerning the relevance of bibliographic records that have been pre-screened by systematic reviewers.
PMCID: PMC1403795  PMID: 16504110
12.  Identifying null meta-analyses that are ripe for updating 
As an increasingly large number of meta-analyses are published, quantitative methods are needed to help clinicians and systematic review teams determine when meta-analyses are not up to date.
We propose new methods for determining when non-significant meta-analytic results might be overturned, based on a prediction of the number of participants required in new studies. To guide decision making, we introduce the "new participant ratio", the ratio of the actual number of participants in new studies to the predicted number required to obtain statistical significance. A simulation study was conducted to study the performance of our methods and a real meta-analysis provides further evidence.
In our three simulation configurations, our diagnostic test for determining whether a meta-analysis is out of date had sensitivity of 55%, 62%, and 49% with corresponding specificity of 85%, 80%, and 90% respectively.
Simulations suggest that our methods are able to detect out-of-date meta-analyses. These quick and approximate methods show promise for use by systematic review teams to help decide whether to commit the considerable resources required to update a meta-analysis. Further investigation and evaluation of the methods is required before they can be recommended for general use.
PMCID: PMC212708  PMID: 12877755
13.  Funding source, trial outcome and reporting quality: are they related? Results of a pilot study 
There has been increasing concern regarding the potential effects of the commercialization of research.
In order to examine the relationships between funding source, trial outcome and reporting quality, recent issues of five peer-reviewed, high impact factor, general medical journals were hand-searched to identify a sample of 100 randomized controlled trials (20 trials/journal). Relevant data, including funding source (industry/not-for-profit/mixed/not reported) and statistical significance of primary outcome (favouring new treatment/favouring conventional treatment/neutral/unclear), were abstracted. Quality scores were assigned using the Jadad scale and the adequacy of allocation concealment.
Sixty-six percent of trials received some industry funding. Trial outcome was not associated with funding source (p= .461). There was a preponderance of favourable statistical conclusions among published trials with 67% reporting results that favored a new treatment whereas 6% favoured the conventional treatment. Quality scores were not associated with funding source or trial outcome.
It is not known whether the absence of significant associations between funding source, trial outcome and reporting quality reflects a true absence of an association or is an artefact of inadequate statistical power, reliance on voluntary disclosure of funding information, a focus on trials recently published in the top medical journals, or some combination thereof. Continued and expanded monitoring of potential conflicts is recommended, particularly in light of new guidelines for disclosure that have been endorsed by the ICMJE.
PMCID: PMC126226  PMID: 12213183
14.  Shorter courses of parenteral antibiotic therapy do not appear to influence response rates for children with acute hematogenous osteomyelitis: a systematic review 
Acute hematogenous osteomyelitis (AHO) occurs primarily in children and is believed to evolve from bacteremia followed by localization of infection to the metaphysis of bones. Currently, there is no consensus on the route and duration of antimicrobial therapy to treat AHO.
We conducted a systematic review of a short versus long course of treatment for AHO due primarily to Staphylococcus aureus in children aged 3 months to 16 years. We searched Medline, Embase and the Cochrane trials registry for controlled trials. Clinical cure rate at 6 months was the primary outcome variable, and groups receiving less than 7 days of intravenous therapy were compared with groups receiving one week or longer of intravenous antimicrobials.
12 eligible prospective studies, one of which was randomized, were identified. The overall cure rate at 6 months for the short course of intravenous therapy was 95.2% (95% CI = 90.4, 97.7) compared to 98.8% (95% CI = 93.6, 99.8) for the longer course of therapy. There was no significant difference in the duration of oral therapy between the two groups.
Given the potential increased morbidity and cost associated with longer courses of intravenous therapy, this finding should be confirmed through a randomized controlled equivalence trial.
PMCID: PMC128824  PMID: 12181082

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