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1.  Evidence summaries (decision boxes) to prepare clinicians for shared decision-making with patients: a mixed methods implementation study 
Decision boxes (Dboxes) provide clinicians with research evidence about management options for medical questions that have no single best answer. Dboxes fulfil a need for rapid clinical training tools to prepare clinicians for clinician-patient communication and shared decision-making. We studied the barriers and facilitators to using the Dbox information in clinical practice.
We used a mixed methods study with sequential explanatory design. We recruited family physicians, residents, and nurses from six primary health-care clinics. Participants received eight Dboxes covering various questions by email (one per week). For each Dbox, they completed a web questionnaire to rate clinical relevance and cognitive impact and to assess the determinants of their intention to use what they learned from the Dbox to explain to their patients the advantages and disadvantages of the options, based on the theory of planned behaviour (TPB). Following the 8-week delivery period, we conducted focus groups with clinicians and interviews with clinic administrators to explore contextual factors influencing the use of the Dbox information.
One hundred clinicians completed the web surveys. In 54% of the 496 questionnaires completed, they reported that their practice would be improved after having read the Dboxes, and in 40%, they stated that they would use this information for their patients. Of those who would use the information for their patients, 89% expected it would benefit their patients, especially in that it would allow the patient to make a decision more in keeping with his/her personal circumstances, values, and preferences. They intended to use the Dboxes in practice (mean 5.6 ± 1.2, scale 1–7, with 7 being “high”), and their intention was significantly related to social norm, perceived behavioural control, and attitude according to the TPB (P < 0.0001). In focus groups, clinicians mentioned that co-interventions such as patient decision aids and training in shared decision-making would facilitate the use of the Dbox information. Some participants would have liked a clear “bottom line” statement for each Dbox and access to printed Dboxes in consultation rooms.
Dboxes are valued by clinicians. Tailoring of Dboxes to their needs would facilitate their implementation in practice.
Electronic supplementary material
The online version of this article (doi:10.1186/s13012-014-0144-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4201673  PMID: 25280742
Clinical practice guidelines; Knowledge translation; Decision support; Evidence-based practice; Barriers; Patient-centred care; User experience; Continuing professional development; Communication competency
2.  Bionimbus: a cloud for managing, analyzing and sharing large genomics datasets 
As large genomics and phenotypic datasets are becoming more common, it is increasingly difficult for most researchers to access, manage, and analyze them. One possible approach is to provide the research community with several petabyte-scale cloud-based computing platforms containing these data, along with tools and resources to analyze it.
Bionimbus is an open source cloud-computing platform that is based primarily upon OpenStack, which manages on-demand virtual machines that provide the required computational resources, and GlusterFS, which is a high-performance clustered file system. Bionimbus also includes Tukey, which is a portal, and associated middleware that provides a single entry point and a single sign on for the various Bionimbus resources; and Yates, which automates the installation, configuration, and maintenance of the software infrastructure required.
Bionimbus is used by a variety of projects to process genomics and phenotypic data. For example, it is used by an acute myeloid leukemia resequencing project at the University of Chicago. The project requires several computational pipelines, including pipelines for quality control, alignment, variant calling, and annotation. For each sample, the alignment step requires eight CPUs for about 12 h. BAM file sizes ranged from 5 GB to 10 GB for each sample.
Most members of the research community have difficulty downloading large genomics datasets and obtaining sufficient storage and computer resources to manage and analyze the data. Cloud computing platforms, such as Bionimbus, with data commons that contain large genomics datasets, are one choice for broadening access to research data in genomics.
PMCID: PMC4215034  PMID: 24464852
cloud computing; biomedical clouds; genomic clouds
3.  Barriers and facilitators to implementing Decision Boxes in primary healthcare teams to facilitate shared decisionmaking: a study protocol 
Decision Boxes are summaries of the most important benefits and harms of health interventions provided to clinicians before they meet the patient, to prepare them to help patients make informed and value-based decisions. Our objective is to explore the barriers and facilitators to using Decision Boxes in clinical practice, more precisely factors stemming from (1) the Decision Boxes themselves, (2) the primary healthcare team (PHT), and (3) the primary care practice environment.
A two-phase mixed methods study will be conducted. Eight Decision Boxes relevant to primary care, and written in both English and in French, will be hosted on a website together with a tutorial to introduce the Decision Box. The Decision Boxes will be delivered as weekly emails over a span of eight weeks to clinicians of PHTs (family physicians, residents and nurses) in five primary care clinics located across two Canadian provinces. Using a web-questionnaire, clinicians will rate each Decision Box with the Information Assessment Method (cognitive impacts, relevance, usefulness, expected benefits) and with a questionnaire based on the Theory of Planned Behavior to study the determinants of clinicians’ intention to use what they learned from that Decision Box in their patient encounter (attitude, social norm, perceived behavioral control). Web-log data will be used to monitor clinicians’ access to the website. Following the 8-week intervention, we will conduct semi-structured group interviews with clinicians and individual interviews with clinic administrators to explore contextual factors influencing the use of the Decision Boxes. Data collected from questionnaires, focus groups and individual interviews will be combined to identify factors potentially influencing implementation of Decision Boxes in clinical practice by clinicians of PHTs.
This project will allow tailoring of Decision Boxes and their delivery to overcome the specific barriers identified by clinicians of PHTs to improve the implementation of shared decision making in this setting.
PMCID: PMC3472191  PMID: 22867107
(3–10); Evidence-based practice; Continuing professional education; Risk communication; Patient-centered care; Counselling; Clinical topic summary; Decision support; Knowledge translation; Implementation science
4.  Angiogenin Levels and ANG Genotypes: Dysregulation in Amyotrophic Lateral Sclerosis 
PLoS ONE  2010;5(11):e15402.
To determine whether 5 single nucleotide polymorphisms (SNPs) associate with ALS in 3 different populations. We also assessed the contribution of genotype to angiogenin levels in plasma and CSF.
Allelic association statistics were calculated for polymorphisms in the ANG gene in 859 patients and 1047 controls from Sweden, Ireland and Poland. Plasma, serum and CSF angiogenin levels were quantified and stratified according to genotypes across the ANG gene. The contribution of SNP genotypes to variance in circulating angiogenin levels was estimated in patients and controls.
All SNPs showed association with ALS in the Irish group. The SNP rs17114699 replicated in the Swedish cohort. No SNP associated in the Polish cohort. Age- and sex-corrected circulating angiogenin levels were significantly lower in patients than in controls (p<0.001). An allele dose-dependent regulation of angiogenin levels was observed in controls. This regulation was attenuated in the ALS cohort. A significant positive correlation between CSF plasma angiogenin levels was present in controls and abolished in ALS.
ANG variants associate with ALS in the Irish and Swedish populations, but not in the Polish. There is evidence of dysregulation of angiogenin expression in plasma and CSF in sporadic ALS. Angiogenin expression is likely to be important in the pathogenesis of ALS.
PMCID: PMC2978104  PMID: 21085671
5.  Paraoxonase promoter and intronic variants modify risk of sporadic amyotrophic lateral sclerosis 
The paraoxonases, PON1–3, play a major protective role both against environmental toxins and as part of the antioxidant defence system. Recently, non‐synonymous coding single nucleotide polymorphisms (SNPs), known to lower serum PON activity, have been associated with sporadic ALS (SALS) in a Polish population. A separate trio based study described a detrimental allele at the PON3 intronic variant INS2+3651 (rs10487132). Association between PON gene cluster variants and SALS requires external validation in an independent dataset.
To examine the association of the promoter SNPs PON1−162G>A and PON1−108T>C; the non‐synonymous functional SNPs PON1Q192R and L55M and PON2C311S and A148G; and the intronic marker PON3INS2+3651A>G, with SALS in a genetically homogenous population.
221 Irish patients with SALS and 202 unrelated control subjects were genotyped using KASPar chemistries. Statistical analyses and haplotype estimations were conducted using Haploview and Unphased software. Multiple permutation testing, as implemented in Unphased, was applied to haplotype p values to correct for multiple hypotheses.
Two of the seven SNPs were associated with SALS in the Irish population: PON155M (OR 1.52, p = 0.006) and PON3INS2+3651 G (OR 1.36, p = 0.03). Two locus haplotype analysis showed association only when both of these risk alleles were present (OR 1.7, p = 0.005), suggesting a potential effect modification. Low functioning promoter variants were observed to influence this effect when compared with wild‐type.
These data provide additional evidence that genetic variation across the paroxanase loci may be common susceptibility factors for SALS.
PMCID: PMC2117866  PMID: 17702780
6.  Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD 
BMC Neurology  2006;6:44.
A new locus for amyotrophic lateral sclerosis – frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p.
We identified chromosome 9p segregating haplotypes within two families with ALS-FTD (F476 and F2) and undertook mutational screening of candidate genes within this locus.
Candidate gene sequencing at this locus revealed the presence of a disease segregating stop mutation (Q342X) in the intraflagellar transport 74 (IFT74) gene in family 476 (F476), but no mutation was detected within IFT74 in family 2 (F2). While neither family was sufficiently informative to definitively implicate or exclude IFT74 mutations as a cause of chromosome 9-linked ALS-FTD, the nature of the mutation observed within F476 (predicted to truncate the protein by 258 amino acids) led us to sequence the open reading frame of this gene in a large number of ALS and FTD cases (n = 420). An additional sequence variant (G58D) was found in a case of sporadic semantic dementia. I55L sequence variants were found in three other unrelated affected individuals, but this was also found in a single individual among 800 Human Diversity Gene Panel samples.
Confirmation of the pathogenicity of IFT74 sequence variants will require screening of other chromosome 9p-linked families.
PMCID: PMC1764752  PMID: 17166276

Results 1-6 (6)