7 research outputs found
Long-term outcomes of patients with Takayasu arteritis and renal artery involvement: a cohort study.
OBJECTIVE: To describe the long-term outcomes of patients with Takayasu arteritis (TAK) and renal artery involvement (RAI). METHODS: A retrospective review of 122 patients with TAK at three tertiary centres in Canada, Sweden and the UK. Data on demographics, laboratory and clinical parameters, medications and angiography findings were collected. Non-renal and renal parameters were compared at baseline and follow-up. RESULTS: A total of 37 patients (30%) with RAI were identified: 18 (49%) with unilateral and 19 (51%) with bilateral RAI. Patients were predominantly female (89%). The median age at diagnosis was 27 years [interquartile range (IQR) 16-38]. The median follow-up time was 7 years (IQR 2-12). Hypertension was seen in 27 patients (73%) at presentation and 25 (68%) at follow-up. The median estimated glomerular filtration (eGFR) at presentation was 94 and 98 ml/min/1.73 m2 in those with unilateral and bilateral RAI, respectively. The corresponding median eGFR at follow-up was 101.5 and 104 ml/min/1.73 m2, respectively. Three patients at presentation and two at follow-up had an eGFR of <60 ml/min/1.73 m2. Five underwent endovascular intervention and three required surgical interventions. Among the 33 patients with radiologic follow-up, 23 (69%) had persistent RAI and 10 (30%) had resolution of RAI. One (6%) patient with unilateral RAI developed bilateral RAI and three (19%) with bilateral RAI regressed to unilateral RAI. Over time, 23 (62%) patients had stable renal function, 7 (19%) had improvement and 4 had a decline in renal function; no patient developed end-stage renal disease (ESRD). CONCLUSION: In this series of TAK patients with RAI, long-term non-renal and renal outcomes were favourable. No patient experienced ESRD or died
CanVasc Consensus Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitis: 2020 Update
Objective In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aimed to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence.
Methods A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014-September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a two-step modified Delphi procedure to reach >80% consensus on the inclusion, wording and grading of each new and revised recommendation.
Results Eleven new and 16 revised recommendations were created, and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary appendix for practical use was revised to reflect the updated recommendations.
Conclusion The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts
Identification of novel genetic alterations in oral squamous cell carcinoma
Oral squamous cell carcinoma (OSCC) is the most common head and neck
neoplasm, affecting approximately 400,000 people annually worldwide. Most cases are
not diagnosed until the advanced stages of the disease resulting in a five-year survival
rate of 50%. Application of high resolution genomic analysis techniques for the detection
of novel molecular markers and targets will greatly benefit the prevention and
management of this disease. Array comparative genomic hybridization (aCGH) enables
the detection of segmental gains and losses of DNA.
We constructed a 3p-arm specific array comprised of 535 near-overlapping BAC
clones for the identification of minimal regions of gain and loss on this chromosome arm.
Application of this array to 19 OSCC specimens enabled the identification and
characterization of five minimal regions of alteration including 4 regions of loss, and,
interestingly, 1 region of gain. 3p loss is a common event in OSCC; however, segmental
gains on this arm have not been previously described. Further construction of a whole
genome sub-megabase resolution tiling set (SMRT) array comprised of 32,433 overlapping
BAC clones spanning the entire human genome made possible the analysis of the
genome of an additional set of 20 OSCC specimens at unprecedented resolution.
Comparison of these OSCC genomes allowed the identification of well-known alterations
as well as novel minimal regions including gains at 3q23, 5pl5.2, 7pl2.3-13, 7q21.2, and
7q35, and losses at 2pl5, 4q34.3, and 16q23.2. Most of these novel alterations are submegabase
in size, suggesting that they may have been missed by conventional, lower resolution techniques. A selection of the novel gains was confirmed through reverse
transcriptase PCR expression analysis of genes within those regions such as TRIO at
5pl5.2, TEM6 at 7pl2.3-13, and CDK6 at 7q21.2, all of which showed elevated
expression in tumours compared to normal oral epithelial cells.
This study represents the first application of tiling resolution aCGH technology
for the detailed analysis of clinical specimens and demonstrates the invaluable power of
tiling resolution aCGH technology for the analysis of OSCC genomes. Here, we
demonstrate that novel sub-megabase minimal regions of alteration are recurrent events
in OSCC genomes. The identification of genes previously implicated in cancer or with
functional roles in the cell-cycle and/or signal transduction within these minimal submegabase
alterations suggests the importance of these alterations in OSCC. Further
assessment of these genes and their respective pathways, both at the expression and
functional level, may lead to the development of novel drug therapies targeting these
gene products.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat
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Long-term outcomes of patients with Takayasu arteritis and renal artery involvement: a cohort study.
Objective: To describe the long-term outcomes of patients with Takayasu arteritis (TAK) and renal artery involvement (RAI). Methods: A retrospective review of 122 patients with TAK at three tertiary centres in Canada, Sweden and the UK. Data on demographics, laboratory and clinical parameters, medications and angiography findings were collected. Non-renal and renal parameters were compared at baseline and follow-up. Results: A total of 37 patients (30%) with RAI were identified: 18 (49%) with unilateral and 19 (51%) with bilateral RAI. Patients were predominantly female (89%). The median age at diagnosis was 27 years [interquartile range (IQR) 16-38]. The median follow-up time was 7 years (IQR 2-12). Hypertension was seen in 27 patients (73%) at presentation and 25 (68%) at follow-up. The median estimated glomerular filtration (eGFR) at presentation was 94 and 98 ml/min/1.73 m2 in those with unilateral and bilateral RAI, respectively. The corresponding median eGFR at follow-up was 101.5 and 104 ml/min/1.73 m2, respectively. Three patients at presentation and two at follow-up had an eGFR of <60 ml/min/1.73 m2. Five underwent endovascular intervention and three required surgical interventions. Among the 33 patients with radiologic follow-up, 23 (69%) had persistent RAI and 10 (30%) had resolution of RAI. One (6%) patient with unilateral RAI developed bilateral RAI and three (19%) with bilateral RAI regressed to unilateral RAI. Over time, 23 (62%) patients had stable renal function, 7 (19%) had improvement and 4 had a decline in renal function; no patient developed end-stage renal disease (ESRD). Conclusion: In this series of TAK patients with RAI, long-term non-renal and renal outcomes were favourable. No patient experienced ESRD or died
Management of Inflammatory Arthritis in pregnancy: a National Cross-Sectional Survey of Canadian rheumatologists
Background:
With improved therapies and management, more women with inflammatory arthritides (IA) are considering pregnancy. Our objective was to survey rheumatologists across Canada about their IA management in pregnancy to identify practice patterns and knowledge gaps.
Methods:
We administered an online survey with questions regarding medications for IA treatment including conventional synthetic disease modifying antirheumatic drugs (csDMARDs) and biologics/small molecules in planned and unplanned pregnancies. Email invitations were sent to members of the Canadian Rheumatology Association. We calculated responses frequencies and a priori set a cut-off of ≥75% to define consensus.
Results:
Ninety rheumatologists participated in the survey (20% participation rate); 57% have been practicing for > 10 years, 32% for ≤10 years, and 11% in training. There was consensus on discontinuation of 4 csDMARDs – cyclophosphamide (100%), leflunomide (98%), methotrexate (96%), and mycophenolate mofetil (89%) – in planned pregnancies but varied responses on when to discontinue them or what to do in unplanned pregnancies. Respondents agreed that 3 csDMARDs – azathioprine (84%), hydroxychloroquine (95%), and sulfasalazine (77%) – were safe to continue in planned and unplanned pregnancies. There was consensus with use of 4 biologics – adalimumab (81%), certolizumab (80%), etanercept (83%), and infliximab (76%) – in planned pregnancies but uncertainty on when they should be discontinued and their use in unplanned pregnancies.
Conclusions:
This national survey shows consensus among rheumatologists on the use of some csDMARDs and biologics/small molecules in IA patients planning pregnancy but varied knowledge on when to discontinue and what to do in unplanned pregnancies.Medicine, Faculty ofPharmaceutical Sciences, Faculty ofOther UBCNon UBCRheumatology, Division ofReviewedFacult
“The medications are the decision-makers…” Making reproductive and medication use decisions among female patients with rheumatoid arthritis: a constructivist grounded theory
Objective
To examine how female patients with RA form decisions about having children, pregnancy, and medication use.
Methods
We employed a constructivist grounded theory design and recruited female participants who are 18 years or older, have a rheumatologist-confirmed RA diagnosis, live in Canada, and are able to communicate in English or French. We collected data through semi-structured individual and focus group interviews using telephone or video conferencing technology. Data collection and analysis were iterative, employed theoretical sampling, reflexive journaling, and peer debriefing, and culminated in a theoretical model.
Results
We recruited 21 participants with a mean age of 34 years and median 10 years since RA diagnosis. Overall, 33% had never been pregnant, 57% had previously been pregnant, and 10% were pregnant at the time of interview. Of those who had experienced pregnancy, 64% had at least one pregnancy while diagnosed with RA and of those, 56% used DMARD(s) during a pregnancy. We constructed a patient-centred framework depicting the dynamic relationships between 4 decision-making processes—(1) using medications, (2) having children, (3) planning pregnancy, and (4) parenting—and the substantial impact of healthcare providers on patients’ experiences making these decisions. These processes were further influenced by participants’ intersecting identities and contextual factors, particularly attitudes towards health and medications, disease onset and severity, familial support system, and experiences interacting with the healthcare system.
Conclusion
Our framework provides insight into how patients make reproductive decisions in the context of managing RA and the opportunities for providers to support them at each decision-making process. A patient-centred care approach is suggested to support female patients with RA in making reproductive and medication choices aligning with their individual desires, needs, and values.Medicine, Faculty ofPharmaceutical Sciences, Faculty ofNon UBCMedicine, Department ofObstetrics and Gynaecology, Department ofRheumatology, Division ofReviewedFacultyResearcherOthe