18 research outputs found
The Alberta Heart Failure Etiology and Analysis Research Team (HEART) study
Background Nationally, symptomatic heart failure affects 1.5-2% of Canadians, incurs $3 billion in hospital costs annually and the global burden is expected to double in the next 1–2 decades. The current one-year mortality rate after diagnosis of heart failure remains high at >25%. Consequently, new therapeutic strategies need to be developed for this debilitating condition.
Methods/Design The objective of the Alberta HEART program (http://albertaheartresearch.ca) is to develop novel diagnostic, therapeutic and prognostic approaches to patients with heart failure with preserved ejection fraction. We hypothesize that novel imaging techniques and biomarkers will aid in describing heart failure with preserved ejection fraction. Furthermore, the development of new diagnostic criteria will allow us to: 1) better define risk factors associated with heart failure with preserved ejection fraction; 2) elucidate clinical, cellular and molecular mechanisms involved with the development and progression of heart failure with preserved ejection fraction; 3) design and test new therapeutic strategies for patients with heart failure with preserved ejection fraction. Additionally, Alberta HEART provides training and education for enhancing translational medicine, knowledge translation and clinical practice in heart failure. This is a prospective observational cohort study of patients with, or at risk for, heart failure. Patients will have sequential testing including quality of life and clinical outcomes over 12 months. After that time, study participants will be passively followed via linkage to external administrative databases. Clinical outcomes of interest include death, hospitalization, emergency department visits, physician resource use and/or heart transplant. Patients will be followed for a total of 5 years.
Discussion Alberta HEART has the primary objective to define new diagnostic criteria for patients with heart failure with preserved ejection fraction. New criteria will allow for targeted therapies, diagnostic tests and further understanding of the patients, both at-risk for and with heart failure
The Alberta Heart Failure Etiology and Analysis Research Team (HEART) study
BACKGROUND: Nationally, symptomatic heart failure affects 1.5-2% of Canadians, incurs $3 billion in hospital costs annually and the global burden is expected to double in the next 1–2 decades. The current one-year mortality rate after diagnosis of heart failure remains high at >25%. Consequently, new therapeutic strategies need to be developed for this debilitating condition. METHODS/DESIGN: The objective of the Alberta HEART program (http://albertaheartresearch.ca) is to develop novel diagnostic, therapeutic and prognostic approaches to patients with heart failure with preserved ejection fraction. We hypothesize that novel imaging techniques and biomarkers will aid in describing heart failure with preserved ejection fraction. Furthermore, the development of new diagnostic criteria will allow us to: 1) better define risk factors associated with heart failure with preserved ejection fraction; 2) elucidate clinical, cellular and molecular mechanisms involved with the development and progression of heart failure with preserved ejection fraction; 3) design and test new therapeutic strategies for patients with heart failure with preserved ejection fraction. Additionally, Alberta HEART provides training and education for enhancing translational medicine, knowledge translation and clinical practice in heart failure. This is a prospective observational cohort study of patients with, or at risk for, heart failure. Patients will have sequential testing including quality of life and clinical outcomes over 12 months. After that time, study participants will be passively followed via linkage to external administrative databases. Clinical outcomes of interest include death, hospitalization, emergency department visits, physician resource use and/or heart transplant. Patients will be followed for a total of 5 years. DISCUSSION: Alberta HEART has the primary objective to define new diagnostic criteria for patients with heart failure with preserved ejection fraction. New criteria will allow for targeted therapies, diagnostic tests and further understanding of the patients, both at-risk for and with heart failure. TRIAL REGISTRATION: ClinicalTrials.gov NCT02052804
Using cone beam CT to assess the upper airway after surgery in children with sleep disordered breathing symptoms and maxillary-mandibular disproportions: a clinical pilot
Abstract Background The surgical excision of anatomic obstructions such as adenoids, palatine or lingual tonsils are commonly performed in children with sleep disordered breathing (SDB). Imaging studies measuring airway changes post-surgery in the SDB pediatric population are scarce, rarely addresses the nasal cavity, and are based on global measures (e.g. volume) that do not represent the complexity of the upper airway anatomy. The purpose of this pilot is to test the feasibility in using cone beam CT (CBCT) to analyze the nasal and pharyngeal airway space post-surgery using meaningful methods of analyses, and correlating imaging findings with clinical outcomes in children with SDB symptoms and maxillary-mandibular disproportion. Methods Twelve non-syndromic children with SDB symptoms and jaw disproportions were evaluated by interdisciplinary airway team before and after upper airway surgery. CBCT and OSA-18 quality of life questionnaire pre and post-operatively were completed. Conventional and new airway variables were measured based on 3D models of the upper airways and correlated with OSA-18. Conventional measures include volume, surface area, and cross-sectional area. New airway measures include constriction and patency; point-based analyses. Results Eight females and four males were 8.8 ± 2 years with mean BMI of 18.7 ± 3. OSA-18 improved, median (lower quartile-upper quartile) from 64.2 (54.7–79.5) to 37.6 (28.7–43) postoperatively, p < 0.001. The median of all airway measures improved however with very wide range. Subjects with the smallest amounts of constriction relief and/or gain in airway patency presented with least improvement in OSA-18. New airway measures show strong correlation with changes in OSA-18 (ρ = 0.44 to 0.71) whereas conventional measures showed very weak correlation (ρ = −0.04 to 0.37). Conclusions Using point-based analyses, new airway measures better explained changes in clinical symptoms compared to conventional measures. Airway patency gained by at least 150% and constriction relief by at least 15% showed marked improvement in OSA-18 by 40–55%, after surgery in the tested cohort
Central Sensitization Inventory in endometriosis
A key clinical problem is identifying the endometriosis patient whose pain is complicated by central nervous system sensitization, where conventional gynecologic treatment (e.g. hormonal therapy or surgery) may not completely alleviate the pain. The Central Sensitization Inventory (CSI) is a questionnaire previously validated in the chronic pain population. The objective of this study was an exploratory proof-of-concept to identify a CSI cut-off in the endometriosis population to discriminate between individuals with significant central contributors (identified by central sensitivity syndromes (CSS)) to their pain compared to those without. We analyzed a prospective data registry at a tertiary referral center for endometriosis, and included subjects aged 18-50 years with endometriosis who were newly or re-referred to the center in 2018. The study sample consisted of 335 subjects with a mean age of 36.0±7.0 years. An increasing number of CSS was significantly correlated with dysmenorrhea, deep dyspareunia, dyschezia, and chronic pelvic pain scores (p’s<.001) and with the CSI score (0-100) (r=.731, p<.001). ROC analysis indicated that a CSI cut-off of 40 had sensitivity 78% (95% CI: 72.7% - 84.6%) and specificity 80% (95% CI: 70.3% - 84.5%) for identifying an endometriosis patient with ≥ 3 CSS. In the group with CSI≥40, 18% retrospectively self-reported pain non-responsive to hormonal therapy and 40% self-reported daily pain, compared to 6% and 20% in the CSI<40 group (p=.003 and .002, respectively). In conclusion, a CSI ≥ 40 may be a practical tool to help identify endometriosis patients with pain contributors related to central nervous system sensitization.Medicine, Faculty ofNon UBCObstetrics and Gynaecology, Department ofReviewedFacultyResearcherPostdoctora
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Genetic analysis of isoform usage in the human anti-viral response reveals influenza-specific regulation of ERAP2 transcripts under balancing selection
While genetic variants are known to be associated with overall gene abundance in stimulated immune cells, less is known about their effects on alternative isoform usage. By analyzing RNA-seq profiles of monocyte-derived dendritic cells from 243 individuals, we uncovered thousands of unannotated isoforms synthesized in response to influenza infection and type 1 interferon stimulation. We identified more than a thousand quantitative trait loci (QTLs) associated with alternate isoform usage (isoQTLs), many of which are independent of expression QTLs (eQTLs) for the same gene. Compared with eQTLs, isoQTLs are enriched for splice sites and untranslated regions, but depleted of sequences upstream of annotated transcription start sites. Both eQTLs and isoQTLs explain a significant proportion of the disease heritability attributed to common genetic variants. At the ERAP2 locus, we shed light on the function of the gene and how two frequent, highly differentiated haplotypes with intermediate frequencies could be maintained by balancing selection. At baseline and following type 1 interferon stimulation, the major haplotype is associated with low ERAP2 expression caused by nonsense-mediated decay, while the minor haplotype, known to increase Crohn's disease risk, is associated with high ERAP2 expression. In response to influenza infection, we found two uncharacterized isoforms expressed from the major haplotype, likely the result of multiple perfectly linked variants affecting the transcription and splicing at the locus. Thus, genetic variants at a single locus could modulate independent gene regulatory processes in innate immune responses and, in the case of ERAP2, may confer a historical fitness advantage in response to virus