Health-Related Quality of Life in Premature Acute Coronary Syndrome: Does Patient Sex or Gender Really Matter?

Background-Limited data exist as to the relative contribution of sex and gender on health-related quality of life (HRQL) among patients with acute coronary syndrome (ACS). This study aims to evaluate the effect of sex and gender-related variables on long-term HRQL among young adults with ACS. Methods and Results-GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-Premature Acute Coronary SYndrome) is a multicenter, prospective cohort study (January 2009 to August 2013) of adults aged 18 to 55 years, hospitalized with ACS. HRQL was measured at baseline, 1, 6, and 12 months using the Short Form-12 and Seattle Angina Questionnaire (SAQ) among 1213 patients. Median age was 49 years. Women reported worse HRQL than men over time post-ACS, both in terms of physical and mental functioning. Gender-related factors were more likely to be predictors of HRQL than sex. Femininity score, social support, and housework responsibility were the most common gender-related predictors of HRQL at 12 months. We observed an interaction between female sex and social support (beta=0.44 [95% confidence interval, 0.01, 0.88]; P=0.047) for the physical limitation subscale of the SAQ. Conclusions-Young women with ACS report significantly poorer HRQL than young men. Gender appears to be more important than sex in predicting long-term HRQL post-ACS. Specific gender-related factors, such as social support, may be amenable to interventions and could improve the HRQL of patients with premature ACS.CIHRHeart and Stroke Foundation of QuebecHeart and Stroke Foundation of Nova ScotiaHeart and Stroke Foundation of AlbertaHeart and Stroke Foundation of OntarioHeart and Stroke Foundation of YukonHeart and Stroke Foundation of British Columbia, CanadaJames McGill Chair at McGill Universit

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Continuous Descending Modulation of the Spinal Cord Revealed by Functional MRI.

Spontaneous variations in spinal cord activity may arise from regulation of any of a number of functions including sensory, motor, and autonomic control. Here, we use functional MRI (fMRI) of healthy participants to identify properties of blood oxygenation-level dependent (BOLD) variations in the spinal cord in response to knowledge that either a noxious stimulus is impending, or that no stimulus is to be expected. Expectation of a noxious stimulus, or no stimulus, is shown to have a significant effect on wide-spread BOLD signal variations in the spinal cord over the entire time period of the fMRI acquisition. Coordination of BOLD responses between/within spinal cord and brainstem regions are also influenced by this knowledge. We provide evidence that such signal variations are the result of continuous descending modulation of spinal cord function. BOLD signal variations in response to noxious stimulation of the hand are also shown, as in previous studies. The observation of both continuous and reactive BOLD responses to emotional/cognitive factors and noxious peripheral stimulation may have important implications, not only for our understanding of endogenous pain modulation, but also in showing that spinal cord activity is under continuous regulatory control

Average time-courses of spinal cord voxels which are significantly correlated with seed regions in (A) (left) the right-dorsal region of C6, and (B) (right) the left-dorsal region of C6.

<p>The voxels are as depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0167317#pone.0167317.g002" target="_blank">Fig 2</a>. Signal intensity patterns obtained during stimulation conditions are shown in blue, and the no-stimulation condition is shown in red. Time-course data were converted to z-scores with mean values of zero. Error bars indicate the standard-error-of-the-mean across fMRI runs. Red and blue asterisks (*) indicate values which are significantly different than the mean value of zero, at p < 10⁻⁴, for no-stimulation and stimulation runs, respectively. Black asterisks indicate intensity values which are significantly different between the two study conditions, at p < 10⁻⁴. Times are indicated corresponding to when participants were informed of the study type, the start of the stimulation period (for studies with heat stimulation), and the time at which the rating scale was displayed in all studies.</p

A structural equation modeling (SEM) analysis was used to investigate input signaling to the spinal cord dorsal horn (DH) in the 6^th cervical segment, from the nucleus raphe magnus (NRM), nucleus gigantocellularis (NGc), and the dorsal reticular nucleus (DRt).

<p>Results are shown for the sub-regions (right panel) which provided the best fit to the BOLD signal intensity variations in the spinal cord DH, when a stimulus was expected and applied, and when a stimulus was not expected and not applied (i.e. no-stimulation). The time-series responses in the identified regions are shown (left panels) for each study condition, as well as the SEM fit to the spinal cord time-series responses (red lines). Plotted values are the average over the region across runs/participants and error bars indicate the standard error of the mean (SE) across participants. The SEM weighting factors that were determined, and used for the fit, are indicated below each time-series plot (± SE). Periods are highlighted when the participants were informed of the study type, and when the stimulus was applied, or was not applied.</p

Connectivity between voxels and selected seed regions.

<p>Anatomical locations of regions with time-courses that are significantly correlated with seed regions in the right/left and dorsal/ventral regions of C6, are shown in colour overlaid on gray-scale anatomical images. Each frame represents a 1 mm thick transverse slice, and slices are shown every 4 mm along the cord (horizontally in the figure) to depict the rostral-caudal range along the spinal cord, and a section of the medulla. The seed regions are identified by the highly correlated (dark red) voxels within the regions. Positions along the cord/brainstem are indicated relative to the seed region center, in millimeters.</p

Dynamic variations in the correlation between time-series responses are shown for the regions identified by the SEM analysis as having the strongest relationships (i.e. the best fit).

<p>Time intervals spanning 41 seconds were selected throughout the fMRI paradigm, and the correlation was computed to investigate how the relationships evolved. Correlations between the cord DH time series and the NRM (red), NGc (green), and DRt (blue), are shown for the no-stimulation condition (brighter tones), and with a stimulus applied (darker tones). Positive correlations are most notable prior to the stimulation period, and are primarily in the NRM, whereas negative correlations predominate during and after the stimulation period, and are primarily in the DRt. Significant correlations are inferred at |R| ≥ 0.74 (indicated by horizontal lines).</p