Massive haplotypes underlie ecotypic differentiation in sunflowers.

Species often include multiple ecotypes that are adapted to different environments1. However, it is unclear how ecotypes arise and how their distinctive combinations of adaptive alleles are maintained despite hybridization with non-adapted populations2-4. Here, by resequencing 1,506 wild sunflowers from 3 species (Helianthus annuus, Helianthus petiolaris and Helianthus argophyllus), we identify 37 large (1-100 Mbp in size), non-recombining haplotype blocks that are associated with numerous ecologically relevant traits, as well as soil and climate characteristics. Limited recombination in these haplotype blocks keeps adaptive alleles together, and these regions differentiate sunflower ecotypes. For example, haplotype blocks control a 77-day difference in flowering between ecotypes of the silverleaf sunflower H. argophyllus (probably through deletion of a homologue of FLOWERING LOCUS T (FT)), and are associated with seed size, flowering time and soil fertility in dune-adapted sunflowers. These haplotypes are highly divergent, frequently associated with structural variants and often appear to represent introgressions from other-possibly now-extinct-congeners. These results highlight a pervasive role of structural variation in ecotypic adaptation.

Enhanced Telehealth Home-Monitoring Intervention for Vulnerable and Frail Patients after Cardiac Surgery (THE-FACS Pilot Intervention Study).

BACKGROUND: Frail cardiac surgery patients have an increased risk of worse postoperative outcomes. The purpose of this study was to evaluate the implementation of a novel Telehealth Home monitoring Enhanced-Frailty And Cardiac Surgery (THE-FACS) intervention and determine its impact on clinical outcomes in frail patients post-cardiac surgery. METHODS: Frail/vulnerable patients defined by Edmonton Frailty Scale (EFS > 4) undergoing cardiac surgery were prospectively enrolled (November 2019 -March 2020) at the New Brunswick Heart Centre. Exclusion criteria included age < 55 years, emergent status, minimally invasive surgery, lack of home support, and > 10-days postoperative hospital stay. Following standard training on THE-FACS, participants were sent home with a tablet device to answer questions about their health/recovery and measure blood pressure for 30-consecutive days. Transmitted data were monitored by trained cardiac surgery follow-up nurses. Patients were contacted only if the algorithm based on the patient's self-collected data triggered an alert. Patients who completed the study were compared to historical controls. The primary outcome of interest was to determine the number of patients that could complete THE-FACS; secondary outcomes included participant/caregiver satisfaction and impact on hospital readmission. RESULTS: We identified 86 eligible (EFS > 4), out of 254 patients scheduled for elective cardiac surgery during the study period (vulnerable: 34%). The patients who consented to participate in THE-FACS (64/86, 74%) had a mean age of 69.1 ± 6.4 years, 25% were female, 79.7% underwent isolated Coronary Artery Bypass Graft (CABG) and median EFS was 6 (5-8). 29/64 (45%) were excluded post-enrollment due to prolonged hospitalization (15/64) or requirement for hospital-to-hospital transfer (12/64). Of the remaining 35 patients, 21 completed the 30-day follow-up (completion rate:60%). Reasons for withdrawal (14/35, 40%) were mostly due to technical difficulties with the tablet. Hospital readmission, although non-significant, was reduced in THE-FACS participants compared to controls (0% vs. 14.3%). A satisfaction survey revealed > 90% satisfaction and ~ 67% willingness to re-use a home monitoring device. CONCLUSIONS: THE-FACS intervention can be used to successfully monitor vulnerable patients returning home post-cardiac surgery. However, a significant number of frail patients could not benefit from THE-FACS given prolonged hospitalization and technological challenges. Our findings suggest that despite overall excellent satisfaction in participants who completed THE-FACS, there remain major challenges for wide-scale implementation of technology-driven home monitoring programs as only 24% completed the study.

Evaluating a new referral pathway from physical therapists to rheumatologists: A qualitative study.

Early referral to rheumatology of people with suspected inflammatory arthritis is associated with better outcomes. Typically, these individuals are seen by a family physician who would assess the need for rheumatology referral. However, some may first consult a physical therapist where no physician referral is required. New interprofessional referral pathways, such as direct referral from a physical therapist to a rheumatologist, could enhance early access to a rheumatologist. Our objective was to explore perceptions of clinicians and people with inflammatory arthritis regarding physical therapists referring directly to rheumatologists. We used purposive and snowball sampling to recruit participants for five focus groups: rheumatologists, family physicians, physical therapists, people with inflammatory arthritis, and a mixed group of physical therapists and people with inflammatory arthritis. Thematic analysis revealed four core themes: difficulties accessing care, reluctance of family physicians and rheumatologists toward the new pathway, interprofessional relationships (or lack thereof), and opportunities along the referral pathway. The conclusions are that care must be optimized by ensuring swift referral for those who require it; and that there is a need for knowledge translation to all actors on the advantages of this new pathway.

Standing variation rather than recent adaptive introgression probably underlies differentiation of the texanus subspecies of Helianthus annuus.

The origins of geographic races in wide-ranging species are poorly understood. In Texas, the texanus subspecies of Helianthus annuus has long been thought to have acquired its defining phenotypic traits via introgression from a local congener, H. debilis, but previous tests of this hypothesis were inconclusive. Here, we explore the origins of H. a. texanus using whole genome sequencing data from across the entire range of H. annuus and possible donor species, as well as phenotypic data from a common garden study. We found that although it is morphologically convergent with H. debilis, H. a. texanus has conflicting signals of introgression. Genome wide tests (Patterson's D and TreeMix) only found evidence of introgression from H. argophyllus (sister species to H. annuus and also sympatric), but not H. debilis, with the exception of one individual of 109 analysed. We further scanned the genome for localized signals of introgression using PCAdmix and found minimal but nonzero introgression from H. debilis and significant introgression from H. argophyllus in some populations. Given the paucity of introgression from H. debilis, we argue that the morphological convergence observed in Texas is probably from standing genetic variation. We also found that genomic differentiation in H. a. texanus is mostly driven by large segregating inversions, several of which have signatures of natural selection based on haplotype frequencies.

Application of Artificial Intelligence in Community-Based Primary Health Care: Systematic Scoping Review and Critical Appraisal.

BACKGROUND: Research on the integration of artificial intelligence (AI) into community-based primary health care (CBPHC) has highlighted several advantages and disadvantages in practice regarding, for example, facilitating diagnosis and disease management, as well as doubts concerning the unintended harmful effects of this integration. However, there is a lack of evidence about a comprehensive knowledge synthesis that could shed light on AI systems tested or implemented in CBPHC. OBJECTIVE: We intended to identify and evaluate published studies that have tested or implemented AI in CBPHC settings. METHODS: We conducted a systematic scoping review informed by an earlier study and the Joanna Briggs Institute (JBI) scoping review framework and reported the findings according to PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Scoping Reviews) reporting guidelines. An information specialist performed a comprehensive search from the date of inception until February 2020, in seven bibliographic databases: Cochrane Library, MEDLINE, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ScienceDirect, and IEEE Xplore. The selected studies considered all populations who provide and receive care in CBPHC settings, AI interventions that had been implemented, tested, or both, and assessed outcomes related to patients, health care providers, or CBPHC systems. Risk of bias was assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Two authors independently screened the titles and abstracts of the identified records, read the selected full texts, and extracted data from the included studies using a validated extraction form. Disagreements were resolved by consensus, and if this was not possible, the opinion of a third reviewer was sought. A third reviewer also validated all the extracted data. RESULTS: We retrieved 22,113 documents. After the removal of duplicates, 16,870 documents were screened, and 90 peer-reviewed publications met our inclusion criteria. Machine learning (ML) (41/90, 45%), natural language processing (NLP) (24/90, 27%), and expert systems (17/90, 19%) were the most commonly studied AI interventions. These were primarily implemented for diagnosis, detection, or surveillance purposes. Neural networks (ie, convolutional neural networks and abductive networks) demonstrated the highest accuracy, considering the given database for the given clinical task. The risk of bias in diagnosis or prognosis studies was the lowest in the participant category (4/49, 4%) and the highest in the outcome category (22/49, 45%). CONCLUSIONS: We observed variabilities in reporting the participants, types of AI methods, analyses, and outcomes, and highlighted the large gap in the effective development and implementation of AI in CBPHC. Further studies are needed to efficiently guide the development and implementation of AI interventions in CBPHC settings.

Cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on health care and cardiac surgery. We report cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic. METHODS: A detailed survey was sent to recruit participating adult cardiac surgery centers in North America. Data regarding cardiac surgeons' perceptions and changes in practice were analyzed. RESULTS: Our study comprises 67 institutions with diverse geographic distribution across North America. Nurses were most likely to be redeployed (88%), followed by advanced care practitioners (69%), trainees (28%), and surgeons (25%). Examining surgeon concerns in regard to COVID-19, they were most worried with exposing their family to COVID-19 (81%), followed by contracting COVID-19 (68%), running out of personal protective equipment (PPE) (28%), and hospital resources (28%). In terms of PPE conservation strategies among users of N95 respirators, nearly half were recycling via decontamination with ultraviolet light (49%), followed by sterilization with heat (13%) and at home or with other modalities (13%). Reuse of N95 respirators for 1 day (22%), 1 week (21%) or 1 month (6%) was reported. There were differences in adoption of methods to conserve N95 respirators based on institutional pandemic phase and COVID-19 burden, with higher COVID-19 burden institutions more likely to resort to PPE conservation strategies. CONCLUSIONS: The present study demonstrates the impact of COVID-19 on North American cardiac surgeons. Our study should stimulate further discussions to identify optimal solutions to improve workforce preparedness for subsequent surges, as well as facilitate the navigation of future healthcare crises.

Increased mast cell density is associated with decreased fibrosis in human atrial tissue.

Fibrotic remodelling of the atria is poorly understood and can be regulated by myocardial immune cell populations after injury. Mast cells are resident immune sentinel cells present in the heart that respond to tissue damage and have been linked to fibrosis in other settings. The role of cardiac mast cells in fibrotic remodelling in response to human myocardial injury is controversial. In this study, we sought to determine the association between mast cells, atrial fibrosis, and outcomes in a heterogeneous population of cardiac surgical patients, including a substantial proportion of coronary artery bypass grafting patients. Atrial appendage from patients was assessed for collagen and mast cell density by histology and by droplet digital polymerase chain reaction (ddPCR) for mast cell associated transcripts. Clinical variables and outcomes were also followed. Mast cells were detected in human atrial tissue at varying densities. Histological and ddPCR assessment of mast cells in atrial tissue were closely correlated. Patients with high mast cell density had less fibrosis and lower severity of heart failure classification or incidence mortality than patients with low mast cell content. Analysis of a homogeneous population of coronary artery bypass graft patients yielded similar observations. Therefore, evidence from this study suggests that increased atrial mast cell populations are associated with decreased clinical cardiac fibrotic remodelling and improved outcomes, in cardiac surgery patients.

The prophylactic use of fibrinogen concentrate in high-risk cardiac surgery.

BACKGROUND: Perioperative blood loss is a major contributor to morbidity and mortality in cardiac surgery. Plasma fibrinogen levels play an essential role in hemostasis and deplete quickly during hemorrhage. The objective of this study was to determine whether prophylactic fibrinogen concentrate administration lowers overall blood product transfusion requirements in high-risk cardiac surgery in patients with low fibrinogen plasma levels. METHODS: The study was performed in a prospective, randomized, and double-blinded design. The investigation included 62 patients undergoing elective, high-risk cardiac surgery. After weaning from cardiopulmonary bypass and reversal of heparin patients received either fibrinogen concentrate or placebo. The primary outcome variable was overall blood product usage 24 hours after intervention. RESULTS: The fibrinogen group received numerically fewer total units of blood products than the placebo group, but the difference was not statistically or clinically significant (for groups n = 27; n = 29 and 19 vs 37 units, respectively, P = .908). The overall transfusion rate in both groups was significantly lower than the institutional average suggested (fibrinogen group 26%, placebo group 28%). The fibrinogen group showed significantly higher fibrinogen levels (2.38 vs 1.83 g/L (end of surgery), P < .001; 3.33 vs 2.68 g/L (12 hours after intervention), P = .003) and improved viscoelastic coagulation parameters (FIBTEM MCF, 27 vs 23 mm, P = .022). CONCLUSION: This randomized, controlled trial demonstrates that point-of-care guided and prophylactic treatment with fibrinogen concentrate does not reduce transfusion of blood products in a setting of unexpectedly low transfusion rate as tested in this cohort, but may improve coagulation parameters in the setting of high-risk cardiac surgery.

Clinical outcomes of mitral valve intervention in patients with mitral annular calcification: A systematic review and meta-analysis.

BACKGROUND: Mitral valve (MV) disease with mitral annular calcification (MAC) poses a surgical challenge and the clinical outcomes of MV surgery as well as transcatheter mitral valve replacement (TMVR) remain relatively unexplored. We performed a systematic review and meta-analysis to assess the effects of MAC on clinical outcomes following MV surgery and TMVR. METHODS: We searched MEDLINE and EMBASE databases until February 2019 for studies comparing clinical outcomes of MV surgery or TMVR in patients with and without MAC. Data were extracted by two independent investigators. Outcomes were perioperative and midterm complications and mortality. RESULTS: Seven observational studies enrolling 2902 patients were included. MAC patients were older, more likely to be female with greater chronic lung disease and kidney failure. Perioperative mortality was similar between patients with and without MAC undergoing MV surgery (risk ratio [RR], 1.15; 95% confidence interval [CI], 0.50-2.65; P = .74). MAC was associated with a higher risk of bleeding, permanent pacemaker implantation, and periprosthetic leak. Midterm mortality was greater in MAC patients undergoing MV surgery (incident rate ratio [IRR], 1.32; 95% CI, 1.05-1.67; P = .02). MAC patients undergoing TMVR had higher perioperative (RR, 4.65; 95% CI, 2.93-7.38; P < .01) and 1-year (RR, 5.44; 95% CI, 3.49-8.49; P < .01) mortality, decreased procedural success, greater left ventricular outflow tract obstruction and need for conversion to surgery when compared with patients undergoing TMVR for dysfunction of a bioprosthetic valve or annuloplasty ring. CONCLUSION: MV procedures in patients with MAC are associated with higher mortality and morbidity. This is largely driven by the high-risk patient profile associated with MAC. TMVR holds promise but has important limitations and should be reserved for select patients.

Variability in opioid prescribing practices among cardiac surgeons and trainees.

BACKGROUND AND AIM: The opioid epidemic has become a major public health crisis in recent years. Discharge opioid prescription following cardiac surgery has been associated with opioid use disorder; however, ideal practices remain unclear. Our aim was to examine current practices in discharge opioid prescription among cardiac surgeons and trainees. METHODS: A survey instrument with open- and closed-ended questions, developed through a 3-round Delphi method, was circulated to cardiac surgeons and trainees via the Canadian Society of Cardiac Surgeons. Survey questions focused on routine prescription practices including type, dosage and duration. Respondents were also asked about their perceptions of current education and guidelines surrounding opioid medication. RESULTS: Eighty-one percent of respondents reported prescribing opioids at discharge following routine sternotomy-based procedures, however, there remained significant variability in the type and dose of medication prescribed. The median (interquartile range) number of pills prescribed was 30 (20-30) with a median total dose of 135 (113-200) Morphine Milligram Equivalents. Informal teaching was the most commonly reported primary influence on prescribing habits and a lack of formal education regarding opioid prescription was associated with a higher number of pills prescribed. A majority of respondents (91%) felt that there would be value in establishing practice guidelines for opioid prescription following cardiac surgery. CONCLUSIONS: Significant variability exists with respect to routine opioid prescription at discharge following cardiac surgery. Education has come predominantly from informal sources and there is a desire for guidelines. Standardization in this area may have a role in combatting the opioid epidemic.

Impact on cardiac surgery volume of a comprehensive partnership with Integrated Health Solutions.

Background: The New Brunswick Heart Centre (NBHC) entered a contractual partnership with Integrated Health Solutions (IHS) to help address increasing wait times in the province of New Brunswick. Methods: Team leaders were identified from each of the target areas, including surgeons, anesthesiologists, nurses (operating room, intensive care unit [ICU] and postoperative ward), access coordinators and administrators. The methodology used was based on Lean principles and involved exercises by stakeholders aimed at identifying opportunities for improvement. A weekly dashboard was created to monitor and facilitate improvement efforts. No additional hospital beds or operating room theatres were added during the study period. Results: After 2 years, the annual number of cardiac surgical interventions increased from 788 to 873, representing a 10.8% increase in capacity. The best median wait time for patients decreased from 52 to 35 days (35% reduction). The best 90th percentile wait time decreased from 126 to 98 days (22% reduction). The overall increase in capacity could be explained in part by the significant increase in fast tracking from the ICU to the ward (> 2-fold) or bypassing the ICU altogether (4-fold increase reaching 13%). Despite these successes, challenges persist as the number of OR cancellations remained around 7.5% of all cases, mainly because of limited ICU resources. Conclusion: The NBHC-IHS partnership on this project has resulted in excellent engagement by stakeholders and promoted team cohesiveness. Furthermore, it has allowed significant reorganization and realignment of efforts to limit wait times and maximize overall capacity.

Contexte: Le New-Brunswick Heart Centre (NBHC) a conclu une entente contractuelle avec Integrated Health Solutions (IHS) pour remédier aux temps d'attente de plus en plus longs au Nouveau-Brunswick. Méthodes: Des chefs d'équipe ont été identifiés pour chaque domaine cible, notamment la chirurgie, l'anesthésie, les soins infirmiers (en salle d'opération, aux soins intensifs et en soins postopératoires), la coordination des soins et la direction. La méthodologie utilisée se fondait sur l'approche Lean et comprenait des exercices visant à relever les possibilités d'amélioration. Un tableau de bord hebdomadaire a été créé pour suivre et faciliter les mesures d'amélioration. On n'a ajouté aucun lit d'hôpital et aucune salle d'opération pendant la période étudiée. Résultats: Après 2 ans, le nombre de chirurgies cardiaques par année est passé de 788 à 873, une augmentation de 10,8 % de la capacité. Le temps d'attente médian pour les patients est tombé de 52 à 35 jours (réduction de 35 %). Le temps d'attente au 90e centile est passé de 126 à 98 jours (réduction de 22 %). L'augmentation générale de la capacité peut s'expliquer en partie par la réduction significative du temps passé aux soins intensifs avant l'admission en soins généraux (> 2 fois) ou par l'élimination complète du passage aux soins intensifs (augmentation de 400 %; 13 % des cas). Malgré ces réussites, des défis demeurent puisque le taux d'annulation des interventions est resté autour de 7,5 % des cas, surtout en raison des ressources limitées aux soins intensifs. Conclusion: Le partenariat NBHC­IHS sur ce projet a permis de mobiliser efficacement les participants et a favorisé la cohésion au sein de l'équipe. Il a en outre permis une importante réorganisation des ressources pour réduire les temps d'attente et augmenter la capacité générale.

Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery.

BACKGROUND: The objectives of the study were to characterize and quantify cellular inflammation and structural remodeling of human atria and correlate findings with molecular markers of inflammation and patient surrogate outcome. METHODS: Voluntary participants undergoing heart surgery were enrolled in the study and blood samples were collected prior to surgery, and right atrium samples were harvested intraoperatively. Blood samples were analyzed by flow cytometry and complete blood counts. Atrial samples were divided for fixed fibrosis analysis, homogenized for cytokine analysis and digested for single cell suspension flow cytometry. RESULTS: A total of 18 patients were enrolled and samples assessed. Isolated cells from the atria revealed a CD45+ population of ~ 20%, confirming a large number of leukocytes. Further characterization revealed this population as 57% lymphocytes and 26% monocyte/macrophages (MoΦ), with the majority of the latter cells being classical (CD14++/CD16-). Interstitial fibrosis was present in 87% of samples and correlated significantly with patient age. Older patients (> 65) had significantly more atrial fibrosis and cellular inflammation. AFib patients had no distinguishing feature of atrial fibrosis and had significantly greater CD45+ MoΦ, increased expression of MMP9 and presented with a significant correlation in length of stay to CCL-2/MCP-1 and NLR (neutrophil-to-lymphocyte ratio). CONCLUSION: Atrial fibrosis is correlated with age and not determinate to AFib. However, severity of atrial leukocyte infiltration and markers of matrix degradation are determinant to AFib. This also correlated with CCL2 (or MCP-1) and NLR-indicative of marked inflammation. These data show the potential importance of diagnostic and prognostic assessments that could inform clinical decision making in regard to the intensity of AFib patient management.

Twelve Lessons Learned for Effective Research Partnerships Between Patients, Caregivers, Clinicians, Academic Researchers, and Other Stakeholders.

Research increasingly means that patients, caregivers, health professionals, other stakeholders, and academic investigators work in partnership. This requires effective collaboration rooted in mutual respect, involvement of all participants, and good communication. Having conducted such partnered research over multiple projects, and having recently completed a project together funded by the Patient-Centered Outcomes Research Institute, we collaboratively developed a list of 12 lessons we have learned about how to ensure effective research partnerships. To foster a culture of mutual respect, hold early in-person meetings, with introductions focused on motivation, offer appropriate orientation for everyone, and maintain awareness of individual and project goals. To actively involve all team members, it is important to ensure sufficient funding for everyone's participation, to ask for and recognize diverse contributions, and to seek the input of quiet members. To facilitate good communication, teams should carefully consider labels, avoid jargon and acronyms, judiciously use homogeneous and heterogeneous subgroups, and keep progress visible. In offering pragmatic, actionable lessons we have learned through our separate and shared experiences, we hope to help foster more patient-centered research via productive and enjoyable research collaborations.

Regional differences in aortic valve replacements: Atlantic Canadian experience.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is evolving rapidly and is increasingly being adopted in the treatment of aortic valve disease. The goal of this study was to examine regional differences in surgical aortic valve replacement (SAVR) and TAVI across Atlantic Canada. METHODS: We identified all patients who underwent SAVR or TAVI between Jan. 1, 2010, and Dec. 31, 2014, in New Brunswick, Nova Scotia and Newfoundland and Labrador. Data obtained included patient demographic characteristics and surgical procedure details. We performed univariate descriptive analyses and calculated crude and age- and sex-adjusted incidence rates. RESULTS: A total of 3042 patients underwent SAVR or TAVI during the study period, 1491 in Nova Scotia, 1042 in New Brunswick and 509 in Newfoundland and Labrador. Patient demographic characteristics were similar across regions. A much higher proportion of patients in Newfoundland and Labrador (43.6%) than in Nova Scotia (4.2%) or New Brunswick (13.6%) received a mechanical versus a bioprosthetic valve. Rates of TAVI increased over the study period, with New Brunswick adopting their program before Nova Scotia (144 v. 74 procedures). Adjusted rates of all AVR procedures remained stable in Nova Scotia (40-50 per 100 000 people). Adjusted rates were lower in New Brunswick and Newfoundland and Labrador than in Nova Scotia; they increased slowly in New Brunswick over the study period. CONCLUSION: Despite geographical proximity and similar patient demographic characteristics, there existed regional differences in the management of aortic valve disease within Atlantic Canada. Further study is required to determine whether the observed differences in age- and sex-adjusted rates of AVR may be explained by geographical disease-related differences, varying practice patterns or barriers in access to care.

CONTEXTE: Le remplacement valvulaire aortique par cathéter, une méthode en pleine évolution, est de plus en plus utilisé pour le traitement des valvulopathies aortiques. Cette étude visait à examiner les différences régionales quant au remplacement valvulaire aortique par cathéter ou par chirurgie dans les provinces de l'Atlantique. MÉTHODES: Nous avons recensé tous les patients ayant subi un remplacement valvulaire aortique entre le 1er janvier 2010 et le 31 décembre 2014 au Nouveau-Brunswick, en Nouvelle-Écosse et à Terre-Neuve-et-Labrador. Nous avons recueilli des données sur les caractéristiques démographiques des patients et les interventions chirurgicales, puis nous avons réalisé une analyse descriptive univariée et avons calculé les taux d'incidence bruts et corrigés selon l'âge et le sexe. RÉSULTATS: En tout, 3042 patients ont subi un remplacement valvulaire aortique par cathéter ou par chirurgie pendant la période à l'étude : 1491 en Nouvelle-Écosse, 1042 au Nouveau-Brunswick et 509 à Terre-Neuve-et-Labrador. Les caractéristiques démographiques des patients étaient semblables d'une région à l'autre. La proportion des patients recevant une prothèse mécanique plutôt qu'une bioprothèse était beaucoup plus élevée à Terre-Neuve-et-Labrador (43,6 %) qu'en Nouvelle-Écosse (4,2 %) ou au Nouveau-Brunswick (13,6 %). Les taux de remplacement par cathéter ont augmenté au cours de la période à l'étude; le Nouveau-Brunswick a adopté un programme à ce sujet avant la Nouvelle-Écosse (144 c. 74 interventions). Les taux corrigés pour tous les remplacements étaient stables en Nouvelle-Écosse (40-50 par 100 000 habitants); ils étaient plus faibles au Nouveau-Brunswick et à Terre-Neuve-et-Labrador, mais ont augmenté lentement au Nouveau-Brunswick pendant la période à l'étude. CONCLUSION: Malgré la proximité géographique des provinces de l'Atlantique et les caractéristiques démographiques semblables des patients, il existait des différences dans la prise en charge des valvulopathies aortiques. D'autres études seront nécessaires pour déterminer si les variations dans les taux de remplacement corrigés selon l'âge et le sexe pourraient s'expliquer par des différences géographiques dans le nombre de cas, des différences dans les pratiques ou des obstacles à l'accès aux soins.

Glucolipotoxicity diminishes cardiomyocyte TFEB and inhibits lysosomal autophagy during obesity and diabetes.

Impaired cardiac metabolism in the obese and diabetic heart leads to glucolipotoxicity and ensuing cardiomyopathy. Glucolipotoxicity causes cardiomyocyte injury by increasing energy insufficiency, impairing proteasomal-mediated protein degradation and inducing apoptosis. Proteasome-evading proteins are degraded by autophagy in the lysosome, whose metabolism and function are regulated by master regulator transcription factor EB (TFEB). Limited studies have examined the impact of glucolipotoxicity on intra-lysosomal signaling proteins and their regulators. By utilizing a mouse model of diet-induced obesity, type-1 diabetes (Akita) and ex-vivo model of glucolipotoxicity (H9C2 cells and NRCM, neonatal rat cardiomyocyte), we examined whether glucolipotoxicity negatively targets TFEB and lysosomal proteins to dysregulate autophagy and cause cardiac injury. Despite differential effects of obesity and diabetes on LC3B-II, expression of proteins facilitating autophagosomal clearance such as TFEB, LAMP-2A, Hsc70 and Hsp90 were decreased in the obese and diabetic heart. In-vivo data was recapitulated in H9C2 and NRCM cells, which exhibited impaired autophagic flux and reduced TFEB content when exposed to a glucolipotoxic milieu. Notably, overloading myocytes with a saturated fatty acid (palmitate) but not an unsaturated fatty acid (oleate) depleted cellular TFEB and suppressed autophagy, suggesting a fatty acid specific regulation of TFEB and autophagy in the cardiomyocyte. The effect of glucolipotoxicity to reduce TFEB content was also confirmed in heart tissue from patients with Class-I obesity. Therefore, during glucolipotoxicity, suppression of lysosomal autophagy was associated with reduced lysosomal content, decreased cathepsin-B activity and diminished cellular TFEB content likely rendering myocytes susceptible to cardiac injury.

Involving members of vulnerable populations in the development of patient decision aids: a mixed methods sequential explanatory study.

BACKGROUND: Patient decision aids aim to present evidence relevant to a health decision in understandable ways to support patients through the process of making evidence-informed, values-congruent health decisions. It is recommended that, when developing these tools, teams involve people who may ultimately use them. However, there is little empirical evidence about how best to undertake this involvement, particularly for specific populations of users such as vulnerable populations. METHODS: To describe and compare the development practices of research teams that did and did not specifically involve members of vulnerable populations in the development of patient decision aids, we conducted a secondary analysis of data from a systematic review about the development processes of patient decision aids. Then, to further explain our quantitative results, we conducted semi-structured telephone interviews with 10 teams: 6 that had specifically involved members of vulnerable populations and 4 that had not. Two independent analysts thematically coded transcribed interviews. RESULTS: Out of a total of 187 decision aid development projects, 30 (16%) specifically involved members of vulnerable populations. The specific involvement of members of vulnerable populations in the development process was associated with conducting informal needs assessment activities (73% vs. 40%, OR 2.96, 95% CI 1.18-7.99, P = .02) and recruiting participants through community-based organizations (40% vs. 11%, OR 3.48, 95% CI 1.23-9.83, P = .02). In interviews, all developers highlighted the importance, value and challenges of involving potential users. Interviews with developers whose projects had involved members of vulnerable populations suggested that informal needs assessment activities served to center the decision aid around users' needs, to better avoid stigma, and to ensure that the topic truly matters to the community. Partnering with community-based organizations may facilitate relationships of trust and may also provide a non-threatening and accessible location for research activities. CONCLUSIONS: There are a small number of key differences in the development processes for patient decision aids in which members of vulnerable populations were or were not specifically involved. Some of these practices may require additional time or resources. To address health inequities, researchers, communities and funders may need to increase awareness of these approaches and plan accordingly.

Nonclassical resident macrophages are important determinants in the development of myocardial fibrosis.

Macrophages are increasingly recognized as a potential therapeutic target in myocardial fibrosis via interactions with fibroblasts. We have characterized macrophage depletion and inhibition of nonclassical macrophage migration, in addition to direct interactions between nonclassical macrophages and fibroblasts in angiotensin II (AngII)-mediated, hypertensive myocardial fibrosis. Macrophage depletion was achieved by daily i.v. clodronate liposomes (-1 day to +3 days) during AngII infusion. Cx3cr1(-/-) mice were used to inhibit nonclassical macrophage migration. Macrophage phenotype (F4/80, CD11b, Ly6C) was characterized by immunofluorescence and flow cytometry. Collagen was assessed by Sirius Red/Fast Green. Quantitative real-time RT-PCR was performed for transcript levels. AngII/wild-type (WT) mice displayed significant infiltrate and fibrosis compared with saline/WT, which was virtually ablated by clodronate liposomes independent of hypertension. In vitro data supported M2 macrophages promoting fibroblast differentiation and collagen production. AngII/Cx3cr1(-/-) mice, however, significantly increased macrophage infiltrate and fibrosis relative to AngII/WT. AngII/Cx3cr1(-/-) mice also showed an M1 phenotypic shift relative to WT mice in, which the predominant phenotype was Ly6C(low), CD206(+) (M2). Myocardial IL-1ß was significantly up-regulated, whereas transforming growth factor ß down-regulated with this M1 shift. We demonstrated that infiltrating macrophages are critical to AngII-mediated myocardial fibrosis by preventing the development of fibrosis after liposomal depletion of circulating monocytes. Our findings also suggest that some macrophages, namely M2, may confer a protective myocardial environment that may prevent excessive tissue injury.

Disruption of collagen homeostasis can reverse established age-related myocardial fibrosis.

Heart failure, the leading cause of hospitalization of elderly patients, is correlated with myocardial fibrosis (ie, deposition of excess extracellular matrix proteins such as collagen). A key regulator of collagen homeostasis is lysyl oxidase (LOX), an enzyme responsible for cross-linking collagen fibers. Our objective was to ameliorate age-related myocardial fibrosis by disrupting collagen cross-linking through inhibition of LOX. The nonreversible LOX inhibitor ß-aminopropionitrile (BAPN) was administered by osmotic minipump to 38-week-old C57BL/6J male mice for 2 weeks. Sirius Red staining of myocardial cross sections revealed a reduction in fibrosis, compared with age-matched controls (5.84 ± 0.30% versus 10.17 ± 1.34%) (P < 0.05), to a level similar to that of young mice at 8 weeks (4.9 ± 1.2%). BAPN significantly reduced COL1A1 mRNA, compared with age-matched mice (3.5 ± 0.3-fold versus 15.2 ± 4.9-fold) (P < 0.05), suggesting that LOX is involved in regulation of collagen synthesis. In accord, fibrotic factor mRNA expression was reduced after BAPN. There was also a novel increase in Ly6C expression by resident macrophages. By interrupting collagen cross-linking by LOX, the BAPN treatment reduced myocardial fibrosis. A novel observation is that BAPN treatment modulated the transforming growth factor-ß pathway, collagen synthesis, and the resident macrophage population. This is especially valuable in terms of potential therapeutic targeting of collagen regulation and thereby age-related myocardial fibrosis.

Effects of remote ischemic preconditioning in high-risk patients undergoing cardiac surgery (Remote IMPACT): a randomized controlled trial.

BACKGROUND: Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery. METHODS: Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase-myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization. RESULTS: We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] -0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI -0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31). INTERPRETATION: Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01071265.

Endocarditis is not an Independent Predictor of Blood Transfusion in Aortic Valve Replacement Patients With Severe Aortic Regurgitation.

OBJECTIVE: This study sought to evaluate if the presence of endocarditis was independently associated with increased perioperative blood transfusion in patients undergoing aortic valve replacements (AVR) with aortic regurgitation. DESIGN: This was a retrospective study. SETTING: Large Canadian tertiary care hospital. PARTICIPANTS: Six hundred sixty-two consecutive patients with aortic regurgitation score of 3 or higher undergoing AVR from 1995 to 2012. INTERVENTIONS: No interventions were performed in this retrospective study. MEASUREMENTS AND MAIN RESULTS: After REB approval, data were obtained from a center-specific database. Univariate analysis was performed to identify variables that may be associated with transfusion of any allogeneic blood product perioperatively. A multivariate logistic regression was generated to identify independent predictors of perioperative transfusion. Unadjusted transfusion rates in patients with no endocarditis and with endocarditis were 32% and 70% (p<0.001), respectively. Independent predictors of any transfusion were moderate-to-severe preoperative anemia, preoperative renal failure, non-isolated AVR, age>70, urgent/emergent surgery, BMI<25, and female sex. Endocarditis was not an independent predictor of transfusion (OR = 0.748; 95% CI = 0.35-1.601). CONCLUSIONS: In patients undergoing AVR, unadjusted perioperative transfusion rates were higher when endocarditis was present. However, after adjustment, aortic valve endocarditis was not independently associated with blood transfusion. The authors' observation could be explained by the higher prevalence of many independent predictors of transfusion, such as comorbidities or more complex surgery, within the endocarditis group. Thus, AV endocarditis, in the absence of other risk factors, was not associated with increased perioperative transfusion risk.