Single Functional Group Platform for Multistimuli Responsivities: Tertiary Amine for CO2/pH/ROS-Triggered Cargo Release in Nanocarriers.

The design of multistimuli-responsive soft nanoparticles (NPs) often presents synthetic complexities and limited breadth in exploiting changes surrounding physiological environments. Nanocarriers that could collectively take advantage of several endogenous stimuli can offer a powerful tool in nanomedicine. Herein, we have capitalized on the chemical versatility of a single tertiary amine to construct miktoarm polymer-based nanocarriers that respond to dissolved CO2, varied pH, reactive oxygen species (ROS), and ROS + CO2. Curcumin (Cur), an anti-inflammatory phytopharmaceutic, was loaded into micelles, and we validated the sensitivity of the tertiary amine in tuning Cur release. An in vitro evaluation indicated that Cur encapsulation strongly suppressed its toxicity at high concentrations, significantly inhibited nigericin-induced secretion of interleukin-1ß by THP-1 macrophages, and the proportion of M2/M1 (anti-inflammatory/pro-inflammatory macrophages) was higher for Cur-loaded NPs than for free Cur. Our approach highlights the potential of a simple-by-design strategy in expanding the scope of polymeric NPs in drug delivery.

"I Just Want to Feel Good Without Making You Feel Bad": Sexual Assertiveness Negotiation in Adolescent Romantic Relationships.

Sexual assertiveness is often conceptualized as an individual's ability to express one's own sexual needs, desires, and limits. Given that sexual assertiveness is embedded in interactions and can affect not only both partners' sexual well-being but also relationship satisfaction, dyadic approaches are needed to investigate sexual assertiveness negotiation within adolescent romantic relationships. This qualitative study aimed to document adolescents' ability to negotiate their sexual needs, desires, and limits with their partners during interactions where they discussed their sexual concerns. A directed content analysis, based on the life positions of the transactional analysis theory, was conducted on the interactions of 40 adolescent romantic dyads aged 14-19 years (M = 16.65; SD = 1.49). The results revealed four categories of strategies: (1) mutual assertiveness: negotiation of one's own sexual needs, desires, and limits with those of the partner; (2) singular passiveness: repression of one's own sexual needs, desires, and limits to privilege those of the partner; (3) singular aggressiveness: prioritization of one's own sexual needs, desires, and limits over those of the partner; and (4) mutual lack of negotiation skills: neglecting both partners' sexual needs, desires, and limits. Among other things, adolescents' ability to be sexually assertive was hindered by anticipations, including assumptions leading to disregarding one's own sexual needs, desires, and limits or fearing to ignore the partner's. To promote mutually rewarding sexual activities and prevent sexual violence, sexual education initiatives should support adolescents' ability to assertively negotiate their sexuality with their partner and avoid passiveness, aggressiveness, and lack of negotiation.

Canadian service providers' perspectives on reproductive coercion and abuse: a participatory action research to address their needs and support their actions.

Reproductive coercion and abuse (RCA) is a form of violence that affects sexual and reproductive health. Women and individuals who experienced RCA in an intimate relationship frequently consult service providers (SPs), such as health professionals or violence counselors. The objective of this article, which is the result of a participative action research project targeting RCA perpetrated by in an intimate partner, is twofold: (1) to better understand the practices as well as the barriers and facilitators encountered by SPs and (2) to develop information and awareness tools with them that meet their needs. To this end, we first held focus groups with 31 SPs. The use of thematic analysis revealed intervention strategies that focus on caring and listening, identifying signs of RCA, and creating a safe environment for disclosure. Their practices also focused on harm-reduction strategies and effective referrals. Despite the importance they gave to this issue, lack of time, inappropriate settings, and inadequate training hindered them from intervening effectively with individuals who were victims of RCA. They also indicated the need for easy-to-follow practice guidelines and patient education tools. Based on these findings and the best practices identified in the grey and scientific literature, we developed a practice guide for SPs and a booklet on RCA. The development of these guide and booklets involved a lot of back and forth to meet the needs expressed by the community and health professionals.

Pharmacogenetics-guided dalcetrapib therapy after an acute coronary syndrome: the dal-GenE trial.

AIMS: In a retrospective analysis of dal-Outcomes, the effect of dalcetrapib on cardiovascular events was influenced by an adenylate cyclase type 9 (ADCY9) gene polymorphism. The dal-GenE study was conducted to test this pharmacogenetic hypothesis. METHODS AND RESULTS: dal-GenE was a double-blind trial in patients with an acute coronary syndrome within 1-3 months and the AA genotype at variant rs1967309 in the ADCY9 gene. A total of 6147 patients were randomly assigned to receive dalcetrapib 600 mg or placebo daily. The primary endpoint was the time from randomization to first occurrence of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 39.9 months, the primary endpoint occurred in 292 (9.5%) of 3071 patients in the dalcetrapib group and 327 (10.6%) of 3076 patients in the placebo group [hazard ratio 0.88; 95% confidence interval (CI) 0.75-1.03; P = 0.12]. The hazard ratios for the components of the primary endpoint were 0.79 (95% CI 0.65-0.96) for myocardial infarction, 0.92 (95% CI 0.64-1.33) for stroke, 1.21 (95% CI 0.91-1.60) for death from cardiovascular causes, and 2.33 (95% CI 0.60-9.02) for resuscitated cardiac arrest. In a pre-specified on-treatment sensitivity analysis, the primary endpoint event rate was 7.8% (236/3015) in the dalcetrapib group and 9.3% (282/3031) in the placebo group (hazard ratio 0.83; 95% CI 0.70-0.98). CONCLUSION: Dalcetrapib did not significantly reduce the risk of occurrence of the primary endpoint of ischaemic cardiovascular events at end of study. A new trial would be needed to test the pharmacogenetic hypothesis that dalcetrapib improves the prognosis of patients with the AA genotype. CLINICAL TRIAL REGISTRATION: Trial registration dal-GenE ClinicalTrials.gov Identifier: NCT02525939.

ADCY9 (Adenylate Cyclase Type 9) Inactivation Protects From Atherosclerosis Only in the Absence of CETP (Cholesteryl Ester Transfer Protein).

BACKGROUND: Pharmacogenomic studies have shown that ADCY9 genotype determines the effects of the CETP (cholesteryl ester transfer protein) inhibitor dalcetrapib on cardiovascular events and atherosclerosis imaging. The underlying mechanisms responsible for the interactions between ADCY9 and CETP activity have not yet been determined. METHODS: Adcy9-inactivated ( Adcy9Gt/Gt) and wild-type (WT) mice, that were or not transgenic for the CETP gene (CETPtg Adcy9Gt/Gt and CETPtg Adcy9WT), were submitted to an atherogenic protocol (injection of an AAV8 [adeno-associated virus serotype 8] expressing a PCSK9 [proprotein convertase subtilisin/kexin type 9] gain-of-function variant and 0.75% cholesterol diet for 16 weeks). Atherosclerosis, vasorelaxation, telemetry, and adipose tissue magnetic resonance imaging were evaluated. RESULTS: Adcy9Gt/Gt mice had a 65% reduction in aortic atherosclerosis compared to WT ( P<0.01). CD68 (cluster of differentiation 68)-positive macrophage accumulation and proliferation in plaques were reduced in Adcy9Gt/Gt mice compared to WT animals ( P<0.05 for both). Femoral artery endothelial-dependent vasorelaxation was improved in Adcy9Gt/Gt mice (versus WT, P<0.01). Selective pharmacological blockade showed that the nitric oxide, cyclooxygenase, and endothelial-dependent hyperpolarization pathways were all responsible for the improvement of vasodilatation in Adcy9Gt/Gt ( P<0.01 for all). Aortic endothelium from Adcy9Gt/Gt mice allowed significantly less adhesion of splenocytes compared to WT ( P<0.05). Adcy9Gt/Gt mice gained more weight than WT with the atherogenic diet; this was associated with an increase in whole body adipose tissue volume ( P<0.01 for both). Feed efficiency was increased in Adcy9Gt/Gt compared to WT mice ( P<0.01), which was accompanied by prolonged cardiac RR interval ( P<0.05) and improved nocturnal heart rate variability ( P=0.0572). Adcy9 inactivation-induced effects on atherosclerosis, endothelial function, weight gain, adipose tissue volume, and feed efficiency were lost in CETPtg Adcy9Gt/Gt mice ( P>0.05 versus CETPtg Adcy9WT). CONCLUSIONS: Adcy9 inactivation protects against atherosclerosis, but only in the absence of CETP activity. This atheroprotection may be explained by decreased macrophage accumulation and proliferation in the arterial wall, and improved endothelial function and autonomic tone.

Preoperative Diaphragm Function Is Associated With Postoperative Pulmonary Complications After Cardiac Surgery.

OBJECTIVES: Postoperative pulmonary complications increase mortality, length, and cost of hospitalization. A better diaphragmatic strength may help face an increased work of breathing postoperatively. We, therefore, sought to determine if a low preoperative diaphragm thickening fraction (TFdi) determined by ultrasonography helped predict the occurrence of postoperative pulmonary complications after cardiac surgery independently of indicators of frailty, sarcopenia, and pulmonary function. DESIGN: Prospective observational cohort study. SETTING: Montreal Heart Institute, an academic cardiac surgery center in Canada. PATIENTS: Adults undergoing nonemergency cardiac surgery. INTERVENTIONS: We measured the preoperative thickness of the right and left hemidiaphragms at their zone of apposition at end-expiration (Tdi,ee) and peak-inspiration (Tdi,ei) with ultrasonography. Maximal thickening fraction of the diaphragm during inspiration (TFdi,max) was calculated using the following formula: TFdi,max = (Tdi,ei-Tdi,ee)/Tdi,ee. We also evaluated other potential risk factors including demographic parameters, comorbidities, Clinical Frailty Scale, grip strength, 5-meter walk test, and pulmonary function tests. We repeated TFdi,max measurements within 24 hours of extubation. The primary composite outcome of this study was the occurrence of postoperative pulmonary complications, defined as pneumonia, clinically significant atelectasis, or prolonged mechanical ventilation (> 24 hr). MEASUREMENT AND MAIN RESULTS: Of the 115 patients included, 34 (29.6%) developed postoperative pulmonary complications, including two with pneumonia, four with prolonged mechanical ventilation, and 32 with clinically significant atelectasis. Those with postoperative pulmonary complications had prolonged ICU and hospital length of stays. They had a lower TFdi,max (37% [interquartile range, 31-45%] vs 44% [interquartile range, 33-58%]; p = 0.03). In multiple logistic regression, a TFdi,max less than 38.1% was associated with postoperative pulmonary complications (odds ratio, 4.9; 95% CI, 1.81-13.50; p = 0.002). All patients who developed pneumonia or prolonged mechanical ventilation had a TFdi,max less than 38.1%. Respiratory rate and diabetes were also independently associated with postoperative pulmonary complications, while pulmonary function tests and the assessed indicators of frailty and sarcopenia were not. CONCLUSIONS: A low preoperative TFdi,max can help to identify patients at increased risk of postoperative pulmonary complications after cardiac surgery.

Acute Right Ventricular Failure in Cardiac Surgery During Cardiopulmonary Bypass Separation: A Retrospective Case Series of 12 Years' Experience With Intratracheal Milrinone Administration.

OBJECTIVE: To report the authors' 12 years of experience with intratracheal milrinone administration and to assess the efficacy and limitations of intratracheal milrinone bolus administration for the treatment of unexpected acute right ventricular (RV) failure in patients undergoing cardiac surgery. DESIGN: Retrospective analysis. SETTING: Single-center university hospital. PARTICIPANTS: One hundred seventy-six patients (4.6%) undergoing on-pump cardiac surgery. INTERVENTIONS: Endotracheal tube administration of milrinone (5-mg bolus) after unexpected acute RV failure during separation from cardiopulmonary bypass (CPB) weaning. RV failure was defined as the simultaneous presence of all of the following criteria: (1) hemodynamic instability or difficult separation from CPB with associated elevated central venous pressure or abnormal RV pressure waveform, (2) >20% reduction of RV fractional area change from baseline evaluated by transesophageal echocardiography, and (3) anatomical visualization of impaired or absent RV wall motion by direct intraoperative visual inspection. MEASUREMENTS AND MAIN RESULTS: Intratracheal milrinone administration was found to improve RV failure in 109 patients (61.9%) whereas RV failure persisted in 67 patients (38.1%). Using a multiple logistic regression model, severely decreased left ventricular ejection fraction (<35% v >50%) (adjusted odds ratio [OR] 3.72; 95% confidence interval [CI] 1.2-11.3; p = 0.012), longer CPB time (adjusted OR 1.014; CI 1.01-1.02; p = 0.001) and elevated postoperative fluid balance (adjusted OR 1.39; CI 1.1-1.8; p = 0.02) were found to be significant predictors of persistent RV failure. CONCLUSION: Intratracheal instillation of milrinone was associated with clinical improvement of RV failure occurring during separation from CPB in almost two-thirds of patients. Factors limiting its therapeutic efficacy include severe left ventricular dysfunction, increased fluid balance, and long CPB time.

Risk Factors for Radial-to-Femoral Artery Pressure Gradient in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass.

OBJECTIVE: To identify risk factors associated with radial-to-femoral pressure gradient during cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: This is a retrospective, observational study. SETTING: Single specialized cardiothoracic hospital in Montreal, Canada. PARTICIPANTS: Consecutive patients that underwent heart surgery with CPB between 2005 and 2015 (n = 435). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A radial-to-femoral pressure gradient occurred in 146 patients of the 435 patients (34%). Based on the 10,000 bootstrap samples, simple logistic regression models identified the 17 most commonly significant variables across the bootstrap runs. Using these variables, a backward multiple logistic model was performed on the original sample and identified the following independent variables: body surface area (m2) (odds ratio [OR] 0.08, 95% confidence interval [CI] 0.030-0.232), clamping time (minutes) (OR 1.01, 95% CI 1.007-1.018), fluid balance (for 1 liter) (OR 0.81, 95% CI 0.669-0.976), and preoperative hypertension (OR 1.801, 95% CI 1.131-2.868). CONCLUSION: A radial-to-femoral pressure gradient occurs in 34% of patients during cardiac surgery. Patients at risk seem to be of smaller stature, hypertensive, and undergo longer and more complex surgeries.

Adenosine-guided pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation: an international, multicentre, randomised superiority trial.

BACKGROUND: Catheter ablation is increasingly used to manage atrial fibrillation, but arrhythmia recurrences are common. Adenosine might identify pulmonary veins at risk of reconnection by unmasking dormant conduction, and thereby guide additional ablation to improve arrhythmia-free survival. We assessed whether adenosine-guided pulmonary vein isolation could prevent arrhythmia recurrence in patients undergoing radiofrequency catheter ablation for paroxysmal atrial fibrillation. METHODS: We did this randomised trial at 18 hospitals in Australia, Europe, and North America. We enrolled patients aged older than 18 years who had had at least three symptomatic atrial fibrillation episodes in the past 6 months, and for whom treatment with an antiarrhythmic drug failed. After pulmonary vein isolation, intravenous adenosine was administered. If dormant conduction was present, patients were randomly assigned (1:1) to additional adenosine-guided ablation to abolish dormant conduction or to no further ablation. If no dormant conduction was revealed, randomly selected patients were included in a registry. Patients were masked to treatment allocation and outcomes were assessed by a masked adjudicating committee. Patients were followed up for 1 year. The primary outcome was time to symptomatic atrial tachyarrhythmia after a single procedure in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01058980. FINDINGS: Adenosine unmasked dormant pulmonary vein conduction in 284 (53%) of 534 patients. 102 (69·4%) of 147 patients with additional adenosine-guided ablation were free from symptomatic atrial tachyarrhythmia compared with 58 (42·3%) of 137 patients with no further ablation, corresponding to an absolute risk reduction of 27·1% (95% CI 15·9-38·2; p<0·0001) and a hazard ratio of 0·44 (95% CI 0·31-0·64; p<0·0001). Of 115 patients without dormant pulmonary vein conduction, 64 (55·7%) remained free from symptomatic atrial tachyarrhythmia (p=0·0191 vs dormant conduction with no further ablation). Occurrences of serious adverse events were similar in each group. One death (massive stroke) was deemed probably related to ablation in a patient included in the registry. INTERPRETATION: Adenosine testing to identify and target dormant pulmonary vein conduction during catheter ablation of atrial fibrillation is a safe and highly effective strategy to improve arrhythmia-free survival in patients with paroxysmal atrial fibrillation. This approach should be considered for incorporation into routine clinical practice. FUNDING: Canadian Institutes of Health Research, St Jude Medical, Biosense-Webster, and M Lachapelle (Montreal Heart Institute Foundation).

A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients.

PURPOSE: Inhaled milrinone (iMil) has been used for the treatment of pulmonary hypertension (PH) but its efficacy, safety, and prophylactic effects in facilitating separation from cardiopulmonary bypass (CPB) and preventing right ventricular (RV) dysfunction have not yet been evaluated in a clinical trial. The purpose of this study was to investigate if iMil administered before CPB would be superior to placebo in facilitating separation from CPB. METHODS: High-risk cardiac surgical patients with PH were randomized to receive iMil or placebo after the induction of anesthesia and before CPB. Hemodynamic parameters and RV function were evaluated by means of pulmonary artery catheterization and transesophageal echocardiography. The groups were compared for the primary outcome of the level of difficulty in weaning from CPB. Among the secondary outcomes examined were the reduction in the severity of PH, the incidence of RV failure, and mortality. RESULTS: Of the 124 patients randomized, the mean (standard deviation [SD]) EuroSCORE II was 8.0 (2.6), and the baseline mean (SD) systolic pulmonary artery pressure (SPAP) was 53 (9) mmHg. The use of iMil was associated with increases in cardiac output (P = 0.03) and a reduction in SPAP (P = 0.04) with no systemic hypotension. Nevertheless, there was no difference in the combined incidence of difficult or complex separation from CPB between the iMil and control groups (30% vs 28%, respectively; absolute difference, 2%; 95% confidence interval [CI], -14 to 18; P = 0.78). There was also no difference in RV failure between the iMil and control groups (15% vs 14%, respectively; difference, 1%; 95% CI, -13 to 12; P = 0.94). Mortality was increased in patients with RV failure vs those without (22% vs 2%, respectively; P < 0.001). CONCLUSION: In high-risk cardiac surgery patients with PH, the prophylactic use of iMil was associated with favourable hemodynamic effects that did not translate into improvement of clinically relevant endpoints. This trial was registered at ClinicalTrials.gov; identifier: NCT00819377.

RéSUMé: OBJECTIF: La milrinone inhalée est utilisée pour traiter l'hypertension pulmonaire (HP) mais son efficacité, son innocuité et ses effets prophylactiques pour faciliter le sevrage de la circulation extracorporelle (CEC) et prévenir la dysfonction ventriculaire droite (VD) n'ont pas encore été évalués dans le cadre d'une étude clinique. L'objectif de cette étude était d'examiner si la milrinone inhalée avant la CEC serait supérieure à un placebo pour faciliter le sevrage de la CEC. MéTHODE: Des patients de chirurgie cardiaque à risque élevé et souffrant d'HP ont été randomisés à recevoir de la milrinone inhalée ou un placebo après l'induction de l'anesthésie et avant la CEC. Les paramètres hémodynamiques et la fonction VD ont été évalués à l'aide d'un cathéter de l'artère pulmonaire et d'une échocardiographie transœsophagienne. Les groupes ont été comparés selon notre critère d'évaluation principal, soit le niveau de difficulté du sevrage de la CEC. Parmi les critères d'évaluation secondaires examinés figuraient la réduction de la gravité de l'HP, l'incidence d'insuffisance cardiaque droite et la mortalité. RéSULTATS: Au total, 124 patients ont été randomisés. Le score EuroSCORE II moyen (écart type [ÉT]) était de 8,0 (2,6), et la pression systolique de l'artère pulmonaire moyenne de base (ÉT) était de 53 (9) mmHg. L'utilisation de milrinone inhalée a été associée à des augmentations du débit cardiaque (P = 0,03) et à une réduction de la pression systolique de l'artère pulmonaire (P = 0,04) sans hypotension systémique. Toutefois, aucune différence n'a été observée dans l'incidence combinée de sevrage difficile ou complexe de la CEC entre le groupe milrinone inhalée et le groupe témoin (30 % vs 28 %, respectivement; différence absolue, 2 %; intervalle de confiance [IC] 95 %, −14 à 18; P = 0,78). Aucune différence n'a été observée non plus en matière d'insuffisance cardiaque droite entre le groupe milrinone inhalée et le groupe témoin (15 % vs 14 %, respectivement; différence, 1 %; IC 95 %, −13 à 12; P = 0,94). La mortalité était augmentée chez les patients avec insuffisance cardiaque droite (22 % vs 2 %, respectivement; P < 0.001). CONCLUSION: Chez les patients de chirurgie cardiaque à risque élevé atteints de HP, l'utilisation prophylactique de milrinone inhalée a été associée à des effets hémodynamiques favorables qui ne se sont pas traduits en améliorations des critères pertinents d'un point de vue clinique. Cette étude a été enregistrée au ClinicalTrials.gov; identifiant : NCT00819377.

Efficacy of amiodarone in patients with atrial fibrillation with and without left ventricular dysfunction: a pooled analysis of AFFIRM and AF-CHF trials.

INTRODUCTION: Despite amiodarone's established safety profile in the setting of heart failure, it is unknown whether its impact on cardiovascular outcomes in patients with atrial fibrillation is modulated by left ventricular function. METHODS AND RESULTS: A pooled analysis of 3,307 patients (age 68.0 ± 0.2 years; 31.1% female) enrolled in AFFIRM and AF-CHF trials was conducted to assess the effect of rhythm control with amiodarone on cardiovascular outcomes, according to left ventricular systolic function. In amiodarone-treated patients (N = 1,107), freedom from recurrent atrial fibrillation was 84% and 45% at 1 and 5 years, respectively, with no differences according to left ventricular function (P = 0.8754). Similarly, the adjusted proportion of time spent in atrial fibrillation (15.0 ± 1.8%) did not vary according to ventricular function (P = 0.6094). Over 40.0 ± 0.3 months of follow-up, 1,963 (59.4%) patients required at least one hospitalization, 1,401 (42.6%) of whom had cardiovascular-related hospitalizations. Adjusted all-cause and cardiovascular hospitalization rates were similar with amiodarone versus rate control in all patients and in subgroups with and without severe left ventricular dysfunction. A total of 729 (22.0%) patients died, 498 (15.1%) from cardiovascular causes. Adjusted all-cause and cardiovascular mortality rates were similar with amiodarone versus rate control overall and in subgroups with and without severe left ventricular dysfunction. CONCLUSION: Amiodarone's efficacy in maintaining sinus rhythm and reducing the burden of atrial fibrillation is similar in the presence or absence of severe left ventricular dysfunction. Rhythm control with amiodarone is associated with comparable hospitalization and mortality rates to rate control in patients with and without left ventricular dysfunction.

A Latent Class Analysis of Reproductive Coercion Experiences Based on Victim-Survivors' Acknowledgment and Disclosure Patterns.

Reproductive coercion (RC) is a form of violence involving behavior that interferes with an individual's contraceptive and reproductive decisions. Like other forms of violence perpetrated by intimate partners, victims of RC do not necessarily identify it as such. Similarly, victim-survivors do not readily disclose their experiences or seek support and treatment. This study identifies patterns of acknowledgment and formal and informal disclosure of RC experiences in a community sample of 317 participants. Latent classes are then compared with respect to characteristics of victims/survivors, RC consequences, and associated contexts. Participants completed measures to assess experiences of RC and violence perpetuated by intimate partners as well as social support, posttraumatic stress symptoms, and consequences for psychological and sexual health. Latent class analysis was performed to identify acknowledgment and disclosure patterns. An optimal three-class solution was selected: High unacknowledgment with ambivalence, High disclosure (41%); High acknowledgment, High disclosure (30%); and Hesitant acknowledgment, No disclosure (29%). Classes were identified according to the presence of social support, living with a disability, victimization experiences, and mental and sexual health consequences. Future studies should explore the relationship between RC acknowledgment and disclosure, which can influence victims' search trajectories for support and services.

Clinical Heart fAilure Management Program: Changing the practice by partnering primary care and specialists (CHAMP-HF).

Background: While significant gains were made in the management of heart failure (HF), most patients are still diagnosed when they are acutely ill in hospital, often with advanced disease. Earlier diagnosis in the community could lead to improved outcomes. Whether a partnership and an educational program for primary care providers (PCP) increase HF awareness and management is unknown. Methods: We conducted an observational study between March 2019 and June 2020 during which HF specialists gave monthly HF conferences to PCP. Using a pre-post design, medical charts and administrative databases were reviewed and a questionnaire was completed by participating PCP. Primary and secondary endpoints included: 1) the number of patients diagnosed with HF, 2) implementation of GDMT for patients with HFrEF; 3) PCPs' experience and confidence. Results: Six PCP agreed to participate. Amongst the 11,909 patients of the clinic, 70 (0.59 %) patients met the criteria for HF. This number increased by 28.6 % (n = 90) after intervention. Increased use of GDMT for HFrEF patients at baseline (n = 35) was observed for all class of agents, with doubling of patients on triple therapies, from 8 (22.9 %) to 16 (45.7 %), p = 0.0047. Self-confidence on HF management was low (1, 16.7 %) but increased after the educational intervention of physicians (3, 50 %). Conclusion: An educational and collaborative approach between HF specialists and community PCP increased the number of new HF cases diagnosed, enhanced implementation of GDMT in patients with HFrEF and increase PCPs' confidence in treating HF, despite being conducted during the COVID-19 pandemic.

Impact of Fontan Fenestration on Adverse Cardiovascular Outcomes: A Multicentre Study.

BACKGROUND: Fenestrating a Fontan baffle has been associated with improved perioperative outcomes in patients with univentricular hearts. However, longer-term potential adverse effects remain debated. We sought to assess the impact of a fenestrated Fontan baffle on adverse cardiovascular events including all-cause mortality, cardiac transplantation, atrial arrhythmias, and thromboemboli. METHODS: A multicentre North American retrospective cohort study was conducted on patients with total cavopulmonary connection Fontan baffle, with and without fenestration. All components of the composite outcome were independently adjudicated. Potential static and time-varying confounders were taken into consideration, along with competing risks. RESULTS: A total of 407 patients were followed for 10.4 (7.1-14.4) years; 70.0% had fenestration of their Fontan baffle. The fenestration spontaneously closed or was deliberately sealed in 79.9% of patients a median of 2.0 years after Fontan completion. In multivariable analysis in which a persistent fenestration was modelled as a time-dependent variable, an open fenestration did not confer a higher risk of the composite outcome (hazard ratio, 1.18; 95% confidence interval, 0.71-1.97; P = 0.521). In secondary analyses, an open fenestration was not significantly associated with components of the primary outcome: that is, mortality or transplantation, atrial arrhythmias, or thromboemboli. However, sensitivity analyses to assess the possible range of error resulting from imprecise dates for spontaneous fenestration closures could not rule out significant associations between an open fenestration and atrial arrhythmias or thromboemboli. CONCLUSIONS: In this multicentre study, no significant association was identified between an open fenestration in the Fontan baffle and major adverse cardiovascular events.

Hemodynamic pressure waveform analysis in predicting fluid responsiveness.

OBJECTIVE: To assess the usefulness of central venous pressure (CVP), diastolic right ventricular pressure, and pulmonary capillary wedge pressure (PCWP) waveform analysis in predicting fluid responsiveness. DESIGN: A prospective observational study. SETTING: Tertiary care university hospital. PATIENTS: Forty-four patients undergoing coronary artery bypass grafting. INTERVENTIONS: Analysis of the a/v wave ratio of the PCWP, CVP, and right ventricular dP/dt to predict an increase in stroke volume >15% after the administration of 500 mL of colloid. MEASUREMENTS AND MAIN RESULTS: Forty-four patients were enrolled in this study and 7 were excluded. There were 24 responders and 13 nonresponders. No differences in mean CVP and PCWP values between the responders and the nonresponders were found. The only parameter associated with a significant response to volume infusion was the ratio of the a/v waves of the PCWP tracing (p = 0.0001). The performance of the a/v wave ratio>1 of the PCWP tracing in predicting fluid responsiveness was evaluated by constructing a receiver operating characteristic curve. The area under the receiver operating characteristic curve was 0.89 (95% confidence interval, 0.79-0.99; p<0.05). CONCLUSIONS: The a/v ratio measured on the PCWP tracing is a predictor of fluid responsiveness in patients with preserved left ventricular function undergoing coronary artery bypass grafting.

A Dyadic Analysis of Sexual Assertiveness and Sexual Outcomes in Adolescent Romantic Relationships.

Amid adolescence, youth are developing the relational skills necessary to form and maintain positive intimate relationships. Sexual assertiveness is a key skill that could be related to couples' sexual outcomes (i.e. sexual satisfaction, sexual concerns, and sexual function). However, dyadic studies are lacking, and associations between sexual assertiveness and adolescents' sexual health and well-being remain underexplored. This cross-sectional dyadic study examined associations between dimensions of sexual assertiveness and sexual outcomes in adolescent romantic relationships. The Actor-Partner Interdependence Model guided analyses of self-reported questionnaires from 110 romantic dyads (aged 14-19 years; M = 16.51). Participants' gender was considered in the models, and gender differences emerged in the associations between study variables. Path analyses revealed that sexual needs and desires communication, refusal of unwanted sex, sexual intimacy initiation, and comfort talking about sex have significant actor and partner effects on adolescents' sexual outcomes in mixed-gender dyads. These findings suggest that authentically expressing one's own sexual needs, desires, and limits in adolescence may influence not only one's own sexual satisfaction, sexual concerns, and sexual function, but also their partner's. The aforementioned dimensions of sexual assertiveness could be important targets for research-based interventions to promote sexual health and well-being in adolescent romantic relationships.

Reproductive Coercion by Intimate Partners: Prevalence and Correlates in Canadian Individuals with the Capacity to be Pregnant.

OBJECTIVES: Despite the large body of research on violence against women, violence that specifically targets women's reproductive autonomy and control over their reproductive health, called reproductive coercion (RC), is poorly documented in Canada. The purpose of this study is to determine the prevalence of RC behaviors in an adult Canadian community sample and to explore associated factors. STUDY DESIGN: A self-report online questionnaire was administered from September 2020 to April 2021 in Quebec and Ontario, Canada. Participants were recruited via social media, sexual and reproductive health clinics, community-based anti-violence organizations, and the project's partner organizations. The questionnaire contained validated RC questionnaire items and new items drawn from previous qualitative work. The sample comprised 427 participants, mostly self-identified as women (92%), aged 18 to 55 years (M = 29.01; SD = 6.64). Descriptive analyses and binary logistic regressions were conducted using SPSS 27. RESULTS: The results of this study show that 63.9% of participants reported at least one lifetime experience of RC. According to our data, contraceptive sabotage was the most common form (62.8%). Of the participants who had been pregnant, 9.8% reported control of pregnancy outcomes. Each RC category shows a different pattern of correlates. The findings also reveal that intimate partner violence (IPV) increases the likelihood of contraceptive sabotage. Moreover, the study suggests that low education level and IPV increase the risk for control of pregnancy outcomes. CONCLUSION: These findings underscore the importance of RC in the lives of many Canadian individuals with the capacity to be pregnant, and they highlight certain factors that place individuals at greater risk for RC. This knowledge can inform the development of prevention efforts and clinical interventions.

Prolonged cardiovascular pharmacological support and fluid management after cardiac surgery.

OBJECTIVE: To identify potentially modifiable risk factors related to prolonged cardiovascular pharmacological support after weaning from cardiopulmonary bypass (CPB). METHODS: This is a secondary analysis of two prospective cohort study in a specialized cardiac surgery institution in adult patients undergoing cardiac surgery with the use of CPB between August 2016 and July 2017. Prolonged cardiovascular pharmacological support was defined by the need for at least one vasopressor or one inotropic agent 24 hours after separation from CPB. Risk factors were identified among baseline characteristics and peri-operative events through multivariable logistic regression. RESULTS: A total of 247 patients were included and 98 (39.7%) developed prolonged pharmacological support. In multivariable analysis, left ventricular ejection fraction ≤ 30% (OR 9.52, 95% confidence interval (CI) 1.14; 79.25), elevated systolic pulmonary artery pressure (sPAP) > 30 and ≤ 55 mmHg (moderate) (OR 2.52, CI 1.15; 5.52) and sPAP > 55 mmHg (severe) (OR 8.12, CI 2.54; 26.03), as well as cumulative fluid balance in the first 24 hours after surgery (OR 1.76, CI 1.32; 2.33) were independently associated with the development of prolonged pharmacological support. CONCLUSIONS: Prolonged cardiovascular pharmacological support is frequent after cardiac surgery on CPB. Severe LV systolic dysfunction, preoperative pulmonary hypertension and postoperative fluid overload are risk factors. Further studies are required to explore if those risk factors could be modified or not.

Portrayal of Domestic Violence Trajectories During the Perinatal Period.

Domestic violence during the perinatal period (DVPP) refers to the various ways that women's partners or ex-partners control and coerce them during pregnancy and the 2 years postpartum. From the descriptions of 17 women with firsthand experience of DVPP, this article reports on its manifestations and the associated contexts. The results reveal escalating violence, diverse forms of violence, and exacerbated consequences over the perinatal period. The contexts that pose additional challenges for the women include financial precariousness and the partner's substance abuse, and to a lesser extent the residential situation.

Oral ferrous sulfate does not increase preoperative hemoglobin in patients scheduled for hip or knee arthroplasty.

BACKGROUND: Low hemoglobin (Hb) concentrations before lower limb joint replacement are associated with the need for blood transfusions and increased mortality. To optimize preoperative Hb, blood conservation protocols often recommend oral iron supplements, even in nonanemic patients. OBJECTIVE: To investigate the impact of ferrous sulfate on the change in Hb prior to hip or knee arthroplasty and evaluate the effect of oral iron on hematocrit, mean corpuscular volume (MCV), ferritin, and transferrin saturation, as well as its tolerability and treatment adherence. METHODS: We conducted a prospective, observational cohort study of adults with Hb concentrations between 10 and 15 g/dL who received iron supplementation prior to hip or knee arthroplasty. Systemic inflammatory diseases, vitamin B(12) or folate deficiency, and current use of iron supplements, intravenous iron, or erythropoietin were exclusion criteria. All participants were prescribed ferrous sulfate 300 mg 3 times daily for a minimum of 3 weeks. Complete blood cell counts and iron studies were performed before therapy and surgery. RESULTS: Eighty-seven patients with a mean (SD) Hb of 13.47 (0.84) g/dL were included in the study. Preoperative Hb decreased after treatment with iron (-0.14 [0.53] g/dL, p = 0.015). Hematocrit also declined (-0.6% [1.8%], p = 0.002), whereas ferritin increased (25.8 [38.6] ng/mL, p < 0.001). No significant change was seen in MCV and transferrin saturation. The most common adverse effects were constipation (33.3%), heartburn (13.8%), and abdominal pain (12.6%). The adherence rate was 67.1%. CONCLUSIONS: Oral ferrous sulfate supplementation is not an effective method to increase preoperative Hb in patients scheduled for hip or knee arthroplasty, and its use is associated with adverse effects.