Multimodal Analgesic Effectiveness on Acute Postoperative Pain Management After Adult Cardiac Surgery: Protocol for a Systematic Review.

BACKGROUND: Many patients report moderate to severe pain in the acute postoperative period. Enhanced recovery protocols recommend multimodal analgesics, but the optimal combination of these is unknown. PURPOSE: The aim of this study was to synthesize the best available evidence about effectiveness of multimodal analgesics on pain after adult cardiac surgery. METHODS: A systematic review to determine the effect of multimodal postoperative analgesics is proposed (International Prospective Register of Systematic Reviews Registration CRD42022355834). Multiple databases including the Cochrane Library, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, American Psychological Association, the Education Resources Information Centre, the Excerpta Medica database, the Medical Literature Analysis and Retrieval System Online, Scopus, Web of Science, and clinical trials databases will be searched. Screening in Covidence and quality assessment will be conducted by 2 authors. A grading of recommendations, assessment, development, and evaluation summary of findings will be presented if meta-analysis is possible.

Multistakeholder Recommendations for Supporting Patients and Families Transitioning From Paediatric to Adult Congenital Heart Disease Care.

Background: Transitioning from paediatric to adult congenital heart disease (CHD) care is a high-risk time for being lost to follow-up. Existing CHD transition programmes have not included patients, caregivers, and health care providers as partners in their development. This study aimed to develop recommendations for a CHD transition programme driven by lived and clinical experiences. Methods: We used a multilevel participatory process that engaged adult and paediatric people living with CHD, their caregivers, and CHD health care providers as members of the research team. We also consulted members of these stakeholder groups through a series of 3 virtual workshops that culminated in the generation of recommendations for the essential components of a CHD transition programme. Results: The Transition Essentials recommendations inform what information, education, or support is required, who should provide it, and when and how it should be provided. Information, education, and support for self-management and knowledge are required for people living with CHD. Caregivers require information, education, and support to build capacity in people living with CHD and navigate their new role in their loved ones' life. The health care team should provide this information, education, and support with peer support options when people living with CHD are 15-22 years of age. This information, education, and support should be individualized, navigate limitations, build over time, have multimodal options, and be available virtually or in person. Conclusions: Engaging those with lived and clinical expertise to develop recommendations for the essential components of a CHD transition programme provides important insights missing from previous studies.

Contexte: La transition des personnes qui vivent avec une cardiopathie congénitale (CC) entre les soins pédiatriques et les soins destinés aux adultes constitue une période où le risque de perte de vue est élevé. Les programmes de transition existants n'ont pas été élaborés avec la participation des patients, des aidants ou des fournisseurs de soins de santé. La présente étude visait à mettre en place des recommandations fondées sur la réalité des personnes concernées et sur l'expérience clinique pour les programmes de transition en contexte de CC. Méthodologie: Nous avons fait appel à un processus participatif à plusieurs niveaux dans lequel des enfants et des adultes vivant avec la CC, des aidants et des fournisseurs de soins de santé du domaine de la CC ont été impliqués comme membres de l'équipe de recherche. Nous avons également mené des consultations auprès de ces groupes d'intervenants dans une série de trois ateliers virtuels qui ont mené à la rédaction de recommandations sur les composantes essentielles d'un programme de transition pour les personnes vivant avec une CC. Résultats: Les recommandations portant sur les impératifs d'une transition réussie énoncent les renseignements, la formation et le soutien nécessaires ainsi que les intervenants qui devraient les offrir, de quelle façon et à quel moment. Les personnes qui vivent avec une CC ont besoin de renseignements, de formation et de soutien pour l'autoprise en charge et l'accès aux connaissances. Quant aux aidants, ils ont aussi besoin de renseignements, de formation et de soutien pour mieux outiller les personnes qui vivent avec une CC et pour mieux comprendre leur nouveau rôle dans la vie de leur proche. Il conviendrait que les professionnels de la santé soient ceux qui offrent ces ressources, lesquelles devraient être personnalisées, tenir compte des lacunes à combler, être cumulatives, offrir des options multimodales et être accessibles en personne ou virtuellement. Les personnes de 15 à 22 ans qui vivent avec une CC devraient également avoir la possibilité de s'entraider. Conclusions: La participation des personnes qui ont une expertise ancrée dans la réalité et une expertise clinique afin de formuler des recommandations sur les éléments essentiels d'un programme de transition pour les personnes qui vivent avec une CC a permis d'obtenir des renseignements intéressants qui ne se trouvaient pas dans les études antérieures.

Integrating harm reduction into acute care: A single center's experience.

Objective: Injection drug use (IDU) is prevalent in North America and is associated with presentations with infective endocarditis. Supporting patients who present with infective endocarditis related to IDU through harm reduction, a pragmatic approach to reduce secondary harms of a health behavior, helps address the underlying IDU. We share a case exemplar of how one acute care facility integrated harm-reduction practices into daily patient care. Methods: We took a 3-stage approach to integrate harm-reduction practices into daily patient care. In stage 1, we raised awareness and knowledge of harm reduction through education. In stage 2, we provided explicit support for harm reduction. In stage 3, we provided tangible tools to support harm reduction. Results: More than 300 staff attended education sessions and reported increased knowledge related to substances, harm reduction, and engaging patients who use substances in conversations. Staff requested the hospital explicitly support harm reduction, which led to stage 2. The creation of a harm-reduction philosophy statement provided permission to engage in harm-reduction practices. Stage 3 included the creation of a harm-reduction supply distribution program and consultations with Addictions Medicine and treatment programs. The implementation of harm-reduction supply distribution was successful and is being spread across the facility. Conclusions: Engaging in harm-reduction practices within an acute care facility is possible through a multistage process focused on education, explicit support, and tangible tools. Spreading harm-reduction integration and working with patients who used substances to evaluate effectiveness are key next steps.

The nutritional supplement taurine activates p53-dependent and independent tumor suppressor mechanisms in various cellular models of ovarian cancer.

Loss of treatment-induced ovarian carcinoma (OC) growth suppression poses a major clinical challenge because it leads to disease recurrence. Therefore, there is a compelling need for well- -tolerated approaches that can support tumor growth-suppression after therapy is stopped. We have profiled ascites as OC tumor microenvironments to search for potential non-toxic soluble components that would activate tumor suppressor pathways in OC cells. Our investigations revealed that low levels of taurine, a non-proteogenic sulfonic amino acid, were present within OC ascites. Taurine supplementation, beyond levels found in ascites, induced growth suppression without causing cytotoxicity in various OC cells, including chemotherapy-resistant cell clones and patient-derived organoids representing primary or chemotherapy recovered disease. Inhibition of proliferation by taurine was linked to increased mutant or wild-type p53 proteins binding to DNA, induction of p21, and independently of p53, TIGAR expression. Taurine-induced activation of p21 and TIGAR was associated with suppression of cell-cycle progression, glycolysis, and mitochondrial respiration. Expression of p21 or TIGAR in OC cells mimicked taurine-induced growth suppression. Our studies support the potential therapeutic value of taurine supplementation in OC.

Validation of the Emory Risk Score in the Transcatheter Aortic Valve Implantation Population: A Canadian Perspective.

Background: Permanent pacemaker (PPM) implantation may be indicated post-transcatheter aortic valve implantation (TAVI). The Emory Risk Score (ERS) is a validated predictive risk score of the need for a PPM post-TAVI using a balloon-expandable valve. Our objectives were to determine the validity of the ERS in our local TAVI population with both balloon-expandable and self-expanding valves and to identify additional electrocardiographic (ECG) parameters predictive of the need for a PPM post-TAVI. Methods: Retrospective chart and electronic database reviews were performed to collect demographic and procedural information. Two expert readers reviewed all ECGs. Independent factors associated with PPM implantation were examined with multivariable logistic regression via a stepwise selection process with calculation of the area under the receiver operating characteristic curve to assess model discrimination. Results: The overall PPM implantation rate was 11.7%; rates were 9% for the Sapien 3 valves, 10% for the Evolut Pro valves, and 17% for the Evolut R valves. The ERS was found to not be predictive of need for PPM post-TAVI for the entire cohort. Right bundle branch block was the only ERS parameter independently associated with new PPM implant (8.5% vs 25%, odds ratio = 3.59, P = 0.01). No additional ECG parameters met the criteria for statistical significance. Conclusions: The poor predictive value of the ERS in determining the need for a PPM post-TAVI in our patient population suggests that further refinement of a formula (or risk-calculator) is warranted. Identification of a precise risk-calculator is likely to facilitate patient mobilization and reduce inpatient healthcare resource utilization.

Introduction: L'implantation d'un stimulateur cardiaque permanent (SCP) peut être indiquée après l'implantation valvulaire aortique par cathéter (post-IVAC). L'Emory Risk Score (ERS) est un score de prédiction du risque validé de la nécessité d'un SCP post-IVAC au moyen d'une valve expansible par ballonnet. Nous avions pour objectif de déterminer la validité de l'ERS auprès de notre population ayant eu une IVAC soit par valve expansible par ballonnet ou valve auto-expansible, et de déterminer d'autres paramètres électrocardiographiques (ECG) prédictifs de la nécessité d'un SCP post-IVAC. Méthodes: Nous avons réalisé des revues rétrospectives de dossiers et de bases de données électroniques pour collecter les données démographiques et interventionnelles. Deux experts ont lu et interprété tous les ECG. Les facteurs indépendants associés à l'implantation du SCP ont été examinés en effectuant la régression logistique multivariée par processus de sélection pas-à-pas au moyen du calcul de la surface sous la courbe caractéristique d'efficacité du récepteur afin d'évaluer la discrimination du modèle. Résultats: Le taux global d'implantation d'un SCP était de 11,7 % ; les taux étaient de 9 % pour les valves Sapien 3, de 10 % pour les valves Evolut Pro et de 17 % pour les valves Evolut R. Nous avons observé que l'ERS ne permettait pas de prédire si l'implantation d'un SCP post-IVAC était nécessaire pour la cohorte entière. Le bloc de branche droit était le seul paramètre de l'ERS indépendamment associé à la nouvelle implantation d'un SCP (8,5 % vs 25 %, rapport de cotes = 3,59, P = 0,01). Aucun autre paramètre ECG ne satisfaisait au critère de signification statistique. Conclusions: La faible valeur prédictive de l'ERS à déterminer la nécessité d'un SCP post-IVAC au sein de notre population de patients montre que des améliorations de la formule (ou calculateur de risques) sont justifiées. L'identification d'un calculateur de risques précis devrait favoriser l'adhésion des patients et réduire l'utilisation des ressources en soins de santé en milieu hospitalier.

Early life trauma and adult leucocyte telomere length.

BACKGROUND: Telomere length, a biomarker of cell division and cellular aging, has been associated with multiple chronic disease endpoints. Experienced trauma over the life course may contribute to telomere shortening via mechanisms of stress embodiment. However, it is unclear how patterns of co-occurring trauma during sensitive periods (e.g., early life) throughout the life course may influence telomere shortening. We examine the relationship between co-occurring early life trauma on adult telomere length and the extent to which adulthood trauma, socioeconomic position, and health and lifestyle factors may mediate this relationship. METHODS: We use data from a sample of participants in the Sister Study (N = 740, analytic sample: n = 602), a prospective cohort of U.S. self-identified females aged 35-74 years at enrollment (2003-2009) for whom leukocyte telomere length was measured in baseline blood samples. Participants reported their experience of 20 different types of trauma, from which we identified patterns of co-occurring early life trauma (before age 18) using latent class analysis. We estimated the direct and indirect effects of early life trauma on leukocyte telomere length using structural equation modeling, allowing for mediating adult pathways. RESULTS: Approximately 47 % of participants reported early life trauma. High early life trauma was associated with shorter telomere length compared to low early life trauma (ß = -0.11; 95 % CI: -0.22, -0.004) after adjusting for age and childhood socioeconomic position. The inverse association between early life trauma and adult leukocyte telomere length was largely attributable to the direct effect of early life trauma on telomere length (ß = -0.12; 95 %CI: -0.23, -0.01). Mediating indirect pathways via adult trauma, socioeconomic position, and health metrics did not substantively contribute the overall association. CONCLUSIONS: These findings highlight the role of patterns of co-occurring early life trauma on shortened telomere length independent of adult pathways.

Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit.

Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D3 by endocytosis, placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy.

"Just think of it as sexercise" - healthcare providers' perceptions about sexual health education in cardiac rehabilitation programs.

PURPOSE: Sexual health education (SHE) is an important rehabilitation component for acute coronary syndrome (ACS) survivors but is not routinely provided. This study's purpose was to explore healthcare providers' experiences of providing SHE to ACS survivors in cardiac rehabilitation programs to identify best practices. METHODS: This qualitative study used convenience sampling and an interpretive descriptive design. Inclusion criteria were a healthcare provider employed within a cardiac rehabilitation program in a Western Canadian province. Eight cardiac rehabilitation healthcare providers volunteered to participate. The first author conducted semi-structured, digitally recorded interviews that were transcribed verbatim. The interviews were guided by a semi-structured interview guide anchored in the strengths-based, sex positive guiding frameworks. A reflective journal and socio-demographic forms served as additional data sources. Data were analyzed using open, axial, and selective coding as well as constant comparative analysis. Credibility was ensured through peer-reviewed evaluation criteria. RESULTS: Eight healthcare providers participated in the study. Participants equated sexuality and sexual health with physical activity and physical health. Findings identified philosophical perspectives and several barriers and facilitators that impact SHE provision. Participants offered strategies that may be used in practice and their recommendations provide a beginning foundation to improve cardiac rehabilitation programs and the health of ACS survivors. CONCLUSION: Healthcare providers in cardiac rehabilitation programs described their SHE experiences as "just think of it as sexercise." Facilitation of SHE is important as previous studies found that SHE may reduce fear, depression, and anxiety and increase the return to sexual activity among ACS survivors.IMPLICATIONS FOR REHABILITATIONSexual health doesn't need to be a taboo topic.Approach sexual health conversations by thinking of it as "sexercise".Don't let silos stop sexual health education - talk to your coworkers and patients about sexual health.Knowledge about sexual health, timing of sexual health education, and communication between care providers and patients are important factors in delivery of sexual health education.

Factors shaping the provision of sexual health education for adults with acute coronary syndrome: A scoping review.

OBJECTIVE: Each year, 63,000 Canadians are diagnosed with acute coronary syndrome (ACS) and 73 % survive. Sexual health education for ACS survivors is recommended but is not routinely provided. A scoping review was performed to inform health care providers about factors shaping sexual health education for ACS survivors. METHODS: Three databases were searched, 208 studies were screened, and 24 were included in this scoping review. Significant points from the selected studies were charted and synthesized. RESULTS: This review confirmed absent to limited provision of sexual health education to individuals with ACS. Key factors influencing lack of provision of sexual health were categorized according to macro, meso, and micro levels. At the macro level, societal and cultural factors were noted. The meso level included healthcare environment and limited healthcare provider knowledge. At the micro level, healthcare professional-healthcare consumer relationships and role clarity were noted. CONCLUSION: A sex positive approach may facilitate provision of sexual health education. PRACTICE IMPLICATIONS: This scoping review points to the need to use a sex positive lens to identify and remove barriers to facilitate the provision of sexual health education. Providing this education may result in reduced fear, depression, and anxiety in ACS survivors.

Surface charge control through the reversible adsorption of a biomimetic polymer on silica particles.

The control of the physicochemical properties of silica particles is of paramount importance to achieve full functionality in specific applications. A novel facile method of silica particle synthesis, requiring only two reactants, was developed. Control of the surface charge of these newly synthesized silica particles was achieved via the rapid electrostatic adsorption and acidic desorption of the branched, biomimetic polymer, polyethylenimine (PEI). Successful adsorption/desorption of PEI was supported by ATR-FTIR spectra, an adsorption isotherm, and ζ-potential curves. PEI adsorption above a threshold PEI concentration was determined to categorically change the topography of the silica particles' ζ-potential curve. The results from our study convey a rapid, reversible, and reliable method of silica particle surface charge control. This may be of particular use in tailoring surface interactions of silica or silica-coated particles for applications in drug delivery, biomedical technologies, catalysis, and coatings.

The Rhodadyns, a New Class of Small Molecule Inhibitors of Dynamin GTPase Activity.

Six focused rhodanine-based libraries, 60 compounds in total, were synthesized and evaluated as potential dynamin I GTPase inhibitors. Twenty-six were more potent than the lead compound with 13 returning IC50 values ≤10 µM, making the Rhodadyn series among the most active dynamin inhibitors reported. Two analogues were highly effective at blocking receptor-mediated endocytosis: C10 and D10 with IC50(RME) = 7.0 ± 2.2 and 5.9 ± 1.0 µM, respectively. These compounds are equipotent with the best reported in-cell dynamin inhibitors.