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OBJECTIVE: To investigate patient reports of physician communication about the 2006 Institute of Medicine (IOM) Guidelines for Survivorship Care, and patient follow-up care behaviors in a sample of African American and Caucasian breast cancer survivors. METHODS: Fifteen-minute telephone interviews were conducted in a cross-sectional study with a sample of African American (n=30) and Caucasian (n=69) breast cancer patients, who were within 5 years of their diagnosis and primary treatment for breast cancer at two Baltimore, Maryland medical centers, during the summer of 2006. Multiple items assessed patient reports of physician discussions about IOM Guidelines, their recurrence concerns, and their follow-up treatment, screening, diet and exercise practices. RESULTS: Patients with higher incomes, more education, female physicians, and of younger ages reported more complete physician discussions of the IOM Guidelines. No significant differences were noted between African American and Caucasian patients. CONCLUSION: Patients at greatest risk for breast cancer recurrence - those with less education, income, and resources - report limited guidance from their physicians about evidence-based, follow-up care guidelines, designed to minimize their risk. PRACTICE IMPLICATIONS: Physicians need strategies for effectively delivering the IOM Guidelines for Survivorship Care to disadvantaged breast cancer patients, to promote enhanced quality of life and reduced risk of recurrence. [ABSTRACT FROM AUTHOR]

Objective: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease., Methods: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation., Results: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs., Conclusion: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs., (© 2024 American College of Rheumatology.)

Objective: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs)., Methods: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations., Results: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs., Conclusion: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs., (© 2024 American College of Rheumatology.)

Children museums provide an engaging learning environment for families with exhibits designed to stimulate caregiver-child interactions. Specific types of questions have been shown to support child language learning by scaffolding more elaborative responses. This study analyzed the use of question form types during caregiver-child interactions in a children's museum, aiming to discern their correlation with child language proficiency. We examined and transcribed two exhibit explorations by 43 caregiver-child dyads (3- to 6-year-old children). Our analysis encompasses various syntactic question types (e.g., yes-no, wh-) and measures of child language proficiency, including lexical diversity, morphosyntactic complexity, and overall language ability. Findings reveal disparities in question form usage among caregivers and children, with caregivers predominantly employing closed questions and children balancing closed and open-ended types. Children of caregivers who predominantly posed closed questions exhibited shorter utterances and lower overall language scores. Details on other question forms are presented (sub-types of polar, wh-, alternative, and echo). These findings contribute to our understanding of how question form influences language development and caregiver-child interactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Thorson, Trumbell and Nesbitt.)

Background: Despite the highest levels of evidence on cardiac rehabilitation (CR) effectiveness, its translation into practice is compromised by low participation., Aim: This study aimed to investigate CR utilisation and effectiveness in South Australia., Methods: This retrospective cohort study used data linkage of clinical and administrative databases from 2016 to 2021 to assess the association between CR utilisation (no CR received, commenced without completing, or completed) and the composite primary outcome (mortality/cardiovascular re-admissions within 12 months after discharge). Cox survival models were adjusted for sociodemographic and clinical data and applied to a population balanced by inverse probability weighting. Associations with non-completion were assessed by logistic regression., Results: Among 84,064 eligible participants, 74,189 did not receive CR, with 26,833 of the 84,064 (31.9%) participants referred. Of these, 9,875 (36.8%) commenced CR, and 7,681 of the 9,875 (77.8%) completed CR. Median waiting time from discharge to commencement was 40 days (interquartile range, 23-79 days). Female sex (odds ratio [OR] 1.12; 95% CI 1.01-1.24; p=0.024), depression (OR 1.17; 95% CI 1.05-1.30; p=0.002), and waiting time >28 days (OR 1.15; 95% CI 1.05-1.26; p=0.005) were associated with higher odds of non-completion, whereas enrolment in a telehealth program (OR 0.35; 95% CI 0.31-0.40; p<0.001) was associated with lower odds of non-completion. Completing CR (hazard ratio [HR] 0.62; 95% CI 0.58-0.66; p<0.001) was associated with a lower risk of 12-month mortality/cardiovascular re-admissions. Commencing without completing was also associated with decreased risk (HR 0.81; 95% CI 0.73-0.90; p<0.001), but the effect was lower than for those completing CR (p<0.001)., Conclusions: Cardiac rehabilitation (CR) attendance is associated with lower all-cause mortality/cardiovascular re-admissions, with CR completion leading to additional benefits. Quality improvement initiatives should include promoting referral, women's participation, access to telehealth, and reduction of waiting times to increase completion., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: D2 aortic stenosis (AS) is the highest risk AS subtype with worse operative and mortality outcomes. This study aimed to investigate the quality of life (QoL) and left ventricular ejection fraction (LVEF) in patients with classic (D2 subtype) low-flow/low-gradient AS who underwent transcatheter aortic valve replacement (TAVR)., Methods: In total, 634 patients with severe AS underwent TAVR at our institution from 2014 to 2020, of whom 76 met criteria for classic D2 AS with reduced LVEF. Echocardiographic and clinical outcomes including mortality, stroke, pacemaker placement (PPM), and readmission at baseline were compared with those at 30 days and 1 year. QoL data were extracted from the Kansas City Cardiomyopathy Questionnaire (KCCQ-12)., Results: The average baseline Society of Thoracic Surgeons risk score for patients with D2 AS was 7.66 ± 6.76. Patients with D2 AS reported improved QoL post-TAVR. The average baseline KCCQ-12 score was 39.5 ± 20, with improvement to 68.9 ± 20.6 at 30 days ( P < .01) and 74.9 ± 17.5 at 1 year ( P < .01). Mortality was 0% at 30 days and 18.4% at 1 year. The average baseline LVEF was 36.1 ± 9.4. Left ventricular function improved to 43.5 ± 12.9 ( P <.001) at 30 days and 46.3 ± 11.2 ( P = .03) at 1 year. Complications post-TAVR at 30 days included stroke (1.3%) and PPM (11.8%). Patients with D2 AS exhibited higher baseline conduction defects including atrial fibrillation and higher postoperative PPM than those with other subtypes., Conclusions: Patients with D2 AS had significantly improved LVEF and QoL following TAVR at 30 days and 1 year. Postoperative rates of new PPM were higher than other subtypes, while stroke, dialysis, and mortality were lower than expected, supporting the benefit of TAVR in this high-risk group.

Antifibrinolytic drugs are used extensively for on-demand treatment of severe acute bleeding. Controlling fibrinolysis may also be an effective strategy to prevent or lessen chronic recurring bleeding in bleeding disorders such as hemophilia A (HA), but current antifibrinolytics have unfavorable pharmacokinetic profiles. Here, we developed a long-lasting antifibrinolytic using small interfering RNA (siRNA) targeting plasminogen packaged in clinically used lipid nanoparticles (LNPs) and tested it to determine whether reducing plasmin activity in animal models of HA could decrease bleeding frequency and severity. Treatment with the siRNA-carrying LNPs reduced circulating plasminogen and suppressed fibrinolysis in wild-type and HA mice and dogs. In HA mice, hemostatic efficacy depended on the injury model; plasminogen knockdown improved hemostasis after a saphenous vein injury but not tail vein transection injury, suggesting that saphenous vein injury is a murine bleeding model sensitive to the contribution of fibrinolysis. In dogs with HA, LNPs carrying siRNA targeting plasminogen were as effective at stabilizing clots as tranexamic acid, a clinical antifibrinolytic, and in a pilot study of two dogs with HA, the incidence of spontaneous or excess bleeding was reduced during 4 months of prolonged knockdown. Collectively, these data demonstrate that long-acting antifibrinolytic therapy can be achieved and that it provides hemostatic benefit in animal models of HA.

Aims: This review aimed to investigate the effectiveness of nurse-led interventions vs. usual care on hypertension management, lifestyle behaviour, and patients' knowledge of hypertension and associated risk factors., Methods: A systematic review with meta-analysis was conducted following Joanna Briggs Institute (JBI) guidelines. MEDLINE (Ovid), EmCare (Ovid), CINAHL (EBSCO), Cochrane library, and ProQuest (Ovid) were searched from inception to 15 February 2022. Randomized controlled trials (RCTs) examining the effect of nurse-led interventions on hypertension management were identified. Title and abstract, full text screening, assessment of methodological quality, and data extraction were conducted by two independent reviewers using JBI tools. A statistical meta-analysis was conducted using STATA version 17.0., Results: A total of 37 RCTs and 9731 participants were included. The overall pooled data demonstrated that nurse-led interventions may reduce systolic blood pressure (mean difference -4.66; 95% CI -6.69, -2.64; I2 = 83.32; 31 RCTs; low certainty evidence) and diastolic blood pressure (mean difference -1.91; 95% CI -3.06, -0.76; I2 = 79.35; 29 RCTs; low certainty evidence) compared with usual care. The duration of interventions contributed to the magnitude of blood pressure reduction. Nurse-led interventions had a positive impact on lifestyle behaviour and effectively modified diet and physical activity, but the effect on smoking and alcohol consumption was inconsistent., Conclusion: This review revealed the beneficial effects of nurse-led interventions in hypertension management compared with usual care. Integration of nurse-led interventions in routine hypertension treatment and prevention services could play an important role in alleviating the rising global burden of hypertension., Registration: PROSPERO: CRD42021274900., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The aim of this study is to report on the development and evaluation of the co-designed website for delivering interactive self-directed cardiac rehabilitation (CR)., Methods and Results: Multi-method user experience design framework was used to co-design the web application and complete usability testing. Participants were recruited based on their eligibility for CR. Thematic analysis collected the participants' design specifications and lived experiences. The System Usability Scale (SUS) was administered at the completion of the website development and the usability testing workshops. This collected the participants' perceptions of the website's effectiveness, efficiency, and their satisfaction. Website development and usability testing workshops included 39 and 35 participants with a mean age of 66.5 (SD 11.7) and 68.6 (SD 11.2), respectively. Both genders were equally represented across both workshops with 19 (48.7%) and 16 (45.7%) women. Workshop themes guided the design process. The mean SUS scores increased from 66.7 (SD 16.8) to 73.6 (21), P = 0.26. Easiness of use (P = 0.03), integration of the website functions (P ≤ 0.001), and consistency (P = 0.038) significantly improved from website development to usability testing. The proportion of participants rating it as excellent increased from 20.5% to 42.9%, P = 0.11., Conclusion: The evolution of our CR website development was completed with an improvement in usability. Upcoming evaluation of this intervention will report on its effectiveness., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Education to improve medication adherence is one of the core components of cardiac rehabilitation (CR) programs. However, the evidence on the effectiveness of CR programs on medication adherence is conflicting. Therefore, we aimed to summarize the effectiveness of CR programs versus standard care on medication adherence in patients with cardiovascular disease., Methods: A systematic review and meta-analysis was conducted. Seven databases and clinical trial registries were searched for published and unpublished articles from database inception to 09 Feb 2022. Only randomised controlled trials and quasi-experimental studies were included. Two independent reviewers conducted the screening, extraction, and appraisal. The JBI methodology for effectiveness reviews and PRISMA 2020 guidelines were followed. A statistical meta-analysis of included studies was pooled using RevMan version 5.4.1., Results: In total 33 studies were included with 16,677 participants. CR programs increased medication adherence by 14 % (RR = 1.14; 95 % CI: 1.07 to 1.22; p = 0.0002) with low degree of evidence certainty. CR also lowered the risk of dying by 17 % (RR = 0.83; 95 % CI: 0.69 to 1.00; p = 0.05); primary care and emergency department visit by mean difference of 0.19 (SMD = -0.19; 95 % CI: -0.30 to -0.08; p = 0.0008); and improved quality of life by 0.93 (SMD = 0.93; 95 % CI: 0.38 to 1.49; p = 0.0010). But no significant difference was observed in lipid profiles, except with total cholesterol (SMD = -0.26; 95 % CI: -0.44 to -0.07; p = 0.006) and blood pressure levels., Conclusions: CR improves medication adherence with a low degree of evidence certainty and non-significant changes in lipid and blood pressure levels. This result requires further investigation., Competing Interests: Authors declare no conflict of interest., (© 2023 The Authors.)

Introduction: Although available evidence demonstrates positive clinical outcomes for patients attending and completing cardiac rehabilitation, the effectiveness of interactive cardiac rehabilitation web applications on programme completion has not been systematically examined., Methods: This JBI systematic review of effects included studies measuring effectiveness of interactive cardiac rehabilitation web applications compared to telephone, and centre-based programmes. Outcome data were pooled under programme completion and clinical outcomes (body mass index, low-density lipoproteins, and blood pressure). Databases including MEDLINE (via Ovid), Cochrane Library, Scopus (via Elsevier) and CINAHL (via EBSCO) published in English were searched. Articles were screened and reviewed by two independent reviewers for inclusion, and the JBI critical appraisal tool and Grading of Recommendations Assessment, Development and Evaluation tool were applied to appraise and assess the certainty of the findings of the included studies. A meta-analysis of the primary and secondary outcomes used random effects models., Results: In total, nine studies involving 1175 participants who participated in web-based cardiac rehabilitation to usual care were identified. The mean critical appraisal tool score was 76 (standard deviation: 9.7) with all (100%) studies scoring >69%, and the certainty of evidence low. Web-based programmes were 43% more likely to be completed than usual care (risk ratio: 1.43; 95% confidence interval: 0.96, 2.13) There was no difference between groups for clinical outcomes., Discussion: Despite the relatively small number of studies, high heterogeneity and the limited outcome measures, the results appeared to favour web-based cardiac rehabilitation with regard to programme completion.

Objective: Women remain a small minority of cardiothoracic surgeons, and within adult cardiac surgery, the gender gap widens. This study examines the career pathway and trajectory of female adult cardiac surgeons., Methods: Female cardiothoracic surgeons were identified from the American Board of Thoracic Surgery diplomates over 58 years. Publicly available information was obtained to determine years in practice, practice type, academic and leadership title(s), and location of practice., Results: The average number of years in practice for female adult cardiac surgeons was 13.1. Those categorized as adult cardiac surgeons composed 25.4% (n = 90) of all female cardiothoracic diplomates and 134 (37.9%) were categorized as other subspecialty practice. Of the adult cardiac surgeons, 33.3% (n = 30) practiced privately and the remainder in academic practice. Academic titles were held by 47.8% (43 out of 90) and 30% (27 out of 90) held a position of leadership. Of those in academic practice, 25% (11 out of 42) are titled professor, whereas 43% (18 out of 42) are assistant professors. Most commonly, those in positions of leadership held the title "director," which reflects 37% (10 out of 27) of individuals. Practice locations were distributed throughout the United States, with the highest number in the northeast (26.7%)., Conclusions: Only a small portion of female cardiothoracic surgeons pursue a career in adult cardiac surgery compared to their male counterparts. From 1999 to 2009, 1300 individuals were board certified cardiothoracic surgeons, of whom only 103 (7.9%) were female. Of these, the majority of female cardiothoracic surgeons entered academic practice. Although the overall number of practicing female adult cardiac surgeons has increased with a growth rate of 10.7%, this number remains extremely low. A discrepancy remains between gender representation of academic titles and leadership positions. Although the field has increased female representation over the past few decades, work remains to ensure all potential talent is encouraged and supported., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Although the concept of immunothrombosis has established a link between inflammation and thrombosis, the role of inflammation in the pathogenesis of deep vein thrombosis remains to be fully elucidated. Further, although various constituents of venous thrombi have been identified, their localizations and cellular and molecular interactions are yet to be combined in a single, multiplexed analysis., Objectives: The objective of this study was to investigate the role of the von Willebrand factor (VWF) in inflammation-associated venous thrombosis. We also performed a proof-of-concept study of imaging mass cytometry to quantitatively and simultaneously analyze the localizations and interactions of 10 venous thrombus constituents., Methods: We combined the murine inferior vena cava stenosis model of deep vein thrombosis with the lipopolysaccharide model of endotoxemia. We also performed a proof-of-concept study of imaging mass cytometry to assess the feasibility of this approach in analyzing the structural composition of thrombi., Results: We found that lipopolysaccharide-treated mice had significantly higher incidences of venous thrombosis, an effect that was mitigated when VWF was inhibited using inhibitory αVWF antibodies. Our detailed structural analysis also showed that most thrombus components are localized in the white thrombus regardless of endotoxemia. Moreover, although endotoxemia modulated the relative representation and interactions of VWF with other thrombus constituents, the scaffolding network, comprised VWF, fibrin, and neutrophil extracellular traps, remained largely unaffected., Conclusions: We observe a key role for VWF in the pathogenesis of inflammation-associated venous thrombosis while providing a more comprehensive insight into the molecular interactions that constitute the architecture of venous thrombi., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this review is to measure the effectiveness of cardiac rehabilitation programs versus standard care on medication adherence in patients with cardiovascular disease., Introduction: Poor adherence to long-term medications increases the risk of morbidity and mortality, and decreases quality of life in patients with cardiovascular diseases. Several strategies have been trialed to improve medication adherence, one of which is cardiac rehabilitation programs. Although evidence has indicated that such programs increase medication adherence, the extent of their effectiveness and translation into clinical practice is not well documented. Our systematic review will collect and analyze the available evidence for clinical practice implementation., Inclusion Criteria: The search will aim to locate randomized controlled trials. Where randomized controlled trials are not available, quasi-experimental studies, case-control studies, observational studies, and other study designs will be included. Studies that measure effectiveness of cardiac rehabilitation programs compared with standard care on medication adherence in cardiovascular disease patients will be included., Methods: Databases, including MEDLINE (Ovid), Emcare (Ovid), Embase (Ovid), Cochrane CENTRAL, Scopus, CINAHL (EBSCO), and unpublished sources will be searched. Articles in English and non-English-language articles with an English abstract, published from database inception to the present, will be included. Articles will be screened and reviewed by 2 independent reviewers for inclusion. Critical appraisal tools will be applied to the included studies. Data will be extracted using the appropriate extraction tools and synthesized for the objectives of the study., Systematic Review Registration Number: PROSPERO CRD42021284705., Competing Interests: SH is a senior associate editor of JBI Evidence Synthesis but had no part in the editorial decision-making for this paper. The other authors declare no conflict of interest., (Copyright © 2022 JBI.)

Objective: The objective of the review is to investigate the effect of activity-monitoring devices and mobile applications on physical activity and health outcomes of patients with cardiovascular disease who are participating in cardiac rehabilitation programs., Introduction: Supporting patients with cardiovascular conditions to achieve and maintain healthy physical activity levels is the cornerstone of cardiac rehabilitation programs. The effectiveness of activity-monitoring devices and mobile applications (such as physical activity interventions) utilizing consumer-grade monitoring devices and applications to support patients to improve exercise levels during and after program completion has been investigated. Several systematic reviews evaluating the effectiveness of monitoring devices and applications have indicated varying clinical impact, depending on patient characteristics, stage of rehabilitation, and type of intervention., Inclusion Criteria: This review will consider systematic reviews and/or meta-analyses of randomized controlled trials of patients who participated in cardiac rehabilitation programs that included a physical activity intervention that incorporated activity monitoring using electronic devices and/or mobile applications and reported activity and patient health outcomes., Methods: MEDLINE, Embase, Sport Discus, the Cochrane Database of Systematic Reviews, Scopus, CINAHL, the International Network of Agencies for Health Technology Assessment database, Epistemonikos, and Web of Science will be searched from inception to the present. PROSPERO will be searched for unpublished reviews. Articles will be screened by two independent reviewers for inclusion, and methodological quality will be assessed using a JBI critical appraisal tool. Data will be extracted from systematic reviews and a data synthesis of findings will be presented. The certainty will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach., Systematic Review Registration Number: PROSPERO CRD42022298877., Competing Interests: SH is a senior associate editor of JBI Evidence Synthesis and was not involved in the editorial processing of this paper. The other authors declare no conflict of interest., (Copyright © 2022 JBI.)

Objective: The objective of the review is to determine the effectiveness of telehealth versus in-person care on health care utilization, health-related quality of life, and well-being in homebound populations., Introduction: Globally, an increasing number of people are becoming homebound. These individuals experience high levels of social isolation and deterioration of their well-being. Reports from homebound people and recent publications suggest that this cohort may benefit from accessing telehealth solutions from their homes to treat and prevent serious issues affecting their health and well-being. This review will synthesize the evidence on the effectiveness of telehealth compared to standard care (in-person care) on health care utilization, health-related quality of life, and well-being in homebound populations., Inclusion Criteria: Studies including people living in community settings, whose daily life is physically limited to the boundary of their homes because of their ongoing health, energy, and psychosocial or socio-functional impairments will be considered for inclusion., Methods: This review will consider relevant, peer-reviewed primary experimental and quasi-experimental studies, with no limit on language or date. Databases to be searched include MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, LILACS, JBI Evidence Synthesis (hand-searched for further studies), and Web of Science. Two independent reviewers will be involved in study selection and data extraction. Eligible studies will be critically appraised for methodological quality using the relevant JBI critical appraisal checklists, and statistical meta-analysis will be done (where possible). Findings will be presented in narrative form., Systematic Review Registration Number: PROSPERO CRD42021289578., Competing Interests: The other authors declare no conflict of interest., (Copyright © 2022 JBI.)

Due to occupational stress and exposure to potentially traumatic events, firefighters are at an increased risk for the development of many behavioral health conditions. While volunteer and career firefighters represent two distinct subgroups, little research has examined differences in the availability of, and barriers to, behavioral health care between these populations. This study examined perceived availability and barriers to behavioral health care services among 2,156 career and 227 volunteer firefighters. Volunteer firefighters were less likely to report availability of drug and alcohol or family and couple services, but more likely to report availability of a trained peer support system and follow-up care compared to career firefighters. Volunteer firefighters were over five times more likely to consider cost a barrier to accessing behavioral health services compared to career firefighters; however, they were less likely to report lack of support from leadership, fear of breach of confidentiality, and clinicians who are unaware of work culture as barriers. Volunteer and career firefighters were equally likely to report stigma as a barrier. These findings have important implications for understanding how to strengthen departmental resources and to design targeted interventions to increase access to behavioral health services. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

We report the genome sequences of two Erysipelothrix isolates from fatal cases of sepsis in bottlenose dolphins (Tursiops truncatus). The genomes were found to be most closely related to Erysipelothrix rhusiopathiae and Erysipelothrix piscisicarius. This information expands our knowledge of the genetic characteristics of this pathogen, which can affect free-ranging marine mammals.

von Willebrand factor (VWF) is an extremely cysteine-rich multimeric protein that is essential for maintaining normal hemostasis. The cysteine residues of VWF monomers form intra- and intermolecular disulfide bonds that regulate its structural conformation, multimer distribution, and ultimately its hemostatic activity. In this study, we investigated and characterized the molecular and pathogenic mechanisms through which a novel cysteine variant p.(Cys1084Tyr) causes an unusual, mixed phenotype form of von Willebrand disease (VWD). Phenotypic data including bleeding scores, laboratory values, VWF multimer distribution, and desmopressin response kinetics were investigated in 5 members (2 parents and 3 daughters) of a consanguineous family. VWF synthesis and secretion were also assessed in a heterologous expression system and in a transient transgenic mouse model. Heterozygosity for p.(Cys1084Tyr) was associated with variable expressivity of qualitative VWF defects. Heterozygous individuals had reduced VWF:GPIbM (<0.40 IU/mL) and VWF:CB (<0.35 IU/mL), as well as relative reductions in high-molecular-weight multimers, consistent with type 2A VWD. In addition to these qualitative defects, homozygous individuals also displayed reduced factor VIII (FVIII):C/VWF:Ag, leading to very low FVIII levels (0.03-0.1 IU/mL) and reduced VWF:Ag (<0.40 IU/mL) and VWF:GPIbM (<0.30 IU/mL). Accelerated VWF clearance and impaired VWF secretion contributed to the fully expressed homozygous phenotype with impaired secretion arising because of disordered disulfide connectivity., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Person-centred care advocates for co-design of all healthcare services and research interventions by the end-user. Co-design is widely used, but the methodological approaches, evaluation, and reporting of outcomes are often poorly defined. One methodology for co-design is the User Experience Design which provides guidance and theoretical frameworks to inform development and reporting measures. This article outlines the application of this approach in the development of a web-based cardiac rehabilitation program and reports on the very positive experiences of the patients involved in the process and how their input strategically influenced outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

Introduction: Despite extensive evidence of its benefits and recommendation by guidelines, cardiac rehabilitation (CR) remains highly underused with only 20%-50% of eligible patients participating. We aim to implement and evaluate the Country Heart Attack Prevention (CHAP) model of care to improve CR attendance and completion for rural and remote participants., Methods and Analysis: CHAP will apply the model for large-scale knowledge translation to develop and implement a model of care to CR in rural Australia. Partnering with patients, clinicians and health service managers, we will codevelop new approaches and refine/expand existing ones to address known barriers to CR attendance. CHAP will codesign a web-based CR programme with patients expanding their choices to CR attendance. To increase referral rates, CHAP will promote endorsement of CR among clinicians and develop an electronic system that automatises referrals of in-hospital eligible patients to CR. A business model that includes reimbursement of CR delivered in primary care by Medicare will enable sustainable access to CR. To promote CR quality improvement, professional development interventions and an accreditation programme of CR services and programmes will be developed. To evaluate 12-month CR attendance/completion (primary outcome), clinical and cost-effectiveness (secondary outcomes) between patients exposed (n=1223) and not exposed (n=3669) to CHAP, we will apply a multidesign approach that encompasses a prospective cohort study, a pre-post study and a comprehensive economic evaluation., Ethics and Dissemination: This study was approved by the Southern Adelaide Clinical Human Research Ethics Committee (HREC/20/SAC/78) and by the Department for Health and Wellbeing Human Research Ethics Committee (2021/HRE00270), which approved a waiver of informed consent. Findings and dissemination to patients and clinicians will be through a public website, online educational sessions and scientific publications. Deidentified data will be available from the corresponding author on reasonable request., Trial Registration Number: ACTRN12621000222842., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We aim to report the co-design of the implementation strategy of a telehealth-enabled cardiac rehabilitation model of care in rural and remote areas of Australia. The goal of this model of care is to increase cardiac rehabilitation attendance and completion by country patients with cardiovascular diseases.We hypothesise that a model of care co-designed with stakeholders will address patients' needs and preferences and increase participation. We applied the Model for Large Scale Knowledge Translation and engaged with patients, clinicians and health service managers across six local health networks in rural South Australia. They informed the design of a web-based cardiac rehabilitation programme and the delivery of the expanded telehealth service.The stakeholders defined face-to-face, telephone, web-based or combinations as choices of mode of delivery to patients referred to cardiac rehabilitation. A case-managed programme supported by a web portal with an interface for patients and clinicians was considered more appropriate to the local context than a self-managed programme. A business model was developed to enable the sustainability of cardiac rehabilitation clinical assessments through primary care. The impact of the model of care on cardiac rehabilitation attendance/completion, clinical outcomes, patient-reported outcomes and patient-reported experiences and cost-effectiveness will be tested in a 12-month follow-up study.

Background: Stabilin-2 is an endocytic scavenger receptor that mediates the clearance of glycosaminoglycans, phosphatidylserine-expressing cells, and the von Willebrand factor-factor VIII (FVIII) complex. In a genome-wide screening study, pathogenic loss-of-function variants in the human STAB2 gene associated with an increased incidence of unprovoked venous thromboembolism (VTE). However, the specific mechanism(s) by which stabilin-2 deficiency influences the pathogenesis of VTE is unknown., Objectives: The aim of this study was to assess the influence of stabilin-2 on deep vein thrombosis (DVT) and to characterize the underlying prothrombotic phenotype of stabilin-2 deficiency in a mouse model., Methods: DVT was induced using the inferior vena cava (IVC) stenosis model in two independent cohorts (littermates and non-littermates) of wild-type (Stab2 +/+ ) and stabilin-2 (Stab2 -/- )-deficient mice. Thrombus structure and contents were quantified by immunohistochemistry. Plasma procoagulant activity was assessed and complete blood counts were performed., Results: Incidence of thrombus formation was not altered between Stab2 +/+ and Stab2 -/- mice. When thrombi were formed, Stab2 -/- mice developed significantly larger thrombi than Stab2 +/+ controls. Thrombi from Stab2 -/- mice contained significantly more leukocytes and citrullinated histone H3 than Stab2 +/+ thrombi. Stab2 -/- mice had increased FVIII activity. Circulating levels of monocytes and granulocytes were significantly elevated in Stab2 -/- mice, and Stab2 -/- mice had elevated plasma cell-free DNA 24 hours post-IVC stenosis compared to their Stab2 +/+ counterparts., Conclusions: These data suggest that stabilin-2 deficiency associates with a prothrombotic phenotype involving elevated levels of neutrophil extracellular trap-releasing leukocytes coupled with endogenous procoagulant activity, resulting in larger and qualitatively distinct venous thrombi., (© 2021 International Society on Thrombosis and Haemostasis.)

Introduction: Minimally invasive partial nephrectomy is standard of care treatment for small renal masses., Objective: We evaluated the relationship between subcutaneous and visceral obesity with high-grade postoperative 30-day complications in patients undergoing minimally invasive partial nephrectomy., Methods: We retrospectively identified 98 patients at our institution from 2014 to 2017 who underwent laparoscopic or robotic-assisted partial nephrectomy due to suspected renal cell carcinoma. Patients were stratified based on presence or absence of high-grade (Clavien ≥ IIIa) 30-day postoperative complications. Means were compared with the independent t test and proportions with chi-square analysis. Multivariate logistic regression was performed to determine independent predictors of high-grade 30-day complications., Results: Mean nephrometry score was 6.7 with 21 (21.4%) patients having hilar tumors. Mean estimation of blood loss was 207 mL, mean operating time was 223 min, and mean warm ischemia time was 23 min. The majority of patients had clear renal cell carcinoma (n = 83, 84.7%) and pT1a disease (n = 76, 77.6%) with negative margins (n = 89, 90.8%) on pathology. There were 5 (5.1%) patients who experienced a high-grade postoperative 30-day complication. Mean visceral fat index was an independent predictor of high-grade 30-day complications (odds ratio: 1.02; 95% confidence interval: 1.002-1.03; p  = 0.027)., Conclusions: Visceral obesity should be considered as a prognostic indicator of outcomes in patients undergoing surgical treatment for a small renal mass., Competing Interests: The authors declare that they have no financial conflict of interest with regard to the content of this report., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc.)

Ancestral sequence reconstruction provides a unique platform for investigating the molecular evolution of single gene products and recently has shown success in engineering advanced biological therapeutics. To date, the coevolution of proteins within complexes and protein-protein interactions is mostly investigated in silico via proteomics and/or within single-celled systems. Herein, ancestral sequence reconstruction is used to investigate the molecular evolution of 2 proteins linked not only by stabilizing association in circulation but also by their independent roles within the primary and secondary hemostatic systems of mammals. Using sequence analysis and biochemical characterization of recombinant ancestral von Willebrand factor (VWF) and coagulation factor VIII (FVIII), we investigated the evolution of the essential macromolecular FVIII/VWF complex. Our data support the hypothesis that these coagulation proteins coevolved throughout mammalian diversification, maintaining strong binding affinities while modulating independent and distinct hemostatic activities in diverse lineages., (© 2021 by The American Society of Hematology.)

Thrombin generation is pivotal to both physiological blood clot formation and pathological development of disseminated intravascular coagulation (DIC). In critical illness, extensive cell damage can release histones into the circulation, which can increase thrombin generation and cause DIC, but the molecular mechanism is not clear. Typically, thrombin is generated by the prothrombinase complex, comprising activated factor X (FXa), activated cofactor V (FVa), and phospholipids to cleave prothrombin in the presence of calcium. In this study, we found that in the presence of extracellular histones, an alternative prothrombinase could form without FVa and phospholipids. Histones directly bind to prothrombin fragment 1 (F1) and fragment 2 (F2) specifically to facilitate FXa cleavage of prothrombin to release active thrombin, unlike FVa, which requires phospholipid surfaces to anchor the classical prothrombinase complex. In vivo, histone infusion into mice induced DIC, which was significantly abrogated when prothrombin F1 + F2 were infused prior to histones, to act as decoy. In a cohort of intensive care unit patients with sepsis (n = 144), circulating histone levels were significantly elevated in patients with DIC. These data suggest that histone-induced alternative prothrombinase without phospholipid anchorage may disseminate intravascular coagulation and reveal a new molecular mechanism of thrombin generation and DIC development. In addition, histones significantly reduced the requirement for FXa in the coagulation cascade to enable clot formation in factor VIII (FVIII)- and FIX-deficient plasma, as well as in FVIII-deficient mice. In summary, this study highlights a novel mechanism in coagulation with therapeutic potential in both targeting systemic coagulation activation and correcting coagulation factor deficiency., (© 2021 by The American Society of Hematology.)

Objective: Obesity is characterized by chronic low-grade inflammation and consequentially a hypercoagulable state, associating with an increased incidence of venous thromboembolism. Increased VWF (von Willebrand factor) plasma concentration and procoagulant function are independent risk factors for venous thromboembolism and are elevated in obese patients. Here, we explore the pathobiological role of VWF in obesity-associated venous thrombosis using murine models. Approach and Results: We first showed that diet-induced obese mice have increased VWF plasma levels and FVIII (factor VIII) activity compared with littermate controls. Elevated VWF levels appeared to be because of both increased synthesis and impaired clearance. Diet-induced obesity-associated venous thrombosis was assessed using the inferior vena cava-stenosis model of deep vein thrombosis. Diet-induced obese mice developed larger venous thrombi that were rich in VWF, erythrocytes, and leukocytes. Administering a polyclonal anti-VWF antibody or an anti-VWF A1 domain nanobody was protective against obesity-mediated thrombogenicity. Delayed administration (3 hours post-inferior vena cava stenosis) similarly reduced thrombus weight in diet-induced obese mice., Conclusions: This study demonstrates the critical role of VWF in the complex, thrombo-inflammatory state of obesity. It adds to the growing rationale for targeting VWF-specific interactions in thrombotic disease.

Aim: To evaluate the effectiveness of education using avatars for improving patients' heart failure knowledge and self-care., Background: A lack of knowledge and self-care contributes to poor outcomes and rehospitalization for people with heart failure., Design: A multi-centred, non-blinded pragmatic randomized controlled trial., Methods: Heart failure patients were randomly assigned to intervention (avatar education application) or usual care groups. Participants were followed up at baseline, 30 and 90 days. ANCOVA was used to compare the scores of heart failure knowledge and self-care, between the two groups. Fisher's exact test was used to compare the two groups' heart failure-cause readmission. Bivariate exact binary logistic regression was used to identify the predictors associated with baseline levels of knowledge., Results: A total of 36 participants were recruited (between October 2018 - March 2019). The mean age of participants was 67.5 (SD 11.3) years. At enrolment, approximately half (47.2%) have been living with Heart Failure for over 5 years. Two groups were comparable at baseline in their demographic and clinical characteristics. At 90 days, the intervention group participants had a higher increase in knowledge score on the Dutch Heart Failure Knowledge Scales compared with the control group (22.2% versus 3.7% P = .002, partial η 2  = 0.262, 95% CI -2.755 to -0.686). There was no between-group difference observed at 30- or 90-day follow-up, on self-care behaviour (Self-care of heart failure index) or healthcare use. Overall satisfaction with the avatar app was 91.3%., Conclusion: The addition of a co-designed avatar app to usual care improved knowledge in our group of Heart Failure participants at 30 days and continued to increase up to 90 days. The results suggest that our avatar app was perceived as an enjoyable and engaging means of delivering critical knowledge and self-care information., Impact: Heart failure is associated with poor clinical outcomes (i.e., readmission rates and mortality rate) and substantial economic burden. The effectiveness of Heart Failure patient education using avatar have not been investigated previously. In this study, the avatar app improved knowledge and self-care behaviours. This innovation could be used at the bedside, at home by nurses, patients and families., Trial Registration: Australian New Zealand Trial Registry ACTRN12617001403325., (© 2020 John Wiley & Sons Ltd.)

The development of neutralizing FVIII antibodies is the most serious complication of hemophilia A treatment. The currently known patient- and treatment-related risk factors for inhibitor development do not accurately predict this adverse event in all patients. The composition of the gut microbiota has been shown to influence immune-mediated diseases at distant anatomical sites (eg, lungs, brain, and joints). We demonstrate that a disrupted gut microbiota can be created in a mouse model of hemophilia A using a broad-spectrum antibiotic. Under controlled conditions, this sustained dysbiosis was associated with an increase in splenic B cells and the development of higher titer, FVIII-specific immunoglobulin G antibodies after FVIII challenge. Splenic and mesenteric lymph node cytokines, T cells, and dendritic cells were unaffected before administration of FVIII. However, the immune transcriptome of both aforementioned secondary lymphoid organs was significantly modified. Short-chain fatty acids (SCFAs), which are immunomodulatory microbial metabolites, were depleted in cecal contents of the dysbiotic mice. Furthermore, supplementation of the drinking water with butyrate, the most immunologically active SCFA, successfully achieved attenuation of the FVIII immune response. Collectively, data from this exploratory study suggest that the composition of the gut microbiota alters the FVIII immune response via the action of specific microbial metabolites on the immune cell transcriptome and that oral supplementation with butyrate effectively reduces the FVIII immune response., (© 2020 by The American Society of Hematology.)

Background: Scavenger receptors play a significant role in clearing aged proteins from the plasma, including the large glycoprotein coagulation factors von Willebrand factor (VWF) and factor VIII (FVIII). A large genome-wide association study meta-analysis has identified genetic variants in the gene SCARA5, which encodes the class A scavenger receptor SCARA5, as being associated with plasma levels of VWF and FVIII., Objectives: The ability of SCARA5 to regulate the clearance of VWF-FVIII was characterized., Methods: VWF-FVIII interactions with SCARA5 were evaluated by solid phase binding assays and in vitro cell based assays. The influence of SCARA5 deficiency on VWF:Ag and half-life was assessed in a murine model. The expression pattern of SCARA5 and its colocalization with VWF was evaluated in human tissues., Results: VWF and the VWF-FVIII complex bound to human recombinant SCARA5 in a dose- and calcium-dependent manner. SCARA5 expressing HEK 293T cells bound and internalized VWF and the VWF-FVIII complex into early endosomes. In vivo, SCARA5 deficiency had a modest influence on the half-life of human VWF. mRNA analysis and immunohistochemistry determined that human SCARA5 is expressed in kidney podocytes and the red pulp, white pulp, and marginal zone of the spleen. VWF was found to colocalize with SCARA5 expressed by littoral cells lining the red pulp of the human spleen., Conclusions: SCARA5 is an adhesive and endocytic receptor for VWF. In human tissues, SCARA5 is expressed by kidney podocytes and splenic littoral endothelial cells. SCARA5 may have a modest influence on VWF clearance in humans., (© 2019 International Society on Thrombosis and Haemostasis.)

Essentials CLEC4M is an endocytic receptor for factor FVIII. CLEC4M interacts with FVIII in a VWF-dependent and independent manner. CLEC4M binds to mannose-containing glycans on FVIII. CLEC4M internalization of FVIII involves clathrin coated pits. SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways. Clearance of VWF-free FVIII is rapid and underlies the pathological basis of some quantitative FVIII deficiencies. The receptor pathways that regulate the clearance of VWF-bound and VWF-free FVIII are incompletely uncharacterized. The human liver-expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown. Objective The interaction between FVIII and CLEC4M was characterized in the presence or absence of VWF. Methods FVIII interactions with CLEC4M were evaluated by in vitro cell-based and solid phase binding assays. Interactions between FVIII and CLEC4M or liver sinusoidal endothelial cells were evaluated in vivo by immunohistochemistry. Results CLEC4M-expressing HEK 293 cells bound and internalized recombinant and plasma-derived FVIII through VWF-dependent and independent mechanisms. CLEC4M binding to recombinant FVIII was dependent on mannose-exposed N-linked glycans. CLEC4M mediated FVIII internalization via a clathrin-coated pit-dependent mechanism, resulting in transport of FVIII from early and late endosomes for catabolism by lysosomes. In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF. Conclusions These findings suggest that CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF., (© 2019 International Society on Thrombosis and Haemostasis.)

Background: The multimeric glycoprotein von Willebrand factor (VWF) mediates platelet adhesion and aggregation at the site of vessel injury. The adhesive activity of VWF is influenced by its multimer length which is regulated by the metalloprotease ADAMTS13. The ability of ADAMTS13 to regulate platelet thrombus growth in a shear-dependent manner has been described, however, the mechanistic basis of this action has not been well characterized., Methods: We developed an mCherry-tagged murine ADAMTS13 protein and utilized an ex vivo flow chamber system to visualize the localization of ADAMTS13 within the platelet thrombus under different conditions of shear. Using this system, we also assessed the influence of platelet-mediated tensile force on ADAMTS13 localization within the thrombus using gain-of-function GPIb binding and loss-of-function GPIIbIIIa binding mutants in VWF/ADAMTS13 DKO mice., Results: ADAMTS13 was visualized on the growing platelet thrombus under very high shear using ADAMTS13-mcherry. ADAMTS13-mCherry localized particularly at the top portion of the thrombus and reduced thrombus size as it grew to occlusion. At the pathological high shear of 7500 s -1 , platelet-mediated tensile force, involving GPIb but not GPIIbIIIa receptors, influenced localization of ADAMTS13 to the thrombus under conditions of shear., Conclusions: Tensile force applied on VWF produced by shear stress and platelet GPIb binding has a crucial role in ADAMTS13 activity at the site of thrombus formation. These results suggest that ADAMTS13 activity at the site of platelet thrombus formation is regulated by a shear stress and platelet-dependent feedback mechanism to prevent vessel occlusion and pathological thrombosis.

Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells. Glycosylation differences have been hypothesized to influence the immunogenicity of these synthetic concentrates. In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared to Chinese hamster ovary cell-derived factor VIII. Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor. Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites. Factor VIII desialylation did not influence binding to murine splenocytes or dendritic cells, nor surface co-stimulatory molecule expression. We did, however, observe increased levels of immunoglobulin M specific to baby hamster kidney-derived factor VIII in naïve hemophilia A mice. De-N-glycosylation enhanced immunoglobulin M binding, suggesting that N-glycan occupancy masks epitopes. Elevated levels of immunoglobulin M and immunoglobulin G specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased immunoglobulin G binding. Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of immunoglobulin M- and immunoglobulin G-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A., (Copyright© 2018 Ferrata Storti Foundation.)

Quantitative abnormalities of the von Willebrand factor-factor VIII (VWF-FVIII) complex associate with inherited bleeding or thrombotic disorders. Receptor-mediated interactions between plasma VWF-FVIII and phagocytic or immune cells can influence their hemostatic and immunogenic activities. Genetic association studies have demonstrated that variants in the STAB2 gene, which encodes the scavenger receptor stabilin-2, associate with plasma levels of VWF-FVIII. However, the mechanistic basis and pathophysiological consequences of this association are unknown. We have demonstrated that stabilin-2-expressing cells bind and internalize human VWF and FVIII in a VWF-dependent manner, and stabilin-2-deficient mice displayed prolonged human VWF-FVIII half-life compared with controls. The stabilin-2 variant p.E2377K significantly decreased stabilin-2 expression and impaired VWF endocytosis in a heterologous expression system, and common STAB2 variants associated with plasma VWF levels in type 1 von Willebrand disease patients. STAB2-deficient mice displayed a decreased immunogenic response to human VWF-FVIII complex, while coinfusion of human VWF-FVIII with the stabilin-2 ligand hyaluronic acid attenuated the immune response to exogenous FVIII. Collectively, these data suggest that stabilin-2 functions as both a clearance and an immunoregulatory receptor for VWF-FVIII, making stabilin-2 a novel molecular target for modification of the half-life of VWF-FVIII and the immune response to VWF-FVIII concentrates.

The development of inhibitory antibodies to factor VIII is the most serious complication of replacement therapy in hemophilia A. Activation of the innate immune system during exposure to this protein contributes to inhibitor development. However, avoidance of factor VIII exposure during innate immune system activation by external stimuli (e.g., vaccines) has not been consistently shown to prevent inhibitors. We hypothesized that dexamethasone, a drug with potent anti-inflammatory effects, could prevent inhibitors by promoting immunologic tolerance to factor VIII in hemophilia A mice. Transient dexamethasone treatment during ainitial factor VIII exposure reduced the incidence of anti-factor VIII immunoglobulin G in both a conventional hemophilia A mouse model (E16KO, 77% vs 100%, P =0.048) and a hemophilia A mouse model with a humanized major histocompatibility complex type II transgene (E17KO/hMHC, 6% vs 33%, P =0.0048). More importantly, among E17KO/hMHC mice that did not develop anti-factor VIII immunoglobulin G after initial exposure, dexamethasone-treated mice were less likely to develop a response after re-exposure six (7% vs 52%, P =0.005) and 16 weeks later (7% vs 50%, P =0.097). Similar results were obtained even when factor VIII re-exposure occurred in the context of lipopolysaccharide (30% vs 100%, P =0.069). The ability of these mice to develop immunoglobulin G to human von Willebrand factor, a structurally unrelated antigen, remained unaffected by treatment. Transient dexamethasone administration therefore promotes antigen-specific immunologic tolerance to factor VIII. This effect is associated with an increase in the percentage of thymic regulatory T cells (12.06% vs 4.73%, P <0.001) and changes in the thymic messenger ribonucleic acid transcription profile., (Copyright© 2018 Ferrata Storti Foundation.)

Background: Most low-risk pregnant women receive the standard model of prenatal care with frequent office visits. Research suggests that a reduced schedule of visits among low-risk women could be implemented without increasing adverse maternal or fetal outcomes, but patient satisfaction with these models varies. We aim to determine the effectiveness and feasibility of a new prenatal care model (OB Nest) that enhances a reduced visit model by adding virtual connections that improve continuity of care and patient-directed access to care., Methods and Design: This mixed-methods study uses a hybrid effectiveness-implementation design in a single center randomized controlled trial (RCT). Embedding process evaluation in an experimental design like an RCT allows researchers to answer both "Did it work?" and "How or why did it work (or not work)?" when studying complex interventions, as well as providing knowledge for translation into practice after the study. The RE-AIM framework was used to ensure attention to evaluating program components in terms of sustainable adoption and implementation. Low-risk patients recruited from the Obstetrics Division at Mayo Clinic (Rochester, MN) will be randomized to OB Nest or usual care. OB Nest patients will be assigned to a dedicated nursing team, scheduled for 8 pre-planned office visits with a physician or midwife and 6 telephone or online nurse visits (compared to 12 pre-planned physician or midwife office visits in the usual care group), and provided fetal heart rate and blood pressure home monitoring equipment and information on joining an online care community. Quantitative methods will include patient surveys and medical record abstraction. The primary quantitative outcome is patient-reported satisfaction. Other outcomes include fidelity to items on the American Congress of Obstetricians and Gynecologists standards of care list, health care utilization (e.g. numbers of antenatal office visits), and maternal and fetal outcomes (e.g. gestational age at delivery), as well as validated patient-reported measures of pregnancy-related stress and perceived quality of care. Quantitative analysis will be performed according to the intention to treat principle. Qualitative methods will include interviews and focus groups with providers, staff, and patients, and will explore satisfaction, intervention adoption, and implementation feasibility. We will use methods of qualitative thematic analysis at three stages. Mixed methods analysis will involve the use of qualitative data to lend insight to quantitative findings., Discussion: This study will make important contributions to the literature on reduced visit models by evaluating a novel prenatal care model with components to increase patient connectedness (even with fewer pre-scheduled office visits), as demonstrated on a range of patient-important outcomes. The use of a hybrid effectiveness-implementation approach, as well as attention to patient and provider perspectives on program components and implementation, may uncover important information that can inform long-term feasibility and potentially speed future translation., Trial Registration: Trial registration identifier: NCT02082275 Submitted: March 6, 2014.

Purpose: Traumatic brain injury (TBI) is a serious public health problem. The impact of TBI on the individual is multifaceted and includes neurocognitive, behavioral, and psychiatric disturbances as well as greater predisposition for dementia. A common but significant problem reported by patients after TBI is sleep disturbance. The purpose of this manuscript is twofold: (1) to describe our experience with implementation of the newly developed sleep hygiene guidelines; and (2) to report our preliminary results of implementation of the sleep hygiene guidelines on TBI patient outcomes., Methods: A mixed methods approach was used to assess implementation of sleep hygiene guidelines and to gather preliminary data on outcomes., Results: Although not statistically significant, the average self-reported sleep duration of these TBI patients was slightly higher in 2010 than 2009, with a FIM score that was similar for both time points. In 2009, the mean change in functional independence measure (FIM) score (n = 34) was 1.44. In 2010, the mean change in FIM score (n = 33) was 1.42. In 2009, most patients (n = 13) admitted to the hospital continued to take medications and were discharged with a sleep aid. In 2010, most patients reported a change in their sleep medication prescriptions (on medications at admission and none at discharge) or had continued to take their prescribed sleep medications from admission to discharge (n = 12)., Conclusion: Sleep disorders have a major impact on health outcomes in patients with TBI. To optimize rehabilitation and ultimately improve functional outcomes of patients with TBI, implementation of evidence-based clinical guidelines for sleep is imperative. We report our initial experience with implementation of sleep guidelines., (© 2013 Association of Rehabilitation Nurses.)

Breast cancer survival rates are lower in African Americans (AAs) than in Caucasians, owing in part to a higher prevalence of obesity in the former, which increases the risk of recurrence and mortality. The Women's Intervention Nutrition Study (WINS) found that Caucasian women who followed a low-fat eating plan experienced a lower rate of cancer recurrence than women who maintained their usual diets. The purpose of this study was to test the feasibility of a WINS plan tailored to the cultural needs of AA breast cancer survivors. This feasibility pilot study was conducted at a university National Cancer Institute-designated comprehensive cancer center outpatient clinic with AA breast cancer survivors. The culturally specific WINS (WINS-c) plan included eight individual counseling sessions, five educational group meetings, and follow-up telephone calls over a 1-year period. Outcome measures included dietary fat, triglyceride, insulin and glucose levels, and fruit and vegetable intake. Participants (n = 8) had a mean age of 61.1 years (standard error of the mean (SEM) 3.1 years) and a mean BMI of 32 kg/m(2) (SEM 4.25 kg/m)(2). Baseline daily fat consumption decreased from 64.6 g (range 36.8-119.6g) to 44.0 g (21.6-73.4g) at 52 weeks (p = 0.07). Mean daily consumption of fruits and vegetables increased by 36% and 15%, respectively. Mean triglyceride levels decreased at 12 months (p < 0.05). Sustained hyperinsulinemia was noted in most participants, including those without diabetes. Mean calcium and vitamin D consumption decreased over the 1-year study period. In AA breast cancer survivors, the WINS-c program resulted in a trend toward reduced fat consumption and may represent a sustainable approach in this population for improvement of diet quality after breast cancer.

Objective: To assess the agreement of transcutaneous carbon dioxide (TcPCO(2)) and end tidal carbon dioxide (PetCO(2)) with arterial carbon dioxide (PaCO(2)) values in infants < 28 weeks gestational age., Study Design: In all, 27 ventilated preterm infants were prospectively studied. PaCO(2) was compared with TcPCO(2) and PetCO(2) measured at three similar time points within first 24 hours after birth., Results: The Intraclass correlation coefficients for TcPCO(2) and PaCO(2) were 0.45, 0.73 and 0.53; and for PetCO(2) and PaCO(2) were 0.61, 0.56 and 0.57 at 4, 12 and 24 hours after birth, respectively., Conclusion: A moderate agreement with a wide variation in individual values was observed between noninvasive methods and PaCO(2) in preterm infants in the first 24 hours. Noninvasive monitoring methods cannot be substituted for PaCO(2) analyses in preterm infants during this critical period.

Many alcohol and drug treatment programs now offer smoking cessation (SC) services to their clients. Little is known about the prevalence of such services in Canadian addiction programs. A telephone survey was conducted of all Canadian adult substance abuse programs with outpatient, day program, and residential treatment to determine: (a) whether the program offered help in quitting smoking; (b) the type of SC services; (c) the overall priority placed on quitting smoking; and (d) for residential programs, what type of smoking ban (indoors, outdoors, or both), if any, is imposed. Over half (54%) of the 223 programs that responded to the survey reported providing help in quitting smoking. Twenty-three programs had formal SC services, most often in the form of group treatment. The majority of programs surveyed stated their program placed 'very little' emphasis on smoking. Smoking was relatively unrestricted in residential programs. The implications of these findings for substance abuse treatment are discussed., (Copyright 2003 Elsevier Science Inc.)

Background: Thoracic surgeons typically perform fiberoptic bronchoscopy (FOB) before thoracotomy, usually on the day of the operation after intubation with a single-lumen endotracheal tube (ETT) and before insertion of a double-lumen ETT. This routine requires two laryngoscopies and two intubations. The laryngeal mask airway (LMA) is an airway device developed in England and approved by the Food and Drug Administration in 1991 for clinical use in the United States. It requires neither mask ventilation nor laryngoscopy and allows FOB visualization of the epiglottis, larynx, and entire trachea. We assessed the LMA as an alternative to a single-lumen ETT for FOB before thoracotomy., Methods: Through prospective assessment, 50 patients underwent FOB after insertion of an LMA before thoracotomy. Pulse rate, blood pressure, ease of insertion of the LMA, quality of FOB, and complications of LMA insertion were assessed., Results: During LMA insertion, blood pressure and pulse rate increased less than 5% from baseline in all patients. The LMA was inserted successfully in all patients within 10 seconds. No complications occurred as a result of LMA insertion., Conclusions: Insertion of the LMA causes minimal hemodynamic response. From the time of induction of general anesthesia, insertion of the LMA is quick, simple, and safe and eliminates the need for endotracheal intubation with a single-lumen ETT before double-lumen tube insertion. The LMA, in contrast to the ETT, allows a complete survey of the larynx and trachea. The LMA is autoclavable, reusable, and cost effective. Therefore, in patients who require FOB immediately before thoracotomy, LMA use should be the standard for airway evaluation.

An algorithm based on the Kalman filter and used for tracking a target in a noisy environment has been applied to monitoring the position of moving boundaries as recorded by a video camera. The method, termed the Probabilistic Data Association Filter, is computationally efficient, allowing simultaneous monitoring at many positions along the boundary at video frame rates of 25 Hz. The present study uses the tracking procedure to investigate and correlate constrictions along lymphatic vessels. The procedure is well suited for real time tracking of visualised biological events including the simultaneous monitoring of constrictions in networks of blood vessels, the movement of cells or the trajectory of intracellular events monitored by intracellular fluorescent markers.

An extremely large Sertoli cell adenoma discovered incidentally in an elderly phenotypically femal patient with testicular feminization syndrome is reported. The patient is alive 3 years following removal of the tumor.