Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials.

BACKGROUND: More women than men have heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: The purpose of this study was to assess baseline characteristics and treatment effect of semaglutide by sex across the STEP-HFpEF (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity) program. METHODS: In a prespecified secondary analysis of pooled data from STEP-HFpEF and STEP-HFpEF DM (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes), patients with heart failure (HF), left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m2, and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to once-weekly semaglutide 2.4 mg or matched placebo for 52 weeks. Dual primary endpoints (KCCQ-CSS change and percentage change in body weight) and confirmatory secondary endpoints (6-minute walking distance [6MWD] change; hierarchical composite endpoint comprising all-cause death, HF events, changes in KCCQ-CSS, and 6MWD; and C-reactive protein) were compared between sexes. RESULTS: Of 1,145 patients, 570 (49.7%) were women. Women had higher body mass index, left ventricular ejection fraction, C-reactive protein, and worse HF symptoms, and were less likely to have atrial fibrillation or coronary artery disease vs men. Semaglutide improved KCCQ-CSS regardless of sex (mean difference in women +7.6 points [95% CI: 4.5-10.7 points]; men +7.5 points [95% CI: 4.3-10.6 points]; P interaction = 0.94) but reduced body weight more in women (mean difference in women -9.6% [95% CI: -10.9% to -8.4%]; men -7.2% [95% CI: -8.4% to -6.0%]; P interaction = 0.006). Semaglutide improved 6MWD (P interaction = 0.21) and the hierarchical composite endpoint (P interaction = 0.66) in both sexes. Fewer serious adverse events were reported with semaglutide vs placebo. CONCLUSIONS: In patients with obesity-related HFpEF, semaglutide 2.4 mg reduced body weight to a greater extent in women, and produced similar improvements in HF-related symptoms, physical limitations, and exercise function, regardless of sex. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511; and Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP HFpEF DM]; NCT04916470).

Pharmacodynamic effects of filgotinib treatment driving clinical improvement in patients with active psoriatic arthritis enrolled in the EQUATOR trial.

OBJECTIVES: The goal of this study was to identify protein and transcriptional biomarkers and pathways associated with baseline disease state, the effect of filgotinib (FIL) treatment on these biomarkers, and to investigate the mechanism of action of FIL on clinical improvement in patients with active psoriatic arthritis (PsA). METHODS: The phase II EQUATOR (NCT03101670) trial evaluated the efficacy of FIL, a Janus kinase 1-preferential inhibitor, in patients with PsA. Peripheral protein and gene expression levels in association with clinical state at baseline and post-treatment were assessed in 121 patients using linear mixed effects models for repeated measures analyses. Mediation analysis and structural equation modelling (SEM) were performed to investigate the mechanism of action of FIL at week 4 on downstream clinical improvement at week 16. RESULTS: Baseline analyses showed that markers of inflammation were significantly associated with multiple PsA clinical metrics, except for Psoriasis Area and Severity Index (PASI), which corresponded to Th17 markers. FIL treatment resulted in sustained transcriptional inhibition of immune genes and pathways, a sustained increase in B-cell fraction and mature B-cells in circulation, and a transient effect on other cell fractions. Mediation analysis revealed that changes in B cells, systemic inflammatory cytokines and neutrophils at week 4 were associated with changes in clinical metrics at week 16. SEM suggested that FIL improved PASI through reduction of IL-23 p19 and IL-12 p40 proteins. CONCLUSIONS: Our results revealed that FIL treatment rapidly downregulates inflammatory and immune pathways associated with PsA disease activity corresponding to clinical improvement in PsA. TRIAL REGISTRATION NUMBER: NCT03101670.

Using video consultations for clinical assessment and decision of treatment readiness before chemotherapy: A mixed-methods study among patients with gastrointestinal cancer and oncology nurses.

Objective: To investigate the feasibility of clinical assessment and decision of treatment readiness before chemotherapy using video consultations, as perceived by gastrointestinal cancer patients and oncology nurses. In addition, to estimate reductions in travel time for patients and environmental carbon dioxide (CO2) emissions. Methods: In a mixed-method study, patients with gastrointestinal cancer who participated in at least one video consultation during April-October 2019 completed a questionnaire on socioeconomic status, time and kilometers saved on travel. Kilometers saved were converted into reduced CO2 emissions. Descriptive statistics were used for analysis. Patients (n = 15) participated in semi-structured individual interviews, and five oncology nurses participated in a focus group interview. Results: A total of 84/119 patients (71%) consented to video consultation and responded to the questionnaire. 69% were male, with a mean age of 66 years. For 46% of patients, a video consultation saved more than an hour of travel time. Avoiding a median travel distance of 120 km per patient (range, 2-450 km) reduced CO2 emissions by 7018 lb. Video consultations had other positive effects on patients, including avoiding waiting rooms, having more energy, and experiencing more focused interactions with nurses. Technical issues occurred rarely. Nurses found technical issues more troublesome, sometimes precluding complete assessments. They reported a need to rethink nursing practice to effectively provide care during video consultations. Conclusions: Video consultations reduced CO2 emissions. In addition, they were beneficial for patients with gastrointestinal cancer. However, providing an optimal clinical assessment and decision of treatment readiness before chemotherapy requires testing patient equipment, technical skills and new oncology nursing competencies.

Video-Based Patient Rounds for Caregivers of Patients With Cancer.

PURPOSE: To investigate caregivers' experiences and level of involvement with video-based patient rounds. PARTICIPANTS & SETTING: 17 caregivers of patients with cancer at Odense University Hospitals in Denmark. METHODOLOGIC APPROACH: Field observation and semistructured interviews were employed. Interpretative phenomenologic analysis was used for data analysis. 17 interviews with caregivers and 190 hours of observations were conducted. FINDINGS: Video-based patient rounds made it possible for caregivers to attend without being physically present at the hospital. This allowed flexibility in caregivers' daily lives. However, caregivers also noted limitations in the use of video, particularly when conversations with healthcare professionals included serious messages. In that context, physical presence was preferred. IMPLICATIONS FOR NURSING: This study highlights the importance caregivers place on involvement and how video-based patient rounds allow caregivers to participate without being physically present at the hospital. The structure of video-based patient rounds and the topic of conversation should be considered.

Patient Rounds With Video-Consulted Relatives: Qualitative Study on Possibilities and Barriers From the Perspective of Healthcare Providers.

BACKGROUND: In cancer settings, relatives are often seen as a resource as they are able to support the patient and remember information during hospitalization. However, geographic distance to hospitals, work, and family obligations are reasons that may cause difficulties for relatives' physical participation during hospitalization. This provided inspiration to uncover the possibility of telehealth care in connection with enabling participation by relatives during patient rounds. Telehealth is used advantageously in health care systems but is also at risk of failing during the implementation process because of, for instance, health care professionals' resistance to change. Research on the implications for health care professionals in involving relatives' participation through virtual presence during patient rounds is limited. OBJECTIVE: This study aimed to investigate health care professionals' experiences in using and implementing technology to involve relatives during video-consulted patient rounds. METHODS: The design was a qualitative approach. Methods used were focus group interviews, short open interviews, and field observations of health care professionals working at a cancer department. The text material was analyzed using interpretative phenomenological analysis. RESULTS: Field observational studies were conducted for 15 days, yielding 75 hours of observation. A total of 14 sessions of video-consulted patient rounds were observed and 15 pages of field notes written, along with 8 short open interviews with physicians, nurses, and staff from management. Moreover, 2 focus group interviews with 9 health care professionals were conducted. Health care professionals experienced the use of technology as a way to facilitate involvement of the patient's relatives, without them being physically present. Moreover, it raised questions about whether this way of conducting patient rounds could address the needs of both the patients and the relatives. Time, culture, and change of work routines were found to be the major barriers when implementing new technology involving relatives. CONCLUSIONS: This study identified a double change by introducing both new technology and virtual participation by relatives at the same time. The change had consequences on health care professionals' work routines with regard to work load, culture, and organization because of the complexity in health care systems.

Real-World Early Treatment with Room Temperature-Stable Recombinant Factor VIIa in Hemophilia A/B and Inhibitors: SMART-7™ Post Hoc Analyses.

Treating hemophilia A or B patients with inhibitors is particularly challenging, as they do not respond to replacement therapy with factor VIII or factor IX concentrates. A room temperature-stable formulation of recombinant activated factor VII (rFVIIa; NovoSeven ® ), which provides improved convenience and treatment access to patients compared with the earlier formulation of rFVIIa, was shown to be safe and effective in a post-authorization, multinational, observational study (Study Monitoring Antibodies against Room Temperature-stable factor 7 [SMART-7™]). In post hoc, subgroup analyses of SMART-7™ data, the hemostatic response following rFVIIa monotherapy in patients with hemophilia A or B with inhibitors by time to first treatment and in different age cohorts was assessed. A total of 482/618 bleeding episodes treated with rFVIIa monotherapy and with (1) valid efficacy assessment, (2) no missing time for bleed start, (3) no missing time for any dose administration, and (4) valid time to first treatment were included in the analyses. Data on the type and location of bleeding episodes treated with rFVIIa monotherapy were also collected. The majority of bleeding episodes treated with rFVIIa monotherapy were treated within 1 hour after bleeding onset (318/482 [66%]) and, among them, 96.5% (307/318) were effectively treated (i.e., bleeding stopped). Hemostatic efficacy remained high for bleeding episodes treated >1 to ≤4 hours after the onset, with 94/101 (93.1%) treated effectively. Cause and location of bleeding varied across the different age groups assessed. Real-world evidence from post hoc, subgroup analyses of SMART-7™ data confirmed that patients were able to treat themselves quickly and that early treatment with rFVIIa was associated with high efficacy.

Increased Contractile Function of Human Saphenous Vein Grafts Harvested by "No-Touch" Technique.

Saphenous vein grafts are the most common conduits used for coronary artery bypass grafting (CABG); however, no more than 60% of vein grafts remain open after 10 years and graft failure is associated with poor clinical outcome. The "no-touch" harvesting technique-where a sheet of perivascular tissue is retained around the vein-improves graft patency to over 80% after 16 years of follow-up, but the mechanism for the improved patency rate is unclear. In this study, we investigated acute functional differences between vein grafts harvested conventionally and by "no-touch" technique and explored the importance of perivascular tissue for reducing surgical trauma, minimizing excessive distension, and releasing vasoactive paracrine factors. Segments of human saphenous veins were obtained from CABG surgery and their functional properties investigated by isometric and isobaric myography. We found a broad diameter-tension relationship for human saphenous veins, with peak capacity for active tension development at diameters corresponding to transmural pressures around 60 mmHg. Across the investigated transmural pressure range between 10 and 120 mmHg, maximal tension development was higher for "no-touch" compared to conventionally harvested saphenous veins. Contractile responses to serotonin, noradrenaline, and depolarization induced with elevated extracellular [K+] were significantly larger for saphenous veins harvested by "no-touch" compared to conventional technique. Conventional vein grafts are routinely pressurized manually in order to test for leaks; however, avoiding this distension procedure did not change the acute contractile function of the conventionally excised saphenous veins. In contrast, even though surgical removal of perivascular tissue during conventional harvesting was associated with a substantial decrease in force development, removal of perivascular tissue by careful dissection under a stereomicroscope only marginally affected contractile responses of veins harvested by "no-touch" technique. In conclusion, we show that saphenous veins harvested by "no-touch" technique have greater contractile capacity than veins harvested by conventional technique. The different capacity for smooth muscle contraction is not due to vasoactive substances released by the perivascular tissue. Instead, we propose that the larger tension development of saphenous veins harvested by "no-touch" technique reflects reduced surgical damage, which may have long-term consequences that contribute to the superior graft patency.