Caregivers of allogeneic hematopoietic stem cell transplant (HCT) cancer patients experience high caregiver burden and carry a significant amount of responsibility. Mindfulness has the potential to ...lessen caregiver burden by aiding in stress management. To date, no studies have examined the efficacy of mindfulness in reducing caregiver burden in this population. Based on our pilot study demonstrating initial feasibility and acceptability of FOCUS (Focusing On mindfulness for Caregivers Under Stress), this 3-arm randomized controlled trial aims to examine the efficacy of a 6-week mindfulness-based stress management program for allogeneic HCT caregivers. Hypotheses include that the FOCUS condition will have lower post-treatment caregiver burden and that patients of these caregivers will have better patient health outcomes compared to other treatment conditions.
Eligible caregivers will be randomly assigned to one of three treatment conditions: FOCUS, Healthy Living (HL; active control), and Enhanced Care (EC; usual care). Caregivers in FOCUS and HL will participate in 6-week weekly individual treatment sessions and will be sent brief daily momentary interventions/messages. Caregivers in all conditions will complete daily diaries over the course of treatment. Patients of enrolled caregivers will be enrolled for assessments only. Participants will complete assessments at baseline, end of treatment, 2- and 6-months post-treatment. Biomarker data will be collected via hair cortisol concentrations from caregivers at baseline and 6 months post-treatment.
Recruitment is ongoing.
The data collected from this study will provide evidence on the efficacy of mindfulness in alleviating HCT caregiver stress and impacting patient health outcomes.
The current study is registered in clinicaltrials.gov (NCT05078229); see https://clinicaltrials.gov/ct2/show/NCT05078229?term=christine+vinci&draw=2&rank=1.
Despite high levels of stress, there are few empirically supported stress management interventions for caregivers of allogeneic hematopoietic stem cell transplant (HCT) cancer patients. This study ...examined the feasibility, acceptability, and various stress‐related outcomes from pre‐ to post‐treatment of a pilot, single‐arm trial of a 6‐week mindfulness‐based intervention (FOCUS) for stress management. Caregivers (N = 21; 76% female; mean age = 57.43) were enrolled prior to patient transplant and received FOCUS during the first 90 days post‐transplant. Findings indicated that FOCUS was highly feasible and acceptable (e.g., 71% attended at least four of six sessions; 100% reported using the skills learned at follow‐up; high treatment engagement). Significant increases in mindfulness, post‐traumatic growth, and general mental health were observed, along with significant decreases in negative affect (all ps < .05).
Caregivers of allogeneic hematopoietic stem cell transplant (HCT) cancer patients experience high caregiver burden and carry a significant amount of responsibility. Mindfulness has the potential to ...lessen caregiver burden by aiding in stress management. To date, no studies have examined the efficacy of mindfulness in reducing caregiver burden in this population. Based on our pilot study demonstrating initial feasibility and acceptability of FOCUS (Focusing On mindfulness for Caregivers Under Stress), this 3-arm randomized controlled trial aims to examine the efficacy of a 6-week mindfulness-based stress management program for allogeneic HCT caregivers. Hypotheses include that the FOCUS condition will have lower post-treatment caregiver burden and that patients of these caregivers will have better patient health outcomes compared to other treatment conditions. Eligible caregivers will be randomly assigned to one of three treatment conditions: FOCUS, Healthy Living (HL; active control), and Enhanced Care (EC; usual care). Caregivers in FOCUS and HL will participate in 6-week weekly individual treatment sessions and will be sent brief daily momentary interventions/messages. Caregivers in all conditions will complete daily diaries over the course of treatment. Patients of enrolled caregivers will be enrolled for assessments only. Participants will complete assessments at baseline, end of treatment, 2- and 6-months post-treatment. Biomarker data will be collected via hair cortisol concentrations from caregivers at baseline and 6 months post-treatment. Recruitment is ongoing. The data collected from this study will provide evidence on the efficacy of mindfulness in alleviating HCT caregiver stress and impacting patient health outcomes.
Interferon regulatory factor‐3 (IRF‐3) activation directs α/β interferon production and interferon‐stimulated gene (ISG) expression, which limits virus infection. Here, we examined the distribution ...of hepatitis C virus (HCV) nonstructural 3 protein, the status of IRF‐3 activation, and expression of IRF‐3 target genes and ISGs during asynchronous HCV infection in vitro and in liver biopsies from patients with chronic HCV infection, using confocal microscopy and functional genomics approaches. In general, asynchronous infection with HCV stimulated a low‐frequency and transient IRF‐3 activation within responsive cells in vitro that was associated with cell‐to‐cell virus spread. Similarly, a subset of HCV patients exhibited the nuclear, active form of IRF‐3 in hepatocytes and an associated increase in IRF‐3 target gene expression in hepatic tissue. Moreover, ISG expression profiles formed disease‐specific clusters for HCV and control nonalcoholic fatty liver disease patients, with increased ISG expression among the HCV patients. We identified the presence of T cell and plasmacytoid dendritic cell infiltrates within all biopsy specimens, suggesting they could be a source of hepatic interferon in the setting of hepatitis C and chronic inflammatory condition. Conclusion: These results indicate that HCV can transiently trigger IRF‐3 activation during virus spread and that in chronic HCV, IRF‐3 activation within infected hepatocytes occurs but is limited. (HEPATOLOGY 2007.)
Viral signaling through retinoic acid-inducible gene-I (RIG-I) and its adaptor protein, IFN promoter-stimulator 1 (IPS-1), activates IFN regulatory factor-3 (IRF-3) and the host IFN-α/β response that ...limits virus infection. The hepatitis C virus (HCV) NS3/4A protease cleaves IPS-1 to block RIG-i signaling, but how this regulation controls the host response to HCV is not known. Moreover, endogenous IPS-1 cleavage has not been demonstrated in the context of HCV infection in vitro or in vivo. Here, we show that HCV infection transiently induces RIG-I- and IPS-1-dependent IRF-3 activation. This host response limits HCV production and constrains cellular permissiveness to infection. However, HCV disrupts this response early in infection by NS3/4A cleavage of IPS-1 at C508, releasing IPS-1 from the mitochondrial membrane. Cleavage results in subcellular redistribution of IPS-1 and loss of interaction with RIG-I, thereby preventing downstream activation of IRF-3 and IFN-β induction. Liver tissues from chronically infected patients similarly demonstrate subcellular redistribution of IPS-1 in infected hepatocytes and IPS-1 cleavage associated with a lack of ISG15 expression and conjugation of target proteins in vivo. Importantly, small-molecule inhibitors of NS3/4A prevent cleavage and restore RIG-I signaling of IFN-² induction. Our results suggest a dynamic model in which early activation of IRF-3 and induction of antiviral genes are reversed by IPS-1 proteolysis and abrogation of RIG-I signaling as NS3/4A accumulates in newly infected cells. HCV protease inhibitors effectively prevent IPS-1 proteolysis, suggesting they may be capable of restoring this innate host response in clinical practice.
Background
Gastric submucosal tumors are often treated by laparoscopic wedge resection. This study aimed to examine the feasibility of gastric full-thickness resection through a totally endoscopic ...approach using the master and slave transluminal endoscopic robot (MASTER), and closure of the luminal defect with an endoscopic suturing device.
Methods
The operation was performed in two live porcine models under general anesthesia. First, the anterior wall of the stomach was slung to the abdominal wall using a percutaneous suturing device. An imaginary 5-cm lesion was marked using a needle knife. After the initial mucosal incision was made using an IT knife, the MASTER was introduced through a long overtube. A circumferential mucosal incision was completed with the MASTER to expose the muscularis propria which was grasped and incised to the serosal layer by electrocautery applied through the hook of the MASTER. The full-thickness resection of the gastric wall was completed with retraction using the grasper and dissection using the hook. While the defect was being created, the luminal space was maintained with traction of the percutaneous sutures. The defect was closed with suture plication using an Apollo Overstitch device.
Results
Two full-thickness gastric resections were performed in two nonsurvival porcine models (body weight = 30 and 35 kg, respectively) using the MASTER. The total procedure time was 56 min for the first model and 70 min for the second model. The luminal view was maintained during the whole procedure, and there was no damage to surrounding organs throughout the whole procedure. The gastric defects were closed successfully using Overstitch, with satisfactory gastric distension and no gas leakage afterward.
Conclusion
The current experiment demonstrated the feasibility and safety of a totally endoscopic approach for the treatment of gastric submucosal tumors: full-thickness resection with the MASTER and successful closure of the defect using Overstitch.
As the population ages, potentially inappropriate prescribing (PIP) in the older adults may become increasingly prevalent. This undermines patient safety and creates a potential source of major ...morbidity and mortality. Understanding the factors that influence prescribing behaviour may allow development of interventions to reduce PIP. The aim of this study is to apply the Theoretical Domains Framework (TDF) to explore barriers to effective prescribing for older adults in the ambulatory setting.
A scoping review was performed based on the five-stage methodological framework developed by Arksey and O'Malley. From 30 Aug 2018 to 5 Sep 2018, we conducted our search on PubMed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, and Web of Science. We also searched five electronic journals, Google and Google Scholar to identify additional sources and grey literature. Two reviewers applied eligibility criteria to the title and abstract screening, followed by full text screening, before systematically charting the data.
A total of 5731 articles were screened. Twenty-nine studies met the selection criteria for qualitative analysis. We mapped our results using the 14-domain TDF, eventually identifying 10 domains of interest for barriers to effective prescribing. Of these, significant domains include physician-related factors such as "Knowledge", "Skills", and "Social/Professional Role and Identity"; issues with "Environmental Context and Resources"; and the impact of "Social Influences" and "Emotion" on prescribing behaviour.
The TDF elicited multiple domains which both independently and collectively lead to barriers to effective prescribing for older adults in the ambulatory setting. Changing the prescribing climate will thus require interventions targeting multiple stakeholders, including physicians, patients and hospital/clinic systems. Further work is needed to explore individual domains and guide development of frameworks to aid guide prescribing for older adults in the ambulatory setting.
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