First-in-human stage III/IV melanoma​ clinical trial of immune priming agent IFx-Hu2.0.

IFx-Hu2.0 was designed to encode part of the Emm55 protein contained within a plasmid in a formulation intended for transfection into mammalian cells. IFx-Hu2.0 promotes both adaptive and innate immune responses in animal studies. Furthermore, previous studies have demonstrated safety/efficacy in equine, canine, and murine species. We present the first-in-human study of IFx-Hu2.0, administered by intralesional injection into melanoma tumors of seven patients with stage III/IV unresectable melanoma. No dose-limiting toxicities attributable to IFx-Hu2.0 were observed. Grade 1/2 injection site reactions were observed in five of seven patients. IgG and IgM responses were seen in the peripheral blood to Emm55 peptides and known melanoma antigens, suggesting that IFx-Hu2.0 acts as an individualized "in-situ vaccine." Three of four patients previously refractory to anti-PD1 experienced clinical benefit upon subsequent anti-PD1-based treatment. Therefore, this approach is feasible, and clinical/correlative outcomes warrant further investigation for treating metastatic melanoma patients as an immune priming agent.

System Issues Leading to "Found-on-Floor" Incidents: A Multi-Incident Analysis.

BACKGROUND: Although attention to patient safety issues in the home care setting is growing, few studies have highlighted health system-level concerns that contribute to patient safety incidents in the home. Found-on-floor (FOF) incidents are a key patient safety issue that is unique to the home care setting and highlights a number of opportunities for system-level improvements to drive enhanced patient safety. METHODS: We completed a multi-incident analysis of FOF incidents documented in the electronic record system of a home health care agency in Toronto, Canada, for the course of 1 year between January 2012 and February 2013. RESULTS: Length of stay (LOS) was identified as the cross-cutting theme, illustrating the following 3 key issues: (1) in the short LOS group, a lack of information continuity led to missed fall risk information by home care professionals; (2) in the medium LOS group, a lack of personal support worker/carer training in fall prevention led to inadequate fall prevention activity; and (3) in the long LOS group, a lack of accountability policy at a system level led to a lack of fall risk assessment follow-up. CONCLUSIONS: Our study suggests that considering LOS in the home care sector helps expose key system-level issues enabling safety incidents such as FOF to occur. Our multi-incident analysis identified a number of opportunities for system-level changes that might improve fall prevention practice and reduce the likelihood of FOF incidents in the home. Specifically, investment in electronic health records that are functional across the continuum of care, further research and understanding of the training and skills of personal support workers, and enhanced incentives or more punitive approaches (depending on the circumstances) to ensure accountability in home safety will strengthen the home care sector and help prevent FOF incidents among older people.

Restricted participation in stroke caregivers: who is at risk?

OBJECTIVE: To identify caregiver-, stroke survivor-, and caregiving situation-related factors that are associated with caregivers' restriction from participation in their normative activities (ie, participation restriction) over the first 2 years poststroke. DESIGN: Longitudinal cohort study. SETTING: Acute care facilities and community. PARTICIPANTS: A secondary data analysis of caregiver/survivor dyads (N=399). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Data were collected at 1, 3, 6, 12, 18, and 24 months poststroke. The primary outcome was caregivers' participation restriction and was assessed using the Caregiver Impact Scale. Caregivers also provided demographic information and completed standardized measures to capture assistance provided, mastery, and depression. From stroke survivors we collected demographic characteristics, stroke severity, and cognitive and physical functioning. Data were analyzed using individual growth curve modeling. RESULTS: Participation restriction level improved over time. Caregiver factors associated with restricted participation included younger age, being employed, higher depression, and lower mastery level. Stroke survivor factors associated with caregivers' restricted participation included hemorrhagic stroke, more severe stroke, more physical and memory impairments, and lower participation. Significant factors related to the caregiving situation included providing high levels of assistance and caring for a spouse. CONCLUSIONS: Depressed younger caregivers, with low levels of mastery, who provide high-intensity support to spouses with cognitive difficulties may be at risk. Screening for these factors may help identify stroke families at risk for poor outcomes and may be used to more efficiently allocate health resources.

Factors that contribute to adult children caregivers' well-being: a scoping review.

The ageing of the population will increasingly result in reliance on the family for care in the community. Existing reviews have provided insights into the needs and health outcomes of family caregivers, but are disproportionately skewed towards spousal caregivers. Presently, a large majority of family caregivers are adult children. Adult children are distinct from spousal caregivers in terms of the combination of roles they occupy and the relationship they have with the care recipient. These unique considerations can have important implications for their well-being. A growing body of literature has investigated the factors that contribute to adult children caregivers' (ACCs) well-being; however, no reviews to date have synthesised this body of literature or appraised its methodological quality. Our objective was to identify the range and types of factors that contribute to ACC well-being across studies. A scoping review was conducted. Medline, Psycinfo, EMBASE and CINAHL databases (January 1996-August, 2012) were systematically searched for studies investigating ACC well-being. Inclusion/exclusion criteria were applied, methodological quality was appraised, the data were charted and a narrative synthesis was conducted. Fifty-five studies met our inclusion criteria. Factors that contribute to ACC well-being were found to be either: (i) care recipient-related (e.g. nature of limitations, amount of care required); (ii) caregiver-related (e.g. psychological dispositions of the ACC); or (iii) socially embedded (e.g. parent-child relationship, multiple role involvement, social support available to the ACC). Socially embedded factors that contribute to ACC well-being have received the most attention in the literature. Among these factors, ACC well-being is uniquely impacted by the quality of the parent-child relationship and combination of roles occupied. The majority of studies were cross-sectional. Future studies should therefore employ a longitudinal design to inform our understanding of the changes that take place in the parent-child relationship and multiple role involvement across the care-giving trajectory.

Adult daughters providing post-stroke care to a parent: a qualitative study of the impact that role overload has on lifestyle, participation and family relationships.

OBJECTIVE: To qualitatively explore daughters' experiences with and response to holding multiple roles while providing post-stroke care to a parent. DESIGN: Qualitative study using a descriptive approach. Semi-structured interviewing was used. Interviews were recorded, transcribed and analyzed to develop themes. SETTING: General community of a metropolitan city. PARTICIPANTS: Twenty-three adult daughters caring for a community-dwelling parent who had suffered a stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Role overload is a salient issue for daughter caregivers. This overload is best captured by the analogy of "juggling" multiple role demands and responsibilities. Two key themes suggest that role overload resulting from parent care affects daughters': 1) valued relationships (e.g. challenges develop in their relationship with children and partner); and 2) ability to participate in valued activities (e.g. reduced involvement in leisure activities and restricted employment). CONCLUSIONS: Future support efforts should help daughters manage the caregiving role in light of other responsibilities. This can mitigate overload-related strain in valued relationships and decreased participation in valued activities, thereby contributing to better health and well-being for daughter caregivers.

Alpha-synuclein as a pathological link between chronic traumatic brain injury and Parkinson's disease.

The long-term consequences of traumatic brain injury (TBI) are closely associated with the development of histopathological deficits. Notably, TBI may predispose long-term survivors to age-related neurodegenerative diseases, such as Parkinson's disease (PD), which is characterized by a gradual degeneration of the nigrostriatal dopaminergic neurons. However, preclinical studies on the pathophysiological changes in substantia nigra (SN) after chronic TBI are lacking. In the present in vivo study, we examined the pathological link between PD-associated dopaminergic neuronal loss and chronic TBI. Sixty days post-TBI, rats were euthanized and brain tissues harvested. Immunostaining was performed using tyrosine hydroxylase (TH), an enzyme required for the synthesis of dopamine in neurons, α-synuclein, a presynaptic protein that plays a role in synaptic vesicle recycling, and major histocompatibility complex II (MHCII), a protein found in antigen presenting cells such as inflammatory microglia cells, all key players in PD pathology. Unbiased stereology analyses revealed significant decrease of TH-positive expression in the surviving dopaminergic neurons of the SN pars compacta (SNpc) relative to sham control. In parallel, increased α-synuclein accumulation was detected in the ipsilateral SN compared to the contralateral SN in TBI animals or sham control. In addition, exacerbation of MHCII+ cells was recognized in the SN and cerebral peduncle ipsilateral to injury relative to contralateral side and sham control. These results suggest α-synuclein as a pathological link between chronic effects of TBI and PD symptoms as evidenced by significant overexpression and abnormal accumulation of α-synuclein in inflammation-infiltrated SN of rats exposed to chronic TBI.

Daughters providing poststroke care: perspectives on the parent-child relationship and well-being.

Stroke is a leading cause of disability and dependence on the family, specifically daughter caregivers. The quality of the parent-child relationship can influence the experiences and well-being of daughters. Little is known about this in the context of stroke caregiving. We aimed to explore daughters' perceptions of changes in the relationship with their parent and how these changes contribute to their well-being. We used a qualitative descriptive design. Twenty-three daughters completed one in-depth interview that was transcribed, reviewed, coded, and categorized to generate themes. The parent-child relationship was central to each of the three themes: It (a) led daughters to take on the caregiving role, (b) changed as a result of caregiving, and (c) contributed to daughters' physical and emotional health. Targeted counseling that addresses changes in the parent-child relationship can help mitigate losses in communication and intimacy between daughters and parents. Insight into temporal relationship changes is needed.

Stroke survivors', caregivers', and health care professionals' perspectives on the weekend pass to facilitate transition home.

OBJECTIVE: To explore stroke survivors', caregivers', and health care professionals' perceptions of weekend passes offered during inpatient rehabilitation and its role in facilitating the transition home. DESIGN: Qualitative descriptive. SUBJECTS: Sixteen stroke survivors, 15 caregivers, and 20 health care professionals' from a rehabilitation hospital. METHODS: Participants discussed their perceptions of the purpose of the weekend pass, experiences with the weekend pass including supports needed, and weekend pass administration. Focus group and interview data were audio recorded, professionally transcribed, checked for accuracy, and analyzed using conventional content analysis. RESULTS: We identified 3 key themes: i) preparing for patients to be safe at home; ii) gaining insight through the weekend pass; and iii) the emotional context of the weekend pass. These themes varied by participant group. CONCLUSIONS: When offering weekend passes, stroke care systems should carefully consider patients' and caregivers' readiness, emotional state, and preparation for weekend passes. The weekend pass experience can inform in-patient therapy, provide patients and caregivers with insight into life after stroke, and help prepare patients and families for the ultimate transition home.

Caregiver burden--a critical discussion.

Currently, 15%, 12.8% and 17.1% of the Canadian, American and European populations, respectively, are 65 years or older. Due to aging-related disabilities, elderly individuals will require support from family members while in the community. Annually, family caregivers save the Canadian and American healthcare systems $25 billion and $350 billion, respectively. However, to maintain the important role they play, caregivers' experiences must be investigated in order to provide appropriate support. Despite the fact that 'caregiver burden' is preponderantly used as an indicator of the caregiving experience, much disagreement remains on what the term entails and how it should be utilized. This paper endeavors to critically discuss the concept of 'caregiver burden', its use in the literature and the implications this has for future research and clinical practice. The vagueness derived from the various 'caregiver burden' definitions limits the term's relevance to policy-making and clinical practice. Additionally, much of the literature on 'caregiver burden' is not theoretically framed, which reduces the conceptual clarity of the term. Quantitative measures are largely used to investigate 'caregiver burden', which can sometimes fail to capture contextual features that are relevant to caregiving outcomes (e.g., culture). Stress theory and role theory are recommended as guiding frameworks for future research that investigates 'caregiver burden'. Future research on 'caregiver burden' would also benefit from integrating qualitative and quantitative approaches into mixed method designs in order to gain a holistic understanding of the concept.