Fishing safely during COVID-19 in Newfoundland and Labrador, Canada: Making it happen.

Globally, fisheries have been the site of multiple documented outbreaks of COVID-19. Existing studies point to the threat posed by the pandemic to livelihoods and health among migrant industrial fishery workers, small-scale fish harvesters, and fishing communities. They show the pandemic enhanced safety, economic, social and political layers of vulnerability in fisheries, while also showcasing examples of resilience. Case studies of COVID-19 response provide an opportunity to explore how existing organizational structures, leadership and networks in fisheries can enable the rapid co-development of customized strategies for fishing safely during large-scale global disruptions such as pandemics. This article contributes to our understanding of governance and fishing safety in small-scale fisheries during the early pandemic, examining the response of small-scale fisheries in the Canadian province of Newfoundland and Labrador. These seasonal fisheries successfully opened with regulator approval after a short delay and operated without documented COVID-19 outbreaks during 2020. Findings draw from key informant interviews with a safety sector association and union leader, complemented with insights from an anonymous online survey of small-scale harvesters. Interviews capture the organizational processes and resources mobilized to rapidly co-develop the COVID-19 Safe Work Practice Guideline. Online survey findings indicate that fifty-nine percent of respondents (crew and skippers) had no COVID-19-related concerns while fishing in 2020; older harvesters and owner-operators were significantly more likely to indicate concerns. When asked about the relative practicality of listed COVID-19 precautions, respondents commonly identified sanitization, reduced interactions with shore workers, social distancing, protection equipment, modifications to eating/rest areas, and reduced crew as impractical. These assessments are generally consistent with those of the interviewed leaders and the Guideline approach. This suggests the co-developed Guideline provided tailored and practical COVID-19 prevention strategies. Pre-existing governance structures and networks can help address small-scale fisheries vulnerabilities to pandemics by supporting co-development of organizational resources and evidence-informed prevention strategies.

Community Palliative Care Initiatives to Reduce End-of-Life Hospital Utilization and In-Hospital Deaths: A Population-Based Observational Study Evaluating Two Home Care Interventions.

CONTEXT: The end-of-life period is characterized by increased hospital utilization despite patients' preferences to receive care and die at home. OBJECTIVES: To evaluate the impact of interventions aimed at planning for a home death (Yellow Folder) and managing symptoms in the home (Symptom Response Kit) on place of death and hospital utilization among palliative home care patients. METHODS: This was an ecologic and retrospective cohort study of palliative home care patients in southeastern Ontario from April 2009 to March 2014. Linked health administrative and clinical databases were used to identify palliative home care patients and their receipt of the interventions, hospitalizations, emergency department visits, and place of death. Bivariable and multivariable regressions were used to evaluate outcomes according to patients' receipt of intervention(s). RESULTS: The proportion of patients who died in the community increased after implementation of the interventions, from 42.8% to 48.5% (P < 0.0001). Compared with patients who received neither intervention, patients who received the Yellow Folder or Symptom Response Kit had an increased likelihood of dying in the community, with the largest relative risk observed in patients who received both interventions (relative risk = 2.20, 95% confidence interval 2.05-2.36). Receipt of these interventions was only associated with reductions in hospitalization or emergency department visit rates in the six months before death. CONCLUSION: Patients who received the Yellow Folder or Symptom Response Kit were more likely remain at home at the end of life. This association was stronger when these interventions were used together.

Elucidating the Kinetics of Expression and Immune Cell Infiltration Resulting from Plasmid Gene Delivery Enhanced by Surface Dermal Electroporation.

The skin is an attractive tissue for vaccination in a clinical setting due to the accessibility of the target, the ease of monitoring and most importantly the immune competent nature of the dermal tissue. While skin electroporation offers an exciting and novel future methodology for the delivery of DNA vaccines in the clinic, little is known about the actual mechanism of the approach and the elucidation of the resulting immune responses. To further understand the mechanism of this platform, the expression kinetics and localization of a reporter plasmid delivered via a surface dermal electroporation (SEP) device as well as the effect that this treatment would have on the resident immune cells in that tissue was investigated. Initially a time course (day 0 to day 21) of enhanced gene delivery with electroporation (EP) was performed to observe the localization of green fluorescent protein (GFP) expression and the kinetics of its appearance as well as clearance. Using gross imaging, GFP expression was not detected on the surface of the skin until 8 h post treatment. However, histological analysis by fluorescent microscopy revealed GFP positive cells as early as 1 h after plasmid delivery and electroporation. Peak GFP expression was observed at 24 h and the expression was maintained in skin for up to seven days. Using an antibody specific for a keratinocyte cell surface marker, reporter gene positive keratinocytes in the epidermis were identified. H&E staining of treated skin sections demonstrated an influx of monocytes and granulocytes at the EP site starting at 4 h and persisting up to day 14 post treatment. Immunological staining revealed a significant migration of lymphocytic cells to the EP site, congregating around cells expressing the delivered antigen. In conclusion, this study provides insights into the expression kinetics following EP enhanced DNA delivery targeting the dermal space. These findings may have implications in the future to design efficient DNA vaccination strategies for the clinic.

Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses.

Despite the development of highly effective prophylactic vaccines against human papillomavirus (HPV) serotypes 16 and 18, prevention of cervical dysplasia and cancer in women infected with high-risk HPV serotypes remains an unmet medical need. We report encouraging phase 1 safety, tolerability, and immunogenicity results for a therapeutic HPV16/18 candidate vaccine, VGX-3100, delivered by in vivo electroporation (EP). Eighteen women previously treated for cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) received a three-dose (intramuscular) regimen of highly engineered plasmid DNA encoding HPV16 and HPV18 E6/E7 antigens followed by EP in a dose escalation study (0.3, 1, and 3 mg per plasmid). Immunization was well tolerated with reports of mild injection site reactions and no study-related serious or grade 3 and 4 adverse events. No dose-limiting toxicity was noted, and pain was assessed by visual analog scale, with average scores decreasing from 6.2/10 to 1.4 within 10 min. Average peak interferon-γ enzyme-linked immunospot magnitudes were highest in the 3 mg cohort in comparison to the 0.3 and 1 mg cohorts, suggesting a trend toward a dose effect. Flow cytometric analysis revealed the induction of HPV-specific CD8(+) T cells that efficiently loaded granzyme B and perforin and exhibited full cytolytic functionality in all cohorts. These data indicate that VGX-3100 is capable of driving robust immune responses to antigens from high-risk HPV serotypes and could contribute to elimination of HPV-infected cells and subsequent regression of the dysplastic process.

Development, implementation, and process evaluation of a regional palliative care quality improvement project.

The delivery of optimal palliative care requires an integrated and coordinated approach of many health care providers across the continuum of care. In response to identified gaps in the region, the Palliative Care Integration Project (PCIP) was developed to improve continuity and decrease variability of care to palliative patients with cancer. The infrastructure for the project included multi-institutional and multisectoral representation on the Steering Committee and on the Development, Implementation and Evaluation Working Groups. After review of the literature, five Collaborative Care Plans and Symptom Management Guidelines were developed and integrated with validated assessment tools (Edmonton Symptom Assessment System and Palliative Performance Scale). These project resources were implemented in the community, the palliative care unit, and the cancer center. Surveys were completed by frontline health professionals (defined as health professionals providing direct care), and two independent focus groups were conducted to capture information regarding: 1) the development of the project and 2) the processes of implementation and usefulness of the different components of the project. Over 90 individuals from more than 30 organizations were involved in the development, implementation, and evaluation of the PCIP. Approximately 600 regulated health professionals and allied health professionals who provided direct care, and over 200 family physicians and medical residents, received education/training on the use of the PCIP resources. Despite unanticipated challenges, frontline health professionals reported that the PCIP added value to their practice, particularly in the community sector. The PCIP showed that a network in which each organization had ownership and where no organization lost its autonomy, was an effective way to improve integration and coordination of care delivery.

Palliative Care Integration Project (PCIP) quality improvement strategy evaluation.

This study evaluated the effectiveness of implementation of common assessment tools, collaborative care plans, and symptom management guidelines for cancer patients as a strategy to improve the quality, coordination, and integration of palliative care service across organizations and health care sectors. A pre-post design to measure the impact on symptom management, caregiver burden and satisfaction with care delivery, and service utilization was used. Two cohorts of eligible patients and caregivers completed Edmonton Symptom Assessment Scales, Caregiver Reaction Assessment and FAMCARE Scales and chart audits were conducted. Administrative data from each participating site were examined for utilization trends. Audits of 53 charts preimplementation and 63 postimplementation showed an increase in documentation of pain from 24.5% to 74.6% (P<0.001) of charts. Administrative data showed a decrease in the percentage of patients with at least one emergency room visit from 94.3% to 84.8% (P<0.001), in the percentage of patients with at least one admission to the acute care hospital (P<0.001), and deaths in acute care 43.1%-35.7% (P=0.133). There was minimal change in the intensity of symptoms (P=0.591), and no change in the burden on the caregiver (P=0.086) or caregiver satisfaction with care (P=0.942). This study showed that implementation of common assessment tools, collaborative care plans, and symptom management guidelines across health sectors can result in some increased documentation of symptoms and efficiencies in care. Future projects should consider imbedding a continuous quality improvement methodology and longer timelines into their projects to improve outcomes.

Defining low risk for coronary heart disease among women with chest pain syndrome: a prospective evaluation.

BACKGROUND: A better understanding of the clinical manifestations of coronary disease in women may lead to earlier recognition and better outcomes. METHODS: One hundred fifty-eight women coming to primary care physicians, emergency rooms, or cardiology clinics with undefined chest pain and at least two risk factors underwent detailed clinical evaluation of risk factor profile and symptom characteristics as well as stress testing. The significance of the presenting symptoms was evaluated on the basis of clinical events during an average 26.2 months of follow-up. Noncardiac pain was diagnosed on the basis of spontaneous resolution of symptoms, establishment of an alternative diagnosis, or negative coronary angiography. Cardiac chest pain was established by the development of cardiac clinical events or angiographic demonstration of coronary disease. RESULTS: Noncardiac chest pain was established in 128 (81%) patients. The remaining 30 (19%) either were found to have had cardiac chest pain or remain symptomatic without definitive diagnosis. Multivariate analysis revealed that noncardiac chest pain was best predicted by a combination of nondiabetic status and negative stress testing. The clinical characteristics of the chest pain syndrome were not significant contributors. CONCLUSIONS: In nondiabetic women with chest pain syndrome and at least two other cardiac risk factors, a negative stress test predicts a benign course in over 2 years of follow-up.

Benign prostate-specific antigen (BPSA) in serum is increased in benign prostate disease.

BACKGROUND: BPSA is a "benign" form of free prostate-specific antigen (PSA) that is increased in prostate transition zone tissues of men with pathologic benign prostatic hyperplasia (BPH). We developed an immunoassay to determine the concentration of BPSA in the serum of men with BPH. METHODS: The BPSA antigen was purified by HPLC, and murine monoclonal antibodies were prepared by standard methods. A fluorogenic ELISA was developed with high specificity for BPSA and no cross-reactivity with other forms of PSA. RESULTS: The BPSA immunoassay had a lower limit of detection of 6 ng/L and a cross-reactivity of <1% with all other clipped and nonclipped forms of PSA. The BPSA antibody was specific for the internal Lys(182) cleavage site that characterizes BPSA. Biopsy-negative men with a median total PSA of 4.8 micro g/L had a median of 0.22 micro g/L BPSA, representing 25% of the free PSA in serum. BPSA ranged from 0% to 60% of the free PSA in serum. BPSA in a cohort of cancer serum also comprised 25% of the free PSA. Control serum from women or men without increased PSA had nondetectable BPSA. CONCLUSIONS: BPSA is a significant percentage of the free PSA in BPH serum but not in control serum. The presence of prostate cancer does not alter the relative proportions of BPSA in sera with <10 micro g/L PSA. BPSA has a wide distribution of concentrations in the serum and may provide clinical information for the study of men with BPH.