A Virtual Coaching Workshop for a Nurse-Led Community-Based Palliative Care Team in Liberia, West Africa, to Promote Staff Well-Being During COVID-19.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented system and clinician strain worldwide, disproportionately impacting resource poor settings. This project describes the use of a virtual nurse coaching session to improve the well-being of a nurse-led community-based palliative care team in Liberia, West Africa. Staff response was overwhelmingly positive. Discussion is underway to expand this educational coaching intervention to support additional teams confronting COVID-19 in both East and West Africa. Virtual nurse coaching is an innovative way to enhance staff well-being, improve global health partnerships and knowledge exchange, and foster communication across all levels of education and clinical practice.

Optimizing the Global Nursing Workforce to Ensure Universal Palliative Care Access and Alleviate Serious Health-Related Suffering Worldwide.

CONTEXT: Palliative care access is fundamental to the highest attainable standard of health and a core component of universal health coverage. Forging universal palliative care access is insurmountable without strategically optimizing the nursing workforce and integrating palliative nursing into health systems at all levels. The COVID-19 pandemic has underscored both the critical need for accessible palliative care to alleviate serious health-related suffering and the key role of nurses to achieve this goal. OBJECTIVES: 1) Summarize palliative nursing contributions to the expansion of palliative care access; 2) identify emerging nursing roles in alignment with global palliative care recommendations and policy agendas; 3) promote nursing leadership development to enhance universal access to palliative care services. METHODS: Empirical and policy literature review; best practice models; recommendations to optimize the palliative nursing workforce. RESULTS: Nurses working across settings provide a considerable untapped resource that can be leveraged to advance palliative care access and palliative care program development. Best practice models demonstrate promising approaches and outcomes related to education and training, policy and advocacy, and academic-practice partnerships. CONCLUSION: An estimated 28 million nurses account for 59% of the international healthcare workforce and deliver up to 90% of primary health services. It has been well-documented that nurses are often the first or only healthcare provider available in many parts of the world. Strategic investments in international and interdisciplinary collaboration, as well as policy changes and the safe expansion of high-quality nursing care, can optimize the efforts of the global nursing workforce to mitigate serious health-related suffering.

High level of PD-1 expression on hepatitis C virus (HCV)-specific CD8+ and CD4+ T cells during acute HCV infection, irrespective of clinical outcome.

We monitored expression of PD-1 (a mediator of T-cell exhaustion and viral persistence) on hepatitis C virus (HCV)-specific CD8(+) and CD4(+) T cells from blood and liver during acute and chronic infections and after the resolved infection stage. PD-1 expression on HCV-specific T cells was high early in acute infection irrespective of clinical outcome, and most cells continued to express PD-1 in resolved and chronic stages of infection; intrahepatic expression levels were especially high. Our results suggest that an analysis of PD-1 expression alone is not sufficient to predict infection outcome or to determine T-cell functionality in HCV infection.

Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-naïve patients.

UNLABELLED: Resistance mutations to hepatitis C virus (HCV) nonstructural protein 3 (NS3) protease inhibitors in <1% of the viral quasispecies may still allow >1000-fold viral load reductions upon treatment, consistent with their reported reduced replicative fitness in vitro. Recently, however, an R155K protease mutation was reported as the dominant quasispecies in a treatment-naïve individual, raising concerns about possible full drug resistance. To investigate the prevalence of dominant resistance mutations against specifically targeted antiviral therapy for HCV (STAT-C) in the population, we analyzed HCV genome sequences from 507 treatment-naïve patients infected with HCV genotype 1 from the United States, Germany, and Switzerland. Phylogenetic sequence analysis and viral load data were used to identify the possible spread of replication-competent, drug-resistant viral strains in the population and to infer the consequences of these mutations upon viral replication in vivo. Mutations described to confer resistance to the protease inhibitors Telaprevir, BILN2061, ITMN-191, SCH6 and Boceprevir; the NS5B polymerase inhibitor AG-021541; and to the NS4A antagonist ACH-806 were observed mostly as sporadic, unrelated cases, at frequencies between 0.3% and 2.8% in the population, including two patients with possible multidrug resistance. Collectively, however, 8.6% of the patients infected with genotype 1a and 1.4% of those infected with genotype 1b carried at least one dominant resistance mutation. Viral loads were high in the majority of these patients, suggesting that drug-resistant viral strains might achieve replication levels comparable to nonresistant viruses in vivo. CONCLUSION: Naturally occurring dominant STAT-C resistance mutations are common in treatment-naïve patients infected with HCV genotype 1. Their influence on treatment outcome should further be characterized to evaluate possible benefits of drug resistance testing for individual tailoring of drug combinations when treatment options are limited due to previous nonresponse to peginterferon and ribavirin.

Atorvastatin does not exhibit antiviral activity against HCV at conventional doses: a pilot clinical trial.

Cholesterol biosynthesis is an integral part of HCV RNA replication. Not only does HCV RNA replicate on lipid rafts, but it also requires cholesterol intermediates to replicate. In addition, it has been shown in vitro that several HMG-CoA reductase inhibitors can decrease HCV RNA replication by > or = 1 log. Therefore, we designed a clinical trial to evaluate the effect of atorvastatin on HCV RNA levels. In this prospective clinical trial, where patients served as their own control, 10 HCV-infected patients who required treatment for high cholesterol were given 20 mg atorvastatin per day. Although serum cholesterol and LDL predictably decreased significantly, there was no statistically significant change in week 4 and week 12 HCV RNA levels compared to pretreatment HCV RNA levels by the paired Student t test. It is unclear whether the addition of an HMG-CoA reductase inhibitor to interferon or a more potent inhibitor of cholesterol biosynthesis may be required to inhibit HCV RNA replication in vivo. In conclusion, atorvastatin, and likely all HMG-CoA reductase inhibitors, does not inhibit HCV RNA replication in vivo at conventional doses.

Immunologic evidence for lack of heterologous protection following resolution of HCV in patients with non-genotype 1 infection.

Chronic hepatitis C virus (HCV) infection is typically characterized by a lack of virus-specific CD4(+) T-cell-proliferative responses, but strong responses have been described in a subset of persons with persistent viremia. One possible explanation for these responses is that they were primed by an earlier resolved infection and do not recognize the current circulating virus. We defined all targeted epitopes using overlapping peptides corresponding to a genotype 1a strain in 44 patients chronically infected with different HCV genotypes (GT). Surprisingly, more HCV-specific CD4(+) T-cell responses were detected in patients with chronic non-GT1 infection compared with patients with chronic GT1 infection (P = .017). Notably, we found serologic evidence of a previous exposure to GT1 in 4 patients with non-GT1 infection, and these persons also demonstrated significantly more responses than non-GT1 patients in whom genotype and HCV serotype were identical (P < .001). Comparison of recognition of GT1-specific peptides to peptides representing autologous virus revealed the absence of cross-recognition of the autologous circulating virus. These data indicate that persistent HCV infection can occur in the presence of an HCV-specific T-cell response primed against a heterologous HCV strain, and suggest that clearance of 1 GT does not necessarily protect against subsequent exposure to a second GT.