ATTAC! Development of a Novel Advanced Trauma Team Application Course.

BACKGROUND: Although existing trauma nurse courses provide basic education, advanced courses with simulation experiences that enhance team leadership, communication, and workflows are lacking. OBJECTIVE: To design and implement the Advanced Trauma Team Application Course (ATTAC) to promote advanced skills for nurses and respiratory therapists with varied experience and skill levels. METHODS: Trauma nurses and respiratory therapists were selected to participate based on years of experience and the novice to expert nurse model. Two nurses from each level (excluding novice) participated, ensuring a diverse cohort to promote development and mentorship. The 11-module course was presented over 12 months. A five-question survey was employed at the end of each module to self-evaluate assessment skills, communication skills, and comfort for trauma patient care. Participants rated skills and comfort on a "0-10" scale, with 0 being "not at all" to 10 being "extensively." RESULTS: The pilot course was conducted from May 2019 to May 2020 at a Level II trauma center in the Northwest United States. Nurses reported ATTAC improved assessment skills, team communication, and comfort in caring for trauma patients (mean = 9.4; 95% CI [9.0, 9.8]; scale of 0-10). Participants indicated scenarios closely mimicked real-world situations; concept application commenced directly following each session. CONCLUSION: This novel approach to advanced trauma education promotes development of advanced skills that enable nurses to anticipate needs rather than being reactive, engage in critical thinking, and adapt to rapidly changing patient conditions.

Evolution of the joint International Atomic Energy Agency (IAEA), International Agency for Research on Cancer (IARC), and WHO cancer control assessments (imPACT Reviews).

Before 2005, cancer and other non-communicable diseases were not yet health and development agenda priorities. Since the 2005 World Health Assembly Resolution, which encouraged WHO, the International Agency for Research on Cancer (IARC), and the International Atomic Energy Agency (IAEA) to jointly work on cancer control, progress was achieved in low-income and middle-income countries on a small scale. Recently, rapid acceleration in UN collaboration and global cancer activities has focused attention in global cancer control. This Policy Review presents the evolution of the IAEA, IARC, and WHO joint advisory service to help countries assess needs and capacities throughout the comprehensive cancer control continuum. We also highlight examples per country, showcasing a snapshot of global good practices to foster an exchange of experiences for continuous improvement in the integrated mission of Programme of Action for Cancer Therapy (imPACT) reviews and follow-up support. The future success of progress in cancer control lies in the high-level political and financial commitments. Linking the improvement of cancer services to the strengthening of health systems after the COVID-19 pandemic will also ensure ongoing advances in the delivery of care across the cancer control continuum.

Situational analysis of breast health care systems: Why context matters.

BACKGROUND: Implementation of evidence-based, resource-appropriate guidelines for breast cancer control should be preceded by a baseline assessment or situational analysis to assess breast health infrastructure, workforce capacity, patient pathways, existing practices, accessibility, and costs. METHODS: To support the assessment of breast health care systems within the broader context in which they exist, the Breast Health Global Initiative (BHGI) developed, tested, and refined a set of situational analysis tools with which to guide the assessment of breast health care capacity, identify the relative strengths and weaknesses of the health system, and support stakeholders in prioritizing actionable items to advance breast cancer care using evidence-based strategies tailored to their setting. The tools address 6 domains of breast health care delivery: 1) breast cancer early detection practices; 2) breast cancer awareness programs; 3) the availability of breast cancer surgery; 4) the availability of pathology; 5) the availability of radiotherapy, and 6) the availability of systemic therapy services. The current study also describes the more comprehensive International Atomic Energy Agency Programme of Action for Cancer Therapy (PACT) integrated missions for PACT (imPACT) review. RESULTS: As of 2020, 5 formal BHGI situational analyses have been performed in India, Brazil, Panama, Tanzania, and Uganda. As of August 2019, a total of 100 imPACT reviews have been conducted in 91 countries. These assessments can contribute to more informed policymaking. CONCLUSIONS: Situational analyses are a prerequisite for the development of resource-appropriate strategies with which to advance breast cancer control in any setting and should assess services across the entire breast health care continuum as well as the broader structural, sociocultural, personal, and financial contexts within which they operate.

A low-passage insect-cell isolate of bluetongue virus uses a macropinocytosis-like entry pathway to infect natural target cells derived from the bovine host.

Bluetongue virus (BTV) causes an economically important disease in domestic and wildlife ruminants and is transmitted by Culicoides biting midges. In ruminants, BTV has a wide cell tropism that includes endothelial cells of vascular and lymphatic vessels as important cell targets for virus replication, and several cell types of the immune system including monocytes, macrophages and dendritic cells. Thus, cell-entry represents a particular challenge for BTV as it infects many different cell types in widely diverse vertebrate and invertebrate hosts. Improved understanding of BTV cell-entry could lead to novel antiviral approaches that can block virus transmission from cell to cell between its invertebrate and vertebrate hosts. Here, we have investigated BTV cell-entry using endothelial cells derived from the natural bovine host (BFA cells) and purified whole virus particles of a low-passage, insect-cell isolate of a virulent strain of BTV-1. Our results show that the main entry pathway for infection of BFA cells is dependent on actin and dynamin, and shares certain characteristics with macropinocytosis. The ability to use a macropinocytosis-like entry route could explain the diverse cell tropism of BTV and contribute to the efficiency of transmission between vertebrate and invertebrate hosts.

National cancer control plans: a global analysis.

There is increasing global recognition that national cancer plans are crucial to effectively address the cancer burden and to prioritise and coordinate programmes. We did a global analysis of available national cancer-related health plans using a standardised assessment questionnaire to assess their inclusion of elements that characterise an effective cancer plan and, thereby, improve understanding of the strengths and limitations of existing plans. The results show progress in the development of cancer plans, as well as in the inclusion of stakeholders in plan development, but little evidence of their implementation. Areas of continued unmet need include setting of realistic priorities, specification of programmes for cancer management, allocation of appropriate budgets, monitoring and evaluation of plan implementation, promotion of research, and strengthening of information systems. We found that countries with a non-communicable disease (NCD) plan but no national cancer control plan (NCCP) were less likely than countries with an NCCP and NCP plan or an NCCP only to have comprehensive, coherent, or consistent plans. As countries move towards universal health coverage, greater emphasis is needed on developing NCCPs that are evidence based, financed, and implemented to ensure translation into action.

Assessment of a fully automated high-throughput DNA extraction method from formalin-fixed, paraffin-embedded tissue for KRAS, and BRAF somatic mutation analysis.

Preoperative biopsies or imbedded cytological cells will become more and more a primary source of tissue for molecular diagnostic analyses as a result of novel neo-adjuvant treatment regimens for several cancer types. Furthermore there is a growing need to examine metastatic cancer tissue. Hence, nucleic acids need to be reliably isolated and analyzed from small amounts of formalin-fixed and paraffin-embedded (FFPE) tissue. The limited numbers of (tumor) cells in these samples make high quality and sensitive DNA isolation challenging. Also demands for faster turnaround times are growing. Therefore, we evaluated a fully automated DNA/RNA isolation system and compared this with a manual, classical routine molecular pathology method. We compared the quality of the isolates from both tissue cores and micro-dissection for detection of hotspot mutations in KRAS, BRAF applying hydrolysis probe assays. In addition we determined whether the automated method decreases the hands-on-time and turnaround times in routine molecular pathology workflow. In conclusion, the automated method delivers high quality DNA from both small FFPE tissue cores and micro-dissected tissue material. In comparison to classical methods, less than 50% of starting tissue was sufficient as input for micro-dissection. Turnaround times decreased significantly and 50% less hands-on time was needed.

Ten Years of the International Cancer Control Partnership: Promoting National Cancer Control Plans to Shape the Health System Response for Cancer Control.

Growing premature mortality because of cancer is an increasing public health concern in all countries. This article reviews 10 years of the International Cancer Control Partnership (ICCP) considering the themes of National Cancer Control Plan (NCCP) support, technical assistance, governance, and the renewed momentum of global calls to action. ICCP has provided key resources for the cancer community by hosting a portal with national cancer control and noncommunicable disease (NCD) plans, strategies, guidelines, and key implementation guides for a growing community of best practices. ICCP partners have responded to the changing needs of country planners, adjusting technical guidance as needs evolve from planning to implementation at the national level with an associated shift to peer-to-peer learning and knowledge exchange. The ICCP offer to assist countries in cancer planning continues to be relevant as countries focus on implementation of global initiatives for breast, cervical, and childhood cancers. These initiatives are important to drive priority actions and a systems approach in the emerging road map on NCDs-a message that will be supported by a second global review of NCCPs in 2023. This is critical for driving national action in all countries on cancer and other NCDs in line with global health commitments made for 2030 and adopted by the United Nations General Assemblies. ICCP sees robust systems and financial planning for implementation, monitoring, and evaluation of NCCPs and protection from cancer-related catastrophic expenditure, as critical to longer-term sustainability and success. ICCP calls for national policymakers to prioritize integration of cancer prevention and control into emerging universal health care approaches, including pandemic preparedness/health system resilience and calls for an equity focus in new NCCPs.

Innovating tuberculosis prevention to achieve universal health coverage in the Philippines.

To contribute to tuberculosis (TB) elimination, TB preventive treatment (TPT) should integrate innovative approaches including tele-contact investigation (TCI), mathematical modelling, and participatory governance. Aligning with the World Health Organisation's primary health care framework, supply is provided by the provincial health system, demand is cultivated by the community, while governance is represented by the governor, who oversees the health leadership structure, local policies, and allocation of resources. A healthy dynamic between these three components is required to achieve universal health coverage (UHC). Because of their potential to integrate health systems and engage communities, primary health care principles underpin an effective approach to TB prevention. First, the provincial health system should connect with the community through TCI to transform the status quo of passive service delivery. Second, community participation should strengthen the linkage between the health system and governance, which ensures that community action plans are aligned with provincial TPT targets. Third, governance should leverage mathematical modelling to allocate resources to those with greatest need. Central to this is a reliable TB information system that should validate a robust mathematical model to measure cost-effectiveness of the intervention. Collectively, this holistic approach to TB prevention could provide a proof-of-concept that investing in primary health care is the key to UHC.

Radiotherapy prioritization in 143 national cancer control plans: Correlation with radiotherapy machine availability, geography and income level.

BACKGROUND: In 2015, the Global Task Force on Radiotherapy for Cancer Control (GTFRCC) called for 80% of National Cancer Control Plans (NCCP) to include radiotherapy by 2020. As part of the ongoing ESTRO Global Impact of Radiotherapy in Oncology (GIRO) project, we assessed whether inclusion of radiotherapy in NCCPs correlates with radiotherapy machine availability, national income, and geographic region. METHODS: A previously validated checklist was used to determine whether radiotherapy was included in each country's NCCP. We applied the CCORE optimal radiotherapy utilisation model to the GLOBOCAN 2020 data to estimate the demand for radiotherapy and compared this to the International Atomic Energy Agency (IAEA) Directory of Radiotherapy Centres (DIRAC) supply data, stratifying by income level and world region. World regions were defined according to the IAEA. FINDINGS: Complete data (including GLOBOCAN 2020, DIRAC and NCCP) was available for 143 countries. Over half (55%, n = 79) included a radiotherapy-specific checklist item within the plan. Countries which included radiotherapy services planning in their NCCP had a higher median number of machines (1.68 vs 0.75 machines/1000 patients needing radiotherapy, p < 0.001). There was significant regional and income-level heterogeneity in the inclusion of radiotherapy-related items in NCCPs. Low-income and Asia-Pacific countries were least likely to include radiation oncology services planning in their NCCP (p = 0.06 and p = 0.003, respectively). Few countries in the Asia-Pacific (18.6%) had a plan to develop or maintain radiation services, compared to 57% of countries in Europe. INTERPRETATION: Only 55% of current NCCPs included any information regarding radiotherapy, below the GTFRCC's target of 80%. Prioritisation of radiotherapy in NCCPs was correlated with radiotherapy machine availability. There was regional and income-level heterogeneity regarding the inclusion of specific radiotherapy checklist items in the NCCPs. Ongoing efforts are needed to promote the inclusion of radiotherapy in future iterations of NCCPs in order to improve global access to radiation treatment. FUNDING: No direct funding was used in this research.

Integration of collaborative medication therapy management in a safety net patient-centered medical home.

OBJECTIVE: To describe the integration of collaborative medication therapy management (CMTM) into a safety net patient-centered medical home (PCMH). SETTING: Federally qualified Health Care for the Homeless clinic in Richmond, VA, from October 2008 to June 2010. PRACTICE DESCRIPTION: A CMTM model was developed by pharmacists, physicians, nurse practitioners, and social workers and integrated with a PCMH. CMTM, as delivered, consisted of (1) medication assessment, (2) development of care plan, and (3) follow-up. PRACTICE INNOVATION: CMTM is integrated with the medical and mental health clinics of PCMH in a safety net setting that serves homeless individuals. MAIN OUTCOME MEASURES: Number of patients having a CMTM encounter, number and type of medication-related problems identified for a subset of patients in the mental health and medical clinics, pharmacist recommendations, and acceptance rate of pharmacist recommendations. RESULTS: Since October 2008, 695 patients have had a CMTM encounter. An analysis of 209 patients in the mental health clinic indicated that 425 medication-related problems were identified (2.0/patient). Pharmacists made 452 recommendations to resolve problems, and 384 (85%) pharmacist recommendations were accepted by providers and/or patients. For 40 patients in the medical clinic, 205 medication-related problems were identified (5.1/patient). Pharmacists made 217 recommendations to resolve the problems, and 194 (89%) recommendations were accepted. CONCLUSION: Integrating CMTM with a safety net PCMH was a valuable patient-centered strategy for addressing medication-related problems among homeless individuals. The high acceptance rate of pharmacist recommendations demonstrates the successful integration of pharmacist services.

High-dose Mycobacterium tuberculosis aerosol challenge cannot overcome BCG-induced protection in Chinese origin cynomolgus macaques; implications of natural resistance for vaccine evaluation.

This study describes the use of cynomolgus macaques of Chinese origin (CCM) to evaluate the efficacy and immunogenicity of the BCG vaccine against high dose aerosol Mycobacterium tuberculosis challenge. Progressive disease developed in three of the unvaccinated animals within 10 weeks of challenge, whereas all six vaccinated animals controlled disease for 26 weeks. Three unvaccinated animals limited disease progression, highlighting the intrinsic ability of this macaque species to control disease in comparison to macaques of other species and genotypes. Low levels of IFNγ were induced by BCG vaccination in CCM suggesting that IFNγ alone does not provide a sufficiently sensitive biomarker of vaccination in this model. An early response after challenge, together with the natural bias towards terminal effector memory T-cell populations and the contribution of monocytes appears to enhance the ability of CCM to naturally control infection. The high dose aerosol challenge model of CCM has value for examination of the host immune system to characterise control of infection which would influence future vaccine design. Although it may not be the preferred platform for the assessment of prophylactic vaccine candidates, the model could be well suited for testing post-exposure vaccination strategies and drug evaluation studies.

Response to antiretroviral therapy after a single, peripartum dose of nevirapine.

BACKGROUND: A single dose of nevirapine during labor reduces perinatal transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to viral nevirapine resistance mutations in mothers and infants. METHODS: We studied the response to nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine. The primary end point for mothers and infants was virologic failure by the 6-month visit after initiation of antiretroviral treatment, estimated within groups by the Kaplan-Meier method. RESULTS: Of 218 women who started antiretroviral treatment, 112 had received a single dose of nevirapine and 106 had received placebo. By the 6-month visit after the initiation of antiretroviral treatment, 5.0% of the women who had received placebo had virologic failure, as compared with 18.4% of those who had received a single dose of nevirapine (P=0.002). Among 60 women starting antiretroviral treatment within 6 months after receiving placebo or a single dose of nevirapine, no women in the placebo group and 41.7% in the nevirapine group had virologic failure (P<0.001). In contrast, virologic failure rates did not differ significantly between the placebo group and the nevirapine group among 158 women starting antiretroviral treatment 6 months or more post partum (7.8% and 12.0%, respectively; P=0.39). Thirty infants also began antiretroviral treatment (15 in the placebo group and 15 in the nevirapine group). Virologic failure by the 6-month visit occurred in significantly more infants who had received a single dose of nevirapine than in infants who had received placebo (P<0.001). Maternal and infant findings did not change qualitatively by 12 and 24 months after the initiation of antiretroviral treatment. CONCLUSIONS: Women who received a single dose of nevirapine to prevent perinatal transmission of HIV-1 had higher rates of virologic failure with subsequent nevirapine-based antiretroviral therapy than did women without previous exposure to nevirapine. However, this applied only when nevirapine-based antiretroviral therapy was initiated within 6 months after receipt of a single, peripartum dose of nevirapine. (ClinicalTrials.gov number, NCT00197587 [ClinicalTrials.gov].).

Substitution of warthog NF-κB motifs into RELA of domestic pigs is not sufficient to confer resilience to African swine fever virus.

African swine fever virus (ASFV) causes a lethal, haemorrhagic disease in domestic swine that threatens pig production across the globe. Unlike domestic pigs, warthogs, which are wildlife hosts of the virus, do not succumb to the lethal effects of infection. There are three amino acid differences between the sequence of the warthog and domestic pig RELA protein; a subunit of the NF-κB transcription factor that plays a key role in regulating the immune response to infections. Domestic pigs with all 3 or 2 of the amino acids from the warthog RELA orthologue have been generated by gene editing. To assess if these variations confer resilience to ASF we established an intranasal challenge model with a moderately virulent ASFV. No difference in clinical, virological or pathological parameters were observed in domestic pigs with the 2 amino acid substitution. Domestic pigs with all 3 amino acids found in warthog RELA were not resilient to ASF but a delay in onset of clinical signs and less viral DNA in blood samples and nasal secretions was observed in some animals. Inclusion of these and additional warthog genetic traits into domestic pigs may be one way to assist in combating the devastating impact of ASFV.

The Translational Research Working Group developmental pathways: introduction and overview.

The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of the National Cancer Institute's investment in translational research and envision its future in an inclusive, representative, and transparent manner. To clarify the challenges facing translational research and facilitate its deliberations, the TRWG conceptualized translational research as a set of developmental processes or pathways focused on various clinical goals. Drawing on the collective knowledge of the TRWG members, six pathways were derived, with two addressing the development of tools designed to characterize an individual's cancer-related health status (biospecimen-based and image-based assessment modalities) and four addressing the development of interventions intended to change cancer-related health status (drugs or biological agents, immune response modifiers, interventive devices, and life-style alterations). The pathways, which share a number of common structural elements, are graphically represented by schematic flowcharts that capture relevant contingencies, decision points, and interdependencies. They are conceived not as comprehensive descriptions of the corresponding real-world processes but as tools designed to serve specific purposes including research program management and research project management, coordination of research efforts, and professional and lay education and communication. Further development of the pathways is encouraged, as is application of the pathway concept to translational research on other diseases.

Knowledge Summaries for Comprehensive Breast Cancer Control.

Breast cancer is the most common cancer in women worldwide, affecting > 1.6 million women each year, projected to increase to 2.2 million cases annually by 2025. A disproportionate number of the > 500,000 women who die as a result of breast cancer each year reside in low-resource settings. Breast cancer control is an important component of cancer control planning and women's health programs, and tools are needed across the care continuum to reduce the cancer burden, especially in low-resource settings. Cancer control planning is complex and multifaceted. Evidence shows that outcomes are improved when prevention, early diagnosis, treatment, and palliation are integrated and synchronously developed within a country/region's health plan. The Knowledge Summaries for Comprehensive Breast Cancer Control are the product of a multiyear collaboration led by the Union for International Cancer Control, Breast Health Global Initiative, Pan American Health Organization, and Center for Global Health of the US National Cancer Institute. Fourteen knowledge summaries distilled from evidence-based, resource-stratified guidelines, and aligned with WHO guidance on breast cancer control, build a framework for resource prioritization pathways and delivery systems for breast cancer control at four levels of available resources: basic, limited, enhanced, and maximal. Each summary contains relevant content to inform breast cancer policy, clinical care, and advocacy, aiding in the development and implementation of policies and programs. These tools provide a common platform for stakeholders, including policymakers, administrators, clinicians, and advocates to engage in decision making appropriate to their local setting. The goal is to facilitate evidence-based policy actions and urgently advance implementation of an integrated approach to reduce breast cancer mortality and improve quality of life.

Building a Network of Health Professionals for Breast and Cervical Cancer Control in the Andean Region.

PURPOSE: Cancer mortality is approximately twice as high in Latin American countries than in more developed countries. In particular, the countries of the high Andean region of Latin America carry a double burden of breast and cervical cancers. In these countries, there are disproportionately higher mortality to incidence ratios compared with other regions in Latin America. The US National Cancer Institute's Center for Global Health, the Pan American Health Organization, and the Ministry of Health in Peru collaborated to design and execute an education and advocacy workshop in Lima, Peru. The workshop was convened to discuss regional challenges and practices, as well as to support the implementation of Plan Esperanza, Peru's national cancer control plan. METHODS: Workshop participants included local and international experts to present the state of the science, health practitioners, and advocacy groups to discuss unique barriers that women in the region experience. RESULTS: Inequalities in access to and distribution of medical expertise, lack of continuity of cancer control plans, and the need for sustained public buy-in emerged as obstacles. CONCLUSION: The workshop provided a forum to discuss key issues regarding breast and cervical cancer control among health professionals and advocates in Peru and the region. This article outlines the resulting recommendations.

Characterization of the Myeloid Cell Populations' Resident in the Porcine Palatine Tonsil.

The palatine tonsil is the portal of entry for food and air and is continuously subjected to environmental challenges, including pathogens, which use the tonsil and pharynx as a primary site of replication. In pigs, this includes the viruses causing porcine respiratory and reproductive syndrome, and classical and African swine fever; diseases that have impacted the pig production industry globally. Despite the importance of tonsils in host defense, little is known regarding the phenotype of the myeloid cells resident in the porcine tonsil. Here, we have characterized five myeloid cell populations that align to orthologous populations defined in other mammalian species: a CD4+ plasmacytoid dendritic cell (DC) defined by expression of the conserved markers E2.2 and IRF-7, a conventional dendritic cell (cDC1) population expressing CADM1highCD172alow and high levels of XCR1 able to activate allogeneic CD4 and CD8 T cells; a cDC2 population of CADM1dim cells expressing FLT3, IRF4, and CSF1R with an ability to activate allogeneic CD4 T cells; CD163+ macrophages (MÏ´s) defined by high levels of endocytosis and responsiveness to LPS and finally a CD14+ population likely derived from the myelomonocytic lineage, which showed the highest levels of endocytosis, a capacity for activation of CD4+ memory T cells, combined with lower relative expression of FLT3. Increased knowledge regarding the phenotypic and functional properties of myeloid cells resident in porcine tonsil will enable these cells to be targeted for future vaccination strategies to current and emerging porcine viruses.