Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera.

SARS-CoV-2 has caused over 2 million deaths in little over a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of the pandemic and error-prone virus replication is leading to the appearance of mutant viruses and potentially escape from antibody responses. Variant B.1.1.7, now dominant in the UK, with increased transmission, harbors 9 amino acid changes in the spike, including N501Y in the ACE2 interacting surface. We examine the ability of B.1.1.7 to evade antibody responses elicited by natural SARS-CoV-2 infection or vaccination. We map the impact of N501Y by structure/function analysis of a large panel of well-characterized monoclonal antibodies. B.1.1.7 is harder to neutralize than parental virus, compromising neutralization by some members of a major class of public antibodies through light-chain contacts with residue 501. However, widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed.

Antibiotic stewardship for urinary tract infection: A program evaluation.

Evidence supporting the use of antibiotic stewardship programs (ASP) is growing in a variety of healthcare settings for its association with improved patient outcomes, decreased resistance, and improved healthcare costs. There have been few studies supporting this evidence in long-term care facilities. This project involved a program evaluation of a long-term care facility's ASP for urinary tract infection (UTI) management. Improvement in appropriate diagnosing and antibiotic prescribing for UTI was noted, but no conclusions could be made regarding the effect on patient outcomes. The ASP was considered beneficial in this facility and highlighted areas for improvement, notably the need for sustained commitment by facility leadership and healthcare providers. Nurse practitioners are equipped with the skills necessary to assist facilities with education and implementation of systematic programs for judicious antibiotic prescribing.

A "Tea and Cookies" Approach: Co-designing Cancer Screening Interventions with Patients Living with Low Income.

BACKGROUND: In our primary care organization, we have observed income gradients in cancer screening for our patients despite outreach. We hypothesized that outreach strategies could be improved upon to be more compelling for our patients living with low income. OBJECTIVE: To use co-design to adapt our current strategies and create new strategies to improve cancer screening uptake for patients living with low income. DESIGN: An exploratory, qualitative study in two phases: interviews and focus groups. PARTICIPANTS: For interviews, we recruited 25 patient participants who were or had been overdue for cancer screening and had been identified by their provider as potentially living with low income. For subsequent focus groups, we recruited 14 patient participants, 11 of whom had participated in Phase I interviews. APPROACH: To analyse written transcripts, we took an iterative, inductive approach using content analysis and drawing on best practices in Grounded Theory methodology. Emergent themes were expanded and clarified to create a derived model of possible strategies to improve the experience of cancer screening and encourage screening uptake for patients living with low income. KEY RESULTS: Fear and competing priorities were two key barriers to cancer screening identified by patients. Patients believed that a warm and encouraging outreach approach would work best to increase cancer screening participation. Phone calls and group education were specifically suggested as potentially promising methods. However, these views were not universal; for example, women were more likely to be in favour of group education. CONCLUSIONS: We used input from patients living with low income to co-design a new approach to cancer screening in our primary care organization, an approach that could be broadly applicable to other contexts and settings. We learned from our patients that a multi-modal strategy will likely be best to maximize screening uptake.

A framework to build capacity for a reflex-testing program for Lynch syndrome.

PURPOSE: Lynch syndrome (LS) is the most common inherited cause of colorectal cancer. Although testing all colorectal tumors for LS is recommended, the uptake of reflex-testing programs within health systems has been limited. This multipronged study describes the design of a provincial program for reflex testing in Ontario, Canada. METHODS: We recruited key stakeholders to participate in qualitative interviews to explore the barriers and facilitators to the implementation of a reflex-testing program. Data were analyzed in an iterative manner, key themes identified, and a framework for a proposed program developed. RESULTS: Twenty-six key informants participated in our interviews, and several themes were identified. These included providing education for stakeholders (patients, primary care providers, surgeons); challenges with sustaining various resources (laboratory costs, increased workload for pathologists); ensuring consistency of reporting test results; and developing a plan to measure program success. Using these themes, a framework for the reflex-testing program was developed. At a subsequent stakeholder meeting, the framework was refined, and recommendations were identified. CONCLUSIONS: This study identifies factors to ensure the effective implementation of a population-level program for reflex LS testing. The final product is a prototype that can be utilized in other jurisdictions, taking into account local environmental considerations.

Learning by Example: An International Perspective on Reflex-Testing for Lynch Syndrome.

BACKGROUND: Lynch syndrome (LS), an autosomal dominant cancer syndrome, is the most common cause of hereditary colon cancer. Currently, however, less than 5% of patients with LS have been identified. Reflex-testing programs (in which tumors of patients with colorectal cancer are routinely evaluated for LS) have been proposed for better identification of affected individuals, yet the uptake of these programs within health care systems is limited. This study explored the structure, implementation challenges, and future directions of existing international population-based reflex LS testing programs. METHODS: The study identified existing reflex-testing LS programs through the current literature and through a qualitative sampling approach. Key informants from each program were interviewed. Qualitative data were analyzed using a grounded theory analytic technique approach. RESULTS: The interviews were completed by 26 informants across seven identified programs. Three key themes were identified: (1) tension between a program imposed on stakeholders (a top-down approach) versus initiation of the program at the stakeholder level (bottom-up approach), (2) identification of pathologists as drivers of program success, and (3) strategies to optimize possible LS patients liaising with genetic counselors. Barriers to successful implementation included lack of stakeholder engagement and concerns regarding cost. Facilitators included strong administration to coordinate patient tracking and flexibility during the implementation process. CONCLUSIONS: Existing reflex-testing LS programs have varying structures, standards, and protocols. Program design can have a direct effect on the uptake of genetic testing. These are important considerations in the large-scale planning of LS reflex-testing programs within health systems.

Treatment preferences of patients with relapsed and refractory multiple myeloma: a qualitative study.

BACKGROUND: Multiple myeloma is a haematological malignancy characterized by significant morbidity and mortality. This study sought to develop an in-depth understanding of patients' lived experiences of relapsed or refractory multiple myeloma (RRMM) and its treatment, and to identify which features of treatment were most important to them. METHODS: Qualitative interviews and focus groups (FGs) were conducted with 32 people living with RRMM across Canada. In Phase 1, interviews focused on participants' accounts of their experiences with the disease and its treatment and laid the groundwork for the FGs (Phase 2). The FGs developed a deeper understanding of patients' treatment priorities. Interview and FG transcripts were coded for emergent themes and patterns. RESULTS: The interviews identified important side effects that had significant impacts on patients' lives, including physical, cognitive, and psychological/emotional side effects. Participants also identified specific treatment features (attributes) that were important to them. These were compiled into a list and used in the FGs to understand patients' priorities. Higher prioritized attributes were: life expectancy, physical and cognitive side effects, and financial impact. Mode of administration, treatment intervals, psychological side effects, and sleep/mood effects were identified as lower priorities. CONCLUSIONS: RRMM and its treatments impact importantly on patients' quality-of-life across a range of domains. Patients prioritized treatment features that could enhance life expectancy, minimize side effects and offset financial burdens. IMPLICATIONS FOR CANCER SURVIVORS: A clear articulation of patient priorities can contribute to efforts to design treatment with patients' concerns in mind, thereby promoting a more patient-centered approach to care.

Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived CMs (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here, we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome. Human ESCs and iPSCs were differentiated into CMs using small molecule inhibitors. Fluorescence-activated cell sorting analysis confirmed ∼85% and ∼83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable with the human fetal heart marked by striated sarcomeres. Sub-acute transplantation of ESC-CMs and iPSC-CMs into nude rats post-MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non-coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective. We demonstrate that both ESC-CMs and iPSC-CMs can facilitate comparable cardiac repair. This is advantageous because, unlike allogeneic ESC-CMs used in therapy, autologous iPSC-CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future. Stem Cells 2017;35:2138-2149.

A nurse developed toolkit for long-term care ombudsmen.

Federal regulations provide all nursing home resident access to third party advocates, known as ombudsmen. The ombudsmen are provided unrestricted access to this vulnerable population for complaint investigation and protection of their federally mandated resident's rights. States autonomously administer their ombudsman programs, allowing latitude in hiring and training practices. The majority of state programs rely on a combination of paid and volunteer staff, with most staff lacking formal healthcare training. In an attempt to educate long-term care ombudsmen on common geriatric clinical diagnoses, a clinical toolkit was developed and ombudsmen employed by Alabama Department of Senior Services agreed to pilot test the toolkit. Results of the pilot test did not show ombudsmen with less experience would find the toolkit more useful. Results revealed that all ombudsmen regardless of length of tenure found the toolkit useful.

Effect of Body Type on Respiratory Kinematics in Female Classical Singers.

Breathing for singing is a highly contested issue in singing pedagogy with a wide variety of strategies recommended by teachers and the tendency for individuals to find more success with some strategies than others. The concept of body type as a determining factor has been suggested and supported by Hixon and Hoit, but little research has been conducted on this topic since and especially little research has been conducted using biologically female subjects. The investigators recruited eight female, classically trained singers and evaluated their body composition based on several anthropometric measurements (height, body mass, body fat percentage, and ectomorphy as determined by the Heath-Carter Somatotype system). Subjects were recruited from the greater San Antonio, Texas area and research was recorded on the campus of the University of Texas at San Antonio. The subjects were then fitted with reflective markers around the abdomen and thorax and stood on a platform with an eight-camera motion capture system recording their chest wall and abdominal movements while they performed a series of singing tasks. These singing tasks include a messa di voce, staccato arpeggio, and the first verse of "My Country 'Tis of Thee" in a variety of pitch ranges. Data on abdominal and thoracic movements was collected and compared according to body type to test the correlation between somatotype and breathing tendencies.

Zambia: A Narrative Review of Success and Challenges in Lymphatic Filariasis Elimination.

The establishment of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to stop the transmission of infection has significantly reduced the incidence of lymphatic filariasis, a debilitating mosquito-borne neglected tropical disease. The primary strategies that have been employed include mass drug administration (MDA) of anthelminthics and morbidity management and disability prevention (MMDP). While some countries have been able to reach elimination status in Africa, there is still active transmission of LF in Zambia. The nematode responsible for the disease is Wuchereria bancrofti, which is transmitted by Anopheles mosquitoes. To alleviate the suffering of those infected by the disease, the Zambian Ministry of Health launched a program to eliminate LF as a public health problem in 2003. This project reviewed the efforts to achieve the elimination of LF in Zambia, past and present government policies, and the anticipated challenges. MDAs have been conducted since 2014 and coverage has been between 87% and 92%. Zambia has now moved towards pre-transmission assessment surveys (PRETAS) and transmission assessment surveys (TAS). MMDP is a major priority and planned to be conducted between 2022 and 2026. COVID-19 presented a new challenge in the control of LF, while climate change, immigration, co-infections, and funding limitations will complicate further progress.

Loss of the E3 ubiquitin ligase TRIM67 alters the post-synaptic density proteome.

The E3 ubiquitin ligase TRIM67 is enriched in the central nervous system and is required for proper neuronal development. Previously we demonstrated TRIM67 coordinates with the closely related E3 ubiquitin ligase TRIM9 to regulate cytoskeletal dynamics downstream of the netrin-1 during axon guidance and axon branching in early neuronal morphogenesis. Interestingly, loss of Trim67 impacts cognitive flexibility in a spatial learning and memory task. Despite this behavioral phenotype, it was previously uninvestigated if TRIM67 was involved in synapse formation or function. Here we demonstrate TRIM67 localizes to the post-synaptic density (PSD) within dendritic spines. Furthermore, we show that loss of Trim67 significantly changes a subset of proteins within the PSD proteome, including changes in the regulation of the actin and microtubule cytoskeletons. Collectively, our data propose a synaptic role for TRIM67.

An analysis of ICAR recommendations for long-term care facilities in Alabama.

The Alabama Long-Term Care Strike Team was established in 2022 to help long-term care facilities build and maintain infection prevention and control (IPC) systems. Infection preventionists use CDC's Infection Control Assessment and Response (ICAR) tools to provide IPC-specific recommendations. Analysis of ICAR recommendations identified the 3 greatest training needs in Alabama: source control, hand hygiene, and environmental cleaning. The ICAR provides a standardized and objective way to monitor and mitigate IPC risk.

Designing a multifaceted survivorship care plan to meet the information and communication needs of breast cancer patients and their family physicians: results of a qualitative pilot study.

BACKGROUND: Following the completion of treatment and as they enter the follow-up phase, breast cancer patients (BCPs) often recount feeling 'lost in transition', and are left with many questions concerning how their ongoing care and monitoring for recurrence will be managed. Family physicians (FPs) also frequently report feeling ill-equipped to provide follow-up care to BCPs. In this three-phase qualitative pilot study we designed, implemented and evaluated a multi-faceted survivorship care plan (SCP) to address the information needs of BCPs at our facility and of their FPs. METHODS: In Phase 1 focus groups and individual interviews were conducted with 35 participants from three stakeholder groups (BCPs, FPs and oncology specialist health care providers (OHCPs)), to identify specific information needs. An SCP was then designed based on these findings, consisting of both web-based and paper-based tools (Phase 2). For Phase 3, both sets of tools were subsequently evaluated via focus groups and interviews with 26 participants. Interviews and focus groups were audio taped, transcribed and content analysed for emergent themes and patterns. RESULTS: In Phase 1 patients commented that web-based, paper-based and human resources components were desirable in any SCP. Patients did not focus exclusively on the post-treatment period, but instead spoke of evolving needs throughout their cancer journey. FPs indicated that any tools to support them must distill important information in a user-friendly format. In Phase 2, a pilot SCP was subsequently designed, consisting of both web-based and paper-based materials tailored specifically to the needs of BCPs as well as FPs. During Phase 3 (evaluation) BCPs indicated that the SCP was effective at addressing many of their needs, and offered suggestions for future improvements. Both patients and FPs found the pilot SCP to be an improvement from the previous standard of care. Patients perceived the quality of the BCP-FP relationship as integral to their comfort with FPs assuming follow-up responsibilities. CONCLUSIONS: This pilot multi-component SCP shows promise in addressing the information needs of BCPs and the FPs who care for them. Next steps include refinement of the different SCP components, further evaluation (including usability testing), and planning for more extensive implementation.

The environmental impact of surgery: A systematic review.

BACKGROUND: Climate change is a significant public health threat. Health care comprises 10% of greenhouse gas emissions in the United States, where surgery is especially resource intensive. We did a systematic review to assess and summarize the published evidence of the environmental impact of surgery. METHODS: We searched Medline, Embase, Web of Science, and GreenFILE databases for publications that report any environmental impact measure by all surgical subspecialties, including anesthesia. Inclusion criteria were published in English, original research, and passed peer review. Because data were heterogeneous and the aim was broad, we conducted a qualitative summary of data. Where possible, we compare impact measures. RESULTS: In the study, 167 articles were identified by our search strategy and reviewed, of which 55 studies met criteria. Eight were about anesthesia, 27 about operating room waste, and 6 were life cycle assessments. Other topics include carbon footprint and greenhouse gas emissions. Nine papers fell into 2 or more categories. Overall, the operating room is a significant source of emissions and waste. Using anesthetic gases with low global warming potential reduces operating room emissions without compromising patient safety. Operating room waste is often disposed of improperly, often due to convenience or knowledge gaps. There are environmental benefits to replacing disposable materials with reusable equivalents, and to proper recycling. Surgeons can help implement these changes at their institution. CONCLUSION: Although there is a clear need to lower the carbon footprint of surgery, the quality of research with which to inform protocol changes is deficient overall. Our attempt to quantify surgery's carbon footprint yielded heterogeneous data and few standardized, actionable recommendations. However, this data serves as a starting point for important future initiatives to decrease the environmental impact of surgery.

Nimble Approach: fast, adapting, calculating and ethically mindful approach to managing colorectal cancer screening programmes during a pandemic.

OBJECTIVE: To describe a conceptual framework that provides understanding of the challenges encountered and the adaptive approaches taken by organised colorectal cancer (CRC) screening programmes during the initial phase of the COVID-19 pandemic. DESIGN: This was a qualitative case study of international CRC screening programmes. Semi-structured interviews were conducted with programme managers/leaders and programme experts, researchers and clinical leaders of large, population-based screening programmes. Data analysis, using elements of grounded theory, as well as cross-cases analysis was conducted by two experienced qualitative researchers. RESULTS: 19 participants were interviewed from seven programmes in North America, Europe and Australasia. A conceptual framework ('Nimble Approach') was the key outcome of the analysis. Four concepts constitute this approach to managing CRC screening programmes during COVID-19: Fast (meeting the need to make decisions and communicate quickly), Adapting (flexibly and creatively managing testing/colonoscopy capacity, access and backlogs), Calculating (modelling and actively monitoring programmes to inform decision-making and support programme quality) and Ethically Mindful (considering ethical conundrums emerging from programme responses). Highly integrated programmes, those with highly integrated communication networks, and that managed greater portions of the screening process seemed best positioned to respond to the crisis. CONCLUSIONS: The Nimble Approach has potentially broad applications; it can be deployed to effectively respond to programme-specific challenges or manage CRC programmes during future pandemics, other health crises or emergencies.

Development of anti-Crimean-Congo hemorrhagic fever virus Gc and NP-specific ELISA for detection of antibodies in domestic animal sera.

Crimean-Congo hemorrhagic fever (CCHF) is a priority emerging disease. CCHF, caused by the CCHF virus (CCHFV), can lead to hemorrhagic fever in humans with severe cases often having fatal outcomes. CCHFV is maintained within a tick-vertebrate-tick cycle, which includes domestic animals. Domestic animals infected with CCHFV do not show clinical signs of the disease and the presence of antibodies in the serum can provide evidence of their exposure to the virus. Current serological tests are specific to either one CCHFV antigen or the whole virus antigen. Here, we present the development of two in-house ELISAs for the detection of serum IgG that is specific for two different CCHFV antigens: glycoprotein Gc (CCHFV Gc) and nucleoprotein (CCHFV NP). We demonstrate that these two assays were able to detect anti-CCHFV Gc-specific and anti-CCHFV NP-specific IgG in sheep from endemic CCHFV areas with high specificity, providing new insight into the heterogeneity of the immune response induced by natural infection with CCHFV in domestic animals.

Use of Long-Term Care Facilities for Primary Care Nurse Practitioner Students.

BACKGROUND: Family and adult-gerontology primary care nurse practitioner (NP) students must obtain patient clinical hours caring for older adults. Primary care occurs in a variety of settings, including long-term care (LTC) facilities. Anecdotal reports indicate that faculty in some primary NP academic programs do not recognize the robust primary care opportunities that exist in LTC settings. METHOD: This article describes a professional nursing organization's process of researching the appropriateness of designating LTC clinical hours as allowable primary care clinical experiences for NP students. RESULTS: The NP serves as an integral member of the LTC team, providing the same elements of primary care provided in traditional ambulatory care settings. CONCLUSION: Older adults receiving primary care in LTC settings have a variety of health care needs, including assessment and management of acute and chronic conditions. A position statement was developed for primary care NP students and endorsed by 22 professional organizations and NP programs. [J Nurs Educ. 2021;60(2):99-102.].

Care in the Community: Opportunities to improve cancer screening uptake for people living with low income.

Despite organized provincial cancer screening programs, people living with low income consistently have lower rates of screening in Ontario, Canada than their more socioeconomically advantaged peers. We previously published results of a two-phase, exploratory qualitative study involving both interviews and focus groups whose objective was to integrate knowledge of people living with low income on how to improve primary care strategies aimed at increasing cancer screening uptake. In the current paper, we report previously unpublished findings from that study that identify how taking a community outreach approach in primary care may lead to increased cancer screening uptake among people living with low income. Participants told us that they saw value in a community outreach approach to cancer screening. They recommended specific actionable approaches, in particular, mobile community-based screening and community information sessions, and recommended taking an ethno-specific lens depending on the communities being targeted. Participants expressed a desire for primary care providers to go out into the community to learn more about the whole patient, such as could be achieved with home visits, but they simultaneously believed that this may be challenging in urban settings and in the context of perceived physician shortages. Models of primary care that provide support to an entire local community and provide some of their services directly in that community may have a meaningful impact on cancer screening for socially marginalized groups.

Quantification of SARS-CoV-2 neutralizing antibody by wild-type plaque reduction neutralization, microneutralization and pseudotyped virus neutralization assays.

Virus neutralization assays measure neutralizing antibodies in serum and plasma, and the plaque reduction neutralization test (PRNT) is considered the gold standard for measuring levels of these antibodies for many viral diseases. We have developed procedures for the standard PRNT, microneutralization assay (MNA) and pseudotyped virus neutralization assay (PNA) for severe acute respiratory syndrome coronavirus 2. The MNA offers advantages over the PRNT by reducing assay time, allowing increased throughput and reducing operator workload while remaining dependent upon the use of wild-type virus. This ensures that all severe acute respiratory syndrome coronavirus 2 antigens are present, but Biosafety Level 3 facilities are required. In addition to the advantages of MNA, PNA can be performed with lower biocontainment (Biosafety Level 2 facilities) and allows for further increases in throughput. For each new vaccine, it is critical to ensure good correlation of the neutralizing activity measured using PNA against the PRNT or MNA. These assays have been used in the development and licensure of the ChAdOx1 nCoV-19 (AstraZeneca; Oxford University) and Ad26.COV2.S (Janssen) coronavirus disease 2019 vaccines and are critical for demonstrating bioequivalence of future vaccines.

Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques.

There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines. We have used ferrets and rhesus macaques challenged with SARS-CoV-2 to assess the potential for VED in animals vaccinated with formaldehyde-inactivated SARS-CoV-2 (FIV) formulated with Alhydrogel, compared to a negative control vaccine. We showed no evidence of enhanced disease in ferrets or rhesus macaques given FIV except for mild transient enhanced disease seen 7 days after infection in ferrets. This increased lung pathology was observed at day 7 but was resolved by day 15. We also demonstrate that formaldehyde treatment of SARS-CoV-2 reduces exposure of the spike receptor binding domain providing a mechanistic explanation for suboptimal immunity.