Care-home Nurses' responses to the COVID-19 pandemic: Managing ethical conundrums at personal cost: A qualitative study

Introduction: The COVID-19 pandemic had an unprecedented effect on those living and working in care-homes for older people, as residents were particularly vulnerable to contracting the SARS-CoV-2 virus, associated with high morbidity and mortality. Often undervalued, care-home nurses (RNs) are leaders, managing complex care while working in isolation from their professional peers. The pandemic made this more apparent, when care and treatments for COVID-19 were initially unknown, isolation increased due to withdrawal of many professional health services, accompanied by staff shortages. Objective: To explore RNs' experiences of working in older people's care-homes during the COVID-19 pandemic. Design: Qualitative interview study. Setting: Care-homes for older people in England and Scotland, UK. Methods: Recruitment via direct contact with care-homes, social media, and links provided by national partners, then purposive sampling for age, gender, type of care-home, and location. Data collected through one-to-one online interviews using topic guide developed collaboratively with care-home nurses, focusing on how COVID-19 impacted on nurses' resilience and mental wellbeing. Data analyzed thematically using Tronto's ethics of care framework to guide development of interpretative themes. Results: Eighteen nurses (16 female; 16 adult, and two mental health nurses) were interviewed March–June 2021; majority aged 46–55 years; mean time registered with Nursing and Midwifery Council: 19 years; 17 had nursed residents with COVID-19. RNs' experiences resonated with Tronto's five tenets of ethical care: attentiveness, responsibility, competence, responsiveness, and solidarity. All nurses described being attentive to needs of others, but were less attentive to their own needs, which came at personal cost. RNs were aware of their professional and leadership responsibilities, being as responsive as they could be to resident needs, processing and sharing rapidly changing guidance and implementing appropriate infection control measures, but felt that relatives and regulatory bodies were not always appreciative. RNs developed enhanced clinical skills, increasing their professional standing, but reported having to compromise care, leading to moral distress. Broadly, participants reported a sense of solidarity across care-home staff and working together to cope with the crisis. Conclusion: Care-home nurses felt unprepared for managing the COVID-19 pandemic, many experienced moral distress. Supporting care-home nurses to recover from the pandemic is essential to maintain a healthy, stable workforce and needs to be specific to care-home RNs, recognizing their unique pandemic experiences. Support for RNs will likely benefit other care-home workers either directly through wider roll-out, or indirectly through improved wellbeing of nurse leaders. Clinical relevance: The COVID-19 pandemic, an international public health emergency, created many challenges for Registered Nurses (RNs) working in long-term care facilities for older people, as residents were particularly vulnerable to the impact of the SARS-CoV-2 virus. Care-home RNs faced challenges distinct from their hospital-based nursing peers and non-nursing social care colleagues due to their isolation, leadership roles, professional legal obligations, and ethical responsibilities, leading to psychological distress on the one hand, but also a newly found confidence in their existing and newly developed skills, and increased recognition by the wider health community of their specialisms

The Changing Face of Water: A Dynamic Reflection of Antibiotic Resistance Across Landscapes

Little is known about the role of surface water in the propagation of antibiotic resistance (AR), or the relationship between AR and water quality declines. While healthcare and agricultural sectors are considered the main contributors to AR dissemination, few studies have been conducted in their absence. Using linear models and Bayesian kriging, we evaluate AR among Escherichia coli water isolates collected bimonthly from the Chobe River in Northern Botswana (n = 1997, n = 414 water samples; July 2011–May 2012) in relation to water quality dynamics (E. coli, fecal coliform, and total suspended solids), land use, season, and AR in wildlife and humans within this system. No commercial agricultural or large medical facilities exist within this region. Here, we identify widespread AR in surface water, with land use and season significant predicators of AR levels. Mean AR was significantly higher in the wet season than the dry season (p = 0.003), and highest in the urban landscape (2.15, SD = 0.098) than the protected landscape (1.39, SD = 0.051). In-water E. coli concentrations were significantly positively associated with mean AR in the wet season (p < 0.001) but not in the dry season (p = 0.110), with TSS negatively associated with mean AR across seasons (p = 0.016 and p = 0.029), identifying temporal and spatial relationships between water quality variables and AR. Importantly, when human, water, and wildlife isolates were examined, similar AR profiles were identified (p < 0.001). Our results suggest that direct human inputs are sufficient for extensive dispersal of AR into the environment, with landscape features, season, and water quality variables influencing AR dynamics. Focused and expensive efforts to minimize pollution from agricultural sources, while important, may only provide incremental benefits to the management of AR across complex landscapes. Controlling direct human AR inputs into the environment remains a critical and pressing challenge

Administration of Intranasal Insulin During Cardiopulmonary Resuscitation Improves Neurological Outcomes After Cardiac Arrest

INTRODUCTION: Over 325,000 people die from cardiac arrest each year. Prognosis is poor and survivors typically experience persistent neurologic deficits. Currently, neuroprotective treatments to reduce brain injury in cardiac arrest survivors are limited and ineffective. This study evaluates the potential neuroprotection induced by high dose intranasal insulin (HD-IN-I) in a rodent model of asphyxial cardiac arrest. METHODS: Male Long Evans rats were block randomized to sham-operated controls or 8-minute asphyxial cardiac arrest treated with placebo or HD-IN-I at the onset of CPR. To investigate mechanism of action, hippocampi were collected 30 minutes post-ROSC and analyzed by Western blot for phosphorylation of Akt. To assess long-term functional outcomes, neurobehavioral evaluation was conducted using neurologic function scores daily and Barnes maze, Rotarod, and passive avoidance on days 7-10 post-ROSC. Histologic quantification of surviving hippocampal CA1 pyramidal neurons was also conducted. RESULTS: Hippocampal phospho-Akt/total Akt ratio increased 2-fold in the placebo group and 5.7-fold in HD-IN-I group relative to shams (p \u3c 0.05). Rats treated with HD-IN-I had significantly improved performance on Rotarod, Barnes maze, and passive avoidance (p \u3c 0.05). HD-IN-I had no significant effect on ROSC rate, 10-day survival, systemic glycemic response, or on the number of surviving CA1 pyramidal neurons compared to placebo treatment. DISCUSSION: This study is the first to demonstrate that HD-IN-I administered at the onset of CPR, causes phosphorylation of brain Akt and results in significant neuroprotection. This primary work strongly suggests that intranasal insulin could be the first highly effective neuroprotective treatment for cardiac arrest patients

Emerging tuberculosis pathogen hijacks social communication behavior in the group-living banded mongoose (Mungos mungo)

An emerging Mycobacterium tuberculosis complex (MTC) pathogen, M. mungi, infects wild banded mongooses (Mungos mungo) in Northern Botswana, causing significant mortality. This MTC pathogen did not appear to be transmitted through a primary aerosol or oral route. We utilized histopathology, spoligotyping, mycobacterial interspersed repetitive unitsvariable number of tandem repeats (MIRU-VNTR), quantitative PCR (qPCR), and molecular markers (regions of difference [RDs] from various MTC members, including region of difference 1 [RD1] from M. bovis BCG [RD1BCG], M. microti [RD1mic], and M. pinnipedii [RD1seal], genes Rv1510 [RD4], Rv1970 [RD7], Rv3877/8 [RD1], and Rv3120 [RD12], insertion element IS1561, the 16S RNA gene, and gene Rv0577 [cfp32]), including the newly characterized mongoose-specific deletion in RD1 (RD1mon), in order to demonstrate the presence of M. mungi DNA in infected mongooses and investigate pathogen invasion and exposure mechanisms. M. mungi DNA was identified in 29% of nasal planum samples (n 52), 56% of nasal rinses and swabs (n 9), 53% of oral swabs (n 19), 22% of urine samples (n 23), 33% of anal gland tissue (n 18), and 39% of anal gland secretions (n 44). The occurrence of extremely low cycle threshold values obtained with qPCR in anal gland and nasal planum samples indicates that high levels of M. mungi can be found in these tissue types. Histological data were consistent with these results, suggesting that pathogen invasion occurs through breaks in the nasal planum and/or skin of the mongoose host, which are in frequent contact with anal gland secretions and urine during olfactory communication behavior. Lesions in the lung, when present, occurred only with disseminated disease. No environmental sources of M. mungi DNA could be found. We report primary environmental transmission of an MTC pathogen that occurs in association with social communication behavior.Data Set S1, XLSX file, 0.1 MB.Data Set S2, XLSX file, 0.1 MB.This work was supported in part by Morris Animal Foundation grant number D14ZO-083 and by National Science Foundation grant number 1518663 as part of the joint NSF-NIH-USDA Ecology and Evolution of Infectious Diseases program. K. A. Alexander was also supported in part through the National Institute of General Medical Sciences of the National Institutes of Health under award number U01GM110748.http://www.sherpa.ac.uk/romeo/issn/2150-7511/am2016Veterinary Tropical Disease

The ABCD's of Texas Education: Assessing the Benefits and Costs of Reducing the Dropout Rate

This Capstone team examined the economic consequences of the high number of high school dropouts in Texas. Their report discusses alternative strategies for measuring the dropout rate, and provides estimates of the dropout rate for different geographic regions and student populations. The team also estimated of the economic benefits and costs associated with reducing the high dropout rate in Texas. Finally, the team reviewed available research regarding dropout prevention programs in order to identify best practices that could be implemented in Texas. One goal of the study was to inform and encourage a broader discussion by the Texas Legislature of the state's high school dropout rate and the societal and economic impact of failing to address the problem

Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining safety in patients with large B-cell lymphoma

The impact of bridging therapy (BT) on CD19-directed chimeric antigen receptor T-cell (CD19CAR-T) outcomes in large B-cell lymphoma (LBCL) is poorly characterised. Current practice is guided by physician preference rather than established evidence. Identification of effective BT modalities and factors predictive of response could improve CAR-T intention to treat and clinical outcomes. We assessed BT modality and response in 375 adult LBCL patients in relation to outcomes following axicabtagene ciloleucel (Axi-cel) or tisagenlecleucel (Tisa-cel). The majority of patients received BT with chemotherapy (57%) or radiotherapy (17%). We observed that BT was safe for patients, with minimal morbidity/mortality. We showed that complete or partial response to BT conferred a 42% reduction in disease progression and death following CD19CAR-T therapy. Multivariate analysis identified several factors associated with likelihood of response to BT, including response to last line therapy, the absence of bulky disease, and the use of Polatuzumab-containing chemotherapy regimens. Our data suggested that complete/partial response to BT may be more important for Tisa-cel than Axi-cel, as all Tisa-cel patients with less than partial response to BT experienced frank relapse within 12 months of CD19CAR-T infusion. In summary, BT in LBCL should be carefully planned towards optimal response and disease debulking, to improve CD19CAR-T patient outcomes. Polatuzumab-containing regimens should be strongly considered for all suitable patients, and failure to achieve complete/partial response to BT pre-Tisa-cel may prompt consideration of further lines of BT where possible

Do returns to education depend on how and whom you ask?

Returns to education remain an important parameter of interest in economic analysis. A large literature estimates these returns, often carefully addressing issues such as selection into wage employment and endogeneity in terms of completed schooling. There has been much less exploration of whether the estimates of Mincerian returns depend on how information about wage work is collected. Relying on a survey experiment in Tanzania, this paper finds that estimates of the returns to education vary by questionnaire design, but not by whether the information on employment and wages is self-reported or collected by a proxy respondent. The differences derived from questionnaire type are substantial, varying from higher returns of 5 percentage points among the most well educated men to 16 percentage points among the least well educated women. These differences are at magnitudes similar to the bias in ordinary least squares estimation, which receives considerable attention in the literature. The findings demonstrate that survey design matters in the estimation of returns to schooling and that care is needed in comparing across contexts and over time, particularly if the data are generated through different surveys

Validation of a HLA-A2 tetramer flow cytometric method, IFNgamma real time RT-PCR, and IFNgamma ELISPOT for detection of immunologic response to gp100 and MelanA/MART-1 in melanoma patients

<p>Abstract</p> <p>Background</p> <p>HLA-A2 tetramer flow cytometry, IFNγ real time RT-PCR and IFNγ ELISPOT assays are commonly used as surrogate immunological endpoints for cancer immunotherapy. While these are often used as research assays to assess patient's immunologic response, assay validation is necessary to ensure reliable and reproducible results and enable more accurate data interpretation. Here we describe a rigorous validation approach for each of these assays prior to their use for clinical sample analysis.</p> <p>Methods</p> <p>Standard operating procedures for each assay were established. HLA-A2 (A*0201) tetramer assay specific for gp100_209(210M)and MART-1_26–35(27L), IFNγ real time RT-PCR and ELISPOT methods were validated using tumor infiltrating lymphocyte cell lines (TIL) isolated from HLA-A2 melanoma patients. TIL cells, specific for gp100 (TIL 1520) or MART-1 (TIL 1143 and TIL1235), were used alone or spiked into cryopreserved HLA-A2 PBMC from healthy subjects. TIL/PBMC were stimulated with peptides (gp100₂₀₉, gp100_pool, MART-1_27–35, or influenza-M1 and negative control peptide HIV) to further assess assay performance characteristics for real time RT-PCR and ELISPOT methods. Validation parameters included specificity, accuracy, precision, linearity of dilution, limit of detection (LOD) and limit of quantification (LOQ). In addition, distribution was established in normal HLA-A2 PBMC samples. Reference ranges for assay controls were established.</p> <p>Results</p> <p>The validation process demonstrated that the HLA-A2 tetramer, IFNγ real time RT-PCR, and IFNγ ELISPOT were highly specific for each antigen, with minimal cross-reactivity between gp100 and MelanA/MART-1. The assays were sensitive; detection could be achieved at as few as 1/4545–1/6667 cells by tetramer analysis, 1/50,000 cells by real time RT-PCR, and 1/10,000–1/20,000 by ELISPOT. The assays met criteria for precision with %CV < 20% (except ELISPOT using high PBMC numbers with %CV < 25%) although flow cytometric assays and cell based functional assays are known to have high assay variability. Most importantly, assays were demonstrated to be effective for their intended use. A positive IFNγ response (by RT-PCR and ELISPOT) to gp100 was demonstrated in PBMC from 3 melanoma patients. Another patient showed a positive MART-1 response measured by all 3 validated methods.</p> <p>Conclusion</p> <p>Our results demonstrated the tetramer flow cytometry assay, IFNγ real-time RT-PCR, and INFγ ELISPOT met validation criteria. Validation approaches provide a guide for others in the field to validate these and other similar assays for assessment of patient T cell response. These methods can be applied not only to cancer vaccines but to other therapeutic proteins as part of immunogenicity and safety analyses.</p

Exploring the Support Needs of Family Caregivers of Patients with Brain Cancer Using the CSNAT: A Comparative Study with Other Cancer Groups

A substantial burden is placed on family caregivers of patients diagnosed with brain cancers. Despite this, the support needs of the caregivers are often under-recognised and not addressed adequately in current routine and patient centred clinical care. The Care Support Needs Assessment Tool (CSNAT) is a validated instrument designed to systematically identify and address caregiver needs. It has been trialled in an Australian palliative care community setting using a stepped wedge cluster design involving 322 family carers of terminally ill patients. The current article reports on a subset from this trial, 29 caregivers of patients with primary brain cancer, and compares their profile and outcomes to those of other cancer groups. Caregiver strain was assessed using the Family Appraisal of Caregiving Questionnaire, caregiver physical and mental wellbeing using SF12 and caregiver workload using a questionnaire on support with activities of daily living (ADL). In comparison to caregivers of patients with all other cancers, the primary brain cancer group had significantly higher levels of caregiver strain, lower levels of mental wellbeing and a higher level of ADL workload. Their physical wellness also deteriorated significantly over time.An action plan approach led to practical solutions for addressing highlighted concerns. Four themes evolved from the family caregivers’ feedback interviews: The extremely challenging caregiver experience with brain cancer; the systematic and practical approach of the CSNAT during rapid changes; connection with health professionals, feeling acknowledged and empowered; and timely advice and assurance of support during the caregiving journey. This preliminary study has demonstrated that the CSNAT provides a practical and useful tool for assessing the support needs of family caregivers of patients with brain cancer and has provided the basis for a larger scale, longitudinal study that allows a more detailed characterisation of the evolving caregiver needs at different stages of the disease