CB307: A Dual Targeting Costimulatory Humabody VH Therapeutic for Treating PSMA-Positive Tumors.

PURPOSE: CD137 is a T- and NK-cell costimulatory receptor involved in consolidating immunologic responses. The potent CD137 agonist urelumab has shown clinical promise as a cancer immunotherapeutic but development has been hampered by on-target off-tumor toxicities. A CD137 agonist targeted to the prostate-specific membrane antigen (PSMA), frequently and highly expressed on castration-resistant metastatic prostate cancer (mCRPC) tumor cells, could bring effective immunotherapy to this immunologically challenging to address disease. EXPERIMENTAL DESIGN: We designed and manufactured CB307, a novel half-life extended bispecific costimulatory Humabody VH therapeutic to elicit CD137 agonism exclusively in a PSMA-high tumor microenvironment (TME). The functional activity of CB307 was assessed in cell-based assays and in syngeneic mouse antitumor pharmacology studies. Nonclinical toxicology and toxicokinetic properties of CB307 were assessed in a good laboratory practice (GLP) compliant study in cynomolgus macaques. RESULTS: CB307 provides effective CD137 agonism in a PSMA-dependent manner, with antitumor activity both in vitro and in vivo, and additional activity when combined with checkpoint inhibitors. A validated novel PSMA/CD137 IHC assay demonstrated a higher prevalence of CD137-positive cells in the PSMA-expressing human mCRPC TME with respect to primary lesions. CB307 did not show substantial toxicity in nonhuman primates and exhibited a plasma half-life supporting weekly clinical administration. CONCLUSIONS: CB307 is a first-in-class immunotherapeutic that triggers potent PSMA-dependent T-cell activation, thereby alleviating toxicologic concerns against unrestricted CD137 agonism.

Factors affecting neurodevelopmental outcome following surgical necrotising enterocolitis: a systematic review.

Surgically treated necrotising enterocolitis (sNEC) is associated with significantly worse neurodevelopmental outcomes than that seen in premature infants without NEC. We aim to review the association between factors involved in the surgical treatment of NEC and subsequent neurodevelopmental outcomes to identify potential areas for improvement. The PubMed and Embase databases were interrogated for articles reporting neurodevelopmental outcomes in babies treated surgically for NEC using key terms including: "Infant", "Necrotising enterocolitis", "Surgical", "Neurodevelopmental" and "Outcomes". The search strategy yielded 1170 articles and after applying inclusion and exclusion criteria 22 studies remained and formed the review. A diverse range of neurodevelopmental outcomes were reported. Extreme prematurity and lower birth weight were associated with worse neurodevelopmental outcomes. The use of peritoneal drains and enterostomies were associated with worse outcomes. Modifications to surgical strategies in NEC may improve neurodevelopmental outcomes but the effect of confounding factors remains unclear. Further large scale studies are required to define the optimum strategies for treating NEC surgically and to develop a core outcome set for research into NEC.

The Disruption of Patient Ambulation Care Processes by COVID-19: Revealing the Value of Visitor Assistance.

OBJECTIVE: To explore the impact of COVID-19 on care processes and ambulation outcomes. BACKGROUND: COVID-19 forced hospital leaders to make systems-level changes that disrupted patient ambulation. The impact of these changes on the ambulation of hospitalized patients was unknown. The Systems Engineering Initiative for Patient Safety model was used to explore ambulation from a systems perspective. METHODS: A single-case study research design was used to investigate patient ambulation in a major medical center. Data from 12 interviews with interdisciplinary leaders were analyzed. RESULTS: Staff shortages and visitor restrictions were identified as the main work system barriers to ambulation. These barriers disrupted usual ambulation processes and supported the value of visitor assistance with ambulation. CONCLUSIONS: This study provides a systems-level perspective of missed ambulation during COVID-19, which revealed the value of ambulation assistance provided by visitors. Findings may be used to support the continued and increased involvement of family members and visitors in the process of ambulation.

Data Science Implementation Trends in Nursing Practice: A Review of the 2021 Literature.

OBJECTIVES: The goal of this work was to provide a review of the implementation of data science-driven applications focused on structural or outcome-related nurse-sensitive indicators in the literature in 2021. By conducting this review, we aim to inform readers of trends in the nursing indicators being addressed, the patient populations and settings of focus, and lessons and challenges identified during the implementation of these tools. METHODS: We conducted a rigorous descriptive review of the literature to identify relevant research published in 2021. We extracted data on model development, implementation-related strategies and measures, lessons learned, and challenges and stakeholder involvement. We also assessed whether reports of data science application implementations currently follow the guidelines of the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by AI (DECIDE-AI) framework. RESULTS: Of 4,943 articles found in PubMed (NLM) and CINAHL (EBSCOhost), 11 were included in the final review and data extraction. Systems leveraging data science were developed for adult patient populations and were primarily deployed in hospital settings. The clinical domains targeted included mortality/deterioration, utilization/resource allocation, and hospital-acquired infections/COVID-19. The composition of development teams and types of stakeholders involved varied. Research teams more frequently reported on implementation methods than implementation results. Most studies provided lessons learned that could help inform future implementations of data science systems in health care. CONCLUSION: In 2021, very few studies report on the implementation of data science-driven applications focused on structural- or outcome-related nurse-sensitive indicators. This gap in the sharing of implementation strategies needs to be addressed in order for these systems to be successfully adopted in health care settings.

University stakeholders largely unaware and unsupportive of university pouring rights contracts with companies supplying sugar-sweetened beverages.

Background: Pouring rights contracts are agreements in which beverage companies pay universities for exclusive marketing and rights to sell sugar-sweetened beverages (SSB) in campus. This study explored university stakeholder's awareness and opinions of university pouring rights contracts. Methods: Nine hundred fifteen university stakeholders self-reported their awareness and support of pouring rights contracts along with several possible determinants of support (age, gender, nutrition education, beliefs about SSBs, beverage intake). Results: About 64.2% of participants reported no awareness of pouring rights contracts whereas only 38% reported agreeing with university pouring rights contracts. Males, undergraduate students, and those who felt individuals are responsible for their SSB consumption were more likely to support pouring rights contracts. Conclusions: University stakeholders were largely unaware of and unsupportive of pouring rights contracts. Universities are encouraged to consider the health impacts and opinions of university stakeholders when deciding whether to enter into pouring rights contracts.

From anticipation to confidence: A descriptive qualitative study of new graduate nurse communication with physicians.

AIM: The aim of this study was to understand how new graduate nurses experience communication with physicians. BACKGROUND: Communication is necessary for high-quality health care delivery. With poor patient outcomes as a driving force, knowledge of the dialogue that occurs between new graduate nurses and physicians has been rarely explored. METHODS: This qualitative descriptive study involved 13 new graduate nurses from an academic teaching hospital in the south-eastern United States. Data for this study were collected using face-to-face and virtual interviews with a focus on having nurses describe their experience communication with physicians in their current practice. RESULTS: Analysis led to four themes that describe new graduate nurses experience communicating with physicians. Those themes were gaps in preparation, developing confidence, learning to communicate, and interprofessional care. CONCLUSIONS: Effective communication with physicians is a stressor for new graduate nurses as they transition to practice. For these nurses, negative emotions in their anticipation of communicating with physicians were developed during their educational experience. IMPLICATIONS FOR NURSING MANAGEMENT: The findings of this study emphasize the importance of enhanced interprofessional training in education and practice that facilitate effective communication between the two professions in the practice environment.

Emerging synthetic cannabinoids detected by a drug checking service in Toronto, Canada.

BACKGROUND: Toronto's Drug Checking Service (DCS) provides people who use drugs with information on the chemical composition of their substances and conducts real-time monitoring of the unregulated drug supply. Presented are first known data of three newly detected synthetic cannabinoids (SCs) in Toronto, Ontario. METHODS: The present data are from samples analyzed between April and November 2020. Samples were collected at partnering harm reduction agencies in Toronto and analyzed using gas or liquid chromatography-mass spectrometry. An intake survey queried about the sample characteristics on submission, including expected drug(s). RESULTS: Samples were analyzed between 1 April and 20 November 2020 (N = 19), which marks the period immediately following imposed COVID-19 border and movement restrictions in Canada. The newly detected, unexpected SCs were ACHMINACA (n = 15), AB-FUBINACA (n = 3), and 4-fluoro-MDMB-BUTINACA (n = 1). Fentanyl was expected in 74% (n = 14). Most SCs were detected in samples containing fentanyl or related analogues (n = 18; 95%), or benzodiazepine-related drugs (i.e., etizolam and flualprazolam) (n = 15; 79%). CONCLUSIONS: This information can inform overdose prevention efforts and drug market monitoring of SCs in Toronto and regions served by the same drug trafficking routes. The detection of SCs during a period marked by COVID-19-related restrictions can contribute to efforts to identify global drug market trends during this time.

Adolescence alcohol exposure impairs fear extinction and alters medial prefrontal cortex plasticity.

After experiencing a traumatic event people often turn to alcohol to cope with symptoms. In those with post-traumatic stress disorder (PTSD) and a co-occurring alcohol use disorder (AUD), PTSD symptoms can worsen, suggesting that alcohol changes how traumatic memory is expressed. The objective of this series of experiments is to identify how alcohol drinking (EtOH), following cued fear conditioning and extinction, impacts fear expression in mice. Molecular (activity-regulated cytoskeleton-associated protein, Arc/arg3.1) and structural (dendrite and spine morphometry) markers of neuronal plasticity were measured following remote extinction retrieval. Mouse age (adolescent and adult) and sex were included as interacting variables in a full factorial design. Females drank more EtOH than males and adolescents drank more EtOH than adults. Adolescent females escalated EtOH intake across drinking days. Adolescent drinkers exhibited more conditioned freezing during extinction retrieval, an effect that persisted for at least 20 days. Heightened cued freezing in the adolescent group was associated with greater Arc/arg3.1 expression in layer (L) 2/3 prelimbic (PL) cortex, greater spine density, and reduced basal dendrite complexity. In adults, drinking was associated with reduced L2/3 infralimbic (IL) Arc expression but no behavioral differences. Few sex interactions were uncovered throughout. Overall, these data identify prolonged age-related differences in alcohol-induced fear extinction impairment and medial prefrontal cortex neuroadaptations.

Family-Centered Primary Care for Older Adults with Cognitive Impairment.

Cognitive impairment (e.g. dementia) presents challenges for individuals, their families, and healthcare professionals alike. The primary care setting presents a unique opportunity to care for older adults living with cognitive impairment, who present with complex care needs that may benefit from a family-centered approach. This indepth systematic review was completed to address three aims: (a) identify the ways in which families of older-adult patients with cognitive impairment are engaged in primary care settings, (b) examine the outcomes of family engagement practices, and (c) organize and discuss the findings using CJ Peek's Three World View. Researchers searched PubMed, Embase, and PsycINFO databases through July 2019. The results included 22 articles out of 6743 identified in the initial search. Researchers provided a description of the emerging themes for each of the three aims. It revealed that family-centered care and family engagement yields promising results including improved health outcomes, quality care, patient experience, and caregiver satisfaction. Furthermore, it promotes and advances the core values of medical family therapy: agency and communion. This review also exposed the inconsistent application of family-centered practices and the need for improved interprofessional education of primary care providers to prepare multidisciplinary teams to deliver family-centered care. Utilizing the vision of Patient- and Family-Centered Care and the lens of the Three World View, this systematic review provides Medical Family Therapists, healthcare administrators, policy makers, educators, and clinicians with information related to family engagement and how it can be implemented and enhanced in the care of patients with cognitive impairment.

Career Adaptability: An Innovative Measurement to Aid Professional Development of New Graduate Nurses.

This cross-sectional quantitative study explored career adaptability and career intentions in newly licensed nurses working in acute care hospitals throughout North Carolina. Data were analyzed from 277 registered nurses completing an online study instrument. Findings demonstrate a relationship between levels of career adaptability and career intentions, offering career adaptability as a new measurement to explore newly licensed nurses' desire to pursue career and educational change and expand transition programs to include developing career trajectories within organizations.

Caregiving burden among informal caregivers of African American cancer survivors.

PURPOSE: Relatively little is known about caregivers of African American cancer survivors. Our goal was to identify the extent of burden among this group of caregivers. METHODS: Responses from 560 informal caregivers of African American participants of the Research on Cancer Survivors (ROCS) study in Detroit, MI, were analyzed including demographics, assistance provided including activities of daily living (ADLs) and instrumental activities of daily living (IADLs), time spent in caregiving, and caregiver burden (CGB). We assessed relationships between CGB and demographic variables, ADLs/IADLs, and level of care. Multivariable logistic regression determined which ADLs and IADLs were associated with high CGB. RESULTS: Over 75% of caregivers were female and 97% identified as African American. Mean age was 52.6 years. Fifty-six percent were employed outside the home, and 90% were related to the survivor. Caregivers averaged 35.7 h/week providing care, assisting with on average 2.8 ADLs and 5.0 IADLs. Despite the many hours and activities reported, no caregivers rated CGB as severe; only 4% rated it moderate to severe. ADLs associated with the top quartile of CGB were feeding and toileting; IADLs were finances, telephoning, housework, and medications. CONCLUSIONS: Caregivers for African American cancer survivors provide many hours of care, yet most describe their CGB as low. Although ADL assistance is often available through the healthcare system, assistance with IADLs presents an opportunity to lessen the burden for these caregivers and their care recipients. IMPLICATIONS FOR CANCER SURVIVORS: African American cancer survivors receive much care from informal family caregivers, who assist with multiple ADLs and IADLs. Formal IADL assistance programs, similar to those available for ADLs, would benefit both survivors and caregivers.

Understanding the peer, manager, and system influence on patient safety.

A unique view of the Hospital Survey on Patient Safety Culture.

New Graduate Nurses' Perceptions of Patient Safety: Describing and Comparing Responses With Experienced Nurses.

BACKGROUND: A significant proportion of the acute health system workforce is composed of new graduate nurses, yet there is a limited understanding of patient safety perceptions among new graduate nurses and how they compare with nurses who have more experience. METHOD: This study used a descriptive approach to complete secondary analysis on two sources of data containing new graduate nurses' (n = 1,613) and experienced nurses' (n = 64,906) responses to the Hospital Survey on Patient Safety Culture. RESULTS: New graduate nurses had a more positive perception of safety culture than more experienced nurses. The greatest differences were observed in perceptions of how nurse managers respond to mistakes. Similarities in perceptions were observed on items associated with communication. CONCLUSION: Educational systems and transitional programs must prepare new graduate nurses for patient care. There is an opportunity for academic and practice partners to collaborate on programs that facilitate the transition of new graduate nurses to the workforce. [J Contin Educ Nurs. 2020;51(7):309-315.].

Fermentation of Cauliflower and White Beans with Lactobacillus plantarum - Impact on Levels of Riboflavin, Folate, Vitamin B12, and Amino Acid Composition.

As diets change in response to ethical, environmental, and health concerns surrounding meat consumption, fermentation has potential to improve the taste and nutritional qualities of plant-based foods. In this study, cauliflower, white beans, and a 50:50 cauliflower-white bean mixture were fermented using different strains of Lactobacillus plantarum. In all treatments containing cauliflower, the pH was reduced to <4 after 18 h, while treatments containing only white beans had an average pH of 4.8 after 18 h. Following fermentation, the riboflavin, folate, and vitamin B12 content of the cauliflower-white bean mixture was measured, and compared against that of an unfermented control. The riboflavin and folate content of the mixture increased significantly after fermentation. Relative to control samples, riboflavin increased by 76-113%, to 91.6 ± 0.6 µg/100 g fresh weight, and folate increased by 32-60%, to 58.8 ± 2.0 µg/100 g fresh weight. For one bacterial strain, L. plantarum 299, a significant 66% increase in vitamin B12 was observed, although the final amount (0.048 ± 0.013 µg/100 g fresh weight) was only a small fraction of recommended daily intake. Measurements of amino acid composition in the mixture revealed small increases in alanine, glycine, histidine, isoleucine, leucine, and valine in the fermented sample compared to the unfermented control.

Getting work done: a grounded theory study of resident physician value of nursing communication.

Poor communication between nurses and physicians results in patient injury and increased healthcare costs. While multiple attempts have been made to improve communication between the two professions, evidence confirms little progress has been made. Previous research focused on standardizing communication processes and protocols between nurses and physicians rather than examining the relational component of these human interactions. The purpose of this study was to explore physician valuing of nursing communication in the context of patient care. Interviews were conducted with 15 internal medicine resident physicians. A constructivist grounded theory approach was used to develop the substantive theory of Getting Work Done. Getting Work Done incorporated three major categories: discerning the team, shifting communication, and accessing nurse knowledge and abilities. Hierarchical behaviors and language, and nurse collusion in both, characterized nurse-physician communication and situated the nurse outside the decision-making team. Complex work environments further devalued nurse-physician communication. Interprofessional education and practice must advance the unique and essential role of all health care professionals such that mutual valuing replaces hierarchical actions with collaborative systems for determining the most effective approaches to patient care.

Fostering scholarship in doctoral education: Using a social capital framework to support PhD student writing groups.

The shortage of nurse scientists in the United States complicates nursing's ability to sustain research-intensive environments, build knowledge for translation, and advance nursing science. More emphasis is needed on the preparation of PhD doctoral students to better equip them for a career of scholarship. Four recent PhD graduates participating in a writing group, examined the influence of social capital on their ability to develop capacity for scholarship. They found that a strong social factor supported their efforts to engage as scholars, be accountable for their writing, and make contributions to the research community. Although the writing group provided a space to practice scholarly writing and increased scholarly productivity, the experience was transformative in building capacity for scholarship. This article includes recommendations for academic leaders to both create and support writing groups within doctoral nursing programs using a social capital framework. Strategies are provided using the three dimensions of social capital: structural, relational, and cognitive. Investing in strategies that build social capital within a community can directly impact the advancement of science by elevating capacity for scholarship.

Obesity bias among preclinical and clinical chiropractic students and faculty at an integrative health care institution: A cross-sectional study.

OBJECTIVE:: The purpose of this study was to assess the prevalence of obesity bias among preclinical and clinical chiropractic students and faculty at an integrative health care academic institution. METHODS:: This was a cross-sectional quantitative, single-method survey with group comparison using the Beliefs About Obese Persons scale (BAOP) and the Attitudes Toward Obese Persons scale. Both instruments were administered as a single 28 question survey via email to 450 students and 46 faculty members in a doctor of chiropractic (DC) program. Differences were determined by 2 tailed t tests. RESULTS:: The response rate for faculty and students was 31% and 65%, respectively. One hundred forty-three DC students, preclinical ( n = 65) and clinical ( n = 78), and 30 DC faculty, preclinical ( n = 15) and clinical ( n = 15) completed the survey. Both students and faculty harbored antiobesity attitudes and moderate antiobesity beliefs. Students demonstrated slightly more positive attitudes toward obese persons than did preclinical faculty. Although preclinical faculty did not demonstrate more biased attitudes than did preclinical students ( p = .057), they were more biased than clinical students ( p = .26). On the BAOP, preclinical faculty scored significantly lower than both preclinical students and clinical students ( p = .013 and .017, respectively). CONCLUSION:: Obesity bias was common among clinical and preclinical chiropractic students and faculty at our institution. A cultural shift that reduces bias may require changes in both the curriculum and cocurriculum.