Integrating genomics and precision health knowledge into practice: A guide for nurse practitioners.

ABSTRACT: Nurse practitioners (NPs) are the fastest growing group of health care providers, with an increase of 8.5% over the past year and anticipated growth of more than 40% by 2031. Improving NPs' knowledge of how genes influence health enables them to assess, diagnose, and manage patients in all states of health in a safe, efficient, and competent manner. Nurse practitioners may also care for patients who obtain direct-to-consumer (DTC) genetic tests without provider oversight and share their results; improved knowledge of genetics can provide NPs with the information and resources needed to interpret and understand DTC test results. The literature indicates that NPs have limited understanding of basic genetic concepts and guidelines for prescribing drugs affected by genomic variability. As a result, NPs report low confidence in their ability to accurately interpret and apply genetic test results, which inhibits genomics-informed precision health care. This article provides resources and clinical recommendations for using the 2021 American Association of Colleges of Nursing Essentials and the American Nurses Association Essentials of Genomic Nursing to facilitate the integration of genomics into NP curricula and practice. These resources will help future and practicing NPs integrate genomics into practice and improve precision health care.

Interactive Screen-Based Activities Predict Worse Actigraphic Sleep Health That Night Among Adolescents.

PURPOSE: To determine the micro-longitudinal effects of duration and timing of screen-based activities on sleep within and between adolescents. METHODS: Daily survey and actigraphy data from the age 15 wave of the Future of Families and Child Wellbeing Study were analyzed using multilevel modeling. Four hundred seventy five adolescents provided three or more days of valid daily survey and nighttime sleep data. RESULTS: Within-person results showed that on days when adolescents played video games more than their daytime average ± SE (1.3 ± 1.2 hours), sleep onset (6 ± 2 minutes, p < .01) and midpoint (4 ± 2 minutes, p < .02) were delayed for each additional hour of gaming. Between-person results showed that for each hour adolescents used screens to communicate with friends across the day, sleep onset was later (11 ± 3 minutes, p < .01), sleep midpoint was later (8 ± 3 minutes, p < .01), and sleep duration was shorter (-5 ± 2 minutes, p < .03). Adolescents who used screens to communicate with friends or play video games in the hour before bed had later sleep onset (30 ± 14 minutes, p < .03) and midpoint (25 ± 13 minutes, p < .05). DISCUSSION: Among adolescents, passive screen usage such as browsing the Internet or watching videos may not affect sleep timing or duration, but limiting interactive screen-based activities could protect adolescent sleep health and well-being.

Continuing Nursing Research During a Pandemic.

The coronavirus disease-2019 pandemic disrupted traditional research practices with the cessation of face-to-face contact with study participants. Researchers needed to respond with alternative methods to continue nurse-led clinical research. A rapid pivot to remote processes for recruitment, enrollment, data collection, and participant incentives can enable research to continue despite restrictions on in-person activities. Technology offers innovative methods in meeting current research needs but is not without challenges and continued need for ethics evaluation.

Feasibility of Using Child Maltreatment Measurement Instruments in the Primary Care Setting: A Systematic Review.

PROBLEM: Child maltreatment is a devastating epidemic affecting millions of children and adolescents in the United States (U.S.) every year. Primary care providers (PCPs) encounter these victims but need resources to aid in the recognition of maltreatment. The purpose of this review is to evaluate child maltreatment measurement instruments and determine feasibility of use by U.S. PCPs. ELIGIBILITY CRITERIA: A systematic search was conducted in the PubMed, CINAHL, and PsycInfo databases from 2014 until 2020. Eligibility criteria included articles conducted in the U.S., with use of a child maltreatment measurement instrument, and subjects less than 18 years old. Eligible articles were reference searched to find the original studies for each instrument and were included if they were published in a peer-reviewed paper, could be located, and addressed the development or validation of the instrument. SAMPLE: Of the 3816 articles, 111 used a child maltreatment measurement instrument. Sixteen of the 27 identified instruments were evaluated for feasibility using a quality rating with criteria including psychometrics, construct measurement, administration, availability, and cost. RESULTS: Six instruments were recommended for use by PCPs. CONCLUSIONS: This is the first review evaluating the use of child maltreatment measurement instruments by PCPs and it highlights the combination of psychometric evaluation and other pertinent feasibility criteria to recommend several instruments for use by PCPs. IMPLICATIONS: Use of these instruments by PCPs may serve to identify children and families who are at risk for or suffering from maltreatment.

Comparisons of Efficiency of Two Formulations of Verbenone (4, 6, 6-trimethylbicyclo [3.1.1] hept-3-en-2-one) for Protecting Whitebark Pine, Pinus albicaulis (Pinales: Pinaceae) From Mountain Pine Beetle (Colopetera: Curculionidae).

Whitebark pine, Pinus albicaulis Engelm., is a subalpine tree endemic to western North America. This species provides multiple ecosystem services and is suffering widespread mortality from mountain pine beetle, Dendroctonus ponderosae Hopkins. Verbenone is a pheromone produced as D. ponderosae feed, and high air concentrations of verbenone deter D. ponderosae from colonizing trees. Synthetic verbenone has been formulated into products used to prevent D. ponderosae from colonizing trees. We compared the ability of verbenone pouches and SPLAT Verb to protect individuals and small stands of P. albicaulis. With individual trees in Montana, all treated trees survived regardless of verbenone formulation and rate, whereas untreated trees suffered 70 and 90% mortality in 2015 and 2016. In plot experiments in California from 2015 to 2017, and Oregon from 2015 to 2018, verbenone was applied to trees spaced ~10 m apart, and survival of small (12.7-23 cm DBH = diameter at 1.37 m height), medium (23.1-33 cm DBH) and large (>33 cm DBH) trees was compared. In California, where >80% of untreated trees survived, pouches increased survival ~2 to 3% and SPLAT Verb increased survival ~4 to 7% regardless of tree size. In Oregon, verbenone pouches and SPLAT Verb performed similarly on medium and small trees, but large trees had greater survival when treated with SPLAT Verb (~93%) than pouches (~82%). Compared to verbenone pouches, SPLAT Verb appears to better protect P. albicaulis from D. ponderosae.

Natural history of insomnia symptoms in the transition from childhood to adolescence: population rates, health disparities, and risk factors.

STUDY OBJECTIVES: To determine the sociodemographic, behavioral, and clinical risk factors associated with the persistence, remission, and incidence of insomnia symptoms in the transition from childhood to adolescence. METHODS: The Penn State Child Cohort is a random, population-based sample of 700 children (5-12 years at baseline), of whom 421 were followed-up as adolescents (12-23 years at follow-up). Subjects underwent polysomnography, clinical history, physical exam, and parent- and self-reported scales at baseline and follow-up. Insomnia symptoms were defined as a parent- or self-report of difficulty falling and/or staying asleep. RESULTS: The 421 subjects with baseline (Mage = 8.8 years) and follow-up (Mage = 17 years) data were 53.9% male and 21.9% racial/ethnic minorities. The persistence of childhood insomnia symptoms (CIS) was 56% (95% CI = 46.5-65.4), with only 30.3% (95% CI = 21.5-39.0) fully remitting. The incidence of adolescent insomnia symptoms was 31.1% (95% CI = 25.9-36.3). Female sex, racial/ethnic minority, and low socioeconomic status as well as psychiatric/behavioral or neurological disorders, obesity, smoking, and evening chronotype were associated with a higher persistence or incidence of insomnia symptoms. CONCLUSIONS: CIS are highly persistent, with full remission occurring in only a third of children in the transition to adolescence. Sex-, racial/ethnic-, and socioeconomic-related disparities in insomnia occur as early as childhood, while different mental/physical health and lifestyle/circadian risk factors play a key role in the chronicity of CIS versus their incidence in adolescence. CIS should not be expected to developmentally remit and should become a focus of integrated pediatric/behavioral health strategies.

Possible acquired gastrointestinal polyposis in a childhood cancer survivor.

Childhood cancer survivors (CCSs) are at an increased risk for secondary cancers, including colorectal, thyroid, lung, and breast. Treatment with abdominal radiotherapy and/or alkylating agent chemotherapy has been associated with an increased risk for colorectal adenomas and colorectal cancer (CRC) in CCSs. The phenotype of therapy-associated polyposis (TAP) is not well-understood, given the paucity of cases described in the literature. Further defining the phenotype of TAP is important to increase the primary care provider's awareness of when to begin CRC screening in these patients. We present a case of a patient with possible acquired polyposis that seems to meet the criteria identified in the literature for TAP. The purpose of this case study is to add to the body of knowledge related to TAP, further defining the phenotype. Better understanding of therapy-related risks in CCSs and hereditary predisposition will provide primary care providers and their patients with an improved plan for CRC screening.

Nurses and nursing assistants decision-making regarding use of safe patient handling and mobility technology: A qualitative study.

AIM: This study explored decision-making regarding use of safe patient handling and mobility (SPHM) technology among registered nurses (RN) and nursing assistants (NA). BACKGROUND: Lifting injuries are common among healthcare workers. Despite development of standards for SPHM, the introduction of regulation for monitoring access to SPHM technology, and implementation of education programs and process improvements, threat of injury remains a concern. Although access to SPHM equipment is associated with decreased workplace injuries, access alone does not guarantee use. Questions remain concerning how healthcare workers make decisions to use SPHM equipment, and how they weigh decisions against personal safety. METHODS: A qualitative descriptive study was conducted. Data collection consisted of four 60min focus groups. Two focus groups consisted of all RNs (n=14) and two consisted of all NAs (n=11). Each focus group was audiotaped and transcribed verbatim. Transcripts were coded, repeating concepts identified, and codes collapsed into themes and subthemes. RESULTS: Qualitative analysis revealed three major themes: barriers to use, perceived risk, and coordination of care. Barriers to use include subthemes of physical barriers, knowledge and skill, and unit culture. Perceived risk includes patient risk and perceived risk to self. Coordination of care includes patient factors and characteristics, assessment of patient needs and abilities, and interprofessional collaboration. CONCLUSIONS: These findings provide new knowledge about the complexity of decision making among care providers in the use of SPHM technology. Interprofessional team approaches to patient assessment and care are important components of confident decision making in use of SPHM technology.

Imaging the Interaction of Pancreatic Cancer and Stellate Cells in the Tumor Microenvironment during Metastasis.

BACKGROUND/AIM: Pancreatic stellate cells are involved in fibrosis of pancreatic cancer termed desmoplasia, which may contribute to both pancreatic cancer growth and metastasis, as well as to drug resistance. A better understanding of pancreatic cancer-cell interactions with stellate cells is therefore critical to our ability to develop effective anti-metastatic therapeutics for pancreatic cancer. MATERIALS AND METHODS: The human pancreatic cancer cell line XPA-1 was engineered to express green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm. Pancreatic stellate cells were engineered to express RFP. The pancreatic cancer cells and stellate cells were co-cultured and their interaction was imaged in vitro. The pancreatic cancer cells and stellate cells were then co-injected in the spleen of transgenic cyan fluorescent protein (CFP) nude mice and imaged in liver, lung and diaphragm metastasis. RESULTS: The interaction of the pancreatic cancer cells expressing GFP in the nucleus and RFP in the cytoplasm and stellate cells expressing RFP was first imaged in vitro. The intimate relationship between the two cell types could be seen. Three hours after splenic co-injection, dual-color pancreatic cancer cells and pancreatic stellate cells were found distributed in the host liver. By 28 days after splenic co-injection of the pancreatic cancer and stellate cells, liver metastases were observed in host CFP nude mice. Metastases were also observed in the lung and diaphragm. Stellate cells were observed along with the pancreatic cancer cells at all metastatic sites suggesting that stellate cells may be necessary for metastasis. With high-resolution intravital imaging afforded by the Olympus FV1000 confocal microscope, the interaction of the dual-colored pancreatic cancer cells and the RFP-expressing pancreatic stellate cells could be clearly imaged in the liver and other metastases, further suggesting that stellate cells participate in metastasis formation. CONCLUSION: Pancreatic cancer cells and stellate stem cells form a very close relationship and accompany each other to distant metastatic sties. Our hypothesis is that pancreatic stellate cells form a niche for metastasis of pancreatic cancer.

A dual-color genetically engineered mouse model for multispectral imaging of the pancreatic microenvironment.

OBJECTIVES: To develop a mouse model for multispectral fluorescence imaging of the pancreas and pancreatic microenvironment. METHODS: Cre/loxP technology was used to develop this model. We crossed mT/mG indicator mice, engineered to constitutively express a conditional tdTomato transgene that converts to green fluorescent protein (GFP) expression after exposure to Cre recombinase, with Pdx1-Cre transgenic mice. To characterize this model for studies of pancreas biology, we performed bright light and fluorescence imaging of body cavities and intact organs and confocal microscopy of pancreata from offspring of Pdx1-Cre and mT/mG crosses. RESULTS: Pdx1-Cre-mT/mG mice demonstrated bright GFP expression within the pancreas and duodenum and intense tdTomato expression in all other organs. Green fluorescent protein expression was mosaic in Pdx1-Cre-mT/mG pancreata, with most showing extensive conversion from tdTomato to GFP expression within the epithelial-derived elements of the pancreatic parenchyma. Because both GFP and tdTomato are membrane targeted, individual cell borders were clearly outlined in confocal images of mT/mG pancreata. CONCLUSIONS: This mouse model enables multispectral fluorescence imaging of individual cells and cell processes at the microscopic level of the pancreatic microenvironment; it should prove valuable for a variety of fluorescence imaging studies, ranging from pancreatic development to pancreatic cancer biology.

Fluorescence-guided surgery of human colon cancer increases complete resection resulting in cures in an orthotopic nude mouse model.

BACKGROUND: We inquired if fluorescence-guided surgery (FGS) could improve surgical outcomes in fluorescent orthotopic nude mouse models of human colon cancer. METHODS: We established fluorescent orthotopic mouse models of human colon cancer expressing a fluorescent protein. Tumors were resected under bright light surgery (BLS) or FGS. Pre- and post-operative images with the OV-100 Small Animal Imaging System (Olympus Corp, Tokyo Japan) were obtained to assess the extent of surgical resection. RESULTS: All mice with primary tumor that had undergone FGS had complete resection compared with 58% of mice in the BLS group (P = 0.001). FGS resulted in decreased recurrence compared with BLS (33% versus 62%, P = 0.049) and lengthened disease-free median survival from 9 to >36 wk. The median overall survival increased from 16 wk in the BLS group to 31 weeks in the FGS group. FGS resulted in a cure in 67% of mice (alive without evidence of tumor at >6 mo after surgery) compared with only 37% of mice that underwent BLS (P = 0.049). CONCLUSIONS: Surgical outcomes in orthotopic nude mouse models of human colon cancer were significantly improved with FGS. The present study can be translated to the clinic by various effective methods of fluorescently labeling tumors.

Detection of colon cancer metastases with fluorescence laparoscopy in orthotopic nude mouse models.

OBJECTIVE: To improve detection of colon cancer metastases using fluorescence laparoscopy (FL). DESIGN: An orthotopic mouse model of human colon cancer was established by intracecal injection of HCT-116 human colon cancer cells expressing green fluorescent protein into 12 mice. One group modeled early disease and the second modeled late metastatic disease. For the early-disease model, 2 weeks after implantation, 6 mice underwent 2 modalities of laparoscopy: bright field laparoscopy (BL) and FL. The number of metastases identified within each of the 4 abdominal quadrants was recorded with both laparoscopy modalities. This process was repeated in the late-metastatic disease group 4 weeks after implantation. All animals were then humanely sacrificed and imaged using open fluorescence laparoscopy (OL) as a positive control to identify metastases. SETTING: Basic science laboratory. PARTICIPANTS: Twelve female, 6-week-old nude mice. INTERVENTIONS: Detection of tumor foci by FL compared with BL. MAIN OUTCOME MEASURES: Number of tumors identified in each quadrant. RESULTS Fluorescence laparoscopy enabled superior visualization of colon cancer metastases compared with BL in the early (P = .03) and late (P = .002) models of colon cancer. Compared with OL, BL was significantly inferior in the early (P = .04) and late (P < .001) groups. Fluorescence laparoscopy was not significantly different from OL in the early (P = .85) or late (P = .46) group. Thus, FL allowed identification of micrometastases that could not be distinguished from surrounding tissue using BL. CONCLUSIONS: The use of FL enables identification of metastases that could not be visualized using standard laparoscopy. This report illustrates the important clinical potential for FL in the surgical treatment of cancer.

Fluorescence-guided surgery allows for more complete resection of pancreatic cancer, resulting in longer disease-free survival compared with standard surgery in orthotopic mouse models.

BACKGROUND: Negative surgical margins are vital to achieve cure and prolong survival in patients with pancreatic cancer. We inquired if fluorescence-guided surgery (FGS) could improve surgical outcomes and reduce recurrence rates in orthotopic mouse models of human pancreatic cancer. STUDY DESIGN: A randomized active-control preclinical trial comparing bright light surgery (BLS) to FGS was used. Orthotopic mouse models of human pancreatic cancer were established using the BxPC-3 pancreatic cancer cell line expressing red fluorescent protein (RFP). Two weeks after orthotopic implantation, tumors were resected with BLS or FGS. Pre- and postoperative images were obtained with the OV-100 Small Animal Imaging System to assess completeness of surgical resection in real time. Postoperatively, noninvasive whole body imaging was done to assess recurrence and follow tumor progression. Six weeks postoperatively, mice were sacrificed to evaluate primary pancreatic and metastatic tumor burden at autopsy. RESULTS: A more complete resection of pancreatic cancer was achieved using FGS compared with BLS: 98.9% vs 77.1%, p = 0.005. The majority of mice undergoing BLS (63.2%) had evidence of gross disease with no complete resections; 20% of mice undergoing FGS had complete resection and an additional 75% had only minimal residual disease (p = 0.0001). The mean postoperative tumor burden was significantly less with FGS compared with BLS: 0.08 ± 0.06 mm(2) vs 2.64 ± 0.63 mm(2), p = 0.001. The primary tumor burden at termination was significantly less with FGS compared with BLS: 19.3 ± 5.3 mm(2) vs 6.2 ± 3.6 mm(2), p = 0.048. FGS resulted in significantly longer disease-free survival than BLS (p = 0.02, hazard ratio = 0.39, 95% CI 0.17, 0.88). CONCLUSIONS: Surgical outcomes were improved in pancreatic cancer using fluorescence-guidance. This novel approach has significant potential to improve surgical treatment of cancer.

An LED light source and novel fluorophore combinations improve fluorescence laparoscopic detection of metastatic pancreatic cancer in orthotopic mouse models.

BACKGROUND: The aim of this study was to improve fluorescence laparoscopy of pancreatic cancer in an orthotopic mouse model with the use of a light-emitting diode (LED) light source and optimal fluorophore combinations. STUDY DESIGN: Human pancreatic cancer models were established with fluorescent FG-RFP, MiaPaca2-GFP, BxPC-3-RFP, and BxPC-3 cancer cells implanted in 6-week-old female athymic mice. Two weeks postimplantation, diagnostic laparoscopy was performed with a Stryker L9000 LED light source or a Stryker X8000 xenon light source 24 hours after tail-vein injection of CEA antibodies conjugated with Alexa 488 or Alexa 555. Cancer lesions were detected and localized under each light mode. Intravital images were also obtained with the OV-100 Olympus and Maestro CRI Small Animal Imaging Systems, serving as a positive control. Tumors were collected for histologic analysis. RESULTS: Fluorescence laparoscopy with a 495-nm emission filter and an LED light source enabled real-time visualization of the fluorescence-labeled tumor deposits in the peritoneal cavity. The simultaneous use of different fluorophores (Alexa 488 and Alexa 555), conjugated to antibodies, brightened the fluorescence signal, enhancing detection of submillimeter lesions without compromising background illumination. Adjustments to the LED light source permitted simultaneous detection of tumor lesions of different fluorescent colors and surrounding structures with minimal autofluorescence. CONCLUSIONS: Using an LED light source with adjustments to the red, blue, and green wavelengths, it is possible to simultaneously identify tumor metastases expressing fluorescent proteins of different wavelengths, which greatly enhanced the signal without compromising background illumination. Development of this fluorescence laparoscopy technology for clinical use can improve staging and resection of pancreatic cancer.

Tumor-specific fluorescence antibody imaging enables accurate staging laparoscopy in an orthotopic model of pancreatic cancer.

BACKGROUND/AIMS: Laparoscopy is important in staging pancreatic cancer, but false negatives remain problematic. Making tumors fluorescent has the potential to improve the accuracy of staging laparoscopy. METHODOLOGY: Orthotopic and carcinomatosis models of pancreatic cancer were established with BxPC-3 human pancreatic cancer cells in nude mice. Alexa488-antiCEA conjugates were injected via tail vein 24 hours prior to laparoscopy. Mice were examined under bright field laparoscopic (BL) and fluorescence laparoscopic (FL) modes. Outcomes measured included time to identification of primary tumor for the orthotopic model and number of metastases identified within 2 minutes for the carcinomatosis model. RESULTS: FL enabled more rapid and accurate identification and localization of primary tumors and metastases than BL. Using BL took statistically significantly longer time than FL (p<0.0001, fold change and 95% CI for BL vs. FL: 8.12 (4.54,14.52)). More metastatic lesions were detected and localized under FL compared to BL and with greater accuracy, with sensitivities of 96% vs. 40%, respectively, when compared to control. FL was sensitive enough to detect metastatic lesions <1mm. CONCLUSIONS: The use of fluorescence laparoscopy with tumors labeled with fluorophore-conjugated anti-CEA antibody permits rapid detection and accurate localization of primary and metastatic pancreatic cancer in an orthotopic model. The results of the present report demonstrate the future clinical potential of fluorescence laparoscopy.

Submillimeter-resolution fluorescence laparoscopy of pancreatic cancer in a carcinomatosis mouse model visualizes metastases not seen with standard laparoscopy.

BACKGROUND: Staging laparoscopy can visualize peritoneal and liver metastases in pancreatic cancer otherwise undetectable by preoperative imaging. However, false-negative rates may be as high as 18%-26%. The aim of the present study was to improve detection of metastatic pancreatic cancer with the use of fluorescence laparoscopy (FL) in a nude-mouse model with the tumors expressing green fluorescent protein (GFP). METHODS: The carcinomatosis mouse model of human pancreatic cancer was established by intraperitoneal injections of green fluorescent protein-expressing MiaPaca-2 human pancreatic cancer cells into 6-week-old female athymic mice. Two weeks later, mice underwent diagnostic laparoscopy. Laparoscopy was performed first under standard brightfield lighting, followed by fluorescent lighting. The number of metastatic foci identified within the four quadrants of the peritoneal cavity was recorded. After laparoscopy, the animals were sacrificed, opened, and imaged with the OV-100 Small Animal Imaging system as a positive control to identify metastasis. Tumors were collected and processed for histologic review. RESULTS: FL enabled visualization of pancreatic cancer metastatic foci not visualized with standard brightfield laparoscopy (BL). Under FL, in 1 representative mouse, 26 separate micrometastatic lesions were identified. In contrast, only very large tumors were seen using BL. Use of the OV-100 images, as positive controls, confirmed the presence of tumor foci. FL thus allowed identification and exact localization of submillimeter tumor foci. Such small-sized tumor foci were not distinguished from surrounding tissue under BL. All malignant lesions were histologically confirmed. CONCLUSIONS: The use of FL enables the identification of tumor foci that cannot be seen with standard laparoscopy. The technology described in this report has important potential for the clinical development of FL.