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The remarkable advances in genetics and genomics over the last three decades have necessitated initiatives on the part of all healthcare disciplines to assist providers in applying this new knowledge in practice. Nursing has responded by planning and implementing a number of projects that address the challenging issues created by genetic and genomic advances. This article presents an overview of the considerable progress made in sequencing the human genome, progress that has provided the opportunity for the remarkable advances we are seeing in healthcare today. It also describes how various professional healthcare groups and associations are working together to enhance nurses' understanding of this genomic revolution, thus paving the way for nurses to develop core competencies, and enabling them to incorporate genomic advances into their daily nursing care. The American Nurses Association Code of Ethics for Nurses is presented as a framework for responding to these rapidly occurring changes. Two case studies illustrate how nurses are applying the emerging science and technology in genetics and genomics to advance the nursing profession and provide competent nursing care to patients faced with genetic and genomic healthcare concerns. © 2008 OJIN: The Online Journal of Issues in Nursing Article published January 31, 2008 [ABSTRACT FROM AUTHOR]

Purpose: Up to 10% of cancers may be associated with an inherited mutation that increases cancer risk. National guidelines emphasize referral for genetic counseling and testing for patients whose personal and/or family history increases their risk of having a hereditary cancer syndrome., Methods: To increase appropriate referrals for cancer genetic counseling and testing, we piloted an automated alert known as a Best Practice Advisory (BPA) in the electronic health record, Epic, to notify oncology providers when a patient had a personal and/or family history that merited referral to cancer genetics. Epic could not gather the complex clinical data needed for the referral decision automatically, necessitating staff completion of a questionnaire. After educating providers, the BPA was implemented with resources to support its use., Results: Initial interaction with the alert was high but rapidly dwindled, resulting in questionnaire completion in 7.2% of more than 32,000 encounters and 14.9% of patients over 9 months. However, cancer genetics referrals increased 95.9% during the pilot ( P < .0001), with 18.5% placed through the BPA and the rest from a non-BPA mechanism. Semistructured interviews with key stakeholders revealed not only general acceptance of the BPA concept but also barriers to completion, such as pressure to room patients quickly in the face of competing BPAs and lack of buy-in from some providers., Conclusion: These results suggest that provider engagement and BPA fatigue are significant obstacles to acceptance of a new automated alert. Despite interest in a tool for cancer genetics, the demand on clinical time for this complex BPA was poorly tolerated.

A 14-year-old girl underwent extraction of an ankylosed primary left second molar as requested by her orthodontist. The developing mandibular left second premolar (tooth 20) was unintentionally removed during extraction of the primary molar. Immediate measures were taken to reimplant tooth 20. Recall appointments over the next 10 years included monitoring of tooth 20. The patient also was followed up closely by her orthodontist during this time. Tooth 20 was monitored for proper eruption, root development, and pulpal vitality. The tooth erupted normally, and the results of pulp testing continued to be within normal limits over the course of 10 years (with the exception of a single higher electric pulp test reading than that for adjacent teeth). Root formation was completed and appeared to be within normal limits. Pulpal calcification also occurred. At the most recent recall, the tooth remained asymptomatic. Monitoring will continue during the patient's regular recall appointments. The success of this case 10 years after reimplantation supports quick action to optimize the potential for long-term clinical success. The fact that tooth 20 was at a developmental stage also likely had a favorable impact on the outcome of this case.

Objective: To provide expert personal perspectives of genomic health care and what is needed for nursing to prepare for today as well as for the future., Data Sources: Personal interviews and published literature., Conclusion: A future that includes genomic information as part of health care is exciting, enlightening, and challenging. Nurses must maintain a holistic vision for implementing genomic health care today and tomorrow., Implications for Nursing Practice: Oncology nurses have opportunities to integrate genomic information within their practice, education, and research to improve patient outcomes., (Copyright © 2018. Published by Elsevier Inc.)

Objective: The debate over use of race as a proxy for genetic risk of disease continues, but little is known about how primary care providers (nurse practitioners and general internal medicine physicians) currently use race in their clinical practice. Our study investigates primary care providers' use of race in clinical practice., Methods: Survey data from three cross-sectional parent studies were used. A total of 178 nurse practitioners (NPs) and 759 general internal medicine physicians were included. The outcome of interest was the Racial Attributes in Clinical Evaluation (RACE) scale, which measures explicit use of race in clinical decision-making. Predictor variables included the Genetic Variation Knowledge Assessment Index (GKAI), which measures the providers' knowledge of human genetic variation., Results: In the final multivariable model, NPs had an average RACE score that was 1.60 points higher than the physicians' score (P=.03). The GKAI score was not significantly associated with the RACE outcome in the final model (P=.67)., Conclusions: Physicians had more knowledge of genetic variation and used patients' race less in the clinical decision-making process than NPs. We speculate that these differences may be related to differences in discipline-specific clinical training and approaches to clinical care. Further exploration of these differences is needed, including examination of physicians' and NPs' beliefs about race, how they use race in disease screening and treatment, and if the use of race is contributing to health care disparities., Competing Interests: Competing Interests: None declared.

Purpose: To examine nurses' self-reported use of race in clinical evaluation., Design: This cross-sectional study analyzed data collected from three separate studies using the Genetics and Genomics in Nursing Practice Survey, which includes items about use of race and genomic information in nursing practice. The Racial Attributes in Clinical Evaluation (RACE) scale was used to measure explicit clinical use of race among nurses from across the United States., Methods: Multivariate regression analysis was used to examine associations between RACE score and individual-level characteristics and beliefs in 5,733 registered nurses., Findings: Analysis revealed significant relationships between RACE score and nurses' race and ethnicity, educational level, and views on the clinical importance of patient demographic characteristics. Asian nurses reported RACE scores 1.41 points higher than White nurses (p < .001), and Black nurses reported RACE scores 0.55 points higher than White nurses (p < .05). Compared to diploma-level nurses, the baccalaureate-level nurses reported 0.69 points higher RACE scores (p < .05), master's-level nurses reported 1.63 points higher RACE scores (p < .001), and doctorate-level nurses reported 1.77 points higher RACE scores (p < .01). In terms of clinical importance of patient characteristics, patient race and ethnicity corresponded to a 0.54-point increase in RACE score (p < .001), patient genes to a 0.21-point increase in RACE score (p < .001), patient family history to a 0.15-point increase in RACE score (p < .01), and patient age to a 0.19-point increase in RACE score (p < .001)., Conclusions: Higher reported use of race among minority nurses may be due, in part, to differential levels of racial self-awareness. A relatively linear positive relationship between level of nursing degree nursing education and use of race suggests that a stronger foundation of knowledge about genetic ancestry, population genetics and the concept "race" and genetic ancestry may increase in clinical decision making could allow nurses to more appropriately use of race in clinical care. Integrating patient demographic characteristics into clinical decisions is an important component of nursing practice., Clinical Relevance: Registered nurses provide care for diverse racial and ethnic patient populations and stand on the front line of clinical care, making them essential for reducing racial and ethnic disparities in healthcare delivery. Exploring registered nurses' individual-level characteristics and clinical use of race may provide a more comprehensive understanding of specific training needs and inform nursing education and practice., (© 2016 Sigma Theta Tau International.)

Genomics is an emerging field with newly developed expectations for all healthcare professionals. Nursing faculty are critical to preparing the future nursing workforce in genomics but faculty knowledge, receptivity, and interest in learning more about this subject were unknown. The authors discuss the process used to assess nursing faculty's readiness to change as a way to substantiate the need for faculty training.

Purpose: The provision of genetic services often occurs in a cascading fashion within families experiencing inherited diseases. This study examines whether previous family experiences with genetic services influences levels of psychological well-being of family members receiving services later., Methods: Two hundred ninety-seven persons from 38 families with Lynch syndrome completed questionnaires before receiving genetic services. Baseline levels of test-related distress, depressive symptoms, and cancer worries were assessed in relationship to the (1) amount of time elapsed since services were provided to the index case and (2) generation of the family member relative to the index case., Results: Family members in the same generation as the index case experienced significant increases in test-related distress (P = 0.003) and cancer worry (P = 0.001) with increasing time between receipt of genetic test results by the index case and provision of services to family members. Change in the number of depressive symptoms was not significant (P = 0.17)., Conclusion: The provision of genetic services through a cascading approach significantly increases distress and worry among family members within the same generation as the index case who receive services at increasingly distant time intervals. Additional research is needed to explore social influences after the introduction of genetic services.

Background: There has been growing emphasis on preconception care as a strategy to improve maternal and child health since the 1980s. Increasingly, development of genetic tests will require primary care providers to make decisions about preconception genetic screening. Limited research has been conducted on how primary care providers interpret patients' characteristics and use constructs, such as ethnicity and race, to decide whom to offer preconception genetic screening., Objective: This report assessed the influence of patient characteristics on decisions to offer preconception genetic screening., Methods: A web-based survey of family physicians was conducted. Physicians reviewed a clinical vignette that was accompanied by a picture of either a black or a white patient. Physicians indicated whether they would offer genetic screening, and if yes, what tests they would offer and what factors influenced their decisions., Results: The majority (69.2%) of physicians reported that they would not offer genetic screening. Respondents who reviewed the vignette accompanied by a picture of the black patient were more likely to offer screening (35% vs. 26%, p = 0.0034) and rated race as more important to their decision to offer testing than those who viewed the picture of the white patient (76% vs. 49%, p < 0.0001)., Conclusions: Our findings suggest that patient race is important to physicians when making decisions about preconception genetic testing and that decision making is influenced by patients' physical characteristics. The reticence of physicians in this sample to offer preconception screening is an important finding for public health and clinical practice.

Purpose: Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary form of colon cancer. Cancer screening recommendations differ between individuals identified to carry an HNPCC mutation and those who do not carry a known family mutation. We assessed the impact of genetic counseling and testing (GCT) on the use of endoscopic screening procedures and adherence to recommended endoscopic screening guidelines in 56 asymptomatic at-risk individuals from families known to carry an HNPCC mutation., Patients and Methods: We analyzed data on colonoscopy and flexible sigmoidoscopy screenings collected before GCT and 6 months and 12 months post-GCT on 17 mutation-positive and 39 true mutation-negative individuals. Main outcome measures were use of endoscopic screening and adherence to recommended guidelines for the relevant mutation status. Mutation status, age, sex, employment, and income were analyzed as predictor variables., Results: Among mutation-negative individuals, use of colonoscopy and flexible sigmoidoscopy decreased significantly between pre- and post-GCT (P <.00001 and P <.0003, respectively). Among mutation-positive individuals, a nonsignificant increase (P =.24) in use was noted. Age was also associated with use of endoscopic screening after GCT (P =.03). Mutation status (odds ratio [OR], 7.5; P =.02) and employment (OR, 8.6; P =.025) were associated with nonadherence to endoscopic screening guidelines. More mutation-negative individuals strictly adhered to guidelines than did mutation-positive individuals (87% v 65%)., Conclusion: Genetic counseling and testing for HNPCC significantly influences the use of colonic endoscopy and adherence to recommendations for colon cancer screening.

With the ongoing and increasingly rapid pace of genetic discoveries, nurses must be able to incorporate genetic knowledge into their everyday practices of promoting the genetic health of individuals, families, and communities. Although development of genetic health knowledge is in its infancy, nurses are currently expected to integrate information about genetic risks, testing, and treatments for clients throughout the clients' entire lifespan. All nurses must have an understanding of the relationship between genetics and health to appropriately identify and address genetic concerns in their clients. To fulfill these roles, nurses need to improve their knowledge base in genetics. This article provides recommendations for genetics curriculum in continuing and entry-level nursing education programs. These recommendations are outcomes of a research project involving genetics nurse experts as well as nurses new to the area of genetics, and a consensus workshop of nursing faculty involved in curriculum changes subsequent to an intensive genetics continuing education program. Nursing educators are beginning to recognize the importance of education of all nurses about genetics. If, however, all educators do not accept this responsibility, nurses will be left behind in designing and offering health care for the 21st century., (Copyright 2001 by W.B. Saunders Company)

The outcomes of genetic research endeavors have the potential to transform health care with significant implications for both providers and consumers of clinical services. Professional and public integration of genetics knowledge is key to successful utilization of genetics information. This article will provide an overview of genetics including a historical perspective, examples of genetic health care, the nursing perspective, and ethical considerations and challenges. New scientific explanations for health, disease, responsiveness to treatment, and design of options for care may create personal and professional dilemmas. Nurses have a responsibility to become active participants in confronting the demands resulting from this new knowledge for education, practice, and policy. The purpose of this article is to provide a foundation from which the profession of nursing can build to enhance current skills and knowledge about genetics to prepare for this transformation in health care.

2',3'-Dideoxyinosine (ddI) is a dideoxynucleoside currently in Phase I, II, and III trials for antiretroviral therapy. It has been shown to cause objective and subjective improvement in people with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). This drug, as with any drug, is not without toxicity. Through thorough patient education and clinical evaluation, incidence of these toxicities may be lessened or avoided.

The hypoxic radiosensitizers misonidazole or demethylmisonidazole were administered i.p. in a 2-liter volume to 6 patients affected by advanced ovarian carcinoma, and the pharmacokinetic course of the two drugs was studied. The clearance of misonidazole and demethylmisonidazole from the peritoneal fluid was 19.1 and 12.4 ml/min, respectively. At 3 hr after drug administration, both radiosensitizers had peritoneal fluid concentrations more than 8 times larger than in the plasma. The concentration x time exposure in the peritoneal fluid was 3.2 times larger than in plasma for misonidazole and 7.6 times for demethylmisonidazole. The advantage of i.p. delivery compared with systemic delivery decreases with distance from the peritoneal surface, but the advantage may be maintained for up to 1 mm or 100 cell layers. These differences between the two routes of administration provide a rational basis for the expectation that a substantial increase of the therapeutic benefits of misonidazole and demethylmisonidazole in potentiating radiation therapy or chemotherapy can be expected in treating tumors confined to the i.p. space.

Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, TCAR) is a synthetic C-nucleoside that demonstrated significant in vivo activity against a variety of animal tumors as well as in vitro activity against human tumor-derived cell lines. Thirteen patients were treated with TCAR administered as a 5-day continuous infusion in this Phase I trial. Seventeen complete cycles were administered in three dose levels ranging from 550 to 1450 mg/M2. Dose-limiting toxicities were myelosuppression and neurotoxicity including severe lethargy. Other toxicities including superficial skin peeling, myalgias, and tearing were seen at all doses. One patient had chest pain on day 4 resulting in stopping the drug, however, there was no evidence of cardiac or pericardial disease. Uric acid levels rose within one day in the absence of allopurinol treatment. There were no treatment related deaths. HPLC measurement of drug levels demonstrated steady-state plasma levels during the infusion, and a half-life following the infusion of 7.7 +/- 0.6 hours. Minor abnormalities in renal function were associated with dramatic changes in pharmacokinetics and toxicity. No clinical responses were observed in this trial.

The plasma pharmacokinetics of Adriamycin and adriamycinol following a 15-min infusion of 75 mg/sq m of Adriamycin were studied in ten patients previously untreated with Adriamycin. The disappearance kinetics of Adriamycin could adequately be described by a biexponential equation with an initial half-life of 8-min and a terminal half-life of 30 hr. The major drug exposure (area under the concentration-time curve) occurs during the terminal phase where drug concentrations are generally less than 10(-7) M (0.05 micrograms/ml). An improvement in the high-performance liquid chromatography sensitivity facilitated the determination of the terminal phase. The plasma kinetics of adriamycinol, the major and only known active metabolite of Adriamycin, show a rapid initial increase in plasma concentration followed by a slow decline which parallels that of Adriamycin during the terminal phase. The relative drug exposure of adriamycinol to Adriamycin was approximately 50%. The relationship between the measured plasma drug levels and free drug available for distribution into tissues was studied by comparing the plasma binding characteristics of Adriamycin and adriamycinol. A constant 20 to 25% of the total plasma concentrations of both Adriamycin and adriamycinol was freely diffusible over the whole range of observed concentrations, 20 nM to 2 microM. Thus, the free drug exposure (area under the concentration-time curve) of tumor and host tissues in vivo can be determined from these plasma measurements, since the free drug exposures in plasma and in extracellular fluid are equivalent. These results can also serve as a guide for the design of clinically relevant in vitro studies of Adriamycin and adriamycinol. The pharmacokinetic parameters determined in this study have been used to simulate plasma concentration-time courses for a variety of Adriamycin treatment schedules. Alternatives are suggested which reduce peak plasma Adriamycin concentration while antitumor area under the concentration-time curve is maintained.

We describe the clinical pharmacology and metabolism of 5-iodo-2'-deoxyuridine (IdUrd) during and after a 12-hour infusion. The kinetics of IdUrd were linear between 250 and 1200 mg/m2. The plasma IdUrd concentration reached steady state in less than 1 hour. Total body clearance of IdUrd was 750 ml/min/m2 and the disappearance t1/2 at the end of the infusion was less than 5 minutes. The primary metabolite, 5-iodouracil (IUra), did not reach steady state during the infusion. At the end of the 1200 mg/m2 infusion, the maximum plasma IUra concentration was 100 mumol/L, or about 10 times the simultaneous IdUrd plasma concentration. During the infusion there was at least a fifty- to 100-fold increase in uracil and thymine plasma concentrations. After the infusion, IUra disappearance from plasma was nonlinear, with an apparent Michaelis constant of 30 mumol/L. Plasma uracil and thymine levels slowly decreased after the IdUrd infusion until IUra fell to less than 30 mumol/L. There was subsequently a parallel and more rapid decrease in the plasma concentrations of uracil and thymine. Uridine, 2'-deoxyuridine, and thymidine plasma levels did not change significantly as a result of IdUrd therapy. These changes in endogenous pyrimidine pools are consistent with competitive inhibition of dihydrouracil dehydrogenase by IUra. An in vitro human bone marrow assay was used to determine the relative toxicity of IdUrd and IUra. Although exposure to IUra was tenfold higher than that to IdUrd, IdUrd was at least 100 times more cytotoxic to marrow cells.

We investigated the clinical pharmacokinetics of azidothymidine (N3TdR) as part of a phase I/II trial in the treatment of acquired immunodeficiency syndrome and related diseases. During the 6-week course of therapy, drug levels in plasma, cerebrospinal fluid, and urine were determined by HLPC. The plasma half-life of N3TdR was 1.1 hour. The total body clearance was 1.3 L/kg/hr. At intravenous doses of 5 mg/kg or oral doses of 10 mg/kg, plasma levels were continuously maintained above the target level of 1 mumol/L. Oral bioavailability was 63% +/- 13%. Substantial penetration of N3TdR into cerebrospinal fluid was demonstrated. At doses of 5 mg/kg intravenously or 10 mg/kg orally, cerebrospinal fluid drug levels exceeded and were maintained close to 1 mumol/L. Nineteen percent of the administered dose was excreted unchanged into the urine. Renal clearance was 0.23 L/kg/hr. N3TdR possesses pharmacokinetic properties that would facilitate the long-term treatment of patients with acquired immunodeficiency syndrome: it can be given orally and it penetrates the central nervous system.