Cancer prevention in cancer predisposition syndromes: A protocol for testing the feasibility of building a hereditary cancer research registry and nurse navigator follow up model.

Monogenic, high penetrance syndromes, conferring an increased risk of malignancies in multiple organs, are important contributors to the hereditary burden of cancer. Early detection and risk reduction strategies in patients with a cancer predisposition syndrome can save their lives. However, despite evidence supporting the benefits of early detection and risk reduction strategies, most Canadian jurisdictions have not implemented programmatic follow up of these patients. In our study site in the province of Newfoundland and Labrador (NL), Canada, there is no centralized, provincial registry of high-risk individuals. There is no continuity or coordination of care providing cancer genetics expertise and no process to ensure that patients are referred to the appropriate specialists or risk management interventions. This paper describes a study protocol to test the feasibility of obtaining and analyzing patient risk management data, specifically patients affected by hereditary breast ovarian cancer syndrome (HBOC; BRCA 1 and BRCA 2 genes) and Lynch syndrome (LS; MLH1, MSH2, MSH6, and PMS2 genes). Through a retrospective cohort study, we will describe these patients' adherence to risk management guidelines and test its relationship to health outcomes, including cancer incidence and stage. Through a qualitative interviews, we will determine the priorities and preferences of patients with any inherited cancer mutation for a follow up navigation model of risk management. Study data will inform a subsequent funding application focused on creating and evaluating a research registry and follow up nurse navigation model. It is not currently known what proportion of cancer mutation carriers are receiving care according to guidelines. Data collected in this study will provide clinical uptake and health outcome information so gaps in care can be identified. Data will also provide patient preference information to inform ongoing and planned research with cancer mutation carriers.

Incivility in practice - incidence and experiences of nursing students in eastern Canada: A descriptive quantitative study.

BACKGROUND: Incivility within nursing is professionally unacceptable. Little research exists regarding student nurses' experiences with incivility from healthcare professionals and others within the clinical environment and particularly within a Canadian context. AIM: To describe the incidence and perceptions of incivility experienced by undergraduate nursing students from healthcare professionals and others within clinical practice. METHOD: This descriptive study used an electronic survey and was conducted at an eastern Canadian university. Descriptive statistics were applied. RESULTS: Of 650 nursing students invited to participate in the study, 260 surveys were fully completed. Of these, 70% of respondents indicated experiencing incivility, mostly in acute care settings. Registered nurses and licensed practical nurses were the major offenders. Discourteous gestures and condescending remarks were the most frequently experienced uncivil acts, resulting in feelings of high anxiety and inadequacy. Participants coped by avoiding communication with the perpetrator. Incivility was rarely reported because of a belief it would be fruitless to do so, lack of awareness of policies and fear of retaliation. CONCLUSIONS: Nursing students experience incivility frequently in clinical practice with serious consequences. Recommendations arising from this study encourage educators and healthcare leaders to collaborate to review, implement and evaluate curricula, policies and processes to address incivility.

Dynamic stormwater management to mitigate phosphorous export.

Altered stormwater flow characteristics and associated changes in nutrient and sediment fluxes due to urbanization threaten the water quality of many water bodies. For example, particle-bound phosphorus in stormwater runoff adds to the nutrient pool that can produce harmful algal blooms, and the associated particulate material can endanger fish and other living organisms in surface waters by increasing turbidity. While many studies have investigated how Total Solids (TS) particle size distributions vary in urban stormwater and the associated design criteria for Best Management Practices (BMPs) to remove TS, few studies have included different forms of phosphorus and their association with particle sizes to characterize design criteria to specifically maximize Total Phosphorus (TP) removal. This highlights a gap in our understanding of how the particle size distributions of TP and TS are related, and how these particle size distributions vary within and between storm events. Bridging this knowledge gap can improve design methods for BMPs specifically targeting phosphorus removal. This study characterizes within event (i.e., hourly) TP and TS particle size distributions and associated fluxes from urban catchments in the City of Cambridge, Massachusetts, to characterize potential TP and TS removal based on four different diversion and treatment strategies. The stormwater diversion strategies integrate new insights on temporal variations in particle size distributions and mass loading characteristics. In terms of diverted stormwater, the volume of stormwater treated tends to control more than what water is treated (e.g., first flush, event high flows, or smaller event flows). Based on the event data obtained in this study, considering flow volume different diversion approaches are optimal for TP vs TS, but treatment combined with particles sizes < 100 µm is best for both TP and TS.

Identifying Indicators of National Council Licensure Examination for Registered Nurses (NCLEX-RN) Success in Nursing Graduates in Newfoundland & Labrador.

In Canada in 2015, the pass rates on the National Council Licensure Examination (NCLEX-RN) were considerably lower than pass rates on the Canadian Registered Nurse Examination (CRNE) causing nurse educators to express concern regarding the NCLEX-RN. The purpose of this study was to examine the relationship between candidate variables (e. g. academic performance, demographics) on their NCLEX-RN outcome (pass/fail). A cross-sectional data linkage design was employed using multiple sources of data on nursing graduates who wrote the NCLEX-RN in 2015, 2016 and 2017 (n = 259). Results showed that fewer questions answered on the NCLEX-RN and higher grades in various nursing courses (e. g. Introduction to Nursing, Statistics) predicted higher odds of passing the NCLEX-RN. To improve pass rates, nurse educators must integrate diverse methods of testing into existing curricula that mimic the NCLEX-RN exam, specifically computer adaptive exams. Further research is needed to determine other possible challenges for countries considering adopting the NCLEX-RN.

The Value of Peer Mentorship as an Educational Strategy in Nursing.

BACKGROUND: The emphasis of this article is to provide nursing instructors with a valuable educational strategy grounded in andragogical principles for reflection and implementation in their educational practice. METHOD: An expository review of the value of peer mentorship as an educational strategy that fits within the humanistic adult education philosophy and social constructivism theory was conducted. RESULTS: The value in peer mentorship is greatest for nursing students as mentors and mentees, predominantly in encouraging self-directed learning, building relationships, providing emotional and educational support, and developing collaboration and leadership skills. In addition, peer mentorship provides value to instructors and educational institutions by supporting a positive student-centered learning environment that enhances student success. CONCLUSION: Peer mentorship as a valuable educational strategy can be recognized for future use within all levels of nursing education and can be applied universally to teaching and learning within other health care educational settings. [J Nurs Educ. 2018;57(4):217-224.].

Hematopoietic Progenitor Cell Mobilization with Ifosfamide, Carboplatin, and Etoposide Chemotherapy versus Plerixafor-Based Strategies in Patients with Hodgkin and Non-Hodgkin Lymphoma.

Studies comparing the efficacy and safety of chemo-mobilization with ifosfamide, carboplatin, and etoposide (ICE) ± rituximab with plerixafor-based approaches in lymphoma patients have not been performed. We analyzed hematopoietic progenitor cell mobilization outcomes in lymphoma patients undergoing chemo-mobilization with ICE (n = 35) compared with either routine plerixafor (n = 30) or "just in time" (JIT) plerixafor-based mobilization (n = 33). Chemo-mobilization provided a significantly higher total CD34(+) cell yield (median collection, 5.35 × 10(6) cells/kg for ICE versus 3.15 × 10(6) cells/kg for routine plerixafor and 3.6 × 10(6) cells/kg for JIT plerixafor, P < .001). The median day 1 yield of CD34(+) cells was not significantly different (median, 2.2 × 10(6) cells/kg in ICE versus 1.9 × 10(6) cells/kg in upfront plerixafor versus 1.7 × 10(6) cells/kg in JIT plerixafor, P = .20). There was no significant difference in the 3 groups in terms of total number of apheresis sessions performed (median, 2 in each group; P = .78). There were no mobilization failures (inability to collect at least 2 × 10(6) cells/kg) in the chemo-mobilization group, whereas 5 patients (16.7%) in the routine plerixafor and 3 patients (9.1%) in JIT group had mobilization failure (P = .04). Mean time to neutrophil engraftment was faster in the chemo-mobilization group, 10.3 days (±1.2) compared with 12.1 days (±3.6) in the routine plerixafor group and 11.6 days (±3.0) in the JIT group (P < .001) and mean time to platelet engraftment was 13.7 days (±.7) in ICE versus 20.3 days (±1.6) in routine plerixafor versus 17.1 days (± .9) in JIT group (P < .001). Red blood cell transfusions were significantly higher in the chemo-mobilization group (34.3% versus 0 versus 3.2% versus 1, P < .001) and so were the platelet transfusions (22.9% versus 0 versus 0, P < .001). Excluding the cost of chemotherapy administration, chemo-mobilization was associated with significantly less mobilization cost (average cost $17,601.76 in ICE versus $28,963.05 in routine and $25,679.81 in JIT, P < .001). Our data suggests that chemo-mobilization with ICE provides a higher total CD34(+) cell yield, lower rates of mobilization failure, faster engraftment, and lower cost compared to plerixafor-based approaches with comparable toxicity profile between the groups, except for higher transfusion requirements with chemo-mobilization.

Hematopoietic progenitor cell mobilization with "just-in-time" plerixafor approach is a cost-effective alternative to routine plerixafor use.

BACKGROUND AIMS: Hematopoietic cell mobilization with granulocyte-colony stimulating factor (G-CSF) and plerixafor results in superior CD34+ cell yield compared with G-CSF alone in patients with myeloma and lymphoma. However, plerixafor-based approaches may be associated with high costs. Several institutions use a "just-in-time" plerixafor approach, in which plerixafor is only administered to patients likely to fail mobilization with G-CSF alone. Whether such an approach is cost-effective is unknown. METHODS: We evaluated 136 patients with myeloma or lymphoma who underwent mobilization with 2 approaches of plerixafor utilization. Between January 2010 and October 2012, 76 patients uniformly received mobilization with G-CSF and plerixafor. Between November 2012 and June 2014, 60 patients were mobilized with plerixafor administered only to those patients likely to fail mobilization with G-CSF alone. RESULTS: The routine plerixafor group had a higher median peak peripheral blood CD34+ cell count (62 versus 29 cells/µL, P < 0.001) and a higher median day 1 CD34+ yield (2.9 × 10(6) CD34+ cells/kg versus 2.1 × 10(6) CD34+ cells/kg, P = 0.001). The median total CD34+ collection was higher with routine plerixafor use (5.8 × 10(6) CD34+ cells/kg versus 4.5 × 10(6) CD34+ cells/kg, P = 0.007). In the "just-in-time" group, 40% (n = 24) completed adequate collection without plerixafor. There was no difference in mobilization failure rates. The mean plerixafor doses used was lower with "just-in-time" approach (1.3 versus 2.1, P = 0.0002). The mean estimated cost in the routine plerixafor group was higher (USD 27,513 versus USD 23,597, P = 0.01). DISCUSSION: Our analysis demonstrates that mobilization with a just-in-time plerixafor approach is a safe, effective, and cost-efficient strategy for HPC collection.

Decisions about prophylactic gynecologic surgery: a qualitative study of the experience of female Lynch syndrome mutation carriers.

BACKGROUND: Women who carry a mutation for Lynch syndrome face complex decisions regarding strategies for managing their increased cancer risks. At present, there is limited understanding of the factors influencing women's prophylactic surgery decisions. METHODS: As part of an exploratory pilot project, semi-structured interviews were conducted with 10 women who were Lynch syndrome mutation carriers and had made prophylactic surgery decisions. Nine of 10 women had chosen to undergo prophylactic hysterectomy and/or oophorectomy as a means of managing their increased gynecological cancer risks. RESULTS: Study findings revealed that surgery decisions were influenced by multiple factors, including demographic variables such as age and parity, as well as psychosocial factors such as cancer worry, in addition to personal and social knowledge of gynecological cancer. While all women were satisfied with their surgery decision, some reported they were not fully informed about the negative impact on their quality of life post-surgery (e.g., complications of surgically-induced menopause), nor about the potential for, or risks and benefits of, hormone replacement therapy. CONCLUSIONS: Study findings highlight some of the factors associated with prophylactic surgery decisions and women's perceptions about pre-surgical information provision and needs. Suggestions are made for improving the information and support provided to female carriers of a Lynch syndrome mutation.

Peripheral blood stem cell mobilization in multiple myeloma patients treat in the novel therapy-era with plerixafor and G-CSF has superior efficacy but significantly higher costs compared to mobilization with low-dose cyclophosphamide and G-CSF.

Studies comparing the efficacy and cost of peripheral blood stem and progenitor cells mobilization with low-dose cyclophosphamide (LD-CY) and granulocyte-colony stimulating factor (G-CSF) against plerixafor and G-CSF, in multiple myeloma (MM) patients treated in the novel therapy-era are not available. Herein, we report mobilization outcomes of 107 patients who underwent transplantation within 1-year of starting induction chemotherapy with novel agents. Patients undergoing mobilization with LD-CY (1.5 gm/m(2)) and G-CSF (n = 74) were compared against patients receiving plerixafor and G-CSF (n = 33). Compared to plerixafor, LD-CY was associated with a significantly lower median peak peripheral blood CD34+ cell count (68/µL vs. 36/µL, P = 0.048), and lower CD34+ cell yield on day 1 of collection (6.9 × 10(6)/kg vs. 2.4 × 10(6)/kg, P = 0.001). Six patients (8.1%) in the LD-CY group experienced mobilization failure, compared to none in the plerixafor group. The total CD34+ cell yield was significantly higher in the plerixafor group (median 11.6 × 10(6)/kg vs. 7 × 10(6)/kg; P-value = 0.001). Mobilization with LD-CY was associated with increased (albeit statistically non-significant) episodes of febrile neutropenia (5.4% vs. 0%; P = 0.24), higher use of intravenous antibiotics (6.7% vs. 3%; P = 0.45), and need for hospitalizations (9.4% vs. 3%; P = 0.24). The average total cost of mobilization in the plerixafor group was significantly higher compared to the LD-CY group ($28,980 vs. $19,626.5 P-value < 0.0001). In conclusion, in MM plerixafor-based mobilization has superior efficacy, but significantly higher mobilization costs compared to LD-CY mobilization. Our data caution against the use of LD-CY in MM patients for mobilization, especially after induction with lenalidomide-containing regimens.

Salvage bone marrow harvest in patients failing plerixafor-based stem cell mobilization attempt: feasibility and autologous transplantation outcomes.

Inadequate mobilization of peripheral blood progenitor cells (PBPC) is sometimes a limiting factor to proceed with an autologous hematopoietic cell transplantation (auto-HCT), in an otherwise eligible patient. In such situations, a bone marrow harvest (BMH) procedure may be considered to achieve the CD34+ target dose for an autograft. Plerixafor-based mobilization has recently been shown to improve PBPC collection yields. However, the feasibility and outcomes of BMH in patients failing plerixafor-based mobilization is not known. We report here, 6 patients who underwent BMH after PBPC mobilization failure with plerixafor. The median CD34+ yield with plerixafor mobilization and BMH were 1.15 x 10^6/Kg (range, 0.2-1.7 × 10^6/Kg) and 0.32 (range, 0.12-0.38 × 10^6/Kg), respectively. Three patients proceeded to an auto-HCT, with only 1 patient receiving CD34+ cell dose of at least 2 × 10^6/Kg. While neutrophil recovery was seen, platelet recovery and red cell transfusion independence were delayed. All 3 autografted patients experienced disease progression by day +100. These data suggest, limited incremental benefit of a salvage BMH after plerixafor mobilization failure, cautioning against routine use of this strategy.

Development and preliminary testing of the psychosocial adjustment to hereditary diseases scale.

BACKGROUND: The presence of Lynch syndrome (LS) can bring a lifetime of uncertainty to an entire family as members adjust to living with a high lifetime cancer risk. The research base on how individuals and families adjust to genetic-linked diseases following predictive genetic testing has increased our understanding of short-term impacts but gaps continue to exist in knowledge of important factors that facilitate or impede long-term adjustment. The failure of existing scales to detect psychosocial adjustment challenges in this population has led researchers to question the adequate sensitivity of these instruments. Furthermore, we have limited insight into the role of the family in promoting adjustment. METHODS: The purpose of this study was to develop and initially validate the Psychosocial Adjustment to Hereditary Diseases (PAHD) scale. This scale consists of two subscales, the Burden of Knowing (BK) and Family Connectedness (FC). Items for the two subscales were generated from a qualitative data base and tested in a sample of 243 participants from families with LS. RESULTS: The Multitrait/Multi-Item Analysis Program-Revised (MAP-R) was used to evaluate the psychometric properties of the PAHD. The findings support the convergent and discriminant validity of the subscales. Construct validity was confirmed by factor analysis and Cronbach's alpha supported a strong internal consistency for BK (0.83) and FC (0.84). CONCLUSION: Preliminary testing suggests that the PAHD is a psychometrically sound scale capable of assessing psychosocial adjustment. We conclude that the PAHD may be a valuable monitoring tool to identify individuals and families who may require therapeutic interventions.

Intermediate-dose versus low-dose cyclophosphamide and granulocyte colony-stimulating factor for peripheral blood stem cell mobilization in patients with multiple myeloma treated with novel induction therapies.

Peripheral blood progenitor cell mobilization with intermediate-dose cyclophosphamide (ID-CY) and granulocyte colony-stimulating factor (G-CSF) has been shown to be more efficacious, albeit more toxic, than low-dose cyclophosphamide (LD-CY) mobilization regimens in patients with multiple myeloma treated with conventional therapies. However, the relative importance of cyclophosphamide dose intensity in peripheral blood progenitor cell mobilization after novel induction regimens is not known. Here we report mobilization outcomes of 123 patients who underwent transplantation within 1 year of starting induction chemotherapy with novel agents. We compared consecutive patients undergoing mobilization with ID-CY/G-CSF (3-4 g/m(2)) at one institution (n = 55) with patients receiving LD-CY/G-CSF (1.5 g/m(2)) at a different transplantation center (n = 68). At baseline, the 2 groups were well balanced, except for more frequent previous lenalidomide use in the ID-CY group (P = .04). Compared with LD-CY, ID-CY use was associated with higher median peak PB CD34(+) cell count (35/µL versus 160/µL; P < .001), CD34(+) cell yield on day 1 of collection (2.6 × 10(6)/kg versus 11.7 × 10(6)/kg, P ≤ .001), and total CD34(+) cell yield (7.5 × 10(6)/kg versus 16.6 × 10(6)/kg; P ≤ .001). Six patients in the LD-CY group had mobilization failure, compared with no patients in the ID-CY group. A significantly higher proportion of patients in the LD-CY group (P < .001) were unable to collect ≥5 × 10(6)/kg and ≥10 × 10(6)/kg CD34(+) cells. Neutrophil and platelet engraftment were significantly faster in the ID-CY group, likely because of higher infused CD34(+) cell doses. In conclusion, compared with LD-CY, ID-CY produced a more robust peripheral blood progenitor cell mobilization and significantly reduced the rates of mobilization failure. These data caution against the use of LD-CY-containing mobilization strategies in patients with multiple myeloma undergoing stem cell collection after novel induction regimens.

Higher infused CD34+ cell dose and overall survival in patients undergoing in vivo T-cell depleted, but not t-cell repleted, allogeneic peripheral blood hematopoietic cell transplantation.

BACKGROUND AND OBJECTIVES: Understanding the effect of cellular graft composition on allogeneic hematopoietic cell transplantation (AHCT) outcomes is an area of great interest. The objective of the study was to analyze the correlation between transplant-related outcomes and administered CD34+, CD3+, CD4+ and CD8+ cell doses in patients who had undergone peripheral blood, AHCT and received either in vivo T-cell depleted or T-cell replete allografts. DESIGN AND SETTING: Comparison of consecutive patients who underwent peripheral blood AHCT in our institution between January 2003 and December 2009. PATIENTS AND METHODS: The cohort of 149 patients was divided into two groups; non T-cell depleted (NTCD) (n=54) and T-cell depleted (TCD) (n=95). Study endpoints were overall survival (OS), progression free survival (PFS), engraftment kinetics (neutrophil and platelet recovery), incidence of acute graft versus host disease (acute GVHD), chronic GVHD, nonrelapse mortality (NRM) and disease relapse. RESULTS: Multivariate analysis showed that higher infused CD34+ cell dose improved OS (relative risk 0.58, 95% CI 0.34-0.98, P=.04), PFS (relative risk 0.59, 95% CI 0.35-1.00, P=.05) and NRM (relative risk 0.49, 95% CI 0.24-0.99, P=.048) in the TCD group. By multivariate analysis, there was no difference in engraftment, grades II-IV acute GVHD, extensive chronic GVHD and relapse in the two groups relative to the infused cell doses. There was a trend towards improved OS (relative risk 0.54, 95% CI 0.29-1.01, P=.05) with higher CD3+ cell dose in the TCD group. CONCLUSION: Our findings suggest that higher CD34+ cell dose imparts survival benefit only to in vivo TCD peripheral blood AHCT recipients.

Lynch syndrome: barriers to and facilitators of screening and disease management.

BACKGROUND: Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC) and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing. METHODS: The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23) were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management. RESULTS: Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers. CONCLUSIONS: Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health.