Avelumab Combined with Stereotactic Ablative Body Radiotherapy in Metastatic Castration-resistant Prostate Cancer: The Phase 2 ICE-PAC Clinical Trial.

BACKGROUND: Immune checkpoint inhibitor monotherapy in metastatic castration-resistant prostate cancer (mCRPC) has produced modest results. High-dose radiotherapy may be synergistic with checkpoint inhibitors. OBJECTIVE: To evaluate the efficacy and safety of the PD-L1 inhibitor avelumab with stereotactic ablative body radiotherapy (SABR) in mCRPC. DESIGN, SETTING, AND PARTICIPANTS: From November 2017 to July 2019, this prospective phase 2 study enrolled 31 men with progressive mCRPC after at least one prior androgen receptor-directed therapy. Median follow-up was 18.0 mo. INTERVENTION: Avelumab 10 mg/kg intravenously every 2 wk for 24 wk (12 cycles). A single fraction of SABR (20 Gy) was administered to one or two disease sites within 5 d before the first and second avelumab treatments. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the disease control rate (DCR), defined as a confirmed complete or partial response of any duration, or stable disease/non-complete response/non-progressive disease for ≥6 mo (Prostate Cancer Clinical Trials Working Group 3-modified Response Evaluation Criteria in Solid Tumours version 1.1). Secondary endpoints were the objective response rate (ORR), radiographic progression-free survival (rPFS), overall survival (OS), and safety. DCR and ORR were calculated using the Clopper-Pearson exact binomial method. RESULTS AND LIMITATIONS: Thirty-one evaluable men were enrolled (median age 71 yr, 71% with ≥2 prior mCRPC therapy lines, 81% with >5 total metastases). The DCR was 48% (15/31; 95% confidence interval [CI] 30-67%) and ORR was 31% (five of 16; 95% CI 11-59%). The ORR in nonirradiated lesions was 33% (four of 12; 95% CI 10-65%). Median rPFS was 8.4 mo (95% CI 4.5-not reached [NR]) and median OS was 14.1 mo (95% CI 8.9-NR). Grade 3-4 treatment-related adverse events occurred in six patients (16%), with three (10%) requiring high-dose corticosteroid therapy. Plasma androgen receptor alterations were associated with lower DCR (22% vs 71%, p = 0.13; Fisher's exact test). Limitations include the small sample size and the absence of a control arm. CONCLUSIONS: Avelumab with SABR demonstrated encouraging activity and acceptable toxicity in treatment-refractory mCRPC. This combination warrants further investigation. PATIENT SUMMARY: In this study of men with advanced and heavily pretreated prostate cancer, combining stereotactic radiotherapy with avelumab immunotherapy was safe and resulted in nearly half of patients experiencing cancer control for 6 months or longer. Stereotactic radiotherapy may potentially improve the effectiveness of immunotherapy in prostate cancer.

Human papillomavirus infection, vaccination, and cervical cancer communication: the protection dilemma faced by women in southern Appalachia.

Human papillomavirus is the most frequently occurring sexually transmitted infection and has been recognized as the necessary cause of cervical cancer. Understanding the shift in public awareness caused by recent changes to cervical prevention is critical to addressing cervical cancer disparities in Appalachia. Since the human papillomavirus vaccine was approved for prevention, little data have been collected regarding human papillomavirus risk assessment and vaccine perceptions among Appalachian women. The purpose of the authors in this study was to investigate communication and cultural issues via a social scripting framework that could influence human papillomavirus vaccine uptake among southern Appalachian women; and explore participants' perceptions of human papillomavirus, cervical cancer, and the vaccine. A qualitative, descriptive design was employed to examine these issues in eight counties in northeast Tennessee and southwest Virginia. Thirty-nine women aged 18-49 years participated in a single individual interview or focus group session from October 2007 through August 2008. Interview and focus group data were audio-taped and transcribed verbatim. Two major themes emerged from the data: the human papillomavirus vaccine protection dilemma and spheres of silence surrounding the human papillomavirus vaccine protection dilemma. Study findings suggested areas for future research and may assist healthcare professionals in approaching southern Appalachian women as they make decisions regarding cervical cancer prevention.

Vitamin D status in veterans with inflammatory bowel disease: relationship to health care costs and services.

Vitamin D deficiency is a global pandemic associated with increased health care costs and could play a role in the pathogenesis and management of inflammatory bowel disease. This study examined vitamin D status in veterans with ulcerative colitis (UC) and Crohn's disease (CD) and assessed its relationship to health care costs and service utilization. Veteran patients (n = 125) with UC or CD and with an available 25-hydroxyvitamin D level were studied. CD patients were more likely to be vitamin D insufficient than the UC group. Despite the higher vitamin D levels among UC patients, they were significantly more likely to utilize laboratory and pharmacy services compared with CD patients, whereas patients with CD had significantly higher radiology and pharmacy costs. Thus, it is likely that disease-specific characteristics rather than vitamin D status determine the costs of health care services in veterans with established inflammatory bowel disease.

Sexual assault in the workplace.

Women are sexually assaulted at an alarming rate, and the workplace is a frequent arena for assault. However, in recent decades, attention has been given to improving responses to sexual assault. Sexual assault is a frequent cause of injury and death for women in the United States. One in five American women admit they have experienced a completed rape during their lifetime. These estimates are conservative because sexual assault and sexual violence are both underreported and underprosecuted. Fear of job loss and discrimination are frequent reasons women do not report sexual assault in the workplace. Women are entering the workplace in greater numbers due in part to more single parent families and the depressed economy. Also, women are entering work environments that have traditionally been the domain of male workers: corporate headquarters, semi trucks, health care providers' offices, rural farms, and rural factories. Employers must have a plan to protect female employees and effectively address any incidents of sexual assault or violence. Occupational health nurses and nurse practitioners can assist both employees and employers to prevent sexual assault and resolve the aftermath of sexual assault. However, to accomplish this goal, occupational health nurses and nurse practitioners must be trained in sexual assault and violence response as well as preventive interventions.

Treating vitamin D insufficiency in primary hyperparathyroidism: a cautionary tale.

Vitamin D deficiency is a poorly recognized pandemic and can be associated with primary hyperparathyroidism, which is not infrequently found in the general population. No formal guidelines exist to guide therapy for suboptimal Vitamin D status in patients with hyperparathyroidism. However, there are many potential benefits to achieving a Vitamin D replete state before parathyroid surgery. Previous reports have indicated that Vitamin D status can be improved without adverse effects in hyperparathyroidism. We report accentuation of hypercalcemia and hypercalciuria with Vitamin D treatment (weekly 50,000 IU ergocalciferol x 8 weeks) in a 64-year-old Caucasian male veteran with primary hyperparathyroidism, osteoporosis and Vitamin D insufficiency. The exacerbation of hypercalcemia and hypercalciuria resolved with cessation of Vitamin D therapy. We propose that clinicians consider using modest doses of Vitamin D such as 1,000 IU daily for replacement in patients with hyperparathyroidism and Vitamin D deficiency. We recommend that serum and urine calcium be monitored if such treatment is implemented.

A phenomenological exploration of reflections on lived space by child sexual abusers.

Child sexual abusers may be better understood by phenomenological exploration of reflections on childhood lived space. Child sexual abusers often suffer from child sexual abuse, physical abuse, and neglect in their childhood lived space. These experiences may be considered a limitation or deformation of the child's lived space, resulting in a distorted self view that contributes to adult behavior. Child sexual abuse is not a new phenomenon; it is a problem that has existed throughout history but has rarely enjoyed the publicity and concern of recent times. Child sexual abusers' reflections on their lived space during childhood were explored by interviewing eight incarcerated child sexual abusers in a US correctional center. Van Manen's descriptive-interpretive theoretical process was used to guide abusers' existential reflections on their childhood lived space. van Manen's phenomenological method is dynamic and was used to organize and analyze data into essential categorical themes, one of which is "failure to root." While the viewpoint is retrospective, participants in this study provided unique perspectives on childhood reflections on lived space. These experiences, as reported by the participants, could be used to assist child victims to cope and to guide nursing practice, education, and future research related to Healthy People 2010's Goal 15 (Healthy People 2010, n.d.).

Childhood experiences of incarcerated male child sexual abusers.

While numerous efforts have been made to understand the impact of child sexual abuse, little has been done to examine the childhood experiences of those who abuse children. Child sexual abusers have been studied from quantitative perspectives using behavioral checklists, parental-bonding surveys, and sexual history questionnaires. The purpose of this study was to explore incarcerated child sexual abusers' recollections of their childhood experiences using the descriptive existential lens of phenomenology. Eight incarcerated male child sexual abusers described their childhood from existential perspectives of lived space, lived other, lived body, and lived time via face-to-face semi-structured interviews. Analysis was accomplished through the qualitative, descriptive method of Max van Manen. Rich descriptions of the participants' insights into their daily childhood life experiences that shaped their self-concepts and contributed to their adult behaviors were gathered. Four major themes were identified: (1) failure to root, (2) what you see is what you learn, (3) stupid is as stupid does, and (4) life's moments. Data from this study suggest that the experiences of childhood significantly contribute to an adult self-concept that can be distorted by the lack of a secure home space, maladaptive relationships, internalization of inappropriate behavior, and a lack of significant family development. This study explores the psychosocial and behavioral consequences of early childhood experiences. The findings support the need for family and psychological mental health nurse practitioners to be more aware of early home environments; improve their assessment of children's developing self-concept and the potential for abusive relationships.

Interdisciplinary practice, education, and research: the expanding role of the occupational health nurse.

The nurses' roles are changing and expanding along with the changing health care system. Occupational health and environmental health nurses are in key positions to coordinate and direct interdisciplinary practice, education, and research. Occupational and environmental health nurses have a broad knowledge base in which they deal with employers, employees, stakeholders in communities, different governmental organizations, and families. Interdisciplinary collaboration is a way to find possible solutions to meet the needs of the work force, their families, communities, and the global community. Nurses must educate the different disciplines about their worth in collaborative interdisciplinary practice, education, and research. No single discipline can help individuals reach their full level of well-being. Interdisciplinary practice, education, and research should be encouraged for nurses to provide the best care for individuals in need of health care.

A progressive nurse practitioner student evaluation tool.

PURPOSE: To describe the process of designing a new progressive nurse practitioner student clinical evaluation tool based on competencies. DATA SOURCES: Selected research articles and professional organization published guidelines. CONCLUSIONS: Evaluation of nurse practitioner students' clinical performance is an important and often complex responsibility of faculty. The clinical evaluation tool should reflect the changing expectations associated with particular courses across the curriculum and be based on the competencies identified by the National Organization of Nurse Practitioner Faculties. Collaboration by faculty is the key to development of an accurate and useful clinical evaluation tool. IMPLICATIONS FOR PRACTICE: The progressive nurse practitioner clinical evaluation tool presented here is the result of integrating specific clinical course outcomes and competencies recognized by key nurse practitioner associations.

Relationship between vitamin D status and ICU outcomes in veterans.

OBJECTIVE: Vitamin D deficiency remains a poorly recognized pandemic and is closely linked to increased health care costs in veterans. Projected health care needs in veterans are expected to increase over the next decade. Intensive care unit (ICU) costs contribute significantly to hospital costs and stem from intervention services and management of sepsis including nosocomial infections. Vitamin D has immunomodulating and antimicrobial properties through antimicrobial peptides such as cathelicidin. DESIGN/METHODS: A retrospective study was undertaken to evaluate if vitamin D deficiency was associated with less than optimal ICU outcomes in veterans. The study included 136 veterans with 25(OH)D levels drawn within a month of admission to ICU. RESULTS: The average 25(OH)D level was 24.6 ng/mL (normal range 30-100) with 38% of patients falling in the vitamin D-deficient category (<20 ng/mL). ICU survivors had a significantly lower rate of vitamin D deficiency compared with nonsurvivors (28% versus 53%). Twenty-nine percent of vitamin D-replete patients were in ICU 3 days or more, whereas 58% of patients with vitamin D deficiency stayed in ICU 3 days or longer. This difference was highly significant translating to twofold increased risk (2.0 Relative Risk [RR]) for 3-day or longer stay in ICU for patients with vitamin D deficiency. Moreover, the risk of death was significantly higher in ICU patients with vitamin D deficiency (RR 1.81). CONCLUSION: A vitamin D-replete state may reduce costs and confer survival advantages in critical illness. We recommend that 25(OH)D levels be routinely checked and deficiencies treated in ICU patients.

Testing for vitamin D deficiency in veterans-is there a seasonal bias?

OBJECTIVE: The present study was undertaken to determine if a seasonal bias was present for vitamin D testing among Northeast Tennessee veterans, in whom vitamin D deficiency is common. DESIGN: Medical chart review. SETTING: VA Medical Center. PARTICIPANTS: Participants were 9447 patients with initial 25(OH) vitamin D levels obtained over a 3-year period. MEASUREMENT: Serum 25-hydroxyvitamin D (25[OH]D) level, date of testing, patient background factors. RESULTS: Vitamin D testing occurred more frequently in September, October, November, and December, whereas the lowest levels of 25(OH) vitamin D levels were found in January, February, and March. Similar results were observed in quarterly data with the greatest number of tests noted in the last quarter of the year, yet the lowest 25(OH) vitamin D levels were noted in the first quarter. The average monthly 25(OH) vitamin D levels were below 30 ng/mL throughout the year in the study population, consistent with highly prevalent vitamin D deficiency. CONCLUSION: Clinicians may have a seasonal bias, favoring testing for vitamin D status in the latter part of the year even though the lowest vitamin D levels are observed in the first part of the year. Although an argument could be made to check for peak 25(OH) vitamin D levels in September and trough levels in March, the seasonal contribution to vitamin D deficiency is overshadowed by ongoing vitamin D deficiency throughout the year. Thus, it may be prudent to test for vitamin D deficiency in patients presenting with fatigue, myalgias, and arthralgias regardless of the season of presentation.

A rural community-based interdisciplinary curriculum: a social work perspective.

Although social workers are frequently part of interdisciplinary teams in health care and community settings, interdisciplinary training is often lacking in social work education (Berg-Weger & Schneider, 1998). This article describes a study of the effects of an interdisciplinary community-based experiential course preparing new health care professionals for work as part of interdisciplinary teams. The interdisciplinary curriculum was established for a summer course taught in 2006 by faculty from five disciplines: social work, nutrition, medicine, nursing, and public health. The course, Quality Improvement in Rural Healthcare, which focused on health literacy in people with a diagnosis of diabetes that live in northeast Tennessee, provided a model environment for learning interdisciplinary teamwork. Evaluation of this course found that social work students displayed a statistically significant increase in positive attitude toward interdisciplinary teamwork. Course strengths, weaknesses, obstacles, and opportunities for curriculum improvement are elaborated.