Sleep disturbances in Phelan-McDermid syndrome: Clinical and metabolic profiling of 56 individuals.

Phelan-McDermid Syndrome (PMS) is caused by deletions at chromosome 22q13.3 or pathogenic/likely pathogenic SHANK3 variants. The clinical presentation is extremely variable and includes global developmental delay/intellectual disability (ID), seizures, neonatal hypotonia, and sleep disturbances, among others. This study investigated the prevalence of sleep disturbances, and the genetic and metabolic features associated with them, in a cohort of 56 individuals with PMS. Sleep data were collected via standardized observer/caregiver questionnaires, while genetic data from array-CGH and sequencing of 9 candidate genes within the 22q13.3 region, and metabolic profiling utilized the Biolog Phenotype Mammalian MicroArray plates. Sleep disturbances were present in 64.3% of individuals with PMS, with the most common problem being waking during the night (39%). Sleep disturbances were more prevalent in individuals with a SHANK3 pathogenic variant (89%) compared to subjects with 22q13.3 deletions of any size (59.6%). Distinct metabolic profiles for individuals with PMS with and without sleep disturbances were also identified. These data are helpful information for recognizing and managing sleep disturbances in individuals with PMS, outlining the main candidate gene for this neurological manifestation, and highlighting potential biomarkers for early identification of at-risk subjects and molecular targets for novel treatment approaches.

Genetic and metabolic profiling of individuals with Phelan-McDermid syndrome presenting with seizures.

Phelan-McDermid syndrome (PMS) (OMIM*606232) is a rare genetic disorder characterized by intellectual disability, autistic features, speech delay, minor dysmorphia, and seizures. This study was conducted to investigate the prevalence of seizures and the association with genetic and metabolic features since there has been little research related to seizures in PMS. For 57 individuals, seizure data was collected from caregiver interviews, genetic data from existing cytogenetic records and Sanger sequencing for nine 22q13 genes, and metabolic profiling from the Phenotype Mammalian MicroArray (PM-M) developed by Biolog. Results showed that 46% of individuals had seizures with the most common type being absence and grand-mal seizures. Seizures were most prevalent in individuals with pathogenic SHANK3 mutations (70%), those with deletion sizes >4 Mb (16%), and those with deletion sizes <4 Mb (71%) suggesting involvement of genes in addition to SHANK3. Additionally, a 3 Mb genomic region on 22q13.31 containing the gene TBC1D22A, was found to be significantly associated with seizure prevalence. A distinct metabolic profile was identified for individuals with PMS with seizures and suggested among other features a disrupted utilization of main energy sources using Biolog plates. The results of this study will be helpful for clinicians and families in anticipating seizures in these children and for researchers to identify candidate genes for the seizure phenotype.

Using the Dermatology Life Quality Index to Assess How Breast Radiodermatitis Affects Patients' Quality of Life.

PURPOSE: The purpose of this study is to report the initial validation process for using the Dermatology Life Quality Index (DLQI) for radiodermatitis of the breast. METHODS: This is an additional analysis of a study designed to report a longitudinal study in skin-related and global quality of life in women with breast radiodermatitis. A total of 40 participants completed the DLQI instrument weekly while receiving external radiotherapy of the female breast. At week 5 on treatment, 31 (78%) participants provided narrative feedback on how each DLQI item affected her life. Agreement between participant DLQI numerical ratings and narrative feedback on items was assessed. Construct validity was estimated using principal component analysis (PCA). Internal consistency of the DLQI was assessed using Cronbach alpha. RESULTS: Percentage of agreement between participant DLQI ratings and narratives ranged from 71% to 98%. Each participant responded "no" to the work and study item leading to zero variance and removal from our analyses. Principal component analysis supported the inclusion of all of the remaining items. The DLQI with nine remaining items demonstrated moderately good internal consistency (α = .69). CONCLUSIONS: The results of our examination of the DLQI when used for breast radiodermatitis are promising. Next steps include additional larger studies among more diverse populations.

Novel measurements for radiodermatitis research and clinical care: A pilot and feasibility study.

PURPOSE: The role of clinician-measured breast length and bra cup size in the development of radiodermatitis over time and the efficacy of using multiple measurements of skin toxicity during radiotherapy were piloted. The feasibility of measures to be used in a larger future study was assessed. METHODS AND MATERIALS: Participants included women receiving normofractionated or accelerated external breast radiotherapy provided in the supine position using 3-dimensional conformal techniques at a US community cancer center. Acute skin toxicity was assessed using the RTOG scale in 7 areas within the treatment field across 6 timepoints. The total score for the 7 areas was calculated each week. Breast length was measured, examined as an acute radiodermatitis risk factor, and compared against reported bra cup size. RM-ANOVAs examined radiodermatitis using maximum skin toxicity and 7 sites in the radiotherapy field over 6 timepoints. Correlation was implemented to explore the relationship between study variables. RESULTS: Forty women consented to this study. Increase in breast length significantly correlated with increase in maximum RTOG score (p = .04); increased RTOG score in the upper medial breast quadrant (p = .04), upper lateral quadrant (p = .02), lower lateral quadrant (p = .02), inframammary fold (p = .001); with increasing BMI (p = .002) and bra cup size (p = .0003). The clinician-measured breast lengths and participant-reported bra cup sizes were discordant. Participants completed all measures and measurements including breast length. CONCLUSIONS: Our results suggest that measuring breast length and assessing radiodermatitis in multiple areas of the treatment field is feasible. These measures may increase the sensitivity of skin toxicity assessment.

Hereditary Breast and Hereditary Ovarian Cancer: Implications for the Oncology Nurse.

OBJECTIVES: To review heredity cancer syndromes involving the breasts, ovaries, or breast and ovaries. To recommend useful professional and patient resources on cancer genetics. A case study of germline BRCA genetic testing after allogeneic bone marrow transplant is presented. DATA SOURCES: National guidelines, evidence-based summaries, peer-reviewed studies, editorials, and professional Web sites. CONCLUSION: Advancing genetic/genomic technology in oncology has led to a renaissance of information about hereditary cancer syndromes. IMPLICATIONS FOR NURSING PRACTICE: Nursing competence in genetics/genomics is necessary to provide evidence-based, personalized care for individuals with cancer. Resources are available to help nurses provide quality cancer genetic informed care.

Skin-related Quality of Life among Midwestern US Community-based Women with Breast Cancer Experiencing Radiodermatitis.

OBJECTIVE: Little is known about the skin-related quality of life (QOL) among women receiving external radiotherapy (EBT) and who experience breast radiodermatitis. This pilot study aimed to describe the thoughts and experiences of women experiencing breast radiodermatitis of the breast at a comprehensive community cancer program. METHODS: A printed survey was used to solicit feedback on the Dermatology Life Quality Index (DLQI) during the 5th week of EBT. An open-ended question inquired which DLQI-related issue was most important and why. A directed qualitative content analysis was conducted on the narrative responses. RESULTS: Twenty-eight women provided a response to the "most important" question. Sixty narratives led to the identification of 35 codes and six themes during content analysis. Themes included perspectives on having radiodermatitis, sensations caused by radiodermatitis, knowledge, and preparation for radiotherapy, prevention of radiodermatitis, emotions induced by skin changes, and physical appearance of the breast skin. CONCLUSIONS: The study results provide a glimpse into the perceptions of skin-related QOL among community-dwelling women who experienced breast radiodermatitis. Some women expressed that radiodermatitis had a profound impact on their QOL while other were surprised that EBT was easy compared to chemotherapy. Our findings parallel those found in a previous study conducted in an urban setting. Results provide insight into the thoughts and needs of women undergoing breast EBT. Assessing individual differences in skin-related QOL can provide needed information for tailoring care to the unique needs of each woman. Additional studies focusing specifically on skin-related QOL are needed.

How American Nurses Association Code of Ethics informs genetic/genomic nursing.

Members of the Ethics and Public Policy Committee of the International Society of Nurses in Genetics prepared this article to assist nurses in interpreting the American Nurses Association (2015) Code of Ethics for Nurses with Interpretive Statements (Code) within the context of genetics/genomics. The Code explicates the nursing profession's norms and responsibilities in managing ethical issues. The nearly ubiquitous application of genetic/genomic technologies in healthcare poses unique ethical challenges for nursing. Therefore, authors conducted literature searches that drew from various professional resources to elucidate implications of the code in genetic/genomic nursing practice, education, research, and public policy. We contend that the revised Code coupled with the application of genomic technologies to healthcare creates moral obligations for nurses to continually refresh their knowledge and capacities to translate genetic/genomic research into evidence-based practice, assure the ethical conduct of scientific inquiry, and continually develop or revise national/international guidelines that protect the rights of individuals and populations within the context of genetics/genomics. Thus, nurses have an ethical responsibility to remain knowledgeable about advances in genetics/genomics and incorporate emergent evidence into their work.

Longitudinal trends in skin-related and global quality of life among women with breast radiodermatitis: A pilot study.

PURPOSE: The purpose of this pilot study was to explore the relationship between skin-related quality of life (SR-QOL) and global quality of life (G-QOL) among women experiencing breast radiodermatitis, measure change in SR-QOL and G-QOL between the start and fifth week on radiotherapy, and examine the trend in SR-QOL and severity of radiodermatitis over time on treatment. METHODS: A descriptive longitudinal study using repeated measurements was implemented. Forty women undergoing whole breast 3-dimensional conformal radiotherapy at a comprehensive community cancer center completed the Dermatology Life Quality Index (DLQI) weekly and Quality of Life-Breast Cancer Patient Version at baseline before and at five weeks on radiotherapy. Skin toxicity was measured weekly using the Radiation Therapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring Criteria-Skin scale. A Kendall's tau correlation explored the relationship between measures of SR-QOL and G-QOL. Paired t-tests measured the change in SR-QOL and G-QOL from baseline to fifth week on radiotherapy. The mean of the baseline and weekly total DLQI and RTOG scores was calculated and plotted on a graph. RESULTS: In general, SR-QOL and G-QOL were highly correlated. SR-QOL changed profoundly (p < .001) while G-QOL did not change (p = .55) between baseline and five weeks on radiotherapy. SR-QOL and radiodermatitis steadily worsened over time. CONCLUSIONS: Radiation-induced skin toxicity has a major impact on SR-QOL but not G-QOL. This study provides much-needed scientific evidence to inform a larger future study in a community setting. Recommendations for future studies include inclusion of a skin-sensitive survey of radiodermatitis; larger, more diverse community-dwelling sample.

Ethics and Genetics: Examining a Crossroads in Nursing Through a Case Study
.

BACKGROUND: The field of genetics and genomics is rapidly expanding, particularly in oncology. Genetics and genomics can lead to ethical concerns. Oncology nurses must balance the need for evidence-based oncology care with that of ethical care for patients and their family members. OBJECTIVES: The purpose of this article is to provide an overview of cancer genetics and ethics and their impact on oncology nurses, patients, and families. METHODS: A case study of familial adenomatous polyposis (FAP) is offered to illustrate the impact of a hereditary cancer syndrome on several generations of a family and ethical issues surrounding cancer genetics. In addition, a brief review of FAP, gene and tissue biobanking, and genome editing is provided.
. FINDINGS: Genetics, genomics, and pharmaco-genomics are ubiquitous in cancer diagnosis and management. Nurses must be knowledgeable about the ethical issues related to cancer genetics and oncology care to advocate for the needs of patients with cancer. Communication with and education of patients and their families before germline genetic testing may reduce the emergence of ethical dilemmas.

A systematic review of patient-reported outcome instruments of dermatologic adverse events associated with targeted cancer therapies.

PURPOSE: Dermatologic adverse events (dAEs) in cancer treatment are frequent with the use of targeted therapies. These dAEs have been shown to have significant impact on health-related quality of life (HRQoL). While standardized assessment tools have been developed for physicians to assess severity of dAEs, there is a discord between objective and subjective measures. The identification of patient-reported outcome (PRO) instruments useful in the context of targeted cancer therapies is therefore important in both the clinical and research settings for the overall evaluation of dAEs and their impact on HRQoL. METHODS: A comprehensive, systematic literature search of published articles was conducted by two independent reviewers in order to identify PRO instruments previously utilized in patient populations with dAEs from targeted cancer therapies. The identified PRO instruments were studied to determine which HRQoL issues relevant to dAEs were addressed, as well as the process of development and validation of these instruments. RESULTS: Thirteen articles identifying six PRO instruments met the inclusion criteria. Four instruments were general dermatology (Skindex-16©, Skindex-29©, Dermatology Life Quality Index (DLQI), and DIELH-24) and two were symptom-specific (functional assessment of cancer therapy-epidermal growth factor receptor inhibitor-18 (FACT-EGFRI-18) and hand-foot syndrome 14 (HFS-14)). CONCLUSIONS: While there are several PRO instruments that have been tested in the context of targeted cancer therapy, additional work is needed to develop new instruments and to further validate the instruments identified in this study in patients receiving targeted therapies.

Cowden syndrome: what oncology nurses need to know about increased risk of developing certain cancers.

Cowden syndrome (CS) is a genetic disorder characterized by multiple benign tissue growths (i.e., hamartomas) and an increased risk of developing specific cancers, such as breast, thyroid, kidney, endometrial, or colorectal cancer (Genetics Home Reference, 2012). This genetic syndrome was named after a person diagnosed with the disorder (Lloyd & Dennis, 1963). CS is part of a larger syndrome called PTEN hamartomatous syndrome, which also includes Bannayan-Riley-Ruvalcaba syndrome, PTEN-related Proteus syndrome, and Proteus-like syndrome (Eng, 2014).

The impact of genomics on oncology nursing.

Since 2003, genetics and genomics information has led to exciting new diagnostics, prognostics, and treatment options in oncology practice. Profiling of cancers offers providers insight into treatment and prognostic factors. Germline testing provides an individual with information for surveillance or therapy that may help them prevent cancer in their lifetime and options for family members as yet untouched by malignancy. This offers a challenge for oncology nurses and other oncology health care providers to become comfortable with incorporating education about genetics/genomics into their clinical practice and patient education.

Reflex immunohistochemistry and microsatellite instability testing of colorectal tumors for Lynch syndrome among US cancer programs and follow-up of abnormal results.

PURPOSE: Immunohistochemistry (IHC) for MLH1, MSH2, MSH6, and PMS2 protein expression and microsatellite instability (MSI) are well-established tools to screen for Lynch syndrome (LS). Although many cancer centers have adopted these tools as reflex LS screening after a colorectal cancer diagnosis, the standard of care has not been established, and no formal studies have described this practice in the United States. The purpose of this study was to describe prevalent practices regarding IHC/MSI reflex testing for LS in the United States and the subsequent follow-up of abnormal results. MATERIALS AND METHODS: A 12-item survey was developed after interdisciplinary expert input. A letter of invitation, survey, and online-survey option were sent to a contact at each cancer program. A modified Dillman strategy was used to maximize the response rate. The sample included 39 National Cancer Institute-designated Comprehensive Cancer Centers (NCI-CCCs), 50 randomly selected American College of Surgeons-accredited Community Hospital Comprehensive Cancer Programs (COMPs), and 50 Community Hospital Cancer Programs (CHCPs). RESULTS: The overall response rate was 50%. Seventy-one percent of NCI-CCCs, 36% of COMPs, and 15% of CHCPs were conducting reflex IHC/MSI for LS; 48% of the programs used IHC, 14% of the programs used MSI, and 38% of the programs used both IHC and MSI. One program used a presurgical information packet, four programs offered an opt-out option, and none of the programs required written consent. CONCLUSION: Although most NCI-CCCs use reflex IHC/MSI to screen for LS, this practice is not well-adopted by community hospitals. These findings may indicate an emerging standard of care and diffusion from NCI-CCC to community cancer programs. Our findings also described an important trend away from requiring written patient consent for screening.