Host genetic susceptibility to Clostridium difficile infections in patients undergoing autologous stem cell transplantation: a genome-wide association study.

BACKGROUND: Clostridium difficile infection (CDI) is the most common hospital-acquired infection. Unfortunately, genes that identify CDI-susceptible patients have not been well described. We performed a genome-wide association study (GWAS) to determine genetic variants associated with the development of CDI. METHODS: A cohort study of Caucasian patients undergoing autologous stem cell transplantation for multiple myeloma was performed. Patients were genotyped using Illumina® Whole Genome Genotyping Infinium chemistry. We then compared CDI-positive to CDI-negative patients using logistic regression for baseline clinical factors and false discovery rate (FDR) for genetic factors [single nucleotide polymorphisms (SNPs)]. SNPs associated with CDI at FDR of p < 0.01 were then incorporated into a logistic regression model combining clinical and genetic factors. RESULTS: Of the 646 patients analyzed (59.7% male), 57 patients were tested CDI positive (cases) and were compared to 589 patients who were tested negative (controls). Hemoglobin, albumin, and hematocrit were lower for cases (p < 0.05). Eight SNPs on five genes (FLJ16171, GORASP2, RLBP1L1, ASPH, ATP7B) were associated with CDI at FDR p < 0.01. In the combined clinical and genetic model, low albumin and three genes RLBP1L1, ASPH, and ATP7B were associated with CDI. CONCLUSION: Low serum albumin and genes RLBP1L1 and ASPH located on chromosome 8 and ATP7B on chromosome 13 were associated with CDI. Of particular interest is ATP7B given its copper modulatory role and the sporicidal properties of copper against Clostridium difficile.

GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis.

PURPOSE: High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems, cancer treatment may have to be interrupted or delayed. In this study, we looked beyond OM's known risk factors of renal function and melphalan dose with a genome-wide association study (GWAS) to evaluate whether genetic variants in conjunction with clinical risk factors influence predisposition for OM. METHODS: Genotyping was performed using Illumina HumanOmni1-Quad v1.0 BeadChip and further assessed for data quality. We tested 892,589 germline single-nucleotide polymorphisms (SNPs) for association with OM among 972 Caucasian patients treated with high-dose melphalan and ASCT in Total Therapy clinical trials (TT2, TT3, TT4) for newly diagnosed MM. Statistical analyses included t tests, stepwise regression modeling, and logistic regression modeling to find baseline clinical factors and genotypes associated with OM. RESULTS: We found that 353 (36.3 %) patients had grades 2-4 OM. Type of treatment protocol, baseline estimated glomerular filtration rate, and melphalan dose along with baseline serum albumin and female gender predicted 43.6 % of grades 2-4 OM cases. Eleven SNPs located in or near matrix metalloproteinase 13, JPH3, DHRS7C, CEP192, CPEB1/LINC00692, FBN2, ALDH1A1, and DMRTA1/FLJ35282 were associated with grades 2-4 OM. The addition of these SNPs increased sensitivity in detecting grades 2-4 OM cases to 52 %. CONCLUSIONS: These SNPs may be important for their roles in inflammatory pathways, epithelial healing, and chemotherapy detoxification.

Sleep measured by polysomnography in patients receiving high-dose chemotherapy for multiple myeloma prior to stem cell transplantation.

PURPOSE/OBJECTIVES: To describe the objective sleep of patients receiving chemotherapy for multiple myeloma (MM) prior to stem cell transplantation. DESIGN: A descriptive study with repeated measures. SETTING: An international referral center in an urban area of the southern United States. SAMPLE: A convenience sample of a subset of 12 patients with MM, recruited from a randomized, controlled trial. METHODS: Objective sleep was assessed using two nights of polysomnography, one obtained before and one after a second cycle of high-dose chemotherapy prior to stem cell transplantation. Demographic and clinical data were obtained through a retrospective chart review. MAIN RESEARCH VARIABLES: Objective sleep including sleep characteristics, sleep-related respiratory events, and periodic limb movements (PLMs) of sleep. FINDINGS: Sleep was characterized by a relatively short sleep time, excessive time spent awake after the onset of sleep, and poor sleep efficiency (objective sleep quality). Patients spent more than the expected percent of time in non-rapid eye movement sleep and less in rapid eye movement sleep. Arterial oxyhemoglobin saturation nadirs reflected episodes of low arterial oxygen saturation. PLMs during sleep were in the mildly elevated range. CONCLUSIONS: Findings suggest that patients had poor sleep efficiency (objective sleep quality) and were slightly better sleepers after receiving a second cycle of high-dose chemotherapy. A number of patients also demonstrated obstructive sleep apnea and frequent PLMs. IMPLICATIONS FOR NURSING: Findings support the need for additional investigation of sleep in patients with MM, particularly poor sleep efficiency and PLMs. Improving sleep may improve quality of life by decreasing associated symptoms such as pain, fatigue, and depression. KNOWLEDGE TRANSLATION: Oncology nurses should consider assessing patients with MM for insomnia symptoms, excessive daytime sleepiness, obstructive sleep apnea, and a history of jerking or kicking their legs when asleep. Those symptoms may suggest the need for additional investigation of a possible sleep disorder, which may negatively influence mood and function.

Personal financial effects of multiple myeloma and its treatment.

BACKGROUND: Improvements in some treatment programs for multiple myeloma (MM) are increasing survival. As patients live longer with MM as a chronic disease, the personal financial effects of MM treatment become a serious concern. OBJECTIVE: The objective of this study was to identify the personal financial effects of MM and its treatment in 5 areas: employment, disability, health/medical and life insurance, retirement, and out-of-pocket expenses. METHODS: We mailed a questionnaire about financial issues to 1015 patients who had received intensive treatment for MM at the study site. Data analysis included descriptive statistics and comparisons using independent t tests. RESULTS: Our sample (n = 762; mean age, 61 [SD, 9.26] years) experienced issues with employment (66% employed at diagnosis and treatment; 33% employed at questionnaire time), disability (35% applied), health/medical and life insurance (29% lost coverage and 8% changed coverage), retirement (13% retired during treatment), and out-of-pocket expenses (36% of income in first treatment year and 28% of income during most recent 12 months). CONCLUSIONS: Issues of employment, disability, health insurance, retirement, and out-of-pocket costs for treatment are major challenges for patients. IMPLICATIONS FOR PRACTICE: In the midst of assessing physical needs during clinical trials for chemotherapy and stem cell transplants, healthcare providers must keep sight of patients' personal financial needs so that we can intervene promptly with referrals to social work, rehabilitation therapy, and other healthcare professions to help patients decrease the personal financial effects of MM and its treatment.

Effects of exercise on fatigue, sleep, and performance: a randomized trial.

PURPOSE/OBJECTIVES: To compare usual care with a home-based individualized exercise program (HBIEP) in patients receiving intensive treatment for multiple myeloma (MM)and epoetin alfa therapy. DESIGN: Randomized trial with repeated measures of two groups (one experimental and one control) and an approximate 15-week experimental period. SETTING: Outpatient setting of the Myeloma Institute for Research and Therapy at the Rockfellow Cancer Center at the University of Arkansas for Medical Sciences. SAMPLE: 187 patients with newly diagnosed MM enrolled in a separate study evaluating effectiveness of the Total Therapy regimen, with or without thalidomide. METHODS: Measurements included the Profile of Mood States fatigue scale, Functional Assessment of Cancer Therapy-Fatigue, ActiGraph® recordings, 6-Minute Walk Test, and hemoglobin levels at baseline and before and after stem cell collection. Descriptive statistics were used to compare demographics and treatment effects, and repeated measures analysis of variance was used to determine effects of HBIEP. MAIN RESEARCH VARIABLES: Fatigue, nighttime sleep, performance (aerobic capacity) as dependent or outcome measures, and HBIEP combining strength building and aerobic exercise as the independent variable. FINDINGS: Both groups were equivalent for age, gender, race, receipt of thalidomide, hemoglobin levels, and type of treatment regimen for MM. No statistically significant differences existed among the experimental and control groups for fatigue, sleep, or performance (aerobic capacity). Statistically significant differences (p < 0.05) were found in each of the study outcomes for all patients as treatment progressed and patients experienced more fatigue and poorer nighttime sleep and performance (aerobic capacity). CONCLUSIONS: The effect of exercise seemed to be minimal on decreasing fatigue, improving sleep, and improving performance (aerobic capacity). IMPLICATIONS FOR NURSING: Exercise is safe and has physiologic benefits for patients undergoing MM treatment; exercise combined with epoetin alfa helped alleviate anemia.

Subjective sleep quality, objective sleep characteristics, insomnia symptom severity, and daytime sleepiness in women aged 50 and older with nonmetastatic breast cancer.

PURPOSE/OBJECTIVES: To examine subjective sleep quality in women aged 50 and older as predicted by cancer status, age, number of comorbidities, and symptoms of depressed mood; and to describe objective sleep characteristics, insomnia symptom severity, and daytime sleepiness. DESIGN: Descriptive. SETTING: Urban university and private oncology clinics in the southern United States. SAMPLE: 32 women with and 35 without nonmetastatic breast cancer, aged 50-90 years (X=64.9, SD=4.67). METHODS: Two telephone interviews, the Pittsburgh Sleep Quality Index, Profile of Mood States, three days of home actigraphy, Insomnia Severity Index, Epworth Sleepiness Scale, and medical records review. MAIN RESEARCH VARIABLES: Subjective quality of sleep; secondary objectives were sleep characteristics, insomnia symptoms, and daytime sleepiness. FINDINGS: Poor subjective sleep quality was predicted by depressed mood (p<0.00005). All mean objective sleep characteristics were similar for the breast cancer and comparison groups. Nocturnal awakenings were excessive (9.2 versus 7.3). Mean sleep onset latency was longer for the breast cancer group than for the comparison group (34.8 versus 15.6 minutes). Mean insomnia severity scores for the breast cancer group indicated subthreshold insomnia symptoms, and no clinically significant insomnia for the comparison group (8.9 versus 6.4). Mean daytime sleepiness scores were normal for both groups (7 versus 6). CONCLUSIONS: Subjective sleep quality was predicted by depressed mood only. Sleep in the breast cancer group was characterized by poor sleep quality, frequent nocturnal awakenings, and insomnia symptoms. IMPLICATIONS FOR NURSING: Screening and monitoring in women aged 50 and older with breast cancer may help promote early sleep intervention; however, additional collaborative research regarding the underlying causes of sleep disruption is needed.

Fatigue, sleep, pain, mood, and performance status in patients with multiple myeloma.

BACKGROUND: Cancer-related fatigue and insomnia are common distressing symptoms and may affect mood and performance status. OBJECTIVE: The objective of this study was to describe fatigue, sleep, pain, mood, and performance status and the relationships among these variables in 187 patients with newly diagnosed multiple myeloma (MM) and conduct an analysis using the correlates of fatigue. METHODS: Data were from baseline measures from the study, using the Profile of Mood States and the Functional Assessment of Cancer Therapy-Fatigue to assess fatigue, the actigraph to measure sleep, the Wong/Baker Faces Pain Rating Scale to assess pain, the Profile of Mood States to assess mood, and the 6-minute walk test along with a back/leg/chest dynamometer to test muscle strength to assess performance status. Data analysis consisted of descriptive statistics, Pearson and Spearman ρ correlations, and multiple regression analysis using fatigue as the dependent variable. All P values were 2-sided, and P<.05 was considered significant. RESULTS: Patients with newly diagnosed MM presented with fatigue, pain, sleep and mood disturbances, and diminished functional performance. The regression model, which included all of these variables along with age, sex, and stage of disease, was statistically significant with a large measure of effect. Mood was a significant individual contributor to the model. CONCLUSIONS: Among patients with MM, fatigue, pain, sleep, mood, and functional performance are interrelated. IMPLICATIONS FOR PRACTICE: Interventions are needed to decrease fatigue and pain and to improve sleep, mood, and functional performance.

Effect of certification in oncology nursing on nursing-sensitive outcomes.

The study compared certified nurses with noncertified nurses for symptom management of nausea, vomiting, and pain; patient satisfaction; and nurse satisfaction to determine the effect of certification in oncology nursing on those nursing-sensitive outcomes. A total of 93 nurses-35 (38%) of them certified in oncology nursing-and 270 patients completed surveys. Chart audits provided additional data on symptom management. Certified nurses scored higher than noncertified nurses on the Nurses' Knowledge and Attitudes Survey Regarding Pain as well as the Nausea Management: Nurses' Knowledge and Attitudes Survey. The chart audits showed that certified nurses followed National Comprehensive Cancer Network guidelines for chemotherapy-induced nausea and vomiting (CINV) management more often than noncertified nurses. The study demonstrated that job satisfaction is fairly high for oncology nurses and patient satisfaction is high. In general, cancer pain and CINV were managed well but improvements can be made. Nurses and physicians continuously should be educated on evidence-based guidelines for symptom management of cancer pain and CINV, and a CINV knowledge and attitude assessment tool should be developed.

Sleep across chemotherapy treatment: a growing concern for women older than 50 with breast cancer.

PURPOSE/OBJECTIVES: To conduct a metasynthesis of human sleep studies that included women aged 50 years and older with breast cancer across chemotherapy treatment. DATA SOURCES: English publications were searched with the terms sleep and breast cancer via Ovid, PubMed, and EBSCO-host databases. Human studies that used sleep-specific instruments published from January 1974-May 2009 were included. Intervention studies also were included if they provided baseline sleep data. Studies that used quality-of-life or symptom instruments or in which patients were prescreened for insomnia were not included. DATA SYNTHESIS: 382 publications were found; 17 met inclusion criteria, and 3 additional studies were located from the literature on fatigue. Two articles reported on the same study, so a total of 19 studies were included in the review. In women with nonmetastatic breast cancer, subjective and objective sleep quality appear to be poor and nocturnal awakenings frequent across chemotherapy treatment. Daytime sleepiness increases in the active phase of chemotherapy, and insomnia symptoms are common before and following chemotherapy treatment. In women with recurrent or metastatic breast cancer, difficulty falling asleep, nocturnal awakenings, difficulty awakening, and daytime sleepiness are problematic at different points in chemotherapy treatment. CONCLUSIONS: Sleep for women, including those older than 50 years, appears to be impaired across chemotherapy treatment, although replication of findings is very limited. IMPLICATIONS FOR NURSING: Future research should investigate sleep in specific age and minority groups, include daytime sleep and sleepiness, and use standard sleep nomenclature and objective measures.

Initial report of a family registry of multiple myeloma.

About 20,000 Americans are diagnosed with multiple myeloma (MM) each year, and more than 10,000 die of MM in the United States annually. The etiology of MM remains unknown, although genetic and environmental factors have been implicated. Patients (n = 68) from the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences and their family members with MM or a related malignancy were interviewed for environmental factors associated with MM and for family history data to complete pedigrees. In collaboration with Dr Henry Lynch at Creighton University, pedigrees of at least 3 generations were analyzed. Eighteen families (27%) have a putative autosomal dominant mode of genetic transmission of MM. Furthermore, the pedigrees indicate that pancreatic cancer, malignant melanoma, breast cancer, and lymphoma may be part of a myeloma syndrome. Environmental factors associated with MM present in this patient population were being born and raised in a rural area, raising cattle or cotton, and exposure to pesticides, insecticides, or herbicides. This work will be part of the efforts to create an international consortium to study familial MM. Research in the area of molecular epidemiology is needed to discover the genetic and environmental determinants of this disease.

Dietary soy intake and breast cancer risk.

PURPOSE/OBJECTIVES: To conduct a metasynthesis of the literature on human studies of the relationship between dietary soy intake and breast cancer risk. DATA SOURCES: Publications in English reporting human studies were searched with the terms soy and breast cancer, using Ovid, PubMed, and EBSCO databases. Only human studies investigating the relationship of soy intake to breast cancer development in women published from January 1997 through June 2008 were included in the review. DATA SYNTHESIS: A total of 364 publications were located; 18 of the studies met the inclusion criteria and 18 additional studies were located through other publications identified in the search. Because four articles reported on the same two studies, a total of 34 studies were included in the review. CONCLUSIONS: The naturally occurring dietary intake of soy food or its components appears safe for women without breast cancer; however, the safety of high supplements of soy or its components is less certain. IMPLICATIONS FOR NURSING: Nurses should become more knowledgeable about soy foods and supplements and include soy intake in dietary assessments. Nurses caring for women at high risk for or with a history of breast cancer should confer with dietitians on current practice recommendations. Women with health issues should avoid initiating high intake of soy dietary supplements until the possible effects are better understood.

Effect of certification in oncology nursing on nursing-sensitive outcomes.

The study compared certified nurses with noncertified nurses for symptom management of nausea, vomiting, and pain; patient satisfaction; and nurse satisfaction to determine the effect of certification in oncology nursing on those nursing-sensitive outcomes. A total of 93 nurses--35 (38%) of them certified in oncology nursing--and 270 patients completed surveys. Chart audits provided additional data on symptom management. Certified nurses scored higher than noncertified nurses on the Nurses' Knowledge and Attitudes Survey Regarding Pain as well as the Nausea Management: Nurses' Knowledge and Attitudes Survey. The chart audits showed that certified nurses followed National Comprehensive Cancer Network guidelines for chemotherapy-induced nausea and vomiting (CINV) management more often than noncertified nurses. The study demonstrated that job satisfaction is fairly high for oncology nurses and patient satisfaction is high. In general, cancer pain and CINV were managed well but improvements can be made. Nurses and physicians continuously should be educated on evidence-based guidelines for symptom management of cancer pain and CINV, and a CINV knowledge and attitude assessment tool should be developed.

Understanding Lynch syndrome: implications for nursing.

Colorectal cancer (CRC) is the second-leading cause of cancer-related death in the United States. Approximately 10% of CRC is hereditary, and hereditary nonpolyposis CRC (HNPCC), or Lynch syndrome I, is the most common form. Lynch syndrome I is characterized by onset at an early age, poor differentiation, predominance of proximal tumors, and an excess of synchronous and metachronous tumors. In Lynch syndrome II, patients exhibit Lynch syndrome I features and also have extracolonic cancers. Lynch syndrome is an inherited autosomal dominant disorder caused by a germline mutation in one of several genes responsible for DNA mismatched repair. Amsterdam I criteria, Amsterdam II criteria, and Bethesda guidelines are the international diagnostic criteria for Lynch syndrome. Nursing care for patients with Lynch syndrome includes identifying patients who would benefit from genetic counseling, providing education, and assessing and meeting patient psychosocial needs.

Obtaining family histories from patients with cancer.

Information obtained from family history data can provide valuable insight into the biologic and environmental etiologies of an individual's personal and family history of disease. The purpose of this article is to provide a brief introduction to cancer genetics and discuss ways to obtain accurate family histories in a time-efficient manner to identify families with a hereditary cancer syndrome. The focus is on gathering family history information, which should be a standard component of the initial intake for any patient and updated regularly to keep the information current.

Short Functional Dependence Scale: development and pilot test in older adults with cancer.

The purpose of this study was to develop and pilot test an instrument, the Short Functional Dependence Scale (SFDS), to measure functional dependence in the older adult receiving cancer treatment. Patients from 2 oncology clinics affiliated with a teaching hospital participated in this descriptive, quantitative study. Participants consisted of older adults (N = 26; mean age 71, SD = 5; 54% female; 85% Caucasian) receiving chemotherapy intravenously for solid tumor cancer. Patients, nurses, oncologists, and social workers helped select instrument items and establish content validity. Measurements using the SFDS included baseline and follow-up visits. Data analysis included Cronbach alpha to determine internal consistency and repeated measures to evaluate SFDS scores and associated variables. Cronbach alpha ranged from 0.737 to 0.919 for the 12 items of the SFDS. Functional dependence increased with age, surgery, radiation therapy, and lower hemoglobin levels. Compared to participants with other types of cancer, participants with lung cancer were more dependent in basic activities of daily living, but participants with breast cancer had the highest degree of overall functional dependence. The SFDS has content validity and internal consistency. Pilot testing showed that the instrument performed well in differentiating the functional dependencies of patients receiving chemotherapy according to variables of interest.

Women's perceptions of the effectiveness of telephone support and education on their adjustment to breast cancer.

PURPOSE/OBJECTIVES: Social support is believed to be important in helping women adjust to breast cancer. Reports have suggested limited positive effects of social support on well-being, mood disturbances, and relationships with significant others for women who receive telephone support. Women's perceptions of the role of social support in recovery, however, has had limited study. The purpose of this study was to describe women's perceptions of their emotional and interpersonal adaptations to breast cancer after their involvement in a randomized clinical trial in which one group received educational materials and telephone support from oncology nurses and another group received educational materials only. RESEARCH APPROACH: Content analysis was used to discover women's perceptions of their emotional and interpersonal adaptation to breast cancer following their participation in a study in which one group received educational materials and telephone support from oncology nurses and another group received educational materials only. SETTING: All participants were interviewed by telephone in their homes. PARTICIPANTS: 77 of 106 women with breast cancer from a randomized clinical trial were interviewed about their expectations of their adaptations and the effectiveness of the experimental and social support intervention delivered by telephone. METHODOLOGIC APPROACH: Telephone interviews were recorded on audiotape and transcribed for analysis. Structured interviews were completed by a non-nurse interviewer. Frequency counts were obtained from the responses to items and comments were clustered for themes. MAIN RESEARCH VARIABLES: Emotional and interpersonal adaptations to breast cancer, educational materials, and telephone support from oncology nurses. FINDINGS: Fifty-four percent of the women who received the telephone support interventions reported improvement in attitude, whereas 43% of the interviewed women in the control group reported improvement. Only three participants, all in the control group, reported worsened emotional status. The percentage of those reporting improved or unchanged physical status was about equal in each group. The majority of participants in both groups indicated that their levels of involvement in activities remained the same or increased. Forty-six percent of participants in the intervention group reported improved relationships with their spouses compared to 38% in the control group. Women from both groups indicated that the diagnosis of cancer had caused them to review their lives and make changes in their relationships and activities. CONCLUSIONS: Participants who received telephone support for one year, in addition to educational materials, reported improvement in their attitudes toward their breast cancer and better relationships with their significant others. INTERPRETATION: The women's perceptions are consistent with quantitative results from the clinical trial. This article reports additional evidence that telephone support is an effective alternative to support groups and may be appropriate for those with limited access to such groups because of geography, work demands, or family situations.