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.

Patient reasoning in palliative surgical oncology.

BACKGROUND: The purpose of this study was to determine the patient reasoning behind treatment choice after palliative surgical consultation. METHODS: Patients undergoing palliative surgical consultation were prospectively enrolled in this observational cohort study (11/2009-5/2011) and administered an open-ended questionnaire asking for their reasoning in choosing their treatment strategy. RESULTS: Of 98 patients enrolled, 54 were treated non-operatively and 44 with surgery. Patient responses indicating their reason for treatment selection were categorized into (1) quality of life or symptom relief, (2) unclear or response not related to treatment strategy, (3) increase length of life, (4) treat the cancer, (5) concerns over surgical complications, (6) doctor's recommendation, (7) religious reasons for treatment choice, and (8) for family. The most frequently cited reason for treatment selection was symptom relief or quality of life improvement in 46 patients. Thirty-eight patients cited their doctor's recommendation while 20 patients selected their treatment to increase length of life or treat their cancer. Only 2 patients cited concerns over surgical complications as their reason for choosing their treatment strategy. CONCLUSIONS: The most common reasons for treatment selection in palliative surgical consultation include symptom relief or improvement in quality of life and the doctor's recommendation with few patients listing concerns over surgical morbidity.

Prophylactic recombinant erythropoietin therapy and thalidomide are predictors of venous thromboembolism in patients with multiple myeloma: limited effectiveness of thromboprophylaxis.

BACKGROUND: Venous thromboembolism (VTE) is a significant but poorly understood complication in patients with newly diagnosed multiple myeloma (NDMM). As a result, most patients receive thromboprophylaxis with low molecular weight heparin (LMWH). The purpose of this retrospective study was to identify risk factors for VTE in NDMM and evaluate the effectiveness of LMWH. METHODS: A total of 604 patients with newly diagnosed myeloma completed 3 induction cycles with multiagent chemotherapy with up-front randomization to thalidomide between 1998 and 2004. Prophylactic enoxaparin was given to thalidomide recipients beginning in June 2001, and 122 subjects received prophylactic epoetin alfa (EPO) as part of an exercise trial. The primary study endpoint was grades 3-4 VTE. RESULTS: A total of 72 patients (11.9%) developed VTE (mostly deep venous thrombosis), with a higher incidence among EPO recipients (P = .001), although only significant for upper extremity DVT (P = .0002). The EPO-treated patients had higher hemoglobin (Hb) levels throughout the study (P < .0005), although no relationship between higher Hb levels and increasing incidence of VTE could be shown. A history of VTE was a strong predictor of VTE on univariate analysis (P < .000005). Enoxaparin did not reduce the rate of VTE (P = .158). Logistic regression analysis identified thalidomide therapy (P = .001; odds ratio [OR], 2.428; 95% confidence interval [CI], 1.418-4.159) and prophylactic EPO (P = .002; OR, 2.488; 95% CI, 1.432-4.324) as risk factors for VTE. Myeloma response and survival were not negatively affected by prophylactic EPO or VTE. CONCLUSIONS: Prophylactic EPO, thalidomide therapy, and VTE history, but not higher Hb levels, were found to increase the risk of VTE among NDMM patients receiving multiagent chemotherapy. This risk was not found to be reduced in this population by LMWH thromboprophylaxis.

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.

Patient advocacy: witnessing informed consent for research in acute care.

Two views exist about witnessing informed consent for research in acute care settings: nurses witness a signature, and nurses witness the informed consent itself. Nurses are obligated to fulfill legal responsibilities and ethical expectations because of their role in the clinical arena, and to serve as advocates for patients to be informed, willing research participants. This role promotes change in institutional policies to keep up with the changing face of research.

Exploring measures of functional dependence in the older adult with cancer.

An aging population and increased incidence of cancer in older adults indicate the need to assess functional status within cancer treatment planning. This type of assessment could affect decisions about treatment options, nursing interventions, and community services for elders with cancer.

Nurse executives' perceptions of end-of-life care provided in hospitals.

CONTEXT: With the aging of our population, almost one in five adults, or 19% of the population, will be older than 65 years by 2030. Many persons have expressed concern about the inadequate preparation of hospitals to provide high-value end-of-life care for the current and anticipated population of older adults. OBJECTIVES: The purpose of this study was to explore the perceptions of nurse executives about the provision of end-of-life care in the hospital setting. METHODS: We conducted a pilot, descriptive, naturalistic, qualitative study using in-person interviews to capture nurse executives' understandings, beliefs, and perceptions of end-of-life care in their facilities. RESULTS: Data were collected from 10 nurse executives. We identified five major factors, three barriers and two facilitators, in their descriptions of provision of end-of-life care provided in the hospital: 1) communication inadequacies, 2) education inadequacies, 3) hospital system constraints, 4) hospice services availability, and 5) nurse executive advocacy. CONCLUSION: These findings highlight the need for interventions that focus on improving communication at the bedside and in transitions of care, enhancing educational interventions, and developing patient-centered care systems, which translate into a higher quality end-of-life experience for patients and their family members. Nurse executives are currently an underused resource in end-of-life care but are poised to be able to champion innovative models and a culture of change that integrates high-value care for patients with serious and chronic illnesses.

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.

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.

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.

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.

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.

Older adults' functional performance loss and adaptation during chemotherapy.

The experience of functional performance change in older adults during chemotherapy was the focus for this qualitative descriptive study. The 9 female and 2 male participants (mean age 70.4, SD 6.6) described their experiences in semistructured, tape-recorded interviews. The interview transcripts were analyzed making constant comparisons as interviews progressed. Results indicated older adults experience losses related to changes in functional performance during chemotherapy and make adaptations to those losses. These findings are congruent with the literature reporting that individuals modify or replace activities using old or new coping methods. Recognizing the impact of functional performance changes may facilitate support of older adults throughout chemotherapy. There are limitations to the study, primarily related to the sample: 82% were female, all were Caucasian, 4 types of cancer were present, but 46% had breast cancer. Future studies, especially intervention studies to prevent or address functional performance loss, may be warranted.