Development and usability testing of a web-based cancer symptom and quality-of-life support intervention.

The feasibility and acceptability of computerized screening and patient-reported outcome measures have been demonstrated in the literature. However, patient-centered management of health information entails two challenges: gathering and presenting data using "patient-tailored" methods and supporting "patient-control" of health information. The design and development of many symptom and quality-of-life information systems have not included opportunities for systematically collecting and analyzing user input. As part of a larger clinical trial, the Electronic Self-Report Assessment for Cancer-II project, participatory design approaches were used to build and test new features and interfaces for patient/caregiver users. The research questions centered on patient/caregiver preferences with regard to the following: (a) content, (b) user interface needs, (c) patient-oriented summary, and (d) patient-controlled sharing of information with family, caregivers, and clinicians. Mixed methods were used with an emphasis on qualitative approaches; focus groups and individual usability tests were the primary research methods. Focus group data were content analyzed, while individual usability sessions were assessed with both qualitative and quantitative methods. We identified 12 key patient/caregiver preferences through focus groups with 6 participants. We implemented seven of these preferences during the iterative design process. We deferred development for some of the preferences due to resource constraints. During individual usability testing (n = 8), we were able to identify 65 usability issues ranging from minor user confusion to critical errors that blocked task completion. The participatory development model that we used led to features and design revisions that were patient centered. We are currently evaluating new approaches for the application interface and for future research pathways. We encourage other researchers to adopt user-centered design approaches when building patient-centered technologies.

Exposures in early life: associations with DNA promoter methylation in breast tumors.

There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in association with several early-life exposures in a population-based case-control study. Promoter methylation of E-cadherin, p16 and RAR-ß2 genes was assessed in archived tumor blocks from 803 cases with real-time methylation-specific PCR. Unconditional logistic regression was used for case-case comparisons of those with and without promoter methylation. We found no differences in the prevalence of DNA methylation of the individual genes by age at menarche, age at first live birth and weight at age 20. In case-case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E-cadherin promoter methylation (OR = 2.79, 95% CI, 1.15-6.82, for ⩽2.5 v. 2.6-2.9 kg); higher adult height with RAR-ß2 methylation (OR = 3.34, 95% CI, 1.19-9.39, for ⩾1.65 v. <1.60 m); and not having been breastfed with p16 methylation (OR = 2.75, 95% CI, 1.14-6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. Being other than first in the birth order was inversely associated with likelihood of ⩾1 of the three genes being methylated for premenopausal breast cancers, but positively associated with methylation in postmenopausal women. These results suggest that there may be alterations in methylation associated with early-life exposures that persist into adulthood and affect breast cancer risk.

Venus's southern polar vortex reveals precessing circulation.

Initial images of Venus's south pole by the Venus Express mission have shown the presence of a bright, highly variable vortex, similar to that at the planet's north pole. Using high-resolution infrared measurements of polar winds from the Venus Express Visible and Infrared Thermal Imaging Spectrometer (VIRTIS) instrument, we show the vortex to have a constantly varying internal structure, with a center of rotation displaced from the geographic south pole by ~3 degrees of latitude and that drifts around the pole with a period of 5 to 10 Earth days. This is indicative of a nonsymmetric and varying precession of the polar atmospheric circulation with respect to the planetary axis.

Preferred and actual participation roles during health care decision making in persons with cancer: a systematic review.

The preferred and actual participation roles during decision making have been studied over the past two decades; however, there is a lack of evidence on the degree of match between patients' preferred and actual participation roles during decision making. A systematic review was carried out to identify published studies that examined preferred and actual participation roles and the match between preferred and actual roles in decision making among patients with cancer. PubMed (1966 to January 2009), PsycINFO (1967 to January 2009), and CINAHL (1982 to January 2009) databases were searched to access relevant medical, psychological, and nursing literature. Twenty-two studies involving patients with breast, prostate, colorectal, lung, gynecological, and other cancers showed discrepancies between preferred and actual roles in decision making. These groups of patients wanted a more shared or an active role versus a less passive role. Across all cancer types, patients wanted more participation than what actually occurred. Research to date documents a pervasive mismatch between patients' preferred and actual roles during decision making. Yet, there is lack of innovative interventions that can potentially increase matching of patients' preferred and actual role during decision making. Role preferences are dynamic and vary greatly during decision making, requiring regular clinical assessment to meet patients' expectations and improve satisfaction with treatment decisions.

Distributed health assessment and intervention research software framework.

The DHAIR software system is a database-driven, web-based survey platform. It implements the delivery of survey instruments in packaged assessments, creation and editing of those assessments, researcher access to the results of the survey application, and a flexible authorization framework.

Acceptability of an Internet treatment decision support program for men with prostate cancer.

We have implemented a customized Internet decision support system designed to engage men in the decision-making process for the management of localized prostate cancer. The system is delivered to patients in the patient education room of the UWMC Prostate Oncology Center. The system interactively guides the patient through a series of surveys, and delivers multi-media interaction modeling and decision support output, both of which are customized for the patient's preferences. The system is currently implemented on an open source platform.

Cancer symptom control: feasibility of a tailored, interactive computerized program for patients.

This study evaluated the feasibility of an innovative computerized symptom assessment tool, SymptomReport, and a computerized, tailored education tool, SymptomConsult, in a sample of 41 outpatients with cancer. After patients completed the computerized programs, an audiotaped telephone interview was conducted to assess patients' impressions. The study found that patients required less than 40 minutes on average to complete SymptomReport. The mean acceptability score was high 11 +/- 2. The 12 patients who completed SymptomConsult did so in an average of 20 minutes. The majority of participants indicated that the computer programs were easy, enjoyable, and informative tools. Initial formative research supports further study of these feasible computerized programs.

Relationships between certification and job perceptions of oncology nurses.

PURPOSE/OBJECTIVES: To explore relationships between oncology nursing certification and oncology nurses' job perceptions. DESIGN: Descriptive, correlational. SETTING: Questionnaire mailed to homes of Oncology Nursing Society (ONS) members. SAMPLE: 703 certified and 514 noncertified ONS members (N = 1,217; 50% response rate). METHODS: Data were collected using survey methods and grouped by respondents' certification status for statistical analysis. MAIN RESEARCH VARIABLES: Certification, group cohesion, organizational commitment, and job satisfaction. FINDINGS: Certification was weakly correlated with cohesion, commitment, and satisfaction. Work setting, rather than certification, accounted for differences in job perceptions. Job perceptions were most positive in settings characterized by a high percentage of patients with cancer (> 75%), a high percentage of RNs (> or = 80%), and monetary support for continuing education. CONCLUSIONS: The hypothesis that oncology nurses' certification status is associated with job perceptions that are valued by employers was not supported. IMPLICATIONS FOR NURSING PRACTICE: Nurses' job perceptions have been linked to control over nursing practice and participation in organizational and clinical decision making. Managerial strategies that empower certified nurses to practice with more autonomy and participate in decisions that affect patient care should be emphasized.

The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex.

The repressor REST/NRSF restricts expression of a large set of genes to neurons by suppressing their expression in non-neural tissues. We find that REST repression involves two distinct repressor proteins. One of these, CoREST, interacts with the COOH-terminal repressor domain of REST (Andres, M. E., Burger, C., Peral-Rubio, M. J., Battaglioli, E., Anderson, M. E., Grimes, J., Dallmanm J., Ballas, N. , and Mandel, G. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 9873-9878). Here we show that the co-repressor mSin3A also interacts with REST. The REST-mSin3A association involves the NH(2)-terminal repressor domain of REST and the paired amphipathic helix 2 domain of mSin3A. REST forms complexes with endogenous mSin3A in mammalian cells, and both mSin3A and CoREST interact with REST in intact mammalian cells. REST repression is blocked in yeast lacking Sin3 and rescued in its presence. In mammalian cells, repression by REST is reduced when binding to mSin3A is inhibited. In mouse embryos, the distribution of mSin3A and REST transcripts is largely coincident. The pattern of CoREST gene expression is more restricted, suggesting that mSin3A is required constitutively for REST repression, whereas CoREST is recruited for more specialized repressor functions.

Germ-line transmission of transgenes in Xenopus laevis.

Adult Xenopus laevis frogs made transgenic by restriction enzyme-mediated integration were bred to test the feasibility of establishing lines of frogs that express transgenes. All of the 19 animals raised to sexual maturity generated progeny that expressed the transgene(s). The patterns and levels of expression of green fluorescent protein transgenes driven by a viral promoter, rat promoter, and four X. laevis promoters were all unaffected by passage through the germ line. These results demonstrate the ease of establishing transgenic lines in X. laevis.

Cancer pain and common pain: a comparison of patient-reported intensities.

PURPOSE/OBJECTIVES: To compare patient reports of present and worst cancer-related pain intensity to the recalled intensity of several commonly experienced types of pain. DESIGN: A secondary analysis on baseline data from patients with cancer pain. SETTING: Tertiary-care facilities and patients' homes. Patients were enrolled between 1988 and 1995. SAMPLE: Patients who were diagnosed with either primary lung cancer or cancer metastatic to bone, able to read and write English, over 18 years of age, and able to provide written informed consent. The sample of 125 patients was 62% male with a mean age of 60 years (SD = 11). METHODS: Patients completed the McGill Pain Questionnaire as a baseline measure in a pain research study. Investigators conducted comparisons among pain intensity scores reported for present pain intensity and worst cancer pain with the worst toothache, headache, and stomachache ever experienced using the Stuart test of marginal homogeneity. MAIN RESEARCH VARIABLES: Present cancer pain intensity and worst toothache, headache, and stomachache pain intensity. FINDINGS: Only 14% of the subjects reported that their present pain intensity was distressing, horrible, or excruciating, but 83% of them reported that their worst cancer pain was at these levels. The subjects reported that they experienced (a) significantly more intense pain with their worst toothache than either their present pain intensity (p < 0.001) or their worst cancer pain (p < 0.001), (b) significantly more intense pain with their worst headache than their present pain intensity (p < 0.001), and (c) significantly more intense pain with their worst stomachache than their present pain intensity (p < 0.001). In contrast, subjects reported that their worst cancer pain was significantly more intense than their worst headache (p = 0.047) or stomachache (p = 0.001). CONCLUSIONS: The findings suggest that present cancer pain is not only experienced at lower intensity levels than common pains, but at lower levels than expected by patients, their families, and the public. Consistent with common beliefs though, the worst cancer pain is severe and not adequately controlled for 9 out of 10 patients. IMPLICATIONS FOR NURSING PRACTICE: Healthcare professionals could use study findings to inspire hope in patients with lung cancer or bone metastasis and their families that present pain in cancer can be controlled successfully. Clinicians should devote greater efforts to relieve the worst cancer pain to levels achieved for the present pain experienced by people with cancer.

Management of breast cancer during pregnancy using a standardized protocol.

PURPOSE: No standardized therapeutic interventions have been reported for patients diagnosed with breast cancer during pregnancy. Of the potential interventions, none have been prospectively evaluated for treatment efficacy in the mother or safety for the fetus. We present our experience with the use of combination chemotherapy for breast cancer during pregnancy. PATIENTS AND METHODS: During the past 8 years, 24 pregnant patients with primary or recurrent cancer of the breast were managed by outpatient chemotherapy, surgery, or surgery plus radiation therapy, as clinically indicated. The chemotherapy included fluorouracil (1,000 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2), administered every 3 to 4 weeks after the first trimester of pregnancy. Care was provided by medical oncologists, breast surgeons, and perinatal obstetricians. RESULTS: Modified radical mastectomy was performed in 18 of the 22 patients, and two patients were treated with segmental mastectomy with postpartum radiation therapy. This group included patients in all trimesters of pregnancy. The patients received a median of four cycles of combination chemotherapy during pregnancy. No antepartum complications temporally attributable to systemic therapy were noted. The mean gestational age at delivery was 38 weeks. Apgar scores, birthweights, and immediate postpartum health were reported to be normal for all of the children. CONCLUSION: Breast cancer can be treated with chemotherapy during the second and third trimesters of pregnancy with minimal complications of labor and delivery.

The expression pattern of thyroid hormone response genes in the tadpole tail identifies multiple resorption programs.

Expression of genes up-regulated by thyroid hormone (TH) during amphibian tail resorption was localized by in situ hybridization. The constitutive thyroid hormone receptor (TRalpha) and its heterodimeric partners (RXRalpha and RXRbeta) are expressed ubiquitously in the resorbing tail. A group of early response genes, including those encoding transcription factors, are expressed at greatest levels within tissues whose cells attempt to grow and differentiate in the tail, but eventually succumb to the resorption program. The TH-inducible TR isoform, TRbeta, is expressed ubiquitously in the tail, but especially high in fibroblasts. Similarly, a group of delayed response genes including two proteolytic enzymes that appear to execute the tail resorption program, is expressed specifically in fibroblasts that line and surround the notochord and lie beneath the epidermal lamella (subepidermal fibroblasts). During active tail resorption these fibroblasts invade their neighboring epidermal and notochord lamellae as part of the resorption process. Expression analysis implicates the single layer of invasive subepidermal fibroblasts as crucial in tail resorption. Stromelysin-3 is up-regulated by TH with early kinetics, and is expressed most actively in fibroblasts within the tail fins. None of the proteases are expressed in the tadpole epidermis, which will be replaced entirely during metamorphosis. While very few TH response genes are expressed in tadpole muscle, many are activated in fibroblasts that surround muscle and could induce muscle cell death by proteolysis of the extracellular matrix. These distinct localization patterns suggest that the common fate of all cell types within the tail is the result of multiple genetic programs.

The expression pattern of thyroid hormone response genes in remodeling tadpole tissues defines distinct growth and resorption gene expression programs.

Thyroid hormone (TH) induces dramatic skeletal and tissue remodeling of the anuran head and body at metamorphosis. The expression pattern of TH up-regulated genes has been correlated with tissues that either grow or resorb at metamorphosis. Whereas the expression of the thyroid hormone receptors in Xenopus laevis tadpoles is ubiquitous, the locations where many of the TH up-regulated genes are activated fall into distinct classes. Genes in the early response class are expressed predominantly in cartilage and brain regions undergoing cell proliferation and at a higher level in the remodeling and growing body than in the resorbing tail. In contrast, expression of genes in the delayed response class is highest in resorbing tissues and higher in the tail than in the body within the subepidermal fibroblast layer, further indicating that this single cell layer is involved in tissue resorption. The expression boundary of delayed response class genes in the subepidermal fibroblasts in the body correlates with epidermal lamella invasion and subsequent adult skin differentiation. Differences in the expression patterns of stromelysin-3 and the delayed response proteinases in the head delineate separate programs of tissue resorption, one for the loss of epithelial structures, and one for the loss of cartilages. Expression of the type III deiodinase is up-regulated in growing tissues nearing completion of their metamorphic changes, suggesting a role for the deiodinase in modulating the influence of TH on these tissues.

Amniotic septostomy for the treatment of twin oligohydramnios-polyhydramnios sequence.

OBJECTIVE: To report our experience with intentional puncture of the intervening membrane ('septostomy') for the treatment of the twin oligohydramnios-polyhydramnios sequence (TOPS). METHODS: 12 patients were diagnosed with TOPS based on ultrasonographic findings. A 20- to 22-gauge spinal needle was used to puncture the membrane between the twins without any attempt at amnioreduction in 9 patients, while the procedure was combined with amnioreductions in 3 patients. RESULTS: Gestational age was 23.1 +/- 3.3 weeks at the time of septostomy and 31.1 +/- 4.4 weeks at delivery. Rapid accumulation of fluid around the 'stuck' fetus occurred in all cases following a single procedure. Three of the 24 fetuses died in utero and 1 died on the fifth day of life, for a combined survival of 83.3%. In the survivors, the septostomy to delivery interval ranged between 0.6 and 13 weeks (mean +/- SD 8.3 +/- 4.8). CONCLUSION: Amniotic septostomy is a promising new method for the management of TOPS and is associated with survival rates that are better than, or comparable to, more invasive modalities. A multicenter trial comparing septostomy to other modalities is warranted.

Candida chorioamnionitis: a report of two cases.

Intra-amniotic infection (IAI) across intact membranes by Candida albicans is a rare occurrence. We report two cases of preterm labor and Candida chorioamnionitis that were diagnosed by intrapartum amniocentesis. The diverse maternal and neonatal outcomes observed indicate that Candida IAI is associated with significant, unpredictable maternal and neonatal morbidity.

A high observed substitution rate in the human mitochondrial DNA control region.

The rate and pattern of sequence substitutions in the mitochondrial DNA (mtDNA) control region (CR) is of central importance to studies of human evolution and to forensic identity testing. Here, we report a direct measurement of the intergenerational substitution rate in the human CR. We compared DNA sequences of two CR hypervariable segments from close maternal relatives, from 134 independent mtDNA lineages spanning 327 generational events. Ten substitutions were observed, resulting in an empirical rate of 1/33 generations, or 2.5/site/Myr. This is roughly twenty-fold higher than estimates derived from phylogenetic analyses. This disparity cannot be accounted for simply by substitutions at mutational hot spots, suggesting additional factors that produce the discrepancy between very near-term and long-term apparent rates of sequence divergence. The data also indicate that extremely rapid segregation of CR sequence variants between generations is common in humans, with a very small mtDNA bottleneck. These results have implications for forensic applications and studies of human evolution.

A set of novel tadpole specific genes expressed only in the epidermis are down-regulated by thyroid hormone during Xenopus laevis metamorphosis.

Four genes were identified in a screen for thyroid hormone-induced down-regulation of gene expression in Xenopus laevis tadpole tails. All four encode extracellular glycoproteins that are expressed exclusively in the apical cell layer of the entire tadpole epidermis, which is the equivalent of the mammalian fetal periderm. The onset of the four novel genes' expression late in embryogenesis, their activity throughout the life of the tadpole, their repression by exogenously added thyroid hormone, and the spontaneous cessation of their expression at the end of tadpole life are closely coordinated. These facts suggest that the protein products of these genes form a novel albeit temporary barrier or other structure in the tadpole epidermis that functions in lieu of the cornified, stratified epithelium of the adult epidermis. We have exploited the cloning of these genes for use as cell-specific markers to follow the appearance and loss of apical cells during development. We were able to demonstrate directly that the apical cells are derived from a stratification of the embryonic ectoderm at the onset of the formation of a true epidermis. The apical cells uniformly cover the surface of the tadpole until metamorphosis, when the expression of the four larval epidermis-specific genes is lost coordinately over the entire tadpole. In contrast, the adult epidermis develops with a distinct regional specificity: adult keratin is first expressed up to a line separating the body and tail epidermis and finally appears in the tail only at metamorphic climax. Finally, our analysis reveals that the TH-induced down-regulated gene expression program during metamorphosis is very different from the previously described up-regulated program which involves multiple cell types and several waves of gene expression changes. The down-regulated program only consists of the repression of a small number of genes which are expressed in larval cells preprogrammed to die during the larval to adult transition at metamorphosis.

Quality of life and the cancer experience: the state-of-the-knowledge.

PURPOSE/OBJECTIVES: To address the state-of-the-knowledge concerning quality of life (QOL) issues and the cancer experience from theoretical, research, clinical, and educational perspectives. DATA SOURCES: Published books and articles and a panel of experienced QOL experts who convened at the Oncology Nursing Society's State-of-the-knowledge Conference on Quality of Life in February 1995. DATA SYNTHESIS: Despite the evolution and support of QOL in oncology nursing practice, education, and research, there remains gaps in theory, research, and practice related to QOL. This article explores these gaps in knowledge and recommends future directions for QOL theory, research, education, and practice. CONCLUSIONS: Further conceptual work and resolution of QOL methodologic issues to guide clinical practice and education are warranted. The impact of cultural variables and precancer life experiences on patients' perceptions of QOL also must be addressed. NURSING IMPLICATIONS: Oncology nurse clinicians, educators, and researchers must continue to work collaboratively to enhance the knowledge base regarding QOL and to improve the nursing care provided to individuals with cancer.

Normovolemic hemodilution before cesarean hysterectomy for placenta percreta.

BACKGROUND: Placenta percreta can create life-threatening hemorrhage at the time of delivery. The additional challenge of patient refusal of blood transfusion for religious reasons requires the use of comprehensive blood-conserving strategies. CASE: A Jehovah's Witness with two previous cesarean deliveries and a placenta previa was diagnosed antenatally as having placenta percreta. Acute normovolemic hemodilution was performed in conjunction with cesarean hysterectomy with no maternal or fetal side effects. CONCLUSION: Acute normovolemic hemodilution can be used safely in the pregnant woman at high risk for excessive intraoperative blood loss and should be considered in obstetric patients who strictly adhere to religious convictions prohibiting the acceptance of blood products.