Reflections on 50 Years of Neuroscience Nursing: Neuro-Oncology, Moving Forward by Looking Back.

During the past 50 years, there have been more than 100 articles published in the Journal of Neuroscience Nursing covering the topic of neuro-oncology. This article will explore the historical implications and milestones from these articles. The analysis highlights the scope and depth of the many articles as they relate to the advancements in neuro-oncology.

Retinopathy of Prematurity and Ethnicity in Hawai'i: A Retrospective Study (1996 - 2006) of Medical Records from Kapi'olani Medical Center for Women and Children.

The objective of this research was to identify risk factors for Retinopathy of Prematurity (ROP) in Hawai'i's ethnically unique population, with a focus on ethnicity. The study design focused on a 10-year retrospective chart review of neonates at Kapi'olani Medical Center in Honolulu, Hawai'i. Results showed that 23.3% of infants of Native Hawaiian and/or Pacific Islander ethnicity (NHPI) developed ROP. Necrotizing enterocolitis, intraventricular hemorrhage, and the severity of respiratory disease were significantly related (P < .001) to the incidence and severity of ROP. In a multiple logistic regression model, gestational age, birth weight, bronchopulmonary dysplasia, and postnatal steroids were significant predictors (P < .001) for presence of ROP. Significant predictors for severe ROP included gestational age (P < .001), birth weight (P = .001), postnatal steroids (P = .001), necrotizing enterocolitis (P = .025), and NHPI ethnicity (P = .004). Further research is recommended.

Dance/movement therapy for improving psychological and physical outcomes in cancer patients.

BACKGROUND: Current cancer care increasingly incorporates psychosocial interventions. Cancer patients use dance/movement therapy to learn to accept and reconnect with their bodies, build new self-confidence, enhance self-expression, address feelings of isolation, depression, anger and fear and to strengthen personal resources. OBJECTIVES: To update the previously published review that examined the effects of dance/movement therapy and standard care versus standard care alone or standard care and other interventions on psychological and physical outcomes in patients with cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 6), MEDLINE (OvidSP, 1950 to June week 4, 2014), EMBASE (OvidSP, 1980 to 2014 week 26), CINAHL (EBSCOhost, 1982 to July 15 2014), PsycINFO (EBSCOhost, 1806 to July 15 2014), LILACS (Virual Health Library, 1982 to July 15 2014), Science Citation Index (ISI, 1974 to July 15 2014), CancerLit (1983 to 2003), International Bibliography of Theatre and Dance (1989 to July 15 2014), the National Research Register (2000 to September 2007), Proquest Digital Dissertations, ClinicalTrials.gov, and Current Controlled Trials (all to July 15 2014). We handsearched dance/movement therapy and related topics journals, reviewed reference lists and contacted experts. There was no language restriction. SELECTION CRITERIA: We included all randomized and quasi-randomized controlled trials of dance/movement therapy interventions for improving psychological and physical outcomes in patients with cancer. We considered studies only if dance/movement therapy was provided by a formally trained dance/movement therapist or by trainees in a formal dance/movement therapy program. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data and assessed the methodological quality, seeking additional information from the trial researchers when necessary. Results were presented using standardized mean differences. MAIN RESULTS: We identified one new trial for inclusion in this update. In total, the evidence for this review rests on three studies with a total of 207 participants.We found no evidence for an effect of dance/movement therapy on depression (standardized mean difference (SMD) = 0.02, 95% confidence interval (CI) -0.28 to 0.32, P = 0.89, I2 = 0%) (two studies, N = 170), stress (SMD = -0.18, 95% CI -0.48 to 0.12, P = 0.24, I2 = 0%) (two studies, N = 170), anxiety (SMD = 0.21, 95% CI -0.09 to 0.51 P = 0.18, I2 = 0%) (two studies, N = 170), fatigue (SMD = -0.36, 95% -1.26 to 0.55, P = 0.44, I² = 80%) (two studies, N = 170) and body image (SMD = -0.13, 95% CI -0.61 to 0.34, P = 0.58, I2 = 0%) (two studies, N = 68) in women with breast cancer. The data of one study with moderate risk of bias suggested that dance/movement therapy had a large beneficial effect on 37 participants' quality of life (QoL) (SMD = 0.89, 95% CI 0.21 to 1.57). One study with a high risk of bias reported greater improvements in vigor and greater reduction in somatization in the dance/movement therapy group compared to a standard care control group (N = 31). The individual studies did not find support for an effect of dance/movement therapy on mood, mental health, and pain. It is unclear whether this was due to ineffectiveness of the treatment, inappropriate outcome measures or limited power of the trials. Finally, the results of one study did not find evidence for an effect of dance/movement therapy on shoulder range of motion (ROM) or arm circumference in 37 women who underwent a lumpectomy or breast surgery. However, this was likely due to large within-group variability for shoulder ROM and a limited number of participants with lymphedema.Two studies presented moderate risk of bias and one study high risk of bias. Therefore, overall, the quality of the evidence is very low. AUTHORS' CONCLUSIONS: We did not find support for an effect of dance/movement therapy on depression, stress, anxiety, fatigue and body image . The findings of individual studies suggest that dance/movement therapy may have a beneficial effect on QoL, somatization, and vigor. However, the limited number of studies prevents us from drawing conclusions concerning the effects of dance/movement therapy on psychological and physical outcomes in cancer patients.

Expression of osteoprotegerin from a replicating adenovirus inhibits the progression of prostate cancer bone metastases in a murine model.

Metastatic involvement of the skeleton is a frequent consequence of advanced prostate cancer. These skeletal metastases cause a number of debilitating complications and are refractory to current treatments. New therapeutic options are being explored, including conditionally replicating adenoviruses (CRAds). CRAds are engineered to selectively replicate in and destroy tumor cells and can be 'armed' with exogenous transgenes for enhanced potency. We hypothesized that a CRAd armed with osteoprotegerin (OPG), an inhibitor of osteoclastogenesis, would inhibit the progression of prostate cancer bone metastases by directly lysing tumor cells and by reducing osteoclast activity. Although prostate cancer bone metastases are predominantly osteoblastic in nature, increased osteoclast activity is critical for the growth of these lesions. Ad5-Δ24-sOPG-Fc-RGD is a CRAd that carries a fusion of the ligand-binding domains of OPG and the Fc region of human IgG1 in place of the viral E3B genes. To circumvent low tumor cell expression of the native adenoviral receptor, an arginine-glycine-aspartic acid (RGD) peptide insertion within the viral fiber knob allows infection of cells expressing α(v) integrins. A 24-base pair deletion (Δ24) within viral E1A limits replication to cells with aberrant retinoblastoma cell cycle regulator/tumor suppressor expression. We have confirmed that Ad5-Δ24-sOPG-Fc-RGD replicates within and destroys prostate cancer cells and, in both murine and human coculture models, that infection of prostate cancer cells inhibits osteoclastogenesis in vitro. In a murine model, progression of advanced prostate cancer bone metastases was inhibited by treatment with Ad5-Δ24-sOPG-Fc-RGD but not by an unarmed control CRAd.

First global forum on education on organ donation and transplantation for schools.

The Transplantation Society, in collaboration with the Canadian Society of Transplantation, organized a forum on education on ODT for schools. The forum included participants from around the world, school boards, and representatives from different religions. Participants presented on their countries' experience in the area of education on ODT. Working groups discussed about technologies for education, principles for sharing of resources globally, and relationships between education, and health authorities and non-governmental organizations. The forum concluded with a discussion about how to best help existing programs and those wishing to start educational programs on ODT.

Conditionally replicating adenovirus expressing TIMP2 increases survival in a mouse model of disseminated ovarian cancer.

Ovarian cancer remains difficult to treat mainly due to presentation of the disease at an advanced stage. Conditionally-replicating adenoviruses (CRAds) are promising anti-cancer agents that selectively kill the tumor cells. The present study evaluated the efficacy of a novel CRAd (Ad5/3-CXCR4-TIMP2) containing the CXCR4 promoter for selective viral replication in cancer cells together with TIMP2 as a therapeutic transgene, targeting the matrix metalloproteases (MMPs) in a murine orthotopic model of disseminated ovarian cancer. An orthotopic model of ovarian cancer was established in athymic nude mice by intraperitonal injection of the human ovarian cancer cell line, SKOV3-Luc, expressing luciferase. Upon confirmation of peritoneal dissemination of the cells by non-invasive imaging, mice were randomly divided into four treatment groups: PBS, Ad-ΔE1-TIMP2, Ad5/3-CXCR4, and Ad5/3-CXCR4-TIMP2. All mice were imaged weekly to monitor tumor growth and were sacrificed upon reaching any of the predefined endpoints, including high tumor burden and significant weight loss along with clinical evidence of pain and distress. Survival analysis was performed using the Log-rank test. The median survival for the PBS cohort was 33 days; for Ad-ΔE1-TIMP2, 39 days; for Ad5/3-CXCR4, 52.5 days; and for Ad5/3-CXCR4-TIMP2, 63 days. The TIMP2-armed CRAd delayed tumor growth and significantly increased survival when compared to the unarmed CRAd. This therapeutic effect was confirmed to be mediated through inhibition of MMP9. Results of the in vivo study support the translational potential of Ad5/3-CXCR4-TIMP2 for treatment of human patients with advanced ovarian cancer.

Conditionally replicating adenovirus expressing TIMP2 for ovarian cancer therapy.

PURPOSE: Current treatments for ovarian cancer have limited therapeutic outcomes due to advanced stage of the disease at diagnosis. Among new therapies, conditionally replicating adenoviruses (CRAds), designed to selectively lyse cancer cells, hold promise. In clinical trials, CRAds exhibited limited efficacy thus far. Second-generation CRAds are being developed to express a therapeutic protein to enhance antitumor efficacy. One attractive target in the tumor microenvironment is the matrix metalloproteinases (MMPs) that degrade the extracellular matrix, and are upregulated in ovarian cancer. Tissue inhibitor of metalloproteinase 2 (TIMP2) is an endogenous inhibitor of MMPs. The present study developed and evaluated a novel CRAd (Ad5/3-CXCR4-TIMP2) for ovarian cancer therapy. EXPERIMENTAL DESIGN: A targeted CRAd, Ad5/3-CXCR4-TIMP2 was developed using the CXCR4 promoter for enhanced replication, and expressing the TIMP2 transgene. The efficacy of this armed CRAd was determined in both established human ovarian cancer cell lines and in primary ovarian tumor samples. RESULTS: Ad5/3-CXCR4-TIMP2 mediated expression of functional TIMP2, as demonstrated by the inhibition of MMP activity. In addition, arming with TIMP2 did not inhibit viral replication or oncolytic potency, as the TIMP2-armed viruses showed enhanced killing of cancer cells when compared to the unarmed viruses. We also examined viral replication in primary ovarian cancer tissues obtained from patients with stage III and IV ovarian cancer. In four of the five tumor samples, Ad5/3-CXCR4-TIMP2 revealed a 21- to 89-fold increase in replication when compared to the Ad5/3 virus. CONCLUSION: Results support the translational potential of Ad5/3-CXCR4-TIMP2 for treatment of patients with advanced ovarian cancer.

Wnt5A regulates expression of tumor-associated antigens in melanoma via changes in signal transducers and activators of transcription 3 phosphorylation.

There are currently no effective therapies for metastatic melanoma and targeted immunotherapy results in the remission of only a very small percentage of tumors. In this study, we show that the noncanonical Wnt ligand, Wnt5A, can increase melanoma metastasis in vivo while down-regulating the expression of tumor-associated antigens important in eliciting CTL responses (e.g., MART-1, GP100, and tyrosinase). Melanosomal antigen expression is governed by MITF, PAX3, and SOX10 and is inhibited upon signal transducers and activators of transcription 3 (STAT3) activation, via decreases in PAX3 and subsequently MITF expression. Increasing Wnt5A in Wnt5A-low cells activated STAT3, and STAT3 was decreased upon Wnt5A knockdown. Downstream targets such as PAX3, MITF, and MART-1 were also affected by Wnt5A treatment or knockdown. Staining of a melanoma tissue array also highlighted the inverse relationship between MART-1 and Wnt5A expression. PKC activation by phorbol ester mimicked Wnt5A effects, and Wnt5A treatment in the presence of STAT3 or PKC inhibitors did not lower MART-1 levels. CTL activation studies showed that increases in Wnt5A correspond to decreased CTL activation and vice versa, suggesting that targeting Wnt5A before immunotherapy may lead to the enhancement of current targeted immunotherapy for patients with metastatic melanoma.

Effects of a neurodevelopmental treatment-based trunk protocol for infants with posture and movement dysfunction.

PURPOSE: This study was used to evaluate the efficacy of a neurodevelopmental treatment (NDT)-based sequenced trunk activation protocol for change in gross motor function of infants aged 4 to 12 months with posture and movement dysfunction. Infants who received a dynamic co-activation trunk protocol were compared with a control group who received a parent-infant interaction and play protocol. METHOD: A repeated measures randomized block design was used. A masked reliable examiner assessed infants before, immediately after, and 3 weeks after intervention using the Gross Motor Function Measure (GMFM). RESULTS: The NDT-based protocol group made significantly (P = 0.048) more progress than the control group from pretest to posttest. CONCLUSIONS: Cautious support was found for (1) sequenced, dynamic trunk co-activation intervention compared to generalized infant play; (2) high-frequency, short-term, task-specific intervention; and (3) direct service by NDT-trained pediatric therapists specializing in infant intervention.

Prospective evaluation of quality of life and neurocognitive effects in patients with multiple brain metastases receiving whole-brain radiotherapy with or without thalidomide on Radiation Therapy Oncology Group (RTOG) trial 0118.

PURPOSE: Radiation Therapy Oncology Group (RTOG) 0118 randomized patients with multiple brain metastases to whole-brain radiotherapy (WBRT) +/- thalidomide. This secondary analysis of 156 patients examined neurocognitive and quality of life (QOL) outcomes. METHODS AND MATERIALS: Quality of life was determined with the Spitzer Quality of Life Index (SQLI). The Folstein Mini-Mental Status Exam (MMSE) assessed neurocognitive function. SQLI and MMSE were administered at baseline and at 2-month intervals. MMSE was scored with a threshold value associated with neurocognitive functioning (absolute cutoff level of 23) and with the use of corrections for age and educational level. RESULTS: Baseline SQLI predicted survival. Patients with SQLI of 7-10 vs. <7 had median survival time (MST) of 4.8 vs. 3.1 months, p = 0.05. Both arms showed steady neurocognitive declines, but SQLI scores remained stable. Higher levels of neurocognitive decline were observed with age and education-level corrections. Of patients considered baseline age/educational level neurocognitive failures, 32% died of intracranial progression. CONCLUSIONS: Quality of life and neuropsychological testing can be prospectively administered on a Phase III cooperative group trial. The MMSE should be evaluated with adjustments for age and educational level. Baseline SQLI is predictive of survival. Despite neurocognitive declines, QOL remained stable during treatment and follow-up. Poor neurocognitive function may predict clinical deterioration. Lack of an untreated control arm makes it difficult to determine the contribution of the respective interventions (i.e., WBRT, thalidomide) to neurocognitive decline. The RTOG has developed a trial to study the role of preventative strategies aimed at forestalling neurocognitive decline in this population.

Symptom clusters and quality of life in survivors of ovarian cancer.

Ovarian cancer has nonspecific symptoms, and no screening tool is available for early diagnosis; therefore, only 19% of ovarian cancers are found at an early stage. Given the late diagnosis, women with ovarian cancer often have a prolonged course of treatment and significant morbidity that lasts into survivorship. However, distressing symptoms and their effects on quality of life have been relatively understudied, particularly in survivors of the disease. The purpose of this study was to describe a symptom cluster and its relationship to quality of life in women with ovarian cancer who were recruited from an online cancer support group. Descriptive statistics and hierarchical regression techniques were used to analyze the data obtained from a larger study testing the psychometric properties of a quality-of-life instrument. Most participants had stage III ovarian cancer, and nearly all (97%) had undergone treatment before the study. A symptom cluster composed of depression and fatigue was identified using work by Kim and colleagues [Symptom clusters: concept analysis and clinical implications for cancer nursing. Cancer Nurs. 2005;28(4):270-282]. The symptom cluster explained 41% (P = .000) of the variance in quality of life. These results suggest that fatigue and depression are significant problems for survivors of ovarian cancer.

Symptom clusters in patients with high-grade glioma.

PURPOSE: To describe the co-occurring symptoms (depression, fatigue, pain, sleep disturbance, and cognitive impairment), quality of life (QoL), and functional status in patients with high-grade glioma. DESIGN: Correlational, descriptive study of 73 participants with high-grade glioma in the U.S. METHODS: Nine brief measures were obtained with a mailed survey. Participants were recruited from the online message board of The Healing Exchange BRAIN TRUST, a nonprofit organization dedicated to improving quality of life for people with brain tumors. FINDINGS: Two symptom cluster models were examined. Four co-occurring symptoms were significantly correlated with each other and explained 29% of the variance in QoL: depression, fatigue, sleep disturbance, and cognitive impairment. Depression, fatigue, sleep disturbance, cognitive impairment, and pain were significantly correlated with each other and explained 62% of the variance in functional status. CONCLUSIONS: The interrelationships of the symptoms examined in this study and their relationships with QoL and functional status meet the criteria for defining a symptom cluster. The differences in the models of QoL and functional status indicates that symptom clusters may have unique characteristics in patients with gliomas.

Symptom clusters and quality of life in survivors of lung cancer.

PURPOSE/OBJECTIVES: To explore the prevalence and intensity of depression, fatigue, and pain in survivors of lung cancer; to examine the relationship of symptoms in a cluster; and to examine the relationship of the symptom cluster to quality of life (QOL). DESIGN: Secondary data analysis. SETTING: Online lung cancer support group. SAMPLE: 51 patients diagnosed with lung cancer. METHODS: Mailed survey with self-report of depression, fatigue, and pain measured by subscales of the Short-Form 36 Health Status Survey and QOL measured by the Fox Simple QOL Scale. Pearson's correlation and multiple regression analyses were used to examine the possible symptom cluster. MAIN RESEARCH VARIABLES: Depression, fatigue, pain, and QOL. FINDINGS: Depression, fatigue, and pain were found in a majority of survivors, with pain being the least common symptom. Fatigue was the most intense of the three symptoms. Two significantly correlated symptoms were depression and fatigue. The cluster explained 29% (p less than 0.01) of the variance in QOL in the lung cancer survivors. CONCLUSIONS: The data provided preliminary support for the presence of a symptom cluster in patients with lung cancer consisting of depression and fatigue. The cluster had a negative relationship with QOL. Survivors of lung cancer have depression and fatigue that affect QOL. IMPLICATIONS FOR NURSING: Healthcare providers must assess the potential for symptoms to cluster, adversely affecting key patient outcomes such as QOL. Through increased knowledge of symptom clusters, clinicians will be able to more effectively target the most distressing set of symptoms for intervention.

Cognitive impairment in patients with brain tumors: assessment and intervention in the clinic setting.

Cognitive impairment is the most common neurologic problem associated with brain tumors and is present in many people with brain tumors from the time of diagnosis. Treatment of primary brain tumors with surgery, radiation, chemotherapy, and adjunctive medications such as corticosteroids results in further adverse effects on cognitive function. To plan the best care for patients with brain tumors, healthcare providers must initiate systematic and accurate assessment of cognitive functioning at the first clinic visit and extend assessment throughout the course of illness. This article outlines the range of cognitive dysfunction that may be seen in patients with primary brain tumors and offers information for clinicians seeking to develop their skills and implement a systematic approach to cognitive screening. The use of cognitive screening to guide timely intervention, such as referral to a neuropsychologist and the provision of anticipatory guidance to people with brain tumors and their families, is discussed.

Managing gastroesophageal reflux disease.

A common condition, gastroesophageal reflux disease (GERD) involves the reflux of gastric contents into the esophagus. GERD may contribute to asthma, noncardiac chest pain, and other problems. This article presents trends in GERD management, including pathophysiology, diagnosis, and treatment. The authors also explore lifestyle modifications, pharmacologic therapy, and gastroenterology referral.

Occult recurrence of nasopharyngeal rhabdomyosarcoma manifesting as isolated increased intracranial pressure.

In this paper we report a child who had extensive neoplastic infiltration of the meninges which defied clinical detection. We believe that any patient with a past or present history of tumor who presents with increased intracranial pressure should be presumed to have intracranial neoplastic involvement, even in the face of negative diagnostic studies. As in this case, other causes of increased intracranial pressure should be systematically excluded.