Effect of a Web-Based Integrative Support Intervention to Improve Family Caregiver Positive Caregiving Experience and Quality of Life: A Randomized Controlled Trial.

BACKGROUND: Cancer caregivers experience significant stress due to their multifaceted role. Current support methods are limited by unidimensional assessments. OBJECTIVE: The aim of this study was to evaluate a Web-based support system aimed at reducing caregiver stress and anxiety, and improving resilience, vigilance, and quality of life, using both subjective and objective measures. METHODS: A randomized controlled trial with a single-center, 2-arm parallel design and longitudinal assessment was conducted in Taiwan. Caregivers of patients recently diagnosed with cancer were randomly allocated to either a standard care group or an intervention group that received enhanced nurse-led support. Metrics including psychological resilience, caregiver burden, anxiety, quality of life, stress levels, and vigilance were systematically evaluated on a monthly basis over a period of 5 months, starting from the initial baseline measurement. RESULTS: Following the intervention, participants in the intervention group exhibited statistically significant reductions in caregiver burden and anxiety, alongside a notable improvement in resilience. Objective evaluations revealed a significant reduction in stress levels within this group. However, there were no discernible differences in vigilance and quality of life metrics between the intervention and control groups. CONCLUSION: The Web-based program effectively reduced caregiver stress and burden, as indicated by multiple metrics. IMPLICATIONS FOR PRACTICE: This accessible and efficient Web-based support is beneficial for cancer caregivers facing diverse challenges.

Caregiving burdens of family members of patients living with hepatocellular carcinoma.

BACKGROUND: Caregiving burden is common among family caregivers (FCs). In Taiwan, no reports have compared caregiving burden according to disease stage, or explored the comprehensive factors of caregiving burden in the FCs of patients with hepatocellular carcinoma (HCC). AIM: The aim of the study was to investigate caregiving burden at different diagnosis stages and its potential predictors in the FCs of patients with hepatocellular carcinoma. METHODS: This descriptive, cross-sectional study included 192 FCs. Caregiving burden was measured using the Caregiver Reaction Assessment tool. The predictive factors of caregiving burden in the FCs of patients with HCC were identified using a linear regression model. RESULTS: The global caregiving burden had no significant differences between the four disease stages. The lack of family support and impact on schedule were significantly higher at the terminal stage than at the earlier stage. The risk factors of caregiving burden were high depression, high financial demand, heavy caregiving tasks, advanced age and frequent patient contact, which obtained a variance of 47.8% in the regression model. CONCLUSION: Healthcare providers need to proactively identify and assess FCs with risk factors of caregiving burden and provide appropriate interventions specific to individual needs at different disease stages.

Fatigue and Vigilance-Related Factors in Family Caregivers of Patients With Advanced Cancer: A Cross-sectional Study.

BACKGROUND: Family caregivers (FCs) commonly experience fatigue during caregiving. The factors of fatigue in the FCs of patients with advanced cancer have not yet been investigated in Taiwan. OBJECTIVE: This study investigated potential predictors of fatigue in the FCs of patients with advanced cancer. METHODS: A descriptive, cross-sectional study was conducted on 184 FCs. Data were collected using the Checklist Individual Strength and the palm-based psychomotor vigilance test. A linear regression model was the main statistical method for identifying the factors predictive of fatigue in FCs. RESULTS: Subjective and objective measurements revealed that 95% of the FCs had fatigue and poor vigilance. Those who spent more time each day on caregiving tasks, had no religious beliefs, had a full- or part-time job, and had a greater caregiver burden experienced greater fatigue. CONCLUSIONS: Fatigue and poor vigilance were common in the Taiwanese FCs of patients with advanced cancer. Family caregivers with risk factors for fatigue must be identified and given access to resources for assistance. IMPLICATION FOR PRACTICE: Healthcare providers must proactively assess FCs for fatigue and vigilance status and provide interventions appropriate for individual needs.

Estimating the survival of elderly patients diagnosed with dementia in Taiwan: A longitudinal study.

BACKGROUND: Dementia is characterized by prolonged progressive disability. Therefore, predicting mortality is difficult. An accurate prediction tool may be useful to ensure that end-of-life patients with dementia receive timely palliative care. PURPOSE: This study aims to establish a survival prediction model for elderly patients with dementia in Taiwan. METHODS: Data from the 2001 to 2010 National Health Insurance Research Database in Taiwan were used to identify 37,289 patients with dementia aged ≥65 years for inclusion in this retrospective longitudinal study. Moreover, this study examined the mortality indicators for dementia among demographic characteristics, chronic physical comorbidities, and medical procedures. A Cox proportional hazards model with time-dependent covariates was used to estimate mortality risk, and risk score functions were formulated using a point system to establish a survival prediction model. The prediction model was then tested using the area under the receiver operating characteristic curve. RESULTS: Thirteen mortality risk factors were identified: age, sex, stroke, chronic renal failure, liver cirrhosis, cancer, pressure injury, and retrospectively retrieved factors occurring in the 6 months before death, including nasogastric tube placement, supplemental oxygen supply, ≥2 hospitalization, receiving ≥1 emergency services, ≥2 occurrences of cardiopulmonary resuscitation, and receiving ≥2 endotracheal intubations. The area under the receiver operating characteristic curves for this prediction model for mortality at 6 and 12 months were 0.726 and 0.733, respectively. CONCLUSIONS: The survival prediction model demonstrated moderate accuracy for predicting mortality at 6 and 12 months before death in elderly patients with dementia. This tool may be valuable for helping health care providers and family caregivers to make end-of-life care decisions.

Effect of integrated caregiver support on caregiver burden for people taking care of people with cancer at the end of life: A cohort and quasi-experimental clinical trial.

BACKGROUND: Previous studies have shown small-to-medium effects of support on reducing the caregiver burden for advanced cancer patients. A dearth of studies utilized longitudinal design to examine and evaluate the effect of support for the caregiving burden till the patient's death. OBJECTIVES: To test the ability of an integrative intervention program for caregivers of advanced cancer patients to lower caregiving burden as death approaches. DESIGN: A two-group comparative design with repeated measures. SETTING: Two cancer wards of a single university hospital. PARTICIPANTS: Advanced cancer patients (N=81) and their caregivers were allocated into two groups: an experimental group (N=40) receiving coping strategies, assistance, recourses, and education intervention and a control group (N=41) receiving standard care. METHODS: Caregivers received training in the caregiver support intervention at least 3 times every 2 weeks to help them reduce their caregiving burden. Subjective (Caregiver Reaction Assessment) and objective (Heart Rate Variability) measures of caregiver burden were evaluated for caregivers of patients approaching death. Only data within 3 months before the patients' death were analyzed. RESULTS: Caregiver self-efficacy significantly increased and the subjective caregiving burden significantly decreased in the experimental group as patients' death approached. Heart Rate Variability also indicated a calming effect of the intervention, helping caregivers face patients' death. CONCLUSIONS: The caregiver support intervention can increase caregiver self-efficacy and reduce the subjective caregiving burden. Heart Rate Variability parameters have the potential to be useful for monitoring caregiver burden in facing patients' death.

Development of an Experience-Based Caregiver Burden Scale in Advanced Cancer.

BACKGROUND: Family caregivers complete caregiving tasks but may not explore their own feelings about their caregiving experience. OBJECTIVES: The objectives of this study were to develop an experience-based caregiving burden scale for caregivers of patients with advanced cancer and to estimate its predictive value for depression. METHODS: The instrument was first systematically constructed on the basis of data obtained from detailed interviews of 12 caregivers. Then, 134 caregivers completed the questionnaire as a field test to estimate the psychometric properties of the developed tool. RESULTS: We achieved a 13-item Caregiver Burden Scale (CBS) with 3 dimensions: health impact, role competence, and resource and growth. The construct validity, criterion-related validity, and internal consistency reliability of the CBS were satisfactory. A CBS score higher than 25.5, or health impact subscale score higher than 10.5, or role performance score higher than 7.5 indicated significant depression and the need for assistance from healthcare providers. CONCLUSION: The CBS has adequate reliability and validity to assess the burden experienced by caregivers of patients with advanced cancer. It was also predictive for significant depression. IMPLICATION FOR PRACTICE: Nurses may use the CBS to provide timely assistance to family caregivers during their caregiving for a patient with advanced-stage cancer.

Sleep disturbances and related factors among family caregivers of patients with advanced cancer.

OBJECTIVE: Sleep disturbances among family caregivers (FCs) are common in advanced cancer. The comprehensive factors for sleep disturbances among the FCs of patients with cancer have not been investigated in Taiwan. The purposes of this study were to investigate the sleep disturbances among the FCs of patients with advanced cancer and to determine predictors of sleep disturbance. METHODS: A descriptive, cross-sectional study was conducted among 172 FCs. Data were collected using the Pittsburgh Sleep Quality Index and wrist actigraphy. A linear regression model was used to identify the predictive factors for sleep quality. RESULTS: Seventy-six percent of the FCs experienced some sleep disturbances. Female gender, more fatigue, greater depression, more caregiving burden, and spending over 16 h per day on caregiving tasks were risk factors for sleep disturbances in caregivers. CONCLUSIONS: Sleep disturbances were common among the Taiwanese FCs of patients with advanced cancer. FCs with risk factors for sleep disturbances should be identified and provided assistance.

The Burden of Caregiving and Sleep Disturbance Among Family Caregivers of Advanced Cancer Patients.

BACKGROUND: Sleep disturbance may cause physical and psychological problems. The relationship between sleep disturbance and the burden of caregiving among family caregivers (FCs) has not previously been investigated. OBJECTIVE: The purposes of this study were to (1) assess subjective and objective information on the sleep patterns of FCs of advanced cancer patients and (2) identify the components of caregiving burden that are risk factors for sleep disturbance among these FCs. METHODS: A prospective, cross-sectional study of 176 FCs was conducted. Subjective and objective tools measuring sleep quality and caregiver burden were used. A hierarchical regression model was applied to identify the predictive factors for sleep disturbance among FCs. RESULTS: Approximately 72.2% of FCs experienced sleep disturbance. The major sleep disturbance was frequent "wake after sleep onset" to provide patient care; a nap during the day was necessary. Correlations were strong between caregiver burden and sleep quality. The final regression model, which included subjective and objective burden, predicted 56.6% of the variance in sleep disturbance. CONCLUSIONS: Sleep disturbance was common in FCs of advanced cancer patient, and our results demonstrated the relationship between sleep disturbance and caregiving burden. IMPLICATIONS FOR PRACTICE: Family caregivers with risk factors for sleep disturbance should be identified and be provided resources for sleep quality improvement.

Dual regeneration of muscle and nerve by intravenous administration of human amniotic fluid-derived mesenchymal stem cells regulated by stromal cell-derived factor-1α in a sciatic nerve injury model.

OBJECT: Human amniotic fluid-derived mesenchymal stem cells (AFMSCs) have been shown to promote peripheral nerve regeneration. The expression of stromal cell-derived factor-1α (SDF-1α) in the injured nerve exerts a trophic effect by recruiting progenitor cells that promote nerve regeneration. In this study, the authors investigated the feasibility of intravenous administration of AFMSCs according to SDF-1α expression time profiles to facilitate neural regeneration in a sciatic nerve crush injury model. METHODS: Peripheral nerve injury was induced in 63 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into 1 of 3 groups: Group I, crush injury as the control; Group II, crush injury and intravenous administration of AFMSCs (5 × 10(6) cells for 3 days) immediately after injury (early administration); and Group III, crush injury and intravenous administration of AFMSCs (5 × 10(6) cells for 3 days) 7 days after injury (late administration). Evaluation of neurobehavior, electrophysiological study, and assessment of regeneration markers were conducted every week after injury. The expression of SDF-1α and neurotrophic factors and the distribution of AFMSCs in various time profiles were also assessed. RESULTS: Stromal cell-derived factor-1α increased the migration and wound healing of AFMSCs in vitro, and the migration ability was dose dependent. Crush injury induced the expression of SDF-1α at a peak of 10-14 days either in nerve or muscle, and this increased expression paralleled the expression of its receptor, chemokine receptor type-4 (CXCR-4). Most AFMSCs were distributed to the lung during early or late administration. Significant deposition of AFMSCs in nerve and muscle only occurred in the late administration group. Significantly enhanced neurobehavior, electrophysiological function, nerve myelination, and expression of neurotrophic factors and acetylcholine receptor were demonstrated in the late administration group. CONCLUSIONS: Amniotic fluid-derived mesenchymal stem cells can be recruited by expression of SDF-1α in muscle and nerve after nerve crush injury. The increased deposition of AFMSCs paralleled the expression profiles of SDF-1α and its receptor CXCR-4 in either muscle or nerve. Administration of AFMSCs led to improvements in neurobehavior and expression of regeneration markers. Intravenous administration of AFMSCs may be a promising alternative treatment strategy in peripheral nerve disorder.

Evidence that music listening reduces preoperative patients' anxiety.

BACKGROUND: Patients often exhibit preoperative fear and anxiety that may influence the process of induction and recovery from anesthesia. Music is thought to be an alternative to medication for relief of fear and anxiety. OBJECTIVES: The purpose of the present study was to explore the feasibility of using heart rate (HR) variability (HRV) for evaluating the efficacy of music listening to relieve the patients' anxiety during their stay in the operation room waiting area and to compare the HRV measures with subjective Visual Analogue Scale (VAS) scores. METHODS: In total, 140 patients were randomly assigned to the experimental (n = 64) or control group (n = 76). The intervention consisted of a 10-min period of exposure to relaxing music delivered through headphones. Anxiety levels were measured by VAS (a 10-point scale) and 5 min of HRV monitoring before and after the music intervention. RESULTS: The music group demonstrated significant reductions in VAS scores, mean HR, low-frequency HRV, and low- to high-frequency ratio and an increase in high-frequency HRV, while patients in the control group showed no changes. The subjective results of patients' VAS anxiety scores were consistent with the objective results of HRV parameters. CONCLUSIONS: Listening to music can significantly lower the anxiety levels of patients before surgery. The frequency-domain parameters of HRV can be indicators for monitoring the change in anxiety level of preoperative patients.

Activation of Rac1 by Src-dependent phosphorylation of Dock180(Y1811) mediates PDGFRα-stimulated glioma tumorigenesis in mice and humans.

Two hallmarks of glioblastoma multiforme, the most common malignant brain cancer in humans, are aggressive growth and the ability of single glioma cells to disperse throughout the brain. These characteristics render tumors resistant to current therapies and account for the poor prognosis of patients. Although it is known that oncogenic signaling caused by overexpression of genes such as PDGFRA is responsible for robust glioma growth and cell infiltration, the mechanisms underlying glioblastoma malignancy remain largely elusive. Here, we report that PDGFRα signaling in glioblastomas leads to Src-dependent phosphorylation of the guanine nucleotide exchange factor Dock180 at tyrosine 1811 (Dock180(Y1811)) that results in activation of the GTPase Rac1 and subsequent cell growth and invasion. In human glioma cells, knockdown of Dock180 and reversion with an RNAi-resistant Dock180(Y1811F) abrogated, whereas an RNAi-resistant Dock180(WT) rescued, PDGFRα-promoted glioma growth, survival, and invasion. Phosphorylation of Dock180(Y1811) enhanced its association with CrkII and p130(Cas), causing activation of Rac1 and consequent cell motility. Dock180 also associated with PDGFRα to promote cell migration. Finally, phosphorylated Dock180(Y1811) was detected in clinical samples of gliomas and various types of human cancers, and coexpression of phosphorylated Dock180(Y1811), phosphorylated Src(Y418), and PDGFRα was predictive of extremely poor prognosis of patients with gliomas. Taken together, our findings provide insight into PDGFRα-stimulated gliomagenesis and suggest that phosphorylated Dock180(Y1811) contributes to activation of Rac1 in human cancers with PDGFRA amplification.

Effectiveness of different music-playing devices for reducing preoperative anxiety: a clinical control study.

BACKGROUND: While waiting for surgery, patients often exhibit fear and anxiety. Music is thought to be an alternative to medication to relieve anxiety. However, due to concerns about infection control, devices other than headphones may be considered for this purpose. OBJECTIVES: The purpose of this study was to determine the anxiety-relieving effect of broadcast versus headphone music playing for patients awaiting surgery. DESIGN: A randomized controlled clinical study. SETTING: The waiting area of an operating theater of a metropolitan teach hospital in Taiwan. PARTICIPANTS: Alert adult with age between 20 and 65 years old waiting for surgery without premedications. METHODS: A total of 167 patients were randomly assigned to the headphone, broadcast and control groups. Both the headphone and the broadcast groups were provided with the same instrumental music, while the control group did not listen to any music. The tools for measuring anxiety were visual analogue scale (VAS) ranging from "not anxious at all" to "extremely anxious" and heart rate variability (HRV). RESULTS: The VAS score exhibited a significant decrease for both the headphone and broadcast groups. The low frequency and low-to-high frequency LF/HF ratio of the broadcast and headphone groups were significantly lower than those of the control group. None of the heart rate variables showed significant differences between the broadcast group and the headphone group. CONCLUSION: Both headphone and broadcast music are effective for reducing the preoperative patient's anxiety in the waiting room. RELEVANCE TO CLINICAL PRACTICE: In order to take infection control into account, broadcast speakers can substitute for headphones for playing music to lower the anxiety level of patients waiting for surgery.

Intradiscal electrothermal therapy in the treatment of chronic low back pain: experience with 93 patients.

BACKGROUND: Low back pain (LBP) has become a main cause of absenteeism and disability in industrialized societies. Chronic LBP is an important health issue in modern countries. Discogenic LBP is one of the causes of chronic low back pain. The management of chronic discogenic LBP has been limited to either conservative treatment or operative treatment. Intradiscal electrothermal therapy (IDET) is now being performed as an alternative treatment. METHODS: Ninety-three consecutive patients undergoing IDET at 134 disc levels from October 2004 to January 2007 were prospectively evaluated. All patients had discogenic disease with chronic LBP, as determined by clinical features, physical examination and image studies, and had failed to improve with conservative treatment for at least 6 months. Follow-up period was from 1 week to 3 or more years postoperatively. RESULTS: There were 50 male and 43 female patients, with a mean age of 46.07 years (range, 21-65 years). The results were classified as symptom free (100% improvement), better (≥50% improvement), slightly better (<50% improvement), unchanged and aggravated. Eighty-nine patients were followed up in the first week; of them, 77 (86.52%) patients had improvement (4, symptom free; 45, better; and 28, slightly better). The improvement rate gradually decreased to 80.90% in 1 year; and 73.91%, in 3 years. CONCLUSIONS: In conclusion, IDET offers a safe, minimally invasive therapy option for carefully selected patients with chronic discogenic LBP who have not responded to conservative treatment. Although IDET appears to provide intermediate-term relief of pain, further studies with long-term follow-up are necessary.

ZD6474, a multitargeted inhibitor for receptor tyrosine kinases, suppresses growth of gliomas expressing an epidermal growth factor receptor mutant, EGFRvIII, in the brain.

Epidermal growth factor receptor (EGFR) vIII is a mutated EGFR that is frequently overexpressed in glioblastomas and implicated in response to receptor tyrosine kinase inhibitors. In this study, we investigate the effect of ZD6474 (ZACTIMA, vandetanib), a dual inhibitor for vascular endothelial growth factor receptor 2 and EGFR on growth and angiogenesis of gliomas expressing EGFRvIII. We used two glioma xenograft models, U87MG cells overexpressing EGFRvIII and short-term cultured primary glioma GBM8 cells with EGFRvIII. ZD6474 inhibited tumor growth and angiogenesis and induced cell apoptosis in various brain gliomas. Moreover, significant inhibition of EGFRvIII-expressing U87MG and GBM8 gliomas was observed compared with their controls. Magnetic resonance imaging analysis using the apparent diffusion coefficient and three-dimensional T2*weighed measurements validated ZD6474 inhibition on tumor growth and angiogenesis in EGFRvIII-expressing GBM8 gliomas. Mechanistically, ZD6474 shows better inhibition of cell growth and survival of U87MG/EGFRvIII, GBM6, and GBM8 cells that express EGFRvIII than U87MG or GBM14 cells that have nondetectable EGFRvIII through attenuation of activated phosphorylation of signal transducer and activator of transcription 3, Akt, and Bcl-X(L) expression. Albeit in lesser extent, ZD6474 also displays suppressions of U87MG/EGFR and GBM12 cells that overexpress wild-type EGFR. Additionally, ZD6474 inhibits activation of extracellular signal-regulated kinase 1/2 in both types of cells, and expression of a constitutively active phosphoinositide 3-kinases partially rescued ZD6474 inhibition in U87MG/EGFRvIII cells. Taken together, these data show that ZD6474 significantly inhibited growth and angiogenesis of gliomas expressing EGFRvIII by specifically blocking EGFRvIII-activated signaling mediators, suggesting a potential application of ZD6474 in treatments for glioblastomas that overexpress EGFRvIII. Mol Cancer Ther; 9(4); 929-41. (c)2010 AACR.

Slit2 inhibits glioma cell invasion in the brain by suppression of Cdc42 activity.

Acquisition of insidious invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways. Slit2, a chemorepulsive factor, controls cell migration of neuronal and glial cells during development and inhibits chemotaxic migration of various types of cells in vitro. However, the role of Slit2 in vitro remains controversial, and the biological significance of Slit2 expression in cancer cell invasion in vivo has not yet been determined. In the present study, we characterized the effects of Slit2 expression on the migration and invasion of invasive glioma cells in vitro and in vivo. By reverse transcriptase polymerase chain reaction (PCR) analyses, Slit2 was found to be expressed at lower levels in primary glioma specimens and invasive glioma cells compared with normal human brain cells and astrocytes. Ectopic expression of Slit2 or treatment with recombinant Slit2 on glioma cells attenuates cell migration and invasion through inhibition of Cdc42 activity in vitro. Cellular depletion of Robo1, a cognate receptor for Slit2, prevented Slit2 inhibition of Cdc42 activity and glioma cell migration. In vivo, expression of Slit2 by invasive SNB19 glioma cells markedly inhibited glioma cell infiltration into the brain of mice. Moreover, impediment of glioma cell invasion by Slit2 did not affect the expression of N-cadherin and beta-catenin in glioma cells. These results provide the first evidence demonstrating that Slit2-Robo1 inhibits glioma invasion through attenuating Cdc42 activity in vitro and in the brain. Understanding the mechanisms of Slit2-Robo1 inhibition of glioma cell invasion will foster new treatments for malignant gliomas.

ADP-ribosylation factor 6 regulates glioma cell invasion through the IQ-domain GTPase-activating protein 1-Rac1-mediated pathway.

A common pathobiological feature of malignant gliomas is the insidious infiltration of single tumor cells into the brain parenchyma, rendering these deadly tumors virtually incurable with available therapies. In this study, we report that ADP-ribosylation factor 6 (ARF6), a Ras superfamily small GTPase, is abundantly expressed in invasive human glioma cells. Cellular depletion of ARF6 by small interfering RNA decreased Rac1 activation, impaired HGF-stimulated and serum-stimulated glioma cell migration in vitro, and markedly decreased the invasive capacity of invasive glioma in the brain. Furthermore, ectopic expression of ARF6 in glioma cells promoted cell migration via the activation of Rac1. Upon stimulation of glioma cells with HGF, we show that IQ-domain GTPase-activating protein 1 (IQGAP1) is recruited and overlaps with ARF6 at the leading edge of migrating cells. However, cellular depletion of ARF6 abrogated this recruitment of IQGAP1 and attenuated the formation of surface protrusions. ARF6 forms complexes with Rac1 and IQGAP1 in glioma cells upon HGF stimulation, and knockdown of IQGAP1 significantly inhibits ARF6-induced Rac1 activation and cell migration. Taken together, these data suggest that ARF6-mediated Rac1 activation is essential for glioma cell invasion via a signaling pathway that requires IQGAP1.

Treatment of neuroblastoma with intraspinal extensions.

Neuroblastoma is the most common malignant cause of spinal compression in the paediatric population. Chemotherapy is commonly considered as the first-line treatment for these patients. The role of neurosurgical decompression and radiotherapy are still controversial. Thirteen children diagnosed as having neuroblastoma with intraspinal extension were included in this report. All patients presented with neurological deficits and were treated with chemotherapy initially, after which 3 patients recovered, 4 improved and 6 were aggravated into paraplegia. Two of the 6 aggravated patients received emergent laminectomy with removal of intraspinal tumour and recovered satisfactorily. Although spread of tumour into the spinal canal indicates an advanced disease, aggressive treatments such as chemotherapy and surgical resection can often improve neurological symptoms and life quality. Neurological decompression is recommended for patients with intraspinal neuroblastoma and rapid neurological deterioration during chemotherapy.