Downregulation of Fes inhibits VEGF-A-induced chemotaxis and capillary-like morphogenesis by cultured endothelial cells.

The aim of this study was to determine whether the downregulation of endogenous Fes by siRNA in cultured endothelial cells affects vascular endothelial growth factor-A (VEGF-A)-induced chemotaxis and capillary-like morphogenesis, which are considered as angiogenic cellular responses in vitro. VEGF-A-treatment induced autophosphorylation of Fes in cultured endothelial cells. LY294002, a phosphoinositide 3-kinase inhibitor, significantly inhibited VEGF-A-induced chemotaxis and capillary-like morphogenesis. Downregulation of Fes attenuated these VEGF-A-induced cellular responses but LY294002 did not produce further inhibition of these responses. Downregulation of Fes neither affected VEGF-A-induced autophosphorylation of VEGF receptor 2 nor mitogen-activated protein kinase activation, but markedly decreased Akt activation. Taken together, our novel results indicate the involvement of Fes in VEGF-A-induced cellular responses by cultured endothelial cells

Implications of sperm banking for health-related quality of life up to 1 year after cancer diagnosis.

Sperm banking is recommended for all men diagnosed with cancer where treatment is associated with risk of long-term gonadatoxicity, to offer the opportunity of fatherhood and improved quality of life. However, uptake of sperm banking is lower than expected and little is known about why men refuse. Our aims were to determine: (i) demographic and medical variables associated with decisions about banking and (ii) differences in quality of life between bankers and non-bankers at diagnosis (Time 1 (T1)) and 1 year later (Time 2 (T2))

Distress and quality of life after autologous stem cell transplantation: a randomized clinical trial to evaluate the outcome of a web-based stepped care intervention

Background Psychological distress (i.e. depression and anxiety) is a strong predictor of functional status and other aspects of quality of life in autologous stem cell transplantation following high-dose chemotherapy. Treatment of psychological distress is hypothesized to result in improvement of functional status and other aspects of quality of life. The aim is to evaluate the outcome of stepped care for psychological distress on functional status and other aspects of quality of life in patients with hematological malignancy treated with autologous stem cell transplantation. Methods/Design The study is designed as a randomized clinical trial with 2 treatment arms: a stepped care intervention program versus care as usual. Patients are randomized immediately pre transplant. Stepped care and care as usual are initiated after a 6 weeks buffer period. Outcome is evaluated at 13, 30, and 42 weeks post transplant. In the experimental group, the first step includes an Internet-based self-help program. If psychological distress persists after the self-help intervention, the second step of the program is executed, i.e. a diagnostic evaluation and a standardized interview, yielding a problem analysis. Based on this information, a contract is made with the patient and treatment is provided consisting of individual face-to-face counseling, medication, or referral to other services. Care as usual comprises an interview with the patient, on ad hoc basis; emotional support and advice, on ad hoc basis; if urgent problems emerge, the patient is referred to other services. Primary outcome variables are psychological distress and functional status. Data are analyzed according to the intention to treat-principle. Discussion This study has several innovative characteristics. First, the outcome of the intervention for psychological distress in patients with hematological malignancy treated with autologous stem cell transplantation is evaluated in a randomized controlled study. Second, the impact of the intervention on functional status is evaluated: it is hypothesized that reduction of psychological distress results in improved functional status. Furthermore, the intervention concerns an Internet-based treatment in the first step. Finally, the intervention is characterized by an emphasis on self-management, efficiency, and a multi-disciplinary approach with nurses taking up a central role

Fatigue in low-grade glioma

Contains fulltext : 80675.pdf (publisher's version ) (Closed access)The aim of this study was to determine the prevalence and severity of fatigue in long-term survivors with a low-grade glioma (LGG), and to analyze the relationship between fatigue and demographic variables, disease duration, tumor characteristics, former tumor treatment modalities, antiepileptic drug (AED) use, self-reported concentration, motivation, and activity. Fifty-four patients with stable disease (age range, 25-73 years) who were diagnosed and treated more than 8 years ago were included in this study. Fatigue was analyzed with the Checklist Individual Strength (CIS). Thirty-nine percent of the LGG patients were severely fatigued, with older patients being most affected. Severe fatigue was associated with AED use, and with reduced self-reported concentration, motivation, and activity. No relation was found between fatigue and gender, histology, tumor laterality, disease duration, type of neurosurgical intervention and radiation treatment. Fatigue is a severe problem in a large proportion of long-term surviving LGG patients

Design of the EXercise Intervention after Stem cell Transplantation (EXIST) study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of an individualized high intensity physical exercise program on fitness and fatigue in patients with multiple myeloma or (non-) Hodgkin's lymphoma treated with high dose chemotherapy and autologous stem cell transplantation

<p>Abstract</p> <p>Background</p> <p>The use of high-dose chemotherapy combined with autologous stem cell transplantation has improved the outcome of hematologic malignancies. Nevertheless, this treatment can cause persistent fatigue and a reduced global quality of life, role and physical function. Physical exercise interventions may be beneficial for physical fitness, fatigue and quality of life. However, the trials conducted so far to test the effects of physical exercise interventions in this group of patients were of poor to moderate methodological quality and economic evaluations are lacking. Hence there is need for a rigorous, appropriately controlled assessment of the effectiveness of exercise programs in these patients. The aims of the present study are (1) to determine the effectiveness of an individualized high intensity strength and interval training program with respect to physiological and psychological health status in patients with multiple myeloma or (non-)Hodgkin's lymphoma who have recently undergone high dose chemotherapy followed by autologous stem cell transplantation; and (2) to evaluate the cost-effectiveness of this program.</p> <p>Methods</p> <p>A multicenter, prospective, single blind randomized controlled trial will be performed. We aim to recruit 120 patients within an inclusion period of 2 years at 7 hospitals in the Netherlands. The patients will be randomly assigned to one of two groups: (1) intervention plus usual care; or (2) usual care. The intervention consists of an 18-week individualized supervised high-intensity exercise program and counselling. The primary outcomes (cardiorespiratory fitness, muscle strength and fatigue) and secondary outcomes are assessed at baseline, at completion of the intervention and at 12 months follow-up.</p> <p>Discussion</p> <p>The strengths of this study include the solid trial design with clearly defined research groups and standardized outcome measures, the inclusion of an economic evaluation and the inclusion of both resistance and endurance exercise in the intervention program.</p> <p>Trial registration</p> <p>This study is registered at the Netherlands Trial Register (NTR2341)</p

Inter-rater reliability of categorical versus continuous scoring of fish vitality: does it affect the utility of the reflex action mortality predictor (RAMP) approach?

Scoring reflex responsiveness and injury of aquatic organisms has gained popularity as predictors of discard survival. Given this method relies upon the individual interpretation of scoring criteria, an evaluation of its robustness is done here to test whether protocol-instructed, multiple raters with diverse backgrounds (research scientist, technician, and student) are able to produce similar or the same reflex and injury score for one of the same flatfish (European plaice, Pleuronectes platessa) after experiencing commercial fishing stressors. Inter-rater reliability for three raters was assessed by using a 3-point categorical scale (‘absent’, ‘weak’, ‘strong’) and a tagged visual analogue continuous scale (tVAS, a 10 cm bar split in three labelled sections: 0 for ‘absent’, ‘weak’, ‘moderate’, and ‘strong’) for six reflex responses, and a 4-point scale for four injury types. Plaice (n = 304) were sampled from 17 research beam-trawl deployments during four trips. Fleiss kappa (categorical scores) and intra-class correlation coefficients (ICC, continuous scores) indicated variable inter-rater agreement by reflex type (ranging between 0.55 and 0.88, and 67% and 91% for Fleiss kappa and ICC, respectively), with least agreement among raters on extent of injury (Fleiss kappa between 0.08 and 0.27). Despite differences among raters, which did not significantly influence the relationship between impairment and predicted survival, combining categorical reflex and injury scores always produced a close relationship of such vitality indices and observed delayed mortality. The use of the continuous scale did not improve fit of these models compared with using the reflex impairment index based on categorical scores. Given these findings, we recommend using a 3-point categorical over a continuous scale. We also determined that training rather than experience of raters minimised inter-rater differences. Our results suggest that cost-efficient reflex impairment and injury scoring may be considered a robust technique to evaluate lethal stress and damage of this flatfish species on-board commercial beam-trawl vessels

Ethical issues in autologous stem cell transplantation (ASCT) in advanced breast cancer: A systematic literature review

BACKGROUND: An effectiveness assessment on ASCT in locally advanced and metastatic breast cancer identified serious ethical issues associated with this intervention. Our objective was to systematically review these aspects by means of a literature analysis. METHODS: We chose the reflexive Socratic approach as the review method using Hofmann's question list, conducted a comprehensive literature search in biomedical, psychological and ethics bibliographic databases and screened the resulting hits in a 2-step selection process. Relevant arguments were assembled from the included articles, and were assessed and assigned to the question list. Hofmann's questions were addressed by synthesizing these arguments. RESULTS: Of the identified 879 documents 102 included arguments related to one or more questions from Hofmann's question list. The most important ethical issues were the implementation of ASCT in clinical practice on the basis of phase-II trials in the 1990s and the publication of falsified data in the first randomized controlled trials (Bezwoda fraud), which caused significant negative effects on recruiting patients for further clinical trials and the doctor-patient relationship. Recent meta-analyses report a marginal effect in prolonging disease-free survival, accompanied by severe harms, including death. ASCT in breast cancer remains a stigmatized technology. Reported health-related-quality-of-life data are often at high risk of bias in favor of the survivors. Furthermore little attention has been paid to those patients who were dying. CONCLUSIONS: The questions were addressed in different degrees of completeness. All arguments were assignable to the questions. The central ethical dimensions of ASCT could be discussed by reviewing the published literature

A systematic review of randomised controlled trials assessing effectiveness of prosthetic and orthotic interventions.

BACKGROUND: Assistive products are items which allow older people and people with disabilities to be able to live a healthy, productive and dignified life. It has been estimated that approximately 1.5% of the world's population need a prosthesis or orthosis. OBJECTIVE: The objective of this study was to systematically identify and review the evidence from randomized controlled trials assessing effectiveness and cost-effectiveness of prosthetic and orthotic interventions. METHODS: Literature searches, completed in September 2015, were carried out in fourteen databases between years 1995 and 2015. The search results were independently screened by two reviewers. For the purpose of this manuscript, only randomized controlled trials which examined interventions using orthotic or prosthetic devices were selected for data extraction and synthesis. RESULTS: A total of 342 randomised controlled trials were identified (319 English language and 23 non-English language). Only 4 of these randomised controlled trials examined prosthetic interventions and the rest examined orthotic interventions. These orthotic interventions were categorised based on the medical conditions/injuries of the participants. From these studies, this review focused on the medical condition/injuries with the highest number of randomised controlled trials (osteoarthritis, fracture, stroke, carpal tunnel syndrome, plantar fasciitis, anterior cruciate ligament, diabetic foot, rheumatoid and juvenile idiopathic arthritis, ankle sprain, cerebral palsy, lateral epicondylitis and low back pain). The included articles were assessed for risk of bias using the Cochrane Risk of Bias tool. Details of the clinical population examined, the type of orthotic/prosthetic intervention, the comparator/s and the outcome measures were extracted. Effect sizes and odds ratios were calculated for all outcome measures, where possible. CONCLUSIONS: At present, for prosthetic and orthotic interventions, the scientific literature does not provide sufficient high quality research to allow strong conclusions on their effectiveness and cost-effectiveness