Monitoring health-related quality of life in paediatric practice: development of an innovative web-based application

<p>Abstract</p> <p>Background</p> <p>Health Related Quality of Life (HRQOL) questionnaires are increasingly used in clinical practice. These Patient Reported Outcomes (PROs) are provided to the paediatrician to facilitate communication with patients during a consultation. The aim of the current article is to describe the development and introduction of a new web-based application for the use of PROs in daily paediatric clinical practice.</p> <p>Methods</p> <p>Currently, the use of PROs in daily clinical practice is very time consuming and often has logistical problems. The use of a web-based programme can overcome these problems and contributes to an improved use of PROs in clinical practice. We therefore developed an easily accessible website (KLIK) for outpatient treatment and a training programme for paediatricians to maximize the effectiveness and the practical use of PROs (KLIK PROfile).</p> <p>Results</p> <p>The KLIK study was launched in August 2008 to evaluate the use of the KLIK PROfile in daily clinical practice. The KLIK study evaluates whether feedback from HRQOL data could influence patient satisfaction with the consultation, the advice given, the type of referrals and topics discussed. In this multicentre study, a control group (without the use of the KLIK PROfile) is compared to an intervention group (with the use of the KLIK PROfile). A sequential cohort design is chosen to avoid contamination between the study groups.</p> <p>Conclusions</p> <p>Based on the positive experiences with the use of the KLIK PROfile acquired during the study we conclude that the KLIK PROfile may contribute to systematically monitor and discuss HRQOL issues during consultations. The next steps will be a comprehensive evaluation of the KLIK study data and the implementation of the KLIK PROfile in daily clinical practice in different patient groups.</p

Review conclusions by Ernst and Canter regarding spinal manipulation refuted

In the April 2006 issue of the Journal of Royal Society of Medicine, Ernst and Canter authored a review of the most recent systematic reviews on the effectiveness of spinal manipulation for any condition. The authors concluded that, except for back pain, spinal manipulation is not an effective intervention for any condition and, because of potential side effects, cannot be recommended for use at all in clinical practice. Based on a critical appraisal of their review, the authors of this commentary seriously challenge the conclusions by Ernst and Canter, who did not adhere to standard systematic review methodology, thus threatening the validity of their conclusions. There was no systematic assessment of the literature pertaining to the hazards of manipulation, including comparison to other therapies. Hence, their claim that the risks of manipulation outweigh the benefits, and thus spinal manipulation cannot be recommended as treatment for any condition, was not supported by the data analyzed. Their conclusions are misleading and not based on evidence that allow discrediting of a large body of professionals using spinal manipulation

Phosphorylation of Rab-coupling protein by LMTK3 controls Rab14-dependent EphA2 trafficking to promote cell:cell repulsion

The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis in vivo is unclear. Here we identify an RTK of the Eph family, EphA2, to be a cargo of an RCP-regulated endocytic pathway which controls cell:cell repulsion and metastasis in vivo. Phosphorylation of RCP at Ser435 by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser897 by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart. Genetic disruption of RCP or EphA2 opposes cell:cell repulsion and metastasis in an autochthonous mouse model of pancreatic adenocarcinoma—whereas conditional knockout of another RCP cargo, α5 integrin, does not suppress pancreatic cancer metastasis—indicating a role for RCP-dependent trafficking of an Eph receptor to drive tumour dissemination in vivo

Mindfulness-Based Childbirth and Parenting Education: Promoting Family Mindfulness During the Perinatal Period

We present the conceptual and empirical foundation and curriculum content of the Mindfulness-Based Childbirth and Parenting (MBCP) program and the results of a pilot study of n = 27 pregnant women participating in MBCP during their third trimester of pregnancy. MBCP is a formal adaptation of the Mindfulness-Based Stress Reduction program and was developed and refined over the course of 11 years of clinical practice with 59 groups of expectant couples. MBCP is designed to promote family health and well-being through the practice of mindfulness during pregnancy, childbirth, and early parenting. Quantitative results from the current study include statistically significant increases in mindfulness and positive affect, and decreases in pregnancy anxiety, depression, and negative affect from pre- to post-test (p < .05). Effect sizes for changes in key hypothesized intervention mediators were large (d > .70), suggesting that MBCP is achieving its intended effects on maternal well-being during pregnancy. Qualitative reports from participants expand upon the quantitative findings, with the majority of participants reporting perceived benefits of using mindfulness practices during the perinatal period and early parenting. Our future research will involve conducting a randomized controlled trial of MBCP to test effects on psychophysiological stress mechanisms and to examine effects on birth outcomes, family relationship quality, and child development outcomes

What do clinicians want? Interest in integrative health services at a North Carolina academic medical center

BACKGROUND: Use of complementary medicine is common, consumer driven and usually outpatient focused. We wished to determine interest among the medical staff at a North Carolina academic medical center in integrating diverse therapies and services into comprehensive care. METHODS: We conducted a cross sectional on-line survey of physicians, nurse practitioners and physician assistants at a tertiary care medical center in 2006. The survey contained questions on referrals and recommendations in the past year and interest in therapies or services if they were to be provided at the medical center in the future. RESULTS: Responses were received from 173 clinicians in 26 different departments, programs and centers. There was strong interest in offering several specific therapies: therapeutic exercise (77%), expert consultation about herbs and dietary supplements (69%), and massage (66%); there was even stronger interest in offering comprehensive treatment programs such as multidisciplinary pain management (84%), comprehensive nutritional assessment and advice (84%), obesity/healthy lifestyle promotion (80%), fit for life (exercise and lifestyle program, 76%), diabetes healthy lifestyle promotion (73%); and comprehensive psychological services for stress management, including hypnosis and biofeedback (73%). CONCLUSION: There is strong interest among medical staff at an academic health center in comprehensive, integrated services for pain, obesity, and diabetes and in specific services in fitness, nutrition and stress management. Future studies will need to assess the cost-effectiveness of such services, as well as their financial sustainability and impact on patient satisfaction, health and quality of life

HHEX is a transcriptional regulator of the VEGFC/FLT4/PROX1 signaling axis during vascular development.

Formation of the lymphatic system requires the coordinated expression of several key regulators: vascular endothelial growth factor C (VEGFC), its receptor FLT4, and a key transcriptional effector, PROX1. Yet, how expression of these signaling components is regulated remains poorly understood. Here, using a combination of genetic and molecular approaches, we identify the transcription factor hematopoietically expressed homeobox (HHEX) as an upstream regulator of VEGFC, FLT4, and PROX1 during angiogenic sprouting and lymphatic formation in vertebrates. By analyzing zebrafish mutants, we found that hhex is necessary for sprouting angiogenesis from the posterior cardinal vein, a process required for lymphangiogenesis. Furthermore, studies of mammalian HHEX using tissue-specific genetic deletions in mouse and knockdowns in cultured human endothelial cells reveal its highly conserved function during vascular and lymphatic development. Our findings that HHEX is essential for the regulation of the VEGFC/FLT4/PROX1 axis provide insights into the molecular regulation of lymphangiogenesis

Involvement of global genome repair, transcription coupled repair, and chromatin remodeling in UV DNA damage response changes during development

Nucleotide Excision Repair (NER), which removes a variety of helix-distorting lesions from DNA, is initiated by two distinct DNA damage-sensing mechanisms. Transcription Coupled Repair (TCR) removes damage from the active strand of transcribed genes and depends on the SWI/SNF family protein CSB. Global Genome Repair (GGR) removes damage present elsewhere in the genome and depends on damage recognition by the XPC/RAD23/Centrin2 complex. Currently, it is not well understood to what extent both pathways contribute to genome maintenance and cell survival in a developing organism exposed to UV light. Here, we show that eukaryotic NER, initiated by two distinct subpathways, is well conserved in the nematode Caenorhabditis elegans. In C. elegans, involvement of TCR and GGR in the UV-induced DNA damage response changes during development. In germ cells and early embryos, we find that GGR is the major pathway contributing to normal development and survival after UV irradiation, whereas in later developmental stages TCR is predominantly engaged. Furthermore, we identify four ISWI/Cohesin and four SWI/SNF family chromatin remodeling factors that are implicated in the UV damage response in a developmental stage dependent manner. These in vivo studies strongly suggest that involvement of different repair pathways and chromatin remodeling proteins in UV-induced DNA repair depends on developmental stage of cells

A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion

Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers β-catenin recruitment and adhesion reinforcement dependent on α-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion. N-cadherin also mediates repolarization of the CAFs away from the cancer cells. In parallel, nectins and afadin are recruited to the cancer cell/CAF interface and CAF repolarization is afadin dependent. Heterotypic junctions between CAFs and cancer cells are observed in patient-derived material. Together, our findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumour invasion