Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular Matrix

Rewiring of synaptic circuitry pertinent to memory formation has been associated with morphological changes in dendritic spines and with extracellular matrix (ECM) remodeling. Here, we mechanistically link these processes by uncovering a signaling pathway involving the serotonin 5-HT7 receptor (5-HT7R), matrix metalloproteinase 9 (MMP-9), the hyaluronan receptor CD44, and the small GTPase Cdc42. We highlight a physical interaction between 5-HT7R and CD44 (identified as an MMP-9 substrate in neurons) and find that 5-HT7R stimulation increases local MMP-9 activity, triggering dendritic spine remodeling, synaptic pruning, and impairment of long-term potentiation (LTP). The underlying molecular machinery involves 5-HT7R-mediated activation of MMP-9, which leads to CD44 cleavage followed by Cdc42 activation. One important physiological consequence of this interaction includes an increase in neuronal outgrowth and elongation of dendritic spines, which might have a positive effect on complex neuronal processes (e.g., reversal learning and neuronal regeneration)

German ambulatory care physicians' perspectives on clinical guidelines – a national survey

BACKGROUND: There has been little systematic research about the extent to which German physicians accept or reject the concept and practice of a) clinical practice guidelines (CPG) and b) evidence based medicine (EBM) The aim of this study was to investigate German office-based physicians' perspective on CPGs and EBM and their application in medical practice. METHODS: Structured national telephone survey of ambulatory care physicians, four thematic blocks with 21 questions (5 point Likert scale). 511 office-based general practitioners and specialists. Main outcome measures were the application of Clinical Practice Guidelines in daily practice, preference for sources of guidelines and degree of knowledge and acceptance of EBM. In the data analysis Pearson's correlation coefficient was used for explorative analysis of correlations. The comparison of groups was performed by Student's t-test. Chi(2 )test was used to investigate distribution of two or more categorical variables. RESULTS: Of the total study population 55.3% of physicians reported already using guidelines in the treatment of patients. Physicians in group practices (GrP) as well as general practitioners (GP) agreed significantly more with the usefulness of guidelines as a basis for patient care than doctors in single practices (SP) or specialists (S) (Student's t-test mean GP 2.57, S 2.84, p < 0.01; mean GrP 2.55, SP 2.80, p < 0.05). 33.1% of the participants demonstrated a strong rejection to the application of guidelines in patient care. Acceptance of guidelines from a governmental institution was substantially lower than from physician networks or medical societies (36.2% vs. 53.4% vs. 62.0%). 73.8% of doctors interpret EBM as a combination of scientific research and individual medical knowledge; 80% regard EBM as the best basis for patient care. CONCLUSION: Despite a majority of physicians accepting and applying CPGs a large group remains that is critical and opposed to the utilization of CPGs in daily practice and to the concept of EBM in general. Doctors in single practice and specialists appear to be more critical than physicians in group practices and GPs. Future research is needed to evaluate the willingness to acquire necessary knowledge and skills for the promotion and routine application of CPGs

The application of foraging theory to the information searching behaviour of general practitioners

<p>Abstract</p> <p>Background</p> <p>General Practitioners (GPs) employ strategies to identify and retrieve medical evidence for clinical decision making which take workload and time constraints into account. Optimal Foraging Theory (OFT) initially developed to study animal foraging for food is used to explore the information searching behaviour of General Practitioners. This study is the first to apply foraging theory within this context.</p> <p>Study objectives were:</p> <p>1. To identify the sequence and steps deployed in identifiying and retrieving evidence for clinical decision making.</p> <p>2. To utilise Optimal Foraging Theory to assess the effectiveness and efficiency of General Practitioner information searching.</p> <p>Methods</p> <p>GPs from the Wellington region of New Zealand were asked to document in a pre-formatted logbook the steps and outcomes of an information search linked to their clinical decision making, and fill in a questionnaire about their personal, practice and information-searching backgrounds.</p> <p>Results</p> <p>A total of 115/155 eligible GPs returned a background questionnaire, and 71 completed their information search logbook.</p> <p>GPs spent an average of 17.7 minutes addressing their search for clinical information. Their preferred information sources were discussions with colleagues (38% of sources) and books (22%). These were the two most profitable information foraging sources (15.9 min and 9.5 min search time per answer, compared to 34.3 minutes in databases). GPs nearly always accessed another source when unsuccessful (95% after 1^stsource), and frequently when successful (43% after 2^ndsource). Use of multiple sources accounted for 41% of searches, and increased search success from 70% to 89%.</p> <p>Conclusions</p> <p>By consulting in foraging terms the most 'profitable' sources of information (colleagues, books), rapidly switching sources when unsuccessful, and frequently double checking, GPs achieve an efficient trade-off between maximizing search success and information reliability, and minimizing searching time. As predicted by foraging theory, GPs trade time-consuming evidence-based (electronic) information sources for sources with a higher information reward per unit time searched. Evidence-based practice must accommodate these 'real world' foraging pressures, and Internet resources should evolve to deliver information as effectively as traditional methods of information gathering.</p

Knowledge translation on dementia: a cluster randomized trial to compare a blended learning approach with a "classical" advanced training in GP quality circles

<p>Abstract</p> <p>Background</p> <p>Thus far important findings regarding the dementia syndrome have been implemented into patients' medical care only inadequately. A professional training accounting for both, general practitioners' (GP) needs and learning preferences as well as care-relevant aspects could be a major step towards improving medical care. In the WIDA-study, entitled "Knowledge translation on dementia in general practice" two different training concepts are developed, implemented and evaluated. Both concepts are building on an evidence-based, GP-related dementia guideline and communicate the guideline's essential insights.</p> <p>Methods/Design</p> <p>Both development and implementation emphasize a procedure that is well-accepted in practice and, thus, can achieve a high degree of external validity. This is particularly guaranteed through the preparation of training material and the fact that general practitioners' quality circles (QC) are addressed. The evaluation of the two training concepts is carried out by comparing two groups of GPs to which several quality circles have been randomly assigned. The primary outcome is the GPs' knowledge gain. Secondary outcomes are designed to indicate the training's potential effects on the GPs' practical actions. In the first training concept (study arm A) GPs participate in a structured case discussion prepared for by internet-based learning material ("blended-learning" approach). The second training concept (study arm B) relies on frontal medical training in the form of a slide presentation and follow-up discussion ("classical" approach).</p> <p>Discussion</p> <p>This paper presents the outline of a cluster-randomized trial which has been peer reviewed and support by a national funding organization – Federal Ministry of Education and Research (BMBF) – and is approved by an ethics commission. The data collection has started in August 2006 and the results will be published independently of the study's outcome.</p> <p>Trial Registration</p> <p>Current Controlled Trials [ISRCTN36550981]</p

Does the level of expressed emotion (LEE) questionnaire have the same factor structure for adolescents as it has for adults?

Background The level of expressed emotion (LEE) is a four-factor questionnaire that measures expressed emotion (EE) as perceived by the recipient. These factors are: perceived lack of emotional support, perceived intrusiveness, perceived irritation, and perceive criticism. The four factors of the LEE has previously been found to be related to psychological disorders and has good psychometric properties for adults. However, it has not previously been studied in adolescent populations. Methods A total of 311 adolescents participated in this study. Using structural equation modeling, confirmatory factor analyses were conducted to examine if the LEE also had the same four-factor structure for adolescents as it does for adults. Results The confirmatory factor analyses demonstrated that the LEE's four-factor structure also applied to adolescents. The internal consistency of the scales were good and all the inter-correlations between the scales were significant. Additionally, the factors were significantly correlated to adolescent depressive and anxiety symptom score dimensions. Conclusion These findings seem to indicate that the LEE may be a good instrument in the measurement of adolescents perceived EE

Parents dealing with anorexia : actions and meanings

This paper examines parents&rsquo; actions in response to anorexia nervosa, and how these are shaped by the ways they construct or understand the eating disorder. The findings indicate that parents try to influence their daughters by searching for help, providing practical support, avoiding confrontation, complying with special requirements, persuading, explaining, and pressuring, using ploys and force, providing emotional support, and mediating interactions. Parents&rsquo; actions are influenced by how they construct anorexia, such as whether they see it as an eating issue, an illness, a psychological problem, a choice, or a mystery. Understanding parents&rsquo; actions and constructions can help clinicians develop collaborative partnerships with parents.<br /

Associations between music education, intelligence, and spelling ability in elementary school

Musical education has a beneficial effect on higher cognitive functions, but questions arise whether associations between music lessons and cognitive abilities are specific to a domain or general. We tested 194 boys in Grade 3 by measuring reading and spelling performance, non verbal intelligence and asked parents about musical activities since preschool. Questionnaire data showed that 53% of the boys had learned to play a musical instrument. Intelligence was higher for boys playing an instrument (p < .001). To control for unspecific effects we excluded families without instruments. The effect on intelligence remained (p < .05). Furthermore, boys playing an instrument showed better performance in spelling compared to the boys who were not playing, despite family members with instruments (p < .01). This effect was observed independently of IQ. Our findings suggest an association between music education and general cognitive ability as well as a specific language link

Labour intensity of guidelines may have a greater effect on adherence than GPs' workload

Background: Physicians' heavy workload is often thought to jeopardise the quality of care and to be a barrier to improving quality. The relationship between these has, however, rarely been investigated. In this study quality of care is defined as care 'in accordance with professional guidelines'. In this study we investigated whether GPs with a higher workload adhere less to guidelines than those with a lower workload and whether guideline recommendations that require a greater time investment are less adhered to than those that can save time. Methods: Data were used from the Second Dutch National survey of General Practice (DNSGP- 2). This nationwide study was carried out between April 2000 and January 2002. A multilevel logistic-regression analysis was conducted of 170,677 decisions made by GPs, referring to 41 Guideline Adherence Indicators (GAIs), which were derived from 32 different guidelines. Data were used from 130 GPs, working in 83 practices with 98,577 patients. GP-characteristics as well as guideline characteristics were used as independent variables. Measures include workload (number of contacts), hours spent on continuing medical education, satisfaction with available time, practice characteristics and patient characteristics. Outcome measure is an indicator score, which is 1 when a decision is in accordance with professional guidelines or 0 when the decision deviates from guidelines. Results: On average, 66% of the decisions GPs made were in accordance with guidelines. No relationship was found between the objective workload of GPs and their adherence to guidelines. Subjective workload (measured on a five point scale) was negatively related to guideline adherence (OR = 0.95). After controlling for all other variables, the variation between GPs in adherence to guideline recommendations showed a range of less than 10%. 84% of the variation in guideline adherence was located at the GAI-level. Which means that the differences in adherence levels between guidelines are much larger than differences between GPs. Guideline recommendations that require an extra time investment during the same consultation are significantly less adhered to: (OR = 0.46), while those that can save time have much higher adherence levels: OR = 1.55). Recommendations that reduce the likelihood of a follow-up consultation for the same problem are also more often adhered to compared to those that have no influence on this (OR = 3.13). Conclusion: No significant relationship was found between the objective workload of GPs and adherence to guidelines. However, guideline recommendations that require an extra time investment are significantly less well adhered to while those that can save time are significantly more often adhered to.

Dementia care initiative in primary practice – study protocol of a cluster randomized trial on dementia management in a general practice setting

<p>Abstract</p> <p>Background</p> <p>Current guidelines for dementia care recommend the combination of drug therapy with non-pharmaceutical measures like counselling and social support. However, the scientific evidence concerning non-pharmaceutical interventions for dementia patients and their informal caregivers remains inconclusive. Targets of modern comprehensive dementia care are to enable patients to live at home as long and as independent as possible and to reduce the burden of caregivers. The objective of the study is to compare a complex intervention including caregiver support groups and counselling against usual care in terms of time to nursing home placement. In this paper the study protocol is described.</p> <p>Methods/Design</p> <p>The IDA (Initiative Demenzversorgung in der Allgemeinmedizin) project is designed as a three armed cluster-randomized trial where dementia patients and their informal caregivers are recruited by general practitioners. Patients in the study region of Middle Franconia, Germany, are included if they have mild or moderate dementia, are at least 65 years old, and are members of the German AOK (Allgemeine Ortskrankenkasse) sickness fund. In the control group patients receive regular treatment, whereas in the two intervention groups general practitioners participate in a training course in evidence based dementia treatment, recommend support groups and offer counseling to the family caregivers either beginning at baseline or after the 1-year follow-up. The study recruitment and follow-up took place from July 2005 to January 2009. 303 general practitioners were randomized of which 129 recruited a total of 390 patients. Time to nursing home admission within the two year intervention and follow-up period is the primary endpoint. Secondary endpoints are cognitive status, activities of daily living, burden of care giving as well as healthcare costs. For an economic analysis from the societal perspective, data are collected from caregivers as well as by the use of routine data from statutory health insurance and long-term care insurance.</p> <p>Discussion</p> <p>From a public health perspective, the IDA trial is expected to lead to evidence based results on the community effectiveness of non-pharmaceutical support measures for dementia patients and their caregivers in the primary care sector. For health policy makers it is necessary to make their decisions about financing new services based on strong knowledge about the acceptance of measures in the population and their cost-effectiveness.</p> <p>Trial registration</p> <p>ISRCTN68329593</p

Pre-post changes in psychosocial functioning among relatives of patients with depressive disorders after Brief Multifamily Psychoeducation: A pilot study

<p>Abstract</p> <p>Background</p> <p>Depressive disorder is often chronic and recurrent, and results in a heavy psychosocial burden on the families of patients with this disorder. This study aims to examine the effectiveness of brief multifamily psychoeducation designed to alleviate their psychosocial burden.</p> <p>Methods</p> <p>Thirty-two relatives of patients with major depressive disorder participated in an open study testing the effectiveness of brief multifamily psychoeducation. The intervention consisted of four sessions over the course of 6 weeks. Outcome measures focused on emotional distress, care burden and Expressed Emotion (EE).</p> <p>Results</p> <p>The emotional distress, care burden and EE of the family all showed statistically significant improvements from baseline to after the family intervention. The proportion of relatives scoring 9 or more on K6, which indicates possible depressive or anxiety disorder, decreased from sixteen relatives (50.0%) at baseline, to only 3 relatives (9.3%) after the intervention.</p> <p>Conclusions</p> <p>This study suggests that brief multifamily psychoeducation is a useful intervention to reduce the psychosocial burden of the relatives of patients with depressive disorder. Further evaluation of family psychoeducation for relatives of patients with depressive disorder is warranted.</p