Serum contactin-1 as a biomarker of long-term disease progression in natalizumab-treated multiple sclerosis.

BACKGROUND: Natalizumab treatment provides a model for non-inflammation-induced disease progression in multiple sclerosis (MS). OBJECTIVE: To study serum contactin-1 (sCNTN1) as a novel biomarker for disease progression in natalizumab-treated relapsing-remitting MS (RRMS) patients. METHODS: Eighty-nine natalizumab-treated RRMS patients with minimum follow-up of 3 years were included. sCNTN1 was analyzed at baseline (before natalizumab initiation), 3, 12, 24 months (M) and last follow-up (median 5.2 years) and compared to 222 healthy controls (HC) and 15 primary progressive MS patients (PPMS). Results were compared between patients with progressive, stable, or improved disability according to EDSS-plus criteria. RESULTS: Median sCNTN1 levels (ng/mL,) in RRMS (baseline: 10.7, 3M: 9.7, 12M: 10.4, 24M: 10.8; last follow-up: 9.7) were significantly lower compared to HC (12.5; p ⩽ 0.001). It was observed that 48% of patients showed progression during follow-up, 11% improved, and 40% remained stable. sCNTN1 levels were significantly lower in progressors both at baseline and at 12M compared to non-progressors. A 1 ng/mL decrease in baseline sCNTN1 was consistent with an odds ratio of 1.23 (95% confidence interval 1.04-1.45) (p = 0.017) for progression during follow-up. CONCLUSION: Lower baseline sCNTN1 concentrations were associated with long-term disability progression during natalizumab treatment, making it a possible blood-based prognostic biomarker for RRMS

Managing the complexity of doing it all : an exploratory study on students' experiences when trained stepwise in conducting consultations

Background: At most medical schools the components required to conduct a consultation, medical knowledge, communication, clinical reasoning and physical examination skills, are trained separately. Afterwards, all the knowledge and skills students acquired must be integrated into complete consultations, an art that lies at the heart of the medical profession. Inevitably, students experience conducting consultations as complex and challenging. Literature emphasizes the importance of three didactic course principles: moving from partial tasks to whole task learning, diminishing supervisors' support and gradually increasing students' responsibility. This study explores students' experiences of an integrated consultation course using these three didactic principles to support them in this difficult task. Methods: Six focus groups were conducted with 20 pre-clerkship and 19 clerkship students in total. Discussions were audiotaped, transcribed and analysed by Nvivo using the constant comparative strategy within a thematic analysis. Results: Conducting complete consultations motivated students in their learning process as future physician. Initially, students were very much focused on medical problem solving. Completing the whole task of a consultation obligated them to transfer their theoretical medical knowledge into applicable clinical knowledge on the spot. Furthermore, diminishing the support of a supervisor triggered students to reflect on their own actions but contrasted with their increased appreciation of critical feedback. Increasing students' responsibility stimulated their active learning but made some students feel overloaded. These students were anxious to miss patient information or not being able to take the right decisions or to answer patients' questions, which sometimes resulted in evasive coping techniques, such as talking faster to prevent the patient asking questions. Conclusion: The complex task of conducting complete consultations should be implemented early within medical curricula because students need time to organize their medical knowledge into applicable clinical knowledge. An integrated consultation course should comprise a step-by-step teaching strategy with a variety of supervisors' feedback modi, adapted to students' competence. Finally, students should be guided in formulating achievable standards to prevent them from feeling overloaded in practicing complete consultations with simulated or real patients

Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design.

INTRODUCTION: The Alzheimer's biomarkers in daily practice (ABIDE) project is designed to translate knowledge on diagnostic tests (magnetic resonance imaging [MRI], cerebrospinal fluid [CSF], and amyloid positron emission tomography [PET]) to daily clinical practice with a focus on mild cognitive impairment (MCI). METHODS: ABIDE is a 3-year project with a multifaceted design and is structured into interconnected substudies using both quantitative and qualitative research methods. RESULTS: Based on retrospective data, we develop personalized risk estimates for MCI patients. Prospectively, we collect MRI and CSF data from 200 patients from local memory clinics and amyloid PET from 500 patients in a tertiary setting, to optimize application of these tests in daily practice. Furthermore, ABIDE will develop strategies for optimal patient-clinician conversations. DISCUSSION: Ultimately, this will result in a set of practical tools for clinicians to support the choice of diagnostic tests and facilitate the interpretation and communication of their results

Professional identity formation in the transition from medical school to working life:a qualitative study of group-coaching courses for junior doctors

BACKGROUND: The transition from student to medical doctor is challenging and stressful to many junior doctors. To practice with confidence and professionalism the junior doctors have to develop a strong professional identity. Various suggestions on how to facilitate formation of professional identity have been offered including the possible positive effect of group-coaching courses. The purpose of this study was to explore how group-coaching might facilitate professional identity formation among junior doctors in the transition period. METHODS: Group-coaching courses comprising three whole-day sessions and five 2 h sessions during a period of 4 months were offered to junior doctors in the first years after graduation. The purpose was to support the participants’ professional development, ability to relate to patients, relatives and staff and career development. The coaches in this study had a background as health professionals combined with coaching educations. Data was obtained through observations, open-ended questionnaires and interviews. A generic thematic analysis was applied. RESULTS: Forty-five doctors participated in six coaching groups. The three main themes emerging in the sessions were: Adoption to medical culture, career planning, and work/life-balance. The junior doctors found the coaching intervention highly useful in order to cope with these challenges. Furthermore, the group was a forum where the junior doctors could share thoughts and feelings with colleagues without being afraid that this would endanger their professional career. Many found new ways to respond to everyday challenges mainly through a new awareness of patterns of thinking and feeling. CONCLUSIONS: The participants found that the group-coaching course supported their professional identity formation (thinking, feeling and acting as a doctor), adoption to medical culture, career planning and managing a healthy work/life-balance. Further studies in different contexts are recommended as well as studies using other methods to test the results of this qualitative study. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12909-016-0684-3) contains supplementary material, which is available to authorized users

Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism

<p>Abstract</p> <p>Background</p> <p>Elevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH) with those from healthy individuals.</p> <p>Methods</p> <p>Cholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography – mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p < 0.05; Benjamini Hochberg correction, False Discovery Rate = 0.05). The differential expression of FH associated genes was validated at the mRNA level by qRT-PCR and/or at the protein level by Western Blot or flow cytometry. Functional validation of monocyte scavenger receptor activities were done by binding assays and dose/time dependent uptake analysis using native and oxidized LDL.</p> <p>Results</p> <p>Using microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells.</p> <p>Conclusion</p> <p>Our data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease.</p

Assessing the Quality of Clinical Teachers: A Systematic Review of Content and Quality of Questionnaires for Assessing Clinical Teachers

BACKGROUND: Learning in a clinical environment differs from formal educational settings and provides specific challenges for clinicians who are teachers. Instruments that reflect these challenges are needed to identify the strengths and weaknesses of clinical teachers. OBJECTIVE: To systematically review the content, validity, and aims of questionnaires used to assess clinical teachers. DATA SOURCES: MEDLINE, EMBASE, PsycINFO and ERIC from 1976 up to March 2010. REVIEW METHODS: The searches revealed 54 papers on 32 instruments. Data from these papers were documented by independent researchers, using a structured format that included content of the instrument, validation methods, aims of the instrument, and its setting. Results : Aspects covered by the instruments predominantly concerned the use of teaching strategies (included in 30 instruments), supporter role (29), role modeling (27), and feedback (26). Providing opportunities for clinical learning activities was included in 13 instruments. Most studies referred to literature on good clinical teaching, although they failed to provide a clear description of what constitutes a good clinical teacher. Instrument length varied from 1 to 58 items. Except for two instruments, all had to be completed by clerks/residents. Instruments served to provide formative feedback ( instruments) but were also used for resource allocation, promotion, and annual performance review (14 instruments). All but two studies reported on internal consistency and/or reliability; other aspects of validity were examined less frequently. CONCLUSIONS: No instrument covered all relevant aspects of clinical teaching comprehensively. Validation of the instruments was often limited to assessment of internal consistency and reliability. Available instruments for assessing clinical teachers should be used carefully, especially for consequential decisions. There is a need for more valid comprehensive instruments