Predicting recurrence after unprovoked venous thromboembolism: prospective validation of the updated Vienna Prediction Model.

The updated Vienna Prediction Model for estimating recurrence risk after an unprovoked venous thromboembolism (VTE) has been developed to identify individuals at low risk for VTE recurrence in whom anticoagulation (AC) therapy may be stopped after 3 months. We externally validated the accuracy of the model to predict recurrent VTE in a prospective multicenter cohort of 156 patients aged ≥65 years with acute symptomatic unprovoked VTE who had received 3 to 12 months of AC. Patients with a predicted 12-month risk within the lowest quartile based on the updated Vienna Prediction Model were classified as low risk. The risk of recurrent VTE did not differ between low- vs higher-risk patients at 12 months (13% vs 10%; P = .77) and 24 months (15% vs 17%; P = 1.0). The area under the receiver operating characteristic curve for predicting VTE recurrence was 0.39 (95% confidence interval [CI], 0.25-0.52) at 12 months and 0.43 (95% CI, 0.31-0.54) at 24 months. In conclusion, in elderly patients with unprovoked VTE who have stopped AC, the updated Vienna Prediction Model does not discriminate between patients who develop recurrent VTE and those who do not. This study was registered at www.clinicaltrials.gov as #NCT00973596.

Diagnostic methods and treatment options for focal cortical dysplasia.

Our inability to adequately treat many patients with refractory epilepsy caused by focal cortical dysplasia (FCD), surgical inaccessibility and failures are significant clinical drawbacks. The targeting of physiologic features of epileptogenesis in FCD and colocalizing functionality has enhanced completeness of surgical resection, the main determinant of outcome. Electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) and magnetoencephalography are helpful in guiding electrode implantation and surgical treatment, and high-frequency oscillations help defining the extent of the epileptogenic dysplasia. Ultra high-field MRI has a role in understanding the laminar organization of the cortex, and fluorodeoxyglucose-positron emission tomography (FDG-PET) is highly sensitive for detecting FCD in MRI-negative cases. Multimodal imaging is clinically valuable, either by improving the rate of postoperative seizure freedom or by reducing postoperative deficits. However, there is no level 1 evidence that it improves outcomes. Proof for a specific effect of antiepileptic drugs (AEDs) in FCD is lacking. Pathogenic mutations recently described in mammalian target of rapamycin (mTOR) genes in FCD have yielded important insights into novel treatment options with mTOR inhibitors, which might represent an example of personalized treatment of epilepsy based on the known mechanisms of disease. The ketogenic diet (KD) has been demonstrated to be particularly effective in children with epilepsy caused by structural abnormalities, especially FCD. It attenuates epigenetic chromatin modifications, a master regulator for gene expression and functional adaptation of the cell, thereby modifying disease progression. This could imply lasting benefit of dietary manipulation. Neurostimulation techniques have produced variable clinical outcomes in FCD. In widespread dysplasias, vagus nerve stimulation (VNS) has achieved responder rates >50%; however, the efficacy of noninvasive cranial nerve stimulation modalities such as transcutaneous VNS (tVNS) and noninvasive (nVNS) requires further study. Although review of current strategies underscores the serious shortcomings of treatment-resistant cases, initial evidence from novel approaches suggests that future success is possible.

Epilepsy priorities in Europe: A report of the ILAE-IBE Epilepsy Advocacy Europe Task Force.

The European Forum on Epilepsy Research (ERF2013), which took place in Dublin, Ireland, on May 26-29, 2013, was designed to appraise epilepsy research priorities in Europe through consultation with clinical and basic scientists as well as representatives of lay organizations and health care providers. The ultimate goal was to provide a platform to improve the lives of persons with epilepsy by influencing the political agenda of the EU. The Forum highlighted the epidemiologic, medical, and social importance of epilepsy in Europe, and addressed three separate but closely related concepts. First, possibilities were explored as to how the stigma and social burden associated with epilepsy could be reduced through targeted initiatives at EU national and regional levels. Second, ways to ensure optimal standards of care throughout Europe were specifically discussed. Finally, a need for further funding in epilepsy research within the European Horizon 2020 funding programme was communicated to politicians and policymakers participating to the forum. Research topics discussed specifically included (1) epilepsy in the developing brain; (2) novel targets for innovative diagnostics and treatment of epilepsy; (3) what is required for prevention and cure of epilepsy; and (4) epilepsy and comorbidities, with a special focus on aging and mental health. This report provides a summary of recommendations that emerged at ERF2013 about how to (1) strengthen epilepsy research, (2) reduce the treatment gap, and (3) reduce the burden and stigma associated with epilepsy. Half of the 6 million European citizens with epilepsy feel stigmatized and experience social exclusion, stressing the need for funding trans-European awareness campaigns and monitoring their impact on stigma, in line with the global commitment of the European Commission and with the recommendations made in the 2011 Written Declaration on Epilepsy. Epilepsy care has high rates of misdiagnosis and considerable variability in organization and quality across European countries, translating into huge societal cost (0.2% GDP) and stressing the need for cost-effective programs of harmonization and optimization of epilepsy care throughout Europe. There is currently no cure or prevention for epilepsy, and 30% of affected persons are not controlled by current treatments, stressing the need for pursuing research efforts in the field within Horizon 2020. Priorities should include (1) development of innovative biomarkers and therapeutic targets and strategies, from gene and cell-based therapies to technologically advanced surgical treatment; (2) addressing issues raised by pediatric and aging populations, as well as by specific etiologies and comorbidities such as traumatic brain injury (TBI) and cognitive dysfunction, toward more personalized medicine and prevention; and (3) translational studies and clinical trials built upon well-established European consortia.

N-WASP is required for B-cell-mediated autoimmunity in Wiskott-Aldrich syndrome.

Mutations of the Wiskott-Aldrich syndrome gene (WAS) are responsible for Wiskott-Aldrich syndrome (WAS), a disease characterized by thrombocytopenia, eczema, immunodeficiency, and autoimmunity. Mice with conditional deficiency of Was in B lymphocytes (B/WcKO) have revealed a critical role for WAS protein (WASP) expression in B lymphocytes in the maintenance of immune homeostasis. Neural WASP (N-WASP) is a broadly expressed homolog of WASP, and regulates B-cell signaling by modulating B-cell receptor (BCR) clustering and internalization. We have generated a double conditional mouse lacking both WASP and N-WASP selectively in B lymphocytes (B/DcKO). Compared with B/WcKO mice, B/DcKO mice showed defective B-lymphocyte proliferation and impaired antibody responses to T-cell-dependent antigens, associated with decreased autoantibody production and lack of autoimmune kidney disease. These results demonstrate that N-WASP expression in B lymphocytes is required for the development of autoimmunity of WAS and may represent a novel therapeutic target in WAS.

Accuracy of cognitive MRI-targeted biopsy in hitting prostate cancer-positive regions of interest.

PURPOSE: Prostate cancer (PCa) diagnosis relies on clinical suspicion leading to systematic transrectal ultrasound-guided biopsy (TRUSGB). Multiparametric magnetic resonance imaging (mpMRI) allows for targeted biopsy of suspicious areas of the prostate instead of random 12-core biopsy. This method has been shown to be more accurate in detecting significant PCa. However, the precise spatial accuracy of cognitive targeting is unknown. METHODS: Consecutive patients undergoing mpMRI-targeted TRUSGB with cognitive registration (MRTB-COG) followed by robot-assisted radical prostatectomy were included in the present analysis. The regions of interest (ROIs) involved by the index lesion reported on mpMRI were subsequently targeted by two experienced urologists using the cognitive approach. The 27 ROIs were used as spatial reference. Mapping on radical prostatectomy specimen was used as reference to determine true-positive mpMRI findings. Per core correlation analysis was performed. RESULTS: Forty patients were included. Overall, 40 index lesions involving 137 ROIs (mean ROIs per index lesion 3.43) were identified on MRI. After correlating these findings with final pathology, 117 ROIs (85 %) were considered as true-positive lesions. A total of 102 biopsy cores directed toward such true-positive ROIs were available for final analysis. Cognitive targeted biopsy hit the target in 82 % of the cases (84/102). The only identified risk factor for missing the target was an anterior situated ROI (p = 0.01). CONCLUSION: In experienced hands, cognitive MRTB-COG allows for an accuracy of 82 % in hitting the correct target, given that it is a true-positive lesion. Anterior tumors are less likely to be successfully targeted.

Nursing discharge planning for older medical inpatients in Switzerland: A cross-sectional study.

Nursing discharge planning for elderly medical inpatients is an essential element of care to ensure optimal transition to home and to reduce post-discharge adverse events. The objectives of this cross-sectional study were to investigate the association between nursing discharge planning components in older medical inpatients, patients' readiness for hospital discharge and unplanned health care utilization during the following 30 days. Results indicated that no patients benefited from comprehensive discharge planning but most benefited from less than half of the discharge planning components. The most frequent intervention recorded was coordination, and the least common was patients' participation in decisions regarding discharge. Patients who received more nursing discharge components felt significantly less ready to go home and had significantly more readmissions during the 30-day follow-up period. This study highlights large gaps in the nursing discharge planning process in older medical inpatients and identifies specific areas where improvements are most needed.

Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Parenteral methotrexate is an effective treatment for patients with Crohn's disease, but has never been adequately evaluated in patients with ulcerative colitis (UC). We conducted a randomized controlled trial to determine its safety and efficacy in patients with steroid-dependent UC. METHODS: We performed a double-blind, placebo-controlled trial to evaluate the efficacy of parenteral methotrexate (25 mg/wk) in 111 patients with corticosteroid-dependent UC at 26 medical centers in Europe from 2007 through 2013. Patients were given prednisone (10 to 40 mg/d) when the study began and were randomly assigned to groups (1:1) given placebo or methotrexate (intramuscularly or subcutaneously, 25 mg weekly) for 24 weeks. The primary end point was steroid-free remission (defined as a Mayo score ≤2 with no item >1 and complete withdrawal of steroids) at week 16. Secondary endpoints included clinical remission (defined as a Mayo clinical subscore ≤2 with no item >1) and endoscopic healing without steroids at weeks 16 and/or 24, remission without steroids at week 24, and remission at both weeks 16 and 24. RESULTS: Steroid-free remission at week 16 was achieved by 19 of 60 patients given methotrexate (31.7%) and 10 of 51 patients given placebo (19.6%)-a difference of 12.1% (95% confidence interval [CI]: -4.0% to 28.1%; P = .15). The proportion of patients in steroid-free clinical remission at week 16 was 41.7% in the methotrexate group and 23.5% in the placebo group, for a difference of 18.1% (95% CI: 1.1% to 35.2%; P = .04). The proportions of patients with steroid-free endoscopic healing at week 16 were 35% in the methotrexate group and 25.5% in the placebo group-a difference of 9.5% (95% CI: -7.5% to 26.5%; P = .28). No differences were observed in other secondary end points. More patients receiving placebo discontinued the study because of adverse events (47.1%), mostly caused by UC, than patients receiving methotrexate (26.7%; P = .03). A higher proportion of patients in the methotrexate group had nausea and vomiting (21.7%) than in the placebo group (3.9%; P = .006). CONCLUSIONS: In a randomized controlled trial, parenteral methotrexate was not superior to placebo for induction of steroid-free remission in patients with UC. However, methotrexate induced clinical remission without steroids in a significantly larger percentage of patients, resulting in fewer withdrawals from therapy due to active UC. ClinicalTrials.gov ID NCT00498589.

Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis.

BACKGROUND & AIMS: It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS: Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0-100); histologic remission was defined as a peak count of <20 eosinophils/mm(2) in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS: Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS: In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263.

Interpretar pedagógicamente las actividades acuáticas para bebés. Aportaciones desde la fenomenología

Esta comunicación presenta una investigación que tiene como objetivo comprender el potencial pedagógico del espacio acuático sobre los bebés. Para hacerlo, parte de un planteamiento metodológico de carácter filosófico que utiliza la fenomenologia como vía de descubierta y en donde el propio proceso formativo de los investigadores se manifiesta como un elemento decisivo. Desde esta postura se justifica la historia y los pasos que se han seguido en el proceso de construcción de la búsqueda los cuales muestran la actitud que lo ha gobernado y que ha permitido seguir un proceso que le ha permitido transitar desde la vivencia más personal al conocimiento consciente, experiencial y transpersonal. En coherencia con la metodología fenomenológica se ha procedido a la búsqueda de las esencias del fenómeno como son la reducción gnoseológica que re-observa las actividades de los bebés en el medio acuático. La reducción eidética ha estudiado las esencias del medio acuático como espacio pluridimensional y el estudio del bebé en su etapa de cero a tres años desde una perspectiva holística integradora de las dimensiones emocional y social, cognitiva y psicomotriz. Para, finalmente, y como resultado de la búsqueda, construir las esencias de una propuesta de acción pedagógica en el medio acuático que se muestra, en ella misma, como el soporte de experiencia formativa.

De columbis

Q.F.F.Q.S.

De imperio civili

Invocatio: Q.B.V.

Den vårdande och helande bilden: möten med bildkonst i vårdandets värld

Denna vårdvetenskapliga avhandling syftar till att avtäcka och belysa en vårdande och helande dimension vid existentiellt lidande patienters möten med bildkonst inom vårdkontext. Kunskapssökandet sker i två studier. Den första (studie I) är en ikonografi sk tolkning av konstnären Matthias Grünewalds (ca 1460–1528) senmedeltida altarskåpsmålningar. I studien uttolkas lidandets uttryck och narrativa budskap samt symboliska gestaltningar av vårdande och helande i valda delar av detta s.k. Isenheimaltares bildprogram. Tolkningen utgår från rekonstruktionen av altarskåpets ursprungskontext, det medeltida Isenheimklostret, där svårt sjuka och döende patienter vårdades. I studie två (II) fortsätter sökandet i den moderna hospicevårdens kontext med hjälp av en kvalitativ intervjustudie som utforskar patienters meningsskapande vid möten med självvald bildkonst (oljemålningar och akvareller av fi nländska konstnärer som donerats till det sjukhus där intervjustudien gjordes). Forskningsansatsen är inspirerad av Hans-Georg Gadamers (1901–2002) hermeneutik. Vidare används några nyare tolkningsteoretiska ansatser inom bildkonstens område. Forskningens tolkningsresultat visar att bildkonsten har potentialer såväl på ett miljöestetiskt plan som på en djupare individuell symbolnivå. Som designkomponent i vårdmiljöns rumsliga gestaltning bygger bildkonsten in estetiska, etiska och andliga kvaliteter utifrån tidsmässiga och kulturella koder. I den medeltida klostervårdens kontext sammanföll bildkonstens dekorativa betydelse med andliga och helande syften. När det gäller självvalda konstverk i den moderna vårdkontexten bidrar de till det enskilda patientrummets atmosfär på ett unikt sätt utifrån patientens personlighet och behov. På en fördjupad mötesnivå, i samspel med bildens symboliska funktion, sker en inlevelsemässig förfl yttning in i bildens värld. Betraktarens inlevelse aktiveras till en transcenderande rörelse som går bortom det faktiska rummets och den reella tidens gränser. Vid resor i konstens bildvärld spelas minnesvärda händelser upp från det förgångna, men även framtiden kommer betraktaren till mötes. I en existentiell livssituation söker människan i konstverkets bildinnehåll efter symbolisk mening som kan ge svar på lidandets frågor. Bilderna iscensätter då helande motbilder som utgör korrektiv i symboliska former när olika existentiella förluster hotar. När livet förbleknats av sjukdom besvarar bildvärlden den lidandes blick med lysande violer som blommar upp, ger livskraft och bekräftar personens värdighet mitt i det förvissnande människolivet. När ångest och otrygghet nalkas inbjuds betraktaren till besök i landskap som utvidgar sjukhusrummets väggar mot hemgårdens trygghet. Där livet hotas av förgänglighet tar bildvärlden människan med sig till naturens eviga återfödelse. Upplevelsen av att vara delaktig i ett större och heligt sammanhang öppnar vägen ut ur lidandets avskurenhet. I medeltidens vårdkontext erbjöd den sakrala bilden en kollektiv och helande Symbolon som genom sin representationskraft synliggjorde det osynliga. Vid bildmöten i den moderna hospicevårdens kontext var det naturteman som gläntade på dörren till ”det hemliga rummet i djupet av hjärtat”. Forskningen antyder att även om meningsskapandet i ett bildmöte är avhängigt tidsepok, betraktarens förförståelse och kulturella kontext samt typen av bilder kan bildsymboliken, generellt förstådd som den saknade formen eller det saknade livssammanhanget, framvisa en helande och hoppingivande ordning i lidandets kaos.

Group mentoring for junior medical students: perceptions of mentees and mentors

Entering medical school can be associated with a number of difficulties that can hinder students' performance. Mentoring programs are designed to help students circumvent difficulties and improve their learning and personal development. The current study aimed to evaluate the perceptions of both students and mentors regarding a recently introduced, group-based mentoring program designed to support first-year students. After one year of regular meetings, students and mentors' perceptions of the program were assessed by means of structured questionnaires. Response content categories were identified through multiple readings. Both regular attendees and non-participating students had positive opinions about the program. Mentors were highly satisfied at having participated and acknowledged that the program has been useful not only for assisting students, but also for fostering their own personal and professional development. In conclusion, the group-based mentoring program is feasible and can elicit positive views from both mentors and students. In addition, faculty members' participation as mentors can also be beneficial, since the program appears to contribute to their own personal and professional development