Symptoms predicting remission after divalproex augmentation with olanzapine in partially nonresponsive patients experiencing mixed bipolar I episode: a post-hoc analysis of a randomized controlled study

<p>Abstract</p> <p>Background</p> <p>Rating scale items in a 6-week clinical trial of olanzapine versus placebo augmentation in patients with mixed bipolar disorder partially nonresponsive to ≥14 days of divalproex monotherapy were analyzed to characterize symptom patterns that could predict remission. At baseline, the two treatment groups were similar.</p> <p>Findings</p> <p>Factor analysis with Varimax rotation was performed <it>post hoc </it>on baseline items of the 21-Item Hamilton Depression Rating Scale (HDRS-21) and Young Mania Rating Scale (YMRS). Backwards-elimination logistic regression ascertained factors predictive of protocol-defined endpoint remission (HDRS-21 score ≤ 8 and YMRS score ≤ 12) with subsequent determination of optimally predictive factor score cutoffs.</p> <p>Factors for Psychomotor activity (YMRS items for elevated mood, increased motor activity, and increased speech and HDRS-21 agitation item) and Guilt/Suicidality (HDRS-21 items for guilt and suicidality) significantly predicted endpoint remission in the divalproex+olanzapine group. No factor predicted remission in the divalproex+placebo group. Patients in the divalproex+olanzapine group with high pre-augmentation psychomotor activity (scores ≥10) were more likely to remit compared to those with lower psychomotor activity (odds ratio [OR] = 3.09, 95% confidence interval [CI] = 1.22-7.79), and patients with marginally high Guilt/Suicidality (scores ≥2) were less likely to remit than those with lower scores (OR = 0.37, 95% CI = 0.13-1.03). Remission rates for divalproex+placebo vs. divalproex+olanzapine patients with high psychomotor activity scores were 22% vs. 45% (p = 0.08) and 33% vs. 48% (p = 0.29) for patients with low Guilt/Suicidality scores.</p> <p>Conclusions</p> <p>Patients who were partially nonresponsive to divalproex treatment with remaining high vs. low psychomotor activity levels or minimal vs. greater guilt/suicidality symptoms were more likely to remit with olanzapine augmentation.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov; <url>http://clinicaltrials.gov/ct2/show/NCT00402324?term=NCT00402324&rank=1</url>, Identifier: NCT00402324</p

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion

A European lens upon adult and lifelong learning in Asia

In this article, we seek to assess the extent to which adult and lifelong learning policies and practices in Asia have distinctiveness by comparison to those found in western societies, through an analysis of inter-governmental, national and regional policies in the field. We also inform our study through the analysis of the work of organisations with an international remit with a specific focus on Asia and Europe. In one case, the Asia–Europe Meeting Lifelong Learning (ASEM LLL) Hub has a specific function of bringing together researchers in Asia and Europe. In another, the PASCAL Observatory has had a particular focus on one aspect of lifelong learning, that of learning cities, with a concentration in its work on Asia and Europe. We focus on learning city development as a particular case of distinction in the field. We seek to identify the extent to which developments in the field in Asia have influenced and have been influenced by practices elsewhere in world, especially in Europe, and undertake our analysis using theories of societal learning/the learning society, learning communities and life-deep learning. We complement our analysis through assessment of material contained in three dominant journals in the field, the International Journal of Lifelong Education, the International Review of Education and Adult Education Quarterly, each edited in the west

Identifying patterns in treatment response profiles in acute bipolar mania: a cluster analysis approach

<p>Abstract</p> <p>Background</p> <p>Patients with acute mania respond differentially to treatment and, in many cases, fail to obtain or sustain symptom remission. The objective of this exploratory analysis was to characterize response in bipolar disorder by identifying groups of patients with similar manic symptom response profiles.</p> <p>Methods</p> <p>Patients (n = 222) were selected from a randomized, double-blind study of treatment with olanzapine or divalproex in bipolar I disorder, manic or mixed episode, with or without psychotic features. Hierarchical clustering based on Ward's distance was used to identify groups of patients based on Young-Mania Rating Scale (YMRS) total scores at each of 5 assessments over 7 weeks. Logistic regression was used to identify baseline predictors for clusters of interest.</p> <p>Results</p> <p>Four distinct clusters of patients were identified: Cluster 1 (n = 64): patients did not maintain a response (YMRS total scores ≤ 12); Cluster 2 (n = 92): patients responded rapidly (within less than a week) and response was maintained; Cluster 3 (n = 36): patients responded rapidly but relapsed soon afterwards (YMRS ≥ 15); Cluster 4 (n = 30): patients responded slowly (≥ 2 weeks) and response was maintained. Predictive models using baseline variables found YMRS Item 10 (Appearance), and psychosis to be significant predictors for Clusters 1 and 4 vs. Clusters 2 and 3, but none of the baseline characteristics allowed discriminating between Clusters 1 vs. 4. Experiencing a mixed episode at baseline predicted membership in Clusters 2 and 3 vs. Clusters 1 and 4. Treatment with divalproex, larger number of previous manic episodes, lack of disruptive-aggressive behavior, and more prominent depressive symptoms at baseline were predictors for Cluster 3 vs. 2.</p> <p>Conclusion</p> <p>Distinct treatment response profiles can be predicted by clinical features at baseline. The presence of these features as potential risk factors for relapse in patients who have responded to treatment should be considered prior to discharge.</p> <p>Trial registration</p> <p>The clinical trial cited in this report has not been registered because it was conducted and completed prior to the inception of clinical trial registries.</p

Composition of lower urinary tract stones in canines in Mexico City

11th International symposium on urolithiasis, Nice, France, 2–5 September 2008 Urological Research (2008) 36:157–232. doi:10.1007/s00240-008-0145-5. http://www.springerlink.com/ content/x263655772684210/fulltext.pdf.Effective long-term management of urolithiasis depends on identification and manipulation of factors contributing to initial stone formation; identification of these factors depends on accurate identification of the mineral composition of the urolith involved. The purpose of this study was to determine the chemical composition of uroliths obtained from the low urinary tract of dogs in Mexico City. One hundred and five cases of urolithiasis were studied in which stones were surgically obtained from the low urinary tracts of dogs treated in different hospitals. The chemical composition of the uroliths was quantita- tively and qualitatively determined by stereoscopic microscopy, IR-spectroscopy, scanning electron micros- copy and X-ray microanalysis. Age of animals ranged from 4 months to 14 years, with a median of 5 years. Compo- sition and distribution of the uroliths were struvite 38.1%,calcium oxalate 26.7%, silica 13.3%, urate 7.6%, mixed 11.4%, compounds 1.9%, and cystine 1%. Most uroliths were found in pure breed dogs (75.2%); 23 different breeds were identified, and more than half of the submissions were from breeds of small size. In our study, the frequency of struvite, calcium oxalate, cystine, urates, mixed and com- pounds stones are in agreement with papers that report on dog populations in America and Europe, but a higher fre- quency of silica uroliths was observed in Mexico City dogs.This work has been partially supported by a project of Waltham Foundation in Mexico

Advanced adenoma diagnosis with FDG PET in a visibly normal mucosa: a case report

<p>Abstract</p> <p>Background</p> <p>An accurate, early diagnosis and treatment of adenomatous polyp can curtail progression to colorectal cancer. F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) reveals the biochemical changes associated with the development of many cancers which precede the appearance of gross anatomical changes that may be visualized during surgical resection or via imaging with MR or CT.</p> <p>Intervention</p> <p>We detail the history of a 64 year old female who had a whole-body FDG PET scan as a part of an employee wellness program. A dose of 12.2 mCi of F-18 labeled FDG was administered.</p> <p>Results</p> <p>A focal cecal uptake with a standardized uptake value (SUV) of 8.9 was found on the PET scan. Conversely, only normal mucosa was observed during a colonoscopy done 2 months after the PET scan. Motivated by the PET scan finding, the colonoscopist performed a biopsy which revealed a villous adenoma without high grade dysplasia. Pathology from tissue extracted during an exploratory laparatomy completed one month later found the lesion to be a villous adenoma with high grade dysplasia.</p> <p>Conclusion</p> <p>Whole-body FDG PET scan revealed the biochemical metabolic changes in malignancy that preceded the appearance of any gross anatomical abnormality. A positive FDG PET scan indicative of colorectal cancer should be followed up with a colonoscopy and biopsy even in a visibly normal mucosa.</p

Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients

Learning to mark: a qualitative study of the experiences and concerns of medical markers

BACKGROUND: Although there is published research on the methods markers use in marking various types of assessment, there is relatively little information on the processes markers use in approaching a marking exercise. This qualitative paper describes the preparation and experiences of general practice (GP) teachers who undertake marking a written assessment in an undergraduate medical course. METHODS: Semi-structured interviews were conducted with seven of the 16 GP tutors on an undergraduate course. The purposive sample comprised two new markers, two who had marked for a couple of years and three experienced markers. Each respondent was interviewed twice, once following a formative assessment of a written case study, and again after a summative assessment. All interviews were audio-taped and analysed for emerging themes. A respondent validation exercise was conducted with all 16 GP tutors. RESULTS: Markers had internal concerns about their ability to mark fairly and made considerable efforts to calibrate their marking. They needed guidance and coaching when marking for the first time and adopted a variety of marking styles, reaching a decision through a number of routes. Dealing with pass/fail borderline scripts and the consequences of the mark on the student were particular concerns. Even experienced markers felt the need to calibrate their marks both internally and externally CONCLUSION: Previous experience of marking appears to improve markers' confidence and is a factor in determining the role which markers adopt. Confidence can be improved by giving clear instructions, along with examples of marking. The authors propose that one method of providing this support and coaching could be by a process of peer review of a selection of papers prior to the main marking. New markers in particular would benefit from further guidance, however they are influenced by others early on in their marking career and course organisers should be mindful of this when arranging double marking

Signs and symptoms of acute mania: a factor analysis

<p>Abstract</p> <p>Background</p> <p>The major diagnostic classifications consider mania as a uni-dimensional illness. Factor analytic studies of acute mania are fewer compared to schizophrenia and depression. Evidence from factor analysis suggests more categories or subtypes than what is included in the classification systems. Studies have found that these factors can predict differences in treatment response and prognosis.</p> <p>Methods</p> <p>The sample included 131 patients consecutively admitted to an acute psychiatry unit over a period of one year. It included 76 (58%) males. The mean age was 44.05 years (SD = 15.6). Patients met International Classification of Diseases-10 (ICD-10) clinical diagnostic criteria for a manic episode. Patients with a diagnosis of mixed bipolar affective disorder were excluded. Participants were evaluated using the Young Mania Rating Scale (YMRS). Exploratory factor analysis (principal component analysis) was carried out and factors with an eigenvalue > 1 were retained. The significance level for interpretation of factor loadings was 0.40. The unrotated component matrix identified five factors. Oblique rotation was then carried out to identify three factors which were clinically meaningful.</p> <p>Results</p> <p>Unrotated principal component analysis extracted five factors. These five factors explained 65.36% of the total variance. Oblique rotation extracted 3 factors. Factor 1 corresponding to 'irritable mania' had significant loadings of irritability, increased motor activity/energy and disruptive aggressive behaviour. Factor 2 corresponding to 'elated mania' had significant loadings of elevated mood, language abnormalities/thought disorder, increased sexual interest and poor insight. Factor 3 corresponding to 'psychotic mania' had significant loadings of abnormalities in thought content, appearance, poor sleep and speech abnormalities.</p> <p>Conclusions</p> <p>Our findings identified three clinically meaningful factors corresponding to 'elated mania', 'irritable mania' and 'psychotic mania'. These findings support the multidimensional nature of manic symptoms. Further evidence is needed to support the existence of corresponding clinical subtypes.</p

Renal artery stenosis-when to screen, what to stent?

Renal artery stensosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Evidence from large clinical trials has led clinicians away from recommending interventional revascularisation towards aggressive medical management. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary oedema, rapidly declining renal function and severe resistant hypertension. The potential benefits in terms of improving hard cardiovascular outcomes may outweigh the risks of intervention in this group, and further research is needed