Effectiveness and cost-effectiveness of transmural collaborative care with consultation letter (TCCCL) and duloxetine for major depressive disorder (MDD) and (sub)chronic pain in collaboration with primary care: design of a randomized placebo-controlled multi-Centre trial: TCC:PAINDIP

__Abstract__ Background: The comorbidity of pain and depression is associated with high disease burden for patients in terms of disability, wellbeing, and use of medical care. Patients with major and minor depression often present themselves with pain to a general practitioner and recognition of depression in such cases is low, but evolving. Also, physical symptoms, including pain, in major depressive disorder, predict a poorer response to treatment. A multi-faceted, patient-tailored treatment programme, like collaborative care, is promising. However, treatment of chronic pain conditions in depressive patients has, so far, received limited attention in research. Cost effectiveness of an integrated approach of pain in depressed patients has not been studied. This article describes the aims and design of a study to evaluate effects and costs of collaborative care with the antidepressant duloxetine for patients with pain symptoms and a depressive disorder, compared to collaborative care with placebo and compared to duloxetine alone

The remodelling index risk stratifies patients with hypertensive left ventricular hypertrophy

Aims Hypertensive left ventricular hypertrophy (LVH) is associated with increased cardiovascular events. We previously developed the remodelling index (RI) that incorporated left ventricular (LV) volume and wall-thickness in a single measure of advanced hypertrophy in hypertensive patients. This study examined the prognostic potential of the RI in reference to contemporary LVH classifications.Methods and results Cardiovascular magnetic resonance was performed in 400 asymptomatic hypertensive patients. The newly derived RI ((3)root EDV/t, where EDV is LV end-diastolic volume and t is the maximal wall thickness across 16 myocardial segments) stratified hypertensive patients: no LVH, LVH with normal RI (LVHNormal-RI), and LVH with low RI (LVHLow-RI). The primary outcome was a composite of all-cause mortality, acute coronary syndromes, strokes, and decompensated heart failure. LVHLow-RI was associated with increased LV mass index, fibrosis burden, impaired myocardial function and elevated biochemical markers of myocardial injury (high-sensitive cardiac troponin I), and wall stress. Over 18.3 +/- 7.0 months (601.3 patient-years), 14 adverse events occurred (2.2 events/100 patient-years). Patients with LVHLow-RI had more than a five-fold increase in adverse events compared to those with LVHNormal-RI (11.6 events/100 patient-years vs. 2.0 events/100 patient-years, respectively; log-rank P < 0.001). The RI provided incremental prognostic value over and above a model consisting of clinical variables, LVH and concentricity; and predicted adverse events independent of clinical variables, LVH, and other prognostic markers. Concentric and eccentric LVH were associated with adverse prognosis (log-rank P = 0.62) that was similar to the natural history of hypertensive LVH (5.1 events/100 patient-years).Conclusion The RI provides prognostic value that improves risk stratification of hypertensive LVH.Cardiolog

Validity of self-reported weight, height, and body mass index among university students in Thailand: Implications for population studies of obesity in developing countries

<p>Abstract</p> <p>Background</p> <p>Large-scale epidemiological studies commonly use self-reported weights and heights to determine weight status. Validity of such self-reported data has been assessed primarily in Western populations in developed countries, although its use is widespread in developing countries. We examine the validity of obesity based on self-reported data in an Asian developing country, and derive improved obesity prevalence estimates using the "reduced BMI threshold" method.</p> <p>Methods</p> <p>Self-reported and measured heights and weights were obtained from 741 students attending an open university in Thailand (mean age 34 years). Receiver operator characteristic techniques were applied to derive "reduced BMI thresholds."</p> <p>Results</p> <p>Height was over-reported by a mean of 1.54 cm (SD 2.23) in men and 1.33 cm (1.84) in women. Weight was under-reported by 0.93 kg (3.47) in men and 0.62 kg (2.14) in women. Sensitivity and specificity for determining obesity (Thai BMI threshold 25 kg/m²) using self-reported data were 74.2% and 97.3%, respectively, for men and 71.9% and 100% for women. For men, reducing the BMI threshold to 24.5 kg/m²increased the estimated obesity prevalence based on self-reports from 29.1% to 33.8% (true prevalence was 36.9%). For women, using a BMI threshold of 24.4 kg/m², the improvement was from 12.0% to 15.9% (true prevalence 16.7%).</p> <p>Conclusion</p> <p>Young educated Thais under-report weight and over-report height in ways similar to their counterparts in developed countries. Simple adjustments to BMI thresholds will overcome these reporting biases for estimation of obesity prevalence. Our study suggests that self-reported weights and heights can provide economical and valid measures of weight status in high school-educated populations in developing countries.</p

Increased Incidence of Choroid Plexus Carcinoma Due to the Germline TP53 R337H Mutation in Southern Brazil

International audienceBACKGROUND: Choroid plexus carcinomas (CPC) are rare tumors predominantly found in children. Given the high frequency of the germline R337H mutation in the TP53 gene in southern Brazil, we have evaluated the frequency of the R337H mutation in families with CPC in children. METHODOLOGY/PRINCIPAL FINDINGS: The present series included 29 patients that were admitted to the same institution from 1992 to 2010, including 22 children with CPC (0.08-13.6 years of age at diagnosis) and 7 children with papilloma of the choroid plexus (Pp; 0.5-9.8 years of age). Surgical resection was possible in 28 children. Blood and/or tumor DNA was extracted and analyzed using PCR-RFLP and results were confirmed by sequencing 240 bp of the TP53 exon 10. The patients, all parents, and some relatives submitted samples for blood DNA analysis. In addition, we have also examined the presence of the mutation in DNA from paraffin-embedded tumor samples to evaluate loss of heterozygosity. We found 63.3% (14/22) of the CPC patients positive for the germline R337H mutation; CPC samples were either heterozygous (n = 7), lost only the wild-type (n = 4), or only the R337H copy (n = 2). One CPC sample was not available. All Pp cases (7/7, 100%) were negative for R337H. Cure (>5 years survival free of disease) was observed in 18.1% of the CPC cases with the R337H mutation (2/11), 71.4% of the Pp (5/7), and 25% of CPC cases negative for the R337H mutation (2/8). Family history of cancer (with 2 or more cancer cases) was exclusively identified on the parental side segregating the R337H mutation, and 50% (7/14) of them were compatible with Li-Fraumeni-like syndrome. SIGNIFICANCE: Our results show for the first time that the R337H TP53 mutation is responsible for 63% of the CPC cases in children, suggesting a higher incidence of CPC in southern Brazil

Reduced durability of hybrid immunity to SARS-CoV-2 in immunocompromised children

BackgroundIn endemic COVID-19, immunocompromised children are vulnerable until vaccinated but the optimal primary vaccination regime and need for booster doses remains uncertain.MethodsWe recruited 19 immunocompromised children (post-solid organ transplantation, have autoimmune disease or were on current or recent chemotherapy for acute lymphoblastic leukemia), and followed them from the start of primary vaccination with BNT162b2 mRNA SARS-CoV-2 until 1-year post-vaccination. We investigated the quality of vaccine immunogenicity, and longevity of hybrid immunity, in comparison to healthy children.ResultsImmunocompromised children failed to produce T cell and memory B cell (MBC) responses reaching thresholds of protection after 2 doses; a third dose however improved both responses. Initially robust hybrid immunity demonstrated significantly more decline in T cell and MBC responses in immunocompromised compared to healthy children, to levels below the protective threshold by month 12.DiscussionImmunocompromised children may benefit from a 3-dose primary vaccination regime, with yearly or twice-yearly booster doses for sustained immunity

Experimental characterisation on the behaviour of PLLA for stretch blowing moulding of bioresorbable vascular scaffolds

Processing tubes from poly (l-lactic acid) (PLLA) by stretch blow moulding (SBM) is used in the manufacture of bioresorbable vascular scaffolds (BVS) to improve their mechanical performance. To better understand this processing technique, a novel experimental setup by free stretch blow inside a water bath was developed to visualise the tube forming process and analyse the deformation behaviour. PLLA tubes were heated, stretched and blown with no mould present inside a temperature-controlled water bath whilst recording the processing parameters (axial force, inflation pressure). The onset of pressure activation relative to the axial stretch was controlled deliberately to produce a simultaneous (SIM) or sequential (SEQ) mode of deformation. Real-time images of the tube during forming were captured using high speed cameras and the surface strain of the patterned tube was extracted using digital image correlation (DIC). The deformation characteristics of PLLA tubes in SBM was quantified by analysis of shape evolution, strain history and stress-strain relationship

Granzyme B Cleaves Decorin, Biglycan and Soluble Betaglycan, Releasing Active Transforming Growth Factor-β1

Objective: Granzyme B (GrB) is a pro-apoptotic serine protease that contributes to immune-mediated target cell apoptosis. However, during inflammation, GrB accumulates in the extracellular space, retains its activity, and is capable of cleaving extracellular matrix (ECM) proteins. Recent studies have implicated a pathogenic extracellular role for GrB in cardiovascular disease, yet the pathophysiological consequences of extracellular GrB activity remain largely unknown. The objective of this study was to identify proteoglycan (PG) substrates of GrB and examine the ability of GrB to release PG-sequestered TGF-b1 into the extracellular milieu. Methods/Results: Three extracellular GrB PG substrates were identified; decorin, biglycan and betaglycan. As all of these PGs sequester active TGF-b1, cytokine release assays were conducted to establish if GrB-mediated PG cleavage induced TGF-b1 release. Our data confirmed that GrB liberated TGF-b1 from all three substrates as well as from endogenous ECM and this process was inhibited by the GrB inhibitor 3,4-dichloroisocoumarin. The released TGF-b1 retained its activity as indicated by the induction of SMAD-3 phosphorylation in human coronary artery smooth muscle cells. Conclusion: In addition to contributing to ECM degradation and the loss of tissue structural integrity in vivo, increase

RAFI replication: easier done than said?

This is a post-peer-review, pre-copyedit version of an article published in The Journal of Asset Management. The definitive publisher-authenticated version Glabadanidis, Paskalis Teodoros; Obaydin, Ivan; Zurbruegg, Ralf, RAFI replication: easier done than said?, The Journal of Asset Management, 2012; 13(3):210-225 is available online at: dx.doi.org/10.1057/jam.2012.7We investigate whether adding fundamental indices to a portfolio provides increased diversification benefits. Our results show that equity investors who care only about portfolio mean and variance will benefit from including a fundamental index in their portfolios. This benefit is especially pronounced during periods of average stock market volatility. We also find that investors can construct a do-it-yourself buy-and-hold replicating portfolio that frequently outperforms the Research Affiliates Fundamental Index®(RAFI®), exchange traded fund out-of-sample.Paskalis Glabadanidis, Ivan Obaydin, Ralf Zurbrueg