Potential Future Impact of a Partially Effective HIV Vaccine in a Southern African Setting.

It is important for public health and within the HIV vaccine development field to understand the potential population level impact of an HIV vaccine of partial efficacy-both in preventing infection and in reducing viral load in vaccinated individuals who become infected-in the context of a realistic future implementation scenario in resource limited settings

Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Antisense oligonucleotides against hTR (As-ODN-hTR) have shown promising results as treatment strategies for various human malignancies. All-trans retinoic acid (ATRA) is a signalling molecule with important roles in differentiation and apoptosis. Biological responses to ATRA are currently used therapeutically in various human cancers. The aim of this study was to evaluate the anti-tumor effects of As-ODN-hTR combined with ATRA in vivo.</p> <p>Methods</p> <p>In situ human oral squamous cell carcinoma (OSCC) models were established by subcutaneous injection of Tca8113 cells. Mice were treated with sense oligonucleotides against hTR(S-ODN-hTR) alone, As-ODN-hTR alone, ATRA alone, As-ODN-hTR plus ATRA, or S-ODN-hTR plus ATRA. Tumor size and weight were assessed in the mice. Telomerase activity was detected by a TRAP assay, apoptotic cells were evaluated with a Tunel assay, the expression of apoptosis-related proteins (Bcl-2 and Bax) was evaluated by immunohistochemistry and ultrastructural morphological changes in the tumor specimen were examined.</p> <p>Results</p> <p>Both As-ODN-hTR and ATRA can significantly inhibit tumor growth in this OSCC xenograft solid-tumor model, and the combination of the two agents had a synergistic anti-tumorogenic effect. We also demonstrated that this anti-tumor effect correlated with inhibition of telomerase activity. Furthermore, significant increases in the number of apoptotic cells, typical apoptotic morphology and a downregulation of the anti-apoptotic protein, bcl-2 were observed in the treated tissues.</p> <p>Conclusion</p> <p>The combination of As-ODN-hTR and ATRA has a synergistic anti-tumor effect. This anti-tumor effect can be mainly attributed to apoptosis induced by a decrease in telomerase activity. Bcl-2 plays an important role in this process. Therefore, combining As-ODN-hTR and ATRA may be an approach for the treatment of human oral squamous cell carcinoma.</p

Eliciting health state utilities for Dupuytren's contracture using a discrete choice experiment

Background and purpose An internet-based discrete choice experiment (DCE) was conducted to elicit preferences for a wide range of Dupuytren’s contracture (DC)-related health states. An algorithm was subsequently developed to convert these preferences into health state utilities that can be used to assess DC’s impact on quality of life and the value of its treatments. Methods Health state preferences for varying levels of DC hand severity were elicited via an internet survey from a sample of the UK adult population. Severity levels were deined using a combination of contractures (0, 45, or 90 degrees) in 8 proximal interphalangeal and metacarpophalangeal joints of the index, middle, ring, and little ingers. Right-handed, left-handed, and ambidextrous respondents indicated which hand was preferable in each of the 10 randomly-selected hand-pairings comparing different DC severity levels. For consistency across comparisons, anatomically precise digital hand drawings were used. To anchor preferences onto the traditional 0–1 utility scale used in health economic evaluations, unaffected hands were assigned a utility of 1.0 whereas the utility for a maximally affected hand (i.e., all 8 joints set at 90 degrees of contracture) was derived by asking respondents to indicate what combination of attributes and levels of the EQ-5D-5L proile most accurately relects the impact of living with such hand. Conditional logistic models were used to estimate indirect utilities, then rescaled to the anchor points on the EQ-5D-5L. Results Estimated utilities based on the responses of 1,745 qualiied respondents were 0.49, 0.57, and 0.63 for completely affected dominant hands, non-dominant hands, or ambidextrous hands, respectively. Utility for a dominant hand with 90-degree contracture in t h e metacarpophalangeal joints of the ring and little ingers was estimated to be 0.89. Separately, reducing the contracture of metacarpophalangeal joint for a little inger from 50 to 12 degrees would improve utility by 0.02. Interpretation DC is associated with substantial utility decrements. The algorithms presented herein provide a robust and lexible framework to assess utility for varying degrees of DC severity

Conceptual Graphs Based Information Retrieval in HealthAgents

This paper focuses on the problem of representing, in a meaningful way, the knowledge involved in the HealthAgents project. Our work is motivated by the complexity of representing Electronic Health-care Records in a consistent manner. We present HADOM (HealthAgents Domain Ontology) which conceptualises the required HealthAgents information and propose describing the sources knowledge by the means of Conceptual Graphs (CGs). This allows to build upon the existing ontology permitting for modularity and °exibility. The novelty of our approach lies in the ease with which CGs can be placed above other formalisms and their potential for optimised querying and retrieval

Should the surgeon or the general practitioner (GP) follow up patients after surgery for colon cancer? A randomized controlled trial protocol focusing on quality of life, cost-effectiveness and serious clinical events

This trial has been registered at ClinicalTrials.gov. The trial registration number is: NCT00572143.© 2008 Augestad et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Influence of the length of hospitalisation in post-discharge outcomes in patients with acute heart failure: Results of the LOHRCA study

Objective: To investigate the relationship between length of hospitalisation (LOH) and post-discharge outcomes in acute heart failure (AHF) patients and to ascertain whether there are different patterns according to department of initial hospitalisation. Methods: Consecutive AHF patients hospitalised in 41 Spanish centres were grouped based on the LOH (15 days). Outcomes were defined as 90-day post-discharge all-cause mortality, AHF readmissions, and the combination of both. Hazard ratios (HRs), adjusted by chronic conditions and severity of decompensation, were calculated for groups with LOH >6 days vs. LOH <6 days (reference), and stratified by hospitalisation in cardiology, internal medicine, geriatrics, or short-stay units. Results: We included 8563 patients (mean age: 80 (SD = 10) years, 55.5% women), with a median LOH of 7 days (IQR 4–11): 2934 (34.3%) had a LOH 15 days. The 90-day post-discharge mortality was 11.4%, readmission 32.2%, and combined endpoint 37.4%. Mortality was increased by 36.5% (95%CI = 13.0–64.9) when LOH was 11–15 days, and by 72.0% (95%CI = 42.6–107.5) when >15 days. Conversely, no differences were found in readmission risk, and the combined endpoint only increased 21.6% (95%CI = 8.4–36.4) for LOH >15 days. Stratified analysis by hospitalisation departments rendered similar post-discharge outcomes, with all exhibiting increased mortality for LOH >15 days and no significant increments in readmission risk. Conclusions: Short hospitalisations are not associated with worse outcomes. While post-discharge readmissions are not affected by LOH, mortality risk increases as the LOH lengthens. These findings were similar across hospitalisation departments