Health and budget impact of combined HIV prevention : first results of the BELHIVPREV model

Objectives: We developed a pragmatic modelling approach to estimate the impact of treatment as prevention (TasP); outreach testing strategies; and pre-exposure prophylaxis (PrEP) on the epidemiology of HIV and its associated pharmaceutical expenses. Methods: Our model estimates the incremental health (in terms of new HIV diagnoses) and budget impact of two prevention scenarios (outreach+TasP and outreach+TasP+PrEP) against a 'no additional prevention' scenario. Model parameters were estimated from reported Belgian epidemiology and literature data. The analysis was performed from a healthcare payer perspective with a 15-year-time horizon. It considers subpopulation differences, HIV infections diagnosed in Belgium having occurred prior to migration, and the effects of an ageing HIV population. Results: Without additional prevention measures, the annual number of new HIV diagnoses rises to over 1350 new diagnoses in 2030 as compared to baseline, resulting in a budget expenditure of (sic)260.5 million. Implementation of outreach+TasP and outreach+TasP+PrEP results in a decrease in the number of new HIV diagnoses to 865 and 663 per year, respectively. Respective budget impacts decrease by (sic)20.6 million and (sic)33.7 million. Conclusion: Foregoing additional investments in prevention is not an option. An approach combining TasP, outreach and PrEP is most effective in reducing the number of new HIV diagnoses and the HIV treatment budget. Our model is the first pragmatic HIV model in Belgium estimating the consequences of a combined preventive approach on the HIV epidemiology and its economic burden assuming other prevention efforts such as condom use and harm reduction strategies remain the same

Increasing the density of nanomedicines improves their ultrasound-mediated delivery to tumours

AbstractNanomedicines have provided fresh impetus in the fight against cancer due to their selectivity and power. However, these agents are limited when delivered intravenously due to their rapid clearance from the bloodstream and poor passage from the bloodstream into target tumours. Here we describe a novel stealthing strategy which addresses both these limitations and thereby demonstrate that both the passive and mechanically-mediated tumour accumulation of the model nanomedicine adenovirus (Ad) can be substantially enhanced. In our strategy gold nanoparticles were thoroughly modified with 2kDa polyethyleneglycol (PEG) and then linked to Ad via a single reduction-cleavable 5kDa PEG. The resulting Ad–gold–PEG construct was compared to non-modified Ad or conventionally stealthed Ad–poly[N-(2-hydroxypropyl)methacrylamide] (Ad–PHPMA). Notably, although Ad–gold–PEG was of similar size and surface charge to Ad–PHPMA the increase in density, resulting from the inclusion of the gold nanoparticles, provided a substantial enhancement of ultrasound-mediated transport. In an in vitro tumour mimicking phantom, the level and distance of Ad–gold–PEG transport was shown to be substantially greater than achieved with Ad–PHPMA. In in vivo studies 0.1% of an unmodified Ad dose was shown to accumulate in tumours, whereas over 12% of the injected dose was recovered from the tumours of mice treated with Ad–gold–PEG and ultrasound. Ultimately, a significant increase in anti-tumour efficacy resulted from this strategy. This stealthing and density-increasing technology could ultimately enhance clinical utility of intravenously delivered nanoscale medicines including viruses, liposomes and antibodies

Omics-directed Reverse Genetics Enables the Creation of New Productivity Traits for the Vegetable Oil Crop Canola

Bayer CropScience is a leader in the oilseed rape seeds business with a 2013 market share of 50% in Canada, based on the creation and use of a unique hybridization system enabling the development of high-yielding canola (B.napus) InVigor® hybrids. For the European markets, Bayer is developing non-transgenic hybrids that will be complemented with differentiating traits. To this end, a highly effective mutagenesis-based and omics-directed reverse genetics platform was established which enables the creation of novel productivity traits in canola.The reverse genetics process involves three major steps described in the following figure.The selection of relevant homoeologs is facilitated by Bayer's B.napus genome sequence and transcript atlas. The genome sequence allows the in silico identification of functional homoeologs and the transcript atlas enables to prioritize on homoeologs that are highly expressed in the right tissues. A new trait is created by stacking relevant mutant alleles in a single line. Bayer CropScience is using its canola reverse genetics platform to improve certain canola characteristics including pod shattering, grain yield and oil composition and to develop traits such as herbicide tolerance. Pod shatter reduction was the first trait developed with the platform. A first pod shatter-reduced InVigor hybrid, L140P, was commercially grown in Canada during the 2014 summer season. Bayer CropScience has established and is successfully using a this biotech-based platform for the improvement of the productivity of canola. The resulting traits do not require regulation and can be deployed in all continents. The major limitation of reverse genetics is that the scope of modification is limited to the crops’ own gene content and the expression levels of these genes

European registry of type A aortic dissection (ERTAAD) - rationale, design and definition criteria

Correction: Volume16 Issue1 Article Number225 DOI10.1186/s13019-021-01606-8Background: Acute Stanford type A aortic dissection (TAAD) is a life-threatening condition. Surgery is usually performed as a salvage procedure and is associated with significant postoperative early mortality and morbidity. Understanding the patient's conditions and treatment strategies which are associated with these adverse events is essential for an appropriate management of acute TAAD. Methods: Nineteen centers of cardiac surgery from seven European countries have collaborated to create a multicentre observational registry (ERTAAD), which will enroll consecutive patients who underwent surgery for acute TAAD from January 2005 to March 2021. Analysis of the impact of patient's comorbidities, conditions at referral, surgical strategies and perioperative treatment on the early and late adverse events will be performed. The investigators have developed a classification of the urgency of the procedure based on the severity of preoperative hemodynamic conditions and malperfusion secondary to acute TAAD. The primary clinical outcomes will be in-hospital mortality, late mortality and reoperations on the aorta. Secondary outcomes will be stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. Discussion: The analysis of this multicentre registry will allow conclusive results on the prognostic importance of critical preoperative conditions and the value of different treatment strategies to reduce the risk of early adverse events after surgery for acute TAAD. This registry is expected to provide insights into the long-term durability of different strategies of surgical repair for TAAD.Peer reviewe