Repair of erosions in rheumatoid arthritis does occur. Results from 2 studies by the OMERACT Subcommittee on Healing of Erosions

The committee was charged with determining whether healing of erosions in rheumatoid arthritis (RA) occurs. Two exercises were performed: The first asked the committee members, as a panel of experts, to express agreement or disagreement with the presence of improvement and features of bone reaction to injury in images submitted by members as examples of healing. The second presented panel members with 28 pairs of serial images, 14 chosen to illustrate progression and 14 chosen to illustrate repair. Agreement was tested on 8 items: global judgment on which image in the pair was better, relative size of the erosion in the 2 images, judgment on which image was first, presence and extent of sclerosis, cortication, filling-in, remodeling, and reconstituting normal structure. Our results showed good agreement, among the 15 respondents, on global assessment of which image was better and which image showed the smaller erosion. Correct assignment of sequence was only slightly better than expected by chance (in 65% of the cases). Agreement was poor regarding the presence of morphologic features of bone repair. A majority of a panel of experts agreed on which 2nd images in a set of paired, serial images represented improvement and which showed progression based on global assessment of which was better and on size of erosion. Features of bone repair were not distinctive and did not enable the panel to deduce the correct sequence of the serial images. This study provides evidence that repair of bone damage in RA does occur, resulting in some degree of improvement, which was recognized by a majority of a panel of experts.     

Recommendations for reporting morbid events after heart valve surgery

Major reasons for the considerable heterogeneity among published results of heart valve surgery are inconsistency in follow up techniques, reporting systems and classification of adverse events. The present recommendations are intended to harmonize the presentation of clinical material in order to improve comparison of data from different sources for the analysis of pooled data. The quality of an observational study is largely, if not entirely, due to the follow up technique, which may be graded according to six categories: Self-reporting of adverse events/well-being by the patients may be classified 'excellent'; if the information is gathered and re-checked at short-term intervals. Data obtained from in-hospital or outpatient examinations by qualified examiners at least twice a year or other personal contact through qualified examiners may be regarded as 'sufficient', if the results are re-checked by contacting the treating home physician. All other follow up techniques may be regarded as inappropriate. Consequences of complications are entirely dependent on severity and possible sequelae. It is therefore recommended to grade any reported complication according to its severity by utilizing a score system. Embolisms are best categorized by utilizing the performance status scale. Bleeding events may be categorized according to severity as fatal, major (requiring hospital transmission with transfusion, surgery or with permanently increased disability) or minor (not requiring hospital admission, surgery or transfusion). In some cases it will remain unclear whether an event was primarily embolic or hemorrhagic. These complications should be summarized as 'not categorized'. The reporting of morbid events due to thrombosis, embolism and bleeding should go along with information regarding the quality of antithrombotic management.     

Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles

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Non‐clinical safety evaluation of single and repeated intramuscular administrations of MAGE‐A3 Cancer Immunotherapeutic in rabbits and cynomolgus monkeys

The MAGE‐A3 recombinant protein combined with AS15 immunostimulant (MAGE‐A3 Cancer Immunotherapeutic) is under development by GlaxoSmithKline for the treatment of lung cancer and melanoma. We performed non‐clinical safety studies evaluating potential local and systemic toxic effects induced by MAGE‐A3 Cancer Immunotherapeutic in rabbits (study 1) and cynomolgus monkeys (study 2). Animals were allocated to two groups to receive a single (rabbits) or 25 repeated (every 2 weeks) injections (monkeys) of MAGE‐A3 Cancer Immunotherapeutic (treatment groups) or saline (control groups). All rabbits were sacrificed 3 days post‐injection and monkeys 3 days following last injection (3/5 per gender per group) or after a 3‐month treatment‐free period (2/5 per gender per group). Local and systemic reactions and MAGE‐A3‐specific immune responses (monkeys) were assessed. Macroscopic and microscopic (for rabbits, injection site only) post‐mortem examinations were performed on all animals. No systemic toxicity or unscheduled mortalities were recorded. Single (rabbits) and repeated (monkeys; up to four times at the same site) injections were well tolerated. Following five to seven repeated injections, limb circumferences increased up to 26% (5 h post‐injection), but returned to normal after 1–8 days. Three days after the last injection, enlargements of iliac, popliteal, axillary and inguinal lymph nodes, and increased incidence or severity of mononuclear inflammatory cell infiltrates was observed in injected muscles of treated monkeys. No treatment‐related macroscopic findings were recorded after the treatment‐free period. MAGE‐A3‐specific antibody and T‐cell responses were raised in all treated monkeys, confirming test item exposure. Single or repeated intramuscular injections of MAGE‐A3 Cancer Immunotherapeutic were well tolerated in rabbits and monkeys. Copyright © 2014 GlaxoSmithKline Vaccines. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.     

Post-exposure prophylaxis after occupational and non-occupational exposures to HIV: an overview of the policies implemented in 27 European countries

The aim of this survey, which was part of an English-French project supported by the Commission of the European Communities, was to compare access to HIV post-exposure prophylaxis (PEP) in the occupational and non-occupational contexts in 27 European countries. A protocol was designed in May 1998 in collaboration with all country consultants. Data were collected at country level by each consultant through interviews, review of local and national recommendations and results of national or local surveys. The final comparative analysis was carried out from the individual country reports and a review of the literature. The large majority of European countries have detailed procedures regarding occupational PEP: 20/27 have produced national guidelines, three have adopted the US CDC recommendations and only four have no official recommendations. Although no standard protocol exists, the more common one is a four-week implementation of a triple combination therapy. In the context of non-occupational exposure to HIV, only five countries have guidelines with specific recommendations and one country has adopted the CDC recommendations. In the majority of cases (13 countries), PEP is never recommended but is only available in a few circumstances, sometimes with major limitations. In the last eight countries, such PEP is not currently available. Although the estimations of HIV transmission risks in occupational and non-occupational contexts are really comparables, easy access to PEP after accidental sexual or blood exposures is not guaranteed for the general population in the majority of European countries.