Publications

Inhaled corticosteroids are recognized as the most effective anti-inflammatory therapy in patients with asthma and their early introduction is recommended by national and international guidelines. Concerns have been raised about potential adverse effects of inhaled corticosteroids on bones and growth, as these appear to be more important clinically than effects on the hypothalamic-pituitary-adrenal axis, which are more commonly measured. This review examines the effects of inhaled corticosteroids on biochemical bone markers, bone density and growth in adults and children with asthma, in view of the recent availability of a substantial amount of new clinical trial data. Examination of relevant retrospective and prospective data, involving 11 studies (1,240 patients) on biochemical bone markers and 14 studies (373 patients) on bone density over a wide dose range, have largely indicated no significant or clinically important effect on these measurements in adults or children with asthma. Markers of bone formation and resorption need to be measured concurrently for a reliable assessment of bone turnover to be made. Knemometry, measuring lower leg growth rate, is a sensitive technique for comparing the systemic activity of different inhaled corticosteroids, but does not relate to long-term growth. The majority of approximately 40 studies on inhaled corticosteroids and statural growth in children, over a wide recommended dose range, including a number of recent long-term, prospective studies, demonstrate little or no effect. Children taking above recommended doses of inhaled corticosteroids should have their growth monitored using stadiometry at least every 6 months by trained personnel. Most of the areas reviewed, particularly the relatively new areas of biochemical bone markers and bone density, require further properly controlled, long-term, prospective investigation, although the long-term value of bone markers appears limited. In summary, the data as it currently stands, suggests that doses of inhaled corticosteroids up to 1,000 microg x day(-1) in adults and 400 microg x day(-1) in children have no significant effect on bones and growth in the large majority of patients with asthma.

Down through history, plagues, including very terrible ones, have struck societies at various times. This article considers plagues throughout history and some Christian responses,

Background— Some but not all studies have reported reduced rates of stent thrombosis (ST) with everolimus-eluting stents (EES) compared with other drug-eluting stents (DES). All of these studies were insufficiently powered to reliably detect differences in ST. We therefore performed a meta-analysis of randomized controlled trials comparing the risk of 2-year definite ST between EES and other DES. Methods and Results— Randomized controlled trials comparing EES versus other DES were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. Information on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. Eleven randomized controlled trials (16 775 patients) were analyzed, including 5 trials (n=7113) of EES versus paclitaxel-eluting stents, 5 trials (n=7370) of EES versus sirolimus-eluting stents, and 1 trial (n=2292) of EES versus zotarolimus-eluting stents. By 2 years definite ST with EES compared with pooled DES occurred in 0.5% versus 1.3% patients, respectively (relative risk, 0.38; 95% CI, 0.24–0.59; P <0.0001). Similar results were observed when the broader definition of definite/probable ST was considered (relative risk, 0.46; 95% CI, 0.33–0.66; P <0.0001). EES compared with other DES reduced the relative risk of early ST (within 30 days), late ST (31 days to 1 year), cumulative 1-year ST, and very late ST (1–2 years). The reduced rate of definite ST observed with EES was consistent across all DES comparators with no interactions apparent during any time interval. Conclusions— EES compared with a pooled group of paclitaxel-eluting stents, sirolimus-eluting stents, and zotarolimus-eluting stents is associated with a significant reduction of definite ST, an effect that appears early and increases in magnitude through at least 2 years.

No abstract is provided for this article.

This study aimed to validate a dedicated software for quantitative videodensitometric angiographic assessment of mitral regurgitation (QMR).Quantitative videodensitometric aortography of aortic regurgitation using the time-density principle is a well-documented technique, but the angiographic assessment of mitral regurgitation (MR) remains at best semi-quantitative and operator dependent.Fourteen sheep underwent surgical mitral valve replacement using 2 different prostheses. Pre-sacrifice left ventriculograms were used to assess MR fraction (MRF) using QMR and MR volume (MRV). In an independent core lab, the CAAS QMR 0.1 was used for QMR analysis. In vitro MRF and MRV were assessed in a mock circulation at a comparable cardiac output to the in vivo one by thermodilution. The correlations and agreements of in vitro and in vivo MRF, MRV, and interobserver reproducibility for QMR analysis were assessed using the averaged cardiac cycles (CCs).In vivo derived MRF by QMR strongly correlated with in vitro derived MRF, regardless of the number of the CCs analyzed (best correlation: 3 CCs y = 0.446 + 0.994x; R = 0.784; p =0.002). The mean absolute difference between in vitro derived MRF and in vivo derived MRF from 3 CCs was 0.01 ± 4.2% on Bland-Altman analysis. In vitro MRV and in vivo MRV from 3 CCs were very strongly correlated (y = 0.196 + 1.255x; R = 0.839; p < 0.001). The mean absolute difference between in vitro MRV and in vivo MRV from 3 CCs was -1.4 ± 1.9 ml. There were very strong correlations of in vivo MRF between 2 independent analysts, regardless of the number of the CCs.In vivo MRF using the novel software is feasible, accurate, and highly reproducible. These promising results have led us to initiate the first human feasibility study comprising patients undergoing percutaneous mitral valve edge-to-edge repair.

This expert opinion review offers a perspective on the future developments in drug-eluting stent design. Initial efforts were focused on reduction of in-stent restenosis, which the drug-eluting stents addressed effectively. Current concerns are predominantly with regard to risk of stent thrombosis and delayed endothelialization. All three components of the stent have been modified to achieve the goal of endothelialization and vessel healing: drug, polymer and the platform. We review different approaches to reduce this risk from design of different drug combinations, through less traumatic metallic stent platforms, via biodegradable polymers and, finally, fully biodegradable stents. It seems at this time that fully biodegradable solutions to stenting hold the greatest promise, but larger long-term studies are needed to evaluate fully their safety and efficacy in 'all-comer' patient populations. At the time of this review, design of a safe drug-eluting stent still remains a challenge.