Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5?mg/kg i.v. 3 weekly for 1?year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56?years (range 18-88?years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5?years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P?=?0.78). At 5?years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P?=?0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P?=?0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P?=?0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P?=?0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64

Experimental performance analysis of wireless links for healthcare applications

Wireless networking is currently being deployed for various applications. However, the application of wireless networking in healthcare remains a challenge mainly because of security and reliability concerns. This paper presents experimental results of performance analysis of a wireless network for healthcare application in the City of Blantyre. The results show that the use of wireless networking in healthcare application will be limited by packet loss, delay and jitter when the number of hops involved in the transmission of information is large. Nevertheless, deployment of wireless networking for healthcare applications is viable when the number of hops a packet has to transverse is small

Prognostic Value of Preprocedural LV Global Longitudinal Strain for Post-TAVR-Related Morbidity and Mortality: A Meta-Analysis.

BACKGROUND: Left ventricular ejection fraction (LVEF) demonstrates limited prognostic value for post-transcatheter aortic valve replacement (TAVR) outcomes. Evidence regarding the potential role of left ventricular global longitudinal strain (LV-GLS) in this setting is inconsistent. OBJECTIVES: The aim of this systematic review and meta-analysis of aggregated data was to evaluate the prognostic value of preprocedural LV-GLS for post-TAVR-related morbidity and mortality. METHODS: The authors searched PubMed, Embase, and Web of Science for studies investigating the association between preprocedural 2-dimensional speckle-tracking-derived LV-GLS and post-TAVR clinical outcomes. An inversely weighted random effects meta-analysis was adopted to investigate the association between LV-GLS vs primary (ie, all-cause mortality) and secondary (ie, major cardiovascular events [MACE]) post-TAVR outcomes. RESULTS: Of the 1,130 identified records, 12 were eligible, all of which had a low-to-moderate risk of bias (Newcastle-Ottawa scale). On average, 2,049 patients demonstrated preserved LVEF (52.6% ± 1.7%), but impaired LV-GLS (-13.6% ± 0.6%). Patients with a lower LV-GLS had a higher all-cause mortality (pooled HR: 2.01; 95% CI: 1.59-2.55) and MACE (pooled odds ratio [OR]: 1.26; 95% CI: 1.08-1.47) risk compared with patients with higher LV-GLS. In addition, each percentage point decrease of LV-GLS (ie, toward 0%) was associated with an increased mortality (HR: 1.06; 95% CI: 1.04-1.08) and MACE risk (OR: 1.08; 95% CI: 1.01-1.15). CONCLUSIONS: Preprocedural LV-GLS was significantly associated with post-TAVR morbidity and mortality. This suggests a potential clinically important role of pre-TAVR evaluation of LV-GLS for risk stratification of patients with severe aortic stenosis. (Prognostic value of left ventricular global longitudinal strain in patients with aortic stenosis undergoing Transcatheter Aortic Valve Implantation: a meta-analysis; CRD42021289626)

The declining quality of late-Holocene ombrotrophic communities and the loss of Sphagnum austinii (Sull. ex Aust.) on raised bogs in Wales

The modern floristic composition of the principal raised bogs of Wales is significantly altered compared with their histories of development from the early to mid Holocene. This paper uses pollen and plant macrofossil records from two raised bogs together with previously published data from a further two sites to explore the key factors contributing to the present condition of Welsh ombrotrophic plant communities. Results show Betula and Molinia invasion is a recent feature of bog development in Wales. Previous Holocene 'dry-phases' were characterized by Ericaceae and Pinus establishment, supporting recent experimental evidence that Betula and Molinia encroachment is primarily a response to nitrogen (N) loading rather than desiccation on intact bogs. Several of the bogs featured in this study also show severe signs of structural damage, not only from peat cutting but, in the case of Cors Caron, from channel processes in the adjacent River Teifi. Radiocarbon dating and inter-site comparisons of peat accumulation rates show that Rhos Goch Common in particular has been heavily impacted by peripheral peat cutting, leading to dewatering, significant subsidence of its peat dome and the spread of hummock and high dry ridge communities. Finally, the decline and local extinction of Sphagnum austinii in bogs across Europe represents one of the most significant changes in ombrotrophic community composition in the late Holocene. Co-registered pollen and macrofossil evidence from Cors Caron demonstrates that increases in landuse intensity over the last 2000 years are temporally associated with reductions in the abundance of S. austinii and ultimately its local disappearance from the palaeoecological record