Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Prendersi cura: la relazione terapeutica e la comunicazione medico-paziente

La cura secondo il modello bio-psico sociale. La comunicazione medico-pazient

Stellar Occultations by Large TNOs on 2012: The February 3rd by (208996) 2003 AZ84, and the February 17th by (50000) Quaoar

International audienceOn February 2012, two stellar occultation's by large Trans-neptunian Objects (TNO's) were observed by our group. On the 3rd, an event by (208996) 2003 AZ84 was recorded from Mont Abu Observatory and IUCAA Girawali Observatory in India and from Weizmann Observatory in Israel. On the 17th, a stellar occultation by (50000) Quaoar was observed from south France and Switzerland. Both occultations are the second observed by our group for each object, and will be used to improve the results obtained on the previous events. The occultation by 2003 AZ84 is the first multi-chord event recorded for this object. From the single chord event on January 8th 2011, Braga-Ribas et al. 2011 obtained a lower limit of 573 /- 21 km. From the 2012 occultation the longest chord has a size of 662 /- 50 km. The other chords will permit to determine the size and shape of the TNO, and derive other physical parameters, such as the geometric albedo. The Quaoar occultation was observed from south of France (Observatoire de la Côte d'Azur, TAROT telescope and Valensole) and from Gnosca, Switzerland. Unfortunately, all three sites in France are almost at the same Quaoar's latitude, so in practice, we have two chords that can be used to fit Quaoar's limb. The resulting fit will be compared with the results obtained by Braga-Ribas et al. 2011. Braga-Ribas F., Sicardy B., et al. 2011, EPSC-DPS2011, 1060.Ribas F., Sicardy B., et al. 2011, EPSC-DPS2011, 1060

Stellar Occultations by Large TNOs on 2012: The February 3rd by (208996) 2003 AZ84, and the February 17th by (50000) Quaoar

International audienceOn February 2012, two stellar occultation's by large Trans-neptunian Objects (TNO's) were observed by our group. On the 3rd, an event by (208996) 2003 AZ84 was recorded from Mont Abu Observatory and IUCAA Girawali Observatory in India and from Weizmann Observatory in Israel. On the 17th, a stellar occultation by (50000) Quaoar was observed from south France and Switzerland. Both occultations are the second observed by our group for each object, and will be used to improve the results obtained on the previous events. The occultation by 2003 AZ84 is the first multi-chord event recorded for this object. From the single chord event on January 8th 2011, Braga-Ribas et al. 2011 obtained a lower limit of 573 /- 21 km. From the 2012 occultation the longest chord has a size of 662 /- 50 km. The other chords will permit to determine the size and shape of the TNO, and derive other physical parameters, such as the geometric albedo. The Quaoar occultation was observed from south of France (Observatoire de la Côte d'Azur, TAROT telescope and Valensole) and from Gnosca, Switzerland. Unfortunately, all three sites in France are almost at the same Quaoar's latitude, so in practice, we have two chords that can be used to fit Quaoar's limb. The resulting fit will be compared with the results obtained by Braga-Ribas et al. 2011. Braga-Ribas F., Sicardy B., et al. 2011, EPSC-DPS2011, 1060.Ribas F., Sicardy B., et al. 2011, EPSC-DPS2011, 1060

Physical models of ten asteroids from an observers' collaboration network

International audienceAims:We present physical models of ten asteroids obtained by means of lightcurve inversion. A substantial part of the photometric data was observed by amateur astronomers. We emphasize the importance of a coordinated network of observers that will be of extreme importance for future all-sky asteroid photometric surveys. Methods: The lightcurve inversion method was used to derive spin states and shape models of the asteroids. Results: We derived spin states and shape model for ten new asteroids: (110) Lydia, (125) Liberatrix, (130) Elektra, (165) Loreley, (196) Philomela, (218) Bianca, (306) Unitas, (423) Diotima, (776) Berbericia, and (944) Hidalgo. This increases the number of asteroid models up to nearly one hundred

2003 AZ84: Size, shape, albedo and first detection of topographic features

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2003 AZ84: Size, shape, albedo and first detection of topographic features

We analyze two multi-chord stellar occultations by the Trans-Neptunian Object (TNO) 2003 AZ84 observed on February 3, 2012 and November 15, 2014.They provide different elliptical limb fits that are consistent to within their respective error bars, but could also suggest a possible precession of the object (assumed here to be a Maclaurin spheroid). The derived equatorial radius and oblateness are R[SUB]e[/SUB] = 393 ± 7 km and ɛ = 0.057 in 2014 and R[SUB]e[/SUB] = 414 ± 13 km and ɛ = 0.165 in 2012, respectively. Those results are consistent with single-chord events observed in January 2011 and December 2013. The figures above provide geometric visual albedos of p[SUB]V(2014)[/SUB] = 0.112 ± 0.008 and p[SUB]V(2012)[/SUB] = 0.114 ± 0.020. Using the Maclaurin assumption, combined with possible rotational periods of 6.67 h and 10.56 h, we estimate density upper limits of 1.89 ± 0.16g/cm[SUP]3[/SUP] and 0.77 ± 0.07g/cm[SUP]3[/SUP] for the two dates, respectively.The 2014 event provides (for the first time during a TNO occultation) a grazing chord with a gradual disappearance of the star behind 2003[SUB]AZ[/SUB]84's limb that lasts for more than 10 seconds. We rule out the possibility of a localized dust concentration as it would imply very high optical depth for that cloud. We favor a local topographic feature (chasm) with minimum width and depth of 22 ± 2.5 km and 7 ± 2.0 km, respectively. Features with similar depths are in fact observed on Pluto's main satellite, Charon, which has a radius of about 605 km, comparable to that of 2003[SUB]AZ[/SUB]84

2003 AZ84: Size, shape, albedo and first detection of topographic features

International audienc