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- Fung, P. P. L., et al.
(author)
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Time to onset of bisphosphonate-related osteonecrosis of the jaws : a multicentre retrospective cohort study
- 2017
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In: Oral Diseases. - : WILEY. - 1354-523X .- 1601-0825. ; 23:4, s. 477-483
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Journal article (peer-reviewed)abstract
- Objectives: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients.Subjects and Methods: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012.Results: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n=88) and 2.2years in those treated with zoledronate (n=218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate.Conclusions: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.
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- Mesal, D., et al.
(author)
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Exploring the R CrA environment with SPHERE Discovery of a new stellar companion
- 2019
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 624
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Journal article (peer-reviewed)abstract
- Aims. R Coronae Australis (R CrA) is the brightest star of the Coronet nebula of the Corona Australis (CrA) star forming region. This star is very red in color, probably due to dust absorption, and is strongly variable. High-contrast instruments allow for an unprecedented direct exploration of the immediate circumstellar environment of this star. Methods. We observed R CrA with the near-infrared (NIR) channels (IFS and IRDIS) of SPHERE at the Very Large Telescope (VET). In this paper, we used four different epochs, three of which are from open time observations while one is from SPHERE guaranteed time. The data were reduced using the data reduction and handling pipeline and the SPHERE Data Center. We implemented custom IDL routines on the reduced data with the aim to subtract the speckle halo. We have also obtained pupil-tracking H-band (1.45-1.85 mu m) observations with the VLT/SINFONI NIR medium-resolution (R similar to 3000) spectrograph. Results. A companion was found at a separation of 0.156 '' from the star in the first epoch and increasing to 0.184 '' in the final epoch. Furthermore, several extended structures were found around the star, the most noteworthy of which is a very bright jet-like structure northeast from the star. The astrometric measurements of the companion in the four epochs confirm that it is gravitationally bound to the star. The SPHERE photometry and SINFONI spectrum, once corrected for extinction, point toward a spectral type object that is early M with a mass between 0.3 and 0.55 M-circle dot. The astrometric analyis provides constraints on the orbit paramenters: e similar to 0.4, semimajor axis at 27-28 au, inclination of similar to 70 degrees, and a period larger than 30 yr. We were also able to put constraints of few M (jup) on the mass of possible other companions down to separations of few tens of au.
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- Farmakis, D., et al.
(author)
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Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper
- 2016
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 222, s. 303-312
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Journal article (peer-reviewed)abstract
- Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps. © 2016 The Authors
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- S, Bouchez, et al.
(author)
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Levosimendan in Acute and Advanced Heart Failure: an Expert Perspective on Posology and Therapeutic Application.
- 2018
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In: Cardiovascular drugs and therapy. - : Springer Science and Business Media LLC. - 1573-7241 .- 0920-3206. ; 32:6, s. 617-624
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Journal article (peer-reviewed)abstract
- Levosimendan, a calcium sensitizer and potassium channel-opener, is widely appreciated by many specialist heart failure practitioners for its effects on systemic and pulmonary hemodynamics and for the relief of symptoms of acute heart failure. The drug's impact on mortality in large randomized controlled trials has been inconsistent or inconclusive but, in contrast to conventional inotropes, there have been no indications of worsened survival and some signals of improved heart failure-related quality of life. For this reason, levosimendan has been proposed as a safer inodilator option than traditional agents in settings, such as advanced heart failure. Positive effects of levosimendan on renal function have also been described. At the HEART FAILURE 2018 congress of the Heart Failure Association of the European Society of Cardiology, safe and effective use levosimendan in acute and advanced heart failure was examined in a series of expert tutorials. The proceedings of those tutorials are summarized in this review, with special reference to advanced heart failure and heart failure with concomitant renal dysfunction. Meta-analysis of clinical trials data is supportive of a renal-protective effect of levosimendan, while physiological observations suggest that this effect is exerted at least in part via organ-specific effects that may include selective vasodilation of glomerular afferent arterioles and increased renal blood flow, with no compromise of renal oxygenation. These lines of evidence require further investigation and their clinical significance needs to be evaluated in specifically designed prospective trials.
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- Calcagno, A., et al.
(author)
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Cerebrospinal fluid abacavir concentrations in HIV-positive patients following once-daily administration
- 2018
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In: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251. ; 84:6, s. 1380-1383
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Journal article (peer-reviewed)abstract
- Abacavir is a widely used nucleotide reverse transcriptase inhibitor, for which cerebrospinal fluid (CSF) exposure has been previously assessed in twice-daily recipients. We studied abacavir CSF concentrations in 61 and nine HIV-positive patients taking abacavir once daily and twice daily, respectively. Patients on once-daily abacavir had higher plasma and CSF concentrations (96 vs. 22ngml(-1), P = 0.038 and 123 vs. 49ngml(-1), P=0.038) but similar CSF-to-plasma ratios (0.8 vs. 0.5, P=0.500). CSF abacavir concentrations were adequate in patients receiving once-daily treatment.
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- Nieminen, Markku S., et al.
(author)
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The patient perspective : Quality of life in advanced heart failure with frequent hospitalisations
- 2015
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 191, s. 256-264
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Research review (peer-reviewed)abstract
- End of life is an unfortunate but inevitable phase of the heart failure patients' journey. It is often preceded by a stage in the progression of heart failure defined as advanced heart failure, and characterised by poor quality of life and frequent hospitalisations. In clinical practice, the efficacy of treatments for advanced heart failure is often assessed by parameters such as clinical status, haemodynamics, neurohormonal status, and echo/MRI indices. From the patients' perspective, however, quality-of-life-related parameters, such as functional capacity, exercise performance, psychological status, and frequency of re-hospitalisations, are more significant. The effects of therapies and interventions on these parameters are, however, underrepresented in clinical trials targeted to assess advanced heart failure treatment efficacy, and data are overall scarce. This is possibly due to a non-universal definition of the quality-of-life-related endpoints, and to the difficult standardisation of the data collection. These uncertainties also lead to difficulties in handling trade-off decisions between quality of life and survival by patients, families and healthcare providers. A panel of 34 experts in the field of cardiology and intensive cardiac care from 21 countries around the world convened for reviewing the existing data on quality-of-life in patients with advanced heart failure, discussing and reaching a consensus on the validity and significance of quality-of-life assessment methods. Gaps in routine care and research, which should be addressed, were identified. Finally, published data on the effects of current i.v. vasoactive therapies such as inotropes, inodilators, and vasodilators on quality-of-life in advanced heart failure patients were analysed.
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