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- Borisov, S, et al.
(författare)
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Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report
- 2019
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 54:6
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Tidskriftsartikel (refereegranskat)abstract
- The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.
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- Ardura-Fabregat, A., et al.
(författare)
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Targeting Neuroinflammation to Treat Alzheimer’s Disease
- 2017
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Ingår i: CNS Drugs. - : Springer Science and Business Media LLC. - 1172-7047 .- 1179-1934. ; 31:12, s. 1-26
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Forskningsöversikt (refereegranskat)abstract
- Over the past few decades, research on Alzheimer’s disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intra-neuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as danger-associated molecular patterns, that—upon engagement of pattern recognition receptors—induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on Neuroinflammation 2016, provides an overview of our current understanding of AD-related immune processes. We describe the principal cellular and molecular players in inflammation as they pertain to AD, examine modifying factors, and discuss potential future therapeutic targets.
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- Lange, C., et al.
(författare)
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Management of patients with multidrug-resistant tuberculosis
- 2019
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D). - 1027-3719 .- 1815-7920. ; 23:6, s. 645-662
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of multidrug-resistant tuberculosis (MDR-TB; defined as resistance to at least rifampicin and isoniazid) represents a growing threat to public health and economic growth. Never before in the history of mankind have more patients been affected by MDR-TB than is the case today. The World Health Organization reports that MDR-TB outcomes are poor despite staggeringly high management costs. Moreover, treatment is prolonged, adverse events are common, and the majority of affected patients do not receive adequate treatment. As MDR-TB strains are often resistant to one or more second-line anti-TB drugs, in-depth genotypic and phenotypic drug susceptibility testing is needed to construct personalised treatment regimens to improve treatment outcomes. For the first time in decades, the availability of novel drugs such as bedaquiline allow us to design potent and well-tolerated personalised MDR-TB treatment regimens based solely on oral drugs. In this article, we present management guidance to optimise the diagnosis, algorithm-based treatment, drug dosing and therapeutic drug monitoring, and the management of adverse events and comorbidities, associated with MDR-TB. We also discuss the role of surgery, physiotherapy, rehabilitation, palliative care and smoking cessation in patients with MDR-TB. We hope that incorporating these recommendations into patient care will be helpful in optimising treatment outcomes, and lead to more MDR-TB patients achieving a relapse-free cure.
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- Plasman, M., et al.
(författare)
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Lithospheric low-velocity zones associated with a magmatic segment of the Tanzanian Rift, East Africa
- 2017
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Ingår i: Geophysical Journal International. - : OXFORD UNIV PRESS. - 0956-540X .- 1365-246X. ; 210:1, s. 465-481
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Tidskriftsartikel (refereegranskat)abstract
- Rifting in a cratonic lithosphere is strongly controlled by several interacting processes including crust/mantle rheology, magmatism, inherited structure and stress regime. In order to better understand how these physical parameters interact, a 2 yr long seismological experiment has been carried out in the North Tanzanian Divergence (NTD), at the southern tip of the eastern magmatic branch of the East African rift, where the southward-propagating continental rift is at its earliest stage. We analyse teleseismic data from 38 broad-band stations ca. 25 km spaced and present here results from their receiver function (RF) analysis. The crustal thickness and Vp/Vs ratio are retrieved over a ca. 200 x 200 km(2) area encompassing the South Kenya magmatic rift, the NTD and the Ngorongoro-Kilimanjaro transverse volcanic chain. Cratonic nature of the lithosphere is clearly evinced through thick (up to ca. 40 km) homogeneous crust beneath the rift shoulders. Where rifting is present, Moho rises up to 27 km depth and the crust is strongly layered with clear velocity contrasts in the RF signal. The Vp/Vs ratio reaches its highest values (ca. 1.9) beneath volcanic edifices location and thinner crust, advocating for melting within the crust. We also clearly identify two major low-velocity zones (LVZs) within the NTD, one in the lower crust and the second in the upper part of the mantle. The first one starts at 15-18 km depth and correlates well with recent tomographic models. This LVZ does not always coexist with high Vp/Vs ratio, pleading for a supplementary source of velocity decrease, such as temperature or composition. At a greater depth of ca. 60 km, a midlithospheric discontinuity roughly mimics the step-like and symmetrically outward-dipping geometry of the Moho butwith a more slanting direction (NE-SW) compared to theNS rift. By comparison with synthetic RF, we estimate the associated velocity reduction to be 8-9 per cent. We relate this interface to melt ponding, possibly favouring here deformation process such as grain-boundary sliding (EAGBS) due to lithospheric strain. Its geometry might have been controlled by inherited lithospheric fabrics and heterogeneous upper mantle structure. We evidence that crustal and mantle magmatic processes represent first order mechanisms to ease and locate the deformation during the first stage of a cratonic lithospheric breakup.
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