| 1. |
- van Bragt, JJMH, et al.
(författare)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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| 2. |
- Menchon, JM, et al.
(författare)
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A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:4, s. 1234-1247
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Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was ‘programming/stimulation’ (in 26 patients), followed by ‘New illness, injury, condition’ (13 patients) and ‘pre-existing condition, worsening or exacerbation’ (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.
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| 3. |
- Farina, D., et al.
(författare)
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Toward higher-performance bionic limbs for wider clinical use
- 2021
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Ingår i: Nature Biomedical Engineering. - : Springer Science and Business Media LLC. - 2157-846X. ; 7:4, s. 473-85
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Tidskriftsartikel (refereegranskat)abstract
- Most prosthetic limbs can autonomously move with dexterity, yet they are not perceived by the user as belonging to their own body. Robotic limbs can convey information about the environment with higher precision than biological limbs, but their actual performance is substantially limited by current technologies for the interfacing of the robotic devices with the body and for transferring motor and sensory information bidirectionally between the prosthesis and the user. In this Perspective, we argue that direct skeletal attachment of bionic devices via osseointegration, the amplification of neural signals by targeted muscle innervation, improved prosthesis control via implanted muscle sensors and advanced algorithms, and the provision of sensory feedback by means of electrodes implanted in peripheral nerves, should all be leveraged towards the creation of a new generation of high-performance bionic limbs. These technologies have been clinically tested in humans, and alongside mechanical redesigns and adequate rehabilitation training should facilitate the wider clinical use of bionic limbs. This Perspective argues that technologies for the neural interfacing of robotic devices with the body that have been clinically tested in humans should be leveraged toward the creation of a new generation of high-performance bionic limbs.
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| 4. |
- Feletti, A., et al.
(författare)
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Ventriculoperitoneal Shunt Complications in the European Idiopathic Normal Pressure Hydrocephalus Multicenter Study
- 2019
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Ingår i: Operative neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 2332-4260 .- 2332-4252. ; 17:1, s. 97-102
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ventriculoperitoneal shunt (VP-shunt) is the standard of treatment for idiopathic normal pressure hydrocephalus (iNPH). However, a thorough investigation of VP-shunt complications in this population is lacking. OBJECTIVE: To present the analysis and the rates of complications progressively occurring during the first year after shunt surgery in the patients with iNPH included in the European multicenter (EU-iNPH) study. METHODS: Patients (n=142) were prospectively included in the EU-iNPH study by 13 institutions. All patients received a programmable VP-shunt. One hundred fifteen patients completed the 12-mo follow-up. Reexaminations were performed 1, 3, and 12 mo after surgery. Data regarding symptomatic over- or underdrainage, infections, malposition, subdural collections, and shunt surgery were collected and analyzed. RESULTS: Thirty patients (26%) experienced symptoms due to shunt underdrainage. Symptomatic overdrainage was reported in 10 (9%). Shunt adjustments were made in 43 (37%). Shunt malposition was recognized as the primary cause of shunt malfunction in 8 (7%), while only 1 infection (0.9%) occurred. Subdural hematoma was diagnosed in 7 (6%) and was treated by increasing the opening pressure of the valve in 5 patients. Hygroma was diagnosed in 10 (9%), requiring surgery in 1 patient. Overall, 17 patients (15%) underwent 19 shunt surgeries. CONCLUSION: The advances in valve technology, a careful opening pressure setting, and rigorous follow-up allow a significant reduction of complications, which can be usually managed nonsurgically within the first 3 to 6 mo. Copyright © 2018 by the Congress of Neurological Surgeons.
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| 5. |
- Ikeda, Fumiyo, et al.
(författare)
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SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis.
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 471:7340, s. 637-641
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Tidskriftsartikel (refereegranskat)abstract
- SHARPIN is a ubiquitin-binding and ubiquitin-like-domain-containing protein which, when mutated in mice, results in immune system disorders and multi-organ inflammation. Here we report that SHARPIN functions as a novel component of the linear ubiquitin chain assembly complex (LUBAC) and that the absence of SHARPIN causes dysregulation of NF-κB and apoptotic signalling pathways, explaining the severe phenotypes displayed by chronic proliferative dermatitis (cpdm) in SHARPIN-deficient mice. Upon binding to the LUBAC subunit HOIP (also known as RNF31), SHARPIN stimulates the formation of linear ubiquitin chains in vitro and in vivo. Coexpression of SHARPIN and HOIP promotes linear ubiquitination of NEMO (also known as IKBKG), an adaptor of the IκB kinases (IKKs) and subsequent activation of NF-κB signalling, whereas SHARPIN deficiency in mice causes an impaired activation of the IKK complex and NF-κB in B cells, macrophages and mouse embryonic fibroblasts (MEFs). This effect is further enhanced upon concurrent downregulation of HOIL-1L (also known as RBCK1), another HOIP-binding component of LUBAC. In addition, SHARPIN deficiency leads to rapid cell death upon tumour-necrosis factor α (TNF-α) stimulation via FADD- and caspase-8-dependent pathways. SHARPIN thus activates NF-κB and inhibits apoptosis via distinct pathways in vivo.
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