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- Tranebjærg, Lisbeth, et al.
(författare)
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The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management
- 2018
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Ingår i: Human Genetics. - : Springer. - 0340-6717 .- 1432-1203. ; 137:2, s. 111-127
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Tidskriftsartikel (refereegranskat)abstract
- Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS) is a rare clinically distinct syndrome caused by a single dominant missense mutation, c.2452G>A, p.Glu818Lys, in ATP1A3, encoding the neuron-specific alpha subunit of the Na+/K+-ATPase α3. Allelic mutations cause the neurological diseases rapid dystonia Parkinsonism and alternating hemiplegia of childhood, disorders which do not encompass hearing or visual impairment. We present detailed clinical phenotypic information in 18 genetically confirmed patients from 11 families (10 previously unreported) from Denmark, Sweden, UK and Germany indicating a specific type of hearing impairment-auditory neuropathy (AN). All patients were clinically suspected of CAPOS and had hearing problems. In this retrospective analysis of audiological data, we show for the first time that cochlear outer hair cell activity was preserved as shown by the presence of otoacoustic emissions and cochlear microphonic potentials, but the auditory brainstem responses were grossly abnormal, likely reflecting neural dyssynchrony. Poor speech perception was observed, especially in noise, which was beyond the hearing level obtained in the pure tone audiograms in several of the patients presented here. Molecular modelling and in vitro electrophysiological studies of the specific CAPOS mutation were performed. Heterologous expression studies of α3 with the p.Glu818Lys mutation affects sodium binding to, and release from, the sodium-specific site in the pump, the third ion-binding site. Molecular dynamics simulations confirm that the structure of the C-terminal region is affected. In conclusion, we demonstrate for the first time evidence for auditory neuropathy in CAPOS syndrome, which may reflect impaired propagation of electrical impulses along the spiral ganglion neurons. This has implications for diagnosis and patient management. Auditory neuropathy is difficult to treat with conventional hearing aids, but preliminary improvement in speech perception in some patients suggests that cochlear implantation may be effective in CAPOS patients.
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| 4. |
- Broesby-Olsen, Sigurd, et al.
(författare)
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Multidisciplinary Management of Mastocytosis : Nordic Expert Group Consensus
- 2016
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 96:5
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Tidskriftsartikel (refereegranskat)abstract
- Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.
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| 5. |
- Egholm, Julie W.M., et al.
(författare)
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Perioperative alcohol cessation intervention for postoperative complications
- 2018
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Ingår i: Cochrane Database of Systematic Reviews. - 1361-6137. ; 2018:11
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Forskningsöversikt (refereegranskat)abstract
- Background: Risky consumption of alcohol is a global problem. More than 3.3 million deaths annually are associated with risky use of alcohol, and global alcohol consumption continues to increase. People who have high alcohol consumption often require planned and emergency surgical procedures. Risky drinking is associated with increased postoperative complications such as infections, cardiopulmonary complications, and bleeding episodes. Alcohol causes disorders of the liver, pancreas, and nervous system. Stopping consumption of alcohol can normalize these organ systems to some degree and may reduce the occurrence of complications after surgery. This review was first published in 2012 and was updated in 2018. Objectives: To assess the effects of perioperative alcohol cessation interventions on rates of postoperative complications and alcohol consumption. Search methods: We searched the following databases up until 21 September 2018: Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; Embase; CINAHL via EBSCOhost; and two trials registers. We scanned the reference lists and citations of included trials and any identified relevant systematic reviews for further references to additional trials. When necessary, we contacted trial authors to ask for additional information. Selection criteria: We included all randomized controlled trials (RCTs) that evaluated the effects of perioperative alcohol cessation interventions on postoperative complications and alcohol consumption. We included participants with risky consumption of alcohol who were undergoing all types of elective or acute surgical procedures under general or regional anaesthesia or sedation, who were offered a perioperative alcohol cessation intervention or no intervention. We defined 'risky drinking' as alcohol consumption equivalent to more than 3 alcoholic units (AU)/d or 21 AU/week (with 1 AU containing 12 grams of ethanol) with or without symptoms of alcohol abuse or dependency. This corresponds to the amount of alcohol associated with increased postoperative complication rates in most clinical studies. Data collection and analysis: We used guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions. We presented main outcomes as dichotomous variables in a meta-analysis. When data were available, we conducted subgroup and sensitivity analyses to explore the risk of bias. Primary outcome measures were postoperative complications and in-hospital and 30-day mortality. Secondary outcomes were successful quitting at the end of the programme, postoperative alcohol use, and length of hospital stay. We assessed the quality of evidence using the GRADE approach. Main results: We included in this updated review one new study (70 participants), resulting in a total of three RCTs (140 participants who drank 3 to 40 AU/d). All three studies were of moderate to good quality. All studies evaluated the effects of intensive alcohol cessation interventions, including pharmacological strategies for alcohol withdrawal symptoms, patient education, and relapse prophylaxis. We identified one ongoing study. Overall, 53 of the 122 participants from three studies who underwent surgery developed any type of postoperative complication that required treatment. Of 61 participants in the intervention groups, 20 had complications, compared with 33 of 61 participants in the control groups (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.40 to 0.96). Results show differences between the three clinical studies regarding outcome measurement and intensity of the interventions. However, all alcohol cessation programmes were intensive and included pharmacological therapy. The overall quality of evidence for this outcome is moderate. In-hospital and 30-day postoperative mortality rates were low in the three studies. Researchers reported one death among 61 participants in the intervention groups, and three deaths among 61 participants in the control groups (RR 0.47, 95% CI 0.07 to 2.96). The quality of evidence for this outcome is low. Investigators describe more successful quitters at the end of the intervention programme than among controls. Forty-one out of 70 participants in the intervention groups successfully quit drinking compared with only five out of 70 participants in the control groups (RR 8.22, 95% CI 1.67 to 40.44). The quality of evidence for this outcome is moderate. All three studies reported postoperative alcohol consumption (grams of alcohol/week) at the end of the programme as median and range values; therefore it was not possible to estimate the mean and the standard deviation (SD). We performed no meta-analysis. All three studies reported length of stay, and none of these studies described a significant difference in length of stay. Data were insufficient for review authors to perform a meta-analysis. No studies reported on the prevalence of participants without risky drinking in the longer term. Authors' conclusions: This systematic review assessed the efficacy of perioperative alcohol cessation interventions for postoperative complications and alcohol consumption. All three studies showed a significant reduction in the number of participants who quit drinking alcohol during the intervention period. Intensive alcohol cessation interventions offered for four to eight weeks to participants undergoing all types of surgical procedures to achieve complete alcohol cessation before surgery probably reduced the number of postoperative complications. Data were insufficient for review authors to assess their effects on postoperative mortality. No studies reported an effect on length of stay, and no studies addressed the prevalence of risky drinking in the longer term. Included studies were few and reported small sample sizes; therefore one should be careful about drawing firm conclusions based on these study results. All three studies were conducted in Denmark, and most participants were men. The included participants may represent a selective group, as they could have been more motivated and/or more interested in participating in clinical research or otherwise different, and effects may have been overestimated for both intervention and control groups in these studies. Trial results indicate that these studies are difficult to perform, that strong research competencies are necessary for future studies, and that further evaluation of perioperative alcohol cessation interventions in high-quality randomized controlled trials is needed. Once published and assessed, the one 'ongoing' study identified may alter the conclusions of this review.
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- Gredal, Hanne Birgit, et al.
(författare)
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Interleukin-6 is increased in plasma and cerebrospinal fluid of community-dwelling domestic dogs with acute ischaemic stroke
- 2017
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Ingår i: NeuroReport. - 0959-4965. ; 28:3, s. 134-140
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory cytokines are potential modulators of infarct progression in acute ischaemic stroke, and are therefore possible targets for future treatment strategies. Cytokine studies in animal models of surgically induced stroke may, however, be influenced by the fact that the surgical intervention itself contributes towards the cytokine response. Community-dwelling domestic dogs suffer from spontaneous ischaemic stroke, and therefore, offer the opportunity to study the cytokine response in a noninvasive set-up. The aims of this study were to investigate cytokine concentrations in plasma and cerebrospinal fluid (CSF) in dogs with acute ischaemic stroke and to search for correlations between infarct volume and cytokine concentrations. Blood and CSF were collected from dogs less than 72 h after a spontaneous ischaemic stroke. Infarct volumes were estimated on MRIs. Interleukin (IL)-2, IL-6, IL-8, IL-10 and tumour necrosis factor in the plasma, CSF and brain homogenates were measured using a canine-specific multiplex immunoassay. IL-6 was significantly increased in plasma (P=0.04) and CSF (P=0.04) in stroke dogs compared with healthy controls. The concentrations of other cytokines, such as tumour necrosis factor and IL-2, were unchanged. Plasma IL-8 levels correlated significantly with infarct volume (Spearman’s r=0.8, P=0.013). The findings showed increased concentrations of IL-6 in the plasma and CSF of dogs with acute ischaemic stroke comparable to humans. We believe that dogs with spontaneous stroke offer a unique, noninvasive means of studying the inflammatory processes that accompany stroke while reducing confounds that are unavoidable in experimental models.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
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| 7. |
- Hansen, Alice Ørts, et al.
(författare)
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An occupation-based intervention in patients with hand-related disorders grouped using the sense of coherence scale—A randomized controlled trial
- 2020
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Ingår i: Journal of Hand Therapy. - : Elsevier BV. - 0894-1130. ; 33:4, s. 455-469
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Tidskriftsartikel (refereegranskat)abstract
- Study Design: A nonblinded randomized controlled trial. Introduction: Occupation-based interventions are superior to physical exercise–based interventions in patients with activity limitations. However, only a few studies have examined the effect in patients with hand-related disorders. Patients recover heterogeneously, which could be due to personal factors, such as sense of coherence (SOC). Purpose of the study: To investigate the effectiveness of an occupation-based intervention for patients with hand-related disorders and whether SOC can give an indication of the expected effects. Methods: A total of 504 patients were stratified into three SOC groups and then randomized to either an occupation-based intervention, including physical exercises (OBI) or a physical exercise–based occupation-focused intervention. The primary outcome, functioning, was measured using the Disability of the Arm, Shoulder and Hand questionnaire. Primary endpoint was at three months. Patients were followed up for a year. Results: No significant difference was found in primary outcome analysis. Nevertheless, patients receiving OBI had a statistically significant and greater change in satisfaction with their occupational performance at one, two, and three months follow-up. Patients with a weak SOC had worse functioning and lower health-related quality of life than those in the other groups, at all times. Conclusions: OBI as delivered in this study was not superior to physical exercise–based occupation-focused intervention in this patient group. However, in taking a client-centered approach, we recommend that OBI be based on individual needs, given that patients had a statistically greater change in score regarding satisfaction with their occupational performance. It is evident that patients with a weaker SOC have a lower level of functioning. This knowledge should inform clinical practice.
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| 8. |
- Lee, Craig M., et al.
(författare)
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A Framework for the Development, Design and Implementation of a Sustained Arctic Ocean Observing System
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
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Forskningsöversikt (refereegranskat)abstract
- Rapid Arctic warming drives profound change in the marine environment that have significant socio-economic impacts within the Arctic and beyond, including climate and weather hazards, food security, transportation, infrastructure planning and resource extraction. These concerns drive efforts to understand and predict Arctic environmental change and motivate development of an Arctic Region Component of the Global Ocean Observing System (ARCGOOS) capable of collecting the broad, sustained observations needed to support these endeavors. This paper provides a roadmap for establishing the ARCGOOS. ARCGOOS development must be underpinned by a broadly endorsed framework grounded in high-level policy drivers and the scientific and operational objectives that stem from them. This should be guided by a transparent, internationally accepted governance structure with recognized authority and organizational relationships with the national agencies that ultimately execute network plans. A governance model for ARCGOOS must guide selection of objectives, assess performance and fitness-to-purpose, and advocate for resources. A requirements-based framework for an ARCGOOS begins with the Societal Benefit Areas (SBAs) that underpin the system. SBAs motivate investments and define the system's science and operational objectives. Objectives can then be used to identify key observables and their scope. The domains of planning/policy, strategy, and tactics define scope ranging from decades and basins to focused observing with near real time data delivery. Patterns emerge when this analysis is integrated across an appropriate set of SBAs and science/operational objectives, identifying impactful variables and the scope of the measurements. When weighted for technological readiness and logistical feasibility, this can be used to select Essential ARCGOOS Variables, analogous to Essential Ocean Variables of the Global Ocean Observing System. The Arctic presents distinct needs and challenges, demanding novel observing strategies. Cost, traceability and ability to integrate region-specific knowledge have to be balanced, in an approach that builds on existing and new observing infrastructure. ARCGOOS should benefit from established data infrastructures following the Findable, Accessible, Interoperable, Reuseable Principles to ensure preservation and sharing of data and derived products. Linking to the Sustaining Arctic Observing Networks (SAON) process and involving Arctic stakeholders, for example through liaison with the International Arctic Science Committee (IASC), can help ensure success.
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