| 1. |
- Montagnese, Sara, et al.
(författare)
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A pilot study of golexanolone, a new GABA-A receptor-modulating steroid antagonist, in patients with covert hepatic encephalopathy
- 2021
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 75:1, s. 98-107
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Golexanolone is a novel small molecule GABA-A receptor-modulating steroid antagonist under development for the treatment of cognitive and vigilance disorders caused by allosteric over-activation of GABA-A receptors by neurosteroids. It restored spatial learning and motor coordination in animal models of hepatic encephalopathy (HE) and mitigated the effects of intravenous allopregnanolone in healthy adults in a dose-dependent fashion. Herein, we report data on the safety, pharmacokinetics (PK) and efficacy of golexanolone in adult patients with cirrhosis.Methods: Following single/multiple ascending dose studies, adults with Child-Pugh A/B cirrhosis and abnormal continuous reaction time (CRT) on screening were randomized to 3 weeks’ dosing with golexanolone (10, 40 or 80 mg BID) or placebo. CRT, psychometric hepatic encephalopathy score (PHES), animal naming test (ANT), Epworth sleepiness scale (ESS) and electroencephalogram (mean dominant frequency [MDF]; delta+theta/alpha+beta ratio [DT/AB]) were obtained at baseline, 10, and 21 days.Results: Golexanolone exhibited satisfactory safety and PK. Baseline characteristics were similar between the 12 and 33 patients randomized to placebo or golexanolone, respectively. By prespecified analyses, golexanolone was associated with directionally favourable changes vs. placebo in ESS (p = 0.047), MDF (p = 0.142) and DT/AB (p = 0.021). All patients also showed directionally favourable changes in CRT, PHES and ANT, but with no statistical difference between golexanolone and placebo. Post hoc analyses taking into account the variability and improvement in CRT, PHES and ANT observed between screening and baseline suggested an efficacy signal by cognitive measures as well.Conclusion: Golexanolone was well tolerated and associated with improvement in cognitive performance. These results implicate GABA-A receptor-modulating neurosteroids in the pathogenesis of HE and support the therapeutic potential of golexanolone.Lay summary: Many patients with cirrhosis experience subtle but disabling cognitive problems, including sleepiness and poor attention span, that impair their ability to be gainfully employed or carry out activities of daily living. This pilot study tested the hypothesis that these problems with cognition, for which there is no approved treatment, might be improved by an experimental drug, golexanolone, designed to normalize the function of receptors which inhibit brain function. The results of this study suggest that golexanolone is well tolerated and may improve cognition, as reflected by measures of sleepiness, attention span and brain wave activity, paving the way for future larger studies of this promising experimental drug.Clinical trial registration number: EudraCT 2016-003651-30.
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| 2. |
- Axén, Elin, et al.
(författare)
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Biochemical recurrence after radical prostatectomy - a large, comprehensive, population-based study with long follow-up
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:4, s. 287-292
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Tidskriftsartikel (refereegranskat)abstract
- Objective We evaluated long-term risk for biochemical recurrence and subsequent prognosis in a population-based cohort. Material and Methods We used register-based data to evaluate 6 675 consecutive patients having radical prostatectomy in Vastra Gotaland county in Sweden during 1995-2014. Patients were followed until death or end of study, 31 December 2014. Data were collected from registers on national, regional and local level and linked by means of the Swedish personal identity number. Biochemical recurrence was defined as PSA >= 0.2 ng/ml; failure as hormonal treatment, metastasis or prostate cancer death. Survival analysis was used to estimate time to biochemical recurrence and time to failure after biochemical recurrence for patients with 0 - 2 years, 2-5 years, 5-10 years and >10 years interval to biochemical recurrence, respectively. Results A total of 1214 men had biochemical recurrence during follow-up. Biochemical recurrence-free survival was 83% (95% confidence interval [CI] 82-84%), 75% (95% CI 74-77%) and 69% (95% CI 67-71%) at 5, 10 and 15 years, respectively. Cumulative incidence of failure for all patients 15 years after biochemical recurrence was 50% (95% CI 43-55%) in competing risk analysis .The risk of failure after biochemical recurrence was highest among patients having biochemical recurrence within 2 years from surgery. Incomplete data on PSA-history is a limitation. Conclusions The risk for biochemical recurrence persists 15 years after surgery. Follow-up should continue as long as treatment would be considered in case of recurrent disease.
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| 3. |
- Frånlund, Maria, et al.
(författare)
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Results from 22 years of Followup in the Göteborg Randomized Population-Based Prostate Cancer Screening Trial
- 2022
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Ingår i: Journal of Urology. - 0022-5347 .- 1527-3792. ; 208:2, s. 292-300
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:Our goal was to analyze results from 22 years of followup in the Göteborg randomized prostate cancer (PC) screening trial.Materials and Methods:In December 1994, 20,000 men born 1930-1944 were randomly extracted from the Swedish population register and were randomized (1:1) into either a screening group (SG) or to a control group (CG). Men in the SG were repeatedly invited for biennial prostate specific antigen testing up to an average age of 69 years. Main endpoints were PC incidence and mortality (intention-to-screen principle).Results:After 22 years, 1,528 men in the SG and 1,124 men in the CG had been diagnosed with PC. In total, 112 PC deaths occurred in the SG and 158 in the CG. Compared with the CG, the SG showed a PC incidence rate ratio (RR) of 1.42 (95% CI, 1.31-1.53) and a PC mortality RR of 0.71 (95% CI, 0.55-0.91). The 22-year cumulative PC mortality rate was 1.55% (95% CI, 1.29-1.86) in the SG and 2.13% (95% CI, 1.83-2.49) in the CG. Correction for nonattendance (Cuzick method) yielded a RR of PC mortality of 0.59 (95% CI, 0.43-0.80). Number needed to invite and number needed to diagnose was estimated to 221 and 9, respectively. PC death risk was increased in the following groups: nontesting men, men entering the program after age 60 and men with >10 years of followup after screening termination.Conclusions:Prostate specific antigen-based screening substantially decreases PC mortality. However, not attending, starting after age 60 and stopping at age 70 seem to be major pitfalls regarding PC death risk.
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| 4. |
- John Mukkattukavil, Deepak, et al.
(författare)
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Resonant inelastic soft x-ray scattering on LaPt2Si2
- 2022
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Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 34:32, s. 324003-
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Tidskriftsartikel (refereegranskat)abstract
- X-ray absorption and resonant inelastic x-ray scattering spectra of LaPt2Si2 single crystal at the Si 2p and La 4d edges are presented. The data are interpreted in terms of density functional theory, showing that the Si spectra can be described in terms of Si s and d local partial density of states (LPDOS), and the La spectra are due to quasi-atomic local 4f excitations. Calculations show that Pt d-LPDOS dominates the occupied states, and a sharp localized La f state is found in the unoccupied states, in line with the observations.
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| 5. |
- Kahn, Robin, et al.
(författare)
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Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms
- 2022
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:2, s. 354-62
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Methods: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively collected between 1 December 2020 and 31 May 2021. All patients met the World Health Organization criteria for MIS-C. The outcomes 2 and 8weeks after diagnosis are presented, and follow-up protocols are suggested. Results: We identified 152 cases, and 133 (87%) participated. When followed up 2weeks after MIS-C was diagnosed, 43% of the 119 patients had abnormal results, including complete blood cell counts, platelet counts, albumin levels, electrocardiograms and echocardiograms. After 8weeks, 36% of 89 had an abnormal patient history, but clinical findings were uncommon. Echocardiogram results were abnormal in 5% of 67, and the most common complaint was fatigue. Older children and those who received intensive care were more likely to report symptoms and have abnormal cardiac results. Conclusion: More than a third (36%) of the patients had persistent symptoms 8weeks after MIS-C, and 5% had abnormal echocardiograms. Older age and higher levels of initial care appeared to be risk factors. Structured follow-up visits are important after MIS-C.
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| 6. |
- Mukkattukavil, Deepak John, 1993-, et al.
(författare)
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Resonant inelastic soft x-ray scattering on LaPt2Si2
- 2022
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Ingår i: Journal of Physics. - : Institute of Physics Publishing (IOPP). - 0953-8984 .- 1361-648X. ; 34:32
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Tidskriftsartikel (refereegranskat)abstract
- X-ray absorption and resonant inelastic x-ray scattering spectra of LaPt2Si2 single crystal at the Si 2p and La 4d edges are presented. The data are interpreted in terms of density functional theory, showing that the Si spectra can be described in terms of Si s and d local partial density of states (LPDOS), and the La spectra are due to quasi-atomic local 4f excitations. Calculations show that Pt d-LPDOS dominates the occupied states, and a sharp localized La f state is found in the unoccupied states, in line with the observations.
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| 7. |
- Månsson, Erik M., et al.
(författare)
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The smoothed reassigned spectrogram for robust energy estimation
- 2021
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Ingår i: 28th European Signal Processing Conference, EUSIPCO 2020 - Proceedings. - 2219-5491. - 9789082797053 ; 2021-January, s. 2210-2214
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Konferensbidrag (refereegranskat)abstract
- The matched window reassigned spectrogram relocates all signal energy of an oscillating transient to the time- and frequency locations, resulting in a sharp peak in the time-frequency plane. However, previous research has shown that the method may result in split energy peaks for close components and in high noise levels, and the peak energy is then erroneously estimated. With use of novel knowledge on the statistics when subjected to noise, we propose a novel method, the smoothed reassigned spectrogram, for obtaining a stable and accurate measure of the signal energy from the peak value, with retained resolution properties. We also suggest a simple set of rules to enhance the reassigned spectrogram and speed up its calculation. Simulations are performed to verify the accuracy and an application example on radar data is shown.
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| 8. |
- Månsson, Linda, 1973-
(författare)
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Digital fall prevention for older adults : Feasibility of a self-managed exercise application and development of a smartphone self-test for balance and leg strength
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- As the numbers of older adults grow, fall prevention is vital to reduce health care needs due to falls and to increase quality of life. Balance and strength exercises have been found to be effective in fall prevention, however, long-term adherence is often poor. The growth of digital technology in society has generated opportunities for fall prevention with eHealth. The aim of this thesis was to evaluate the feasibility and use of a new digital fall prevention exercise programme, and to develop and investigate a smartphone self-test application for balance and leg strength. Three different studies included community-dwelling older adults ≥ 70 years, who were able to rise from a chair and stand without support. A feasibility study evaluated a new digital exercise programme (DP) compared to a paper booklet exercise programme (PB) for self-managed fall prevention in a four-month controlled participant preference trial (n = 67) (Paper I & II). Self-reported data on adherence, falls efficacy, and functional ability were collected and analysed, along with performance-based measures of gait speed, balance, and chair stand test. In Paper II the feasibility was explored of using the self-reported scales and performance-based outcome measures. A self-test application was also developed (Paper III) in co-creation with 10 participants, who met during five sessions to design the application’s instructions and user interface. The participants’ preference for and their contribution to the application design was analysed with qualitative content analysis with a deductive-inductive approach. A concurrent validity study (n = 31) (Paper IV) assessed the correlations between variables from the self-test prototype and outcome measures from clinical instruments. Results from the feasibility study show that 43% chose the DP and 57% PB, and the attrition rate was 17% and 37% respectively. Both groups had similar adherence, but for the subgroup that exercised most, participants in the DP group reported significantly more exercise time (Paper I). Participants in both groups reported a boost in balance after the intervention, and in the DP group also improved leg strength. Significantly more participants continued to use the DP at 12 months. The self-managed exercise intervention (Paper II) resulted in improvements in functional leg strength, which positively correlated with exercise time, but no other performance-based outcomes showed any significant improvements. Performance-based measurements of balance as well as the self- reported balance confidence and fear of falling revealed ceiling effects. Pre-assessments of self-reported outcomes and performance-based measures showed significant but low correlations, no such correlations were seen in change scores. The deductive-inductive analysis of the co-creation process resulted in 17 subcategories within the seven facets of the Optimized Honeycomb model for iii user experience (Paper III). The main results were that participants desired clear and appropriate information to understand why things were done in a certain way, and their contributions enhanced the user experience of the self-test. The concurrent validity testing of the self-test prototype (IV) showed low to moderate correlations for the strength test but limited correlations for the balance test. In conclusion the DP group showed comparable adherence to the programme as the PB group, as well as to previous studies, indicating it was feasible to use the new DP. DP participants also reported better exercise maintenance after 12 months. Positive self-reported effects were expressed in addition to leg strength improvement. Outcome measures for balance and falls efficacy revealed ceiling effects, consequently, these instruments might not be suitable for assessments in all community-dwelling older adults. In particular, for balance related outcomes there is a need for new more sensitive measurements. The co-creation of the smartphone self-test was feasible and valuable for user experience, but further validity and reliability testing are needed before it can serve as an independent assessment tool.
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| 9. |
- Månsson, Linda, et al.
(författare)
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Feasibility of performance-based and self-reported outcomes in self-managed falls prevention exercise interventions for independent older adults living in the community
- 2022
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Ingår i: BMC Geriatrics. - : BioMed Central. - 1471-2318. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about associations between performance-based measurements and self-reported scales, nor about ceiling effects or sensitivity to change to evaluate effects in the target population for self-managed exercise interventions. This study aimed to explore the feasibility of using performance-based outcomes for gait speed, functional leg strength and balance, and self-reported outcomes of falls-efficacy and functional ability in two self-managed falls prevention exercise interventions for community dwelling older adults.METHODS: Independent living, community-dwelling older adults (n = 67) exercised with one of two self-managed falls prevention exercise programmes, a digital programme (DP) or a paper booklet (PB) in a 4-month participant preference trial. Pre- and post-assessments, by blinded assessors, included Short Physical Performance Battery (SPPB) and 30s Chair stand test (30s CST). Participants completed self-reported questionnaires: Activities-specific and Balance Confidence scale (ABC), Iconographical Falls Efficacy Scale (Icon-FES), Late-Life Function and Disability Instrument Function Component (LLFDI-FC). In addition, improvement in balance and leg strength was also self-rated at post-assessment. Participants' mean age was 76 ± 4 years and 72% were women.RESULTS: Ceiling effects were evident for the balance sub-component of the SPPB, and also indicated for ABC and Icon-FES in this high functioning population. In SPPB, gait speed, 30s CST, and LLFDI-FC, 21-56% of participants did not change their scores beyond the Minimal Clinically Important Difference (MCID). At pre-assessment all performance-based tests correlated significantly with the self-reported scales, however, no such significant correlations were seen with change-scores. Improvement of performance-based functional leg strength with substantial effect sizes and significant correlations with self-reported exercise time was shown. There were no differences in outcomes between the exercise programmes except that DP users reported improved change of leg strength to a higher degree than PB users.CONCLUSION: The LLFDI-FC and sit-to-stand tests were feasible and sensitive to change in this specific population. The balance sub-component of SPPB and self-reported measures ABC and Icon-FES indicated ceiling effects and might not be suitable as outcome measures for use in a high functioning older population. Development and evaluation of new outcome measures are needed for self-managed fall-preventive interventions with high functioning community-dwelling older adults.
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| 10. |
- Månsson, Linda, et al.
(författare)
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Older adults' preferences for, adherence to and experiences of two self-management falls prevention home exercise programmes : a comparison between a digital programme and a paper booklet
- 2020
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Ingår i: BMC Geriatrics. - : BioMed Central. - 1471-2318. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fall prevention exercise programmes are known to be effective, but access to these programmes is not always possible. The use of eHealth solutions might be a way forward to increase access and reach a wider population. In this feasibility study the aim was to explore the choice of programme, adherence, and self-reported experiences comparing two exercise programmes – a digital programme and a paper booklet.Methods: A participant preference trial of two self-managed fall prevention exercise interventions. Community-dwelling adults aged 70 years and older exercised independently for four months after one introduction meeting. Baseline information was collected at study start, including a short introduction of the exercise programme, a short physical assessment, and completion of questionnaires. During the four months intervention period, participants self-reported their performed exercises in an exercise diary. At a final meeting, questionnaires about their experiences, and post-assessments, were completed. For adherence analyses data from diaries were used and four subgroups for different levels of participation were compared. Exercise maintenance was followed up with a survey 12 months after study start.Results: Sixty-seven participants, with mean age 77 ± 4 years were included, 72% were women. Forty-three percent chose the digital programme. Attrition rate was 17% in the digital programme group and 37% in the paper booklet group (p = .078). In both groups 50–59% reported exercise at least 75% of the intervention period. The only significant difference for adherence was in the subgroup that completed ≥75% of exercise duration, the digital programme users exercised more minutes per week (p = .001). Participants in both groups were content with their programme but digital programme users reported a significantly higher (p = .026) degree of being content, and feeling supported by the programme (p = .044). At 12 months follow-up 67% of participants using the digital programme continued to exercise regularly compared with 35% for the paper booklet (p = .036).Conclusions: Exercise interventions based on either a digital programme or a paper booklet can be used as a self-managed, independent fall prevention programme. There is a similar adherence in both programmes during a 4-month intervention, but the digital programme seems to facilitate long-term maintenance in regular exercise.
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