| 1. |
- Ajello, M., et al.
(author)
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Fermi and Swift Observations of GRB 190114C : Tracing the Evolution of High-energy Emission from Prompt to Afterglow
- 2020
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 890:1
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Journal article (peer-reviewed)abstract
- We report on the observations of gamma-ray burst (GRB) 190114C by the Fermi Gamma -ray Space Telescope and the Neil Gehrels Swift Observatory. The prompt gamma-ray emission was detected by the Fermi GRB Monitor (GBM), the Fermi Large Area Telescope (LAT), and the Swift Burst Alert Telescope (BAT) and the long-lived afterglow emission was subsequently observed by the GBM, LAT, Swift X-ray Telescope (XRT), and Swift UV Optical Telescope. The early -time observations reveal multiple emission components that evolve independently, with a delayed power-law component that exhibits significant spectral attenuation above 40 MeV in the first few seconds of the burst. This power-law component transitions to a harder spectrum that is consistent with the afterglow emission observed by the XRT at later times. This afterglow component is clearly identifiable in the GBM and BAT light curves as a slowly fading emission component on which the rest of the prompt emission is superimposed. As a result, we are able to observe the transition from internal-shock- to external-shock-dominated emission. We find that the temporal and spectral evolution of the broadband afterglow emission can be well modeled as synchrotron emission from a forward shock propagating into a wind -like circumstellar environment. We estimate the initial bulk Lorentz factor using the observed high-energy spectral cutoff. Considering the onset of the afterglow component, we constrain the deceleration radius at which this forward shock begins to radiate in order to estimate the maximum synchrotron energy as a function of time. We find that even in the LAT energy range, there exist high-energy photons that are in tension with the theoretical maximum energy that can be achieved through synchrotron emission from a shock. These violations of the maximum synchrotron energy are further compounded by the detection of very high-energy (VHE) emission above 300 GeV by MAGIC concurrent with our observations. We conclude that the observations of VHE photons from GRB 190114C necessitates either an additional emission mechanism at very high energies that is hidden in the synchrotron component in the LAT energy range, an acceleration mechanism that imparts energy to the particles at a rate that is faster than the electron synchrotron energy -loss rate, or revisions of the fundamental assumptions used in estimating the maximum photon energy attainable through the synchrotron process.
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| 2. |
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| 3. |
- Abdollahi, S., et al.
(author)
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Fermi Large Area Telescope Fourth Source Catalog
- 2020
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 247:1
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Journal article (peer-reviewed)abstract
- We present the fourth Fermi Large Area Telescope catalog (4FGL) of gamma-ray sources. Based on the first eight years of science data from the Fermi Gamma-ray Space Telescope mission in the energy range from 50 MeV to 1 TeV, it is the deepest yet in this energy range. Relative to the 3FGL catalog, the 4FGL catalog has twice as much exposure as well as a number of analysis improvements, including an updated model for the Galactic diffuse gamma-ray emission, and two sets of light curves (one-year and two-month intervals). The 4FGL catalog includes 5064 sources above 4 sigma significance, for which we provide localization and spectral properties. Seventy-five sources are modeled explicitly as spatially extended, and overall, 358 sources are considered as identified based on angular extent, periodicity, or correlated variability observed at other wavelengths. For 1336 sources, we have not found plausible counterparts at other wavelengths. More than 3130 of the identified or associated sources are active galaxies of the blazar class, and 239 are pulsars.
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| 4. |
- Ajello, M., et al.
(author)
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Fermi Large Area Telescope Performance after 10 Years of Operation
- 2021
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 256:1
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Journal article (peer-reviewed)abstract
- The Large Area Telescope (LAT), the primary instrument for the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering the energy range from 30 MeV to more than 300 GeV. We describe the performance of the instrument at the 10 yr milestone. LAT performance remains well within the specifications defined during the planning phase, validating the design choices and supporting the compelling case to extend the duration of the Fermi mission. The details provided here will be useful when designing the next generation of high-energy gamma-ray observatories.
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| 5. |
- Ajello, M., et al.
(author)
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High-energy emission from a magnetar giant flare in the Sculptor galaxy
- 2021
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In: Nature Astronomy. - : Springer Nature. - 2397-3366. ; 5:4, s. 385-391
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Journal article (peer-reviewed)abstract
- Magnetars are the most highly magnetized neutron stars in the cosmos (with magnetic field 1013–1015 G). Giant flares from magnetars are rare, short-duration (about 0.1 s) bursts of hard X-rays and soft γ rays1,2. Owing to the limited sensitivity and energy coverage of previous telescopes, no magnetar giant flare has been detected at gigaelectronvolt (GeV) energies. Here, we report the discovery of GeV emission from a magnetar giant flare on 15 April 2020 (refs. 3,4 and A. J. Castro-Tirado et al., manuscript in preparation). The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope detected GeV γ rays from 19 s until 284 s after the initial detection of a signal in the megaelectronvolt (MeV) band. Our analysis shows that these γ rays are spatially associated with the nearby (3.5 megaparsecs) Sculptor galaxy and are unlikely to originate from a cosmological γ-ray burst. Thus, we infer that the γ rays originated with the magnetar giant flare in Sculptor. We suggest that the GeV signal is generated by an ultra-relativistic outflow that first radiates the prompt MeV-band photons, and then deposits its energy far from the stellar magnetosphere. After a propagation delay, the outflow interacts with environmental gas and produces shock waves that accelerate electrons to very high energies; these electrons then emit GeV γ rays as optically thin synchrotron radiation. This observation implies that a relativistic outflow is associated with the magnetar giant flare, and suggests the possibility that magnetars can power some short γ-ray bursts.
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| 9. |
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| 10. |
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| 11. |
- Raj, Satish R, et al.
(author)
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Postural orthostatic tachycardia syndrome (POTS) : Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2
- 2021
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In: Autonomic Neuroscience: Basic & Clinical. - : Elsevier BV. - 1872-7484. ; 235
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Journal article (peer-reviewed)abstract
- The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension. Patients often experience a host of other related disabling symptoms. The functional and economic impacts of this disorder are significant. The pathophysiology remains incompletely understood. Beyond the significant gaps in understanding the disorder itself, there is a paucity of evidence to guide treatment which can contribute to suboptimal care for this patient population. The vast majority of physicians have minimal to no familiarity or training in the assessment and management of POTS. Funding for POTS research remains very low relative to the size of the patient population and impact of the syndrome. In addition to efforts to improve awareness and physician education, an investment in research infrastructure including the development of standardized disease-specific evaluation tools and outcome measures is needed to facilitate effective collaborative research. A national POTS research consortium could facilitate well-controlled multidisciplinary clinical research studies and therapeutic trials. These priorities will require a substantial increase in the number of research investigators and the amount of research funding in this area.
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| 12. |
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| 13. |
- Vernino, Steven, et al.
(author)
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Postural orthostatic tachycardia syndrome (POTS) : State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1
- 2021
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In: Autonomic Neuroscience: Basic and Clinical. - : Elsevier BV. - 1566-0702. ; 235
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Journal article (peer-reviewed)abstract
- Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence. The onset of POTS may be precipitated by immunological stressors such as a viral infection. A variety of pathophysiologies are involved in the abnormal postural tachycardia response; however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted. Clinicians and researchers focused on POTS convened at the National Institutes of Health in July 2019 to discuss the current state of understanding of the pathophysiology of POTS and to identify priorities for POTS research. This article, the first of two articles summarizing the information discussed at this meeting, summarizes the current understanding of this disorder and best practices for clinical care. The evaluation of a patient with suspected POTS should seek to establish the diagnosis, identify co-morbid conditions, and exclude conditions that could cause or mimic the syndrome. Once diagnosed, management typically begins with patient education and non-pharmacologic treatment options. Various medications are often used to address specific symptoms, but there are currently no FDA-approved medications for the treatment of POTS, and evidence for many of the medications used to treat POTS is not robust.
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| 14. |
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| 15. |
- Le, Trang, et al.
(author)
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Analysis of the Human Protein Atlas Weakly Supervised Single-Cell Classification competition
- 2022
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In: Nature Methods. - : Springer Nature. - 1548-7091 .- 1548-7105. ; 19:10, s. 1221-1229
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Journal article (peer-reviewed)abstract
- While spatial proteomics by fluorescence imaging has quickly become an essential discovery tool for researchers, fast and scalable methods to classify and embed single-cell protein distributions in such images are lacking. Here, we present the design and analysis of the results from the competition Human Protein Atlas – Single-Cell Classification hosted on the Kaggle platform. This represents a crowd-sourced competition to develop machine learning models trained on limited annotations to label single-cell protein patterns in fluorescent images. The particular challenges of this competition include class imbalance, weak labels and multi-label classification, prompting competitors to apply a wide range of approaches in their solutions. The winning models serve as the first subcellular omics tools that can annotate single-cell locations, extract single-cell features and capture cellular dynamics.
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| 16. |
- Marteinsson, Steinthor A., et al.
(author)
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Reoperation for bleeding following coronary artery bypass surgery with special focus on long-term outcomes
- 2020
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In: Scandinavian Cardiovascular Journal. - : TAYLOR & FRANCIS LTD. - 1401-7431 .- 1651-2006. ; 54:4, s. 265-273
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Journal article (peer-reviewed)abstract
- Objectives: We studied the incidence and risk factors of reoperation for bleeding following CABG in a nationwide cohort with focus on long-term complications and survival.Design: A retrospective study on 2060 consecutive, isolated CABG patients operated 2001-2016. Outcome of reoperated patients (n = 130) were compared to non-reoperated ones (n = 1930), including major adverse cardiac and cerebrovascular events (MACCE) and overall survival. Risk factors for reoperation were determined using multivariate logistic regression and a Cox proportional hazards model to assess prognostic factors of long-term survival. Median follow-up was 7.6 years.Results: One hundred thirty patients (6.3%) were reoperated with an annual decrease of 4.1% per year over the study period (p=.04). Major complications (18.5 vs. 9.6%) and 30-day mortality (8.5 vs. 1.9%,) were higher in the reoperation group (p<.001). The use of clopidogrel preoperatively (OR 3.62, 95% CI: 1.90-6.57) and reduced left ventricular ejection fraction (OR 2.23, 95% CI: 1.25-3.77) were the strongest predictors of reoperation, whereas off-pump surgery was associated with a lower reoperation risk (OR 0.44, 95% CI: 0.22-0.85). After exluding patients that died within 30 days postoperatively, no difference in long-term survival or freedom from MACCE was found between groups, and reoperation was not an independent risk factor for long-term mortality in multivariate analysis.Conclusions: The reoperation rate in this study was relatively high but decreased significantly over time. Reoperation was associated with twofold increased risk for major complications and fourfold 30-day mortality, but comparable long-term MACCE and survival rates. This implies that if patients survive the first 30 days following reoperation, their long-term outcome is comparable to non-reoperated patients.
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| 17. |
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| 18. |
- Svenningsson, A., et al.
(author)
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Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: a rater-blinded, phase 3, randomised controlled trial
- 2022
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In: Lancet Neurology. - : Elsevier BV. - 1474-4422. ; 21:8, s. 693-703
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Journal article (peer-reviewed)abstract
- Background B-cell depleting therapies are highly efficacious in relapsing-remitting multiple sclerosis but one such therapy, rituximab, is not approved for multiple sclerosis and no phase 3 trial data are available. We therefore examined the safety and efficacy of rituximab compared with dimethyl fumarate in patients with relapsing-remitting multiple sclerosis to obtain data that might allow inclusion of rituximab in treatment guidelines. Methods RIFUND-MS was a multicentre, rater-blinded, active-comparator, phase 3, randomised controlled trial done at 17 Swedish university and community hospitals. Key inclusion criteria for participants were: age 18-50 years; relapsing-remitting multiple sclerosis or clinically isolated syndrome according to prevailing McDonald criteria; 10 years or less since diagnosis; untreated or only exposed to interferons or glatiramer acetate; and with clinical or neuroradiological disease activity in the past year. Patients were automatically randomly assigned (1:1) by the treating physician using a randomisation module in the Swedish multiple sclerosis registry, without stratification, to oral dimethyl fumarate 240 mg twice daily or to intravenous rituximab 1000 mg followed by 500 mg every 6 months. Relapse evaluation, Expanded Disability Status Scale rating, and assessment of MRI scans were done by examining physicians and radiologists masked to treatment allocation. The primary outcome was the proportion of patients with at least one relapse (defined as subacute onset of new or worsening neurological symptoms compatible with multiple sclerosis with a duration of more than 24 h and preceded by at least 30 days of clinical stability), assessed in an intention-to-treat analysis using log-binomial regression with robust standard errors. This trial is registered at ClinicalTrials.gov, NCT02746744. Findings Between July 1, 2016, and Dec 18, 2018, 322 patients were screened for eligibility, 200 of whom were randomly assigned to a treatment group (100 assigned to rituximab and 100 assigned to dimethyl fumarate). The last patient completed 24-month follow-up on April 21, 2021. 98 patients in the rituximab group and 97 patients in the dimethyl fumarate group were eligible for the primary outcome analysis. Three (3%) patients in the rituximab group and 16 (16%) patients in the dimethyl fumarate group had a protocol-defined relapse during the trial, corresponding to a risk ratio of 0.19 (95% CI 0.06-0.62; p=0.0060). Infusion reactions (105 events [40.9 per 100 patient-years]) in the rituximab group and gastrointestinal reactions (65 events [47.4 per 100 patient-years]) and flush (65 events [47.4 per 100 patient-years]) in the dimethyl fumarate group were the most prevalent adverse events. There were no safety concerns. Interpretation RIFUND-MS provides evidence that rituximab given as 1000 mg followed by 500 mg every 6 months is superior to dimethyl fumarate in preventing relapses over 24 months in patients with early relapsing-remitting multiple sclerosis. Health economic and long-term safety studies of rituximab in patients with multiple sclerosis are needed.
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| 19. |
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| 20. |
- Andresen Bergström, Moa, 1978, et al.
(author)
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Rethinking Drug Analysis in Health Care: High-Throughput Analysis of 71 Drugs of Abuse in Oral Fluid Using Ion Mobility-High-Resolution Mass Spectrometry
- 2022
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In: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 0146-4760 .- 1945-2403. ; 46:7, s. 765-775
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Journal article (peer-reviewed)abstract
- We have identified a clinical need for a sensitive, specific, flexible, comprehensive and affordable analytical technology to efficiently detect polydrug use. In addition, the current standard practice of surveilled urine sampling is uncomfortable for the patient; hence, more patient-friendly sample collection methods are requested. To fill these needs, we have developed and validated a high-throughput liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method for the analysis of drugs of abuse (DoA) in oral fluid (OF). The method covers a panel of 71 substances including traditional DoA, prescription narcotics and new psychoactive substances (NPS), with a guaranteed limit of identification of <3 mu g/L for 87% of the analytes. Method validation showed high accuracy (>99.7%), sensitivity (>99.7%) and specificity (100%). Most analytes had a high process efficiency during the salting-out liquid-liquid extraction sample preparation and no or only a minor matrix effect during the analysis. We have implemented this method in clinical routine and present data from 18,579 OF samples collected during routine patient treatment in mainly psychiatric and addiction clinics in West Sweden between September 2020 and June 2021. Seventy-one percent of the samples were positive and a total of 41,472 DoA findings were detected. Amphetamine (27%), buprenorphine (25%), nordiazepam (18%) and alprazolam (16%) were most prevalent. New psychoactive substances were detected in 189 samples (1.0%). The occurrence of polydrug use was common; 34% of the positive samples contained three analytes or more and 12% six or more. To the best of our knowledge, this is the first method for comprehensive analysis of DoA in OF using LC-HRMS and the largest dataset published on the detection of DoA in OF. With the current complex and variable drug use pattern, this broad, cost-effective and reliable method has largely replaced immunoassay screening in urine in our laboratory.
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| 21. |
- Axelsson, Kristian F, 1973, et al.
(author)
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Eating disorders are associated with increased risk of fall injury and fracture in Swedish men and women
- 2022
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 33, s. 1347-1355
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Journal article (peer-reviewed)abstract
- A Summary In this retrospective cohort study, men and women with eating disorders (n = 8867) had higher risk of injurious falls and hip fractures than age, sex, and county-matched controls (n = 88670). Introduction Eating disorders have been associated with decreased bone mineral density and increased fracture risk, but the association with fall injuries without fracture has not previously been investigated. Furthermore, fracture risk in men with eating disorders has been insufficiently studied. Methods In the present study, 8867 patients (9.4% men) with a diagnosed eating disorders and 88670 age-, sex-, and county-matched controls were investigated. Results The mean (standard deviation) age of the patients and controls was 41.6 (13.7) years and the follow-up time 9.6 (5.2, 14.4) years (median, interquartile range) for patients and 10.1 (5.5, 14.2) years for controls. The proportions of injurious falls without fracture (17.3% vs. 9.0%) and of hip fracture (1.6% vs. 0.7%) were substantially greater in patients with an eating disorder than in their corresponding population controls. In an unadjusted Cox proportional hazards model, individuals with an eating disorder had a higher risk of injurious falls without fracture (Hazard ratio (HR) 95% confidence interval (CI): 2.07 (1.96-2.18), and hip fracture (HR 2.30 (1.92-2.75)) than the risk observed in the controls. The HR for any investigated outcome associated with an eating disorder did not differ by sex or age (interaction term p > 0.10). The risk of injurious falls without fracture and hip fracture was increased in both women (HR 2.07 (1.95-2.19) and HR 2.41 (1.98-2.93), respectively) and men (HR 2.09 (1.76-2.49) and HR 1.84(1.12-3.02), respectively), with an eating disorder. Conclusion The risk of injurious falls without fracture and of hip fracture is increased in both women and men with eating disorders, indicating measures to prevent both falls and fractures are important in these patients, regardless of age and
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| 22. |
- Axelsson, Malin, et al.
(author)
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Lived experiences: a focus group pilot study within the MentALLY project of mental healthcare among European users
- 2020
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In: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 20:1
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Journal article (peer-reviewed)abstract
- BackgroundMental healthcare is an important component in societies' response to mental health problems. Although the World Health Organization highlights availability, accessibility, acceptability and quality of healthcare as important cornerstones, many Europeans lack access to mental healthcare of high quality. Qualitative studies exploring mental healthcare from the perspective of people with lived experiences would add to previous research and knowledge by enabling in-depth understanding of mental healthcare users, which may be of significance for the development of mental healthcare. Therefore, the aim of the current study was to describe experiences of mental healthcare among adult Europeans with mental health problems.MethodIn total, 50 participants with experiences of various mental health problems were recruited for separate focus group interviews in each country. They had experiences from both the private and public sectors, and with in- and outpatient mental healthcare. The focus group interviews (N=7) were audio recorded, transcribed verbatim and analysed through thematic analysis. The analysis yielded five themes and 13 subthemes.ResultsThe theme Seeking and trying to find help contained three subthemes describing personal thresholds for seeking professional help, not knowing where to get help, and the importance of receiving help promptly. The theme Awaiting assessment and treatment contained two subthemes including feelings of being prioritized or not and feelings of being abandoned during the often-lengthy referral process. The theme Treatment: a plan with individual parts contained three subthemes consisting of demands for tailored treatment plans in combination with medications and human resources and agreement on treatment. The theme Continuous and respectful care relationship contained two subthemes describing the importance of continuous care relationships characterised by empathy and respect. The theme Suggestions for improvements contained three subthemes highlighting an urge to facilitate care contacts and to increase awareness of mental health problems and a wish to be seen as an individual with potential.ConclusionFacilitating contacts with mental healthcare, a steady contact during the referral process, tailored treatment and empathy and respect are important aspects in efforts to improve mental healthcare. Recommendations included development of collaborative practices between stakeholders in order to increase general societal awareness of mental health problems.
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| 23. |
- Azeli, Y., et al.
(author)
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Clinical outcomes and safety of passive leg raising in out-of-hospital cardiac arrest : a randomized controlled trial
- 2021
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In: Critical Care. - : Springer Nature. - 1364-8535 .- 1466-609X. ; 25:1
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Journal article (peer-reviewed)abstract
- Background: There are data suggesting that passive leg raising (PLR) improves hemodynamics during cardiopulmonary resuscitation (CPR). This trial aimed to determine the effectiveness and safety of PLR during CPR in out-of-hospital cardiac arrest (OHCA).Methods: We conducted a randomized controlled trial with blinded assessment of the outcomes that assigned adults OHCA to be treated with PLR or in the flat position. The trial was conducted in the Camp de Tarragona region. The main end point was survival to hospital discharge with good neurological outcome defined as cerebral performance category (CPC 1–2). To study possible adverse effects, we assessed the presence of pulmonary complications on the first chest X-rays, brain edema on the computerized tomography (CT) in survivors and brain and lungs weights from autopsies in non-survivors.Results: In total, 588 randomized cases were included, 301 were treated with PLR and 287 were controls. Overall, 67.8% were men and the median age was 72 (IQR 60–82) years. At hospital discharge, 3.3% in the PLR group and 3.5% in the control group were alive with CPC 1–2 (OR 0.9; 95% CI 0.4–2.3, p = 0.91). No significant differences in survival at hospital admission were found in all patients (OR 1.0; 95% CI 0.7–1.6, p = 0.95) and among patients with an initial shockable rhythm (OR 1.7; 95% CI 0.8–3.4, p = 0.15). There were no differences in pulmonary complication rates in chest X-rays [7 (25.9%) vs 5 (17.9%), p = 0.47] and brain edema on CT [5 (29.4%) vs 10 (32.6%), p = 0.84]. There were no differences in lung weight [1223 mg (IQR 909–1500) vs 1239 mg (IQR 900–1507), p = 0.82] or brain weight [1352 mg (IQR 1227–1457) vs 1380 mg (IQR 1255–1470), p = 0.43] among the 106 autopsies performed.Conclusion: In this trial, PLR during CPR did not improve survival to hospital discharge with CPC 1–2. No evidence of adverse effects has been found.Clinical trial registration ClinicalTrials.gov: NCT01952197, registration date: September 27, 2013, https://clinicaltrials.gov/ct2/show/NCT01952197. [Figure not available: see fulltext.]
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| 24. |
- Eriksen, J., et al.
(author)
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Contagiousness in treated HIV-1 infection
- 2021
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In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 53:1, s. 1-8
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Research review (peer-reviewed)abstract
- Background Effective antiretroviral treatment of HIV-1, defined as continuously undetectable virus in blood, has substantial effects on the infectiousness and spread of HIV. Aim This paper outlines the assessment of the Swedish Reference Group for Antiviral Therapy (RAV) and Public Health Agency of Sweden regarding contagiousness of HIV-infected persons on antiretroviral therapy (ART). Results and Conclusion:The expert group concludes that there is no risk of transmission of HIV during vaginal or anal intercourse if the HIV-infected person fulfils the criteria for effective ART. Summary:The effective antiretroviral therapy (ART) for HIV-1 infection has dramatically reduced the morbidity and mortality among people who live with HIV. ART also has a noticeable effect on the infectiousness and on the spread of the disease in society. Knowledge about this has grown gradually. For ART to be regarded effective, the level of the HIV RNA in the plasma should be repeatedly and continuously undetectable and the patient should be assessed as continually having high adherence to treatment. Based on available knowledge the Swedish Reference Group for Antiviral Therapy (RAV) and the Public Health Agency of Sweden make the following assessment: There is no risk of HIV transmission during vaginal or anal intercourse if the HIV positive person fulfils the criteria for effective treatment. This includes intercourse where a condom is not used. However, there are a number of other reasons for recommending the use of condoms, primarily to protect against the transmission of other STIs (sexually transmitted infections) and hepatitis, as well as unwanted pregnancy. The occurrence of other STIs does not affect the risk of HIV transmission in persons on effective ART. It is plausible that the risk for transmission of HIV infection between people who inject drugs and share injection equipment is reduced if the individual with HIV is on effective ART, but there are no studies that directly show this. The risk of transmission from mother to child during pregnancy, labour and delivery is very low if the mother's treatment is initiated well before delivery and if the treatment aim of undetectable virus levels is attained. This is dependent on healthcare services being aware of the mother's HIV infection at an early stage. In most contacts with health and medical care, including dental care, the risk of transmission is not significant if the patient is on effective treatment, but the risk may remain, although considerably reduced, in more advanced interventions such as surgery. When an incident with risk of transmission occurs, the patient must always inform those potentially exposed about his or her HIV infection.
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| 25. |
- Forsgård, Richard A., 1987-, et al.
(author)
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Limosilactobacillus reuteri DSM 17938 supplementation and SARS-CoV-2 specific antibody response in healthy adults : a randomized, triple-blinded, placebo-controlled trial
- 2023
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In: Gut microbes. - : Taylor & Francis. - 1949-0976 .- 1949-0984. ; 15:1
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Journal article (peer-reviewed)abstract
- Studies have shown that probiotics can decrease the symptoms of respiratory tract infections as well as increase antibody responses following certain vaccinations. We examined the effect of probiotic supplementation on anti-SARS-CoV-2 specific antibody responses upon SARS-CoV-2 infection as well as after COVID-19 vaccination. In this randomized, triple-blinded, placebo-controlled intervention study with a parallel design, 159 healthy adults without prior SARS-CoV-2 infection or COVID-19 vaccination and any known risk factors for severe COVID-19 were randomly allocated into two study arms. The active treatment arm consumed a probiotic product containing a minimum of 1 × 108 colony-forming units of Limosilactobacillus reuteri DSM 17938 + 10 μg vitamin D3 twice daily for 6 months. The placebo arm consumed identical tablets containing only 10 μg vitamin D3. Anti-SARS-CoV-2 specific antibodies and virus neutralizing antibody titers were analyzed from blood samples collected at baseline, after 3 months, and after 6 months. Differences in serum antibody titers between the two study arms were tested with independent t-test using log-transformed values. In the intention-to-treat (ITT) analysis, SARS-CoV-2 infected individuals in the active treatment arm (n = 6) tended to have higher serum anti-spike IgG (609 [168-1480] BAU/ml vs 111 [36.1-1210] BAU/ml, p = 0.080) and anti-receptor binding domain (RBD) IgG (928 [212-3449] BAU/ml vs (83.7 [22.8-2094] BAU/ml, p = 0.066) levels than individuals in the placebo arm (n = 6). Considering individuals who were fully vaccinated with mRNA-based COVID-19 vaccines, the active treatment arm (n = 10) exhibited significantly higher serum levels of anti-RBD IgA (135 [32.9-976] BAU/ml vs 61.3 [26.7-97.1] BAU/ml, p = 0.036) than the placebo arm (n = 7) >28 days postvaccination. Supplementation with specific probiotics might improve the long-term efficacy of mRNA-based COVID-19 vaccines via enhanced IgA response.
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| 26. |
- Forte, Castela, et al.
(author)
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Deep Learning for Identification of Acute Illness and Facial Cues of Illness
- 2021
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In: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
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Journal article (peer-reviewed)abstract
- Background: The inclusion of facial and bodily cues (clinical gestalt) in machine learning (ML) models improves the assessment of patients' health status, as shown in genetic syndromes and acute coronary syndrome. It is unknown if the inclusion of clinical gestalt improves ML-based classification of acutely ill patients. As in previous research in ML analysis of medical images, simulated or augmented data may be used to assess the usability of clinical gestalt.Objective: To assess whether a deep learning algorithm trained on a dataset of simulated and augmented facial photographs reflecting acutely ill patients can distinguish between healthy and LPS-infused, acutely ill individuals.Methods: Photographs from twenty-six volunteers whose facial features were manipulated to resemble a state of acute illness were used to extract features of illness and generate a synthetic dataset of acutely ill photographs, using a neural transfer convolutional neural network (NT-CNN) for data augmentation. Then, four distinct CNNs were trained on different parts of the facial photographs and concatenated into one final, stacked CNN which classified individuals as healthy or acutely ill. Finally, the stacked CNN was validated in an external dataset of volunteers injected with lipopolysaccharide (LPS).Results: In the external validation set, the four individual feature models distinguished acutely ill patients with sensitivities ranging from 10.5% (95% CI, 1.3-33.1% for the skin model) to 89.4% (66.9-98.7%, for the nose model). Specificity ranged from 42.1% (20.3-66.5%) for the nose model and 94.7% (73.9-99.9%) for skin. The stacked model combining all four facial features achieved an area under the receiver characteristic operating curve (AUROC) of 0.67 (0.62-0.71) and distinguished acutely ill patients with a sensitivity of 100% (82.35-100.00%) and specificity of 42.11% (20.25-66.50%).Conclusion: A deep learning algorithm trained on a synthetic, augmented dataset of facial photographs distinguished between healthy and simulated acutely ill individuals, demonstrating that synthetically generated data can be used to develop algorithms for health conditions in which large datasets are difficult to obtain. These results support the potential of facial feature analysis algorithms to support the diagnosis of acute illness.
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- Kalarakis, G, et al.
(author)
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Combining contrast-enhanced ultrasound, CT perfusion and 99mTc-Sestamibi SPECT/CT to guide diagnosis in a case of solid renal tumour
- 2021
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In: BJR case reports. - : British Institute of Radiology. - 2055-7159. ; 7:1, s. 20200115-
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Journal article (other academic/artistic)abstract
- Definitive, pre-operative differentiation of solid renal lesions by ultrasound, contrast-enhanced multiphasic CT or MRI examinations is often not possible. An increasing amount of literature indicates the added value of 99mTc-Sestamibi SPECT/CT, CT perfusion and contrast-enhanced ultrasound in the pre-operative characterisation of solid renal tumours. This case report presents the diagnostic approach of a solid renal tumour that turned out to be a hybrid oncocytic chromophobe tumour in a patient with Stage 3 renal failure by combining the three aforementioned modern examination techniques.
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- Larsson, Berit A M, et al.
(author)
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One leg standing time predicts fracture risk in older women independent of clinical risk factors and BMD
- 2022
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 33, s. 185-194
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Journal article (peer-reviewed)abstract
- In women of ages 75-80 years, a low one leg standing time (OLST) was associated with an increased risk of incident fractures, independently of bone mineral density and clinical risk factors. OLST contributed substantially to fracture probability, indicating that the test should be considered when evaluating fracture risk in older women. Introduction Physical function and risk of falls are important risk factors for fracture. A few previous studies have suggested that a one leg standing time (OLST) less than 10 s predicts fracture risk, but the impact of OLST, in addition to known clinical risk factors, for fracture probability is unknown. The aim of this study was to determine the independent contribution of OLST to fracture probability in older women. Methods The Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study of 3028 women 75-80 years old, recruited from the greater Gothenburg area in Sweden. At baseline, information on risk factors was collected using questionnaires, bone mineral density was measured with dual-energy X-ray absorptiometry (DXA), and OLST was performed. Results During a median follow-up of 3.6 years (IQR 1.5 years), X-ray-verified incident fractures were identified using health records. OLST was available in 2405 women. OLST less than 10 s was associated with an increased risk for incident hip fracture (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) [1.49-6.10]), major osteoporotic fracture (HR 95% CI 1.76 [1.34-1.46]), and nonvertebral fracture (HR 95% CI 1.61 [1.26-2.05]) in Cox regression analyses adjusted for age, height, and weight. Depending on BMD, the 4-year fracture probability increased by a factor of 1.3 to 1.5 in a 75-year-old woman with a low OLST (<10 s). Conclusion A low OLST has a substantial impact on fracture probability and should be considered when evaluating fracture risk in older women.
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| 35. |
- Larsson, B. A. M., et al.
(author)
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The timed up and go test predicts fracture risk in older women independently of clinical risk factors and bone mineral density
- 2021
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In: Osteoporosis International. - : SPRINGER LONDON LTD. - 0937-941X .- 1433-2965. ; 32, s. 75-84
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Journal article (peer-reviewed)abstract
- The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. In older women, TUG time predicts the risk of major osteoporotic fracture and hip fracture independently of clinical risk factors and bone mineral density, and has a substantial impact on fracture probabilities. Introduction The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. A slow TUG has been associated with an increased fracture risk, but it is unclear whether the association is independent of clinical risk factors and bone mineral density (BMD). The aim of this study was to investigate if TUG time was associated with fracture risk independently of clinical risk factors and BMD and to determine its impact on fracture probabilities in older women. Methods A standardized questionnaire was used to assess information regarding clinical risk factors in the large population-based SUPERB study of 3028 older women (75-80 years). At baseline, the TUG test was performed and BMD measured with DXA. The association between TUG time and the risk of hip fracture and major osteoporotic fracture (MOF) was examined using an extension of Poisson regression. Results Fracture incidence increased steeply with increasing TUG time up to 12 s and subsequently started to level off. A slow TUG time was therefore defined as TUG > 12 s, a cutoff level then used in Cox models to study the association between slow TUG and fracture risk. A slow TUG time was associated with an increased risk of fracture (MOF 2.39 [1.80-3.18] and hip fracture 2.96 [1.62-5.40]). These associations were slightly attenuated but remained significant after adjustment for clinical risk factors and femoral neck BMD. Depending on BMD, the 4-year fracture probability of MOF increased by a factor of 1.5-1.9 in a 75-year-old woman with slow TUG (> 12 s). Conclusion The TUG time predicts the risk of MOF and hip fracture independently of clinical risk factors and BMD and has a substantial impact on fracture probabilities, indicating that inclusion of the TUG test in patient evaluation should be considered in order to improve fracture prediction in older women.
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| 39. |
- Siltari, A., et al.
(author)
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How Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis
- 2023
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In: Clinical Genitourinary Cancer. - : Elsevier BV. - 1558-7673. ; 21:2, s. 1-316
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Journal article (peer-reviewed)abstract
- Objectives: Genome-wide association studies have revealed over 200 genetic susceptibility loci for prostate cancer (PCa). By combining them, polygenic risk scores (PRS) can be generated to predict risk of PCa. We summarize the published evidence and conduct meta-analyses of PRS as a predictor of PCa risk in Caucasian men. Patients and methods: Data were extracted from 59 studies, with 16 studies including 17 separate analyses used in the main meta-analysis with a total of 20,786 cases and 69,106 controls identified through a systematic search of ten databases. Random effects meta-analysis was used to obtain pooled estimates of area under the receiver-operating characteristic curve (AUC). Meta-regression was used to assess the impact of number of single-nucleotide polymorphisms (SNPs) incorporated in PRS on AUC. Heterogeneity is expressed as I2 scores. Publication bias was evaluated using funnel plots and Egger tests. Results: The ability of PRS to identify men with PCa was modest (pooled AUC 0.63, 95% CI 0.62-0.64) with moderate consistency (I2 64%). Combining PRS with clinical variables increased the pooled AUC to 0.74 (0.68-0.81). Meta-regression showed only negligible increase in AUC for adding incremental SNPs. Despite moderate heterogeneity, publication bias was not evident. Conclusion: Typically, PRS accuracy is comparable to PSA or family history with a pooled AUC value 0.63 indicating mediocre performance for PRS alone. © 2022
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- Altena, Renske, et al.
(author)
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Current status of contemporary diagnostic radiotracers in the management of breast cancer : first steps toward theranostic applications
- 2023
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In: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 13:1
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Research review (peer-reviewed)abstract
- BackgroundExpanding therapeutic possibilities have improved disease-related prospects for breast cancer patients. Pathological analysis on a tumor biopsy is the current reference standard biomarker used to select for treatment with targeted anticancer drugs. This method has, however, several limitations, related to intra- and intertumoral as well as spatial heterogeneity in receptor expression as well as the need to perform invasive procedures that are not always technically feasible.Main bodyIn this narrative review, we focus on the current role of molecular imaging with contemporary radiotracers for positron emission tomography (PET) in breast cancer. We provide an overview of diagnostic radiotracers that represent treatment targets, such as programmed death ligand 1, human epidermal growth factor receptor 2, polyadenosine diphosphate-ribose polymerase and estrogen receptor, and discuss developments in therapeutic radionuclides for breast cancer management.ConclusionImaging of treatment targets with PET tracers may provide a more reliable precision medicine tool to find the right treatment for the right patient at the right time. In addition to visualization of the target of treatment, theranostic trials with alpha- or beta-emitting isotopes provide a future treatment option for patients with metastatic breast cancer.
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| 44. |
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| 45. |
- Andreasson, Anna, et al.
(author)
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Poor sleep quality is associated with worse self-rated health in long sleep duration but not short sleep duration
- 2021
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In: Sleep Medicine. - : Elsevier BV. - 1389-9457 .- 1878-5506. ; 88, s. 262-266
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Journal article (peer-reviewed)abstract
- Unhealthy sleep duration, either short or long, is associated with worse health and central subjective dimensions of sleep and health such as fatigue. It has been argued that the link between sleep duration and health may depend on the quality of the slept hours, and on its functional impact (ie, fatigue). The present study therefore assessed whether the relationship between last night's sleep duration and general self-rated health (SRH) differs as a function of sleep quality, and secondly, whether current fatigue and sleep quality are factors linking sleep duration and SRH. The present cross-sectional dataset involved 1304 individuals (57% female, M age = 28.8, range 18-79). Participants completed surveys for general SRH, previous night's sleep duration and sleep quality, and current fatigue. Results showed the expected inverted U-shaped (ie, quadratic) relation between last night's sleep duration and SRH and a linear relation between last night's sleep quality and SRH. However, long sleep duration was only associated with poorer SRH in individuals who also reported poor sleep quality. Further, the quadratic relationship between sleep duration and SRH was partially mediated by fatigue and sleep quality. The results of this multi-study analysis suggest that SRH is particularly poor in those who slept both long and with poor quality the night before, while good sleep quality may protect those with a long sleep duration from poor SRH. Thus, last night's long sleep does not seem to be associated with poor subjective health unless it is coupled with poor sleep quality. Furthermore, fatigue and sleep quality are potential pathways linking short and long sleep duration with SRH. Different dimensions of sleep interact in their association with health, and future research will benefit from an integrative approach.
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| 46. |
- Ashton, Nicholas J., et al.
(author)
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A multicentre validation study of the diagnostic value of plasma neurofilament light
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-12
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Journal article (peer-reviewed)abstract
- Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
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- Axelsson, Kristian F, 1973, et al.
(author)
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Analysis of Comorbidities, Clinical Outcomes, and Parathyroidectomy in Adults With Primary Hyperparathyroidism
- 2022
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In: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:6
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Journal article (peer-reviewed)abstract
- IMPORTANCE Patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials. OBJECTIVE To investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes. DESIGN, SETTING, AND PARTICIPANTS This cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022. MAIN OUTCOMES AND MEASURES The primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs). RESULTS A total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pH PT group and 803 522 person-years for the control group. Compared with the control group, the pH PT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65). CONCLUSIONS AND RELEVANCE Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.
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