| 1. |
- Bergqvist, Michael, et al.
(författare)
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Real world utilization of EGFR TKIs and prognostic factors for survival in NSCLC during 2010-2016 in Sweden : A nationwide observational study
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:9, s. 2510-2517
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of our study was to investigate time trends in treatment pattern and prognostic factors for overall survival (OS) in epidermal growth factor receptor (EGFR) targeting tyrosine kinase inhibitors (TKIs) treated nonsmall cell lung cancer (NSCLC) patients. Utilizing Swedish nationwide registers, we identified all Stage IIIB-IV NSCLC patients treated with EGFR TKIs and followed them from diagnosis (2010-2015) until death or end of observation (2016). Multivariable Cox regression analyses were performed to test associations of patient-, tumor-related factors with OS. Of 9,992 Stage IIIB-IV NSCLC patients, the 1,419 (14%) who initiated EGFR TKI treatment during observation were younger (median age 68 vs. 71 years), less >= 1 comorbidities (34% vs. 46%), more often female (59% vs. 47%), Stage IV (89% vs. 85%) and adenocarcinoma (85% vs. 66%) compared to non-TKI treated patients. After TKI initiation, 7% (n = 100) of the patients switched, 4% (n = 62) rechallenged a TKI treatment, 65% (n = 919) discontinued and 24% (n = 338) had died. A more recent diagnosis demonstrated shorter time to EGFR TKI initiation, prolonged treatment length and longer median OS (15.3 months 2010-2011; 14.4 months 2012-2013; 18.6 months 2014-2015). Prognostic factors for longer OS when treated with EGFR TKIs were younger age, adenocarcinoma, less advanced clinical stage and less comorbid disease. In conclusion, during the observation period, survival improved for EGFR TKI treated NSCLC patients, as did the accessibility for targeted therapies for these patients.
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| 2. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 3. |
- Danielsson, Mattias, et al.
(författare)
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Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery.
- 2021
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Ingår i: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 126:2, s. 467-76
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Tidskriftsartikel (refereegranskat)abstract
- Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function.In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid β (Aβ1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery.CSF and blood concentrations of T-tau, neurone-specific enolase, and Aβ1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aβ1-42.The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.
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| 4. |
- Holmner, Åsa, et al.
(författare)
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How stable is lung function in patients with stable chronic obstructive pulmonary disease when monitored using a telehealth system? : A longitudinal and home-based study
- 2020
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Ingår i: BMC Medical Informatics and Decision Making. - : BioMed Central. - 1472-6947. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many telehealth systems have been designed to identify signs of exacerbations in patients with chronic obstructive pulmonary disease (COPD), but few previous studies have reported the nature of recorded lung function data and what variations to expect in this group of individuals. The aim of the study was to evaluate the nature of individual diurnal, day-to-day and long-term variation in important prognostic markers of COPD exacerbations by employing a telehealth system developed in-house.Methods: Eight women and five men with COPD performed measurements (spirometry, pulse oximetry and the COPD assessment test (CAT)) three times per week for 4-6 months using the telehealth system. Short-term and long-term individual variations were assessed using the relative density and weekly means respectively. Quality of the spirometry measurements (forced expiratory volume in one second (FEV1) and inspiratory capacity (IC)) was assessed employing the criteria of American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines.Results: Close to 1100 measurements of both FEV1 and IC were performed during a total of 240 patient weeks. The two standard deviation ranges for intra-individual short-term variation were approximately +/- 210 mL and +/- 350 mL for FEV1 and IC respectively. In long-term, spirometry values increased and decreased without notable changes in symptoms as reported by CAT, although it was unusual with a decrease of more than 50 mL per measurement of FEV1 between three consecutive measurement days. No exacerbation occurred. There was a moderate to strong positive correlation between FEV1 and IC, but weak or absent correlation with the other prognostic markers in the majority of the participants.Conclusions: Although FEV1 and IC varied within a noticeable range, no corresponding change in symptoms occurred. Therefore, this study reveals important and, to our knowledge, previously not reported information about short and long-term variability in prognostic markers in stable patients with COPD. The present data are of significance when defining criteria for detecting exacerbations using telehealth strategies.
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| 5. |
- Janson, Christer, et al.
(författare)
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Management and Risk of Mortality in Patients Hospitalised Due to a First Severe COPD Exacerbation
- 2020
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : DOVE MEDICAL PRESS LTD. - 1176-9106 .- 1178-2005. ; 15, s. 2673-2682
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reducing the need for hospitalisation in patients with chronic obstructive pulmonary disease (COPD) is an important goal in COPD management. The aim of this study was to evaluate re-hospitalisation, treatment, comorbidities and mortality in patients with COPD who were hospitalised for the first time due to a COPD exacerbation.Methods: This was a retrospective, population-based observational cohort study of Swedish patients using linked data from three mandatory national health registries to assess re-hospitalisation rates, medication use and mortality. Rate of hospitalisation was calculated using the number of events divided by the number of person-years at risk; risk of all-cause and COPD-related mortality were assessed using Cox proportional hazard models.Results: In total, 51,247 patients were identified over 10 years; 35% of patients were not using inhaled corticosteroid, long-acting muscarinic antagonist or long-acting beta(2)-agonist treatment prior to hospitalisation, 38% of whom continued without treatment after being discharged. Re-hospitalisation due to a second severe exacerbation occurred in 11.5%, 17.8% and 24% of the patients within 30, 90 and 365 days, respectively. Furthermore, 24% died during the first year following hospitalisation and risk of all-cause and COPD-related mortality increased with every subsequent re-hospitalisation. Comorbidities, including ischaemic heart disease, heart failure and pneumonia, were more common amongst patients who were re-hospitalised than those who were not.Conclusion: Following hospitalisation for first severe COPD exacerbation, many patients did not collect the treatment recommended by current guidelines. Risk of mortality increased with every subsequent re-hospitalisation. Patients with concurrent comorbidities had an increased risk of being re-hospitalised.
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| 6. |
- Månsson, Linda, et al.
(författare)
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Co-Creation with Older Adults to Improve User-Experience of a Smartphone Self-Test Application to Assess Balance Function
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- This co-creation study aimed to develop a smartphone self-test application for balance and leg strength in collaboration between older adults and the research team. The paper describes older participants' preferences for, and their contribution to, the application design. Technology to assess movements is available in smartphones with built-in sensors, and one of the challenges is to develop a valuable self-test for older adults. The participants contributed to the design of the application's instructions and user interface. Multiple data collection methods were used: user-test with Think aloud method, mock-ups, homework assignment as co-researcher, audio and video recordings. Qualitative content analysis with a deductive-inductive approach was used, guided by the Optimized Honeycomb model for user experience (UX) as a categorization matrix. The analysis resulted in 17 subcategories within the seven facets of the UX Honeycomb model (findable, accessible, usable, desirable, credible, useful, and valuable), and describes the older participants' preferences and experiences. The main results were participants' desire to know why, to get clear and appropriate information, and expectations of the self-test to be useful. It was feasible and valuable to develop the self-test application in co-creation with the intended user-group, in order to get direct feedback and suggestions for the development.
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| 7. |
- 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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| 8. |
- Nwaru, Bright I, 1978, et al.
(författare)
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Overuse of short-acting β2-agonists in asthma is associated with increased risk of exacerbation and mortality : A nationwide cohort study of the global SABINA programme
- 2020
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 55:4
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Tidskriftsartikel (refereegranskat)abstract
- Overuse of short-acting β2-agonists (SABA) may indicate poor asthma control and adverse health outcomes. Contemporary population-based data on use, risk factors and impact of SABA (over)use on asthma exacerbations and mortality are scarce, prompting initiation of the global SABINA (SABA use IN Asthma) programme.MethodsBy linking data from Swedish national registries, asthma patients aged 12–45 years with two or more collections of drugs for obstructive lung disease during 2006–2014 were included. SABA overuse was defined as collection of more than two SABA canisters in a 1-year baseline period following inclusion. SABA use was grouped into 3–5, 6–10 and ≥11 canisters per baseline-year. Cox regression was used to examine associations between SABA use and exacerbation (hospitalisations and/or oral corticosteroid claims) and mortality.ResultsThe analysis included 365 324 asthma patients (mean age 27.6 years; 55% female); average follow-up was 85.4 months. 30% overused SABA, with 21% collecting 3–5 canisters per year, 7% collecting 6–10 canisters per year and 2% collecting ≥11 canisters per year. Increasing number of collected SABA canisters was associated with increased risk of exacerbation, as follows. 3–5 canisters: hazard ratio (HR) 1.26 (95% CI 1.24–1.28); 6–10 canisters: 1.44 (1.41–1.46); and ≥11 canisters: 1.77 (1.72–1.83), compared to two or fewer canisters per year. Higher SABA use was associated with incrementally increased mortality risk (2564 deaths observed), as follows. 3–5 canisters: HR 1.26 (95% CI 1.14–1.39); 6–10 canisters 1.67 (1.49–1.87); and ≥11 canisters: 2.35 (2.02–2.72) compared to two or fewer canisters per year.ConclusionOne-third of asthma patients in Sweden collected three or more SABA canisters annually. SABA overuse was associated with increased risks of exacerbation and mortality. These findings emphasise that monitoring of SABA usage should be key in improving asthma management.
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| 9. |
- Nylund, Patrick, et al.
(författare)
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A distinct metabolic response characterizes sensitivity to EZH2 inhibition in multiple myeloma
- 2021
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Ingår i: Cell Death and Disease. - : Springer Nature. - 2041-4889. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a heterogeneous haematological disease that remains clinically challenging. Increased activity of the epigenetic silencer EZH2 is a common feature in patients with poor prognosis. Previous findings have demonstrated that metabolic profiles can be sensitive markers for response to treatment in cancer. While EZH2 inhibition (EZH2i) has proven efficient in inducing cell death in a number of human MM cell lines, we hereby identified a subset of cell lines that despite a global loss of H3K27me3, remains viable after EZH2i. By coupling liquid chromatography-mass spectrometry with gene and miRNA expression profiling, we found that sensitivity to EZH2i correlated with distinct metabolic signatures resulting from a dysregulation of genes involved in methionine cycling. Specifically, EZH2i resulted in a miRNA-mediated downregulation of methionine cycling-associated genes in responsive cells. This induced metabolite accumulation and DNA damage, leading to G2 arrest and apoptosis. Altogether, we unveiled that sensitivity to EZH2i in human MM cell lines is associated with a specific metabolic and gene expression profile post-treatment.
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