| 1. |
- Angelstam, Per, et al.
(författare)
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Learning about the history of landscape use for the future : consequences for ecological and social systems in Swedish Bergslagen
- 2013
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 42:2, s. 146-159
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Tidskriftsartikel (refereegranskat)abstract
- Barriers and bridges to implement policies about sustainable development and sustainability commonly depend on the past development of social-ecological systems. Production of metals required integration of use of ore, streams for energy, and wood for bioenergy and construction, as well as of multiple societal actors. Focusing on the Swedish Bergslagen region as a case study we (1) describe the phases of natural resource use triggered by metallurgy, (2) the location and spatial extent of 22 definitions of Bergslagen divided into four zones as a proxy of cumulative pressure on landscapes, and (3) analyze the consequences for natural capital and society. We found clear gradients in industrial activity, stream alteration, and amount of natural forest from the core to the periphery of Bergslagen. Additionally, the legacy of top-down governance is linked to today's poorly diversified business sector and thus municipal vulnerability. Comparing the Bergslagen case study with other similar regions in Russia and Germany, we discuss the usefulness of multiple case studies.
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| 2. |
- Arruda, Lucas C. M., et al.
(författare)
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A novel CD34-specific T-cell engager efficiently depletes acute myeloid leukemia and leukemic stem cells in vitro and in vivo
- 2022
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 107:8, s. 1786-1795
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Tidskriftsartikel (refereegranskat)abstract
- Less than a third of patients with acute myeloid leukemia (AML) are cured by chemotherapy and/or hematopoietic stem cell transplantation, highlighting the need to develop more efficient drugs. The low efficacy of standard treatments is associated with inadequate depletion of CD34(+) blasts and leukemic stem cells, the latter a drug-resistant subpopulation of leukemia cells characterized by the CD34(+)CD38(-) phenotype. To target these drug-resistant primitive leukemic cells better, we have designed a CD34/CD3 bi-specific T-cell engager (BTE) and characterized its anti-leukemia potential in vitro, ex vivo and in vivo. Our results show that this CD34-specific BTE induces CD34-dependent T-cell activation and subsequent leukemia cell killing in a dose-dependent manner, further corroborated by enhanced T-cell-mediated killing at the singlecell level. Additionally, the BTE triggered efficient T-cell-mediated depletion of CD34(+) hematopoietic stem cells from peripheral blood stem cell grafts and CD34(+) blasts from AML patients. Using a humanized AML xenograft model, we confirmed that the CD34-specific BTE had in vivo efficacy by depleting CD34(+) blasts and leukemic stem cells without side effects. Taken together, these data demonstrate that the CD34-specific BTE has robust antitumor effects, supporting development of a novel treatment modality with the aim of improving outcomes of patients with AML and myelodysplastic syndromes.
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| 3. |
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| 4. |
- Axelsson, Kristian F, 1973, et al.
(författare)
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Analysis of Comorbidities, Clinical Outcomes, and Parathyroidectomy in Adults With Primary Hyperparathyroidism
- 2022
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Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:6
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Axelsson, Kristian F, 1973, et al.
(författare)
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Association Between Alendronate Use and Hip Fracture Risk in Older Patients Using Oral Prednisolone
- 2017
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Ingår i: Jama-Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 318:2, s. 146-155
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Oral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids. OBJECTIVE To investigate whether alendronate treatment in older patients using oral prednisolone is associated with decreased hip fracture risk and adverse effects. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using a national database (N = 433 195) of patients aged 65 years or older undergoing a health evaluation (baseline) at Swedish health care facilities; 1802 patients who were prescribed alendronate after at least 3 months of oral prednisolone treatment (>= 5mg/d) were identified. Propensity score matching was used to select 1802 patients without alendronate use from 6076 patients taking prednisolone with the same dose and treatment time criteria. Follow-up occurred between January 2008 and December 2014. EXPOSURES Alendronate vs no alendronate use; no patients had previously taken alendronate at the time of prednisolone initiation. MAIN OUTCOMES AND MEASURES The primary outcome was incident hip fracture. RESULTS Of the 3604 included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34 years), there were 27 hip fractures in the alendronate group and 73 in the no-alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and 27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate difference of -17.6 (95% CI, -24.8 to -10.4). The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3-18.0] per 1000 person-years; P=.40) or peptic ulcers (10.9 [95% CI, 7.7-15.5] vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years; P=.86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group. CONCLUSIONS AND RELEVANCE Among older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group.
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| 6. |
- Axelsson, Kristian F., et al.
(författare)
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Association Between Recurrent Fracture Risk and Implementation of Fracture Liaison Services in Four Swedish Hospitals: A Cohort Study
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:7, s. 1216-1223
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research Structured secondary preventions programs, called fracture liaison services (FLSs), increase the rate of evaluation with bone densitometry and use of osteoporosis medication after fracture. However, the evidence regarding the effect on the risk of recurrent fracture is insufficient. The aim of this study was to investigate if implementation of FLS was associated with reduced risk of recurrent fractures. In this retrospective cohort study, electronic health records during 2012 to 2017 were used to identify a total of 21,083 patients from four hospitals in Western Sweden, two with FLS (n = 15,449) and two without (n = 5634). All patients aged 50 years or older (mean age 73.9 [SD 12.4] years, 76% women) with a major osteoporotic index fracture (hip, clinical spine, humerus, radius, and pelvis) were included. The primary outcome was recurrent major osteoporotic fracture. All patients with an index fracture during the FLS period (n = 13,946) were compared with all patients in the period before FLS implementation (n = 7137) in an intention-to-treat analysis. Time periods corresponding to the FLS hospitals were used for the non-FLS hospitals. In the hospitals with FLSs, there were 1247 recurrent fractures during a median follow-up time of 2.2 years (range 0–6 years). In an unadjusted Cox model, the risk of recurrent fracture was 18% lower in the FLS period compared with the control period (hazard ratio = 0.82, 95% confidence interval [CI] 0.73–0.92, p = 0.001), corresponding to a 3-year number needed to screen of 61, and did not change after adjustment for clinical risk factors. In the hospitals without FLSs, no change in recurrent fracture rate was observed. Treatment decisions were made according to the Swedish treatment guidelines. In conclusion, implementation of FLS was associated with a reduced risk of recurrent fracture, indicating that FLSs should be included routinely at hospitals treating fracture patients. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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| 7. |
- Axelsson, Kristian F, 1973, et al.
(författare)
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Comparison of Fractures Among Older Adults Who Are Ambulatory vs Those Who Use Wheelchairs in Sweden
- 2023
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Ingår i: JAMA NETWORK OPEN. - : American Medical Association (AMA). - 2574-3805. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- ImportanceSeveral diseases and conditions, such as cerebrovascular disease, arthritis, previous fractures, neurological diseases, or amputation, can result in severe immobility justifying wheelchair use for increased mobility. Immobility results in disuse osteoporosis and is considered a risk factor for fracture, although there are no large cohort studies that have investigated fracture risk in patients who use wheelchairs compared with an ambulatory control group.ObjectiveTo investigate whether immobilized adults who used wheelchairs had a different risk of fracture and injurious falls compared with matched ambulatory controls.Design, Setting, and ParticipantsThis retrospective cohort study compared patients who used wheelchairs and controls (propensity score matched 1:1 using 22 variables relating to anthropometrics, general condition, comorbidity, and fall and fracture risk), identified through a national database of adults 65 years or older who underwent a health evaluation (baseline) at Swedish health care facilities. Patients were followed up from January 1, 2007, to December 31, 2017, and data analysis was performed between June 1 and 30, 2022.Main Outcomes and MeasuresIncident fracture, injurious falls without fracture, and deaths.ResultsA total of 55 442 adults using wheelchairs were included in the analysis (mean [SD] age, 83.2 [8.3] years; 60.5% women). Those who used wheelchairs and the 55 442 matched controls were followed up for a median of 2.0 (IQR, 0.5-3.2) and 2.3 (IQR, 0.8-3.6) years, respectively. Patients who used wheelchairs had a lower risk of any fracture (hazard ratio [HR], 0.43 [95% CI, 0.41-0.44]), major osteoporotic fracture (HR, 0.32 [95% CI, 0.31-0.33]), and hip fracture (HR, 0.30 [95% CI, 0.28-0.32]) compared with the ambulatory controls, associations that were only marginally affected by multivariable (same as the matching variables) adjustment. The risk of fall injury was lower among those who used wheelchairs than among ambulatory controls (unadjusted HR for Cox proportional hazards models, 0.48 [95% CI, 0.47-0.50]) and remained highly similar after adjustments. Patients who used wheelchairs had a significantly increased risk of death (HR, 1.35 [95% CI, 1.33-1.36]) compared with controls. Association between wheelchair use and fracture outcomes and injurious falls, calculated using a Fine and Gray model with death as a competing risk, was similar to associations obtained using Cox proportional hazards regression for all fracture outcomes.Conclusions and RelevanceIn this retrospective cohort study of older adults, wheelchair use was associated with a lower risk of fracture than observed in ambulatory controls. These findings suggest that immobility associated with wheelchair use should not be considered a risk factor for fracture.
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| 8. |
- Axelsson, Kristian F, 1973, et al.
(författare)
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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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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 33, s. 1347-1355
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Axelsson, K. F., et al.
(författare)
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Effectiveness of a minimal resource fracture liaison service
- 2016
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 27:11, s. 3165-3175
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this study was to investigate if a 2-year intervention with a minimal resource fracture liaison service (FLS) was associated with increased investigation and medical treatment and if treatment was related to reduced re-fracture risk.METHODS: The FLS started in 2013 using existing secretaries (without an FLS coordinator) at the emergency department and orthopaedic wards to identify risk patients. All patients older than 50 years of age with a fractured hip, vertebra, shoulder, wrist or pelvis were followed during 2013-2014 (n = 2713) and compared with their historic counterparts in 2011-2012 (n = 2616) at the same hospital. Re-fractures were X-ray verified. A time-dependent adjusted (for age, sex, previous fracture, index fracture type, prevalent treatment, comorbidity and secondary osteoporosis) Cox model was used.RESULTS: The minimal resource FLS increased the proportion of DXA-investigated patients after fracture from 7.6 to 39.6 % (p < 0.001) and the treatment rate after fracture from 12.6 to 31.8 %, which is well in line with FLS types using the conventional coordinator model. Treated patients had a 51 % lower risk of any re-fracture than untreated patients (HR 0.49, 95 % CI 0.37-0.65 p < 0.001).CONCLUSIONS: We found that our minimal resource FLS was effective in increasing investigation and treatment, in line with conventional coordinator-based services, and that treated patients had a 51 % reduced risk of new fractures, indicating that also non-coordinator based fracture liaison services can improve secondary prevention of fractures.
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| 10. |
- Axelsson, Kristian F, 1973, et al.
(författare)
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Fracture risk after gastric bypass surgery – a retrospective cohort study
- 2018
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Ingår i: Journal of Bone and Mineral Research. - : Wiley-Blackwell Publishing Inc.. - 0884-0431 .- 1523-4681. ; 33:12, s. 2122-2131
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Tidskriftsartikel (refereegranskat)abstract
- Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone loss, but fracture risk following surgery has been insufficiently studied. Furthermore, the association between gastric bypass and fracture risk has not been studied in patients with diabetes, which is a risk factor for fracture and affected by surgery. In this retrospective cohort study using Swedish national databases, 38 971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31 213 without. An equal amount of well-balanced controls were identified through multivariable 1:1 propensity score matching. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation one-year post- surgery was investigated. During a median follow-up time of 3.1 (IQR 1.7-4.6) years, gastric bypass was associated with increased risk of any fracture, in patients with and without diabetes using a multivariable Cox model (HR 1.26, 95% CI 1.05- 1.53 and HR 1.32, 95% CI 1.18-1.47, respectively). Using flexible parameter models, the fracture risk appeared to increase with time. The risk of fall injury without fracture was also increased after gastric bypass. Larger weight loss or poor calcium and vitamin D supplementation after surgery were not associated with increased fracture risk. In conclusion, gastric bypass surgery is associated with an increased fracture risk, which appears to be increasing with time and not associated with degree of weight loss or calcium and vitamin D supplementation following surgery. An increased risk of fall injury was seen after surgery, which could contribute to the increased fracture risk. This article is protected by copyright. All rights reserved.
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