| 1. |
- Bergdahl, Carl, et al.
(författare)
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Completeness in the Swedish Fracture Register and the Swedish National Patient Register: An Assessment of Humeral Fracture Registrations
- 2021
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Ingår i: Clinical Epidemiology. - 1179-1349. ; 13, s. 325-333
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Register-based clinical research is important. However, it is essential that the collected data are reliable for the registers to be a valuable source of information. This study evaluated the quality of humeral fracture data in the Swedish Fracture Register (SFR) and in the Swedish National Patient Register (NPR). Furthermore, a model for improved case ascertainment was developed for future validation processes. Materials and Methods: Data were obtained from the NPR and SFR for all individuals aged >= 16 years with an acute humeral fracture ICD-code treated at Sahlgrenska University Hospital. The true number of humeral fractures ("gold standard") was determined by crosslinkage between the two registers and a medical charts review. The completeness of registrations in each register was measured as the proportion of registrations compared with the gold standard, and accuracy was measured as positive predictive values (PPV). Results: The NPR demonstrated a high level of completeness (97%) and lower accuracy (PPV 70%) for acute humeral fractures, whereas the SFR had slightly lower completeness (88%) but perfect accuracy (PPV 100%). The most common systematic error was the registration of re-admissions as acute fractures in the NPR (84% of all erroneous registrations). With this knowledge, an adjustment model for NPR data was constructed to increase the accuracy of fracture registrations (PPV 92%) without excluding valid registrations. Conclusion: Data from the NPR tend to overestimate the true number of fractures, and proper case selection is needed in order for the data to function as a solid basis for epidemiological research and healthcare planning. In contrast, the SFR constitutes a complete, accurate and efficient source of information.
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| 2. |
- Bergvall, M., et al.
(författare)
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Validity of classification of distal radial fractures in the Swedish fracture register
- 2021
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Ingår i: Bmc Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDistal radial fractures (DRF) are one of the most common fractures with a small peak in incidence among young males and an increasing incidence with age among women. The reliable classification of fractures is important, as classification provides a framework for communicating effectively on clinical cases. Fracture classification is also a prerequisite for data collection in national quality registers and for clinical research. Since its inception in 2011, the Swedish Fracture Register (SFR) has collected data on more than 490,000 fractures. The attending physician classifies the fracture according to the AO/OTA classification upon registration in the SFR. Previous studies regarding the classification of distal radial fractures (DRF) have shown difficulties in inter- and intra-observer agreement. This study aims to assess the accuracy of the registration of DRF in adults in the SFR as it is carried out in clinical practice.MethodsA reference group of three experienced orthopaedic trauma surgeons classified 128 DRFs, randomly retrieved from the SFR, at two classification sessions 6 weeks apart. The classification the reference group agreed on was regarded as the gold standard classification for each fracture. The accuracy of the classification in the SFR was defined as the agreement between the gold standard classification and the classification in the SFR. Inter- and intra-observer agreement was evaluated and the degree of agreement was calculated as Cohen's kappa.ResultsThe accuracy of the classification of DRF in the SFR was kappa=0.41 (0.31-0.51) for the AO/OTA subgroup/group and kappa=0.48 (0.36-0.61) for the AO/OTA type. This corresponds to moderate agreement. Inter-observer agreement ranged from kappa 0.22-0.48 for the AO/OTA subgroup/group and kappa 0.48-0.76 for the AO/OTA type. Intra-observer agreement ranged from kappa 0.52-0.70 for the AO/OTA subgroup/group and kappa 0.71-0.76 for the AO/OTA type.ConclusionsThe study shows moderate accuracy in the classification of DRF in the SFR. Although the degree of accuracy for DRF appears to be lower than for other fracture locations, the accuracy shown in the current study is similar to that in previous studies of DRF.
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| 3. |
- Schmidt, Viktor, et al.
(författare)
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Epidemiology, treatment, and mortality of 3,983 scapula fractures from the Swedish fracture register
- 2024
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Ingår i: Journal of shoulder and elbow surgery. - : Elsevier. - 1058-2746 .- 1532-6500.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Scapula fractures are relatively uncommon, accounting for <1% of all fractures and approximately 3-5% of shoulder girdle fractures. This study comprehensively describes the epidemiology, fracture classification, treatment, and mortality associated with scapula fractures within a large adult Swedish population.METHODS: This observational study included all patients ≥18 years old at the time of injury with a scapula fracture (ICD S42.1) registered in the Swedish Fracture Register between March 2011 and June 2020. Variables studied were age, sex, and injury mechanism, including energy level, fracture classification, associated fractures, treatment, and mortality.RESULTS: We included 3,930 patients (mean age 58 years, SD 18, 64% men) with 3,973 scapula fractures. Some 22% of the fractures were caused by high-energy trauma and 21% had at least one associated fracture. High energy-injuries were most common in glenoid neck (44%) and scapular body (35%) fractures. However, same-level falls were the most common cause of glenoid rim (62%) and intra-articular glenoid (55%) fractures. Clavicle fractures (9%) and proximal humerus fractures (5%) were the most commonly associated fractures. The most common fracture types were the glenoid rim (n=1,289, 32%) and scapular body (n=1,098, 28%) fractures. Nonoperative treatment was performed in 81% of patients. Glenoid rim and intra-articular glenoid fractures were treated operatively in over 30% of cases. The mortality rate for the whole cohort was 4% at 1 year.CONCLUSIONS: Scapula fractures are predominately sustained by men. High energetic injuries and associated fractures are present in one in five patients. Nonoperative treatment is chosen in four of five patients, but for some fracture types one in three undergo surgery.
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| 4. |
- Amilon, Sofia, 1982, et al.
(författare)
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How common are refractures in childhood? a study based on 40,000 paediatric fractures from the Swedish Fracture Register
- 2023
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Ingår i: Bone & Joint Journal. - 2049-4394. ; 105B:8, s. 928-934
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Tidskriftsartikel (refereegranskat)abstract
- Aims The aim of this study was to describe the incidence of refractures among children, follow-ing fractures of all long bones, and to identify when the risk of refracture decreases. Methods All patients aged under 16 years with a fracture that had occurred in a bone with ongo-ing growth (open physis) from 1 May 2015 to 31 December 2020 were retrieved from the Swedish Fracture Register. A new fracture in the same segment within one year of the pri-mary fracture was regarded as a refracture. Fracture localization, sex, lateral distribution, and time from primary fracture to refracture were analyzed for all long bones. Results Of 40,090 primary fractures, 348 children (0.88%) sustained a refracture in the same long bone segment. The diaphyseal forearm was the long bone segment most commonly affected by refractures (n = 140; 3.4%). The median time to refracture was 147 days (inter-quartile range 82 to 253) in all segments of the long bones combined. The majority of the refractures occurred in boys (n = 236; 67%), and the left side was the most common side to refracture (n = 220; 62%). The data in this study suggest that the risk of refracture decreas-es after 180 days in the diaphyseal forearm, after 90 days in the distal forearm, and after 135 days in the diaphyseal tibia. Conclusion Refractures in children are rare. However, different fractured segments run a different threat of refracture, with the highest risk associated with diaphyseal forearm fractures. The data in this study imply that children who have sustained a distal forearm fracture should avoid hazardous activities for three months, while children with a diaphyseal forearm fracture should avoid these activities for six months, and for four and a half months if they have sustained a diaphyseal tibia fracture.
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| 5. |
- Bergdahl, Carl
(författare)
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Humeral fractures - Epidemiology, treatment and reoperations in the Swedish Fracture Register
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fractures are common, but the knowledge on outcomes, treatment methods or the actual number of fractures treated each year has been sparse. With the introduction of the Swedish Fracture Register (SFR) in 2011, the prospective registration and analysis of detailed population-based fracture data was made possible for the first time. Aim: The overall aim of this thesis was to analyse the quality of data in the SFR and to determine whether, and to which extent, the SFR can be used in epidemiological research. Particularly, the incidence of humeral fractures and the mortality associated with proximal humeral fractures were analysed, and changes in treatment practice for proximal humeral fractures in recent years were evaluated. Methods: All the papers in this thesis were based on fracture registrations in the SFR. Comparisons with other data sources were made; fracture registrations in the National Patient Register (NPR) were used to examine data quality, and information from Statistics Sweden were used to calculate fracture incidence and to compare mortality rates between fracture patients and the general population. Result: In this thesis, Study I demonstrates that 88% of humeral fractures were registered in the SFR, and that all registrations were valid fracture registrations. The SFR therefore constitutes a complete, accurate and efficient source of information, well suited to epidemiological research. In contrast, data from the NPR contain a large proportion of non-valid fracture registrations and need to be improved in order to function as a solid basis for epidemiological research. Studies II-IV in this thesis demonstrate that the incidence of humeral fractures, regardless of fractured segment, increases significantly after the age of 50 years and is predominantly related to low-energy falls. This indicates the important influence of age-related risk factors, such as osteoporosis. Moreover, a proximal humeral fracture is associated with a substantially increased mortality, especially within the first weeks following the fracture. Male gender and low-energy trauma mechanisms were two independent risk factors for death following a humeral fracture. Finally, there was no significant change in the overall proportion of patients treated surgically between 2011 and 2017. However, considerable changes within the different surgical treatment modalities were observed. The use of plate fixation decreased significantly, while the use of intramedullary nails and reversed shoulder arthroplasty increased. Unfortunately, these changes in treatment practice did not affect the reoperation rate, which continued to be high throughout the study period. Conclusion: The SFR is a reliable tool for population-based observational research. Data from the SFR demonstrate that proximal humeral fractures predominately affect frail people. A surprisingly high reoperation rate calls for awareness of the importance of choosing the right treatment to the right patient.
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| 6. |
- Bergdahl, Carl, et al.
(författare)
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Mortality after a proximal humeral fracture
- 2020
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Ingår i: Bone and Joint Journal. - 2049-4394 .- 2049-4408. ; 102-B, s. 1484-1490
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The British Editorial Society of Bone & Joint Surgery Aims The aims of this study were to investigate the mortality following a proximal humeral fracture. Data from a large population-based fracture register were used to quantify 30-day, 90-day, and one-year mortality rates after a proximal humeral fracture. associations between the risk of mortality and the type of fracture and its treatment were assessed, and mortality rates were compared between patients who sustained a fracture and the general population. methods all patients with a proximal humeral fracture recorded in the Swedish Fracture register between 2011 and 2017 were included in the study. Those who died during follow-up were identified via linkage with the Swedish Tax Agency population register. Age- and sex-adjusted controls were retrieved from Statistics Sweden and standardized mortality ratios (Smrs) were calculated. results a total of 18,452 patients who sustained a proximal humeral fracture were included. Their mean age was 68.8 years (16 to 107) and the majority (13,729; 74.4%) were women. a total of 310 (1.68%) died within 30 days, 615 (3.33%) within 90 days, and 1,445 (7.83%) within one year after the injury. The mortality in patients sustaining a fracture and the general population was 1,680/100,000 and 326/100,000 at 30 days, 3,333/100,000 and 979/100,000 at 90 days, and 7,831/100,000 and 3,970/100,000 at one year, respectively. Increasing age, male sex, low-energy trauma, type a fracture, concomitant fractures, and non-surgical treatment were all independent factors associated with an increased risk of mortality. Conclusion Compared with the general population, patients sustaining a proximal humeral fracture have a significantly higher risk of mortality up to one year after the injury. The risk of mortality is five times higher during the first 30 days, diminishing to two times higher at one year, suggesting that these patients constitute a strikingly frail group, in whom appropriate immediate management and medical optimization are required.
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| 7. |
- Bergdahl, Carl, et al.
(författare)
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No change in reoperation rates despite shifting treatment trends: a population-based study of 4,070 proximal humeral fractures
- 2021
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 92:6, s. 651-657
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Clear and acknowledged treatment algorithms for proximal humeral fractures (PHFs) are lacking. Nevertheless, a change in treatment trends, including a change towards more reversed shoulder arthroplasties (RSA), has been observed during recent years. We examined the effect of these changes on reoperation rates. Patients and methods - Between 2011 and 2017, 4,070 PHFs treated at Sahlgrenska University Hospital were registered prospectively in the Swedish Fracture Register (SFR) and followed up until 2019 (mean follow-up of 4.5 years). Data on all reoperations were gathered from the SFR and from medical records. Results - The majority of PHFs were treated non-surgically and the proportion increased slightly, but not statistically significantly, during the study period (from 76% to 79%). Of the surgically treated fractures, the proportion fixed with a plate decreased from 47% to 25%, while the use of RSA increased 9-fold (from 2.0% to 19%). 221 patients underwent 302 reoperations. For those primarily treated surgically, the reoperation rate was 17%. Among treatment modalities, plate fixation was associated with the highest reoperation rate (21%). Rate of reoperations remained constant during the study period, both for the entire study cohort and for the surgically treated patients Interpretation - During the study period, treatment changes that are in accordance with recently published treatment recommendations were observed. However, these treatment changes did not affect the reoperation rate. Treatment with a plate, intramedullary nail, or hemiarthroplasty was associated with the highest reoperation rates. The fact that almost every 4th surgical procedure was a reoperation indicates a need for further improvement of modern treatment concepts for PHFs.
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| 8. |
- Hugosson, Jonas, 1955, et al.
(författare)
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Eighteen-year follow-up of the Göteborg Randomized Population-based Prostate Cancer Screening Trial : effect of sociodemographic variables on participation, prostate cancer incidence and mortality
- 2018
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 52:1, s. 27-37
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study examined whether previously reported results, indicating that prostate-specific antigen (PSA) screening can reduce prostate cancer (PC) mortality regardless of sociodemographic inequality, could be corroborated in an 18 year follow-up. Materials and methods: In 1994, 20,000 men aged 50–64 years were randomized from the Göteborg population register to PSA screening or control (1:1) (study ID: ISRCTN54449243). Men in the screening group (n = 9950) were invited for biennial PSA testing up to the median age of 69 years. Prostate biopsy was recommended for men with PSA ≥2.5 ng/ml. Last follow-up was on 31 December 2012. Results: In the screening group, 77% (7647/9950) attended at least once. After 18 years, 1396 men in the screening group and 962 controls had been diagnosed with PC [hazard ratio 1.51, 95% confidence interval (CI) 1.39–1.64]. Cumulative PC mortality was 0.98% (95% CI 0.78–1.22%) in the screening group versus 1.50% (95% CI 1.26–1.79%) in controls, an absolute reduction of 0.52% (95% CI 0.17–0.87%). The rate ratio (RR) for PC death was 0.65 (95% CI 0.49–0.87). To prevent one death from PC, the number needed to invite was 231 and the number needed to diagnose was 10. Systematic PSA screening demonstrated greater benefit in PC mortality for men who started screening at age 55–59 years (RR 0.47, 95% CI 0.29–0.78) and men with low education (RR 0.49, 95% CI 0.31–0.78). Conclusions: These data corroborate previous findings that systematic PSA screening reduces PC mortality and suggest that systematic screening may reduce sociodemographic inequality in PC mortality.
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| 9. |
- Hugosson, Jonas, 1955, et al.
(författare)
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Mortality results from the Göteborg randomised population-based prostate-cancer screening trial.
- 2010
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Ingår i: The lancet oncology. - 1474-5488. ; 11:8, s. 725-32
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world. One strategy to decrease the risk of death from this disease is screening with prostate-specific antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate.
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| 10. |
- Möller, Michael, 1957, et al.
(författare)
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The Swedish Fracture Register - ten years of experience and 600,000 fractures collected in a National Quality Register
- 2022
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Before the creation of the Swedish Fracture Register (SFR), there was no national quality register that prospectively collects data regarding all types of fractures regardless of treatment in an emergency setting. Observational data on fractures registered in a sustainable way may provide invaluable tools for quality improvements in health care and research. Description Ten years after its implementation, the Swedish Fracture Register has 100% coverage among orthopaedic and trauma departments in Sweden. The completeness of registrations reached in 2020 69-96% for hip fractures at the different departments, with the majority reporting a completeness above 85%. The Swedish Fracture Register is a fully web-based national quality register created and run by orthopaedic professionals, with financial support from public healthcare providers and the government. All users have full access to both the registration platform and all aggregated statistics in real time. The web-based platform was created for use in health quality registers and it has easily gained acceptance among users. The register has gradually developed by the addition of more fracture types and skeletal parts. Research activity is high and 31 scientific publications have been published since 2016. The strategy from the start was to publish validation data and basic epidemiological data. However, over the past few years, publications on outcomes, such as re-operations and mortality, have been published and four register-based, randomised, controlled trials are ongoing. Conclusion It is possible to create a fracture register, to gain professional acceptance and to collect fracture data in a sustainable way on a national level if the platform is easy to use. Such a platform can also be used as a randomisation platform for prospective studies.
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| 11. |
- Schillemans, Tessa, et al.
(författare)
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Associations of PFAS-related plasma metabolites with cholesterol and triglyceride concentrations
- 2023
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 216
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Tidskriftsartikel (refereegranskat)abstract
- The wide-spread environmental pollutants per- and polyfluoroalkyl substances (PFAS) have repeatedly been associated with elevated serum cholesterol in humans. However, underlying mechanisms are still unclear. Furthermore, we have previously observed inverse associations with plasma triglycerides. To better understand PFAS-induced effects on lipid pathways we investigated associations of PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations. We used 290 PFAS-related metabolite features that we previously discovered from untargeted liquid chromatography-mass spectometry metabolomics in a case-control study within the Swedish Västerbotten Intervention Programme cohort. Herein, we studied associations of these PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations in plasma samples from 187 healthy control subjects collected on two occasions between 1991 and 2013. The PFAS-related features did not associate with cholesterol, but 50 features were associated with triglycerides. Principal component analysis on these features indicated that one metabolite pattern, dominated by glycerophospholipids, correlated with longer chain PFAS and associated inversely with triglycerides (both cross-sectionally and prospectively), after adjustment for confounders. The observed time-trend of the metabolite pattern resembled that of the longer chain PFAS, with higher levels during the years 2004–2010. Mechanisms linking PFAS exposures to triglycerides may thus occur via longer chain PFAS affecting glycerophospholipid metabolism. If the results reflect a cause-effect association, as implied by the time-trend and prospective analyses, this may affect the general adult population.
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| 12. |
- Schillemans, Tessa, et al.
(författare)
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Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes – A nested case-control study
- 2021
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. There is evidence that PFAS induce metabolic perturbations in humans, but underlying mechanisms are still unknown. In this exploratory study, we investigated PFAS-related plasma metabolites for their associations with type 2 diabetes (T2D) to gain potential mechanistic insight in these perturbations. We used untargeted LC-MS metabolomics to find metabolites related to PFAS exposures in a case-control study on T2D (n = 187 matched pairs) nested within the Västerbotten Intervention Programme cohort. Following principal component analysis (PCA), six PFAS measured in plasma appeared in two groups: 1) perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid and 2) perfluorohexane sulfonic acid, perfluorooctane sulfonic acid and perfluorooctanoic acid. Using a random forest algorithm, we discovered metabolite features associated with individual PFAS and PFAS exposure groups which were subsequently investigated for associations with risk of T2D. PFAS levels correlated with 171 metabolite features (0.16 ≤ |r| ≤ 0.37, false discovery rate (FDR) adjusted p < 0.05). Out of these, 35 associated with T2D (p < 0.05), with 7 remaining after multiple testing adjustment (FDR < 0.05). PCA of the 35 PFAS- and T2D-related metabolite features revealed two patterns, dominated by glycerophospholipids and diacylglycerols, with opposite T2D associations. The glycerophospholipids correlated positively with PFAS and associated inversely with risk for T2D (Odds Ratio (OR) per 1 standard deviation (1-SD) increase in metabolite PCA pattern score = 0.2; 95% Confidence Interval (CI) = 0.1–0.4). The diacylglycerols also correlated positively with PFAS, but they associated with increased risk for T2D (OR per 1-SD = 1.9; 95% CI = 1.3–2.7). These results suggest that PFAS associate with two groups of lipid species with opposite relations to T2D risk.
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| 13. |
- Shi, Lin, 1988, et al.
(författare)
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Joint Analysis of Metabolite Markers of Fish Intake and Persistent Organic Pollutants in Relation to Type 2 Diabetes Risk in Swedish Adults
- 2019
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 149:8, s. 1413-1423
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND : There is conflicting evidence regarding the association between fish intake and type 2 diabetes (T2D) incidence, possibly owing to measurement errors in self-reported intake and coexposure to persistent organic pollutants (POPs) present in fish. OBJECTIVE : The aim of this study was to identify plasma metabolites associated with fish intake and to assess their association with T2D risk, independently of POPs, in Swedish adults. METHODS : In a case-control study nested in the Swedish Västerbotten Intervention Programme, fasting plasma samples from 421 matched T2D case-control pairs of men and women aged 30-60 y at baseline and 10-y follow-up samples from a subset of 149 pairs were analyzed using untargeted metabolomics. Moreover, 16 plasma POPs were analyzed for the 149 pairs who had repeated samples available. Fish-related plasma metabolites were identified using multivariate modelling and partial correlation analysis. Reproducibility of metabolites and metabolite patterns, derived via principal component analysis (PCA), was assessed by intraclass correlation. A unique component of metabolites unrelated to POPs was dissected by integrating metabolites and POPs using 2-way orthogonal partial least squares regression. ORs of T2D were estimated using conditional logistic regression. RESULTS : We identified 31 metabolites associated with fish intake that had poor to good reproducibility. A PCA-derived metabolite pattern strongly correlated with fish intake (ρ = 0.37, P < 0.001) but showed no association with T2D risk. Integrating fish-related metabolites and POPs led to a unique metabolite component independent of POPs, which tended to be inversely associated with T2D risk (OR: 0.75; 95% CI: 0.54, 1.02, P = 0.07). This component mainly consisted of metabolites reflecting fatty fish intake. CONCLUSIONS: Our results suggest that fatty fish intake may be beneficial for T2D prevention, after removing the counteractive effects of coexposure to POPs in Swedish adults. Integrating metabolite markers and POP exposures appears a promising approach to advance the understanding of associations between fish intake and T2D incidence.
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| 14. |
- Shi, Lin, 1988, et al.
(författare)
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Plasma metabolite biomarkers of boiled and filtered coffee intake and their association with type 2 diabetes risk
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 287:4, s. 405-421
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Tidskriftsartikel (refereegranskat)abstract
- Habitual coffee intake has been associated with a lower risk of developing type 2 diabetes (T2D), but few studies used biomarkers to reflect intake and investigated different coffee brews, that is boiled and filtered, separately. Objectives: To identify plasma metabolites associated with boiled or filtered coffee intake and to examine their association with T2D risk in Swedish adults. Methods: In a case–control study nested within the Västerbotten Intervention Programme, baseline plasma samples from 421 case–control pairs and samples from a subset of 149 pairs at a 10-year follow-up were analysed using untargeted LC-MS metabolomics. We identified metabolites associated with food frequency questionnaires (FFQ)-estimated coffee intake and assessed odds ratios of T2D. Results: In total, 24 and 32 metabolites were associated with boiled or filtered coffee intake. We determined robust metabolite panels for highly specific prediction of boiled or filtered coffee. We observed an inverse association between the metabolite panel of filtered coffee and T2D risk. No association with T2D was observed for the panel of boiled coffee intake. Similar results were observed for FFQ-estimated coffee intake. Conclusions: We identified plasma metabolites specifically associated with boiled or filtered coffee intake, which might be used as selective biomarkers. Our study supports a protective role of habitual intake of filtered coffee on T2D development. The lack of association for boiled coffee intake might be due to the lack of a protective effect of boiled coffee or due to the limited number of boiled coffee consumers in this population, but it warrants further investigation.
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| 15. |
- Shi, Lin, 1988, et al.
(författare)
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Plasma metabolites associated with healthy Nordic dietary indexes and risk of type 2 diabetes-a nested case-control study in a Swedish population
- 2018
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 108:3, s. 564-575
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiologic evidence on the association of a healthy Nordic diet and future type 2 diabetes (T2D) is limited. Exploring metabolites as biomarkers of healthy Nordic dietary patterns may facilitate investigation of associations between such patterns and T2D. Objectives: We aimed to identify metabolites related to a priori-defined healthy Nordic dietary indexes, the Baltic Sea Diet Score (BSDS) and Healthy Nordic Food Index (HNFI), and evaluate associations with the T2D risk in a case-control study nested in a Swedish population-based prospective cohort. Design: Plasma samples from 421 case-control pairs at baseline and samples from a subset of 151 healthy controls at a 10-y follow-up were analyzed with the use of untargeted liquid chromatography-mass spectrometry metabolomics. Index-related metabolites were identified through the use of random forest modelling followed by partial correlation analysis adjustment for lifestyle confounders. Metabolite patterns were derived via principal component analysis (PCA). ORs of T2D were estimated via conditional logistic regression. Reproducibility of metabolites was assessed by intraclass correlation (ICC) in healthy controls. Associations were also assessed for 10 metabolites previously identified as linking a healthy Nordic diet with T2D. Results: In total, 31 metabolites were associated with BSDS and/or HNFI (-0.19 <= r <= 0.21, 0.10 <= ICC <= 0.59). Two PCs were determined from index-related metabolites: PC1 strongly correlated to the indexes (r = 0.27 for BSDS, r = 0.25 for HNFI, ICC = 0.45) but showed no association with T2D risk. PC2 was weakly associated with the indexes, but more strongly with foods not part of the indexes, e.g., pizza, sausages, and hamburgers. PC2 was also significantly associated with T2D risk. Predefined metabolites were confirmed to be reflective of consumption of whole grains, fish, or vegetables, but not related to T2D risk. Conclusions: Our study did not support an association between healthy Nordic dietary indexes and T2D. However, foods such as hamburger, sausage, and pizza not covered by the indexes appeared to be more important for T2D risk in the current population.
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| 16. |
- Shi, Lin, 1988, et al.
(författare)
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Plasma metabolites associated with type 2 diabetes in a Swedish population: a case-control study nested in a prospective cohort
- 2018
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 61:4, s. 849-861
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The aims of the present work were to identify plasma metabolites that predict future type 2 diabetes, to investigate the changes in identified metabolites among individuals who later did or did not develop type 2 diabetes over time, and to assess the extent to which inclusion of predictive metabolites could improve risk prediction. Methods We established a nested case-control study within the Swedish prospective population-based Vasterbotten Intervention Programme cohort. Using untargeted liquid chromatography-MS metabolomics, we analysed plasma samples from 503 case-control pairs at baseline (a median time of 7 years prior to diagnosis) and samples from a subset of 187 case-control pairs at 10 years of follow-up. Discriminative metabolites between cases and controls at baseline were optimally selected using a multivariate data analysis pipeline adapted for large-scale metabolomics. Conditional logistic regression was used to assess associations between discriminative metabolites and future type 2 diabetes, adjusting for several known risk factors. Reproducibility of identified metabolites was estimated by intra-class correlation over the 10 year period among the subset of healthy participants; their systematic changes over time in relation to diagnosis among those who developed type 2 diabetes were investigated using mixed models. Risk prediction performance of models made from different predictors was evaluated using area under the receiver operating characteristic curve, discrimination improvement index and net reclassification index. Results We identified 46 predictive plasma metabolites of type 2 diabetes. Among novel findings, phosphatidylcholines (PCs) containing odd-chain fatty acids (C19: 1 and C17:0) and 2-hydroxyethanesulfonate were associated with the likelihood of developing type 2 diabetes; we also confirmed previously identified predictive biomarkers. Identified metabolites strongly correlated with insulin resistance and/or beta cell dysfunction. Of 46 identified metabolites, 26 showed intermediate to high reproducibility among healthy individuals. Moreover, PCs with odd-chain fatty acids, branched-chain amino acids, 3-methyl-2-oxovaleric acid and glutamate changed over time along with disease progression among diabetes cases. Importantly, we found that a combination of five of the most robustly predictive metabolites significantly improved risk prediction if added to models with an a priori defined set of traditional risk factors, but only a marginal improvement was achieved when using models based on optimally selected traditional risk factors. Conclusions/interpretation Predictive metabolites may improve understanding of the pathophysiology of type 2 diabetes and reflect disease progression, but they provide limited incremental value in risk prediction beyond optimal use of traditional risk factors.
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| 17. |
- Späth, Florentin, et al.
(författare)
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Biomarker Dynamics in B-cell Lymphoma : A Longitudinal Prospective Study of Plasma Samples Up to 25 Years before Diagnosis
- 2017
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 77:6, s. 1408-1415
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Tidskriftsartikel (refereegranskat)abstract
- The B-cell activation markers CXCL13, sCD23, (S)CD27, and sCD30 are associated with future lymphoma risk. However, a lack of information about the individual dynamics of markerdisease association hampers interpretation. In this study, we identified 170 individuals who had donated two prediagnostic blood samples before B-cell lymphoma diagnosis, along with 170 matched cancer-free controls from the Northern Sweden Health and Disease Study. Lymphoma risk associations were investigated by subtype and marker levels measured at baseline, at the time of the repeated sample, and with the rate of change in the marker level. Notably, we observed strong associations between CXCL13, sCD23, sCD27, and sCD30 and lymphoma risk in blood samples collected 15 to 25 years before diagnosis. B-cell activation marker levels increased among future lympho-ma cases over time, while remaining stable among controls. Associations between slope and risk were strongest for indolent lymphoma subtypes. We noted a marked association of sCD23 with chronic lymphocytic leukemia (ORSlope - 28, Ptrend(-)7.279 x 10 (-10)). Among aggressive lymphomas, the association between diffuse large B-cell lymphoma risk and slope was restricted to CXCL13. B-cell activation seemed to play a role in B-cell lymphoma development at early stages across different subtypes. Furthermore, B-cell activation presented differential trajectories in future lymphoma patients, mainly driven by indolent subtypes. Our results suggest a utility of these markers in predicting the presence of early occult disease and/or the screening and monitoring of indolent lymphoma in individual patients.
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| 18. |
- Späth, Florentin, 1980-, et al.
(författare)
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Immune marker changes and risk of multiple myeloma : a nested case-control study using repeated prediagnostic blood samples
- 2019
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Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 104:12, s. 2456-2464
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Tidskriftsartikel (refereegranskat)abstract
- Biomarkers reliably predicting progression to multiple myeloma (MM) are lacking. Myeloma risk has been associated with low blood levels of monocyte chemotactic protein-3 (MCP-3), macrophage inflammatory protein-1 alpha (MIP-1 alpha), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), fractalkine, and transforming growth factor-alpha (TGF-alpha). In this study, we aimed to replicate these findings and study the individual dynamics of each marker in a prospective longitudinal cohort, thereby examining their potential as markers of myeloma progression. For this purpose, we identified 65 myeloma cases and 65 matched cancer-free controls each with two donated blood samples within the Northern Sweden Health and Disease Study. The first and repeated samples from myeloma cases were donated at a median 13 and 4 years, respectively, before the myeloma was diagnosed. Known risk factors for progression were determined by protein-, and immunofixation electrophoresis, and free light chain assays. We observed lower levels of MCP-3, VEGF, FGF-2, and TGF-alpha in myeloma patients than in controls, consistent with previous data. We also observed that these markers decreased among future myeloma patients while remaining stable in controls. Decreasing trajectories were noted for TGF-alpha (P=2.5 x 10(-4)) indicating progression to MM. Investigating this, we found that low levels of TGF-alpha assessed at the time of the repeated sample were independently associated with risk of progression in a multivariable model (hazard ratio = 3.5; P=0.003). TGF-alpha can potentially improve early detection of MM.
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| 19. |
- Späth, Florentin, 1980-, et al.
(författare)
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Intraindividual long-term immune marker stability in plasma samples collected in median 9.4 Years apart in 304 adult cancer-free individuals
- 2021
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadephia : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 30:11, s. 2052-2058
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Tidskriftsartikel (refereegranskat)abstract
- Background: Changes in immune marker levels in the blood could be used to improve the early detection of tumor-associated inflammatory processes. To increase predictiveness and utility in cancer detection, intraindividual long-term stability in cancer-free individuals is critical for biomarker candidates as to facilitate the detection of deviation from the norm.Methods: We assessed intraindividual long-term stability for 19 immune markers (IL10, IL13, TNFa, CXCL13, MCP-3, MIP-1a, MIP-1b, fractalkine, VEGF, FGF-2, TGFa, sIL2Ra, sIL6R, sVEGF-R2, sTNF-R1, sTNF-R2, sCD23, sCD27, and sCD30) in 304 cancer-free individuals. Repeated blood samples were collected up to 20 years apart. Intraindividual reproducibility was assessed by calculating intraclass correlation coefficients (ICC) using a linear mixed model.Results: ICCs indicated fair to good reproducibility (ICCs ≥ 0.40 and < 0.75) for 17 of 19 investigated immune markers, including IL10, IL13, TNFa, CXCL13, MCP-3, MIP-1a, MIP-1b, fractalkine, VEGF, FGF-2, TGFa, sIL2Ra, sIL6R, sTNF-R1, sTNF-R2, sCD27, and sCD30. Reproducibility was strong (ICC ≥ 0.75) for sCD23, while reproducibility was poor (ICC < 0.40) for sVEGF-R2. Using a more stringent criterion for reproducibility (ICC ≥ 0.55), we observed either acceptable or better reproducibility for IL10, IL13, CXCL13, MCP-3, MIP-1a, MIP-1b, VEGF, FGF-2, sTNF-R1, sCD23, sCD27, and sCD30.Conclusions: IL10, IL13, CXCL13, MCP-3, MIP-1a, MIP-1b, VEGF, FGF-2, sTNF-R1, sCD23, sCD27, and sCD30 displayed ICCs consistent with intraindividual long-term stability in cancer-free individuals. Impact: Our data support using these markers in prospective longitudinal studies seeking early cancer detection biomarkers.
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| 20. |
- Späth, Florentin, 1980-
(författare)
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Molecular epidemiology approach : nested case-control studies in glioma and lymphoid malignancies
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Nested case-control studies aim to link molecular markers with a certain outcome. Repeated prediagnostic samples may improve the evaluation of marker-disease associations. However, data regarding the benefit of repeated samples in such studies are sparse. We aimed to assess the relationship between blood levels of various proteins and risk of glioma, B cell lymphoma, and multiple myeloma to gain further understanding of disease etiology and to evaluate the clinical relevance of the studied markers. To this end, marker-disease associations were evaluated considering the natural history of the studied disease and the time between blood sample collection and diagnosis using both single (I-II) and repeated prediagnostic blood samples (III-IV).PATIENTS AND METHODS: We conducted four nested case-control studies and one meta-analysis using samples from three prospective cohorts: the Janus Serum Bank, the Northern Sweden Health and Disease study, and the European Prospective Investigation into Cancer and Nutrition study. The following studied endpoints and relationships were included: I) glioma risk and the association with the receptor tyrosine kinases (soluble) sEGFR and sERBB2; II) B cell lymphoma risk and the association with the immune markers sCD27 and sCD30; III) B cell lymphoma risk and the association with immune markers (CXCL13, sTNF-R1, sCD23, sCD27, and sCD30) and their trends over time; and IV) multiple myeloma risk and the association with ten immune markers and growth factors (MCP-3, MIP-1α, MIP-1β, VEGF, FGF-2, fractalkine, TGF-α, IL-13, TNF-α, and IL-10) and their trends over time.RESULTS: Risk of developing I) glioma was weakly associated with high blood levels of sERBB2. In addition, high levels of both sEGFR and sERBB2 assessed 15 years before diagnosis were associated with glioblastoma risk.Risk of II) B cell lymphoma was associated with high levels of sCD30, whereas high levels of sCD27 were particularly associated with risk of chronic lymphocytic leukemia. Meta-analyses showed consistent results for sCD30 across cohorts and lymphoma subtypes, whereas results for sCD27 were less consistent across cohorts and subtypes.In addition, III) B cell lymphoma risk was associated with levels of CXCL13, sCD23, sCD27, and sCD30 assessed in samples collected 17 years before diagnosis. Marker levels increased in cases closer to diagnosis, particularly for indolent lymphoma with a marked association for chronic lymphocytic leukemia and sCD23. Increasing marker levels closer to diagnosis were also observed for CXCL13 in future diffuse large B cell lymphoma patients.Risk of IV) multiple myeloma was associated with low levels of MCP-3, VEGF, FGF-2, fractalkine, and TGF-α. Levels of these markers decreased in myeloma cases over time, especially for TGF-α. TGF-α assessed at time of the prediagnostic repeated sample seemed to help predict progression to multiple myeloma.CONCLUSIONS: Both the natural history of the studied disease and the time between sample collection and diagnosis are crucial for the evaluation of marker-disease associations. Using repeated blood samples improves the understanding of marker-disease associations and might help to identify useful biomarker candidates.
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| 21. |
- Stigevall, Caroline, et al.
(författare)
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Patients with more complex ankle fractures are associated with poorer patient-reported outcome : an observational study of 11,733 patients from the Swedish Fracture Register
- 2024
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden. - 1745-3674 .- 1745-3682. ; 95, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Patient-reported outcome measures (PROMs) following ankle fractures, including all fracture types, have not been reported. It is therefore unclear whether fracture morphology correlates with outcome. We aimed to analyze PROMs in patients with an ankle fracture in relation to the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) fracture classification using population-based register data from the Swedish Fracture Register (SFR).Methods: All patients aged ≥ 18 years with an ankle fracture (AO/OTA 44A1–C3) registered in the SFR between 2012 and 2019 were retrieved from the register. Patients with completed PROM questionnaires (Short Musculoskeletal Function Assessment and EuroQol-Visual Analogue Scale) on both day 0 (pre-trauma) and 1-year post-trauma were included. The difference in PROMs between day 0 and 1 year was calculated for each patient (delta value) and mean delta values were calculated at group level, based on the AO/OTA fracture classification.Results: 11,733 patients with 11,751 fractures with complete PROMs were included. According to the AO/OTA classification, 21% were A fractures, 67% were B fractures and 12% were C fractures. All groups of patients, regardless of fracture class (A1–C3), displayed an impairment in PROMs after 1 year compared with day 0. Type C fractures displayed a larger impairment in PROMs at group level than type B, which in turn had a greater impairment than type A. The same pattern was seen in groups 3, 2, and 1 for A and B fractures.Conclusion: We found that the AO/OTA classification is prognostic, where more complex fractures were associated with poorer PROMs.
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| 22. |
- Stigevall, Caroline, et al.
(författare)
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Patients with more complex ankle fractures are associated with poorer patient-reported outcome: an observational study of 11,733 patients from the Swedish Fracture Register.
- 2024
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Ingår i: Acta orthopaedica. - : Medical Journals Sweden. - 1745-3682 .- 1745-3674. ; 95, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- Patient-reported outcome measures (PROMs) following ankle fractures, including all fracture types, have not been reported. It is therefore unclear whether fracture morphology correlates with outcome. We aimed to analyze PROMs in patients with an ankle fracture in relation to the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) fracture classification using population-based register data from the Swedish Fracture Register (SFR).All patients aged ≥ 18 years with an ankle fracture (AO/OTA 44A1-C3) registered in the SFR between 2012 and 2019 were retrieved from the register. Patients with completed PROM questionnaires (Short Musculoskeletal Function Assessment and EuroQol-Visual Analogue Scale) on both day 0 (pre-trauma) and 1-year post-trauma were included. The difference in PROMs between day 0 and 1 year was calculated for each patient (delta value) and mean delta values were calculated at group level, based on the AO/OTA fracture classification.11,733 patients with 11,751 fractures with complete PROMs were included. According to the AO/OTA classification, 21% were A fractures, 67% were B fractures and 12% were C fractures. All groups of patients, regardless of fracture class (A1-C3), displayed an impairment in PROMs after 1 year compared with day 0. Type C fractures displayed a larger impairment in PROMs at group level than type B, which in turn had a greater impairment than type A. The same pattern was seen in groups 3, 2, and 1 for A and B fractures.We found that the AO/OTA classification is prognostic, where more complex fractures were associated with poorer PROMs.
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| 23. |
- Thor, Anna, et al.
(författare)
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Primary retroperitoneal lymph node dissection as treatment for low-volume metastatic seminoma in a population-based cohort : the Swedish Norwegian testicular cancer group experience
- 2024
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 65, s. 13-19
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: There is an unmet need to avoid long-term morbidity associated with standard cytotoxic treatment for low-volume metastatic seminoma. Our aim was to assess the oncological efficacy and surgical safety of retroperitoneal lymph node dissection (RPLND) as treatment in a population-based cohort of metastatic seminoma patients with limited retroperitoneal lymphadenopathy.Methods: Sixty-two seminoma patients in Norway and Sweden were included in the cohort from 2019 to 2022. Patients with lymphadenopathy ≤3 cm, having primary clinical stage (CS) IIA/B or CS I with a relapse, were operated with uni- or bilateral template RPLND, open or robot assisted. The outcome measures included surgical complications as per Clavien-Dindo, and Kaplan-Meier survival estimates for 24-mo progression-free survival (PFS) and overall survival (OS).Key findings and limitations: In the cohort, 33 (53%) had CS I with a relapse during surveillance, six (10%) CS I with a relapse following adjuvant chemotherapy, and 23 (37%) initial CS IIA/B. Metastatic seminoma was verified in 58 patients (94%) with a median largest diameter of 18 mm (interquartile range [IQR] 13–24). Robot-assisted RPLND was performed in 40 patients (65%). Clavien-Dindo III complications were observed in three patients (5%); no grade ≥IV complications occurred. Eighteen patients (29%) received adjuvant chemotherapy after surgery. The median follow-up was 23 mo (IQR 16–30), and recurrence occurred in six patients (10%) after a median of 8 mo (IQR 4–14). PFS was 90% (95% confidence interval: 0.86–1) and OS was 100% at 24 mo.Conclusions and clinical implications: RPLND as primary treatment is an option for selected low-stage seminomas with a limited burden of disease, showing low complications and low relapse rates, with the potential to reduce long-term morbidity.Patient summary: In seminoma patients with limited metastatic spread, surgery is a treatment option offering an alternative to chemotherapy or radiation. This paper covers the first 62 patients operated in Norway and Sweden.
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| 24. |
- Wennergren, David, et al.
(författare)
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Epidemiology and incidence of tibia fractures in the Swedish Fracture Register
- 2018
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Ingår i: Injury-International Journal of the Care of the Injured. - : Elsevier BV. - 0020-1383 .- 1879-0267. ; 49:11, s. 2068-2074
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: There is a lack of epidemiological studies of fractures in all segments of the tibia classified by orthopaedic surgeons according to the AO/OTA classification. Since 2011, the Swedish Fracture Register (SFR) has provided prospectively collected, population-based data on fractures of all types, treated both surgically and non-surgically. The aim of this study was to describe the epidemiology and incidence of fractures in all segments of the tibia in a cohort of consecutive tibia fractures over a period of five years at Sahlgrenska University Hospital, Gothenburg, Sweden. Methods: Information on age, gender, date and mechanism of injury, fracture classification according to AO/OTA, affected side and high- or low-energy trauma was extracted from the SFR for all patients, aged 16 years and above, with tibia fractures treated at Sahlgrenska University Hospital, Gothenburg, during the five-year period 1 January 2011 to 31 December 2015. Results: 1325 patients sustained 1371 tibia fractures. There were 712 proximal tibia fractures, 417 tibial shaft fractures and 242 distal tibia fractures. Patients with proximal tibia fractures had a higher mean age (54.3) and 58% were women, whereas patients with shaft and distal fractures had a slightly lower mean age (47.0 and 48.7 respectively) and a dominance of men (59% and 54% respectively). The overall incidence of tibia fractures was 51.7 per 100,000 and year. The incidence of proximal, diaphyseal and distal tibia fractures was 26.9, 15.7 and 9.1 respectively per 100,000 and year. Among women, tibia fractures showed an increasing incidence with age in all segments, whereas men had a fairly flat incidence curve, except for tibial shaft fractures, which displayed a peak among young males. The incidence of tibia fractures and graphs for age-specific incidence for each segment of the tibia are presented. Conclusions: This study describes the epidemiology and incidence of fractures in the whole of the tibia classified by orthopaedic surgeons according to the AO/OTA classification. (C) 2018 Elsevier Ltd. All rights reserved.
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| 25. |
- Wennergren, David, et al.
(författare)
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Treatment and re-operation rates in one thousand and three hundred tibial fractures from the Swedish Fracture Register
- 2021
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Ingår i: European Journal of Orthopaedic Surgery and Traumatology. - : Springer Science and Business Media LLC. - 1633-8065 .- 1432-1068. ; 31:1, s. 143-154
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Approximately, 50 persons per 100,000 per year sustain a tibial fracture. There is, however, a lack of large cohort studies that describe the treatment and re-operation frequencies of tibial fractures. The aim of this study was to describe the treatment and re-operation rates of tibial fractures in all segments of the tibia. Methods: Data related to all patients aged 16 and above treated for tibial fractures (ICD-10 S82.10-31) at Sahlgrenska University Hospital in 2011–2015 were extracted from the Swedish Fracture Register. To make sure all re-operations were included in the study, the operation planning system was checked for all patients included in the study. Results: The study comprised 1371 tibial fractures − 712 proximal, 417 diaphyseal and 242 distal tibial fractures. Among the proximal and distal tibial fractures, plate fixation was the most commonly used surgical method, whereas among tibial shaft fractures, an intramedullary nail was the most commonly used surgical method. Almost 30% (29.8%) of all surgically treated tibial fractures underwent re-operation. Among proximal tibial fractures, 24.0% underwent re-operation; tibial shaft fractures 37.0% and distal tibial fractures 26.8%. Re-operations due to infection were more or less equally common in all segments (3.9–5.4%). Conclusion: This study describes the treatment and re-operation rates after tibial fractures in a cohort of 1371 tibial fractures at Sahlgrenska University Hospital during a period of 5years. The study shows an overall re-operation rate of 29.8% for fractures in all segments of the tibia. © 2020, The Author(s).
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