| 1. |
- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 2. |
- Levinsen, Mette, et al.
(författare)
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Leukemic blasts are present at low levels in spinal fluid in one-third of childhood acute lymphoblastic leukemia cases
- 2016
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 63:11, s. 1935-1942
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Tidskriftsartikel (refereegranskat)abstract
- Background: Central nervous system (CNS) involvement is associated with relapse in childhood acute lymphoblastic leukemia (ALL) and is a diagnostic challenge. Procedure: In a Nordic/Baltic prospective study, we assessed centralized flow cytometry (FCM) of locally fixed cerebrospinal fluid (CSF) samples versus local conventional cytospin-based cytology (CC) for detecting leukemic cells and evaluating kinetics of elimination of leukemic cells in CSF. Results: Among 300 patients with newly diagnosed ALL, 87 (29%) had CSF involvement by FCM, while CC was positive in 30 (10%) of 299 patients with available CC data (P < 0.001). Patients with FCM+/CC+ had higher CSF leukemic blast counts compared to patients positive by FCM only (medians: 0.10 vs. 0.017 leukemic blasts/μl, P = 0.006). Patients positive by FCM had higher white blood cell counts in peripheral blood than patients negative by FCM (medians: 45 × 109/l vs. 10 × 109/l, P < 0.001), were younger (medians: 3 years vs. 4 years, P = 0.03), and more frequently had T-cell ALL (18/87 vs. 16/213, P = 0.001). At treatment day 15, five of 52 patients (10%) who had CSF positive by FCM at diagnosis remained so despite at least two doses of weekly intrathecal chemotherapy. Conclusions: Longer follow-up is needed to clarify whether FCM positivity has prognostic significance and is an indicator for intensified CNS-directed therapy.
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| 3. |
- Roswall, Nina, et al.
(författare)
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Long-Term Exposure to Transportation Noise and Risk of Incident Stroke : A Pooled Study of Nine Scandinavian Cohorts
- 2021
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Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 129:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transportation noise is increasingly acknowledged as a cardiovascular risk factor, but the evidence base for an association with stroke is sparse.Objective: We aimed to investigate the association between transportation noise and stroke incidence in a large Scandinavian population.Methods: We harmonized and pooled data from nine Scandinavian cohorts (seven Swedish, two Danish), totaling 135,951 participants. We identified residential address history and estimated road, railway, and aircraft noise for all addresses. Information on stroke incidence was acquired through linkage to national patient and mortality registries. We analyzed data using Cox proportional hazards models, including socioeconomic and lifestyle confounders, and air pollution.Results: During follow-up (median=19.5y), 11,056 stroke cases were identified. Road traffic noise (Lden) was associated with risk of stroke, with a hazard ratio (HR) of 1.06 [95% confidence interval (CI): 1.03, 1.08] per 10-dB higher 5-y mean time-weighted exposure in analyses adjusted for individual- and area-level socioeconomic covariates. The association was approximately linear and persisted after adjustment for air pollution [particulate matter (PM) with an aerodynamic diameter of ≤2.5μm (PM2.5) and NO2]. Stroke was associated with moderate levels of 5-y aircraft noise exposure (40–50 vs. ≤40 dB) (HR=1.12; 95% CI: 0.99, 1.27), but not with higher exposure (≥50 dB, HR=0.94HR; 95% CI: 0.79, 1.11). Railway noise was not associated with stroke.Discussion: In this pooled study, road traffic noise was associated with a higher risk of stroke. This finding supports road traffic noise as an important cardiovascular risk factor that should be included when estimating the burden of disease due to traffic noise.
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| 4. |
- Domazet, Sidsel L., et al.
(författare)
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Low-grade inflammation in persons with recently diagnosed type 2 diabetes : The role of abdominal adiposity and putative mediators
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Ingår i: Diabetes, Obesity and Metabolism. - 1462-8902.
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To determine the magnitude of the association between abdominal adiposity and low-grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities. Materials and Methods: We measured waist circumference, clinical characteristics, and inflammatory markers i.e. tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), in >9000 persons with recently diagnosed T2D. We applied multiple mediation analysis using structural equation modelling, with adjustment for age and sex. Results: Waist circumference as a proxy for abdominal adiposity was positively associated with all inflammatory markers. Hence, a one-standard deviation (SD) increase in waist circumference (SD = 15 cm) was associated with a 22%, 35%, and 46% SD increase in TNF-α (SD = 1.5 pg/mL), IL-6 (SD = 4.4 pg/mL), and hsCRP (SD = 6.9 mg/L), respectively. The level of hyperinsulinaemia assessed by fasting C-peptide was quantitatively the most important mediator, accounting for 9%–25% of the association between abdominal adiposity and low-grade inflammation, followed by low physical activity (5%–7%) and high triglyceride levels (2%–6%). Although mediation of adiposity-induced inflammation by greater comorbidity and higher glycated haemoglobin levels reached statistical significance, their impact was minor (1%–2%). Conclusions: In persons with recently diagnosed T2D, there was a clear association between abdominal adiposity and low-grade inflammation. A considerable part (20%–40%) of this association was mediated by other factors, with hyperinsulinaemia as a potentially important driver of adiposity-induced inflammation in T2D.
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| 6. |
- Ostergaard, Henrik, et al.
(författare)
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Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 118:8, s. 2333-2341
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Tidskriftsartikel (refereegranskat)abstract
- Current management of hemophilia B entails multiple weekly infusions of factor IX (FIX) to prevent bleeding episodes. In an attempt to make a longer acting recombinant FIX (rFIX), we have explored a new releasable protraction concept using the native N-glycans in the activation peptide as sites for attachment of polyethylene glycol (PEG). Release of the activation peptide by physiologic activators converted glycoPEGylated rFIX (N9-GP) to native rFIXa and proceeded with normal kinetics for FXIa, while the Km for activation by FVIIa-tissue factor (TF) was increased by 2-fold. Consistent with minimal perturbation of rFIX by the attached PEG, N9-GP retained 73%-100% specific activity in plasma and whole-blood-based assays and showed efficacy comparable with rFIX in stopping acute bleeds in hemophilia B mice. In animal models N9-GP exhibited up to 2-fold increased in vivo recovery and a markedly prolonged half-life in mini-pig (76 hours) and hemophilia B dog (113 hours) compared with rFIX (16 hours). The extended circulation time of N9-GP was reflected in prolonged correction of coagulation parameters in hemophilia B dog and duration of effect in hemophilia B mice. Collectively, these results suggest that N9-GP has the potential to offer efficacious prophylactic and acute treatment of hemophilia B patients at a reduced dosing frequency. (Blood. 2011; 118(8): 2333-2341)
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| 7. |
- Persson, Asa, et al.
(författare)
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Long-term exposure to transportation noise and obesity: A pooled analysis of eleven Nordic cohorts
- 2024
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Ingår i: ENVIRONMENTAL EPIDEMIOLOGY. - 2474-7882. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Background:Available evidence suggests a link between exposure to transportation noise and an increased risk of obesity. We aimed to assess exposure-response functions for long-term residential exposure to road traffic, railway and aircraft noise, and markers of obesity. Methods:Our cross-sectional study is based on pooled data from 11 Nordic cohorts, including up to 162,639 individuals with either measured (69.2%) or self-reported obesity data. Residential exposure to transportation noise was estimated as a time-weighted average L-den 5 years before recruitment. Adjusted linear and logistic regression models were fitted to assess beta coefficients and odds ratios (OR) with 95% confidence intervals (CI) for body mass index, overweight, and obesity, as well as for waist circumference and central obesity. Furthermore, natural splines were fitted to assess the shape of the exposure-response functions. Results:For road traffic noise, the OR for obesity was 1.06 (95% CI = 1.03, 1.08) and for central obesity 1.03 (95% CI = 1.01, 1.05) per 10 dB L-den. Thresholds were observed at around 50-55 and 55-60 dB L-den, respectively, above which there was an approximate 10% risk increase per 10 dB L-den increment for both outcomes. However, linear associations only occurred in participants with measured obesity markers and were strongly influenced by the largest cohort. Similar risk estimates as for road traffic noise were found for railway noise, with no clear thresholds. For aircraft noise, results were uncertain due to the low number of exposed participants. Conclusion:Our results support an association between road traffic and railway noise and obesity.
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| 8. |
- Pyko, Andrei, et al.
(författare)
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Long-Term Exposure to Transportation Noise and Ischemic Heart Disease: A Pooled Analysis of Nine Scandinavian Cohorts.
- 2023
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Ingår i: Environmental health perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 131:1
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Tidskriftsartikel (refereegranskat)abstract
- Transportation noise may induce cardiovascular disease, but the public health implications are unclear.The study aimed to assess exposure-response relationships for different transportation noise sources and ischemic heart disease (IHD), including subtypes.Pooled analyses were performed of nine cohorts from Denmark and Sweden, together including 132,801 subjects. Time-weighted long-term exposure to road, railway, and aircraft noise, as well as air pollution, was estimated based on residential histories. Hazard ratios (HRs) were calculated using Cox proportional hazards models following adjustment for lifestyle and socioeconomic risk factors.A total of 22,459 incident cases of IHD were identified during follow-up from national patient and mortality registers, including 7,682 cases of myocardial infarction. The adjusted HR for IHD was 1.03 [95% confidence interval (CI) 1.00, 1.05] per 10 dB Lden for both road and railway noise exposure during 5 y prior to the event. Higher risks were indicated for IHD excluding angina pectoris cases, with HRs of 1.06 (95% CI: 1.03, 1.08) and 1.05 (95% CI: 1.01, 1.08) per 10 dB Lden for road and railway noise, respectively. Corresponding HRs for myocardial infarction were 1.02 (95% CI: 0.99, 1.05) and 1.04 (95% CI: 0.99, 1.08). Increased risks were observed for aircraft noise but without clear exposure-response relations. A threshold at around 55 dB Lden was suggested in the exposure-response relation for road traffic noise and IHD.Exposure to road, railway, and aircraft noise in the prior 5 y was associated with an increased risk of IHD, particularly after exclusion of angina pectoris cases, which are less well identified in the registries. https://doi.org/10.1289/EHP10745.
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| 9. |
- Roswall, Nina, et al.
(författare)
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Long-term exposure to traffic noise and risk of incident colon cancer : A pooled study of eleven Nordic cohorts
- 2023
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 224
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundColon cancer incidence is rising globally, and factors pertaining to urbanization have been proposed involved in this development. Traffic noise may increase colon cancer risk by causing sleep disturbance and stress, thereby inducing known colon cancer risk-factors, e.g. obesity, diabetes, physical inactivity, and alcohol consumption, but few studies have examined this.ObjectivesThe objective of this study was to investigate the association between traffic noise and colon cancer (all, proximal, distal) in a pooled population of 11 Nordic cohorts, totaling 155,203 persons.MethodsWe identified residential address history and estimated road, railway, and aircraft noise, as well as air pollution, for all addresses, using similar exposure models across cohorts. Colon cancer cases were identified through national registries. We analyzed data using Cox Proportional Hazards Models, adjusting main models for harmonized sociodemographic and lifestyle data.ResultsDuring follow-up (median 18.8 years), 2757 colon cancer cases developed. We found a hazard ratio (HR) of 1.05 (95% confidence interval (CI): 0.99–1.10) per 10-dB higher 5-year mean time-weighted road traffic noise. In sub-type analyses, the association seemed confined to distal colon cancer: HR 1.06 (95% CI: 0.98–1.14). Railway and aircraft noise was not associated with colon cancer, albeit there was some indication in sub-type analyses that railway noise may also be associated with distal colon cancer. In interaction-analyses, the association between road traffic noise and colon cancer was strongest among obese persons and those with high NO2-exposure.DiscussionA prominent study strength is the large population with harmonized data across eleven cohorts, and the complete address-history during follow-up. However, each cohort estimated noise independently, and only at the most exposed façade, which may introduce exposure misclassification. Despite this, the results of this pooled study suggest that traffic noise may be a risk factor for colon cancer, especially of distal origin.
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| 10. |
- Thacher, Jesse D., et al.
(författare)
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Exposure to long-term source-specific transportation noise and incident breast cancer : A pooled study of eight Nordic cohorts
- 2023
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 178
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Tidskriftsartikel (refereegranskat)abstract
- Background: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence.Methods: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution.Results: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th–95th percentile) 5-year residential road traffic noise was 54.8 (40.0–67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2–65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99–1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96–1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using <60 dB as a cutoff, we found HRs of 1.08 (0.99–1.18) for road traffic and 1.19 (0.95–1.49) for railway noise.Conclusions: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway and aircraft noise before conclusions regarding noise as a risk factor for breast cancer can be made.
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