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  • Thompson, B.A., et al. (författare)
  • Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
  • Tidskriftsartikel (refereegranskat)abstract
    • The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
  • Edfors, R., et al. (författare)
  • Use of proteomics to identify biomarkers associated with chronic kidney disease and long-term outcomes in patients with myocardial infarction
  • 2020
  • Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 288:5, s. 581-592
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. Methods: A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. Results: A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min−1/1.73 m2 were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. Conclusion: In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.
  • Gordin, D., et al. (författare)
  • The effects of baroreflex activation therapy on blood pressure and sympathetic function in patients with refractory hypertension: the rationale and design of the Nordic BAT study
  • 2017
  • Ingår i: Blood Pressure. - : Taylor & Francis. - 0803-7051 .- 1651-1999. ; 26:5, s. 294-302
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension.Methods: This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months. A second randomization will take place after 16 months to BAT or BAT off for 3 months. Eligible patients have a daytime systolic ambulatory blood pressure (ABPM) of 145mm Hg, and/or a daytime diastolic ABPM of 95mm Hg after witnessed drug intake (including 3 antihypertensive drugs, preferably including a diuretic).Results: The primary end point is the reduction in 24-hour systolic ABPM by BAT at 8 months, as compared to pharmacotherapy. Secondary and tertiary endpoints are effects of BAT on home and office blood pressures, measures of indices of cardiac and vascular structure and function during follow-up, and safety.Conclusions: This academic initiative will increase the understanding of mechanisms and role of BAT in the refractory hypertension.
  • Thorén, A., et al. (författare)
  • ECG-monitoring of in-hospital cardiac arrest and factors associated with survival
  • 2020
  • Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 150, s. 130-138
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: ECG-monitoring is a strong predictor for 30-days survival after in-hospital cardiac arrest (IHCA). The aim of the study is to investigate factors influencing the effect of ECG-monitoring on 30-days survival after IHCA and elements of importance in everyday clinical practice regarding whether patients are ECG-monitored prior to IHCA. Methods: In all, 19.225 adult IHCAs registered in the Swedish Registry for Cardiopulmonary Resuscitation (SRCR) were included. Cox-adjusted survival curves were computed to study survival post IHCA. Logistic regression was used to study the association between 15 predictors and 30-days survival. Using logistic regression we calculated propensity scores (PS) for ECG-monitoring; the PS was used as a covariate in a logistical regression estimating the association between ECG-monitoring and 30-days survival. Gradient boosting was used to study the relative importance of all predictors on ECG-monitoring. Results: Overall 30-days survival was 30%. The ECG-monitored group (n = 10.133, 52%) had a 38% lower adjusted mortality (HR 0.62 95% CI 0.60−0.64). We observed tangible variations in ECG-monitoring ratio at different centres. The predictors of most relative influence on ECG-monitoring in IHCA were location in hospital and geographical localization. Conclusion: ECG-monitoring in IHCA was associated to a 38% lower adjusted mortality, despite this finding only every other IHCA patient was monitored. The significant variability in the frequency of ECG-monitoring in IHCA at different centres needs to be evaluated in future research. Guidelines for in-hospital ECG-monitoring could contribute to an improved identification and treatment of patients at risk, and possibly to an improved survival. © 2020 Elsevier B.V.
  • Bartels-Rausch, T., et al. (författare)
  • A review of air-ice chemical and physical interactions (AICI): Liquids, quasi-liquids, and solids in snow
  • 2014
  • Ingår i: Atmospheric Chemistry And Physics. - 1680-7316 .- 1680-7324. ; 14:3, s. 1587-1633
  • Tidskriftsartikel (refereegranskat)abstract
    • Snow in the environment acts as a host to rich chemistry and provides a matrix for physical exchange of contaminants within the ecosystem. The goal of this review is to summarise the current state of knowledge of physical processes and chemical reactivity in surface snow with relevance to polar regions. It focuses on a description of impurities in distinct compartments present in surface snow, such as snow crystals, grain boundaries, crystal surfaces, and liquid parts. It emphasises the microscopic description of the ice surface and its link with the environment. Distinct differences between the disordered air-ice interface, often termed quasi-liquid layer, and a liquid phase are highlighted. The reactivity in these different compartments of surface snow is discussed using many experimental studies, simulations, and selected snow models from the molecular to the macro-scale. Although new experimental techniques have extended our knowledge of the surface properties of ice and their impact on some single reactions and processes, others occurring on, at or within snow grains remain unquantified. The presence of liquid or liquid-like compartments either due to the formation of brine or disorder at surfaces of snow crystals below the freezing point may strongly modify reaction rates. Therefore, future experiments should include a detailed characterisation of the surface properties of the ice matrices. A further point that remains largely unresolved is the distribution of impurities between the different domains of the condensed phase inside the snowpack, i.e. in the bulk solid, in liquid at the surface or trapped in confined pockets within or between grains, or at the surface. While surface-sensitive laboratory techniques may in the future help to resolve this point for equilibrium conditions, additional uncertainty for the environmental snowpack may be caused by the highly dynamic nature of the snowpack due to the fast metamorphism occurring under certain environmental conditions. Due to these gaps in knowledge the first snow chemistry models have attempted to reproduce certain processes like the long-term incorporation of volatile compounds in snow and firn or the release of reactive species from the snowpack. Although so far none of the models offers a coupled approach of physical and chemical processes or a detailed representation of the different compartments, they have successfully been used to reproduce some field experiments. A fully coupled snow chemistry and physics model remains to be developed. © Author(s) 2014.
  • Hasselstrom, J., et al. (författare)
  • The Swedish Primary Care Cardiovascular Database (SPCCD): 74 751 hypertensive primary care patients
  • 2014
  • Ingår i: Blood Pressure. - 0803-7051 .- 1651-1999. ; 23:2, s. 116-125
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To describe the Swedish Primary Care Cardiovascular Database, SPCCD. Design. Longitudinal data from electronic medical records, linked to national registers. Setting. 48 primary healthcare centres in urban (south-western Stockholm) and rural (Skaraborg) regions in Sweden. Subjects. Patients diagnosed with hypertension 2001-2008. Main outcome measures. Blood pressure (BP) and impact of retrieval of data on BP levels, clinical characteristics, co-morbidity and pharmacological treatment. Results. The SPCCD contains 74 751 individuals, 56% women. Completeness of data ranged from >99% for drug prescriptions to 34% for smoking habits. BP was recorded in 98% of patients during 2001-2008 and in 63% in 2008. Mean BP based on the last recorded value in 2008 was 142 +/- 17/80 +/- 13 mmHg. Digit preference in BP measurements differed between the two regions, p < 0.001. Antihypertensive drugs were prescribed in primary healthcare to 88% of the patients in 2008; however, when all prescribers were included 96% purchased their drugs. Cardiovascular co-morbidity and diabetes mellitus were present in 28% and 22%, respectively. Conclusion. This large and representative database shows that there is room for improvement of BP control in Sweden. The SPCCD will provide a rich source for further research of hypertension and its complications.
  • Holmqvist, Lina, et al. (författare)
  • Drug adherence in treatment resistant and in controlled hypertension - Results from the Swedish Primary Care Cardiovascular Database (SPCCD)
  • 2018
  • Ingår i: Pharmacoepidemiology and Drug Safety. - 1053-8569 .- 1099-1557. ; 27:3, s. 315-321
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose To assess drug adherence in patients treated with 3 antihypertensive drug classes, with both controlled and uncontrolled blood pressure and describe associated factors for nonadherence. Methods Patients with hypertension, without cardiovascular comorbidity, aged >30years treated with 3 antihypertensive drug classes were followed for 2years. Both patients with treatment resistant hypertension (TRH) and patients with controlled hypertension were included. Clinical data were derived from a primary care database. Pharmacy refill data from the Swedish Prescribed drug registry was used to calculate proportion of days covered (PDC). Patients with a PDC level80% were included. Results We found 5846 patients treated 3 antihypertensive drug classes, 3508 with TRH (blood pressure140/90), and 2338 with controlled blood pressure (<140/90mmHg). TRH patients were older (69.1 vs 65.8years, P<.0001) but had less diabetes (28.5 vs 31.7%, P<.009) compared with patients with controlled blood pressure. The proportion of patients with PDC80% declined with 11% during the first year in both groups. Having diabetes was associated with staying adherent at 1year (RR 0.82; 95% CI, 0.68-0.98) whilst being born outside Europe was associated with nonadherence at one and (RR 2.05; 95% CI, 1.49-2.82). ConclusionsPatients with multiple antihypertensive drug therapy had similar decline in adherence over time regardless of initial blood pressure control. Diabetes was associated with better adherence, which may imply that the structured caregiving of these patients enhances antihypertensive drug treatment.
  • Kahan, Thomas, et al. (författare)
  • Risk prediction in stable angina pectoris
  • 2013
  • Ingår i: European Journal of Clinical Investigation. - 0014-2972 .- 1365-2362. ; 43:2, s. 141-151
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Although stable angina pectoris often carries a favourable prognosis, it remains important to identify patients with an increased risk of cardiovascular (CV) complications. Many new markers of disease activity and prognosis have been described. We evaluated whether common and easily accessible markers in everyday care provide sufficient prognostic information.MATERIALS AND METHODS:The Angina Pectoris Prognosis Study in Stockholm treated 809 patients (248 women) with stable angina pectoris with metoprolol or verapamil double blind during a median follow-up of 3·4 years, with a registry-based extended follow-up after 9·1 years. Clinical and mechanistic variables, including lipids and glucose, renal function, ambulatory and exercise-induced ischaemia, heart rate variability, cardiac and vascular ultrasonography, and psychosocial variables were included in an integrated analysis. Main outcome measures were nonfatal myocardial infarction (MI) and CV death combined.RESULTS: In all, 139 patients (18 women) suffered a main outcome. Independent predictive variables were (odds ratio [95% confidence intervals]), age (1·04 per year [1·00;1·08], P = 0·041), female sex (0·33 [0·16;0·69], P = 0·001), fasting blood glucose (1.29 per mM [1.14; 1.46], P < 0·001), serum creatinine (1·02 per μM [1·00;1·03], P < 0·001) and leucocyte counts (1·21 per 106 cells/L [1·06;1·40], P = 0·008). Smoking habits, lipids and hypertension or a previous MI provided limited additional information. Impaired fasting glucose was as predictive as manifest diabetes and interacted adversely with serum creatinine. Sexual problems were predictive among men.CONCLUSIONS:Easily accessible clinical and demographic variables provide a good risk prediction in stable angina pectoris. Impaired glucose tolerance and an elevated serum creatinine are particularly important.
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