| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Adler, Eric D., et al.
(författare)
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Improving risk prediction in heart failure using machine learning
- 2020
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:1, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Predicting mortality is important in patients with heart failure (HF). However, current strategies for predicting risk are only modestly successful, likely because they are derived from statistical analysis methods that fail to capture prognostic information in large data sets containing multi-dimensional interactions. Methods and results: We used a machine learning algorithm to capture correlations between patient characteristics and mortality. A model was built by training a boosted decision tree algorithm to relate a subset of the patient data with a very high or very low mortality risk in a cohort of 5822 hospitalized and ambulatory patients with HF. From this model we derived a risk score that accurately discriminated between low and high-risk of death by identifying eight variables (diastolic blood pressure, creatinine, blood urea nitrogen, haemoglobin, white blood cell count, platelets, albumin, and red blood cell distribution width). This risk score had an area under the curve (AUC) of 0.88 and was predictive across the full spectrum of risk. External validation in two separate HF populations gave AUCs of 0.84 and 0.81, which were superior to those obtained with two available risk scores in these same populations. Conclusions: Using machine learning and readily available variables, we generated and validated a mortality risk score in patients with HF that was more accurate than other risk scores to which it was compared. These results support the use of this machine learning approach for the evaluation of patients with HF and in other settings where predicting risk has been challenging.
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| 3. |
- Amisten, Stefan, et al.
(författare)
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The P2Y(13) Met-158-Thr Polymorphism, Which Is in Linkage Disequilibrium with the P2Y(12) Locus, Is Not Associated with Acute Myocardial Infarction.
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The aims of this study were to investigate (1) if P2Y(12) polymorphisms defining the P2Y(12) H2 allele are associated with any other SNPs that may explain the previously reported association with increased ADP induced platelet activation and association with peripheral arterial disease and coronary artery disease and (2) if such variants are associated with acute myocardial infarction (AMI) or classical risk factors for AMI. METHODS AND RESULTS: The P2Y(13) Met-158-Thr polymorphism was found to be in linkage disequilibrium (LD) with the P2Y(12) H2 haplotype (all examined SNPs: D' = 1.0, r(2) = 0.936-1.0), defining a novel P2Y(12) H2/P2Y(13) Thr-158 haplotype. Genotyping of an AMI case control population (n = 1244 cases, 2488 controls) revealed no association of the P2Y(13) Thr-158 allele with AMI (OR = 0.96, 95% C.I. 0.82-1.12, P = 0.63). Also, no differences between the genotype frequencies of P2Y(13) Met-158-Met and Met-158-Thr/Thr-158-Thr were seen in AMI case-control subpopulations (early onset AMI OR = 1.06, 95% C.I. 0.85-1.31, P = 0.62); family history of AMI (OR = 0.98, 95% C.I. 0.78-1.22, P = 0.83) nor in early onset AMIs with family history of AMI (OR = 1.0, 95% C.I. 0.74-1.36, P = 1.0). Genotyping of the P2Y(13) Met-158-Thr polymorphism in a population based sample (n = 6055) revealed no association with cardiovascular risk factors. In addition, the P2Y(13) Met-158-Thr polymorphism was genotyped in a diabetes case-control population, and associations were found neither with DM nor with any examined DM risk factors. CONCLUSION GENOTYPING: The P2Y(13) Met-158-Thr polymorphism is in tight LD with the P2Y(12) locus but is not associated with AMI or classical cardiovascular risk factors.
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| 4. |
- Bui, Quan M., et al.
(författare)
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The value of Stanford integrated psychosocial assessment for transplantation (SIPAT) in prediction of clinical outcomes following left ventricular assist device (LVAD) implantation
- 2019
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Ingår i: Heart and Lung. - : Elsevier BV. - 0147-9563. ; 48:2, s. 85-89
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Stanford integrated psychosocial assessment for transplantation (SIPAT) is a validated psychosocial evaluation tool in the transplant population. Objective: We evaluated SIPAT in predicting post-left ventricular assist device (LVAD) outcomes, including cumulative re-admissions, driveline infections, pump malfunction, pump thrombosis, gastrointestinal bleeding, major bleeding, stroke and right ventricular failure. Methods: This retrospective study included 50 LVAD patients at an academic institution in the United States who had a pre-implant SIPAT score during the years 2015-2017. Patients were split into two groups based on SIPAT score, separating a “excellent”/“good” from a “minimally acceptable”/“poor” candidate. Poisson regression, using SIPAT as both a categorical and continuous variable, was used to compare the incidence rates of the primary outcome of cumulative re-admissions and secondary outcomes of LVAD complications. Results: The patient cohort was predominantly male 93.5% vs 89.4% (p = 0.629) with a median age of 67.0 vs 58.0 years (p = 0.037), planned destination therapy 48.4% vs 68.4% (p = 0.242) and median LVAD follow-up time of 241 vs 379 days (p = 0.10) in the low- and high- SIPAT groups, respectively. SIPAT was not a significant predictor for cumulative re-admissions, but there was an association between higher SIPAT scores and major bleeding. Conclusion: In this single-center retrospective study, SIPAT did not predict cumulative re-admissions. Further study is required to validate SIPAT before clinical implementation.
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| 5. |
- Dahl, Martin, et al.
(författare)
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Impacts of land-use change and urban development on tropical seagrass carbon sinks
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Seagrass meadows store significant carbon stocks at a global scale, but land-use change and anthropogenic activities can alter the natural process of organic carbon (Corg) accumulation. Here, we assessed the carbon accumulation history of two seagrass meadows in Zanzibar (Tanzania) that experienced different degrees of disturbance. The meadow at Stone Town has been highly exposed to urban development during the 20th century, while the Mbweni meadow is located in an area with relatively low impacts but historical clearing of adjacent mangroves. The results showed that the two sites had similar sedimentary Corg accumulation rates (22–25 g m-2 yr-1) since the 1940s, while during the last two decades (~1998 until 2018) they exhibited 24–30% higher accumulation of Corg, which was linked to shifts in Corg sources. The increase in the δ13C isotopic signature of sedimentary Corg (towards a higher seagrass contribution) at the Stone Town site since 1998 points to improved seagrass meadow conditions and Corg accumulation capacity of the meadow after the relocation of a major sewage outlet in the mid–1990s. In contrast, the decrease in the δ13C signatures of sediment Corg in the Mbweni meadow since the early 2010s was likely linked to Corg transport from mangrove/terrestrial material run-off following the mangrove deforestation. This study exemplifies two different pathways by which land-based human activities can alter the carbon storage capacity of seagrass meadows (i.e. sewage waste management and mangrove deforestation) and showcases opportunities for management of vegetated coastal Corg sinks
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| 6. |
- Gernhofer, Yan K., et al.
(författare)
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Which advanced heart failure therapy strategy is optimal for patients over 60 years old?
- 2019
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Ingår i: The Journal of cardiovascular surgery. - 0021-9509. ; 60:2, s. 251-258
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The optimal advanced heart failure (HF) therapy strategy for patients aged 60 or older with end-stage HF refractory to optimal medical therapy remains uncertain. This study compares outcomes of three advanced HF therapy strategies in this patient population. METHODS: A single-center retrospective study was conducted in 95 patients aged 60-73 years who had undergone isolated heart transplantation (HTx) or continuous flow left ventricular assist device (LVAD) implantation from 2010 to 2017. Patients were stratified into three cohorts by strategy; HTx-only (N.=25), LVAD-to-HTx (N.=29), and LVAD-only (N.=41). Primary end point was 2-year overall survival. Secondary end points included incidence of post-operative adverse events, freedom from first readmission at 1 year, and percentage of days spent in hospital following advanced HF therapy. RESULTS: Two-year survival was 91% in HTx-only patients, 88% in LVAD-to-HTx patients, and 49% in LVAD-only patients (P=0.0008). No significant difference in post-transplant survival was found between patients with or without LVAD-related adverse events preceding transplantation (P=0.42). One-year freedom from first readmission was 38.3% in HTx-only patients, 17.2% in LVAD-to-HTx patients and 7.3% in LVAD-only patients (P=0.0028). Patients in LVAD-to-HTx cohort had higher incidences of gastrointestinal bleeding (38% vs. 3%; P<0.01), major bleeding (28% vs. 3%; P=0.02), and right heart failure (69% vs. 31%; P<0.01) during post-LVAD period compared with post-HTx period. Their percentage of days spent in hospital during post-LVAD period was significantly higher than post-HTx period (7.9% vs. 1.2%; P<0.001). CONCLUSIONS: Our experience with patients over 60 years old undergoing advanced therapy suggests that HTx-only and LVAD-to-HTx strategies had superior medium-term survival than LVAD-only strategy. LVAD-to-HTx strategy is effective in reducing incidence of adverse events and percentage of hospitalized days in this specific patient population.
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| 7. |
- Gjesdal, Grunde, et al.
(författare)
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Waiting list and post-transplant outcome in Sweden after national centralization of heart transplant surgery
- 2024
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Ingår i: JOURNAL OF HEART AND LUNG TRANSPLANTATION. - 1053-2498 .- 1557-3117. ; 43:8, s. 1318-1325
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have demonstrated an association between transplantation rate per center and postoperative mortality after heart transplantation. In 2011, Sweden centralized heart transplants and waiting lists, reducing the number of centers from 3 to 2. We aimed to assess the active waiting time and pre- and post-transplant mortality before and after centralization. Methods: Heart transplantations performed in Sweden between January 1, 2001 and December 31, 2020 were included. Background and donor organ supply data were collected from Scandiatransplant, the Swedish Thoracic Transplant Registry, and the Swedish Cardiac Surgery Registry. The Fine and Gray methods were applied to visualize cumulative incidence curves and conduct competing risk regressions. A Cox model was used to adjust for factors influencing time to post-transplant death. Results: When comparing the two eras, the median active waiting time increased from 54 to 71 days (p = 0.015). The risk of mortality on the waiting list decreased in the later era (subhazard ratio 0.43; [95% confidence interval {CI} 0.25-0.74]; p = 0.002). The number of heart transplantation procedures (including pediatric patients) increased by 53%. There was a significant difference in organ utilization between eras (p = 0.033; chi-square test). 30-day and 1-year survival post-transplant rates for adults increased from 90.8% to 97.8% (p < 0.001) and from 87.9% to 94.6% (p < 0.001), respectively. 1-year mortality was reduced by 63% (hazard ratio 0.37; 95% CI 0.22-0.61). Conclusions: This nationwide study examined patients listed for and undergoing heart transplantation before and after the centralization of waiting lists and surgeries in Sweden. Waiting list mortality decreased, and 1-year post-transplantation survival was improved.
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| 8. |
- Högberg, Carl, et al.
(författare)
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Mild hypothermia does not attenuate platelet aggregation and may even increase ADP-stimulated platelet aggregation after clopidogrel treatment
- 2009
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Ingår i: Thrombosis Journal. - : Springer Science and Business Media LLC. - 1477-9560. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mild hypothermia is currently standard of care for cardiac arrest patients in many hospitals and a common belief is that hypothermia attenuates platelet aggregation. We wanted to examine the effects of clopidogrel on platelet aggregation during hypothermia.METHODS: Platelet reactivity at 37° C and 33° C was evaluated by light transmission aggregometry and vasodilator-stimulated phosphoprotein (VASP) in blood from healthy volunteers before, and 24 hours after, a 600 mg loading dose of clopidogrel.RESULTS: Collagen, 5-HT, epinephrine, U46619 and ADP-induced platelet aggregation was unaltered or even increased by hypothermia. After clopidogrel, there was a significant increase in platelet aggregation for 5 and 20 muM ADP at 33° C compared to 37° C (46 ± 5 vs. 34 ± 5% and 58 ± 4 vs. 47 ± 4%, p < 0.001, n = 8). Hypothermia also increased ADP-induced aggregation after pretreatment with the P2Y1 antagonist MRS2500. The decreased responsiveness to clopidogrel during hypothermia could be overcome by addition of the reversible P2Y12 antagonist AZD6140. ADP-induced inhibition of VASP-phosphorylation was unaffected by hypothermia both in the presence and absence of clopidogrel. A dose-response curve for ADP-induced platelet aggregation revealed increased potency for ADP during hypothermia with no difference in efficacy.CONCLUSION: Mild hypothermia did not attenuate platelet aggregation, instead it even increased ADP-stimulated platelet aggregation after clopidogrel treatment. Dual platelet inhibition with aspirin and a P2Y12 receptor antagonist is probably needed for patients with acute coronary syndromes treated with mild hypothermia, and it is possible that future ADP blockers could be of benefit.
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| 9. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 10. |
- Merino, Jordi, et al.
(författare)
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Quality of dietary fat and genetic risk of type 2 diabetes : individual participant data meta-analysis
- 2019
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Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 366
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes.DESIGN Individual participant data meta-analysis.DATA SOURCES Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators.REVIEW METHODS Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score.RESULTS Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I-2 = 7.1%, tau(2) = 0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I-2 = 18.0%, tau(2) = 0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I-2 = 58.8%, tau(2) = 0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I-2 = 25.9%, tau(2) = 0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed.CONCLUSIONS These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.
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