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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 3. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 4. |
- Andersson, Ulrika, et al.
(författare)
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Variability in home blood pressure and its association with renal function and pulse pressure in patients with treated hypertension in primary care
- 2023
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Ingår i: Journal of Human Hypertension. - : SPRINGERNATURE. - 0950-9240 .- 1476-5527.
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure variability (BPV) represents a cardiovascular risk factor, regardless of mean level of blood pressure (BP). In this post-hoc analysis from the PERson-centredness in Hypertension management using Information Technology (PERHIT) study, we aimed to explore BPV in daily home measurements in hypertensive patients from primary care, to identify factors associated with high BPV and to investigate whether estimated glomerular filtration rate (eGFR) and pulse pressure, as markers of target organ damage (TOD), are associated with BPV. For eight consecutive weeks, 454 participants reported their daily BP and heart rate in their mobile phone, along with reports of lifestyle and hypertension-related factors. Systolic BP (SBP) values were used to calculate BPV with coefficient of variation (CV) as primary estimate. Background characteristics and self-reports were tested between fifths of CV in a linear regression model, adjusted for age and sex. Associations between BPV and eGFR and pulse pressure were tested with linear and logistic regression models. Higher home BPV was associated with higher age, BP, heart rate, and smoking. BPV was lower for participants with low alcohol consumption and treatment with calcium channel blockers. There was a significant association between BPV and pulse pressure (P = 0.015), and between BPV and eGFR (P = 0.049). Participants with high BPV reported more dizziness and palpitations. In conclusion, pulse pressure and eGFR were significantly associated with home BPV. Older age, high BP, heart rate, and smoking were associated with high BPV, but treatment with calcium channel blockers and low alcohol consumption was associated with low BPV. Trial registration: The study was registered with ClinicalTrials.gov [NCT03554382].
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| 5. |
- Bolmsjö, Beata Borgström, et al.
(författare)
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Risk factors and consequences of decreased kidney function in nursing home residents : A longitudinal study
- 2017
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Ingår i: Geriatrics & Gerontology International. - : Wiley. - 1444-1586 .- 1447-0594. ; 17:5, s. 791-797
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of the present study was to study the renal function and the relationship of deterioration in renal function with major outcomes in elderly nursing home residents. A second aim was to compare the internationally recommended formulae for estimated glomerular filtration rate (eGFR) consisting of both creatinine and cystatinC in a nursing home population. Methods: A total of 429 patients from 11 nursing homes were included during 2008-2011. GFR was estimated, from formulae based on both creatinine and cystatinC, at baseline and after 1 and 2years. The patients were divided into groups based on chronic kidney disease level, and comparisons were made for mortality, morbidity, the use of medications and between the different formulae for eGFR. Results: Survival was lower in the groups with lower renal function. Over 60% of the residents had impaired renal function. Those with impaired renal function were older, had a higher number of medications and a higher prevalence of heart failure. Higher number of medications was associated with a greater risk of rapid decline in renal function with an odds ratio of 1.2 (95% confidence interval 1.06-1.36, P=0.003). The compared eGFR formulae based on both cystatinC and creatinine were in excellent concordance with each other. Conclusions: Decreased renal function was associated with increased mortality. A majority of nursing home residents had declining renal function, which should be considered when prescribing medications. The more medications, the higher the risk for rapidly declining renal function.
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| 6. |
- Caleres, Gabriella, et al.
(författare)
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Medication Discrepancies in Discharge Summaries and Associated Risk Factors for Elderly Patients with Many Drugs
- 2020
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Ingår i: Drugs - Real World Outcomes. - : Springer Science and Business Media LLC. - 2199-1154 .- 2198-9788. ; 7:1, s. 53-62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Elderly patients are at high risk for medication errors in care transitions. The discharge summary aims to counteract drug-related problems due to insufficient information transfer in care transitions, hence the accuracy of its medication information is of utmost importance. The purpose of this study was to describe the medication discrepancy rate and associated risk factors in discharge summaries for elderly patients.METHODS: Pharmacists collected random samples of discharge summaries from ten hospitals in southern Sweden. Medication discrepancies, organisational, and patient- and care-specific factors were noted. Patients aged ≥ 75 years with five or more drugs were further included. Descriptive and logistic regression analyses were performed.RESULTS: Discharge summaries for a total of 933 patients were included. Average age was 83.1 years, and 515 patients (55%) were women. Medication discrepancies were noted for 353 patients (38%) (mean 0.87 discrepancies per discharged patient, 95% confidence interval 0.76-0.98). Unintentional addition of a drug was the most common discrepancy type. Central nervous system drugs/analgesics were most commonly affected. Major risk factors for the presence of discrepancies were multi-dose drug dispensing (adjusted odds ratio 3.42, 95% confidence interval 2.48-4.74), an increasing number of drugs in the discharge summary (adjusted odds ratio 1.09, 95% confidence interval 1.05-1.13) and discharge from departments of surgery (adjusted odds ratio 2.96, 95% confidence interval 1.55-5.66). By contrast, an increasing number of drug changes reduced the odds of a discrepancy (adjusted odds ratio 0.93, 95% confidence interval 0.88-0.99).CONCLUSIONS: Medication discrepancies were common. In addition, we identified certain circumstances in which greater vigilance may be of considerable value for increased medication safety for elderly patients in care transitions.
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| 7. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 8. |
- Gorski, Mathias, et al.
(författare)
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Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- 2021
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
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Tidskriftsartikel (refereegranskat)abstract
- Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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| 9. |
- Lenander, Cecilia, et al.
(författare)
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Use of Antipsychotic Drugs by Elderly Primary Care Patients and the Effects of Medication Reviews: A Cross-Sectional Study in Sweden
- 2017
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Ingår i: Drugs - Real World Outcomes. - : Springer Science and Business Media LLC. - 2199-1154 .- 2198-9788. ; 4:3, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Background Antipsychotics form a class of drugs that should be used with caution among elderly people because of a high risk of adverse events. Despite the risks and modest effects, their use is estimated to be high, especially in nursing homes. Objective The aim was to explore the effects of medication reviews on antipsychotic drug use for elderly primary care patients and describe the extent of, and reasons for, the prescription of antipsychotics.Methods In this cross-sectional study in primary care in Skane, Sweden, patients aged >75 years living in nursing homes or in their own homes with home care were included. The effects of medication reviews were documented, as were the use of antipsychotics and the differences in characteristics between patients receiving or not receiving antipsychotics.Results A total of 1683 patients aged 87.6 (±5.7) years were included in the analysis. Medication reviews reduced the use of antipsychotics by 23% (p\0.001) in this study. Of the 206 patients using antipsychotics, 43% (n = 93) had an approved indication, while for 15% (n = 32) the indication was not given. Antipsychotic drug use was more common with increasing number of drugs (p = 0.001), and in nursing home residents (p\0.01). It was also morefrequent in patients with cognitive impairment, depressive symptoms or sleeping problems.Conclusion The use of antipsychotic drugs is high in elderly patients in nursing homes. They are often given for indications that are not officially approved or are poorly documented. Medication reviews appear to offer one usefulstrategy for reducing excessive use of these drugs.
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| 10. |
- Pikkemaat, Miriam, et al.
(författare)
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C-peptide predicts all-cause and cardiovascular death in a cohort of individuals with newly diagnosed type 2 diabetes. The Skaraborg diabetes register
- 2019
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 150, s. 174-183
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To study the association between baseline level of C-peptide and all-cause death, cardiovascular death and cardiovascular complications among persons with newly diagnosed type 2 diabetes. Methods: The Skaraborg Diabetes Register contains data on baseline C-peptide concentrations among 398 persons <65 years with newly diagnosed type 2 diabetes 1996–1998. National registries were used to determine all-cause death, cardiovascular death and incidence of myocardial infarction and ischemic stroke until 31 December 2014. The association between baseline C-peptide and outcomes were evaluated with adjustment for multiple confounders by Cox regression analysis. Missing data were handled by multiple imputation. Results: In the imputed and fully adjusted model there was a significant association between 1 nmol/l increase in C-peptide concentration and all-cause death (HR 2.20, 95% CI 1.49–3.25, p < 0.001, number of events = 104), underlying cardiovascular death (HR 2.69, 1.49–4.85, p = 0.001, n = 35) and the composite outcome of underlying cardiovascular death, myocardial infarction or ischemic stroke (HR 1.61, 1.06–2.45, p = 0.027, n = 90). Conclusions: Elevated C-peptide levels at baseline in persons with newly diagnosed type 2 diabetes are associated with increased risk of all-cause and cardiovascular mortality. C-peptide might be used to identify persons at high risk of cardiovascular complications and premature death.
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