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  • 1
    In: The Journals of Gerontology: Series A, Oxford University Press (OUP), Vol. 61, No. 10 ( 2006-10), p. 1065-1069
    Type of Medium: Online Resource
    ISSN: 1758-535X , 1079-5006
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2006
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    SSG: 12
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  • 2
    In: European Heart Journal - Cardiovascular Pharmacotherapy, Oxford University Press (OUP), Vol. 9, No. 6 ( 2023-09-20), p. 536-545
    Abstract: The efficacy of statin therapy is hindered by intolerance to the therapy, leading to discontinuation. Variants in SLCO1B1, which encodes the hepatic transporter OATB1B1, influence statin pharmacokinetics, resulting in altered plasma concentrations of the drug and its metabolites. Current pharmacogenetic guidelines require sequencing of the SLCO1B1 gene, which is more expensive and less accessible than genotyping. In this study, we aimed to develop an easy, clinically implementable functional gene risk score (GRS) of common variants in SLCO1B1 to identify patients at risk of statin intolerance. Methods and results A GRS was developed from four common variants in SLCO1B1. In statin users from Tayside, Scotland, UK, those with a high-risk GRS had increased odds across three phenotypes of statin intolerance [general statin intolerance (GSI): ORGSI 2.42; 95% confidence interval (CI): 1.29–4.31, P = 0.003; statin-related myopathy: ORSRM 2.51; 95% CI: 1.28–4.53, P = 0.004; statin-related suspected rhabdomyolysis: ORSRSR 2.85; 95% CI: 1.03–6.65, P = 0.02]. In contrast, using the Val174Ala genotype alone or the recommended OATP1B1 functional phenotypes produced weaker and less reliable results. A meta-analysis with results from adjudicated cases of statin-induced myopathy in the PREDICTION-ADR Consortium confirmed these findings (ORVal174Ala 1.99; 95% CI: 1.01–3.95, P = 0.048; ORGRS 1.76; 95% CI: 1.16–2.69, P = 0.008). For those requiring high-dose statin therapy, the high-risk GRS was more consistently associated with the time to onset of statin intolerance amongst the three phenotypes compared with Val174Ala (GSI: HRVal174Ala 2.49; 95% CI: 1.09–5.68, P = 0.03; HRGRS 2.44; 95% CI: 1.46–4.08, P  & lt; 0.001). Finally, sequence kernel association testing confirmed that rare variants in SLCO1B1 are associated with the risk of intolerance (P = 0.02). Conclusion We provide evidence that a GRS based on four common SLCO1B1 variants provides an easily implemented genetic tool that is more reliable than the current recommended practice in estimating the risk and predicting early-onset statin intolerance.
    Type of Medium: Online Resource
    ISSN: 2055-6837 , 2055-6845
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 3
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: Survival comparison between peritoneal dialysis (PD) and hemodialysis (HD) is still controversial. While some retrospective studies have shown better survival in PD, particularly in the first year, others have not identified this difference. The only RCT published so far showed a 3-year mortality rate similar between two groups. However, the number of patients was too small to provide sufficient statistical power to identify any survival differences between the two dialysis techniques. Aim of this study was to compare HD and PD in term of survival rate and factors possibly involved in a ten-years observational study. Method We retrospectively evaluated all the incident patients that started a dialytic treatment, either HD or PD, due to uremia from 01-01-2008 to 31-12-2018 at the U.O. Nephrology ASST Spedali Civili of Brescia. Exclusion criteria were: duration of dialysis treatment less than 3 months, and previous dialytic treatment or kidney transplantation. For each patient anthropometric, clinical-anamnestic data and comorbidities at dialysis start were recorded. Results One thousand and six patients were identified. 130 patients were excluded due to dialysis treatment less than 3 months. A total 876 patients were analyzed. 77% of patients started dialysis on HD while 23% chose PD. Age was significantly higher in HD patients (69±15 vs 65±16 years; p & lt;0.05). No differences were found in the incidence of: ischemic heart disease (HD 24%, PD 25%, p=0.90), diabetes (32% vs 32%, p=0.83), cancer (20% vs 17%, p=0.37), cardiac arrhythmia (20% vs 25%, p=0.08) and peripheral vascular disease (25% vs 25%, p=0.89). An increased incidence of COPD (HD 17% vs PD 8%, p & lt;0.05) and hypertension (73% vs 87%, p & lt;0.05) was present in PD patients. During follow-up, 17% of patients treated with PD shifted to HD due to catheter malfunction, recurrent infections, insufficient dialytic adequacy or ultrafiltration failure. Kidney transplants were performed more frequently in PD patients (HD 12%; PD 24%, p & lt;0.05). At an intention to treat analysis of the data, univariate analysis showed better survival in PD patients (p & lt;0.05, Figure 1). This difference was not confirmed at multivariate analysis (Figure 2), where age, cardiac arrhythmia, cirrhosis, diabetes and peripheral vascular disease were independently associated with an increased risk of mortality. No independent influence on mortality of the dialysis treatment modality was found. Conclusion This ten years observational study shows that HD and PD are similar in term of patient survival. Age and comorbidities seem to play the most important role in patient survival.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 4
    Online Resource
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    Oxford University Press (OUP) ; 2020
    In:  Nephrology Dialysis Transplantation Vol. 35, No. Supplement_3 ( 2020-06-01)
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: EDTA published data gathered between 2012 and 2016 showed greatly reduced survival in elderly prevalent dialysis patients as compared to similar aged individuals in the general population: a 70 year-old dialysis patient had a life expectancy of 5 years (instead of 16), an 80 year-old patient could expect to survive 3 years (instead of 9). This was due to the multiple comorbidities often present in elderly patients with advanced Chronic Kidney Disease (CKD). This burden of disease is further increased by dialysis itself, in particular by hemodynamic instability during treatment and by vascular access problems which often determine the need for central venous catheter insertion and for hospitalization. In 2007 the DODE study (a randomized, controlled, multicentric study in which our center took part) validated a conservative treatment of uremia based upon a Very Low Protein Diet supplemented with ketoanalogues (sVLPD): survival in patients on conservative management was similar to that of patients on chronic dialysis; also, no negative effect on nutritional status was observed. Our aim was to analyse clinical and epidemiologic data and outcomes of patients treated at our center with a sVLPD. Method We analized 222 selected from a group of approximately 300 patients with stage 5 CKD managed conservatively with a sVLPD (0.3 g/kg/day proteins). The inclusion criterion was active follow-up for at least six months; patients unable to maintain fluid and electrolyte balance with medical therapy were excluded. Except for one patient, all subjects were aged 75 years and older. Clinical and epidemiologic data were recorded at the beginning, during and at the end of follow-up. Results Mean age at the beginning of observation was 80 ± 7 years (51-96); 48% of patients were male (107), 52% were female (115). Median initial Renal Residual Function (RRF, ml/min) was 6,3 ± 2,1 ml/min, at the end of follow-up it was 5,3 ± 2,9 ml/min. The most common significant comorbidities were hypertension (84,5%), heart (61,4%) and vascular disease (48,6%); these and other significant comorbidities are illustrated in Fig. 1. Conservative management allowed to delay the initiation of dialysis by an average of one year; 24% of patients continued on the sVLPD for two year and some patients reached a duration of treatment of 7 years. Median duration of sVLPD is shown in Fig. 2. At the end of follow-up 40% of patients had begun chronic hemodialysis and 9% peritoneal dialysis, 8% were still on conservative management, 27% were deceased (Fig. 3). Conclusion The supplemented Very Low Protein Diet is an effective treatment which can delay the beginning of chronic dialysis in elderly stage 5 CKD patients with multiple comorbidities. It is a safe treatment and does not increase morbility and mortality. Current epidemiologic data (incident patients in dialysis: 170 pmp/year, 50% aged over 70 years old) support the use of this conservative strategy which can represent a valid alternative to dialysis in selected patients.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 5
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 31, No. suppl_1 ( 2016-05), p. i550-i550
    Type of Medium: Online Resource
    ISSN: 1460-2385 , 0931-0509
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
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  • 6
    In: European Heart Journal: Acute Cardiovascular Care, Oxford University Press (OUP), Vol. 8, No. 8 ( 2019-12), p. 703-707
    Abstract: Microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) leads to higher incidence of both early and late complications. A number of single nucleotide polymorphisms in 9p21 chromosome have been shown to affect angiogenesis in response to ischaemia. In particular, Rs1333040 with its three genotypic vriants C/C, T/C and T/T might influence the occurrence of MVO after pPCI. Methods: We enrolled ST-elevation myocardial infarction (STEMI) patients undergoing pPCI. The Rs1333040 polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism using restriction endonucleases (Bsml). Two expert operators unaware of the patients’ identity performed the angiographic analysis; collaterals were assessed applying Rentrop’s classification. Angiographic MVO was defined as a post-pPCI Thrombolysis In Myocardial Infarction (TIMI) 〈 3 or TIMI 3 with myocardial blush grade 0 or 1, whereas electrocardiographic MVO was defined as ST segment resolution 〈 70% one hour after pPCI. Results: Among our 133 STEMI patients (mean age 63 ± 11 years, men 72%), 35 (26%) and 53 (40%) respectively experienced angiographic or electrocardiographic MVO. Angiographic and electrocardiographic MVO were different among the three variants ( p= 0.03 and p=0.02 respectively). In particular, T/T genotype was associated with a higher incidence of both angiographic and electrocardiographic MVO compared with C/C genotype ( p=0.04 and p=0.03 respectively). Moreover, Rentrop score 〈 2 detection rate differed among the three genotypes ( p=0.03). In particular T/T genotype was associated with a higher incidence of a Rentrop score 〈 2 as compared with C/C genotype ( p= 0.02). Conclusion: Rs1333040 polymorphism genetic variants portend different MVO incidence. In particular, T/T genotype is related to angiographic and electrocardiographic MVO and to worse collaterals towards the culprit artery.
    Type of Medium: Online Resource
    ISSN: 2048-8726 , 2048-8734
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2663340-1
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