scholarly journals Implementation and management outcomes of pharmacogenetic CYP2C19 testing for clopidogrel therapy in clinical practice

2020 ◽  
Author(s):  
Stefan Russmann ◽  
Ali Rahmany ◽  
David Niedrig ◽  
Karl-Dietrich Hatz ◽  
Katja Ludin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Practice ◽  
Successful Implementation ◽  
Control Analysis ◽  
Loss Of Function ◽  
Increased Risk ◽  
Clopidogrel Therapy ◽  
Management Recommendations ◽  
Case Control Analysis ◽  
Ischemic Events

Abstract Purpose The antiplatelet prodrug clopidogrel is bioactivated by the polymorphic enzyme CYP2C19. Prospective clinical studies demonstrated an association between CYP2C19 loss of function (LoF) variants and an increased risk of thrombotic events under clopidogrel, but pharmacogenetic (PGx) testing is not frequently implemented in clinical practice. We report our experience with PGx-guided clopidogrel therapy with particular regard to clinically relevant patient management changes. Methods We conducted an observational study analyzing patients that underwent PGx testing for clopidogrel therapy at two Swiss hospitals. Primary outcome was the proportion of patients with clinically relevant PGx-based management recommendations and their implementation. The association of recurrent ischemic events under clopidogrel with CYP2C19 LoF variants and other factors was explored in a multivariate case-control analysis. Results Among 56 patients undergoing PGx testing, 18 (32.1%) were classified as CYP2C19 intermediate or poor metabolizers. This resulted in 17 recommendations for a change of antiplatelet therapy, which were implemented in 12 patients (70.1%). In the remaining five patients, specific reasons for non-implementation could be identified. Recurrent ischemic events under clopidogrel were associated with LoF variants (OR 2.2, 95% CI 0.3–14.4) and several cardiovascular risk factors. Associations were not statistically significant in our small study, but plausible and in line with estimates from large prospective studies. Conclusion PGx-guided clopidogrel therapy can identify patients with an elevated risk of ischemic events and offer evidence-based alternative treatments. Successful implementation in clinical practice requires a personalized interdisciplinary service that evaluates indications and additional risk factors, provides specific recommendations, and proactively follows their implementation.

scholarly journals Children at risk of giardiasis in Auckland: a case–control analysis

2003 ◽  
Vol 131 (1) ◽  
pp. 655-662 ◽  
Author(s):  
M. E. HOQUE ◽  
V. T. HOPE ◽  
R. SCRAGG ◽  
T. KJELLSTRÖM
Keyword(s):  
Risk Factors ◽  
Drinking Water ◽  
Developed Countries ◽  
Case Control ◽  
Vulnerable Groups ◽  
Control Analysis ◽  
Increased Risk ◽  
History Of ◽  
Group A ◽  
Case Control Analysis

The incidence rate of giardiasis in New Zealand is one of the highest among developed countries, peaking in the 1–4 year age group. A case–control study was undertaken to identify risk factors for giardiasis among Auckland children under 5 years of age. The exposure history of 69 cases and 98 controls were analysed. Ninety-five per cent cases and 86% controls used water from the Auckland Metropolitan mains (AMM) supply for domestic purpose, 44 cases and 42 controls swam and 59 cases and 54 controls wore nappies. Children wearing nappies were at significantly increased risk of the disease (OR=3·0, 95% CI=1·01–8·9), as were those from households which had more than one child wearing a nappy (6·5, 1·8–23·4). The Auckland metropolitan mains water supply was associated with a reduced risk compared to other drinking water sources. Significantly increased risks were also associated with drinking water consumed away from home (4·7, 2·2–10·1), swimming at least once a week (2·4, 1·1–5·3) and travelling domestically (2·5, 1·03–6·0). The study identified vulnerable groups and modifiable risk factors for diarrhoeal diseases, particularly Giardia infection. Nappy wearing was an independent risk factor for infection. Further study is advocated to ensure better protection of public health, especially for children.

Risk Factors of Recurrent Ischemic Events after Acute Noncardiogenic Ischemic Stroke

2020 ◽  
Vol 25 (45) ◽  
pp. 4827-4834 ◽  
Author(s):  
Limin Zhang ◽  
Xingang Li ◽  
Dongzhi Wang ◽  
Hong Lv ◽  
Xuezhong Si ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Ischemic Stroke ◽  
Operating Characteristic ◽  
Control Group ◽  
Case Group ◽  
Stroke Patients ◽  
Clopidogrel Therapy ◽  
Ischemic Events

Background: A considerable proportion of acute noncardiogenic ischemic stroke patients continue to experience recurrent ischemic events after standard therapy. Aim: We aimed to identify risk factors for recurrent ischemic event prediction at an early stage. Methods : 286 non-cardioembolic ischemic stroke patients with the onset of symptoms within 24 hours were enrolled. Vascular risk factors, routine laboratory data on admission, thromboelastography test seven days after clopidogrel therapy and any recurrent events within one year were assessed. Patients were divided into case group (patients with clinical adverse events, including ischemic stokes, transient ischemic attack, myocardial infarction and vascular related mortality) and control group (events-free patients). The risk of the recurrent ischemic events was determined by the receiver operating characteristic curve and multivariable logistic regression analysis. Results: Clinical adverse events were observed in 43 patients (case group). The mean levels of Mean Platelet Volume (MPV), Platelet/Lymphocyte Ratio (PLR), Lymphocyte Count (LY) and Fibrinogen (Fib) on admission were significantly higher in the case group as compared to the control group (P<0.001). Seven days after clopidogrel therapy, the ADP-induced platelet inhibition rate (ADP%) level was lower in the case group, while the Maximum Amplitude (MA) level was higher in the case group as compared to the control group (P<0.01). The Area Under the Curve (AUC) of receiver operating characteristic(ROC) curve of LY, PLR, , Fib, MA, ADP% and MPV were 0.602, 0.614, 0.629, 0.770, 0.800 and 0.808, respectively. The logistic regression analysis showed that MPV, ADP% and MA were indeed predictive factors. Conclusion: MPV, ADP% and MA were risk factors of recurrent ischemic events after acute noncardiogenic ischemic stroke. Urgent assessment and individual drug therapy should be offered to these patients as soon as possible.

A case control analysis investigating risk factors and outcomes for nephrocalcinosis and renal calculi in neonates

2017 ◽  
Vol 13 (4) ◽  
pp. 356.e1-356.e5 ◽  
Author(s):  
Melissa Huynh ◽  
Roderick Clark ◽  
Jenny Li ◽  
Guido Filler ◽  
Sumit Dave
Keyword(s):  
Risk Factors ◽  
Renal Calculi ◽  
Case Control ◽  
Control Analysis ◽  
Case Control Analysis

scholarly journals Prevalence and Risk Factors Associated with Vancomycin-Resistant Staphylococcus aureus Precursor Organism Colonization among Patients with Chronic Lower-Extremity Wounds in Southeastern Michigan

2013 ◽  
Vol 34 (9) ◽  
pp. 954-960 ◽  
Author(s):  
Pritish K. Tosh ◽  
Simon Agolory ◽  
Bethany L. Strong ◽  
Kerrie VerLee ◽  
Jennie Finks ◽  
...  
Keyword(s):  
Risk Factors ◽  
Staphylococcus Aureus ◽  
Lower Extremity ◽  
Chronic Wounds ◽  
Cohort Analysis ◽  
Case Control ◽  
Control Analysis ◽  
Vancomycin Resistant ◽  
Clinical Records ◽  
Case Control Analysis

Background.Of the 13 US vancomycin-resistant Staphylococcus aureus (VRSA) cases, 8 were identified in southeastern Michigan, primarily in patients with chronic lower-extremity wounds. VRSA infections develop when the vanA gene from vancomycin-resistant enterococcus (VRE) transfers to S. aureus. Incl8-like plasmids in VRE and pSK41-like plasmids in S. aureus appear to be important precursors to this transfer.Objective.Identify the prevalence of VRSA precursor organisms.Design.Prospective cohort with embedded case-control study.Participants.Southeastern Michigan adults with chronic lower-extremity wounds.Methods.Adults presenting to 3 southeastern Michigan medical centers during the period February 15 through March 4, 2011, with chronic lower-extremity wounds had wound, nares, and perirectal swab specimens cultured for S. aureus and VRE, which were tested for pSK41-like and Incl8-like plasmids by polymerase chain reaction. We interviewed participants and reviewed clinical records. Risk factors for pSK41-positive S. aureus were assessed among all study participants (cohort analysis) and among only S. aureus-colonized participants (case-control analysis).Results.Of 179 participants with wound cultures, 26% were colonized with methicillin-susceptible S. aureus, 27% were colonized with methicillin-resistant S. aureus, and 4% were colonized with VRE, although only 17% consented to perirectal culture. Six participants (3%) had pSK41-positive S. aureus, and none had Incl8-positive VRE. Having chronic wounds for over 2 years was associated with pSK41-positive S. aureus colonization in both analyses.Conclusions.Colonization with VRSA precursor organisms was rare. Having long-standing chronic wounds was a risk factor for pSK41-positive S. aureus colonization. Additional investigation into the prevalence of VRSA precursors among a larger cohort of patients is warranted.

Abstract 357: DNA Methylation Profiles of African American Val122Ile-Transthyretin Mutation Carriers Reveals Genes Involved in Amyloidosis Regulation

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Gita Pathak ◽  
Frank Wendt ◽  
Antonella De Lillo ◽  
Yari Nunez ◽  
Aranyak Goswami ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Heart Disease ◽  
Hippocampal Neurons ◽  
Cardiac Fibrosis ◽  
African Descent ◽  
Amyloid Deposition ◽  
Control Analysis ◽  
Increased Risk ◽  
Altered Gene ◽  
Case Control Analysis

The Transthyretin ( TTR ) Val122Ile mutation causes a rare life-threatening disorder attributable to amyloid deposition. This mutation is mainly present in people of African descent; carriers have an increased risk of congestive heart failure and several other non-cardiac phenotypes such as carpal tunnel syndrome, peripheral edema, and arthroplasty. Cardiac disease in Val122Ile carriers may not depend solely on this mutation and other uninvestigated factors could contribute to clinical heterogeneity. One possible mechanism is through DNA methylation, the addition of a methyl group on CG-dinucleotides, which can result in altered gene expression. We investigated methylation changes contributing to heart disease in Val122Ile carriers to identify non-TTR regulatory mechanisms. We investigated 96 Val122Ile carriers of genetically-confirmed African descent using the Illumina EPIC array, which covers 850,000 methylation sites across the genome. We found changes in five methylated sites associated with heart disease. These map to FAM129B, SKI, WDR27, GLS , and an intergenic site near RP11-550A5.2 (p=1.6 to 4.6e-8), and a methylated region containing KCNA6 and GALNT3 (p=1.1e-12). Weighted methylated sites mapped to PPI network analysis identified ABCA1 gene (p=0.001). We also found six cis-mQTLs associated with the FAM129B CpG site (p=4.1e-24 to 2.8e-14). We replicated two of the aforementioned CpG sites near RP11-550A5.2 (p=0.021) and in FAM129B (p=0.016) at nominal significance in a case-control analysis of confirmed cases of TTR amyloidosis. GLS encodes glutaminase, which catalyzes the conversion of glutamine to glutamate. Its expression is increased in amyloid-beta neurons and neurofibrillary tangles. ABCA1 regulates cholesterol transport and interacts with APOA1 and APP ; its dysregulation increases amyloid deposition. Increasing FAM129B expression improves the clearance of amyloid deposits and rescues hippocampal neurons from apoptosis. The SKI expression modulates TGF-beta , resulting in cardiac fibrosis. Of note, SKI and FAM129B together are involved in the regularion of various muscle tissues. Collectively, these findings suggest that a complex amyloid-related gene circuit could explain diverse symptoms in Val122Ile carriers.

A Case–Control Analysis of Risk Factors in HIV Transmission in South India

1997 ◽  
Vol 14 (3) ◽  
pp. 290-293 ◽  
Author(s):  
Soshamma George ◽  
Mary Jacob ◽  
T. Jacob John ◽  
Manoj K. Jain ◽  
Nawab Nathan ◽  
...  
Keyword(s):  
Risk Factors ◽  
South India ◽  
Hiv Transmission ◽  
Case Control ◽  
Control Analysis ◽  
Case Control Analysis

scholarly journals Lymphoma in patients treated with anti-TNF: results of the 3-year prospective French RATIO registry

2009 ◽  
Vol 69 (2) ◽  
pp. 400-408 ◽  
Author(s):  
X Mariette ◽  
F Tubach ◽  
H Bagheri ◽  
M Bardet ◽  
J M Berthelot ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Inflammatory Diseases ◽  
Antibody Therapy ◽  
Case Control ◽  
Hodgkin's Lymphoma ◽  
Control Analysis ◽  
Barr Virus ◽  
Increased Risk ◽  
Epstein Barr ◽  
Case Control Analysis

Objective:To describe cases of lymphoma associated with anti-TNF therapy, identify risk factors, estimate the incidence and compare the risks for different anti-TNF agents.Methods:A national prospective registry was designed (Research Axed on Tolerance of bIOtherapies; RATIO) to collect all cases of lymphoma in French patients receiving anti-TNF therapy from 2004 to 2006, whatever the indication. A case–control analysis was conducted including two controls treated with anti-TNF per case and an incidence study of lymphoma with the French population was used as the reference.Results:38 cases of lymphoma, 31 non-Hodgkin’s lymphoma (NHL) (26 B cell and five T cell), five Hodgkin’s lymphoma (HL) and two Hodgkin’s-like lymphoma were collected. Epstein–Barr virus was detected in both of two Hodgkin’s-like lymphoma, three of five HL and one NHL. Patients receiving adalimumab or infliximab had a higher risk than those treated with etanercept: standardised incidence ratio (SIR) 4.1 (2.3–7.1) and 3.6 (2.3–5.6) versus 0.9 (0.4–1.8). The exposure to adalimumab or infliximab versus etanercept was an independent risk factor for lymphoma in the case–control study: odds ratio 4.7 (1.3–17.7) and 4.1 (1.4–12.5), respectively. The sex and age-adjusted incidence rate of lymphoma was 42.1 per 100 000 patient-years. The SIR was 2.4 (95% CI 1.7 to 3.2).Conclusion:The two to threefold increased risk of lymphoma in patients receiving anti-TNF therapy is similar to that expected for such patients with severe inflammatory diseases. Some lymphomas associated with immunosuppression may occur, and the risk of lymphoma is higher with monoclonal-antibody therapy than with soluble-receptor therapy.

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