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Preanalytical Challenges During Capillary Fingerstick Sampling Preclude Its Widespread Use in Adult Hospitalized Patients.
Jankowski, CA, Casapao, AM, Siller, S, Isache, C, Cani, KV, Claudio, AM, Brown, M, Milstid, B, Feldhammer, M
American journal of clinical pathology. 2021;(3):412-417
Abstract
OBJECTIVES Patient compliance with laboratory testing is one of the most underrecognized challenges in developing a treatment plan for acute and chronically ill patients. The ability to offer alternatives to standard venipuncture blood draws would greatly increase a laboratory's ability to provide testing to patients and health care providers. METHODS We performed a prospective observational study on paired venous and fingerstick capillary blood samples from admitted patients undergoing vancomycin therapy. Paired specimens were analyzed for vancomycin and a basic metabolic panel (BMP: calcium, carbon dioxide, chloride, potassium, sodium, creatinine, glucose, serum urea nitrogen) on the core laboratory's automated chemistry and immunochemistry platforms. RESULTS A total of 59 paired fingerstick and venous blood specimens from 56 unique inpatients were analyzed. Paired samples were comparable for all the analytes tested with the exception of bicarbonate and potassium, which were significantly different among the capillary sample group. Patients required multiple fingers be lanced in 15% of cases to obtain sufficient blood to carry out the testing. Capillary sample rejection rates due to insufficient volumes were as high as 30% in the initial 30 patients enrolled in the study. CONCLUSIONS Vancomycin and the BMP, with the exception of potassium and bicarbonate, were determined to be analytically comparable. However, significant preanalytical issues should preclude laboratories and providers from more widespread adoption of fingerstick-derived capillary blood as an alternative sampling method except in the most extenuating of circumstances.
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Usefulness of daily folic acid supplementation during methotrexate treatment of Japanese patients with rheumatoid arthritis.
Sasaki, K, Tsuji, T, Kimoto, Y, Yanagihara, Y, Masuguchi, K, Chikamori, A, Watanabe, H, Murakami, T, Oryoji, D, Hashimoto, M, et al
Modern rheumatology. 2021;(1):108-113
Abstract
OBJECTIVES We investigated the effect of daily folic acid supplementation on methotrexate (MTX) toxicity and efficacy in Japanese patients with rheumatoid arthritis (RA). METHODS We followed 19 patients treated with MTX who switched from taking weekly 5 mg folic acid supplementation (weekly regimen) to 1.25 mg daily (daily regimen). White blood cell (WBC) and platelet (PLT) counts, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were collected for 24 weeks following the change. RESULTS We observed no significant changes in WBC or PLT counts. AST and ALT levels, which had exceeded the upper limits of their normal ranges at the beginning of the study, were improved significantly at weeks 4 and 8, no subsequent deterioration in liver function was found. Further, no significant changes in ESR and CRP levels were observed. CONCLUSION Our data indicate that supplementing 1.25 mg of folic acid daily rather than 5 mg weekly reduces toxicity caused by MTX without affecting its efficacy.
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Fasting Status and Circadian Variation Must be Considered When Performing AUC-based Therapeutic Drug Monitoring of Tacrolimus in Renal Transplant Recipients.
Gustavsen, MT, Midtvedt, K, Robertsen, I, Woillard, JB, Debord, J, Klaasen, RA, Vethe, NT, Bergan, S, Åsberg, A
Clinical and translational science. 2020;(6):1327-1335
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Abstract
Therapeutic drug monitoring (TDM) is mandatory for the immunosuppressive drug tacrolimus (Tac). For clinical applicability, TDM is performed using morning trough concentrations. With recent developments making tacrolimus concentration determination possible in capillary microsamples and Bayesian estimator predicted area under the concentration curve (AUC), AUC-guided TDM may now be clinically applicable. Tac circadian variation has, however, been reported, with lower systemic exposure following the evening dose. The aim of the present study was to investigate tacrolimus pharmacokinetic (PK) after morning and evening administrations of twice-daily tacrolimus in a real-life setting without restrictions regarding food and concomitant drug timing. Two 12 hour tacrolimus investigations were performed; after the morning dose and the following evening dose, respectively, in 31 renal transplant recipients early after transplantation both in a fasting-state and under real-life nonfasting conditions (14 patients repeated the investigation). We observed circadian variation under fasting-conditions: 45% higher peak-concentration and 20% higher AUC following the morning dose. In the real-life nonfasting setting, the PK-profiles were flat but comparable after the morning and evening doses, showing slower absorption rate and lower AUC compared with the fasting-state. Limited sampling strategies using concentrations at 0, 1, and 3 hours predicted AUC after fasting morning administration, and samples obtained at 1, 3, and 6 hours predicted AUC for the other conditions (evening and real-life nonfasting). In conclusion, circadian variation of tacrolimus is present when performed in patients who are in the fasting-state, whereas flatter PK-profiles and no circadian variation was present in a real-life, nonfasting setting.
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Frequency of Clinical Monitoring of Serum Concentrations of Digoxin, Potassium, and Creatinine, and Recording of Electrocardiograms in Digoxin-Treated Patients: A Japanese Claims Database Analysis.
Ooba, N, Sente, A, Abe, M, Watanabe, F, Tsutsumi, D, Nakamura, K, Nakayama, T, Kimura, K, Fukuoka, N
Biological & pharmaceutical bulletin. 2020;(5):913-916
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Abstract
Guidelines for cardiovascular drug therapy recommend monitoring serum digoxin concentration (SDC) in patients receiving digoxin treatment, especially those with renal dysfunction and hypokalemia. However, only a few studies have reported the prevalence of SDC monitoring and laboratory testing in clinical practice. Therefore, the aim of this study was to describe the frequency of SDC monitoring and laboratory testing in digoxin users and to assess the association between SDC monitoring and patient characteristics. We used the Japanese insurance claims data covering approximately 1.7 million patients aged 20-74 years between January 1, 2005 and March 31, 2014. All patients who had at least one prescription for digoxin were included. The frequency of SDC and laboratory tests was calculated and the association between patient characteristics and SDC monitoring was assessed using logistic regression analysis. A total of 98867 prescriptions of digoxin were issued to 3458 patients between 2005 and 2014. The annual mean frequencies of monitoring SDC, serum potassium level and serum creatinine level and of recording electrocardiograms was 16.8, 34.8, 38.7, and 24.1%, respectively. Atrial fibrillation, chronic heart failure, renal diseases, and use of oral anticoagulants were associated with SDC monitoring. We found the frequency of SDC monitoring to be relatively low in Japanese clinical practice.
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Neuroleptic malignant syndrome: evaluation of drug safety data from the AMSP program during 1993-2015.
Schneider, M, Regente, J, Greiner, T, Lensky, S, Bleich, S, Toto, S, Grohmann, R, Stübner, S, Heinze, M
European archives of psychiatry and clinical neuroscience. 2020;(1):23-33
Abstract
Neuroleptic malignant syndrome (NMS) is a rare, but severe adverse drug reaction of drugs with anti-dopaminergic properties. The main symptoms are fever and rigor. In addition, other symptoms such as creatine kinase elevation, alteration of consciousness and various neurological symptoms may occur. A total of 52 NMS cases have been documented in the drug safety program 'Arzneimittelsicherheit in der Psychiatrie' from 1993 to 2015. We calculated incidences and analyzed imputed substances and additional risk factors to study the impact of changing therapy regimes. The overall incidence was 0.16‰. High-potency first-generation antipsychotics (FGAs) had the highest incidences, e.g. flupentixol with 0.61‰. Second-generation antipsychotics (SGAs) had lower incidences. Low-potency FGAs had very low incidences, comparable to SGAs, but in contrast to SGAs, had not been imputed alone in any case of NMS. Preexisting organic pathologies of the central nervous system, lithium treatment, infection/exsiccosis and the withdrawal of medication with anticholinergic properties or alcohol were found to be additional risk factors. With the increasing use of SGAs, one should always be aware of the risk of NMS. Better suited diagnostic criteria for 'atypical NMS' would lead to a better understanding and, therefore, to improved treatment possibilities.
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Real-Life Use of Neurohormonal Antagonists and Loop Diuretics in Chronic Heart Failure: Analysis of Serial Biomarker Measurements and Clinical Outcome.
Brankovic, M, Akkerhuis, KM, van Boven, N, Manintveld, O, Germans, T, Brugts, J, Caliskan, K, Umans, V, Constantinescu, A, Kardys, I
Clinical pharmacology and therapeutics. 2018;(2):346-355
Abstract
We determined the temporal effects of neurohormonal antagonists and loop diuretics on serially assessed (3-monthly) cardiorenal biomarkers, functional status, and clinical outcomes in 250 patients with chronic heart failure (CHF) with reduced ejection fraction. In blood, we measured NT-proBNP, troponin T, C-reactive protein, creatinine, cystatin C; in urine, N-acetyl-beta-d-glucosaminidase and kidney-injury-molecule-1. Angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) were inversely associated with cardiac impairment, inflammation, and renal tubular damage, but not with glomerular dysfunction. Diuretics were associated with worse biomarker profiles and with a hazard ratio for adverse clinical outcome of 1.12 (95% confidence interval: 1.03-1.22) per 40 mg higher doses. ACE-inhibitors/ARBs were more frequently downtitrated and diuretics more frequently uptitrated in patients who experienced endpoints than in those who did not. In conclusion, a decrease or withholding of ACE-inhibitors/ARBs solely based on glomerular function is not justified because of the beneficial effects on the heart, inflammation, and renal tubules. Higher and increased diuretic doses mark progression towards endstage CHF.
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In vivo monitoring of topical therapy for acne with reflectance confocal microscopy.
Manfredini, M, Greco, M, Farnetani, F, Mazzaglia, G, Ciardo, S, Bettoli, V, Virgili, A, Pellacani, G
Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI). 2017;(1):36-40
Abstract
BACKGROUND Acne vulgaris is a common disease of the pilosebaceous unit. The aim of the study was to evaluate compartment-specific treatment action through the microscopic non-invasive imaging of skin changes. METHODS Mild-moderate acne patients, that were prescribed a topical anti-acne product, were followed by clinical and reflectance confocal microscopy (RCM) imaging every 14 days to 6 weeks. Mean and standard deviation of the scores were analyzed for each time point. RESULTS After 2 weeks, the RCM count of papules/pustules and the RCM scores of exocytosis and dermal inflammation, decreased substantially. After 4 weeks, the RCM number of comedos was reduced. After 6 weeks, the number of regular follicles increased, while the infundibula with thickened bright border decreased significantly. CONCLUSION The progressive reduction in the clinical scores was correlated with the improvement of the RCM parameters. RCM study of acne skin showed a different timing for inflammatory and hyperkeratotic components to achieve a significant reduction during topical therapy with the association of retinoid and antibacterial molecules. The microscopic changes observed showed the regularization of the skin and the improvement of acne related features. RCM may represent a useful tool for the objective assessment of treatment efficacy and individual response evaluation.
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Diagnostic Accuracy of a Novel Chromogenic Direct Thrombin Inhibitor Assay: Clinical Experiences for Dabigatran Monitoring.
Poli, S, Härtig, F, Spencer, C, Ebner, M, Birschmann, I, Kuhn, J, Faix, S, Ziemann, U, Häring, HU, Lehmann, R, et al
Thrombosis and haemostasis. 2017;(12):2369-2375
Abstract
Background Direct oral anticoagulants (DOACs) are increasingly replacing vitamin K antagonists (VKA) for clinical indications requiring long-term oral anticoagulation. In contrast to VKA, treatment with DOAC including dabigatran—the only direct thrombin inhibitor amongst them—does not require therapeutic drug monitoring. However, in case of treatment complications (e.g., major haemorrhage) and conditions requiring urgent surgery or thrombolytic therapy, information about actual DOAC plasma levels is needed to guide treatment decisions. Due to short reagent stability, limited accuracy at low dabigatran levels and high heparin sensitivity, the applicability of the widely used Hemoclot thrombin inhibitor (HTI) coagulation assay is limited in the emergency setting. Methods Dabigatran concentrations of 288 citrated plasma samples taken from 48 dabigatran-treated patients with drug concentrations of up to 300 ng/mL were measured with the chromogenic anti-IIa Biophen direct thrombin inhibitor (BDTI) assay and results compared with HTI using ultra performance liquid chromatography—tandem mass spectrometry as the reference method for measuring dabigatran plasma concentrations. Results BDTI results showed a very strong correlation with dabigatran concentrations (r = 0.965, p < 0.0001) as well as a low intra- and inter-assay variation of <5%. Compared with HTI, BDTI provides an improved on-board reagent stability of 72 hours, rapid turnaround times comparable to routine coagulation assays, high accuracy at low drug levels and reduced heparin sensitivity. Conclusion The BDTI is an ideal coagulation assay for the around-the-clock determination of dabigatran plasma levels in clinical routine including emergency situations.
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Total Thrombus-Formation Analysis System (T-TAS) Can Predict Periprocedural Bleeding Events in Patients Undergoing Catheter Ablation for Atrial Fibrillation.
Ito, M, Kaikita, K, Sueta, D, Ishii, M, Oimatsu, Y, Arima, Y, Iwashita, S, Takahashi, A, Hoshiyama, T, Kanazawa, H, et al
Journal of the American Heart Association. 2016;(1)
Abstract
BACKGROUND Non-vitamin K antagonist oral anticoagulants are used to prevent thromboembolism in patients with atrial fibrillation. The T-TAS "Total Thrombus-formation Analysis System" (Fujimori Kogyo Co Ltd) was developed for quantitative analysis of thrombus formation using microchips with thrombogenic surfaces (collagen, platelet chip [PL] ; collagen plus tissue factor, atheroma chip [AR]). We evaluated the utility of T-TAS in predicting periprocedural bleeding in atrial fibrillation patients undergoing catheter ablation (CA). METHODS AND RESULTS After exclusion of 20 from 148 consecutive patients undergoing CA, the remaining 128 patients were divided into 2 treatment groups: the warfarin group (n=30) and the non-vitamin K antagonist oral anticoagulants group (n=98). Blood samples obtained on the day of CA (anticoagulant-free point) and at 3 and 30 days after CA were used in T-TAS to compute the thrombus formation area under the curve (AUC; AUC for the first 10 minutes for PL tested at flow rate of 24 μL/min [PL24-AUC10]; AUC for the first 30 minutes for AR tested at flow rate of 10 μL/min [AR10-AUC30]). AR10-AUC30 and PL24-AUC10 levels were similar in the 2 groups on the day of CA. Levels of AR10-AUC30, but not PL24-AUC10, were significantly lower in the 2 groups at days 3 and 30 after CA. Multiple logistic regression analyses identified the AR10-AUC30 level on the day of CA as a significant predictor of periprocedural bleeding events (odds ratio 5.7; 95% CI 1.54-21.1; P=0.009). Receiver operating characteristic analysis showed that the AR10-AUC30 level on the day of CA significantly predicted periprocedural bleeding events (AUC 0.859, 95% CI 0.766-0.951; P<0.001). The cutoff AR10-AUC30 level was 1648 for identification of periprocedural bleeding events. CONCLUSIONS These results suggested that the AR10-AUC30 level determined by T-TAS is a potentially useful marker for prediction of bleeding events in atrial fibrillation patients undergoing CA.
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The HIPOGAIA study: Monitoring of oral anticoagulation with vitamin K antagonists in the municipality of Gaia.
Guedes, M, Rego, C
Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology. 2016;(9):459-65
Abstract
INTRODUCTION Anticoagulant therapy is an effective measure in preventing thromboembolic adverse events. Of the diseases in which this treatment is indicated, atrial fibrillation (AF) has the highest incidence worldwide, with a prevalence of 1.5-2%. OBJECTIVES To assess the quality of monitoring of patients with non-valvular AF under oral anticoagulation with vitamin K antagonists in Vila Nova de Gaia healthcare units. METHODS This was a retrospective observational analytical study of the population registered at the 37 healthcare units of the Vila Nova de Gaia and Espinho health center area under oral anticoagulation with vitamin K antagonists during 2014. The data were collected using TAONet(®) software. The variables studied were health units, age, gender, INR value, time in therapeutic range (TTR) and medication. TTR was calculated for each patient using the Rosendaal linear interpolation method. It was stipulated that each patient should have undergone at least six INR measurements. Data were analyzed using Microsoft Excel(®) 2010 and SPSS(®) version 21, using descriptive and inferential statistical techniques. RESULTS A total of 479 patients with non-valvular AF were studied, corresponding to 5883 INR tests. Mean TTR was 67.4±6.5%, and 35.3% of patients exhibited poor control (TTR <60%). DISCUSSION Our study showed moderate control of coagulation parameters, but better than in many international clinical trials and in another Portuguese observational study. Nevertheless, there is still room for improvement in anticoagulation monitoring in primary health care.