bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemorrhagic and Thrombotic Events Associated with Generic Substitution of Warfarin in Patients with Atrial Fibrillation: A Retrospective Analysis
Authors: Ghate Sameer R , Biskupiak Joseph E , Ye Xiangyang , Hagan Michael , Kwong Winghan Jacqueline , Fox Eben S , Brixner Diana I 
Published: June 2011

BACKGROUND: Substitution of generic warfarin for imprint warfarin (Coumadin; DuPont/Bristol-Myers Squibb) has been a controversial issue due to bioavailability and bioequivalence concerns. OBJECTIVE: To assess the risk of thrombotic and hemorrhagic events following substitution of warfarin formulations in patients with atrial fibrillation (AF). METHODS: Historical cohort analysis was performed using a commercial insurance claims database. Adults with a diagnosis of AF between January 2003 and December 2007, with 16 or more months of continuous eligibility, a warfarin prescription within 30 days after index AF diagnosis, and at least 3 warfarin prescription fills during the follow-up period were included. Individuals with AF diagnosis or warfarin prescription during the pre-index period were excluded. Cox proportional hazard regression models controlling for sex and baseline comorbidities (Charlson comorbidity index, CCI) were used to evaluate the risks of thrombotic and hemorrhagic events following warfarin formulation switches. RESULTS: Of 37,756 subjects included in the analysis (mean age 70.96 years, 42.3% females), 12,996 (34.4%) switched warfarin formulations, 20,292 (53.7%) used only 1 generic product, and 4468 (11.8%) used only Coumadin during follow-up. Compared with continued use of Coumadin, switching from that product to the generic formulation was associated with a significantly higher risk of thrombotic events (HR = 1.81; 95% CI 1.42 to 2.31). Similar findings were observed for switching from generic warfarin to Coumadin (HR = 1.76; 95% CI 1.35 to 2.30), and from 1 generic to another generic product (HR = 1.89; 95% CI 1.57 to 2.29). Similarly, switching from Coumadin to generic warfarin (HR = 1.51; 95% CI 1.17 to 1.93), generic warfarin to Coumadin (HR = 1.60; 95% CI 1.23 to 2.1), and from 1 generic to another generic product (HR = 1.74; 95% CI 1.45 to 2.11) were associated with significantly higher risk of hemorrhage than remaining on Coumadin. CONCLUSIONS: Switching warfarin formulations exposed patients with AF to a higher risk of bleeding events compared to remaining on a single product. Maintaining patients on a product with consistent bioavailability may optimize the risk-benefit balance of anticoagulation therapy.
Effectiveness of Amlodipine-Valsartan Single-Pill Combinations: Hierarchical Modeling of Blood Pressure and Total Cardiovascular Disease Risk Outcomes (the EXCELLENT Study)
Authors: Lins Robert , Aerts Ann , Coen Nicolas , Hermans Christine , MacDonald Karen , Brié Heidi , Lee Christopher , Shen Yu-Ming , Vancayzeele Stefaan , Mecum Natalie , Abraham Ivo 
Published: June 2011

BACKGROUND: Both patient- and physician-related factors have been shown to explain variability in the outcomes of antihypertensive treatment. Total cardiovascular risk (TCVR) is increasingly used as a determinant of treatment effectiveness but has also been proposed as a treatment outcome. To our knowledge, no studies have reported how antihypertensive treatment impacts blood pressure and TCVR outcomes. OBJECTIVE: To examine in patients treated with a regimen including single-pill combinations (SPCs) of amlodipine/valsartan (1) blood pressure (BP) reduction and control, total cardiovascular risk (TCVR) change, and TCVR reduction of 1 class or more; (2) hierarchical patient- and physician-level determinants of these outcomes; and (3) predictors of uncontrolled BP and improved TCVR classification. METHODS: A prospective (90 days), multicenter, multilevel pharmacoepidemiologic study was conducted in 3546 patients with hypertension treated with SPC amlodipine/valsartan by 698 general practitioners. Statistical analysis included hierarchical linear and logistic modeling of BP and TCVR outcomes. RESULTS: Mean (SD) systolic BP (SBP) reductions were 20.1 (15.5) mm Hg and diastolic BP (DBP) reductions were 9.8 (10.3) mm Hg, with higher reductions among high-risk patients. SBP, DBP, and SBP/DBP control rates were 33.3%, 45.3%, and 25.5%, respectively, with lower rates among high-risk patients. Mean TCVR improvement was a reduction of 0.73 (0.96) classes (-4 [best] to +4 [worst]), with higher reductions for high-risk patients; 58.2% of patients achieved a TCVR reduction of 1 or more classes, with lower percentages for high-risk patients. Twenty-two percent of systolic variability and 26% of diastolic variability in 90-day BP values were attributable to a physician class effect, as was 16% of TCVR change. CONCLUSIONS: Regimens that include SPC amlodipine/valsartan formulations are effective in reducing BP and TCVR in a real-world observational setting. Hierarchical modeling identified patient- and physician-related determinants of BP values and TCVR change, as well as independent predictors of uncontrolled BP and reduced TCVR. TCVR is a scientifically feasible and clinically relevant effectiveness outcome of antihypertensive treatment.
Use of Recalibrated Serum Creatinine Concentrations for Adjustment of Drug Dosages: Determination of Values Compatible with Conventional Dosing Recommendations
Authors: Jones Michael A , Golightly Larry K , Stolpman Nancy M 
Published: June 2011

BACKGROUND: Measurement of serum creatinine concentration is central to evaluation of kidney function. Recent efforts to increase the accuracy of this evaluation have led to recalibration of laboratory instruments. Recalibrated creatinine concentrations often are lower than previously reported. OBJECTIVES: To derive a method for converting recalibrated serum creatinine (R-SCr) concentrations into values that are compatible with recommended equations for calculation of estimated creatinine clearance. METHODS: Beginning with a proprietary array of recalibrated and corresponding non-recalibrated serum creatinine (NR-SCr) numerical data provided by the instrument manufacturer, relationships were examined with exponential and linear regression analyses. The validity of derived values for NR-SCr obtained through these analyses was tested by comparison of proprietary and derived serum creatinine concentrations and calculated creatinine clearance values. RESULTS: Analyses revealed that relationships between R-SCr and NR-SCr creatinine were essentially linear. Rearranging and solving the equation for a straight line described this relationship as x = (y - b)/m, where x is the derived creatinine value, y is the R-SCr concentration, and, for our laboratory instrument, best parameters for m and b equal to 0.987 and −0.07, respectively. Use of these parameters to derive NR-SCr values was shown to significantly decrease positive bias in subsequent creatinine clearance calculations. CONCLUSIONS: As compared to R-SCr concentrations, use of derived NR-SCr values can improve the predictive performance of conventional equations used to calculate estimated creatinine clearance.
Ulipristal Acetate for Emergency Contraception
Authors: Snow Sara E , Melillo Stephanie N , Jarvis Courtney I 
Published: June 2011

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of data of ulipristal acetate, a new emergency contraceptive approved for use up to 120 hours after unprotected intercourse. DATA SOURCES: Articles pertaining to the topic were identified and reviewed through searches of PubMed (1994-March 2011) and clinicaltrials.gov , using the key terms ulipristal and CDB-2914. Ella approval documents were obtained and reviewed from Drugs@FDA on the Food and Drug Administration (FDA) Web site. STUDY SELECTION AND DATA EXTRACTION: All published data and FDA approval documents examining pharmacologic, pharmacokinetic, and clinical studies related to ulipristal acetate as an emergency contraceptive were evaluated. Selected studies included 3 randomized trials and 1 meta-analysis. DATA SYNTHESIS: Ulipristal acetate is a progesterone agonist/antagonist emergency contraceptive approved for the prevention of pregnancy to be taken as soon as possible, within 120 hours after unprotected intercourse or a known or suspected contraceptive failure. Based upon results of the Phase 3 clinical trials used to obtain approval, ulipristal acetate administration was at least as effective as levonorgestrel in the reduction of pregnancy rate when studied alone after unprotected intercourse and when taken up to 120 hours after unprotected intercourse. Commonly reported adverse effects associated with ulipristal acetate in trials included headache, breast tenderness, nausea, and abdominal pain. CONCLUSIONS: Ulipristal acetate is effective as an emergency contraceptive for up to 120 hours after unprotected intercourse. Because ulipristal is available only via prescription, it may be covered by insurance. However, the additional factors of travel expenses and time to make and attend a physician appointment must be taken into account when considering use of ulipristal as an emergency contraceptive. Due to the similarity of its structure to mifepristone, controversy regarding ulipristal's mechanism of action has arisen.
High-Dose Dexmedetomidine for Sedation in the Intensive Care Unit: An Evaluation of Clinical Efficacy and Safety
Authors: Jones G Morgan , Murphy Claire V , Gerlach Anthony T , Goodman Erin M , Pell Lindsay J 
Published: June 2011

BACKGROUND: Dexmedetomidine is an α2-receptor agonist used for sedation in the intensive care unit (ICU). Although dexmedetomidine is labeled for sedation in critically ill patients at doses up to 0.7 μg/kg/h, recent studies have used more liberal dosing regimens. However, to our knowledge, no study has assessed the clinical impact of doses greater than 0.7 μg/kg/h when compared to doses within the Food and Drug Administration-approved labeling. OBJECTIVE: To compare the clinical efficacy and safety of high (HD) and low (LD) dses of dexmedetomidine for sedation in the ICU. METHODS: This retrospective study included a sample of patients who received dexmedetomidine in medical, surgical, medical/surgical, and cardiothoracic ICUs between January 1, 2008, and December 1, 2009. Patients were included in the LD group if their maximum dose was less than 0.7 μg/kg/h or in the HD group if any dose was more than 0.7 μg/kg/h. Efficacy was determined by the percentage of Richmond Agitation and Sedation Scale (RASS) scores for each patient maintained at goal sedation (-1 to +1), and safety was determined by the incidence of hypotension and bradycardia. RESULTS: Forty-three of 133 patients received HD dexmedetomidine. Patients in the LD group had a significantly higher percentage of RASS scores at goal (60.0% vs 48.6%; p = 0.03), while those in the HD group experienced a higher percentage of RASS scores classified as undersedated (19.2% vs 4.9%; p = 0.001). There was no significant difference in the incidence of hypotension or bradycardia between groups. CONCLUSIONS: Patients treated with HD dexmedetomidine had fewer RASS scores at goal. Our data suggest that increasing the dose of dexmedetomidine may not enhance sedation efficacy or lead to an increased incidence of adverse effects. Patients who have not achieved goal sedation at doses of 0.7 μg/kg/h or less may not respond further to increased doses.
Oral Ferrous Sulfate Does Not Increase Preoperative Hemoglobin in Patients Scheduled for Hip or Knee Arthroplasty
Authors: Lachance Kim , Savoie Michel , Bernard Maryse , Rochon Stéphanie , Fafard Josée , Robitaille Robert , Vendittoli Pascal-André , Lévesque Sylvie , de Denus Simon 
Published: June 2011

BACKGROUND: Low hemoglobin (Hb) concentrations before lower limb joint replacement are associated with the need for blood transfusions and increased mortality. To optimize preoperative Hb, blood conservation protocols often recommend oral iron supplements, even in nonanemic patients. OBJECTIVE: To investigate the impact of ferrous sulfate on the change in Hb prior to hip or knee arthroplasty and evaluate the effect of oral iron on hematocrit, mean corpuscular volume (MCV), ferritin, and transferrin saturation, as well as its tolerability and treatment adherence. METHODS: We conducted a prospective, observational cohort study of adults with Hb concentrations between 10 and 15 g/dL who received iron supplementation prior to hip or knee arthroplasty. Systemic inflammatory diseases, vitamin B12 or folate deficiency, and current use of iron supplements, intravenous iron, or erythropoietin were exclusion criteria. All participants were prescribed ferrous sulfate 300 mg 3 times daily for a minimum of 3 weeks. Complete blood cell counts and iron studies were performed before therapy and surgery. RESULTS: Eighty-seven patients with a mean (SD) Hb of 13.47 (0.84) g/dL were included in the study. Preoperative Hb decreased after treatment with iron (-0.14 [0.53] g/dL, p = 0.015). Hematocrit also declined (-0.6% [1.8%], p = 0.002), whereas ferritin increased (25.8 [38.6] ng/mL, p < 0.001). No significant change was seen in MCV and transferrin saturation. The most common adverse effects were constipation (33.3%), heartburn (13.8%), and abdominal pain (12.6%). The adherence rate was 67.1%. CONCLUSIONS: Oral ferrous sulfate supplementation is not an effective method to increase preoperative Hb in patients scheduled for hip or knee arthroplasty, and its use is associated with adverse effects.
Methadone Toxicity Due to Smoking Cessation—A Case Report on the Drug-Drug Interaction Involving Cytochrome P450 Isoenzyme IA2
Authors: Wahawisan Joy , Kolluru Srikanth , Nguyen Tu , Molina Christina , Speake Joseph 
Published: June 2011

OBJECTIVE: To report the potential clinically significant pharmacokinetic interaction that may result from smoking cessation in patients on methadone maintenance therapy. CASE SUMMARY: A 46-year-old white man was admitted to the step-down intensive care unit with decreased respirations and altered mental status related to methadone toxicity. The patient had been on a stable dose of methadone for chronic back pain, and he reported a 1 pack per day, 33-year history of cigarette smoking. After methadone was held for 3 days, his mental status improved. It was later revealed that he had initiated smoking cessation. He was discharged home on a reduced dose of methadone with no further complications. DISCUSSION: While the potential for toxicity exists for patients who are maintained on methadone and decrease the number of cigarettes they smoke, to our knowledge, there is no recent peer-reviewed literature on this interaction. Methadone is a synthetic opioid primarily metabolized by CYP3A4 and, to a lesser degree, by other isoenzymes, including CYP1A2. Polycyclic aromatic hydrocarbons found in tobacco smoke are known CYP1A2 inducers. Decreased intake of cigarette smoke can lead to a reduction in methadone metabolism, resulting in higher serum concentrations. Our case is an example of methadone toxicity secondary to smoking cessation in a patient on methadone maintenance therapy. An objective causality assessment based on the Horn Drug Interaction Probability Scale revealed the interaction to be probable. CONCLUSIONS: Patients on methadone should be monitored for signs of methadone toxicity upon the start of smoking cessation, and the dose of methadone should be adjusted accordingly. Additional information and reports cautioning clinicians and patients about this potential interaction would be beneficial.
The Formation of Illite from Nontronite by Mesophilic and Thermophilic Bacterial Reaction
Authors: Jaisi Deb P. , Eberl Dennis D. , Dong Hailiang , Kim Jinwook 
Published: June 2011

AbstractThe formation of illite through the smectite-to-illite (S-I) reaction is considered to be one of the most important mineral reactions occurring during diagenesis. In biologically catalyzed systems, however, this transformation has been suggested to be rapid and to bypass the high temperature and long time requirements. To understand the factors that promote the S-I reaction, the present study focused on the effects of pH, temperature, solution chemistry, and aging on the S-I reaction in microbially mediated systems. Fe(III)-reduction experiments were performed in both growth and non-growth media with two types of bacteria: mesophilic (Shewanella putrefaciensCN32) and thermophilic (Thermus scotoductusSA-01). Reductive dissolution of NAu-2 was observed and the formation of illite in treatment with thermophilic SA-01 was indicated by X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM). A basic pH (8.4) and high temperature (65°C) were the most favorable conditions forthe formation of illite. A long incubation time was also found to enhance the formation of illite. K-nontronite (non-permanent fixation of K) was also detected and differentiated from the discrete illite in the XRD profiles. These results collectively suggested that the formation of illite associated with the biologically catalyzed smectite-to-illite reaction pathway may bypass the prolonged time and high temperature required for the S-I reaction in the absence of microbial activity.
Epigenetic regulation of matrix metalloproteinases and their collagen substrates in cancer
Authors: Chernov Andrei V. , Strongin Alex Y. 
Published: June 2011

AbstractOur review covers the recent epigenetic data that are focused on matrix metalloproteinases (MMPs), their inhibitors (tissue inhibitors of MMPs; TIMPs) and collagen substrates. Twenty-four MMPs, four TIMPs and at least 28 collagen types are known in humans. The MMP activity regulates the functionality of multiple extracellular matrix proteins, cytokines, growth factors and cell signaling and adhesion receptors. Aberrantly enhanced MMP proteolysis affects multiple cell functions, including proliferation, migration and invasion. This aberrant MMP proteolysis is frequently recorded in cancer. Recent evidence, however, indicates that several MMPs function as tumor suppressors in cancer. Their inhibition could have pro-tumorigenic effects (making them anti-targets), counterbalancing the benefits of target inhibition and leading to adverse effects in cancer patients. The current epigenetic data suggest that there are distinct multi-layered epigenetic mechanisms that regulate MMPs, TIMPs and collagens. We show that in certain cancer types, epigenetic signatures of selected MMPs exhibit stem cell-like characteristics. Epigenetic mechanisms appear to play an especially important role in glioblastoma multiforme. Glioblastomas/gliomas synthesize de novo and then deposit collagens into the brain parenchyma. The collagen deposition, combined with an enhanced MMP activity in glioblastomas/gliomas, facilitates rapid invasion of tumor cells through the brain. It is tempting to hypothesize that the epigenetic mechanisms which control MMPs, TIMPs and collagens and, consequently, tumor cell invasion, represent promising drug targets and that in the near future these targets will be challenged pharmacologically.
Customer satisfaction survey to improve the European cystic fibrosis external quality assessment scheme
Authors: Berwouts Sarah , Dequeker Elisabeth 
Published: June 2011

Abstract

Background: The Cystic Fibrosis European Network, coordinated from within the Katholieke Universiteit Leuven, is the provider of the European cystic fibrosis external quality assessment (EQA) scheme. The network aimed to seek feedback from laboratories that participated in the cystic fibrosis scheme in order to improve services offered. In this study we analysed responses to an on-line customer satisfaction survey conducted between September and November 2009.

Methods: The survey was sent to 213 laboratories that participated in the cystic fibrosis EQA scheme of 2008; 69 laboratories (32%) responded. Scores for importance and satisfaction were obtained from a five-point Likert scale for 24 attributes. A score of one corresponded to very dissatisfied/very unimportant and five corresponded to very satisfied/very important. Means were calculated and placed in a two-dimensional grid (importance-satisfaction analysis). Means were subtracted from each other to obtain gap values (gap-analysis).

Results: No attribute had a mean score below 3.63. The overall mean of satisfaction was 4.35. Opportunities for improvement enclosed clarity, usefulness and completeness of the general report and individual comments, and user-friendliness of the electronic datasheet.

Conclusions: This type of customer satisfaction survey was a valuable instrument to identify opportunities to improve the cystic fibrosis EQA scheme. It should be conducted on a regular basis to reveal new opportunities in the future and to assess effectiveness of actions taken. Moreover, it could be a model for other EQA providers seeking feedback from participants. Overall, the customer satisfaction survey provided a powerful quality of care improvement tool.
N Latex FLC – new monoclonal high-performance assays for the determination of free light chain kappa and lambda
Authors: Velthuis Henk te , Knop Ingrid , Stam Peter , van den Broek Monic , Bos Hannie Klaasse , Hol Suzanne , Teunissen Elisa , Fischedick Karin Schulte , Althaus Harald , Schmidt Brigitta , Wagner Carola , Melsert Roel 
Published: June 2011

Abstract

Background: High serum concentrations of monoclonal free light chain (FLC) kappa or lambda are markers of plasma cell dyscrasia.

Methods: We developed new, latex-enhanced, specific nephelometric assays based on monoclonal antibodies for the determination of FLC kappa and lambda in serum, EDTA plasma and Li-heparin plasma for use on the Siemens BN™ systems.

Results: Reference ranges were determined from 369 samples: FLC kappa 6.7–22.4 mg/L, FLC lambda 8.3–27.0 mg/L and kappa/lambda ratio 0.31–1.56. Protection from falsely low results due to antigen excess is obtained with a built-in pre-reaction in the assay protocols. Lot-to-lot consistency between three different lots of reagent, calibrators and supplementary reagent lots showed normalized differences <7.5%. The reproducibility of serum samples varied between 4% and 7%. The method comparison with Freelite™ assays showed normalized differences of 19.7%, 32.7% and 21.7%, respectively, for FLC kappa, lambda and ratio, correlations of 0.94, 0.77 and 0.73, and concordance rates of 99.2%, 94.2% and 95%.

Conclusions: N Latex FLC demonstrates high precision, good lot-to-lot consistency and freedom from a high-dose hook effect. The method comparison between Freelite™ and the N Latex FLC assays showed good clinical concordance. Further studies need to reveal the clinical value of the new FLC assays.
Golgi protein 73(GP73), a useful serum marker in liver diseases
Authors: Liu Xiangyi , Wan Xiaohua , Li Zhongwu , Lin Changqing , Zhan Yutao , Lu Xinxin 
Published: June 2011

Abstract

Background: This study was performed to quantify the expression of Golgi protein-73 (GP73) in healthy controls and in patients with liver disease, and to evaluate the correlations between GP73 and other serum markers in different liver diseases.

Methods: Serum GP73 was measured in 478 healthy controls and 296 patients with different types of liver disease. Quantitative hepatitis B virus (HBV) DNA was determined in two chronic hepatitis B (CHB) groups. Other serum liver fibrosis markers were measured in the liver fibrosis group and α-fetoprotein (AFP) was measured in hepatocellular carcinoma (HCC) group. The correlations between GP73 and these markers were evaluated.

Results: The GP73 value in hepatitis B e antigen (HBeAg)-positive CHB group, HBeAg-negative CHB group, liver fibrosis group and HCC group was significantly higher (p<0.001) than that in healthy controls. GP73 showed significant correlation with other markers in the liver fibrosis group and with AFP in the HCC group.

Conclusions: Compared with healthy controls, GP73 in patients with liver disease was significantly increased. With the progression of liver disease, GP73 showed a significantly increasing trend. These results suggest that GP73 might be used as a serum marker for the diagnosis of liver diseases and for monitoring disease progression.