Laboratory Testing Monitoring Research Articles

Dabigatran and Kidney Disease

Dabigatran is an oral direct thrombin inhibitor widely used to prevent and treat various thromboembolic complications. An advantage of this agent over other anticoagulants is that routine laboratory monitoring and related dose adjustments are considered unnecessary. A major disadvantage is the absence of a reliable means of reversing its anticoagulant effect. After U.S. Food and Drug Administration approval, recently emerged data suggest a higher bleeding risk with dabigatran, especially in the elderly. Clinicians are thus faced with caring for patients with serious bleeding events without readily available tests to measure drug levels or the anticoagulant effects of dabigatran and without effective antidotes to rapidly reverse the anticoagulant effect. On the basis of dabigatran's pharmacokinetic profile, hemodialysis and continuous renal replacement therapy have been used to remove dabigatran with the hope, still unproven, that this would rapidly reverse the anticoagulant effect and reduce bleeding in patients with normal and those with reduced kidney function. However, the best clinical approach to the patient with serious bleeding is not known, and the risks of placing a hemodialysis catheter in an anticoagulated patient can be substantial. This article reviews this issue, addressing clinical indications, drug pharmacokinetics, clinical and laboratory monitoring tests, and dialytic and nondialytic approaches to reduce bleeding in dabigatran-treated patients.

Relation of Atrial Fibrillation Burden and N-Terminal Pro-Brain Natriuretic Peptide

Previous studies have noted a correlation between the presence of atrial fibrillation (AF) and elevated brain natriuretic peptide hormone level, although the exact nature of this association is unclear. Understanding the relation between AF and brain natriuretic peptide may enhance care for this patient population. The aim of this study was to establish the relationship between AF burden and N-terminal pro-brain natriuretic peptide (NT-proBNP) level. One hundred eighty-four patients who presented to the University of North Carolina electrophysiology clinic with AF underwent baseline questionnaires, laboratory testing (including NT-proBNP), echocardiography, and 1-week ambulatory rhythm monitoring. Multivariate linear regression was used to determine the association between AF burden and NT-proBNP level. Increased AF burden was associated with increased NT-proBNP level, and this association remained significant after adjusting for possible confounders. Compared with a 0% AF burden, those with an AF burden of 1% to 25% had a nearly 1.5-fold increase (p = 0.102), those with an AF burden of 26% to 99% had a nearly fourfold increase (p <0.001), and those with an AF burden of 100% had a nearly 4.5-fold increase (p <0.001). In conclusion, AF burden as assessed by continuous 1-week ambulatory rhythm monitoring is directly associated with NT-proBNP level. NT-proBNP may act as a useful surrogate for assessing AF burden.

Seasonal Soil Freezing Characters in Daxinganling

For understanding the transport of groundwater existing in the seasonal freezing soil，laboratory test and field monitoring (frozen depth、moisture content and ground temperature in five months) were carried out in Daxinganling. A translocation model is built to analyze water behavior. The result shows that thermal conductivity will increase approximately one percent when temperature decreases 1°C. A transition function is used to prevent non-convergence in the numerical simulation. The simulation proves that the modified numerical simulation can reveal the law of moisture and heat translocation, and further offer guidance in practice.

Pharmacokinetics and Safety of Levodropropizine Controlled Release Tablet after Repeated Dosing in Healthy Male Volunteers

Background: Levodropropizine is non-opioid agent whose peripheral antitussive action may result from its modulation of sensory neuropeptide levels. Currently, levodropropizine 60 mg is taken three-times daily. A controlled release formulation of levodropropizine (levodropropizine CR) 90 mg was developed, which can be taken twice daily. The aim of this study was to evaluate the safety and pharmacokinetic characteristics after multiple oral administrations of levodropropizine CR 90 mg tablets in healthy male volunteers. Methods: A randomized, open-label, cross-over study was conducted in 24 healthy male volunteers. Each subject received levodropropizine syrup 60 mg three times daily or levodropropizine CR 90 mg twice daily for 3 days. Blood samples for pharmacokinetic analysis were collected pre-dose and up to 24 hours on day 4. Pharmacokinetic analysis was conducted by non-compartmental method. Safety assessments including monitoring adverse events, laboratory tests, vital signs, physical examinations and ECGs were performed throughout the study. Results: A total of 20 male volunteers completed the study. The maximum steady-state plasma concentration (Css,max) of levodropropizine syrup and levodropropizine CR were 313.28 ng/mL and 285.31 ng/mL and time to reach Css,max (Tmax,ss) were 0.48 hr and 0.88 hr, respectively. The area under the concentration-time curve to the last measured concentration of two groups were 2345.36 hr × ng/mL and 2553.81 hr × ng/mL, respectively. There was no serious adverse event. Conclusion: Levodropropizine CR 90 mg tablet was safe and well-tolerated when administered twice daily for 3 days. No statistically significant differences were seen in Css,max and AUCss,24hr between the two formulations. This study provided pharmacokinetic evidences that the twice-daily dosing regimen of levodropropizine 90 mg may substitute the conventional 3-times-daily regimen of levodropropizine 60 mg.

Follow-up of analytical parameters in Internal Medicine patients to detect adverse events

To analyze the prevalence of prescription drugs, previously selected, that should be monitored by their analytical test, and the rate of alteration in these tests, with the aim of establishing priorities to facilitate monitoring. Prospective observational study in the Internal Medicine department of a referral hospital of 350 beds. In a first phase, we selected some drugs which analytical monitoring is recommended for the medical literature, and after that, we reviewed the pharmacological treatment of all patients admitted with any of these drugs. The study was conducted in the last two month of 2011. We included 271 patients, 128 (47%) were women. The mean age was 74.5 ± 14.4 years and the average stay of 7 ± 5.8 days. These patients accounted for 83% of all patients admitted to Internal Medicine during the study period. There were 828 drugs that must be monitored; each patient had an average of 3.1 ± 2.3. We reviewed 1837 analytical test, of which 401 (22%) were altered and 154 patients (57%) were affected for it. The pairs drug-analytical test altered most frequently found were creatinine increased and nephrotoxic drugs, hypokalemia in patients taking high efficiency diuretics and thrombocytopenia in patients treated with low molecular weight heparins. Our study highlights the importance of monitoring laboratory test associated with some drugs from the pharmacy department, as it demonstrates a high incidence of warning results. Our proposal for selection of drugs makes monitoring easier, and reaches large numbers of patients.

Bioequivalence and Pharmacokinetic Evaluation of Two Formulations of Risperidone 2 mg

BackgroundRisperidone is a benzisoxazole derivate and is effective in the treatment of schizophrenia and other psychiatric illnesses in adults and children. Although there are a few reports in the literature regarding the pharmacokinetic characteristics of risperidone, insufficient data on its pharmacokinetic properties in a Chinese population are available.ObjectiveTo meet the requirements for marketing a new generic product, this study was designed to compare the pharmacokinetic properties and bioequivalence of two 2 mg tablet formulations of risperidone: a newly developed generic formulation (test) and a branded formulation (reference) in healthy adult male Chinese volunteers.MethodsA single-dose, open-label, randomized-sequence, 2 × 2 crossover study was conducted in fasted healthy male Chinese volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 1 tablet (2 mg each) of the test formulation (Risperidone tablet; Dr. Reddy’s Laboratories Ltd., Hyderabad, India) or the reference formulation (Risperdal® tablet; Xian-Janssen Pharmaceutical Ltd., Xi-an, China), followed by a 2-week washout period and subsequent administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Plasma samples were collected over 96 hours. Plasma concentrations of the parent drug, risperidone, and its active metabolite, 9-hydroxy-risperidone, were analyzed by a liquid chromatography–tandem mass spectrometry method. The formulations would be considered bioequivalent if the 90% confidence intervals (CIs) of the natural log-transformed values were within the predetermined 80–125% equivalence range for the maximum plasma drug concentration (Cmax) and the area under the plasma concentration–time curve (AUC), in accordance with guidelines issued by the US Food and Drug Administration. Assessment of tolerability was based on recording of adverse events (AEs), monitoring of vital signs, electrocardiograms, and laboratory tests at baseline and at completion of the study.ResultsA total of 24 healthy male Chinese volunteers (mean age 22.9 years [standard deviation (SD) 2.7, range 19.2–27.1]; weight 63.2 kg [SD 7.0, range 52.0–78.0]; and height 171.3 cm [SD 6.1, range 162.0–187.0]) were enrolled, and all completed the study. For the parent drug, risperidone, the 90% CIs of the relative values (test vs. reference) of the Cmax, AUC from time zero to time t (AUCt), and AUC from time zero to infinity (AUC∞) were 97.0–124.0%, 92.7–115.1%, and 92.8–114.2%, respectively. For the active metabolite, 9-hydroxy-risperidone, the values were 104.4–117.7%, 101.0–113.7%, and 100.4–113.4%, respectively. The two formulations met the predetermined criteria for bioequivalence. A total of 73 AEs were observed in 24 subjects during the study. The most common AE was sedation (48 events), followed by nasal reactions (14 events), postural hypotension (3 events), hypertriglyceridemia (2 events), dizziness (4 events), nausea (1 event), and anorexia (1 event). Their severity was as follows: 16 were mild, 57 were moderate, and none were severe. The majority of the AEs were considered to be related (48 events) or probably related (23 events) to the study medication. No clinically significant abnormalities on physical examination, vital sign measurements, or electrocardiographic recordings were reported. No serious AEs were reported.ConclusionsThe data from this study in healthy adult male Chinese subjects suggest that the test formulation met the regulatory criteria for bioequivalence to the reference formulation, on the basis of the rate and extent of absorption. Both formulations were well tolerated.

Discussions on Zonal Disintegration around Tunnel in Deep Rock Mass

Questions related to zonal disintegration such as difference between results from laboratory test and field monitoring test, as well as the effect of multi-axial stress level on zonal disintegration were discussed through numerical modeling by using a 3D numerical code called RFPA3D. Results show that the much smaller fracture spacing captured by laboratory test on zonal disintegration is due to the heterogeneity extent of the tested material. Zonal disintegration is an inherent character of heterogeneous rock mass, the more the heterogeneous the rock is, the larger the spacing between the adjacent fractures will be. The configuration of zonal disintegration is influenced by combination of stress level in three directions. Intact fracture rings can not be formed unless a nearly hydrostatic stress state exists in directions perpendicular to tunnel axis.

Comparison of Pharmacokinetic Characteristics and the Safety between Amlodipine Maleate Tablet 5 mg and Amlodipine Besylate Tablet 5 mg

1 Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Korea, University of Ulsan College of Medicine, School of Military Medicine, The First Republic of Korea Army, Department of Clinical Pharmacology and Therapeutics, Inje University Pusan Paik Hospital, Pusan, Korea, 5 Division of Clinical Pharmacology, Clinical Trials Center, Pusan National University Hospital, Division of Clinical Pharmacology, Clinical Trial Center, Samsung Medical Center, Technical research center, CKD research institute, Chong Kun Dang Pharmaceutical Co, Ltd Background: Amlodipine is a third-generation dihydropyridine calcium channel blocker for treating hypertension. Though marketed primarily as a besylate salt, there have been some efforts to find other comparable salts. Among them, maleate is the salt that has been considered favorable for many drugs. The aim of this study was to compare the pharmacokinetics, as well as safety and tolerability of amlodipine maleate with amlodipine besylate. Methods: This study was open, randomized, two-period crossover design investigated in twelve healthy male volunteers over a 144 h period after administrating two forms of amlodipine 5 mg, respectively. Each period was separated with 2 weeks. Plasma concentrations of amlodipine were determined by liquid chromatography-tandem mass spectrometry. Safety profiles were assessed by vital signs, physical examinations, electrocardiograms, laboratory testing and adverse events monitoring. Results: All subjects were completed this study. Geometric mean ratios (GMRs) of amlodipine maleate/amlodipine besylate of Cmax and AUClast for amlodipine were 0.92 (90 % confidence interval, 0.81 ∼ 1.05) and 1.05 (0.96 ∼ 1.16), respectively. No serious adverse events were reported, and no clinically relevant changes were observed in safety profiles during this trial. Conclusion: Pharmacokinetics, tolerability and the safety were comparable between amlodipine maleate and amlodipine besylate in healthy individuals.

Hot-Mix Asphalt Permanent Deformation Evaluated by Hamburg Wheel Tracking, Dynamic Modulus, and Repeated Load Tests

Permanent deformation (or rutting) is a common distress in hot-mix asphalt (HMA) pavements. As part of the HMA mix and structural design processes to optimize field performance, the Hamburg wheel-tracking, dynamic modulus, and uniaxial repeated load permanent deformation tests have been developed to characterize the HMA rutting resistance potential. The primary objective of this study was to compare the three laboratory rutting tests of HMA mixes and to relate their rutting predictive potential to actual field performance. The research methodology incorporated a two-phase approach: laboratory testing and field performance monitoring of selected mixes under both conventional traffic loading and accelerated pavement testing. For the HMA mixes evaluated, a good correlation was observed in the three laboratory tests and in comparison with actual in situ field performance. Overall, the findings indicated that the Hamburg wheel-tracking test was the most feasible test for daily routine HMA mix design and screening, while both the dynamic modulus and repeated load permanent deformation tests exhibited greater potential for comprehensive characterization of HMA material property (e.g., modulus) and applications for pavement structural design as research-level test tools.

A cluster randomised trial of educational messages to improve the primary care of diabetes

BackgroundRegular laboratory test monitoring of patient parameters offers a route for improving the quality of chronic disease care. We evaluated the effects of brief educational messages attached to laboratory test reports on diabetes care.MethodsA programme of cluster randomised controlled trials was set in primary care practices in one primary care trust in England. Participants were the primary care practices' constituent healthcare professionals and patients with diabetes. Interventions comprised brief educational messages added to paper and electronic primary care practice laboratory test reports and introduced over two phases. Phase one messages, attached to Haemoglobin A1c (HbA1c) reports, targeted glycaemic and cholesterol control. Phase two messages, attached to albumin:creatinine ratio (ACR) reports, targeted blood pressure (BP) control, and foot inspection. Main outcome measures comprised practice mean HbA1c and cholesterol levels, diastolic and systolic BP, and proportions of patients having undergone foot inspections.ResultsInitially, 35 out of 37 eligible practices participated. Outcome data were available for a total of 8,690 patients with diabetes from 32 practices. The BP message produced a statistically significant reduction in diastolic BP (-0.62 mmHg; 95% confidence interval -0.82 to -0.42 mmHg) but not systolic BP (-0.06 mmHg, -0.42 to 0.30 mmHg) and increased the odds of achieving target BP control (odds ratio 1.05; 1.00, 1.10). The foot inspection message increased the likelihood of a recorded foot inspection (incidence rate ratio 1.26; 1.18 to 1.36). The glycaemic control message had no effect on mean HbA1c (increase 0.01%; -0.03 to 0.04) despite increasing the odds of a change in likelihood of HbA1c tests being ordered (OR 1.06; 1.01, 1.11). The cholesterol message had no effect (decrease 0.01 mmol/l, -0.04 to 0.05).ConclusionsThree out of four interventions improved intermediate outcomes or process of diabetes care. The diastolic BP reduction approximates to relative reductions in mortality of 3% to 5% in stroke and 3% to 4% in ischaemic heart disease over 10 years. The lack of effect for other outcomes may, in part, be explained by difficulties in bringing about further improvements beyond certain thresholds of clinical performance.Trial RegistrationCurrent Controlled Trials, ISRCTN2186314.

Management of Large Intentional Overdose of Enoxaparin with Protamine Sulfate

Abstract 4330 Introduction:Enoxaparin, a low molecular weight heparin (LMWH), is used for prophylaxis and treatment of venous and arterial thromboembolism. Due to its safety profile, there has been little literature regarding management and treatment of overdoses. Two reports of enoxaparin overdose have been described in the literature; a neonate received a 10-fold overdose and a 64-year old man received an extra daily dose. Both cases were treated with an approximate 1 to 1 ratio of protamine sulfate to LMWH (30 mg and 20 mg, respectively) and showed incomplete reversal of anticoagulation. Plasma levels of LMWH can be monitored by measuring anti-factor Xa levels; however, studies correlating large overdoses have not been performed. Peak plasma levels of LMWH are found 3–4 hours after administration, and the half-life of the drug is 4.5–7 hours. Anti-factor Xa levels, however, are not readily available at most institutions. We report a challenging case of a large overdose of LMWH, successfully treated despite the lack of appropriate laboratory monitoring tests. Case Report:A 50-year old Caucasian man with a past medical history significant for bipolar disorder, schizophrenia, hypertension, and pulmonary embolism secondary to a hypercoagulable state caused by tetrahydrofolate reductase deficiency was found unresponsive and transported to the emergency department. Upon admission, he reported self-administration of 20 subcutaneous injections of 100 mg of enoxaparin (2000 mg) and 8 tablets of quetiapine (400 mg/tablet) in an attempt to commit suicide. He was somnolent but arousable with bruising noted around multiple injection sites on his abdomen. The remainder of his physical exam was unremarkable, and he exhibited no overt signs of bleeding. Initial laboratory assessment, approximately 2 hours post-suicide attempt, revealed an elevated aPTT of >150 seconds (reference range 23–38 seconds). Anti- factor Xa levels were not available at the time of treatment. An initial dose of protamine sulfate, 250 mg mixed in 500 ml of 0.9% sodium chloride, was infused over 3–4 hours. Repeat aPTT was 61 seconds. A second infusion of protamine sulfate was administered 2 hours later, and the aPTT decreased further to 49 seconds. Rebound phenomenon was noted 3–8.5 hours later as the aPTT increased (70 to 89 seconds), however, no additional protamine sulfate was given. At 24 hours, the aPTT was 46 seconds. The patient did not exhibit any signs of bleeding during treatment, and tolerated the infusions of protamine sulfate without any adverse effects. Subsequent testing for anti-factor Xa revealed an initial level of 4.72 IU/mL upon admit (therapeutic range 0.50 – 1.10 IU/mL), decreasing to 4.52 and 3.82 IU/mL after the infusions of protamine sulfate. The anti-factor Xa level at 24 hours was 1.39 IU/mL. Conclusion:The reversal of an enoxaparin overdose is challenging and frequently difficult to manage. Reversal with protamine sulfate is often incomplete, and infusion of the recommended dosage of 1 mg for each 1 mg of enoxaparin can be risky in large dosages. Ideally, Factor Xa levels, when available, can assist in management decision, however in emergency situations as described here, the aPTT and clinical symptoms must be used to guide treatment. Disclosures:No relevant conflicts of interest to declare.

Comparison of Prothrombin Time INR Derived From Point-of-Care and Laboraotry Test According to Fibrinogen Level

Abstract 4325Coumarin-derived anticoagulants such as warfarin inhibit the vitamin K expoxide reductase (VKORC1) and block vitamin K cycle rendering coagulation factors II, VII, IX, X left in functionally null state (PIVKAs). Because of the narrow therapeutic range of warfarin, prothrombin time standardized into international normalized ratio (INR) should be frequently measured to prevent unwanted bleeding or recurring thrombosis. Point of care (POC) tests for patient self monitoring of anticoagulation was developed with the intention that more frequent monitoring of would enhance the compliance of the patients and prevent overdose. The accordance between results derived from these POCs tests and clinical laboratory tests has been repeatedly reported and the patients self monitoring strategy is now generally accepted as a reliable way for maintaining safer anticoagulation therapy. However, we pointed out that the POC test, especially CoaguChek (Roche) wide in use domestically, can show different correlation pattern with laboratory tests according to fibrinogen level, because the assay principle of the POC test is basically measuring thrombin activity. We found negative bias of POC INR compared with laboratory test from specimen with fibrinogen level lower than 130 mg/dl while positive biases were observed from that with fibrinogen level higher than 130 mg/dl. The difference in INR range from −0.7 to 1.7 and the maximum differences in both directions were observed in specimen with INR above 3.0, that is exceeding therapeutic range. These results suggest that patient selection according to fibrinogen status should precede the implementation of patient self monitoring and periodic laboratory tests and comparison with POC results should be continued as before the initiation of self monitoring. Disclosures:No relevant conflicts of interest to declare.

C-C5-04: Can Claims Data Accurately Identify Graft Type and Infections Following Anterior Cruciate Ligament Repairs?

> 85%, while the completion rate for anticonvulsants ranged from 30-75%. The lowest test completion rate was for phenobarbital levels to monitor phenobarbital (30%). For all cardiovascular and anticonvulsant drugs, the proportion of recommended tests not ordered by the clinician ranged from 5% to 60%. The lowest test order prevalence was for phenobarbital level for phenobarbital use (35%), followed by valproic acid level for valproate use(48%), and carbamazepine level for carbamazepine use (60%). Rates of patient noncompletion of ordered tests for all drugs was generally <10%. Conclusion: Completion of laboratory monitoring tests for high-risk cardiovascular medications was higher than for high-risk anticonvulsants according to HEDIS guidelines. Clinician ordering behavior exhibited more variation than patient adherence to test orders. Underestimation of HEDIS quality of care monitoring due to patient non-adherence is minimal for cardiovascular medications, but higher for anticonvulsants. Background: The frequency of human tissue allograft contamination leading to infection is unknown. Attributing infections to allograft contamination versus surgical factors is elusive. National claims data may facilitate study of allograft-associated infections but first require accurate algorithms to identify implantations and infections. We explored the feasibility of using claims data to identify anterior cruciate ligament (ACL) allograft implants and infections. Methods: We selected candidate diagnosis, procedure, visit type, and antibiotic prescription criteria to identify ACL allograft repairs and infections. Candidate criteria were categorized by likelihood of infection and putative pathogen type. Criteria were then applied to HMO Research Network Virtual Data Warehouse files for 2000-2008 from six sites. We defined the infection risk period as 90 days following ACL repair. We reviewed charts flagged by each criterion to determine implant type and to assess for infection. Sensitivity and positive predictive values (PPV) were calculated. Results: Preliminary results are available from five of six sites. Procedure codes 29888 and 81.45 (ACL repair, unspecified) flagged 11,202 episodes of care. Diagnosis codes compatible with infection flagged 139 episodes (1.2%) of which 71 were categorized as high probability (0.63%). Microbiology and infection management procedure codes flagged 1,029 episodes (9.2%) and 68 episodes (0.6%) respectively. Antibiotics were prescribed for 1,523 episodes (14%) of which 580 were deemed high likelihood prescriptions (5.2%). There were 1011 hospitalizations within 90 days of ACL implantation (9.0%), 787 emergency department visits (7.0%), and 43 infectious disease specialist visits (0.4%). Over 1500 chart reviews are planned of which 107 have been completed thus far. The PPV for allograft implantation is 33% (95% CI 25-43%). Sufficient data are currently available to confirm 14 infections. Antibiotic prescribing was the most sensitive criterion while infectious disease visit had the highest PPV (sensitivities 86% and 7%, PPVs 35% and 100% respectively). Conclusions: Claims data do not discriminate between allografts and autografts in ACL repair but do identify a subset of patients with possible infections. Once chart

Evaluation of a pharmacist-managed amiodarone monitoring program.

Because of the potential for serious adverse effects, patients treated with amiodarone must be carefully screened and routinely monitored for potential liver, thyroid, and pulmonary toxicity. However, laboratory and pulmonary monitoring rates have been found to be substantially lower than recommended in guidelines, including those of the North American Society of Pacing and Electrophysiology (NASPE, 2007). To (a) assess rates of laboratory monitoring of liver, thyroid, and pulmonary function and adverse events in a pharmacist-managed amiodarone monitoring program compared with usual care in an integrated health care system and (b) estimate return on investment (ROI) from this intervention. This retrospective cohort study used clinic and enrollment data to identify those patients in the pharmacist-managed program and usual care who received at least 100 days of amiodarone therapy with the first prescription for amiodarone (index) from June 1, 2007, through May 31, 2009 (index date). Laboratory test monitoring was recorded at baseline (up to 6 months before the index date), from 1-6 months after the index date, 7-12 months after the index date, and at any time during the year (months 1-12). Alanine aminotransferase (ALT) was evaluated for liver function. Thyroid-stimulating hormone (TSH) and, for patients with abnormal TSH ( less than 0.4 micro international units [uIU] per mL or greater than 4.0 uIU per mL), free thyroxine (T4) were evaluated for thyroid function. Rates of pulmonary function testing (PFT) were measured by the diffusion capacity of carbon monoxide tests (DLCO) and annual chest x-rays (CXR); electrocardiograms were not counted. Monitoring rates were compared using Pearson chi-square tests, and logistic regression was used to compare the odds of testing (ALT, TSH, T4, CXR, PFT) between the 2 groups at any time during the year after the index date. Concomitant uses of amiodarone with high-dose statins and of amiodarone with digoxin were compared using Pearson chi-square tests. Hospitalizations and emergency room (ER) visits during the 12-month follow-up period were counted for (a) interstitial lung disease; (b) rhabdomyolysis for patients who received amiodarone with high-dose statins (either lovastatin greater than 40 mg per day or greater than 20 mg per day of simvastatin or atorvastatin); and (c) for patients with abnormal digoxin, ALT, TSH, or T4 levels, if the hospitalization occurred within 2 days of the abnormal laboratory value. There were 2,292 patients who received at least 100 days of amiodarone therapy and met the other inclusion criteria, of whom 181 patients (7.9%) were in the pharmacist-managed group and 2,111 received usual care. There were 90 (49.7%) new amiodarone users in the pharmacist-managed group and 990 (46.9%) in usual care. The 2 groups had similar demographic characteristics except race, with more whites and fewer African Americans, Asians, and Hispanics in usual care. Laboratory monitoring rates for ALT, TSH, and T4 were significantly higher in the pharmacist-managed group than usual care at the first and second 6 months and at baseline for ALT and TSH but not T4. Baseline CXR rates were significantly higher for the pharmacist-managed group than usual care (59.1% vs. 49.3%; P=0.011). Few patients in either group received PFT tests at baseline, 6.6% versus 3.6% (P=0.042). After controlling for covariates (age, gender, race, new vs. continuing use, and comorbidities), pharmacist-managed patients were significantly more likely to have at least 1 ALT test within the year after the index prescription (odds ratio [OR]=3.13, 95% CI=1.12-8.71), as well as a TSH test (OR=8.13, 95% CI=3.27-20.21) and T4 (OR=2.51, 95% CI=1.67-3.75). PFTs were also more likely to be given to these patients (OR=5.89, 95% CI=3.86-8.99). A higher percentage of patients in the pharmacist-managed group than in usual care were taking a high-dose statin during the 12-month follow-up period (47.5% vs. 36.2%, P=0.003), but of those patients, a greater proportion were switched to another statin (14.0% [n=12] vs. 7.5% [n=57], P=0.037) or a lower dose (9.3% [n=8] vs. 3.9% [n=30], P=0.022). Six patients in the usual care group (0.79% of patients on high-dose statins) developed rhabdomyolysis, and 5 (0.24% of all patients in usual care) had an admission for interstitial lung disease. The proportions of patients using amiodarone and digoxin concomitantly were similar in the 2 groups (35.9% vs. 31.3%, P=0.197). Among patients with abnormal laboratory results for ALT, TSH, and T4, or digoxin, there were 2 all-cause hospitalizations and 1 ER visit in the pharmacist-managed group and 34 all-cause hospitalizations and 18 ER visits in the usual care group during the follow-up year. Assuming that all hospitalizations and ER visits incurred in the usual care group were avoid- able, approximately $2.14 could be saved for every dollar spent on the pharmacist-managed amiodarone monitoring program. Pharmacist management of patients treated with amiodarone was associated with improved monitoring of recommended laboratory tests and PFTs.

A Case Study on the in-situ Matrix Suction Monitoring and Undisturbed-Sample Laboratory Test for the Unsaturated Colluvium Slope

ABSTRACT Huafan University is located on the slope of the Ta-Lun Mountain area. The slope surface in this area is a colluvium soil cover layer with loose non-uniform particles, with high permeability. Because it is situated above a rapidly changing water table, the pore water pressure varies dynamically, depending on the weather conditions. In the dry season, most of the topsoil behaves in the unsaturated condition such that the matrix suction in the soil increases its shearing strength. In contrast, when heavy rainfall occurs, the seepage by precipitation tends to destroy the existing matrix suction. This reduction in soil strength frequently results in slope failure. This study, focuses on the variation of matrix suction of the colluvium soil in different precipitation conditions with varying vegetation at the campus of Huafan University. The analysis of the in-situ monitoring results and the laboratory test results for the undisturbed specimens taken from the field, with shearing strength and matrix suction taken into account. It is expected the results to be a useful reference for disaster protection on slopes.

Revisión sobre la interacción entre fármacos y nutrición enteral

Article on the drug administration of concomitant enteral nutrition. Objective: To find the available evidence in the literature that addresses the issue of drug interaction and enteral nutrition administered by tube. Methodology: review that used data from electronic databases. Results: 62 articles were found and seven were selected. Discussion: The classes of drug were antiepileptics (43%), antibiotics (43%) and anticoagulants (14%). The class that has most risk of interaction with enteral nutrition was that of antiepileptics, especially with phenytoin. Antibiotics showed no significant decreases in serum and warfarin, the only anticoagulant mentioned, also presented a risk of interaction with enteral nutrition. Conclusion: it is necessary to develop initiatives such as the habit of washing the probe, stopping the enteral feeding, monitoring laboratory tests to prevent possible interactions between drugs and enteral nutrition.

Vancomycin-Associated Spontaneous Cutaneous Adverse Drug Reactions

PurposeWith the increase in vancomycin use, adverse drug reactions (ADRs) associated with vancomycin have been reported increasingly more often. However, the characteristics of cutaneous ADRs with and without systemic reactions (SRs) have not been described. This study investigated the characteristics of spontaneously reported and assessed ADRs associated with vancomycin by a pharmacovigilance center.MethodsADRs (n=121) associated with vancomycin in 96 patients were collected from 2008 to 2009. Records from physician- and nurse-reported suspected cases of vancomycin ADRs, ADR type, latent period, and laboratory results were compared between cutaneous ADRs with and without SRs.ResultsThe main vancomycin-related ADRs were skin rashes (47.9%), hematologic abnormalities (17.36%), fever (12.4%), and elevated serum creatinine (12.4%). Significant differences were observed in latent period (days) and the mean change in eosinophils (%) between cutaneous (9.21±9.71 and 1.4±3.4, respectively) and other ADRs (14.03±11.71 and -0.5±3.5, respectively). Twelve cases of cutaneous ADRs with SRs had been initially reported as cutaneous ADRs only. Mean changes in the eosinophil count were significantly higher for cutaneous ADRs with SRs compared to those without SRs.ConclusionsSkin rashes accompanied by peripheral eosinophilia, representing suspected immune-mediated delayed hypersensitivity reactions, are a common vancomycin ADR. For the early and exact detection of ADRs associated with vancomycin administration, close monitoring of laboratory tests, including complete blood counts with differential analysis, is recommended.

Monitoring Antiretroviral Therapy in HIV-Infected Children in Resource-Limited Countries: A Tale of Two Epidemics

Twenty-nine years into the HIV epidemic, several advances have been made; however, there remain several challenges particularly with pediatric HIV in resource-limited countries. The obstacles facing pediatric antiretroviral therapy (ART) delivery in resource-limited countries are multifaceted: lack of health care infrastructure, limited availability of pediatric drug formulations, lack of early HIV diagnostic and monitoring techniques, limited manpower with expertise in pediatric HIV care, limited donor funding, and competing public health priorities with limited health care budget. In this paper, the challenges with various ART monitoring tools in resource-limited countries are discussed. Noninvasive (e.g., patient, clinical events outcome, and adherence) and invasive (e.g., immunologic and virologic) monitoring tools are discussed. Several cheap and technically less complex laboratory tests for monitoring are becoming available. Funding agencies and country programs should invest in validating the use of current technologies to optimize pediatric HIV care in resource-limited countries.

Relationship of 24-hour ambulatory blood pressure and heart rate with markers of hepatic function in cirrhotic patients

BackgroundThere is evidence that in cirrhotic patients, certain hemodynamic parameters, such as blood pressure and heart rate, are related to the severity of liver disease. This study investigated whether non-invasive 24-hour ambulatory blood pressure and heart rate are more closely associated with markers of liver disease severity than conventional office measurements.MethodsAmbulatory patients with cirrhosis underwent office blood pressure and heart rate measurements, 24-hour ambulatory blood pressure monitoring and blood laboratory tests.ResultsFifty-one patients (32 men, mean age 57.4 ± 11.3 years) completed the study. Twenty six patients had compensated liver cirrhosis (group A) and 25 patients had more advanced liver disease (group B). Group A and B patients differed significantly both in ambulatory asleep diastolic blood pressure (p < 0.05) and office diastolic blood pressure (p < 0.01), which were lower in more advanced liver disease. Office blood pressure and heart rate correlations were similar to or even stronger than ambulatory ones. Ambulatory blood pressure and heart rate awake-asleep variation (dipping) showed a relatively flat pattern as markers of liver dysfunction were deteriorating. The strongest correlations were found with both ambulatory and office heart rate, which increased as indicators of severity of liver disease were worsening.ConclusionsHeart rate seems to be a more reliable marker of ongoing liver dysfunction than blood pressure. Evaluation of blood pressure and heart rate with 24-hour ambulatory measurement does not seem to offer more information than conventional office measurements.

Pharmacokinetics and bioequivalence evaluation of two losartan potassium 50-mg tablets: A single-dose, randomized-sequence, open-label, two-way crossover study in healthy Chinese male volunteers

Background: Losartan is a nonpeptide angiotensin II receptor antagonist used as an antihypertensive agent. The relative bioavailability of a newly developed tablet compared with an established branded formulation has not been reported in a Chinese population. Objective: To meet the requirements for marketing a new generic product, the study was designed to compare the pharmacokinetic parameters and relative bioavailability of a new generic losartan potassium 50-mg tablet (test formulation) with a branded 50-mg tablet (reference formulation) in healthy Chinese male volunteers. Methods: A single-dose, randomized-sequence, openlabel, 2-way crossover study was conducted in healthy Chinese male volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive a single 50-mg tablet of the test or reference formulation, followed by a 1-week washout period and then administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Plasma samples were collected over 36 hours. Tolerability was evaluated by recording adverse events (AEs) and monitoring vital signs, ECGs, and laboratory tests at baseline and at completion of the study. Plasma concentrations of losartan and its active metabolite (EXP3174) were analyzed by LC-MS/MS. Pharmacokinetic parameters, including C max, AUC 0–36, and AUC 0−∞, were calculated. If the 90% CIs for the log-transformed values of AUC were within 80% to 125%, and that of C max was within 70% to 143%, the 2 products would be considered bioequivalent according to the guidelines of the US Food and Drug Administration and the State Food and Drug Administration of China. Results: Twenty–seven healthy Chinese male volunteers participated in this study (mean [SD] age, 24.5 [2.3] years [range, 20–29 years]; weight, 64.6 [4.0] kg [range, 60.0-75.0 kg]; height, 172.2 [4.8] cm [range, 165.0183.0 cm]; and body mass index, 21.8 [1.2] kg/m 2 [range, 20.0–25.0 kg/m 2]). One volunteer (3.7%) experienced an AE (microscopic hematuria) after administration of the test formulation. This resolved spontaneously after 10 days and was considered by the investigator as mild; the relationship with the study drug was uncertain. No serious AEs were reported. Both formulations were associated with significant reductions in systolic and diastolic blood pressure and significant increases in heart rate compared with baseline values (all, P < 0.05). No period, formulation, or sequence effects were observed for any pharmacokinetic parameter, except for a significant subject effect. For parent losartan, the 90% CIs for the ratios (test/reference) of C max, AUC 0–36, and AUCAUC 0−∞ were 83.65% to 113.36%, 89.79% to 98.25%, and 90.95% to 99.55%, respectively. For the metabolite EXP3174, the 90% CIs for the ratios of C max, AUC 0–36, and AUCAUC 0−∞ were 93.49% to 103.61%, 96.79% to 104.09%, and 97.06% to 105.83%. Both C max and AUC met the predetermined criteria for assuming bioequivalence. The relative bioavailability of the test formulation to the reference formulation was 93.92% for losartan and 100.40% for EXP3174. Conclusions: In this small study in healthy Chinese male volunteers, a single 50-mg oral dose of a losartan potassium tablet (test formulation) met the regulatory criteria for assuming bioequivalence to the established reference formulation. Both formulations were well tolerated.