Risk of Hepatotoxicity Associated with the Use of Telithromycin: A Signal Detection Using Data Mining Algorithms (December).

Ann Pharmacother. 2008 Nov 25;

Authors: Chen Y, Guo JJ, Healy DP, Lin X, Patel NC

BACKGROUND: With the exception of case reports, limited data are available regarding the risk of hepatotoxicity associated with the use of telithromycin. OBJECTIVE: To detect the safety signal regarding the reporting of hepatotoxicity associated with the use of telithromycin using 4 commonly employed data mining algorithms (DMAs). METHODS: Based on the Adverse Events Reporting System (AERS) database of the Food and Drug Administration, 4 DMAs, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the Gamma Poisson Shrinker (GPS), were applied to examine the association between the reporting of hepatotoxicity and the use of telithromycin. The study period was from the first quarter of 2004 to the second quarter of 2006. The reporting of hepatotoxicity was identified using the preferred terms indexed in the Medical Dictionary for Regulatory Activities. The drug name was used to identify reports regarding the use of telithromycin. RESULTS: A total of 226 reports describing hepatotoxicity associated with the use of telithromycin were recorded in the AERS. A safety problem of telithromycin associated with increased reporting of hepatotoxicity was clearly detected by 4 algorithms as early as 2005, signaling the problem in the first quarter by the ROR and the IC, in the second quarter by the PRR, and in the fourth quarter by the GPS. CONCLUSIONS: A safety signal was indicated by the 4 DMAs suggesting an association between the reporting of hepatotoxicity and the use of telithromycin. Given the wide use of telithromycin and serious consequences of hepatotoxicity, clinicians should be cautious when selecting telithromycin for treatment of an infection. In addition, further observational studies are required to evaluate the utility of signal detection systems for early recognition of serious, life-threatening, low-frequency drug-induced adverse events.

PMID: 19033479 [PubMed - as supplied by publisher]

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Novel Algorithm for More Accurate Calculation of Renal Function in Adults with Cancer (December).

Ann Pharmacother. 2008 Nov 25;

Authors: Holweger K, Lipp HP, Dietz K, Hartmann JT, Bokemeyer C

BACKGROUND: Cytotoxic agents have a narrow therapeutic window. A high percentage of some of them is renally excreted in unchanged form. Accurate assessment of an individual's glomerular filtration rate (GFR) helps to predict the pharmacokinetic behavior of those drugs more precisely. GFR calculations, however, have their limitations. OBJECTIVE: To establish a more accurate calculation of renal function over a broad range of constitutive GFR values. METHODS: Patients with cancer were included in the analysis. Serum levels of cystatin C, creatinine, urea, albumin, and beta-trace protein were measured, and GFR was calculated by 8 mathematical formulas. The results were compared with creatinine clearance (CrC1) calculated from timed urine specimens. RESULTS: One hundred two patients were evaluated: median age, 57.5 years (range 20-91); females, 52; males, 50; and mean urinary CrCl, 77.0 mL/min. The bias (mean percentage error) was -2% and the precision (mean absolute percentage error) was 23% for the Modification of Diet in Renal Disease (MDRD) estimation of GFR. All equations significantly overestimated CrCl in patients with measured clearance less than 50 mL/min (p < 0.05), with the exception of the modified Salazar-Corcoran formula. All equations underestimated CrCl in patients with measured clearance greater than 100 mL/min. The Wright formula was the least biased and most precise (-5%, 16%, respectively). In patients with measured CrCl 50-100 mL/min, the MDRD calculation had a bias of -4% and a precision of 17%. The Jelliffe and Larsson equations were associated with significant sex bias (p < 0.05). CONCLUSIONS: These observations suggest that individual GFR values over a broad range cannot be calculated accurately enough with only one selected formula. It may be useful to classify renal function of patients with cancer according to the novel algorithm by using MDRD first and then to subsequently calculate GFR in higher and lower ranges with the Wright and modified Salazar-Corcoran formulas, respectively. This algorithm should be validated using larger numbers of patients.

PMID: 19033483 [PubMed - as supplied by publisher]

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Multidrug-Resistant Pseudomonas aeruginosa Ventilator-Associated Pneumonia: The Role of Endotracheal Aspirate Surveillance Cultures (January).

Ann Pharmacother. 2008 Nov 25;

Authors: Yang K, Zhuo H, Guglielmo BJ, Wiener-Kronish J

BACKGROUND: Inappropriate antibacterial treatment of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) pathogens is associated with increased mortality. Endotracheal aspirate (ETA) surveillance cultures potentially identify MDR pathogens, particularly MDR Pseudomonas aeruginosa, resulting in improved selection of therapy in patients who subsequently develop VAP. OBJECTIVE: To investigate the role of ETA surveillance cultures in the identification of MDR P. aeruginosa in newly intubated adults who subsequently develop VAP. METHODS: Daily ETA surveillance cultures for P. aeruginosa were collected in all adults newly intubated for 48 hours or more. Patients with preexisting lung disease or colonization or infection with P. aeruginosa were excluded. Risk factors and outcomes of patients newly colonized with MDR P. aeruginosa were assessed. RESULTS: Seventy-five patients newly colonized with P. aeruginosa were identified. Twenty (27%) of these patients were colonized with a P. aeruginosa isolate that was MDR (resistant to >/=3 classes of antibiotics). Six patients were colonized by an isolate resistant to all tested classes of antibiotics. Forty-five percent of patients colonized with MDR P. aeruginosa subsequently developed VAP. Prior receipt of fluoroquinolones was an independent predictor of colonization with MDR P. aeruginosa (OR 11.82; 95% CI 2.10 to 66.46; p = 0.005). CONCLUSIONS: Performance of routine surveillance cultures may aid in the early detection of MDR P. aeruginosa, improving the initiation of early and appropriate antibiotic therapy for patients who subsequently develop VAP.

PMID: 19033484 [PubMed - as supplied by publisher]

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BMJ. 2008;337:a2097

Authors: Walker AS, Spiegelhalter D, Crook DW, Wyllie D, Morris J, Peto TE

PMID: 19022838 [PubMed - in process]

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Diagnosis and management of headache in adults: summary of SIGN guideline.

BMJ. 2008;337:a2329

Authors: Duncan CW, Watson DP, Stein A,

PMID: 19022842 [PubMed - as supplied by publisher]

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Relation of Mortality to Failure to Prescribe Beta Blockers Acutely in Patients With Sustained Ventricular Tachycardia and Ventricular Fibrillation Following Acute Myocardial Infarction (from the VALsartan In Acute myocardial iNfarcTion trial [VALIANT] Registry).

Am J Cardiol. 2008 Dec 1;102(11):1427-32

Authors: Piccini JP, Hranitzky PM, Kilaru R, Rouleau JL, White HD, Aylward PE, Van de Werf F, Solomon SD, Califf RM, Velazquez EJ

Sustained ventricular arrhythmias and heart failure are well-recognized complications after acute myocardial infarction (AMI) and have been associated with worse outcomes and increased mortality. The use of and outcomes associated with acute beta-blocker therapy in patients with AMI complicated by sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and heart failure were investigated. Of 5,391 patients in the VALIANT Registry, sustained VT/VF occurred in 306 (5.7%), with an in-hospital mortality rate of 20.3%. Multivariable logistic regression identified sustained VT/VF as a major predictor of in-hospital death (relative risk 4.18, 95% confidence interval 2.91 to 5.93). Of those with sustained VT/VF, 55.2% were treated with intravenous or oral beta blockade in the first 24 hours. After adjusting for baseline characteristics, propensity for acute beta-blocker use, and the interaction between Killip classification and beta-blocker therapy, beta-blocker therapy within 24 hours was associated with decreased in-hospital mortality in patients with sustained VT/VF (relative risk 0.28, 95% confidence interval 0.10 to 0.75, p = 0.013) without evidence of worsening heart failure. Patients with sustained VT/VF were less likely to receive beta blockers within 24 hours (p = 0.001). In conclusion, sustained VT/VF was common after AMI. In patients with sustained VT/VF, beta-blocker therapy in the first 24 hours after AMI was associated with decreased early mortality without worsening heart failure. Unfortunately, beta blockers were underused acutely in patients with sustained VT/VF.

PMID: 19026290 [PubMed - in process]

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Role of myocardial perfusion imaging in patients with end-stage renal disease undergoing coronary angiography.

Am J Cardiol. 2008 Dec 1;102(11):1451-6

Authors: Venkataraman R, Hage FG, Dorfman T, Heo J, Aqel RA, de Mattos AM, Iskandrian AE

Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. This study examined the prognostic power of stress myocardial perfusion imaging (MPI) in 150 patients with ESRD (mean age 53 +/- 9 years; 30% women; 66% with diabetes mellitus) being evaluated for renal transplantation with known coronary anatomy using angiography. Baseline data in addition to perfusion and angiographic parameters were compared between survivors and nonsurvivors. All-cause mortality was defined as the outcome measure. An abnormal MPI result was present in 85% of patients, 30% had left ventricular (LV) ejection fraction (EF) </=40%, and 40% had multivessel coronary artery disease using angiography. At a mean follow-up of 3.4 +/- 1.5 years, 53 patients died (35%). LVEF </=40%, LV dilatation (LV end-diastolic volume >90 ml), and diabetes mellitus were associated with higher mortality (all p <0.05). Both total perfusion defect size and mean number of narrowed coronary arteries using angiography were significantly higher in those who died (p <0.05). In a multivariate model, abnormal MPI results (low LVEF or abnormal perfusion) and diabetes alone were independent predictors of death, whereas number of narrowed arteries using coronary angiography was not. Thus, MPI was a strong predictor of all-cause mortality in patients with ESRD. In conclusion, abnormal MPI results independently predicted worse survival and provided more powerful prognostic data than coronary angiography.

PMID: 19026294 [PubMed - in process]

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Comparison of Myocardial Reperfusion in Patients With Fasting Blood Glucose </=100, 101 to 125, and >125 mg/dl and ST-Elevation Myocardial Infarction With Percutaneous Coronary Intervention.

Am J Cardiol. 2008 Dec 1;102(11):1457-62

Authors: Fefer P, Hod H, Ilany J, Shechter M, Segev A, Novikov I, Guetta V, Matetzky S

Diabetes and impaired fasting glucose (FG) were associated with worse outcomes in patients with acute myocardial infarction (MI). Because the underlying mechanism is not entirely clear, 376 consecutive patients with ST-elevation MI who underwent primary percutaneous coronary intervention (PPCI) were investigated. Patients were divided into 3 groups based on FG </=100, FG of 101 to 125, and FG >125 mg/dl or previously diagnosed diabetes mellitus (DM) and studied for electrocardiographic signs of myocardial reperfusion (both spontaneous and after PPCI) and clinical outcomes. Clinical reperfusion was less likely with increasing FG: FG </=100 mg/dl, 26%; FG of 101 to 125, 19%; and FG >125 and/or DM, 16% (p for trend = 0.03). Accordingly, angiographic TIMI grade 3 flow on initial angiography was 22% for FG </=100 mg/dl, 13% for FG of 101 to 125, and 14% for FG >125 and/or DM (p for trend = 0.05). Despite similar TIMI flow after PPCI, early ST-segment resolution (>/=70%) was noted in 76%, 63%, and 60% in patients with FG </=100 mg/dl, FG of 101 to 125, and FG >125 and/or DM, respectively (p for trend <0.01). Peak creatine phosphokinase (CPK) increased gradually, whereas left ventricular ejection fraction decreased with increased FG. Worse outcomes were observed with increasingly higher FG for heart failure (9%, 23%, and 26%; p for trend <0.01), cardiogenic shock (5%, 7%, and 13%; p for trend = 0.02), in-hospital mortality (1%, 2%, and 6%; p for trend = 0.01), and long-term mortality (2.5%, 4.5%, and 12%; p for trend <0.01) for patients with FG </=100 mg/dl, FG of 101 to 125, and FG >125 and/or DM, respectively. In conclusion, increased FG and previously diagnosed DM were associated with less spontaneous reperfusion and less myocardial reperfusion after PPCI, resulting in worse clinical outcomes.

PMID: 19026295 [PubMed - in process]

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Two-year clinical outcome with drug-eluting stents versus bare-metal stents in a real-world registry of unprotected left main coronary artery stenosis from the italian society of invasive cardiology.

Am J Cardiol. 2008 Dec 1;102(11):1463-8

Authors: Palmerini T, Marzocchi A, Tamburino C, Sheiban I, Margheri M, Vecchi G, Sangiorgi G, Santarelli A, Bartorelli A, Briguori C, Vignali L, Di Pede F, Ramondo A, Inglese L, De Carlo M, Bolognese L, Benassi A, Palmieri C, Filippone V, Sangiorgi D, De Servi S

Data are limited about the relative efficacy of drug-eluting stents (DESs) versus bare-metal stents (BMSs) for the treatment of unprotected left main coronary artery (ULMCA) stenosis. The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study involving 19 high-volume Italian centers of patients with ULMCA stenosis treated using percutaneous coronary intervention (PCI). From January 2002 to December 2006, of 1,453 patients identified with ULMCA stenosis treated with PCI, 1,111 were treated with DESs and 342 were treated with BMSs. During a 2-year follow-up, risk-adjusted survival free from cardiac death was significantly higher in patients treated with DESs than in those treated with BMSs. The propensity-adjusted hazard ratio for risk of 2-year cardiac mortality after DES versus BMS implantation was 0.49 (95% confidence interval 0.32 to 0.77). The benefit of DESs in reducing cardiac mortality was obtained in the period from 3 to 6 months and maintained up to 2 years. In conclusion, for patients with ULMCA stenosis undergoing PCI, DES implantation was associated with higher adjusted rates of 2-year survival free from cardiac death. The benefit of DESs in reducing cardiac mortality was obtained in the period in which clinical manifestations of restenosis usually peak.

PMID: 19026296 [PubMed - in process]

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Emergency Pretreatment for Contrast Allergy Before Direct Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

Am J Cardiol. 2008 Dec 1;102(11):1469-72

Authors: Hubbard CR, Blankenship JC, Scott TD, Skelding KA, Berger PB

Patients with previous adverse contrast reactions occasionally present with ST-segment elevation myocardial infarction. Whether they can undergo catheterization safely using current contrast and medications is unknown. We reviewed catheterization laboratory records of all 501 patients (January 2005 to December 2006) presenting with ST-segment elevation myocardial infarction who underwent emergency coronary angiography. Six patients (1.2%) reported a previous contrast reaction including rash, acute bronchospasm, or anaphylaxis. All received a combination of intravenous steroids and H1 and H2 blockers in the emergency department or catheterization laboratory before catheterization. None of these had complications or evidence of allergy in any patient. In conclusion, some patients with previous contrast reaction may undergo emergency catheterization without adverse consequences, although the safety of this approach has not been proved.

PMID: 19026297 [PubMed - in process]

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Risk predictors of retroperitoneal hemorrhage following percutaneous coronary intervention.

Am J Cardiol. 2008 Dec 1;102(11):1473-6

Authors: Tiroch KA, Arora N, Matheny ME, Liu C, Lee TC, Resnic FS

Retroperitoneal hemorrhage (RPH) is a potentially catastrophic complication after percutaneous coronary intervention (PCI). Previous studies identified female gender, body surface area, and high arterial puncture location as independent risk factors for RPH. There have been conflicting reports regarding the association with vascular closure devices (VCDs). Chronic renal insufficiency (CRI) and diabetes mellitus have been associated with both peripheral vascular disease and vascular access-site complications. The putative association of VCDs, CRI, and diabetes mellitus with RPH in the contemporary PCI era was investigated. A total of 3,062 consecutive patients undergoing 3,482 PCIs at Brigham and Women's Hospital from January 2005 to April 2007 were evaluated for the study. All 3,311 patients with femoral angiography underwent hand-caliper-based quantitative vascular analysis and were included in this analysis. Multivariate analysis was performed using a backwards selection algorithm, and a propensity adjustment was developed to control for possible confounding variables regarding VCD use. The incidence of RPH was 0.49% (17 of 3,482 patients). After multivariate and propensity analyses, covariates that significantly influenced the risk of RPH were CRI, glycoprotein IIb/IIIa inhibitors, and high arterial puncture (p </=0.007). VCD use was not independently associated with the development of RPH (p = 0.74). In conclusion, this large prospective cohort study identified CRI, but not VCD use, as an independent predictor for RPH and peripheral vascular disease.

PMID: 19026298 [PubMed - in process]

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Incidence of bleeding and compliance on prolonged dual antiplatelet therapy (aspirin + thienopyridine) following drug-eluting stent implantation.

Am J Cardiol. 2008 Dec 1;102(11):1477-81

Authors: Latib A, Morici N, Cosgrave J, Airoldi F, Godino C, Brambilla N, Chieffo A, Bonizzoni E, Carlino M, Bedogni F, Montorfano M, Sangiorgi GM, Briguori C, Colombo A

Prolonged periods of dual antiplatelet therapy (DAT), i.e., aspirin plus a thienopyridine, are currently recommended to prevent late drug-eluting stent (DES) thrombosis. The aim of our study was to determine the risk and predictors of bleeding and compliance associated with such prolongation of DAT. In this observational study we examined 2,355 consecutive patients undergoing successful DES implantation at 4 hospitals in Italy from June 2002 to December 2004. Bleeding events occurring on DAT and warfarin or in the first 30 days after stent implantation were excluded. Median duration of DAT was 209 days (interquartile range 178 to 444) and only 158 patients (6.7%) prematurely discontinued DAT. The overall bleeding rate was 1.9% (45), with major bleeding in 19 (0.8%) and minor bleeding in 26 (1.1%). Independent predictors of bleeding were DAT (hazard ratio 19.8, 95% confidence interval [CI] 3.69 to 106.34, p <0.001) and age >65 years (hazard ratio 2.15, 95% CI 1.16 to 4.00, p = 0.02). In patients on DAT, the incidence rate (30 days to 18 months) of any bleeding event was 2.57 per 100 person-years (95% CI 1.85 to 3.48) and major bleeding was 1.10 per 100 person-years (95% CI 0.65 to 1.74). In conclusion, DAT after DES implantation is well tolerated and associated with a very low risk of major bleeding.

PMID: 19026299 [PubMed - in process]

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Efficacy and Safety of Ezetimibe Added on to Atorvastatin (20 mg) Versus Uptitration of Atorvastatin (to 40 mg) in Hypercholesterolemic Patients at Moderately High Risk for Coronary Heart Disease.

Am J Cardiol. 2008 Dec 1;102(11):1489-94

Authors: Conard SE, Bays HE, Leiter LA, Bird SR, Rubino J, Lowe RS, Tomassini JE, Tershakovec AM

The aim of this study was to evaluate the efficacy and safety of ezetimibe 10 mg added to atorvastatin 20 mg compared with doubling atorvastatin to 40 mg in patients with hypercholesterolemia at moderately high risk for coronary heart disease who did not reach low-density lipoprotein (LDL) cholesterol levels <100 mg/dl with atorvastatin 20 mg. In this 6-week, multicenter, double-blind, randomized, parallel-group study, 196 patients treated with atorvastatin 20 mg received atorvastatin 20 mg plus ezetimibe 10 mg or atorvastatin 40 mg for 6 weeks. Adding ezetimibe 10 mg to atorvastatin 20 mg produced significantly greater reductions in LDL cholesterol than increasing atorvastatin to 40 mg (-31% vs -11%, p <0.001). Significantly greater reductions were also seen in non-high-density lipoprotein cholesterol, total cholesterol, and apolipoprotein B (p <0.001). Significantly more patients reached LDL cholesterol levels <100 mg/dl with atorvastatin 20 mg plus ezetimibe compared with atorvastatin 40 mg (84% vs 49%, p <0.001). The 2 treatment groups had comparable results for high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and high-sensitivity C-reactive protein. The incidences of clinical and laboratory adverse experiences were generally similar between groups. In conclusion, the addition of ezetimibe 10 mg to atorvastatin 20 mg was generally well tolerated and resulted in significantly greater lipid-lowering efficacy compared with doubling atorvastatin to 40 mg in patients with hypercholesterolemia at moderately high risk for coronary heart disease.

PMID: 19026302 [PubMed - in process]

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Efficacy and Safety of Ezetimibe Added on to Atorvastatin (40 mg) Compared With Uptitration of Atorvastatin (to 80 mg) in Hypercholesterolemic Patients at High Risk of Coronary Heart Disease.

Am J Cardiol. 2008 Dec 1;102(11):1495-501

Authors: Leiter LA, Bays H, Conard S, Bird S, Rubino J, Hanson ME, Tomassini JE, Tershakovec AM

The percentage of change from baseline in low-density lipoprotein (LDL) cholesterol after the addition of ezetimibe 10 mg to atorvastatin 40 mg was compared with uptitration to atorvastatin 80 mg. In this multicenter, double-blind, parallel-group study, adult hypercholesterolemic patients using atorvastatin 40 mg/day were randomly assigned to atorvastatin 40 mg plus ezetimibe 10 mg or uptitration to atorvastatin 80 mg. After 6 weeks of treatment, compared with atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe significantly reduced the primary end point of LDL cholesterol by -27% versus atorvastatin 80 mg by -11% (p <0.001), as well as significantly reduced non-high-density lipoprotein cholesterol, apolipoprotein B, total cholesterol, and triglycerides significantly more than atorvastatin 80 mg (all p <0.001). Percentages of change in high-sensitivity C-reactive protein, high-density lipoprotein cholesterol, and apolipoprotein A-I were similar between groups. Significantly more patients treated with atorvastatin 40 mg plus ezetimibe reached LDL cholesterol <70 mg/dl versus patients treated with atorvastatin 80 mg (74% vs 32%; p <0.001). Safety and tolerability profiles and incidence of liver and muscle adverse experiences were generally similar between groups. In conclusion, these results showed that adding ezetimibe to atorvastatin 40 mg was significantly more effective than uptitrating to atorvastatin 80 mg at lowering LDL cholesterol and other lipid parameters. Both treatments were generally well tolerated (clinical trial no. NCT00276484).

PMID: 19026303 [PubMed - in process]

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Reproducibility of electrocardiographic findings in patients with suspected reflex neurally-mediated syncope.

Am J Cardiol. 2008 Dec 1;102(11):1518-23

Authors: Moya A, Brignole M, Sutton R, Menozzi C, Garcia-Civera R, Wieling W, Andresen D, Benditt DG, Garcia-Sacristán JF, Beiras X, Grovale N, Vardas P,

The reproducibility of electrocardiographic (ECG) recordings in syncopal recurrences and the diagnostic role of nonsyncopal arrhythmias are not well known. The objective of this study was to analyse the reproducibility of the ECG findings recorded with implantable loop recorders in 41 patients with suspected neurally-mediated syncope who were included in the International Study on Syncope of Uncertain Origin-2 study and that had >/=2 events recorded by implantable loop recorders. In these patients, the electrocardiogram obtained with the first documented syncope (index syncope) was compared with other recorded events. Twenty-two patients had >/=2 syncopes, and their electrocardiograms were reproducible in 21 (95%): 15 with sinus rhythm, 5 with asystole, and 1 with ventricular tachycardia; 1 had asystole at first syncope and sinus rhythm at recurrent syncope. In 32 patients with nonsyncopal episodes, an arrhythmia was documented in 9, and all of them had the same arrhythmia during the index syncope (100% reproducibility); conversely, when sinus rhythm was documented (23 patients) during nonsyncopal episodes, an arrhythmia was still documented in 6 during the index syncope (70% reproducibility; p = 0.0004). In conclusion, the ECG findings during the first syncope are highly reproducible in subsequent syncopes. The presence of an arrhythmia during nonsyncopal episodes is also highly predictive of the mechanism of syncope, but the presence of sinus rhythm does not rule out the possibility of arrhythmia during syncope. Therefore the finding of an arrhythmia during a nonsyncopal episode allows the etiologic diagnosis of syncope, and eventually to anticipate treatment, without waiting for syncope.

PMID: 19026307 [PubMed - in process]

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