2009 February 25

Hospital-wide impact of a standardized order set for the management of bacteremic severe sepsis.

Feb 252009

Hospital-wide impact of a standardized order set for the management of bacteremic severe sepsis.

Crit Care Med. 2009 Mar;37(3):819-24

Authors: Thiel SW, Asghar MF, Micek ST, Reichley RM, Doherty JA, Kollef MH

OBJECTIVE: To evaluate the hospital-wide impact of a standardized order set for the management of bacteremic severe sepsis on processes of medical care and patient outcomes. DESIGN: Retrospective, before and after study design. SETTING: Barnes-Jewish Hospital, a 1200-bed academic medical center. PATIENTS: Bacteremic patients with severe sepsis (200 from the 18-month before period and 200 from the 18-month after period). INTERVENTIONS: Hospital-wide implementation of a standardized order set for the management of bacteremic severe sepsis. MEASUREMENTS AND MAIN RESULTS: A total of 400 patients with bacteremia and severe sepsis were selected at random within the specified time periods. Patients in the after group received more intravenous fluids in the first 12 hours after onset of hypotension (1627 +/- 1862 mL vs. 2054 +/- 2237 mL; p = 0.04) and were more likely to receive appropriate initial antibiotic therapy (53.0% vs. 65.5%, p = 0.01). In-hospital mortality was statistically decreased in the after group (55.0% vs. 39.5%, p < 0.01), as was the hospital length of stay (28.7 +/- 30.1 days vs. 22.4 +/- 20.9 days; p = 0.02). Compared with the before group, the after group had reduced occurrence of renal failure (49.0% vs. 36.0%, p < 0.01), cardiovascular failure (70.5% vs. 57.0%, p < 0.01), and were less likely to require vasopressors after initial fluid resuscitation (68.5% vs. 52.5%, p < 0.01). CONCLUSIONS: The implementation of a hospital-wide standardized order set for the management of bacteremic severe sepsis was associated with greater fluid administration, improved antibiotic therapy, decreased incidence of organ failure, and improved survival.

PMID: 19237883 [PubMed - in process]

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Predictors of Initial Nontherapeutic Anticoagulation With Unfractionated Heparin in ST-Segment Elevation Myocardial Infarction.

Circulation Start a Discussion »

Feb 252009

Predictors of Initial Nontherapeutic Anticoagulation With Unfractionated Heparin in ST-Segment Elevation Myocardial Infarction.

Circulation. 2009 Feb 23;

Authors: Cheng S, Morrow DA, Sloan S, Antman EM, Sabatine MS

BACKGROUND: -Although weight-based nomograms have improved the efficacy and safety of dosing unfractionated heparin in ST-segment elevation myocardial infarction, achieving therapeutic anticoagulation in practice remains challenging. Methods and Results-In the Enoxaparin and Thrombolysis in Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 study, 20 506 patients with ST-segment elevation myocardial infarction were randomized to enoxaparin or unfractionated heparin, the latter dosed according to the American College of Cardiology/American Heart Association weight-based nomogram with centrally monitored activated partial thromboplastin times (aPTTs). A total of 6055 patients received study unfractionated heparin and a fibrin-specific lytic and had an initial aPTT drawn within 4 to 8 hours of starting therapy. Despite close adherence to recommended dosing, only 33.8% of initial aPTTs were therapeutic (1.50 to 2.00 times control); 13.2% were markedly low (<1.25 times); and 16.3% were markedly high (>/=2.75 times). Markedly high aPTTs were more likely in patients who were older (adjusted risk ratio [RRadj], 1.14 per decade; P=0.001), were female (RRadj, 1.46; P<0.001), were of lower weight (RRadj, 1.19 per 10-kg decrease; P<0.001) or had renal dysfunction (RRadj, 1.08 per 0.2-mg/dL increase in serum creatinine; P=0.006). Markedly high aPTTs were associated with increased risk of TIMI major or minor bleeding by 48 hours (odds ratio, 2.11; P=0.004); markedly low aPTTs tended to be associated with increased risk of fatal or nonfatal reinfarction by 48 hours (odds ratio, 2.19; P=0.057). Conclusions-Despite the use of a standard weight-based unfractionated heparin nomogram in ST-segment elevation myocardial infarction, nontherapeutic anticoagulation is frequent and more likely among certain vulnerable patient groups, with excess anticoagulation associated with increased bleeding and inadequate anticoagulation associated with reinfarction. These findings should be considered when dosing unfractionated heparin in support of fibrinolytic therapy.

PMID: 19237657 [PubMed - as supplied by publisher]

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Risk factors for fluconazole-resistant Candida glabrata bloodstream infections.

Arch Intern Med Start a Discussion »

Feb 252009

Risk factors for fluconazole-resistant Candida glabrata bloodstream infections.

Arch Intern Med. 2009 Feb 23;169(4):379-83

Authors: Lee I, Fishman NO, Zaoutis TE, Morales KH, Weiner MG, Synnestvedt M, Nachamkin I, Lautenbach E

BACKGROUND: Bloodstream infections (BSIs) caused by Candida glabrata have increased substantially. Candida glabrata is often associated with resistance to fluconazole therapy. However, to our knowledge, risk factors for fluconazole-resistant C glabrata BSIs have not been studied. METHODS: A case-case-control study was conducted at 3 hospitals from January 1, 2003, to May 31, 2007. The 2 case groups included patients with fluconazole-resistant C glabrata BSIs (minimum inhibitory concentration > or =16 microg/mL) and patients with fluconazole-susceptible C glabrata BSIs (minimum inhibitory concentration < or =8 microg/mL). Hospitalized patients without C glabrata BSIs were randomly selected for inclusion in the control group and were frequency matched to cases on the basis of time at risk. Two case-control studies were performed using this shared control group. The primary risk factor of interest, previous fluconazole use, was evaluated at multivariate analyses, adjusting for demographic data, comorbid conditions, and antimicrobial exposures. RESULTS: We included 76 patients with fluconazole-resistant C glabrata BSIs, 68 patients with fluconazole-susceptible C glabrata BSIs, and 512 control patients. Previous fluconazole use (adjusted odds ratio [95% confidence interval], 2.3 [1.3-4.2]) and linezolid use (4.6 [2.2-9.3]) were independent risk factors for fluconazole-resistant C glabrata BSIs; previous cefepime use (2.2 [1.2-3.9]) and metronidazole use (2.0 [1.1-3.5]) were independent risk factors for fluconazole-susceptible C glabrata BSIs. CONCLUSIONS: Previous fluconazole use is a significant risk factor for health care-associated fluconazole-resistant C glabrata BSIs. Future studies will be needed to evaluate the effect of decreasing fluconazole use on rates of fluconazole-resistant C glabrata BSIs.

PMID: 19237722 [PubMed - in process]

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Milnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trial.

Clin Ther Start a Discussion »

Feb 252009

Milnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trial.

Clin Ther. 2008 Nov;30(11):1988-2004

Authors: Clauw DJ, Mease P, Palmer RH, Gendreau RM, Wang Y

BACKGROUND: Preclinical and clinical studies have suggested that milnacipran, a dual norepinephrine-serotonin reuptake inhibitor, may be efficacious in the treatment of fibromyalgia (FM). OBJECTIVE: This study was conducted to evaluate the efficacy and tolerability of milnacipran in treating the multiple domains of FM. METHODS: This was a multicenter, double-blind, placebo-controlled trial. Adult patients (age 18-70 years) who met 1990 American College of Rheumatology criteria for FM were randomized to receive milnacipran 100 mg/d, milnacipran 200 mg/d, or placebo for 15 weeks. Because this was a pivotal registration trial, the primary end points were chosen to investigate efficacy for 2 potential indications: the treatment of FM and the treatment of FM pain. Thus, the 2 primary efficacy end points were rates of FM composite responders and FM pain composite responders. FM composite responders were defined as patients concurrently experiencing clinically meaningful improvements in the following 3 domain criteria: pain (> or = 30% improvement, as recorded in an electronic diary); patients' global status (a rating of very much improved or much improved on the Patient Global Impression of Change [PGIC] scale); and physical function (a > or = 6-point improvement on the 36-item Short-Form Health Survey [SF-36] Physical Component Summary score). FM pain composite responders were defined as those who met the pain and PGIC criteria. Adverse events reported by patients or observed by investigators were recorded throughout the trial. RESULTS: Of 2270 patients screened, 1196 were randomized to receive milnacipran 100 mg/d (n = 399), milnacipran 200 mg/d (n = 396), or placebo (n = 401). The majority of patients were female (96.2%) and white (93.5%). The population had a mean age of 50.2 years, a mean baseline weight of 180.8 pounds, and a mean baseline body mass index of 30.6 kg/m(2). Compared with placebo, significantly greater proportions of milnacipran-treated patients were FM composite responders (100 mg/d: P = 0.01; 200 mg/d: P = 0.02) and FM pain composite responders (100 mg/d: P = 0.03; 200 mg/d: P = 0.004). Milnacipran was associated with significant improvements in pain after 1 week of treatment (100 mg/d: P = 0.004; 200 mg/d: P = 0.04), as well as significant improvements in multiple secondary efficacy end points, including global status (PGIC: P<0.001 for both doses), physical function (SF-36 physical functioning domain-100 mg/d: P < 0.001; 200 mg/d: P = 0.02), and fatigue (Multidimensional Fatigue Inventory- 100 mg/d: P = 0.04). The most commonly reported adverse events with milnacipran were nausea (100 mg/d, 34.3%; 200 mg/d, 37.6%), headache (18.0% and 17.7%, respectively), and constipation (14.3% and 17.9%). Adverse events resulted in premature study discontinuation in 19.5% and 23.7% of those who received milnacipran 100 and 200 mg/d, respectively, compared with 9.5% of placebo recipients. CONCLUSION: In these adult patients with FM, both doses of milnacipran (100 and 200 mg/d) were associated with significant improvements in pain and other symptoms. Clinical Trials Identification Number: NCT00098124.

PMID: 19108787 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

A 52-week, multinational, open-label, parallel-group, noninferiority, treat-to-target trial comparing insulin detemir with insulin glargine in a basal-bolus regimen with mealtime insulin aspart in patients with type 2 diabetes.

Clin Ther Start a Discussion »

Feb 252009

A 52-week, multinational, open-label, parallel-group, noninferiority, treat-to-target trial comparing insulin detemir with insulin glargine in a basal-bolus regimen with mealtime insulin aspart in patients with type 2 diabetes.

Clin Ther. 2008 Nov;30(11):1976-87

Authors: Hollander P, Cooper J, Bregnhøj J, Pedersen CB

OBJECTIVE: This trial compared the efficacy and safety profiles of the insulin analogues detemir and glargine as the basal insulin component of a basal-bolus regimen in patients with type 2 diabetes mellitus (T2DM) who were being treated with oral antidiabetic drugs (OADs) or insulin with or without OADs. METHODS: This was a multinational, 52-week, openlabel, parallel-group, noninferiority, treat-to-target trial. Patients with a diagnosis of T2DM for > or = 12 months who had been receiving an OAD or insulin, with or without OADs, for > 4 months were randomized in a 2:1 ratio to receive detemir or glargine. According to the approved labeling, detemir could be administered once or twice daily, and glargine was administered once daily. Insulin aspart was given at mealtimes. Insulin secretagogues and a-glucosidase inhibitors were discontinued at study entry, and existing OADs were continued. Doses of detemir and glargine were titrated to achieve a prebreakfast (and predinner for detemir administered twice daily) plasma glucose target of < or = 6.0 mmol/L. Patients monitored their plasma glucose levels before breakfast and dinner on the 3 days before each of 13 scheduled visits, recorded their insulin doses on 1 of these 3 days, and recorded their 10-point self-monitored plasma glucose (SMPG) at baseline and after 24 and 52 weeks. The primary efficacy end point was glycosylated hemoglobin (HbA(1c)) at 52 weeks; secondary efficacy end points included changes in fasting plasma glucose (FPG), postprandial plasma glucose, insulin doses, and weight change at 52 weeks. Safety end points included the frequency of hypoglycemia and adverse events (AEs). RESULTS: The intention-to-treat population included 319 patients (58.0% male, 42.0% female; 78.4% white; mean age, 58 years; mean weight, 92.8 kg; mean duration of diabetes, 13.6 years). At study entry, 46.1% of patients were receiving insulin and > or = 1 OAD, 35.4 were receiving insulin only, and 18.5% were receiving > or = 1 OAD only. At 52 weeks, there was no significant difference between detemir and glargine in terms of mean HbA(1c) (7.19% and 7.03%, respectively; mean difference, 0.17% [95% CI, -0.07 to 0.40]) or the mean decrease in HbAlc from baseline (-1.52% and -1.68%). The reduction in HbA(1c) was not significantly affected by whether detemir was administered once or twice daily. There were no significant differences between groups in terms of mean FPG (7.05 and 6.68 mmol/L) or the mean change in FPG from baseline (-2.56 and -2.92 mmol/L; mean difference, 0.36; 95% CI, -0.26 to 0.99). The overall shape of the 10-point SMPG profiles was not significantly different between groups. Mean weight gain at 52 weeks was significantly lower with detemir than with glargine (2.8 vs 3.8 kg; mean difference, -1.04; 95% CI, -2.08 to -0.01; P < 0.05). Doses of basal and prandial insulins at the end of the study were not significantly different between groups. Major hypoglycemic episodes were reported by 4.7% and 5.7% of patients in the respective treatment groups. There was no significant difference in the risk of hypoglycemia between groups. The proportion of patients with AEs and the number of AEs per patient were comparable between groups (185/214 patients [86.4%] reporting 743 AEs and 88/105 patients [83.8%] reporting 377 AEs). CONCLUSIONS: when used as indicated as part of a basal-bolus regimen in patients with T2DM who had previously received other insulin and/or OAD regimens, detemir was noninferior to glargine in its effects on overall glycemic control. Both basal insulins were associated with clinically relevant reductions in hyperglycemia. Both were well tolerated, with no significant difference in the frequency of hypoglycemia or AEs.

PMID: 19108786 [PubMed - indexed for MEDLINE]

Link to Article at PubMed