Mar 202010
 
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Early invasive versus conservative strategies for unstable angina and non-ST elevation myocardial infarction in the stent era.

Cochrane Database Syst Rev. 2010;3:CD004815

Authors: Hoenig MR, Aroney CN, Scott IA

BACKGROUND: In patients with unstable angina and non-ST elevation myocardial infarction (UA/NSTEMI) two strategies are possible, either a routine invasive strategy where all patients undergo coronary angiography shortly after admission and, if indicated, coronary revascularization; or a conservative strategy where medical therapy alone is used initially, with selection of patients for angiography based on clinical symptoms or investigational evidence of persistent myocardial ischemia. OBJECTIVES: To determine the benefits of an invasive compared to conservative strategy for treating UA/NSTEMI in the stent era. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 1), MEDLINE and EMBASE were searched (1996 to February 2008) with no language restrictions. SELECTION CRITERIA: Included studies were prospective trials comparing invasive with conservative strategies in UA/NSTEMI. DATA COLLECTION AND ANALYSIS: We identified five studies (7818 participants). Using intention-to-treat analysis with random-effects models, summary estimates of relative risk (RR) with 95% confidence interval (CI) were determined for primary end-points of all-cause death, fatal and non-fatal myocardial infarction, all-cause death or non-fatal myocardial infarction, and refractory angina. Further analysis of included studies was undertaken based on whether glycoprotein IIb/IIIa receptor antagonists were used routinely. Heterogeneity was assessed using Chi(2) and variance (I(2) statistic) methods. MAIN RESULTS: In the all-study analysis, mortality during initial hospitalization showed a trend to hazard with an invasive strategy (RR 1.59, 95% CI 0.96 to 2.64). The invasive strategy did not reduce death on longer-term follow up. Myocardial infarction rates assessed at 6 to 12 months (5 trials) and 3 to 5 years (3 trials) were significantly decreased by an invasive strategy (RR 0.73, 95% CI 0.62 to 0.86; and RR 0.78, 95% CI 0.67 to 0.92 respectively). The incidence of early (< 4 month) and intermediate (6 to 12 month) refractory angina were both significantly decreased by an invasive strategy (RR 0.47, 95% CI 0.32 to 0.68; and RR 0.67, 95% CI 0.55 to 0.83 respectively), as were early and intermediate rehospitalization rates (RR 0.60, 95% CI 0.41to 0.88; and RR 0.67, 95% CI 0.61 to 0.74 respectively). The invasive strategy was associated with a two-fold increase in the RR of peri-procedural myocardial infarction (as variably defined) and a 1.7-fold increase in the RR of (minor) bleeding with no hazard of stroke. AUTHORS' CONCLUSIONS: Compared to a conservative strategy for UA/NSTEMI, an invasive strategy is associated with reduced rates of refractory angina and rehospitalization in the shorter term and myocardial infarction in the longer term. However, the invasive strategy is associated with a doubled risk of procedure-related heart attack and increased risk of bleeding and procedural biomarker leaks. Available data suggest that an invasive strategy may be particularly useful in those at high risk for recurrent events.

PMID: 20238333 [PubMed - in process]

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Mar 202010
 
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Benzodiazepines for alcohol withdrawal.

Cochrane Database Syst Rev. 2010;3:CD005063

Authors: Amato L, Minozzi S, Vecchi S, Davoli M

BACKGROUND: Alcohol abuse and dependence represents a serious health problem worldwide with social, interpersonal and legal interpolations. Benzodiazepines have been widely used for the treatment of alcohol withdrawal symptoms. Moreover it is unknown whether different benzodiazepines and different regimens of administration may have the same merits. OBJECTIVES: To evaluate the effectiveness and safety of benzodiazepines in the treatment of alcohol withdrawal. SEARCH STRATEGY: Cochrane Drugs and Alcohol Group' Register of Trials (December 2009), PubMed, EMBASE, CINAHL (January 1966 to December 2009), EconLIT (1969 to December 2009). Parallel searches on web sites of health technology assessment and related agencies, and their databases. SELECTION CRITERIA: Randomized controlled trials examining effectiveness, safety and risk-benefit of benzodiazepines in comparison with placebo or other pharmacological treatment and between themselves. All patients were included regardless of age, gender, nationality, and outpatient or inpatient therapy. DATA COLLECTION AND ANALYSIS: Two authors independently screened and extracted data from studies. MAIN RESULTS: Sixty four studies, 4309 participants, met the inclusion criteria.- Comparing benzodiazepines versus placebo, benzodiazepines performed better for seizures, 3 studies, 324 participants, RR 0.16 (0.04 to 0.69), no statistically significant difference for the other outcomes considered.- Comparing benzodiazepines versus other drugs, there is a trend in favour of benzodiazepines for seizure and delirium control, severe life threatening side effect, dropouts, dropouts due to side effects and patient's global assessment score. A trend in favour of control group was observed for CIWA-Ar scores at 48 hours and at the end of treatment. The results reach statistical significance only in one study, with 61 participants, results on Hamilton anxiety rating scale favour control MD -1.60 (-2.59 to -0.61)- Comparing different benzodiazepines among themselves,results never reached statistical significance but chlordiazepoxide performed better- Comparing benzodiazepine plus other drug versus other drug, results never reached statistical significance.- In the comparison of fixed-schedule versus symptom-triggered regimens, results from a single study, with 159 participants, favour symptom-triggered regimens MD -1.10 [-3.27, 1.07] for CIWA-Ar scores at the end of treatment. Differences in isolated trials should be interpreted very cautiously. AUTHORS' CONCLUSIONS: Benzodiazepines showed a protective benefit against alcohol withdrawal symptoms, in particular seizures, when compared to placebo and a potentially protective benefit for many outcomes when compared with other drugs. Nevertheless, no definite conclusions about the effectiveness and safety of benzodiazepines was possible, because of the heterogeneity of the trials both in interventions and the assessment of outcomes.

PMID: 20238336 [PubMed - in process]

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Mar 202010
 
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Anticonvulsants for alcohol withdrawal.

Cochrane Database Syst Rev. 2010;3:CD005064

Authors: Minozzi S, Amato L, Vecchi S, Davoli M

BACKGROUND: Alcohol abuse and dependence represents a most serious health problem worldwide with major social, interpersonal and legal interpolations. Besides benzodiazepines, anticonvulsants are often used for the treatment of alcohol withdrawal symptoms. Anticonvulsants drugs are indicated for the treatment of alcohol withdrawal syndrome, alone or in combination with benzodiazepine treatments. In spite of the wide use, the exact role of the anticonvulsants for the treatment of alcohol withdrawal has not yet bee adequately assessed. OBJECTIVES: To evaluate the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal. SEARCH STRATEGY: We searched Cochrane Drugs and Alcohol Group' Register of Trials (December 2009), PubMed, EMBASE, CINAHL (1966 to December 2009), EconLIT (1969 to December 2009). Parallel searches on web sites of health technology assessment and related agencies, and their databases. SELECTION CRITERIA: Randomized controlled trials (RCTs) examining the effectiveness, safety and overall risk-benefit of anticonvulsants in comparison with a placebo or other pharmacological treatment. All patients were included regardless of age, gender, nationality, and outpatient or inpatient therapy. DATA COLLECTION AND ANALYSIS: Two authors independently screened and extracted data from studies. MAIN RESULTS: Fifty-six studies, with a total of 4076 participants, met the inclusion criteria. Comparing anticonvulsants with placebo, no statistically significant differences for the six outcomes considered.Comparing anticonvulsant versus other drug, 19 outcomes considered, results favour anticonvulsants only in the comparison carbamazepine versus benzodiazepine (oxazepam and lorazepam) for alcohol withdrawal symptoms (CIWA-Ar score): 3 studies, 262 participants, MD -1.04 (-1.89 to -0.20), none of the other comparisons reached statistical significance.Comparing different anticonvulsants no statistically significant differences in the two outcomes considered.Comparing anticonvulsants plus other drugs versus other drugs (3 outcomes considered), results from one study, 72 participants, favour paraldehyde plus chloral hydrate versus chlordiazepoxide, for the severe-life threatening side effects, RR 0.12 (0.03 to 0.44). AUTHORS' CONCLUSIONS: Results of this review do not provide sufficient evidence in favour of anticonvulsants for the treatment of AWS. There are some suggestions that carbamazepine may actually be more effective in treating some aspects of alcohol withdrawal when compared to benzodiazepines, the current first-line regimen for alcohol withdrawal syndrome. Anticonvulsants seem to have limited side effects, although adverse effects are not rigorously reported in the analysed trials.

PMID: 20238337 [PubMed - in process]

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Mar 202010
 
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Glucocorticoids for the treatment of anaphylaxis.

Cochrane Database Syst Rev. 2010;3:CD007596

Authors: Choo KJ, Simons FE, Sheikh A

BACKGROUND: Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may result in death. Anaphylaxis guidelines recommend glucocorticoids for the treatment of people experiencing anaphylaxis. OBJECTIVES: We sought to assess the benefits and harms of glucocorticoid treatment during episodes of anaphylaxis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid) (1966 to September 2009), EMBASE (Ovid) (1988 to September 2009), CINAHL (EBSCOhost) (to September 2009) and The Science Citation Index Expanded (SCI-EXPANDED) (1945 to September 2009). We also searched the UK National Research Register and websites listing ongoing trials, and contacted international experts in anaphylaxis in an attempt to locate unpublished material. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing glucocorticoids with any control (either placebo, adrenaline (epinephrine), an antihistamine, or any combination of these). DATA COLLECTION AND ANALYSIS: Two authors independently assessed articles for inclusion. MAIN RESULTS: We found no studies that satisfied the inclusion criteria. AUTHORS' CONCLUSIONS: We are, based on this review, unable to make any recommendations for the use of glucocorticoids in the treatment of anaphylaxis.

PMID: 20238355 [PubMed - in process]

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Mar 202010
 
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Clinically-indicated replacement versus routine replacement of peripheral venous catheters.

Cochrane Database Syst Rev. 2010;3:CD007798

Authors: Webster J, Osborne S, Rickard C, Hall J

BACKGROUND: Centers for Disease Control Guidelines recommend replacement of peripheral intravenous (IV) catheters every 72 to 96 hours. Routine replacement is thought to reduce the risk of phlebitis and bacteraemia. Catheter insertion is an unpleasant experience for patients and replacement may be unnecessary if the catheter remains functional and there are no signs of inflammation. Costs associated with routine replacement may be considerable. OBJECTIVES: To assess the effects of removing peripheral IV catheters when clinically indicated compared with removing and re-siting the catheter routinely. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched October 2009) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue Issue 4, 2009). We also searched MEDLINE (last searched October 2009). SELECTION CRITERIA: Randomised controlled trials that compared routine removal of peripheral IV catheters with removal only when clinically indicated in hospitalised or community dwelling patients receiving continuous or intermittent infusions. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trial quality and extracted data. MAIN RESULTS: In five trials (3408 participants) there was a 44% reduction in suspected catheter-related bacteraemia in the clinically-indicated group (0.2 versus 0.4%) but this was not statistically significant (odds ratio (OR) 0.57; 95% confidence interval (CI) 0.17 to 1.94; P = 0.37). Phlebitis was assessed in six trials (3455 patients); there was a non-significant increase in phlebitis in the clinically-indicated group (9% versus 7.2%); the OR was 1.24 (95% CI 0.97 to 1.60; P = 0.09). We also measured phlebitis per 1000 device days using data from five trials, (8779 device days). No statistical differences in the incidence of phlebitis per 1,000 device days was found (clinically indicated 1.6 cases per 1,000 catheter days versus 1.5 cases per 1,000 catheter days in the routine-replacement group).The combined OR was 1.04 (95% CI 0.81 to 1.32; P = 0.77). Cost was measured in two trials (961 patients). Cannulation costs were significantly reduced in the clinically-indicated group (mean difference (MD) -6.21; 95% CI -9.32 to -3.11; P = < 0.000). AUTHORS' CONCLUSIONS: The review found no conclusive evidence of benefit in changing catheters every 72 to 96 hours. Consequently, health care organisations may consider changing to a policy whereby catheters are changed only if clinically indicated. This would provide significant cost savings and would also be welcomed by patients, who would be spared the unnecessary pain of routine re-sites in the absence of clinical indications.

PMID: 20238356 [PubMed - in process]

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Mar 202010
 

Enoxaparin - effective dosage for intensive care patients: double-blinded, randomised clinical trial.

Crit Care. 2010 Mar 18;14(2):R41

Authors: Robinson S, Zincuk A, Strom T, Larsen TB, Rasmussen B, Toft P

ABSTRACT: INTRODUCTION: Intensive care unit (ICU) patients are predisposed to thromboembolism. Routine prophylactic anticoagulation is widely recommended. Low-molecular-weight heparins such as enoxaparin, are increasingly utilised due to predictable pharmacokinetics. This study aims to determine the subcutaneous (sc) dose of enoxaparin, which would give the best anti-factor Xa levels in ICU patients. METHODS: 72 patients admitted to a mixed ICU at Odense University Hospital (OUH) in Denmark were randomised into 4 groups to receive 40, 50, 60 or 70 mg sc enoxaparin for a period of 24 hours. Anti-factor Xa activity (aFXa) was measured before, and at 4, 12, and 24 hours post administration. AFXa between 0.1 to 0.3 IU/ml was considered evidence of effective antithrombotic activity. RESULTS: Median peak (= 4 hours post administration) aFXa levels increased significantly with an increase in enoxaparin dose, from: 0.13 IU/ml at 40 mg, to 0.14 IU/ml at 50 mg, 0.27 IU/ml at 60 mg and 0.29 IU/ml at 70 mg respectively (P = 0.002*) . At 12 hours post administration, median aFXa levels were still within therapeutic range for those patients who received 60 mg (P= 0.02). CONCLUSIONS: Our study confirmed that a standard dose of 40 mg enoxaparin yielded sub- therapeutic levels of aFXa in critically ill patients. Higher doses resulted in better peak aFXa levels, with a ceiling effect observed at 60 mg. The present study seems to suggest inadequate dosage as one of the possible mechanisms for the higher failure rate of enoxaparin in ICU patients. Trial Registration: ISRCTN03037804.

PMID: 20298591 [PubMed - as supplied by publisher]

Link to Article at PubMed

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