Efficacy and safety of bemiparin compared with enoxaparin: Meta-analysis of randomized controlled trials.

BACKGROUND: Potential advantages of bemiparin compared to enoxaparin are a longer half-life, once-a-day dosage, and possibly a better safety profile due to the more selective antagonistic action toward Xa coagulation factor. We evaluated the efficacy and safety of bemiparin compared with enoxaparin as prophylaxis or treatment of venous thromboembolic disease. MATERIALS AND METHODS: We searched PubMed, Embase, Cochrane Library, Clinical Trials.gov, Google academics, and Conference Abstracts (2014 - 2019) of the American Society of Hematology and the Spanish Society of Hematology and Hemotherapy. Randomized trials that included bemiparin and enoxaparin were included as treatment arms. The outcomes evaluated were the incidence of venous thromboembolic disease and the proportion of adverse events in each group. Two independent researchers selected, evaluated, and extracted the data in duplicate. Four studies with a total of 5,473 patients were included. RESULTS: Most patients were included in prevention studies (N = 5,161). Bemiparin proved the non-inferiority in terms of efficacy with respect to enoxaparin (relative risk: 0.76; 95% confidence interval (95% CI): 0.56 - 1.01; p = 0.06) (heterogeneity I2 = 34%). We recorded 222 adverse events in 2,742 patients treated with bemiparin and 288 adverse events in 2,731 patients treated with enoxaparin (8.1 vs. 10.5 adverse events per 100 patients, respectively; p = 0.003). However, the meta-analysis for safety showed a significant heterogeneity making not possible to pool the result across the trials. CONCLUSION: Bemiparin proved a non-inferior efficacy compared to enoxaparin with a significant reduction in adverse events per 100 patients treated.

Effects of Acute Ethanol Administration on Brain Oxidative Status: The Role of Acetaldehyde.

BACKGROUND: Ethanol (EtOH), one of the most widely consumed substances of abuse, can induce brain damage and neurodegeneration. EtOH is centrally metabolized into acetaldehyde, which has been shown to be responsible for some of the neurophysiological and cellular effects of EtOH. Although some of the consequences of chronic EtOH administration on cell oxidative status have been described, the mechanisms by which acute EtOH administration affects the brain's cellular oxidative status and the role of acetaldehyde remain to be elucidated in detail. METHODS: Swiss CD-I mice were pretreated with the acetaldehyde-sequestering agent d-penicillamine (DP; 75 mg/kg, i.p.) or the antioxidant lipoic acid (LA; 50 mg/kg, i.p.) 30 minutes before EtOH (2.5 g/kg, i.p.) administration. Animals were sacrificed 30 minutes after EtOH injection. Glutathione peroxidase (GPx) mRNA levels; GPx and glutathione reductase (GR) enzymatic activities; reduced glutathione (GSH), glutathione disulfide (GSSG), glutamate, g-L-glutamyl-L-cysteine (Glut-Cys), and malondialdehyde (MDA) concentrations; and protein carbonyl group (CG) content were determined in whole-brain samples. RESULTS: Acute EtOH administration enhanced GPx activity and the GSH/GSSG ratio, while it decreased GR activity and GSSG concentration. Pretreatment with DP or LA only prevented GPx activity changes induced by EtOH. CONCLUSIONS: Altogether, these results show the capacity of a single dose of EtOH to unbalance cellular oxidative homeostasis.

Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: meta-analysis of randomized controlled trials.

BACKGROUND: We carried out a meta-analysis since there is not enough evidence to recommend for or against therapeutic-dose anticoagulation compared with thromboprophylaxis in noncritically ill patients hospitalized with Covid-19. METHODS: We performed a systematic literature search using PubMed, Embase, Cochrane Library, and MedRxiv for randomized trials that included therapeutic-dose with low-molecular-weight heparin (LMW) or thromboprophylaxis with LMW heparin in noncritically ill patients admitted to the hospital with Covid-19. We identified five open-label studies for analysis with a total of 3220 patients. Two independent researchers selected, assessed, and extracted the data in duplicate. The outcomes evaluated were all-cause mortality, progression to invasive mechanical ventilation, incidence of venous thromboembolism, and major bleeding. The studies did not show risk for selection, detection, attrition, or reporting bias. RESULTS: Therapeutic-dose anticoagulation with LMW heparin compared with thromboprophylaxis with LMW heparin had no significant effect of all-cause death (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.67-1.07; P = 0.16; I2 = 48%), or progression to invasive mechanical ventilation (RR 0.89; CI 0.73-1.08; P = 0.24; I2: 0%). Therapeutic-dose anticoagulation significantly reduced the risk of venous thromboembolic disease (RR 0.42; 95% CI 0.28-0.62; P = 0.0001; I2 = 0%) [Number needed to treat = 37]. Major bleeding occurred in 1.79% of the patients receiving therapeutic-dose anticoagulation and in 0.97% of those receiving thromboprophylaxis [Number needed to harm 125]. CONCLUSION: Therapeutic-dose anticoagulation in noncritically ill patients with Covid-19 could be indicated for patients at high risk of venous thromboembolic disease and low risk of bleeding.

Use of safety devices and the prevention of percutaneous injuries among healthcare workers.

OBJECTIVE: To study the effectiveness of safety devices intended to prevent percutaneous injuries.Design. Quasi-experimental trial with before-and-after intervention evaluation. SETTING: A 350-bed general hospital that has had an ongoing educational program for the prevention of percutaneous injuries since January 2002. METHODS: In October 2005, we implemented a program for the use of engineered devices to prevent percutaneous injury in the emergency department and half of the hospital wards during the following procedures: intravascular catheterization, vacuum phlebotomy, blood-gas sampling, finger-stick blood sampling, and intramuscular and subcutaneous injections. The nurses in the wards that participated in the intervention received a 3-hour course on occupationally acquired bloodborne infections, and they had a 2-hour "hands-on" training session with the devices. We studied the percutaneous injury rate and the direct cost during the preintervention period (October 2004 through March 2005) and the intervention period (October 2005 through March 2006). RESULTS: We observed a 93% reduction in the relative risk of percutaneous injuries in areas where safety devices were used (14 vs 1 percutaneous injury). Specifically, rates decreased from 18.3 injuries (95% confidence interval [CI], 5.9-43.2 injuries) to 0 injuries per 100,000 patients in the emergency department (P=.002) and from 44.0 injuries (95% CI, 20.1-83.6 injuries) to 5.2 injuries (95% CI, 0.1-28.8 injuries) per 100,000 patient-days in hospital wards (P=.007). In the control wards of the hospital (ie, those where the intervention was not implemented), rates remained stable. The direct cost increase was 0.558 euros (US$0.753) per patient in the emergency department and 0.636 euros (US$0.858) per patient-day in the hospital wards. CONCLUSION: Proper use of engineered devices to prevent percutaneous injury is a highly effective measure to prevent these injuries among healthcare workers. However, education and training are the keys to achieving the greatest preventative effect.

Short-course therapy with rifampin plus isoniazid, compared with standard therapy with isoniazid, for latent tuberculosis infection: a meta-analysis.

BACKGROUND: A major difficulty associated with the use of standard therapy with isoniazid for latent tuberculosis infection is poor patient adherence to therapy because of the prolonged course required. Shorter courses of therapy involving > or =2 drugs have been proposed as an alternative to standard therapy, but they have not undergone enough testing. METHODS: We performed a meta-analysis to determine the equivalence of daily short-course therapy with rifampin plus isoniazid for 3 months and standard therapy with isoniazid for 6-12 months. The end points that were evaluated were development of active tuberculosis, severe adverse drug reactions, and death. We searched published information in the Cochrane Library, MEDLINE, and Embase databases, as well as unpublished information in the Cambridge Scientific Abstracts Internet database, Conference Papers Index, AIDS and Cancer Research Abstracts, and ClinicalTrials.gov. We also scanned the reference lists of articles. We only included trials in which individuals were randomly allocated to receive treatment. Two reviewers independently applied the criteria for trial selection, assessed trial quality, and extracted data. RESULTS: Five trials comprising 1926 adults from Hong Kong, Spain, and Uganda were identified. The mean duration of follow-up varied from 13 to 37 months. Overall, development of active tuberculosis was equivalent in association with both regimens (pooled risk difference, 0%; 95% confidence interval [CI], -1% to 2%; percentage of total variation across the studies that is the result of heterogeneity rather than chance [I2], 0%; P=.86). Severe adverse effects were reported with a similar frequency for both regimens (pooled risk difference, -1%; 95% CI, -7% to 5%) but with statistically significant heterogeneity detected (I2, 78%; P=.001). However, a subanalysis of high-quality trials (including 74% of the sample size) suggested that both regimens were equally safe. In 3 trials (comprising 1390 patients) that provided data on mortality, the regimens showed equivalence (pooled risk difference, -1%; 95% CI, -4% to 2%; I2, 2.7%; P=.38). CONCLUSION: Short-course therapy with rifampin plus isoniazid was equivalent to standard therapy with isoniazid in terms of efficacy, the proportion of severe side effects that occurred, and mortality.

Short-course treatment of latent tuberculosis infection in patients with rheumatic conditions proposed for anti-TNF therapy.

Tuberculosis reactivation is a serious threat in patients treated with anti-tumour necrosis factor therapy. A 6-month regimen with isoniazid is considered as the standard of care, but patient adherence is a major shortcoming. We carried out an open-label, single-arm intervention study to assess the efficacy, the completion rate and the tolerability of a 3-month regimen with isoniazid plus rifampin. Seventy-eight patients with rheumatic conditions proposed for anti-tumour necrosis factor (TNF) therapy and at risk of tuberculosis reactivation were offered to participate in the study. Nine patients were excluded due to deficit of glucose-6-phosphate dehydrogenase (n = 1), salicylate hypersensitivity (n = 1), declining to participate (n = 5) or preferring a 6-month isoniazid regimen (n = 6). Sixty-nine patients were treated with a 3-month regimen with isoniazid and rifampin. No cases of tuberculosis were observed after a mean follow-up of 90 months (range from 66 to 121 months). Sixty (87 %) patients completed the therapy. Nine (13 %) patients discontinued the therapy due to rifampin hypersensitivity (n = 1), symptomatic grade 3-4 hepatotoxicity (n = 2), abdominal discomfort (n = 2), pruritus (n = 1), arthritis (n = 1) and personal concerns (n = 2). A short course treatment with isoniazid and rifampin provided efficacy, good tolerability and good completion rate in patients with rheumatic conditions proposed for anti-TNF therapy.