Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate

https://www.bmj.com/content/bmj/343/bmj.d5928.full.pdf

The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

http://xoomer.virgilio.it/lusebra/NuoviFile/PrevenzioneTVP.pdf

Prevention of venous thromboembolism

https://www.chpso.org/sites/main/files/file-attachments/chest-2008-geerts-381s-453s.pdf

Prevention of Venous Thromboembolism* American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition)

Prevention of Venous Thromboembolism : The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

Results Pooled relative risks from high-quality trials ranged from 0.63 (95% confidence interval [CI], 0.44-0.90) to 0.90 (95% CI, 0.67-1.21) vs 0.52 (95% CI, 0.241.09) to 1.13 (95% CI, 0.70-1.82) for low-quality trials. For 6 scales, relative risks of high-quality trials were close to unity, indicating that LMWH was not significantly superior to standard heparin, whereas low-quality trials showed better protection with LMWH (P,.05). Seven scales showed the opposite: high quality trials showed an effect whereas low quality trials did not. For the remaining 12 scales, effect estimates were similar in the 2 quality strata. In regression analysis, summary quality scores were not significantly associated with treatment effects. There was no significant association of treatment effects with allocation concealment and handling of withdrawals. Open outcome assessment, however, influenced effect size with the effect of LMWH, on average, being exaggerated by 35% (95% CI, 1%-57%; P = .046). Conclusions Our data indicate that the use of summary scores to identify trials of high quality is problematic. Relevant methodological aspects should be assessed individually and their influence on effect sizes explored. JAMA. 1999;282:1054-1060 www.jama.com

https://jamanetwork.com/journals/jama/articlepdf/191652/JOC81641.pdf

The hazards of scoring the quality of clinical trials for meta-analysis.

OBJECTIVE--To determine whether prophylactic treatment with low molecular weight heparin reduces the incidence of thrombosis in patients who have had general or orthopaedic surgery. DESIGN--Meta-analysis of results from 52 randomised, controlled clinical studies (29 in general surgery and 23 in orthopaedic surgery) in which low molecular weight heparin was compared with placebo, dextran, or unfractionated heparin. SUBJECTS--Patients who had had general or orthopaedic surgery. INTERVENTION--Once daily injection of a low molecular weight heparin compared with placebo, dextran, or unfractionated heparin. MAIN OUTCOME MEASURES--Incidence of deep venous thrombosis, pulmonary embolism, major haemorrhages, and death. RESULTS--The results confirm that low molecular weight heparins are more efficacious for the prophylactic treatment of deep venous thrombosis than placebo (common odds ratio 0.31, 95% confidence interval 0.22 to 0.43; p

https://www.bmj.com/content/bmj/305/6859/913.full.pdf

Low molecular weight heparin in prevention of perioperative thrombosis.

Objectives To compare the components of the time delay involved in pre-hospital and hospital thrombolytic therapy in patients presenting with suspected acute myocardial infarction.

Material and methods From October 1988 to January 1992 a total of 198 mobile emergency units in 15 European countries and Canada randomized 5469 patients to receive either pre-hospital thrombolytic treatment, followed by placebo in hospital (pre-hospital group), or pre-hospital placebo, followed by thrombolytic treatment in hospital (hospital group) in the European Myocardial Infarction Project trial. We performed a post hoc analysis of these data to correlate components of the interval between symptom onset and treatment with baseline patient characteristics.

Results The delay between onset of symptoms and calling for an ambulance was significantly longer for female patients ( P 0·0001), older patients (>65 years old; P =0·0001), those who had experienced pain within the previous 24 h ( P =0·0001), and those with pulmonary oedema ( P =0·04). This delay was significantly shorter in patients with previous myocardial infarction ( P =0·02), those with ventricular fibrillation ( P =0·0001), and those in shock ( P 0·0001). The delay between the two injections was significantly longer for older patients (>65 years old; P =0·02), those with previous myocardial infarction ( P =0·03), and those in shock ( P =0·003).

Conclusions Action undertaken to reduce delays between symptom onset and treatment should focus on modifiable factors such as patients who are likely to be late callers, i.e. women and those over 65 years of age.

/pdf/pre-hospital-and-hospital-time-delays-in-thrombolytic-1rnk44nfut.pdf

Pre-hospital and hospital time delays in thrombolytic treatment in patients with suspected acute myocardial infarction: Analysis of data from the EMIP study

A multicentre, double-blind, randomised trial was conducted to compare the efficacy of a low-molecular-weight (LMW) heparin, Logiparin, with that of an unfractionated (UF) heparin in the prophylactic treatment of thrombosis in patients undergoing general surgery. A total of 1,290 patients were randomised to receive a single daily dose of Logiparin (2,500 IU: 431 patients; 3,500 IU: 430 patients) or UF heparin (2 x 5,000 IU: 429 patients). The incidence of the main end point, deep venous thrombosis, was found to be significantly different between the groups (p = 0.03), whereas the incidence of severe haemorrhage was not (p = 0.05). The plasma anti-Xa activity was found to be correlated with body weight, but correlated only very weakly with antithrombotic activity (p = 0.045) after adjustment in a stepwise multivariate analysis, and did not significantly correlate with the incidence of haemorrhage. Logiparin at 3,500 IU and UF heparin showed similar efficacy. Although a correlation between plasma anti-Xa activity and body weight was observed, there is not sufficient evidence to recommend the adjustment of the Logiparin dose on patient's weight for prophylaxis in general surgery patients.

M. C. Haugh

Papers

Low molecular weight heparin in prevention of perioperative thrombosis.

Pre-hospital and hospital time delays in thrombolytic treatment in patients with suspected acute myocardial infarction: Analysis of data from the EMIP study

Factor Xa inhibition: correlation between the plasma levels of anti-Xa activity and occurrence of thrombosis and haemorrhage.