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Hip: A. T. Cohen, J. A. Skinner, D. Warwick, and I. Brenkel The use of graduated compression stockings in association with fondaparinux in surgery of the hip: A MULTICENTRE, MULTINATIONAL, RANDOMISED, OPEN-LABEL, PARALLEL-GROUP COMPARATIVE STUDY J Bone Joint Surg Br 2007; 89-B: 887-892 [Abstract] [Full text] [PDF]

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Alexander T Cohen, John A Skinner, D Warwick, I Brenkel   (20 December 2007)

The use of graduated compression stockings in association with fondaparinux in surgery of the hip

Ihab R. Boutros, Priyan R. Landham, Richard R. Brown, Harminder S. Gosal   (18 October 2007)

A discussion on the role of chemical prophylaxis of thromboembolic disease

Augusto Sarmiento   (5 September 2007)

Authors' reply: 20 December 2007
Alexander T Cohen, Consultant Physician King's College Hospital, London SE59RS, UK, John A Skinner, D Warwick, I Brenkel Send letter to journal: Re: Authors' reply: alexander.cohen{at}kcl.ac.uk Alexander T Cohen, et al.	Sir, We thank Mr Boutros and colleagues for their interest in our paper and for raising this issue. There are three main common reasons for stopping a study. They are safety reasons, the findings of overwhelming superiority and the findings of a lack of difference, resulting in futility. Mr Boutros and colleagues are correct that a type II error may occur if there are lesser differences or a lower frequency of events found than hypothesised. In that case it would be reasonable not only to continue the study to completion, but also to consider increasing the sample size to find a smaller, but clinically (and statistically) significant difference. However, in our study the results were so similar that the chances of finding a difference were minute, and more importantly the differences seen were clinically insignificant. An estimated sample size of over 31,000 would have been required to demonstrate such a clinically significant difference. Therefore, stopping the trial for reasons of futility were appropriate. A.T. COHEN, MSc, MD, FRACP, Consultant Vascular Physician, J.A. SKINNER, FRCS, FRCS(Orth), Consultant Orthopaedic Surgeon, D. WARWICK, MD, FRCS, FRCS(Orth), Consultant Orthopaedic Surgeon, I. BRENKEL, MBChB, FRCSEd, Orthopaedic Surgeon, King's College Hospital, London, UK.
The use of graduated compression stockings in association with fondaparinux in surgery of the hip 18 October 2007
Ihab R. Boutros, Specialist Registrar in Orthopaedic Surgery Cheltenham General Hospital, Cheltenham, GLOS., UK, Priyan R. Landham, Richard R. Brown, Harminder S. Gosal Send letter to journal: Re: The use of graduated compression stockings in association with fondaparinux in surgery of the hip ihabboutros{at}btinternet.com Ihab R. Boutros, et al.	Sir, We read this paper with interest. The study showed no difference in venous thromboembolism rates between the group that was administered fondaparinux alone and that given fondaparinux and graduated compression stockings. The authors therefore suggested the use of graduated compression stockings following hip surgery be reconsidered when fondaparinux thromboprophylaxis is used. The methodology included an initial calculation of required sample size. Various factors were considered, including an assumed event rate (rate of venous thromboembolism) for fondaparinux alone and with stockings, and allowing for 10% of patients missing the end-point, 80% power and a 5% significance level required sample size of 1072 patients (536 per group) was postulated. We noticed, however, that “the study was stopped early because the differences between the groups were so small that it would have been futile to continue”. After various exclusions, 856 patients were included in the study, some 200 patients short of the target study size. We question the decision to stop the study early and suggest this is a serious limitation to the methodology. If one treatment group had vastly superior results to the other, there would be ethical grounds to stop the study early. However, when there is no early difference between the groups, the study must be continued until the required sample size is attained so that the study has sufficient power. Otherwise there is the risk of a type II error - that a significant difference between the two treatments is not detected when in reality there is one. We would welcome the authors’ comments on this point. I.R. Boutros, Specialist Registrar in Orthopaedic Surgery, P.R. Landham, R.R. Brown, H.S. Gosal, Cheltenham General Hospital, Cheltenham, UK.
A discussion on the role of chemical prophylaxis of thromboembolic disease 5 September 2007
Augusto Sarmiento, Professor Emeritus University of Miami, Miami, FL, USA Send letter to journal: Re: A discussion on the role of chemical prophylaxis of thromboembolic disease asarm{at}bellsouth.net Augusto Sarmiento	Sir, I have read this well-documented article, but find myself questioning several points made by the authors. The authors state that their study, containing 974 patients (of whom 795 could be evaluated), is "by far" the largest dealing with the subject. The authors failed to notice in their review of the literature our 2004 study based on 1,835 hip arthroplasties. In our study the prophylactic protocol consisted of the administration of a 10-grain Aspirin suppository immediately after surgery, followed by the oral ingestion of 325 mg twice a day for the length of their hospitalisation. In addition, there were intra-operative passive exercises and early post-operative exercises.1 We compared, among several other findings, the results obtained in patients who received graded compression stockings (60.8%) and those who had intermittent compression stockings (39.1%). Deep venous thrombosis (DVT) was diagnosed in 0.85% of patients fitted with graded elastic stockings and in 1.5% among those fitted with intermittent compression stockings. The authors of the paper under discussion stated, "The prevalence of deep-vein thrombosis was similar in the two groups 5.5%... in the fundaparinux group and 4.8 ... in the fondaparinux plus stocking group..." It might be argued that we did not conduct routine ultrasound testing or Doppler studies, hence our failure to recognise the true incidence of DVT. However, our very low incidence of DVT (0.9%), fatal pulmonary embolism (0.1%), and non-fatal pulmonary embolism (0.9%), strongly suggests that the addition of expensive, aggressive, and risk-associated approaches to asymptomatic DVT is not warranted. It is obvious that the authors are familiar with studies indicating that mortality after total hip replacement performed without chemical prophylaxis is extremely low. Murray et al2 reported 0.30%, and Warwick et al3 (one of the authors of the paper under discussion) reported fatal pulmonary embolism in 0.34% of a large number of patients who never received chemical prophylaxis. In light of the evidence presented by the authors, it is probably safe to speculate that low-molecular heparin prophylaxis following total hip arthroplasty, rather than being beneficial, is an unnecessary problem-producing intervention. The authors’ high incidence of vein thrombosis was probably enhanced by the drug, as further suggested by the fact that the use of graded stockings had no bearing on the development of DVT. A. Sarmiento, MD, Professor and Chairman Emeritus, University of Miami, Miami, FL, USA. 1. Sarmiento A, Goswami A. Thromboembolic disease prophylaxis in total hip aArthroplasty. Clin Orthop Relat Res 2005;436:138-43. 2. Murray DW, Britton AR, Bulstrode CJ. Thromboprophylaxis and death after total hip replacement. J Bone and Joint Surg [Br] 1996;78-B:863-70. 3. Warwick D, Williams MH, Bannister, GC. Death and thromboembolic disease after total hip replacement. A series of 1162 cases with no routine chemical prophylaxis. J Bone and Joint Surg [Br] 1995;77-B:6-10.