Combined (mechanical and pharmacological) modalities for the prevention of venous thromboembolism in joint replacement surgery.

We performed a systematic review and meta-analysis to compare the efficacy of intermittent mechanical compression combined with pharmacological thromboprophylaxis, against either mechanical compression or pharmacological prophylaxis in preventing deep-vein thrombosis (DVT) and pulmonary embolism in patients undergoing hip or knee replacement. A total of six randomised controlled trials, evaluating a total of 1399 patients, were identified. In knee arthroplasty, the rate of DVT was reduced from 18.7% with anticoagulation alone to 3.7% with combined modalities (risk ratio (RR) 0.27, p = 0.03; number needed to treat: seven). There was moderate, albeit non-significant, heterogeneity (I(2) = 42%). In hip replacement, there was a non-significant reduction in DVT from 8.7% with mechanical compression alone to 7.2% with additional pharmacological prophylaxis (RR 0.84) and a significant reduction in DVT from 9.7% with anticoagulation alone to 0.9% with additional mechanical compression (RR 0.17, p < 0.001; number needed to treat: 12), with no heterogeneity (I(2) = 0%). The included studies had insufficient power to demonstrate an effect on pulmonary embolism. We conclude that the addition of intermittent mechanical leg compression augments the efficacy of anticoagulation in preventing DVT in patients undergoing both knee and hip replacement. Further research on the role of combined modalities in thromboprophylaxis in joint replacement and in other high-risk situations, such as fracture of the hip, is warranted.

Can combined (mechanical and pharmacological) modalities prevent fatal VTE?

AIM: The aim of this paper was to perform a systemic review and meta-analysis of the efficacy of combined modalities (intermittent pneumatic leg compression and pharmacological prophylaxis, treatment group) against single modalities alone (control group) in preventing pulmonary embolism (PE), including fatal PE and deep-vein thrombosis (DVT) in high-risk patients. METHODS: Databases searched included the Cochrane Central Register of Controlled Trials, the Specialized Register of the Peripheral Vascular Diseases Group, MEDLINE and EMBASE. RESULTS: Seventeen studies, six of them randomized controlled trials (RCTs), which enrolled a total of 9998 patients in a variety of specialties were identified. Sixteen of the included studies evaluated the role of combined modalities on the incidence of symptomatic PE. These showed a reduction in symptomatic PE from 2.83% (122/4313) in the control group to 0.86% (33/3838) in the treatment group. Odds ratio was 0.34, 95% Confidence interval (CI) 0.23 to 0.50. Fatal PE was reduced from 0.56% (11/1972) in the control group to 0.07% (1/1377) in the treatment group (results were available in 10 studies). Odds ratio was 0.37 (95% CI; 0.09 to 1.48). Fourteen studies investigated the role of combined modalities on the incidence of DVT. These showed a reduction in DVT from 6.18% (200/3238) in the control group to 2.05% (63/3074) in the treatment group. Odds ratio was 0.31, 95% CI 0.23 to 0.43. CONCLUSION: Combined prophylactic modalities decrease significantly the incidence of PE and DVT, compared to single modalities, but the reduction seen in fatal PE did not reach statistical significance. Further research on the role of combined modalities in reducing DVT and PE is necessary.

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thrombo-embolism in high-risk patients.

BACKGROUND: It has been suggested that combined modalities (methods of treatment) are more effective than single modalities in preventing venous thrombo-embolism (defined as deep vein thrombosis and pulmonary embolism, or both) in high-risk patients. OBJECTIVES: To assess the efficacy of intermittent pneumatic leg compression combined with pharmacological prophylaxis versus single modalities in preventing venous thrombo-embolism in high-risk patients. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched the reference lists of their Specialised Register (last searched 17 July 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched The Cochrane Library 2008, issue 3) for relevant articles to identify additional trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) of combined intermittent pneumatic leg compression and pharmacological interventions used to prevent venous thrombo-embolism in high-risk patients. DATA COLLECTION AND ANALYSIS: Data extraction was undertaken independently by two review authors using data extraction sheets.

Cilostazol for peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) affects 4% to 12% of people aged 55 to 70 years and 20% of people over 70 years. The most common complaint is intermittent claudication (IC) characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age-matched controls, people with IC have a three- to six-fold increase in cardiovascular mortality. Symptoms of IC, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise program. Antiplatelet treatment is beneficial in patients with IC for the reduction of vascular events but has not been shown to influence claudication distance. OBJECTIVES: To determine the effect of cilostazol on improving walking distance and in reducing vascular mortality and cardiovascular events in patients with stable IC. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their specialised register (last searched August 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2007). We searched MEDLINE (1966 to November 2005), EMBASE (1980 to November 2005), several more specialised databases, and reference lists of articles. SELECTION CRITERIA: Double-blind, randomised controlled trials of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable IC or patients undergoing vascular surgical intervention for PAD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for selection and all three authors independently extracted data. MAIN RESULTS: Seven randomised controlled trials comparing cilostazol with placebo were included. The weighted mean difference (WMD) for the initial claudication distance (ICD) was improved following treatment with cilostazol 100 mg twice daily (WMD 31.1 m; 95% confidence interval (CI): 21.3 to 40.9 m) and 50 mg twice daily (WMD 41.3 m; 95% CI: -7.1 to 89.7 m) compared with placebo. Participants receiving cilostazol 150 mg twice daily had an increased ICD (WMD 15.7 m; 95% CI: -9.6 to 41.0 m) compared with those receiving placebo. One study also included a comparison with pentoxifylline. In this study, participants receiving cilostazol had significant improvement in ICD compared with placebo. There was no increase in major adverse events including cardiovascular events or mortality in patients receiving cilostazol compared with placebo. AUTHORS' CONCLUSIONS: Patients with IC should receive secondary prevention for cardiovascular disease. Cilostazol has been shown to be of benefit in improving walking distance in people with IC. There are no data on whether it results in a reduction of adverse cardiovascular events.

Cilostazol for peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) affects 4% to 12% of people aged 55 to 70 years and 20% of people over 70 years. The most common complaint is intermittent claudication (IC) characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age-matched controls, people with IC have a three- to six-fold increase in cardiovascular mortality. Symptoms of IC, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise program. Antiplatelet treatment is beneficial in patients with IC for the reduction of vascular events but has not been shown to influence claudication distance. OBJECTIVES: To determine the effect of cilostazol on improving walking distance and in reducing vascular mortality and cardiovascular events in patients with stable IC. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their specialised register (last searched August 2006) and the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2006). We searched MEDLINE (1966 to November 2005), EMBASE (1980 to November 2005), several more specialised databases, and reference lists of articles. SELECTION CRITERIA: Double-blind, randomised controlled trials of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable IC or patients undergoing vascular surgical intervention for PAD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for selection and all three authors independently extracted data. MAIN RESULTS: Eight randomised controlled trials comparing cilostazol with placebo were included. The weighted mean difference (WMD) for the initial claudication distance (ICD) was improved following treatment with cilostazol 100 mg twice daily (WMD 31.1; 95% confidence interval (CI): 21.4 to 40.9) and 50 mg twice daily (WMD 41.3; 95% CI: -7.1 to 89.7) compared with placebo. Participants receiving cilostazol 150 mg twice daily had an increased ICD (WMD 15.7; 95% CI: -9.6 to 41.0) compared with those receiving placebo. One study also included a comparison with pentoxifylline. In this study, participants receiving cilostazol had significant improvement in ICD compared with placebo. There was no increase in major adverse events including cardiovascular events or mortality in patients receiving cilostazol compared with placebo. AUTHORS' CONCLUSIONS: Patients with IC should receive secondary prevention for cardiovascular disease. Cilostazol has been shown to be of benefit in improving walking distance in people with IC. There are no data on whether it results in a reduction of adverse cardiovascular events.

Increased platelet aggregation and activation in peripheral arterial disease.

OBJECTIVES: patients with peripheral arterial disease (PAD) have a threefold increase in cardiovascular mortality. Standard antiplatelet treatment may not confer uniform benefit in different patient groups. This study aimed to compare platelet function in patients with lower limb PAD, carotid disease and abdominal aortic aneurysm (AAA) with age- and sex-matched healthy controls. METHODS: patients with lower limb PAD (n = 20), carotid disease (n = 40), AAA (n = 13) and age/sex matched healthy controls (n= 20) were studied. Whole blood methods to detect spontaneous platelet aggregation (SPA), and adenosine diphosphate (ADP) and collagen-induced aggregation were used. The detection of platelet P-selectin and the PAC-1 antigen by flow cytometry were also used as markers of platelet activation and aggregation. RESULTS: patients with lower limb PAD or AAA had higher baseline SPA compared to normal controls (p < 0.01). There was significantly higher collagen-induced aggregation in IC patients compared to normal controls (p < 0.01). However, there was no difference in ADP-induced aggregation between lower limb PAD and control patients. There was no difference in PAC-1 binding between control patients and the patients with lower limb PAD, carotid disease or AAA. Patients with carotid disease had a higher expression of P-selectin compared to normal controls (p < 0.05). CONCLUSIONS: this study provides further evidence that platelet hyperactivity is present in patients with PAD despite the use of antiplatelet therapy. Further antiplatelet strategies may be indicated to protect these patients.

Possible role of endothelin-1 in the rabbit urinary bladder hyperplasia secondary to partial bladder outlet obstruction.

OBJECTIVES: Urinary bladder hypertrophy and hyperplasia are common features of bladder outlet obstruction (BOO). The urinary bladder is known to synthesize endothelin-1 (ET-1), which is a potent vasoconstrictor peptide with mitogenic properties. Using an animal model of partial BOO, we investigated the potential role of ET-1 and its receptor subtypes (ET(A) and ET(B)) in bladder smooth muscle cell (SMC) proliferation. MATERIALS AND METHODS: Partial BOO was produced in adult male New Zealand White rabbits. After 3 weeks, the bladder was removed and SMCs from the dome and bladder neck were grown using standard explant methodology. At passage 2, the cells were made quiescent and then further incubated in foetal calf serum (FCS), control age-matched rabbit serum (CRS) or partial BOO serum (BRS) in the presence or absence of ET(A)-antagonist (BQ123) or ET(B)-antagonist (BQ788). SMC proliferation was then measured 24 h later with 5-bromo-2'deoxy-uracil and by cell counting using a haemocytometer at 48 h. Immunostaining for alpha-actin was performed on detrusor and bladder neck cells to confirm the presence of smooth muscle cells. RESULTS: BQ123 and BQ788 did not influence detrusor or bladder neck SMC proliferation in FCS or CRS. However, in the presence of BRS, BQ123 and BQ788 (100 nmol/L) significantly (p = 0.008) inhibited detrusor and bladder neck SMC proliferation. Cell counts were significantly reduced from the detrusor (p = 0.03, p = 0.01 with BQ123 and BQ788, respectively) and bladder neck (p = 0.01 for both BQ123 and BQ78). CONCLUSIONS: These results suggest that ET antagonists may have a role in preventing SMC hyperplasia associated with partial BOO.

Use of the hepatic arterial circulation for renal revascularisation.

Renal artery stenosis is increasingly being diagnosed as a cause of hypertension and renal impairment. Surgical intervention can restore function and improve hypertension in selected cases. Over a 42 month period, 12 patients with atherosclerotic renovascular disease underwent surgical revascularisation using the hepatic arterial circulation. All had disease of both renal arteries and 11 had some degree of renal impairment, with five requiring dialysis before operation. There were two deaths within 30 days of operation, eight patients had improved renal function after operation and three of the patients previously on dialysis became dialysis free. The hepatorenal method of renal revascularisation is described and its advantages discussed.

Buerger's disease and cigarette smoking in Bangladesh.

Buerger's disease is rare in the West but common in parts of Asia and the Middle East. A total of 39 patients with Buerger's disease were investigated in the setting of a hospital in Bangladesh. All but one were male and the mean age at onset of symptoms was 34 years. All but two were current smokers with a mean duration of smoking history of 17 years before the onset of symptoms. No other risk factors were identified. The majority of patients had ulceration or gangrene at presentation, and all but one had palpable femoral pulses. Vascular reconstruction was not possible in this institution and the main treatment options adopted were antibiotics, analgesia, chemical sympathectomy and amputation.

Measurement of liver blood flow: a review.

The study of hepatic haemodynamics is of importance in understanding both hepatic physiology and disease processes as well as assessing the effects of portosystemic shunting and liver transplantation. The liver has the most complicated circulation of any organ and many physiological and pathological processes can affect it. This review surveys the methods available for assessing liver blood flow, examines the different parameters being measured and outlines problems of applicability and interpretation for each technique. The classification of these techniques is to some extent arbitrary and several so called "different" methods may share certain common principles. The methods reviewed have been classified into two groups (Table 1): those primarily reflecting flow through discrete vessels or to the whole organ and those used to assess local microcirculatory blood flow. All techniques have their advantages and disadvantages and in some situations a combination may provide the most information. In addition, because of the many factors affecting liver blood flow and sinusoidal perfusion, readings in a single subject may vary depending on positioning, recent food intake, anxiety, anaesthesia and drug therapy. This must be borne in mind if different studies are to be meaningfully compared.

Renovascular hypertension secondary to renal artery aneurysm detected by captopril-renography.

A case is described of a renal artery aneurysm which presented initially as hypertension. A captopril-renogram suggested a renal artery stenosis although none was found on arteriography or at surgery. After resection of the aneurysm the captopril-renogram was restored to normal.