Deep-vein thrombosis in Europe - Burden of illness in relationship to healthcare resource utilization and return to work.

OBJECTIVES: Deep-vein thrombosis (DVT) forms a major healthcare burden in Europe, but exact estimates concerning the economic burden on society are lacking. This study reports results from the PREFER in VTE study concerning resource utilization and absence from work in DVT patients. METHODS: The PREFER in VTE registry was a prospective, observational, multicenter study carried out in Europe (France, Italy, Spain, the UK, and DACH [Germany, Switzerland and Austria]), designed to provide data concerning treatment patterns, resource utilization, mortality and quality of life. Patients with a first-time and/or recurrent DVT, were recruited and followed for 12 months. Data about resource utilization concerns resource utilization related to DVT. Specifically, treatment pattern, re-hospitalization rate, length of hospital stay, ambulatory/office visit, and proportion of patients returning to work, were analyzed and presented. Subgroup analysis by country and active cancer were also conducted. The length of hospital stay was analyzed as a function of demographics, previous events and co-morbidities using zero-inflated binomial negative regression. Similarly, time until return to work was analyzed using Cox regression. RESULTS: A total of 2056 patients with DVT were recruited, with an average age of 60 years. Patients with active cancer were mostly treated with heparin (83.9%), while patients without active cancer were treated with combinations of heparin, VKA and DOACs. DOACs were less often used in Spain and Italy (<7.0%). Following the management of their initial DVT 20.5% of the patients with and 12.2% of patients without active cancer (n = 88; n = 1462) were hospitalized for on average 8.2 and 10.1 days, respectively. The hospitalization-rate was highest in Italy (16.7%) and lowest in France (7.7%). Furthermore, the average length of stay was highest in Italy (16.6 days) and lowest in DACH (5.2 days). Physician visits were highest in DACH (9.3), lowest in the UK (2.6). Of those working, 50% returned to work at 1 month; >30% did not return to work within the year. CONCLUSIONS: Medical treatment of DVT differed between patients with active cancer and those without. Post-VTE or VTE-related resource utilization differs remarkably between countries. Work-loss seems high, but questions may be raised concerning the causality due to the presence of co-morbidities.

Safety assessment of new antithrombotic agents: lessons from the EXTEND study on ximelagatran.

BACKGROUND: Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged administration. OBJECTIVES AND METHODS: The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. RESULTS: Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to >2x upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. CONCLUSIONS: Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agents.

Extended thromboprophylaxis following lower limb arthroplasty: what do the clinical trials mean?

Patients undergoing major orthopaedic surgery are at high risk of thromboembolic complications. Of the available options for pharmacologic prophylaxis, the low-molecular-weight heparins (LMWHs) have been shown to be most effective in reducing the incidence of venous thromboembolic complications and are well tolerated. However, as the risk of venous thromboembolism persists for several weeks post-discharge, there is controversy regarding the ideal duration of prophylaxis. Six recent studies have examined the efficacy and safety of prolonged prophylaxis in this setting. Five of these studies have demonstrated that prolonged LMWH prophylaxis (either enoxaparin or dalteparin) for 4--5 weeks is beneficial and significantly superior to conventional prophylaxis for 7--15 days. The other study, using ardeparin, examined clinical endpoints and showed a minor trend but no significant reduction in these events. Furthermore, two of the studies -- one with enoxaparin and one with dalteparin -- also demonstrated a significant reduction in the incidence of proximal deep vein thrombosis. Analysis of all clinical events from the five studies that have published that information shows a halving or 51% reduction in favour of prolonged prophylaxis. On the basis of current evidence, prolonged thromboprophylaxis with LMWH for up to 35 days after major orthopaedic surgery is recommended.

Economic evaluation of enoxaparin as postdischarge prophylaxis for deep vein thrombosis (DVT) in elective hip surgery.

OBJECTIVES: Clinical trials indicate enoxaparin thromboprophylaxis (Clexane) can be effective and safe when used in an outpatient setting and that extending the length of thromboprophylaxis with enoxaparin to the postdischarge period may be more effective than inpatient thromboprophylaxis alone. This may increase the cost of thromboprophylaxis. The objective of the study was to estimate the expected cost-effectiveness of using enoxaparin for hospital admission only vs. enoxaparin for hospital admission and for 21 days postdischarge. METHODS: Decision analysis was used to combine probability, resource use and unit cost data, using the framework of cost-effectiveness analysis. The model used a societal perspective to estimate the expected costs of treatment and outcomes to patients undergoing orthopedic surgery for elective hip replacement. Incremental cost-effectiveness ratios were calculated to provide estimates of the cost per life gained, cost per year life year gained and cost per quality-adjusted life year gained with extended use of enoxaparin thromboprophylaxis. RESULTS: There was an expected cost per quality-adjusted life year gained of pounds 5732 associated with extended enoxaparin thromboprophylaxis. The results were sensitive to the percentage of patients who could administer enoxaparin injections at home, the rate of DVT associated with standard enoxaparin thromboprophylaxis and the rate of PE associated with standard and extended enoxaparin thromboprophylaxis. CONCLUSIONS: The analyses indicated that in most cases extended enoxaparin thromboprophylaxis resulted in increased costs for health care services. In all cases, extended thromboprophylaxis with enoxaparin was associated with improved survival and life-years gained.

Applying risk assessment models in orthopaedic surgery: effective risk stratification.

Deep vein thrombosis (DVT) and pulmonary embolism remain important causes of morbidity and mortality. Without prophylaxis, at least 60% of patients undergoing orthopaedic or trauma surgery develop DVT, and the rate may still be as high as 20-45% even with the best prophylaxis available. The rate of thrombosis may be reduced by wider use of established prophylactic measures and targeting more intense prophylaxis to very-high-risk patients. Novel agents such as pentasaccharides and recombinant hirudins may provide more effective prophylaxis in very-high-risk settings, but their optimal use requires accurate assessment of thromboembolic risk. Risk levels are influenced both by the clinical setting and patient factors, such as obesity and malignancy. There is now growing interest in the influence of molecular risk factors, including acquired thrombophilias and congenital coagulation disorders. Activated protein C resistance and hyperhomocysteinaemia have been recently identified as potential risk factors. Further investigations are needed to clarify the individual contribution of different clinical and molecular factors to overall thromboembolic risk, and the effects of interactions between them. Screening for clotting disorders and other additional risk factors may assist identification of very-high-risk patients and allow appropriate targeting of intensive prophylactic therapy.

Assessment of alfentanil by intravenous infusion as long-term sedation in intensive care.

The use of an alfentanil infusion for sedation of critically ill patients in intensive care was investigated in 16 patients who were entered consecutively into the study. The mean duration of stay was 8 days. Supplements of Diazemuls and muscle relaxants were administered if required. The success of the technique was judged by nursing and medical staff and, in particular, the wakefulness of patients was noted. No patient could recall events that occurred during their infusion. An outline protocol is described.

[Nutrition surveys in children attending kindergartens in the city of Cordoba]. / Encuesta nutricional realizada en niños concurrentes a jardines de niños de la ciudad de Córdoba.

A nutritional inquest was carried out in 1857 children attending kindergartens in Córdoba, Argentina, in 1974. Determinations were made for the socioeconomical level each child belonged (NES) and clinical and anthropometric examinations. Nutritional inquests were carried out in 414 of these children, psychological examinations in 51, and biochemical inquests in 61 children.