Search

The principle that personal information is used to provide an individualized prognosis and therapy is an old maxim. Personalized medicine aims to add genetic and molecular information to routinely obtained clinical care data. Thus far, this additional information has not improved prognostic ability in many clinical conditions. Moreover, for most conditions, genetic or molecular knowledge that was used to guide therapeutic decisions has not been shown to improve the clinical outcome.

In recent years, the association between air travel and the incidence of deep-vein thrombosis or pulmonary embolism has become clearer. Epidemiologic studies reveal an increased relative risk of thromboembolism after flights of more than 8 hours and especially in subjects at higher risk for this disease, due, for example, to congenital thrombophilia or the use of oral contraceptives. However, the absolute risk of deep-vein thrombosis or pulmonary embolism after prolonged air travel is very small. Studies have shown that a combination of factors present during prolonged air travel may account for increased activation of coagulation. There is no definitive proof that elastic stockings are effective in reducing the incidence of clinically relevant thromboembolism during air travel. Acetylsalicylic acid is not effective in the prevention of thrombosis during air travel and may be dangerous. Prophylactic subcutaneous low molecular weight heparin may be effective to prevent air travel-associated thrombosis. However, pending more solid evidence, this strategy should only be used cautiously, e.g. only in patients with a high risk of thrombosis who are planning a long flight.

The views on the effects of postmenopausal hormone-replacement therapy (HRT) on cardiovascular disease have moved from one end of the spectrum to the other over the past decades. The presumed beneficial effects of HRT on arterial cardiovascular disease were based on observational findings and have led to the widespread use of these agents. However, recent large-scale randomised, placebo-controlled trials have demonstrated that HRT in women with a history of arterial diseases initially increases the risk of recurrent disease, while offering no benefit in the long term. Healthy postmenopausal women on HRT have an increased risk of arterial cardiovascular events compared with those taking placebo (relative risk 1.29; 95% CI: 1.02-1.63). Finally, the risk of venous thrombosis and pulmonary embolism is increased with the use of HRT. These results demonstrate that bias and confounding can play an important role in observational research and underscore the importance of randomised, placebo-controlled trials when studying the efficacy of drugs.

Studies that have methodological shortcomings may still lead to the right conclusion. Sometimes, the bias is small, or the shortcoming is not relevant for the issue being studied. It is also possible that a perfectly designed and executed study does not yield the 'right' answer. For example, chance circumstances might lead to the incomparability of groups. Bayes' theorem clarifies why different experts may come to opposite conclusions based on the same studies. The ultimate truth remains elusive.

Several case-control studies have shown that factor VIII levels > or = 150 IU/100 ml lead to a greatly increased risk of venous thrombosis. High levels of factor VIII are also associated with an increased risk of recurrences of thrombosis. The prevalence of high factor VIII levels is 25% in patients with a first episode of venous thrombosis and 11% among healthy controls. The contribution of high factor VIII levels to the onset of venous thrombosis in the population is 16%. The mechanism causing high factor VIII levels is largely unknown and probably consists of both genetic and acquired factors. At present, the routine screening of thrombosis patients for high factor VIII levels is not recommended.

Small relative risks (a twofold or lesser increase in disease frequency) become scientifically acceptable with (a) repeated consistent findings from studies that (b) address the most important forms of bias and confounding, and (c) when there is a plausible biologic mechanism. The third-generation oral contraceptive controversy is an example of such a relevant but small relative risk and demonstrates the problem of interpretation and implementation into medical practice guidelines.

In recent years research was done to elucidate the relation between an increased homocysteine concentration and arterial as well as venous thrombosis. Several case control studies showed that an elevated homocysteine concentration is an independent risk factor for primary and secondary venous thromboembolism. It is not clear whether lowering homocysteine levels by administration of folic acid, whether or not in combination with vitamin B12 and vitamin B6, decreases the risk of vascular events. Randomized secondary prevention trials are being conducted at this moment. It is recommended to await the results of these trials before screening for and treating of individuals with hyperhomocysteinaemia.

A new study design was evaluated for the estimation of the incidence of thromboembolic complications, bleeding complications and endocarditis in patients with prosthetic heart valves. Thromboembolism is a serious complication in patients with artificial heart valves. Consequently lifelong anticoagulation therapy is indicated for such patients. In the Netherlands the intensity of the anticoagulation is monitored by a network of regional anticoagulation services. The computerized patient information system of the Leiden anticoagulation service was used for a two year follow-up study of patients with mechanical heart valves. In these years anticoagulation was monitored in 273 patients with a total follow-up period of 442 patient-years. The incidence figures for thromboembolism, bleeding complications and endocarditis were 0.9/100 patient-years, 5.6/100 patient-years and 0.2/100 patient-years, respectively. The findings are similar to those of classical follow-up studies. This method is not suitable for detection of the direct early postoperative mortality or for follow-up of patient with heterografts. We conclude that the detection and follow-up by means of regional anticoagulation service offers an opportunity to investigate patients with mechanical heart valves in an efficient way without notable selection.

To determinate whether the stressful lifestyle of members of parliament (MP) might lead to excess mortality, as suggested in British Medical Journal in 1989, we investigated the mortality and life expectancy of 1589 members of the Dutch parliament over the period 1848-1989. Total mortality (all causes) for members of parliament who had been in function for at least one year (n = 1472) was compared to that of the general population of the Netherlands, adjusted for age, sex and calendar period. We calculated a standardized mortality ratio (SMR) from beginning of exposure as well as from ten years after entry in order to correct for a healthy cohort effect. The total number of deaths was 986 (863 with follow-up after 10 years after entry) and did not exceed the expected number of deaths based on population mortality rates. We conclude that MPs have no higher death risk than those who elected them, although one might have expected a lower death risk because of their social background.

The influence of modern substitution therapy on social functioning of haemophiliacs was studied by means of surveys of education and employment in 1972, 1978 and 1985. In addition we studied the physical mobility of the patients. Non-attendance at school and educational delay decreased substantially over thirteen years and the educational level of adult patients is the same as that of the general male population. Sick leave decreased also but the number of disabled did not. Considering the general rise in the number of disabled, the general unemployment situation may be partly blamed for this. Younger patients have a better physical mobility than the older ones who did not have appropriate treatment of bleedings when they were young. Trends in reduction of joint impairment and increase of physical mobility are expected to continue in the coming decades, with a positive effect on social functioning.