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Antiphospholipid syndrome (APS) is an auto-immune syndrome defined by thrombosis and/or pregnancy morbidity in the persistent presence of antiphospholipid antibodies. Antiphospholipid antibodies are a group of antibodies predominantly directed at phospholipid-bound plasma proteins. The more antibodies a patient has the higher the risk of thrombosis. The origin of the antibodies and the precise prothrombotic mechanism are incompletely understood. A diagnosis of APS can in certain clinical scenarios implicate a longer treatment with anticoagulants after a venous thromboembolism. High level evidence is absent. In addition, APS patients with a high risk antibody profile had a higher risk of arterial thrombosis in randomized trials when treated with direct oral anticoagulants compared to vitamin K antagonists. The number needed to screen in light of these possible consequences of an APS diagnosis for treatment, appears to high to justify routine screening. In this review we suggest indications for APS testing in the context of venous thromboembolism.

Direct-acting oral anticoagulants (DOAC's) have surpassed vitamin K antagonists (VKAs) as the preferred anticoagulant therapy in patients with non-valvular atrial fibrillation or venous thromboembolism. In most patients, the benefits of anticoagulant therapy, i.e. prevention of thromboembolism including stroke risk outweigh the risks of bleeding complications. However, in older and frail patients, uptake of DOAC's is limited by concerns of bleeding. Recent developments, with therapeutics that specifically target factor XI, carry a promise to be a game changer. Activated factor XI is thought to contribute to clot progression and thrombosis, but has only a minor effect on clot consolidation during hemostasis. In this paper we will discuss the latest findings of clinical studies on factor XI inhibitors and speculate on future perspectives, including the proposal to use consistent terminology for this emerging class of DOAC's.

In the middle of the worldwide COVID-19 crisis, the whole of Europe was alarmed about a possible side effect of the AstraZeneca vaccine against COVID-19. Consequently, the use of this AstraZeneca vaccine was temporarily suspended in many European nations including the Netherlands. In this article, we chronologically describe the decisions that were made about the use of this vaccine in the Netherlands and we discuss the risk-benefit ratios of these actions as well as possible non-medical reasons that may explain why these actions were taken.

Objective: To evaluate the efficacy and safety of thromboprophylaxis with a low of low-molecular-weight heparin (LMWH) in women with an intermediate to high risk of pregnancy-related venous thromboembolism (VTE)., Design: Retrospective cohort study., Methods: We collected data from all pregnant women with an intermediate or high risk of VTE in the period 1996-2009. In accordance with protocol, pregnant women with an intermediate risk of VTE were treated with a prophylactic dose of LMWH for 6 weeks post partum, and pregnant women with a high risk were treated with a prophylactic dose of LMWH during the pregnancy and for 6 weeks post partum. Efficacy was defined as the incidence of VTE during pregnancy or < 3 months post partum, and safety as the incidence of post-partum haemorrhage (PPH) (> 500 ml blood loss) or severe PPH (> 1,000 ml blood loss)., Results: We analysed 34 women (44 pregnancies) with an intermediate risk and 57 women (82 pregnancies) with a high risk of VTE. The incidence of pregnancy-related VTE despite thromboprophylaxis was 5.5% (95% CI: 2.4-12.3). All VTEs occurred in high-risk women, and risk was higher post partum than ante partum: 7.0% (95% CI: 2.9-16.7) and 1.8% (95% CI: 0.4-9.2%), respectively. The risk of PPH was 21.6% (95% CI: 14.3-31.3) and of severe PPH 9.1% (95% CI: 4.7-16.9) and was comparable in women who used LMWH during pregnancy and those who started LMWH post partum., Conclusion: There was a considerable risk of pregnancy-related VTE in high-risk women despite a prophylactic dose of LMWH during pregnancy and in the post partum period. For these women thromboprophylaxis with a low, prophylactic dose of LMWH appeared to be insufficient.

The NOSTRADAMUS study (ISRCTN07836779) was prematurely terminated due to low inclusion rates. There were several causes for this low inclusion: delay of approval by medical ethics committees, competition with industry-initiated intervention studies with a higher financial compensation, and the lack of study staff and allowance of expenses. We advise restraint with respect to testing for thrombophilia in patients with a first deep vein thrombosis or pulmonary embolism, as the benefit of this procedure has yet to be demonstrated.

Erectile dysfunction is a common multifactorial complication of diabetes mellitus. In recent years, phosphodiesterase type 5 (PDE-5) inhibitors have been introduced in the management of erectile dysfunction. A recent Cochrane systematic review assessed the effects ofPDE-5 inhibitors in patients with diabetes mellitus and erectile dysfunction from 8 randomized placebo-controlled trials (a total of 1759 participants). The duration of therapy was mainly 12 weeks. The weighted mean difference (WMD) for the International Index of Erectile Function (erectile dysfunction domain) at the end of the study period was 6.6 in favour of the PDE-5 inhibitors arm. The relative risk for answering 'yes' to a global efficacy question ('did the treatment improve your erections?') was 3.8 in the PDE-5 inhibitors arm compared with the control arm. Headache and flushing were the most common adverse events, followed by flu-like symptoms, dyspepsia, myalgia, vision disorders and lower back pain. The overall risk ratio for developing any adverse reaction was 4.8 in the PDE-5 inhibitors arm as compared to the control arm. It was concluded that sufficient evidence exists that treatment with PDE-5 inhibitors can improve erectile dysfunction in diabetic men.

A recent Cochrane systematic review assessed the effects of wearing compression stockings during long-distance flights on the risk of deep-vein thrombosis (DVT). Ten randomised trials were included, 9 of which compared wearing compression stockings on both legs during the whole flight (at least 7 hours) with not wearing compression stockings. In these 9 trials, 50 of 2637 participants with 1 week of follow-up had asymptomatic DVT; 3 had worn stockings, 47 had not (odds ratio: 0.10; 95% CI: 0.04-0.25). No deaths, pulmonary emboli or symptomatic DVTs were reported. Wearing stockings had a significant impact in reducing oedema of the lower legs. No significant adverse effects of wearing stockings were reported.

Observational studies in the early nineteen-nineties have strongly suggested that hormone replacement therapy (HRT) has benefits for reducing cardiovascular events in postmenopausal women. A recent Cochrane systematic review assessed the effects of HRT in primary and secondary prevention of cardiovascular disease in postmenopausal women from ten randomized placebo-controlled trials published in the last decade. No protective effect of HRT was seen for any of the cardiovascular outcomes assessed. In contrast, higher risks of venous thromboembolic events, pulmonary embolus and stroke were found in postmenopausal women randomized to HRT compared to a placebo. Initiating HRT in postmenopausal women (with or without cardiovascular disease) for the sole reason of preventing cardiovascular disease should not be recommended. Further, in the case of other risk factors for venous thromboembolic events, the use of HRT for preventive purposes should be discouraged.

Approximately 30% of people over 65 years of age and living in the community fall each year; the percentage is higher in institutions. A fifth of the incidents require medical attention. A Cochrane systematic review of 62 studies, encompassing 21,668 elderly people, showed that several interventions are effective in preventing falls, especially in people who have already fallen once, including multidisciplinary interventions targeting multiple risk factors, individually prescribed muscle strengthening combined with balance training at home, cardiac pacing for hypersensitivity of the sinus node, and withdrawal of psychotropic medication. Individually tailored interventions delivered by a health professional were more effective than standard or group-delivered programmes. Some potential interventions were of unknown effectiveness or unlikely to be beneficial. Examples of these are physical exercises, the use of dietary supplements and the correction of impaired vision.

A Cochrane systematic review of 30 randomised clinical trials assessed the effects of current treatments for adults with mild-to-severe changes in facial and forearm skin that occurred as a result of prolonged exposure to the sun ('photodamage'). Topical tretinoin > or = 0.02% improved the appearance of mild-to-severe photodamage. Tazarotene 0.01-0.1% and isotretinoin 0.1% provided benefit to patients with moderate photodamage. The treatment duration was 4-11 months. Adverse effects were pain and redness. Both the efficacy and adverse effects were dose-dependent. Other treatments, such as polysaccharides, hydroxy acids, surgical procedures and laser, cannot be recommended.

Removing dental plaque plays a key role in maintaining oral health and reducing gingivitis and parodontitis. A systematic Cochrane review ofrandomised controlled trials encompassing participants from the general public with uncompromised manual dexterity showed that when compared to the use of manual toothbrushes, the use of powered toothbrushes with a rotating oscillation action for a period of three months reduced gingivitis and (although not statistically significantly) plaque. The long-term clinical relevance of the differences is unclear. Electric toothbrushes that did not have an oscillating rotating movement were not consistently better than manual toothbrushes.

Sweeping ('stripping') of the membranes has the potential to initiate labour by increasing local production of prostaglandins and, thus, to reduce pregnancy duration or to pre-empt formal induction of labour with either oxytocin, prostaglandins or amniotomy. A Cochrane systematic review of 22 trials (2797 women) comparing membrane sweeping with no treatment, with prostaglandins and with oxytocin revealed that stripping of the membranes was associated with reduced frequency of pregnancy continuing beyond 41 and 42 weeks. To avoid formal induction of labour in one instance, membrane sweeping must be performed in 8 women. Discomfort during vaginal examination and other adverse effects (bleeding, irregular contractions) were reported more frequently by women allocated to sweeping. When used as a means of inducing labour, the reduction in the use of more formal methods of induction must be balanced against the resulting discomfort and other adverse effects.

The routine use of nasogastric tubes after abdominal operations is intended primarily to hasten the return of bowel function. A Cochrane systematic review of 28 studies, encompassing 4195 patients (2108 randomised to routine tube use and 2087 randomised to temporary or no tube use), showed that routine prophylactic nasogastric decompression was not effective in achieving its primary goal. It also appeared not to be statistically significantly effective in achieving secondary goals, such as the prevention of pulmonary complications, wound infection, and ventral hernia, nor in increasing patient comfort and shortening hospital stay. Routine nasogastric decompression should be abandoned in favour of temporary use of the nasogastric tube.

In 70% to 80% of patients with venous thromboembolism, a thrombophilic defect can be identified. The most important defects are: antibodies to phospholipids or lupus anticoagulants, mutation of factor V Leiden, prothrombin mutation, mild hyperhomocysteinaemia, and increased factor VIII levels. Deficiencies of antithrombin, protein C or protein S are rare. Whether or not screening for thrombophilia in patients with idiopathic venous thromboembolism is justified, depends on the potential benefits for the patients, or their relatives. At present, patients with a thrombophilic defect do not appear to have a much higher risk for recurrent venous thromboembolism, than patients with thrombosis but without a defect. The absolute risks of venous thromboembolism in asymptomatic relatives with a thrombophilic defect are too low to justify initiating a general policy of family screening. In conclusion, a conservative approach towards thrombophilia screening in idiopathic venous thromboembolism is warranted.

Use of oral contraceptives induce changes in haemostatic parameters: changes occur in the procoagulant, anticoagulant, and fibrinolytic systems. The increased risk of venous thromboembolism with use of third, as compared with second generation oral contraceptives, found in epidemiological studies, has stimulated new research in haemostatic changes induced by both generations of oral contraceptives. A randomized crossover study showed that use of the third generation pill caused a greater increase of factor VII and prothrombin and a more pronounced decrease of factor V than the second generation pill. Acquired resistance to activated protein C (APC) was induced more strongly by preparations of the third than by those of the second generation. The concentration of protein S decreased markedly exclusively during use of the third generation pill, while it did not change during use of the second generation pill. The oral contraception-related effects on the anticoagulant system strongly resemble those of some forms of hereditary thrombophilia. If a woman with hereditary APC resistance (caused by factor V Leiden) uses oral contraceptives as well, and especially when she uses those of the third generation, she is subject to a considerable increase of the risk of venous thrombosis and becomes even more resistant to the anticoagulant action of protein C. In view of the epidemiological backgrounds of the difference in risk of thrombosis between second and third generation contraceptives, the second generation pill is recommended as the first choice for oral contraception.