Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism.

Preliminary data and clinical experience have suggested an increased risk of abnormal uterine bleeding (AUB) in women of reproductive age treated with anticoagulants, but solid data are lacking. The TEAM-VTE study was an international multicenter prospective cohort study in women aged 18 to 50 years diagnosed with acute venous thromboembolism (VTE). Menstrual blood loss was measured by pictorial blood loss assessment charts at baseline for the last menstrual cycle before VTE diagnosis and prospectively for each cycle during 3 to 6 months of follow-up. AUB was defined as an increased score on the pictorial blood loss assessment chart (>100 or >150) or self-reported AUB. AUB-related quality of life (QoL) was assessed at baseline and the end of follow-up using the Menstrual Bleeding Questionnaire. The study was terminated early because of slow recruitment attributable to the COVID-19 pandemic. Of the 98 women, 65 (66%) met at least one of the 3 definitions of AUB during follow-up (95% confidence interval [CI], 57%-75%). AUB occurred in 60% of women (36 of 60) without AUB before VTE diagnosis (new-onset AUB; 95% CI, 47%-71%). Overall, QoL decreased over time, with a mean Menstrual Bleeding Questionnaire score increase of 5.1 points (95% CI, 2.2-7.9), but this decrease in QoL was observed only among women with new-onset AUB. To conclude, 2 of every 3 women who start anticoagulation for acute VTE experience AUB, with a considerable negative impact on QoL. These findings should be a call to action to increase awareness and provide evidence-based strategies to prevent and treat AUB in this setting. This was an academic study registered at www.clinicaltrials.gov as #NCT04748393; no funding was received.

Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome.

Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65-80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1-24. In the second cycle, cytarabine 1000 mg/m2 twice daily, days 1-6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69-91%) vs. 59% (45-72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl ).

Diffuse alveolar hemorrhage as an early complication of alemtuzumab treatment: A case report of a multiple sclerosis patient and an overview of 14 cases.

Alemtuzumab is effective in relapsing remitting multiple sclerosis (RRMS). Serious adverse events have led to a renewed safety reassessment by the European Medicines Agency (EMA), leading to an approval under strict conditions. We report a RRMS patient experiencing diffuse alveolar hemorrhage (DAH) on day 4 of her first alemtuzumab cycle. In addition, we present an overview of the cases of alemtuzumab-induced DAH that were included in EMA's review procedure, additional well documented cases reported to the EMA and those cases reported in the literature. Combining these cases revealed striking similarities. Importantly, DAH was an early complication. All RRMS patients with known outcome showed complete recovery.

[The polypill: not an effective strategy for reduction of cardiovascular disease]. / De 'polypil': geen effectieve strategie tegen hart- en vaatziekten.

The implementation of the intriguing concept of the polypill to prevent cardiovascular events remains doubtful due to a lack of evidence, expected adherence problems, the inevitable overtreatment and undertreatment of individuals, and potential side effects. Lifestyle changes and individual interventions are more preferable strategies.

[Pleiotropic effects of statins]. / Pleiotrope effecten van statinen.

Statins safely and effectively reduce the morbidity and mortality due to cardiovascular disease. In the trials conducted so far, which have been carried out predominantly on high-risk patients, the observed risk reduction is probably completely attributable to the reduction of the cholesterol level. However, statins also influence the atherosclerotic disease process in a lipid-independent way. This includes beneficial effects on the early pathogenetic components of atherosclerosis, such as endothelial dysfunction and inflammation. These effects are probably not visible in the large clinical trials that usually follow up cohorts of patients with late stages of atherosclerosis during a relatively short period of time. These cholesterol-independent effects do affect intermediate factors in the atherosclerotic process, such as endothelial dysfunction. In clinical practice, where not only short-term effects in patients with manifest vascular disease but also the prevention of the long-term complications of atherosclerosis in high-risk patients is an important goal, these so-called pleiotropic effects may contribute to risk reduction.

Misoprostol versus curettage in women with early pregnancy failure: impact on women's health-related quality of life. A randomized controlled trial.

BACKGROUND: We aimed to compare patients' health-related quality of life after a misoprostol strategy to a curettage in women with early pregnancy failure after failed expectant management. METHODS: A multicentre randomized clinical trial was performed in The Netherlands. In all, 154 women with early pregnancy failure confirmed at ultrasonography who had been managed expectantly unsuccessfully for > or =1 week were randomly assigned to undergo either treatment with misoprostol (n=79) or curettage (n=75). The main outcome measures were health-related quality of life and satisfaction with treatment. RESULTS: In the misoprostol strategy 47% of the women needed additional curettage, as compared to 4% after curettage. In both groups, health-related quality of life was impaired most severely 2 days after treatment. In the misoprostol group, health-related quality of life was more severely impaired; after 2 days this was due to more pain and after 2 and 6 weeks this was due to a worse general health perception. Health-related quality of life was temporarily significantly more impaired in women in whom misoprostol failed as compared to women in whom misoprostol treatment was successful. In both treatment groups, an equal percentage of women (58%) would choose the same treatment in the future. In women treated with misoprostol, however, this choice depended on the initial success of misoprostol: in cases where misoprostol had caused complete evacuation, 76% of the women would opt for the same treatment, whereas only 38% of women who needed curettage after unsuccessful misoprostol would do so (P<0.01). CONCLUSION: Our study shows that, although both the misoprostol strategy and the curettage strategy resulted in complete evacuation in the end, women are willing to accept some disadvantages of misoprostol to avoid curettage. A treatment inconvenience using misoprostol is accepted as long as initial evacuation rate is high. This finding should be an integral part of counselling women when deciding upon management of early pregnancy failure.