Patients with severe infection have an increased risk of cardiovascular events. A possible underlying mechanism is inflammation-induced platelet aggregation. We investigated whether... Show morePatients with severe infection have an increased risk of cardiovascular events. A possible underlying mechanism is inflammation-induced platelet aggregation. We investigated whether hyperaggregation occurs during infection, and whether aspirin inhibits this. In this multicentre, open-label, randomised controlled trial, patients hospitalised due to acute infection were randomised to receive 10 days of aspirin treatment (80 mg 1dd or 40 mg 2dd) or no intervention (1:1:1 allocation). Measurements were performed during infection (T1; days 1-3), after intervention (T2; day 14) and without infection (T3; day > 90). The primary endpoint was platelet aggregation measured by the Platelet Function Analyzer (R) closure time (CT), and the secondary outcomes were serum and plasma thromboxane B2 (sTxB2 and pTxB2). Fifty-four patients (28 females) were included between January 2018 and December 2020. CT was 18% (95%CI 6;32) higher at T3 compared with T1 in the control group (n = 16), whereas sTxB2 and pTxB2 did not differ. Aspirin prolonged CT with 100% (95%CI 77; 127) from T1 to T2 in the intervention group (n = 38), while it increased with only 12% (95%CI 1;25) in controls. sTxB2 decreased with 95% (95%CI - 97; - 92) from T1 to T2, while it increased in the control group. pTxB2 was not affected compared with controls. Platelet aggregation is increased during severe infection, and this can be inhibited by aspirin. Optimisation of the treatment regimen may further diminish the persisting pTxB2 levels that point towards remaining platelet activity. This trial was registered on 13 April 2017 at EudraCT (2016-004303-32). Show less
Testosterone therapy is the cornerstone in the care of men with hypogonadism and transgender males. Gel and intramuscular injections are most frequently used and are registered and included in the... Show moreTestosterone therapy is the cornerstone in the care of men with hypogonadism and transgender males. Gel and intramuscular injections are most frequently used and are registered and included in the international guidelines. The specific preparation should be selected according to the patient's preference, cost, availability, and formulation-specific properties. As the majority of men with hypogonadism and transgender males require lifelong treatment with testosterone, it is important to utilize a regimen that is effective, safe, inexpensive, and convenient to use with optimal mimicking of the physiological situation. This systematic review reviews current literature on differences between the three most used testosterone preparations in adult men with hypogonadism and transgender males. Although it appeared hardly any comparative studies have been carried out, there are indications of differences between the preparations, for example, on the stability of testosterone levels, hematocrit, bone mineral density, and patient satisfaction. However, there are no studies on the effects of testosterone replacement on endpoints such as cardiovascular disease in relation to hematocrit or osteoporotic fractures in relation to bone mineral density. The effect of testosterone therapy on health-related quality of life is strongly underexposed in the reviewed studies, while this is a highly relevant outcome measure from a patient perspective. In conclusion, current recommendations on testosterone treatment appear to be based on data primarily from non-randomized clinical studies and observational studies. The availability of reliable comparative data between the different preparations will assist in the process of individual decision-making to choose the most suitable formula. Show less
Diemen, J.J.K. van; Madsen, M.C.; Vrancken, P.; Bie, K. de; Bom, J.G. van der; Veen, G.; ... ; Thijs, A. 2020
Cardiovascular events occur most frequently in the early morning. Similarly, the release of reticulated platelets (RP) by megakaryocytes has a peak in the late night and early morning. Which... Show moreCardiovascular events occur most frequently in the early morning. Similarly, the release of reticulated platelets (RP) by megakaryocytes has a peak in the late night and early morning. Which aspirin regimen most effectively inhibits platelets during these critical hours is unknown. Hence, the primary objective of this trial was to assess platelet function and RP levels at 8.00 AM, in stable cardiovascular (CVD) patients, during three different aspirin regimens. In this open-label randomized cross-over study subjects were allocated to three sequential aspirin regimens: once-daily (OD) 80 mg morning; OD-evening, and twice-daily (BID) 40 mg. Platelet function was measured at 8.00 AM & 8.00 PM by serum Thromboxane B-2(sTxB(2)) levels, the Platelet Function Analyzer (PFA)-200 (R) Closure Time (CT), Aspirin Reaction Units (ARU, VerifyNow (R)), and RP levels. In total, 22 patients were included. At 8.00 AM, sTxB(2)levels were the lowest after OD-evening in comparison with OD-morning (p= <0.01), but not in comparison with BID. Furthermore, RP levels were similar at 8.00 AM, but statistically significantly reduced at 8.00 PM after OD-evening (p= .01) and BID (p= .02) in comparison with OD-morning. OD-evening aspirin intake results in higher levels of platelet inhibition during early morning hours and results in a reduction of RP levels in the evening. These findings may, if confirmed by larger studies, be relevant to large groups of patients taking aspirin to reduce cardiovascular risk. Show less
