Effect of two dosages of sodium chloride intake on the blood pressure response to caffeinated coffee in humans in vivo.

High sodium intake increases cardiovascular risk by increasing blood pressure. The intake of coffee elevates blood pressure acutely. Preclinical evidence shows that this action of caffeine is enhanced by high salt intake. We hypothesised that high sodium intake augments the acute blood pressure response to coffee in humans. A randomised cross-over study (n = 15) was performed comparing the effect of lower (6 g/d; LS) with higher (12 g/d; HS) sodium chloride diet on blood pressure before and 2 h after regular coffee intake. Baseline blood pressure was 115 ± 4/84 ± 2/68 ± 1 during LS and 121 ± 4/89 ± 2/69 ± 1 mmHg during HS (SBP/Mean Arterial Pressure (MAP)/DBP; mean ± SE, p < 0.05 for SBP). During LS, blood pressure increased to 121 ± 4/91 ± 2/73 ± 1 (p < 0.05 for SBP, MAP, DBP versus baseline). HS did not significantly affect the impact of coffee on blood pressure (p > 0.3 for SBP, DBP; p > 0.05 for MAP). Sodium intake does not relevantly modulate the impact of regular coffee consumption on blood pressure.

Initial anticoagulation in patients with pulmonary embolism: thrombolysis, unfractionated heparin, LMWH, fondaparinux, or DOACs?

The initial treatment of haemodynamically stable patients with pulmonary embolism (PE) has dramatically changed since the introduction of low molecular weight heparins (LMWHs). With the recent discovery of the direct oral anticoagulant drugs (DOACs), initial treatment of PE will be simplified even further. In several large clinical trials it has been demonstrated that DOACs are not inferior to standard therapy for the initial treatment of PE, and because of their practicability they are becoming the agents of first choice. However, many relative contraindications to DOACs were exclusion criteria in the clinical trials. Therefore, LMWHs will continue to play an important role in initial PE treatment and in some cases there still is a role for unfractionated heparin (UFH). In this review we will give an overview of the biophysical, pharmacokinetic and pharmacodynamic properties of anticoagulants currently available for the initial management of PE. In addition, we will provide a comprehensive overview of the indications for the use of UFH, LMWHs and DOACs in the initial management of PE from a pharmacokinetic/-dynamic point of view.

Medication Adherence to Direct Oral Anticoagulants: Extent and Impact of Side Effects.

Purpose: Arterial and venous thromboembolism are a leading cause of mortality. Direct oral anticoagulants (DOACs) are highly effective in both stroke prevention and prevention of venous thrombotic events. Medication adherence is a prerequisite for optimal protection against thromboembolic complications. Recent studies have shown that good adherence cannot be taken for granted by DOACs. In this cross-sectional study adherence among DOAC users was investigated and associations between beliefs about medication, perceived side effects and adherence were explored. Patients and Methods: We included 100 randomly selected adult DOAC users visiting one of the two participating Dutch community pharmacies in the summer of 2020. The self-reported adherence (primary outcome) was assessed with the Medication Adherence Rating Scale-5 (MARS-5) using three different cut-off scores. Beliefs about DOACs were assessed with the Beliefs about Medicine Questionnaire Specific (BMQ-S), while side effects and side effect burden were assessed with a self-developed questionnaire based on the Lareb Intensive Monitoring (LIM) system. Results: Of the participants, 9% reported non-adherence on the primary MARS-5 cut-off score <24. For the MARS-5 scores <23 and <25 non-adherence percentages of, respectively, 3 and 33% were calculated. Associations were found between adherence and both side effects and side effect burden, regardless of the MARS-5 cut-off score. Bruising and minor bleeds were the most reported side effects (both 20%). For all patients, the necessity beliefs outweighed the concern beliefs. No associations were found between adherence and either gender, indication, DOAC or dosage. Conclusion: This study confirms that adherence in patients on DOACs cannot be taken for granted. High necessity beliefs do not guarantee good adherence, as side effects impair adherence even in patients having high necessity beliefs. Therefore, we recommend that both physicians and pharmacists evaluate both adherence and side effects with these patients on a regular base.

The issue Thrombosis affects many people. Complications like stroke and lung embolism are a major cause of health damage, disability and even death. Direct oral anticoagulants (DOACs) are highly effective drugs at preventing these complications. However, patients need to take their medication properly to get the best protection. Recent studies showed that not all patients consistently take their DOACs. What's new? In this study, we discovered that patients experiencing bothersome side effect were less likely to stick to their medication schedule. The most common side effects reported were bruising and minor bleeding, by 20% each. There were no differences in how well patients took their medication based on gender, medical condition, type of DOAC or prescribed dosage. Most patients believed their medication was necessary for their health. Why is this important? This study shows that side effects hinder patients taking their medication correctly even when they believe their medication is necessary for their health. This means that patients on DOAC therapy who experience side effects may be less protected against stroke and lung embolism. Therefore, we recommend that doctors and pharmacists regularly check in with patients about any side effects they experience and how consistently they take their DOACs. What's next? This study highlights the importance of developing, testing, and implementing practical tools to find and help patients who do not take their DOACs correctly, to ensure they are better protected against blood clots.

Co-trimoxazole induced hyperkalemia and potassium monitoring in hospitalized patients.

Background Co-trimoxazole is an antibiotic combination used for the treatment of Pneumocystis jirovecii pneumonia, amongst others. Co-trimoxazole is known to increase serum potassium. For this reason, Dutch guidelines advise serum potassium monitoring in high-risk patients. Objective This study aimed to determine average serum potassium rise after administration of intravenous co-trimoxazole in hospitalized patients, compared to intravenous ceftriaxone. This study also aimed to determine adherence to Dutch guidelines by measuring the incidence of serum potassium monitoring in these patients. Setting Five departments of the Canisius Wilhelmina Hospital, a teaching hospital in Nijmegen, the Netherlands. Method Data was collected and compared from patients that received intravenous co-trimoxazole (n = 66) and intravenous ceftriaxone (n = 132) in the period of November 2008-November 2017. For each patient using co-trimoxazole, two patients using ceftriaxone were included in a paired fashion. Baseline and follow-up potassium were collected, if available. Additionally, it was tested if serum potassium was measured around the initiation of antibiotic therapy. Main outcome measure Changes in serum potassium where obtainable in 30 patients using cotrimoxazole and 40 patients using ceftriaxone. When compared to ceftriaxone, administration of intravenous co-trimoxazole was associated with a significant mean increase in serum potassium (+ 0.55 mmol/l, 95% CI 0.29-0.80, p < 0.001). After correction for confounders (baseline potassium, estimated glomerular filtration rate 30 to < 60, the presence of haematological malignancies and the usage of corticosteroids), this effect shrunk noticeably, but remained significant (+ 0.28 mmol/l, 95% CI 0.03-0.53, p = 0.031). Results The incidence of hyperkalemia at follow-up was 20% in the cotrimoxazole group, compared to 5% in the ceftriaxone group. Despite this, serum potassium was often not measured in patients using intravenous cotrimoxazole, being 76% at baseline and 55% in the period of 48-120 h after antibiotic therapy initiation, compared to 87% and 34% in the ceftriaxone group respectively. Conclusion Adherence to Dutch guidelines was poor as serum potassium monitoring was often not performed. As intravenous co-trimoxazole usage is associated with a significant increase in mean serum potassium, monitoring is strongly recommended.

Co-trimoxazole induced hyperkalemia and potassium monitoring in hospitalized patients.

Background Co-trimoxazole is an antibiotic combination used for the treatment of Pneumocystis jirovecii pneumonia, amongst others. Co-trimoxazole is known to increase serum potassium. For this reason, Dutch guidelines advise serum potassium monitoring in high-risk patients. Objective This study aimed to determine average serum potassium rise after administration of intravenous co-trimoxazole in hospitalized patients, compared to intravenous ceftriaxone. This study also aimed to determine adherence to Dutch guidelines by measuring the incidence of serum potassium monitoring in these patients. Setting Data was collected retrospectively from patients in five departments of the Canisius Wilhelmina Hospital, a teaching hospital in Nijmegen, the Netherlands. Method Data was collected and compared from patients that received intravenous co-trimoxazole (n = 66) and intravenous ceftriaxone (n = 132) in the period of November 2008-November 2017. For each patient using co-trimoxazole, two patients using ceftriaxone were included in a paired fashion. Baseline and follow-up potassium were collected, if available. Additionally, it was tested if serum potassium was measured around the initiation of antibiotic therapy. Main outcome measure Changes in serum potassium where obtainable in 30 patients using cotrimoxazole and 40 patients using ceftriaxone. When compared to ceftriaxone, administration of intravenous co-trimoxazole was associated with a significant mean increase in serum potassium (+0.55 mmol/l, 95% CI 0.29-0.80, p < 0.001). After correction for confounders (baseline potassium, estimated glomerular filtration rate 30 ≤ 60, the presence of haematological malignancies and the usage of corticosteroids), this effect shrunk noticeably, but remained significant (+0.28 mmol/l, 95% CI 0.03-0.53, p = 0.031). Results The incidence of hyperkalemia at follow-up was 20% in the cotrimoxazole group, compared to 5% in the ceftriaxone group. Despite this, serum potassium was often not measured in patients using intravenous cotrimoxazole, being 76% at baseline and 55% in the period of 48-120 h after antibiotic therapy initiation, compared to 87% and 34% in the ceftriaxone group respectively. Conclusion Adherence to Dutch guidelines was poor as serum potassium monitoring was often not performed. As intravenous co-trimoxazole usage is associated with a significant increase in mean serum potassium, monitoring is strongly recommended.