Comparison of two methods for the assessment of intra-erythrocyte magnesium and its determinants: Results from the LifeLines cohort study.

BACKGROUND: Direct methods for the assessment of intra-erythrocyte magnesium (dIEM) require extensive sample preparation, making them labor intensive. An alternative, less labor intensive method is indirect calculation of intra-erythrocyte magnesium (iIEM). We compared dIEM and iIEM and studied determinants of dIEM and iIEM, plasma magnesium and 24-h urinary magnesium excretion in a large population-based cohort study. METHODS: dIEM and iIEM were measured using a validated inductively coupled plasma mass spectrometry (ICP-MS) method in 1669 individuals from the second screening from the LifeLines Cohort Study. We used linear regression analyses to study the determinants of IEM, plasma magnesium and 24-h urinary magnesium excretion. RESULTS: Mean dIEM and iIEM were 0.20 ± 0.04 mmol/1012 cells and 0.25 ± 0.04 mmol/1012 cells, respectively. We found a strong correlation between dIEM and iIEM (r = 0.75). Passing-Bablok regression analyses showed an intercept of 0.015 (95% CI: 0.005; 0.023) and a slope of 1.157 (95% CI: 1.109; 1.210). In linear regression analyses, plasma levels of total- and LDL -cholesterol, and triglycerides were positively associated dIEM, iIEM, and plasma magnesium, while glucose and HbA1c were inversely associated with plasma magnesium. CONCLUSIONS: We observed a strong correlation between dIEM and iIEM, suggesting that iIEM is a reliable alternative for the labor intensive dIEM method.

Quantitative assessment of required separator fluid volume in multi-infusion settings.

BACKGROUND: Administering a separator fluid between incompatible solutions can optimize the use of intravenous lumens. Factors affecting the required separator fluid volume to safely separate incompatible solutions are unknown. METHODS: An intravenous tube (2-m, 2-mL, 6-French) containing methylene blue dye was flushed with separator fluid until a methylene blue concentration ⩽2% from initial was reached. Independent variables were administration rate, dye solvent (glucose 5% and NaCl 0.9%), and separator fluid. In the second part of the study, methylene blue, separator fluid, and eosin yellow were administered in various administration profiles using 2- and 4-mL (2 × 2 m, 4-mL, 6-French) intravenous tubes. RESULTS: Neither administration rate nor solvent affected the separator fluid volume (p = 0.24 and p = 0.12, respectively). Glucose 5% as separator fluid required a marginally smaller mean ± SD separator fluid volume than NaCl 0.9% (3.64 ± 0.13 mL vs 3.82 ± 0.11 mL, p < 0.001). Using 2-mL tubing required less separator fluid volume than 4-mL tubing for methylene blue (3.89 ± 0.57 mL vs 4.91 ± 0.88 mL, p = 0.01) and eosin yellow (4.41 ± 0.56 mL vs 5.63 ± 0.15 mL, p < 0.001). Extended tubing required less separator fluid volume/mL of tubing than smaller tubing for both methylene blue (2 vs 4 mL, 1.54 ± 0.22 vs 1.10 ± 0.19, p < 0.001) and eosin yellow (2 vs 4 mL, 1.75 ± 0.22 vs 1.25 ± 0.03, p < 0.001). CONCLUSION: The separator fluid volume was neither affected by the administration rate nor by solvent. Glucose 5% required a marginally smaller separator fluid volume than NaCl 0.9%, however its clinical impact is debatable. A larger intravenous tubing volume requires a larger separator fluid volume. However, the ratio of separator fluid volume to the tubing's volume decreases as the tubing volume increases.

Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial.

BACKGROUND: There is an urgent need to develop additional treatment strategies for patients with treatment-resistant depression (TRD). The rapid but short-lived antidepressant effects of intravenous (IV) ketamine as a racemic mixture have been shown repeatedly in this population, but there is still a paucity of data on the efficacy and safety of (a) different routes of administration, and (b) ketamine's enantiomers esketamine and arketamine. Given practical advantages of oral over IV administration and pharmacodynamic arguments for better antidepressant efficacy of esketamine over arketamine, we designed a study to investigate repeated administration of oral esketamine in patients with TRD. METHODS: This study features a triple-blind randomized placebo-controlled trial (RCT) comparing daily oral esketamine versus placebo as add-on to regular antidepressant medications for a period of 6 weeks, succeeded by a follow-up of 4 weeks. The methods support examination of the efficacy, safety, tolerability, mechanisms of action, and economic impact of oral esketamine in patients with TRD. DISCUSSION: This is the first RCT investigating repeated oral esketamine administration in patients with TRD. If shown to be effective and tolerated, oral esketamine administration poses important advantages over IV administration. TRIAL REGISTRATION: Dutch Trial Register, NTR6161. Registered 21 October 2016.

Prevention of drug-related complications in cystic fibrosis.

PURPOSE OF REVIEW: Due to continuous development of new drugs and better treatment strategies, survival of patients with cystic fibrosis has changed dramatically. Recently, targeted therapy of cystic fibrosis transmembrane conductance regulator (CFTR) modulators have become available. Despite these promising developments, treatment of this complex multiorgan disease constitutes a high and variable amount of other drugs. Complications of pharmacotherapeutic treatment are, therefore, expected to become more prevalent. This gives cause to review drug-related side effects in this new era in cystic fibrosis treatment. RECENT FINDINGS: We will discuss cystic fibrosis-related pharmacotherapies with a focus on indication of treatment, side effects and their complications, drug--drug interactions, and options to monitor and prevent drug-induced toxicity. Many recent publications about pharmacotherapy in cystic fibrosis, focus on antifungal therapy and CFTR modulators. We will give an overview of the most important studies. SUMMARY: With increased life expectancy which is, in part, because of better treatment options, the burden of pharmacotherapy in cystic fibrosis patients will increase. This has a high impact on quality of life as pharmacotherapy is time consuming and may cause side effects. Therefore, it is very important to be aware of possible pharmacotherapy-related side effects and their complications, drug--drug interactions, and options to monitor and prevent drug-induced toxicity.

Quality Assessment of Dried Blood Spots from Patients With Tuberculosis from 4 Countries.

BACKGROUND: Dried blood spot (DBS) sampling is a blood collection tool that uses a finger prick to obtain a blood drop on a DBS card. It can be used for therapeutic drug monitoring, a method that uses blood drug concentrations to optimize individual treatment. DBS sampling is believed to be a simpler way of blood collection compared with venous sampling. The aim of this study was to evaluate the quality of DBSs from patients with tuberculosis all around the world based on quality indicators in a structured assessment procedure. METHODS: Total 464 DBS cards were obtained from 4 countries: Bangladesh, Belarus, Indonesia, and Paraguay. The quality of the DBS cards was assessed using a checklist consisting of 19 questions divided into 4 categories: the integrity of the DBS materials, appropriate drying time, blood volume, and blood spot collection. RESULTS: After examination, 859 of 1856 (46%) blood spots did not comply with present quality criteria. In 625 cases (34%), this was due to incorrect blood spot collection. The DBS cards from Bangladesh, Indonesia, and Paraguay seemed to be affected by air humidity, causing the blood spots not to dry appropriately. CONCLUSIONS: New tools to help obtain blood spots of sufficient quality are necessary and environmental specific recommendations to determine plasma concentration correctly. In addition, 3% of the DBS cards were rejected because the integrity of the materials suggesting that the quality of plastic ziplock bags currently used to protect the DBS cards against contamination and humidity may not be sufficient.