Time from approval to publication of completed academic drug trials.

<p>(n = 114).</p

Number and proportion of initiated, completed, and published academic drug trials by year of approval of clinical trial application.

<p>Number and proportion of initiated, completed, and published academic drug trials by year of approval of clinical trial application.</p

Characteristics of included academic drug trials by publication status.

<p>Characteristics of included academic drug trials by publication status.</p

Time from approval to publication of completed academic drug randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs).

<p>Time from approval to publication of completed academic drug randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs).</p

Reasons for non-initiation, non-completion, and non-publication of academic drug trials.

<p>Reasons for non-initiation, non-completion, and non-publication of academic drug trials.</p

Therapeutic drug monitoring of imatinib – how far are we in the leukemia setting?

Tyrosine kinase inhibitors (TKIs) have revolutionized survival rates of chronic myeloid leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) and replaced hematopoietic stem cell transplantation (hSCT) as the key treatment option for these patients. More recently, the so-called Philadelphia chromosome-like (Ph-like) ALL has similarly benefitted from TKIs. However, many patients shift from the first generation TKI, imatinib, due to treatment-related toxicities or lack of treatment efficacy. A more personalized approach to TKI treatment could counteract these challenges and potentially be more cost-effective. Therapeutic drug monitoring (TDM) has led to higher response rates and less treatment-related toxicity in adult CML but is rarely used in ALL or in childhood CML. This review summarizes different antileukemic treatment indications for TKIs with focus on imatinib and its pharmacokinetic/-dynamic properties as well as opportunities and pitfalls of TDM for imatinib treatment in relation to pharmacogenetics and co-medication for pediatric and adult Ph+/Ph-like leukemias. TDM of imatinib adds value to standard monitoring of ABL-class leukemia by uncovering non-adherence and potentially mitigating adverse effects. Clinically implementable pharmacokinetic/-dynamic models adjusted for relevant pharmacogenetics could improve individual dosing. Prospective trials of TDM-based treatments, including both children and adults, are needed.</p

Fewer adverse effects associated with a modified two-bag intravenous acetylcysteine protocol compared to traditional three-bag regimen in paracetamol overdose

<p><b>Context:</b> The intravenous (IV) N-acetylcysteine (NAC) regimen used worldwide in paracetamol overdose is complex with three separate weight-based doses and is associated with a high incidence of adverse events including non-allergic anaphylactoid reactions (NAARs). In 2012, Denmark adopted the two-bag IV NAC regimen which combined the first two infusions of the three-bag regimen and kept the third infusion unchanged. We compared the safety and efficacy of the two-bag IV NAC regimen with the traditional Danish three-bag regimen.</p> <p><b>Methods:</b> A medical chart review was conducted in three Danish medical centers from January 2012 through December 2014. Safety and efficacy data were compared for patients who received the traditional infusion protocol in Denmark or the 20-h two-bag IV regimen.</p> <p><b>Results:</b> Four hundred and ninety-three cases received the two-bag regimen and 274 received the three-bag regimen. The overall incidence of NAARs was 9% with all being mild to moderate in intensity. Fewer subjects in the two-bag group (4%) developed NAARs compared to 17% in the three-bag group (<i>p</i> < .001). Overall, 31 patients (4%) developed hepatotoxicity. There was no apparent difference in hepatotoxicity rates between the groups and no deaths or liver transplants. Patients receiving the two-bag regimen had fewer interruptions or delays (5%) compared to the three-bag regimen cohort (12%). Overall, there were very few medication errors reported (1%).</p> <p><b>Conclusions:</b> The incidence of NAARs was lower in patients receiving acetylcysteine in a two-bag regimen compared to the traditional Danish three-bag regimen without an apparent reduction in efficacy.</p