Pharmacotherapy
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As better international normalized ratio (INR) control and self-testing reduce events in warfarin-treated patients, and vitamin K supplementation may improve INR control, our primary objective was to evaluate the effect of a system combining frequent INR self-testing with online remote monitoring and management (STORM₂) and low-dose vitamin K supplementation on INR control; our secondary objectives were to assess the impact of STORM₂ on clinician time and to evaluate the influence of pharmacogenomics on INR stability and warfarin dose after vitamin K supplementation. ⋯ The 25% point improvement in TTR with STORM₂ is a greater improvement than reported previously with other efforts to improve TTR. STORM₂ required a minimum amount of clinician time. Pharmacogenomics were not predictive of improved INR control or the magnitude of the warfarin dose after vitamin K supplementation, although the content of the product was unreliable. Patients with the GG VKORC1 genotype required a higher warfarin dose than predicted by the product information. The potential clinical impact of improved INR control with this method warrants comparisons with conventionally managed warfarin and with the new oral anticoagulants.
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Randomized Controlled Trial Comparative Study
Single-dose and multiple-dose pharmacokinetics and dose proportionality of intravenous and intramuscular HPβCD-diclofenac (Dyloject) compared with other diclofenac formulations.
To evaluate single- and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. ⋯ Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPβCD-diclofenac compared with Voltarol and after IM administration of HPβCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPβCD-diclofenac was equivalent to IV administration of HPβCD-diclofenac and IV administration of Voltarol. Study 2: HPβCD-diclofenac showed dose proportionality after single- and multiple-dose administration and no accumulation of HPβCD-diclofenac. HPβCD-diclofenac was safe and well tolerated following IV and IM administration.
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As second-generation antipsychotic long-acting injections (SGA-LAIs) are rapidly replacing depot first-generation antipsychotics as first-line agents in treating schizophrenia spectrum disorders, a systematic assessment of their adverse effects is timely. English-language, peer-reviewed articles reporting original data on the safety and tolerability of SGA-LAIs were identified electronically by searching the MEDLINE, EMBASE, PsycINFO, and DARE databases and the Cochrane Library (January 2001-April 2013). In addition to second-generation (atypical) antipsychotics and long-acting injection (depot) antipsychotics, a separate search was performed for each available drug: aripiprazole LAI, olanzapine pamoate, paliperidone palmitate, and risperidone LAI. ⋯ The reviewed information seems to suggest that worsening of psychotic symptoms and depression could also be associated with both risperidone-LAI and paliperidone palmitate. The leading cause of death among patients enrolled in risperidone-LAI studies was suicide. Given the exponential growth in the clinical use of SGA-LAIs, further studies must be urgently performed in order to confirm or exclude the potential safety signals associated with such drugs.
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To use pharmacokinetic/pharmacodynamic (PK/PD) modeling to correlate predicted antibiotic efficacy with actual clinical outcomes in patients with serious infections. ⋯ PK/PD modeling did not accurately predict clinical or microbiologic success in patients with P. aeruginosa pneumonia. This study highlights the difficulties in applying PK/PD modeling at the level of the individual patient due to extreme PK variability and issues such as severity of illness. Antibiotic dosing based on sound PK/PD principles is strongly advocated, but additional studies are needed to confirm the role of PK/PD modeling in optimizing outcomes of patients with serious bacterial infections.
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To categorize institutional review board (IRB) challenges and solutions encountered in a multicenter practice-based research network (PBRN) study and to assess the impact of IRB requirements on the willingness of individual principal investigators (PIs) to participate in future PBRN studies. ⋯ Significant time and resources were required to address various challenges associated with IRB approval, which had a negative impact on an individual PI's willingness to participate in future PBRN projects. A revision of current rules and regulations regarding the protection of human subjects for practice-based studies, improvement in IRB processes, and support from coordinating centers may decrease the burden associated with IRB approval and increase participation in practice-based research.