Clinical drug investigation
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A non-oncology dose selection phase II trial tests multiple active doses in a controlled fashion, and it not only needs to determine whether the treatment is effective but also to select the 'lowest efficacious' dose if the treatment is indeed efficacious. Few approaches exist in the literature for designing phase II non-oncology dose selection trials, and the standard design with a fixed sample size has been widely used. The objective of this study was to develop a more efficient design for phase II dose selection trials that terminates the trial early for futility and adjusts the sample size and number of doses at interim analyses when appropriate. ⋯ Once a confident answer to either or both of these questions can be obtained, the trial may either be terminated early or some of the lower doses may be dropped to prevent assigning more patients to inferior doses and thus reduce the total sample size needed. Theoretical analyses and simulation studies show that the proposed adaptive design significantly outperforms the standard design with a fixed sample size. The proposed adaptive design should be preferred over the standard design especially in cases where enrolment is slow and efficacy can be measured after a relatively short period of time.
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Intravenous dexmedetomidine (Precedex(®)) provides both effective sedation in mechanically ventilated patients in an intensive care setting and effective procedural sedation. In these patient populations, it reduces the need for rescue sedation with intravenous propofol or intravenous midazolam and reduces opioid requirements. ⋯ Intravenous dexmedetomidine is generally well tolerated and is not associated with respiratory depression. Although the utilization of dexmedetomidine is associated with hypotension and bradycardia, both usually resolve without intervention.
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A 48-year-old woman suddenly lost consciousness as a result of a right rostral pontine tegmentum haemorrhage. The patient presented with decerebrate rigidity (DR) and regained full consciousness 5 days after the initial onset. ⋯ The patients' preserved consciousness and motor-evoked potentials to transcranial magnetic stimulation indicated a derangement of the extrapyramidal tracts with preservation of the pyramidal tracts. This case report discusses the possible mechanisms of action of gabapentin in DR.
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In patients with impaired renal function, the pharmacokinetics of a drug may be altered, resulting in decreased renal excretion or metabolism, and altered absorption, plasma protein binding or distribution. Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder. Vilazodone is extensively hepatically metabolized with minimal renal excretion. The primary objective of this study was to assess the pharmacokinetics of a single 20-mg dose of vilazodone in subjects with mild or moderate renal impairment. ⋯ This study suggests that systemic exposure of vilazodone is not affected by mild or moderate renal impairment. No dose adjustments are recommended in patients with mild or moderate renal impairment.
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Severe sepsis and septic shock have posed significant treatment challenges for many years. Recently, a number of circulating apoptosis biomarkers have emerged, such as full-length and caspase-cleaved cytokeratin 18 (CK18) and nucleosomal DNA (nDNA), that may be predictive of likely outcome. This non-interventional study aimed to assess the ability of enzyme-linked immunosorbent assays (ELISAs) for these biomarkers to provide clinically useful information to guide the management of sepsis. ⋯ Despite the small numbers of subjects assessed in the current study, these results confirm that measurement of apoptosis biomarkers may help to provide clinically useful information to manage sepsis and expedite development of novel therapeutics. However, further investigations to fully assess their prognostic value are required.