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Use of quinine decreased substantially, although diagnoses of leg cramps persist. To our knowledge, this is the first demonstration of an association for quinine and ITP and TMA in claims data.

INTRODUCTIONTrauma is the fifth principal cause of death in Singapore, with traumatic brain injury (TBI) being the leading specific subordinate cause. METHODSThis study was an eight-year retrospective review of the demographic profiles of patients with severe TBI who were admitted to the neurointensive care unit (NICU) of the National Neuroscience Institute at Tan Tock Seng Hospital, Singapore, between 2004 and RESULTS A total of 780 TBI patients were admitted during the study period; 365 (46.8%) patients sustained severe TBI (i.e. Glasgow Coma Scale score ≤ 8), with the majority (75.3%) being male. The ages of patients with severe TBI ranged from 14-93 years, with a bimodal preponderance in young adults (i.e. 21-40 years) and elderly persons (i.e. > 60 years). Motor vehicle accidents (48.8%) and falls (42.5%) were the main mechanisms of injury. Invasive line monitoring was frequently employed; invasive arterial blood pressure monitoring and central venous pressure monitoring were used in 81.6% and 60.0% of the patients, respectively, while intracranial pressure (ICP) measurement was required in 47.4% of the patients. The use of tiered therapy to control ICP (e.g. sedation, osmotherapy, cerebrospinal fluid drainage, moderate hyperventilation and barbiturate-induced coma) converged with international practices. CONCLUSIONThe high-risk groups for severe TBI were young adults and elderly persons involved in motor vehicle accidents and falls, respectively. In the NICU, the care of patients with severe TBI requires heavy utilisation of resources. The healthcare burden of these patients extends beyond the acute critical care phase.

Although current quetiapine labeling recommends that its dosage should be lowered 6‐fold when coadministered with strong cytochrome P450 (CYP)3A inhibitors, a reported case of coma in a patient receiving quetiapine with lopinavir and ritonavir prompted the reevaluation of labeling recommendations for the dosing of quetiapine when coadministered with human immunodeficiency virus (HIV) protease inhibitors. Literature and database (FDA Adverse Event Reporting System and United States Symphony Health Solutions’ Integrated Dataverse Database) searches allowed us to identify cases of coma and related adverse events involving the coadministration of quetiapine and HIV protease inhibitors and to estimate the frequency of concomitant use. Literature review and physiologically based pharmacokinetic modeling allowed us to estimate the potential for CYP3A inhibition to contribute to adverse events related to HIV protease inhibitor–quetiapine coadministration. We identified excess sedation following coadministration of quetiapine and an HIV protease inhibitor in 3 reports without obvious confounders. In prescription claims data, 0.4% of quetiapine patients were dispensed a concurrent ritonavir prescription. The quetiapine dose was not reduced on ritonavir initiation in 90% of therapy episodes. Available data indicate to us that all HIV protease inhibitors combined with ritonavir are likely to be strong CYP3A inhibitors. We predicted that ritonavir would increase quetiapine exposure comparable to the strong CYP3A inhibitor ketoconazole. The current dosing recommendations for use of quetiapine with strong CYP3A inhibitors (ie, 6‐fold lower quetiapine dose) are appropriate and should be followed when quetiapine is coadministered with HIV protease inhibitors.