Research

Current Research Projects

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Pharmacotherapy optimization in patients with aneurysmal subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is a neurological emergency characterized by the extravasation of blood into the subarachnoid space. Although SAH accounts for 5% of all strokes, given the relatively younger age at onset, it has a significant burden on productive-life years. The average mortality rate for SAH has been reported to range from 30-50%, with a significant proportion of survivors left with disability. Neurological and medical complications are common after SAH and contribute significantly to the overall prognosis. Cerebral vasospasm and delayed cerebral ischemia are significant contributors to disability in SAH patients who survive the initial bleed. Several agents have been proposed to target vasospasm or provide neuroprotection in animal models; however, when tested in randomized controlled trials those agents failed to provide significant improvement in patient outcomes. The only agent that provided clinical benefit in trials is nimodipine. Nimodipine has been shown to improve outcomes following SAH. Guidelines recommend that all patients receive nimodipine fixed doses for 21 days. However, pharmacokinetic studies reported extensive variability of nimodipine concentrations. It is not clear if minimal or lack of systemic exposure to nimodipine denies its benefit and contributes to worsening outcomes. The aim of this research is individualization of nimodipine treatment for the sake improving patient outcomes.

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Pharmacotherapy optimization in neurocritical care patients exhibiting augmented renal clearance
 

Stroke, severe brain injury, status epilepticus and bacterial meningitis are the most common life-threatening neurological illnesses in the world with an estimated combined annual hospital management cost of up to 44 billion dollars. Seizures and infections are common complications following acute neurological illnesses and contribute significantly to poor outcomes if not promptly treated with appropriately dosed anti-seizure medications and antimicrobials, respectively. Many of the commonly administered medications used to treat such complications are renally eliminated and the patient’s kidney function should be taken into consideration to allow appropriate dosing. Therefore, clinicians are vigilant in adjusting drug dosage regimens in patients with various degrees of kidney impairment to avoid potential toxicities. On the other hand, little attention is given if patients exhibit an augmented renal clearance (ARC) or, in other words, enhanced kidney function. ARC has a significant influence on how medications are removed from the body potentially resulting in insufficient doses and treatment failure subsequently leading to poor patient outcomes and increased health care cost. Therefore, patients with ARC require higher medication doses; however, ARC is largely undetected using kidney assessment methods currently used in practice. In addition, it is not clear how medications should be dosed in those with ARC. The majority of ARC research has not focused on neurocritical care patients where ARC predominantly exists. Thus, clinicians are likely under-dosing vital medications in those patients, and completely unaware. There is an immediate need to address the gap in knowledge. Therefore, our research aims to characterize the phenomenon of ARC in patients with life-threatening neurological illnesses through identifying the prevalence, risk factors and clinical impact of ARC and to guide improved dosing strategies of commonly used drugs in the ICU. 

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Optimization of epilepsy and status epilepticus management in patients with comorbid conditions

Epilepsy affects more than 50 million people worldwide and is characterized by recurrent unprovoked seizures. One of the main goals of treatment is to improve patient quality of life by optimizing the balance between seizure control and side effects of the antiseizure medications (ASMs). Although the majority of patients can be adequately controlled with ASMs, a significant number, estimated to be as high as 30 % stay uncontrolled with conventional medical treatment. This can be further complicated if a patient has other comorbidities contributing to poor control.  The aim of this research is pharmacotherapy optimization of ASMs in epilepsy patients with superimposing comorbidities.

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Status epilepticus (SE) is the second most common life-threatening neurological illness in the world. It is defined by the International League Against Epilepsy (ILAE) as “a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.” Due to the significant amount of morbidity and mortality associated with SE, determination of the most effective therapies, particularly in refractory forms of SE, is essential. The aim of this research is pharmacotherapy optimization of existing therapies and translation of new therapeutics in SE for the sake improving patient outcomes.

 

Optimization of Herpes Encephalitis management

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Herpes encephalitis is a life-threatening viral infection of the brain caused primarily by herpes simplex viruses (types 1 and 2) and, less commonly, the varicella-zoster virus. Early administration of acyclovir significantly reduces morbidity and mortality. Without optimal treatment, the mortality rate is approximately 70%, but this can be reduced to around 20% with prompt initiation of acyclovir. The primary aim of this research is to optimize pharmacotherapy and facilitate the translation of new treatments for herpes encephalitis.