Knox, Molly

Background: Stroke is a leading cause of disability worldwide. Selective serotonin reuptake inhibitors are often prescribed following stroke due to high rates of depression. Interest in selective serotonin reuptake inhibitor use for poststroke motor and functional recovery was generated after the publication of the Fluoxetine for motor recovery after acute ischemic stroke (FLAME) trial in 2011, which showed improved motor recovery in ischemic stroke patients with moderate to severe motor deficits. The objective of this study was to critically assess current evidence regarding the use of fluoxetine compared with placebo for poststroke functional recovery. Methods: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario and question, literature search, critical appraisal, results, evidence summary, commentary, and clinical bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, clinical epidemiologists, and content experts in the field of cerebrovascular neurology and physical medicine and rehabilitation. Results: A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared the functional outcomes of subjects poststroke receiving fluoxetine versus placebo. There was no significant difference in functional outcome measured by the Modified Rankin Scale between the 2 groups. Prespecified secondary analysis showed significantly decreased rates of depression in the fluoxetine group, but significantly increased rates of bone fracture. Conclusion: Among patients with stroke, early initiation of fluoxetine did not result in improved functional recovery. Lower rates of depression were observed in the fluoxetine-treated group; however these patients experienced higher rates of bone fracture.

Alternating electrical fields can disrupt mitosis leading to apoptosis of rapidly dividing cancer cells. The device that utilizes this mechanism is known as tumor-treating fields (TTFields). TTFields can be applied by ceramic transducer arrays on a shaved scalp to deliver the alternating electric activity to patients with glioblastoma (GBM). It has FDA approval for use in both recurrent and newly diagnosed GBM. The objective is to critically appraise the current evidence for the use of TTFields as adjunctive treatment to newly diagnosed GBM. The objective was addressed through the development of a structured, critically appraised topic. We incorporated a clinical scenario, background information, a structured question, literature search strategy, evidence summary, clinical bottom lines, and expert discussion. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of neurooncology. A randomized controlled trial was selected for critical appraisal. Patients with newly diagnosed GBM completing standard radiation and chemotherapy with temozolomide (TMZ) were subsequently randomized to receive maintenance TMZ with TTFields, or TMZ alone. With the addition of TTFields, median progression-free survival was 6.7 months compared with 4 months without the addition of TTFields (95% confidence interval, 0.52-0.76; P<0.001) and overall survival was 20.9 months compared with 16.0 months without the addition of TTFields (95% confidence interval, 0.53-0.76; P<0.001). TTFields may increase both progression-free and overall survival in patients receiving standard chemoradiation therapy for GBM.