Drug Repositioning of Pioglitazone in Management and Improving the Cognitive Function among the Patients With Mild to Moderate Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Background: Disease-modifying agents like Pioglitazone have shown promising effects on neuroinflammation and homeostasis of amyloid plaques, but there is a lack of research papers providing conclusive evidence. Objectives: This study is aimed to determine the safety and efficacy of Pioglitazone in improving cognitive function in patients with mild-moderate Alzheimer's disease (AD). Materials and Methods: Trials published in the last 12 years were identified from PubMed, Scopus, Cochrane Central, and other trial registries. Five hundred twenty-five records were obtained, from which five studies were included for quantitative analysis. Studies comparing Pioglitazone with a suitable placebo or other oral hypoglycemic agent were considered for review. Data was extracted using a pretested form, which was followed by a risk of bias assessment (ROB) with Cochrane's ROB assessment tool. Results: This meta-analysis included studies where Pioglitazone (15-30 mg) was compared to other oral hypoglycemic agents, placebo, or diabetic diet for a minimum duration of 6 months. Pioglitazone did not show a statistically significant improvement in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores [mean difference (MD): -1.16; 95% confidence interval (CI): -4.14-1.81]. By conducting sensitivity analysis with the removal of one study, significant efficacy was obtained [MD: -2.75; 95% CI: -4.84--0.66]. The Wechsler Memory Scale-Revised logical memory I (WMS-R) scores had a significant improvement in the Pioglitazone group [MD: 2.02; 95% CI: 0.09-3.95]. Conclusion: Pioglitazone is a safe medication that has a promising effect in slowing the advancement of AD.

Phenytoin-Induced Paradoxical Seizures and Blood Dyscrasias in a Patient Receiving Rapid Intravenous Infusion: A Case Report.

Paradoxical seizure is an unusual reaction of seizure aggravation or change in its pattern due to antiepileptics. Decrease in seizure threshold with phenytoin is bound to occur with an increase in serum levels. We herein report a 51-year-old female, who was brought to the intensive care unit with complaints of episodic seizures and frothing. She is a known case of tonic-clonic epilepsy on oral phenytoin 100 mg for past 6 months. Rapid intravenous infusion of 700 mg phenytoin in 100 mL normal saline over a rate of 15 minutes was initiated on admission. This was followed by a sudden abnormality of her baseline blood parameters and an occurrence of paradoxical seizure. The dose of phenytoin was tapered which reversed her condition. The patient was followed up regularly and monitored for fluctuations in her hematological parameters. The mainstay treatment for phenytoin-induced paradoxical seizure and blood dyscrasias is to monitor the patient and dose titration. Dosing of phenytoin remains a challenge for all clinicians which increase the need for such reports.