Objective: To confirm the critical factors affecting seizure susceptibility in acute pentylenetetrazole (PTZ) mouse epilepsy models and evaluate the prior literature for these factors. Methods: Serial cohorts of wild-type mice administered intraperitoneal (IP)-PTZ were aggregated and analyzed by multivariate logistic regression for the effect of sex, age, background strain, dose, and physiologic stress (i.e., EEG implantation and/or single-housing) on seizure response. We assessed the reporting of these factors in a comprehensive literature review over the last 10 years (2010-2020). Results: We conducted aggregated analysis of pooled data of 307 mice (220 C57BL/6J mice and 87 mixed background mice; 202 males, 105 females) with median age of 10 weeks (range: 6-49 weeks) with acute PTZ injection (dose range 40-65 mg/kg). Significance in multivariate analysis was found between seizures and increased PTZ dose (odds ratio (OR) 1.149, 95% confidence interval (CI) 1.102-1.205), older age (OR 1.1, 95% CI 1.041-1.170), physiologic stress (OR 17.36,, and mixed background strain (OR 0.4725, 95% CI 0.2315-0.9345). Literature review identified 97 papers using acute PTZ-seizure models. Age, housing, sex, and background were omitted by 61% (59/97), 51% (49/97), 18% (17/97), and 8% (8/ 97) papers, respectively. Only 17% of publications specified all four factors (16/ 97). Interpretation: Our analysis and literature review demonstrate a critical gap in standardization of acute PTZ-induced seizure paradigm in mice. We recommend that future studies specify and control for age, background strain, sex, and housing conditions of experimental animals.
Introduction: In this article, we describe a pilot telehealth project for identifying women at risk of developing serious complications early and for instituting timely, appropriate, and up-to-date management even in situations with limited resources and skilled obstetric services. Maternal mortality remains unacceptably high, with less than two-thirds of the signatories to the 2015 Millennium Development Goals achieving the outlined 75% reduction in maternal mortality ratio (MMR) from 1990 to 2015. Looking forward to 2030, the Sustainable Development Goals (SDGs) lay out a target of reducing the MMR in every country to below 70 per 100,000 live births. This will require progress in low-and-middle-income countries at a rate much greater than that seen over the past 15 years. Given that 94% of the global maternal deaths occur in low- and-middle-income countries, a solution to meet the unique challenges of these countries will be necessary to achieve the SDG. The Women’s Obstetrical Neonatal Death and Reduction (WONDER) telehealth system described here offers a potential telehealth solution to reduce mortality and morbidity rates in resource-limited environments by early identification of risk indicators and initiation of care. Materials and methods: The WONDER system consists of a cloud-based electronic health record with a Clinical Decision Support tool and a color-coded alert system. The Clinical Decision Support tool is based upon Maternal Early Warning Signs and provides real-time assistance to caregivers via relevant national treatment guidelines. This system uses inexpensive computing hardware, displays, and cell-phone technology. This system was tested in a 2-year pilot study in India. A total of 15,184 patients were monitored during labor and the postpartum period. Results: Within limitations of the study, the incidence of in-hospital eclampsia was reduced by 91.7%, and in 95% of cases, timely treatment was started within an hour of identifying the abnormality in vital signs. Maternal mortality was reduced by 50.1% over local benchmark figures. Conclusions: The WONDER system identified at-risk patients, directed skilled care to those patients at risk for complications, and helped to institute effective, timely treatment, demonstrating a potential solution for women in resource-limited locations.
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