Using the monocyte activation test as a stand-alone release test for medical devices.

Monocyte activation tests (MAT) are widely available but rarely used in place of animal-based pyrogen tests for safety assessment of medical devices. To address this issue, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods and the PETA International Science Consortium Ltd. convened a workshop at the National Institutes of Health on September 18-19, 2018. Participants included representatives from MAT testing laboratories, medical device manufacturers, the U.S. Food and Drug Administration's Center for Devices and Radiologic Health (CDRH), the U.S. Pharmacopeia, the International Organization for Standardization, and experts in the development of MAT protocols. Discussions covered industry experiences with the MAT, remaining challenges, and how CDRH's Medical Device Development Tools (MDDT) Program, which qualifies tools for use in evaluating medical devices to streamline device development and regulatory evaluation, could be a pathway to qualify the use of MAT in place of the rabbit pyrogen test and the limulus amebocyte lysate test for medical device testing. Workshop outcomes and follow-up activities are discussed.

Comparison of LAL and rFC Assays-Participation in a Proficiency Test Program between 2014 and 2019.

Endotoxin (lipopolysaccharide) testing of drugs is routinely required in pharmaceutical industries. Suitable compendial assays are defined by national pharmacopoeias. At this time, Limulus Amoebocyte Lysate (LAL) assays are the gold standard. LAL is used in vitro for specific detection of endotoxin based on endotoxin-activated Factor C-mediated clotting cascade. However, alternative mediated pathways (e.g., Factor G), impurities, and further factors may influence test results. Some of these influencing factors are eliminated by recombinant Factor C (rFC) test, which represents a promising alternative. rFC not only enables highly specific endotoxin testing, as interfering Horseshoe Crab blood components are eliminated, but also offers ethical and ecological advantages compared to classical LAL assays. However, the question remains whether rFC-based tests are robust test systems, equivalent or superior to LAL and suitable for routine bacterial endotoxin testing. Pharmaceutical test users have validated the test successfully for their specific products, but no long-term studies have been published that combine testing of unknown samples, inter-laboratory, -operator, and -lot changes. Thus, it was of great interest to investigate rFC test performance in a routine setting within a proficiency test program set-up. Over a period of six years comparative endotoxin testing was conducted with one kinetic chromogenic LAL assay and two rFC-based assays. Results of this study demonstrate that both rFC-based assays were comparable to LAL. All results met acceptance criteria defined by compendial bacterial endotoxin testing. RFC-based methods generated results with even better endotoxin recovery rates compared to LAL. Therefore, rFC-based tests were found to represent reliable methods, as equivalent or even superior to LAL assays and suitable for routine bacterial endotoxin testing.

Depression and mental health help-seeking behaviors in a predominantly African American population of children and adolescents with epilepsy.

PURPOSE: To determine whether previously undetected symptoms of depression and psychiatric help-seeking behaviors are associated with demographic or epilepsy-related variables in a predominantly African American sample of pediatric epilepsy patients. METHODS: Ninety-six serially recruited parent-child dyads (55% African American, 39% Caucasian) completed the Short Mood and Feelings Questionnaire (SMFQ). Regression analyses determined whether depressive symptoms measured by the SMFQ were associated with demographic (age, gender, and ethnic background) or epilepsy-related variables (age of seizure onset, duration of epilepsy, seizure type, time since last seizure, and number of antiepileptic drugs). Dyads with positive SMFQ screens (score > or = 12) received information about depression and were advised to seek mental health services. Six months later, parents completed follow-up interviews to ascertain mental health service utilization. RESULTS: Thirty-five participants (36.5%) screened positive for probable depression. Greater number of antiepileptic drugs was the only predictor variable independently associated with greater (worse) depression scores (p = 0.005). At 6-month follow-up, 12 patients (36.4%) had received mental health care, whereas 21 guardians (63.6%) denied depressive symptoms in their child and never sought mental health services (two dyads lost to follow-up). Logistic regression analyses found no associations between demographic, epilepsy-related, or depressive variables and psychiatric help-seeking. DISCUSSION: This study indicates the necessity and feasibility of screening for previously undetected symptoms of depression in pediatric epilepsy clinics serving diverse populations, particularly among patients receiving antiepileptic polytherapy. Additional research on the correlates of depressive symptoms and determinants of psychiatric help-seeking is needed to develop evidence-based interventions for youths with epilepsy and symptoms of depression.