Catatonia, Pregnancy, and Electroconvulsive Therapy (ECT).

Background: Catatonia is a neuropsychiatric syndrome, which typically occurs in the context of another psychiatric or medical condition, with a significant morbidity and mortality risk. Significant medical conditions resulting from catatonia include nutritional deficiencies, skin ulcerations, electrolyte disturbances, aspiration pneumonia, and venous thromboembolism. As a result, prompt treatment is required. Gold standard treatment consists of benzodiazepines, followed by electroconvulsive therapy (ECT) if pharmacotherapy alone is ineffective. With pregnancy and catatonia, there is a high risk of adverse maternal/fetal outcomes, and the risks/benefits of treatment must be carefully considered. Case: Here, we present a case of a young pregnant woman with schizoaffective disorder whose catatonic state was not successfully resolved with lorazepam, therefore requiring ECT. Patient presented to the emergency department at 20 weeks of pregnancy, displaying symptoms of catatonia and psychosis. She was admitted to the inpatient behavioral health unit, where she was treated with lorazepam for catatonia. Treatment occurred in close collaboration with the obstetrics team. While initially, the patient appeared to have a positive response to lorazepam, she became increasingly catatonic with minimal oral intake, mutism, and urinary retention. As a result, she was transferred to the medical floor, where ECT was initiated due to the ineffectiveness of lorazepam. Her catatonia was successfully resolved with 12 total treatments of ECT; there were no adverse effects to the fetus. Patient delivered her baby at 39 weeks with no complications. She continued to receive inpatient psychiatric care until she was stable for discharge to an extended acute care unit. Objectives: In this report, we will review relevant literature on catatonia in pregnancy, with focus on treatment with ECT. Conclusions: Though the literature on these topics is limited and typically presented in case reports format, there appears to be a favorable view toward the use of ECT for pregnant catatonic patients. This case could be considered a vital contribution to the literature, as it provides a successful example of treating catatonia in pregnancy with no known adverse effects to the mother or child.

Evaluation of patient/caregiver and healthcare provider knowledge, attitudes and behavior for safety and use of pexidartinib.

Aim: Pexidartinib was approved for the treatment of tenosynovial giant cell tumors with a required Risk Evaluation and Mitigation Strategy (REMS) to ensure its safe use. As required by the REMS, a survey was conducted to document the knowledge, attitudes and behavior (KAB) of patients/caregivers and healthcare providers (HCPs) regarding the risk of serious and potentially fatal liver injury due to pexidartinib, the need for liver testing prior to and during treatment and the need for patient counseling about this risk. Patients & methods: The KAB survey was conducted among 40 patients and 18 HCPs enrolled in the pexidartinib REMS. Results: Among patients, 87.5% demonstrated understanding of key risk message (KRM) 1 (risk of serious liver injury), 87.5% demonstrated understanding of KRM2 (liver testing requirement) and 77.5% demonstrated understanding of both KRMs. Among HCPs, 83.3% demonstrated understanding of KRM1, 88.9% demonstrated understanding of KRM2, 100% demonstrated understanding of KRM3 (patient counseling) and 83.3% demonstrated understanding of all three KRMs. Conclusion: The KAB surveys demonstrated that the educational goals of the pexidartinib REMS were being achieved.

Lay abstract Pexidartinib is a prescription medicine used to treat adults who have a tenosynovial giant cell tumor that is not likely to improve with surgery. Because of the risk of serious liver problems, pexidartinib is available only through a restricted program called a Risk Evaluation and Mitigation Strategy (REMS) that enrolls both patients and healthcare providers (HCPs). As part of the REMS, information is collected about their knowledge, attitudes and behavior (KAB) regarding the potential for pexidartinib to cause liver problems that may be severe and can lead to death. This KAB survey was conducted among 40 patients and 18 HCPs enrolled in the pexidartinib REMS. The results indicated that among patients, over three-quarters demonstrated understanding of the risk of serious liver injury and the need for regular liver testing. Among HCPs, 83.3­100% demonstrated understanding of the risk of serious liver injury, the need for regular liver testing and the requirement to counsel their patients about this risk. In conclusion, the KAB surveys demonstrated that the educational goals of the pexidartinib REMS were being achieved.

Cardiac levels of NOS1AP RNA from right ventricular tissue recovered during lead extraction.

BACKGROUND: There is a scarcity of cardiac tissue available for research. OBJECTIVE: (1) To investigate the feasibility of obtaining myocardial tissue from extracted pacemaker and defibrillator leads for gene expression analysis and (2) to examine the nitric oxide 1 adaptor protein (NOS1AP) RNA expression as a function of patient genotype. METHODS: Seventeen patients (age = 56 ± 20 years; 12 men; 5 pacemakers; 12 defibrillators) undergoing lead extractions for standard indications (5 device erosion; 1 vascular occlusion; 11 lead malfunction or recall) were genotyped for 2 NOS1AP single nucleotide polymorphisms-rs10494366 (T to G) and rs10918594 (C to G)-and had RNA levels measured by real-time polymerase chain reaction for collagen I, troponin I, Ca(v)1.2, Kv4.3, HERG, KvLQT1, connexin 43, NOS1AP, and sodium-calcium exchanger. Ventricular tissue obtained from 3 failing hearts at transplantation served as reference. RESULTS: A high ratio of cardiac troponin I/collagen I RNA identified 9 of the 17 patient samples (muscle rich), in which the gene expression profile was similar to that of the reference ventricular samples and significantly different (P < .003) from the expression profile of samples with a low troponin I/collagen ratio (muscle poor). TT and CC polymorphisms were associated with significantly lower NOS1AP RNA levels (P < .01 compared with the GG genotype). CONCLUSIONS: Performing gene expression analyses on right ventricular tissue samples extracted with pacemaker and defibrillator leads is feasible. A significant number of samples contain cardiomyocytes that express troponin I and ion channels at levels comparable to those seen in explanted hearts. Decreased NOS1AP expression in rs10494366 TT and rs10918594 CC homozygotes may underlie shorter repolarization times.

Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of heart failure and death. The etiology of DCM is genetically heterogeneous. OBJECTIVES: We sought to define the prevalence of mutations in the RNA splicing protein RBM20 in a large cohort with DCM and to determine whether genetic variation in RBM20 is associated with clinical outcomes. METHODS: Subjects included in the Genetic Risk Assessment of Defibrillator Events (GRADE) study were aged at least 18 years, had an ejection fraction of ≤30%, and an implantable cardioverter-defibrillator (ICD). The coding region and splice junctions of RBM20 were screened in subjects with DCM; 2 common polymorphisms in RBM20, rs942077 and rs35141404, were genotyped in all GRADE subjects. RESULTS: A total of 1465 subjects were enrolled in the GRADE study, and 283 with DCM were screened for RBM20 mutations. The mean age of subjects with DCM was 58 ± 13 years, 64% were males, and the mean follow-up time was 24.2 ± 17.1 months after ICD placement. RBM20 mutations were identified in 8 subjects with DCM (2.8%). Mutation carriers had a similar survival, transplantation rate, and frequency of ICD therapy compared with nonmutation carriers. Three of 8 subjects with RBM20 mutations (37.5%) had atrial fibrillation (AF), whereas 19 subjects without mutations (7.4%) had AF (P = .02). Among all GRADE subjects, rs35141404 was associated with AF (minor allele odds ratio = 0.62; 95% confidence interval = 0.44-0.86; P = .006). In the subset of GRADE subjects with DCM, rs35141404 was associated with AF (minor allele odds ratio = 0.58; P = .047). CONCLUSIONS: Mutations in RBM20 were observed in approximately 3% of subjects with DCM. There were no differences in survival, transplantation rate, and frequency of ICD therapy in mutation carriers.