Organizational Characteristics of High- and Low-Clozapine-Utilization Clinics in the Veterans Health Administration

Objective: Treatment-resistance schizophrenia occurs in 20-30% of patients. Clozapine is the only medication proven effective for treatment-resistant schizophrenia. However, less than 25% of treatment-resistant schizophrenia patients receive clozapine in most settings. Therefore, this study was conducted to identify facilitators and barriers to clozapine use, to inform development of interventions to maximize appropriate clozapine-utilization. Methods: Seventy semi-structured phone interviews were conducted with five high- and five low-utilization VA Medical Centers, from different US regions including urban and rural areas. Interviewees were key informants of clozapine processes, including mental health leadership, psychiatrists, clinical pharmacists and advanced practice nurses. Interviews were analyzed using an emergent thematic strategy to identify barriers and facilitators to clozapine prescribing. Results: Key elements associated with high-utilization included integration of non-physician psychiatric providers and clear organizational processes and infrastructure for treatment of severe mental illness (e.g. clozapine clinics, larger mental health intensive case management services). Low-utilization was associated with lack of champions to support clozapine processes and limited-capacity care systems. Obstacles identified at both high- and low-utilization sites included complex time-consuming paperwork, reliance on few individuals to facilitate processes, and issues related to transportation for patients living far from care facilities. Conclusions: Implementation efforts to organize, streamline and simplify clozapine processes, development of a multidisciplinary clozapine clinic, increasing the size and capacity of existing clinics, and provision of transportation are reasonable targets to increase clozapine utilization

Effects of maternal modafinil treatment on fetal development and neonatal growth parameters - a multicenter case series of the European Network of Teratology Information Services (ENTIS).

In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, although study results were conflicting. Our investigation aims to examine previously reported safety signals. Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events. One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%-84.8%), 9.3% (95% CI, 5.0%-16.9%), and 13.9% (95% CI, 8.1%-23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%-6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of -0.28 SDS (95% CI, -0.45 to -0.10) for BW and of -0.28 SDS (95% CI, -0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes. The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy

Investigation of the roles of non-neuronal acetylcholine in chronic myeloid leukemic cells and their erythroid or megakaryocytic differentiated lines

Background: Many studies suggested that Acetylcholine (ACh) might serve as an autocrine/paraerine growth factor in several types of tumors or tumor cell lines. High levels of Acetylcholinesterase (AChE) activity have been reported in primary brain tumors, ovarian, colon and lung tumors. Objectives: The role of cholinergic signaling needs to be clarified in in leukemia. Method: K562 cells were derived from a chronic myelogenous leukemia patient during blast crisis serving as pluripotent hematopoietic stein cells. K562 cells were incubated with various cholinergic agonists or antagonists to investigate the role of ACh in different differentiated cell lines. Results: Our experiments showed that AChE activity was increased in response to ACh in undifferentiated K562 cells, but in the erythroid differentiated K562 cells a high concentration of ACh (1 mM) decreased the AChE activity. ACh failed to elevate the AChE activity in the megakaryocytic differentiated K562 cells. An AChE inhibitor, eserine, also suppressed the AChE activity in a concentration-dependent manner. Choline uptake inhibition by hemicholinium did increase the AChE activity but not in the erythroid differentiated K562 DOS cell line. Likewise, megakaryocytic differentiated K562 cells also displayed a similar pattern. Vesamicole, a vesicular choline uptake inhibitor, produced similar results. Curare, a nicotinic antagonist, elevated the cell counts of the megakaryocytic differentiated cells. Conclusion: Our findings may suggest excess extracellular ACh will decrease the cell growth in undifferentiated and megakaryocytic differentiated K562 cell lines through nicotinic type cholinoceptors