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Patients may be reluctant to start clozapine (CLZ) because of the frequent blood sampling needed for white blood cell monitoring, but also therapeutic drug monitoring of CLZ. Finger prick, instead of venepuncture, might lower the threshold to CLZ use. The aim of this study was to determine whether CLZ concentrations are the same in capillary and venous blood samples. Capillary blood was drawn by finger prick and collected in the Hem-Col tube. Paired capillary and venous blood samples were collected from inpatients and outpatients of a mental health institute. Patients were asked to rate pain, experience, and preference for blood sampling method. Passing-Bablok analysis of 40 paired samples showed that CLZ concentrations were statistically equal in capillary and venous samples {slope 0.96 [95% confidence interval (CI): 0.88–1.04], intercept −6.86 (95% CI: −30.75 to 24.13)}. Venepuncture was the preferred method based on the experience (P = 0.009) and preference (P = 0.043) items. In conclusion, CLZ concentrations were similar in venous and capillary blood samples. Venepuncture appeared to be preferred to finger prick for blood sampling. Our results emphasize the importance of consulting patients’ individual preference for blood sampling method.

Mast cell accumulation is a hallmark of a number of diseases, including allergic asthma and systemic mastocytosis. Immunoglobulin E–mediated crosslinking of the FcεRI receptors causes mast cell activation and contributes to disease pathogenesis. The mast cell lineage is one of the least studied among the hematopoietic cell lineages, and controversies remain about whether FcεRI expression appears during the mast cell progenitor stage or during terminal mast cell maturation. Here, we used single-cell transcriptomics analysis to reveal a temporal association between the appearance of FcεRI and the mast cell gene signature in CD34+ hematopoietic progenitors in adult peripheral blood. In agreement with these data, the FcεRI+ hematopoietic progenitors formed morphologically, phenotypically, and functionally mature mast cells in long-term culture assays. Single-cell transcriptomics analysis further revealed the expression patterns of prospective cytokine receptors regulating development of mast cell progenitors. Culture assays showed that interleukin-3 (IL-3) and IL-5 promoted disparate effects on progenitor cell proliferation and survival, respectively, whereas IL-33 caused robust FcεRI downregulation. Taken together, we showed that FcεRI expression appears at the progenitor stage of mast cell differentiation in peripheral blood. We also showed that external stimuli regulate FcεRI expression of mast cell progenitors, providing a possible explanation for the variable FcεRI expression levels during mast cell development.

ABSTRACTBackgroundSystematically registering ADRs in electronic health records (EHRs) likely contribute to patient safety as it enables the exchange of drug safety data. Currently, ADRs registrations by healthcare professionals (HCPs) is suboptimal. This study aimed to identify barriers and facilitators perceived by HCPs to register ADRs systematically in EHRs.Research Design and MethodsA qualitative study with individual interviews was conducted among specialist physicians and hospital pharmacists from 10 different Dutch hospitals. A semi-structured interview guide was used to identify experienced barriers and facilitators for systematically registering ADRs. Data was analyzed following thematic analysis. Themes within barriers and facilitators were aligned with the Capability–Opportunity-Motivation–Behavior (COM-B) framework.ResultsIn total, 16 HCPs were interviewed. Identified barriers were: lack of knowledge to recognize ADRs, time constraints, inadequate IT system, lack of support, stuck in routine, and not recognizing the importance of registering ADRs. Identified facilitators were: enhanced knowledge and awareness of ADRs, functional IT systems, expanding accountability for registration, and motivation toward registering.ConclusionsBarriers and facilitators for registering spanned all aspects of the COM-B model and occurred in individual, social and environmental domains. Addressing these aspects could improve the registration of ADRs and may contribute to patient safety.

Supplemental digital content is available in the text.Headache is a common side effect of electroconvulsive therapy (ECT), but reports on its incidence vary widely. A broad array of treatment regimens have been proposed in the literature. The pathophysiology of post-ECT headache is unclear but a vascular origin has been suggested. A systematic literature search was executed in PubMed and Embase to identify relevant articles. Articles were screened on title, abstract, and full text according to predefined inclusion and exclusion criteria. Study characteristics and results concerning the incidence of post-ECT headache were extracted, and a weighted mean incidence was calculated. Forty-seven relevant articles were found, of which 36 reported on the incidence of post-ECT headache in patients and 9 on the incidence in sessions. The incidence of post-ECT headache varied greatly in the literature. The weighted mean incidence in patients was 32.8%, as 786 of a total population of 2399 patients experienced headache. The weighted mean incidence in sessions was between 9.4% (246 of 2604 sessions) and 12.1% (236/1958 sessions). The variation in incidences of post-ECT headache found might be due to different methods of measuring headache, different study designs, and different drugs used for anesthesia. The mean-weighted incidence of post-ECT headache in patients was 32.8% and in sessions between 9.4% and 12.1%.

Hematopoietic stem cells differentiate into all types of blood cells, including peripheral tissue-resident mast cells. The early mast cell differentiation takes place in the bone marrow, after which the progenitor cells enter the circulation and mature once reaching their target organ. Early results from single-cell culture experiments and colony-forming assays have produced the classic hierarchical tree model of hematopoiesis. The introduction of high-throughput, single-cell RNA sequencing is now revolutionizing our understanding of the differentiation process, questioning the classic tree-based models. By integrating the results from early cell culture experiments with single-cell transcriptomics, we present a differentiation landscape model of hematopoiesis and discuss it with focus on mast cells. The review also describes how the hematologic neoplasm systemic mastocytosis can be used to model human hematopoiesis using naturally occurring cell barcoding by means of the common KITD816V mutation.

Human hematopoietic progenitors are generally assumed to require stem cell factor (SCF) and KIT signaling during differentiation for the formation of mast cells. Imatinib treatment, which inhibits KIT signaling, depletes mast cells in vivo. Furthermore, the absence of SCF or imatinib treatment prevents progenitors from developing into mast cells in vitro. However, these observations do not mean that mast cell progenitors require SCF and KIT signaling throughout differentiation. Here, we demonstrate that circulating mast cell progenitors are present in patients undergoing imatinib treatment. In addition, we show that mast cell progenitors from peripheral blood survive, mature, and proliferate without SCF and KIT signaling in vitro. Contrary to the prevailing consensus, our results show that SCF and KIT signaling are dispensable for early mast cell development.

Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women. We report the design of a study that aims to replicate earlier findings concerning the efficacy of raloxifene augmentation in reducing persisting symptoms and cognitive impairment in postmenopausal women, and to extend these findings to a male and peri/premenopausal population of patients with schizophrenia. The study is a multisite, placebo-controlled, double-blind, randomised clinical trial in approximately 110 adult men and women with schizophrenia. Participants are randomised 1:1 to adjunctive raloxifene 120 mg or placebo daily during 12 weeks. The treatment phase includes measurements at three time points (week 0, 6 and 12), followed by a follow-up period of two years. The primary outcome measure is change in symptom severity, as measured with the Positive and Negative Syndrome Scale (PANSS), and cognition, as measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Secondary outcome measures include social functioning and quality of life. Genetic, hormonal and inflammatory biomarkers are measured to assess potential associations with treatment effects. If it becomes apparent that raloxifene reduces psychotic symptoms and/or improves cognition, social functioning and/or quality of life as compared to placebo, implementation of raloxifene in clinical psychiatric practice can be considered.

No relevant conflicts of interest to declare.