Burning pain secondary to clozapine use: a case report.

BACKGROUND: The first of the atypical antipsychotics introduced in the 1970s, clozapine remains the most efficacious neuroleptic to this day. However, serious and potentially fatal side effects have necessitated careful regular monitoring among prescribing clinicians. Some adverse effects (e.g. ischaemic bowel) remain under recognized, while newly identified adverse effects continue to be described in the literature. CASE PRESENTATION: In this report, we describe a healthy 43-year old Caucasian male who experienced onset of a full body deep burning pain several months after the onset of treatment with clozapine. The pain worsened over time, ceased with cessation of treatment, and returned soon after the patient was rechallenged. CONCLUSION: We describe an unusual adverse effect from clozapine treatment that has not been described elsewhere to our knowledge. We present the time course of the pain symptom, relationship to dose, associated laboratory results, and ultimately how it was dealt with and how it improved for the benefit of clinicians who may encounter it in the future

Apixaban Concentrations with Lower than Recommended Dosing in Older Adults with Atrial Fibrillation

OBJECTIVES: Lower than recommended doses of direct-acting oral anticoagulants are often prescribed to older adults with nonvalvular atrial fibrillation (NVAF). Our goal was to determine the consequences of lower than recommended dosing on plasma apixaban concentrations during the clinical care of older adults with NVAF. DESIGN: Convenience sample of patients receiving anticoagulation during 2017. SETTING: Academic medical center. PARTICIPANTS: Stable adults older than 65 years with NVAF receiving apixaban on a chronic basis. MEASUREMENTS: Patient age, weight, creatinine, co-medications, and apixaban concentrations. RESULTS: A total of 110 older adults with NVAF (mean age = 80.4 y; range = 66-100 y with 45% women) were studied. Overall, 48 patients received recommended dosing of 5 mg twice/day, and 42 received lower than recommended dosing. One patient in each category had concentrations below the expected 5% to 95% range at time of peak concentrations. Differences in proportion of apixaban concentrations within or outside expected ranges were not significant between patients receiving lower than recommended doses and those dosed as recommended at 5 mg twice/day (P =.35). However, in patients dosed as recommended with 5 mg twice/day, four had concentrations above the 5% to 95% range for peak levels expected at 3 to 4 hours after dosing; in two, this occurred around the midpoint of the dosing interval. Twenty patients received 2.5 mg twice/day as recommended. One-third had apixaban concentrations higher than expected peak concentrations compared with the clinical trials, and more than two-thirds had levels above the reported median for peak concentrations. CONCLUSIONS: Apixaban concentrations in older adults with NVAF seen clinically were higher than expected based on clinical trial data. The findings raise questions about the optimal dosing of apixaban in older adults with NVAF encountered outside of clinical trials and suggest a role for the monitoring of apixaban concentrations during care of patients that differ from those in randomized trials or when considering dosing outside of published guidelines. J Am Geriatr Soc 67:1902–1906, 2019

Drug interactions and pharmacogenetic factors contribute to variation in apixaban concentration in atrial fibrillation patients in routine care

Factor Xa-inhibitor apixaban is an oral anticoagulant prescribed in atrial fibrillation (AF) for stroke prevention. Its pharmacokinetic profile is known to be affected by cytochrome P450 (CYP)3A metabolism, while it is also a substrate of the efflux transporters ATP-binding cassette (ABC)B1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein, BCRP). In this study, we assessed the impact of interacting medication and pharmacogenetic variation to better explain apixaban concentration differences among 358 Caucasian AF patients. Genotyping (ABCG2, ABCB1, CYP3A4*22, CYP3A5*3) was performed by TaqMan assays, and apixaban quantified by mass spectrometry. The typical patient was on average 77.2 years old, 85.5 kg, and had a serum creatinine of 103.1 µmol/L. Concomitant amiodarone, an antiarrhythmic agent and moderate CYP3A/ABCB1 inhibitor, the impaired-function variant ABCG2 c.421C \u3e A, and sex predicted higher apixaban concentrations when controlling for age, weight and serum creatinine (multivariate regression; R2 = 0.34). Our findings suggest that amiodarone and ABCG2 genotype contribute to interpatient apixaban variability beyond known clinical factors

Testing for (in)finite moments

This paper proposes a test to verify whether the k-th moment of a random variable is Önite. We use the fact that, under general assumptions, sample moments either converge to a Önite number or diverge to inÖnity according as the corresponding population moment is Önite or not. Building on this, we propose a test for the null that the k-th moment does not exist. Since, by construction, our test statistic diverges under the null and converges under the alternative, we propose a randomised testing procedure to discern between the two cases. We study the application of the test to raw data, and to regression residuals. Monte Carlo evidence shows that the test has the correct size and good power; the results are further illustrated through an application to Önancial data

Fluid consistencies. Material relationality in human engagements with water

Material things are not just passive recipients of human categories, meanings and values, nor mere subjects of human agency. Their particular characteristics and behaviours are formative of human–non-human relations. The common material properties of things, and the shared cognitive and phenomenological processes through which people interact with them, generate recurrent ideas and patterns of engagement in diverse cultural and historical contexts. Despite growing instrumentalism in human ‘management’ of the material world, and the emergence of new relational forms, these patterns persist

Predictors of Hepatitis Knowledge Improvement Among Methadone Maintained Clients Enrolled in a Hepatitis Intervention Program

This randomized, controlled study (n = 256) was conducted to compare three interventions designed to promote hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination completion, among clients undergoing methadone maintenance treatment (MMT) in Los Angeles and Santa Monica. The participants were randomized into three groups: Motivational Interviewing-Single Session (MI-Single), Motivational Interviewing-Group (MI-Group), or Nurse-Led Hepatitis Health Promotion (HHP). All three treatment groups received the 3-series HAV/HBV vaccine. The MI sessions were provided by trained therapists, the Nurse-Led HHP sessions were delivered by a research nurse. The main outcome variable of interest was improvement in HBV and HCV knowledge, measured by a 6-item HBV and a 7-item HCV knowledge and attitude tool that was administered at baseline and at 6-month follow-up. The study results showed that there was a significant increase in HBV- and HCV-related knowledge across all three groups (p < 0.0001). There were no significant differences found with respect to knowledge acquisition among the groups. Irrespective of treatment group, gender (P = 0.008), study site (P < 0.0001) and whether a participant was abused as a child (P = 0.017) were all found to be predictors of HCV knowledge improvement; only recruitment site (P < 0.0001) was found to be a predictor of HBV knowledge. The authors concluded that, although MI-Single, MI-Group and Nurse-Led HHP are all effective in promoting HBV and HCV knowledge acquisition among MMT clients, Nurse-Led HHP may be the method of choice for this population as it may be easier to integrate and with additional investigation may prove to be more cost efficient

Protective Effector Memory CD4 T Cells Depend on ICOS for Survival

Memory CD4 T cells play a vital role in protection against re-infection by pathogens as diverse as helminthes or influenza viruses. Inducible costimulator (ICOS) is highly expressed on memory CD4 T cells and has been shown to augment proliferation and survival of activated CD4 T cells. However, the role of ICOS costimulation on the development and maintenance of memory CD4 T cells remains controversial. Herein, we describe a significant defect in the number of effector memory (EM) phenotype cells in ICOS−/− and ICOSL−/− mice that becomes progressively more dramatic as the mice age. This decrease was not due to a defect in the homeostatic proliferation of EM phenotype CD4 T cells in ICOS−/− or ICOSL−/− mice. To determine whether ICOS regulated the development or survival of EM CD4 T cells, we utilized an adoptive transfer model. We found no defect in development of EM CD4 T cells, but long-term survival of ICOS−/− EM CD4 T cells was significantly compromised compared to wild-type cells. The defect in survival was specific to EM cells as the central memory (CM) ICOS−/− CD4 T cells persisted as well as wild type cells. To determine the physiological consequences of a specific defect in EM CD4 T cells, wild-type and ICOS−/− mice were infected with influenza virus. ICOS−/− mice developed significantly fewer influenza-specific EM CD4 T cells and were more susceptible to re-infection than wild-type mice. Collectively, our findings demonstrate a role for ICOS costimulation in the maintenance of EM but not CM CD4 T cells