Methamidophos poisoning: A paediatric case report.

Methamidophos is a highly hazardous organophosphate and is known to cause an acute cholinergic toxidrome. Methamidophos use is not allowed in South Africa and therefore local data pertaining to methamidophos poisoning is very limited, with no paediatric clinical cases described. Methamidophos is an active metabolite of acephate, a commonly used organophosphate, registered for agricultural use in South Africa. We present a paediatric case of methamidophos poisoning with prolonged clinical effects. The patient experienced a prolonged cholinergic toxidrome lasting 10 days, with a period of near-full recovery during this time. We discuss the biological plausibility of the detected methamidophos being a byproduct of acephate. In addition, we highlight the importance of closer monitoring of patients with organophosphate poisoning in areas where acephate is commonly used.

Aspergillus fumigatus: a rare cause of peritonitis in a peritoneal dialysis patient (a case report).

Although fungal organisms remain an uncommon cause of peritonitis in patients undergoing peritoneal dialysis, it carries significant morbidity and mortality. We describe a 36-year-old woman who presented with peritoneal dialysis-related peritonitis caused by dual infection with Staphylococcus caprae and Aspergillus fumigatus and discuss the challenges that were confronted regarding microbiological diagnosis and the selection of optimal antifungal treatment with subsequent successful resumption of peritoneal dialysis.

Pharmacogenetics of the Late-Onset Efavirenz Neurotoxicity Syndrome (LENS).

BACKGROUND: The late-onset efavirenz neurotoxicity syndrome (LENS) presents as ataxia and/or encephalopathy with supratherapeutic efavirenz plasma concentrations (>4 µg/mL). Efavirenz is primarily metabolized by cytochrome P450 2B6 (CYP2B6), with CYP2A6 as an accessory pathway. We hypothesized that participants with LENS would predominantly be CYP2B6 slow metabolizers. The aim of our study was to determine the frequency of CYP2B6 slow metabolizers in participants with LENS. METHODS: Adult HIV-positive participants on efavirenz-based antiretroviral therapy presenting with LENS were prospectively enrolled. Genetic polymorphisms known to be associated with increased efavirenz plasma concentrations in CYP2B6 (rs3745274, rs28399499, rs4803419) and CYP2A6 (rs28399433) were selected and used to determine proportions of slow metabolizers. Pharmacokinetic analyses were performed using liquid chromatography-tandem mass spectrometry. Median (IQR) plasma efavirenz and 8-hydroxyefavirenz were described. RESULTS: Fifteen participants were enrolled. Thirteen (13/15) were Black-African and 13 were female. Median weight was 49.9kg with a median duration on efavirenz of 2.2 years. All 15 participants were successfully genotyped as slow CYP2B6 metabolizers, with 6 participants additionally having CYP2A6 heterozygous genotype. Thirteen were receiving the CYP2A6 enzyme inhibitor isoniazid, and all 15 were genotypic NAT2 slow or intermediate acetylators. Efavirenz plasma concentration was markedly increased at 50.5 (47.0-65.4) µg/mL; 8-hydroxyefavirenz concentration was markedly decreased at 0.10 (0.07-0.15) µg/mL. CONCLUSIONS: Our cohort provides definitive evidence that LENS is associated with the CYP2B6 slow metabolizer genotype, with a median efavirenz plasma concentration >12-fold higher than the defined upper limit of the therapeutic range. Isoniazid and low body weight are important contributors to LENS development.

An Approach to the Pharmacotherapy of Neuroleptic Malignant Syndrome.

Neuroleptic malignant syndrome is a rare, idiosyncratic emergency associated with exposure to dopamine antagonists, commonly antipsychotic drugs. The typical clinical picture consists of altered consciousness, muscular rigidity, fever, and autonomic instability. While the condition has generally been well described, the pathophysiology is still poorly understood. The importance of this case report is to highlight the lack of robust evidence-based treatment for this emergency. We submit an approach to the pharmacotherapy of neuroleptic malignant syndrome based on the available evidence.

Screening for Adult ADHD in Patients with Fibromyalgia Syndrome.

Objective: Fibromyalgia syndrome (FMS) is a common chronic pain disorder associated with altered activity of neurotransmitters involved in pain sensitivity such as dopamine, serotonin, and noradrenaline. FMS may significantly impact an individual's functioning due to the presence of chronic pain, fatigue, and cognitive impairment. Dyscognition may be more disabling than the chronic pain but is mostly under-recognized. This study aimed to assess the potential co-occurrence of FMS and adult attention deficit hyperactivity disorder (ADHD), a chronic neurodevelopmental disorder also associated with impaired cognition and dopaminergic function. Methods: In a cross-sectional observational study, 123 previously confirmed FMS patients were screened for adult ADHD using the World Health Organization Adult ADHD Self Report scale v1.1. The Revised Fibromyalgia Impact Questionnaire (FIQ-R) was used to assess the impact of FMS. Cognitive assessment was based on self-report in accordance with the 2011 modified American College of Rheumatology criteria and the FIQ-R, respectively. Results: Of the 123 participants, 44.72% (N = 55) screened positive for adult ADHD. Participants with both FMS and a positive adult ADHD screening test scored higher on the FIQ-R score (64.74, SD = 17.66, vs 54.10, SD = 17.10). Self-reported cognitive impairment was rated higher in the combined group (odds ratio = 10.61, 95% confidence interval; 3.77-29.86, P < 0.01). Conclusions: These results indicate that the co-occurrence of adult ADHD in FMS may be highly prevalent and may also significantly impact the morbidity of FMS. Patients with FMS should be assessed for the presence of adult ADHD.