Inorganic Arsenic Poisoning Following An Intentional Overdose Of Realgar-Containing Niu Huang Jie Du Pian: A Case report and Literature Review

Background: Niu Huang Jie Du Pian (NHJDP) is a widely used realgar-containing Chinese medicine remedy. Most brands are composed of eight ingredients: Niuhuang (Calculus Bovis), Xionghuang (realgar), gypsum (calcium sulphate), Dahuang (Radix et Rhizoma Rhei), Huangqin (Radix Scutellariae), Jugeng (Platycodon grandiflorum), Bingpian (borneol), and Gancao (Radix Glycyrrhizae uralensis, licorice root). Most users are not aware that Xionghuang (realgar) contains arsenic disulphide [As2S2]. Inorganic arsenic poisoning after therapeutic overdoses has been reported in Chinese literature, but no report of acute, intentional overdose of NHJDP has been published. We report a case of intentional overdose of NHJDP leading to arsenic poisoning. Case Presentation: A 33-year-old woman ingested approximately 100 tablets of NHJDP bought over the counter, along with her usual antidepressants. She presented with somnolence, agitation, epigastric pain and repeated vomiting, compatible with clinical toxicities of NHJDP reported in Chinese literature. At presentation, blood and spot urine arsenic levels were 440.9 and 7,495 nmol/L, respectively. The patient’s condition improved rapidly after admission and chelation therapy was not deemed to be necessary. Discussion: Despite the self-limiting clinical course, the high arsenic level in the patient’s blood and urine raises safety concerns regarding the use of NHJDP in the community. Inconsistencies in the sales regulation of arsenic-containing products, and a lack of product label warning regarding arsenic content, may potentiate inadvertent arsenic poisoning.  Conclusion: Clinician should be aware of the possibility of inorganic arsenic poisoning when treating patients with overdose of Chinese medicine remedies that contain Xionghuang (realgar). Proper product labelling may help reduce inadvertent arsenic poisoning

Early sepsis care with the National Early Warning Score 2-guided Sepsis Hour-1 Bundle in the emergency department: hybrid type 1 effectiveness-implementation pilot stepped wedge randomised controlled trial (NEWS-1 TRIPS) protocol

Introduction Early sepsis treatment in the emergency department (ED) is crucial to improve patient survival. Despite international promulgation, the uptake of the Surviving Sepsis Campaign (SSC) Hour-1 Bundle (lactate measurement, blood culture, broad-spectrum antibiotics, 30 mL/kg crystalloid for hypotension/lactate ≥4 mmol/L and vasopressors for hypotension during/after fluid resuscitation within 1 hour of sepsis recognition) is low across healthcare settings. Delays in sepsis recognition and a lack of high-quality evidence hinder its implementation. We propose a novel sepsis care model (National Early Warning Score, NEWS-1 care), in which the SSC Hour-1 Bundle is triggered objectively by a high NEWS-2 (≥5). This study aims to determine the feasibility of a full-scale type 1 hybrid effectiveness-implementation trial on the NEWS-1 care in multiple EDs.Methods and analysis We will conduct a pilot type 1 hybrid trial and prospectively recruit 200 patients from 4 public EDs in Hong Kong cluster randomised in a stepped wedge design over 10 months. All study sites will start with an initial period of standard care and switch in random order at 2-month intervals to the NEWS-1 care unidirectionally. The implementation evaluation will employ mixed methods guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, which includes qualitative and quantitative data from focus group interviews, staff survey and clinical record reviews. We will analyse the 14 feasibility outcomes as progression criteria to a full-scale trial, including trial acceptability to patients and staff, patient and staff recruitment rates, accuracy of sepsis screening, protocol adherence, accessibility to follow-up data, safety and preliminary clinical impacts of the NEWS1 care, using descriptive statistics.Ethics and dissemination The institutional review boards of all study sites approved this study. This study will establish the feasibility of a full-scale hybrid trial. We will disseminate the findings through peer-reviewed publications, conference presentations and educational activities.Trial registration number NCT05731349

Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria

Background!#!Antibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear. Bacteria in the lumen of the gastrointestinal tract may limit fungal colonization and invasion. Antibiotic drugs targeting bacteria are therefore seen as an important risk factor for fungal infections and induced allergies. However, antibiotic effects on gut bacterial-fungal interactions, including disruption and resilience of fungal community compositions, were not investigated in humans. We analysed stool samples collected from 14 healthy human participants over 3 months following a 6-day antibiotic administration. We integrated data from shotgun metagenomics, metatranscriptomics, metabolomics, and fungal ITS2 sequencing.!##!Results!#!While the bacterial community recovered mostly over 3 months post treatment, the fungal community was shifted from mutualism at baseline to competition. Half of the bacterial-fungal interactions present before drug intervention had disappeared 3 months later. During treatment, fungal abundances were associated with the expression of bacterial genes with functions for cell growth and repair. By extending the metagenomic species approach, we revealed bacterial strains inhibiting the opportunistic fungal pathogen Candida albicans. We demonstrated in vitro how C. albicans pathogenicity and host cell damage might be controlled naturally in the human gut by bacterial metabolites such as propionate or 5-dodecenoate.!##!Conclusions!#!We demonstrated that antibacterial drugs have long-term influence on the human gut mycobiome. While bacterial communities recovered mostly 30-days post antibacterial treatment, the fungal community was shifted from mutualism towards competition. Video abstract