Clinical features of seven patients poisoned with a tolfenpyrad-based insecticide in Thailand.

INTRODUCTION: Tolfenpyrad, a novel insecticide originating from Japan and first approved in 2002, has been marketed in numerous countries. Data on tolfenpyrad exposure in humans are limited. This study aimed to characterize the clinical features and outcomes of acute poisoning from tolfenpyrad-based insecticides in Thailand. METHODS: This retrospective study analyzed cases of tolfenpyrad exposure reported to the Ramathibodi Poison Center from 2012 to 2022. RESULTS: A total of seven patients were identified, with the majority being male (n = 5). Deliberate tolfenpyrad exposure accounted for three cases. The median age was 33 (range 1-46) years. Severe systemic effects were evident at presentation in the four patients ingesting tolfenpyrad. These included altered mental status (n = 4), mydriasis (n = 2), cardiac arrest (n = 1), hypotension (n = 4), bradycardia (n = 2), and high anion gap metabolic acidosis (n = 4). The median time from exposure to hospital presentation was 30 (range 15-60) minutes. All four patients ingesting tolfenpyrad died, whereas the three patients exposed via inhalation and dermally developed only mild clinical effects, and all were discharged following supportive care. DISCUSSION: We observed many of the clinical features reported previously, including vomiting, mydriasis, altered mental status, metabolic acidosis, and hypotension. We also noted a combination of bradycardia and hypotension while not observing respiratory depression. CONCLUSIONS: Tolfenpyrad insecticide poisoning has been reported infrequently. Rapid systemic toxicity can follow ingestion, resulting in a high mortality. Larger-scale studies are essential to identify predictors of severity and determine the optimal treatment for tolfenpyrad-poisoned patients.

Subcutaneous fast-acting insulin analogues, alone or in combination with long-acting insulin, versus intravenous regular insulin infusion in patients with diabetic ketoacidosis: protocol for an updated systematic review and meta-analysis of randomised trials.

INTRODUCTION: Diabetic ketoacidosis (DKA) is traditionally managed using intravenous regular insulin infusion (RII) in intensive care unit (ICU)/high dependency unit (HDU). Subcutaneous fast-acting insulin analogues (FAIAs) may help to manage DKA outside ICU/HDU. Furthermore, combining subcutaneous long-acting insulin (LAI) with subcutaneous FAIAs may accelerate ketoacidosis resolution. The latest (2016) Cochrane review was inconclusive regarding subcutaneous FAIAs versus intravenous RII in DKA. It was limited by small sample sizes, unclear risk of bias (RoB) in primary trials and did not examine subcutaneous FAIAs with subcutaneous LAI versus intravenous RII in DKA. We report the protocol for an updated meta-analysis on the safety and benefits of subcutaneous FAIAs with/without subcutaneous LAI versus intravenous RII in DKA. METHODS AND ANALYSIS: We will search Medline, Embase, CINAHL and Cochrane Library, from inception until December 2022, without language restrictions, for randomised trials on subcutaneous FAIAs with/without subcutaneous LAI versus intravenous RII in DKA. We also search ClinicalTrials.gov, ClinicalTrialsRegister.eu and reference lists of included trials. Primary outcomes include all-cause in-hospital mortality, time to DKA resolution, in-hospital DKA recurrence and hospital readmission for DKA post-discharge. Secondary outcomes include resource utilisation and patient satisfaction. Safety outcomes include important complications of DKA and insulin. Reviewers will extract data, assess overall RoB and quality of evidence using Grading of Recommendations, Assessment, Development and Evaluation. We will assess statistical heterogeneity by visually inspecting forest plots and the I2 statistic. We will synthesise data using the random-effects model. Predefined subgroup analyses are: mild versus moderate versus severe DKA; age <20 vs ≥20 years; pregnant versus non-pregnant; infective versus non-infective DKA precipitating cause; subcutaneous FAIAs alone versus subcutaneous FAIAs and subcutaneous LAI; and high versus low overall RoB. We will also perform trial sequential analysis for primary outcomes. ETHICS AND DISSEMINATION: Ethics board approval is not required. Results will be disseminated through publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022369518.

Benefits and safety of transdermal glyceryl trinitrate in acute stroke: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Transdermal glyceryl trinitrate (GTN) has potential beneficial properties in acute stroke including intracerebral hemorrhage (ICH) and possible clinical benefits suggested in ultra-early stroke (≤6 h). Our meta-analysis updated the evidence on its safety and benefits in acute stroke. METHODS: We searched major electronic databases for randomized trials comparing transdermal GTN versus placebo/control in acute stroke. Primary outcomes were mortality, 90-day modified Rankin Scale (mRS), and blood pressure (BP) effects. Secondary outcomes included early, late, resource utilization, and surrogate outcomes. Safety outcomes were adverse events. Reviewers identified studies, extracted data, and assessed risk of bias (RoB) using a modified Cochrane RoB instrument and quality of evidence (QoE) using GRADE. We also performed a priori subgroup and trial sequential analyses (TSA) on primary outcomes. These subgroup analyses were ICH versus ischemic stroke, minor (NIHSS ≤5) versus major (NIHSS >5) ischemic stroke, ischemic stroke with versus without thrombolysis, prehospital versus non prehospital settings, time from stroke to randomization ≤6 h versus >6 h, and high versus low overall RoB studies. RESULTS: Seven eligible primary trials enrolled 5363 patients. GTN reduced BP (mean difference [MD] = -4.74 mm Hg, 95% confidence interval [CI] = -6.03 to -3.45 mm Hg] and diastolic BP (MD = -2.94 mm Hg, 95% CI = -3.74 to -2.13 mm Hg) 24 h posttreatment but did not affect 4- to 10-day mortality (relative risk [RR] = 1.11, 95% CI = 0.82 to 1.49), 90-day mortality (RR = 0.96, 95% CI = 0.77 to 1.19), and 90-day mRS >2 (RR = 0.98, 95% CI = 0.93 to 1.03) compared to control/placebo. The QoE was high for primary outcomes with no subgroup effects detected. GTN did not affect secondary outcomes and increased risk of headache and hypotension. TSA generally supported our conclusions regarding primary outcomes. CONCLUSIONS: Transdermal GTN reduces BP in acute stroke but does not alter clinical outcomes even in ultra-early stroke (≤6 h).