2-methyl-4-chlorophenoxyacetic acid and bromoxynil herbicide death.

CASE REPORT: We report a fatal case of a 37 year old gentleman who ingested a MCPA/bromoxynil co-formulation herbicide. Although clinically well on initial examination, our patient declined dramatically over his 18 h admission with increasing CO2 production, hyperthermia and metabolic derangement to eventually die from cardiac asystole 20 h post ingestion. Two hours after ingestion the MCPA concentration was 83.9 μg/mL and bromoxynil concentration was 137 μg/mL. DISCUSSION: The patients' mechanism of death appeared to be uncoupling of oxidative phosphorylation, excess CO2 production and hyperthermia. There is limited knowledge on the acute toxicity of these herbicides, in particular bromoxynil, and this case highlights the relentless progression of severe toxicity in humans.The collaboration was supported by an NHMRC Program Grant (1055176). Geoff Isbister is supported by an NHMRC Senior Research Fellowship ID 1061041 and Mike Roberts is supported by an NHMRC Senior Principal Research Fellowship ID 1002611

Parameters for the mathematical modelling of Clostridium difficile acquisition and transmission: a systematic review

INTRODUCTION: Mathematical modelling of Clostridium difficile infection dynamics could contribute to the optimisation of strategies for its prevention and control. The objective of this systematic review was to summarise the available literature specifically identifying the quantitative parameters required for a compartmental mathematical model of Clostridium difficile transmission. METHODS: Six electronic healthcare databases were searched and all screening, data extraction and study quality assessments were undertaken in duplicate. Results were synthesised using a narrative approach. RESULTS: Fifty-four studies met the inclusion criteria. Reproduction numbers for hospital based epidemics were described in two studies with a range from 0.55 to 7. Two studies provided consistent data on incubation periods. For 62% of cases, symptoms occurred in less than 4 weeks (3-28 days) after infection. Evidence on contact patterns was identified in four studies but with limited data reported for populating a mathematical model. Two studies, including one without clinically apparent donor-recipient pairs, provided information on serial intervals for household or ward contacts, showing transmission intervals of <1 week in ward based contacts compared to up to 2 months for household contacts. Eight studies reported recovery rates of between 75%-100% for patients who had been treated with either metronidazole or vancomycin. Forty-nine studies gave recurrence rates of between 3% and 49% but were limited by varying definitions of recurrence. No study was found which specifically reported force of infection or net reproduction numbers. CONCLUSIONS: There is currently scant literature overtly citing estimates of the parameters required to inform the quantitative modelling of Clostridium difficile transmission. Further high quality studies to investigate transmission parameters are required, including through review of published epidemiological studies where these quantitative estimates may not have been explicitly estimated, but that nonetheless contain the relevant data to allow their calculation

Mirtazapine overdose is unlikely to cause major toxicity

Objective: There is limited information on mirtazapine overdose, but cases of severe effects (seizures, serotonin toxicity and coma) have been reported. We aimed to investigate the clinical effects and complications of mirtazapine overdose. Methods: This was an observational case series of mirtazapine overdoses (> 120 mg) identified from admissions to a toxicology unit between January 1987 and August 2013. Demographic information, details of ingestion, clinical effects, ECG parameters (HR, QT and QRS), and length of stay were extracted from a clinical database. Results: From 267 mirtazapine overdoses, there were 89 single-agent mirtazapine ingestions and 178 cases where mirtazapine was taken with at least one other drug. The median age of the 89 single-agent mirtazapine ingestions was 36 years [interquartile range (IQR): 26 – 49 years; Range: 15 – 81 years]; 45 were female (51%). The median ingested dose was 420 mg (IQR: 270 – 750 mg; Range: 150 – 1350 mg) and 41 patients (46%) had a Glasgow coma score (GCS) < 15, but the minimum GCS was 10. There were no seizures, serotonin toxicity or delirium. Tachycardia occurred in 29 patients (33%) and hypertension in 32 patients (36%). The median QRS was 80 ms (Range: 80 – 120 ms) and there were no cases with QT prolongation. There were no arrhythmias and no deaths. The median length of stay was 14 h (IQR: 8.8 – 18.2 h; Range:2.2 – 75 h). No single-agent mirtazapine patient was admitted to intensive care. The 178 patients taking co-ingestants had more severe toxicity depending on the co-ingested drug. Conclusion: Mirtazapine appears to be relatively benign in overdose, associated with tachycardia, mild hypertension and mild CNS depression not requiring intervention

Ein fädiger DNS-Phage und ein sphärischer RNS-Phage III Biologisches Verhalten

fd and fr adsorb to male strains of E. coli and infect female cells, after the fd-DNA (or the fr-RNA 15) have been deproteinized by phenol and after the cells have been converted to the form of spheroplasts. fd is very heat resistant, highly antigenic and poorly adsorbing. The latency period of intracellular multiplication is 10 min (in Tryptone broth at 37 °C). The most unusual property seems to be that fd is the only phage on record which is liberated by the host cell without destruction of the host cell. The evidence for this is threefold: 1. in infected cultures phage is liberated at the rate of about 300 phage particles per bacterium per cell generation, and the growth rate of these cultures is indistinguishable from that of controls. 2. In such cultures no significant amounts of bacterial enzyme are liberated. 3. In single burst experiments it appears that more than 60% of the individual cells have liberated around 450 phage particles after about 20 min. and later produce bacterial growth as shown by turbidity. Non-lytic infection gives rise to an unstable carrier state. The phage is lost from the cells if superinfection is prevented by the addition of fd-antiserum. Lytic mutants of fd have been recorded. fr in its properties is similar to f2 and the other RNA phages and seems to be liberated by bacteriolysis, fr, due to the chemical nature of its nucleobases, is highly sensitive to hydroxylamine in slightly alkaline solution. Infection with fr in rare cases is non-lytic and leads to an unstable carrier state

Purification of escherichia coli DNA helicase I from plasmid-transformed cells

DNA helicase I was purified in large quantity from Escherichia coli cells harboring a plasmid that carries the gene encoding helicase I--the traI gene of the F sex factor--cloned in a high copy number vector. Electron microscopic studies on the purified material reveal new properties of the enzyme protein

Cost-effectiveness of romosozumab for the treatment of postmenopausal women with severe osteoporosis at high risk of fracture in Sweden

Summary: Romosozumab is a novel bone-building drug that reduces fracture risk. This health economic analysis indicates that sequential romosozumab-to-alendronate can be a cost-effective treatment option for postmenopausal women with severe osteoporosis at high risk of fracture. Purpose: To estimate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate (“romosozumab-to-alendronate”) compared with alendronate alone in patients with severe osteoporosis at high risk of fracture in Sweden. Methods: A microsimulation model with a Markov structure was used to simulate fractures, costs, and quality-adjusted life years (QALYs), for women treated with romosozumab-to-alendronate or alendronate alone. Patients aged 74 years with a recent major osteoporotic fracture (MOF) were followed from the start of treatment until the age of 100 years or death. Treatment with romosozumab for 12 months was followed by alendronate for up to 48 months or alendronate alone with a maximum treatment duration of 60 months. The analysis had a societal perspective. Efficacy of romosozumab and alendronate were derived from phase III randomized controlled trials. Resource use and unit costs were collected from the literature. Cost-effectiveness was estimated using incremental cost-effectiveness ratio (ICER) with QALYs as effectiveness measures. Results: The base case analysis showed that sequential romosozumab-to-alendronate treatment was associated with 0.089 additional QALYs at an additional cost of €3002 compared to alendronate alone, resulting in an ICER of €33,732. At a Swedish reference willingness-to-pay per QALY of €60,000, romosozumab-to-alendronate had a 97.9% probability of being cost-effective against alendronate alone. The results were most sensitive to time horizon, persistence assumptions, patient age, and treatment efficacy. Conclusion: The results of this study indicate that sequential romosozumab-to-alendronate can be a cost-effective treatment option for postmenopausal women with severe osteoporosis at high risk of fracture