Economic evaluation of the NET intervention versus guideline dissemination for management of mild head injury in hospital emergency departments

Background

Evidence-based guidelines for the management of mild traumatic brain injury (mTBI) in the emergency department (ED) are now widely available, and yet, clinical practice remains inconsistent with the guidelines. The Neurotrauma Evidence Translation (NET) intervention was developed to increase the uptake of guideline recommendations and improve the management of minor head injury in Australian emergency departments (EDs). However, the adoption of this type of intervention typically entails an upfront investment that may or may not be fully offset by improvements in clinical practice, health outcomes and/or reductions in health service utilisation. The present study estimates the cost and cost-effectiveness of the NET intervention, as compared to the passive dissemination of the guideline, to evaluate whether any improvements in clinical practice or health outcomes due to the NET intervention can be obtained at an acceptable cost.

Methods and findings

Study setting: The NET cluster randomised controlled trial [ACTRN12612001286831]. Study sample: Seventeen EDs were randomised to the control condition and 14 to the intervention. One thousand nine hundred forty-three patients were included in the analysis of clinical practice outcomes (NET sample). A total of 343 patients from 14 control and 10 intervention EDs participated in follow-up interviews and were included in the analysis of patient-reported health outcomes (NET-Plus sample). Outcome measures: Appropriate post-traumatic amnesia (PTA) screening in the ED (primary outcome). Secondary clinical practice outcomes: provision of written information on discharge (INFO) and safe discharge (defined as CT scan appropriately provided plus PTA plus INFO). Secondary patient-reported, post-discharge health outcomes: anxiety (Hospital Anxiety and Depression Scale), post-concussive symptoms (Rivermead), and preference-based health-related quality of life (SF6D). Methods: Trial-based economic evaluations from a health sector perspective, with time horizons set to coincide with the final follow-up for the NET sample (2 months post-intervention) and to 1-month post-discharge for the NET-Plus sample. Results: Intervention and control groups were not significantly different in health service utilisation received in the ED/inpatient ward following the initial mTBI presentation (adjusted mean difference $23.86 per patient; 95%CI ??$106, $153; p?=?0.719) or over the longer follow-up in the NET-plus sample (adjusted mean difference $341.78 per patient; 95%CI ??$58, $742; p?=?0.094). Savings from lower health service utilisation are therefore unlikely to offset the significantly higher upfront cost of the intervention (mean difference $138.20 per patient; 95%CI $135, $141; p?<?0.000). Estimates of the net effect of the intervention on total cost (intervention cost net of health service utilisation) suggest that the intervention entails significantly higher costs than the control condition (adjusted mean difference $169.89 per patient; 95%CI $43, $297, p?=?0.009). This effect is larger in absolute magnitude over the longer follow-up in the NET-plus sample (adjusted mean difference $505.06; 95%CI $96, $915; p?=?0.016), mostly due to additional health service utilisation. For the primary outcome, the NET intervention is more costly and more effective than passive dissemination; entailing an additional cost of $1246 per additional patient appropriately screened for PTA ($169.89/0.1363; Fieller’s 95%CI $525, $2055). For NET to be considered cost-effective with 95% confidence, decision-makers would need to be willing to trade one quality-adjusted life year (QALY) for 25 additional patients appropriately screened for PTA. While these results reflect our best estimate of cost-effectiveness given the data, it is possible that a NET intervention that has been scaled and streamlined ready for wider roll-out may be more or less cost-effective than the NET intervention as delivered in the trial.

Conclusions

While the NET intervention does improve the management of mTBI in the ED, it also entails a significant increase in cost and—as delivered in the trial—is unlikely to be cost-effective at currently accepted funding thresholds. There may be a scope for a scaled-up and streamlined NET intervention to achieve a better balance between costs and outcomes.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12612001286831, date registered 12 December 2012.

     

Chinook and Coho salmon hybrids linked to habitat and climatic changes on Vancouver Island,British Columbia

Between 2013 and 2019, 63 presumed Chinook salmon Oncorhynchus tshawytscha sampled primarily in the Strait of Georgia (0.63% of total sample) were identified as potential Chinook–Coho (Oncorhynchus kisutch) hybrids by the presence of anomalous microsatellite genotypes. Their hybrid origin was confirmed by single nucleotide polymorphism amplification of two species‐specific amplicons. Mitochondrial DNA indicated that most of these fish resulted from the hybridization of Coho salmon females and Chinook salmon males. Although no diagnostic external features were identified, several individuals displayed an abnormal scale arrangement on the caudal peduncle. One hybrid juvenile examined for meristics exhibited a pyloric caeca count intermediate between published values for Chinook and Coho salmon. Most hybrids originated in the Cowichan River during the 2014 brood year. Their prevalence in the watershed is a naturally occurring event, likely exacerbated by prolonged low water levels which limit habitat and delay Chinook salmon spawning, in addition to the differential abundance of the parental species. This research is the first to document ongoing natural hybridization (Chinook–Coho salmon crosses) and link it to habitat and climatic changes, and includes the identification of eight F1 adults and two juvenile backcross or F2 hybrids. The potential negative impacts of hybridization, particularly in Coho salmon through potential introgression, warrant hybrid identification as an ecosystem monitoring tool within a survey program.     

Natriuretic peptides modify <Emphasis Type="Italic">Pseudomonas fluorescens</Emphasis> cytotoxicity by regulating cyclic nucleotides and modifying LPS structure

Background  

Nervous tissues express various communication molecules including natriuretic peptides, i.e. Brain Natriuretic Peptide (BNP) and C-type Natriuretic Peptide (CNP). These molecules share structural similarities with cyclic antibacterial peptides. CNP and to a lesser extent BNP can modify the cytotoxicity of the opportunistic pathogen Pseudomonas aeruginosa. The psychrotrophic environmental species Pseudomonas fluorescens also binds to and kills neurons and glial cells, cell types that both produce natriuretic peptides. In the present study, we investigated the sensitivity of Pseudomonas fluorescens to natriuretic peptides and evaluated the distribution and variability of putative natriuretic peptide-dependent sensor systems in the Pseudomonas genus.     

Involvement of a phospholipase C in the hemolytic activity of a clinical strain of <Emphasis Type="Italic">Pseudomonas fluorescens</Emphasis>

Background  

Pseudomonas fluorescens is a ubiquitous Gram-negative bacterium frequently encountered in hospitals as a contaminant of injectable material and surfaces. This psychrotrophic bacterium, commonly described as unable to grow at temperatures above 32°C, is now considered non pathogenic. We studied a recently identified clinical strain of P. fluorescens biovar I, MFN1032, which is considered to cause human lung infection and can grow at 37°C in laboratory conditions.     

Colonisation and mass rearing: learning from others

Mosquitoes, just as other insects produced for the sterile insect technique (SIT), are subjected to several unnatural processes including laboratory colonisation and large-scale factory production. After these processes, sterile male mosquitoes must perform the natural task of locating and mating with wild females. Therefore, the colonisation and production processes must preserve characters necessary for these functions. Fortunately, in contrast to natural selection which favours a suite of characteristics that improve overall fitness, colonisation and production practices for SIT strive to maximize only the few qualities that are necessary to effectively control populations.However, there is considerable uncertainty about some of the appropriate characteristics due to the lack of data. Development of biological products for other applications suggest that it is possible to identify and modify competitiveness characteristics in order to produce competitive mass produced sterile mosquitoes. This goal has been pursued - and sometimes achieved - by mosquito colonisation, production, and studies that have linked these characteristics to field performance. Parallels are drawn to studies in other insect SIT programmes and aquaculture which serve as vital technical reference points for mass-production of mosquitoes, most of whose development occurs - and characteristics of which are determined - in an aquatic environment. Poorly understood areas that require further study are numerous: diet, mass handling and genetic and physiological factors that influence mating competitiveness. Compromises in such traits due to demands to increase numbers or reduce costs, should be carefully considered in light of the desired field performance.     

AB5 toxins: structures and inhibitor design

High-resolution crystal structures of AB₅ toxins in their native form or in complex with a variety of ligands have led to the structure-based design and discovery of inhibitors targeting different areas of the toxins. The most significant progress is the development of highly potent multivalent ligands that block binding of the toxins to their receptors.     

A novel Trichoderma species isolated from soil in Guizhou, T. guizhouense

A new species of Trichoderma, Trichoderma guizhouense, isolated from soil in Guizhou Province, is described based on morphology and phylogenetic analyses. This species exhibits characteristic Trichoderma morphology but is distinct from related species based on characters of phialides and conidia. Two DNA markers, the translation elongation factor 1 alpha (tef1) and RNA polymerase II subunit b (rpb2) were used for phylogenetic analyses. The correlation between morphological and molecular-based clustering demonstrated two studied isolates are a new species.     

The small-subunit ribosomal RNA gene sequences from the hypotrichous ciliates Oxytricha nova and Stylonychia pustulata

We have determined the complete nucleotide sequence of the small- subunit ribosomal RNA genes for the ciliate protozoans Stylonychia pustulata and Oxytricha nova. The sequences are homologous and sufficiently similar that these organisms must be closely related. In a phylogeny inferred from comparisons of several eukaryotic small-subunit ribosomal RNAs, the divergence of the ciliates from the eukaryotic line of descent is seen to coincide with the radiation of the plants, the animals, and the fungi. This radiation is preceded by the divergence of the slime mold, Dictyostelium discoideum.      

Diversity of saprobic microfungi

The data needed to derive an accurate estimate of saprobic microfungi are insufficient, incomplete and contradictory. We therefore address issues that will ultimately reveal whether there are 1.5 million global fungal species, which is the generally accepted working estimate. Our data indicates that large numbers of fungi occur on host families, such as Musaceae, host genera such as Nothofagus and individual host species such as Eucalyptus globulus, and that fungi may be specific or recurrent on different plant groups. Recent studies have shown that fungal numbers on hosts may be larger than originally thought as saprobes are organ-specific/-recurrent and changes in fungal communities occur as substrata decays. Other issues, such as the impact of geography, of methodology and of taxonomy are also addressed. There is evidence that fungi on the same host at different locations also differs; site-specific factors and geographic distance may be more important than host/substrate in shaping fungal assemblages. Methodology impacts on estimates of species diversity with many more taxa observed using indirect isolation protocols as compared to direct isolations from leaves. Our understanding of fungal species numbers in speciose genera is important. In some fungal groups accepted species have been reduced to a few species, while in other groups many cryptic species are being uncovered. While we make a number of generalisations from the studies reported here, this review also highlights some of the limitations mycologists currently have to contend with. A large body of knowledge exists for certain groups of microfungi or for microfungi occurring on certain substrata/hosts. However, it is likely that we are drawing conclusions from data that are somewhat biased toward fungi and host/substrata that are of interest to human endeavours. The discrepancy between the numbers of fungi described from only one economically important genus, Eucalyptus, and all the other members of the Myrtaceae is but one example of this bias. By incorporating the large body of work that is already available and adding appropriate complementary studies, we can accelerate our understanding of microfungal diversity and this will eventually lead us to a realistic estimate of global fungal species numbers.