Establishing diagnostic reference levels for pediatric fluoroscopic examinations in a tertiary hospital.

BACKGROUND: Diagnostic reference levels (DRLs) identify unusually high patient radiation exposures and are required for dose optimisation. DRLs for pediatric fluoroscopic examinations are not widely determined in Australia. OBJECTIVE: Our objectives were to establish DRLs for pediatric fluoroscopic examinations in a South Australian tertiary hospital and compare these to previously published data and to explore relationships between patient dose area product (DAP), age and fluoroscopy times. MATERIALS AND METHODS: Dose data from 365 pediatric patients undergoing 5 fluoroscopic examinations were retrospectively collected for a 3-year period commencing January 2018 to develop local DRLs. Relationships between DAP, age and fluoroscopy time were explored using scatterplots, Spearman's correlation, and regression analyses. RESULTS: Local DRLs were significantly lower than data published previously, possibly reflecting technological and procedural advancements. Each 1-year increase in patient age was associated with a 0.77 µGy·m2 increase in DAP for barium meal and follow-through studies (95% confidence interval [CI]=0.055, 1.48) (P=0.04), and a 1.37 µGy·m2 increase in DAP for barium swallow studies (95% CI=0.61, 2.12) (P<0.001). A low correlation was demonstrated between DAP and fluoroscopy time for micturating cystourethrography studies (r=0.35, 95% CI=0.15, 0.51, P<0.001) and barium meal and follow-through studies (r=0.37, 95% CI= -0.011, 0.65, P=0.05). Age and fluoroscopy time were not significantly related. CONCLUSION: This study provides updated Australian pediatric fluoroscopic DRLs, with the intention of promoting a national database for benchmarking pediatric doses. The local DRLs can be used for dose comparisons and optimisation between facilities.

Diagnostic accuracy of the Ottawa Knee Rule in adult acute knee injuries: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the current evidence on the diagnostic accuracy of the Ottawa Knee Rule (OKR) for acute knee injuries in adults. METHODS: A literature search of Embase (Elsevier), MEDLINE (U.S. National Library of Medicine), PubMed and Scopus databases (1995 to date; English language) was performed and the relevant references were assessed. Original articles documenting OKR use by emergency physicians to assess adult acute knee injuries were included. Study methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Results of eligible studies were pooled using random effects or fixed effects modelling to calculate the diagnostic performance of the OKR. The Higgins I2 test and Begg's association test were performed to assess between-study heterogeneity and publication bias respectively, with Spearman's correlation test for threshold effect. RESULTS: Eight studies, including 7385 patients, were enrolled and pooled using the random effects model. Sensitivity, specificity, negative likelihood ratio, positive likelihood ratio and diagnostic odds ratio were 0.99 (95% CI, 0.97 to 1.00), 0.49 (95% CI, 0.47 to 0.51), 0.07 (95% CI, 0.02 to 0.24), 1.86 (95% CI, 1.72 to 2.01) and 25.10 (95% CI, 7.18 to 87.70) respectively. Based on the QUADAS-2 criteria, most studies presented low risk of bias and concern regarding applicability. CONCLUSIONS: Application of the OKR can rule out knee fracture and thus avoid unnecessary radiography. These results also translate to improved efficiency, lower medical costs and reduced waiting times. KEY POINTS: • The Ottawa Knee Rule helps clinicians to rule out fracture in adults with an acute knee injury. • The rule allows a reduction in radiography requests, patient waiting time in the emergency department and healthcare costs.

Combination of Ambiguous and Unambiguous Data in the Restraint-driven Docking of Flexible Peptides with HADDOCK: The Binding of the Spider Toxin PcTx1 to the Acid Sensing Ion Channel (ASIC) 1a.

Peptides that bind to ion channels have attracted much interest as potential lead molecules for the development of new drugs and insecticides. However, the structure determination of large peptide-channel complexes using experimental methods is challenging. Thus structural models are often derived from combining experimental information with restraint-driven docking approaches. Using the complex formed by the venom peptide PcTx1 and the acid sensing ion channel (ASIC) 1a as a case study, we have examined the effect of different combinations of restraints and input structures on the statistical likelihood of (a) correctly predicting the structure of the binding interface and (b) the ability to predict which residues are involved in specific pairwise peptide-channel interactions. For this, we have analyzed over 200,000 water-refined docked structures obtained with various amounts and types of restraints of the peptide-channel complex predicted using the docking program HADDOCK. We found that increasing the number of restraints or even the use of pairwise interaction data resulted in only a modest improvement in the likelihood of finding a structure within a given accuracy. This suggests that shape complementarity and the force field make a large contribution to the accuracy of the predicted structure. The results also showed that there are large variations in the accuracy of the predicted structure depending on the precise combination of residues used as restraints. Finally, we reflect on the limitations of relying on geometric criteria such as root-mean square deviations to assess the accuracy of docking procedures. We propose that in addition to currently used measures, the likelihood of finding a structure within a given level of accuracy should be also used to evaluate docking methods.

Mammographic compression practices of force- and pressure-standardisation protocol: A scoping review.

INTRODUCTION: As an efficient, effective and moderately inexpensive modality, mammography has been implemented as a cancer screening tool and in diagnostic management. However, appropriate breast compression is necessary for optimal outcomes. Current key measures of compression force are subjective and variable, giving rise to the concept of a 'personalised' pressure-standardisation protocol. METHODS: A scoping review of the literature was performed using the Arksey and O'Malley framework to explore the existing force- and pressure-standardisation protocols in clinical application. A comprehensive search strategy and standardised study selection and evaluation were completed. This synthesis of existing knowledge can lead to the implementation of mechanically standardised mammographic compression pressure as a feasible tailored approach to clinical practice. Four databases (PubMed, MEDLINE, Embase and Scopus) were searched from the databases' inception to 13 December 2019 for relevant information, and eighteen articles were selected for analysis. RESULTS: In addition to current protocol comparison, emerging key concepts include the reasoning behind standardisation, the benefits of improved diagnostic outcomes/decreased pain with negligible change in image quality and average glandular dose (AGD), and the recommendation of a 10kPa (approximate) pressure-standardisation protocol. Research to date is largely based abroad (Netherlands), with a strong focus on screening practices. Consequently, several gaps in the current literature were identified as potential directions for future investigation. CONCLUSIONS: As a suggested mammographic guideline, compression pressures of approximately 10kPa aid in image acquisition reproducibility both within and between women; pain levels decrease, with minimal variations to breast thickness, AGD and image quality.

Validation of the Ottawa knee rule in adults: A single centre study.

INTRODUCTION: This clinical audit aimed to evaluate performance of the Ottawa Knee Rule (OKR) and degree of compliance by emergency referrers for acute knee injuries in adults. METHODS: Knee radiography requests were analysed retrospectively for eligibility. Data were extracted from eligible requests under headings describing the OKR criteria, patient history, diagnosis and referrer profession. Sensitivity, specificity, negative likelihood ratio and positive likelihood ratio were calculated with 95% CI for the entire sample and each profession (consultant doctors, resident medical officers [RMO], physiotherapists and triage nurses) individually. The frequency of each OKR criterion and correlation with fracture, referrer compliance to the rule and the relative reduction in radiography were also calculated. RESULTS: Of 713 patients identified, 149 were enrolled by the eligibility criteria. The overall sensitivity, specificity, negative likelihood ratio and positive likelihood ratio of the OKR for knee fracture were 71% (95%CI, 49-87%), 46% (95%CI, 37-55%), 0.64 (95%CI, 0.33-1.22) and 1.3 (95%CI, 0.96-1.76), respectively. Physiotherapists and triage nurses demonstrated better rule performance than consultant doctors and RMOs, with a sensitivity of 100% and negative likelihood ratio of 0.0. Physiotherapists were most compliant at 73% (19/26). Only 85 requests were OKR positive and, when abiding by the rule, this would have reduced radiography by 43% (64/149). CONCLUSIONS: In this first Australian study, moderate OKR performance and variable compliance by emergency referrers were observed. This led to unnecessary irradiation of patients without a fracture. The findings suggest emergency referrers could benefit from education on applying and documenting the OKR on radiography requests.

Adequacy of clinical information in X-ray referrals for traumatic ankle injury with reference to the Ottawa Ankle Rules-a retrospective clinical audit.

STUDY OBJECTIVE: To assess the adequacy of clinical information with reference to the Ottawa Ankle Rules (OAR) in X-ray referrals for adults with traumatic ankle injury in the ED of a South Australian tertiary hospital and report upon referring trends between emergency department clinicians. METHODS: A retrospective clinical audit of adult ankle X-ray referrals in the emergency department was conducted. Eligible referrals were screened for their adherence to the OAR, patient details, clinical history and referrer. A logistic regression was used to determine the influence of these factors on the likelihood of being referred for X-rays despite not meeting the OAR criteria. Sensitivity, specificity, positive and negative likelihood ratios and their associated confidence intervals were calculated to assess the diagnostic accuracy of the OAR for those referred. RESULTS: Out of the 262 eligible referrals, 163 were deemed to have met the criteria for the OAR. Physiotherapists showed the highest OAR compliance of 77.3% and were the most accurate in their use of the rules, with a sensitivity of 0.86. Medical officers, registrars and interns were 2.5 times more likely to still refer a patient for X-ray if they did not meet the OAR criteria, compared to physiotherapists as the baseline. Patient age, duration of injury etc. were not significantly associated with likelihood of referral (even when they did not meet OAR criteria). The overall sensitivity, specificity, positive and negative likelihood ratios of the OAR were 0.59 (95% CI [0.47-0.71]), 0.37 (95% CI [0.30-0.44]), 0.93 (95% CI [0.76-1.16]) and 1.10 (95% CI [0.82-1.48]) respectively. CONCLUSION: The results of this audit demonstrated poor sensitivity and moderate compliance by referrers with the rule. Reasonable evidence exists for the implementation of individual and/or institutional-based change strategies to improve clinician compliance and accuracy with use of the OAR.

Routine and pulse vaccination for Lassa virus could reduce high levels of endemic disease: A mathematical modelling study.

Lassa fever is an acute viral illness caused by Lassa virus (LASV), a rodent-borne pathogen. LASV is endemic to much of Sub-Saharan West Africa, where seasonal outbreaks cause significant morbidity and mortality. Increased global awareness of LASV has led to development of improved diagnostic tests, treatments and vaccines. As vaccine candidates are trialled, it is essential to assess the potential outcomes of introducing a LASV vaccination program in endemic regions. This study investigates the potential outcomes of routine and pulse vaccination strategies using a deterministic mathematical model that captures seasonal LASV transmission between rodents and humans. For plausible parameter values, we find that immunization of 40% of infants at 70% vaccine effectiveness achieves a population-level reduction in infectious case numbers of 30%, while coverage of 60% at 90% vaccine effectiveness achieves a 56% reduction. Similar reductions can be achieved more rapidly via population-wide pulse vaccination at 11% coverage (30% reduction at 70% effectiveness) or 23% coverage (56% reduction at 90% effectiveness) repeated every 10 years. Similar pulse vaccine doses delivered at reduced frequency, but increased coverage achieves a greater reduction in infectious cases. Findings around infant vaccination are sensitive to our assumption that immunity is life-long, while pulse-vaccination has only slightly reduced effect if immunity lasts 10-30 years. An effective LASV vaccination program would incorporate pulse vaccination in addition to routine childhood immunization to limit disease. Estimates of feasible vaccine coverage and effectiveness are needed to fully quantify the likely benefits of a vaccination program in LASV endemic regions.