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Real-world evaluation of rapid and laboratory-free COVID-19 triage for emergency care: external validation and pilot deployment of artificial intelligence driven screening.
No full textBACKGROUND
Uncertainty in patients' COVID-19 status contributes to treatment delays, nosocomial transmission, and operational pressures in hospitals. However, the typical turnaround time for laboratory PCR remains 12-24 h and lateral flow devices (LFDs) have limited sensitivity. Previously, we have shown that artificial intelligence-driven triage (CURIAL-1.0) can provide rapid COVID-19 screening using clinical data routinely available within 1 h of arrival to hospital. Here, we aimed to improve the time from arrival to the emergency department to the availability of a result, do external and prospective validation, and deploy a novel laboratory-free screening tool in a UK emergency department.
METHODS
We optimised our previous model, removing less informative predictors to improve generalisability and speed, developing the CURIAL-Lab model with vital signs and readily available blood tests (full blood count [FBC]; urea, creatinine, and electrolytes; liver function tests; and C-reactive protein) and the CURIAL-Rapide model with vital signs and FBC alone. Models were validated externally for emergency admissions to University Hospitals Birmingham, Bedfordshire Hospitals, and Portsmouth Hospitals University National Health Service (NHS) trusts, and prospectively at Oxford University Hospitals, by comparison with PCR testing. Next, we compared model performance directly against LFDs and evaluated a combined pathway that triaged patients who had either a positive CURIAL model result or a positive LFD to a COVID-19-suspected clinical area. Lastly, we deployed CURIAL-Rapide alongside an approved point-of-care FBC analyser to provide laboratory-free COVID-19 screening at the John Radcliffe Hospital (Oxford, UK). Our primary improvement outcome was time-to-result, and our performance measures were sensitivity, specificity, positive and negative predictive values, and area under receiver operating characteristic curve (AUROC).
FINDINGS
72 223 patients met eligibility criteria across the four validating hospital groups, in a total validation period spanning Dec 1, 2019, to March 31, 2021. CURIAL-Lab and CURIAL-Rapide performed consistently across trusts (AUROC range 0·858-0·881, 95% CI 0·838-0·912, for CURIAL-Lab and 0·836-0·854, 0·814-0·889, for CURIAL-Rapide), achieving highest sensitivity at Portsmouth Hospitals (84·1%, Wilson's 95% CI 82·5-85·7, for CURIAL-Lab and 83·5%, 81·8-85·1, for CURIAL-Rapide) at specificities of 71·3% (70·9-71·8) for CURIAL-Lab and 63·6% (63·1-64·1) for CURIAL-Rapide. When combined with LFDs, model predictions improved triage sensitivity from 56·9% (51·7-62·0) for LFDs alone to 85·6% with CURIAL-Lab (81·6-88·9; AUROC 0·925) and 88·2% with CURIAL-Rapide (84·4-91·1; AUROC 0·919), thereby reducing missed COVID-19 cases by 65% with CURIAL-Lab and 72% with CURIAL-Rapide. For the prospective deployment of CURIAL-Rapide, 520 patients were enrolled for point-of-care FBC analysis between Feb 18 and May 10, 2021, of whom 436 received confirmatory PCR testing and ten (2·3%) tested positive. Median time from arrival to a CURIAL-Rapide result was 45 min (IQR 32-64), 16 min (26·3%) sooner than with LFDs (61 min, 37-99; log-rank p<0·0001), and 6 h 52 min (90·2%) sooner than with PCR (7 h 37 min, 6 h 5 min to 15 h 39 min; p<0·0001). Classification performance was high, with sensitivity of 87·5% (95% CI 52·9-97·8), specificity of 85·4% (81·3-88·7), and negative predictive value of 99·7% (98·2-99·9). CURIAL-Rapide correctly excluded infection for 31 (58·5%) of 53 patients who were triaged by a physician to a COVID-19-suspected area but went on to test negative by PCR.
INTERPRETATION
Our findings show the generalisability, performance, and real-world operational benefits of artificial intelligence-driven screening for COVID-19 over standard-of-care in emergency departments. CURIAL-Rapide provided rapid, laboratory-free screening when used with near-patient FBC analysis, and was able to reduce the number of patients who tested negative for COVID-19 but were triaged to COVID-19-suspected areas.
FUNDING
The Wellcome Trust, University of Oxford Medical and Life Sciences Translational Fund
Borrowing information across patient subgroups in clinical trials, with application to a paediatric trial.
No full textBACKGROUND
Clinical trial investigators may need to evaluate treatment effects in a specific subgroup (or subgroups) of participants in addition to reporting results of the entire study population. Such subgroups lack power to detect a treatment effect, but there may be strong justification for borrowing information from a larger patient group within the same trial, while allowing for differences between populations. Our aim was to develop methods for eliciting expert opinions about differences in treatment effect between patient populations, and to incorporate these opinions into a Bayesian analysis.
METHODS
We used an interaction parameter to model the relationship between underlying treatment effects in two subgroups. Elicitation was used to obtain clinical opinions on the likely values of the interaction parameter, since this parameter is poorly informed by the data. Feedback was provided to experts to communicate how uncertainty about the interaction parameter corresponds with relative weights allocated to subgroups in the Bayesian analysis. The impact on the planned analysis was then determined.
RESULTS
The methods were applied to an ongoing non-inferiority trial designed to compare antiretroviral therapy regimens in 707 children living with HIV and weighing ≥ 14 kg, with an additional group of 85 younger children weighing < 14 kg in whom the treatment effect will be estimated separately. Expert clinical opinion was elicited and demonstrated that substantial borrowing is supported. Clinical experts chose on average to allocate a relative weight of 78% (reduced from 90% based on sample size) to data from children weighing ≥ 14 kg in a Bayesian analysis of the children weighing < 14 kg. The total effective sample size in the Bayesian analysis was 386 children, providing 84% predictive power to exclude a difference of more than 10% between arms, whereas the 85 younger children weighing < 14 kg provided only 20% power in a standalone frequentist analysis.
CONCLUSIONS
Borrowing information from a larger subgroup or subgroups can facilitate estimation of treatment effects in small subgroups within a clinical trial, leading to improved power and precision. Informative prior distributions for interaction parameters are required to inform the degree of borrowing and can be informed by expert opinion. We demonstrated accessible methods for obtaining opinions
Effect of high-flow nasal therapy on patient-centred outcomes in patients at high risk of postoperative pulmonary complications after cardiac surgery: a study protocol for a multicentre adaptive randomised controlled trial.
No full textBACKGROUND
High-flow nasal therapy is a non-invasive form of respiratory support that delivers low-level, flow dependent positive airway pressure. The device can be better tolerated by patients than alternatives such as continuous positive airway pressure. The primary objective is to determine if prophylactic high-flow nasal therapy after tracheal extubation can result in an increase in the number of days alive and at home within the first 90 days after surgery, when compared with standard oxygen therapy. The co-primary objective is to estimate the incremental cost-effectiveness and cost-utility of high-flow nasal therapy vs standard oxygen therapy at 90 days, from the view-point of the public sector, the health service and patients.
METHODS
This is an adaptive, multicentre, international parallel-group, randomised controlled trial with embedded cost-effectiveness analysis comparing the use of high-flow nasal therapy with control in patients at high risk of respiratory complications following cardiac surgery. Participants will be randomised before tracheal extubation and allocated either high-flow nasal therapy or standard oxygen therapy for a minimum of 16 h immediately post extubation. Participants will be followed up until 90 days after surgery. The total sample size needed to detect a 2-day increase in DAH90 with 90% power with an intention to treat analysis is 850 patients. The adaptive design includes an interim sample size re-estimation which will provide protection against deviations from the original sample size assumptions made from the single-centre pilot study and will allow for a maximum sample size increase to 1152 patients.
DISCUSSION
Evidence to support routine use of high-flow nasal therapy will inform the development of effective enhanced recovery care bundles. Reducing complications should reduce length of stay and re-admission to hospital and provide an important focus for cost reduction. However; high-quality studies evaluating the clinical and cost effectiveness of high-flow nasal therapy after cardiothoracic surgery are lacking.
TRIAL REGISTRATION
The study has been registered with ISRCTN ( ISRCTN14092678 , 13/05/2020) Clinicaltrials.gov Registration Pending
SARS-CoV-2 Testing in the Community: Testing Positive Samples with the TaqMan SARS-CoV-2 Mutation Panel To Find Variants in Real Time.
No full textGenome sequencing is a powerful tool for identifying SARS-CoV-2 variant lineages; however, there can be limitations due to sequence dropout when used to identify specific key mutations. Recently, ThermoFisher Scientific has developed genotyping assays to help bridge the gap between testing capacity and sequencing capability to generate real-time genotyping results based on specific variants. Over a 6-week period during the months of April and May 2021, we set out to assess the ThermoFisher TaqMan mutation panel genotyping assay, initially for three mutations of concern and then for an additional two mutations of concern, against SARS-CoV-2-positive clinical samples and the corresponding COVID-19 Genomics UK Consortium (COG-UK) sequencing data. We demonstrate that genotyping is a powerful in-depth technique for identifying specific mutations, is an excellent complement to genome sequencing, and has real clinical health value potential, allowing laboratories to report and take action on variants of concern much more quickly
Training and redeployment of healthcare workers to intensive care units (ICUs) during the COVID-19 pandemic: a systematic review.
No full textOBJECTIVES
The rapid influx of patients with COVID-19 to intensive care at a rate that exceeds pre-existing staff capacity has required the rapid development of innovative redeployment and training strategies, which considered patient care and infection control. The aim of this study was to provide a detailed understanding of redeployment and training during the first year of the COVID-19 pandemic by capturing and considering the merit of the strategies enlisted and the experiences and needs of redeployed healthcare workers (HCWs).
DESIGN
The review involved a systematic search of key terms related to intensive care AND training AND redeployment AND healthcare workers within nine databases (Medline, CINAHL, PsychINFO, MedRxiv, Web of Science, The Health Management Consortium database, Social Science Research Network, OpenGrey and TRIP), which took place on 16 July 2021. Analysis consisted of a synthesis of quantitative study outputs and framework-based thematic analysis of qualitative study outputs and grey literature. These results were then combined applying an interpretative synthesis. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and the review protocol was available online.
RESULTS
Forty papers were analysed. These took place primarily in the UK (n=15, 37.5%) and USA (n=17, 42.5%). Themes presented in the results are . Based on this, key principles for successful redeployment and training were proposed.
CONCLUSIONS
The COVID-19 pandemic presents unique challenges to develop flexible redeployment strategies and deliver training promptly while following infection control recommendations. This review synthesises original approaches to tackle these challenges, which are relevant to inform the development of targeted and adaptative training and redeployment plans considering the needs of HCWs
Covariate analysis query: Hospital surgical volume-outcome relationship in caesarean hysterectomy for placenta accreta spectrum.
No full textEffect of Different Corticosteroid Dosing Regimens on Clinical Outcomes in Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial.
No full textImportance
Corticosteroids improve strength and function in boys with Duchenne muscular dystrophy. However, there is uncertainty regarding the optimum regimen and dosage.
Objective
To compare efficacy and adverse effects of the 3 most frequently prescribed corticosteroid regimens in boys with Duchenne muscular dystrophy.
Design, Setting, and Participants
Double-blind, parallel-group randomized clinical trial including 196 boys aged 4 to 7 years with Duchenne muscular dystrophy who had not previously been treated with corticosteroids; enrollment occurred between January 30, 2013, and September 17, 2016, at 32 clinic sites in 5 countries. The boys were assessed for 3 years (last participant visit on October 16, 2019).
Interventions
Participants were randomized to daily prednisone (0.75 mg/kg) (n = 65), daily deflazacort (0.90 mg/kg) (n = 65), or intermittent prednisone (0.75 mg/kg for 10 days on and then 10 days off) (n = 66).
Main Outcomes and Measures
The global primary outcome comprised 3 end points: rise from the floor velocity (in rise/seconds), forced vital capacity (in liters), and participant or parent global satisfaction with treatment measured by the Treatment Satisfaction Questionnaire for Medication (TSQM; score range, 0 to 100), each averaged across all study visits after baseline. Pairwise group comparisons used a Bonferroni-adjusted significance level of .017.
Results
Among the 196 boys randomized (mean age, 5.8 years [SD, 1.0 years]), 164 (84%) completed the trial. Both daily prednisone and daily deflazacort were more effective than intermittent prednisone for the primary outcome (P < .001 for daily prednisone vs intermittent prednisone using a global test; P = .017 for daily deflazacort vs intermittent prednisone using a global test) and the daily regimens did not differ significantly (P = .38 for daily prednisone vs daily deflazacort using a global test). The between-group differences were principally attributable to rise from the floor velocity (0.06 rise/s [98.3% CI, 0.03 to 0.08 rise/s] for daily prednisone vs intermittent prednisone [P = .003]; 0.06 rise/s [98.3% CI, 0.03 to 0.09 rise/s] for daily deflazacort vs intermittent prednisone [P = .017]; and -0.004 rise/s [98.3% CI, -0.03 to 0.02 rise/s] for daily prednisone vs daily deflazacort [P = .75]). The pairwise comparisons for forced vital capacity and TSQM global satisfaction subscale score were not statistically significant. The most common adverse events were abnormal behavior (22 [34%] in the daily prednisone group, 25 [38%] in the daily deflazacort group, and 24 [36%] in the intermittent prednisone group), upper respiratory tract infection (24 [37%], 19 [29%], and 24 [36%], respectively), and vomiting (19 [29%], 17 [26%], and 15 [23%]).
Conclusions and Relevance
Among patients with Duchenne muscular dystrophy, treatment with daily prednisone or daily deflazacort, compared with intermittent prednisone alternating 10 days on and 10 days off, resulted in significant improvement over 3 years in a composite outcome comprising measures of motor function, pulmonary function, and satisfaction with treatment; there was no significant difference between the 2 daily corticosteroid regimens. The findings support the use of a daily corticosteroid regimen over the intermittent prednisone regimen tested in this study as initial treatment for boys with Duchenne muscular dystrophy.
Trial Registration
ClinicalTrials.gov Identifier: NCT01603407
Anaesthetic management of a parturient patient with a malignant hyperthermia partner.
No full textMalignant hyperthermia (MH) is a rare but deleterious anaesthetic emergency that has an autosomal dominant inheritance. Successful management of the MH-susceptible fetus hinges on early suspicion and preparation. This case highlights the importance of knowing paternal anaesthetic risk as well as maternal in the parturient population. Paternal anaesthetic history is paramount in this situation, especially with a normal maternal risk, and preparation of the patient, staff and equipment is at the centre of the peripartum management of these patients
Opportunities and Risks of UK Medical Device Reform.
No full textOBJECTIVES
To identify the potential opportunities and risks around future UK regulatory reform of medical devices.
DESIGN
A mixed methods approach, comprising a rapid literature review, one-to-one, semi-structured interviews with key stakeholders, a multidisciplinary stakeholder workshop, and a post-workshop survey.
SETTING
United Kingdom.
PARTICIPANTS
32 key stakeholders across the medical device sector were identified both from the public and private sectors.
RESULTS
Opportunities relating to regulatory independence were identified, including the potential to create and implement a regulatory framework that ensures availability of medical devices; innovation and investment potential; and safety to the citizens of the UK. The most significant risks identified included threats to the safety of individual patients and the wider health system arising from the delay in awaiting regulatory approval due to the shortage of approved bodies; and reduced competitiveness of UK market and device manufacturers. Recommendations were identified to mitigate risks, centred on harnessing broader cross-sector collaborations, promoting patient and public partnership, and maximizing international engagement.
CONCLUSIONS
The UK's medical device sector is at a time-critical juncture to construct a regulatory framework to navigate its exit of Europe and respond to Europe's transition to new medical device regulations whilst also addressing the ongoing demand for rapid approval for new devices in response to the global pandemic. Investment, capacity-building, and international engagement will play a central role in mitigating risks and maximizing opportunities for medical device regulation
Open coraco-clavicular ligament reconstruction (CCLR) in treatment of displaced distal clavicle fractures has low complication rate and excellent union rate: a systematic review.
No full textBACKGROUND
It is well established that non-operative treatment of displaced distal clavicle fractures (DDCF) leads to a high non-union rate. A number of open surgical treatments in the past have shown good to excellent outcomes including shoulder function and union rate. Despite this there is no consensus on the outcome of open coraco-clavicular ligament reconstruction (CCLR). The aim of this systematic review was to assess the union rate, complications and shoulder function of open CCLR techniques in the treatment of DDCF.
PATIENTS AND METHODS
A review of the online databases MEDLINE and Embase was conducted on 1 January 2021 according to PRISMA guidelines. The review was registered prospectively in the PROSPERO database. Clinical studies reporting union rate, complications and shoulder function were included. The studies were appraised using the Methodological Index for Non-Randomized Studies (MINORS) tool.
RESULTS
The search strategy identified 18 studies eligible for inclusion with a total of 330 patients. These included 12 retrospective case series and 5 nonrandomized retrospective comparative studies and one RCT. All but one study reported on shoulder function, while all the studies reported on union rate and complications. The overall shoulder function was good to excellent using Constant-Murley score. The overall union rate was 97.6% and complication rate was 7.6%.
CONCLUSION
Open CCLR for displaced distal clavicle fractures that have a disruption of CC ligament, is a reliable treatment with excellent union rate and good to excellent shoulder functional scores.
LEVEL OF EVIDENCE
IV; Systematic review