Direct and indirect costs of paediatric asthma in the UK: a cost analysis.

OBJECTIVE: To estimate the cost of paediatric asthma from a UK National Health Service (NHS) and societal perspective and explore determinants of these costs. DESIGN: Cost analysis based on data from a large clinical trial between 2017 and 2019. Case report forms recorded healthcare resource use and productivity losses attributable to asthma over a 12-month period. These were combined with national unit cost data to generate estimates of health service and indirect costs. SETTING: Asthma clinics in primary and secondary care in England and Scotland. MAIN OUTCOME MEASURES: Cost per asthma attack stratified by highest level of care received. Total annual health service and indirect costs. Modelled effect of sex, age, severity, number of attacks and adherence on total annual costs. RESULTS: Of 506 children included in the analysis, 252 experienced at least one attack. The mean (SD) cost per attack was £297 (806) (median £46, IQR 40-138) and the mean total annual cost to the NHS was £1086 (2504) (median £462, IQR 296-731). On average, children missed 6 days of school and their carers missed 13 hours of paid work, contributing to a mean annual indirect cost of £412 (879) (median £30, IQR 0-477). Health service costs increased significantly with number of attacks and participant age (>11 years). Indirect costs increased with asthma severity and number of attacks but were found to be lower in older children. CONCLUSIONS: Paediatric asthma imparts a significant economic burden on the health service, families and society. Efforts to improve asthma control may generate significant cost savings. TRIAL REGISTRATION NUMBER: ISRCTN 67875351.

Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage: The UK-REBOA Randomized Clinical Trial.

Importance: Bleeding is the most common cause of preventable death after trauma. Objective: To determine the effectiveness of resuscitative endovascular balloon occlusion of the aorta (REBOA) when used in the emergency department along with standard care vs standard care alone on mortality in trauma patients with exsanguinating hemorrhage. Design, Setting, and Participants: Pragmatic, bayesian, randomized clinical trial conducted at 16 major trauma centers in the UK. Patients aged 16 years or older with exsanguinating hemorrhage were enrolled between October 2017 and March 2022 and followed up for 90 days. Intervention: Patients were randomly assigned (1:1 allocation) to a strategy that included REBOA and standard care (n = 46) or standard care alone (n = 44). Main Outcomes and Measures: The primary outcome was all-cause mortality at 90 days. Ten secondary outcomes included mortality at 6 months, while in the hospital, and within 24 hours, 6 hours, or 3 hours; the need for definitive hemorrhage control procedures; time to commencement of definitive hemorrhage control procedures; complications; length of stay; blood product use; and cause of death. Results: Of the 90 patients (median age, 41 years [IQR, 31-59 years]; 62 [69%] were male; and the median Injury Severity Score was 41 [IQR, 29-50]) randomized, 89 were included in the primary outcome analysis because 1 patient in the standard care alone group declined to provide consent for continued participation and data collection 4 days after enrollment. At 90 days, 25 of 46 patients (54%) had experienced all-cause mortality in the REBOA and standard care group vs 18 of 43 patients (42%) in the standard care alone group (odds ratio [OR], 1.58 [95% credible interval, 0.72-3.52]; posterior probability of an OR >1 [indicating increased odds of death with REBOA], 86.9%). Among the 10 secondary outcomes, the ORs for mortality and the posterior probabilities of an OR greater than 1 for 6-month, in-hospital, and 24-, 6-, or 3-hour mortality were all increased in the REBOA and standard care group, and the ORs were increased with earlier mortality end points. There were more deaths due to bleeding in the REBOA and standard care group (8 of 25 patients [32%]) than in standard care alone group (3 of 18 patients [17%]), and most occurred within 24 hours. Conclusions and Relevance: In trauma patients with exsanguinating hemorrhage, a strategy of REBOA and standard care in the emergency department does not reduce, and may increase, mortality compared with standard care alone. Trial Registration: isrctn.org Identifier: ISRCTN16184981.

The effect of the COVID-19 pandemic on the incidence and survival outcomes of EMS-witnessed out-of-hospital cardiac arrest.

AIM: We sought to examine the impact of the COVID-19 pandemic on the incidence and survival outcomes of emergency medical service (EMS)-witnessed out-of-hospital cardiac arrest (OHCA) in Victoria, Australia. METHODS: We performed an interrupted time-series analysis of adult EMS-witnessed OHCA patients of medical aetiology. Patients treated during the COVID-19 period (1st March 2020 to 31st December 2021) were compared to a historical comparator period (1st January 2012 and 28th February 2020). Multivariable poisson and logistic regression models were used to examine changes in incidence and survival outcomes during the COVID-19 pandemic, respectively. RESULTS: We included 5,034 patients, 3,976 (79.0%) in the comparator period and 1,058 (21.0%) in the COVID-19 period. Patients in the COVID-19 period had longer EMS response times, fewer public location arrests and were significantly more likely to receive mechanical CPR and laryngeal mask airways compared to the historical period (all p < 0.05). There were no significant differences in the incidence of EMS-witnessed OHCA between the comparator and COVID-19 periods (incidence rate ratio 1.06, 95% CI: 0.97-1.17, p = 0.19). Also, there was no difference in the risk-adjusted odds of survival to hospital discharge for EMS-witnessed OHCA occurring during COVID-19 period compared to the comparator period (adjusted odd ratio 1.02, 95% CI: 0.74-1.42; p = 0.90). CONCLUSION: Unlike the reported findings in non-EMS-witnessed OHCA populations, changes during the COVID-19 pandemic did not influence incidence or survival outcomes in EMS-witnessed OHCA. This may suggest that changes in clinical practice that sought to limit the use of aerosol generating procedures did not influence outcomes in these patients.

Non-invasive testing for early detection of neovascular macular degeneration in unaffected second eyes of older adults: EDNA diagnostic accuracy study.

BACKGROUND: Neovascular age-related macular degeneration is a leading cause of sight loss, and early detection and treatment is important. For patients with neovascular age-related macular degeneration in one eye, it is usual practice to monitor the unaffected eye. The test used to diagnose neovascular age-related macular degeneration, fundus fluorescein angiography, is an invasive test. Non-invasive tests are available, but their diagnostic accuracy is unclear. OBJECTIVES: The primary objective was to determine the diagnostic monitoring performance of tests for neovascular age-related macular degeneration in the second eye of patients with unilateral neovascular age-related macular degeneration. The secondary objectives were the cost-effectiveness of tests and to identify predictive factors of developing neovascular age-related macular degeneration. DESIGN: This was a multicentre, prospective, cohort, comparative diagnostic accuracy study in a monitoring setting for up to 3 years. A Cox regression risk prediction model and a Markov microsimulation model comparing cost-effectiveness of the index tests over 25 years were used. SETTING: This took place in hospital eye services. PARTICIPANTS: Participants were adults (aged 50-95 years) with newly diagnosed (within the previous 6 weeks) neovascular age-related macular degeneration in one eye and an unaffected second (study) eye who were attending for treatment injections in the first eye and who had a study eye baseline visual acuity of ≥ 68 Early Treatment Diabetic Retinopathy Study letters. INTERVENTIONS: The index tests were Amsler chart (completed by participants), fundus clinical examination, optical coherence tomography, self-reported vision assessment (completed by participants) and visual acuity. The reference standard was fundus fluorescein angiography. MAIN OUTCOME MEASURES: The main outcome measures were sensitivity and specificity; the performance of the risk predictor model; and costs and quality-adjusted life-years. RESULTS: In total, 552 out of 578 patients who consented from 24 NHS hospitals (n = 16 ineligible; n = 10 withdrew consent) took part. The mean age of the patients was 77.4 years (standard deviation 7.7 years) and 57.2% were female. For the primary analysis, 464 patients underwent follow-up fundus fluorescein angiography and 120 developed neovascular age-related macular degeneration on fundus fluorescein angiography. The diagnostic accuracy [sensitivity (%) (95% confidence interval); specificity (%) (95% confidence interval)] was as follows: optical coherence tomography 91.7 (85.2 to 95.6); 87.8 (83.8 to 90.9)], fundus clinical examination [53.8 (44.8 to 62.5); 97.6 (95.3 to 98.9)], Amsler [33.7 (25.1 to 43.5); 81.4 (76.4 to 85.5)], visual acuity [30.0 (22.5 to 38.7); 66.3 (61.0 to 71.1)] and self-reported vision [4.2 (1.6 to 9.8); 97.0 (94.6 to 98.5)]. Optical coherence tomography had the highest sensitivity across all secondary analyses. The final prediction model for neovascular age-related macular degeneration in the non-affected eye included smoking status, family history of neovascular age-related macular degeneration, the presence of nodular drusen with or without reticular pseudodrusen, and the presence of pigmentary abnormalities [c-statistic 0.66 (95% confidence interval 0.62 to 0.71)]. Optical coherence tomography monitoring generated the greatest quality-adjusted life-years gained per patient (optical coherence tomography, 5.830; fundus clinical examination, 5.787; Amsler chart, 5.736, self-reported vision, 5.630; and visual acuity, 5.600) for the lowest health-care and social care costs (optical coherence tomography, £19,406; fundus clinical examination, £19,649; Amsler chart, £19,751; self-reported vision, £20,198; and visual acuity, £20,444) over the lifetime of the simulated cohort. Optical coherence tomography dominated the other tests or had an incremental cost-effectiveness ratio below the accepted cost-effectiveness thresholds (£20,000) across the scenarios explored. LIMITATIONS: The diagnostic performance may be different in an unselected population without any history of neovascular age-related macular degeneration; the prediction model did not include genetic profile data, which might have improved the discriminatory performance. CONCLUSIONS: Optical coherence tomography was the most accurate in diagnosing conversion to neovascular age-related macular degeneration in the fellow eye of patients with unilateral neovascular age-related macular degeneration. Economic modelling suggests that optical coherence tomography monitoring is cost-effective and leads to earlier diagnosis of and treatment for neovascular age-related macular degeneration in the second eye of patients being treated for neovascular age-related macular degeneration in their first eye. FUTURE WORK: Future works should investigate the role of home monitoring, improved risk prediction models and impact on long-term visual outcomes. STUDY REGISTRATION: This study was registered as ISRCTN48855678. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 8. See the NIHR Journals Library website for further project information.

Wet age-related macular degeneration is the leading cause of sight loss in older people. It is diagnosed using fundus fluorescein angiography, which involves photographing the retina after the injection of a dye into a vein in the arm, which may result in allergic reactions. Many people with wet age-related macular degeneration in one eye will also develop it in their second eye. To avoid regular fundus fluorescein angiography, non-invasive tests are used to routinely monitor for wet age-related macular degeneration in the second eye of patients with wet age-related macular degeneration already in one eye. We studied five commonly used and easily performed non-invasive tests to see which best detected the onset of wet age-related macular degeneration. The five tests were: self-report of visionself-completion of an Amsler charta standard sight testexamination of the retina by a specialistoptical coherence tomography, which is a non-invasive scan of the central retina. If any tests suggested wet age-related macular degeneration, fundus fluorescein angiography was performed to compare results. In total, 552 hospital eye clinic patients who had wet age-related macular degeneration in only one eye took part. Over a 3-year period, wet age-related macular degeneration developed in the second eye in 145 people (26%), of whom 120 had undergone fundus fluorescein angiography. In 25 people with wet age-related macular degeneration, fundus fluorescein angiography was not carried out for safety reasons or because the patient did not want to undergo it. Of all the tests, only optical coherence tomography was good at detecting wet age-related macular degeneration correctly (92% sensitivity) and at detecting those who did not have wet age-related macular degeneration (88% specificity). All other tests either did not detect wet age-related macular degeneration consistently when it occurred or gave a false positive result when it had not occurred. This study confirmed that optical coherence tomography detected wet age-related macular degeneration correctly in the second eye of people with wet age-related macular degeneration in their first eye, and may offer cost saving for the NHS.

Reducing asthma attacks in children using exhaled nitric oxide (RAACENO) as a biomarker to inform treatment strategy: a multicentre, parallel, randomised, controlled, phase 3 trial.

BACKGROUND: The benefit of fractional exhaled nitric oxide (FeNO) in guiding asthma treatment is uncertain. We evaluated the efficacy of adding FeNO to symptom-guided treatment in children with asthma versus only symptom-guided treatment. METHODS: RAACENO was a multicentre, parallel, randomised, controlled, phase 3 trial done in 35 secondary care centres and 17 primary care recruitment sites (only seven primary care sites managed to recruit patients) in the UK. Patients with a confirmed asthma diagnosis, aged 6-15 years, prescribed inhaled corticosteroids, and who received a course of oral corticosteroids for at least one asthma exacerbation during the 12 months before recruitment were included. Participants were randomly assigned to either FeNO plus symptom-guided treatment (intervention) or symptom-guided treatment alone (standard care) using a 24 h in-house, web-based randomisation system. Participants and the clinical and research teams were not masked to the group allocation. A web-based algorithm gave treatment recommendations based on the Asthma Control Test (ACT) or Childhood ACT (CACT) score; current asthma treatment; adherence to study treatment in the past 3 months; and use of FeNO (in the intervention group). Follow-up occurred at 3-month intervals for 12 months. The primary outcome was any asthma exacerbation treated with oral corticosteroids in the 12 months after randomisation, assessed in the intention-to-treat population. This study is registered with the International Standard Randomised Controlled Trial Registry, ISRCTN67875351. FINDINGS: Between June 22, 2017, and Aug 8, 2019, 535 children were assessed for eligibility, 20 were ineligible and six were excluded post-randomisation. 509 children were recruited and at baseline, the mean age of participants was 10·1 years (SD 2·6), and 308 (60·5%) were male. The median FeNO was 21 ppb (IQR 10-48), mean predicted FEV1 was 89·6% (SD 18·0), and median daily dose of inhaled corticosteroids was 400 µg budesonide equivalent (IQR 400-1000). Asthma was partly or fully controlled in 256 (50·3%) of 509 participants. The primary outcome, which was available for 506 (99%) of 509 participants, occurred in 123 (48·2%) of 255 participants in the intervention group and 129 (51·4%) of 251 in the standard care group, the intention-to-treat adjusted odds ratio (OR) was 0·88 (95% CI 0·61 to 1·27; p=0·49). The adjusted difference in the percentage of participants who received the intervention in whom the primary outcome occurred compared with those who received standard care was -3·1% (-11·9% to 5·6%). In 377 (21·3%) of 1771 assessments, the algorithm recommendation was not followed. Adverse events were reported by 27 (5·3%) of 509 participants (15 in the standard care group and 12 in the intervention group). The most common adverse event was itch after skin prick testing (reported by eight participants in each group). INTERPRETATION: We found that the addition of FeNO to symptom-guided asthma treatment did not lead to reduced exacerbations among children prone to asthma exacerbation. Asthma symptoms remain the only tool for guiding treatment decisions. FUNDING: National Institute for Health Research.

Early detection of neovascular age-related macular degeneration: an economic evaluation based on data from the EDNA study.

BACKGROUND/AIMS: To evaluate the cost-effectiveness of non-invasive monitoring tests to detect the onset of neovascular age-related macular degeneration (nAMD) in the unaffected second eye of patients receiving treatment for unilateral nAMD in a UK National Health Service (NHS) hospital outpatient setting. METHODS: A patient-level state transition model was constructed to simulate the onset, detection, and treatment of nAMD in the second eye. Five index tests were compared: self-reported change in visual function, Amsler test, clinic measured change in visual acuity from baseline, fundus assessment by clinical examination or colour photography, and spectral domain optical coherence tomography (SD-OCT). Diagnosis of nAMD was confirmed by fundus fluorescein angiography (FFA) before prompt initiation of antivascular endothelial growth factor treatment. Quality-adjusted life-years (QALYs) and costs of health and social care were modelled over a 25-year time horizon. RESULTS: SD-OCT generated more QALYs (SD-OCT, 5.830; fundus assessment, 5.787; Amsler grid, 5.736, patient's subjective assessment, 5.630; and visual acuity, 5.600) and lower health and social care costs (SD-OCT, £19 406; fundus assessment, £19 649; Amsler grid, £19 751; patient's subjective assessment, £20 198 and visual acuity, £20 444) per patient compared with other individual monitoring tests. Probabilistic sensitivity analysis indicated a high probability (97%-99%) of SD-OCT being the preferred test across a range of cost-effectiveness thresholds (£13 000-£30 000) applied in the UK NHS. CONCLUSIONS: Early treatment of the second eye following FFA confirmation of SD-OCT positive findings is expected to maintain better visual acuity and health-related quality of life and may reduce costs of health and social care over the lifetime of patients.

Different strategies to initiate and maintain hyperventilation: their effect on continuous estimates of dynamic cerebral autoregulation.

OBJECTIVE: Capnography is a key monitoring intervention in several neurologically vulnerable clinical states. Cerebral autoregulation (CA) describes the ability of the cerebrovascular system to maintain a near constant cerebral blood flow throughout fluctuations in systemic arterial blood pressure, with the partial pressure of arterial carbon dioxide known to directly influence CA. Previous work has demonstrated dysautoregulation lasting around 30 s prior to the anticipated augmentation of hyperventilation-associated hypocapnia. In order assess to potential benefit of hypocapnic interventions in an acute stroke setting, minimisation of dysregulation is paramount. APPROACH: Hyperventilation strategies to induce and maintain hypocapnia were performed in 61 healthy participants, effects on temporal estimates of dynamic cerebral autoregulation (autoregulation index, ARI) were assessed to validate the most effective strategy for inducing and maintaining hypocapnia. MAIN RESULTS: The extent of initial decrease was significantly smaller in the continuous metronome strategy compared to the delayed metronome and voluntary strategies (▵ARI 0.33 ± 1.18, 2.80 ± 3.33 and 3.69 ± 2.79 respectively, p  < 0.017). SIGNIFICANCE: The use of a continuous metronome to induce hypocapnia rather than the sudden inception of an auditory stimulus appears to reduce the initial decrease in autoregulatory capacity seen in previous studies. Dysautoregulation can be minimised by continuous metronome use during hyperventilation-induced hypocapnia. This advancement in understanding of the behaviour of CA during hypocapnia permits safer delivery of CA targeted interventions, particularly in neurologically vulnerable patient populations.