Effectiveness of a symptom-clinic intervention delivered by general practitioners with an extended role for people with multiple and persistent physical symptoms in England: the Multiple Symptoms Study 3 pragmatic, multicentre, parallel-group, individually randomised controlled trial.

BACKGROUND: People with multiple and persistent physical symptoms have impaired quality of life and poor experiences of health care. We aimed to evaluate the effectiveness of a community-based symptom-clinic intervention in people with multiple and persistent physical symptoms, hypothesising that this symptoms clinic plus usual care would be superior to usual care only. METHODS: The Multiple Symptoms Study 3 was a pragmatic, multicentre, parallel-group, individually randomised controlled trial conducted in 108 general practices in the UK National Health Service in four regions of England between Dec 6, 2018, and June 30, 2023. Participants were individually randomised (1:1) to the symptom-clinic intervention plus usual care or to usual care only via a computer-generated, pseudo-random list stratified by trial centre. Allocation was done by the trial statistician and concealed with a centralised, web-based randomisation system; masking participants was not possible due to the nature of the intervention. The symptom-clinic intervention was a sequence of up to four medical consultations that aimed to elicit a detailed clinical history, fully hear and validate the participant, offer rational explanations for symptoms, and assist the participant to develop ways of managing their symptoms; it was delivered by general practitioners with an extended role. The primary outcome was Patient Health Questionnaire-15 (PHQ-15) score 52 weeks after randomisation, analysed by intention to treat. The trial is registered on the ISRCTN registry (ISRCTN57050216). FINDINGS: 354 participants were randomly assigned; 178 (50%) were assigned to receive the community-based symptoms clinic plus usual care and 176 (50%) were assigned to receive usual care only. At the primary-outcome point of 52 weeks, PHQ-15 scores were 14·1 (SD 3·7) in the group receiving usual care and 12·2 (4·5) in the group receiving the intervention. The adjusted between-group difference of -1·82 (95% CI -2·67 to -0·97) was statistically significantly in favour of the intervention group (p<0·0001). There were 39 adverse events in the group receiving usual care and 36 adverse events in the group receiving the intervention. There were no statistically significant between-group differences in the proportion of participants who had non-serious adverse events (-0·03, 95% CI -0·11 to 0·05) or serious adverse events (0·02, -0·02 to 0·07). No serious adverse event was deemed to be related to the trial intervention. INTERPRETATION: Our symptom-clinic intervention, which focused on explaining persistent symptoms to participants in order to support self-management, led to sustained improvement in multiple and persistent physical symptoms. FUNDING: UK National Institute for Health and Care Research.

A model-based economic analysis of the CFHealthHub intervention to support adherence to inhaled medications for people with cystic fibrosis in the UK.

BACKGROUND: Adherence to preventative inhaled therapies in people with cystic fibrosis (CF) is low, resulting in potentially avoidable health losses and the need for costly rescue therapies. OBJECTIVES: To estimate the cost-effectiveness of the CFHealthHub (CFHH) intervention to support adherence to inhaled medications. METHODS: A state transition model was developed to assess the cost-effectiveness of the CFHH intervention versus usual care from the perspective of the UK National Health Service and Personal Social Services over a lifetime horizon. Costs and health outcomes were discounted at a rate of 3.5 percent per annum. Costs were valued at 2021/22 prices. The model structure includes health states defined by survival status, level of lung function, and transplant history. Treatment effects were modeled by changing the probabilities of transitioning between lung function states and reducing exacerbation rates. Model parameters were informed by the CFHH trial, CF Registry data, routine cost databases, literature, and expert opinion. Deterministic and probabilistic sensitivity analyses were undertaken to assess uncertainty. RESULTS: The CFHH intervention is expected to generate additional health gains and cost savings compared with usual care. Assuming that it is delivered for 10 years, the CFHH intervention is expected to generate 0.17 additional quality-adjusted life years and cost savings of GBP 1,600 (EUR 1,662) per patient. CONCLUSIONS: The CFHH intervention is expected to dominate usual care, irrespective of the duration over which the intervention is delivered. The modeled benefits and cost savings are smaller than initially expected and are sensitive to relative treatment effects on lung function.

Prehospital early warning scores for adults with suspected sepsis: retrospective diagnostic cohort study.

BACKGROUND: Ambulance services need to identify and prioritise patients with sepsis for early hospital assessment. We aimed to determine the accuracy of early warning scores alongside paramedic diagnostic impression to identify sepsis that required urgent treatment. METHODS: We undertook a retrospective diagnostic cohort study involving adult emergency medical cases transported to Sheffield Teaching Hospitals ED by Yorkshire Ambulance Service in 2019. We used routine ambulance service data to calculate 21 early warning scores and categorise paramedic diagnostic impressions as sepsis, infection, non-specific presentation or other presentation. We linked cases to hospital records and identified those meeting the sepsis-3 definition who received urgent hospital treatment for sepsis (reference standard). Analysis determined the accuracy of strategies that combined early warning scores at varying thresholds for positivity with paramedic diagnostic impression. RESULTS: We linked 12 870/24 955 (51.6%) cases and identified 348/12 870 (2.7%) with a positive reference standard. None of the strategies provided sensitivity greater than 0.80 with positive predictive value greater than 0.15. The area under the receiver operating characteristic curve for the National Early Warning Score, version 2 (NEWS2) applied to patients with a diagnostic impression of sepsis or infection was 0.756 (95% CI 0.729, 0.783). No other early warning score provided clearly superior accuracy to NEWS2. Paramedic impression of sepsis or infection had sensitivity of 0.572 (0.519, 0.623) and positive predictive value of 0.156 (0.137, 0.176). NEWS2 thresholds of >4, >6 and >8 applied to patients with a diagnostic impression of sepsis or infection, respectively, provided sensitivities and positive predictive values of 0.522 (0.469, 0.574) and 0.216 (0.189, 0.245), 0.447 (0.395, 0.499) and 0.274 (0.239, 0.313), and 0.314 (0.268, 0.365) and 0.333 (0.284, 0.386). CONCLUSION: No strategy is ideal but using NEWS2 alongside paramedic diagnostic impression of infection or sepsis could identify one-third to half of sepsis cases without prioritising unmanageable numbers. No other score provided clearly superior accuracy to NEWS2. TRIAL REGISTRATION NUMBER: researchregistry5268, https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/5de7bbd97ca5b50015041c33/.

Self-management intervention to reduce pulmonary exacerbations by supporting treatment adherence in adults with cystic fibrosis: a randomised controlled trial.

INTRODUCTION: Recurrent pulmonary exacerbations lead to progressive lung damage in cystic fibrosis (CF). Inhaled medications (mucoactive agents and antibiotics) help prevent exacerbations, but objectively measured adherence is low. We investigated whether a multi-component (complex) self-management intervention to support adherence would reduce exacerbation rates over 12 months. METHODS: Between October 2017 and May 2018, adults with CF (aged ≥16 years; 19 UK centres) were randomised to the intervention (data-logging nebulisers, a digital platform and behavioural change sessions with trained clinical interventionists) or usual care (data-logging nebulisers). Outcomes included pulmonary exacerbations (primary outcome), objectively measured adherence, body mass index (BMI), lung function (FEV1) and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Analyses were by intent to treat over 12 months. RESULTS: Among intervention (n=304) and usual care (n=303) participants (51% female, median age 31 years), 88% completed 12-month follow-up. Mean exacerbation rate was 1.63/year with intervention and 1.77/year with usual care (adjusted ratio 0.96; 95% CI 0.83 to 1.12; p=0.64). Adjusted mean differences (95% CI) were in favour of the intervention versus usual care for objectively measured adherence (9.5% (8.6% to 10.4%)) and BMI (0.3 (0.1 to 0.6) kg/m2), with no difference for %FEV1 (1.4 (-0.2 to 3.0)). Seven CFQ-R subscales showed no between-group difference, but treatment burden reduced for the intervention (3.9 (1.2 to 6.7) points). No intervention-related serious adverse events occurred. CONCLUSIONS: While pulmonary exacerbations and FEV1 did not show statistically significant differences, the intervention achieved higher objectively measured adherence versus usual care. The adherence difference might be inadequate to influence exacerbations, though higher BMI and lower perceived CF treatment burden were observed.

A descriptive study of samples sizes used in agreement studies published in the PubMed repository.

INTRODUCTION: A sample size justification is required for all studies and should give the minimum number of subjects to be recruited for the study to achieve its primary objective. The aim of this review is to describe sample sizes from agreement studies with continuous or categorical endpoints and different methods of assessing agreement, and to determine whether sample size justification was provided. METHODS: Data were gathered from the PubMed repository with a time interval of 28th September 2018 to 28th September 2020. The search returned 5257 studies of which 82 studies were eligible for final assessment after duplicates and ineligible studies were excluded. RESULTS: We observed a wide range of sample sizes. Forty-six studies (56%) used a continuous outcome measure, 28 (34%) used categorical and eight (10%) used both. Median sample sizes were 50 (IQR 25 to 100) for continuous endpoints and 119 (IQR 50 to 271) for categorical endpoints. Bland-Altman limits of agreement (median sample size 65; IQR 35 to 124) were the most common method of statistical analysis for continuous variables and Kappa coefficients for categorical variables (median sample size 71; IQR 50 to 233). Of the 82 studies assessed, only 27 (33%) gave justification for their sample size. CONCLUSIONS: Despite the importance of a sample size justification, we found that two-thirds of agreement studies did not provide one. We recommend that all agreement studies provide rationale for their sample size even if they do not include a formal sample size calculation.

Composite Outcomes in Clinical Prediction Modeling: Are We Trying to Predict Apples and Oranges?

Composite outcomes are widely used in clinical research. Existing literature has considered the pros and cons of composite outcomes in clinical trials, but their extensive use in clinical prediction has received much less attention. Clinical prediction assists decision-making by directing patients with higher risks of adverse outcomes toward interventions that provide the greatest benefits to those at the greatest risk. In this article, we summarize our existing understanding of the advantages and disadvantages of composite outcomes, consider how these relate to clinical prediction, and highlight the problem of key predictors having markedly different associations with individual components of the composite outcome. We suggest that a "composite outcome fallacy" may occur when a clinical prediction model is based on strong associations between key predictors and one component of a composite outcome (such as mortality) and used to direct patients toward intervention when these predictors actually have an inverse association with a more relevant component of the composite outcome (such as the use of a lifesaving intervention). We propose that clinical prediction scores using composite outcomes should report their accuracy for key components of the composite outcome and examine for inconsistencies among predictor variables.

Prognostic accuracy of triage tools for adults with suspected COVID-19 in a prehospital setting: an observational cohort study.

BACKGROUND: Tools proposed to triage patient acuity in COVID-19 infection have only been validated in hospital populations. We estimated the accuracy of five risk-stratification tools recommended to predict severe illness and compared accuracy to existing clinical decision making in a prehospital setting. METHODS: An observational cohort study using linked ambulance service data for patients attended by Emergency Medical Service (EMS) crews in the Yorkshire and Humber region of England between 26 March 2020 and 25 June 2020 was conducted to assess performance of the Pandemic Respiratory Infection Emergency System Triage (PRIEST) tool, National Early Warning Score (NEWS2), WHO algorithm, CRB-65 and Pandemic Medical Early Warning Score (PMEWS) in patients with suspected COVID-19 infection. The primary outcome was death or need for organ support. RESULTS: Of the 7549 patients in our cohort, 17.6% (95% CI 16.8% to 18.5%) experienced the primary outcome. The NEWS2 (National Early Warning Score, version 2), PMEWS, PRIEST tool and WHO algorithm identified patients at risk of adverse outcomes with a high sensitivity (>0.95) and specificity ranging from 0.3 (NEWS2) to 0.41 (PRIEST tool). The high sensitivity of NEWS2 and PMEWS was achieved by using lower thresholds than previously recommended. On index assessment, 65% of patients were transported to hospital and EMS decision to transfer patients achieved a sensitivity of 0.84 (95% CI 0.83 to 0.85) and specificity of 0.39 (95% CI 0.39 to 0.40). CONCLUSION: Use of NEWS2, PMEWS, PRIEST tool and WHO algorithm could improve sensitivity of EMS triage of patients with suspected COVID-19 infection. Use of the PRIEST tool would improve sensitivity of triage without increasing the number of patients conveyed to hospital.

Prognostic accuracy of emergency department triage tools for adults with suspected COVID-19: the PRIEST observational cohort study.

BACKGROUND: The WHO and National Institute for Health and Care Excellence recommend various triage tools to assist decision-making for patients with suspected COVID-19. We aimed to compare the accuracy of triage tools for predicting severe illness in adults presenting to the ED with suspected COVID-19. METHODS: We undertook a mixed prospective and retrospective observational cohort study in 70 EDs across the UK. We collected data from people attending with suspected COVID-19 and used presenting data to determine the results of assessment with the WHO algorithm, National Early Warning Score version 2 (NEWS2), CURB-65, CRB-65, Pandemic Modified Early Warning Score (PMEWS) and the swine flu adult hospital pathway (SFAHP). We used 30-day outcome data (death or receipt of respiratory, cardiovascular or renal support) to determine prognostic accuracy for adverse outcome. RESULTS: We analysed data from 20 891 adults, of whom 4611 (22.1%) died or received organ support (primary outcome), with 2058 (9.9%) receiving organ support and 2553 (12.2%) dying without organ support (secondary outcomes). C-statistics for the primary outcome were: CURB-65 0.75; CRB-65 0.70; PMEWS 0.77; NEWS2 (score) 0.77; NEWS2 (rule) 0.69; SFAHP (6-point rule) 0.70; SFAHP (7-point rule) 0.68; WHO algorithm 0.61. All triage tools showed worse prediction for receipt of organ support and better prediction for death without organ support. At the recommended threshold, PMEWS and the WHO criteria showed good sensitivity (0.97 and 0.95, respectively) at the expense of specificity (0.30 and 0.27, respectively). The NEWS2 score showed similar sensitivity (0.96) and specificity (0.28) when a lower threshold than recommended was used. CONCLUSION: CURB-65, PMEWS and the NEWS2 score provide good but not excellent prediction for adverse outcome in suspected COVID-19, and predicted death without organ support better than receipt of organ support. PMEWS, the WHO criteria and NEWS2 (using a lower threshold than usually recommended) provide good sensitivity at the expense of specificity. TRIAL REGISTRATION NUMBER: ISRCTN56149622.

Post-exertion oxygen saturation as a prognostic factor for adverse outcome in patients attending the emergency department with suspected COVID-19: a substudy of the PRIEST observational cohort study.

BACKGROUND: Measurement of post-exertion oxygen saturation has been proposed to assess illness severity in suspected COVID-19 infection. We aimed to determine the accuracy of post-exertional oxygen saturation for predicting adverse outcome in suspected COVID-19. METHODS: We undertook a substudy of an observational cohort study across 70 emergency departments during the first wave of the COVID-19 pandemic in the UK. We collected data prospectively, using a standardised assessment form, and retrospectively, using hospital records, from patients with suspected COVID-19, and reviewed hospital records at 30 days for adverse outcome (death or receiving organ support). Patients with post-exertion oxygen saturation recorded were selected for this analysis. We constructed receiver-operating characteristic curves, calculated diagnostic parameters, and developed a multivariable model for predicting adverse outcome. RESULTS: We analysed data from 817 patients with post-exertion oxygen saturation recorded after excluding 54 in whom measurement appeared unfeasible. The c-statistic for post-exertion change in oxygen saturation was 0.589 (95% CI 0.465 to 0.713), and the positive and negative likelihood ratios of a 3% or more desaturation were, respectively, 1.78 (1.25 to 2.53) and 0.67 (0.46 to 0.98). Multivariable analysis showed that post-exertion oxygen saturation was not a significant predictor of adverse outcome when baseline clinical assessment was taken into account (p=0.368). Secondary analysis excluding patients in whom post-exertion measurement appeared inappropriate resulted in a c-statistic of 0.699 (0.581 to 0.817), likelihood ratios of 1.98 (1.26 to 3.10) and 0.61 (0.35 to 1.07), and some evidence of additional prognostic value on multivariable analysis (p=0.019). CONCLUSIONS: Post-exertion oxygen saturation provides modest prognostic information in the assessment of selected patients attending the emergency department with suspected COVID-19. TRIAL REGISTRATION NUMBER: ISRCTN Registry (ISRCTN56149622) http://www.isrctn.com/ISRCTN28342533.

Reproducibility of Liver-to-Thorax Area Ratio Ultrasound Measurements in Congenital Diaphragmatic Hernia.

OBJECTIVES: The aim of this study was to investigate the reproducibility of a standardized method to assess the ultrasound liver-to-thoracic area ratio in fetuses with congenital diaphragmatic hernia. METHODS: We selected 24 images of 9 fetuses diagnosed with left-sided at our institution between January 2010 and December 2017. Eight operators (1 maternal-fetal medicine specialist and 7 sonographers) reviewed the selected images and assessed the ultrasound liver-to-thoracic area ratio according to a standardized protocol. We evaluated the correlation between operators using the intraclass correlation coefficient and compared agreement between the sonographers and a physician with experience in measuring the ultrasound liver-to-thoracic area ratio using a Bland-Altman analysis. RESULTS: Good intraoperator reproducibility was observed for the standardized ultrasound liver-to-thoracic area ratio (intraclass correlation coefficient, 0.78). Good agreement among sonographers and the physician was also observed for the standardized measurements (bias, 0.01; precision, 0.03; limits of agreement, -0.05 to + 0.07). CONCLUSIONS: We demonstrated that good intraoperator and interoperator reproducibility of ultrasound liver-to-thoracic area ratio assessment is feasible after standardizing the method in our center.

Standardization and reproducibility of sonographic stomach position grades in fetuses with congenital diaphragmatic hernia.

OBJECTIVES: The purpose of this study was to evaluate the reproducibility of stomach position grading in congenital diaphragmatic hernia (CDH) as proposed by Cordier et al and Basta et al after standardization of the methods at our center. METHODS: We collected sonographic images from 23 fetuses with left-sided CDH at our center from 2010 to 2018. Nine operators (one maternal fetal medicine expert and eight sonographers) reviewed the selected images and graded the stomach position according to the methods of Cordier et al and Basta et al. We assessed the interoperator agreement with Fleiss's kappa statistics. RESULTS: Overall agreement amongst all operators was moderate for both methods proposed by Cordier et al (k = 0.60, SE 0.07, 95% CI 0.47-0.73, P < .0001) and Basta et al (k = 0.60, SE 0.06, 95% CI 0.47-0.73, P < .0001). Interoperator agreement was moderate for grade 3 with the method by Cordier et al (k = 0.45, SE 0.09, 95% CI 0.27-0.64, P < .0001) and fair for grade 4 with the method by Basta et al (k = 0.33, SE 0.08, 95% CI 0.18-0.49 P < .0001). CONCLUSIONS: Our study demonstrates a fair to moderate interoperator agreement of the stomach position grading methods proposed in the literature after standardization of the methods at our center. Further multicenter studies are needed to confirm our results.

Reproducibility of Lung-to-Head Ratio Ultrasound Measurements in Congenital Diaphragmatic Hernia.

OBJECTIVES: This study investigated the reproducibility of standardization of lung-to-head ratio measurements in congenital diaphragmatic hernia (CDH) at our center among sonographers after we standardized the method. METHODS: We reviewed ultrasound images of 12 fetuses with CDH at Mayo Clinic from 2010 to 2016. Nine operators (1 maternal-fetal medicine specialist with experience in measuring the lung-to-head ratio and 8 sonographers), who were blinded to previous findings, reviewed 33 selected images from 12 fetuses with left CDH. The method for lung-to-head ratio measurement was standardized before starting the measurements. The lung-to-head ratio was assessed by different methods to obtain the lung areas: anteroposterior, longest, and area tracing. We evaluated the correlation between operators using the intraclass correlation coefficient (ICC). We also compared agreement between the sonographers and a physician with experience in measuring the lung-to-head ratio using a Bland-Altman analysis. RESULTS: The methods with the best interoperator reproducibility were the standardized anteroposterior lung-to-head ratio (ICC, 0.69) and the standardized lung-to-head ratio tracing (ICC, 0.65) compared to the longest lung-to-head ratio (ICC, 0.56). The standardized lung-to-head ratio tracing had the best agreement among sonographers and the physician (bias, 0.11; limits of agreement, -0.27 to +0.49) than the anteroposterior lung-to-head ratio (bias, 0.35; limits of agreement, -0.13 to + 0.83) and the longest lung-to-head ratio (bias, 0.27; limits of agreement, -0.35 to +0.89). CONCLUSIONS: We demonstrated that the lung-to-head ratio tracing method has high interoperator reproducibility and the best agreement among the operators at our center. Further multicenter studies are necessary to confirm our results.

Adapting the stroke therapy outcome measure for use by Multidisciplinary Teams: considering reliability.

PURPOSE: The Therapy Outcome Measure (TOM) comprises many profession and client group-specific adapted scales based on the International Classification of Functioning Model, used by different Health Care Professionals (HCPs). A new Multidisciplinary stroke TOM scale (MDT Stroke TOMs) was developed by amalgamating the relevant scales. This study aimed to develop a scale to describe patients' abilities and improve communication and collaboration within the stroke Multidisciplinary Team (MDT). The present study investigated the inter-rater and intra-rater reliability of this adaptation. MATERIALS AND METHODS: The MDT Stroke TOM Scale was developed by combining and rewording four profession-specific adapted TOM scales following iterative trials and discussions leading to an agreed version. 150 stroke Allied Health Professional (AHPs) and nurses were trained virtually in TOM and the MDT Stroke TOM Scale. Ten AHP and nursing raters from five professions evaluated ten composite stroke case studies for inter-rater reliability. Six participated in the intra-rater reliability review of the same three case studies at different time points. Reliability was quantified using intraclass correlation coefficients and measurement error using the smallest detectable change. RESULTS: There was good to excellent concordance between the raters in terms of scoring. Raters' scores were also consistent. The MDT Stroke TOMs is being used consistently across the South West London Stroke Network. CONCLUSION: The Stroke MDT TOMs is psychometrically robust and should assist with improving team work in the rehabilitation of stroke patients and their carers. Future research may use MDT Stroke TOM to promote interprofessional team working and facilitate communication in Stroke Rehabilitation.

The introduction of a new Multidisciplinary Team (MDT) Stroke Therapy Outcome measure to encourage interdisciplinary working and collaboration.One measure to complete and document for busy MDTs, which has good - excellent reliability.Early and timely MDT discussions regarding patient care and needs.Using this reliable outcome measure facilitates audit and benchmarking of services.

Implementing absolute cardiovascular disease risk assessment into pathology collection services.

BACKGROUND: Pathology services represent an ideal setting to integrate absolute cardiovascular disease (CVD) risk estimation when patients attend for routine cholesterol testing. This study aimed to explore the process of implementing CVD risk estimation into point-of-care service delivery by pathology staff to inform future implementation and sustainability. METHODS: A new service for CVD risk estimation via a self-directed screening station was implemented into 14 pathology service sites across Tasmania, Australia. Before implementation, observations at pathology services (n = 26) and semi-structured interviews were undertaken with 26 pathology staff (88% female, 77% aged 41-60 years) to identify factors that could impact implementation of the service. The process of implementation was then evaluated using participant observations and clinical trial recruitment data. Transcripts and field notes were analysed thematically according to the Medical Research Council Framework and used to develop a programme logic model to understand how the service could be adapted to be successfully integrated into routine workflow at pathology services. RESULTS: Eight key themes were identified during the pre-implementation phase as important factors that could impact upon integration of CVD risk estimation into pathology services. Themes related to factors within the organisation, including available resources, logistics and workflow, as well as having sufficient time to complete the intervention. Additional factors related to the individual motivations of staff, collaborative leadership and patient characteristics. Success of implementation varied among sites, requiring the trialling of different strategies to support uptake of the service and patient recruitment. CONCLUSIONS: Implementing CVD risk estimation into point-of-care pathology services required an understanding of the core implementation components specific to each context, and for implementation strategies to be targeted to the individual and organisational contexts. The generated programme logic model may be useful in guiding future implementation endeavours within these services and aiding the selection of apt implementation strategies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04896021, registered 19/05/2021, https://clinicaltrials.gov/study/NCT04896021.

How do general practitioners manage patient health literacy differences in cardiovascular disease prevention consultations? An interview study.

OBJECTIVES: Low health literacy is associated with worse health outcomes, including for cardiovascular disease (CVD). However, general practitioners (GPs) have limited support to identify and address patient health literacy needs in CVD prevention consultations. This study explored GPs' experiences of patient health literacy needs during CVD risk assessment and management consultations. METHODS: Semi-structured interviews with 18 GPs in Tasmania, Australia in 2021. A Framework Analysis approach was used to code transcripts to a thematic framework. RESULTS: GPs perceptions on patient health literacy informed three themes: 1. Methods of estimating health literacy; 2. GPs' perceptions about the impact of health literacy on CVD prevention including risk factor knowledge and behaviours; and 3. Strategies for communicating with patients experiencing health literacy challenges. The findings show that while no formal tools were used to assess health literacy in this sample, perceived health literacy can change GPs' communication and prevention strategies. CONCLUSION: The findings raise concerns about the equity of choices made available to patients, based on subjective perceptions of their health literacy level. PRACTICE IMPLICATION: GPs could be better supported to assess and address patient health literacy needs in CVD prevention consultations.

Prehospital early warning scores for adults with suspected sepsis: the PHEWS observational cohort and decision-analytic modelling study.

Background: Guidelines for sepsis recommend treating those at highest risk within 1 hour. The emergency care system can only achieve this if sepsis is recognised and prioritised. Ambulance services can use prehospital early warning scores alongside paramedic diagnostic impression to prioritise patients for treatment or early assessment in the emergency department. Objectives: To determine the accuracy, impact and cost-effectiveness of using early warning scores alongside paramedic diagnostic impression to identify sepsis requiring urgent treatment. Design: Retrospective diagnostic cohort study and decision-analytic modelling of operational consequences and cost-effectiveness. Setting: Two ambulance services and four acute hospitals in England. Participants: Adults transported to hospital by emergency ambulance, excluding episodes with injury, mental health problems, cardiac arrest, direct transfer to specialist services, or no vital signs recorded. Interventions: Twenty-one early warning scores used alongside paramedic diagnostic impression, categorised as sepsis, infection, non-specific presentation, or other specific presentation. Main outcome measures: Proportion of cases prioritised at the four hospitals; diagnostic accuracy for the sepsis-3 definition of sepsis and receiving urgent treatment (primary reference standard); daily number of cases with and without sepsis prioritised at a large and a small hospital; the minimum treatment effect associated with prioritisation at which each strategy would be cost-effective, compared to no prioritisation, assuming willingness to pay £20,000 per quality-adjusted life-year gained. Results: Data from 95,022 episodes involving 71,204 patients across four hospitals showed that most early warning scores operating at their pre-specified thresholds would prioritise more than 10% of cases when applied to non-specific attendances or all attendances. Data from 12,870 episodes at one hospital identified 348 (2.7%) with the primary reference standard. The National Early Warning Score, version 2 (NEWS2), had the highest area under the receiver operating characteristic curve when applied only to patients with a paramedic diagnostic impression of sepsis or infection (0.756, 95% confidence interval 0.729 to 0.783) or sepsis alone (0.655, 95% confidence interval 0.63 to 0.68). None of the strategies provided high sensitivity (> 0.8) with acceptable positive predictive value (> 0.15). NEWS2 provided combinations of sensitivity and specificity that were similar or superior to all other early warning scores. Applying NEWS2 to paramedic diagnostic impression of sepsis or infection with thresholds of > 4, > 6 and > 8 respectively provided sensitivities and positive predictive values (95% confidence interval) of 0.522 (0.469 to 0.574) and 0.216 (0.189 to 0.245), 0.447 (0.395 to 0.499) and 0.274 (0.239 to 0.313), and 0.314 (0.268 to 0.365) and 0.333 (confidence interval 0.284 to 0.386). The mortality relative risk reduction from prioritisation at which each strategy would be cost-effective exceeded 0.975 for all strategies analysed. Limitations: We estimated accuracy using a sample of older patients at one hospital. Reliable evidence was not available to estimate the effectiveness of prioritisation in the decision-analytic modelling. Conclusions: No strategy is ideal but using NEWS2, in patients with a paramedic diagnostic impression of infection or sepsis could identify one-third to half of sepsis cases without prioritising unmanageable numbers. No other score provided clearly superior accuracy to NEWS2. Research is needed to develop better definition, diagnosis and treatments for sepsis. Study registration: This study is registered as Research Registry (reference: researchregistry5268). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/136/10) and is published in full in Health Technology Assessment; Vol. 28, No. 16. See the NIHR Funding and Awards website for further award information.

Sepsis is a life-threatening condition in which an abnormal response to infection causes heart, lung or kidney failure. People with sepsis need urgent treatment. They need to be prioritised at the emergency department rather than waiting in the queue. Paramedics attempt to identify people with possible sepsis using an early warning score (based on simple measurements, such as blood pressure and heart rate) alongside their impression of the patient's diagnosis. They can then alert the hospital to assess the patient quickly. However, an inaccurate early warning score might miss cases of sepsis or unnecessarily prioritise people without sepsis. We aimed to measure how accurately early warning scores identified people with sepsis when used alongside paramedic diagnostic impression. We collected data from 71,204 people that two ambulance services transported to four different hospitals in 2019. We recorded paramedic diagnostic impressions and calculated early warning scores for each patient. At one hospital, we linked ambulance records to hospital records and identified who had sepsis. We then calculated the accuracy of using the scores alongside diagnostic impression to diagnose sepsis. Finally, we used modelling to predict how many patients (with and without sepsis) paramedics would prioritise using different strategies based on early warning scores and diagnostic impression. We found that none of the currently available early warning scores were ideal. When they were applied to all patients, they prioritised too many people. When they were only applied to patients whom the paramedics thought had infection, they missed many cases of sepsis. The NEWS2, score, which ambulance services already use, was as good as or better than all the other scores we studied. We found that using the NEWS2, score in people with a paramedic impression of infection could achieve a reasonable balance between prioritising too many patients and avoiding missing patients with sepsis.

Navigating the maze of osteoarthritis treatment: A qualitative study exploring the experience of individuals with osteoarthritis in Tasmania, Australia.

OBJECTIVE: Using a qualitative design this study aimed to (1) explore the experience of people living with osteoarthritis (OA), (2) gain an understanding of their navigation of the health system and, (3) explore their opinions on the role of exercise and joint replacement surgery for the management of OA. METHODS: Purposive sampling was used to recruit 26 participants with knee OA, aged 45 years and over, from Tasmania, Australia. Semi-structured interviews were audio-recorded, transcribed, coded, and thematically analysed to document participant understanding and experience of OA and their opinions on the role of exercise and surgery in managing OA. RESULTS: Of the 26 participants, 80% (n = 21) were female with a mean age of 66 years. The main theme identified was that individuals with knee OA were navigating a maze of OA treatments. Three related subthemes were that participants: (i) perceived their general practitioner did not have an ongoing role in their OA care, (ii) self-directed their management and, (iii) sampled from a 'smorgasbord' of treatment options, including low-value care options. Two other major themes were: the role of exercise for OA management, and surgery as a last resort. CONCLUSION: Our findings suggest that OA patients may not be choosing consistent, high-value care for their OA. This highlights the importance of an evidence-based multi-disciplinary approach to guide patients to self-manage their OA and support their navigation of the health system. Reducing emphasis on the pathway to surgery and streamlining access to conservative management strategies may assist people to receive high-value care.

Influence of adaptive analysis on unnecessary patient recruitment: reanalysis of the RATPAC trial.

STUDY OBJECTIVE: Recruitment to clinical trials is a challenging but essential activity in emergency medicine. Conventional fixed-sample trials may continue to recruit patients after efficacy has been demonstrated or when further recruitment is futile. Adaptive trials make use of emerging information to modify aspects of a trial or terminate it prematurely, potentially resulting in savings in terms of sample size, time, and cost. We aim to use sequential testing procedures to reanalyze data from a fixed-sample trial, the Randomised Assessment of Treatment Using Panel Assay of Cardiac Markers (RATPAC) trial, and investigate the potential for adaptive designs to reduce unnecessary recruitment. METHODS: The trial was reanalyzed with a triangular group sequential design, with interim analyses planned every 3 months. Patients were analyzed in the order in which they entered the original trial. RESULTS: We found that the RATPAC trial could potentially have stopped 1 year earlier, with 722 patients enrolled compared with 2,243 patients in the original trial, making a potential saving of approximately $390,000. Estimates of effect were similar, and the qualitative conclusions of the original and group sequential RATPAC trials were in agreement. However, the group sequential approach is not without limitations and would have resulted in less precise estimates of effect and less information available for the subsequent evaluation of secondary endpoints. CONCLUSION: Sequential designs are well suited in emergency medicine because of the rapidly obtained outcomes and the need to avoid unnecessary recruitment. We recommend that group sequential designs be considered for clinical trials in emergency medicine.

Correct use and ease-of-use of placebo ELLIPTA dry-powder inhaler in adult patients with chronic obstructive pulmonary disease.

BACKGROUND: Inhaler technique errors are common in chronic obstructive pulmonary disease (COPD) treatment, potentially leading to poor disease management. Our pooled analysis approach assessed correct use and ease-of-use of a placebo ELLIPTA dry-powder inhaler (DPI) in patients with COPD. METHODS: Adults with COPD from open-label/non-blinded studies evaluating a placebo ELLIPTA DPI and reporting outcomes of correct use (based on the ELLIPTA DPI patient information leaflet [PIL]) and/or ease-of-use were included. Correct use and ease-of use at study end were primary and secondary endpoints, respectively. Data from patients in the placebo ELLIPTA DPI arm of each study were pooled, and the intent-to-treat (ITT) population was used for all analyses. RESULTS: Four placebo ELLIPTA DPI studies, reporting correct use (n = 4) and ease-of-use (n = 2), were included in the analysis. The ITT population comprised 1232 patients (mean age 66.2 years). For the primary endpoint, 80.1% (n = 975/1217) of patients demonstrated correct use at study end (95% confidence interval [CI]: 77.8%-82.3%). For the secondary endpoint, 95.7% (n = 797/833) of patients rated placebo ELLIPTA DPI use "easy"/"very easy" at study end (95% CI: 94.1%-97.0%). Correct use and "easy"/"very easy" user ratings remained high across younger (40-64 years) and older (≥65 years) age groups. CONCLUSIONS: Across age groups, most patients used the placebo ELLIPTA DPI correctly and rated it "easy"/"very easy" to use. Consistent with the Global Initiative for Chronic Obstructive Lung Disease 2021 report, our findings emphasize that proper training and clear instructions on PILs are important for optimal inhaler use.

Accuracy of emergency medical service telephone triage of need for an ambulance response in suspected COVID-19: an observational cohort study.

OBJECTIVE: To assess accuracy of emergency medical service (EMS) telephone triage in identifying patients who need an EMS response and identify factors which affect triage accuracy. DESIGN: Observational cohort study. SETTING: Emergency telephone triage provided by Yorkshire Ambulance Service (YAS) National Health Service (NHS) Trust. PARTICIPANTS: 12 653 adults who contacted EMS telephone triage services provided by YAS between 2 April 2020 and 29 June 2020 assessed by COVID-19 telephone triage pathways were included. OUTCOME: Accuracy of call handler decision to dispatch an ambulance was assessed in terms of death or need for organ support at 30 days from first contact with the telephone triage service. RESULTS: Callers contacting EMS dispatch services had an 11.1% (1405/12 653) risk of death or needing organ support. In total, 2000/12 653 (16%) of callers did not receive an emergency response and they had a 70/2000 (3.5%) risk of death or organ support. Ambulances were dispatched to 4230 callers (33.4%) who were not conveyed to hospital and did not deteriorate. Multivariable modelling found variables of older age (1 year increase, OR: 1.05, 95% CI: 1.04 to 1.05) and presence of pre-existing respiratory disease (OR: 1.35, 95% CI: 1.13 to 1.60) to be predictors of false positive triage. CONCLUSION: Telephone triage can reduce ambulance responses but, with low specificity. A small but significant proportion of patients who do not receive an initial emergency response deteriorated. Research to improve accuracy of EMS telephone triage is needed and, due to limitations of routinely collected data, this is likely to require prospective data collection.