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.

DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis - a randomised controlled trial.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in death, usually from respiratory failure, within 2-3 years of symptom onset. Non-invasive ventilation (NIV) is a treatment that when given to patients in respiratory failure leads to improved survival and quality of life. Diaphragm pacing (DP), using the NeuRx/4(®) diaphragm pacing system (DPS)™ (Synapse Biomedical, Oberlin, OH, USA), is a new technique that may offer additional or alternative benefits to patients with ALS who are in respiratory failure. OBJECTIVE: The Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis (DiPALS) trial evaluated the effect of DP on survival over the study duration in patients with ALS with respiratory failure. DESIGN: The DiPALS trial was a multicentre, parallel-group, open-label, randomised controlled trial incorporating health economic analyses and a qualitative longitudinal substudy. PARTICIPANTS: Eligible participants had a diagnosis of ALS (ALS laboratory-supported probable, clinically probable or clinically definite according to the World Federation of Neurology revised El Escorial criteria), had been stabilised on riluzole for 30 days, were aged ≥ 18 years and were in respiratory failure. We planned to recruit 108 patients from seven UK-based specialist ALS or respiratory centres. Allocation was performed using 1 : 1 non-deterministic minimisation. INTERVENTIONS: Participants were randomised to either standard care (NIV alone) or standard care (NIV) plus DP using the NeuRX/4 DPS. MAIN OUTCOME MEASURES: The primary outcome was overall survival, defined as the time from randomisation to death from any cause. Secondary outcomes were patient quality of life [assessed by European Quality of Life-5 Dimensions, three levels (EQ-5D-3L), Short Form questionnaire-36 items and Sleep Apnoea Quality of Life Index questionnaire]; carer quality of life (EQ-5D-3L and Caregiver Burden Inventory); cost-utility analysis and health-care resource use; tolerability and adverse events. Acceptability and attitudes to DP were assessed in a qualitative substudy. RESULTS: In total, 74 participants were randomised into the trial and analysed, 37 participants to NIV plus pacing and 37 to standard care, before the Data Monitoring and Ethics Committee advised initial suspension of recruitment (December 2013) and subsequent discontinuation of pacing (on safety grounds) in all patients (June 2014). Follow-up assessments continued until the planned end of the study in December 2014. The median survival (interquartile range) was 22.5 months (lower quartile 11.8 months; upper quartile not reached) in the NIV arm and 11.0 months (6.7 to 17.0 months) in the NIV plus pacing arm, with an adjusted hazard ratio of 2.27 (95% confidence interval 1.22 to 4.25; p = 0.01). CONCLUSIONS: Diaphragmatic pacing should not be used as a routine treatment for patients with ALS in respiratory failure. FUTURE WORK: It may be that certain population subgroups benefit from DP. We are unable to explain the mechanism behind the excess mortality in the pacing arm, something the small trial size cannot help address. Future research should investigate the mechanism by which harm or benefit occurs further. TRIAL REGISTRATION: Current Controlled Trials ISRCTN53817913. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 45. See the HTA programme website for further project information. Additional funding was provided by the Motor Neurone Disease Association of England, Wales and Northern Ireland.

Preventing and lessening exacerbations of asthma in school-age children associated with a new term (PLEASANT): study protocol for a cluster randomised control trial.

BACKGROUND: Within the UK, during September, there is a pronounced increase in the number of unscheduled medical contacts by school-aged children (4-16 years) with asthma. It is thought that that this might be caused by the return back to school after the summer holidays, suddenly mixing with other children again and picking up viruses which could affect their asthma. There is also a drop in the number of prescriptions administered in August. It is possible therefore that children might not be taking their medication as they should during the summer contributing to them becoming ill when they return to school.It is hoped that a simple intervention from the GP to parents of children with asthma at the start of the summer holiday period, highlighting the importance of maintaining asthma medication can help prevent increased asthma exacerbation, and unscheduled NHS appointments, following return to school in September. METHODS/DESIGN: PLEASANT is a cluster randomised trial. A total of 140 General Practices (GPs) will be recruited into the trial; 70 GPs randomised to the intervention and 70 control practices of "usual care". An average practice is expected to have approximately 100 children (aged 4-16 with a diagnosis of asthma) hence observational data will be collected on around 14000 children over a 24-month period. The Clinical Practice Research Datalink will collect all data required for the study which includes diagnostic, prescription and referral data. DISCUSSION: The trial will assess whether the intervention can reduce exacerbation of asthma and unscheduled medical contacts in school-aged children associated with the return to school after the summer holidays. It has the potential to benefit the health and quality of life of children with asthma while also improving the effectiveness of NHS services by reducing NHS use in one of the busiest months of the year.An exploratory health economic analysis will gauge any cost saving associated with the intervention and subsequent impacts on quality of life. If results for the intervention are positive it is hoped that this could be adopted as part of routine care management of childhood asthma in general practice. TRIAL REGISTRATION: Current controlled trials: ISRCTN03000938 (assigned 19/10/12) http://www.controlled-trials.com/ISRCTN03000938/. UKCRN ID: 13572.

Protocol for diaphragm pacing in patients with respiratory muscle weakness due to motor neurone disease (DiPALS): a randomised controlled trial.

BACKGROUND: Motor neurone disease (MND) is a devastating illness which leads to muscle weakness and death, usually within 2-3 years of symptom onset. Respiratory insufficiency is a common cause of morbidity, particularly in later stages of MND and respiratory complications are the leading cause of mortality in MND patients. Non Invasive Ventilation (NIV) is the current standard therapy to manage respiratory insufficiency. Some MND patients however do not tolerate NIV due to a number of issues including mask interface problems and claustrophobia. In those that do tolerate NIV, eventually respiratory muscle weakness will progress to a point at which intermittent/overnight NIV is ineffective. The NeuRx RA/4 Diaphragm Pacing System was originally developed for patients with respiratory insufficiency and diaphragm paralysis secondary to stable high spinal cord injuries. The DiPALS study will assess the effect of diaphragm pacing (DP) when used to treat patients with MND and respiratory insufficiency. METHOD/DESIGN: 108 patients will be recruited to the study at 5 sites in the UK. Patients will be randomised to either receive NIV (current standard care) or receive DP in addition to NIV. Study participants will be required to complete outcome measures at 5 follow up time points (2, 3, 6, 9 and 12 months) plus an additional surgery and 1 week post operative visit for those in the DP group. 12 patients (and their carers) from the DP group will also be asked to complete 2 qualitative interviews. DISCUSSION: The primary objective of this trial will be to evaluate the effect of Diaphragm Pacing (DP) on survival over the study duration in patients with MND with respiratory muscle weakness. The project is funded by the National Institute for Health Research, Health Technology Assessment (HTA) Programme (project number 09/55/33) and the Motor Neurone Disease Association and the Henry Smith Charity. TRIAL REGISTRATION: Current controlled trials ISRCTN53817913. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.