Recent Outcomes Research in Helicopter Emergency Medical Services: A Scoping Review of Publication Year 2023 Additions to the Helicopter Outcomes Assessment Research Database.

OBJECTIVE: The purpose of this scoping review was to identify and characterize helicopter emergency medical services (HEMS) outcomes literature from 2023, with the goal of describing updates to the Critical Care Transport Collaborative Outcomes Research Effort HEMS Outcomes Assessment Research Database (HOARD). METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, a multireviewer approach was used to source and review articles published or in preprint databases from 2023. The articles included assessed a patient-centered outcome for HEMS versus a non-HEMS control group. Article characteristics included the journal impact factor (JIF), diagnostic group (trauma or nontrauma), and geographic origin. Categoric analyses comparing 2023 studies with HOARD studies from the previous decade (2013-2022) were executed with the Fisher exact test; nonnormal JIF data were described using median and interquartile range and analyzed (vs 2013-2022) with rank sum testing. RESULTS: Of the initial records (N = 4,486), 4,410 were screened out, leaving 76 for full-text review. Of these, 58 were discarded, and 18 were classified as eligible for addition to HOARD. Most studies (14/18, 78%) focused on trauma, and an equally high proportion (14/18, 78%) came from North America. The median JIF was 2.4 (interquartile range, 1.2-3.6). Compared with HOARD studies from the previous decade, 2023 studies were similar with respect to diagnostic focus (P = .779), geographic origin (P = .171), and JIF (P = .531). CONCLUSION: This scoping review provides information on 18 HEMS outcomes studies new to the evidence base in 2023.

Success with incrementally faster times to endovascular therapy (SWIFT-EVT): A systematic review and meta-analysis.

BACKGROUND: A major systematic review and meta-analysis assessing trial data through 2014 (the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials, HERMES) demonstrated that particularly over the initial six hours of acute ischemic stroke (AIS), rapid performance of endovascular therapy (EVT) markedly improves outcomes. The current analysis, Success with Incrementally Faster Times to EVT (SWIFT-EVT), aimed to provide an updated metric summarizing latest estimates for modified Rankin Scale (mRS) improvements accrued by streamlining time to EVT. METHODS: A systematic review and meta-analysis was conducted using electronic databases. Eligible studies reported a time-benefit slope with times from AIS onset (or time last known normal) to EVT commencement; the predictor was onset-to-groin (OTG) time. Primary and secondary outcomes were 90-day functional independence (mRS 0-2) and 90-day excellent function (mRS 0-1), respectively. RESULTS: Five studies were included. Results showed increased change of good outcome with each hour of pre-EVT time savings for mRS 0-2 for 0-270' (OR 1.25, 95 % CI 1.16-1.35, I2 40 %) and 271-360' time frame (1.22, 95 % CI 1.12-1.33, I2 58 %). For the studies assessing mRS 0-1, estimates were found appropriate for both the 0-270' time frame (OR 1.34, 95 % CI 1.19-1.51, I2 27 %) and the 271-360' time frame (OR 1.20, 95 % CI 1.03-1.38, I2 60 %). CONCLUSIONS: Each hour saved from AIS onset to EVT start is associated with a 22-25 % increased odds of achieving functional independence, a useful metric to inform patient-specific and systems planning decisions.

Oxygen-enhanced MRI detects incidence, onset and heterogeneity of radiation-induced hypoxia modification in HPV-associated oropharyngeal cancer.

PURPOSE: Hypoxia mediates treatment resistance in solid tumors. We evaluated if oxygen-enhanced (OE)-MRI-derived hypoxic volume (HVMRI) is repeatable and can detect radiotherapy-induced hypoxia modification in HPV-associated oropharyngeal head and neck squamous cell cancer (HNSCC). EXPERIMENTAL DESIGN: 27 patients were recruited prospectively between March 2021 and January 2024. HVMRI was measured in primary and nodal tumors prior to standard-of-care (chemo)radiotherapy then at weeks 2 and 4 (W2, W4) into therapy. Two pre-treatment scans assessed biomarker within-subject coefficient of variation (wCV) and repeatability coefficient (RC). Cohort treatment response was measured using mixed-effects modelling. Responding lesions were identified by comparing HVMRI change to RC limits of agreement (LOA). RESULTS: OE-MRI identified hypoxia in all lesions. HVMRI wCV was 24.6% and RC LOA were -45.7% to 84.1%. Cohort median pre-treatment HVMRI of 11.3 cm3 reduced to 6.9 cm3 at W2 and 5.9 cm3 at W4 (both p < 0.001). HVMRI was reduced in 54.5% of individual lesions by W2 and in 88.2% by W4. All lesions with W2 hypoxia reduction showed persistent modification at W4. HVMRI reduced in some lesions that showed no overall volume change. Hypoxia modification was discordant between primary and nodal tumors in 50.0% of patients. CONCLUSIONS: Radiation-induced hypoxia modification can occur as early as W2, but onset varies between patients and was not necessarily associated with overall size change. Half of all patients had discordant changes in primary and nodal tumors. These findings have implications for patient selection and timing of dose de-escalation strategies in HPV-associated oropharyngeal carcinoma.

Descriptive Epidemiology of Female Suicides by Race and Ethnicity.

Each year millions of females develop serious mental illnesses (SMI), which are major risk factors for suicides. Using the Web-Based Injury Statistics Query and Reporting System (WISQARS) for the years 2000, 2010 and 2020, we found in 2020 9,428 females (almost 190/week) committed suicide, losing 328,653 years off potential life before age 80 years. There were pronounced increases in female suicides from 2000 to 2020 across all racial and ethnic groups. The greatest number of suicides were in non-Hispanic white females, but the highest rate of suicides was in non-Hispanic American Indians /Alaska Natives, and in females 15-24 years of age. The West had the highest female suicide rates, with methods used to commit suicides varying by census regions and race and ethnicity. Suffocation to commit suicide increased for most racial and ethnic groups and poisonings decreased for most groups between 2000 and 2020, These underscore the need for targeted primary prevention of suicides for females based on age, geographic location and method of suicide, to mitigate female suicides improved access (e.g. geographically and financially) to mental health care services is essential.

Increased survival for resuscitated Utstein-comparator group patients conveyed directly to cardiac arrest centres in a large rural and suburban population in England.

AIM: The cohort of patients in which cardiac arrest centres (CAC) in rural and suburban populations confer the greatest survival benefit remains unclear. The aim of this study was to assess whether the transfer of resuscitated Utstein-comparator out-of-hospital cardiac arrest (OHCA) patients direct to a CAC was associated with improved survival to hospital discharge compared to patients conveyed to non-specialist centres. METHODS: A consecutive sample of adult (≥18 years old) Utstein-comparator patients (witnessed collapse and initial shockable rhythm) were included from the East of England Ambulance Service NHS Trust Utstein resuscitation registry; 2018-2022. Logistic regression was used to compare survival to discharge in patients transported to CACs compared with patients transported to non-specialist centres. RESULTS: During the study period, resuscitation was attempted in 18,276 OHCA patients. N = 2448 (13.4%) met the Utstein-comparator definition and 1151 patients were included in the final analysis; per protocol. Survival was greater for patients conveyed directly to a CAC (n = 768, 60.7%) compared to non-specialist centres (n = 383, 47.3%); adjusted OR 1.44 (95%CI 1.07-1.94),p = 0.017. Amongst the centres analysed in this study, there was significant inter-hospital variability in survival between CACs (p = 0.017). There was no association between patient volume and survival (p = 0.850). CONCLUSION: Direct transport to a cardiac arrest centre was associated with a 44% increase in the odds of survival compared to conveyance to a non-specialist centre for resuscitated adult patients presenting with witnessed collapse and initial shockable OHCA rhythm.

The association between prehospital post-return of spontaneous circulation core temperature and survival after out-of-hospital cardiac arrest.

BACKGROUND AND IMPORTANCE: Following the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA), a low body temperature on arrival at the hospital and on admission to the ICU is reportedly associated with increased mortality. Whether this association exists in the prehospital setting, however, is unknown. OBJECTIVE: The objective of this study was to investigate whether the initial, prehospital core temperature measured post-ROSC is independently associated with survival to hospital discharge in adult patients following OHCA. DESIGN, SETTING AND PARTICIPANTS: This retrospective observational study was conducted at East Anglian Air Ambulance, a physician-paramedic staffed Helicopter Emergency Medical Service in the East of England, UK. Adult OHCA patients attended by East Anglian Air Ambulance from 1 February 2015 to 30 June 2023, who had post-ROSC oesophageal temperature measurements were included. OUTCOME MEASURE AND ANALYSIS: The primary outcome measure was survival to hospital discharge. Core temperature was defined as the first oesophageal temperature recorded following ROSC. Multivariable logistic regression evaluated the adjusted association between core temperature and survival to hospital discharge. MAIN RESULTS: Resuscitation was attempted in 3990 OHCA patients during the study period, of which 552 patients were included in the final analysis. The mean age was 61 years, and 402 (72.8%) patients were male. Among them, 194 (35.1%) survived to hospital discharge. The mean core temperature was lower in nonsurvivors compared with those who survived hospital discharge; 34.6 and 35.2 °C, respectively (mean difference, -0.66; 95% CI, -0.87 to -0.44; P  < 0.001). The adjusted odds ratio for survival was 1.41 (95% CI, 1.09-1.83; P  = 0.01) for every 1.0 °C increase in core temperature between 32.5 and 36.9 °C. CONCLUSION: In adult patients with ROSC following OHCA, early prehospital core temperature is independently associated with survival to hospital discharge.

The incidence of admission ionised hypocalcaemia in paediatric major trauma-A systematic review and meta-analysis.

OBJECTIVES: In adult major trauma patients admission hypocalcaemia occurs in approximately half of cases and is associated with increased mortality. However, data amongst paediatric patients are limited. The objectives of this review were to determine the incidence of admission ionised hypocalcaemia in paediatric major trauma patients and to explore whether hypocalcaemia is associated with adverse outcomes. METHODS: A systematic review was conducted following PRISMA guidelines. All studies including major trauma patients <18 years old, with an ionised calcium concentration obtained in the Emergency Department (ED) prior to the receipt of blood products in the ED were included. The primary outcome was incidence of ionised hypocalcaemia. Random-effects Sidik-Jonkman modelling was executed for meta-analysis of mortality and pH difference between hypo- and normocalcaemia, Odds ratio (OR) was the reporting metric for mortality. The reporting metric for the continuous variable of pH difference was Glass' D (a standardized difference). Results are reported with 95% confidence intervals (CIs) and significance was defined as p <0.05. RESULTS: Three retrospective cohort studies were included. Admission ionised hypocalcaemia definitions ranged from <1.00 mmol/l to <1.16 mmol/l with an overall incidence of 112/710 (15.8%). For mortality, modelling with low heterogeneity (I2 39%, Cochrane's Q p = 0.294) identified a non-significant (p = 0.122) estimate of hypocalcaemia increasing mortality (pooled OR 2.26, 95% CI 0.80-6.39). For the pH difference, meta-analysis supported generation of a pooled effect estimate (I2 57%, Cochrane's Q p = 0.100). The effect estimate of the mean pH difference was not significantly different from null (p = 0.657), with the estimated pH slightly lower in hypocalcaemia (Glass D standardized mean difference -0.08, 95% CI -0.43 to 0.27). CONCLUSION: Admission ionised hypocalcaemia was present in at least one in six paediatric major trauma patients. Ionised hypocalcaemia was not identified to have a statistically significant association with mortality or pH difference.

Service Evaluation of MyChristie-MyHealth, an Electronic Patient-Reported Outcome Measure Integrated Into Clinical Cancer Care.

PURPOSE: Electronic patient-reported outcome measures (ePROMs) are digitalized health questionnaires used to gauge patients' subjective experience of health and disease. They are becoming prevalent in cancer care and have been linked to a host of benefits including improved survival. MyChristie-MyHealth is the ePROM established at the Christie NHS Foundation Trust in 2019. We conducted an evaluation of this service to understand user experiences, as well as strategies to improve its functioning. METHODS: Data collection: Patients who had opted never to complete MyChristie-MyHealth (n = 87), and those who had completed at least one (n = 87) were identified. Demographic data included age, sex, ethnicity, postcode, diagnosis, treatment intent, and trial status. Semistructured interviews were held with noncompleters (n = 30) and completers (n = 31) of MyChristie-MyHealth, as well as clinician users (n = 6), covering themes such as accessibility, acceptability and usefulness, and open discourse on ways in which the service could be improved. RESULTS: Noncompleters of MyChristie-MyHealth were older (median age 72 v 66 years, P = .005), receiving treatment with curative rather than palliative intent (odds ratio [OR], 1.45; P = .045), and less likely to be enrolled on a clinical trial (OR, 0.531; P = .011). They were less likely to own a smartphone (33% v 97%) or have reliable Internet access (45% v 100%). Satisfaction with MyChristie-MyHealth was high in both groups: 93% (n = 29) of completers and 87% (n = 26) noncompleters felt generally happy to complete. Completers of MyChristie-MyHealth wanted their results to be acknowledged by their clinicians. Clinicians wanted results to be displayed in a more user-friendly way. CONCLUSION: We have broadly characterized noncompleters of the Christie ePROM to identify those in need of extra support or encouragement in the clinic. An action plan resulting from this review has been compiled and will inform the future development of MyChristie-MyHealth.

Prehospital invasive arterial blood pressure monitoring in critically ill patients attended by a UK helicopter emergency medical service- a retrospective observational review of practice.

BACKGROUND: Accurate haemodynamic monitoring in the prehospital setting is essential. Non-invasive blood pressure measurement is susceptible to vibration and motion artefact, especially at extremes of hypotension and hypertension: invasive arterial blood pressure (IABP) monitoring is a potential solution. This study describes the largest series to date of cases of IABP monitoring being initiated prehospital. METHODS: This retrospective observational study was conducted at East Anglian Air Ambulance (EAAA), a UK helicopter emergency medical service (HEMS). It included all patients attended by EAAA who underwent arterial catheterisation and initiation of IABP monitoring between 1st February 2015 and 20th April 2023. The following data were retrieved for all patients: sex; age; aetiology (medical cardiac arrest, other medical emergency, trauma); site of arterial cannulation; operator role (doctor/paramedic); time of insertion and, where applicable, times of pre-hospital emergency anaesthesia, and return of spontaneous circulation following cardiac arrest. Descriptive analyses were performed to characterise the sample. RESULTS: 13,556 patients were attended: IABP monitoring was initiated in 1083 (8.0%) cases, with a median age 59 years, of which 70.8% were male. 546 cases were of medical cardiac arrest: in 22.4% of these IABP monitoring was initiated during cardiopulmonary resuscitation. 322 were trauma cases, and the remaining 215 were medical emergencies. The patients were critically unwell: 981 required intubation, of which 789 underwent prehospital emergency anaesthesia; 609 received vasoactive medication. In 424 cases IABP monitoring was instituted en route to hospital. CONCLUSION: This study describes over 1000 cases of prehospital arterial catheterisation and IABP monitoring in a UK HEMS system and has demonstrated feasibility at scale. The high-fidelity of invasive arterial blood pressure monitoring with the additional benefit of arterial blood gas analysis presents an attractive translation of in-hospital critical care to the prehospital setting.

"Why am I still suffering?": Experience of long-term fatigue and neurocognitive changes in oropharyngeal cancer survivors following (chemo)radiotherapy.

Background: Late effects of cancer treatment, such as neurocognitive deficits and fatigue, can be debilitating. Other than head and neck-specific functional deficits such as impairments in swallowing and speech, little is known about survivorship after oropharyngeal cancer. This study examines the lived experience of fatigue and neurocognitive deficits in survivors of oropharyngeal squamous cell cancer and impact on their daily lives. Methods: This work is part of the multicentre mixed method ROC-oN study (Radiotherapy for Oropharyngeal Cancer and impact on Neurocognition), evaluating fatigue and neurocognitive function in patients following radiotherapy +/- chemotherapy for oropharyngeal cancer and impact on quality of life. Semi-structured interviews were conducted in adults treated with radiotherapy (+/-chemotherapy) for oropharyngeal squamous cell carcinoma >/=24 months from completing treatment. Reflexive thematic analysis performed. Results: 21 interviews (11 men and 10 women; median age 58 years and median time post-treatment 5 years) were conducted and analysed, yielding six themes: (1) unexpected burden of fatigue, (2) noticing changes in neurocognitive function, (3) the new normal, (4) navigating changes, (5)insufficient awareness and (6)required support. Participants described fatigue that persisted beyond the acute post-treatment period and changes in neurocognitive abilities across several domains. Paid and unpaid work, emotions and mood were impacted. Participants described navigating the new normal by adopting self-management strategies and accepting external support. They reported lack of recognition of these late effects, being poorly informed and being unprepared. Follow-up services were thought to be inadequate. Conclusions: Fatigue and neurocognitive impairment were frequently experienced by survivors of oropharyngeal cancer, at least two years after treatment. Patients felt ill-prepared for these late sequelae, highlighting opportunities for improvement of patient information and support services.

Agreement between arterial and end-tidal carbon dioxide in adult patients admitted with serious traumatic brain injury.

BACKGROUND: Low-normal levels of arterial carbon dioxide (PaCO2) are recommended in the acute phase of traumatic brain injury (TBI) to optimize oxygen and CO2 tension, and to maintain cerebral perfusion. End-tidal CO2 (ETCO2) may be used as a surrogate for PaCO2 when arterial sampling is less readily available. ETCO2 may not be an adequate proxy to guide ventilation and the effects on concomitant injury, time, and the impact of ventilatory strategies on the PaCO2-ETCO2 gradient are not well understood. The primary objective of this study was to describe the correlation and agreement between PaCO2 and ETCO2 in intubated adult trauma patients with TBI. METHODS: This study was a retrospective analysis of prospectively-collected data of intubated adult major trauma patients with serious TBI, admitted to the East of England regional major trauma centre; 2015-2019. Linear regression and Welch's test were performed on each cohort to assess correlation between paired PaCO2 and ETCO2 at 24-hour epochs for 120 hours after admission. Bland-Altman plots were constructed at 24-hour epochs to assess the PaCO2-ETCO2 agreement. RESULTS: 695 patients were included, with 3812 paired PaCO2 and ETCO2 data points. The median PaCO2-ETCO2 gradient on admission was 0.8 [0.4-1.4] kPa, Bland Altman Bias of 0.96, upper (+2.93) and lower (-1.00), and correlation R2 0.149. The gradient was significantly greater in patients with TBI plus concomitant injury, compared to those with isolated TBI (0.9 [0.4-1.5] kPa vs. 0.7 [0.3-1.1] kPa, p<0.05). Across all groups the gradient reduced over time. Patients who died within 30 days had a larger gradient on admission compared to those who survived; 1.2 [0.7-1.9] kPa and 0.7 [0.3-1.2] kPa, p<0.005. CONCLUSIONS: Amongst adult patients with TBI, the PaCO2-ETCO2 gradient was greater than previously reported values, particularly early in the patient journey, and when associated with concomitant chest injury. An increased PaCO2-ETCO2 gradient on admission was associated with increased mortality.

Firearm Mortality of Non-Hispanic Black Americans by Law Enforcement, 2011-2020.

Law enforcement officers in the U.S. are more likely to use lethal force against non-Hispanic Black citizens than on their non-Hispanic White counterparts. The purpose of this study was to assess estimates of the national prevalence of fatal firearm violence by law enforcement officers (LEOs) against non-Hispanic Black Americans. The Web-Based Injury Statistics Query and Reporting System (WISQARS) from the Centers for Disease Control and Prevention (CDC) were analyzed using descriptive statistics and joinpoint regression from 2011 to 2020. During the decade (2011-2020) LEOs fatally shot 5,073 citizens and 1,170 were non-Hispanic Black (23%). The vast majority (96%) were males and two-thirds (66%) of those killed were ages 20-39 years. The region with the highest number of LEO fatal shootings was the Western U.S. Firearm deaths of non-Hispanic Blacks were the dominant (82%) method of LEO-induced deaths. Non-Hispanic Black Americans experience LEO firearm-related injuries and deaths at a much higher rate than their non-Hispanic White counterparts. In the context of the racial disparities among people who die following LEO-related gunshot wounds, changes to police training systems and an examination of implicit biases among LEOs should be investigated as the next step in reducing the use of lethal force practices.

Association of follow-up imaging frequency with temporal incidence and patterns of distant failure following (chemo) radiotherapy for HPV related oropharyngeal cancer.

OBJECTIVES: Emerging data supports radical intent therapy for oligometastatic (OM) relapsed human papilloma virus (HPV+) related oropharyngeal cancer (OPC). We assess the association of follow-up imaging frequency amongst HPV + OPC, with temporal and spatial patterns of distant relapse, to inform rationalisation of routine post-treatment imaging. MATERIALS AND METHODS: A retrospective single centre cohort study was carried out of consecutive HPV + OPC patients treated with radical intent (chemo)radiotherapy ((CT)RT) between 2011 and 2019. OM state was defined as ≤ 5 metastasis, none larger than 3 cm (OMs) or, if interval from last negative surveillance imaging > 6-months, then ≤ 10 metastasis, none larger than 5 cm, (OMp). Patients not meeting OMs / OMp criteria were deemed to have incurable diffuse metastatic disease (DMdiffuse). RESULTS: 793 HPV-OPC patients were identified with median follow-up 3.15years (range 0.2-8.9). 52 (6.6 %) patients had radiologically identified DM at first failure and were considered for analysis. The median time to recurrence was 15.1 months (range: 2.6-63 months). 87 % of distant metastasis (DM) occurred in the first two years after treatment. Twenty-seven (52 %) patients had OM (OMs or OMp) at time of failure, with 31 % having OMs. The median time from completion of treatment to diagnosis of DMdiffuse vs OM was 22.2 months (range: 2.6-63.1 months) vs 11.6 months (range: 3.5-32.5 months). The probability of being diagnosed with OM vs DMdiffuse increased with reducing interval from last negative surveillance scan to imaging identifying DM (≤6 months 88.9 %, 7-12 months 71.4 %, 13-24 months 35 %, > 24 months 22.2 %). CONCLUSION: We demonstrate that a reduced interval between last negative imaging and subsequent radiological diagnosis of DM is associated with increased likelihood of identification of OM disease. Consideration of increased frequency of surveillance imaging during the first two years of follow up is supported, particularly for patients at high risk of distant failure.

Fatal Firearm Violence Among American Indians and Alaska Natives.

There is a dearth of population-based studies regarding firearm-related deaths and years of potential life lost among American Indians and Alaska Natives (AI/AN). Using the Centers for Disease Control and Prevention's (CDC) We Based Injury Statistics Query and Reporting System (WISQARS) data for the three most recent years (2018-2020), we analyzed the demographic characteristics of AI/ANs who succumbed to firearm violence. AI/ANs averaged almost 500 firearm-related deaths per year. The majority of these deaths were observed among individuals 20-39 years of age (53%), males (84.4%), and in the West (55.3%). A plurality of these firearm-related deaths were suicides (48.9%) followed by homicides (43.5%). During the 3-year study period, the age-adjusted firearm death rate increased almost 5 times the growth of the AI/AN population. Also, a staggering 67,050 years of potential life were lost before the age of 80 years (YPLL80) during this period. Firearm suicides were responsible for the largest proportion of YPLL80s (48.5%). Traditional legal interventions [e.g., child access prevention (CAP) laws and extreme risk protection orders (ERPO)], if expanded to more states could potentially help reduce AI/AN firearm mortality. None of the 10 states with the highest firearm mortality of AI/AN have ERPOs and 8 of the 10 do not have CAP laws. Also, a renewed focus on cultural continuity and indigenous protective factors is essential to ameliorate the level of firearm violence in AI/ANs.

Randomized Phase 3 Trial of the Hypoxia Modifier Nimorazole Added to Radiation Therapy With Benefit Assessed in Hypoxic Head and Neck Cancers Determined Using a Gene Signature (NIMRAD).

PURPOSE: Tumor hypoxia is an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). We assessed whether patients with hypoxic HNSCC benefited from the addition of nimorazole to definitive intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: NIMRAD was a phase 3, multicenter, placebo-controlled, double-anonymized trial of patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive IMRT (NCT01950689). Patients were randomized 1:1 to receive IMRT (65 Gy in 30 fractions over 6 weeks) plus nimorazole (1.2 g/m2 daily, before IMRT) or placebo. The primary endpoint was freedom from locoregional progression (FFLRP) in patients with hypoxic tumors, defined as greater than or equal to the median tumor hypoxia score of the first 50 patients analyzed (≥0.079), using a validated 26-gene signature. The planned sample size was 340 patients, allowing for signature generation in 85% and an assumed hazard ratio (HR) of 0.50 for nimorazole effectiveness in the hypoxic group and requiring 66 locoregional failures to have 80% power in a 2-tail log-rank test at the 5% significance level. RESULTS: Three hundred thirty-eight patients were randomized by 19 centers in the United Kingdom from May 2014 to May 2019, with a median follow-up of 3.1 years (95% CI, 2.9-3.4). Hypoxia scores were available for 286 (85%). The median patient age was 73 years (range, 44-88; IQR, 70-76). There were 36 (25.9%) locoregional failures in the hypoxic group, in which nimorazole + IMRT did not improve FFLRP (adjusted HR, 0.72; 95% CI, 0.36-1.44; P = .35) or overall survival (adjusted HR, 0.96; 95% CI, 0.53-1.72; P = .88) compared with placebo + IMRT. Similarly, nimorazole + IMRT did not improve FFLRP or overall survival in the whole population. In total (N = 338), 73% of patients allocated nimorazole adhered to the drug for ≥50% of IMRT fractions. Nimorazole + IMRT caused more acute nausea compared with placebo + IMRT (Common Terminology Criteria for Adverse Events version 4.0 G1+2: 56.6% vs 42.4%, G3: 10.1% vs 5.3%, respectively; P < .05). CONCLUSIONS: Addition of the hypoxia modifier nimorazole to IMRT for locally advanced HNSCC in older and less fit patients did not improve locoregional control or survival.

Critical hypertension in trauma patients following prehospital emergency anaesthesia: a multi-centre retrospective observational study.

BACKGROUND: Critical hypertension in major trauma patients is associated with increased mortality. Prehospital emergency anaesthesia (PHEA) is performed for 10% of the most seriously injured patients. Optimising oxygenation, ventilation, and cerebral perfusion, whilst avoiding extreme haemodynamic fluctuations are the cornerstones of reducing secondary brain injury. The aim of this study was to report the differential determinants of post-PHEA critical hypertension in a large regional dataset of trauma patients across three Helicopter Emergency Medical Service (HEMS) organisations. METHODS: A multi-centre retrospective observational study of consecutive adult trauma patients undergoing PHEA across three HEMS in the United Kingdom; 2015-2022. Critical hypertension was defined as a new systolic blood pressure (SBP) > 180mmHg within 10 min of induction of anaesthesia, or > 10% increase if the baseline SBP was > 180mmHg prior to induction. Purposeful logistical regression was used to explore variables associated with post-PHEA critical hypertension in a multivariable model. Data are reported as number (percentage), and odds ratio (OR) with 95% confidence interval (95%CI). RESULTS: 30,744 patients were attended by HEMS during the study period; 2161 received PHEA and 1355 patients were included in the final analysis. 161 (11.9%) patients had one or more new episode(s) of critical hypertension ≤ 10 min post-PHEA. Increasing age (compared with 16-34 years): 35-54 years (OR 1.76, 95%CI 1.03-3.06); 55-74 years (OR 2.00, 95%CI 1.19-3.44); ≥75 years (OR 2.38, 95%CI 1.31-4.35), pre-PHEA Glasgow Coma Scale (GCS) motor score four (OR 2.17, 95%CI 1.19-4.01) and five (OR 2.82, 95%CI 1.60-7.09), patients with a pre-PHEA SBP > 140mmHg (OR 6.72, 95%CI 4.38-10.54), and more than one intubation attempt (OR 1.75, 95%CI 1.01-2.96) were associated with post-PHEA critical hypertension. CONCLUSION: Delivery of PHEA to seriously injured trauma patients risks haemodynamic fluctuation. In adult trauma patients undergoing PHEA, 11.9% of patients experienced post-PHEA critical hypertension. Increasing age, pre-PHEA GCS motor score four and five, patients with a pre-PHEA SBP > 140mmHg, and more than intubation attempt were independently associated with post-PHEA critical hypertension.