Response to mass casualty events: from the battlefield to the Stop the Bleed campaign

In the aftermath of a number of episodes of mass casualty events, we must be reminded of how important it is to be prepared and to reflect on the knowledge accumulated over the past 15 years of war in Iraq and Afghanistan

Withdrawal of Life-Sustaining Therapy in Injured Patients: Variations Between Trauma Centers and Nontrauma Centers

Background—We sought to identify patient and institutional variables predictive of a withdrawal of care order (WOCO) in trauma patients. We hypothesized that the frequency of WOCO would be higher at trauma centers. Methods—Data from the National Study on the Costs and Outcomes of Trauma (NSCOT) was used to determine associations between WOCO status and patient characteristics, institutional characteristics, and hospital course. Chi-square, t-tests and multivariate analysis was used to identify variables predictive of WOCO. Results—Of 14,190 patients, 618 (4.4%) had WOCO, which accounted for 60.9% of patients who died in hospital. Age (p=<0.001), race (p=<0.001), co-morbidity (p=<0.001) and injury mechanism were associated with WOCO (p=0.03). WOCO patients had higher NISS (p=<0.001), lower GCS motor scores (p=<0.001) and higher incidence of midline shift on head CT (p=0.01). Trauma center status (OR 1.56 (95% CI 1.06,2.30)) and closed ICU (OR 1.53 (95% CI 1.03,2.25)) were also predictive of WOCO. There was sizeable variation (0 to 16%) in the percentage of patients with WOCO across centers. Conclusion—Most trauma patients who die in hospital do so after a WOCO. Although trauma center status and closed ICU are predictive of WOCO, variation in the percentage of patients with WOCO across all centers speaks to the complexity of these decisions. Further investigation is needed to understand how WOCO is applied to trauma patients

Predictors of Mortality Up to 1 Year After Emergency Major Abdominal Surgery in Older Adults

ackground The number of older patients who undergo emergent major abdominal procedures is expected to increase yet little is known about mortality beyond 30 days after surgery. Objective Identify factors associated with mortality among older patients at 30, 180 and 365 days after emergency major abdominal surgery. Design A retrospective study of the Health and Retirement Study (HRS) linked to Medicare Claims from 2000-2010. Setting N/A Participants Medicare beneficiaries > 65.5 years enrolled in the Health and Retirement Study (HRS) from 2000-2010, with at least one urgent/emergent major abdominal surgery and a core interview from the HRS within 3 years prior to surgery. Main Outcomes and Measures Survival analysis was used to describe all-cause mortality at 30, 180 and 365 days after surgery. Complementary log-log regression was used to identify patient characteristics and postoperative events associated with worse survival. Results 400 patients had one of the urgent/emergent surgeries of interest. Of these 24% were > 85 years; 50% had coronary artery disease, 48% had cancer, and 33% had congestive heart failure; and 37% experienced a postoperative complication. Postoperative mortality was 20%, 31% and 34% at 30, 180 days and 365 days. Among those > 85 years, 50% were dead one year after surgery. After multivariate adjustment including postoperative complications, dementia (Hazard ratio (HR) 2.02, 95%CI 1.24-3.31), hospitalization within 6 months before surgery (HR 1.63, 95% CI 1.12-2.28) and complications (HR 3.45, 95%CI (2.32-5.13) were independently associated with worse one-year survival. Conclusion Overall mortality is high up to one year after surgery in many older patients undergoing emergency major abdominal surgery. The occurrence of a complication is the clinical factor most strongly associated with worse survival

Mortality and Readmission After Cervical Fracture from a Fall in Older Adults: Comparison with Hip Fracture Using National Medicare Data

Background Cervical fractures from falls are a potentially lethal injury in older patients. Little is known about their epidemiology and outcomes. Objectives To examine the prevalence of cervical spine fractures after falls among older Americans and show changes in recent years. Further, to compare 12-month outcomes in patients with cervical and hip fracture after falls. Design, Setting, and Participants A retrospective study of Medicare data from 2007–2011 including patients ≥65 with cervical fracture and hip fracture after falls treated at acute care hospitals. Measurements Rates of cervical fracture, 12-month mortality and readmission rates after injury. Results Rates of cervical fracture increased from 4.6/10,000 in 2007 to 5.3/10,000 in 2011, whereas rates of hip fracture decreased from 77.3/10,000 in 2007 to 63.5/10,000 in 2011. Patients with cervical fracture without and with spinal cord injury (SCI) were more likely than patients with hip fracture, respectively, to receive treatment at large hospitals (54.1%, 59.4% vs. 28.1%, p< 0.001), teaching hospitals (40.0%, 49.3% vs. 13.4%, p< 0.001), and regional trauma centers (38.5%, 46.3% vs. 13.0%, p< 0.001). Patients with cervical fracture, particularly those with SCI, had higher risk-adjusted mortality rates at one year than those with hip fracture (24.5%, 41.7% vs. 22.7%, p<0.001). By one year, more than half of patients with cervical and hip fracture died or were readmitted to the hospital (59.5%, 73.4% vs. 59.3%, p<0.001). Conclusion Cervical spine fractures occur in one of every 2,000 Medicare beneficiaries annually and appear to be increasing over time. Patients with cervical fractures had higher mortality than those with hip fractures. Given the increasing prevalence and the poor outcomes of this population, hospitals need to develop processes to improve care for these vulnerable patients

Racial Disparities in Emergency General Surgery: Do Differences in Outcomes Persist Among Universally Insured Military Patients?

Research Objective: Described as one of the most serious health problems affecting the nation, racial disparities are estimated to account for \u3e83,000 deaths, \u3e$57 billion per year. They have been identified in multiple surgical settings, including differences in outcomes by race among emergency general surgery(EGS) patients. As many minority patients are uninsured, increasing access to care is thought to be a viable solution to mitigate inequities. The objectives of this study were to determine whether racial disparities in 30/90/180day outcomes exist within a universally-insured population of military/civilian-dependent EGS patients and whether differences in outcomes differentially persist in care received at military-vs-civilian hospitals and among sponsors who are enlisted-service members-vs-officers. It also considered longer-term outcomes of care. Study Design: Risk-adjusted survival analyses using Cox proportional-hazards models assessed race-based differences in mortality, major morbidity, and readmission from index-hospital admission (discharge for readmission) through 30/90/180days. Models accounted for hospital clustering and possible biases associated with missing race (reweighted-estimating equations). Sub-analyses considered effects restricted to operative interventions, stratified by 24 EGS-diagnostic categories defined by the American Association for the Surgery of Trauma(AAST), and effect modification related to rank (SES-proxy: officers-vs-enlisted-sponsors) and military-vs-civilian-hospital care. Population Studied: Five years of national TRICARE Prime/Prime-plus data, which provides insurance to active/reserve/retired members of the US Armed Services and dependents, were queried for adults (≥18y) with primary EGS conditions, defined by the AAST. Patients who did not have an index admission between 01/01/2006-01/07/2010 (minimum 180days follow-up) or who were not continuously enrolled in TRICARE for 180days were excluded. Non-surviving patients were retained while they survived. Principal Findings: A total of 101,011 patients were included: 73.5% White, 14.5% Black, 4.4% Asian, 7.7% other. Risk-adjusted analyses reported equivalent-or-better mortality and readmission outcomes among minority patients at 30/90/180days—even when restricted to civilian hospitals where studies suggest that EGS disparities are found. Readmissions within military hospitals were lower among minority patients. Major morbidity was higher among Black versus White patients (HR[95%CI]): 30day-1.23[1.13-1.35], 90day-1.18[1.09-1.28], 180day-1.15[1.07-1.24]—a finding driven by appendiceal disorders (HR:1.69-1.70). No other diagnostic category-based HR was significant. When considered by rank, significant effects were isolated to enlisted-service members. However, given the relatively small number of patients who were (dependents of) officers, it is difficult to determine whether rank-based findings are a result of social determinants or influenced by the limited number of minority patients. Conclusions: The first of its kind to examine racial disparities in longer-term outcomes of EGS care, this longitudinal analysis of military patients demonstrated apparent mitigation of racial disparities within a universally-insured health system when compared to the overall US health system. Efforts to explain findings based on consideration of care provided in military-vs-civilian hospitals, among specific EGS-diagnostic categories, and based on sponsor rank revealed modification of the association between race and outcomes to some extent for all three. Implications for Policy or Practice: The contrast between results for universally-insured military/civilian-dependent patients and reported disparities among all US civilian patients merits consideration. The data speak to the importance of insurance-coverage in the development of disparities interventions nationwide and will help to inform policy within the DoD

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)