Would You Rather: Quantifying Traumatic Brain Injury Survivor Perceptions of Functional Status Through Their Surrogates.

OBJECTIVE: To quantify health utilities of the Glasgow Outcome Scale-Extended (GOSE) states after actual traumatic brain injury (TBI). BACKGROUND: Recovery after TBI is measured using the GOSE, a validated clinical trial endpoint. A recent public survey quantified the health utilities of some GOSE states after hypothetical TBI as worse than death. However, no health utilities exist for disability after actual TBI. METHODS: This national computer-adaptive survey followed Enhancing the Quality and Transparency of Health Research-Checklist for Reporting Results of Internet E-Surveys guidelines and recruited adult TBI survivors (injury >1 year prior) through their available surrogates. Using a standard gamble approach in randomized order, participants gave preferences for post-TBI categorical health states ranging from GOSE 2 to GOSE 8. We calculated median (interquartile range) health utilities for each GOSE state, from -1 (worse than death) to 1 (full health), with 0 as reference (death, GOSE 1). RESULTS: Of 515 eligible, 298 surrogates (58%) consented and completed the scenarios on TBI survivors' behalf. TBI survivors had a current median GOSE 5 (3-7). GOSE 2, GOSE 3, and GOSE 4 were rated worse than death by 89%, 64%, and 38%, respectively. The relationship was nonlinear, and intervals were unequal between states, with a bimodal distribution for GOSE 4. CONCLUSIONS: In this index study of actual post-TBI disability, poor neurological outcomes represented by GOSE 2 to GOSE 4 were perceived as worse than death by at least one in 3 survivors. Similar to previously reported public perceptions after a hypothetical TBI, these long-term perceptions may inform earlier post-TBI shared decision-making, as well as help shape value-based research and quality of care. LEVEL OF EVIDENCE: Level II-economic and value-based evaluations.

Association Between Emergency Medical Service Agency Volume and Mortality in Trauma Patients.

OBJECTIVE: The aim of this study was to evaluate the association of annual trauma patient volume on outcomes for emergency medical services (EMS) agencies. BACKGROUND: Regionalization of trauma care saves lives. The underlying concept driving this is a volume-outcome relationship. EMS are the entry point to the trauma system, yet it is unknown if a volume-outcome relationship exists for EMS. METHODS: A retrospective analysis of prospective cohort including 8 trauma centers and 20 EMS air medical and metropolitan ground transport agencies. Patients 18 to 90 years old with injury severity scores ≥9 transported from the scene were included. Patient and agency-level risk-adjusted regression determined the association between EMS agency trauma patient volume and early mortality. RESULTS: A total of 33,511 were included with a median EMS agency volume of 374 patients annually (interquartile range: 90-580). Each 50-patient increase in EMS agency volume was associated with 5% decreased odds of 6-hour mortality (adjusted odds ratio=0.95; 95% CI: 0.92-0.99, P =0.03) and 3% decreased odds of 24-hour mortality (adjusted odds ratio=0.97; 95% CI: 0.95-0.99, P =0.04). Prespecified subgroup analysis showed EMS agency volume was associated with reduced odds of mortality for patients with prehospital shock, requiring prehospital airway placement, undergoing air medical transport, and those with traumatic brain injury. Agency-level analysis demonstrated that high-volume (>374 patients/year) EMS agencies had a significantly lower risk-standardized 6-hour mortality rate than low-volume (<374 patients/year) EMS agencies (1.9% vs 4.8%, P <0.01). CONCLUSIONS: A higher volume of trauma patients transported at the EMS agency level is associated with improved early mortality. Further investigation of this volume-outcome relationship is necessary to leverage quality improvement, benchmarking, and educational initiatives.

Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis.

BACKGROUND: Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown. METHODS: In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 µg per kilogram of body weight per hour) or propofol (5 to 50 µg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months. RESULTS: Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 µg per kilogram per hour, and 208 received propofol at a median dose of 10.21 µg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups. CONCLUSIONS: Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.).

Adverse event comparison between glucagon-like peptide-1 receptor agonists and other antiobesity medications following bariatric surgery.

AIM: To compare the incidence of adverse events (AEs) related to antiobesity medications (AOMs; glucagon-like peptide-1 receptor agonists [GLP-1RAs] vs. non-GLP-1RAs) after bariatric surgery. METHODS: This single-centre retrospective cohort included patients (aged 16-65 years) who had undergone laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy (cohort entry date) and initiated AOMs. Participants were categorized as users of US Food and Drug Administration (FDA)-approved, off-label, or GLP-1RA AOMs if documented as receiving the medication on or after cohort entry date. Non-GLP-1RA AOMs were phentermine, orlistat, topiramate, canagliflozin, dapagliflozin, empagliflozin, naltrexone, bupropion/naltrexone and phentermine/topiramate. GLP-1RA AOMs included: semaglutide, dulaglutide, exenatide and liraglutide. The primary outcome was AE incidence. Logistic regression was used to determine the association of AOM exposure with AEs. RESULTS: We identified 599 patients meeting our inclusion criteria, 83% of whom were female. Their median (interquartile range [IQR]) age was 47.8 (40.9-55.4) years. The median duration of surgery to AOM exposure was 30 months. GLP-1RAs use was not associated with higher odds of AEs: adjusted odds ratio (aOR) 1.1 (95% confidence interval [CI] 0.5-2.6) and aOR 1.1 (95% CI 0.6-2.3) for GLP-1RA versus FDA-approved and off-label AOM use, respectively. AOM initiation ≥12 months after surgery was associated with lower risk of AEs compared to <12 months (aOR 0.01 [95% CI 0.0-0.01]; p < 0.001). CONCLUSION: Our results showed that GLP-1RA AOMs were not associated with an increased risk of AEs compared to non-GLP-1RA AOMs in patients who had previously undergone bariatric surgery. Prospective studies are needed to identify the optimal timeframe for GLP-1RA initiation.

Prehospital Time Following Traumatic Injury Is Independently Associated With the Need for In-Hospital Blood and Early Mortality for Specific Injury Types.

OBJECTIVE: Treating traumatic hemorrhage is time sensitive. Prehospital care and transport modes (eg, helicopter and ground) may influence in-hospital events. We hypothesized that prehospital time (on-scene time [OST] and total prehospital time [TPT]) and transport mode are associated with same-day transfusion and mortality. Furthermore, we sought to identify regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. METHODS: We obtained prehospital, in-hospital, and trauma registry data from an 8-center cohort of adult nonburn trauma patients from 2017 to 2022 directly transported from the scene to the hospital and having an Injury Severity Score (ISS) > 9 for the Task Order 1 project of the Linking Investigators in Trauma and Emergency Services research network. We excluded patients missing prehospital times, patients < 18 years of age, patients from interfacility transfers, and recipients of prehospital blood. Our same-day outcomes were in-hospital transfusions within 4 hours and 24-hour mortality. Each outcome was adjusted using multivariable logistic regression for covariates of prehospital phases (OST and TPT), mode of transport (helicopter and ground), age, sex, ISS, Glasgow Coma Scale motor subscale score < 6, and field hypotension (systolic blood pressure < 90 mm Hg). We evaluated the association of prehospital time on outcomes for scene missions by transport mode across severe injury patterns defined by Abbreviated Injury Scale > 2 body regions. RESULTS: Of 78,198 subjects, 34,504 were eligible for the study with a mean age of 47.6 ± 20.3 years, ISS of 18 ± 11, OST of 15.9 ± 9.5 minutes, and TPT of 48.7 ± 20.3 minutes. Adjusted for injury severity and demographic factors, transport type significantly modified the relationship between prehospital time and outcomes. The association of OST and TPT with the odds of 4-hour transfusion was absent for the ground emergency medical services (GEMS) cohort and present for the helicopter emergency medical services (HEMS) ambulance cohort, whereas these times were associated with decreased 24-hour mortality for both transport types. When stratifying by injury to most anatomic regions, OST and TPT were associated with a decreased need for 4-hour transfusions in the GEMS cohort. However, OST was associated with increased early transfusion only among patients with severe injuries of the thorax, and this association persisted after adjusting additionally for injury type (odds ratio [OR] = 1.03; 95% confidence interval [CI], 1.00-1.05; P = .02). The presence of polytrauma supported an association between prehospital time and decreased 24-hour mortality for the GEMS cohort (OST: OR = 0.97; 95% CI, 0.95-0.99; P < .01; TPT: OR = 0.99; 95% CI, 0.98-0.99; P = .02), whereas no injuries showed significant association of helicopter prehospital time on mortality after adjustment. CONCLUSION: We determined that transport type affects the relationship between prehospital time and hospital outcomes (4-hour transfusion: positive relationship for HEMS and negative for GEMS, 24-hour mortality: negative for both transport types). Furthermore, we identified regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. Of these regions, most notable were severe isolated injuries to the thorax that supported a positive relationship between HEMS OST and 4-hour transfusions and polytrauma that showed a negative relationship between GEMS OST or TPT and 24-hour mortality after adjustment.

Standardising the biochemical confirmation of adult male hypogonadism: A joint position statement by the Society for Endocrinology and Association of Clinical Biochemistry and Laboratory Medicine.

BACKGROUND: Inter-assay variation between different immunoassays and different mass spectrometry methods hampers the biochemical confirmation of male hypogonadism. Furthermore, some laboratories utilise assay manufacturer reference ranges that do not necessarily mirror assay performance characteristics, with the lower limit of normality ranging from 4.9 nmol/L to 11 nmol/L. The quality of the normative data underlying commercial immunoassay reference ranges is uncertain. DESIGN: A working group reviewed published evidence and agreed upon standardised reporting guidance to augment total testosterone reports. RESULTS: Evidence-based guidance on appropriate blood sampling, clinical action limits, and other major factors likely to affect the interpretation of results are provided. CONCLUSIONS: This article aims to improve the quality of the interpretation of testosterone results by non-specialist clinicians. It also discusses approaches for assay harmonisation which have been successful in some but not all healthcare systems.

The Geography of Injuries in Trauma Systems: Using Home as a Proxy for Incident Location.

INTRODUCTION: Effective trauma system organization is crucial to timely access to care and requires accurate understanding of injury and resource locations. Many systems rely on home zip codes to evaluate geographic distribution of injury; however, few studies have evaluated the reliability of home as a proxy for incident location after injury. METHODS: We analyzed data from a multicenter prospective cohort collected from 2017 to 2021. Injured patients with both home and incident zip codes were included. Outcomes included discordance and differential distance between home and incident zip code. Associations of discordance with patient characteristics were determined by logistic regression. We also assessed trauma center catchment areas based on home versus incident zip codes and variation regionally at each center. RESULTS: Fifty thousand one hundred seventy-five patients were included in the analysis. Home and incident zip codes were discordant in 21,635 patients (43.1%). Injuries related to motor vehicles (aOR: 4.76 [95% CI 4.50-5.04]) and younger adults 16-64 (aOR: 2.46 [95% CI 2.28-2.65]) were most likely to be discordant. Additionally, as injury severity score increased, discordance increased. Trauma center catchment area differed up to two-thirds of zip codes when using home versus incident location. Discordance rate, discordant distance, and catchment area overlap between home and incident zip codes all varied significantly by geographic region. CONCLUSIONS: Home location as proxy for injury location should be used with caution and may impact trauma system planning and policy, especially in certain populations. More accurate geolocation data are warranted to further optimize trauma system design.

Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial.

OBJECTIVE: To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). BACKGROUND: Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit. METHODS: This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16-64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study. RESULTS: Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (- 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes. CONCLUSION: Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.

Insight on nano drug delivery systems with targeted therapy in treatment of oral cancer.

Oral cancer is a type of cancer that develops in the mouth and is one of the deadliest malignancies in the world. Currently surgical, radiation therapy, and chemotherapy are most common treatments. Better treatment and early detection strategies are required. Chemotherapeutic drugs fail frequently due to toxicity and poor tumor targeting. There are high chances of failure of chemotherapeutic drugs due to toxicity. Active, passive, and immunity-targeting techniques are devised for tumor-specific activity. Nanotechnology-based drug delivery systems are the best available solution and important for precise targeting. Nanoparticles, liposomes, exosomes, and cyclodextrins are nano-based carriers for drug delivery. Nanotechnology is being used to develop new techniques such as intratumoral injections, microbubble mediated ultrasonic therapy, phototherapies, and site-specific delivery. This systematic review delves into the details of such targeted and nano-based drug delivery systems in order to improve patient health and survival rates in oral cancer.

Prevalence and Risk Factors for Intensive Care Unit Delirium After Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: Delirium remains understudied after traumatic brain injury (TBI). We sought to identify independent predictors of delirium among intensive care unit (ICU) patients with TBI. METHODS: This single-center retrospective cohort study evaluated adult patients with TBI requiring ICU admission. Outcomes included delirium days within the first 14 days, as assessed by the Confusion Assessment Method-ICU (CAM-ICU). Models were adjusted for age, sex, insurance, Marshall head computed tomography classification, presence of subarachnoid hemorrhage (SAH), Injury Severity Score (ISS), need for cardiopulmonary resuscitation, maximum admission Glasgow Coma motor score, glucose level, hemoglobin level, and pupil reactivity. RESULTS: Delirium prevalence was 60%, with a median duration of 4 days (interquartile range: 2-8) among ICU patients with TBI (n = 2,664). Older age, higher ISS, maximum motor score < 6, Marshall class II-IV, and SAH were associated with risk of increased delirium duration (all p < 0.001). CONCLUSIONS: In this large cohort, ICU delirium after TBI affected three of five patients for a median duration of 4 days. Age, general injury severity, motor score, and features of intracranial hemorrhage were predictive of more TBI-associated delirium days. Given the high prevalence of ICU delirium after TBI and its impact on hospitalization, further work is needed to understand the impact of delirium and TBI on outcomes and to determine whether delirium risk can be minimized.

Risk Factors associated with COVID-19 Patients in India: A Single Center Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) outbreak has caused a worldwide pandemic, resulting in >3.8 million deaths. Our aim is to identify the risk factors associated with in-hospital mortality using survival analysis considering the characteristics and outcomes of COVID-19 patients admitted to a dedicated tertiary-care hospital in Mumbai, India. MATERIALS AND METHODS: In a retrospective cohort study, 565 patients admitted from 28th March 2020 to 30th June 2020 were enrolled, and a follow-up was conducted till August 2020. To investigate the impact of COVID-19, survival analysis was performed using the Kaplan-Meier method. Potential risk factors associated with mortality were analyzed using logistic regression models for multivariate analysis and the Cox proportional hazards model for estimating hazard ratios (HRs). RESULTS: From the 565 positive COVID-19 cases, 49 patients died (8.7%) and 516 (91.3%) were discharged. Overall, 119 patients (20%) required intensive care unit (ICU) admission, of which 70 (58%) patients survived. The Kaplan-Meier survival curve showed a significant association of COVID-19 infection with age (≥60; p = 0.008), hypertension (p = 0.03), dialysis (p = 0.0001), lung commodities (p = 0.01), breathlessness (p = 0.0001), severe disease upon high-resolution computed tomography (HRCT) analysis (p = 0.0001), ICU admission (p = 0.0001), and low lymphocyte count at admission (p = 0.0001). Additionally, patients receiving tocilizumab (p = 0.0001) and deprived of hydroxychloroquine (HCQ) + azithromycin (azee) (p = 0.0001) were estimated at a high risk of mortality. INTERPRETATION AND CONCLUSION: Coronavirus disease 2019 (COVID-19) increased the risk of mortality in patients with increased age, comorbidities, and severe symptoms upon treatment with an immunosuppressant (tocilizumab). However, patients treated with HCQ + azee showed favorable results due to their antiviral effects in vitro.

Multicenter International Cohort Validation of a Modified Sequential Organ Failure Assessment Score Using the Richmond Agitation-sedation Scale.

OBJECTIVE: In a multicenter, international cohort, we aimed to validate a modified Sequential Organ Failure Assessment (mSOFA) using the Richmond Agitation-Sedation Scale, hypothesized as comparable to the Glasgow Coma Scale (GCS)-based Sequential Organ Failure Assessment (SOFA). SUMMARY BACKGROUND DATA: The SOFA score, whose neurologic component is based on the GCS, can predict intensive care unit (ICU) mortality. But, GCS is often missing in lieu of other assessments, such as the also reliable and validated Richmond Agitation Sedation Scale (RASS). Single-center data suggested an RASS-based SOFA (mSOFA) predicted ICU mortality. METHODS: Our nested cohort within the prospective 2016 Fourth International Study of Mechanical Ventilation contains 4120 ventilated patients with daily RASS and GCS assessments (20,023 patient-days, 32 countries). We estimated GCS from RASS via a proportional odds model without adjustment. ICU mortality logistic regression models and c-statistics were constructed using SOFA (measured GCS) and mSOFA (measured RASS-estimated GCS), adjusted for age, sex, body-mass index, region (Europe, USA-Canada, Latin America, Africa, Asia, Australia-New Zealand), and postoperative status (medical/surgical). RESULTS: Cohort-wide, the mean SOFA=9.4+/-2.8 and mean mSOFA = 10.0+/-2.3, with ICU mortality = 31%. Mean SOFA and mSOFA similarly predicted ICU mortality (SOFA: AUC = 0.784, 95% CI = 0.769-0.799; mSOFA: AUC = 0.778, 95% CI = 0.763-0.793, P = 0.139). Across models, other predictors of mortality included higher age, female sex, medical patient, and African region (all P < 0.001). CONCLUSIONS: We present the first SOFA modification with RASS in a "real-world" international cohort. Estimating GCS from RASS preserves predictive validity of SOFA to predict ICU mortality. Alternative neurologic measurements like RASS can be viably integrated into severity of illness scoring systems like SOFA.

In-Hospital Depressed Level of Consciousness and Long-Term Functional Outcomes in ICU Survivors.

OBJECTIVES: Among critically ill patients, acutely depressed level of consciousness is associated with mortality, but its relationship to long-term outcomes such as disability and physical function is unknown. We investigated the relationship of level of consciousness during hospitalization with long-term disability and physical function in ICU survivors. DESIGN: Multi-center observational cohort study. SETTING: Medical or surgical ICUs at five U.S. centers. PATIENTS: Adult survivors of respiratory failure or shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Depressed level of consciousness during hospitalization was defined using the Richmond Agitation Sedation Scale (RASS) score (including all negative scores) by calculating the area under the curve using linear interpolation. Sedative-associated level of consciousness was similarly defined for all hospital days that sedation was received. We measured disability in basic activities of daily living (BADLs), instrumental activities of daily living (IADLs), discharge destination, and self-reported physical function. In separate models, we evaluated associations between these measures of level of consciousness and outcomes using multivariable regression, adjusted for age, sex, race, body mass index, education level, comorbidities, baseline frailty, baseline IADLs and BADLs, hospital type (civilian vs veteran), modified mean daily Sequential Organ Failure Assessment score, duration of severe sepsis, duration of mechanical ventilation, and hospital length of stay. Of the 1,040 patients enrolled in the ICU, 781 survived to hospital discharge. We assessed outcomes in 624 patients at 3 months and 527 patients at 12 months. After adjusting for covariates, there was no association between depressed level of consciousness (total or sedation-associated) with BADLs or IADLs at either 3- or 12-month follow-up. There was also no association with self-reported physical function at 3 or 12 months or with discharge destination. CONCLUSIONS: Depressed level of consciousness, as defined by the RASS, was not associated with disability or self-reported physical function. Future studies should investigate additional modifiable in-hospital risk factors for disability and poor physical function following critical illness.

Long-Term Time Series Forecasting and Updates on Survival Analysis of Glioblastoma Multiforme: A 1975-2018 Population-Based Study.

OBJECTIVE: Glioblastomas multiforme (GBMs) are the most common primary CNS tumors. Epidemiologic studies have investigated the effect of demographics on patient survival, but the literature remains inconclusive. METHODS: This study included all adult patients with intracranial GBMs reported in the surveillance epidemiology and end results (SEER)-9 population database (1975-2018). The sample consisted of 32,746 unique entries. We forecast the annual GBM incidence in the US population through the year 2060 using time series analysis with autoregressive moving averages. A survival analysis of the GBM-specific time to death was also performed. Multivariate Cox proportional hazards (PH) regression revealed frank violations of the PH assumption for multiple covariates. Parametric models best described the GBM population's survival pattern; the results were compared to the semi-parametric analysis and the published literature. RESULTS: We predicted an increasing GBM incidence, which demonstrated that by the year 2060, over 1,800 cases will be reported annually in the SEER. All eight demographic variables were significant in the univariable analysis. The calendar year 2005 was the cutoff associated with an increased survival probability. A male survival benefit was eliminated in the year-adjusted Cox. Infratentorial tumors, nonmetropolitan areas, and White patient race were the factors erroneously associated with survival in the multivariate Cox analysis. Accelerated Failure Time (AFT) lognormal regression was the best model to describe the survival pattern in our patient population, identifying age >30 years old as a poor prognostic and patients >70 years old as having the worst survival. Annual income >USD 75,000 and supratentorial tumors had good prognostics, while surgical intervention provided the strongest survival benefit. CONCLUSIONS: Annual GBM incidence rates will continue to increase by almost 50% in the upcoming 30 years. Cox regression analysis should not be utilized for time-to-event predictions in GBM survival statistics. AFT lognormal distribution best describes the GBM-specific survival pattern, and as an inherent population characteristic, it should be implemented by researchers for future studies. Surgical intervention provides the strongest survival benefit, while patient age >70 years old is the worst prognostic. Based on our study, the demographics such as gender, race, and county type should not be considered as meaningful prognostics when designing future trials.

Association between cholinesterase activity and critical illness brain dysfunction.

BACKGROUND: Delirium is a frequent manifestation of acute brain dysfunction and is associated with cognitive impairment. The hypothesized mechanism of brain dysfunction during critical illness is centered on neuroinflammation, regulated in part by the cholinergic system. Point-of-care serum cholinesterase enzyme activity measurements serve as a real-time index of cholinergic activity. We hypothesized that cholinesterase activity during critical illness would be associated with delirium in the intensive care unit (ICU) and cognitive impairment after discharge. METHODS: We enrolled adults with respiratory failure and/or shock and measured plasma acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity on days 1, 3, 5, and 7 after enrollment. AChE values were also normalized per gram of hemoglobin (AChE/Hgb). We assessed for coma and delirium twice daily using the Richmond Agitation Sedation Scale and the Confusion Assessment Method for the ICU to evaluate daily mental status (delirium, coma, normal) and days alive without delirium or coma. Cognitive impairment, disability, and health-related quality of life were assessed at up to 6 months post-discharge. We used multivariable regression to determine whether AChE, AChE/Hgb, and BChE activity were associated with outcomes after adjusting for relevant covariates. RESULTS: We included 272 critically ill patients who were a median (IQR) age 56 (39-67) years and had a median Sequential Organ Failure Assessment score at enrollment of 8 (5-11). Higher daily AChE levels were associated with increased odds of being delirious versus normal mental status on the same day (Odds Ratio [95% Confidence Interval] 1.64 [1.11, 2.43]; P = 0.045). AChE/Hgb and BChE activity levels were not associated with delirious mental status. Lower enrollment BChE was associated with fewer days alive without delirium or coma (P = 0.048). AChE, AChE/Hgb, and BChE levels were not significantly associated with cognitive impairment, disability, or quality of life after discharge. CONCLUSION: Cholinesterase activity during critical illness is associated with delirium but not with outcomes after discharge, findings that may reflect mechanisms of acute brain organ dysfunction. TRIAL REGISTRATION: NCT03098472. Registered 31 March 2017.

Research Needs for Inpatient Management of Severe Alcohol Withdrawal Syndrome: An Official American Thoracic Society Research Statement.

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0-T4 continuum to advance the care of hospitalized patients who experience SAWS. Methods: Clinicians and researchers with unique and complementary expertise in basic, clinical, and implementation research related to unhealthy alcohol consumption and alcohol withdrawal were invited to participate in a workshop at the American Thoracic Society 2019 International Conference. The committee was subdivided into four groups on the basis of interest and expertise: T0-T1 (basic science research with translation to humans), T2 (research translating to patients), T3 (research translating to clinical practice), and T4 (research translating to communities). A medical librarian conducted a pragmatic literature search to facilitate this work, and committee members reviewed and supplemented the resulting evidence, identifying key knowledge gaps. Results: The committee identified several investigative opportunities to advance the care of patients with SAWS in each domain of the translational science spectrum. Major themes included 1) the need to investigate non-γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice. Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.

A 30-day Survival and Safety of Percutaneous Tracheostomy in Moderate-to-severe COVID-19 Pneumonia Patients: A Single-center Experience.

Aims and objectives: In coronavirus disease-2019 (COVID-19) pneumonia, guidelines on timing and method of tracheostomy are evolving. The aim of the study was to analyze the outcomes of moderate-to-severe COVID-19 pneumonia patients who required tracheostomy and the safety with regard to the risk of transmission to the healthcare workers. Materials and methods: We retrospectively analyzed 30-day survival outcome of a total of 70 moderate-to-severe COVID-19 pneumonia patients on a ventilator, wherein tracheostomy was performed only in 28 (tracheostomy group), and the remaining were with endotracheal intubation beyond 7 days (non-tracheostomy group). Besides demographics, comorbidities and clinical data including 30-day survival and complications of tracheostomy were analyzed in both groups with respect to the timing of tracheostomy from the day of intubation. Healthcare workers were monitored for COVID-19 symptoms by carrying out periodical COVID tests. Results: The 30-day survival of the tracheostomy group was 75% as compared to 26.2% of the non-tracheostomy group. The majority of the patients (71.4%) had severe disease with PaO2/FiO2 (P/F ratio) <100. The first wave showed an 80% (4/5) while the second wave 100% (8/8) thirty days survival in the tracheostomy group performed before 13 days. All patients during the second wave underwent tracheostomy before 13 days with a median of 12th day from the day of intubation. These tracheostomies were performed percutaneously at the bedside, without any major complications and no transmission of disease to healthcare workers. Conclusion: Early percutaneous tracheostomy within 13 days of intubation demonstrated a good 30-day survival rate in severe COVID-19 pneumonia patients. How to cite this article: Shah M, Bhatuka N, Shalia K, Patel M. A 30-day Survival and Safety of Percutaneous Tracheostomy in Moderate-to-severe COVID-19 Pneumonia Patients: A Single-center Experience. Indian J Crit Care Med 2022;26(10):1120-1125.

Clinical Profile of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection Developing Pulmonary Barotrauma on Mechanical Ventilation.

Background: There is limited information on clinical profile and outcomes of patients on mechanical ventilation (MV) who developed pulmonary barotrauma (PBT) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients and methods: In a retrospective observational study, all SARS-CoV-2 pneumonia patients admitted from March 28, 2020, to August 31, 2020, at Sir HN Reliance Foundation Hospital and Research Center and Seven Hills Hospital (Reliance Facility), Mumbai, India, of 18 years and above on MV and developed PBT, were included. Results: A total of 14 SARS-CoV-2 patients of 45 on MV (31.0%) developed PBT of 1,029 hospitalized. All patients were male and divided as per admission into PaO2/FiO2 (P/F) ≤100 (median 80) and P/F >100 (median 222) group. Pneumothorax developed in seven and six cases of P/F ≤100 and P/F >100 groups, respectively. Three patients in each group developed subcutaneous emphysema, while four developed pneumomediastinum in P/F >100 group. Twelve patients (7, P/F ≤100, and 5, P/F >100) were on invasive, while two (P/F >100) were on noninvasive MV. The mean P/F on the day of PBT was reduced by 27.5 and 65.3%, while peak inspiratory pressure was elevated with a median of 36 and 28 cm H2O in P/F ≤100 and P/F >100 groups, respectively. The median highest tidal volume (420 mL), positive-end expiratory pressure (8 vs 6 cm H2O) on the day of PBT, and length of hospital stay (11 vs 25 days) did not differ between two groups. Survival was 28.6% (4/14). Conclusion: SARS-CoV-2 patients requiring MV with PBT had poor outcomes. Clinicians should be vigilant about the diagnosis of PBT. How to cite this article: Kargirwar KV, Rathod D, Kumar V, Patel M, Shah M, Choudhury H, et al. Clinical Profile of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection Developing Pulmonary Barotrauma on Mechanical Ventilation. Indian J Crit Care Med 2022;26(5):613-618.

Worse Than Death: Survey of Public Perceptions of Disability Outcomes After Hypothetical Traumatic Brain Injury.

OBJECTIVE: The aim of this study was to determine the health utility states of the most commonly used traumatic brain injury (TBI) clinical trial endpoint, the Extended Glasgow Outcome Scale (GOSE). SUMMARY BACKGROUND DATA: Health utilities represent the strength of one's preferences under conditions of uncertainty. There are insufficient data to indicate how an individual would value levels of disability after a TBI. METHODS: This was a cross-sectional web-based online convenience sampling adaptive survey. Using a standard gamble approach, participants evaluated their preferences for GOSE health states 1 year after a hypothetical TBI. The categorical GOSE was studied from vegetative state (GOSE2) to upper good recovery (GOSE8). Median (25th percentile, 75th percentile) health utility values for different GOSE states after TBI, ranging from -1 (worse than death) to 1 (full health), with 0 as reference (death). RESULTS: Of 3508 eligible participants, 3235 (92.22%) completed the survey. Participants rated lower GOSE states as having lower utility, with some states rated as worse than death, though the relationship was nonlinear and intervals were unequal between health states. Over 75% of participants rated a vegetative state (GOSE2, absence of awareness and bedridden) and about 50% rated lower severe disability (GOSE3, housebound needing all-day assistance) as conditions worse than death. CONCLUSIONS: In the largest investigation of public perceptions about post-TBI disability, we demonstrate unequally rated health states, with some states perceived as worse than death. Although limited by selection bias, these results may guide future comparative-effectiveness research and shared medical decision-making after neurologic injury.

Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness.

BACKGROUND: There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS: In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. RESULTS: Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. CONCLUSIONS: The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .).