The Effect of COVID-19 on Rib Fracture Patients in Michigan.

This study aims to compare outcomes of rib fracture patients with and without COVID-19 in Michigan. Data from the Michigan Trauma Quality Improvement Program (MTQIP) identified adults hospitalized from January 1, 2020, to October 31, 2022, with at least one rib fracture and a completed COVID-19 test on admission. Patients were propensity score matched 1:1 using 20 variables. The primary outcome was hospital length of stay (LOS). Secondary outcomes were mortality, ventilator days, intensive care unit (ICU) LOS, pneumonia, and ventilator-assisted pneumonia (VAP). 13,305 total patients were identified. 232 patients matched into both the COVID+ and COVID- groups. COVID was associated with increased LOS (7 days vs. 5 days, P < 0.001). There were no significant differences between the two groups when evaluating secondary outcomes. Our study indicates that although COVID-19 infection is associated with increased LOS, COVID may not contribute to additional morbidity or mortality in traumatic rib fracture patients.

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Systematic Review and Patient-Level Meta-Analysis.

Importance: Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor. Objective: To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. Data Sources: MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Study Selection: Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI. Data Extraction and Synthesis: Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data. Main Outcomes and Measures: The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding. Results: Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04). Conclusions and Relevance: This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.

The Single-Syringe Versus the Double-Syringe Techniques of Adenosine Administration for Supraventricular Tachycardia: A Systematic Review and Meta-Analysis.

INTRODUCTION: The intravenous double-syringe technique (DST) of adenosine administration is the first-line treatment for stable supraventricular tachycardia (SVT). Alternatively, the single-syringe technique (SST) was recently found to be potentially beneficial in several studies. This study aimed to perform a meta-analysis of the SST versus the DST of adenosine administration for the treatment of SVT. METHODS: We assessed EMBASE, PubMed, Cochrane, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) and non-randomized studies of intervention (NRSIs) comparing the DST to the SST of adenosine administration in patients with SVT. Outcomes included termination rate, termination rate at first dose, total administered dose, adverse effects, and discharge rate. RESULTS: We included four studies (three RCTs and one NRSI) with a total of 178 patients, of whom 99 underwent the SST of adenosine administration. No significant difference was found between treatment groups regarding termination rate, termination rate restricted to RCTs, total administered dose, and discharge rate. Termination rate at first dose (odds ratio 2.87; confidence interval 1.11-7.41; p = 0.03; I2 = 0%) was significantly increased in patients who received the SST. Major adverse effects were observed in only one study. CONCLUSIONS: The SST is probably as safe as the DST and at least as effective for SVT termination, SVT termination at first dose, and discharge rate from the emergency department. However, definitive superiority of one technique is not feasible given the limited sample size. REGISTRATION: PROSPERO identifier nº CRD42022345125.

Evaluation of Optic Disc Edema in Long-Duration Spaceflight Crewmembers Using Retinal Photography.

BACKGROUND: Long-duration spaceflight crewmembers are at risk for spaceflight-associated neuro-ocular syndrome (SANS). One of the earliest manifestations of SANS is optic disc edema (ODE), which could be missed using the subjective Frisén scale. The primary objective of this study is to determine the inter-rater and intrarater reliability of Frisén grade for SANS-induced ODE among a trained observer cohort. The secondary objective is to propose a standardized evaluation process for SANS-induced ODE across International Space Station Partner Agencies. METHODS: Retrospective, double-blinded diagnostic study. Preflight and postflight fundus photographs were presented to subject matter experts who identified and graded ODE. Pairs of images were also compared side-by-side for disc ranking. Grader concordance was assessed for Frisén grading and disc ranking. RESULTS: Expert graders identified Grade 1 ODE in 17.35% of images from 62 crewmembers (9 female, mean [SD] age, 47.81 [5.19] years). Grades 2 and 3 were identified less than 2% of the time. Concordance in Frisén grades among pairs of graders was 70.99%. Graders identified a difference in preflight and postflight fundus photographs 17.21% of the time when using disc ranking. Pairs of graders had complete concordance in disc ranking 79.79% of the time. Perfect intrarater agreement between Frisén grade and disc ranking occurred 77.7% of the time. CONCLUSIONS: These findings demonstrate intergrader and intragrader variability when using the Frisén scale to identify SANS-induced ODE, which is typically milder in presentation than terrestrial cases of idiopathic intracranial hypertension. It is possible to miss early ODE on fundoscopy alone, making it insufficient as a sole criterion for the diagnosis of SANS. A more sensitive and objective method of surveillance is necessary to monitor international crewmembers for ODE, perhaps using a multimodal approach that includes technology such as optical coherence tomography.

Factor XI Inhibitors in Early Clinical Trials: A Meta-analysis.

BACKGROUND: Phase II randomized controlled trials (RCTs) on factor(F)XI inhibitors have shown promising results but they were burdened by low statistical power for clinical outcomes. METHODS: We performed a systematic review and meta-analysis of RCT comparing FXI inhibitors versus other anticoagulants (enoxaparin or direct oral anticoagulants, DOACs) or versus placebo on top of antiplatelet therapy. RESULTS: Eight RCTs testing FXI inhibitors (ISIS 416858, osocimab, abelacimab, milvexian, asundexian) and enrolling 9,216 patients were included. Compared with enoxaparin, FXI inhibitors were associated with reduced any-bleeding (risk ratio [RR]: 0.49, 95% confidence interval [CI]: 0.31-0.77), no difference in major bleeding (RR: 0.96, 95% CI: 0.41-2.28), and reduced trial-defined efficacy endpoint (RR: 0.62, 95% CI: 0.49-0.79), the latter driven by the high-dose regimens. Compared with DOACs, FXI inhibitors were associated with a trend toward reduced any-bleeding (RR: 0.66, 95% CI: 0.31-1.38) and no difference in major bleeding (RR: 1.03, 95% CI: 0.22-4.78) or in trial-defined efficacy endpoint (RR: 1.23, 95% CI: 0.88-1.70). Compared with placebo, FXI inhibitors were associated with increased any-bleeding (RR: 1.25, 95% CI: 1.08-1.43) and a trend toward increased major bleeding (RR: 1.21, 95% CI: 0.75-1.93), both driven by high-dose regimens, with no difference in trial-defined efficacy endpoint (RR: 1.02, 95% CI: 0.92-1.13). CONCLUSION: Results of this meta-analysis on FXI inhibitors suggest increased safety and efficacy compared with enoxaparin and modest increased safety compared with DOACs. The use of FXI inhibitors in adjunct to antiplatelet therapy versus placebo appears to be associated with a dose-dependent increase in bleeding without any difference in efficacy. STUDY REGISTRATION: This study is registered in PROSPERO (CRD42022367706).

P2Y12 Inhibitor Monotherapy or Dual Antiplatelet Therapy After Complex Percutaneous Coronary Interventions.

BACKGROUND: It remains unclear whether P2Y12 inhibitor monotherapy preserves ischemic protection while limiting bleeding risk compared with dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI). OBJECTIVES: We sought to assess the effects of P2Y12 inhibitor monotherapy after 1-month to 3-month DAPT vs standard DAPT in relation to PCI complexity. METHODS: We pooled patient-level data from randomized controlled trials comparing P2Y12 inhibitor monotherapy and standard DAPT on centrally adjudicated outcomes after coronary revascularization. Complex PCI was defined as any of 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was all-cause mortality, myocardial infarction, and stroke. The key safety endpoint was Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding. RESULTS: Of 22,941 patients undergoing PCI from 5 trials, 4,685 (20.4%) with complex PCI had higher rates of ischemic events. The primary efficacy endpoint was similar between P2Y12 inhibitor monotherapy and DAPT among patients with complex PCI (HR: 0.87; 95% CI: 0.64-1.19) and noncomplex PCI (HR: 0.91; 95% CI: 0.76-1.09; Pinteraction = 0.770). The treatment effect was consistent across all the components of the complex PCI definition. Compared with DAPT, P2Y12 inhibitor monotherapy consistently reduced BARC 3 or 5 bleeding in complex PCI (HR: 0.51; 95% CI: 0.31-0.84) and noncomplex PCI patients (HR: 0.49; 95% CI: 0.37-0.64; Pinteraction = 0.920). CONCLUSIONS: P2Y12 inhibitor monotherapy after 1-month to 3-month DAPT was associated with similar rates of fatal and ischemic events and lower risk of major bleeding compared with standard DAPT, irrespective of PCI complexity. (PROSPERO [P2Y12 Inhibitor Monotherapy Versus Standard Dual Antiplatelet Therapy After Coronary Revascularization: Individual Patient Data Meta-Analysis of Randomized Trials]; CRD42020176853).

Out of sight, out of mind? The impact on trauma patient opioid use when the medicine administration schedule is not displayed.

INTRODUCTION: The impact of a visual pain medication schedule on opioid use among hospitalized trauma patients is unknown. We examined whether removal of this displayed schedule would decrease oral morphine equivalent (OME) use. METHODS: This retrospective cohort study compared OME use in trauma patients in the inpatient setting before and after removing the patient-facing pain medication schedule that is typically displayed on the patient's white board for all trauma admissions. RESULTS: 707 patients were included. The control (n = 308, 43.6%) and intervention (n = 399, 56.4%) groups were similar in age (p = 0.06). There was no difference in total inpatient OME use between the control and intervention groups, median 50 (IQR: 22.5-118) vs 60 (IQR: 22.5-126), p = 0.79, respectively. No difference in total OME use was observed when patients were stratified by age, sex, race, ISS, and length of hospital stay. CONCLUSION: Removing a visual display of the pain medication schedule did not decrease OME use in inpatient trauma patients.

Ticagrelor with and without aspirin in patients with a prior coronary artery bypass graft undergoing percutaneous coronary intervention: the TWILIGHT-CABG study.

BACKGROUND: Prior coronary artery bypass graft surgery (CABG) patients undergoing percutaneous coronary intervention (PCI) are often older and present with multiple comorbidities. Ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) has emerged as an effective bleeding-avoidance strategy among high-risk patients. AIMS: We aimed to examine the effects of ticagrelor with or without aspirin in prior CABG patients undergoing PCI within the TWILIGHT trial. METHODS: After 3 months of ticagrelor plus aspirin, patients were randomised to either aspirin or placebo, in addition to ticagrelor, for 12 months and compared by prior CABG status. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. The key secondary endpoint was all-cause death, myocardial infarction (MI), or stroke. RESULTS: Out of 7,119 patients, a total of 703 (10.8%) patients had prior CABG within the randomised cohort. Prior CABG patients had more comorbidities and a higher incidence of BARC type 2, 3, or 5 bleeding and death, MI or stroke at 1 year after randomisation, compared with patients without prior CABG. Ticagrelor monotherapy was associated with significantly less BARC 2, 3, or 5 bleeding among prior CABG patients compared with DAPT (4.9% vs 9.6%, hazard ratio [HR] 0.50, 95% confidence interval [CI]: 0.28 to 0.90; pinteraction=0.676) and similar rates of death, MI or stroke (10.0% vs 8.7%, HR 1.14, 95% CI: 0.70 to 1.87; pinteraction=0.484). When comparing target vessel type, treatment effects were consistent among graft- and native-vessel interventions. CONCLUSIONS: In high-risk patients with prior CABG, ticagrelor monotherapy reduced bleeding without compromising ischaemic outcomes compared with ticagrelor plus aspirin.

Ride the Wave: Continuous Electroencephalography is Indicated in the Management of Traumatic Brain Injury.

Introduction: Patients with traumatic brain injury (TBI) are at risk for seizures and other abnormalities that can have permanent adverse effects on the brain. We aimed to report the incidence of seizures and continuous EEG (cEEG) abnormalities after TBI and identify any risk factors associated with the development of these abnormalities. Materials and Methods: This retrospective study identified 245 adult patients with mild to severe TBI who had a cEEG performed within one week of admission to a Midwest Level 1 Trauma Center between July 2014 and July 2019. Trauma registry and electronic medical record (EPIC) data were extracted. Results: Twelve percent of patients with TBI developed seizures and an additional 23% demonstrated electrographic patterns that are correlated with risk for seizures (such as lateralized periodic patterns and sporadic epileptiform discharges). Fifty three percent of seizures would have been missed unless a cEEG was performed. Age, history of epilepsy or prior TBI, hypertension, bleeding disorder, and dementia were associated with an increased risk of developing seizures or higher risk patterns. Conclusions: Thirty-five percent of patients who presented with TBI were noted to have seizures or electrographic patterns associated with a higher risk of seizures. The incidence of cEEG abnormalities in this study is higher than previously reported and these patients are at risk for permanent neurological injury. We recommend the routine use of cEEG for all critically ill patients with TBI as over half of the seizures would have been missed if cEEG was not employed.

Does Long-Duration Exposure to Microgravity Lead to Dysregulation of the Brain and Ocular Glymphatic Systems?

Spaceflight-associated neuro-ocular syndrome (SANS) has been well documented in astronauts both during and after long-duration spaceflight and is characterized by the development of optic disc edema, globe flattening, choroidal folds, and hyperopic refractive error shifts. The exact mechanisms underlying these ophthalmic abnormalities remain unclear. New findings regarding spaceflight-associated alterations in cerebrospinal fluid spaces, specifically perivascular spaces, may shed more light on the pathophysiology of SANS. The preliminary results of a recent brain magnetic resonance imaging study show that perivascular spaces enlarge under prolonged microgravity conditions, and that the amount of fluid in perivascular spaces is linked to SANS. The exact pathophysiological mechanisms underlying enlargement of perivascular spaces in space crews are currently unclear. Here, we speculate that the dilation of perivascular spaces observed in long-duration space travelers may result from impaired cerebral venous outflow and compromised cerebrospinal fluid resorption, leading to obstruction of glymphatic perivenous outflow and increased periarterial cerebrospinal fluid inflow, respectively. Further, we provide a possible explanation for how dilated perivascular spaces can be associated with SANS. Given that enlarged perivascular spaces in space crews may be a marker of altered venous hemodynamics and reduced cerebrospinal fluid outflow, at the level of the optic nerve and eye, these disturbances may contribute to SANS. If confirmed by further studies, brain glymphatic dysfunction in space crews could potentially be considered a risk factor for the development of neurodegenerative diseases, such as Alzheimer's disease. Furthermore, long-duration exposure to microgravity might contribute to SANS through dysregulation of the ocular glymphatic system. If prolonged spaceflight exposure causes disruption of the glymphatic systems, this might affect the ability to conduct future exploration missions, for example, to Mars. The considerations outlined in the present paper further stress the crucial need to develop effective long-term countermeasures to mitigate SANS-related physiologic changes during long-duration spaceflight.

To Tranexamic Acid or Not to Tranexamic Acid? Accuracy of Antifibrinolytic Administration at Altitude.

OBJECTIVE: Tranexamic acid (TXA) has demonstrated a reduction in all-cause mortality in trauma patients with hemorrhage. Administering TXA in the prehospital setting presents unique challenges because the identification of bleeding is based on clinical suspicion without advanced imaging or diagnostic tools. The objective of this study was to examine whether prehospital suspicion of bleeding is validated by in-hospital computed tomographic imaging and examination and to determine if patients received TXA in the absence of hemorrhage. The study was conducted at a level 1 trauma center supported by air medical transport services. METHODS: This is a retrospective cohort study examining 88 trauma patients receiving prehospital TXA to treat suspected hemorrhage. Adult trauma patients who received TXA during the study period and were transported to our level 1 trauma center were included. A panel of trauma surgeons reviewed CT imaging and examination findings to retrospectively identify significant hemorrhage. RESULTS: Forty-three percent of patients who received TXA during air medical transport did not have confirmed hemorrhage upon arrival. CONCLUSION: TXA was given to a significant number of patients who did not have confirmed hemorrhage upon arrival. We recommend that institutions using TXA perform this internal validation to ensure they are accurately identifying hemorrhage in the prehospital setting.

Optic Disc Edema in Astronauts from a Choroidal Point of View.

INTRODUCTION: Optic disc edema has been well documented in astronauts both during and after long-duration spaceflight and is hypothesized to largely result from increased pressure within the orbital subarachnoid space brought about by a generalized rise in intracranial pressure or from sequestration of cerebrospinal fluid within the orbital subarachnoid space with locally elevated optic nerve sheath pressure. In addition, a recent prospective study documented substantial spaceflight-associated peripapillary choroidal thickening, which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. In the present article, based on the above, we offer a new perspective on the pathogenesis of microgravity-induced optic disc edema from a choroidal point of view. We propose that prolonged microgravity exposure may result in the transudation of fluid from the choroidal vasculature, which, in turn, may reach the optic nerve head, and ultimately may lead to fluid stasis within the prelaminar region secondary to impaired ocular glymphatic outflow. If confirmed, this viewpoint would shed new light on the development of optic disc edema in astronauts.Wostyn P, Gibson CR, Mader TH. Optic disc edema in astronauts from a choroidal point of view. Aerosp Med Hum Perform. 2022; 93(4):396-398.

Clinical events classification (CEC) in clinical trials: Report on the current landscape and future directions - proceedings from the CEC Summit 2018.

IMPORTANCE: Clinical events adjudication is pivotal for generating consistent and comparable evidence in clinical trials. The methodology of event adjudication is evolving, but research is needed to develop best practices and spur innovation. OBSERVATIONS: A meeting of stakeholders from regulatory agencies, academic and contract research organizations, pharmaceutical and device companies, and clinical trialists convened in Chicago, IL, for Clinical Events Classification (CEC) Summit 2018 to discuss key topics and future directions. Formal studies are lacking on strategies to optimize CEC conduct, improve efficiency, minimize cost, and generally increase the speed and accuracy of the event adjudication process. Major challenges to CEC discussed included ensuring rigorous quality of the process, identifying safety events, standardizing event definitions, using uniform strategies for missing information, facilitating interactions between CEC members and other trial leadership, and determining the CEC's role in pragmatic trials or trials using real-world data. Consensus recommendations from the meeting include the following: (1) ensure an adequate adjudication infrastructure; (2) use negatively adjudicated events to identify important safety events reported only outside the scope of the primary endpoint; (3) conduct further research in the use of artificial intelligence and digital/mobile technologies to streamline adjudication processes; and (4) emphasize the importance of standardizing event definitions and quality metrics of CEC programs. CONCLUSIONS AND RELEVANCE: As novel strategies for clinical trials emerge to generate evidence for regulatory approval and to guide clinical practice, a greater understanding of the role of the CEC process will be critical to optimize trial conduct and increase confidence in the data generated.

Hotter Than It Looks: A Retrospective Review of Patients With Cholecystitis and With Negative Imaging.

INTRODUCTION: Ultrasound is the gold standard for workup of cholecystitis in the emergency department, and findings heavily influence clinical decision-making. Patients with negative imaging for acute cholecystitis may be inappropriately sent home. The purpose of our study was to review the pathology and outcomes of patients presenting with biliary pain and negative ultrasound findings of acute cholecystitis. MATERIALS AND METHODS: Emergency department patients who underwent laparoscopic cholecystectomy between January 2015 and February 2019 were reviewed retrospectively. Only patients with negative or equivocal imaging were included. The primary outcome was the incidence of cholecystitis on final pathology. RESULTS: Two hundred fifty-seven patients underwent laparoscopic cholecystectomy. Pathology demonstrated cholecystitis in 84% of patients. Only 15% of patients had cholelithiasis without cholecystitis on pathology. The incidence of cholecystitis was similar in negative and equivocal imaging groups (84% versus 83%; P = 0.960). The median time from admission to the operating room was 12.1 h (interquartile range 7.1-18.3 h), and hospital length of stay was 1.2 d (interquartile range 0.8-1.7 d). CONCLUSIONS: This study found that patients with negative or equivocal imaging had cholecystitis on pathology. On review of patient outcomes, those patients who underwent surgical intervention had a low rate of complications and short hospital stay.

Comparative effects of guided vs. potent P2Y12 inhibitor therapy in acute coronary syndrome: a network meta-analysis of 61 898 patients from 15 randomized trials.

AIMS: Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this limitation. We aimed at evaluating the comparative safety and efficacy of guided vs. routine selection of potent P2Y12 inhibiting therapy in patients with ACS. METHODS AND RESULTS: We performed a network meta-analysis of randomized controlled trials (RCTs) comparing different oral P2Y12 inhibitors currently recommended for the treatment of patients with ACS (clopidogrel, prasugrel, and ticagrelor). RCTs including a guided approach (i.e. platelet function or genetic testing) vs. standard selection of P2Y12 inhibitors among patients with ACS were also included. Incidence rate ratios (IRR) and associated 95% confidence intervals (CIs) were estimated. P-scores were used to estimate hierarchies of efficacy and safety. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was all bleeding. A total of 61 898 patients from 15 RCTs were included. Clopidogrel was used as reference treatment. A guided approach was the only strategy associated with reduced MACE (IRR: 0.80, 95% CI: 0.65-0.98) without any significant trade-off in all bleeding (IRR: 1.22, 95% CI: 0.96-1.55). A guided approach and prasugrel were associated with reduced myocardial infarction. A guided approach, prasugrel, and ticagrelor were associated with reduced stent thrombosis. Ticagrelor was also associated with reduced total and cardiovascular mortality. Prasugrel was associated with increased major bleeding. Prasugrel and ticagrelor were associated with increased minor bleeding. The incidence of stroke did not differ between treatments. CONCLUSION: In patients with an ACS, compared with routine selection of potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection of P2Y12 inhibiting therapy is associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided approach for the selection of P2Y12 inhibiting therapy in patients with ACS. STUDY REGISTRATION NUMBER: This study is registered in PROSPERO (CRD42021258603). KEY QUESTION: A guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing improves outcomes among patients undergoing percutaneous coronary intervention. Nevertheless, the comparative safety and efficacy of a guided versus routine selection of potent P2Y12-inhibiting therapy in acute coronary syndrome has not been explored. KEY FINDING: In a comprehensive network meta-analysis including the totality of available evidence and using clopidogrel as treatment reference, a guided approach was the only strategy associated with reduced major adverse cardiovascular events without any significant trade-off in bleeding. Prasugrel and ticagrelor increased bleeding and only ticagrelor reduced mortality. TAKE HOME MESSAGE: A guided selection of P2Y12-inhibiting therapy represents the strategy associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided P2Y12 inhibiting therapy in patients with acute coronary syndrome.

Cost-Consequence Analysis of Using Cangrelor in High Angiographic Risk Percutaneous Coronary Intervention Patients: A US Hospital Perspective.

OBJECTIVES: The objective of this study was to evaluate a US hospital's cost implications and outcomes of cangrelor use in percutaneous coronary intervention (PCI) patients with two or more angiographic high-risk features (HRFs), including avoidance of oral P2Y12 inhibitor pretreatment in patients requiring cardiac surgery. Intravenous cangrelor provides direct, immediate onset and rapid-offset P2Y12 inhibition, which may reduce the necessity for oral P2Y12 pretreatment. METHODS: A decision analytic model was developed, estimating the annual impact over 3 years of cangrelor availability. Ischemic and bleeding events (48 h) from randomized clinical trial data were extrapolated to 30 days. Event costs were from the CHAMPION PHOENIX Economics substudy. Rates of coronary artery disease (CAD) presentation, PCI, oral P2Y12 pretreatment, and inpatient hospitalization costs were from published literature and clinical experts. Scenario analyses evaluated the impact of cangrelor availability on potential reduced P2Y12 pretreatment rates by 50-100%. Drug costs were 2019 wholesale acquisition costs and, where necessary, all costs were adjusted to 2019 dollars. RESULTS: In a hospital treating 1000 CAD PCI inpatients annually, increasing cangrelor use from 11 to 32% resulted in a reduction in 48-h ischemic events/year by 5.7%, while bleeding events increased by 2.9%. Total costs of $1,135,472 declined 12.8%, with a 50% reduction in P2Y12 pretreatment or 30% with no pretreatment. Savings were driven by a decrease in ischemic events, decrease in glycoprotein IIb/IIIa inhibitor use, and less need for and shorter oral P2Y12 inhibitor washout period for surgery patients. CONCLUSION: Use of cangrelor in patients with two or more angiographic HRFs may improve outcomes and lower hospital budgets, mainly from avoiding surgery delays necessitated by oral P2Y12 inhibitor pretreatment.

The odyssey of the ocular and cerebrospinal fluids during a mission to Mars: the "ocular glymphatic system" under pressure.

A significant proportion of the astronauts who spend extended periods in microgravity develop ophthalmic abnormalities including optic disc edema, globe flattening, chorioretinal folds, and hyperopic refractive error shifts. A constellation of these neuro-ophthalmic findings has been termed "spaceflight-associated neuro-ocular syndrome". Understanding this syndrome is currently a top priority for NASA, especially in view of future long-duration missions (e.g., Mars missions). The recent discovery of an "ocular glymphatic system" can potentially help to unlock mechanisms underlying microgravity-induced optic disc edema. Indeed, a major paradigm shift is currently occurring in our understanding of transport of fluids and solutes through the optic nerve following the recent discovery of an optic nerve glymphatic pathway for influx of cerebrospinal fluid. In addition, the recent identification of an entirely new glymphatic pathway for efflux of ocular fluid may have profound implications for fluid dynamics in the eye. Observations pertaining to this ocular glymphatic pathway provide critical new insights into how intracranial pressure can alter basic fluid transport in the eye. We believe that these novel findings have the potential to be game changers in our understanding of the pathogenesis of optic disc edema in astronauts. In the present review, we integrate these new insights with findings on the intracranial and neuro-ophthalmologic effects of microgravity in one coherent conceptual framework. Further studies in this area of investigation could not only provide exciting new insights into the mechanisms underlying microgravity-induced optic disc edema but also offer opportunities to develop countermeasure strategies.