Early Release Science of the exoplanet WASP-39b with JWST NIRCam.

Measuring the metallicity and carbon-to-oxygen (C/O) ratio in exoplanet atmospheres is a fundamental step towards constraining the dominant chemical processes at work and, if in equilibrium, revealing planet formation histories. Transmission spectroscopy (for example, refs. 1,2) provides the necessary means by constraining the abundances of oxygen- and carbon-bearing species; however, this requires broad wavelength coverage, moderate spectral resolution and high precision, which, together, are not achievable with previous observatories. Now that JWST has commenced science operations, we are able to observe exoplanets at previously uncharted wavelengths and spectral resolutions. Here we report time-series observations of the transiting exoplanet WASP-39b using JWST's Near InfraRed Camera (NIRCam). The long-wavelength spectroscopic and short-wavelength photometric light curves span 2.0-4.0 micrometres, exhibit minimal systematics and reveal well defined molecular absorption features in the planet's spectrum. Specifically, we detect gaseous water in the atmosphere and place an upper limit on the abundance of methane. The otherwise prominent carbon dioxide feature at 2.8 micrometres is largely masked by water. The best-fit chemical equilibrium models favour an atmospheric metallicity of 1-100-times solar (that is, an enrichment of elements heavier than helium relative to the Sun) and a substellar C/O ratio. The inferred high metallicity and low C/O ratio may indicate significant accretion of solid materials during planet formation (for example, refs. 3,4,) or disequilibrium processes in the upper atmosphere (for example, refs. 5,6).

A remnant planetary core in the hot-Neptune desert.

The interiors of giant planets remain poorly understood. Even for the planets in the Solar System, difficulties in observation lead to large uncertainties in the properties of planetary cores. Exoplanets that have undergone rare evolutionary processes provide a route to understanding planetary interiors. Planets found in and near the typically barren hot-Neptune 'desert'1,2 (a region in mass-radius space that contains few planets) have proved to be particularly valuable in this regard. These planets include HD149026b3, which is thought to have an unusually massive core, and recent discoveries such as LTT9779b4 and NGTS-4b5, on which photoevaporation has removed a substantial part of their outer atmospheres. Here we report observations of the planet TOI-849b, which has a radius smaller than Neptune's but an anomalously large mass of [Formula: see text] Earth masses and a density of [Formula: see text] grams per cubic centimetre, similar to Earth's. Interior-structure models suggest that any gaseous envelope of pure hydrogen and helium consists of no more than [Formula: see text] per cent of the total planetary mass. The planet could have been a gas giant before undergoing extreme mass loss via thermal self-disruption or giant planet collisions, or it could have avoided substantial gas accretion, perhaps through gap opening or late formation6. Although photoevaporation rates cannot account for the mass loss required to reduce a Jupiter-like gas giant, they can remove a small (a few Earth masses) hydrogen and helium envelope on timescales of several billion years, implying that any remaining atmosphere on TOI-849b is likely to be enriched by water or other volatiles from the planetary interior. We conclude that TOI-849b is the remnant core of a giant planet.

Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty.

BACKGROUND: Clinical trials and meta-analyses have suggested that aspirin may be effective for the prevention of venous thromboembolism (proximal deep-vein thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but comparisons with direct oral anticoagulants are lacking for prophylaxis beyond hospital discharge. METHODS: We performed a multicenter, double-blind, randomized, controlled trial involving patients who were undergoing total hip or knee arthroplasty. All the patients received once-daily oral rivaroxaban (10 mg) until postoperative day 5 and then were randomly assigned to continue rivaroxaban or switch to aspirin (81 mg daily) for an additional 9 days after total knee arthroplasty or for 30 days after total hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism (the primary effectiveness outcome) and bleeding complications, including major or clinically relevant nonmajor bleeding (the primary safety outcome). RESULTS: A total of 3424 patients (1804 undergoing total hip arthroplasty and 1620 undergoing total knee arthroplasty) were enrolled in the trial. Venous thromboembolism occurred in 11 of 1707 patients (0.64%) in the aspirin group and in 12 of 1717 patients (0.70%) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], -0.55 to 0.66; P<0.001 for noninferiority and P=0.84 for superiority). Major bleeding complications occurred in 8 patients (0.47%) in the aspirin group and in 5 (0.29%) in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, -0.65 to 0.29; P=0.42). Clinically important bleeding occurred in 22 patients (1.29%) in the aspirin group and in 17 (0.99%) in the rivaroxaban group (difference, 0.30 percentage points; 95% CI, -1.07 to 0.47; P=0.43). CONCLUSIONS: Among patients who received 5 days of rivaroxaban prophylaxis after total hip or total knee arthroplasty, extended prophylaxis with aspirin was not significantly different from rivaroxaban in the prevention of symptomatic venous thromboembolism. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT01720108 .).

Body Mass Index and Risk for Intubation or Death in SARS-CoV-2 Infection : A Retrospective Cohort Study.

BACKGROUND: Obesity is a risk factor for pneumonia and acute respiratory distress syndrome. OBJECTIVE: To determine whether obesity is associated with intubation or death, inflammation, cardiac injury, or fibrinolysis in coronavirus disease 2019 (COVID-19). DESIGN: Retrospective cohort study. SETTING: A quaternary academic medical center and community hospital in New York City. PARTICIPANTS: 2466 adults hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection over a 45-day period with at least 47 days of in-hospital observation. MEASUREMENTS: Body mass index (BMI), admission biomarkers of inflammation (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]), cardiac injury (troponin level), and fibrinolysis (D-dimer level). The primary end point was a composite of intubation or death in time-to-event analysis. RESULTS: Over a median hospital length of stay of 7 days (interquartile range, 3 to 14 days), 533 patients (22%) were intubated, 627 (25%) died, and 59 (2%) remained hospitalized. Compared with overweight patients, patients with obesity had higher risk for intubation or death, with the highest risk among those with class 3 obesity (hazard ratio, 1.6 [95% CI, 1.1 to 2.1]). This association was primarily observed among patients younger than 65 years and not in older patients (P for interaction by age = 0.042). Body mass index was not associated with admission levels of biomarkers of inflammation, cardiac injury, or fibrinolysis. LIMITATIONS: Body mass index was missing for 28% of patients. The primary analyses were conducted with multiple imputation for missing BMI. Upper bounding factor analysis suggested that the results are robust to possible selection bias. CONCLUSION: Obesity is associated with increased risk for intubation or death from COVID-19 in adults younger than 65 years, but not in adults aged 65 years or older. PRIMARY FUNDING SOURCE: National Institutes of Health.

The contribution of the C5 protein subunit of Escherichia coli ribonuclease P to specificity for precursor tRNA is modulated by proximal 5' leader sequences.

Recognition of RNA by RNA processing enzymes and RNA binding proteins often involves cooperation between multiple subunits. However, the interdependent contributions of RNA and protein subunits to molecular recognition by ribonucleoproteins are relatively unexplored. RNase P is an endonuclease that removes 5' leaders from precursor tRNAs and functions in bacteria as a dimer formed by a catalytic RNA subunit (P RNA) and a protein subunit (C5 in E. coli). The P RNA subunit contacts the tRNA body and proximal 5' leader sequences [N(-1) and N(-2)] while C5 binds distal 5' leader sequences [N(-3) to N(-6)]. To determine whether the contacts formed by P RNA and C5 contribute independently to specificity or exhibit cooperativity or anti-cooperativity, we compared the relative kcat/Km values for all possible combinations of the six proximal 5' leader nucleotides (n = 4096) for processing by the E. coli P RNA subunit alone and by the RNase P holoenzyme. We observed that while the P RNA subunit shows specificity for 5' leader nucleotides N(-2) and N(-1), the presence of the C5 protein reduces the contribution of P RNA to specificity, but changes specificity at N(-2) and N(-3). The results reveal that the contribution of C5 protein to RNase P processing is controlled by the identity of N(-2) in the pre-tRNA 5' leader. The data also clearly show that pairing of the 5' leader with the 3' ACCA of tRNA acts as an anti-determinant for RNase P cleavage. Comparative analysis of genomically encoded E. coli tRNAs reveals that both anti-determinants are subject to negative selection in vivo.

Geographic disparities in donor lung supply and lung transplant waitlist outcomes: A cohort study.

Despite the Final Rule mandate for equitable organ allocation in the United States, geographic disparities exist in donor lung allocation, with the majority of donor lungs being allocated locally to lower-priority candidates. We conducted a retrospective cohort study of 19 622 lung transplant candidates waitlisted between 2006 and 2015. We used multivariable adjusted competing risk survival models to examine the relationship between local lung availability and waitlist outcomes. The primary outcome was a composite of death and removal from the waitlist for clinical deterioration. Waitlist candidates in the lowest quartile of local lung availability had an 84% increased risk of death or removal compared with candidates in the highest (subdistribution hazard ratio [SHR]: 1.84, 95% confidence interval [CI]: 1.51-2.24, P < .001). The transplantation rate was 57% lower in the lowest quartile compared with the highest (SHR: 0.43, 95% CI: 0.39-0.47). The adjusted death or removal rate decreased by 11% with a 50% increase in local lung availability (SHR: 0.89, 95% CI: 0.85-0.93, P < .001) and the adjusted transplantation rate increased by 19% (SHR: 1.19, 95% CI: 1.17-1.22, P < .001). There are geographically disparate waitlist outcomes in the current lung allocation system. Candidates listed in areas of low local lung availability have worse waitlist outcomes.

A high C/O ratio and weak thermal inversion in the atmosphere of exoplanet WASP-12b.

The carbon-to-oxygen ratio (C/O) in a planet provides critical information about its primordial origins and subsequent evolution. A primordial C/O greater than 0.8 causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth; the atmosphere can also differ from those in the Solar System. The solar C/O is 0.54 (ref. 3). Here we report an analysis of dayside multi-wavelength photometry of the transiting hot-Jupiter WASP-12b (ref. 6) that reveals C/O ≥ 1 in its atmosphere. The atmosphere is abundant in CO. It is depleted in water vapour and enhanced in methane, each by more than two orders of magnitude compared to a solar-abundance chemical-equilibrium model at the expected temperatures. We also find that the extremely irradiated atmosphere (T > 2,500 K) of WASP-12b lacks a prominent thermal inversion (or stratosphere) and has very efficient day-night energy circulation. The absence of a strong thermal inversion is in stark contrast to theoretical predictions for the most highly irradiated hot-Jupiter atmospheres.

Comparison of self-expandable and balloon-expanding stents for hybrid ductal stenting in hypoplastic left heart complex.

OBJECTIVES: We aimed to compare the procedural and mid-term performance of a specifically designed self-expanding stent with balloon-expandable stents in patients undergoing hybrid palliation for hypoplastic left heart syndrome and its variants. BACKGROUND: The lack of specifically designed stents has led to off-label use of coronary, biliary, or peripheral stents in the neonatal ductus arteriosus. Recently, a self-expanding stent, specifically designed for use in hypoplastic left heart syndrome, has become available. METHODS: We carried out a retrospective cohort comparison of 69 neonates who underwent hybrid ductal stenting with balloon-expandable and self-expanding stents from December, 2005 to July, 2014. RESULTS: In total, 43 balloon-expandable stents were implanted in 41 neonates and more recently 47 self-expanding stents in 28 neonates. In the balloon-expandable stents group, stent-related complications occurred in nine patients (22%), compared with one patient in the self-expanding stent group (4%). During follow-up, percutaneous re-intervention related to the ductal stent was performed in five patients (17%) in the balloon-expandable stent group and seven patients (28%) in self-expanding stents group. CONCLUSIONS: Hybrid ductal stenting with self-expanding stents produced favourable results when compared with the results obtained with balloon-expandable stents. Immediate additional interventions and follow-up re-interventions were similar in both groups with complications more common in those with balloon-expandable stents.

Dose assessment from chronic exposure to industrial NORM in iron ore processing.

Radiological exposures due to naturally occurring radioactive material (NORM) can occur during a wide range of work-related activities in the mineral processing and chemical industries. However, evaluation of such exposures in industrial settings remains a difficult exercise owing inter alia to the large number of personnel, operations and plants affected; assumptions that often have to be made concerning the actual duration and frequency of exposures; the complex chemistry and radioactive disequilibria involved and typically, the paucity of historical data. In our study, the challenges associated with assessing chronic exposure to fugitive dust enriched in 210Pb and 210Po and the determination of the associated internal dose by inhalation and ingestion are described by reference to a case study undertaken at an iron ore sintering plant between June 2013 and July 2015. The applicability of default dose coefficients and biokinetic models provided by the International Commission for Radiological Protection (ICRP) was verified by combining air and dust monitoring with information on the characteristics of the aerosols and in-vitro solubility experiments. The disparity between particulate matter 100 microns or less in diameter (PM100), particulate matter 10 microns or less in diameter (PM10) and 210Pb/210Po activity concentrations observed over the different monitoring campaigns and sampling locations confirmed that use of positional short-term monitoring surveys to extrapolate intake over a year was not appropriate and could lead to unrealistic intake and dose figures. Personal air sampling is more appropriate for estimating the dose in such situations, though it is not always practical and may collect insufficient quantities of material for radiochemical analysis; this is an important constraint when dealing with low specific activity materials.

Dose assessment from chronic exposure to industrial NORM in iron ore processing.

Radiological exposures due to naturally occurring radioactive material (NORM) can occur during a wide range of work-related activities in the mineral processing and chemical industries. However, evaluation of such exposures in industrial settings remains a difficult exercise owing inter alia to the large number of personnel, operations and plants affected; assumptions that often have to be made concerning the actual duration and frequency of exposures; the complex chemistry and radioactive disequilibria involved and typically, the paucity of historical data. In our study, the challenges associated with assessing chronic exposure to fugitive dust enriched in 210Pb and 210Po and the determination of the associated internal dose by inhalation and ingestion are described by reference to a case study undertaken at an iron ore sintering plant between June 2013 and July 2015. The applicability of default dose coefficients and biokinetic models provided by the International Commission for Radiological Protection was verified by combining air and dust monitoring with information on the characteristics of the aerosols and in-vitro solubility experiments. The disparity between particulate matter 100 microns or less in diameter (PM100), particulate matter 10 microns or less in diameter (PM10) and 210Pb/210Po activity concentrations observed over the different monitoring campaigns and sampling locations confirmed that use positional short-term monitoring surveys to extrapolate intake over a year was not appropriate and could lead to unrealistic intake and dose figures. Personal air sampling is more appropriate for estimating the dose in such situations, though it is not always practical and may collect insufficient quantities of material for radiochemical analysis; this is an important constraint when dealing with low specific activity materials.

Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial.

BACKGROUND: Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS. METHODS: We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov, number NCT00143598, and Current Controlled Trials, number ISRCTN71334751. FINDINGS: From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73-1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings. INTERPRETATION: ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT. FUNDING: Canadian Institutes of Health Research.

Association of dual-antiplatelet therapy with reduced major adverse cardiovascular events in patients with symptomatic peripheral arterial disease.

OBJECTIVE: This study was conducted to determine whether there is additive benefit of dual-antiplatelet therapy (DAPT) with aspirin (acetylsalicylic acid [ASA]) and clopidogrel compared with ASA monotherapy among patients with symptomatic peripheral arterial disease. METHODS: This was an observational cohort analysis that included 629 patients with claudication or critical limb ischemia. The prevalence of patients taking ASA monotherapy vs DAPT was assessed monthly for up to 3 years. A propensity model was constructed to adjust for baseline demographic characteristics and to assess the effect of DAPT on major adverse cardiovascular events (MACEs) and major adverse limb events. RESULTS: At baseline, 348 patients were taking DAPT and 281 were taking ASA monotherapy. During 3 years of follow-up, 50 events (20%) occurred in the DAPT group vs 59 (29%) in the ASA monotherapy group. After propensity weighting, DAPT use was associated with a decreased risk of MACEs (adjusted hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44-0.96) and overall mortality (adjusted HR, 0.55; 95% CI, 0.35-0.89). No association was found between DAPT use and the risk of major amputation (adjusted HR, 0.69; 95% CI, 0.37-1.29). In a subgroup of 94 patients who underwent point-of-care platelet function testing, 21% had decreased response to ASA and 55% had a decreased response to clopidogrel. No association was found between a reduced response to ASA or clopidogrel and adverse events at 1 year. CONCLUSIONS: DAPT may be associated with reduced rates of MACEs and death among patients with symptomatic peripheral arterial disease.

Selectively targeting an inactive conformation of interleukin-2-inducible T-cell kinase by allosteric inhibitors.

ITK (interleukin-2-inducible T-cell kinase) is a critical component of signal transduction in T-cells and has a well-validated role in their proliferation, cytokine release and chemotaxis. ITK is an attractive target for the treatment of T-cell-mediated inflammatory diseases. In the present study we describe the discovery of kinase inhibitors that preferentially bind to an allosteric pocket of ITK. The novel ITK allosteric site was characterized by NMR, surface plasmon resonance, isothermal titration calorimetry, enzymology and X-ray crystallography. Initial screening hits bound to both the allosteric pocket and the ATP site. Successful lead optimization was achieved by improving the contribution of the allosteric component to the overall inhibition. NMR competition experiments demonstrated that the dual-site binders showed higher affinity for the allosteric site compared with the ATP site. Moreover, an optimized inhibitor displayed non-competitive inhibition with respect to ATP as shown by steady-state enzyme kinetics. The activity of the isolated kinase domain and auto-activation of the full-length enzyme were inhibited with similar potency. However, inhibition of the activated full-length enzyme was weaker, presumably because the allosteric site is altered when ITK becomes activated. An optimized lead showed exquisite kinome selectivity and is efficacious in human whole blood and proximal cell-based assays.

Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial.

BACKGROUND: The role of aspirin in thromboprophylaxis after total hip arthroplasty (THA) is controversial. OBJECTIVE: To compare extended prophylaxis with aspirin and dalteparin for prevention of symptomatic venous thromboembolism (VTE) after THA. DESIGN: Multicenter randomized, controlled trial with a noninferiority design based on a minimal clinically important difference of 2.0%. Randomization was electronically generated; patients were assigned to a treatment group through a Web-based program. Patients, physicians, study coordinators, health care team members, outcome adjudicators, and data analysts were blinded to interventions. (Current Controlled Trials: ISRCTN11902170). SETTING: 12 tertiary care orthopedic referral centers in Canada. PATIENTS: 778 patients who had elective unilateral THA between 2007 and 2010. INTERVENTION: After an initial 10 days of dalteparin prophylaxis after elective THA, patients were randomly assigned to 28 days of dalteparin (n = 400) or aspirin (n = 386). MEASUREMENTS: Symptomatic VTE confirmed by objective testing (primary efficacy outcome) and bleeding. RESULTS: Five of 398 patients (1.3%) randomly assigned to dalteparin and 1 of 380 (0.3%) randomly assigned to aspirin had VTE (absolute difference, 1.0 percentage point [95% CI, -0.5 to 2.5 percentage points]). Aspirin was noninferior (P < 0.001) but not superior (P = 0.22) to dalteparin. Clinically significant bleeding occurred in 5 patients (1.3%) receiving dalteparin and 2 (0.5%) receiving aspirin. The absolute between-group difference in a composite of all VTE and clinically significant bleeding events was 1.7 percentage points (CI, -0.3 to 3.8 percentage points; P = 0.091) in favor of aspirin. LIMITATION: The study was halted prematurely because of difficulty with patient recruitment. CONCLUSION: Extended prophylaxis for 28 days with aspirin was noninferior to and as safe as dalteparin for the prevention of VTE after THA in patients who initially received dalteparin for 10 days. Given its low cost and greater convenience, aspirin may be considered a reasonable alternative for extended thromboprophylaxis after THA. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Pneumatic Retinopexy with Focal Laser Photocoagulation for Myopic Foveoschisis with Macular Detachment.

PURPOSE: To describe the clinical course and imaging of a case of myopic foveoschisis (MF) with macular detachment (MD), microbreak and epiretinal membrane (ERM) managed with pneumatic retinopexy (PR) and focal laser photocoagulation (FLP) of the microbreak. METHODS: Retrospective Case Review of a highly myopic, phakic Caucasian man who developed vision loss due to MF with MD. RESULTS: 66 year old phakic man with a refractive error of -13.25-2.25x150 in his left eye (OS) and one month visual loss who was diagnosed with MF with MD, microbreak and ERM developed recurrent, isolated, posterior, partial macular detachment one month after PR. CMT was 901um. Repeat PR with supplemental FLP surrounding the inferior macular periarteriolar microbreak achieved re-attachment and improvement in the retinoschisis with return of visual acuity from 20/150 to baseline 20/40+ at 18 month follow-up. CONCLUSION: PR with FLP may provide an alternative to vitrectomy and MP for the repair of MF with MD and ERM.

Sudden vision loss heralding COVID-19-associated aspergillosis. Report of 2 cases.

Purpose: To describe clinical, radiographic, laboratory and cytopathologic findings in 2 patients who developed vision loss due to endogenous aspergillus endophthalmitis during hospitalization for COVID-19 pneumonia. Observations: Two unvaccinated sexagenarian male smokers lost vision within one month of contracting COVID-19 pneumonia. Initially, both received high dose steroids, nasal cannula oxygen and remdesivir. Immunomodulators tocilizumab or baricitinib were added during week 2 in case 1 and 2 respectively. Upon presentation after discharge from a post-COVID rehabilitation unit, visual acuities were light perception and hand motion. In both cases, inpatient blood and ocular fluid cultures were negative, serum 1,3-beta-D-glucan was positive, and vitreous cytopathology revealed filamentous fungi and PCR was positive for Aspergillus fumigatus. Large solitary intravitreal fungus balls were debulked in patient 1 and excised in patient 2. Final visual acuities were no light perception and 20/200 respectively. MRI revealed previously unsuspected brain and lung lesions consistent with disseminated aspergillosis in patient 2. Conclusions: Vision loss due to fungal endophthalmitis may be the first or only sign of systemic aspergillosis associated with COVID-19 pneumonia. Aspergillosis should be suspected in patients who develop vision loss. Diagnosis limited by negative fungal cultures may be confirmed by vitreous cytopathology and PCR. Systemic imaging for disseminated aspergillosis is indicated. Ultimate visual acuity may depend upon surgical approach.

Rationing scarce healthcare capacity: A study of the ventilator allocation guidelines during the COVID-19 pandemic.

In the United States, even though national guidelines for allocating scarce healthcare resources are lacking, 26 states have specific ventilator allocation guidelines to be invoked in case of a shortage. While several states developed their guidelines in response to the recent COVID-19 pandemic, New York State developed these guidelines in 2015 as "pandemic influenza is a foreseeable threat, one that we cannot ignore." The primary objective of this study is to assess the existing procedures and priority rules in place for allocating/rationing scarce ventilator capacity and propose alternative (and improved) priority schemes. We first build machine learning models using inpatient records of COVID-19 patients admitted to New York-Presbyterian/Columbia University Irving Medical Center and an affiliated community health center to predict survival probabilities as well as ventilator length-of-use. Then, we use the resulting point estimators and their uncertainties as inputs for a multiclass priority queueing model with abandonments to assess three priority schemes: (i) SOFA-P (Sequential Organ Failure Assessment based prioritization), which most closely mimics the existing practice by prioritizing patients with sufficiently low SOFA scores; (ii) ISP (incremental survival probability), which assigns priority based on patient-level survival predictions; and (iii) ISP-LU (incremental survival probability per length-of-use), which takes into account survival predictions and resource use duration. Our findings highlight that our proposed priority scheme, ISP-LU, achieves a demonstrable improvement over the other two alternatives. Specifically, the expected number of survivals increases and death risk while waiting for ventilator use decreases. We also show that ISP-LU is a robust priority scheme whose implementation yields a Pareto-improvement over both SOFA-P and ISP in terms of maximizing saved lives after mechanical ventilation while limiting racial disparity in access to the priority queue.

The risk of major bleeding in patients with factor V Leiden or prothrombin G20210A gene mutation while on extended anticoagulant treatment for venous thromboembolism.

BACKGROUND: Thrombophilia predisposes to venous thromboembolism (VTE) because of acquired or hereditary factors. Among them, it has been suggested that gene mutations of the factor V Leiden (FVL) or prothrombin G20210A mutation (PGM) might reduce the risk of bleeding, but little data exist for patients treated using anticoagulants. OBJECTIVES: To assess whether thrombophilia is protective against bleeding. METHODS: This multicentre, multinational, prospective cohort study evaluated adults receiving long-term anticoagulants after a VTE event. We analyzed the incidence of major bleeding as the primary outcome, according to the genotype for FVL and PGM (wild-type and heterozygous/homozygous carriers). RESULTS: Of 2260 patients with genotype testing, during a median follow-up of 3 years, 106 patients experienced a major bleeding event (17 intracranial and 7 fatal). Among 439 carriers of FVL, 19 experienced major bleeding and there were no differences between any mutation vs wild-type (hazard ratio [HR], 0.89 [0.53-1.49]; p = .66). The comparison of major bleeding events between the 158 patients with any-PGM mutation (heterozygous or homozygous) vs wild-type also showed a nonstatistically significant difference with HR of 0.53 (0.19-1.43), p = .21. However, multivariate analysis demonstrated that major bleeds or clinically relevant nonmajor bleeding were statistically less likely for patients with either FVL and/or PGM compared with patients with both wild-type factor V and prothrombin genes (HR, 0.73; 95% CI = 0.55-0.97; p = .03). CONCLUSION: This study demonstrates that thrombophilia, defined as the presence of either FVL or the prothrombin G20210A mutation, is related with a lower rate of major/clinically relevant nonmajor bleeding while on anticoagulants in the extended treatment for VTE.