Tocilizumab Associated With Survival in Patients Hospitalized for COVID-19 Acute Respiratory Distress Syndrome and Low Urine Output.

BACKGROUND: Acute respiratory distress syndrome (ARDS) with oliguria is associated with increased mortality. Interleukin-6 (IL-6) plays an integral role in the pathophysiology of both disease processes. Patients who experience severe COVID-19 have demonstrated higher IL-6 levels compared to baseline, and use of tocilizumab has demonstrated efficacy in such cohorts. We set out to investigate the relationship between tocilizumab use, COVID-19 ARDS, low urine output, and mortality. METHODS: Retrospective cohort review of adult patients aged ≥ 18 years with COVID-19 and moderate or severe ARDS, admitted to the intensive care unit (ICU) of a tertiary referral center in metropolitan Detroit. Patients were analyzed based on presence of oliguria (defined as ≤ 0.7 mL/kg/h) on the day of intubation and exposure to tocilizumab while inpatient. The primary outcome was inpatient mortality. RESULTS: One hundred and twenty-eight patients were analyzed, 103 (80%) with low urine output, of whom 30 (29%) received tocilizumab. In patients with low urine output, risk factors associated with mortality on univariate analysis included Black race (P = .028), lower static compliance (P = .015), and tocilizumab administration (P = .002). Tocilizumab (odds ratio 0.245, 95% confidence interval 0.079-0.764, P = .015) was the only risk factor independently associated with survival on multivariate logistic regression analysis. CONCLUSION: In this retrospective cohort review of patients hospitalized with COVID-19 and moderate or severe ARDS, tocilizumab administration was independently associated with survival in patients with low urine output ≤ 0.7 mL/kg/h on the day of intubation. Prospective studies are needed to investigate the impact of urine output on efficacy of interleukin-targeted therapies in the management of ARDS.

A last resort? A scoping review of patient and healthcare worker attitudes toward strike action.

While strike action has been common since the industrial revolution, it often invokes a passionate and polarising response, from the strikers themselves, from employers, governments and the general public. Support or lack thereof from health workers and the general public is an important consideration in the justification of strike action. This systematic review sought to examine the impact of strike action on patient and clinician attitudes, specifically to explore (1) patient and health worker support for strike action and (2) the predictors for supporting strike action and the reasons given for engaging in strike action. A systematic scoping review was employed to identify all relevant literature, followed by a textual narrative synthesis. A total of 34 studies met inclusion criteria. Support for strike action was largely context-dependent. A range of factors impact support for strike action; broader cultural and structural factors, such as unionisation and general acceptance of strike action; systemic factors, such as the nature of the healthcare system, including infrastructure and work conditions; the strike itself and a range of individual factors, the most notable of which was being a student or in an early career stage. There were also some surprising results, for example, during doctors strike, nurses were provided with the opportunity to expand their role, which led to greater professional autonomy and job satisfaction.

Progression to Critical Illness and Death in Patients With Breakthrough Hospitalizations.

Background: Characterization of disease progression and outcomes after coronavirus disease 2019 (COVID-19)-related hospitalization in vaccinated compared with unvaccinated individuals is limited. Methods: This was a retrospective case-control study of symptomatic vaccinated (cases) and unvaccinated (controls) participants hospitalized for COVID-19 between December 30, 2020, and September 30, 2021, in Southeast Michigan. Hospitalized adult patients with lab-confirmed COVID-19 were identified through daily census report. Breakthrough infection was defined as detection of severe acute respiratory syndrome coronavirus 2 ≥14 days after completion of the primary vaccination series. The association between prior vaccination and critical COVID-19 illness (composite of intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], 28-day mortality) was examined. Results: Two hundred ten (39%) fully vaccinated and 325 (61%) unvaccinated patients were evaluated. Compared with controls, cases were older, had more comorbidities (4 [3-7] vs 2 [1-4]; P < .001), and were more likely to be immunocompromised. Cases had less severe symptoms compared with controls (2 [1-2] vs 2 [2-3]; P < .001) and were less likely to progress to critical COVID-19 illness (33.3% vs 45.5%; P < .001); 28-day mortality was significantly lower in cases (11.0% vs 24.9%; P < .001). Symptom severity (odds ratio [OR], 2.59; 95% CI, 1.61-4.16; P < .001) and modified Sequential Organ Failure Assessment score on presentation (OR, 1.74; 95% CI, 1.48-2.06; P < .001) were independently associated with development of critical COVID-19 illness. Prior vaccination (OR, 0.528; 95% CI, 0.307-0.910; P = .020) was protective. Conclusions: COVID-19-vaccinated patients were less likely to develop critical COVID-19 illness and more likely to survive. Disease severity at presentation was a predictor of adverse outcomes regardless of vaccination status.

Probing the Exit Channel of the OH + CH3OH → H2O + CH3O Reaction by Photodetachment of CH3O-(H2O).

Transition state dynamics of bimolecular reactions can be probed by photodetachment of a precursor anion when the Franck-Condon region of the corresponding neutral potential energy surface is near a saddle point. In this study, photodetachment of anions at m/z = 49 enabled investigation of the exit channel of the OH + CH3OH → H2O + CH3O reaction using photoelectron-photofragment coincidence spectroscopy. High-level coupled-cluster calculations of the stationary points on the anion surface show that the methoxide-water cluster CH3O-(H2O) is the stable minimum on the anion surface. Photodetachment at a 3.20 eV photon energy leads to long-lived H2O(CH3O) complexes and H2O + CH3O products consistent with both direct dissociative photodetachment and resonance mediated processes on the neutral surface. The partitioning of total kinetic energy in the system indicates that water stretch and bend excitation is induced in dissociative photodetachment and evidence for long-lived complexes consistent with vibrational Feshbach resonances is reported.

Dissociative Photodetachment Dynamics of the OH-(C2H4) Anion Complex.

Photoelectron-photofragment coincidence (PPC) measurements on OH-(C2H4) anions at a photon energy of 3.20 eV revealed stable and dissociative photodetachment product channels, OH-C2H4 + e- and OH + C2H4 + e-, respectively. The main product channel observed was dissociation to the reactants (>67%), OH + C2H4 (v = 0, 1, 2) + e-, where vibrational excitation in the C-H stretching modes of the C2H4 photofragments corresponds to a minor channel. The low kinetic energy release (KER) of the dissociating fragments is consistent with weak repulsion between the OH + C2H4 reactants near the transition state as well as the partitioning of energy into rotation of the dissociation products. An impulsive model was used to account for rotational energy partitioning in the dissociative photodetachment (DPD) process and showed good agreement with the experimental results. The low KER of the dissociating fragments and the similarities in the photoelectron spectra between stable and dissociative events support a mechanism involving the van der Waals complex formed upon photodetachment of OH-(C2H4) as an intermediate in the dominant OH + C2H4 + e- dissociative channel.

Secondary angiodysplasia-associated gastrointestinal bleeding in end-stage renal disease: Results from the nationwide inpatient sample.

BACKGROUND: Chronic kidney disease is associated with angiodysplasia of gastrointestinal tract leading to increased risk of gastrointestinal bleeding. AIM: To determine the nationwide prevalence, trends, predictors and resource utilization of angiodysplasia-associated gastrointestinal bleeding in end-stage renal disease hospitalizations. METHODS: The Nationwide Inpatient Sample database from 2009 to 2014, was utilized to conduct a retrospective study on patients with angiodysplasia associated- gastrointestinal bleeding and end-stage renal disease. Hospitalizations with end-stage renal disease were included in the Nationwide Inpatient Sample database and a subset of hospitalizations with end-stage renal disease and angiodysplasia-associated gastrointestinal bleeding were identified with International Classification of Diseases, 9th revision, Clinical Modification codes for both end-stage renal disease (585.6) and Angiodysplasia (569.85, 537.83). RESULTS: The prevalence of angiodysplasia-associated gastrointestinal bleeding was 0.45% (n = 24709) among all end-stage renal disease patients (n = 5505252) that were hospitalized. Multivariate analysis indicated that the following were significant factors associated with higher odds of angiodysplasia associated-gastrointestinal bleeding in end-stage renal disease patients: an increasing trend from 2009-2014 (P < 0.01), increasing age (P < 0.0001); African American race (P = 0.0206); increasing Charlson-Deyo Comorbidity Index (P < 0.01); hypertension (P < 0.0001); and tobacco use (P < 0.0001). Diabetes mellitus (P < 0.0001) was associated with lower odds of angiodysplasia associated-gastrointestinal bleeding in end-stage renal disease patients. In comparison with urban teaching hospitals, rural and urban nonteaching hospitals were associated with decreased odds of angiodysplasia associated-gastrointestinal hemorrhage. CONCLUSION: Angiodysplasia-associated gastrointestinal bleeding in end-stage renal disease patients showed an increasing trend from 2009-2014. Advanced age, African American race, overall high comorbidities, hypertension and smoking were significant factors for angiodysplasia-associated gastrointestinal bleeding in end-stage renal disease hospitalized patients.

Quantum Chemical and Statistical Rate Theory Studies of the Vinyl Hydroperoxides Formed in trans-2-Butene and 2,3-Dimethyl-2-butene Ozonolysis.

The vinyl hydroperoxide (VHP), the major isomerization product of the syn-alkyl Criegee intermediate (CI) formed in alkene ozonolysis, is a direct precursor of hydroxyl radical (OH), the most important oxidant in the troposphere. While simulations of CI reactivity have usually assumed the VHP to be a prompt and quantitative source of OH, recent quantum chemical studies have revealed subtleties in VHP reactivity such as a barrier to peroxy bond homolysis and a possible rearrangement to a hydroxycarbonyl. In this work, we use M06-L, Weizmann-1 Brueckner Doubles, and equation-of-motion spin-flip coupled-cluster theories to calculate a comprehensive reaction mechanism for the syn and anti conformers of the parent VHP formed in trans-2-butene ozonolysis and the 1-methyl VHP formed in 2,3-dimethyl-2-butene ozonolysis. We predict that for the parent VHP the anti homolysis transition structure (TS) is 3 kcal mol-1 lower in energy than the syn TS, but for the 1-methyl system, the syn TS is 2 kcal mol-1 lower in energy. Statistical rate theory simulations based on the quantum chemical data predict that the parent VHP preferentially decomposes to vinoxy and OH radicals under all tropospheric conditions, while the 1-methyl VHP preferentially decomposes to 1-methylvinoxy and OH radicals only close to 298 K; at 200 K, the 1-methyl VHP preferentially rearranges to hydroxyacetone. Lower temperatures and higher pressures favor the temporary accumulation of both the parent and the 1-methyl VHP.