Avoidable intensive care unit resource use and costs of unvaccinated patients with COVID-19: a historical population-based cohort study.

PURPOSE: SARS-CoV-2 vaccines have been proven effective at preventing poor outcomes from COVID-19; however, voluntary vaccination rates have been suboptimal. We assessed the potential avoidable intensive care unit (ICU) resource use and associated costs had unvaccinated or partially vaccinated patients hospitalized with COVID-19 been fully vaccinated. METHODS: We conducted a retrospective, population-based cohort study of persons aged 12 yr or greater in Alberta (2021 population ~ 4.4 million) admitted to any ICU with COVID-19 from 6 September 2021 to 4 January 2022. We used publicly available aggregate data on COVID-19 infections, vaccination status, and health services use. Intensive care unit admissions, bed-days, lengths of stay, and costs were estimated for patients with COVID-19 and stratified by vaccination status. RESULTS: In total, 1,053 patients admitted to the ICU with COVID-19 were unvaccinated, 42 were partially vaccinated, and 173 were fully vaccinated (cumulative incidence 230.6, 30.8, and 5.5 patients/100,000 population, respectively). Cumulative incidence rate ratios of ICU admission were 42.2 (95% confidence interval [CI], 39.7 to 44.9) for unvaccinated patients and 5.6 (95% CI, 4.1 to 7.6) for partially vaccinated patients when compared with fully vaccinated patients. During the study period, 1,028 avoidable ICU admissions and 13,015 bed-days were recorded for unvaccinated patients and the total avoidable costs were CAD 61.3 million. The largest opportunity to avoid ICU bed-days and costs was in unvaccinated patients aged 50 to 69 yr. CONCLUSIONS: Unvaccinated patients with COVID-19 had substantially greater rates of ICU admissions, ICU bed-days, and ICU-related costs than vaccinated patients did. This increased resource use would have been potentially avoidable had these unvaccinated patients been vaccinated against SARS-CoV-2.

RéSUMé: OBJECTIF: Les vaccins contre le SRAS-CoV-2 se sont avérés efficaces pour prévenir les devenirs défavorables associés à la COVID-19; toutefois, les taux de vaccination volontaire ont été sous-optimaux. Nous avons évalué l'utilisation potentiellement évitable des ressources des unités de soins intensifs (USI) et les coûts associés si les patients non vaccinés ou partiellement vaccinés qui ont dû être hospitalisés pour la COVID-19 avaient été complètement vaccinés. MéTHODE: Nous avons réalisé une étude de cohorte rétrospective basée sur la population de personnes âgées de 12 ans ou plus en Alberta (population de 2021 ~ 4,4 millions) admises dans une unité de soins intensifs et atteintes de COVID-19 du 6 septembre 2021 au 4 janvier 2022. Nous avons utilisé des données agrégées accessibles au public sur les infections à la COVID-19, le statut vaccinal et l'utilisation des services de santé. Les admissions aux soins intensifs, les journées-patients, les durées de séjour et les coûts ont été estimés pour les patients atteints de la COVID-19 et stratifiés selon le statut vaccinal. RéSULTATS: Au total, 1053 patients admis à l'USI souffrant de la COVID-19 n'étaient pas vaccinés, 42 étaient partiellement vaccinés et 173 étaient complètement vaccinés (incidence cumulative 230,6, 30,8 et 5,5 patients / 100 000 habitants, respectivement). Les taux d'incidence cumulés des admissions aux soins intensifs étaient de 42,2 (intervalle de confiance [IC] à 95 %, 39,7 à 44,9) pour les patients non vaccinés et de 5,6 (IC 95 %, 4,1 à 7,6) pour les patients partiellement vaccinés par rapport aux patients entièrement vaccinés. Au cours de la période à l'étude, 1028 admissions évitables aux soins intensifs et 13 015 journées-patients ont été enregistrées pour les patients non vaccinés, et les coûts totaux évitables étaient de 61,3 millions de dollars canadiens. L'économie potentielle la plus importante en matière de journées-patients et de coûts en soins intensifs touchait les patients non vaccinés âgés de 50 à 69 ans. CONCLUSION: Les patients non vaccinés atteints de COVID-19 ont affiché des taux beaucoup plus élevés d'admissions à l'USI, de journées-patients à l'USI et de coûts liés à l'USI que les patients vaccinés. Cette utilisation accrue des ressources aurait été potentiellement évitable si ces patients non vaccinés avaient été vaccinés contre le SRAS-CoV-2.

Appendicular Lean Mass and Frailty among Geriatric Outpatients.

The objective of this observational study was to examine the association between appendicular lean mass and frailty in adults aged 60 years and older. This study was conducted in the Outpatient Department of the National Geriatric Hospital in Hanoi, Vietnam. Appendicular lean mass (kg) was assessed by using Dual energy X-ray absorptiometry scans. Frailty was defined according to Fried's frailty criteria. A total of 560 outpatients were included in the study, with a mean age of 70 years. The prevalence of frailty was 12.0%. Frail patients had significantly lower appendicular lean mass compared with non-frail outpatients (9.6 ± 2.0 kg vs. 11.7 ± 3.1 kg, p<0.001). On multivariable logistic regression models, higher appendicular lean mass was associated with significantly reduced odds for frailty (adjusted OR = 0.74, 95%CI 0.59 - 0.93). These findings suggest that the assessment of appendicular lean mass should be considered in older patients attending outpatient geriatric clinics.

Association Between Pandemic Coronavirus Disease 2019 Public Health Measures and Reduction in Critical Care Utilization Across ICUs in Alberta, Canada.

OBJECTIVES: The coronavirus disease 2019 pandemic has disrupted critical care services across the world. In anticipation of surges in the need for critical care services, governments implemented "lockdown" measures to preserve and create added critical care capacity. Herein, we describe the impact of lockdown measures on the utilization of critical care services and patient outcomes compared with nonlockdown epochs in a large integrated health region. DESIGN: This was a population-based retrospective cohort study. SETTING: Seventeen adult ICUs across 14 acute care hospitals in Alberta, Canada. PATIENTS: All adult (age ≥ 15 yr) patients admitted to any study ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main exposure was ICU admission during "lockdown" occurring between March 16, 2020, and June 30, 2020. This period was compared with two nonpandemic control periods: "year prior" (March 16, 2019, to June 30, 2019) and "pre lockdown" immediately prior (November 30, 2019, to March 15, 2020). The primary outcome was the number of ICU admissions. Secondary outcomes included the following: daily measures of ICU utilization, ICU duration of stay, avoidable delay in ICU discharge, and occupancy; and patient outcomes. Mixed multilevel negative binomial regression and interrupted time series regression were used to compare rates of ICU admissions between periods. Multivariable regressions were used to compare patient outcomes between periods. During the lockdown, there were 3,649 ICU admissions (34.1 [8.0] ICU admissions/d), compared with 4,125 (38.6 [9.3]) during the prelockdown period and 3,919 (36.6 [8.7]) during the year prior. Mean bed occupancy declined significantly during the lockdown compared with the nonpandemic periods (78.7%, 95.9%, and 96.4%; p < 0.001). Avoidable ICU discharge delay also decreased significantly (42.0%, 53.2%, and 58.3%; p < 0.001). During the lockdown, patients were younger, had fewer comorbid diseases, had higher acuity, and were more likely to be medical admissions compared with the nonpandemic periods. Adjusted ICU and hospital mortality and ICU and hospital lengths of stay were significantly lower during the lockdown compared with nonpandemic periods. CONCLUSIONS: The coronavirus disease 2019 lockdown resulted in substantial changes to ICU utilization, including a reduction in admissions, occupancy, patient lengths of stay, and mortality.

Spectroscopic Study of the Basicity of 4,6-Dihydroxypyrimidine Derivatives.

The protonation of a number of 4,6-dihydroxypyrimidine derivatives is studied, and the features of the electronic spectra of free bases and protonated forms are considered. It is shown that the alkyl substituents in position 2 increase the basicity of the compound, and the nitro group in position 5 leads to its decrease. In an acid medium (0.1-99.5% H2SO4), 4,6-dihydroxypyrimidine, 6-hydroxy-2-methylpyrimidine-4(3H)-one, and 6-hydroxy-2-ethylpyrimidine-4(3H)-one have two protonation stages, barbituric acid is protonated in three stages, and 6-hydroxy-2-methyl-5-nitropyrimidine-4(3H)-one and 6-hydroxy-2-ethyl-5-nitropyrimidine-4(3H)-one form a monocation.

Kinetic modelling of molecular hydrogen transport in microporous carbon materials.

The proposal of kinetic molecular sieving of hydrogen isotopes is explored by employing statistical rate theory methods to describe the kinetics of molecular hydrogen transport in model microporous carbon structures. A Lennard-Jones atom-atom interaction potential is utilized for the description of the interactions between H(2)/D(2) and the carbon framework, while the requisite partition functions describing the thermal flux of molecules through the transition state are calculated quantum mechanically in view of the low temperatures involved in the proposed kinetic molecular sieving application. Predicted kinetic isotope effects for initial passage from the gas phase into the first pore mouth are consistent with expectations from previous modeling studies, namely, that at sufficiently low temperatures and for sufficiently narrow pore mouths D(2) transport is dramatically favored over H(2). However, in contrast to expectations from previous modeling, the absence of any potential barrier along the minimum energy pathway from the gas phase into the first pore mouth yields a negative temperature dependence in the predicted absolute rate coefficients-implying a negative activation energy. In pursuit of the effective activation barrier, we find that the minimum potential in the cavity is significantly higher than in the pore mouth for nanotube-shaped models, throwing into question the common assumption that passage through the pore mouths should be the rate-determining step. Our results suggest a new mechanism that, depending on the size and shape of the cavity, the thermal activation barrier may lie in the cavity rather than at the pore mouth. As a consequence, design strategies for achieving quantum-mediated kinetic molecular sieving of H(2)/D(2) in a microporous membrane will need, at the very least, to take careful account of cavity shape and size in addition to pore-mouth size in order to ensure that the selective step, namely passage through the pore mouth, is also the rate determining step.

New method for atomistic modeling of the microstructure of activated carbons using hybrid reverse Monte Carlo simulation.

We propose a new hybrid reverse Monte Carlo (HRMC) procedure for atomistic modeling of the microstructure of activated carbons whereby the guessed configuration for the HRMC construction simulation is generated using the characterization results (pore size and pore wall thickness distributions) obtained by the interpretation of argon adsorption at 87 K using our improved version of the slit-pore model, termed the finite wall thickness (FWT) model (Nguyen, T. X.; Bhatia, S. K. Langmuir 2004, 20, 3532) . This procedure overcomes limitations arising from the use of short-range potentials in the conventional HRMC method, which make the latter unsuitable for carbons such as activated carbon fibers that are anisotropic with medium-range ordering induced by their complex pore structure. The newly proposed approach is applied specifically for the atomistic construction of an activated carbon fiber ACF15, provided by Kynol Corporation (Nguyen, T. X.; Bhatia, S. K. Carbon 2005, 43, 775) . It is found that the PSD of the ACF15's constructed microstructure is in good agreement with that determined using argon adsorption at 87 K. Furthermore, we have also found that the use of the Lennard-Jones (LJ) carbon-fluid interaction well depth obtained from scaling the flat graphite surface-fluid interaction well depth taken from Steele (Steele, W. A. Surf. Sci. 1973, 36, 317) provides an excellent prediction of experimental adsorption data including the differential heat of adsorption of simple gases (Ar, N(2), CH(4), CO(2)) over a wide range of temperatures and pressures. This finding is in agreement with the enhancement of the LJ carbon-fluid well depth due to the curvature of the carbon surface, found by the use of ab initio calculations (Klauda, J. B.; Jiang, J.; Sandler, S. I. J. Phys. Chem. B 2004, 108, 9842) .

Outcomes following reirradiation of patients with head and neck cancer.

BACKGROUND: This study reports the outcomes for patients with head and neck cancer who received reirradiation with palliative or curative intent. METHODS: A retrospective review of 41 patients treated with curative (n = 28) or palliative (n = 13) reirradiation was conducted. Survival was calculated from the start of the reirradiation. Radiation-related toxicities were classified according to Radiation Therapy Oncology Group criteria. Disease-related problems included adverse events during or after reirradiation that were not directly related to reirradiation. RESULTS: The observed 1-year survival for all patients was 39.0% (23.0% palliative, 46.3% curative). Median survival for all patients was 10.2 months. Seventy-five percent of curative and 53.8% of palliative patients had grade 3 or 4 radiation-related toxicities and/or major disease-related problems. CONCLUSION: A second course of radiotherapy in patients with head and neck cancer should be offered with a clear understanding that survival is poor and many of these patients will suffer severe radiation-related or disease-related insults to their quality of life during and after treatment.

Kinetic restriction of simple gases in porous carbons: transition-state theory study.

The separation of simple gases such as N2, Ar, CO2, and CH4 is an industrially important problem, particularly for the mitigation of greenhouse emissions. Furthermore, these gases are widely accepted as standard probing gases for the characterization of the microstructure of porous solids. However, a consistent set of microstructural parameters of a microporous solid determined from the use of adsorption measurements of these different gases is not always achieved because of differences in their pore accessibility. This is a long-standing and poorly understood problem. Here, we present the calculated results of the crossing time of N2, Ar, CO2, and CH4 between two neighboring cages through a constricted window in a realistic structural model of saccharose char, generated from hybrid reverse Monte Carlo (HRMC) simulation (Nguyen, T. X.; Bhatia, S. K.; Jain, S. K.; Gubbins, K. E. Mol. Simul. 2006, 32, 567-577) using transition state theory (TST), as described in our recent work (Nguyen, T. X.; Bhatia, S. K. J. Phys. Chem. 2007, 111, 2212-2222). The striking feature in these results is that whereas very fast diffusion of carbon dioxide within the temperature range of 273-343 K, with crossing time on the molecular dynamics scale (10-4-10-6 s), leads to instantaneous equilibrium and no hysteresis on the experimental time scale, slower diffusion of Ar and N2 at the low temperature of analysis indicates an accessibility problem. These results rationalize the experimental results of hysteresis for N2 at 77 K and Ar at 87 K but not for CO2 at 273 K in Takeda 3 A carbon molecular sieves. Furthermore, it is shown that CH4 diffusion through narrow pore mouths can be hindered even at ambient temperature. Finally, we show that the use of pore size and wall thickness distributions extracted from the adsorption of Ar at 87 K using the finite wall thickness (FWT) model (Nguyen, T. X.; Bhatia, S. K. Langmuir 2004, 20, 3532-3535 and Nguyen, T. X.; Bhatia, S. K. J. Phys. Chem. B 2004, 108, 14032-14042) provides the correct prediction of experimental CO2 adsorption in BPL and PCB carbons whereas that from N2 at 77 K gives a significant underprediction for both CO2 and CH4 in the BPL carbon. These trends are in excellent agreement with those predicted using the calculated crossing times.

Dose response and local control using radiotherapy in non-metastatic Ewing sarcoma.

BACKGROUND: To determine prognostic factors for local control in the radiotherapeutic management of non-metastatic Ewing sarcoma. PROCEDURE: Forty patients with localized Ewing sarcoma (ES) were treated with primary site RT at one institution. Median RT dose was 55.8 Gy (range, 25.5-76 Gy). Chemotherapy was given to 34 patients (85%) with the most common regimen being vincristine, dactinomycin, cyclophosphamide, doxorubicin alternating with ifosfamide and etoposide (VACA + IE) in 10. Median follow-up for surviving patients was 12.3 years (range, 1.7-26.4 years). RESULTS: The 5- and 10-year local control rate was 78.2%. On multivariate analysis, RT dose was the only prognostic factor to impact on local control. The 5- and 10-year local control rate was 88.7% for RT dose >or=49 Gy and was 37.5% for <49 Gy (P = 0.0002, log-rank test). For tumors or=49 Gy and 50.0% for RT dose <49 Gy (P = 0.01, log-rank test). For tumors >8 cm, the 5- and 10-year local control rate was 85.7% for RT dose >or=54 Gy and 26.7% for RT dose <54 Gy (P = 0.006, log-rank test). CONCLUSIONS: Radiotherapy dose was found to influence local control in ES. In particular, patients who received RT doses >or=49 Gy for tumor size or=54 Gy for tumor size >8 cm had improved local control.

An analysis of primary site control and late effects according to local control modality in non-metastatic Ewing sarcoma.

PURPOSE: To examine prognostic factors for primary site control and analyze late effects according to local treatment modality in non-metastatic Ewing sarcoma (ES). MATERIALS AND METHODS: From 1976 to 2001, 76 patients with localized ES and a median age of 14.5 years were seen and treated at one institution. Tumors were located in the extremity in 38, pelvis in 13, spine in 11, trunk in 8, and head and neck in 6. Tumor size was < or = 8 cm in 44 and >8 cm in 32. Local therapy included radiotherapy (RT) alone in 40, surgery (S) alone in 27, and surgery followed by postoperative radiotherapy (S + RT) in 9. Chemotherapy (CT) was delivered to 65 patients (86%). Median follow-up for surviving patients was 9.7 years. RESULTS: The 5- and 10-year overall survival rates were 57.5% and 52.1% while the 5- and 10-year local control rate was 79.2%. The 5- and 10-year local control rates were 78.2% for RT, 77.6% for surgery, and 88.9% for S + RT (P = 0.68). Multivariate analysis showed that only the use of CT was found to be a prognostic factor for local control (P = 0.014). The 5- and 10-year local control rates were 83.7% for those receiving CT and 51.1% for those not receiving CT. For patients followed at least 5 years from diagnosis, late effects were seen in 10 of 19 (52.6%) receiving RT, 2 of 5 (40%) receiving S + RT, and 4 of 16 (25%) receiving surgery alone. The most common late effects with RT were muscular atrophy, limb length growth delay, and development of second malignancy. Scoliosis and decrease range of motion of an extremity were seen regardless of local treatment modality. Three patients who had surgery alone had an amputation whereas two who had RT had an amputation secondary to relapse or development of osteosarcoma. CONCLUSION: In this single institution study, the use of CT was the only factor found to impact on local control. Late effects were common regardless of local control strategy.

Prediction of high-pressure adsorption equilibrium of supercritical gases using density functional theory.

In this paper, we present the results of the prediction of the high-pressure adsorption equilibrium of supercritical gases (Ar, N2, CH4, and CO2) on various activated carbons (BPL, PCB, and Norit R1 extra) at various temperatures using a density-functional-theory-based finite wall thickness (FWT) model. Pore size distribution results of the carbons are taken from our recent previous work,(1,2) using this approach for characterization. To validate the model, isotherms calculated from the density functional theory (DFT) approach are comprehensively verified against those determined by grand canonical Monte Carlo (GCMC) simulation, before the theoretical adsorption isotherms of these investigated carbons calculated by the model are compared with the experimental adsorption measurements of the carbons. We illustrate the accuracy and consistency of the FWT model for the prediction of adsorption isotherms of the all investigated gases. The pore network connectivity problem occurring in the examined carbons is also discussed, and on the basis of the success of the predictions assuming a similar pore size distribution for accessible and inaccessible regions, it is suggested that this is largely related to the disordered nature of the carbon.

Probing the pore wall structure of nanoporous carbons using adsorption.

Hitherto, adsorption has been traditionally used to study only the porous structure in disordered materials, while the structure of the solid phase skeleton has been probed by crystallographic methods such as X-ray diffraction. Here we show that for carbons density functional theory, suitably adapted to consider heterogeneity of the pore walls, can be reliably used to probe features of the solid structure hitherto accessibly only approximately even by crystallographic methods. We investigate a range of carbons and determine pore wall thickness distributions using argon adsorption, with results corroborated by X-ray diffraction.

Brain metastasis in children with sarcoma, neuroblastoma, and Wilms' tumor.

PURPOSE: To determine the incidence and prognosis of children who develop brain metastasis. MATERIALS AND METHODS: The medical and tumor registry records of 611 children treated at the University of Iowa Hospitals and Clinics between 1965 and 2000 for a sarcoma, neuroblastoma, or Wilms' tumor were reviewed. RESULTS: Thirty children (4.9%) were found to have brain metastasis. Brain metastasis occurred in 9 of 113 (8%) neuroblastoma, 7 of 104 (6.7%) rhabdomyosarcoma, 6 of 105 (5.7%) Ewing's sarcoma, 5 of 106 (4.7%) osteosarcoma, 2 of 83 (2.4%) nonrhabdomyosarcoma soft-tissue sarcoma, and 1 of 100 (1%) Wilms' tumor patients. There were 22 male and 8 female patients, with a median age of 14 years at the time of diagnosis of brain metastasis (range 8 months-20 years). Four patients were diagnosed at autopsy, whereas five had brain metastasis at initial diagnosis. For the 25 children who did not have brain metastasis at initial presentation, the median interval from initial diagnosis to development of brain metastasis was 5 months (range 1-43 months). Twenty-nine (97%) had concurrent or prior history of distant metastasis. Eighteen (60%) had solitary brain metastasis. Treatment for the 26 non-autopsy-diagnosed children included surgery (S), followed by postoperative radiotherapy (RT) and chemotherapy (CT) in 2, S and postoperative RT in 1, RT and CT in 16, S alone in 2, CT alone in 2, RT alone in 1, and no treatment in 2. Median survival was 4 months after diagnosis of brain metastasis, with a 1-year survival rate of 11.5%. On multivariate analysis, only the use of RT was found to positively influence freedom from neurologic progression (p = 0.005). CONCLUSION: Brain metastasis is uncommon in children with a diagnosis of sarcoma, neuroblastoma, or Wilms' tumor and is often accompanied by concurrent distant disease. Children treated with RT for brain metastasis had a better freedom from neurologic progression rate than those who did not receive radiotherapy.

Local control of parameningeal rhabdomyosarcoma: outcomes in non-complete responders to chemoradiation.

PURPOSE: To determine whether there is a role for surgery in Group III and IV patients with residual parameningeal rhabdomyosarcoma (PM-RMS) after radiotherapy (RT). MATERIALS AND METHODS: From 1965 to 2000, 29 patients with PM-RMS (Group III 27, Group IV 2) were diagnosed and treated with RT at the University of Iowa. All patients received chemotherapy consisting of vincristine, dactinomycin, and cyclophosphamide (VAC) in 17 (59%), VAC + doxorubicin in six (21%), VC + doxorubicin in three (10%), and other in three. RT was given to the primary site. Median dose was 50.4 Gy (range, 41.4-65 Gy). Two had hyperfractionated RT (59.4 Gy in 54 fractions). Median follow-up time for surviving patients was 17.9 years (range, 1.5-31.5 years). RESULTS: The 2- and 5-year overall survival rates were 78.9% and 45.7% while the 2- and 5-year freedom from local progression rates were 56.8% and 42.1%. For the 11 patients who did not achieve a complete response to chemoradiotherapy at the primary site, eight underwent surgical resection 1.5-7 months after RT. The 2- and 5-year survival rates for the eight who had a surgical salvage were 100% and 60%. None of the other three survived. Six of 18 patients (33%) relapsed at the primary site after a complete response to chemoradiation and all died. CONCLUSION: Surgical salvage after an incomplete response to chemoradiation in PM-RMS is feasible and can be curative in some cases.