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Kristin Kostka,1,2 Talita Duarte-Salles,3 Albert Prats-Uribe,4 Anthony G Sena,5,6 Andrea Pistillo,3 Sara Khalid,4 Lana YH Lai,7 Asieh Golozar,8,9 Thamir M Alshammari,10 Dalia M Dawoud,11 Fredrik Nyberg,12 Adam B Wilcox,13,14 Alan Andryc,5 Andrew Williams,15 Anna Ostropolets,16 Carlos Areia,17 Chi Young Jung,18 Christopher A Harle,19 Christian G Reich,1,2 Clair Blacketer,5,6 Daniel R Morales,20 David A Dorr,21 Edward Burn,3,4 Elena Roel,3,22 Eng Hooi Tan,4 Evan Minty,23 Frank DeFalco,5 Gabriel de Maeztu,24 Gigi Lipori,19 Hiba Alghoul,25 Hong Zhu,26 Jason A Thomas,13 Jiang Bian,19 Jimyung Park,27 Jordi Martínez Roldán,28 Jose D Posada,29 Juan M Banda,30 Juan P Horcajada,31 Julianna Kohler,32 Karishma Shah,33 Karthik Natarajan,16,34 Kristine E Lynch,35,36 Li Liu,37 Lisa M Schilling,38 Martina Recalde,3,22 Matthew Spotnitz,14 Mengchun Gong,39 Michael E Matheny,40,41 Neus Valveny,42 Nicole G Weiskopf,21 Nigam Shah,29 Osaid Alser,43 Paula Casajust,42 Rae Woong Park,27,44 Robert Schuff,21 Sarah Seager,1 Scott L DuVall,35,36 Seng Chan You,45 Seokyoung Song,46 Sergio Fernández-Bertolín,3 Stephen Fortin,5 Tanja Magoc,19 Thomas Falconer,16 Vignesh Subbian,47 Vojtech Huser,48 Waheed-Ul-Rahman Ahmed,33,49 William Carter,38 Yin Guan,50 Yankuic Galvan,19 Xing He,19 Peter R Rijnbeek,6 George Hripcsak,16,34 Patrick B Ryan,5,16 Marc A Suchard,51 Daniel Prieto-Alhambra4 1IQVIA, Cambridge, MA, USA; 2OHDSI Center at The Roux Institute, Northeastern University, Portland, ME, USA; 3Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; 4Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, UK; 5Janssen Research & Development, Titusville, NJ, USA; 6Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands; 7School of Medical Sciences, University of Manchester, Manchester, UK; 8Regeneron Pharmaceuticals, Tarrytown, NY, USA; 9Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 10College of Pharmacy, Riyadh Elm University, Riyadh, Saudi Arabia; 11National Institute for Health and Care Excellence, London, UK; 12School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 13Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA; 14Unviersity of Washington Medicine, Seattle, WA, USA; 15Tufts Institute for Clinical Research and Health Policy Studies, Boston, MA, USA; 16Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA; 17Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 18Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, South Korea; 19University of Florida Health, Gainesville, FL, USA; 20Division of Population Health and Genomics, University of Dundee, Dundee, UK; 21Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA; 22Universitat Autònoma de Barcelona, Barcelona, Spain; 23O’Brien Institute for Public Health, Faculty of Medicine, University of Calgary, Calgary, Canada; 24IOMED, Barcelona, Spain; 25Faculty of Medicine, Islamic University of Gaza, Gaza, Palestine; 26Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 27Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea; 28Director of Innovation and Digital Transformation, Hospital del Mar, Barcelona, Spain; 29Department of Medicine, School of Medicine, Stanford University, Redwood City, CA, USA; 30Georgia State University, Department of Computer Science, Atlanta, GA, USA; 31Department of Infectious Diseases, Hospital del Mar, Institut Hospital del Mar d’Investigació Mèdica (IMIM), Universitat Autònoma de Barcelona, Universitat Pompeu Fabra, Barcelona, Spain; 32United States Agency for International Development, Washington, DC, USA; 33Botnar Research Centre, NDORMS, University of Oxford, Oxford, UK; 34New York-Presbyterian Hospital, New York, NY, USA; 35VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA; 36Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; 37Biomedical Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 38Data Science to Patient Value Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 39Institute of Health Management, Southern Medical University, Guangzhou, People’s Republic of China; 40Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, USA; 41Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA; 42Real-World Evidence, TFS, Barcelona, Spain; 43Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 44Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea; 45Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea; 46Department of Anesthesiology and Pain Medicine, Catholic University of Daegu, School of Medicine, Daegu, South Korea; 47College of Engineering, The University of Arizona, Tucson, AZ, USA; 48National Library of Medicine, National Institutes of Health, Bethesda, MD, USA; 49College of Medicine and Health, University of Exeter, St Luke’s Campus, Exeter, UK; 50DHC Technologies Co. Ltd., Beijing, People’s Republic of China; 51Departments of Biostatistics, Computational Medicine, and Human Genetics, University of California, Los Angeles, CA, USACorrespondence: Daniel Prieto-Alhambra, Botnar Research Centre, Windmill Road, Oxford, OX37LD, UK, Email daniel.prietoalhambra@ndorms.ox.ac.ukPurpose: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.Patients and Methods: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services.Results: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed.Conclusion: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.Keywords: OHDSI, OMOP CDM, descriptive epidemiology, real world data, real world evidence, open science

While studies support the effectiveness of community health worker (CHW) services, best approaches for CHW integration in health systems are not well understood. We describe early outcomes from a partnership between a safety-net hospital systems' social work department and CHWs to address adverse social determinants of health of high-risk patients.

Adsorption is one of the most successful physicochemical approaches for removing heavy metal contaminants from polluted water. The use of residual biomass for the production of adsorbents has attracted a lot of attention due to its cheap price and environmentally friendly approach. The transformation of Sargassum-an invasive brown macroalga-into activated carbon (AC) via phosphoric acid thermochemical activation was explored in an effort to increase the value of Sargassum seaweed biomass. Several techniques (nitrogen adsorption, pH PZC , Boehm titration, FTIR and XPS) were used to characterize the physicochemical properties of the activated carbons. The SAC600 3/1 was predominantly microporous and mesoporous (39.6% and 60.4%, respectively) and revealed a high specific surface area (1695 m 2 ·g -1 ). To serve as a comparison element, a commercial reference activated carbon with a large specific surface area (1900 m 2 ·g -1 ) was also investigated. The influence of several parameters on the adsorption capacity of AC was studied: solution pH, solution temperature, contact time and Cr(VI) concentration. The best adsorption capacities were found at very acid (pH 2) solution pH and at lower temperatures. The adsorption kinetics of SAC600 3/1 fitted well a pseudo-second-order type 1 model and the adsorption isotherm was better described by a Jovanovic-Freundlich isotherm model. Molecular dynamics (MD) simulations confirmed the experimental results and determined that hydroxyl and carboxylate groups are the most influential functional groups in the adsorption process of chromium anions. MD simulations also showed that the addition of MgCl 2 to the activated carbon surface before adsorption experiments, slightly increases the adsorption of HCrO 4 - and CrO 4 2- anions. Finally, this theoretical study was experimentally validated obtaining an increase of 5.6% in chromium uptake.

Defined surface functionalities can control the properties of a material. The layer-by-layer method is an experimentally simple yet very versatile method to coat a surface with nanoscale precision. The method is widely used to either control the chemical properties of the surface via the introduction of functional moieties bound to the polymer or create nanoscale surface topographies if one polymeric species is replaced by a colloidal dispersion. Such roughness can enhance the stability of a liquid film on top of the surface by capillary adhesion. Here, we investigate whether a similar effect allows an increased retention of liquid films within a porous surface and thus potentially increases the stability of ionic liquid films infused within a porous matrix in the supported ionic liquid-phase catalysis. The complex geometry of the porous material, long diffusion pathways, and small sizes of necks connecting individual pores all contribute to difficulties to reliably coat the required porous materials. We optimize the coating process to ensure uniform surface functionalization via two steps. Diffusion limitations are overcome by force-wetting the pores, which transports the functional species convectively into the materials. Electrostatic repulsion, which can limit pore accessibility, is mitigated by the addition of electrolytes to screen charges. We introduce nanoscale topography in microscale porous SiC monoliths to enhance the retention of an ionic liquid film. We use γ-Al 2 O 3 to coat monoliths and test the retention of 1-butyl-2,3-dimethylimidazolium chloride under exposure to a continuous gas stream, a setup commonly used in the water-gas shift reaction. Our study showcases that a hierarchical topography can improve the stability of impregnated ionic liquid films, with a potential advantage of improved supported ionic liquid-phase catalysis., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Ru-based coordination compounds have important applications as photosensitizers and catalysts. [Ru II (bpy) 2 (bpyNO)] 2+ (bpy = 2,2'-bipyridine and bpyNO = 2,2'-bipyridine- N -oxide) was reported to be extremely light-sensitive, but its light-induced transformation pathways have not been analyzed. Here, we elucidated a mechanism of the light-induced transformation of [Ru II (bpy) 2 (bpyNO)] 2+ using UV-vis, EPR, resonance Raman, and NMR spectroscopic techniques. The spectroscopic analysis was augmented with the DFT calculations. We concluded that upon 530-650 nm light excitation, 3 [Ru III (bpyNO -• )(bpy) 2 ] 2+ is formed similarly to the 3 [Ru III (bpy -• )(bpy) 2 ] 2+ light-induced state of the well-known photosensitizer [Ru II (bpy) 3 ] 2+ . An electron localization on the bpyNO ligand was confirmed by obtaining a unique EPR signal of reduced [Ru II (bpy) 2 (bpyNO -• )] + ( g xx = 2.02, g yy = 1.99, and g zz = 1.87 and 14 N hfs A xx = 12 G, A yy = 34 G, and A zz = 11 G). 3 [Ru III (bpyNO -• )(bpy) 2 ] 2+ may evolve via breaking of the Ru-O-N fragment at two different positions resulting in [Ru IV ═O(bpy) 2 (bpy out )] 2+ for breakage at the O-|-N bond and [Ru II (H 2 O)(bpy) 2 (bpyNO out )] 2+ for breakage at the Ru-|-O bond. These pathways were found to have comparable Δ G . A reduction of [Ru IV ═O(bpy) 2 (bpy out )] 2+ may result in water elimination and formation of [Ru II (bpy) 3 ] 2+ . The expected intermediates, [Ru III (bpy) 2 (bpyNO)] 3+ and [Ru III (bpy) 3 ] 3+ , were detected by EPR. In addition, a new signal with g xx = 2.38, g yy = 2.10, and g zz = 1.85 was observed and tentatively assigned to a complex with the dissociated ligand, such as [Ru III (H 2 O)(bpy) 2 (bpyNO out )] 3+ . The spectroscopic signatures of [Ru IV ═O(bpy) 2 (bpy out )] 2+ were not observed, although DFT analysis and [Ru II (bpy) 3 ] 2+ formation suggest this intermediate. Thus, [Ru II (bpy) 2 (bpyNO)] 2+ has potential as a light-induced oxidizer.

Artificial photosynthesis could promise abundant, carbon-neutral energy, but implementation is currently limited by a lack of control over the multi-electron catalysis of water oxidation. Discoveries of the most active catalysts still rely heavily on serendipity. [Ru(tpy)(bpy)(H 2 O)] 2+ ( 1 ; bpy = 2,2'-bipyridine, tpy = 2,2';6',2″-terpyridine) is representative of the largest known class of water oxidation catalysts. We undertook an extensive spectroscopic analysis of the prototypical 1 water oxidation catalyst and its fastest known analog [Ru(EtO-tpy)(bpy)(H 2 O)] 2+ ( 2 ), capable of 10 times faster water oxidation, to investigate the mechanism of action and factors controlling catalytic activity. EPR and resonance Raman spectroscopy did not detect the proposed [Ru V ═O] intermediate in 1 and 2 but indicated the possible formation of N-oxides. A lag phase was observed prior to O 2 evolution, suggesting catalyst modification before the onset of catalysis. The reactive intermediate [Ru(tpy)(bpy-NO)(H 2 O)] 2+ ( 1-NO ; bpy-NO = 2,2'-bipyridine-N-oxide) proposed by combined spectroscopic and DFT analysis was de novo synthesized and demonstrated 100-fold greater catalytic activity than 1 . Thus, in situ transient formation of small amounts of the Ru complex with N-oxide ligands can significantly activate single-site Ru-based catalysts. Furthermore, the rate of O 2 evolution was found to correlate with the redox potential of the ligand. This observation might assist with rational design of new catalysts.

Mononuclear nonheme manganese(IV)-oxo complexes binding calcium ion and other redox-inactive metal ions, [(dpaq)Mn IV (O)] + -M n+ (1-M n+ , M n+ = Ca 2+ , Mg 2+ , Zn 2+ , Lu 3+ , Y 3+ , Al 3+ , and Sc 3+ ) (dpaq = 2-[bis(pyridin-2-ylmethyl)]amino- N-quinolin-8-yl-acetamidate), were synthesized by reacting a hydroxomanganese(III) complex, [(dpaq)Mn III (OH)] + , with iodosylbenzene (PhIO) in the presence of redox-inactive metal ions (M n+ ). The Mn(IV)-oxo complexes were characterized using various spectroscopic techniques. In reactivity studies, we observed contrasting effects of M n+ on the reactivity of 1-M n+ in redox reactions such as electron-transfer (ET), oxygen atom transfer (OAT), and hydrogen atom transfer (HAT) reactions. In the OAT and ET reactions, the reactivity order of 1-M n+ , such as 1-Sc 3+ ≈ 1-Al 3+ > 1-Y 3+ > 1-Lu 3+ > 1-Zn 2+ > 1-Mg 2+ > 1-Ca 2+ , follows the Lewis acidity of M n+ bound to the Mn-O moiety; that is, the stronger the Lewis acidity of M n+ , the higher the reactivity of 1-M n+ becomes. In sharp contrast, the reactivity of 1-M n+ in the HAT reaction was reversed, giving the reactivity order 1-Ca 2+ > 1-Mg 2+ > 1-Zn 2+ > 1-Lu 3+ > 1-Y 3+ > 1-Al 3+ ≈ 1-Sc 3+ ; that is, the higher is Lewis acidity of M n+ , the lower the reactivity of 1-M n+ in the HAT reaction. The latter result implies that the Lewis acidity of M n+ bound to the Mn-O moiety can modulate the basicity of the metal-oxo moiety, thus influencing the HAT reactivity of 1-M n+ ; cytochrome P450 utilizes the axial thiolate ligand to increase the basicity of the iron-oxo moiety, which enhances the reactivity of compound I in C-H bond activation reactions.

Artificial photosynthesis carries promise to deliver abundant clean energy for the needs of a growing population. Deep mechanistic understanding is required to achieve rational design of fast and durable water oxidation catalysts. Here we provided first evidence for a new mechanism of the O-O bond formation via radical coupling of the oxidized metal═oxo of radicaloid character (Ru IV ═O) and ligand based radical ([ligand-NO] +• cation radical). O-O bond formation is facilitated via spin alignment and takes place via a virtually barrier less pathway inside the single metal complex. In situ reactive intermediate conversion was monitored by mass spectrometry, resonance Raman (RR) and EPR. Computational analysis have shown that the formation of [ligand-NO] +• happens at a lower overpotential than the formation of the [Ru V ═O(ligand)] 3+ intermediate. Overall, the presented paradigm for O-O bond formation opens new opportunities for rational catalyst design.

In order to prepare lubricant-infused repellent coatings on silica nanostructures using low vapor pressure ionic liquids as lubricants, we study the wetting behavior of a set of imidazolium-based ionic liquids with different alkyl side chains as a function of the applied surface functionalities. We take advantage of the structural color of inverse opals prepared from a colloidal coassembly technique to study the infiltration of ionic liquids into these nanoporous structures. We find that the more hydrophobic ionic liquids with butyl and hexyl side chains can completely infiltrate inverse opals functionalized with mixed self-assembled monolayers composed of imidazole groups and aliphatic hydrocarbon chains, which we introduce via silane chemistry. These molecular species reflect the chemical nature of the ionic liquid, thereby increasing the affinity between the liquid and solid surface. The mixed surface chemistry provides sufficiently small contact angles with the ionic liquid to infiltrate the nanopores while maximizing the contact angle with water. As a result, the mixed monolayers enable the design of a stable ionic liquid/solid interface that is able to repel water as a test liquid. Our results underline the importance of matching chemical affinities to predict and control the wetting behavior in complex, multiphase systems.

Improvement of the oxygen evolution reaction (OER) is a challenging step toward the development of sustainable energy technologies. Enhancing the OER rate and efficiency relies on understanding the water oxidation mechanism, which entails the characterization of the reaction intermediates. Very active Ru-bda type (bda is 2,2'-bipyridine-6,6'-dicarboxylate) molecular OER catalysts are proposed to operate via a transient 7-coordinate Ru V ═O intermediate, which so far has never been detected due to its high reactivity. Here we prepare and characterize a well-defined supported Ru(bda) catalyst on porous indium tin oxide (ITO) electrode. Site isolation of the catalyst molecules on the electrode surface allows trapping of the key 7-coordinate Ru V ═O intermediate at potentials above 1.34 V vs NHE at pH 1, which is characterized by electron paramagnetic resonance and in situ X-ray absorption spectroscopies. The in situ extended X-ray absorption fine structure analysis shows a Ru═O bond distance of 1.75 ± 0.02 Å, consistent with computational results. Electrochemical studies and density functional theory calculations suggest that the water nucleophilic attack on the surface-bound Ru V ═O intermediate (O-O bond formation) is the rate limiting step for OER catalysis at low pH.

Water oxidation, a key component in artificial photosynthesis, requires high overpotentials and exhibits slow reaction kinetics that necessitates the use of stable and efficient heterogeneous water-oxidation catalysts (WOCs). Here, we report the synthesis of UiO-67 metal-organic framework (MOF) thin films doped with [Ru(tpy)(dcbpy)OH 2 ] 2+ (tpy=2,2':6',2''-terpyridine, dcbpy=5,5'-dicarboxy-2,2'-bipyridine) on conducting surfaces and their propensity for electrochemical water oxidation. The electrocatalyst oxidized water with a turnover frequency (TOF) of (0.2±0.1) s -1 at 1.71 V versus the normal hydrogen electrode (NHE) in buffered solution (pH∼7) and exhibited structural and electrochemical stability. The electroactive sites were distributed throughout the MOF thin film on the basis of scan-ratedependent voltammetry studies. This work demonstrates a promising way to immobilize large concentrations of electroactive WOCs into a highly robust MOF scaffold and paves the way for future photoelectrochemical water-splitting systems., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The realization of artificial photosynthesis carries the promise of cheap and abundant energy, however, significant advances in the rational design of water oxidation catalysts are required. Detailed information on the structure of the catalyst under reaction conditions and mechanisms of O-O bond formation should be obtained. Here, we used a combination of electron paramagnetic resonance (EPR), stopped flow freeze quench on a millisecond-second time scale, X-ray absorption (XAS), resonance Raman (RR) spectroscopy, and density functional theory (DFT) to follow the dynamics of the Ru-based single site catalyst, [Ru II (NPM)(4-pic) 2 (H 2 O)] 2+ (NPM = 4-t-butyl-2,6-di(1',8'-naphthyrid-2'-yl)pyridine, pic = 4-picoline), under the water oxidation conditions. We report a unique EPR signal with g-tensor, g x = 2.30, g y = 2.18, and g z = 1.83 which allowed us to observe fast dynamics of oxygen atom transfer from the Ru IV ═O oxo species to the uncoordinated nitrogen of the NPM ligand. In few seconds, the NPM ligand modification results in [Ru III (NPM-NO)(4-pic) 2 (H 2 O)] 3+ and [Ru III (NPM-NO,NO)(4-pic) 2 ] 3+ complexes. A proposed [Ru V (NPM)(4-pic) 2 ═O] 3+ intermediate was not detected under the tested conditions. We demonstrate that while the proximal base might be beneficial in O-O bond formation via nucleophilic water attack on an oxo species as shown by DFT, the noncoordinating nitrogen is impractical as a base in water oxidation catalysts due to its facile conversion to the N-O group. This study opens new horizons for understanding the real structure of Ru catalysts under water oxidation conditions and points toward the need to further investigate the role of the N-O ligand in promoting water oxidation catalysis.

Mepyramine-theophylline-acetate (MTA), a theophylline derivative combined with an antihistamine, is used to treat patients with asthma. A double-blind, randomized, prospective, parallel-group study was conducted to evaluate the efficacy and safety of MTA in the treatment of asthmatic crisis in children 2 to 6 years of age. Forty patients with mild-to-moderate asthma were admitted to the study. The MTA group received 8 mg/kg per day of MTA by mouth in three divided doses for 7 days. The other group received 50 microL/kg per day of placebo in three divided doses for 7 days. Salbutamol (albuterol) syrup was used as the rescue drug if manifestations of asthma persisted. Both the MTA group and the placebo group had similar demographic characteristics at baseline. Both groups showed improvement of the asthma symptoms (cough, dyspnea, hypoventilation, and wheezing), as evaluated by the investigators at days 3 and 7. Patient diary scores showed earlier improvements in the MTA group than in the placebo group. Both groups showed improvement in peak flow at days 3 and 7 (P = 0.005). The control group used more doses of salbutamol than the MTA group on days 2 through 6 and globally (mean +/- SD, 6.79 +/- 9.11 doses vs 1.29 +/- 2.23 doses). The improvements in the placebo group were thought to be due to salbutamol. Three MTA patients dropped out of the trial, one because the parents felt that the treatment was not effective and two because of gastrointestinal manifestations (epigastric discomfort and vomiting). In the placebo group, two patients dropped out. One patient had epigastric discomfort and the other had to be treated in the emergency department for an exacerbation of the asthma. We conclude that MTA may be a good therapeutic option for the treatment of asthmatic crisis in children 2 to 6 years of age.