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Article: Inhibition of the activated sludge-associated enzyme phosphatase by transition metal oxyanions.

Böger, Beatriz / Wacht, Marion / Leuck, Michaela / de O Vilhena, Raquel / Riese, Maria / Fischer, Klaus

Water science and technology : a journal of the International Association on Water Pollution Research

2021 Volume 83, Issue 11, Page(s) 2629–2639

Abstract: Organic esters of phosphoric acid and other organophosphorous compounds are enzymatically hydrolyzed during wastewater treatment by microbial phosphoesterases, especially by phosphomonoesterase (phosphatase). For physiological reasons, the enzyme is ... ...

Abstract	Organic esters of phosphoric acid and other organophosphorous compounds are enzymatically hydrolyzed during wastewater treatment by microbial phosphoesterases, especially by phosphomonoesterase (phosphatase). For physiological reasons, the enzyme is inhibited by its main inorganic reaction product, ortho-phosphate. It is known that oxyanions of transition metals, resembling the molecular topology of ortho-phosphate, e.g. vanadate and tungstate, are more potent inhibitors for microbial alkaline phosphatase than phosphate. To proof this effect for activated sludge, a multitude of samples from a communal wastewater treatment plant was exposed at pH values from 7.00 to 8.50 to tungstate, vanadate, and molybdate. Inhibition effects were determined by a sensitive fluorimetric microplate assay and characteristic parameters (IC
MeSH term(s)	Kinetics ; Molybdenum ; Phosphates ; Phosphoric Monoester Hydrolases ; Sewage ; Vanadates
Chemical Substances	Phosphates ; Sewage ; Vanadates (3WHH0066W5) ; Molybdenum (81AH48963U) ; Phosphoric Monoester Hydrolases (EC 3.1.3.2)
Language	English
Publishing date	2021-06-16
Publishing country	England
Document type	Journal Article
ZDB-ID	764273-8
ISSN	1996-9732 ; 0273-1223
ISSN (online)	1996-9732
ISSN	0273-1223
DOI	10.2166/wst.2021.172
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Article ; Online: A Systematic Review and Meta-analyses of Longitudinal Studies on Drug Treatments for Gaucher Disease.

Leonart, Letícia Paula / Fachi, Mariana M / Böger, Beatriz / Silva, Mariana Ribeiro da / Szpak, Renata / Lombardi, Natália Fracaro / Pedroso, Maria Lucia Alves / Pontarolo, Roberto

The Annals of pharmacotherapy

2022 Volume 57, Issue 3, Page(s) 267–282

Abstract: Objective: Gaucher disease (GD) is a rare disorder linked to the absence/deficiency of glucocerebrosidase. GD can be treated by enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). The aim of this systematic review (SR) is to assess ... ...

Abstract	Objective: Gaucher disease (GD) is a rare disorder linked to the absence/deficiency of glucocerebrosidase. GD can be treated by enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). The aim of this systematic review (SR) is to assess the effectiveness of drugs used for GD treatment. Data sources: Searches were conducted in PubMed and Scopus, in April 2021. The search strategies encompassed the name of the disease and of the drug treatments. Manual search was also conducted. Study selection and data extraction: Observational and interventional longitudinal studies evaluating ERT and SRT for GD were included. Single mean meta-analyses were conducted for each drug using R. Data synthesis: The initial search retrieved 2246 articles after duplicates were removed. Following screening and eligibility assessment, 68 reports were included. The studies evaluated imiglucerase, velaglucerase alfa, taliglucerase alfa, miglustat, and eliglustat. The results showed that ERT is effective as a treatment in both naïve and experienced patients. Miglustat did not significantly improve blood outcomes in naïve patients and resulted in a decrease in the platelet levels of experienced patients. Eliglustat was mainly assessed for experienced patients and resulted in stable outcome values. Relevance to patient care and clinical practice: This extensive SR confirms the effectiveness of GD treatments in short- and long-term follow-ups. Conclusions: The results were favorable for all ERTs and for eliglustat. Based on the assessed evidence, miglustat did not achieved expressive results. However, all evidence should be interpreted considering its limitations and does not replace well-conducted randomized trials.
MeSH term(s)	Humans ; Gaucher Disease/drug therapy ; Gaucher Disease/diagnosis ; Glucosylceramidase/therapeutic use ; Glucosylceramidase/adverse effects ; 1-Deoxynojirimycin/therapeutic use ; Blood Platelets ; Enzyme Replacement Therapy/methods
Chemical Substances	miglustat (ADN3S497AZ) ; Glucosylceramidase (EC 3.2.1.45) ; 1-Deoxynojirimycin (19130-96-2)
Language	English
Publishing date	2022-07-11
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1101370-9
ISSN	1542-6270 ; 1060-0280
ISSN (online)	1542-6270
ISSN	1060-0280
DOI	10.1177/10600280221108443
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Article ; Online: Comparative efficacy and safety of systemic antifungal agents for candidemia: a systematic review with network meta-analysis and multicriteria acceptability analyses.

Domingos, Eric L / Vilhena, Raquel O / Santos, Josiane M M F / Fachi, Mariana M / Böger, Beatriz / Adam, Livia M / Tonin, Fernanda S / Pontarolo, Roberto

International journal of antimicrobial agents

2022 Volume 60, Issue 2, Page(s) 106614

Abstract: Aim: Invasive candidiasis is the most common fungal infection in patients attending health services and is associated with high mortality rates and prolonged hospital stay. The aim of this review was to evaluate and compare efficacy and safety of ... ...

Abstract	Aim: Invasive candidiasis is the most common fungal infection in patients attending health services and is associated with high mortality rates and prolonged hospital stay. The aim of this review was to evaluate and compare efficacy and safety of antifungal agents for the treatment of candidemia. Methods: A systematic review with network meta-analysis (NMA), surface under the cumulative ranking analysis (SUCRA) and stochastic multicriteria acceptability analyses (SMAA) was performed (PROSPERO-CRD42020149264). Searches were conducted in PubMed and Scopus (Nov-2021). Randomised controlled trials evaluating the effect of oral antifungals (any dose or regimen) on mycological cure, discontinuation rates and adverse events were included. Results: Overall, 13 trials (n=3632) were analysed. There were no significant differences between therapies for the efficacy outcomes; however, caspofungin (50-150 mg), rezafungin (200-400 mg) and micafungin (100-150 mg) had higher rates of clinical and mycological responses (SUCRA overall response >60%) and were considered the most promising therapies. Fluconazole (400 mg) rated worst for overall response (17%). Rezafungin (200-400 mg) and micafungin (100 mg) were associated with lower discontinuation rates (<40%). Conventional amphotericin B (0.6-0.7 mg/kg) was more likely to be discontinued (odds ratio [OR] 0.08; 95% credibility interval [CrI] 0.00-0.95 vs. caspofungin 150 mg) and may impair liver function (87%). Conclusion: Echinocandins are recommended as first-line treatments for invasive candidiasis following a priority order of caspofungin then micafungin. Rezafungin, an echinocandin under development, represents a potential option that should be further investigated. Azoles and liposomal amphotericin B can be used as second-line treatments in cases of fungal resistance or hypersensitivity.
MeSH term(s)	Antifungal Agents/therapeutic use ; Candidemia/drug therapy ; Candidiasis, Invasive/drug therapy ; Caspofungin/therapeutic use ; Echinocandins/therapeutic use ; Humans ; Lipopeptides/therapeutic use ; Micafungin/therapeutic use ; Network Meta-Analysis
Chemical Substances	Antifungal Agents ; Echinocandins ; Lipopeptides ; Caspofungin (F0XDI6ZL63) ; Micafungin (R10H71BSWG)
Language	English
Publishing date	2022-06-09
Publishing country	Netherlands
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2022.106614
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Zs.A 3368: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Systematic review with meta-analysis of the accuracy of diagnostic tests for COVID-19.

Böger, Beatriz / Fachi, Mariana M / Vilhena, Raquel O / Cobre, Alexandre F / Tonin, Fernanda S / Pontarolo, Roberto

American journal of infection control

2020 Volume 49, Issue 1, Page(s) 21–29

Abstract: Objective: To collate the evidence on the accuracy parameters of all available diagnostic methods for detecting SARS-CoV-2.: Methods: A systematic review with meta-analysis was performed. Searches were conducted in Pubmed and Scopus (April 2020). ... ...

Abstract	Objective: To collate the evidence on the accuracy parameters of all available diagnostic methods for detecting SARS-CoV-2. Methods: A systematic review with meta-analysis was performed. Searches were conducted in Pubmed and Scopus (April 2020). Studies reporting data on sensitivity or specificity of diagnostic tests for COVID-19 using any human biological sample were included. Results: Sixteen studies were evaluated. Meta-analysis showed that computed tomography has high sensitivity (91.9% [89.8%-93.7%]), but low specificity (25.1% [21.0%-29.5%]). The combination of IgM and IgG antibodies demonstrated promising results for both parameters (84.5% [82.2%-86.6%]; 91.6% [86.0%-95.4%], respectively). For RT-PCR tests, rectal stools/swab, urine, and plasma were less sensitive while sputum (97.2% [90.3%-99.7%]) presented higher sensitivity for detecting the virus. Conclusions: RT-PCR remains the gold standard for the diagnosis of COVID-19 in sputum samples. However, the combination of different diagnostic tests is highly recommended to achieve adequate sensitivity and specificity.
MeSH term(s)	Antibodies, Viral/immunology ; COVID-19/diagnosis ; COVID-19/immunology ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; COVID-19 Testing ; Coronavirus Envelope Proteins/genetics ; Coronavirus RNA-Dependent RNA Polymerase/genetics ; Humans ; Immunoglobulin G/immunology ; Immunoglobulin M/immunology ; Lung/diagnostic imaging ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Sensitivity and Specificity ; Tomography, X-Ray Computed
Chemical Substances	Antibodies, Viral ; Coronavirus Envelope Proteins ; Immunoglobulin G ; Immunoglobulin M ; envelope protein, SARS-CoV-2 ; Coronavirus RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; NSP12 protein, SARS-CoV-2 (EC 2.7.7.48)
Keywords	covid19
Language	English
Publishing date	2020-07-10
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	392362-9
ISSN	1527-3296 ; 0196-6553
ISSN (online)	1527-3296
ISSN	0196-6553
DOI	10.1016/j.ajic.2020.07.011
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Article ; Online: Sensitivity and specificity of multibacillary and paucibacillary leprosy laboratory tests: A systematic review and meta-analysis.

Torres, Reginaldo Thuler / Fachi, Mariana Millan / Böger, Beatriz / Marson, Breno Maurício / Ferreira, Vinicíus Lins / Pontarolo, Roberto / Guimarães, Thais Martins

Diagnostic microbiology and infectious disease

2021 Volume 100, Issue 2, Page(s) 115337

Abstract: This systematic review (number register: CRD42018112736) was performed to compare the sensitivity and specificity of leprosy diagnostic methods. The search was conducted in 3 electronic databases in January 2021. Studies evaluating leprosy diagnostic ... ...

Abstract	This systematic review (number register: CRD42018112736) was performed to compare the sensitivity and specificity of leprosy diagnostic methods. The search was conducted in 3 electronic databases in January 2021. Studies evaluating leprosy diagnostic tests were included according the eligibility criteria. Meta-analysis was performed to calculate the sensibility and specificity of the groups. We included 36 studies. The test sensitivity for paucibacillary patients was 0.31 (95%CI: 0.29-0.33) and the specificity was 0.92 (95%CI: 0.92-0.93). In multibacillary patients, the sensitivity was 0.78 (95%CI: 0.77-0.80) and specificity was 0.92 (95%CI: 0.92-0.93). Comparing the sensitivity and specificity of the different techniques included, it should be noted that polymerase chain reaction (PCR) test presented the highest sensitivity for paucibacillary patients, while the western blot technique showed the highest sensitivity for multibacillary patients. However, further studies are needed to optimise the diagnosis of leprosy, requiring research with a larger number of samples and more uniform protocols.
MeSH term(s)	Blotting, Western/methods ; Leprosy, Multibacillary/diagnosis ; Leprosy, Paucibacillary/diagnosis ; Polymerase Chain Reaction/methods ; Sensitivity and Specificity
Language	English
Publishing date	2021-02-03
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	604920-5
ISSN	1879-0070 ; 0732-8893
ISSN (online)	1879-0070
ISSN	0732-8893
DOI	10.1016/j.diagmicrobio.2021.115337
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Article ; Online: MACHINE LEARNING-BASED VIRTUAL SCREENING, MOLECULAR DOCKING, DRUG-LIKENESS, PHARMACOKINETICS AND TOXICITY ANALYSES TO IDENTIFY NEW NATURAL INHIBITORS OF THE GLYCOPROTEIN SPIKE (S1) of SARS-CoV-2

Alexandre de F. Cobre / Beatriz Böger / Mariana M. Fachi / Carlos A. Ehrenfried / Dile P. Stremel / Eduardo B. De Melo / Fernanda S. Tonin / Roberto Pontarolo

Química Nova, Vol 46, Iss 5, Pp 450-

2023 Volume 459

Abstract: To identify natural bioactive compounds (NBCs) as potential inhibitors of spike (S1) by means of in silico assays. NBCs with previously proven biological in vitro activity were obtained from the ZINC database and analyzed through virtual screening and ... ...

Abstract	To identify natural bioactive compounds (NBCs) as potential inhibitors of spike (S1) by means of in silico assays. NBCs with previously proven biological in vitro activity were obtained from the ZINC database and analyzed through virtual screening and molecular docking to identify those with higher affinity to the spike protein. Eight machine learning models were used to validate the results: Principal Component Analysis (PCA), Artificial Neural Network (ANN), Support Vector Machine (SVM), k-Nearest Neighbors (KNN), Partial Least Squares-Discriminant Analysis (PLS-DA), Gradient Boosted Tree Discriminant Analysis (XGBoostDA), Soft Independent Modelling of Class Analogies (SIMCA) and Logistic Regression Discriminate Analysis (LREG). Selected NBCs were submitted to drug-likeness prediction using Lipinski’s and Veber’s rule of five. A prediction of pharmacokinetic parameters and toxicity was also performed (ADMET). Antivirals currently used for COVID-19 (remdesivir and molnupiravir) were used as a comparator. A total of 170,906 compounds were analyzed. Of these, 34 showed greater affinity with the S1 (affinity energy < -7 kcal mol-1). Most of these compounds belonged to the class of coumarins (benzopyrones), presenting a benzene ring fused to a lactone (group of heterosides). The PLS-DA model was able to reproduce the results of the virtual screening and molecular docking (accuracy of 97.0%). Of the 34 compounds, only NBC5 (feselol), NBC14, NBC15 and NBC27 had better results in ADMET predictions. These had similar binding affinity to S1 when compared to remdesivir and molnupirvir. Feselol and three other NBCs were the most promising candidates for treating COVID-19. In vitro and in vivo studies are needed to confirm these findings.
Keywords	Chemistry ; QD1-999
Subject code	540
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Sociedade Brasileira de Química
Document type	Article ; Online
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Article ; Online: Legal demands of the tiotropium bromide for treatment of chronic obstructive pulmonary disease and their financial impact for the State of Paraná, Brazil.

Szpak, Renata / Strapasson, Giovanna Chipon / Böger, Beatriz / Rattmann, Yanna Dantas / Gomes, Eliane Carneiro

Einstein (Sao Paulo, Brazil)

2019 Volume 18, Page(s) eGS4442

Abstract: Objective: To analyze the legal demands of tiotropium bromide to treat chronic obstructive pulmonary disease.: Methods: We included secondary data from the pharmaceutical care management systems made available by the Paraná State Drug Center.: ... ...

Abstract	Objective: To analyze the legal demands of tiotropium bromide to treat chronic obstructive pulmonary disease. Methods: We included secondary data from the pharmaceutical care management systems made available by the Paraná State Drug Center. Results: Public interest civil action and ordinary procedures, among others, were the most common used by the patients to obtain the medicine. Two Health Centers in Paraná (Londrina and Umuarama) concentrated more than 50% of the actions. The most common specialty of physicians who prescribed (33.8%) was pulmonology. There is a small financial impact of tiotropium bromide on general costs with medicines of the Paraná State Drug Center. However, a significant individual financial impact was observed because one unit of the medicine represents 38% of the Brazilian minimum wage. Conclusion: Our study highlights the need of incorporating this medicine in the class of long-acting anticholinergic bronchodilator in the Brazilian public health system.
MeSH term(s)	Brazil ; Bronchodilator Agents/economics ; Drugs, Essential/economics ; Drugs, Essential/supply & distribution ; Health Services Accessibility/economics ; Health Services Accessibility/legislation & jurisprudence ; Health Services Accessibility/trends ; Health Services Needs and Demand/economics ; Health Services Needs and Demand/legislation & jurisprudence ; Health Services Needs and Demand/trends ; Humans ; Judicial Role ; National Health Programs ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Pulmonary Disease, Chronic Obstructive/economics ; Retrospective Studies ; Statistics, Nonparametric ; Time Factors ; Tiotropium Bromide/economics
Chemical Substances	Bronchodilator Agents ; Drugs, Essential ; Tiotropium Bromide (XX112XZP0J)
Language	Portuguese
Publishing date	2019-09-26
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2418293-X
ISSN	2317-6385 ; 1679-4508
ISSN (online)	2317-6385
ISSN	1679-4508
DOI	10.31744/einstein_journal/2020GS4442
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Article ; Online: Systematic review with network meta-analysis on the treatments for latent tuberculosis infection in children and adolescents.

Santos, Josiane M / Fachi, Mariana M / Beraldi-Magalhães, Francisco / Böger, Beatriz / Junker, Allan M / Domingos, Eric L / Imazu, Priscila / Fernandez-Llimos, Fernando / Tonin, Fernanda S / Pontarolo, Roberto

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

2022 Volume 28, Issue 12, Page(s) 1645–1653

Abstract: Background: We aimed to synthesize the evidence on the efficacy and safety of different treatment regimens for latent tuberculosis infection (LTBI) in children and adolescents.: Methods: A systematic review with network meta-analysis was performed ( ... ...

Abstract	Background: We aimed to synthesize the evidence on the efficacy and safety of different treatment regimens for latent tuberculosis infection (LTBI) in children and adolescents. Methods: A systematic review with network meta-analysis was performed (CRD142933). Searches were conducted in Pubmed and Scopus (Nov-2021). Randomized controlled trials comparing treatments for LTBI (patients up to 15 years), and reporting data on the incidence of the disease, death or adverse events were included. Networks using the Bayesian framework were built for each outcome of interest. Results were reported as odds ratio (OR) with 95% credibility intervals (CrI). Rank probabilities were calculated via the surface under the cumulative ranking analysis (SUCRA) (Addis-v.1.16.8). GRADE approach was used to rate evidence's certainty. Results: Seven trials (n = 8696 patients) were included. Placebo was significantly associated with a higher incidence of tuberculosis compared to all active therapies. Combinations of isoniazid (15-25 mg/kg/week) plus rifapentine (300-900 mg/week), followed by isoniazid plus rifampicin (10 mg/kg/day) were ranked as best approaches with lower probabilities of disease incidence (10% and 19.5%, respectively in SUCRA) and death (20%). Higher doses of isoniazid monotherapy were significantly associated to more deaths (OR 18.28, 95% ICr [1.02, 48.60] of 4-6 mg/kg/day vs. 10 mg/kg/3x per week). Conclusions: Combined therapies of isoniazid plus rifapentine or rifampicin for short-term periods should be used as the first-line approach for treating LTBI in children and adolescents. The use of long-term isoniazid as monotherapy and at higher doses should be avoided for this population.
MeSH term(s)	Adolescent ; Antitubercular Agents/adverse effects ; Bayes Theorem ; Child ; Humans ; Isoniazid/adverse effects ; Latent Tuberculosis/drug therapy ; Latent Tuberculosis/epidemiology ; Network Meta-Analysis ; Rifampin/therapeutic use
Chemical Substances	Antitubercular Agents ; Isoniazid (V83O1VOZ8L) ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2022-09-06
Publishing country	Netherlands
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	1355399-9
ISSN	1437-7780 ; 1341-321X
ISSN (online)	1437-7780
ISSN	1341-321X
DOI	10.1016/j.jiac.2022.08.023
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Article: A multivariate analysis of risk factors associated with death by Covid-19 in the USA, Italy, Spain, and Germany.

Cobre, Alexandre de Fátima / Böger, Beatriz / Vilhena, Raquel de Oliveira / Fachi, Mariana Millan / Dos Santos, Josiane Marlei Muller Fernandes / Tonin, Fernanda Stumpf

Zeitschrift fur Gesundheitswissenschaften = Journal of public health

2020 Volume 30, Issue 5, Page(s) 1189–1195

Abstract: Aim: Our aim was to investigate the risk factors associated with death from COVID-19 in four countries: The USA, Italy, Spain, and Germany.: Subject and methods: We used data from the Institute for Health Metrics and Evaluation with projection ... ...

Abstract	Aim: Our aim was to investigate the risk factors associated with death from COVID-19 in four countries: The USA, Italy, Spain, and Germany. Subject and methods: We used data from the Institute for Health Metrics and Evaluation with projection information from January-August 2020. A multivariate analysis of logistic regression was performed. The following factors were analyzed (per day): number of beds needed for the hospital services, number of intensive care units (ICU) beds required, number of ventilation devices, number of both hospital and ICU admissions due to COVID-19. Nagelkerke's R Results: Among the evaluated countries, Italy presented greater need for ICU beds/day (≤ 98; OR = 2315.122; CI 95% [334.767-16,503.502]; Conclusions: Further investments in hospitals' infrastructure, as well as the development of innovative devices for patient's ventilation, are paramount to fight the pandemic in the USA, Italy, Spain, and Germany.
Keywords	covid19
Language	English
Publishing date	2020-10-19
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1149070-6
ISSN	2198-1833 ; 0943-1853
ISSN	2198-1833 ; 0943-1853
DOI	10.1007/s10389-020-01397-7
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Article ; Online: Systematic review with meta-analysis of the accuracy of diagnostic tests for COVID-19

Böger, Beatriz / Fachi, Mariana M. / Vilhena, Raquel O. / Cobre, Alexandre F. / Tonin, Fernanda S. / Pontarolo, Roberto

American Journal of Infection Control ; ISSN 0196-6553

2020

Keywords	Public Health, Environmental and Occupational Health ; Health Policy ; Epidemiology ; Infectious Diseases ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
DOI	10.1016/j.ajic.2020.07.011
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