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1.
Rev Med Suisse ; 16(676-7): 55-58, 2020 Jan 15.
Artigo em Francês | MEDLINE | ID: mdl-31961085

RESUMO

Among carefully selected patients, an early oral antibiotic switch is safe and efficient in severe bacterial infections. New data are available on dual antibiotherapy in severe Staphylococcus aureus infections. Neisseria gonorrhoeae strains resistant to ceftriaxone emerge, highlighting the necessity to develop new therapeutic strategies. Alongshan virus is a new tick-borne virus discovered in China. Ebola continues to rage in Democratic Republic of Congo, while Europe and Switzerland face measles outbreaks. North american guidelines for the diagnosis and management of Influenza have been updated, shortly before the FDA approval of baloxavir marboxil, a new antiviral treatment for Influenza infections.


Assuntos
Antibacterianos , Doenças Transmissíveis , Antibacterianos/uso terapêutico , China , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/epidemiologia , Congo , Surtos de Doenças , Europa (Continente) , Humanos , Suíça
2.
Mini Rev Med Chem ; 19(19): 1560-1563, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31833463

RESUMO

This work discusses the idea that drug discovery, instead of being performed through a series of filtering-based stages, should be viewed as a multi-scale optimization problem. Here, the most promising multi-scale models are analyzed in terms of their applications, advantages, and limitations in the search for more potent and safer chemicals against infectious diseases. Multi-scale de novo drug design is highlighted as an emerging paradigm, able to accelerate the discovery of more effective antimicrobial agents.


Assuntos
Anti-Infecciosos/química , Doenças Transmissíveis/tratamento farmacológico , Desenho de Drogas , Modelos Biológicos , Anti-Infecciosos/uso terapêutico , Doenças Transmissíveis/patologia , Humanos , Relação Quantitativa Estrutura-Atividade
3.
PLoS Negl Trop Dis ; 13(11): e0007847, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31751336

RESUMO

INTRODUCTION: Individuals and communities affected by NTDs are often the poorest and most marginalised; ensuring a gender and equity lens is centre stage will be critical for the NTD community to reach elimination goals and inform Universal Health Coverage (UHC). NTDs amenable to preventive chemotherapy have been described as a 'litmus test' for UHC due to the high mass drug administration (MDA) coverage rates needed to be effective and their model of community engagement. However, until now highly aggregated coverage data may have masked inequities in availability, accessibility and acceptability of medicines, slowing down the equitable achievement of elimination goals. METHODS: We conducted qualitative programmatic analysis across different country contexts through the novel application of the Tanahashi Coverage Framework enhanced by gendered intersectional theory to interrogate different components of programme coverage: availability, accessibility, acceptability, contact and effective. Drawing on communities and health implementers perspectives (using focus groups, interviews, and participatory methods) from varying levels of the health system, across four African country contexts (Cameroon, Ghana, Liberia and Nigeria), we show who is left behind and provide recommendations for programmes to respond. FINDINGS: We have unmasked inequities in programme delivery that repeatedly leave vulnerable populations underserved in relation to the prevention and treatment of PC NTDs across all components of coverage explored within the Tanahashi framework. Inequities are influenced by health systems challenges and limitations, due to lack of consideration of gender, power and equity issues. Effective treatment for individuals and communities is shaped by individual identities and the intersecting axes of inequity that converge to shape these positions including gender, age, disability, and geography. Health systems are inherently social and gendered thus they become mediators in managing the impact that social and structural processes have on individual health outcomes. SIGNIFICANCE: To our knowledge this is the only paper which has combined a comprehensive equity framework with intersectional feminist theory, to establish a fuller understanding of who is left behind and why in MDA across countries and contexts. Ensuring the most vulnerable have continued access to future treatment options will contribute to the progressive realisation of UHC, allowing the NTD community to continue to support their vision of being a true 'litmus test'.


Assuntos
Anti-Infecciosos/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/epidemiologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Administração Massiva de Medicamentos/métodos , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/epidemiologia , África , Feminino , Humanos , Masculino
4.
Chem Commun (Camb) ; 55(100): 15020-15032, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31782426

RESUMO

With the rapid spread of resistance among parasites and bacterial pathogens, antibiotic-resistant infections have drawn much attention worldwide. Consequently, there is an urgent need to develop new strategies to treat neglected diseases and drug-resistant infections. Here, we outline several new strategies that have been developed to counter pathogenic microorganisms by designing and constructing antimicrobial peptides (AMPs). In addition to traditional discovery and design mechanisms guided by chemical biology, synthetic biology and computationally-based approaches offer useful tools for the discovery and generation of bioactive peptides. We believe that the convergence of such fields, coupled with systematic experimentation in animal models, will help translate biological peptides into the clinic. The future of anti-infective therapeutics is headed towards specifically designed molecules whose form is driven by computer-based frameworks. These molecules are selective, stable, and active at therapeutic doses.


Assuntos
Anti-Infecciosos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/química , Doenças Transmissíveis/tratamento farmacológico , Algoritmos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Doenças Transmissíveis/patologia , Desenho de Drogas , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Engenharia de Proteínas , Pseudomonas/fisiologia
5.
BMC Infect Dis ; 19(1): 900, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660862

RESUMO

BACKGROUND: Carbapenem resistance among Acinetobacter species has become a life-threatening problem. As a last resort in the treatment of gram-negative bacteria infection, resistance to colistin is also a serious problem. The aim of study was to analyze the mechanism of resistance and perform genotyping of carbapenem-resistant Acinetobacter from clinical infection and fecal survey samples in Southern China. METHODS: One hundred seventy and 74 carbapenem-resistant Acinetobacter were isolated from clinical infection samples and fecal survey samples, respectively. We detected the related genes, including carbapenemase genes (blaKPC, blaIMP, blaSPM, blaVIM, blaNDM, blaOXA-23-like, blaOXA-24/40-like, blaOXA-51-like, and blaOXA-58-like), colistin resistance-related genes (mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5), a porin gene (carO), efflux pump genes (adeA, adeB, adeC, adeI, adeJ, and adeK), mobile genetic element genes (intI1, intI2, intI3, tnpU, tnp513, IS26, ISAba1, and ISAba125), and the integron variable region. Genotyping was analyzed by enterobacterial repetitive intergenic consensus (ERIC)-PCR and dendrogram cluster analysis. RESULTS: Among the 244 carbapenem-resistant Acinetobacter, the common carbapenemase-positive genes included the following: blaOXA-51-like, 183 (75.00%); blaOXA-23-like, 174 (71.30%); blaNDM-1, 57 (23.40%); and blaOXA-58-like, 30 (12.30%). The coexistence of mcr-1 and blaNDM-1 in five strains of A. junii was found for the first time. Eleven distinct carO gene variants were detected in 164 (67.20%) strains, and ten novel variants, which shared 92-99% identity with sequences in the Genbank database, were first reported. Efflux system genes were present in approximately 70% of the isolates; adeABC and adeIJK were observed in 76.23 and 72.13%, respectively. Class 1 integrons were detected in 180 (73.80%) strains and revealed that four gene cassette arrays contained 11 distinct genes. The genotyping by ERIC-PCR demonstrated a high genetic diversity of non-baumannii Acinetobacter, and greater than 90% similarity to A. baumannii. CONCLUSIONS: The blaNDM-1 gene was identified in up to 77% of the carbapenem-resistant Acinetobacter isolated from fecal survey samples, indicating that the gut might be a reservoir of resistant opportunistic bacteria. Intestinal bacteria can be transmitted through the fecal-hand, which is a clinical threat, thus, the monitoring of carbapenem-resistant bacteria from inpatients' feces should be improved, especially for patients who have been using antibiotics for a long time.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/genética , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Carbapenêmicos/efeitos adversos , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana/genética , Acinetobacter baumannii/isolamento & purificação , Proteínas de Bactérias/genética , China , Colistina/efeitos adversos , Colistina/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Fezes/microbiologia , Variação Genética , Genótipo , Humanos , Integrons/genética , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNA , beta-Lactamases/genética
8.
Inflammopharmacology ; 27(5): 871-883, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407196

RESUMO

Ginseng has been traditionally used as an herbal nutritional supplement in Asian countries, including Korea, China, Japan, and Vietnam for several millennia. Most studies have focused on the role of ginseng on anti-oxidative stress, anti-inflammatory, and anti-cancer activities. Recently, modulator activities of ginseng on the immune responses during pathogenic bacterial and viral infections and beneficial effects of ginseng in infectious diseases have been elucidated. In vivo and in vitro studies revealed the potential of ginseng extracts and ginsenosides Rg1, Rg3, Rb1, Rb2, Rb3, compound K, Re, Rd, Rh2 for treatment of several infectious diseases. The molecular mechanisms of these effects mainly involve inflammatory cytokines (TNF-α, IL-6, IL-1ß, IFN-γ, IL-10), apoptotic pathway (bcl-2, bcl-xL), PI3K/Akt pathway, MAPKs pathway, JAK2/STAT5, NF-κB pathway, and the inflammasome. In this review, we will summarize the current knowledge on the effects of ginseng in the immune responses during the infections and its bioactivities on the prevention of infectious diseases as well as its underlying mechanisms. Moreover, the therapeutic potential of ginseng as an anti-bacterial and anti-viral medication and vaccine adjuvant will be discussed as well.


Assuntos
Doenças Transmissíveis/tratamento farmacológico , Ginsenosídeos/farmacologia , Panax/química , Animais , Doenças Transmissíveis/metabolismo , Citocinas/metabolismo , Humanos , Imunidade/efeitos dos fármacos , Inflamação/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos
9.
Eur J Med Chem ; 182: 111591, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31419779

RESUMO

Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) - stimulator of interferon genes (STING) signaling pathway plays the critical role in the immune response to DNA. Pharmacological modulation of the STING pathway has been well characterized both from structural and functional perspectives, which paves the way for the drug design of small modulators by medicinal chemists. Here, we outline recent progress in studies on the STING pathway, the structure and biological function of STING, the STING related disease, as well as the rationale and progress in the development of STING modulators. Our review demonstrates that STING is a promising drug target, and providing clues for the discovery of novel STING agonists and antagonists for the potential treatment of various disease including microbial infectious diseases, cancer, and autoimmune disease.


Assuntos
Descoberta de Drogas , Proteínas de Membrana , Neoplasias/tratamento farmacológico , Nucleotídeos/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Xantonas/farmacologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/metabolismo , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/metabolismo , Humanos , Proteínas de Membrana/agonistas , Proteínas de Membrana/antagonistas & inibidores , Neoplasias/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
PLoS Comput Biol ; 15(8): e1007223, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31404059

RESUMO

Antimicrobial resistance is one of the major public health threats of the 21st century. There is a pressing need to adopt more efficient treatment strategies in order to prevent the emergence and spread of resistant strains. The common approach is to treat patients with high drug doses, both to clear the infection quickly and to reduce the risk of de novo resistance. Recently, several studies have argued that, at least in some cases, low-dose treatments could be more suitable to reduce the within-host emergence of antimicrobial resistance. However, the choice of a drug dose may have consequences at the population level, which has received little attention so far. Here, we study the influence of the drug dose on resistance and disease management at the host and population levels. We develop a nested two-strain model and unravel trade-offs in treatment benefits between an individual and the community. We use several measures to evaluate the benefits of any dose choice. Two measures focus on the emergence of resistance, at the host level and at the population level. The other two focus on the overall treatment success: the outbreak probability and the disease burden. We find that different measures can suggest different dosing strategies. In particular, we identify situations where low doses minimize the risk of emergence of resistance at the individual level, while high or intermediate doses prove most beneficial to improve the treatment efficiency or even to reduce the risk of resistance in the population.


Assuntos
Doenças Transmissíveis/tratamento farmacológico , Anti-Infecciosos/administração & dosagem , Doenças Transmissíveis/microbiologia , Doenças Transmissíveis/transmissão , Biologia Computacional , Simulação por Computador , Surtos de Doenças/estatística & dados numéricos , Relação Dose-Resposta a Droga , Resistência Microbiana a Medicamentos/genética , Epidemias/estatística & dados numéricos , Metas , Interações entre Hospedeiro e Microrganismos , Humanos , Modelos Biológicos , Mutação , Medicina de Precisão , Probabilidade , Análise de Sistemas , Resultado do Tratamento
12.
Nat Microbiol ; 4(9): 1432-1442, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31439928

RESUMO

Several interconnected human, animal and environmental habitats can contribute to the emergence, evolution and spread of antibiotic resistance, and the health of these contiguous habitats (the focus of the One Health approach) may represent a risk to human health. Additionally, the expansion of resistant clones and antibiotic resistance determinants among human-associated, animal-associated and environmental microbiomes have the potential to alter bacterial population genetics at local and global levels, thereby modifying the structure, and eventually the productivity, of microbiomes where antibiotic-resistant bacteria can expand. Conversely, any change in these habitats (including pollution by antibiotics or by antibiotic-resistant organisms) may influence the structures of their associated bacterial populations, which might affect the spread of antibiotic resistance to, and among, the above-mentioned microbiomes. Besides local transmission among connected habitats-the focus of studies under the One Health concept-the transmission of resistant microorganisms might occur on a broader (even worldwide) scale, requiring coordinated Global Health actions. This Review provides updated information on the elements involved in the evolution and spread of antibiotic resistance at local and global levels, and proposes studies to be performed and strategies to be followed that may help reduce the burden of antibiotic resistance as well as its impact on human and planetary health.


Assuntos
Resistência Microbiana a Medicamentos , Saúde Global , Saúde Única , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/epidemiologia , Microbiologia Ambiental , Saúde Global/legislação & jurisprudência , Saúde Global/normas , Humanos , Microbiota/efeitos dos fármacos , Saúde Única/legislação & jurisprudência , Saúde Única/normas
13.
BMC Infect Dis ; 19(1): 618, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299893

RESUMO

BACKGROUND: The increased transmission of multidrug-resistant (MDR) tuberculosis (TB) poses a challenge to tuberculosis prevention and control in Sri Lanka. Isoniazid (INH) is a key element of the first line anti tuberculosis treatment regimen. Resistance to INH may lead to development of MDR TB. Therefore, early detection of INH resistance is important to curb spread of resistance. Due to the limited availability of rapid molecular methods for detection of drug resistance in Sri Lanka, this study was aimed at developing a simple and rapid gold nanoparticle (AuNP) based lateral flow strip for the simultaneous detection of the most common INH resistance mutation (katG S315 T, 78.6%) and Mycobacterium tuberculosis (MTb). METHODS: Lateral flow strip was designed on an inert plastic backing layer containing a sample pad, nitrocellulose membrane and an absorption pad. Biotin labeled 4 capture probes which separately conjugated with streptavidin were immobilized on the nitrocellulose. The test sample was prepared by multiplex PCR using primers to amplify codon 315 region of the katG gene and MTb specific IS6110 region. The two detection probes complementary to the 5' end of each amplified fragment was conjugated with gold nanoparticles (20 nm) and coupled with the above amplified PCR products were applied on the sample pad. The hybridization of the amplified target regions to the respective capture probes takes place when the sample moves towards the absorption pad. Positive hybridization is indicated by red colour lines. RESULTS: The three immobilized capture probes on the strip (for the detection of TB, katG wild type and mutation) were 100 and 96.6% specific and 100 and 92.1% sensitive respectively. CONCLUSION: The AuNP based lateral flow assay was capable of differentiating the specific mutation and the wild type along with MTb identification within 3 h.


Assuntos
Doenças Transmissíveis/diagnóstico , Nanotecnologia/métodos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Antituberculosos/uso terapêutico , Proteínas de Bactérias/genética , Catalase/genética , Doenças Transmissíveis/tratamento farmacológico , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/metabolismo , Ouro/química , Humanos , Isoniazida/uso terapêutico , Limite de Detecção , Nanopartículas Metálicas/química , Reação em Cadeia da Polimerase Multiplex , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Sri Lanka , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
14.
Int J Antimicrob Agents ; 54(3): 273-282, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31260741

RESUMO

BACKGROUND: The World Health Organization Essential Medicines List (WHO-EML) includes 'access' antibiotics, judged essential to treat common infections. The European Society of Clinical Microbiology and Infectious Diseases Study Group for Antimicrobial Stewardship defined a list of 'forgotten' antibiotics, some old and often off-patent antibiotics, which have particular value for specific indications. OBJECTIVE: To investigate which WHO-EML 'access' and 'forgotten' antibiotics are approved at national level in a sample of low- to middle-income countries (LMICs). METHODS: The Scientific Committee used a consensus procedure to select 26 WHO-EML 'access' and 15 'forgotten' antibiotics. Paediatric formulations were explored for 14 antibiotics. An internet-based questionnaire was circulated to 40 LMIC representatives. Antibiotics were defined as approved if an official drug regulatory agency and/or the national ministry of health licensed their use, making them, at least theoretically, available on the market. RESULTS: Twenty-eight LMICs (11 in Africa, 11 in Asia and six in America) were surveyed. Nine WHO-EML 'access' antibiotics (amoxicillin, ampicillin, benzylpenicillin, ceftriaxone, clarithromycin, ciprofloxacin, doxycycline, gentamicin and metronidazole) were approved in all countries, and all 26 'access' antibiotics were approved in more than two-thirds of countries. Among the 15 'forgotten' antibiotics, only one was approved in more than two-thirds of countries. The median number of approved antibiotics per country was 30 (interquartile range 23-35). Six of 14 paediatric formulations (amoxicillin, amoxicillin-clavulanic acid, oral antistaphylococcal penicillin, cotrimoxazole, erythromycin and metronidazole) were approved in more than two-thirds of countries. CONCLUSIONS: WHO-EML 'access' antibiotics and the most frequently used formulations for paediatrics were approved in the vast majority of the 28 surveyed LMICs. This was not the case for many of the 'forgotten' antibiotics, despite their important role, particularly in areas with high prevalence of multi-drug-resistant bacteria.


Assuntos
Antibacterianos/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Países em Desenvolvimento , Doenças Transmissíveis/epidemiologia , Saúde Global , Humanos , Prevalência , Organização Mundial da Saúde
15.
J Pharm Pract ; 32(5): 546-557, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31327285

RESUMO

PURPOSE: To summarize the top 10 most influential peer-reviewed infectious diseases (ID) pharmacotherapy articles published in the year 2018. SUMMARY: Members of the Houston Infectious Diseases Network (HIDN) nominated articles that were thought to have most notably contributed to ID pharmacotherapy in 2018, including those related to human immunodeficiency virus (HIV). A total of 26 articles were nominated: 22 articles pertaining to general ID pharmacotherapy and 4 articles involving HIV/AIDS. To select the most significant articles of 2018, a survey was created and distributed to members of the Society of Infectious Diseases Pharmacists (SIDP) asking members to vote on their top 10 general ID publications and 1 HIV publication. Of the 462 members surveyed, 213 (46%) and 108 (23%) voted for general ID pharmacotherapy- and HIV-related articles, respectively. The top article(s) for both categories are summarized. CONCLUSION: With the increased emphasis on antimicrobial stewardship initiatives and the growing problem of multidrug-resistant (MDR) organisms, the amount of ID literature centered on stewardship, appropriate treatment durations, and newly approved antimicrobial agents continues to expand, making it challenging for clinicians to stay informed on the most relevant publications. This review summarizes significant ID-related publications in 2018 with the goal of aiding clinicians in staying up to date on the most noteworthy publications in ID pharmacotherapy.


Assuntos
Anti-Infecciosos/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Revisão por Pares/normas , Publicações Periódicas como Assunto/normas , Doenças Transmissíveis/epidemiologia , Tratamento Farmacológico/métodos , Tratamento Farmacológico/normas , Humanos , Revisão por Pares/métodos
20.
Int J Antimicrob Agents ; 54(3): 338-345, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31200022

RESUMO

Antimicrobial stewardship programmes (ASPs) are designed to improve antibiotic use. A survey was systematically developed to assess ASP prerequisites, objectives and improvement strategies in hospitals. This study assessed the current state of ASPs in acute-care hospitals throughout Europe. A survey containing 46 questions was disseminated to acute-care hospitals: all Dutch (n = 80) and Slovenian (n = 29), 215 French (25%, random stratified sampling) and 62 Italian (49% of hospitals with an infectious diseases department, convenience sampling) acute-care hospitals, for a Europe-wide assessment. Response rates for the Netherlands (Nl), Slovenia (Slo), France (Fr) and Italy (It) were 80%, 86%, 45% and 66%. There was variation between countries in the prerequisites met and the objectives and improvement strategies chosen. A formal ASP was present mainly in the Netherlands (90%) and France (84%) compared with Slovenia (60%) and Italy (60%). Presence of an antimicrobial stewardship (AMS) team ranged from 42% (Fr) to 94% (Nl). Salary support for AMS teams was provided in 68% (Fr), 51% (Nl), 33% (Slo) and 12% (It) of surveyed hospitals. Quantity of antibiotic use was monitored in the majority of hospitals, ranging from 72% (Nl) to 100% (Slo and Fr) of acute-care hospitals. Participating countries varied substantially in the use of 'prospective monitoring and advice' as a strategy to improve AMS objectives. ASP prerequisites, objectives and improvement activities vary considerably across Europe, with room for improvement. Stimulating appropriate system prerequisites throughout Europe, e.g. by introducing staffing standards and financial support for ASPs, seems a first priority.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/métodos , Doenças Transmissíveis/tratamento farmacológico , Uso de Medicamentos/normas , Serviços Médicos de Emergência/métodos , Estudos Transversais , Uso de Medicamentos/estatística & dados numéricos , Europa (Continente) , Hospitais , Humanos , Inquéritos e Questionários
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