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2.
Respir Res ; 21(1): 265, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050900

RESUMO

BACKGROUND: Patients with severe, uncontrolled asthma, particularly those with a non-eosinophilic phenotype, have a great unmet need for new treatments that act on a broad range of inflammatory pathways in the airway. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine. In the PATHWAY phase 2b study (NCT02054130), tezepelumab reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline eosinophilic inflammatory status. This article reports the design and objectives of the phase 2 CASCADE study. METHODS: CASCADE is an ongoing exploratory, phase 2, randomized, double-blind, placebo-controlled, parallel-group study aiming to assess the anti-inflammatory effects of tezepelumab 210 mg administered subcutaneously every 4 weeks for 28 weeks in adults aged 18-75 years with uncontrolled, moderate-to-severe asthma. The primary endpoint is the change from baseline to week 28 in airway submucosal inflammatory cells (eosinophils, neutrophils, T cells and mast cells) from bronchoscopic biopsies. Epithelial molecular phenotyping, comprising the three-gene-mean technique, will be used to assess participants' type 2 (T2) status to enable evaluation of the anti-inflammatory effect of tezepelumab across the continuum of T2 activation. Other exploratory analyses include assessments of the impact of tezepelumab on airway remodelling, including reticular basement membrane thickening and airway epithelial integrity. At the onset of the COVID-19 pandemic, the protocol was amended to address the possibility that site visits would be limited. The amendment allowed for: at-home dosing of study drug by a healthcare professional, extension of the treatment period by up to 6 months so patients are able to attend an onsite visit to undergo the end-of-treatment bronchoscopy, and replacement of final follow-up visits with a virtual or telephone visit. DISCUSSION: CASCADE aims to determine the mechanisms by which tezepelumab improves clinical asthma outcomes by evaluating the effect of tezepelumab on airway inflammatory cells and remodelling in patients with moderate-to-severe, uncontrolled asthma. An important aspect of this study is the evaluation of the anti-inflammatory effect of tezepelumab across patients with differing levels of eosinophilic and T2 inflammation. TRIAL REGISTRATION: NCT03688074 (ClinicalTrials.gov). Registered 28 September 2018.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Adolescente , Adulto , Idoso , Antiasmáticos/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Asma/diagnóstico , Asma/imunologia , Ensaios Clínicos Fase II como Assunto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 4491-4497, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018992

RESUMO

Spirometry test, a measure of the patient's lung function, is the gold standard for diagnosis and monitoring of chronic pulmonary diseases. Spirometry is currently being done in hospital settings by having the patients blow the air out of their lungs forcefully and into the spirometer's tubes under the supervision and constant guidance of clinicians. This test is expensive, cumbersome and not easily applicable to every-day monitoring of these patients. The lung mechanism when performing a cough is very similar to when spirometry test is done. That includes a big inhalation, air compression and forceful exhalation. Therefore, it is reasonable to assume that obstruction of lung airways should have a similar effect on both cough features and spirometry measures. This paper explores the estimation of lung obstruction using cough acoustic features. A total number of 3695 coughs were collected from patients from 4 different conditions and 4 different severity categories along with their lung function measures in a clinical setting using a smartphone's microphone and a hospital-grade spirometry lab. After feature-set optimization and model hyperparameter tuning, the lung obstruction was estimated with MAE (Mean Absolute Error) of 8% for COPD and 9% for asthma populations. In addition to lung obstruction estimation, we were able to classify patients' disease state with 91% accuracy and patients' severity within each disease state with 95% accuracy.Clinical Relevance- This enables effort-independent estimation of lung function spirometry parameters which could potentially lead to passive monitoring of pulmonary patients.


Assuntos
Asma , Tosse , Acústica , Asma/diagnóstico , Tosse/diagnóstico , Humanos , Pulmão , Espirometria
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5673-5677, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019264

RESUMO

While there have been several efforts to use mHealth technologies to support asthma management, none so far offer personalised algorithms that can provide real-time feedback and tailored advice to patients based on their monitoring. This work employed a publicly available mHealth dataset, the Asthma Mobile Health Study (AMHS), and applied machine learning techniques to develop early warning algorithms to enhance asthma self-management. The AMHS consisted of longitudinal data from 5,875 patients, including 13,614 weekly surveys and 75,795 daily surveys. We applied several well-known supervised learning algorithms (classification) to differentiate stable and unstable periods and found that both logistic regression and naïve Bayes-based classifiers provided high accuracy (AUC > 0.87). We found features related to the use of quick-relief puffs, night symptoms, frequency of data entry, and day symptoms (in descending order of importance) as the most useful features to detect early evidence of loss of control. We found no additional value of using peak flow readings to improve population level early warning algorithms.


Assuntos
Asma , Autogestão , Telemedicina , Asma/diagnóstico , Teorema de Bayes , Humanos , Aprendizado de Máquina
7.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32934151

RESUMO

OBJECTIVES: Although the airway microbiota is a highly dynamic ecology, the role of longitudinal changes in airway microbiota during early childhood in asthma development is unclear. We aimed to investigate the association of longitudinal changes in early nasal microbiota with the risk of developing asthma. METHODS: In this prospective, population-based birth cohort study, we followed children from birth to age 7 years. The nasal microbiota was tested by using 16S ribosomal RNA gene sequencing at ages 2, 13, and 24 months. We applied an unsupervised machine learning approach to identify longitudinal nasal microbiota profiles during age 2 to 13 months (the primary exposure) and during age 2 to 24 months (the secondary exposure) and examined the association of these profiles with the risk of physician-diagnosed asthma at age 7 years. RESULTS: Of the analytic cohort of 704 children, 57 (8%) later developed asthma. We identified 4 distinct longitudinal nasal microbiota profiles during age 2 to 13 months. In the multivariable analysis, compared with the persistent Moraxella dominance profile during age 2 to 13 months, the persistent Moraxella sparsity profile was associated with a significantly higher risk of asthma (adjusted odds ratio, 2.74; 95% confidence interval, 1.20-6.27). Similar associations were observed between the longitudinal changes in nasal microbiota during age 2 to 24 months and risk of asthma. CONCLUSIONS: Children with an altered longitudinal pattern in the nasal microbiota during early childhood had a high risk of developing asthma. Our data guide the development of primary prevention strategies (eg, early identification of children at high risk and modification of microbiota) for childhood asthma. These observations present a new avenue for risk modification for asthma (eg, microbiota modification).


Assuntos
Asma/etiologia , Microbiota , Nariz/microbiologia , Aerococcaceae/isolamento & purificação , Fatores Etários , Asma/diagnóstico , Asma/microbiologia , Criança , Pré-Escolar , Feminino , Finlândia , Seguimentos , Perfilação da Expressão Gênica/métodos , Haemophilus/isolamento & purificação , Humanos , Incidência , Lactente , Recém-Nascido , Aprendizado de Máquina , Masculino , Microbiota/genética , Moraxella/isolamento & purificação , Análise Multivariada , Estudos Prospectivos , RNA Ribossômico 16S/genética , Infecções Respiratórias/complicações , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Risco , Streptococcus/isolamento & purificação
8.
Yonsei Med J ; 61(9): 797-804, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882764

RESUMO

PURPOSE: Climate and lifestyle changes increase an individual's susceptibility to various allergens and also the incidence of allergic diseases. We aimed to examine the changes in sensitization rate for aeroallergens over a 10-year period in Korean children. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 4493 children who visited the allergy clinic at a tertiary hospital in Korea for allergic rhinitis or asthma from January 2009 to December 2018. The serum specific immunoglobulin E (IgE) levels were measured to confirm the sensitization against Dermatophagoides farinae (D. farinae), Alternaria, weed and tree pollen mixtures, as well as cat and dog dander through ImmunoCAP test. RESULTS: D. farinae was the most common sensitizing aeroallergen (45.9%) during the 10-year span. The sensitization rate for tree pollen mixture (p for trend <0.001), weed pollen mixtures (p for trend <0.001), dog dander (p for trend=0.025), and cat dander (p for trend=0.003) showed ascending trends during the 10-year study period. Furthermore, the sensitization rate for multiple allergens (≥2) in 2018 increased significantly compared to that in 2009 (p for trend=0.013). Compared with children without sensitization to D. farinae, those with sensitization to D. farinae showed higher sensitization rates to other aeroallergens (p for interaction <0.001). CONCLUSION: Children's sensitization rate to cat and dog dander and weed and tree pollen mixtures significantly increased during the 10-year period in Korea. Children with sensitization to D. farinae are likely to be sensitized to other aeroallergens as well.


Assuntos
Alérgenos/imunologia , Asma/imunologia , Hipersensibilidade/diagnóstico , Imunoglobulina E/sangue , Rinite Alérgica/imunologia , Alérgenos/efeitos adversos , Animais , Asma/diagnóstico , Asma/epidemiologia , Gatos , Criança , Dermatophagoides farinae , Cães , Feminino , Humanos , Hipersensibilidade/imunologia , Masculino , Pólen/imunologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Rinite Alérgica/diagnóstico
9.
Nat Commun ; 11(1): 3865, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737319

RESUMO

Polygenic scores (PGS) have been widely used to predict disease risk using variants identified from genome-wide association studies (GWAS). To date, most GWAS have been conducted in populations of European ancestry, which limits the use of GWAS-derived PGS in non-European ancestry populations. Here, we derive a theoretical model of the relative accuracy (RA) of PGS across ancestries. We show through extensive simulations that the RA of PGS based on genome-wide significant SNPs can be predicted accurately from modelling linkage disequilibrium (LD), minor allele frequencies (MAF), cross-population correlations of causal SNP effects and heritability. We find that LD and MAF differences between ancestries can explain between 70 and 80% of the loss of RA of European-based PGS in African ancestry for traits like body mass index and type 2 diabetes. Our results suggest that causal variants underlying common genetic variation identified in European ancestry GWAS are mostly shared across continents.


Assuntos
Asma/genética , Diabetes Mellitus Tipo 2/genética , Hipertensão/genética , Modelos Genéticos , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Adulto , África/epidemiologia , Idoso , Alelos , Ásia/epidemiologia , Asma/diagnóstico , Asma/epidemiologia , Asma/etnologia , Índice de Massa Corporal , Colesterol/sangue , Simulação por Computador , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Europa (Continente)/epidemiologia , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/etnologia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Prognóstico , Característica Quantitativa Herdável , Risco
10.
J Allergy Clin Immunol ; 146(4): 808-812, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32735807
11.
J Allergy Clin Immunol ; 146(4): 790-798, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32810517

RESUMO

BACKGROUND: There is inconclusive and controversial evidence of the association between allergic diseases and the risk of adverse clinical outcomes of coronavirus disease 2019 (COVID-19). OBJECTIVE: We sought to determine the association of allergic disorders with the likelihood of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and with clinical outcomes of COVID-19 (admission to intensive care unit, administration of invasive ventilation, and death). METHODS: A propensity-score-matched nationwide cohort study was performed in South Korea. Data obtained from the Health Insurance Review & Assessment Service of Korea from all adult patients (age, >20 years) who were tested for SARS-CoV-2 in South Korea between January 1, 2020, and May 15, 2020, were analyzed. The association of SARS-CoV-2 test positivity and allergic diseases in the entire cohort (n = 219,959) and the difference in clinical outcomes of COVID-19 were evaluated in patients with allergic diseases and SARS-CoV-2 positivity (n = 7,340). RESULTS: In the entire cohort, patients who underwent SARS-CoV-2 testing were evaluated to ascertain whether asthma and allergic rhinitis were associated with an increased likelihood of SARS-CoV-2 test positivity. After propensity score matching, we found that asthma and allergic rhinitis were associated with worse clinical outcomes of COVID-19 in patients with SARS-CoV-2 test positivity. Patients with nonallergic asthma had a greater risk of SARS-CoV-2 test positivity and worse clinical outcomes of COVID-19 than patients with allergic asthma. CONCLUSIONS: In a Korean nationwide cohort, allergic rhinitis and asthma, especially nonallergic asthma, confers a greater risk of susceptibility to SARS-CoV-2 infection and severe clinical outcomes of COVID-19.


Assuntos
Asma/complicações , Betacoronavirus/patogenicidade , Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Dermatite Atópica/complicações , Complicações do Diabetes/diagnóstico , Pneumonia Viral/complicações , Rinite Alérgica/complicações , Adulto , Idoso , Asma/diagnóstico , Asma/imunologia , Asma/mortalidade , Betacoronavirus/imunologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/mortalidade , Técnicas de Laboratório Clínico , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Dermatite Atópica/mortalidade , Complicações do Diabetes/imunologia , Complicações do Diabetes/mortalidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/imunologia , Diabetes Mellitus/mortalidade , Suscetibilidade a Doenças , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Rinite Alérgica/diagnóstico , Rinite Alérgica/imunologia , Rinite Alérgica/mortalidade , Índice de Gravidade de Doença , Análise de Sobrevida
13.
Clin Chest Med ; 41(3): 395-403, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32800194

RESUMO

The term asthma chronic obstructive pulmonary disease (COPD) overlap (ACO) has been popularized to describe people who simultaneously have features of both diseases. Analysis of the basis of disease classification and comparison of the clinical, pathophysiological, and therapeutic features of asthma and COPD concludes that it is not useful to use the term ACO. Rather, it is important to make the individual diagnoses, recognizing that both diseases may coexist. If a concurrent diagnosis of COPD is suspected in people with asthma, pharmacotherapy should primarily follow asthma guidelines, but pharmacologic and nonpharmacologic approaches also may be needed for COPD.


Assuntos
Asma/diagnóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Asma/patologia , Feminino , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/patologia
16.
Allergy Asthma Proc ; 41(4): 296-300, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32605700

RESUMO

Underlying lung disease, especially asthma, has recently been found to be associated with a higher risk of hospitalization with coronavirus disease 2019 (COVID-19) infection. Inhaled corticosteroids (ICS) are the most commonly used controller medications in patients with asthma. It is unclear whether ICS use increases the risk for severe COVID-19 infection. At the current time, asthma organizations are still recommending the continued use of ICS and other asthma medications to minimize the risk of uncontrolled asthma. However, for patients with asthma and who have recovered from COVID-19 infection, the timing of resumption of asthma therapy is equally uncertain. Pulmonary function testing and exhaled oral nitric oxide testing are aerosol-generating procedures and are currently being severely restricted at most health-care facilities. We presented a case of a patient with cough-variant asthma who developed severe COVID-19 associated acute respiratory distress syndrome with the need for intubation and prolonged mechanical ventilation. We highlighted the potential utility of using COVID-19 RNA detection as well as immunoglobulin G antibody testing to help guide the timing of resumption of asthma therapy.


Assuntos
Corticosteroides/uso terapêutico , Asma/complicações , Asma/tratamento farmacológico , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Algoritmos , Asma/diagnóstico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/genética , Biomarcadores , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Gerenciamento Clínico , Humanos , Masculino , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Testes de Função Respiratória , Resultado do Tratamento
17.
PLoS One ; 15(7): e0235069, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628682

RESUMO

BACKGROUND: Pneumonia is the leading cause of death among children and young people (CYP) with severe cerebral palsy (CP). Only a few studies used nomogram for assessing risk factors and the probability of pneumonia. Therefore, we aimed to identify risk factors and devise a nomogram for identifying the probability of severe pneumonia in CYP with severe CP. METHODS: This retrospective nationwide population-based cohort study examined CYP with newly diagnosed severe CP before 18 years old between January 1st, 1997 and December 31st, 2013 and followed them up through December 31st, 2013. The primary endpoint was defined as the occurrence of severe pneumonia with ≥ 5 days of hospitalization. Logistic regression analysis was used for determining demographic factors and comorbidities associated with severe pneumonia. These factors were assigned integer points to create a scoring system to identify children at high risk for severe pneumonia. RESULTS: Among 6,356 CYP with newly diagnosed severe CP, 2,135 (33.59%) had severe pneumonia. Multivariable logistic regression analysis revealed that seven independent predictive factors, namely age <3 years, male sex, and comorbidities of pressure ulcer, gastroesophageal reflux, asthma, seizures, and perinatal complications. A nomogram was devised by employing these seven significant predictive factors. The prediction model presented favorable discrimination performance. CONCLUSIONS: The nomogram revealed that age, male sex, history of pressure ulcer, gastroesophageal reflux, asthma, seizures, and perinatal complications were potential risk factors for severe pneumonia among CYP with severe CP.


Assuntos
Paralisia Cerebral/diagnóstico , Paralisia Cerebral/epidemiologia , Nomogramas , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/epidemiologia , Doença Aguda , Adolescente , Fatores Etários , Asma/diagnóstico , Asma/fisiopatologia , Paralisia Cerebral/complicações , Paralisia Cerebral/mortalidade , Criança , Pré-Escolar , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/fisiopatologia , Humanos , Modelos Logísticos , Masculino , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/mortalidade , Lesão por Pressão/diagnóstico , Lesão por Pressão/fisiopatologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Convulsões/diagnóstico , Convulsões/fisiopatologia , Fatores Sexuais , Análise de Sobrevida , Taiwan/epidemiologia
18.
PLoS One ; 15(7): e0235606, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614906

RESUMO

INTRODUCTION: People Living with HIV (PLHIV) bear a disproportionate burden of non-communicable diseases (NCDs). Despite their significant toll across populations globally, the NCD burden among key populations (KP) in Kenya remains unknown. The burden of four NCD-categories (cardiovascular diseases, cancer, chronic respiratory diseases and diabetes) was evaluated among female sex workers (FSWs) and men who have sex with men (MSM) at the Sex Workers Outreach Program (SWOP) clinics in Nairobi Kenya. METHODS: A retrospective medical chart review was conducted at the SWOP clinics among KP clients ≥15 years living with HIV enrolled between October 1, 2012 and September 30, 2015. The prevalence of the four NCD-categories were assessed at enrollment and during subsequent routine quarterly follow-up care visits as per the Ministry of Health guidelines. Prevalence at enrollment was determined and distributions of co-morbidities assessed using Chi-square and t-tests as appropriate during follow-up visits. Univariate and multivariate analysis were conducted to identify factors associated with NCD diagnoses. RESULTS: Overall, 1,478 individuals' records were analyzed; 1,392 (94.2%) were from FSWs while 86 (5.8%) were from MSM over the three-year period. FSWs' median age was 35.3 years (interquartile range (IQR) 30.1-41.6) while MSM were younger at 26.8 years (IQR 23.2-32.1). At enrollment into the HIV care program, most KPs (86.6%) were at an early WHO clinical stage (stage I-II) and 1462 (98.9%) were on first-line anti-retroviral therapy (ART). A total of 271, 18.3% (95% CI: 16.4-20.4%), KPs living with HIV had an NCD diagnosis in their clinical chart records during the study period. Majority of these cases, 258 (95.2%) were noted among FSWs. Cardiovascular disease that included hypertension was present in 249/271, 91.8%, of KPs with a documented NCD. Using a proxy of two or more elevated blood pressure readings taken < 12 months apart, prevalence of hypertension rose from 1.0% (95% CI: 0.6-1.7) that was documented in the charts during the first year to 16.3% (95% CI: 14.4-18.3) in the third year. Chronic respiratory disease mainly asthma was present in 16/271, a prevalence of 1.1% (95% CI: 0.6-1.8) in the study population. Cancer in general was detected in 10/271, prevalence of 0.7% (95% CI: 0.3-1.2) over the same period. Interestingly, diabetes was not noted in the study group. Lastly, significant associations between NCD diagnosis with increasing age, body-mass index and CD4 + cell-counts were noted in univariate analysis. However, except for categories of ≥ BMI 30 kg/m2 and age ≥ 45, the associations were not sustained in adjusted risk estimates. CONCLUSION: In Kenya, KP living with HIV and on ART have a high prevalence of NCD diagnoses. Multiple NCD risk factors were also noted against a backdrop of a changing HIV epidemic in the study population. This calls for scaling up focus on both HIV and NCD prevention and care in targeted populations at increased risk of HIV acquisition and transmission. Hence, KP programs could include integrated HIV-NCD screening and care in their guidelines.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Doenças não Transmissíveis/epidemiologia , Adolescente , Adulto , Fatores Etários , Asma/diagnóstico , Asma/epidemiologia , Índice de Massa Corporal , Feminino , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Profissionais do Sexo , Adulto Jovem
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