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1.
Environ Res ; 252(Pt 3): 118913, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38643821

RESUMO

Exposome studies are advancing in high-income countries to understand how multiple environmental exposures impact health. However, there is a significant research gap in low- and middle-income and tropical countries. We aimed to describe the spatiotemporal variation of the external exposome, its correlation structure between and within exposure groups, and its dimensionality. A one-year follow-up cohort study of 506 children under 5 in two cities in Colombia was conducted to evaluate asthma, acute respiratory infections, and DNA damage. We examined 48 environmental exposures during pregnancy and 168 during childhood in eight exposure groups, including atmospheric pollutants, natural spaces, meteorology, built environment, traffic, indoor exposure, and socioeconomic capital. The exposome was estimated using geographic information systems, remote sensing, spatiotemporal modeling, and questionnaires. The median age of children at study entry was 3.7 years (interquartile range: 2.9-4.3). Air pollution and natural spaces exposure decreased from pregnancy to childhood, while socioeconomic capital increased. The highest median correlations within exposure groups were observed in meteorology (r = 0.85), traffic (r = 0.83), and atmospheric pollutants (r = 0.64). Important correlations between variables from different exposure groups were found, such as atmospheric pollutants and meteorology (r = 0.76), natural spaces (r = -0.34), and the built environment (r = 0.53). Twenty principal components explained 70%, and 57 explained 95% of the total variance in the childhood exposome. Our findings show that there is an important spatiotemporal variation in the exposome of children under 5. This is the first characterization of the external exposome in urban areas of Latin America and highlights its complexity, but also the need to better characterize and understand the exposome in order to optimize its analysis and applications in local interventions aimed at improving the health conditions and well-being of the child population and contributing to environmental health decision-making.


Assuntos
Exposição Ambiental , Expossoma , Humanos , Colômbia/epidemiologia , Pré-Escolar , Feminino , Exposição Ambiental/análise , Masculino , Poluentes Atmosféricos/análise , Gravidez , Poluição do Ar/análise , Estudos de Coortes
2.
Public Health ; 236: 459-465, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39357331

RESUMO

OBJECTIVES: This study analyzed adherence rates to conventional cytology and associated factors in a cohort of women at a health service provider institution in Medellin, Colombia. STUDY DESIGN: Observational cohort study with repeated measures. METHODS: Clinical and sociodemographic data were obtained from databases for screenings between January 2018 and December 2022. Adherence, defined as undergoing 1, 2, or 3 cytology tests according to national guidelines, was the outcome. Statistical analysis involved a Poisson model with robust errors to identify factors associated with adherence. RESULTS: In total, 26,445 women were included, with a median age of 25 years (IQR: 22-27). Adherence rate was 20.4%. Having just high school education (RR = 0.51; 95% CI: 0.49-0.55), a history of pregnancy (RR = 0.63; 95% CI: 0.54-0.75), and a history of sexually transmitted infections (RR = 0.88; 95% CI: 0.78-0.99) decreased adherence. Conversely, the human papillomavirus (HPV) vaccination history increased adherence (RR = 2.11; 95% CI: 1.60-2.80). CONCLUSION: It is vital to monitor cytology programs to improve demand-induced and spontaneous consultations. Diligent follow-up, focusing on patients with factors linked to low adherence, along with appointment reminders, can enhance adherence to the screening protocol.

3.
Sensors (Basel) ; 23(22)2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-38005502

RESUMO

Arthrogenic muscle inhibition (AMI) refers to muscular alterations that are generated, producing biomechanical motor control and movement problems, leading to deficiencies in strength and atrophy. Currently, there exist methods that involve virtual reality (VR) and have been well perceived by physiotherapists. The present research measured the potential benefits in terms of therapeutic adherence and speed of recovery, through a comparative analysis in a healthcare provider institution, in Medellín, Colombia, with and without the aid of VR. For this purpose, dynamometry, and surface electromyography (sEMG) signal acquisition tools were used. The treatment involved neuromodulation, ranges of motion and mobility work, strengthening and reintegration into movement, complemented with TENS, NMENS and therapeutic exercise, where the patient was expected to receive a satisfactory and faster adherence and recovery. A group of 15 people with AMI who include at least 15 min of VR per session in their treatment were compared with another group who received only the base treatment, i.e., the control group. Analyzing the variables individually, it is possible to affirm that VR, as a complement, statistically significantly improved the therapeutic adherence in 33.3% for CG and 37.5% for IG. Additionally, it increased strength with both legs, the symmetry between them, and decreased the level of pain and stiffness that is related to mobility.


Assuntos
Força Muscular , Realidade Virtual , Humanos , Força Muscular/fisiologia , Terapia por Exercício/métodos , Movimento , Eletromiografia
4.
Crit Care ; 26(1): 130, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534867

RESUMO

BACKGROUND: The detection of coinfections is important to initiate appropriate antimicrobial therapy. Molecular diagnostic testing identifies pathogens at a greater rate than conventional microbiology. We assessed both bacterial coinfections identified via culture or the BioFire® FilmArray® Pneumonia Panel (FA-PNEU) in patients infected with SARS-CoV-2 in the ICU and the concordance between these techniques. METHODS: This was a prospective study of patients with SARS-CoV-2 who were hospitalized for no more than 48 h and on mechanical ventilation for no longer than 24 h in 8 ICUs in Medellín, Colombia. We studied mini-bronchoalveolar lavage or endotracheal aspirate samples processed via conventional culture and the FA-PNEU. Coinfection was defined as the identification of a respiratory pathogen using the FA-PNEU or cultures. Serum samples of leukocytes, C-reactive protein, and procalcitonin were taken on the first day of intubation. We analyzed the empirical antibiotics and the changes in antibiotic management according to the results of the FA-PNEUM and cultures. RESULTS: Of 110 patients whose samples underwent both methods, FA-PNEU- and culture-positive samples comprised 24.54% versus 17.27%, respectively. Eighteen samples were positive in both techniques, 82 were negative, 1 was culture-positive with a negative FA-PNEU result, and 9 were FA-PNEU-positive with negative culture. The two bacteria most frequently detected by the FA-PNEU were Staphylococcus aureus (37.5%) and Streptococcus agalactiae (20%), and those detected by culture were Staphylococcus aureus (34.78%) and Klebsiella pneumoniae (26.08%). The overall concordance was 90.1%, and when stratified by microorganism, it was between 92.7 and 100%. The positive predictive value (PPV) was between 50 and 100% and were lower for Enterobacter cloacae and Staphylococcus aureus. The negative predictive value (NPV) was high (between 99.1 and 100%); MecA/C/MREJ had a specificity of 94.55% and an NPV of 100%. The inflammatory response tests showed no significant differences between patients whose samples were positive and negative for both techniques. Sixty-one patients (55.45%) received at least one dose of empirical antibiotics. CONCLUSIONS: The overall concordance was 90.1%, and it was between 92.7% and 100% when stratified by microorganisms. The positive predictive value was between 50 and 100%, with a very high NPV.


Assuntos
COVID-19 , Coinfecção , Pneumonia , Antibacterianos/uso terapêutico , Bactérias , COVID-19/diagnóstico , Colômbia , Hospitais , Humanos , Unidades de Terapia Intensiva , Reação em Cadeia da Polimerase Multiplex/métodos , Pneumonia/tratamento farmacológico , Estudos Prospectivos , SARS-CoV-2
5.
BMC Pediatr ; 22(1): 169, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361166

RESUMO

BACKGROUND: Pneumonia is the leading cause of mortality in pediatric population. The etiology of pneumonia in this population is variable and changes according to age and disease severity and where the study is conducted. Our aim was to determine the etiology of community-acquired pneumonia (CAP) in children aged 1 month to 17 years admitted to 13 Colombian hospitals. METHODS: Prospective cohort study. Hospitalized children with radiologically confirmed CAP and ≤ 15 days of symptoms were included and followed together with a control group. Induced sputum (IS) was submitted for stains and cultures for pyogenic bacteria and Mycobacterium tuberculosis, and multiplex PCR (mPCR) for bacteria and viruses; urinary antigens for pneumococcus and Legionella pneumophila; nasopharyngeal swabs for viruses, and paired serology for atypical bacteria and viruses. Additional cultures were taken at the discretion of primary care pediatricians. RESULTS: Among 525 children with CAP, 71.6% had non-severe pneumonia; 24.8% severe and 3.6% very severe pneumonia, and no fatal cases. At least one microorganism was identified in 84% of children and 61% were of mixed etiology; 72% had at least one respiratory virus, 28% pyogenic bacteria and 21% atypical bacteria. Respiratory syncytial virus, Parainfluenza, Rhinovirus, Influenza, Mycoplasma pneumoniae, Adenovirus and Streptococcus pneumoniae were the most common etiologies of CAP. Respiratory syncytial virus was more frequent in children under 2 years and in severe pneumonia. Tuberculosis was diagnosed in 2.3% of children. IS was the most useful specimen to identify the etiology (33.6%), and blood cultures were positive in 3.6%. The concordance between all available diagnostic tests was low. A high percentage of healthy children were colonized by S. pneumoniae and Haemophilus influenzae, or were infected by Parainfluenza, Rhinovirus, Influenza and Adenovirus. CONCLUSIONS: Respiratory viruses are the most frequent etiology of CAP in children and adolescents, in particular in those under 5 years. This study shows the challenges in making an etiologic diagnosis of CAP in pediatric population because of the poor concordance between tests and the high percentage of multiple microorganisms in healthy children. IS is useful for CAP diagnosis in pediatric population.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Adolescente , Criança , Infecções Comunitárias Adquiridas/epidemiologia , Técnicas e Procedimentos Diagnósticos/efeitos adversos , Humanos , Lactente , Mycoplasma pneumoniae , Pneumonia/complicações , Estudos Prospectivos
6.
Rev Panam Salud Publica ; 43: e97, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31892926

RESUMO

OBJECTIVE: Determine the percentage of children under 5 years of age who completed isoniazid preventive therapy (IPT) in health facilities in Quito, Ecuador, and assess related factors. METHODS: Operations research with cohort design. Data were obtained from treatment reports on children in IPT between 2014 and 2016, and from ad hoc surveys of caregivers of children who received IPT in 2018. RESULTS: Children under 5 represented 29.3% of all contacts of index cases; 73% completed IPT and 88.9% had at least six months of therapy. Associations were found with the bacterial load of the index case, with living in a given district, and with the year in which treatment was initiated. Surveys were conducted with nine staff members of health facilities and nine caregivers of children; diverse responses were given regarding the causative agent of tuberculosis, its transmission, and the characteristics of preventive therapy. CONCLUSIONS: The majority of children under 5 years of age who initiated IPT completed at least 80% of the prescribed doses, with varying associations and knowledge on the part of their caregivers. In this context, there is a need for further operations research in order to learn more about adherence and about the knowledge, attitudes, and practices of health professionals and those affected by tuberculosis, and their environment.


OBJETIVO: Conhecer a porcentagem de adesão à terapia preventiva com isoniazida (TPI) nas unidades de saúde de Quito, Equador, e os fatores associados à adesão em crianças com menos de 5 anos de idade. MÉTODOS: Pesquisa operacional com desenho de coorte, na qual foram obtidos dados de relatórios e dos cartões de administração de TPI em crianças entre 2014 e 2016, bem como de questionários ad hoc aplicados aos cuidadores das crianças que receberam TPI durante o ano de 2018. RESULTADOS: As crianças com menos de 5 anos de idade representaram 29,3% do total dos contatos dos casos índices; 73% aderiram à TPI e 88,9% completaram pelo menos 6 meses de tratamento. Identificamos associações com a carga bacilar do caso índice, com o distrito de residência do paciente e com o ano de início. Realizamos inquéritos com 9 funcionários das unidades de saúde e com 9 responsáveis pelas crianças, registrando respostas variadas sobre o agente causal da tuberculose, sua transmissão e as características da terapia preventiva. CONCLUSÕES: Em sua maioria, as crianças com menos de 5 anos de idade que iniciaram a TPI aderiram a pelo menos 80% das doses prescritas, havendo associações com certos fatores e com os conhecimentos dos cuidadores. Neste contexto, fica clara a necessidade de realizar novos estudos operacionais para compreender melhor a adesão ao tratamento e os conhecimentos, atitudes e práticas dos profissionais da saúde, dos afetados pela tuberculose e das pessoas em seu entorno.

7.
Rev Panam Salud Publica ; 43: e14, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31093238

RESUMO

OBJECTIVE: To determine factors associated with delays in pulmonary tuberculosis diagnosis and treatment initiation in the city of Cali, Colombia. METHODS: This was a retrospective cohort study of cases of tuberculosis (TB) reported in the TB control program of Cali between January and December 2016. The information was collected from the databases of the TB control program, individual treatment cards, and clinical histories. The variables considered were sociodemographic factors, clinical factors, substance use, and performance of the health service. RESULTS: A total of 623 cases were identified, of which 57.0% were male. The median age was 42 years (interquartile range (IQR): 27-60). The median time from onset of symptoms to TB diagnosis was 57 days (IQR: 21-117), and from onset of symptoms to TB treatment initiation was 72 days (IQR: 35-145). A factor associated with longer time from the onset of symptoms to TB treatment was being a previously treated TB patient (coefficient: 123.8 days, 95% confidence interval (CI): 48.3 to 199.3). In contrast, being incarcerated was a protective factor for earlier TB treatment initiation (coefficient: -57.3 days; 95% CI: -92.4 to -22.3). CONCLUSIONS: Our results provide important information concerning risk factors that are associated with delays in the diagnosis and treatment of tuberculosis, and that are subject to future interventions. Health insurance program managers must work together with health care providers on issues that include patient care, health promotion, and updating TB protocols and standards.

8.
Rev Panam Salud Publica ; 43: e102, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31892928

RESUMO

OBJECTIVE: To describe the socio-demographic and clinical-epidemiological characteristics and to determine the factors associated with the mortality of people diagnosed with tuberculosis (TB) in Paraguay. METHODS: Operational research with a retrospective cohort design of cases diagnosed with TB in Paraguay between 2015-2016. The database of the National Tuberculosis Control Program was used. Chi-square and relative risk (RR) tests with a 95% confidence interval (95% CI) were used to determine the factors associated with mortality; in addition, a robust Poisson multiple regression model was adjusted. A significance level of 5% was used. RESULTS: Five hundred and forty-one cases of TB were studied, of which 11.5% died. The factors increasing the risk of death were male sex (RR 1.26; 95% CI 1.1-1.50), infection with human immunodeficiency virus (RR 4.78; 95% CI 4.04-5.65) and chronic obstructive pulmonary disease (RR 1.70; 95% CI 1.19-2.42). Being deprived of one's liberty was a protective factor (RR 0.37; 95% CI 0.24-0.61). CONCLUSIONS: The highest risk of death is presented by men and people with TB/HIV coinfection and the lowest risk is presented by people deprived of liberty. There is a need to improve diagnosis and follow-up of TB cases, with effective implementation of directly observed treatment (DOTS) and timely management of associated diseases such as HIV and chronic obstructive pulmonary disease.


OBJETIVO: Descrever as características sociodemográficas e clínico-epidemiológicas e determinar os fatores associados à mortalidade de pessoas diagnosticadas com tuberculose (TB) no Paraguai. MÉTODOS: Pesquisa operacional com desenho de coorte retrospectivo de casos diagnosticados com TB no Paraguai entre 2015-2016. Foi utilizada a base de dados do Programa Nacional de Controle da Tuberculose. Testes de qui-quadrado e risco relativo (RR) com intervalo de confiança de 95% (IC95%) foram utilizados para determinar os fatores associados à mortalidade; além disso, um robusto modelo de regressão múltipla de Poisson foi ajustado. Foi utilizado nível de significância de 5%. RESULTADOS: Foram estudados quinhentos e quarenta e um casos de TB, dos quais 11,5% morreram. Os fatores que aumentaram o risco de morte foram sexo masculino (RR 1,26; IC95% 1,1-1,50), infecção por vírus da imunodeficiência humana (RR 4,78; IC95% 4,04-5,65) e doença pulmonar obstrutiva crônica (RR 1,70; 95 % CI 1,19-2,42). Ser privado de liberdade foi um fator protetor (RR 0,37; IC 95% 0,24-0,61). CONCLUSÕES: O maior risco de morte é apresentado por homens e pessoas com co-infecção TB / HIV e o menor risco é apresentado por pessoas privadas de liberdade. É necessário melhorar o diagnóstico e o acompanhamento dos casos de TB, com a implementação efetiva do tratamento diretamente observado (DOTS) e o gerenciamento oportuno de doenças associadas, como o HIV e a doença pulmonar obstrutiva crônica.

9.
Rev Panam Salud Publica ; 43: e105, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31892931

RESUMO

OBJECTIVE: To estimate the national and regional prevalence of tuberculosis (TB) and diabetes mellitus (DM) co-morbidity and identify the factors associated with this co-morbidity in Paraguay. METHODS: Cross-sectional study in patients with TB notified in 2016 and 2017 and registered in the database of the National TB Control Program. The prevalence of self-reported DM was estimated in patients with TB. A multivariate binomial regression model was used to know the factors associated with TB-DM co-morbidity to adjust the prevalence ratios (PR) according to standard errors by health region. RESULTS: Between 2016 and 2017, 5 315 cases of TB were reported. The prevalence of TB-DM co-morbidity was 6.3% in 2016, 6.0% in 2017, and 6.2% in both years. It was highest in Itapua (9.2%), Alto Paraguay (8.0%), Alto Parana (7.5%), Central (7.4%) and Asuncion (7.2%). The median age of people with DM was higher than that of those without DM (55 vs 33 years; P < 0.001). Being older than 45 years (RP = 18.3), history of hypertension (RP = 2.17), diagnostic baciloscopy +++ (RP 1.98), and history of chronic obstructive pulmonary disease (COPD) (RP 1.68) were associated with greater co-morbidity. A lower co-morbidity was associated with belonging to the indigenous population (RP = 0.26), human immunodeficiency virus infection (RP = 0.44), history of drug dependence (RP = 0.49), male sex (RP = 0.64), and extrapulmonary TB (RP = 0.75). CONCLUSIONS: The prevalence of self-reported co-morbidity of TB-DM in Paraguay was 6.2% in 2016-2017 and varied between health regions. Age, sex, high bacillary burden at diagnosis and co-morbidity with hypertension and COPD were associated with higher co-morbidity. These findings will allow prioritizing population groups to increase screening performance, diagnosis, treatment and prevention of TB-DM co-morbidity in Paraguay.


OBJETIVO: Estimar a prevalência nacional e regional de comorbidade entre tuberculose (TB) e diabetes mellitus (DM) no Paraguai e identificar os fatores associados a essa comorbidade. MÉTODOS: Estudo transversal em pacientes com TB notificados em 2016 e 2017 e cadastrados na base de dados do Programa Nacional de Controle da TB. A prevalência de DM, definida por autorrelato, foi estimada em pacientes com TB. Para conhecer os fatores associados à comorbidade TB-DM, foi utilizado um modelo de regressão binomial multivariada para ajustar as razões de prevalência (RP) de acordo com os erros padrão do cluster da região de saúde. RESULTADOS: Em 2016 e 2017 foram notificados 5 315 casos de TB. A prevalência de comorbidade TB-DM foi de 6,3% em 2016, 6,0% em 2017 e 6,2% para o período dos 2 anos. As prevalências mais altas foram observadas em Itapúa (9,2%), Alto Paraguai (8,0%), Alto Paraná (7,5%), Central (7,4%) e Assunção (7,2%). A mediana de idade foi mais alta em pessoas com DM do que naquelas sem DM (55 e 33 anos; P <0,001). Ter idade superior a 45 anos (RP = 18,3), história de hipertensão arterial (HAS) (RP = 2,17), baciloscopia diagnóstica (+++) (RP = 1,98) e história de doença pulmonar obstrutiva crônica (DPOC) (RP = 1,68) foram associados a maior comorbidade. Por sua vez, pertencer à população indígena (RP = 0,26), infecção pelo vírus da imunodeficiência humana (RP = 0,44), histórico de dependência de drogas (RP = 0,49), sexo masculino (RP = 0,64) e TB extrapulmonar (RP = 0,75) estiveram associados a menor comorbidade. CONCLUSÕES: A prevalência de comorbidade TB-DM no Paraguai, determinada a partir de autorrelato, foi de 6,2% no período 2016-2017 e variou entre as regiões de saúde. Idade, sexo, alta carga bacilar no diagnóstico e comorbidade com HAS e DPOC foram fatores associados a maior comorbidade. Esses achados permitirão priorizar grupos populacionais para aumentar o desempenho da triagem, diagnóstico, tratamento e prevenção da comorbidade TB-DM no Paraguai.

10.
Rev Panam Salud Publica ; 43: e91, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31892925

RESUMO

OBJECTIVE: Determine the incidence of loss to follow-up (LTFU) in patients treated for rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant tuberculosis (RR/MDR-TB), and the factors associated with this discharge status in Ecuador. METHODS: Retrospective cohort study of patients with RR/MDR-TB who followed the World Health Organization's 18-24-month treatment regimen in 2014 and 2015, as reported by the Ministry of Health of Ecuador. The incidence of LTFU was determined, and clinical and epidemiological manifestations of cases discharged as LTFU were compared with those discharged as successfully treated. Survival was analyzed with Cox regression in order to evaluate factors associated with LTFU. RESULTS: Of 328 cases, 270 (82.3%) were analyzed because they had a reported discharge status. Discharge as LTFU accounted for 39.6% of cases, and as successfully treated, 50.4%. The risk factors associated with LTFU were: previous discharge as LTFU in a previous TB episode [hazard ratio (HR): 2.96 (1.53-5.73), P < 0.001]; addiction to alcohol or drugs [HR: 2.82 (1.10-7.23), P = 0.031]; and having an Xpert® diagnosis (TB-RR) [HR: 1.53 (1.0-2.35), P = 0.048]. Of the total LTFU, 43% occurred after nine months of treatment. CONCLUSION: The incidence of LTFU in patients with RR/MDR-TB in Ecuador is above the average for the Region of the Americas. The three identified factors support implementation of shorter regimens and patient-centered care, in line with the End TB Strategy.


OBJETIVO: Determinar o percentual de perda de seguimento de pacientes tratados para tuberculose resistente à rifampicina (TB-RR) ou tuberculose multirresistente a medicamentos (TB-MR) e os fatores associados à interrupção do tratamento no Equador. MÉTODOS: Estudo de coorte retrospectivo de casos de pacientes com TB-RR/TB-MR tratados em 2014 e 2015 com o esquema farmacológico de 18 a 24 meses de duração da Organização Mundial da Saúde (OMS) que foram notificados ao Ministério da Saúde do Equador. Foi determinado o percentual de perda de seguimento e foram comparadas as características clínicas e epidemiológicas dos casos de interrupção do tratamento por perda de seguimento e daqueles com alta por sucesso no tratamento. Uma análise da sobrevida com o modelo de regressão de Cox foi realizada para avaliar os fatores associados à perda de seguimento. RESULTADOS: De 328 casos registrados, 270 (82,3%) foram incluídos na análise por terem tido sua interrupção ou alta notificadas. Houve interrupção por perda de seguimento em 39,6% dos casos e alta por sucesso no tratamento em 50,4%. Os fatores de risco associados à perda de seguimento foram: história de perda de seguimento em tratamento anterior de TB, razão de riscos (hazard ratio, HR) 2,96 (1,53­5,73, P < 0,001); consumo excessivo de álcool ou drogas, HR 2,82 (1,10­7,23, P = 0,031); e diagnóstico de tuberculose pelo teste Xpert® (TB-RR), HR 1,53 (1,0­2,35, P = 0,048). A perda de seguimento ocorreu após nove meses de tratamento em 43% dos casos. CONCLUSÃO: O percentual de perda de seguimento de pacientes com TB-RR/TB-MR no Equador está acima da média da Região das Américas. Os três fatores identificados no estudo reforçam ser necessário implementar esquemas de tratamento mais curtos e prestar atenção centrada no paciente, segundo as recomendações da Estratégia pelo Fim da Tuberculose.

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