SNPs in genes related to the repair of damage to DNA in clinical isolates of M. tuberculosis: A transversal and longitudinal approach.

The presence of SNPs in genes related to DNA damage repair in M. tuberculosis can trigger hypermutagenic phenotypes with a higher probability of generating drug resistance. The aim of this research was to compare the presence of SNPs in genes related to DNA damage repair between sensitive and DR isolates, as well as to describe the dynamics in the presence of SNPs in M. tuberculosis isolated from recently diagnosed TB patients of the state of Veracruz, Mexico. The presence of SNPs in the coding regions of 65 genes related to DNA damage repair was analyzed. Eighty-six isolates from 67 patients from central Veracruz state, Mexico, were sequenced. The results showed several SNPs in 14 genes that were only present in drug-resistant genomes. In addition, by following of 15 patients, it was possible to describe three different dynamics of appearance and evolution of non-synonymous SNPs in genes related to DNA damage repair: 1) constant fixed SNPs, 2) population substitution, and 3) gain of fixed SNPs. Further research is required to discern the biological significance of each of these pathways and their utility as markers of DR or for treatment prognosis.

Whole genome sequencing analysis to evaluate the influence of T2DM on polymorphisms associated with drug resistance in M. tuberculosis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been associated with treatment failure, and the development of drug resistance in tuberculosis (TB). Also, whole-genome sequencing has provided a better understanding and allowed the growth of knowledge about polymorphisms in genes associated with drug resistance. Considering the above, this study analyzes genome sequences to evaluate the influence of type 2 diabetes mellitus in the development of mutations related to tuberculosis drug resistance. M. tuberculosis isolates from individuals with (n = 74), and without (n = 74) type 2 diabetes mellitus was recovered from online repositories, and further analyzed. RESULTS: The results showed the presence of 431 SNPs with similar proportions between diabetics, and non-diabetics individuals (48% vs. 52%), but with no significant relationship. A greater number of mutations associated with rifampicin resistance was observed in the T2DM-TB individuals (23.2% vs. 16%), and the exclusive presence of rpoBQ432L, rpoBQ432P, rpoBS441L, and rpoBH445L variants. While these variants are not private to T2DM-TB cases they are globally rare highlighting a potential role of T2DM. The phylogenetic analysis showed 12 sublineages, being 4.1.1.3, and 4.1.2.1 the most prevalent in T2DM-TB individuals but not differing from those most prevalent in their geographic location. Four clonal complexes were found, however, no significant relationship with T2DM was observed. Samples size and potential sampling biases prevented us to look for significant associations. CONCLUSIONS: The occurrence of globally rare rifampicin variants identified only in isolates from individuals with T2DM could be due to the hyperglycemic environment within the host. Therefore, further studies about the dynamics of SNPs' generation associated with antibiotic resistance in patients with diabetes mellitus are necessary.

Interventions to Improve Clinical Coordination between Levels: Participatory Experience in a Public Healthcare Network in Xalapa, Mexico.

INTRODUCTION: Coordination of care can be improved through an intervention or a combination of several ones. In addition, it is recommended to encourage the active involvement of professionals in the design, implementation and assessment of coordination mechanisms. OBJECTIVE: To analyse the factors that influence the implementation of participatively designed interventions and their effects on clinical coordination between levels of care in a public healthcare network of health services in Xalapa, Veracruz, Mexico. METHODS: A qualitative, descriptive-interpretative study, for which individual interviews and discussion groups with a criterion sample of participants: Local Steering Committee and the Professional Platform. A content analysis, with mixed category generation and segmentation by intervention and topics, was carried out. According to the problem analysis, participants designed two sequential interventions: offline virtual consultation, and joint training meetings on maternal health and chronic diseases. RESULTS: Respondents perceived a differentiated impact on clinical coordination according to intervention: greater in the case of joint maternal health trainings and limited for the chronic diseases meetings, as they were the offline virtual consultation was rarely used. CONCLUSION: The involvement of professionals in designing the interventions, as well as institutional support and reflexive methods for training, all decisively improved clinical coordination between levels.

[Nanoparticles as drug transporters: a promising tool against tuberculosis]. / Nanopartículas como transportadores de fármacos: una herramienta prometedora contra la tuberculosis.

The World Health Organization (WHO) places Tuberculosis (TB) as one of the most important health problems today. According to the WHO, this disease requires novel actions to control its expansion and, in this way, achieve one of the goals established in the sustainable development goals: to reduce TB morbidity and incidence by 2030 and regain control. To achieve this goal, the tools currently used for diagnosis and treatment are no longer adequate. In this sense, it is necessary to develop new drugs and vaccines, as well as novel drug administration procedures that generate a better response, reduce times, and optimize treatments. Nanotechnology has incorporated in recent years a considerable number of new tools that significantly increase the diversity of mechanisms for the administration of anti-tuberculosis drugs. Therefore, the present review briefly describes the current state of drug resistance in tuberculosis, as well as the general characteristics of nanoparticles being evaluated as tools to transport new antibiotics against tuberculosis.

La Organización Mundial de la Salud (OMS) ubica a la tuberculosis (TB) como uno de los problemas de salud más preocupantes en la actualidad, y señala que se requieren de acciones novedosas para controlar su expansión y, de esta manera, alcanzar una de las metas establecidas en los Objetivos de Desarrollo Sostenible: reducir para 2030 la morbilidad e incidencia de TB. Para lograr este objetivo, está claro que las herramientas empleadas actualmente para su diagnóstico y tratamiento ya no son las adecuadas. En este sentido, es necesario desarrollar nuevos medicamentos y vacunas, así como novedosos procedimientos de administración de fármacos que generen una mejor respuesta, disminuyan el tiempo y optimicen los tratamientos. La nanotecnología ha incorporado en los últimos años un gran número de nuevas herramientas que incrementan considerablemente, la diversidad de mecanismos para la administración de tratamientos antituberculosos. Dicho esto, la presente revisión describe brevemente el estado actual de la farmacorresistencia en TB, así como las características generales de las nanopartículas que están evaluándose como herramientas para transportar antibióticos antituberculosos.

[Barriers and factors associated with the use of coordination mechanisms between levels of care in Mexico]. / Barreras y factores asociados al uso de mecanismos de coordinación entre niveles de atención en México.

The aim was to analyze the level and characterize the use of clinical coordination mechanisms between levels of care, and their associated factors, in two public networks of health services in Mexico. A cross-sectional study was carried out using the COORDENA questionnaire to primary and specialized care physicians in the state of Veracruz. Differences were found between networks and levels of care, according to the mechanism. In both, the referral/counter-referral is mostly used to channel the patient to another level, mainly by primary care physicians. A high reception of referrals by specialists was identified, but few counterreferences in primary care. Being a man and recognizing the primary care physician, as responsible for monitoring the patient in his/her healthcare career, were factors associated with the frequent sending of the counter-referral by specialists. The discharge report is used in both networks to send clinical information to the other level, with more sending by specialist doctors, but with less reception in primary care. In both networks, the follow-up to the recommendations of the mechanisms to standardize clinical care was greater by primary care physicians than specialized ones. The use of coordination mechanisms between levels of care is deficient and limited, with greater use of mechanisms to transfer information than for clinical management. The need to implement strategies that consider the participation of professionals is evident, to favor local adaptation, appropriation and improve their use.

El objetivo fue analizar el nivel y caracterizar el uso de mecanismos de coordinación clínica entre niveles de atención, y sus factores asociados, en dos redes públicas de servicios de salud en México. Se realizó estudio transversal mediante el cuestionario COORDENA a médicos de atención primaria y especializada del estado de Veracruz. Se encontraron diferencias entre redes y niveles de atención, según el mecanismo. En ambas, la referencia/contrarreferencia es sobre todo utilizada para canalizar al paciente a otro nivel, principalmente por parte de los médicos de atención primaria. Se identificó una alta recepción de referencias por especialistas, pero escasa recepción de contrarreferencias en atención primaria. Ser hombre y reconocer al médico/a de atención primaria como responsable del seguimiento del paciente en su trayectoria asistencial, fueron factores asociados al envío frecuente de la contrarreferencia por especialistas. El informe de alta se utiliza en ambas redes para enviar información clínica al otro nivel, con mayor envío por médicos/as especialistas, y con menor recepción en atención primaria. En ambas redes, el seguimiento a las recomendaciones de los mecanismos para estandarizar la atención clínica (guías de práctica clínica, etc.) por parte médicos/as de atención primaria que de especializada. La utilización de mecanismos de coordinación entre niveles de atención es deficiente y limitada, con mayor uso de mecanismos para transferir información que para la gestión clínica. Se evidencia la necesidad de implementar estrategias que consideren la participación de los profesionales, para favorecer la adaptación local, apropiación y mejorar su uso.

O objetivo era analisar o nível e caracterizar o uso de mecanismos de coordenação clínica entre níveis de atenção e seus fatores associados em duas redes públicas de saúde no México. Estudo transversal por meio do questionário COORDENA aplicados a médicos da atenção primaria e especializada do Estado de Veracruz. Foram encontradas diferenças entre redes e níveis de atenção conforme o mecanismo. Em ambas, a referência/contrarreferência é sobre tudo utilizada para encaminhar o paciente para outro nível, principalmente por parte dos médicos da atenção primária. Foi identificado um alto recebimento de referências por especialistas, porém raras são as contrarreferências na atenção primária. Ser homem e reconhecer o médico/a de atenção primária como responsável pelo acompanhamento do paciente na sua trajetória de atendimento foram fatores associados ao envio frequente da contrarreferência por especialistas. O relatório de alta é utilizado nas duas redes para enviar informação clínica ao outro nível, com mais envios por médicos/as especialistas e menos recebimentos na atenção primária. Em ambas as redes, a observância das recomendações de mecanismos para padronizar a atenção clínica foi maior por parte dos médicos/as da atenção primária do que da especializada. O uso de mecanismos de coordenação entre níveis de atenção é deficiente e limitado, com o emprego maior de mecanismos para transmitir informação do que para a gestão clínica. Ficou evidenciada a necessidade de implementar estratégias que levem em conta a participação dos profissionais, para promover a adequação local, a apropriação e melhorar a sua utilização.

Nanopartículas como transportadores de fármacos: una herramienta prometedora contra la tuberculosis / Nanoparticles as drug transporters: a promising tool against tuberculosis

RESUMEN La Organización Mundial de la Salud (OMS) ubica a la tuberculosis (TB) como uno de los problemas de salud más preocupantes en la actualidad, y señala que se requieren de acciones novedosas para controlar su expansión y, de esta manera, alcanzar una de las metas establecidas en los Objetivos de Desarrollo Sostenible: reducir para 2030 la morbilidad e incidencia de TB. Para lograr este objetivo, está claro que las herramientas empleadas actualmente para su diagnóstico y tratamiento ya no son las adecuadas. En este sentido, es necesario desarrollar nuevos medicamentos y vacunas, así como novedosos procedimientos de administración de fármacos que generen una mejor respuesta, disminuyan el tiempo y optimicen los tratamientos. La nanotecnología ha incorporado en los últimos años un gran número de nuevas herramientas que incrementan considerablemente, la diversidad de mecanismos para la administración de tratamientos antituberculosos. Dicho esto, la presente revisión describe brevemente el estado actual de la farmacorresistencia en TB, así como las características generales de las nanopartículas que están evaluándose como herramientas para transportar antibióticos antituberculosos.

ABSTRACT The World Health Organization (WHO) places Tuberculosis (TB) as one of the most important health problems today. According to the WHO, this disease requires novel actions to control its expansion and, in this way, achieve one of the goals established in the sustainable development goals: to reduce TB morbidity and incidence by 2030 and regain control. To achieve this goal, the tools currently used for diagnosis and treatment are no longer adequate. In this sense, it is necessary to develop new drugs and vaccines, as well as novel drug administration procedures that generate a better response, reduce times, and optimize treatments. Nanotechnology has incorporated in recent years a considerable number of new tools that significantly increase the diversity of mechanisms for the administration of anti-tuberculosis drugs. Therefore, the present review briefly describes the current state of drug resistance in tuberculosis, as well as the general characteristics of nanoparticles being evaluated as tools to transport new antibiotics against tuberculosis.

Nanopartículas como transportadores de fármacos: una herramienta prometedora contra la tuberculosis / Nanoparticles as drug transporters: a promising tool against tuberculosis

RESUMEN La Organización Mundial de la Salud (OMS) ubica a la tuberculosis (TB) como uno de los problemas de salud más preocupantes en la actualidad, y señala que se requieren de acciones novedosas para controlar su expansión y, de esta manera, alcanzar una de las metas establecidas en los Objetivos de Desarrollo Sostenible: reducir para 2030 la morbilidad e incidencia de TB. Para lograr este objetivo, está claro que las herramientas empleadas actualmente para su diagnóstico y tratamiento ya no son las adecuadas. En este sentido, es necesario desarrollar nuevos medicamentos y vacunas, así como novedosos procedimientos de administración de fármacos que generen una mejor respuesta, disminuyan el tiempo y optimicen los tratamientos. La nanotecnología ha incorporado en los últimos años un gran número de nuevas herramientas que incrementan considerablemente, la diversidad de mecanismos para la administración de tratamientos antituberculosos. Dicho esto, la presente revisión describe brevemente el estado actual de la farmacorresistencia en TB, así como las características generales de las nanopartículas que están evaluándose como herramientas para transportar antibióticos antituberculosos.

ABSTRACT The World Health Organization (WHO) places Tuberculosis (TB) as one of the most important health problems today. According to the WHO, this disease requires novel actions to control its expansion and, in this way, achieve one of the goals established in the sustainable development goals: to reduce TB morbidity and incidence by 2030 and regain control. To achieve this goal, the tools currently used for diagnosis and treatment are no longer adequate. In this sense, it is necessary to develop new drugs and vaccines, as well as novel drug administration procedures that generate a better response, reduce times, and optimize treatments. Nanotechnology has incorporated in recent years a considerable number of new tools that significantly increase the diversity of mechanisms for the administration of anti-tuberculosis drugs. Therefore, the present review briefly describes the current state of drug resistance in tuberculosis, as well as the general characteristics of nanoparticles being evaluated as tools to transport new antibiotics against tuberculosis.

Barreras y factores asociados al uso de mecanismos de coordinación entre niveles de atención en México / Barriers and factors associated with the use of coordination mechanisms between levels of care in Mexico / Entraves e fatores associados ao uso de mecanismos de coordenação entre níveis de atenção no México

Resumen: El objetivo fue analizar el nivel y caracterizar el uso de mecanismos de coordinación clínica entre niveles de atención, y sus factores asociados, en dos redes públicas de servicios de salud en México. Se realizó estudio transversal mediante el cuestionario COORDENA a médicos de atención primaria y especializada del estado de Veracruz. Se encontraron diferencias entre redes y niveles de atención, según el mecanismo. En ambas, la referencia/contrarreferencia es sobre todo utilizada para canalizar al paciente a otro nivel, principalmente por parte de los médicos de atención primaria. Se identificó una alta recepción de referencias por especialistas, pero escasa recepción de contrarreferencias en atención primaria. Ser hombre y reconocer al médico/a de atención primaria como responsable del seguimiento del paciente en su trayectoria asistencial, fueron factores asociados al envío frecuente de la contrarreferencia por especialistas. El informe de alta se utiliza en ambas redes para enviar información clínica al otro nivel, con mayor envío por médicos/as especialistas, y con menor recepción en atención primaria. En ambas redes, el seguimiento a las recomendaciones de los mecanismos para estandarizar la atención clínica (guías de práctica clínica, etc.) por parte médicos/as de atención primaria que de especializada. La utilización de mecanismos de coordinación entre niveles de atención es deficiente y limitada, con mayor uso de mecanismos para transferir información que para la gestión clínica. Se evidencia la necesidad de implementar estrategias que consideren la participación de los profesionales, para favorecer la adaptación local, apropiación y mejorar su uso.

Abstract: The aim was to analyze the level and characterize the use of clinical coordination mechanisms between levels of care, and their associated factors, in two public networks of health services in Mexico. A cross-sectional study was carried out using the COORDENA questionnaire to primary and specialized care physicians in the state of Veracruz. Differences were found between networks and levels of care, according to the mechanism. In both, the referral/counter-referral is mostly used to channel the patient to another level, mainly by primary care physicians. A high reception of referrals by specialists was identified, but few counterreferences in primary care. Being a man and recognizing the primary care physician, as responsible for monitoring the patient in his/her healthcare career, were factors associated with the frequent sending of the counter-referral by specialists. The discharge report is used in both networks to send clinical information to the other level, with more sending by specialist doctors, but with less reception in primary care. In both networks, the follow-up to the recommendations of the mechanisms to standardize clinical care was greater by primary care physicians than specialized ones. The use of coordination mechanisms between levels of care is deficient and limited, with greater use of mechanisms to transfer information than for clinical management. The need to implement strategies that consider the participation of professionals is evident, to favor local adaptation, appropriation and improve their use.

Resumo: O objetivo era analisar o nível e caracterizar o uso de mecanismos de coordenação clínica entre níveis de atenção e seus fatores associados em duas redes públicas de saúde no México. Estudo transversal por meio do questionário COORDENA aplicados a médicos da atenção primaria e especializada do Estado de Veracruz. Foram encontradas diferenças entre redes e níveis de atenção conforme o mecanismo. Em ambas, a referência/contrarreferência é sobre tudo utilizada para encaminhar o paciente para outro nível, principalmente por parte dos médicos da atenção primária. Foi identificado um alto recebimento de referências por especialistas, porém raras são as contrarreferências na atenção primária. Ser homem e reconhecer o médico/a de atenção primária como responsável pelo acompanhamento do paciente na sua trajetória de atendimento foram fatores associados ao envio frequente da contrarreferência por especialistas. O relatório de alta é utilizado nas duas redes para enviar informação clínica ao outro nível, com mais envios por médicos/as especialistas e menos recebimentos na atenção primária. Em ambas as redes, a observância das recomendações de mecanismos para padronizar a atenção clínica foi maior por parte dos médicos/as da atenção primária do que da especializada. O uso de mecanismos de coordenação entre níveis de atenção é deficiente e limitado, com o emprego maior de mecanismos para transmitir informação do que para a gestão clínica. Ficou evidenciada a necessidade de implementar estratégias que levem em conta a participação dos profissionais, para promover a adequação local, a apropriação e melhorar a sua utilização.