Impact of mental disorders on active TB treatment outcomes: a systematic review and meta-analysis.

BACKGROUND: Comorbid mental disorders in patients with TB may exacerbate TB treatment outcomes. We systematically reviewed current evidence on the association between mental disorders and TB outcomes.METHODS: We searched eight databases for studies published from 1990 to 2018 that compared TB treatment outcomes among patients with and without mental disorders. We excluded studies that did not systematically assess mental disorders and studies limited to substance use. We extracted study and patient characteristics and effect measures and performed a meta-analysis using random-effects models to calculate summary odds ratios (ORs) with 95% confidence intervals (CIs).RESULTS: Of 7687 studies identified, 10 were included in the systematic review and nine in the meta-analysis. Measurement of mental disorders and TB outcomes were heterogeneous across studies. The pooled association between mental disorders and any poor outcome, loss to follow-up, and non-adherence were OR 2.13 (95%CI 0.85-5.37), 1.90 (95%CI 0.33-10.91), and 1.60 (95%CI 0.81-3.02), respectively. High statistical heterogeneity was present.CONCLUSION: Our review suggests that mental disorders in TB patients increase the risk of poor TB outcomes, but pooled estimates were imprecise due to small number of eligible studies. Integration of psychological and TB services might improve TB outcomes and progress towards TB elimination.

Is effective patient support missing in the global response to multidrug-resistant tuberculosis?

Multidrug-resistant tuberculosis (MDR-TB) is a threat to the achievement of the global targets to the World Health Organization (WHO) End TB by 2030 Strategy. The WHO consolidated guidelines for the treatment of drug-resistant TB emphasise the importance of addressing health systems issues, including supporting patients during treatment, contributing to improved adherence, reduced catastrophic costs and better treatment outcomes. The recently published results of the STREAM (Standardised Treatment Regimen of Anti-TB Drugs for Patients with MDR-TB) clinical trial and the Delamanid 213 Trial suggest that the implementation of a proper patient-centred approach to the clinical and programmatic management of MDR-TB as per the WHO guidelines is key to improving treatment outcomes in MDR-TB patients.

An assessment of current tuberculosis patient care and support policies in high-burden countries.

CONTEXT: Adherence to treatment for tuberculosis (TB) is an important predictor of treatment outcomes. The World Health Organization guidelines recommend a patient-centred approach to adherence support; however, the extent to which policies in high-burden countries facilitate this approach remains uncertain.DESIGN: A cross-sectional survey of current national patient care and support policies in high TB burden countries was performed.RESULT: Responses were provided by TB care programmes in 23 of the 30 high TB burden countries, comprising 77.4% of TB cases globally. Clinic-based and household adherence support and patient education were recommended in all countries, while policies for digital technologies and social supports have been adopted in a small minority of countries. Financial or material support (such as reimbursement for transportation) and psychological support to patients-if included in the policies-was mainly recommended only for specific sub-groups of patients.CONCLUSION: National policies in many countries have not yet fully adopted global recommendations for patient care and support. Further scale-up of evidence-based approaches to care is required to improve quality of care for patients in high TB burden settings.

Palliative care and symptom relief for people affected by multidrug-resistant tuberculosis.

The World Health Organization (WHO) defines palliative care as the prevention and relief of the physical, psychological, social and spiritual suffering of adults and children with life-threatening illnesses and psycho-social support for their families. Palliative care and symptom relief (PCSR) also addresses suffering in nonlife-threatening situations such as after cure. PCSR should never be considered a substitute for tuberculosis (TB) prevention and treatment, but should be accessible by everyone in need. PCSR can reduce suffering and improve quality of life of patients with end-stage chronic illnesses while reducing costs for health care systems and providing financial risk protection for patients' families. It also may help enable patients to adhere to long and noxious treatments and thereby reduce mortality and help protect public health. Basic PCSR can be taught easily to TB specialists as well as primary care clinicians and delivered in hospitals, clinics or patients' homes combined with infection control. For these reasons, integration of PCSR into multidrug-resistant (MDR) and extensively drug-resistant TB (XDR-TB) treatment programs is medically and morally imperative. We propose an essential package of PCSR for people with M/XDR-TB that includes a set of safe, effective and inexpensive medicines and equipment, social supports for patients and caregivers living in extreme poverty, and necessary human resources. The package aligns with WHO guidance on programmatic management of drug-resistant (DR) TB and should be universally accessible by people affected by M/XDR-TB. We also describe the ethical practice of PCSR for people with M/XDR-TB and identify needed areas of research in PCSR for people with M/XDR-TB.

Grain grinding size of cereals in complete pelleted diets for growing lambs: Effects on animal performance, carcass and meat quality traits.

The main goal of the present study was to clarify the effects of different grinding particle size of grains (2-mm vs. 6-mm) included in complete pelleted diets (CPD) for fattening lambs on animal performance, carcass and meat quality. Twenty male merino lambs (14.8 kg; n = 10 per group) were fed the corresponding diet ad libitum and slaughtered when they reached 27 kg. No differences were observed in the feed conversion ratio or carcass characteristics. However, lambs fed coarser diets (6 mm) were more efficient with less residual feed intake (-14.0 vs. 15.4 g DM/animal/d; P < .05) than lambs fed the 2 mm CPD. Lambs fed the 6-mm CPD showed higher levels of intramuscular fat and saturated fatty acids. Consequently, increasing the particle size of the grains included in CPD allows for improving feed efficiency and intramuscular fat in fattening lambs.

Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells / Síntesis y evaluación citotoxica de derivados halogenados y peracetylados de nucleósidos en celulas de cancer de mama

Objectives. To make the synthesis of halogenated derivatives on the nitrogenous base and their respective acyl ester and amide type derivatives for all hydroxyl and amine groups of the uridine and cytarabine nucleosides, and evaluate cytotoxicity against breast cancer cell line. Methods. First, it was accomplished the halogenation reaction on the 5-position of the nitrogenous base, subsequently, the ester and amide derivatives were performed for all hydroxyl and amine group present in the nucleosides. Besides, the uridine acetonide derivatives as prepared by acid catalysis. The products were characterized by nuclear magnetic resonance spectroscopy (1H RMN y 13C RMN) and mass spectrometry in positive mode by direct injection. Derivatives were evaluated in Chinese hamster ovary (CHO-K1) and human breast cancer (MCF-7) cell lines. Results. The four derivatives were obtained with chlorine and bromine for the uridine and cytarabine, respectively, their respective per-acetylated derivatives, the per-acetylated nucleoside and the uridine. acetonide; the compounds were obtained with efficiency over 90%. The per-acetylated nucleosides and the halogenated and per-acetylated derivatives did not show inhibitory effects on cell viability in MCF-7 cell line. However, the per-acetylated and halogenated derivatives presented a higher cytotoxic activity than their respective per-acetylated nucleoside. The uridine 3',4'-acetonide showed a significant cytotoxicity on both cell lines. Conclusions. The per-acetylated nucleoside, and the respective halogenated derivatives with chlorine and bromine were obtained with high yields, nevertheless, these compounds did not exhibit a significant anti-proliferative activity (p˂0.05), possibly due to a low intra-cellular activation

Objetivos: Sintetizar derivados halogenados sobre la base nitrogenada, sus respectivos derivados tipo éster o amida de todos los grupos hidroxilo y amina presentes en los nucleósidos uridina y citarabina, y evaluar su actividad citotóxica sobre una línea celular de cáncer de mama. Metodología: primero se realizó la reacción de halogenación en la posición 5 de la base nitrogenada, posteriormente se formaron los ésteres y amidas de todos los grupos hidroxilos y amino presentes en los nucleósidos. Además, se preparó el derivado acetónido con catálisis ácida. Los compuestos se caracterizaron por espectroscopía de resonancia magnética nuclear (RMN 1H y RMN 13C) y espectrometría de masas por inyección directa en modo positivo. Los derivados se evaluaron sobre líneas celulares de tumor de Ovario de Hámster Chino (CHO) y de cáncer de mamá (MCF-7). Resultados: Se obtuvieron 4 derivados mono-halogenados con cloro y bromo de la uridina y citarabina, respectivamente, sus respectivos derivados per-acetilados, los nucleósidos per-acetilados y el acetónido de la uridina; los compuestos se obtuvieron con rendimientos superiores a 90%. Los nucleósidos per-acetilados, y los derivados per-acetilados y halogenados no exhibieron una inhibición significativa de la viabilidad celular en ambas líneas celulares, sin embargo, de estos, los derivados per-acetilados y halogenados presentaron mayor actividad citotóxica que los respectivos nucleósidos per-acetilados. El derivado acetónido de la uridina mostró citotoxicidad significativa sobre ambas líneas celulares. Conclusiones: se obtuvieron los nucleósidos per-acetilados y los respectivos derivados clorados y bromados de estos, con rendimientos altos, sin embargo, estos compuestos no exhibieron una actividad anti-proliferativa significativa (p ˂ 0,05), posiblemente debido a una baja activación intra-celular de los nucleósidos

Defining the research agenda to measure and reduce tuberculosis stigmas.

Crucial to finding and treating the 4 million tuberculosis (TB) patients currently missed by national TB programmes, TB stigma is receiving well-deserved and long-delayed attention at the global level. However, the ability to measure and evaluate the success of TB stigma-reduction efforts is limited by the need for additional tools. At a 2016 TB stigma-measurement meeting held in The Hague, The Netherlands, stigma experts discussed and proposed a research agenda around four themes: 1) drivers: what are the main drivers and domains of TB stigma(s)?; 2) consequences: how consequential are TB stigmas and how are negative impacts most felt?; 3) burden: what is the global prevalence and distribution of TB stigma(s) and what explains any variation? 4): intervention: what can be done to reduce the extent and impact of TB stigma(s)? Each theme was further subdivided into research topics to be addressed to move the agenda forward. These include greater clarity on what causes TB stigmas to emerge and thrive, the difficulty of measuring the complexity of stigma, and the improbability of a universal stigma 'cure'. Nevertheless, these challenges should not hinder investments in the measurement and reduction of TB stigma. We believe it is time to focus on how, and not whether, the global community should measure and reduce TB stigma.

Prácticas familiares en el cuidado de los menores de la zona rural de Sopetrán, Antioquia / Family practices in the care of children from the rural areas of Sopetrán, Antioquia / Práticas familiares no cuidado dos menores da zona rural de Sopetrán, Antioquia

Objetivo: determinar la aplicación de prácticas familiares clave de la estrategia de atención integral a las enfermedades prevalentes en la infancia, por parte de los padres de niños inscritos en hogares del Instituto Colombiano de Bienestar Familiar, en la zona rural del municipio de Sopetrán, Antioquia, en 2014. Metodología: estudio descriptivo, transversal. La fuente primaria fue el universo de padres o cuidadores. Resultados: participaron 79 padres o cuidadores de nueve Hogares comunitarios de ocho veredas del municipio. En promedio, las madres tenían 28 años y los padres 32. El 74.7% de las familias fue de estrato socioeconómico nivel uno; la frecuencia de familias de tipo nuclear fue del 48%. Las verduras, los vegetales, los lácteos, las calabazas y las zanahorias fueron los alimentos menos consumidos por los menores. El 54.4% de las familias obtiene el agua de nacimiento y el 21.5% no le realiza tratamiento antes de consumirla. El 5.1% deposita excretas a campo abierto. El 15.2% y el 35.4% desconocen los signos de peligro que ponen en riesgo la vida del menor por infección respiratoria y por enfermedad diarreica aguda, respectivamente. En el 89.9% de los casos las madres se encargan del cuidado de los menores, con poca o nula participación del padre. Conclusión: los padres desconocen las prácticas clave relacionadas con la identificación temprana de signos de alarma de enfermedades prevalentes en la infancia. Además, el derecho al agua potable y saneamiento básico no es una realidad para todas las familias participantes. Adicionalmente, muchas no hierven el agua para consumirla, lo que podría incrementar algunas enfermedades prevalentes.

Objective: To determine to what extent the parents of children participating in the Colombian Institute for Family Wellbeing community homes implemented key family practices as a part of integrated management of childhood illness in the rural areas of Sopetrán, Antioquia in 2014. Methodology: cross-sectional descriptive study. The main source was the universe of parents or caregivers. Results: Seventy-nine parents or caregivers participated from nine community wellbeing homes in eight rural communities. The average age of mothers and fathers was 28 and 32, respectively. Of all families, 74.7% belonged to the lowest socioeconomic strata, and 48% of families were nuclear families. Vegetables, dairy products, pumpkins, and carrots were the least consumed foods by children. Over half of families (54.4%) get water from springs, 21.5% do not treat the water before drinking it, and 5.1% still practice open defecation. In fact, 15.2% and 35.4% remain unaware of the warning signs of infant respiratory infection and acute diarrhea, respectively. In 89.9% of cases, mothers care for children with little or no help from fathers. Conclusion: Parents are unaware of the key practices related to the early identification of warning signs in diseases common to children. In addition, not all participating families have access to treated drinking water and basic sanitary conditions. Lastly, many families do not boil water prior to drinking it, which could increase the prevalence of certain diseases.

Objetivo: determinar a aplicação de práticas familiares chave da estratégia de atenção integral às doenças prevalentes na infância, por parte dos pais de crianças inscritas nos lares do Instituto Colombiano de Bienestar Familiar, na zona rural do município de Sopetrán, Antioquia, em 2014. Metodologia: estudo descritivo, transversal. A fonte primária foi o universo de pais ou cuidadores. Resultados: participaram 79 pais ou cuidadores de nove Lares comunitários de oito bairros rurais do município. Em média, as mães tinham 28 anos e os pais 32. 74.7% das famílias foi de estrato socioeconômico nível um; a frequência de famílias de tipo nuclear foi de 48%. As verduras, os vegetais, os lácteos, as abóbora e as cenouras foram os alimentos menos consumidos pelos menores. 54.4% das famílias obtém a água de nascimento e 21.5% não se realiza tratamento antes de consumir. 5.1% deposita resíduos a campo aberto. 15.2% e o 35.4% desconhecem os signos de perigo que colocam em risco a vida do menor por infecção respiratória e por doença diarreica aguda, respectivamente. Em 89.9% dos casos as mães se encarregam do cuidado dos menores, com pouca ou nula participação do pai. Conclusão: os padres desconhecem as práticas chave relacionadas com a identificação precoce de signos de alarme de doenças prevalentes na infância. Ademais, o direito à água potável e saneamento básico não é uma realidade para todas as famílias participantes. Adicionalmente, muitas não fervem a água para consumir, o que poderia aumentar algumas doenças prevalentes.

Development of Lactococcus lactis encoding fluorescent proteins, GFP, mCherry and iRFP regulated by the nisin-controlled gene expression system.

Fluorescent proteins are useful reporter molecules for a variety of biological systems. We present an alternative strategy for cloning reporter genes that are regulated by the nisin-controlled gene expression (NICE) system. Lactoccocus lactis was genetically engineered to express green fluorescent protein (GFP), mCherry or near-infrared fluorescent protein (iRFP). The reporter gene sequences were optimized to be expressed by L. lactis using inducible promoter pNis within the pNZ8048 vector. Expression of constructions that carry mCherry or GFP was observed by fluorescence microscopy 2 h after induction with nisin. Expression of iRFP was evaluated at 700 nm using an infrared scanner; cultures induced for 6 h showed greater iRFP expression than non-induced cultures or those expressing GFP. We demonstrated that L. lactis can express efficiently GFP, mCherry and iRFP fluorescent proteins using an inducible expression system. These strains will be useful for live cell imaging studies in vitro or for imaging studies in vivo in the case of iRFP.

Concepciones de salud mental en el campo de la salud pública / Conceptions about mental health in the field of public health

Aun cuando existe un reconocimiento de la importancia de la salud mental en el campo de la salud pública y de la amplia utilización de este concepto en los ámbitos profesionales, académicos y políticos, no obstante enfrenta importantes dificultades epistemológicas y prácticas para precisar qué se entiende por lo “mental”, cómo se relacionan “la salud” y “lo mental” y, en consecuencia, cómo se investiga e interviene en el ámbito de la salud mental, puesto que, en la práctica, la orientación de las acciones y de las investigaciones no obedecen a definiciones “universales”, sino a concepciones construidas a partir de los diferentes enfoques de salud-enfermedad. En el presente trabajo se discuten las concepciones de salud mental que se configuran a partir de los enfoques biomédico, comportamental y socioeconómico, así como de las nociones de “lo mental” en las cuales se soportan dichas concepciones y sus implicaciones para la intervención en el campo de la salud pública.

In the field of public health, mental health has had a great deal of relevance. This concept has been used extensively in the professional, academic, and political fields. Despite that, the different definitions of mental health face significant epistemological and practical problems. These difficulties are encountered by those who try to specify the meaning of "mental", the relationship between "health" and "mental", and, consequently, how research and intervention actions are to be carried out in the field of mental health. In practice, the orientation of actions and research involving mental health is not based on “universal” definitions in the field of public health. It is rather based on conceptions constructed from different approaches to the health-disease issue. This paper discusses the conceptions of mental health that have been configured from the biomedical, behavioral, and socio-economic approaches, the notions of "mind" underlying these conceptions, and their implications for intervention in the field of public health.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

The social determinants of health: key to global tuberculosis control.

Improved tuberculosis (TB) diagnosis and treatment through the DOTS and Stop TB strategies have saved millions of lives; however, their impact on TB incidence has been disappointing and the scale of the epidemic remains overwhelming. To reduce the incidence of TB, the drivers of the epidemic and social determinants of TB need to be addressed. These include co-morbidities and substance use and, moreover, the social and economic conditions that determine both the course of the TB epidemic and exposure to these risk factors. Doing so builds on the history of TB prevention and treatment during the public health revolution that resulted in a dramatic reduction in incidence in many countries. Addressing the social determinants is also imperative to address pervasive inequities in the incidence, mortality and morbidity of TB between different population groups, including in the performance of health systems in delivering diagnostic and treatment interventions, and in the financial consequences of people seeking care. Action on the social determinants can be categorised in terms of health-sector interventions, intersectoral policies impacting across society, and measurement and research to better understand inequities and links between TB and other factors. TB programmes cannot carry out these actions alone; however, they can make important contributions in the delivery of interventions and in advocating and negotiating for intersectoral efforts. The considerable progress seen in the clinical care of TB needs to be sustained; however, the attainment of TB targets, including elimination by 2050, will require expansion of the lens of TB control efforts beyond 'business as usual' to address the social determinants of the disease.

Cash transfer and microfinance interventions for tuberculosis control: review of the impact evidence and policy implications.

OBJECTIVE: To quantify the impact of cash transfer and microfinance interventions on a selected list of tuberculosis (TB) risk factors and assess their potential role in supporting TB control. DATA SOURCE: Published and unpublished references identified from clinical and social electronic databases, grey literature and web sites. METHODS: Eligible interventions had to be conducted in middle- or low-income countries and document an impact evaluation on any of the following outcomes: 1) TB or other respiratory infections; 2) household socio-economic position; and 3) factors mediating the association between low household socio-economic position and TB, including inadequate health-seeking behaviours, food insecurity and biological TB risk factors such as human immunodeficiency virus (HIV) and adult malnutrition. Interventions targeting special populations were excluded. RESULTS: Fifteen cash transfer schemes (four unconditional and 11 conditional) and seven microfinance programmes met the eligibility criteria. No intervention addressed TB or any other respiratory infection. Of 11 cash transfer and four microfinance interventions, respectively seven and four reported a positive impact on indicators of economic well-being. A positive impact on household food security was documented in respectively eight of nine and three of five cash transfer and microfinance interventions. Improved health care access was documented respectively in 10 of 12 cash transfer and four of five microfinance interventions. The only intervention evaluating impact on HIV incidence was a microfinance project that found no effect. No cash transfer or microfinance interventions had an impact on adult malnutrition. CONCLUSIONS: Cash transfer and microfinance interventions can positively impact TB risk factors. Evaluation studies are urgently needed to assess the impact of these social protection interventions on actual TB indicators.

Bacteriologic monitoring of multidrug-resistant tuberculosis patients in five DOTS-Plus pilot projects.

BACKGROUND: Multidrug-resistant tuberculosis programs in DOTS-Plus pilot sites in five countries. OBJECTIVES: To calculate sputum conversion time and its relationship to treatment outcome, document the frequency of culture reversions and examine concordance of smear and culture to assess the potential consequences of monitoring by smear microscopy alone. DESIGN: Retrospective cohort analysis of 1926 patients receiving individualized, second-line therapy. RESULTS: Among 1385 sputum culture-positive cases at baseline, 1146 (83%) experienced at least one culture conversion during treatment. Conversion, however, was not sustained in all patients: 201 (15%) experienced initial culture conversion and at least one subsequent culture reversion to positive; 1064 (77%) achieved sustained culture conversion. Median time to culture conversion was 3 months. Among 206 patients whose nal conversion occurred 7-18 months after the initiation of therapy, 71% were cured or had completed treatment. CONCLUSIONS: Prolonged treatment for patients with delayed conversion may be beneficial, as 71% of late converters still achieved cure or completed treatment. This has implications for programs with de ned end points for treatment failure. The interval between rst and nal conversion among patients whose initial con- version is not sustained raises concern with respect to the ongoing debate regarding duration of treatment and the definition of cure.

La metáfora de no-lugar / The noplace metaaphor

El propósito del escrito consiste en explorar la metáfora levinasiana del no-lugar, precisar sus sentidos y evaluar críticamente su pertinencia en el ámbito de las reflexiones contemporáneas. Para ello, contextualizaremos la propuesta levinasiana en torno al no-lugar, especialmente bajo los conceptos de sensibilidad, proximidad e infinito; reconstruiremos algunas de las críticas de Levinas a lo que denominamos: "filosofías del regreso a casa"; y, finalmente, sugeriremos algunos aspectos en los cuales las tesis del filósofo judío podrían hacerse pertinentes. Este último propósito lo acompañaremos con una investigación social adelantada al respecto.

The purpose of this writing is to explore the Levinasian no-place metaphor, in order to clarify its meanings as well as to critically evaluate its pertinence under the light of contemporary reflections. In order to do this, we will contextualize the Levinasian proposal around the no-place, especially under the concepts of sensitivity, proximity, and infinite; we will reconstruct some Levinas's critiques which we will call "philosophies of the coming back home", and finally we will suggest some aspects in which the Jew philosopher theses might be pertinent. This last purpose will be accompanied by a social research carried out about this issue.