Correction: Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India.

[This corrects the article DOI: 10.1371/journal.pone.0263759.].

Concomitant bedaquiline and delamanid therapy in patients with drug-resistant extra-pulmonary tuberculosis in Mumbai, India.

Background: World Health Organization suggests concurrent bedaquiline-delamanid (BDQ-DLM) as part of individualised regimens for eligible patients with pulmonary drug-resistant tuberculosis (DR-TB); however, data for patients with drug-resistant extrapulmonary tuberculosis (EPTB) is extremely limited. This study documents the treatment outcomes and adverse events associated with concurrent BDQ-DLM-based regimens in patients with drug-resistant EPTB at a Médecins Sans Frontières clinic in Mumbai, India. Methods: Retrospective cohort study based on routinely collected programmatic data. Individualised regimens were based on drug-susceptibility testing and previous drug exposure. Drug-resistant EPTB patients initiated on regimens containing concurrent BDQ and DLM from April 2016 to October 2019 were included. Patients who completed treatment were followed up at 12 months. Results: Of 17 patients, median age was 23 years (IQR = 21-30 years) and 12/17 (71 %) were female. Pre-extensively drug-resistant tuberculosis and extensively drug-resistant TB was reported in 13/17 (76.4 %) and 2/17 (11.7 %) patients respectively. Microbiological reports were unavailable for two patients with central nervous system TB. Lymph node TB was the commonest form of EPTB in 9/17 (53 %) of patients. Median duration of treatment was 18.9 months. At least one grade three or four severe adverse event (SAE) was reported by 13/17 (76.4 %) patients. Thirteen (76.4 %) patients had favourable outcomes. None of the patients relapsed or died in the one-year period of post-treatment follow-up. Conclusion: Concurrent BDQ-DLM-based regimens in drug-resistant EPTB were effective and associated with manageable adverse events.

Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India.

BACKGROUND: People with drug-resistant tuberculosis (DR-TB) are known to suffer from many mental-health disorders. This study aims to describe the proportion of patients diagnosed with psychiatric comorbidities, the different psychiatric diagnoses made, and treatment outcomes among DR-TB patients with or without psychiatric comorbidity and initiated on DR-TB treatment between January 2012 and March 2019 at Médecins Sans Frontières independent clinic in Mumbai, India. METHODS: This is a retrospective study using routinely collected clinical data. DR-TB care included individualised treatment, psychosocial support, and integrated psychiatric care. RESULTS: During the study period, 341 DR-TB patients were enrolled, with a median age of 25 years (IQR:20.0-36.5 years), 185 (54.2%) females, 143 (41.9%) with PreXDR-TB, and 140 (41.0%) with XDR-TB. All 341 patients were screened by a counsellor, 119 (34.9%) were referred for psychiatric evaluation, and 102 (29.9% of 341) were diagnosed with a psychiatric comorbidity. Among 102 diagnosed with a psychiatric comorbidity, 48 (47.0%) were diagnosed at baseline, and 86 (84.3%), or 25.2% of all 341 patients enrolled, were treated with psychotropic drugs. Depressive disorders were diagnosed in 49 (48.0%), mixed anxiety and depression in 24 (23.5%), neurocognitive disorders and anxiety in five (4.9%), and medication induced psychosis in two (2.0%). No anti-TB drugs were significantly associated with psychiatric comorbidities developed during treatment. Of 102 DR-TB patients with a psychiatric comorbidity, 75.5% (77) had successful DR-TB treatment outcomes, compared to 61.1% (146/239) not diagnosed with a psychiatric comorbidity (p = 0.014). CONCLUSION: In our setting, among people started on DR-TB treatment, and with a complex TB resistance profile, about one in three patients experienced a psychiatric comorbidity, of which half developed this comorbidity during treatment. With comprehensive psychiatric care integrated into DR-TB care delivery, treatment outcomes were at least as good among those with psychiatric comorbidities compared to those without such comorbidities.

Tobacco and end stage renal disease: a multicenter, cross-sectional study in Argentinian Northern Patagonia.

BACKGROUND: Smoking and chronic kidney disease are major public health problems with common features -high prevalence and mortality, high cardiovascular risk, gender differences and high prevalence in low income people-, but the link between them is poorly recognized. Our objectives were to investigate the exposure of dialysis patients to tobacco and to know their smoking behavior. METHODS: We performed a multicenter, cross-sectional study in nine dialysis units in the Argentinian Northern Patagonia. We investigated smoker status, lifetime tobacco consumption, current tobacco use, breath carbon monoxide and % carboxyhaemoglobin. Fagerström and Richmond tests were performed for active smokers. STATISTICAL ANALYSIS: one way ANOVA and Tukey's test for post hoc test. For exploratory analysis, frequency tables through chi-square distribution and single correspondence analysis were performed. RESULTS: Six hundred thirty six patients (60.9 % males, 39.1 % females) were interviewed. Almost 70 % of them had had tobacco exposure. Excluding light smokers, the lifetime consumption was significantly different (p = 0.0052) between sexes (33.1 ± 2.4 pack/years in males and 18.2 ± 2.1 pack/years in females) The distribution of etiologies changed significantly (χ (2) p < 0.0001) with smoker status and the dose of tobacco smoking, with an increase in the diagnosis of nephrosclerosis in patients with high and very high lifetime consumption (from 16.1 % in non-smokers to 28.2 and 27 % respectively), and in passive smokers (from 16.1 to 27.3 %). The male preponderance of end-stage renal disease disappeared when only non-smokers were considered and grew with the increase in the lifetime consumption. Active smokers have small consumption, both low CO level and % COHb, low dependence and a good motivation to quit, but a high lifetime consumption. CONCLUSIONS: Exposure of dialysis patients to tobacco is high and could be related to the progression to the final stage of the renal disease. It seems that tobacco renal damage is mostly hidden in the diagnosis of nephrosclerosis. The gender difference observed in these patients could also have a nexus with the men's higher tobacco exposure. Active smokers have a low current consumption but a high lifetime tobacco dose.

INTRODUCCIÓN: Tabaquismo y enfermedad renal crónica son importantes problemas de salud pública que comparten: alta prevalencia, alta morbi-mortalidad, alto riesgo cardiovascular, diferencias de género y mayor prevalencia en personas de bajos ingresos. Sin embargo, el nexo entre ellas es poco reconocido. Objetivos: mensurar la carga tabáquica de los enfermos en diálisis y conocer su patrón de consumo. MATERIAL Y MÉTODOS: Participaron nueve unidades de diálisis de la Norpatagonia Argentina. Investigamos condición de fumador, carga tabáquica y, en fumadores activos, consumo actual, tests de Richmond y Fagerström, monóxido de carbono en aire espirado y % de carboxihemoglobina. Análisis estadístico: ANOVA de una vía y test de Tukey para análisis post hoc. En el análisis exploratorio, utilizamos tablas de frecuencias a través de la distribución Ji cuadrado y análisis de correspondencia simple. RESULTADOS: Seiscientos treinta y seis pacientes (60.9 % varones, 39.1 % mujeres) fueron encuestados. Casi un 70 % de ellos había estado expuesto al tabaco. Excluyendo los fumadores leves, la carga tabáquica (CT) fue 33 ± 2.4 paquetes/año en hombres y 18.2 ± 2.1 paquetes/año en mujeres (p = 0.0052). La distribución de las etiologías de ingreso a diálisis cambió significativamente (χ2p < 0.0001) según el estado de fumador y la CT, con aumento en el diagnóstico de nefroesclerosis en fumadores pasivos (de 16.1 % en no fumadores a 27.3 %) y en pacientes con elevadas CT (de 15.2 y 16 % en CT leve y media a 28.2 y 27 % en CT alta y muy alta). La preponderancia masculina de la población desapareció en no fumadores y creció con el incremento en la CT (χ2p < 0.0001). Los fumadores activos tienen bajo consumo, bajo nivel de CO y carboxihemoglobina, baja dependencia y están bien motivados para dejar, pero tienen una elevada CT. CONCLUSIONES: La alta CT de los enfermos en diálisis podría generar o contribuir a la progresión de la enfermedad renal crónica. El daño renal por tabaco se esconde principalmente en el diagnóstico de nefroesclerosis y se relaciona con la CT. La diferencia de género de estos pacientes podría relacionarse con su exposición al tabaco. Los fumadores activos tienen bajo consumo pero elevada CT.

Aspectos metabólicos y complicaciones de la hiperuricemia / Metabolic aspects and complications of hyperuricemia

El resultado de observaciones epidemiológicas inicia en la actualidad una reevaluación del ácido úrico en diferentes enfermedades metabólicas, enfermedad cardiovascular y renal. El rol de la hiperuricemia como factor de riesgo cardiovascular independiente es difícil de evaluar aún en análisis de modelos multivariados, dado que existen resultados inconclusos e inconsistentes en la mayoría de los estudios. Esta dificultad se observa por la fuerte asociación del ácido úrico con otros factores clásicos de riesgo cardiovascular que no permiten diferenciar el riesgo. Durante muchos años se lo consideró una sustancia biológicamente inerte, pero posteriormente se encontró que tiene muchas propiedades biológicas que podrían ser beneficiosas o perjudiciales para los seres humanos. Existen en la actualidad una controversia sobre si su rol es protector por tener propiedades anti-oxidante o lesivo por sus propiedades pro-oxidantes en la placa arterioesclerótica y en tejido adiposo lo que podría determinar que no solo se trate de un marcador de riesgo, sino que conforme un factor causal en las enfermedades metabólicas como la diabetes mellitus, el síndrome metabólico, las enfermedades cardiovasculares y/o renales. En esta revisión hemos actualizado estos conceptos de manera de intentar esclarecer dicho rol, para en un futuro se pueda instituir normas, que actualmente no están establecidas, para decidir si se debe tratar la hiperuricemia, en qué casos, con que niveles de corte y cuáles serían sus objetivos terapéuticos en cada circunstancia.

The results of epidemiological observations have led to a revaluation of uric acid role in different metabolic, cardiovascular and renal illnesses. The role of hyperuricemia as an independent cardiovascular risk factor is difficult to evaluate even in multivariate models analysis, since there are inconclusive and weak results in most studies. This difficulty is observed due to the strong association of uric acid with other classic cardiovascular risk factors which do not allow its distinction as an independently risk factor. For many years it was considered a biologically inert substance, but later, it was found that it has many biological properties which could be beneficial or harmful for human beings. Nowadays there is a controversial discussion about its role, whether it is protective for having anti-oxidant properties or harmful due to its pro-oxidants in the atherosclerotic plaque and in adipose tissue which could determine that it is not only a risk marker, but also a causal factor for metabolic illnesses as diabetes mellitus, metabolic syndrome, cardiovascular and/or renal illnesses. In this consensus we have updated these concepts trying to clarify the mentioned role, so that in the future, regulations could be introduced, which are not established so far, in order to decide whether hyperuricemia must be treated, in which cases, which cut-off levels must be used and which should be the therapeutic objectives in each circumstance.