Recurrence of tuberculosis in a low-incidence setting: a retrospective cross-sectional study augmented by whole genome sequencing.

BACKGROUND: The recurrence of tuberculosis (TB) disease in treated patients can serve as a marker of the efficacy of TB control programs. Recurrent disease represents either endogenous reactivation with the same strain of Mycobacterium tuberculosis due to non-compliance or inadequate therapy or exogenous reinfection with a new strain. Genotyping or whole genome sequencing (WGS) of M. tuberculosis isolates from initial and recurrent cases can differentiate between reinfection and reactivation. This study examined cases of recurrent TB in New South Wales, Australia, using genotyping and WGS. METHODS: Culture-confirmed TB cases diagnosed at least 12 months apart between January 2011 and December 2016 were included. Isolates of M. tuberculosis from patients were compared using 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-24) typing and WGS. RESULTS: Eighteen cases of recurrent disease were identified but isolates from only 15 (83%) were available for study. MIRU-24 findings classified 13 (13/15; 87%) as reactivation and two (13%), as reinfection. Sequencing 13 cultivable paired isolates demonstrated 11 reactivations and two reinfections. There was genomic similarity in 10 out of 13 pairs while one case (1/13; 8%) had 12 SNPS differences. Two other cases (2/13;15%) had > 200 SNPs differences and were classified as reinfection. No phenotypic or genomic evidence of drug resistance was observed. CONCLUSION: TB control programs can achieve consistently low rates of recurrent disease in low incidence settings. WGS of implicated isolates augments the differentiation between reactivation and reinfection and indicates that the majority of recurrences are due to reactivation rather than reinfection. Predominance of reactivation over reinfection indicates high-quality public health practices and a low risk of local transmission. TRIAL REGISTRATION: This study was approved by the Western Sydney Local Health District (WSLHD) Human Research Ethics Committee (HREC Ref: AU RED LNR/17/WMEAD/190; SSA Ref: LNR SSA/17/WMEAD/191).

Classrooms in Peace Within Violent Contexts: Field Evaluation of Aulas en Paz in Colombia.

Classrooms in Peace (Aulas en Paz) is an elementary school-based multicomponent program for prevention of aggression and promotion of peaceful relationships. Inspired by international programs and socio-emotional research, it includes (1) a classroom universal curriculum, (2) parent workshops and home visits to parents of the 10% most aggressive children, and (3) extracurricular peer groups of two aggressive and four prosocial children. Activities seek to promote socio-emotional competencies such as empathy, anger management, creative generation of alternatives, and assertiveness. A 2-year quasi-experimental evaluation was conducted with 1154 students from 55 classrooms of seven public schools located in neighborhoods with the presence of youth gangs, drug cartels, and high levels of community violence in two Colombian cities. Despite several implementation (e.g., about half of the activities were not implemented) and evaluation (e.g., randomization problems, large number of missing data, and changes between treatment and control groups) challenges, positive results were found in prosocial behavior and in reduction of aggressive behavior, according to teacher reports, and in assertiveness and reduction of verbal victimization, according to student reports. Furthermore, implementation cost (25 US dollars per student per year) was very low compared to other programs in developed countries. This study shows that the Classrooms in Peace program has an important potential to generate positive results and highlights the challenges of implementing and evaluating prevention programs in highly violent environments.

[Mini bronchoalveolar lavage in patients with severe respiratory failure]. / Resultados preliminares y factibilidad del mini lavado bronco-alveolar en pacientes cursando falla respiratoria severa.

BACKGROUND: To recognize the etiological agent responsible for severe acute respiratory failure (ARF) in patients in mechanical ventilation (MV) is important to determine their treatment and prognosis, and to avoid the excessive use of antibiotics. Mini bronchoalveolar lavage (mini BAL) is a blind, non bronchoscopic procedure, used to obtain samples from the lower respiratory tract from patients on mechanical ventilation (MV). AIM: To assess the feasibility, complications and preliminary results of mini BAL among patients with severe ARF on MV. MATERIAL AND METHODS: Prospective study in 17 patients with acute lung injury (ALI ) or acute respiratory distress syndrome (ARDS) on MV and with negative conventional microbiological studies. Mini BAL was performed using standardized protocols. Hemodynamic and respiratory parameters where measured before and after the procedure. Samples obtained were sent to quantitative cultures. RESULTS: At baseline: APACHE II score of 22 ± 6,7, PaO2/FiO2 ratio was 176.6 ± 48.6 and the oxygenation index was 9.74 ± 3.78. All procedures were performed by an ICU resident. Thirty five percent of the procedures had positive cultures and no complications related to the procedures were reported. The procedure lasted an average of 12 minutes and the instilled and rescued volume were 60 ml and 19.6 ml, respectively. There were no significant differences between hemodynamic and respiratory variables before and after the procedure. CONCLUSIONS: Mini BAL is a safe, fast and easy technique for obtaining samples from the inferior airway in patients with ALI or ARDS on MV.

Can colony-forming unit testing be used to extend the shelf life of BCG vaccines?

A recent shortage in supply of Bacille Calmette-Guérin (BCG), the live attenuated vaccine given to protect against tuberculosis (TB) caused major disruption to global vaccination programs. In this study, we assessed whether quantification of viable bacteria, could be used to inform the use of the BCG vaccine beyond its manufacturer-assigned expiration date. The viability of a single batch of BCG-Denmark was tested in three independent laboratories. There was high inter-vial and inter-laboratory variability in viability counts, however all three laboratories detected a decrease in BCG viability over time. Despite this, there was no difference in the rate of BCG scar formation in infants who were vaccinated with this batch of BCG before and after its manufacturer-assigned expiration date. This study demonstrates the potential for using BCG viability counts to guide the use of BCG vaccine beyond the manufacturer-assigned expiration date.

Optimal length of triple therapy for H pylori eradication in a population with high prevalence of infection in Chile.

AIM: To compare the efficacy of 7-d versus 14-d triple therapy for the treatment of H pylori infection in Chile, with a prevalence of 73% in general population. METHODS: H pylori-infected patients diagnosed by rapid urease test, with non-ulcer dyspepsia or peptic ulcer disease were randomized to receive omeprazole 20 mg bid, amoxicillin 1 g bid, and clarithromycin 500 mg bid for 7 (OAC7) or 14 (OAC14) d. Primary outcome was eradication rate 6 wk after the treatment. Subgroup analysis was carried out considering the eradication rate among patients with or without peptic ulcer disease and eradication rate among smokers or non-smokers. RESULTS: One hundred and thirty-one patients were randomized to OAC7 (n = 69) or OAC14 (n = 62). The overall eradication rate (intention-to-treat) was 78.3% in OAC7 and 85.5% in OAC14 groups, without a significant difference (P =0.37). No significant difference in the eradication rate was found among the patients with peptic ulcer disease (n = 31) between the OAC7 group (85.7%) and OAC14 group (87.5%). However, smokers had an obviously lower eradication rate compared to non-smokers, particularly in the OAC7 group (57.1% in smokers vs 83.6% in non-smokers; P = 0.06). Adverse effects rate were similar between both groups. CONCLUSION: Short-term efficacy of triple therapy with OAC for 7 d is comparable to 14 d in this high-prevalence population. Longer follow-up, and studies focused to some subgroups of patients (smokers and non-ulcer patients) are necessary to support widespread use of 7-d instead of 10-14-d triple therapy in a developing country like Chile.

The boundaries of mild chronic obstructive pulmonary disease (COPD): design of the searching clinical COPD onset (SOON) study.

INTRODUCTION: Clinical onset of chronic obstructive pulmonary disease (COPD) is the point at which the disease is first identifiable by physicians. It is a poorly defined stage which seems to include both mild spirometric and non-spirometric disease, and could be described as early grade COPD, for practical purposes. While dyspnoea; chronic bronchitis and CT imaging evidence of emphysema and airway disease may be present very early, the lone significance of dyspnoea, the most relevant symptom in COPD in identifying these individuals, has been scarcely assessed.The Searching Clinical COPD Onset (SOON) Study was designed primarily to detect clinical, physiological and structural differences between dyspnoeic and non-dyspnoeic individuals with early grade COPD. It is hypothesised that presence of dyspnoea in early disease may identify a subtype of individuals with reduced exercise capacity, notwithstanding of their spirometry results. In addition, dyspnoeic individuals will share worse quality of life, lower physical activity, greater lung hyperinflation greater emphysema and airway thickness and reduced peripheral muscle mass than their non-dyspnoeic counterpart. METHODS AND ANALYSIS: SOON is a monocentric study, with a cross sectional design aimed at obtaining representative samples of current or ex-smoker-adults aged ≥45 and ≤80 years. Two hundred and forty participants will be enrolled into four strata, according to normal spirometry or mild spirometric obstruction and presence or not of dyspnoea modified Medical Research Council score ≥1. The primary outcome will be the difference between dyspnoeic and non-dyspnoeic individuals on the 6-min walk test performance, regardless of their spirometry results. To account for the confounding effect of heart failure on dyspnoea, stress echocardiography will be also performed. Secondary outcomes will include clinical (quality of life, physical activity), physiological (exercise testing) and structural characteristics (emphysema, airway disease and peripheral muscle mass by CT imaging). ETHICS AND DISSEMINATION: The Institutional Ethics Committee from Pontificia Universidad Católica de Chile has approved the study protocol and signed informed consent will be obtained from all participants. The findings of the trial will be disseminated through relevant peer-reviewed journals and international conference presentations. TRIAL REGISTRATION NUMBER: NCT03026439.

Monitoreo de pulsioximetría en extracciones dentales bajo protocolo de exodoncia simple y quirúrgico / Pulse oximetry measure in dental extractions under simple and surgical exodoncy protocol

INTRODUCCIÓN. El uso de un oxímetro como método de monitoreo no invasivo para el paciente permite al profesional odontólogo detectar, evaluar y prevenir situaciones de urgencia. OBJETIVO. Analizar la pulsioximetría en pacientes atendidos por extracciones dentales en el Centro Quirúrgico de la Facultad de Odontología de la Universidad Central del Ecuador. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo realizado a 30 pacientes bajo protocolo de exodoncia quirúrgica y 30 bajo protocolo de exodoncia simple; a los cuales se monitoreó constantes vitales con pulsioxímetro, los datos se pro-cesaron con el programa estadístico International Business Machines Statistical Package for the Social Sciences Versión 2.0 para determinar varianza a través de distribución de frecuencias, medias, desviación estándar, pruebas de T Student y Anova. RESULTADOS. Existió mayor alteración en pulso durante la fase de exodoncia en ambos protocolos de atención, mientras que la saturación de oxígeno aumentó desde la fase de anestesia, sin tener varianzas significativas. Las mujeres presentaron valores elevados de saturación de oxígeno 95,5% y pulso (87,07 ± 1,39 latidos por minuto) en comparación con los hombres durante todas las fases de ambos protocolos. Existieron variaciones significativas de pul-so en pacientes sometidos a exodoncias quirúrgicas con ansiedad leve o nula mientras que en exodoncia simple existió mayor varianza de pulso en aquellos con ansiedad mode-rada según la Escala de Ansiedad de Corah. Se presentaron cuatro urgencias 6,66% (4; 60). CONCLUSIÓN. El monitoreo constante mediante el pulsioxímetro durante la atención odontológica permitió identificar a tiempo eventos que hubiesen comprometido la integri-dad del paciente y evitar que se conviertan en emergencia.

INTRODUCTION. The use of an oximeter as a non-invasive monitoring method for a pa-tient, allows dentist to detect, evaluate and prevent emergency situations. OBJECTIVE. Analyze the pulse oximetry in patients attended for dental extractions in the Faculty of Dentistry ́s Surgical Center at the Universidad Central del Ecuador. MATERIALS AND ME-THODS. Observational, descriptive study of 30 patients treated under surgical exodontics protocol and 30 under simple exodontics protocol.Vital signs were measured with pulse oximeter and the data was processed with the International Business Machines Statistical Package for the Social Sciences Version 2.0 to determine the variance through distribution of frequencies, means, standard deviation, Student T tests and Anova. RESULTS. The-re was a greater alteration in pulse, during the exodontic phase in both protocols, while oxygen saturation increased at the anesthesic phase, without having relevant variances. Women patients have increased values of oxygen saturation (95,5%) and pulse (87,07 ± 1,39 beats per minute) compared to men during all phases of both protocols. There were significant pulse variations in patients who had surgical extractions with mild level anxiety. In the other hand, in simple extractions, there was greater pulse variance in patients who have moderate anxiety according to the Corha Anxiety Scale. During the study four ur-gencies 6,66% (4; 60) were identified. CONCLUSION. Constant monitoring by the pulse oximeter during dental care, allowed to identify events that might have compromised the integrity of the patient, in order to prevent and avoid they become an emergency situation.

Antibiotic susceptibility of diverse Mycobacterium abscessus complex strains in New South Wales, Australia.

Members of the Mycobacterium abscessus complex are emerging pathogens of increasing importance, causing both respiratory and soft tissue infections, but precise speciation is problematic. This study was performed to examine the subspecies and antibiotic susceptibility of M. abscessus complex isolates collected during 2013 at the statewide New South Wales Mycobacterium Reference Laboratory (NSW MRL), Australia. Mycobacterium abscessus subsp. abscessus accounted for more than half of all M. abscessus isolates (n = 24, 57.1%), and M. abscessus subsp. massiliense comprised the remainder of the isolates (n = 18, 42.9%). There were no M. abscessus subsp. bolletii isolates. The prevalence of antibiotic resistance to all antibiotics, apart from amikacin was high, with 26.3% of isolates being reliably susceptible to only amikacin. Most M. abscessus subsp. abscessus isolates (80%) demonstrated inducible clarithromycin resistance whereas the majority of M. abscessus subsp. massiliense isolates (94.4%) remained susceptible to clarithromycin. There was a good correlation between the erm(41) genotype and clarithromycin susceptibility results after 14 days of incubation for most isolates with only three exceptions. Further studies correlating in vitro susceptibility profiles with clinical outcomes of M. abscessus infections treated with combination antimicrobial therapy are warranted.

[Hairy cell leukemia during pregnancy: report of one case]. / Leucemia de células velludas en el embarazo: Caso clínico.

Hairy cell leukemia (HCL) is a rare chronic B cell lymphoproliferative disorder that affects mostly men. It usually presents with pancytopenia, splenomegaly and bone marrow infiltration, without lymphadenopathy. Diagnosis is based on the presence of mononuclear cells with cytoplasmic projections in a blood smear, the typical bone marrow infiltration pattern and the immunophenotypic profile. HCL occurs seldom in young women and even more exceptionally during pregnancy. We report a 31-year-old woman in whom a splenomegaly was detected during routine prenatal care. Pancytopenia with 25% of hairy cells was found in her blood count. The patient was subjected to an open splenectomy and had an uneventful pregnancy. After two years of follow up, she has a normal blood count and has not required chemotherapy.

Differences in lung glutathione metabolism may account for rodent susceptibility in elastase-induced emphysema development.

Syrian Golden hamsters develop more severe emphysema than Sprague-Dawley rats after intratracheal instillation of the same dose of elastase/body weight. Although species variations in antielastase defenses may largely explain these results, other variables, such as differences in lung antioxidants, cannot be overlooked since oxidative stress modulates antiprotease activity. We propose that elastase instillation might affect lung glutathione (GSH) metabolism differently in these species. Our aim was to study in hamsters and rats, lung glutathione metabolism at different times, from the stage of diffuse alveolar damage to advanced emphysema. We measured total and oxidized glutathione content as well as activity and expression of enzymes related to GSH synthesis and redox cycling: gamma-glutamylcysteine synthetase, glutathione peroxidase, and glutathione reductase. Whereas rats showed no significant changes in these measurements, hamsters showed significant derangement in GSH metabolism early after elastase instillation: 25% fall in total GSH (P < 0.05) with no increase in oxidized glutathione associated with reduced enzyme activities 24 h after elastase [60% for gamma-glutamylcysteine synthetase (P < 0.01), 30% for glutathione peroxidase (P < 0.01), and 75% for glutathione reductase (P < 0.001)]. GSH homeostasis was restored at the end of the first week, involving transient increased expression of these enzymes. We conclude that elastase induces significant alterations in GSH metabolism of hamster lungs and no overall change in rat lungs. Although differences in disease severity may account for our findings, the hamster becomes vulnerable to functional inhibition of alpha(1)-antitrypsin by oxidants and thus, even more susceptible to injury than it would be, considering only its low alpha(1)-antitrypsin level.

Resultados preliminares y factibilidad del mini lavado bronco-alveolar en pacientes cursando falla respiratoria severa / Mini bronchoalveolar lavage in patients with severe respiratory failure

Background: To recognize the etiological agent responsible for severe acute respiratory failure (ARF) in patients in mechanical ventilation (MV) is important to determine their treatment and prognosis, and to avoid the excessive use of antibiotics. Mini bronchoalveolar lavage (mini BAL) is a blind, non bronschoscopic procedure, used to obtain samples from the lower respiratory tract from patients on mechanical ventilation (MV). Aim: To assess the feasibility, complications and preliminary results of mini BAL among patients with severe ARF on MV. Material and Methods: Prospective study in 17 patients with acute lung injury (ALI ) or acute respiratory distess syndrome (ARDS) on MV and with negative conventional microbiological studies. Mini BAL was performed using standardized protocols. Hemodynamic and respiratory parameters where measured before and after the procedure. Samples obtained were sent to quantitative cultures. Results: At baseline: APACHE II score of 22 ± 6,7, PaO2/FiO2 ratio was 176.6 ± 48.6 and the oxygenation index was 9.74 ± 3.78. All procedures were performed by an ICU resident. Thirty five percent of the procedures had positive cultures and no complications related to the procedures were reported. The procedure lasted an average of 12 minutes and the instilled and rescued volume were 60 ml and 19.6 ml, respectively. There were no significant differences between hemodynamic and respiratory variables before and after the procedure. Conclusions: Mini BAL is a safe, fast and easy technique for obtaining samples from the inferior airway in patients with ALI or ARDS on MV.

Leucemia de células velludas en el embarazo: Caso clínico / Hairy cell leukemia during pregnancy: Report of one case

Hairy cell leukemia (HCL) is a rare chronic B cell lymphoproliferative disorder that affects mostly men. It usually presents with pancytopenia, splenomegaly and bone marrow infiltration, without lymphadenopathy. Diagnosis is based on the presence of mononuclear cells with cytoplasmic projections in a blood smear, the typical bone marrow infiltration pattern and the immunophenotypic profile. HCL occurs seldom in young women and even more exceptionally during pregnancy. We report a 31-year-old woman in whom a splenomegaly was detected during routine prenatal care. Pancytopenia with 25 percent of hairy cells was found in her blood count. The patient was subjected to an open splenectomy and had an uneventful pregnancy. After two years of follow up, she has a normal blood count and has not required chemotherapy.