Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis.

BACKGROUND: Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures. OBJECTIVES: We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV. METHODS: In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-ßAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing. RESULTS: Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers. CONCLUSIONS: SST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810).

Locus-specific expression of transposable elements in single cells with CELLO-seq.

Transposable elements (TEs) regulate diverse biological processes, from early development to cancer. Expression of young TEs is difficult to measure with next-generation, single-cell sequencing technologies because their highly repetitive nature means that short complementary DNA reads cannot be unambiguously mapped to a specific locus. Single CELl LOng-read RNA-sequencing (CELLO-seq) combines long-read single cell RNA-sequencing with computational analyses to measure TE expression at unique loci. We used CELLO-seq to assess the widespread expression of TEs in two-cell mouse blastomeres as well as in human induced pluripotent stem cells. Across both species, old and young TEs showed evidence of locus-specific expression with simulations demonstrating that only a small number of very young elements in the mouse could not be mapped back to the reference with high confidence. Exploring the relationship between the expression of individual elements and putative regulators revealed large heterogeneity, with TEs within a class showing different patterns of correlation and suggesting distinct regulatory mechanisms.

Neonatal Feeding Trajectories in Mothers With Bipolar Disorder Taking Lithium: Pharmacokinetic Data.

Purpose: Women who take lithium during pregnancy and continue after delivery may choose to breastfeed, formula feed, or mix these options. The aim of the study was to evaluate the neonatal lithium serum concentrations based on these three feeding trajectories. Methods: We followed 24 women with bipolar disorder treated with lithium monotherapy during late pregnancy and postpartum (8 per trajectory). Lithium serum concentrations were determined by an AVL 9180 electrolyte analyser with a 0.10 mEq/L detection limit and a 0.20 mEq/L limit of quantification (LoQ). Results: There was complete lithium placental passage at delivery, with a mean ratio of lithium concentration in the umbilical cord to maternal serum of 1.12 ± 0.17. The median times to LoQ were 6-8, 7-8, and 53-60 days for formula, mixed, and exclusive breastfeeding respectively. The generalized log-rank testing indicated that the median times to LoQ differ according to feeding trajectory (p = 0.037). According to the multivariate analysis-adjusted lithium serum concentrations at birth, times to LoQ are, on average, longer under exclusive breastfeeding (formula, p = 0.015; mixed, p = 0.012). No lithium accumulation was observed in infants under either exclusive or mixed breastfeeding. During the lactation follow-up, there was no acute growth or developmental delays in any neonate or infant. Indeed, lithium concentrations in the three trajectories declined in all cases. However, the time needed to reach the LoQ was much longer for those breastfeeding exclusively. Conclusions: In breastfeed infant no sustained accumulation of lithium and no adverse effects on development or growth were observed.

Case Report: Clinical and Pharmacokinetic Profile of Lithium Monotherapy in Exclusive Breastfeeding. A Follow-Up Case Series.

Background: Most guidelines advise that women taking lithium should not breastfeed. The variation in transfer is just one reason behind this advice. Objectives: To present clinical and pharmacokinetic data of nine mother-infant pairs exposed to lithium monotherapy during late pregnancy and exclusive breastfeeding at the Perinatal Psychiatric Unit (2006-2018). Methods: We obtained sociodemographic data, medical risk factors, obstetric variables, and family and personal psychiatric history by semi-structured interview, and assessed maternal psychopathology with the Hamilton Depression Rating Scale and Young Mania Rating Scale. A senior neonatologist reviewed neonatal outcomes at birth using the Peripartum Events Scale. Paired maternal and cord blood and infant venous blood samples were collected. During the breastfeeding period, we monitored serum lithium and creatinine concentrations in mother-infant pairs at delivery, and at days 1-5, 7-11, 30, and 60 postpartum, and monthly until 6-months. Results: Lithium equilibrated completely across the placenta [1.13 (0.10), range (1.02-1.30)]. No women presented symptoms of postpartum lithium intoxication, two of the neonates presented transient hypotonia (22%). Lithium exposure was significantly less during breastfeeding than during late pregnancy, and serum lithium concentrations decreased up to 44% overtime from delivery to the first-month, and up to 60% to the third-month postpartum. There was no growth or developmental delay in the follow-up period. One woman had a manic episode with psychotic features at 45 days postpartum. Conclusions: In carefully selected women with bipolar disorder, lithium therapy when breastfeeding can be an appropriate option if coupled with close monitoring of the mother-infant pair.

Psychiatric Clinical Profiles and Pharmacological Interactions in COVID-19 Inpatients Referred to a Consultation Liaison Psychiatry Unit: a Cross-Sectional Study.

The Coronavirus Disease 2019 (COVID-19) can affect mental health in different ways. There is little research about psychiatric complications in hospitalized patients with COVID-19. The aim of the study was to describe the psychiatric clinical profile and pharmacological interactions in COVID-19 inpatients referred to a Consultation-Liaison Psychiatry (CLP) unit. This is a cross-sectional study, carried out at a tertiary hospital in Spain, in inpatients admitted because of COVID-19 and referred to our CLP Unit from March 17,2020 to April 28,2020. Clinical data were extracted from electronic medical records. The patients were divided in three groups depending on psychiatric diagnosis: delirium, severe mental illness (SMI) and non-severe mental illness (NSMI). Of 71 patients included (median [ICR] age 64 [54-73] years; 70.4% male), 35.2% had a delirium, 18.3% had a SMI, and 46.5% had a NSMI. Compared to patients with delirium and NSMI, patients with SMI were younger, more likely to be institutionalized and were administered less anti-COVID19 drugs. Mortality was higher among patients with delirium (21.7%) than those with SMI (0%) or NSMI (9.45%). The rate of side effects due to interactions between anti-COVID19 and psychiatric drugs was low, mainly drowsiness (4.3%) and borderline QTc prolongation (1.5%). Patients affected by SMI were more often undertreated for COVID-19. However, the rate of interactions was very low, and avoidable with a proper evaluation and drug-dose adjustment. Half of the patients with SMI were institutionalized, suggesting that living conditions in residential facilities could make them more vulnerable to infection.

Substance use during pregnancy and personality dimensions. / Consumo de substancias durante el embarazo y dimensiones de personalidad.

Our aim was to assess personality traits associated with substance use during pregnancy in a population-based, multicentre study of 1804 pregnant women. On day 2-3 postpartum, participants completed a semi-structured interview, including self-reported drug use (alcohol, tobacco, caffeine, cannabis, cocaine, opioids) during pregnancy, and socio-demographic, reproductive and obstetric variables, personal and family psychiatric history, social support, and the Eysenck personality questionnaire, short version (EPQ-RS). Logistic regression models were conducted. Fifty per cent of women reported substance use during pregnancy: 40% caffeine, 21% tobacco, 3.5% alcohol, and 0.3 % cannabis. Mean T-scores (SD) for personality dimensions were 51.1 (9.6) for extraversion, 48 (8.9) for psychoticism, and 43.6 (8.5) for neuroticism. Extroversion (p = .029) and psychoticism (p = .009) were identified as risk factors after adjustment by age, level of education, employment status during pregnancy, low social support, and previous psychiatric history. For each increment of 10 units in their scores, the odds of substance use increased by 12% and 16% respectively. Low education, being on leave during pregnancy, and previous psychiatric history were independent factors (p < .05) associated with substance use during pregnancy. Primiparity was a protective factor (p = .001). The final models showed a good fit (p = .26). The screening of substance use during pregnancy should include personality dimensions apart from psychosocial variables and history of psychiatric disorders. It is important to identify the associated risk factors for substance use during pregnancy to prevent and improve foetal/neonatal and maternal health during perinatal period.

Este estudio evalúa los patrones de consumo de substancias durante el embarazo y las dimensiones de personalidad asociadas, en una muestra multicéntrica de 1804 mujeres de población general. En el 2-3 día posparto, completaron una entrevista auto-administrada sobre el consumo de alcohol, tabaco, cafeína, cannabis, cocaína, opiáceos, drogas de diseño, además de variables socio-demográficas, obstétricas/reproductivas, historia psiquiátrica previa, apoyo social durante el embarazo y el cuestionario de personalidad de Eysenck (EPQ-RS). Se generaron modelos de regresión logística múltiple. La prevalencia del consumo fue del 50% (N=909): 40% cafeína, 21% tabaco, 3,5% alcohol, y 0,3 cannabis. Las puntuaciones T medias (DE) de personalidad fueron: extraversión 51,1 (9,6), psicoticismo 48 (8,9) y neuroticismo 43,6 (8,5). Las dimensiones de extraversión (p=0,029) y psicoticismo (p=0,009), fueron identificadas como factores de riesgo tras ajustar por edad, nivel educación, estatus laboral durante el embarazo, bajo apoyo social, e historia psiquiátrica previa. Para cada incremento de 10 unidades en sus puntuaciones, el odds de consumo de substancias durante el embarazo se incrementó un 12% y un 16% respectivamente. Menor educación, estar de baja, y antecedentes psiquiátricos fueron también factores independientes (p<0,05) asociados al consumo. Ser primípara fue factor protector (p=0,001). El modelo final mostró un ajuste satisfactorio (p=0,26). El cribaje de las mujeres con riesgo de consumo de substancias durante el embarazo debería incluir la personalidad además de variables psicosociales y antecedentes psiquiátricos. Identificar los factores de riesgo asociados es importante para prevenir y mejorar la salud materna y fetal/neonatal durante el embarazo y posparto.

Souporcell: robust clustering of single-cell RNA-seq data by genotype without reference genotypes.

Methods to deconvolve single-cell RNA-sequencing (scRNA-seq) data are necessary for samples containing a mixture of genotypes, whether they are natural or experimentally combined. Multiplexing across donors is a popular experimental design that can avoid batch effects, reduce costs and improve doublet detection. By using variants detected in scRNA-seq reads, it is possible to assign cells to their donor of origin and identify cross-genotype doublets that may have highly similar transcriptional profiles, precluding detection by transcriptional profile. More subtle cross-genotype variant contamination can be used to estimate the amount of ambient RNA. Ambient RNA is caused by cell lysis before droplet partitioning and is an important confounder of scRNA-seq analysis. Here we develop souporcell, a method to cluster cells using the genetic variants detected within the scRNA-seq reads. We show that it achieves high accuracy on genotype clustering, doublet detection and ambient RNA estimation, as demonstrated across a range of challenging scenarios.

Interaction between the functional SNP rs2070951 in NR3C2 gene and high levels of plasma corticotropin-releasing hormone associates to postpartum depression.

Postpartum depression (PPD) is a common mood disorder that occurs after delivery with a prevalence of approximately 10%. Recent reports have related placental corticotropin-releasing hormone (pCRH) to postpartum depressive symptoms. The aim of this study was to determine whether pCRH, ACTH, and cortisol (measured 48 h after delivery) and glucocorticoid and mineralocorticoid receptor genotypes (NR3C1 and NR3C2) and their interaction are associated with PPD. A longitudinal 32-week prospective study of five hundred twenty-five Caucasian depression-free women that were recruited from obstetric units at two Spanish general hospitals immediately after delivery. Of the women included in the sample, forty-two (8%) developed PPD. A strong association between PPD and the interaction between the pCRH and NR3C2 rs2070951 genotype was observed. The mean level of pCRH in rs2070951GG carriers with PPD was 56% higher than the mean in the CG and CC genotype groups (P < 0.00005). Carriers of the rs2070951GG genotype with high levels of pCRH had a higher risk of developing PPD (OR = 1.020, 95% CI 1.007-1.034, P = 0.002). This association remained even after controlling for variables such as neuroticism, obstetric complications and the number of stressful life events during pregnancy. There is an important interaction between pCRH 48 h postpartum and the NR3C2 rs2070951GG genotype. This interaction moderately associates with the presence of PPD. These results may open a new line of research and, if confirmed in other settings, will help to identify better risk predictors and the treatment for PPD.

Clinical Lactation Studies of Lithium: A Systematic Review.

Background: There is substantial evidence that postpartum prophylaxis with lithium lowers the rate of relapse in bipolar disorder. However, it is contraindicated during breastfeeding due to the high variability of the transfer into breast milk. Aims: We conducted a systematic review of the current evidence of studies assessing the transfer of lithium to lactating infants and short-term infant outcomes. Methods: An a priori protocol was designed based on PRISMA guidelines. Searches in PubMed and LactMed were conducted until September 2018. Studies assessing lithium pharmacokinetic parameters and short-term infant outcomes were included. Quality was assessed using a checklist based on international guidelines (i.e., FDA). Results: From 344 initial studies, 13 case reports/series with 39 mother-child dyads were included. Only 15% of studies complied with ≥50% of the items on the quality assessment checklist. Infants breastfeed a mean (SD) of 58.9 (83.3) days. Mean maternal lithium dose was 904 (293) mg/day, corresponding lithium plasma/serum concentration was 0.73(0.26) mEq/L, and breast milk concentration was 0.84(0.14) mEq/L. Mean infant lithium plasma/serum concentration was 0.23(0.26) mEq/L. Twenty-six (80%) infants had concentrations ≤0.30 mEq/L without adverse effects. Eight (20%) showed a transient adverse event (i.e., acute toxicity or thyroid alterations). All of them were also prenatally exposed to lithium monotherapy or polytherapy. Conclusion: The current evidence comes from studies with a degree of heterogeneity and of low-moderate quality. However, it identifies areas of improvement for future clinical lactation studies of lithium and provides support for some clinical recommendations.

Training tuberculosis laboratory workers in LED-fluorescence microscopy: experience learned in Argentina.

OBJECTIVE: To assess a LED-fluorescence microscopy (LED-FM) capacitation program for the training of laboratory technicians without previous experience in FM. METHODS: We evaluated a teaching program that consists of a three-day course followed by an "in situ" two-month phase in which technicians acquired skills without the help of a FM expert; in order to gain confidence to recognize auramine-stained bacillus, during this phase, technicians examined duplicate slides stained by Ziehl Neelsen (ZN) and FM in a unblinded way. Technicians with acceptable performance, continued with a blinded-training period. Testing panels and rechecking process were used to evaluate proficiency after different length of experience. RESULTS: Post-course panel results showed that 70% of trainees made Low False Positive errors (LFPs). Analysis of two other panels showed that LFPs significantly decreased (Chi-squared test, p<0.05) as the "in situ" training phase progressed. Processing at least three slides/day was associated with acceptable performance. During the blinded-training period, results of the rechecking process showed that sensitivity (96.8%) and specificity (99.8%) levels were satisfactory. CONCLUSION: Moderate training (a three-day course) is not enough to make technicians proficient in LED-FM; however, great ability can be reached after a short "in situ" training phase even without the presence of experienced staff available in field to review doubtful results. Training was more effective in services with a minimum workload of 750 slides/year.

Training tuberculosis laboratory workers in LED-fluorescence microscopy: experience learned in Argentina / Capacitación de trabajadores de laboratorios de tuberculosis en microscopia de fluorescencia LED: experiencia en Argentina

ABSTRACT Objective To assess a LED-fluorescence microscopy (LED-FM) capacitation program for the training of laboratory technicians without previous experience in FM. Methods We evaluated a teaching program that consists of a three-day course followed by an "in situ" two-month phase in which technicians acquired skills without the help of a FM expert; in order to gain confidence to recognize auramine-stained bacillus, during this phase, technicians examined duplicate slides stained by Ziehl Neelsen (ZN) and FM in a unblinded way. Technicians with acceptable performance, continued with a blinded-training period. Testing panels and rechecking process were used to evaluate proficiency after different length of experience. Results Post-course panel results showed that 70% of trainees made Low False Positive errors (LFPs). Analysis of two other panels showed that LFPs significantly decreased (Chi-squared test, p<0.05) as the "in situ" training phase progressed. Processing at least three slides/day was associated with acceptable performance. During the blinded-training period, results of the rechecking process showed that sensitivity (96.8%) and specificity (99.8%) levels were satisfactory. Conclusion Moderate training (a three-day course) is not enough to make technicians proficient in LED-FM; however, great ability can be reached after a short "in situ" training phase even without the presence of experienced staff available in field to review doubtful results. Training was more effective in services with a minimum workload of 750 slides/year.(AU)

RESUMEN Objetivo Evaluar un programa de capacitación en microscopía de fluorescencia LED (MF-LED) para el entrenamiento de técnicos de laboratorio sin experiencia en MF. Métodos Se evaluó un programa de capacitación que consiste en un curso de tres días seguido de dos meses de entrenamiento «in situ¼, en donde los técnicos adquirieron habilidades sin presencia de un experto en la práctica diaria; para alcanzar confianza en el reconocimiento del bacilo, los técnicos, durante estos meses, examinaron en forma «no cegada¼ extendidos duplicados teñidos por Ziehl Neelsen (ZN) y MF. Aquellos laboratoristas que lograron rendimiento aceptable continuaron su entrenamiento «a ciegas¼. Su desempeño fue evaluado en distintos períodos del entrenamiento mediante paneles de láminas y relectura de extendidos. Resultados Los resultados de un panel posterior al curso mostraron que 70% de los participantes cometieron errores falsos positivos bajos (FPB). Dos paneles posteriores evidenciaron que los FPB disminuían significativamente (prueba de Chi cuadrado, p<0.05) a medida que el entrenamiento avanzaba. El procesamiento de al menos tres extendidos/ día se asoció con desempeño aceptable. Durante el período a ciegas, la relectura de láminas evidenció que la sensibilidad (96,8%) y especificidad (99,8%) fueron satisfactorias. Conclusiones Una capacitación moderada (curso de tres días) no es suficiente para adquirir competencia en MF-LED; sin embargo, se puede alcanzar habilidad después de una corta capacitación «in situ¼, incluso si no hay personal con experiencia disponible en el servicio para revisar los resultados dudosos diariamente. El entrenamiento fue más efectivo en servicios con carga de trabajo mínima de 750 extendidos/año.(AU)

Performance of LED fluorescence microscopy for the detection of acid-fast bacilli from respiratory samples in peripheral laboratories in Argentina / Rendimiento de la microscopía de fluorescencia LED para la detección de bacilos ácido-alcohol resistentes en muestras respiratorias en laboratorios periféricos de Argentina

ABSTRACT Introduction: Light-emitting diode fluorescence microscopy (LED-FM) has been endorsed by the World Health Organization (WHO) for tuberculosis diagnosis, but its accuracy in HIV-infected patients remains controversial, and only some few studies have explored procedural factors that may affect its performance. Objective: To evaluate the performance of LED-FM for tuberculosis diagnosis in patients with and without HIV infection using a newer, less expensive LED lamp. Materials and methods: We compared the performance of LED-FM and Ziehl-Neelsen (ZN) microscopy on respiratory specimen smears from tuberculosis (TB) suspects and patients on treatment examined by different technicians blinded for HIV-status and for the result of the comparative test. We analyzed the effect of concentrating specimens prior to microscopy using different examination schemes and user-appraisal of the LED device. Results: Of the 6,968 diagnostic specimens collected, 869 (12.5%) had positive Mycobacterium tuberculosis cultures. LED-FM was 11.4% more sensitive than ZN (p<0.01). Among HIV-positive TB patients, sensitivity differences between LED-FM and ZN (20.6%) doubled the figure obtained in HIV-negative patients or in those with unknown HIV status (9.3%). After stratifying by direct and concentrated slides, the superiority of LED-FM remained. High specificity values were obtained both with LED-FM (99.9%) and ZN (99.9%).The second reading of a sample of slides showed a significantly higher positive detection yield using 200x magnification (49.4 %) than 400x magnification (33.8%) (p<0.05). The LED-device had a very good acceptance among the technicians. Conclusion: LED-FM better performance compared with ZN in HIV-infected patients and user-appraisal support the rapid roll-out of LED-FM. Screening at 200x magnification was essential to achieve LED-FM increased sensitivity.

RESUMEN Introducción. La microscopía de fluorescencia con lámpara LED (MF-LED) ha sido recomendada por la Organización Mundial de la Salud (OMS) para el diagnóstico de la tuberculosis, pero su precisión en pacientes con HIV continúa siendo controversial y en pocos estudios se han explorado los factores metodológicos que pueden afectar su utilidad. Objetivo. Evaluar el rendimiento de la MF-LED en el diagnóstico de la tuberculosis en pacientes con HIV y sin él mediante un novedoso dispositivo LED. Materiales y métodos. Se comparó el rendimiento de la MF-LED y la microscopía en frotis de muestras respiratorias con tinción de Ziehl-Neelsen (M-ZN) examinados por técnicos cegados en cuanto al estado de HIV y el resultado de la prueba comparativa. Se analizó el efecto de concentrar muestras antes de la microscopía, usar diferentes esquemas de observación y la valoración con el dispositivo LED. Resultados. De las 6.968 muestras recolectadas, 869 (12,5 %) resultaron con cultivo positivo para Mycobacterium tuberculosis. La MF-LED fue 11,4 % más sensible que la M-ZN (p<0,01). Entre los pacientes con tuberculosis positivos para HIV, la diferencia de sensibilidad entre la MF-LED y la M-ZN (20,6 %) duplicó la cifra obtenida en pacientes negativos para HIV o con estatus desconocido (9,3 %). Al estratificar los frotis en directos y concentrados, se mantuvo la superioridad de la MF-LED. Las especificidades de la MF-LED (99,9 %) y la M-ZN (99,9 %) resultaron elevadas. La lectura de una muestra de frotis mostró una positividad significativamente mayor con un aumento de 200X (49,4 %) que con uno de 400X (33,8 %) (p<0,05). El dispositivo LED tuvo una buena aceptación entre los técnicos. Conclusión. Debido al mejor desempeño de la MF-LED comparada con la M-ZN en pacientes con HIV y su fácil utilización, se recomienda su adopción. La utilización del aumento de 200X fue esencial para el incremento de la sensibilidad de la MF-LED.

[Performance of LED fluorescence microscopy for the detection of acid-fast bacilli from respiratory samples in peripheral laboratories in Argentina].

INTRODUCTION: Light-emitting diode fluorescence microscopy (LED-FM) has been endorsed by the World Health Organization (WHO) for tuberculosis diagnosis, but its accuracy in HIV-infected patients remains controversial, and only some few studies have explored procedural factors that may affect its performance. OBJECTIVE: To evaluate the performance of LED-FM for tuberculosis diagnosis in patients with and without HIV infection using a newer, less expensive LED lamp. MATERIALS AND METHODS: We compared the performance of LED-FM and Ziehl-Neelsen (ZN) microscopy on respiratory specimen smears from tuberculosis (TB) suspects and patients on treatment examined by different technicians blinded for HIV-status and for the result of the comparative test. We analyzed the effect of concentrating specimens prior to microscopy using different examination schemes and user-appraisal of the LED device. RESULTS: Of the 6,968 diagnostic specimens collected, 869 (12.5%) had positive Mycobacterium tuberculosis cultures. LED-FM was 11.4% more sensitive than ZN (p;0.01). Among HIV-positive TB patients, sensitivity differences between LED-FM and ZN (20.6%) doubled the figure obtained in HIVnegative patients or in those with unknown HIV status (9.3%). After stratifying by direct and concentrated slides, the superiority of LED-FM remained. High specificity values were obtained both with LED-FM(99.9%) and ZN (99.9%).The second reading of a sample of slides showed a significantly higher positive detection yield using 200x magnification (49.4 %) than 400x magnification (33.8%) (p;0.05). The LEDdevice had a very good acceptance among the technicians. CONCLUSION: LED-FM better performance compared with ZN in HIV-infected patients and user-appraisal support the rapid roll-out of LED-FM. Screening at 200x magnification was essential to achieve LEDFM increased sensitivity.

LED fluorescence microscopy in the diagnosis of tuberculosis: Fading and restaining of smears for external quality assessment.

Blinded rechecking is a method proposed for external quality assurance (EQA) of auramine-stained acid-fast bacilli (AFB) smears using fluorescence microscopy (FM), however, this procedure is not well developed and slides fading over time could compromise its implementation. Since bleaching of fluorescent molecules involves temperature-dependent chemical reactions, it is likely that low temperatures could slow down this process. We stored auramine-stained slides under different environmental conditions, including -20°C, and examined them over time. The slides stored in all the environments faded. At -20°C, fading was not reduced in relation to room temperature. Restaining and re-examining smears after five months showed that the slides containing saliva and storage at -20°C were associated with failure in AFB reappearance. In conclusion, the practice of freezing slides until they are viewed should be discouraged as it has a negative effect on blinded rechecking by reducing reading concordance after restaining. Specimen quality should be considered when interpreting FM-EQA results.

Maladaptive family dysfunction and parental death as risk markers of childhood abuse in women

This study aims to examine the prevalence and characteristics of physical, emotional and sexual childhood abuse. It also examines whether other non-abuse types of childhood adversities related to maladaptive family functioning and separations during childhood can be used as markers for the presence of childhood abuse. Participants (N = 237) were women at 2-3 days after delivery that completed the Spanish-validated version of the Early Trauma Inventory Self Report (ETI-SR; Bremner, Bolus, & Mayer, 2007; Plaza et al., 2011), designed to assess the presence of childhood adversities. Results show that 29% of the women had experienced some type of childhood abuse, and 10% more than one type. Logistic regression analyses indicate that childhood parental death is a risk marker for childhood emotional abuse (OR: 3.77; 95% CI: 1.327-10.755; p <.013), childhood parental substance abuse is a risk marker for childhood sexual (OR: 3.72; 95% CI: 1.480-9.303; p < .005) and physical abuse (OR: 2.610; 95% CI: 1.000-6.812; p < .05) and that childhood family mental illness is a risk marker for childhood emotional (OR: 2.95; 95% CI: 1.175-7.441; p < .021) and sexual abuse (OR: 2.55; 95% CI: 1.168-5.580; p < .019). The high prevalence of childhood abuse indicates a need for assessment during the perinatal period. Screening for childhood family mental illness, parental substance abuse, and parental death - all identified risk factors for reporting childhood abuse - can help to identify women that should be assessed specifically regarding abuse (AU)

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[Treatment of pulmonary tuberculosis in a low-prevalence urban area. Compliance and sputum conversion]. / Tratamiento de la tuberculosis pulmonar en un área urbana de baja prevalencia. Cumplimiento y negativización bacteriológica.

Several factors could be responsible for a delay in bacteriological conversion of sputum in patients with pulmonary tuberculosis (pTB) even under proper treatment. We aimed to determine those factors associated with follow-up test compliance and bacteriologic conversion at month two of treatment in patients with pTB who were receiving directly controlled treatment (DOT) in an urban area with low TB burden (notification rate: 14.9 cases/100 000, 2010-2011). We retrospectively analyzed the clinical, demographic, radiological, microbiological and therapeutic characteristics of 196 new smear-positive pTB cases. The proportion of patients who underwent bacteriological examination was 79.1% (155/196) and 74.7% (121/162) at the second and last month of treatment. Smear examinations were significantly more frequent in patients with co-morbidities or receiving DOT in health facilities with laboratory access. Diabetes (OR 17.4, 95% CI 2.0 - 27.0) and high smear grade (OR 13.8, 95% CI 1.8 - 108.0) were highly associated with persistent positive smears. Cavitation (OR 4.6, 95%, CI 1.1 - 20.5) and diabetes (OR 3.3, 95% CI 1.1 - 10.5) were associated with persistent positive cultures. Smear examination results at two months of treatment indicated a sensitivity of 63.9% (23/36) and a specificity of 82.4% (98/119) in relation to culture. The limited predictive value of smear examination relative to culture results indicated the need to find other markers for sputum conversion. Identification of risk factors associated with persistent sputum positivity could contribute to patient care and resource allocation. Prolonged infectiousness in patients with diabetes could indicate the need to review TB control strategies.

Tratamiento de la tuberculosis pulmonar en un área urbana de baja prevalencia: Cumplimiento y negativización bacteriológica / Treatment of pulmonary tuberculosis in a low-prevalence urban area: Compliance and sputum conversion

Varios factores podrían relacionarse con la demora en la negativización bacteriológica de la tuberculosis pulmonar (TBp), aun con adecuado tratamiento. Para determinar su papel en la negativización bacteriológica al segundo mes de tratamiento, se analizaron retrospectivamente las características clínicas, demográficas, radiológicas, microbiológicas y terapéuticas de 196 casos nuevos de TBp con baciloscopia positiva bajo tratamiento directamente observado (TDO) en un área urbana de baja prevalencia de TB (tasa notificada: 14.9 casos/100 000 habitantes, 2010-2011). El porcentaje de pacientes con exámenes bacteriológicos fue 79.1% (155/196) al segundo mes y 74.7% (121/162) al final del tratamiento; aquellos con comorbilidades o que realizaban TDO en servicios con laboratorio tuvieron porcentajes significativamente mayores. La alta carga bacilar (OR 13.8, 95% IC 1.8-108.0) y la diabetes (OR 7.4, 95% IC 2.0-27.0) se asociaron a la persistencia de baciloscopia positiva; la presencia de cavernas (OR 4.6, 95% IC 1.1-20.5) y diabetes (OR 3.3, 95% IC 1.1-10.5) se relacionaron con la persistencia del cultivo positivo. La sensibilidad de la baciloscopia con respecto al cultivo positivo al segundo mes de tratamiento fue 63.9% (23/36) y su especificidad 82.4% (98/119); el limitado valor predictivo de la baciloscopia sobre los resultados del cultivo evidencia la necesidad de encontrar otros marcadores de esterilización del esputo. La identificación de los factores asociados a la persistencia de la infecciosidad contribuye al cuidado de pacientes y a la asignación de recursos. La prolongada infecciosidad de los pacientes diabéticos indicaría la necesidad de rever las estrategias de control de la TB.

Several factors could be responsible for a delay in bacteriological conversion of sputum in patients with pulmonary tuberculosis (pTB) even under proper treatment. We aimed to determine those factors associated with follow-up test compliance and bacteriologic conversion at month two of treatment in patients with pTB who were receiving directly controlled treatment (DOT) in an urban area with low TB burden (notification rate: 14.9 cases/100 000, 2010-2011). We retrospectively analyzed the clinical, demographic, radiological, microbiological and therapeutic characteristics of 196 new smear-positive pTB cases. The proportion of patients who underwent bacteriological examination was 79.1% (155/196) and 74.7% (121/162) at the second and last month of treatment. Smear examinations were significantly more frequent in patients with co-morbidities or receiving DOT in health facilities with laboratory access.. Diabetes (OR 17.4, 95% CI 2.0 - 27.0) and high smear grade (OR 13.8, 95% CI 1.8 - 108.0) were highly associated with persistent positive smears. Cavitation (OR 4.6, 95%, CI 1.1-20.5) and diabetes (OR 3.3, 95% CI 1.1-10.5) were associated with persistent positive cultures. Smear examination results at two months of treatment indicated a sensitivity of 63.9% (23/36) and a specificity of 82.4% (98/119) in relation to culture. The limited predictive value of smear examination relative to culture results indicated the need to find other markers for sputum conversion. Identification of risk factors associated with persistent sputum positivity could contribute to patient care and resource allocation. Prolonged infectiousness in patients with diabetes could indicate the need to review TB control strategies.

Tratamiento de la tuberculosis pulmonar en un área urbana de baja prevalencia: Cumplimiento y negativización bacteriológica / Treatment of pulmonary tuberculosis in a low-prevalence urban area: Compliance and sputum conversion

Varios factores podrían relacionarse con la demora en la negativización bacteriológica de la tuberculosis pulmonar (TBp), aun con adecuado tratamiento. Para determinar su papel en la negativización bacteriológica al segundo mes de tratamiento, se analizaron retrospectivamente las características clínicas, demográficas, radiológicas, microbiológicas y terapéuticas de 196 casos nuevos de TBp con baciloscopia positiva bajo tratamiento directamente observado (TDO) en un área urbana de baja prevalencia de TB (tasa notificada: 14.9 casos/100 000 habitantes, 2010-2011). El porcentaje de pacientes con exámenes bacteriológicos fue 79.1% (155/196) al segundo mes y 74.7% (121/162) al final del tratamiento; aquellos con comorbilidades o que realizaban TDO en servicios con laboratorio tuvieron porcentajes significativamente mayores. La alta carga bacilar (OR 13.8, 95% IC 1.8-108.0) y la diabetes (OR 7.4, 95% IC 2.0-27.0) se asociaron a la persistencia de baciloscopia positiva; la presencia de cavernas (OR 4.6, 95% IC 1.1-20.5) y diabetes (OR 3.3, 95% IC 1.1-10.5) se relacionaron con la persistencia del cultivo positivo. La sensibilidad de la baciloscopia con respecto al cultivo positivo al segundo mes de tratamiento fue 63.9% (23/36) y su especificidad 82.4% (98/119); el limitado valor predictivo de la baciloscopia sobre los resultados del cultivo evidencia la necesidad de encontrar otros marcadores de esterilización del esputo. La identificación de los factores asociados a la persistencia de la infecciosidad contribuye al cuidado de pacientes y a la asignación de recursos. La prolongada infecciosidad de los pacientes diabéticos indicaría la necesidad de rever las estrategias de control de la TB.(AU)

Several factors could be responsible for a delay in bacteriological conversion of sputum in patients with pulmonary tuberculosis (pTB) even under proper treatment. We aimed to determine those factors associated with follow-up test compliance and bacteriologic conversion at month two of treatment in patients with pTB who were receiving directly controlled treatment (DOT) in an urban area with low TB burden (notification rate: 14.9 cases/100 000, 2010-2011). We retrospectively analyzed the clinical, demographic, radiological, microbiological and therapeutic characteristics of 196 new smear-positive pTB cases. The proportion of patients who underwent bacteriological examination was 79.1% (155/196) and 74.7% (121/162) at the second and last month of treatment. Smear examinations were significantly more frequent in patients with co-morbidities or receiving DOT in health facilities with laboratory access.. Diabetes (OR 17.4, 95% CI 2.0 - 27.0) and high smear grade (OR 13.8, 95% CI 1.8 - 108.0) were highly associated with persistent positive smears. Cavitation (OR 4.6, 95%, CI 1.1-20.5) and diabetes (OR 3.3, 95% CI 1.1-10.5) were associated with persistent positive cultures. Smear examination results at two months of treatment indicated a sensitivity of 63.9% (23/36) and a specificity of 82.4% (98/119) in relation to culture. The limited predictive value of smear examination relative to culture results indicated the need to find other markers for sputum conversion. Identification of risk factors associated with persistent sputum positivity could contribute to patient care and resource allocation. Prolonged infectiousness in patients with diabetes could indicate the need to review TB control strategies.(AU)