Somatic symptoms in the general population of Spain: Validation and normative data of the Patient Health Questionnaire-15 (PHQ-15).

OBJECTIVE: The Patient Health Questionnaire (PHQ-15) has been widely used to assess somatic symptoms. This study aimed to analyze the psychometric properties of the Spanish version of the PHQ-15, its structure and score distribution across demographic variables in a Spanish sample. In addition, we examined variations in somatic symptoms among different demographic subgroups. METHOD: 1495 individuals from the Spanish population answered a series of self-reported measures, including PHQ-15. To examine the factorial structure of the PHQ-15, Confirmatory Factor Analysis (CFA) was performed. Additionally, a bifactor CFA model was examined using the Exploratory Structural Equation Modeling (ESEM) framework. RESULTS: Women showed more somatic symptoms than men, and younger individuals showed more somatic symptoms than the older ones. It was also revealed positive associations between somatic symptoms and levels of depression, anxiety, and suspiciousness, while negative associations were found between somatic symptoms and perceived resilience and happiness. Regarding the factorial structure of the PHQ-15, although the one-factor and bifactor models were suitable, the bifactor model underscores the presence of a robust general factor. LIMITATIONS: It is a cross-sectional study, not including non-institutionalized individuals. CONCLUSION: Somatic symptoms are more frequent in women and younger individuals. Furthermore, the presence of physical symptoms is associated to other psychological aspects, such as depression or anxiety. Finally, bifactor model was the most appropriate to explain the factorial structure of the PHQ-15.

Effects of dietary supplementation of cobiotic based on Agave fructans on growth performance, blood parameters, oxidative damage and immune status of broiler.

This study evaluated the effect of cobiotic (CO) composed of organic fructans powder of Agave tequilana and turmeric powder of Curcuma longa L. as an alternative of antibiotic growth promoters (AGPs) on growth performance, blood parameters, intestinal pH, oxidative stress, and cytokines serum levels of broiler chickens. A total of 135 one-day-old Ross 308 broilers distributed to five experimental groups, which included starter or finisher standard diets without AGPs (CON), CON + 0.25 COLI-ZIN g/kg feed (AGP), CON + 0.1 g Agave fructans/kg feed (AF), CON + 0.5 g turmeric powder/kg feed (TP) and CON + 0.1 g AF + 0.5 g TP /kg feed (CO), for 49 days. AF followed by TP, decreased feed intake, obtaining the best FCR. AGP increased the heterophil-lymphocyte ratio compared to other groups. CO significantly decreased the pH of the cecal content. AF increased IL-10 levels, while TP decreased it. AF decreased the IL-1ß levels. The present study showed that including a cobiotic based on AF and TP or components separately in a broilers diet improved growth performance, modified intestinal and cecum pH, and stimulated the immune system, which suggests CO as a safe alternative to AGP.

Co-infection by Toxoplasma gondii and Neospora caninum in Goats Reared in Extensive System of Mexico.

Background: The aim of the present study was to describe the presence of co-infection by Toxoplasma gondii and Neospora caninum in goats reared in extensive systems from Mexico. Materials and Methods: A cross-sectional study was conducted to determine the frequency of T. gondii and N. caninum, by detecting antibodies to each parasite by mean commercial ELISA kits. A total of 176 blood samples were randomly collected from mature females reared in extensive system herds from 20 municipalities of state of Guanajuato, Mexico. Results: The general seroprevalence was 23.9 and 21.0% for T. gondii and N. caninum, respectively, while co-infection rate was 3.6%. For geographic and environmental variables, no differences were observed among T. gondii and coinfection; however, it was observed that altitude, annual precipitation, annual average temperature, and rainy period showed significant differences with N. caninum seropositive goats. Conclusion: The seroprevalence of both parasites was appreciated in most of the studied herds. The present study is the first report of T. gondii and N. caninum co-infection in goats from extensive herds in Mexico.

Validation of the Montreal Pain and Affective Face Clips (MPAFC): The role of sex and participants’ pain status / Validación del set Montreal Pain and Affective Face Clips (MPAFC): rol del sexo y estado de dolor de los participantes

Background: The use of pain-related stimuli in experimental psychology studies has increased in the last few years. Consequently, various sets of stimuli have been created for this purpose. Aims: To analyze the validity of the pain faces of Montreal Pain and Affective Face Clips (MPAFC), in Spanish participants with and without pain. Method: A total of 291 participants completed psychological self-report and pain measures and were asked to rate the prototypicality and emotional intensity of the eight pain-related faces from the MPAFC by rating. The sample was divided into three groups depending on the participants’ pain status (chronic, acute, or pain-free). Results: Three of the eight pain faces did not reach a higher rating than 5 (on a 0-10 points scale) in both dimensions. Regarding the pain status, there were no significant differences in the ratings between groups of participants. Female faces were rated as significantly more prototypical and emotionally intense than male faces. Limitations:As we used the last image of every clip, this study is based just on static images of the pain facial expression, which may be less representative of the emotion. Conclusion: Overall, the presence of pain in participants did not significantly affect their assessment of the faces. Female faces were significantly rated as more prototypical and more emotionally intense than male faces. From our results, we conclude that experimental studies about pain should explore and report the validity of the selected stimuli to optimize the adequacy of the stimuli. (AU)

Antecedentes: El uso de estímulos relacionados con el dolor en los estudios de psicología experimental ha aumentado en los últimos años. En consecuencia, se ha creado una variedad de conjuntos de estímulos para este fin. Objetivos: Analizar la validez de las caras de dolor del Montreal Pain and Affective Face Clips (MPAFC), en participantes españoles con y sin dolor. Método: Un total de 291 participantes completaron medidas psicológicas de autoinforme y de dolor y valoraron la prototipicidad y la intensidad emocional de las ocho caras de dolor del MPAFC. La muestra se dividió en tres grupos en función del dolor de los participantes (crónico, agudo o sin dolor). Resultados: Tres de las ocho caras de dolor no alcanzaron una valoración superior a 5 (en una escala de 0-10 puntos) en ambas dimensiones. En cuanto al estado de dolor, no hubo diferencias significativas en las puntuaciones entre los grupos. Los rostros femeninos se calificaron como significativamente más prototípicos y emocionalmente más intensos que los masculinos. Limitaciones:Este estudio se basa sólo en imágenes estáticas de la expresión facial del dolor, que pueden ser menos representativas de la emoción. Conclusiones: En general, la presencia de dolor en los participantes no afectó significativamente a su valoración de los rostros. Los rostros femeninos fueron valorados significativamente como más prototípicos y más intensos emocionalmente que los masculinos. Como conclusión, los estudios experimentales sobre dolor deberían explorar e informar sobre la validez de los estímulos seleccionados para optimizar la adecuación de los estímulos. (AU)

Development of a tamarind-based functional beverage with partially-hydrolyzed agave syrup and the health effects of its consumption in C57BL/6 mice.

Excess consumption of sweetened beverages is associated with a global rise in metabolic diseases. Tamarind and partially-hydrolyzed agave syrup have potential for developing healthier beverages. Our objective was to develop a functional beverage using these ingredients (PH-AS-B). We also evaluate shelf-life stability (physicochemical, microbiological, and antioxidant properties) and health effects in C57BL/6 mice compared with tamarind beverages sweetened with glucose or fructose. Optimal tamarind extraction conditions were a 1:10 ratio (g pulp/mL water) and boiling for 30 min, and the resulting beverage had a shelf life of two months at 4 °C. Non-volatile metabolites were identified using HPLC/MS. PH-AS-B was associated with decreased blood cholesterol (5%) and triglyceride (20-35%) concentrations in healthy mice as well as lower lipid (82%) concentrations and evidence of protein oxidation (42%) in the liver, compared with glucose- and fructose-sweetened tamarind beverages. In conclusion, PH-AS-B was stable and associated with beneficial metabolic properties in healthy mice.

Antimicrobial activities of Agave fructans against multi-resistant and biofilm-producing Staphylococcus aureus isolated from bovine mastitis.

Bovine mastitis is an emerging disease that causes large economic losses. Staphylococcus aureus its main etiological agent, is multi-resistant to antimicrobials and produces biofilm. The objective of this study was to investigate the effect of Agave fructans (AF), a type of prebiotic, on multi-resistant and biofilm-forming isolates of S. aureus. Ten isolates of S. aureus from bovine subclinical mastitis previously characterized as highly resistant to antimicrobials and biofilm formers were used in this study. The growth kinetics of S. aureus in the presence of AF was evaluated by the Baranyi and Roberts microbial growth model using the DMFit program. The antibacterial activity of AF against S. aureus was studied by the well-diffusion method and the effect on biofilm formation by the crystal violet method. All assays were performed in triplicate for each isolate and an ANOVA with Tukey's post hoc was performed considering p < 0.05 as significant. The AF showed a decrease in maximum growth rate (µmax) and OD max levels (Ymax) in all isolates with all concentrations. Also, zones of inhibition were observed due to the effect of all AF concentrations in all isolates in a dose-dependent manner. Interestingly, S. aureus biofilm formation was inhibited by all AF concentrations assessed in this study. More investigations are required to elucidate the mechanisms of action of AF on S. aureus as well as in vivo studies to evaluate its therapeutic efficacy for bovine mastitis.

Predictors of fall risk in older adults using the G-STRIDE inertial sensor: an observational multicenter case-control study.

BACKGROUND: There are a lot of tools to use for fall assessment, but there is not yet one that predicts the risk of falls in the elderly. This study aims to evaluate the use of the G-STRIDE prototype in the analysis of fall risk, defining the cut-off points to predict the risk of falling and developing a predictive model that allows discriminating between subjects with and without fall risks and those at risk of future falls. METHODS: An observational, multicenter case-control study was conducted with older people coming from two different public hospitals and three different nursing homes. We gathered clinical variables ( Short Physical Performance Battery (SPPB), Standardized Frailty Criteria, Speed 4 m walk, Falls Efficacy Scale-International (FES-I), Time-Up Go Test, and Global Deterioration Scale (GDS)) and measured gait kinematics using an inertial measure unit (IMU). We performed a logistic regression model using a training set of observations (70% of the participants) to predict the probability of falls. RESULTS: A total of 163 participants were included, 86 people with gait and balance disorders or falls and 77 without falls; 67,8% were females, with a mean age of 82,63 ± 6,01 years. G-STRIDE made it possible to measure gait parameters under normal living conditions. There are 46 cut-off values of conventional clinical parameters and those estimated with the G-STRIDE solution. A logistic regression mixed model, with four conventional and 2 kinematic variables allows us to identify people at risk of falls showing good predictive value with AUC of 77,6% (sensitivity 0,773 y specificity 0,780). In addition, we could predict the fallers in the test group (30% observations not in the model) with similar performance to conventional methods. CONCLUSIONS: The G-STRIDE IMU device allows to predict the risk of falls using a mixed model with an accuracy of 0,776 with similar performance to conventional model. This approach allows better precision, low cost and less infrastructures for an early intervention and prevention of future falls.

Assessing falls in the elderly population using G-STRIDE foot-mounted inertial sensor.

Falls are one of the main concerns in the elderly population due to their high prevalence and associated consequences. Guidelines for the management of the elder with falls are comprised of multidimensional assessments, especially gait and balance. Daily clinical practice needs for timely, effortless, and precise tools to assess gait. This work presents the clinical validation of the G-STRIDE system, a 6-axis inertial measurement unit (IMU) with onboard processing algorithms, that allows the calculation of walking-related metrics correlated with clinical markers of fall risk. A cross-sectional case-control study was conducted with 163 participants (falls and non-falls groups). All volunteers were assessed with clinical scales and conducted a 15-min walking test at a self-selected pace while wearing the G-STRIDE. G-STRIDE is a low-cost solution to facilitate the transfer to society and clinical evaluations. It is open hardware and flexible and, thus, has the advantage of providing runtime data processing. Walking descriptors were derived from the device, and a correlation analysis was conducted between walking and clinical variables. G-STRIDE allowed measuring walking parameters in non-restricted walking conditions (e.g. hallway). Walking parameters statistically discriminate between falls and non-falls groups. We found good/excellent estimation accuracy (ICC = 0.885; [Formula: see text]) for walking speed, showing good/excellent correlation between gait speed and several clinical variables. G-STRIDE can calculate walking-related metrics that allow for discrimination between falls and non-falls groups, which correlates with clinical indicators of fall risk. A preliminary fall-risk assessment based on the walking parameters was found to improve the Timed Up and Go test in the identification of fallers.

External clinical validation of automated software to identify structural abnormalities and microhaemorrhages in nailfold videocapillaroscopy images.

OBJECTIVES: Automated systems to analyse nailfold videocapillaroscopy (NVC) images are needed to promptly and comprehensively characterise patients with systemic sclerosis (SSc) or Raynaud's phenomenon (RP). We previously developed, and validated in-house, a deep convolutional neural network-based algorithm to classify NVC-captured images according to the presence/absence of structural abnormalities and/or microhaemorrhages. We present its external clinical validation. METHODS: A total of 1,164 NVC images of RP patients were annotated by 5 trained capillaroscopists according to the following categories: normal capillary; dilation; giant capillary; abnormal shape; tortuosity; microhaemorrhage. The images were also presented to the algorithm. Matches and discrepancies between algorithm predictions and those annotations obtained by consensus of ≥3 or ≥4 interobservers were analysed. RESULTS: Consensus among ≥3 capillaroscopists was achieved in 86.9% of images, 75.8% of which were correctly predicted by the algorithm. Consensus among ≥4 experts occurred in 52.0% of cases, in which 87.1% of the algorithm's results matched with those of the expert panel. The algorithm's positive predictive value was >80% for microhaemorrhages and unaltered, giant or abnormal capillaries. Sensitivity was >75% for dilations and tortuosities. Negative predictive value and specificity were >89% for all categories. CONCLUSIONS: This external clinical validation suggests that this algorithm is useful to assist in the diagnosis and follow-up of SSc or RP patients in a timely manner. It may also be helpful in the management of patients with any pathology presenting with microvascular changes, as the algorithm has been designed to also be useful for research aiming at extending the usage of nailfold capillaroscopy to more conditions.

Tofacitinib Is an Effective Treatment for Refractory Scleromyositis Associated With Anti-PM/Scl.

Scleromyositis is a rare autoimmune disease characterized by overlapping scleroderma and myositis. This case report discusses the presentation and management of a 28-year-old male with scleromyositis presenting with myositis, arthritis, Raynaud's phenomenon, refractory calcinosis, interstitial lung disease, and myocarditis. This case highlights key points in the systematic approach to immunosuppressive treatment and proposes a novel therapeutic option.

Cardiac involvement in a Spanish unicentric prospective cohort of patients with systemic lupus erythematosus.

BACKGROUND: Cardiac involvement is one of the most frequent manifestations of Systemic Lupus Erythematosus (SLE). Transthoracic echocardiogram (TTE) may be valuable for the early detection of cardiac abnormalities in SLE. Few studies analyze both TTE findings in SLE and the risk factors that predispose to different cardiac manifestations in a long follow-up cohort. We aimed to investigate cardiac involvement's prevalence, risk factors, and outcomes in a Spanish Lupus Clinic. METHODS: Spanish single-center prospective study of cardiac involvement in SLE. Two hundred and one patients met the 2019 EULAR/ACR classification criteria, performed TTE, and were eligible for the study. RESULTS: Cardiac involvement was present in 43.8%. Patients with older age, hypertension, hyperlipidemia, higher body mass index, peripheral arterial disease, thrombosis, and major cardiovascular events had significantly more cardiac involvement. Neurological, hematological, and serosal involvement (pleuritis and/or pericarditis) were clinical risk factors for abnormal TTE. The combination of the four clinical variables (dyspnea, chest pain, cough, and/or syncope) was present in 40.9% of the patients with abnormal TTE in the follow-up and was superior to each of the manifestations separately. Troponin I (TnI) ≥ 0.2 ng/mL and NTproBNP ≥ 300 pg/mL were excellent biomarkers with a good correlation with cardiac abnormalities. Anti-B2GP1 was the only autoantibody associated with cardiac involvement in our cohort. Presenting cardiac involvement was correlated with higher SLICC Damage Index and increased mortality risk in the 2-year follow-up period. CONCLUSIONS: Cardiac involvement in SLE is diverse, heterogeneous, and highly prevalent. Presenting a pathological TTE was associated with greater damage accrual and greater mortality. Based on our results, we consider that echocardiographic screening of patients with SLE is essential, especially those symptomatic and/or with risk factors, to diagnose and treat cardiac involvement earlier.

Dietary encapsulated Bifidobacterium animalis and Agave fructans improve growth performance, health parameters, and immune response in broiler chickens.

OBJECTIVE: The present study was conducted to evaluate the effects of dietary supplementation with Bifidobacterium animalis, Agave fructans, and symbiotic of both encapsulated on growth performance, feed efficiency, blood parameters, and immune status in broiler chickens, and to compare these with diets including antibiotic growth promoters and without additives. METHODS: A comparative experimental study was carried out with 135 male Ross 308 broiler chickens. Each trial was divided into 5 equal groups. Control group (CON) received a standard diet without growth promoter; GPA, a standard diet with colistin sulfate and zinc bacitracin (0.25 g/kg of feed); PRE, a standard diet with 1% Agave fructans; PRO, a standard diet with Bifidobacterium animalis (11.14±0.70 log CFU/g); SYM, a standard diet with B. animalis and Agave fructans. RESULTS: A significant decrease in food consumption was found for the GPA, PRE, and SYM, compared to the CON group. The results show a better feed conversion index in PRE and GPA with respect to the CON group with the highest conversion index. Interestingly, the weight of the gastrointestinal tract shows a statistically significant difference between GPA and PRE groups. Moreover, the length of the gastrointestinal tract of the GPA group was less than the PRE group. In the total leukocyte count, there was a statistically significant increase in the GPA group compared to the CON, PRE, and PRO groups, and the heterophiles-lymphocytes index was lower in PRO. Regarding the cytokines, interleukin 10 (IL-10) decreased in PRO compared to CON and PRE, while IL-1ß increased in the SYM group. CONCLUSION: Alternative treatments were shown to achieve similar productive results as growth-promoting antibiotics and showed improvement over diet without additives; however, they have immunomodulatory properties and improved the development of the gastrointestinal tract compared to the treatment of growth-promoting antibiotics.

The challenge of comprehensive nailfold videocapillaroscopy practice: a further contribution.

OBJECTIVES: Although classification systems and scores for capillaroscopy interpretation have been published, there is a lack of homogenization for the procedure, especially in the way and place the images are taken, the counting of the capillaries and the measuring of their size. Our objective is to provide a deep learning-based software to obtain objective and exhaustive data for the whole nailfold without increasing the time or effort needed to do the examination, or requiring expensive equipment. METHODS: An automated software to count nailfold capillaries has been designed, through an exploratory image dataset of 2,713 images with 18,000 measurements of 3 different types. Subsequently, application rules have been created to detect the morphology of nailfold videocapillaroscopy images, through a training set of images. The software reliability has been evaluated with standard metrics used in the machine learning field for object detection tasks, comparing automatic and manual counting on the same NVC images. RESULTS: A mean average precision (mAP) of 0.473 is achieved for detecting and classifying capillaries and haemorrhages by their shape, and a mAP of 0.515 is achieved for detecting and classifying capillaries by their size. A precision of 83.84% and a recall of 92.44% in the identification of capillaries was estimated. CONCLUSIONS: Deep learning is a useful tool in nailfold videocapillaroscopy that allows to analyse objectively and homogeneously images taken with multiple devices. It should make the assessment of the capillary morphology in nailfold video capillaroscopy easier, quicker, more complete and accessible to everyone.

Phytosterol Extract Decreases the Oxidative Damage in the Brains of Diabetic db/db Mice.

Introduction: Hypercaloric diets induce oxidative stress, and consequently induce hyperglycemia and type 2 diabetes mellitus (T2DM). Thus, oxidative stress is significantly increased in T2DM, leading to oxidative damage to brain, which might contribute to cognitive deficits and neurodegenerative diseases. Therefore, reducing the oxidative stress is important to preserving cognitive functions, and it has been suggested that phytosterols may reduce the oxidative stress. Objective: The objective of the present study was to determine the effects of phytosterols derived from corn on oxidative damage in the cerebellum, frontal cortex, and hippocampus of diabetic db/db mice. Materials and Methods: A phytosterol extract was isolated from yellow corn (Zea mays L.) and 100 mg/kg of the extract was administrated daily to diabetic mice for 8 weeks. At the end of the treatment period, tissues were isolated to determine the levels of oxidized lipid and protein. Results: The phytosterol treatment increased body weight in diabetic db/db mice, but this treatment did not have any effects on body weight in wild-type mice. Moreover, the phytosterol treatment decreased levels of oxidized lipids in the cerebellum, frontal cortex, and hippocampus, and also decreased the levels of oxidized proteins in the cerebellum and frontal cortex in diabetic db/db mice. Conclusion: These important results show that phytosterol treatment can reduce oxidative damage in the brains of diabetic mice.

Postbiotics in human health: Possible new functional ingredients?

The human intestinal microbiota is a set of microorganisms that inhabit the gastrointestinal tract and have a symbiotic relationship with the host. These microorganisms are involved in the regulation of many host metabolic pathways and are related to the host's immune and neurological responses. Probiotic beneficial bacteria and their mechanisms have been extensively studied. However, the health effects of its metabolites or structural components, such as functional ingredients on health have been less explored. Postbiotics can be classified as structural, such as peptides, teichoic acids and plasmalogens. They can also be classified; as well as the metabolites generated by the microbiota; these are short chain fatty acids (SCFAs), vitamins and enzymes. Studies with other types of postbiotics, mainly derived from Lactobacillus, have demonstrated their immunological effects by raising mucin levels and, promoting the development of claudin and occluding. They have also demonstrated decreasing several interleukins of immunological interest. Furthermore, recognized as possible functional ingredients compared to other biotics, they have a longer shelf life and an excellent potential to develop fermented products, being a very good alternative to generate foods with specific health effects. The objective of this review is to describe the characteristics and mechanisms of action of different postbiotics, as well as to present the benefits found in in vitro, clinical trials and in the food industry, proposing them as possible new functional ingredients.

Self-reported cognitive biases in depression: A meta-analysis.

Despite the influence of Beck's cognitive models of depression, the presence and magnitude of the specific proposed cognitive biases have not been systematically investigated. After a systematic search in PsycInfo and PubMED, studies reporting self-reported outcomes on cognitive biases and depressive symptoms in depressed and/or healthy groups were included. From a total of 4840 records, two different meta-analyses were conducted. 23 studies on 4865 participants provided data about catastrophising and depression (g = 0.95, 95% CI [0.64; 1.26]) and 40 studies on 4678 participants provided data about interpretation bias in depression (g = 0.78, 95% CI [0.43; 1.13]). Moderation analyses showed that the relationship between catastrophising and depression was higher in studies with more women, when the corresponding author was from a Western country, and when the instrument to measure depression was the DSM criteria, the SCL-90, the BDI, or the DASS. The relationship between interpretation bias and depressive symptoms was significant only in studies comparing depressed and healthy groups, and when using specific instruments to measure symptoms (DSM/RDC criteria plus a scale cut-off score) and cognitive bias (CDQ/CBQ, SCT, AST-D, other). Some limitations are acknowledged, but risk of publication bias was found to be low, and these results support the utility of some self-reported measures of cognitive biases in depression.

Antibacterial activity of agave fructans against salmonella typhimurium.

The objective of this study was to evaluate the antimicrobial effect of Agave fructans against the Salmonella Typhimurium in "in vitro" experiments. The result of the antimicrobial activity was 263.89 ± 0, 414.95 ± 12.83, 494.54 ± 13.88, 522.29 ± 0, 580.41 ± 14.92 AU for 10, 20, 30, 40 and 50% of Agave fructans (AF) respectively. In addition, there is a significant effect on the growth of the bacteria with all the percentages of AF evaluated (p < 0.001, R2 = 0.859) with respect to the control. The growth rate of Salmonella with 25% AF was statistically significant compared to the control (-0.7353 ± 0.586, 0.0079 ± 0.002 D.O./h, respectively; p > 0.01). Agave fructans could be an alternative to prevent the infections caused by Salmonella.

Surveillance of adverse events in the treatment of drug-resistant tuberculosis: A global feasibility study.

The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries. The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs. Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile. A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019.