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Background Water is the lifeblood of river networks, and its quality plays a crucial role in sustaining both aquatic ecosystems and human societies. Real-time monitoring of water quality is increasingly reliant on in-situ sensor technology. Anomaly detection is crucial for identifying erroneous patterns in sensor data, but can be a challenging task due to the complexity and variability of the data, even under typical conditions. This paper presents a solution to the challenging task of anomaly detection for river network sensor data, which is essential for accurate and continuous monitoring. Methods We use a graph neural network model, the recently proposed Graph Deviation Network (GDN), which employs graph attention-based forecasting to capture the complex spatio-temporal relationships between sensors. We propose an alternate anomaly threshold criteria for the model, GDN+, based on the learned graph. To evaluate the model’s efficacy, we introduce new benchmarking simulation experiments with highly-sophisticated dependency structures and subsequence anomalies of various types. We also introduce software called gnnad. Results We further examine the strengths and weaknesses of this baseline approach, GDN, in comparison to other benchmarking methods on complex real-world river network data. Conclusions Findings suggest that GDN+ outperforms the baseline approach in high-dimensional data, while also providing improved interpretability.

ObjectiveCharacterize the neurophysiological effects of mild hypothermia on stroke and spreading depolarizations (SDs) in gyrencephalic brains.MethodsLeft middle cerebral arteries (MCAs) of six hypothermic and six normothermic pigs were permanently occluded (MCAo). Hypothermia began 1 h after MCAo and continued throughout the experiment. ECoG signals from both frontoparietal cortices were recorded. Five-minute ECoG epochs were collected 5 min before, at 5 min, 4, 8, 12, and 16 h after MCAo, and before, during, and after SDs. Power spectra were decomposed into fast (alpha, beta, and gamma) and slow (delta and theta) frequency bands.ResultsIn the vascular insulted hemisphere under normothermia, electrodes near the ischemic core exhibited power decay across all frequency bands at 5 min and the 4th hour after MCAo. The same pattern was registered in the two furthest electrodes at the 12th and 16th hour. When mild hypothermia was applied in the vascular insulted hemispheres, the power decay was generalized and seen even in electrodes with uncompromised blood flow. During SD analysis, hypothermia maintained increased delta and beta power during the three phases of SDs in the furthest electrode from the ischemic core, followed by the second furthest and third electrode in the beta band during preSD and postSD segments. However, in hypothermic conditions, the third electrode showed lower delta, theta, and alpha power.ConclusionMild hypothermia attenuates all frequency bands in the vascularly compromised hemisphere, irrespective of the cortical location. During SD formation, it preserves power spectra more significantly in electrodes further from the ischemic core.

Abstract We develop a novel global perspective of the complexity of the relationships between three COVID-19 datasets, the standardised per-capita growth rate of COVID-19 cases and deaths, and the Oxford Coronavirus Government Response Tracker COVID-19 Stringency Index (CSI) which is a measure describing a country’s stringency of lockdown policies. We use a state-of-the-art heterogeneous intrinsic dimension estimator implemented as a Bayesian mixture model, called Hidalgo. Our findings suggest that these highly popular COVID-19 statistics may project onto two low-dimensional manifolds without significant information loss, suggesting that COVID-19 data dynamics are generated from a latent mechanism characterised by a few important variables. The low dimensionality imply a strong dependency among the standardised growth rates of cases and deaths per capita and the CSI for countries over 2020–2021. Importantly, we identify spatial autocorrelation in the intrinsic dimension distribution worldwide. The results show how high-income countries are more prone to lie on low-dimensional manifolds, likely arising from aging populations, comorbidities, and increased per capita mortality burden from COVID-19. Finally, the temporal stratification of the dataset allows the examination of the intrinsic dimension at a more granular level throughout the pandemic.

Various methods have been developed to combine inference across multiple sets of results for unsupervised clustering, within the ensemble clustering literature. The approach of reporting results from one 'best' model out of several candidate clustering models generally ignores the uncertainty that arises from model selection, and results in inferences that are sensitive to the particular model and parameters chosen. Bayesian model averaging (BMA) is a popular approach for combining results across multiple models that offers some attractive benefits in this setting, including probabilistic interpretation of the combined cluster structure and quantification of model-based uncertainty. In this work we introduce clusterBMA, a method that enables weighted model averaging across results from multiple unsupervised clustering algorithms. We use clustering internal validation criteria to develop an approximation of the posterior model probability, used for weighting the results from each model. From a combined posterior similarity matrix representing a weighted average of the clustering solutions across models, we apply symmetric simplex matrix factorisation to calculate final probabilistic cluster allocations. In addition to outperforming other ensemble clustering methods on simulated data, clusterBMA offers unique features including probabilistic allocation to averaged clusters, combining allocation probabilities from 'hard' and 'soft' clustering algorithms, and measuring model-based uncertainty in averaged cluster allocation. This method is implemented in an accompanying R package of the same name. We use simulated datasets to explore the ability of the proposed technique to identify robust integrated clusters with varying levels of separation between subgroups, and with varying numbers of clusters between models. Benchmarking accuracy against four other ensemble methods previously demonstrated to be highly effective in the literature, clusterBMA matches or exceeds the performance of competing approaches under various conditions of dimensionality and cluster separation. clusterBMA substantially outperformed other ensemble methods for high dimensional simulated data with low cluster separation, with 1.16 to 7.12 times better performance as measured by the Adjusted Rand Index. We also explore the performance of this approach through a case study that aims to identify probabilistic clusters of individuals based on electroencephalography (EEG) data. In applied settings for clustering individuals based on health data, the features of probabilistic allocation and measurement of model-based uncertainty in averaged clusters are useful for clinical relevance and statistical communication.

AimTo describe the spatial and temporal electrocorticographic (ECoG) changes after middle cerebral artery occlusion (MCAo), including those caused by spreading depolarization (SD) in the pig brain.MethodsThe left middle cerebral arteries (MCAs) were clipped in six pigs. The clipping procedure lasted between 8 and 12 min, achieving a permanent occlusion (MCAo). Five-contact ECoG stripes were placed bilaterally over the frontoparietal cortices corresponding to the irrigation territory of the MCA and anterior cerebral artery (ACA). ECoG recordings were performed around 24 h: 1 h before and 23 h after the MCAo, and SDs were quantified. Five-minute ECoG signal segments were sampled before, 5 min, and 4, 8, and 12 h after cerebral artery occlusion and before, during, and after the negative direct current shift of the SDs. The power spectrum of the signals was decomposed into delta, theta, alpha, beta, and gamma bands. Descriptive statistics, Wilcoxon matched-pairs signed-rank tests, and Friedman tests were performed.ResultsElectrodes close to the MCAo showed instant decay in all frequency bands and SD onset during the first 5 h. Electrodes far from the MCAo exhibited immediate loss of fast frequencies and progressive decline of slow frequencies with an increased SD incidence between 6 and 14 h. After 8 h, the ACA electrode reported a secondary reduction of all frequency bands except gamma and high SD incidence within 12–17 h. During the SD, all electrodes showed a decline in all frequency bands. After SD passage, frequency band recovery was impaired only in MCA electrodes.ConclusionECoG can identify infarct progression and secondary brain injury. Severe disturbances in all the frequency bands are generated in the cortices where the SDs are passing by.

Two Sustainable Development Goals are focused directly on combating the impacts of climate change on coral reef communities: Goal 13, Climate Action (Take urgent action to combat climate change and its impacts) and Goal 14, Life Below Water (Conserve and sustainably use the oceans, seas and marine resources for sustainable development). Citizen science (CS) features prominently in a range of programs that have been developed to address the SDGs. One such program is Virtual Reef Diver, which is designed to help monitor the health of the Great Barrier Reef in Australia. This program engages citizen scientists in two ways. Scuba-divers are asked to take geo-coded underwater images of the reef and upload them to an online virtual reef. Members of the public across the world are then asked to classify these images with respect to key reef indicators such as coral. Through the lens of a Virtual Reef Diver event held as part of Australia’s National Science Week 2021, we describe important features of this program that positively address common concerns about CS data, including the scientific trustworthiness of the data, the ability to incorporate these data with other more traditional data sources, and the quantifiable improvement in information about reef health using these data for management decisions. This demonstrates the important role that citizen science can play in achieving the SDGs by supporting the development of global policies for coral reef conservation.

Abstract The ability of photoacoustic imaging to measure functional tissue properties, such as blood oxygenation sO $$_2$$ 2 , enables a wide variety of possible applications. sO $$_2$$ 2 can be computed from the ratio of oxyhemoglobin HbO $$_2$$ 2 and deoxyhemoglobin Hb, which can be distuinguished by multispectral photoacoustic imaging due to their distinct wavelength-dependent absorption. However, current methods for estimating sO $$_2$$ 2 yield inaccurate results in realistic settings, due to the unknown and wavelength-dependent influence of the light fluence on the signal. In this work, we propose learned spectral decoloring to enable blood oxygenation measurements to be inferred from multispectral photoacoustic imaging. The method computes sO $$_2$$ 2 pixel-wise, directly from initial pressure spectra $$S_{\text {p}_0}(\lambda , \mathbf {x})$$ S p 0 ( λ , x ) , which represent initial pressure values at a fixed spatial location $$\mathbf {x}$$ x over all recorded wavelengths $$\lambda$$ λ . The method is compared to linear unmixing approaches, as well as pO $$_2$$ 2 and blood gas analysis reference measurements. Experimental results suggest that the proposed method is able to obtain sO $$_2$$ 2 estimates from multispectral photoacoustic measurements in silico, in vitro, and in vivo.

Abstract Objective Spreading depolarizations (SD) are characterized by breakdown of transmembrane ion gradients and excitotoxicity. Experimentally, N-methyl-d-aspartate receptor (NMDAR) antagonists block a majority of SDs. In many hospitals, the NMDAR antagonist s-ketamine and the GABAA agonist midazolam represent the current second-line combination treatment to sedate patients with devastating cerebral injuries. A pressing clinical question is whether this option should become first-line in sedation-requiring individuals in whom SDs are detected, yet the s-ketamine dose necessary to adequately inhibit SDs is unknown. Moreover, use-dependent tolerance could be a problem for SD inhibition in the clinic. Methods We performed a retrospective cohort study of 66 patients with aneurysmal subarachnoid hemorrhage (aSAH) from a prospectively collected database. Thirty-three of 66 patients received s-ketamine during electrocorticographic neuromonitoring of SDs in neurointensive care. The decision to give s-ketamine was dependent on the need for stronger sedation, so it was expected that patients receiving s-ketamine would have a worse clinical outcome. Results S-ketamine application started 4.2 ± 3.5 days after aSAH. The mean dose was 2.8 ± 1.4 mg/kg body weight (BW)/h and thus higher than the dose recommended for sedation. First, patients were divided according to whether they received s-ketamine at any time or not. No significant difference in SD counts was found between groups (negative binomial model using the SD count per patient as outcome variable, p = 0.288). This most likely resulted from the fact that 368 SDs had already occurred in the s-ketamine group before s-ketamine was given. However, in patients receiving s-ketamine, we found a significant decrease in SD incidence when s-ketamine was started (Poisson model with a random intercept for patient, coefficient − 1.83 (95% confidence intervals − 2.17; − 1.50), p

Background: Disease progression and delayed neurological complications are common after aneurysmal subarachnoid hemorrhage (aSAH). We explored the potential of quantitative blood-brain barrier (BBB) imaging to predict disease progression and neurological outcome. Methods: Data were collected as part of the Co-Operative Studies of Brain Injury Depolarizations (COSBID). We analyzed retrospectively, blinded and semi-automatically magnetic resonance images from 124 aSAH patients scanned at 4 time points (24–48 h, 6–8 days, 12–15 days and 6–12 months) after the initial hemorrhage. Volume of brain with apparent pathology and/or BBB dysfunction (BBBD), subarachnoid space and lateral ventricles were measured. Neurological status on admission was assessed using the World Federation of Neurosurgical Societies and Rosen-Macdonald scores. Outcome at ≥6 months was assessed using the extended Glasgow outcome scale and disease course (progressive or non-progressive based on imaging-detected loss of normal brain tissue in consecutive scans). Logistic regression was used to define biomarkers that best predict outcomes. Receiver operating characteristic analysis was performed to assess accuracy of outcome prediction models. Findings: In the present cohort, 63% of patients had progressive and 37% non-progressive disease course. Progressive course was associated with worse outcome at ≥6 months (sensitivity of 98% and specificity of 97%). Brain volume with BBBD was significantly larger in patients with progressive course already 24–48 h after admission (2.23 (1.23–3.17) folds, median with 95%CI), and persisted at all time points. The highest probability of a BBB-disrupted voxel to become pathological was found at a distance of ≤1 cm from the brain with apparent pathology (0·284 (0·122–0·594), p

Virtual reality (VR) technology is an emerging tool that is supporting the connection between conservation research and public engagement with environmental issues. The use of VR in ecology consists of interviewing diverse groups of people while they are immersed within a virtual ecosystem to produce better information than more traditional surveys. However, at present, the relatively high level of expertise in specific programming languages and disjoint pathways required to run VR experiments hinder their wider application in ecology and other sciences. We present R2VR, a package for implementing and performing VR experiments in R with the aim of easing the learning curve for applied scientists including ecologists. The package provides functions for rendering VR scenes on web browsers with A-Frame that can be viewed by multiple users on smartphones, laptops, and VR headsets. It also provides instructions on how to retrieve answers from an online database in R. Three published ecological case studies are used to illustrate the R2VR workflow, and show how to run a VR experiments and collect the resulting datasets. By tapping into the popularity of R among ecologists, the R2VR package creates new opportunities to address the complex challenges associated with conservation, improve scientific knowledge, and promote new ways to share better understanding of environmental issues. The package could also be used in other fields outside of ecology.

Manufacturing processes are often based on more than one quality characteristic. When these variables are correlated the process capability analysis should be performed using multivariate statistical methodologies. Although there is a growing interest in methods for evaluating the capability of multivariate processes, little attention has been given to developing user friendly software for supporting multivariate capability analysis. In this work we introduce the package MPCI for R, which allows to compute multivariateprocess capability indices. MPCI aims to provide a useful tool for dealing with multivariate capability assessment problems. We illustrate the use of MPCI package through both simulated and real examples.

Home energy monitoring has recently become a very important issue and a means to reduce energy consumption in the residential sector. Sensors and control systems are deployed at various locations in a house and an intelligent system is used to efficiently manage the consumed energy. Low power communication systems are used to provide low power consumption from a smart meter. Several of these systems are battery operated. Other systems use AC/DC adapters to supply power to sensors and communication systems. However, even using low-power technology, such as ZigBee, the power consumption of a router can be high because it must always be powered on. In this work, to evaluate power consumption, a system for monitoring energy usage and indoor air quality was developed. A technique is proposed to efficiently supply power to the components of the system. All sensor nodes are battery operated, and relays are used to control the battery charging process. In addition, an energy harvesting system based on solar energy was developed to power the proposed system.

Purpose - The paper aims to study the friction behaviour of alumina and zirconia against steel DIN-Ck45K under water lubricated conditions. Design/methodology/approach - The tests were performed with a contact stress of 3.5?MPa and a constant sliding velocity of 0.5?m/s for 5.35?km of sliding distance, using a pin-on-disk tribometer. Findings - The friction coefficient and the energy dissipated in the contact were considered in this comparative study. The zirconia ceramic present less friction coefficient and contact temperature than alumina ceramic. The zirconia present about 70 per cent of the energy dissipated against when compared with the alumina. Abrasive scars of the surface ploughing were observed on every wear track for two pairs in contact. Research limitations/implications - This research used only one test condition. Originality/value - The paper describes the tribological conditions used and a new methodology based on the energy dissipated in the contact is proposed. [ABSTRACT FROM AUTHOR]

Background and Objectives: Antiplatelet therapy is recommended as the standard treatment for patients with acute ischemic stroke (AIS) who, for several reasons, did not receive thrombolysis or thrombectomy. However, whether tirofiban or aspirin provides greater benefits for these patients remains unclear. Therefore, we aimed to perform a meta-analysis comparing the functional outcomes and hemorrhagic risks associated with tirofiban and aspirin in the management of AIS., Methods: We searched PubMed, EMBASE, Web of Science, and Cochrane Library for studies comparing tirofiban to aspirin in patients with AIS who did not receive thrombolysis or thrombectomy until September 2024. Outcomes were modified Rankin Scale (mRS) and mortality at 90 days, symptomatic intracranial hemorrhage, and any bleeding events. Statistical analysis was performed using the R Studio (version 2024.04.1+748)., Results: We included 3 randomized controlled trials with a total of 1959 patients, of whom 996 (50.8 %) were in the tirofiban group. Excellent (mRS 0-1) functional outcome (RR 1.25, 95 % CI: 1.05-1.49; I 2 = 70 %) and favorable (mRS 0-2) functional outcome at 90 days (RR 1.09, 95 % CI: 1.01-1.16; I 2 = 35 %) were significantly higher in tirofiban compared to aspirin. Furthermore, tirofiban showed no difference in mortality (RR 0.77, 95 % CI: 0.24-2.53; I 2 = 56 %), or symptomatic intracranial hemorrhage (RR 3.42, 95 % CI: 0.27-43.30; I 2 = 38 %). However, any bleeding event (RR 1.75, 95 % CI: 1.25-2.45; I 2 = 0 %) was more common in the tirofiban group. Lastly, the meta-regression analysis showed that the outcomes were not influenced by the initial NIHSS of the included studies (p > 0.05)., Conclusion: Tirofiban is associated with better functional outcomes at 90 days, with no difference in mortality. Additionally, despite being associated with higher bleeding events, there is no difference in symptomatic intracranial hemorrhage. Therefore, our results suggest that tirofiban is a promising alternative to aspirin., Competing Interests: Conflict of Interest The authors declare no conflicts of interest related to the research, authorship, or publication of this scientific paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cutaneous leishmaniasis (CL), caused by Leishmania braziliensis , is closely associated with a severe form of the disease, indicated by a positive Leishmania skin test (LST) that assesses and reflects the presence of immune T cells specific to Leishmania antigens. In this study, we compare the clinical, immunologic, and histopathologic features between Leishmania skin test-positive (LST+) and Leishmania skin test-negative (LST-) in CL. Compared to LST+ patients, LST- patients had larger lesions and had been sicker for longer, presented with more instances of therapeutic failure with meglumine antimonate, (MA) and the healing times were higher than LST+. While granulomas were less frequent and the parasite load was higher in LST-, there were more CD8+ T cells and an enhanced production of Granzyme B in the supernatants of biopsies from LST- subjects. This study shows that in LST-, an impairment in Th1 immune response is associated with a high parasite burden, and the pathology is mediated by CD8+ T cells and the enhanced production of Granzyme B. The abnormalities in the immunologic response in LST- patients lead to a more severe disease with a high rate of failure to therapy.

Background: The Brazilian Policy for Comprehensive Care for People with Rare Diseases was implemented in 2014; however, national epidemiological data on rare diseases (RDs) are scarce and mainly focused on specific disorders. To address this gap, University Hospitals, Reference Services for Neonatal Screening, and Reference Services for Rare Diseases, all of which are public health institutions, established the Brazilian Rare Diseases Network (RARAS) in 2020. The objective of this study was to perform a comprehensive nationwide epidemiological investigation of individuals with RDs in Brazil. This retrospective survey collected data from patients receiving care in 34 healthcare facilities affiliated with RARAS in 2018 and 2019., Results: The survey included 12,530 participants with a median age of 15.0 years, with women representing 50.5% of the cohort. Classification according to skin color demonstrated that 5044 (47.4%) participants were admixed. Most had a confirmed diagnosis (63.2%), with a predominance of phenylketonuria (PKU), cystic fibrosis (CF), and acromegaly. Common clinical manifestations included global developmental delay and seizures. The average duration of the diagnostic odyssey was 5.4 years (± 7.9 years). Among the confirmed diagnoses, 52.2% were etiological (biochemical: 42.5%; molecular: 30.9%), while 47.8% were clinical. Prenatal diagnoses accounted for 1.2%. Familial recurrence and consanguinity rates were 21.6% and 6.4%, respectively. Mainstay treatments included drug therapy (55.0%) and rehabilitation (15.6%). The Public Health System funded most diagnoses (84.2%) and treatments (86.7%). Hospitalizations were reported in 44.5% of cases, and the mortality rate was 1.5%, primarily due to motor neuron disease and CF., Conclusion: This study marks a pioneering national-level data collection effort for rare diseases in Brazil, offering novel insights to advance the understanding, management, and resource allocation for RDs. It unveils an average diagnostic odyssey of 5.4 years and a higher prevalence of PKU and CF, possibly associated with the specialized services network, which included newborn screening services., (© 2024. The Author(s).)

The efficacy and safety of dual antiplatelet therapy (DAPT) relative to intravenous (IV) alteplase in patients with acute minor ischemic stroke are insufficiently established. Therefore, we aimed to perform a meta-analysis to compare DAPT with IV alteplase in patients with acute minor stroke. MEDLINE, Embase, and Cochrane were searched for studies comparing DAPT with IV alteplase in patients with minor stroke. Functional and safety outcomes in 90 days were analyzed. Statistical analysis was performed using Rstudio 4.3.1. Subanalyses were performed restricted to non-disabling minor strokes and NIHSS score ≤ 3. PROSPERO (CRD42023440986). We included five studies with a total of 6,340 patients, of whom 4,050 (63.9%) received DAPT. The follow-up period for all included studies was 90 days. There was no significant difference for individual outcomes of mRS 0-1 (OR 1.26; 95% CI 0.85-1.89; p = 0.25), mRS 0-2 (OR 0.99; 95% CI 0.69-1.43; p = 0.97), or all-cause mortality (OR 0.80; 95% CI 0.20-3.13; p = 0.75) between groups. Symptomatic intracranial hemorrhage (sICH) was significantly lower (OR 0.11; 95% CI 0.003-0.36; p < 0.001) in patients treated with DAPT compared with IV alteplase. In terms of mRS 0-1 and mRS 0-2, we found no significant difference in both subgroup analyses. We found no statistically significant difference between DAPT and IV alteplase regarding functional outcome (mRS scores of 0-1 and 0-2) or all-cause mortality at 90 days in patients with minor ischemic stroke. Additionally, DAPT was associated with a significantly lower rate of sICH., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate the association between occupational stressors and common mental disorders (CMD) among "invisible" health workers in the context of the COVID-19 pandemic., Method: Cross-sectional study including a probabilistic sample of 1,014 health workers from three municipalities in Bahia. CMDs were assessed using the SRQ-20. The Effort-Reward Imbalance (ERI) scale and the Demand-Control Model assessed occupational stressors. Descriptive, bivariate, and multiple analysis to evaluate the association between the variables of interest., Results: The global prevalence of CMD was 39.9%; it was higher among CHA/EDCA (47.2%), followed by management and surveillance staff (38.6%), technicians (35.4%), and support/maintenance/cleaning staff (29.9%). The association between occupational stressors and CMD varied among occupations: 1. Excessive work commitment (EWC), effort-reward imbalance (ERI), and psychological demand were associated with CMD among support/maintenance/cleaning workers; 2. EWC and ERI were associated with CMD among CHA/EDCA; 3. EWC, ERI, and low control over work were associated with CMD among technicians; 4. Among management and surveillance workers, only ERI remained associated with CMD., Conclusions: Occupational stressors played a relevant role in mental illness, with variation between occupational strata, demanding attention, monitoring, and control.

The objectives of this study were to assess the adequacy of physical parameters/factors (temperature, relative humidity, noise, and illuminance levels) of the work environment in PHC facilities, to evaluate the association between the adequacy of these measured physical parameters and the physical characteristics of the PHC facilities and their surroundings and to assess the association between health professionals' perceptions about exposure to physical risks in the PHC work environment and the adequacy of physical parameters measured in the same facilities. The study monitored 23 PHC facilities in southern Brazil and interviewed 210 health professionals. Data analysis involved Pearson's chi-square, Fisher's exact test, Spearman's correlation, and multivariate linear regression analysis was used to control for confounding factors. The significance level was set at 5% ( p ≤ 0.05). The combination of temperature and relative humidity presented thermal comfort levels outside the adopted criteria for adequacy in consultation (outdoor relative humidity, p = 0.013) and procedure rooms (front door open, p = 0.034). Inadequate sound comfort (noise) levels in the morning shift were found in the vaccination (front door open, p = 0.021) and consultation rooms (movement of people, p = 0.016). In PHC facilities where reception rooms had insufficient lighting, internal curtains were opened less frequently ( p = 0.047). The analysis of health professionals' perceptions of physical factors demonstrated that physicians more frequently perceive the physical risk of temperature and humidity ( p = 0.044). The higher the number of nurses ( p = 0.004) and oral health technicians in the PHC facilities ( p = 0.031), the greater the general percentage of adequacy of monitored physical parameters. It was also confirmed that the higher the perception of moderate or severe physical risk among health professionals, the lower the general percentage of the adequacy of the physical parameters of the work environment of the PHC facilities evaluated (r s = -0.450, p = 0.031). This study's evidence contributes to a better understanding of physical conditions and future occupational interventions to ensure the comfort, safety, and well-being of PHC workers., Competing Interests: Author Joana Cezar Vaz was employed by the Vibra Energia Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: The treatment of leprosy reactions (LRs) involves thalidomide, corticosteroids, and other immunomodulatory medications. This study evaluated the effect of these treatments on the association between periodontitis and LRs, as well as factors associated with LRs., Methods: This case-control study was conducted on 283 individuals followed at a leprosy outpatient clinic in Brazil. The case group was comprised of 158 individuals presenting type 1 or type 2 LRs, and the control group of 125 leprosy individuals without reactions. A complete oral examination was performed to diagnose periodontitis, the independent variable. Antireaction medication used was collected from medical records, and participants were classified according to the use of prednisone and/or thalidomide, time of use, or non-use of medication. Socioeconomic-demographic, clinical, and lifestyle covariables were collected by interview. Unconditional logistic regression analysis by subgroups evaluated the effect of antireaction medication on the association between periodontitis and LRs, estimating the odds ratio with a 95% confidence interval (OR; 95% CI)., Results: A relationship between periodontitis and LRs was observed only in the subgroup using the association prednisone and thalidomide: OR adjusted  = 0.32; 95% CI = 0.11-0.95. Conversely, more severe periodontal clinical parameters were observed in cases versus controls. Several socioeconomic, health conditions, and lifestyle factors were associated with the presence of LRs., Conclusions: Although periodontal disease indicators were worse among the cases, the findings showed a negative relationship between periodontitis and LRs in individuals receiving associated prednisone and thalidomide. These medications appear to influence the inflammatory cascade between diseases, modifying and masking the manifestations of periodontitis., (© 2024 American Academy of Periodontology.)

Introduction: This study evaluated outcomes and risk factors for COVID-19 in 91 Brazilian multiple myeloma (MM) patients between April 2020 and January 2022., Results: Of the 91 MM patients diagnosed with COVID-19, 64% had comorbidities and 66% required hospitalization due to COVID-19, with 44% needing ventilatory support and 37% intensive care. Age (OR 2.02; 95%CI 1.02 - 7.7) and hypertension OR 4.5; 95%CI 1.3 - 15.5) were independently associated with hospitalization and certain MM therapies (corticosteroids and monoclonal drugs) were associated with ventilatory support (OR 4.3; 95%CI 1.3 - 14 and OR 5.7; 95%CI 1.8 - 18, respectively), while corticosteroids and immunomodulatory drugs were linked to ICU admission (OR 5.1; 95% CI 1.4 - 18 and OR 3.4; 95%CI 1.1 - 10, respectively). The overall mortality rate was 30%, with the highest rate observed in the ICU (73%). Additionally, the ECOG performance status was linked to increased mortality (OR 11.5; 95%CI 1.9 - 69). The MM treatment was delayed in 63% of patients who recovered from COVID-19., Conclusions: The findings highlight the need for preventing COVID-19 and prioritizing vaccination among MM patients, as they have high rates of severe outcomes in the event of COVID-19. It is also essential to monitor the potential clinical impacts of COVID-19 on MM patients in the long-term. Given the limited resources available in treating MM patients in Brazil during the COVID-19 pandemic, outcomes might be worse in this population., Competing Interests: Conflicts of interest None of the authors has any conflicts of interest (direct or indirect) concerning the manuscript's contents., (Copyright © 2023 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Mucopolysaccharidosis type IIIB (MPS IIIB) is caused by deficiency of alpha-N-acetylglucosaminidase, leading to storage of heparan sulphate. The disease is characterized by intellectual disability and hyperactivity, among other neurological and somatic features. Here we studied retrospective data from a total of 19 MPS IIIB patients from Brazil, aiming to evaluate disease progression. Mean age at diagnosis was 7.2 years. Speech delay was one of the first symptoms to be identified, around 2-3 years of age. Behavioral alterations include hyperactivity and aggressiveness, starting around age four. By the end of the first decade, patients lost acquired abilities such as speech and ability to walk. Furthermore, as disease progresses, respiratory, cardiovascular and joint abnormalities were found in more than 50% of the patients, along with organomegaly. Most common cause of death was respiratory problems. The disease progression was characterized in multiple systems, and hopefully these data will help the design of appropriate clinical trials and clinical management guidelines.

Introduction: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), is a neurodegenerative autosomal recessive disease caused by TPP1 gene variants , with a spectrum of classic and atypical phenotypes. The aim of treatment is to slow functional decline as early as possible in an attempt to improve quality of life and survival. This study describes the clinical characteristics as well as the response to treatment with cerliponase alfa., Materials and Methods: A retrospective study was conducted in five Latin-American countries, using clinical records from patients with CLN2. Clinical follow-up and treatment variables are described. A descriptive and bivariate statistical analysis was performed., Results: A total of 36 patients were observed (range of follow-up of 61-110 weeks post-treatment). At presentation, patients with the classic phenotype ( n  = 16) exhibited regression in language (90%), while seizures were the predominant symptom (87%) in patients with the atypical phenotype ( n  = 20). Median age of symptom onset and time to first specialized consultation was 3 (classical) and 7 (atypical) years, while the median time interval between onset of symptoms and treatment initiation was 4 years (classical) and 7.5 (atypical). The most frequent variant was c.827 A > T in 17/72 alleles, followed by c.622C > T in 6/72 alleles. All patients were treated with cerliponase alfa, and either remained functionally stable or had a loss of 1 point on the CLN2 scale, or up to 2 points on the Wells Cornel and Hamburg scales, when compared to pretreatment values., Discussion and Conclusion: This study reports the largest number of patients with CLN2 currently on treatment with cerliponase alfa in the world. Data show a higher frequency of patients with atypical phenotypes and a high allelic proportion of intron variants in our region. There was evidence of long intervals until first specialized consultation, diagnosis, and enzyme replacement therapy. Follow-up after the initiation of cerliponase alfa showed slower progression or stabilization of the disease, associated with adequate clinical outcomes and stable functional scores. These improvements were consistent in both clinical phenotypes., Competing Interests: Dr. Atanacio has been a lecturer for the Biomarin Laboratory. Dr. Denzler has been a speaker for BioMarin. Dr. Durand has maintained a financial relationship with BioMarin through service contracts as speaker. Dr. Erlane has received travel grants, speaker fees, and educational grants from Biomarin. Dr. Espitia Segura reports a relationship with BioMarin Pharmaceutical Inc., including speaker fees and travel reimbursement. Dr. N Guelbert has received speaker fees from Biomarin. Dr. Pessoa has been a speaker for Biomarin. Dr. Naranjo and Dr. Tavera report a relationship with BioMarin Pharmaceutical Inc. that includes speaker and conference fees, as well as travel reimbursement., (© 2024 The Authors.)

Historically, all efforts against tuberculosis were focused on rapid diagnosis and effective treatment to break the chain of transmission of Mycobacterium tuberculosis. However, in the last few years, more and more evidence has been found on the dramatic consequences of the condition defined as post-tuberculosis lung disease (PTLD). Approximately one third of patients surviving pulmonary tuberculosis face considerable ongoing morbidities, including respiratory impairment, psychosocial challenges, and reduced health-related quality of life after treatment completion. Given the important global and local burden of tuberculosis, as well as the estimated burden of PTLD, the development of a consensus document by a Brazilian scientific society-Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)-was considered urgent for the prevention and management of this condition in order to allocate resources to and within tuberculosis services appropriately and serve as a guide for health care professionals. A team of eleven pulmonologists and one methodologist was created by the SBPT to review the current evidence on PTLD and develop recommendations adapted to the Brazilian context. The expert panel selected the topics on the basis of current evidence and international guidelines. During the first phase, three panel members drafted the recommendations, which were divided into three sections: definition and prevalence of PTLD, assessment of PTLD, and management of PTLD. In the second phase, all panel members reviewed, discussed, and revised the recommendations until a consensus was reached. The document was formally approved by the SBPT in a special session organized during the 2023 SBPT Annual Conference.

Patients with cutaneous leishmaniasis (CL) present an exacerbated inflammatory response associated with tissue damage and ulcer development. In recent years, higher rates of failure to pentavalent antimoniate therapy have been observed, yet the underlying reason remains poorly understood. We hypothesize that the eicosanoid PGE2 favours the establishment of infection by L. braziliensis , which contributes to therapeutic failure. The aim of the present study was to investigate the influence of PGE2 on the survival of L. braziliensis in macrophages and rates of therapeutic failure in CL patients. PGE2, an eicosanoid derived from the metabolism of arachidonic acid by the COX-2 enzyme, plays several roles in immune response. We found that increased PGE2 decreases the microbicidal function of macrophages and is associated with disease severity and therapeutic failure. Additionally, the neutralization of COX-2 by NS398, a selective NSAID, increases the ability of macrophages to kill L. braziliensis and protects against the pathological inflammatory response. Our data suggest that NS398 may serve as an adjunct treatment for CL patients.

Objectives: To present evidence-based guidelines for clinical practice regarding religiosity and spirituality in mental health care in Brazil., Methods: A systematic review was conducted to identify potentially eligible articles indexed in the PubMed, PsycINFO, SciELO, LILACS, and Cochrane databases. A summary of recommendations and their levels of evidence was produced in accordance with Oxford Centre for Evidence-Based Medicine guidelines., Results: The systematic review identified 6,609 articles, 41 of which satisfied all inclusion criteria. Taking a spiritual history was found to be an essential part of a compassionate and culturally sensitive approach to care. It represents a way of obtaining relevant information about the patient's religiosity/spirituality, potential conflicts that could impact treatment adherence, and improve patient satisfaction. Consistent evidence shows that reported perceptual experiences are unreliable for differentiating between anomalous experiences and psychopathology. Negative symptoms, cognitive and behavioral disorganization, and functional impairment are more helpful for distinguishing pathological and non-pathological anomalous experiences., Conclusion: Considering the importance of religiosity/spirituality for many patients, a spiritual history should be routinely included in mental health care. Anomalous experiences are highly prevalent, requiring a sensitive and evidence-based approach to differential diagnosis., Competing Interests: The authors report no conflicts of interest.

Objective: We sought to compare virologic outcomes on antiretroviral therapy (ART) between people with HIV (PWH) also treated for tuberculosis in the different countries who participated to two randomized trials., Design: Pooled analysis of two randomized clinical trials., Methods: In the phase II Reflate TB and phase III Reflate TB2 trials conducted in Brazil, Côte d'Ivoire, Mozambique and Vietnam, ART-naïve PWH treated for tuberculosis were randomized to receive raltegravir or efavirenz. We assessed country differences in baseline characteristic using Wilcoxon tests and chi-square, or Fisher's exact test. We used logistic regression to analyze determinants of virologic success, defined as week-48 plasma HIV-1 RNA <50 copies/ml., Results: Of 550 participants (140 from Brazil, 170 from Côte d'Ivoire, 129 from Mozambique and 111 from Vietnam) with median baseline HIV-1 RNA of 5.4 log 10  copies/ml, 362 (65.8%) achieved virologic success at week 48. Virologic success rates were: 105/140 (75.0%) in Brazil, 99/170 (58.2%) in Côte d'Ivoire, 84/129 (65.1%) in Mozambique and 74/111 (66.7%) in Vietnam ( P  = 0.0233). Baseline HIV-1 RNA, but not the country, was independently associated with virologic success: baseline HIV-1 RNA ≥500 000 copies/ml (reference), HIV RNA <100 000 copies/ml odds ratio 3.12 [95% confidence interval (CI) 1.94; 5.01] and HIV-1 RNA 100 000-499 999 copies/ml odds ratio: 1.80 (95% CI 1.19; 2.73). Overall, 177/277 (63.9%) patients treated with raltegravir and 185/273 (67.9%) patients treated with efavirenz had a plasma HIV-1 RNA <50 copies/ml at week 48., Conclusions: Virologic response to antiretroviral therapy in PWH with TB varied across countries but was mainly driven by levels of pretreatment HIV-1 RNA., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There is an increased risk of second primary malignancies (SMPs) in patients with multiple myeloma (MM). This multinational 'real-world' retrospective study analyzed the characteristics and outcomes of MM patients that developed SPMs., Results: 165 patients were analyzed: 62.4% males; 8.5% with a prior cancer; 113 with solid SPMs, mainly ≥stage 2; and 52 with hematological SPM (hemato-SPM), mainly MDS/AML. Patients with hemato-SPM were younger ( p = 0.05) and more frequently had a prior AutoHCT ( p = 0.012). The time to SPM was shorter in the older (>65 years) and more heavily pretreated patients. One hundred patients were actively treated at the time of SPM detection. Treatment was discontinued in 52, substituted with another anti-MM therapy in 15, and continued in 33 patients. Treatment discontinuation was predominant in the patients diagnosed with hemato-SPM (76%). The median OS following SPM detection was 8.5 months, and the main cause of death was SPM. A poor ECOG status predicted a shorter OS (PS 3 vs. 0, HR = 5.74, 2.32-14.21, p < 0.001), whereas a normal hemoglobin level (HR = 0.43, 0.19-0.95, p = 0.037) predicted longer OS., Conclusions: With the continuing improvement in OS, a higher proportion of MM patients might develop SPM. The OS following SPM diagnosis is poor; hence, frequent surveillance and early detection are imperative to improve outcomes.

The aim of the study was to evaluate the association between salivary anti-Porphyromonas gingivalis IgA antibodies and the leprosy reaction. The levels of salivary anti - P. gingivalis IgA antibodies, together with salivary flow and pH were measured in individuals diagnosed with leprosy and associated with the development of the leprosy reaction. Saliva was collected from 202 individuals diagnosed with leprosy at a reference leprosy treatment center, 106 cases with the leprosy reaction and 96 controls without the leprosy reaction. Anti - P. gingivalis IgA was evaluated by indirect immunoenzyme assay. Non-conditional logistic regression analysis was employed to estimate the association between antibody levels and the leprosy reaction. There was a positive statistically significant association between the levels of anti - P. gingivalis IgA and the presence of the leprosy reaction, controlling for confounders: age, sex, level of education and alcoholic beverage consumption: OR ajusted : 2.55; IC 95%: 1.34-4.87. Individuals with leprosy who had high levels of salivary anti - P. gingivalis IgA had approximately twice as many chances of developing the leprosy reaction. The findings suggest a possible relationship between salivary anti - P. gingivalis IgA antibodies and the leprosy reaction., (© 2023. The Author(s).)

Background: Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios., Methods: In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs., Findings: The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11 415 per quality-adjusted life-year (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian cost-effectiveness threshold ($18 107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER., Interpretation: HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide., Funding: None., Translations: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests LC reports receipt of funding from AbbVie, Roche, and AstraZeneca for participation in advisory boards, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disorder caused by disruption of type I collagen synthesis. Previous Brazilian molecular OI studies have been restricted to case reports or small cohorts. The Brazilian OI Network (BOIN) is a multicenter study collecting clinical OI treatment data from five reference centers in three regions of Brazil., Objective: To describe the molecular analysis of a large cohort of OI registered at BOIN., Methods: Targeted next-generation sequencing (NGS) was performed at a centralized laboratory with the Ion Torrent platform, covering 99.6 % of the coding regions of 18 OI-associated genes. Clinical information was obtained from a clinical database., Results: We included 156 subjects in the molecular analyses. Variants were detected in 121 subjects: 65 (53.7 %) in COL1A1, 42 (34.7 %) in COL1A2, 2 (1.7 %) in IFITM5, one (0.8 %) in CRTAP, three (2.5 %) in P3H1, two (1.7 %) in PPIB, four (3.3 %) FKBP10, one (0.8 %) in SERPINH1, and one (0.8 %) in TMEM38B. Ninety-one distinct variants were identified, of which 26 were novel. Of the 107 variants identified in COL1A1 and COL1A2, 24.5 % cause mild OI, while the remaining 75.5 % cause moderate, severe, or lethal OI, of which 49.3 % are glycine to serine substitutions. A single variant in FKBP10 (c.179A>C; p.Gln60Pro) was found in three unrelated and non-consanguineous participants living in the same geographic area in Northeast Brazil, suggesting a possible founder effect., Conclusion: Consistent with the literature, 88.4 % of the subjects had a variant in the COL1A1 and COL1A2 genes, with 10 % inherited in an autosomal recessive manner. Notably, one variant in FKBP10 with a potential founder effect requires further investigation. Data from this large cohort improves our understanding of genotype-phenotype correlations for OI in Brazil., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Chimeric antigen receptor T (CAR-T) cell therapy is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) that is a multi-step process involving various stakeholders. Appropriate education on the practical logistics is therefore paramount to ensure treatment success., Methods: A group of key opinion leaders met to explore the key elements of setting up and running a CAR-T center in Brazil. For each step in the CAR-T cell therapy process, the experts agreed on basic requirements, gave their key recommendations from practical experience, and considered any remaining unanswered questions., Results: This paper presents best-practice recommendations and advice on how to overcome common challenges for each step in the CAR-T cell therapy process, with a focus on the current situation in Brazil. Key themes throughout the process are collaboration within the multidisciplinary team and with the referring physician, along with communication and education for patients and their caregivers., Conclusion: We believe that the expert insights presented in this paper, in particular on optimal patient selection and timing of CAR-T cell therapy, will deepen understanding of the CAR-T process and aid implementation of this novel therapy for patients with RRMM in Brazil., Competing Interests: Conflicts of interest AAP: Honoraria from lectures: BMS, Janssen, Gilead-Kite, Astellas, Jazz Pharmaceuticals Participation in Advisory Board meetings: BMS, Jazz Pharmaceuticals Consultant: Astellas AM: Honoraria from lectures: BMS, Janssen, Sanofi, Amgen, Takeda Participation in Advisory Board meetings: BMS, Janssen, Sanofi, Takeda, Pfizer Consultant: BMS, Pfizer, Astra Zeneca, Novartis, Janssen EC: Research funding: Janssen JSF: Honoraria from lectures and Advisory Boards: Janssen, Novartis, Kite/Gilead, BMS, Abbvie, Amgen. RM: Honoraria for lectures and boards: Janssen, Sanofi, Takeda, Amgen, BMS PRO: Honoraria from lectures: BMS, Janssen, Sanofi, GSK, Amgen, Regeneron, Takeda Participation in Advisory Board meetings: BMS, Janssen, Sanofi, Kite Pharma, Abbvie, Oncopeptides, Takeda, Pfizer, GSK Consultant: BMS, Pfizer VH: Honoraria from lectures: Amgen, BMS, GSK, Janssen, Sanofi, Takeda Participation in Advisory Board meetings: BMS, Janssen, Pfizer, Sanofi, (Copyright © 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To assess Brazilian pediatric intensivists' general knowledge of extracorporeal membrane oxygenation, including evidence for its use, the national funding model, indications, and complications., Methods: This was a multicenter cross-sectional survey including 45 Brazilian pediatric intensive care units. A convenience sample of 654 intensivists was surveyed regarding their knowledge on managing patients on extracorporeal membrane oxygenation, its indications, complications, funding, and literature evidence., Results: The survey addressed questions regarding the knowledge and experience of pediatric intensivists with extracorporeal membrane oxygenation, including two clinical cases and 6 optional questions about the management of patients on extracorporeal membrane oxygenation. Of the 45 invited centers, 42 (91%) participated in the study, and 412 of 654 (63%) pediatric intensivists responded to the survey. Most pediatric intensive care units were from the Southeast region of Brazil (59.5%), and private/for-profit hospitals represented 28.6% of the participating centers. The average age of respondents was 41.4 (standard deviation 9.1) years, and the majority (77%) were women. Only 12.4% of respondents had taken an extracorporeal membrane oxygenation course. Only 19% of surveyed hospitals have an extracorporeal membrane oxygenation program, and only 27% of intensivists reported having already managed patients on extracorporeal membrane oxygenation. Specific extracorporeal membrane oxygenation management questions were responded to by only 64 physicians (15.5%), who had a fair/good correct response rate (median 63.4%; range 32.8% to 91.9%)., Conclusion: Most Brazilian pediatric intensivists demonstrated limited knowledge regarding extracorporeal membrane oxygenation, including its indications and complications. Extracorporeal membrane oxygenation is not yet widely available in Brazil, with few intensivists prepared to manage patients on extracorporeal membrane oxygenation and even fewer intensivists recognizing when to refer patients to extracorporeal membrane oxygenation centers.

Background: Rosacea prevalence varies worldwide and there is a lack of information in Brazil., Objectives: To describe the epidemiological profile of rosacea in subjects who consulted in dermatological outpatient clinics in Brazil., Materials & Methods: A cross-sectional study was conducted in 13 dermatological outpatient clinics across the country. Patients with rosacea diagnosis were eligible for the study according to the investigator's clinical assessment. Clinical, social and demographic data were collected. The overall and regional rosacea prevalence was calculated, and association with baseline characteristics was analysed., Results: A total of 3,184 subjects were enrolled, and rosacea prevalence was 12.7%. The southern region of Brazil presented a higher prevalence, followed by the southeast. The subjects in the rosacea group were older than those without rosacea (52.5 ±14.9 vs. 47.5 ±17.5; p<0.001). Moreover, the rosacea group was associated with Fitzpatrick's phototypes I and II, Caucasian ethnicity, a family history of rosacea, and facial erythema, however, no association with gender was found. The most prevalent clinical sign and clinical subtype in rosacea patients were erythema and erythematotelangiectatic, respectively., Conclusion: Rosacea is highly prevalent in Brazil, mostly in the southern region, associated with phototypes I and II and a family history.

Background: Treatment guidance for children and older adult patients affected by cutaneous leishmaniasis (CL) is unclear due to limited representation of these groups in clinical trials., Methods: We conducted a collaborative retrospective study to describe the effectiveness and safety of antileishmanial treatments in children ≤ 10 and adults ≥ 60 years of age, treated between 2014 and 2018 in ten CL referral centers in Latin America., Results: 2,037 clinical records were assessed for eligibility. Of them, the main reason for non-inclusion was lack of data on treatment follow-up and therapeutic response (182/242, 75% of children and 179/468, 38% of adults). Data on 1,325 eligible CL patients (736 children and 589 older adults) were analyzed. In both age groups, disease presentation was mild, with a median number of lesions of one (IQR: 1-2) and median lesion diameter of less than 3 cm. Less than 50% of the patients had data for two or more follow-up visits post-treatment (being only 28% in pediatric patients). Systemic antimonials were the most common monotherapy regimen in both age groups (590/736, 80.2% of children and 308/589, 52.3% of older adults) with overall cure rates of 54.6% (95% CI: 50.5-58.6%) and 68.2% (95% CI: 62.6-73.4%), respectively. Other treatments used include miltefosine, amphotericin B, intralesional antimonials, and pentamidine. Adverse reactions related to the main treatment were experienced in 11.9% (86/722) of children versus 38.4% (206/537) of older adults. Most adverse reactions were of mild intensity., Conclusion: Our findings support the need for greater availability and use of alternatives to systemic antimonials, particularly local therapies, and development of strategies to improve patient follow-up across the region, with special attention to pediatric populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Castro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)