Customizable orodispersible films: Inkjet printing and data matrix encoding for personalized hydrocortisone dosing.

The aim of this study was to exploit the versatility of inkjet printing to develop flexible doses of drug-loaded orodispersible films that encoded information in a data matrix pattern, and to introduce a specialised data matrix-generator software specifically focused on the healthcare sector. Pharma-inks (drug-loaded inks) containing hydrocortisone (HC) were developed and characterised based on their rheological properties and drug content. Different strategies were investigated to improve HC solubility: formation of ß-cyclodextrin complexes, Soluplus® based micelles, and the use of co-solvent systems. The software automatically adapted the data matrix size and identified the number of layers for printing. HC content deposited in each film layer was measured, and it was found that the proportion of co-solvent used directly affected the drug solubility and simultaneously played a role in the modification of the viscosity and surface tension of the inks. The formation of ß-cyclodextrin complexes improved the drug quantity deposited in each layer. On the contrary, micelle-based inks were not suitable for printing. Orodispersible films containing flexible and low doses of personalised HC were successfully prepared, and the development of a code generator software oriented to medical use provided an additional, innovative, and revolutionary advantage to personalised medicine safety and accessibility.

In vitro Evaluation of the Antileishmanial and Antischistosomal Activities of p-Coumaric Acid Prenylated Derivatives.

We have evaluated eight p-coumaric acid prenylated derivatives in vitro for their antileishmanial activity against Leishmania amazonensis promastigotes and their antischistosomal activity against Schistosoma mansoni adult worms. Compound 7 ((E)-3,4-diprenyl-4-isoprenyloxycinnamic alcohol) was the most active against L. amazonensis (IC50=45.92 µM) and S. mansoni (IC50=64.25 µM). Data indicated that the number of prenyl groups, the presence of hydroxyl at C9, and a single bond between C7 and C8 are important structural features for the antileishmanial activity of p-coumaric acid prenylated derivatives.

Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique.

This publication is an update of the "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.

Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique

Abstract This publication is an update of the "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.

Early intervention in psoriasis: Where do we go from here?

Patients with psoriasis often have comorbidities and are at increased risk of developing several complications compared with the general population. Knowledge on the role of immune mediators and systemic inflammation in psoriasis has led to the hypothesis that early intervention with systemic therapy has the potential to modify the course of the disease and reduce the risk of long-term adverse outcomes. In this article, we address some potential issues that need to be considered before early intervention can be implemented routinely. The first is determining what constitutes "early" intervention for psoriasis. A second point is whether the intervention should be considered for patients with early disease or for selected subsets based on risk stratification. A third important consideration is defining success for early intervention. Finally, adoption of early and effective intervention should be based on high-level evidence. Ideally, randomized trials would be the best strategy to compare early vs. late systemic treatment in patients with psoriasis, probably using the frequency of long-term outcomes as primary endpoint, with cutaneous and pharmacoeconomic outcomes assessed secondarily.

Physical activity phenotypes and mortality in older adults: a novel distributional data analysis of accelerometry in the NHANES.

Physical activity is deemed critical to successful ageing. Despite evidence and progress, there is still a need to determine more precisely the direction, magnitude, intensity, and volume of physical activity that should be performed on a daily basis to effectively promote the health of individuals. This study aimed to assess the clinical validity of new physical activity phenotypes derived from a novel distributional functional analysis of accelerometer data in older adults. A random sample of participants aged between 65 and 80 years with valid accelerometer data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 was used. Five major clinical phenotypes were identified, which provided a greater sensitivity for predicting 5-year mortality and survival outcomes than age alone, and our results confirm the importance of moderate-to-vigorous physical activity. The new clinical physical activity phenotypes are a promising tool for improving patient prognosis and for directing to more targeted intervention planning, according to the principles of precision medicine. The use of distributional representations shows clear advantages over more traditional metrics to explore the effects of the full spectrum of the physical activity continuum on human health.

Kernel machine learning methods to handle missing responses with complex predictors. Application in modelling five-year glucose changes using distributional representations.

BACKGROUND AND OBJECTIVES: Missing data is a ubiquitous problem in longitudinal studies due to the number of patients lost to follow-up. Kernel methods have enriched the machine learning field by successfully managing non-vectorial predictors, such as graphs, strings, and probability distributions, and have emerged as a promising tool for the analysis of complex data stemming from modern healthcare. This paper proposes a new set of kernel methods to handle missing data in the response variables. These methods will be applied to predict long-term changes in glycated haemoglobin (A1c), the primary biomarker used to diagnose and monitor the progression of diabetes mellitus, making emphasis on exploring the predictive potential of continuous glucose monitoring (CGM). METHODS: We propose a new framework of non-linear kernel methods for testing statistical independence, selecting relevant predictors, and quantifying the uncertainty of the resultant predictive models. As a novelty in the clinical analysis, we used a distributional representation of CGM as a predictor and compared its performance with that of traditional diabetes biomarkers. RESULTS: The results show that, after the incorporation of CGM information, predictive ability increases from R2=0.61 to R2=0.71. In addition, uncertainty analysis is useful for characterising some subpopulations where predictivity is worsened, and a more personalised clinical follow-up is advisable according to expected patient uncertainty in glucose values. CONCLUSIONS: The proposed methods have proven to deal effectively with missing data. They also have the potential to improve the results of predictive tasks by including new complex objects as explanatory variables and modelling arbitrary dependence relations. The application of these methods to a longitudinal study of diabetes showed that the inclusion of a distributional representation of CGM data provides greater sensitivity in predicting five-year A1c changes than classical diabetes biomarkers and traditional CGM metrics.

Comportamento de adolescentes do sexo feminino acerca da utilização de preservativos / Comportamiento de adolescentes de sexo femenino ante el uso del condón / Behavior of female adolescents in the use of condoms

Objetivo: caracterizar o conhecimento e a prática acerca da utilização de preservativos por parte de adolescentes do sexo feminino, estudantes do ensino médio de uma escola da rede estadual do interior de Sergipe, Brasil. Materiais e método: pesquisa de corte transversal, realizada em uma escola da rede pública localizada no interior do Estado de Sergipe, Região Nordeste do Brasil. A coleta de dados ocorreu em fevereiro e março de 2017, na escola com o maior número de adolescentes matriculados do Estado. Resultados: entre as 94 participantes do estudo, a média de idade foi de 17,3 anos (DP = 1,2); a maioria das adolescentes referiu renda familiar mensal de até um salário-mínimo (61,3 %). A religião predominante foi a católica (74,5 %). Apenas 4,3 % das adolescentes afirmaram ter filho e uma delas encontrava-se gestante (1,1 %). Quanto à iniciação sexual, 51,1 % das adolescentes participantes referiram não ter tido as primeiras relações sexuais, enquanto 48,9 % apresentavam vida sexual ativa. A maior frequência de relações sexuais e uso de preservativo entre as adolescentes foi encontrada entre aquelas que referiram a ingesta de bebidas alcoólicas (40 [42,5 %]; p < 0,05). Sobre preservativos, 92,6 % das adolescentes conheciam e já haviam tido contato com o preservativo masculino, enquanto apenas 62,8 % conheciam e tinham visualizado o feminino. Conclusões: as adolescentes apresentam conhecimento frágil sobre preservativos e adotam prática sexual insegura; portanto, é fundamental o desenvolvimento de estratégias de educação sexual que visem melhorar o conhecimento e as habilidades das adolescentes sobre o tema.

Objetivo: caracterizar el conocimiento y la práctica en el uso del condón por parte de las estudiantes de secundaria de una escuela de la red pública del estado del interior de Sergipe, Brasil. Materiales y método: investigación transversal realizada en una escuela de la red pública ubicada en el interior del estado de Sergipe, región Nordeste de Brasil. La recolección de datos se llevó a cabo entre febrero y marzo de 2017 en las instalaciones de la institución educativa con mayor número de adolescentes matriculados del estado. Resultados: la edad media de las 94 participantes del estudio fue de 17,3 años (DP = 1,2), quienes en su mayoría reportaron un ingreso familiar mensual de hasta un salario mínimo (61,3 %). La religión predominante entre las participantes fue el catolicismo (74,5 %). Solo 4,3 % de las adolescentes afirmó tener un hijo y una de ellas (1,1 %) se encontraba en estado de embarazo al momento de la recolección de datos. En cuanto a la iniciación sexual, el 51,1 % de las participantes refirió no haber tenido su primera relación sexual, mientras que 48,9 % llevaba una vida sexual activa. La mayor frecuencia de relaciones sexuales y uso del condón fue identificada entre las adolescentes que reportaron la ingesta de bebidas alcohólicas (40 [42,5 %]; p< 0,05). Con respecto a los preservativos, 92,6 % de las adolescentes conocía y había tenido contacto con el condón masculino, mientras que solo el 62,8 % reportó lo mismo para el condón femenino. Conclusiones: las adolescentes que participaron de esta investigación tienen poco conocimiento sobre el condón y adoptan prácticas sexuales inseguras. Por ello, es fundamental desarrollar estrategias de educación sexual orientadas a mejorar los conocimientos y las habilidades de las adolescentes frente al tema.

Objective: To characterize the knowledge and practice regarding the use of condoms by high school female students from a public school in the state of Sergipe, Brazil. Materials and method: Cross-sectional research carried out at a public school in the state of Sergipe, northeastern Brazil. Data collection was performed between February and March 2017 at the school with the highest number of adolescents enrolled from the state. Results: The mean age among the 94 participants of the study was 17.3 years (SD: 1.2). Most adolescents reported a monthly family income of up to one minimum wage (61.3 %). The predominant religion in the sample was Catholicism (74.5 %). Only 4.3 % of these adolescents reported having a child and one of them was pregnant at the time of data collection (1.1 %). As for sexual initiation, 51.1 % of the participants reported they had not had their first sexual intercourse, while 48.9 % had an active sexual life. The highest frequency of sexual intercourse and condom use was found among those who reported alcohol consumption (40 [42.5 %]; p < 0.05). Finally, 92.6 % of the participants knew and had already visualized the male condom, while only 62.8 % stated the same for the female condom. Conclusions: The adolescents that participated in this study show a weak knowledge about condoms and adopt unsafe sexual practices. Therefore, it becomes essential to develop sexual education strategies aimed at improving the knowledge and skills regarding this issue among the studied population.

Portable Device for Optical Quantification of Hemozoin in Diluted Blood Samples.

OBJECTIVE: This paper focuses on a novel and portable device prototype with optical detectors to quickly and efficiently detect hemozoin (Hz) in blood, aiming at malaria diagnostics. METHODS: Taking advantage of the particular features of malaria parasite in infected blood, particularly the Hz formation, the main innovation described is a portable device for the optical quantification of parasitic Hz in blood, through optical absorbance spectrophotometry. This device comprises detection chambers for fluidic samples, an optical emission and detection system, and a power supply system to provide autonomy. The working principle is based on colorimetric detection, by absorbance, at six specific wavelengths. A detection algorithm relates the absorbance values at all wavelengths to quantify the Hz concentration, thus working as a biomarker of malaria presence and stage. RESULTS: Under the tested conditions, e.g., in fluidic samples containing synthetic Hz, hemoglobin, and diluted whole blood, the device detected Hz above 1 µg/mL concentrations with 100% sensitivity and 96.3% specificity. CONCLUSION: This paper features an autonomous, portable, 1-min analysis time, and low-cost per test device, without the need for samples, centrifugation, allowing the use of whole blood. SIGNIFICANCE: The presented device is a step ahead for meeting the growing clinical demands for reliable, rapid, portable, and quantitative malaria diagnosis.

Positive and Negative Evidence Accumulation Clustering for Sensor Fusion: An Application to Heartbeat Clustering.

In this work, a new clustering algorithm especially geared towards merging data arising from multiple sensors is presented. The algorithm, called PN-EAC, is based on the ensemble clustering paradigm and it introduces the novel concept of negative evidence. PN-EAC combines both positive evidence, to gather information about the elements that should be grouped together in the final partition, and negative evidence, which has information about the elements that should not be grouped together. The algorithm has been validated in the electrocardiographic domain for heartbeat clustering, extracting positive evidence from the heartbeat morphology and negative evidence from the distances between heartbeats. The best result obtained on the MIT-BIH Arrhythmia database yielded an error of 1.44%. In the St. Petersburg Institute of Cardiological Technics 12-Lead Arrhythmia Database database (INCARTDB), an error of 0.601% was obtained when using two electrocardiogram (ECG) leads. When increasing the number of leads to 4, 6, 8, 10 and 12, the algorithm obtains better results (statistically significant) than with the previous number of leads, reaching an error of 0.338%. To the best of our knowledge, this is the first clustering algorithm that is able to process simultaneously any number of ECG leads. Our results support the use of PN-EAC to combine different sources of information and the value of the negative evidence.

Diagnostic and therapeutic guidelines for plaque psoriasis - Brazilian Society of Dermatology.

Psoriasis is a chronic inflammatory disease that affects 1.3% of the Brazilian population. The most common clinical manifestations are erythematous, scaling lesions that affect both genders and can occur on any anatomical site, preferentially involving the knees, elbows, scalp and genitals. Besides the impact on the quality of life, the systemic nature of the disease makes psoriasis an independent risk factor for cardiovascular disease, especially in young patients with severe disease. By an initiative of the Brazilian Society of Dermatology, dermatologists with renowned clinical experience in the management of psoriasis were invited to form a work group that, in a partnership with the Brazilian Medical Association, dedicated themselves to create the Plaque Psoriasis Diagnostic and Treatment Guidelines. The relevant issues for the diagnosis (evaluation of severity and comorbidities) and treatment of plaque psoriasis were defined. The issues generated a search strategy in the Medline-PubMed database up to July 2018. Subsequently, the answers to the questions of the recommendations were devised, and each reference selected presented the respective level of recommendation and strength of scientific evidence. The final recommendations for making up the final text were worded by the coordinators.

Diagnostic and therapeutic guidelines for plaque psoriasis - Brazilian Society of Dermatology

Abstract: Psoriasis is a chronic inflammatory disease that affects 1.3% of the Brazilian population. The most common clinical manifestations are erythematous, scaling lesions that affect both genders and can occur on any anatomical site, preferentially involving the knees, elbows, scalp and genitals. Besides the impact on the quality of life, the systemic nature of the disease makes psoriasis an independent risk factor for cardiovascular disease, especially in young patients with severe disease. By an initiative of the Brazilian Society of Dermatology, dermatologists with renowned clinical experience in the management of psoriasis were invited to form a work group that, in a partnership with the Brazilian Medical Association, dedicated themselves to create the Plaque Psoriasis Diagnostic and Treatment Guidelines. The relevant issues for the diagnosis (evaluation of severity and comorbidities) and treatment of plaque psoriasis were defined. The issues generated a search strategy in the Medline-PubMed database up to July 2018. Subsequently, the answers to the questions of the recommendations were devised, and each reference selected presented the respective level of recommendation and strength of scientific evidence. The final recommendations for making up the final text were worded by the coordinators.

Gait Event Detection in Controlled and Real-Life Situations: Repeated Measures From Healthy Subjects.

A benchmark and time-effective computational method is needed to assess human gait events in real-life walking situations using few sensors to be easily reproducible. This paper fosters a reliable gait event detection system that can operate at diverse gait speeds and on diverse real-life terrains by detecting several gait events in real time. This detection only relies on the foot angular velocity measured by a wearable gyroscope mounted in the foot to facilitate its integration for daily and repeated use. To operate as a benchmark tool, the proposed detection system endows an adaptive computational method by applying a finite-state machine based on heuristic decision rules dependent on adaptive thresholds. Repeated measurements from 11 healthy subjects (28.27 ± 4.17 years) were acquired in controlled situations through a treadmill at different speeds (from 1.5 to 4.5 km/h) and slopes (from 0% to 10%). This validation also includes heterogeneous gait patterns from nine healthy subjects (27 ± 7.35 years) monitored at three self-selected paces (from 1 ± 0.2 to 2 ± 0.18 m/s) during forward walking on flat, rough, and inclined surfaces and climbing staircases. The proposed method was significantly more accurate ( ) and time effective (< 30.53 ± 9.88 ms, ) in a benchmarking analysis with a state-of-the-art method during 5657 steps. Heel strike was the gait event most accurately detected under controlled (accuracy of 100%) and real-life situations (accuracy > 96.98%). Misdetection was more pronounced in middle mid swing (accuracy > 90.12%). The lower computational load, together with an improved performance, makes this detection system suitable for quantitative benchmarking in the locomotor rehabilitation field.

Partnership for productive development of biosimilar products: perspectives of access to biological products in the Brazilian market.

The manufacturing process for biological products is complex, expensive and critical to the final product, with an impact on their efficacy and safety. They have been increasingly used to treat several diseases, and account for approximately 50% of the yearly budget for the Brazilian public health system. As the patents of biological products expire, several biosimilars are developed. However, there are concerns regarding their efficacy and safety; therefore, the regulatory agencies establish rules to approve and monitor these products. In Brazil, partnership programs between national government-owned companies and private technology holders have been implemented, aiming at knowledge sharing, capacity-building and technological transfer. Such partnerships locally promote manufacturing of these strategic drugs at reduced costs to the public health system. These agreements offer mutual advantages to both the government and patent holders: for the former, a biotechnological development flow is established and enables potential cost reduction and self-sufficient production; whereas for the latter, exclusive sales of the product are ensured during technological transfer, for a fixed period.

Assessment of psoriasis severity in Brazilian patients with chronic plaque psoriasis attending outpatient clinics: a multicenter, population-based cross-sectional study (APPISOT).

PURPOSE: Data on chronic plaque psoriasis severity and its potential clinical and lifestyle implications in the Brazilian population are limited. The primary aim of this study was to assess the clinical severity of plaque psoriasis in Brazil. Further objectives included evaluating potential associations between disease severity and demographic, lifestyle, and clinical characteristics, health-related quality of life (HRQOL), and work productivity. MATERIALS AND METHODS: This observational (non-interventional) cross-sectional study was conducted in 26 dermatologic clinics across 11 Brazilian states. Psoriasis severity was assessed using investigator judgment and Finlay's Rule of Tens: a Psoriasis Area and Severity Index (PASI) score >10, a Body Surface Area (BSA) > 10%, or a Dermatology Life Quality Index (DLQI) score >10. RESULTS: Among 1125 patients, 205 (18.2%) had moderate-to-severe disease. On multiple regression analyses, psoriasis severity was significantly (directly) associated with the presence of physical inactivity and comorbid pain, anxiety, and depression; and significantly (inversely) associated with HRQOL and work productivity. LIMITATIONS: Cross-sectional studies cannot assess temporal trends, and observational studies cannot conclusively determine causality or exclude biases and confounding due to unmeasured variables. CONCLUSIONS: Among Brazilian patients with moderate-to-severe psoriasis, disease severity had far-reaching adverse impacts on lifestyle, comorbidities, HRQOL, and work productivity.

Endobronchial carcinoid tumor: Radiological findings of a clinical case.

We describe the case of a female patient, 21 years old, complaining of dyspnea attacks and wheezing 2 years ago. Chest radiography showed volume loss in the left lower lobe and ipsilateral retrocardiac triangular basal opacity. CT scan showed an extensive solid mass with apex protruding into the left main and lower lobar bronchi, causing distal atelectasis. Histopathological and immunohistochemical study of transbronchial biopsy of the lesion revealed a typical carcinoid tumor, confirmed after tumor resection with total left pneumectomy.

Endobronchial carcinoid tumor: Radiological findings of a clinical case / Tumor carcinoide endobrônquico: aspectos radiológicos em um caso clínico

Summary We describe the case of a female patient, 21 years old, complaining of dyspnea attacks and wheezing 2 years ago. Chest radiography showed volume loss in the left lower lobe and ipsilateral retrocardiac triangular basal opacity. CT scan showed an extensive solid mass with apex protruding into the left main and lower lobar bronchi, causing distal atelectasis. Histopathological and immunohistochemical study of transbronchial biopsy of the lesion revealed a typical carcinoid tumor, confirmed after tumor resection with total left pneumectomy.

Resumo Descrevemos um caso de paciente do gênero feminino, 21 anos, apresentando crises de dispneia e sibilância há 2 anos. Radiografia torácica evidenciou perda volumétrica do lobo inferior esquerdo e opacidade triangular basal retrocardíaca ipsilateral. Tomografia computadorizada mostrou formação expansiva sólida com ápice protruindo para o interior dos brônquios principal e lobar inferior esquerdos, promovendo atelectasia distal. Estudos anatomopatológico e imuno-histoquímico após biópsia transbrônquica da lesão diagnosticaram um tumor carcinoide típico, confirmado após ressecção tumoral com pneumectomia total esquerda.

Heartbeat Classification Using Abstract Features From the Abductive Interpretation of the ECG.

OBJECTIVE: This paper aims to prove that automatic beat classification on ECG signals can be effectively solved with a pure knowledge-based approach, using an appropriate set of abstract features obtained from the interpretation of the physiological processes underlying the signal. METHODS: A set of qualitative morphological and rhythm features are obtained for each heartbeat as a result of the abductive interpretation of the ECG. Then, a QRS clustering algorithm is applied in order to reduce the effect of possible errors in the interpretation. Finally, a rule-based classifier assigns a tag to each cluster. RESULTS: The method has been tested with the MIT-BIH Arrhythmia Database records, showing a significantly better performance than any other automatic approach in the state-of-the-art, and even improving most of the assisted approaches that require the intervention of an expert in the process. CONCLUSION: The most relevant issues in ECG classification, related to a large extent to the variability of the signal patterns between different subjects and even in the same subject over time, will be overcome by changing the reasoning paradigm. SIGNIFICANCE: This paper demonstrates the power of an abductive framework for time-series interpretation to make a qualitative leap in the significance of the information extracted from the ECG by automatic methods.