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Abstract Background Medication errors are likely common in low- and middle-income countries (LMICs). In neonatal hospital care where the population with severe illness has a high mortality rate, around 14.9% of drug prescriptions have errors in LMICs settings. However, there is scant research on interventions to improve medication safety to mitigate such errors. Our objective is to improve routine neonatal care particularly focusing on effective prescribing practices with the aim of achieving reduced gentamicin medication errors. Methods We propose to conduct an audit and feedback (A&F) study over 12 months in 20 hospitals with 12 months of baseline data. The medical and nursing leaders on their newborn units had been organised into a network that facilitates evaluating intervention approaches for improving quality of neonatal care in these hospitals and are receiving basic feedback generated from the baseline data. In this study, the network will (1) be expanded to include all hospital pharmacists, (2) include a pharmacist-only professional WhatsApp discussion group for discussing prescription practices, and (3) support all hospitals to facilitate pharmacist-led continuous medical education seminars on prescription practices at hospital level, i.e. default intervention package. A subset of these hospitals (n = 10) will additionally (1) have an additional hospital-specific WhatsApp group for the pharmacists to discuss local performance with their local clinical team, (2) receive detailed A&F prescription error reports delivered through mobile-based dashboard, and (3) receive a PDF infographic summarising prescribing performance circulated to the clinicians through the hospital-specific WhatsApp group, i.e. an extended package. Using interrupted time series analysis modelling changes in prescribing errors over time, coupled with process fidelity evaluation, and WhatsApp sentiment analysis, we will evaluate the success with which the A&F interventions are delivered, received, and acted upon to reduce prescribing error while exploring the extended package’s success/failure relative to the default intervention package. Discussion If effective, these theory-informed A&F strategies that carefully consider the challenges of LMICs settings will support the improvement of medication prescribing practices with the insights gained adapted for other clinical behavioural targets of a similar nature. Trial registration PACTR, PACTR202203869312307 . Registered 17th March 2022.

Resumen: Las enfermedades raras, pese a su baja frecuencia individual, afectan globalmente al 7% de la población, por lo que el profesional de Atención Primaria (AP) tendrá varios de estos pacientes bajo seguimiento. El 80% de estas enfermedades tienen base genética, lo que hace fundamental un asesoramiento genético adecuado. El seguimiento de pacientes con síndrome de Wolfram (SW) puede servir para diseñar un protocolo susceptible de ser utilizado en el diagnóstico y manejo de otras entidades y ser utilizado por profesionales sanitarios para dar soporte a los pacientes, contando con la participación de profesionales sanitarios e investigadores especializados en el SW, los propios pacientes y su entorno. Se desarrollan los pasos fundamentales de todo procedimiento clínico genético, en el que la AP es clave para dar soporte a estas familias y transmitir de forma comprensible la información sobre los aspectos genéticos. Abstract: Rare diseases, despite their individual low frequency, affect 7% of the population all combined. Consequently, every primary care practitioner (PCP) will have several of these patients under his care. 80% of rare diseases are genetically determined, which makes genetic counseling fundamental in these cases. The follow-up of patients with Wolfram syndrome (WS) can be used to design a protocol to support these patients, with the participation of researchers and healthcare professionals specialized in WS, the patients themselves and their familial environment. This protocol can be suitable for the diagnosis and management of other diseases as well. The main steps of every genetic clinical procedure are developed in this article, emphasizing the role of PCP in supporting patients and their families and in transmitting genetic information in a comprehensible manner.

BackgroundThe optimal isolation time of COVID-19 patients in intensive care unit (ICU) is debated. We investigated the impact of two different COVID-19 patient isolation time strategies on healthcare workers (HCW) contamination, intensity of nursing care and potential associated adverse events.MethodsWe prospectively included all consecutive COVID-19 patients and HCW in our ICU in the first two pandemic waves (March to May 2020 and August to November 2020). Specific isolation measures for COVID-19 patients were released after two negative RT-PCR assays in the first wave and 14 days after the onset of symptoms in the second wave. Contamination of HCW was assessed at the end of each pandemic wave by combining both a RT-PCR assay and a serological test.ResultsOverall, 117 COVID-19 patients and 73 HCW were included. Despite an earlier release from isolation after ICU admission in the second than in the first wave [6 (4–8) vs. 15 (11–19) days, p < 0.01], the proportion of HCW with a positive serological test (16 vs. 17%, p = 0.94) or with a positive RT-PCR assay (3 vs. 5%, p = 0.58) was not different between the two waves. Although a lower nurse-to-bed ratio, the intensity of nursing care was higher in the second than in the first wave. A longer isolation time was associated with accidental extubation (OR = 1.18, 95%CI:1.07–1.35, p = 0.005) but neither with ventilator-associated pneumonia nor with dysglycemia.ConclusionA shorter isolation time of COVID-19 patients in ICU was not associated with higher HCW contamination, while a longer isolation time seemed to be associated with higher accidental extubation.

Objective: To describe the primary cardiovascular disorders manifested in patients infected with the zika virus and understand the pathophysiological process. Methods: This integrative literature review occurred in January 2021 through the PICO strategy, which answered the guiding question: “What are the main cardiovascular disorders manifested in patients infected with zika virus?” For this, a time interval of 5 years was defined, using the descriptors “Zika Virus”,“Heart” and “Cardiovascular Diseases” in English, Portuguese and Spanish. The contemplated databases were MEDLINE, LILACS, and BDENF. Results: There were a total of 77,872 articles, of which, after the exclusion and inclusion processes, it was summarized in eight articles included in this review. The main cardiovascular findings present were apical muscular ventricular septal defect and ostium secundum, in addition to atrial fibrillation and heart failure with reduced ejection fraction. Conclusions: Further studies with more robustness that clearly establish the mechanism of cellular tropism for cardiac muscle cells and involve the pathophysiological process of cardiac alterations more clearly and reliably are needed.

Abstract Nonhospitalized COVID‐19 and hepatitis C‐coinfected patient presented prolonged RNA shedding and mild course of infection. This finding demonstrated the importance of long follow‐up of these patients.

Abstract Background The new P-STEP® (Personalised Space Technology Exercise Platform) app is designed to bring together tailored exercise guidance and up-to-date air quality information. The app allows individuals to plan outdoor exercise walking routes while minimising their exposure to air pollution. Individuals with chronic long-term conditions, particularly respiratory and cardiovascular conditions, can use the app in order to minimise the risk of their symptoms being exacerbated by pollution, while still gaining the benefits of outdoor exercise. Methods This study will measure the usability and acceptability of the P-STEP® app. The study will take the form of a single-arm 12-week app pilot study based in Leicestershire, United Kingdom (UK). We will recruit a maximum of 380 participants from an existing cohort study to pilot the app for 12 weeks. Questionnaire data will be collected at three timepoints, baseline, 6 weeks and 12 weeks. The primary outcome is the System Usability Scale at 12 weeks. Secondary outcomes include the User Engagement Scale Short Form, SF-12, Recent Physical Activity Questionnaire (RPAQ), bespoke, app specific usability questions, and feasibility outcomes. Additional data collected includes participant demographic information, technology self-efficacy and adverse events. Weekly anonymised usage data from the app will also be collected by the app team and analysed separately to complement the questionnaire data. Discussion This study will help us better understand the feasibility and acceptability of using the P-STEP® in the community. The results will also help inform future studies. Ethics and dissemination This study has received ethical approval from the South West Frenchay Research Ethics (23/SW/0060) Committee. There is no need for further approval from the Health Research Authority as the study is not taking place in the NHS. The ClinicalTrials.gov ID number is NCT05830318.

Abstract In humans, blood Classical CD14+ monocytes contribute to host defense by secreting large amounts of pro-inflammatory cytokines. Their aberrant activity causes hyper-inflammation and life-threatening cytokine storms, while dysfunctional monocytes are associated with ‘immunoparalysis’, a state of immune hypo responsiveness and reduced pro-inflammatory gene expression, predisposing individuals to opportunistic infections. Understanding how monocyte functions are regulated is critical to prevent these harmful outcomes. We reveal platelets’ vital role in the pro-inflammatory cytokine responses of human monocytes. Naturally low platelet counts in patients with immune thrombocytopenia or removal of platelets from healthy monocytes result in monocyte immunoparalysis, marked by impaired cytokine response to immune challenge and weakened host defense transcriptional programs. Remarkably, supplementing monocytes with fresh platelets reverses these conditions. We discovered that platelets serve as reservoirs of key cytokine transcription regulators, such as NF-κB and MAPK p38, and pinpointed the enrichment of platelet NF-κB2 in human monocytes by proteomics. Platelets proportionally restore impaired cytokine production in human monocytes lacking MAPK p38α, NF-κB p65, and NF-κB2. We uncovered a vesicle-mediated platelet-monocyte-propagation of inflammatory transcription regulators, positioning platelets as central checkpoints in monocyte inflammation.

Abstract Background Canada’s immigrants and refugees have often settled in large Canadian cities, but this is changing with rising costs of living and rural settlement initiatives. However, little consideration is made regarding systemic changes needed to accommodate this distribution, particularly in healthcare in medium-sized cities or smaller communities. For most Canadians, primary care is an entry point into the healthcare system but immigrants and refugees face unique barriers to accessing care compared to the general Canadian population. This project aimed to better understand the barriers to accessing primary care among newcomers in Peterborough, Ontario from the perspective of newcomer service providers. Methodology Participants were recruited from community organizations identified by the local settlement agency, the New Canadians Centre, as having regular interactions with newcomer clients including clinics, not-for-profit organizations, and volunteer groups. Four focus groups were completed, each with three participants (n=12). A coding grid was deductively developed to guide thematic analysis by adapting Levesque et al.’s conceptual framework defining access to healthcare with five specific dimensions: approachability, acceptability, availability and accommodation, affordability, and appropriateness. Results Participants identified lack of awareness of the healthcare system, stigma, competing priorities, and direct costs as some of the barriers for newcomers. Participants highlighted barriers unique to Peterborough including proximity to services, social isolation, and a shortage of family physicians. The results also highlighted strengths in the community such as its maternal-child health programming. Conclusion The results provide a glimpse of the challenges to accessing primary care among newcomers in medium-sized communities and identify opportunities to prepare for changing settlement patterns.

Paulo Cruchinho,1 María Dolores López-Franco,2 Manuel Luís Capelas,3 Sofia Almeida,4 Phillippa May Bennett,5– 7 Marcelle Miranda da Silva,1,8 Gisela Teixeira,1 Elisabete Nunes,1 Pedro Lucas,1 Filomena Gaspar1 On Behalf of the Handovers4SafeCare1Nursing Research, Innovation and Development Center (CIDNUR) of Lisbon, Nursing School of Lisbon, Lisboa, Portugal; 2CTS-464 Nursing and Innovation in Healthcare, University of Jaén, Jaén, Spain; 3Universidade Católica Portuguesa, Faculty of Health Sciences and Nursing, Center for Interdisciplinary Research in Health (CIIS), Lisboa, Portugal; 4Universidade Católica Portuguesa, Faculty of Health Sciences and Nursing, Center for Interdisciplinary Research in Health (CIIS), Porto, Portugal; 5Center for English, Translation, and Anglo-Portuguese Studies (CETAPS), Lisboa, Portugal; 6Faculty of Social Sciences and Humanities of the New University of Lisbon, Lisboa, Portugal; 7Faculty of Arts and Humanities of the University of Coimbra, Department of Languages, Literatures and Cultures, Coimbra, Portugal; 8Federal University of Rio de Janeiro, Anna Nery Nursing School, Rio de Janeiro, BrazilCorrespondence: Paulo Cruchinho, Nursing School of Lisbon, Avenida Prof. Egas Moniz, Lisboa, 1600-190, Portugal, Tel +351 217913400, Email pjcruchinho@esel.ptAbstract: Cross-cultural validation of self-reported measurement instruments for research is a long and complex process, which involves specific risks of bias that could affect the research process and results. Furthermore, it requires researchers to have a wide range of technical knowledge about the translation, adaptation and pre-test aspects, their purposes and options, about the different psychometric properties, and the required evidence for their assessment and knowledge about the quantitative data processing and analysis using statistical software. This article aimed: 1) identify all guidelines and recommendations for translation, cross-cultural adaptation, and validation within the healthcare sciences; 2) describe the methodological approaches established in these guidelines for conducting translation, adaptation, and cross-cultural validation; and 3) provide a practical guideline featuring various methodological options for novice researchers involved in translating, adapting, and validating measurement instruments. Forty-two guidelines on translation, adaptation, or cross-cultural validation of measurement instruments were obtained from “CINAHL with Full Text” (via EBSCO) and “MEDLINE with Full Text”. A content analysis was conducted to identify the similarities and differences in the methodological approaches recommended. Bases on these similarities and differences, we proposed an eight-step guideline that includes: a) forward translation; 2) synthesis of translations; 3) back translation; 4) harmonization; 5) pre-testing; 6) field testing; 7) psychometric validation, and 8) analysis of psychometric properties. It is a practical guideline because it provides extensive and comprehensive information on the methodological approaches available to researchers. This is the first methodological literature review carried out in the healthcare sciences regarding the methodological approaches recommended by existing guidelines.Keywords: cross-cultural comparison, decision-making, psychometric properties, research design, validation studies, health services research

Abstract Background Based on previous in vivo studies and human trials, intrathecal cell delivery is a safe and relevant therapeutic tool for improving patient's quality of life with neurological conditions. We aimed to characterise the safety profile of intrathecally delivered Mesenchymal stem cells (MSCs). Methods Ovid MEDLINE, Embase, Scopus, Cochrane Library, KCI-Korean Journal Database, and Web of Science. Databases were searched from their inception until April 13, 2023. Randomised Controlled Trials (RCTs) that compared intrathecal delivery of MSCs to controls in adult populations were included. Adverse events (AEs) were pooled and meta-analysed using DerSimonian-Laird random effects models with a correction factor 0.5 added to studies with zero count cells. Pooled AEs were described using Risk ratio (RR) and 95% confidence intervals (95% CI). Then, a random-effects meta-regress model on study-level summary data was performed to explore the relationship between the occurrence of AEs and covariates thought to modify the overall effect estimate. Finally, publication bias was assessed. Results 303 records were reviewed, and nine RCTs met the inclusion criteria and were included in the quantitative synthesis (n = 540 patients). MSCs delivered intrathecally, as compared to controls, were associated with an increased probability of AEs of musculoskeletal and connective tissue disorders (categorised by Common Terminology Criteria for Adverse Events—CTCAE version 5.0) (RR: 1.61, 95% CI 1.19–2.19, I2 = 0%). The random-effects meta-regress model suggested that fresh MSCs increased the probability of occurrence of AEs compared to cryopreserved MSCs (RR: 1.554; p-value = 0.048; 95% CI 1.004–2.404), and the multiple-dose, decreased the probability of AEs by 36% compared to single doses (RR: 0.644; p-value = 0.048; 95% CI 0.416–0.996); however, univariate random effects meta-regression models revealed a not significant association between the occurrence of AEs from MSCs intrathecal delivery and each covariate. Conclusions Intrathecal delivery of MSCs was associated with a slight increase in AEs associated with musculoskeletal and connective tissue disorders, albeit without serious AEs. We conclude that intrathecal MSCs delivery is safe for patients with neurological conditions. However, further high-quality, large-scale RCTs are needed to confirm these findings.

Introduction: Prevention of diabetes requires sustained lifestyle changes as well as identification of groups at higher risk. Objective: The aim of this research was to estimate the risk of diabetes in vulnerable subjects from a primary care center in northern Argentina, with no known glucose abnormalities, using the FINDRISC questionnaire, investigate the relationship between survey variables and the final score, and explore its association with metabolic risk factors and body composition. Methodology: This cross-sectional design included 498 patients without type 2 diabetes or known glycemic abnormalities. All subjects underwent a complete medical history and completed the FINDRISC questionnaire. Results: The predominant age group was 18-45 years old. Around 64% were physically active and 44% reported daily consumption of fruit and vegetables. Most of them had a BMI higher than 25 kg/m2. Regarding the risk of developing type 2 diabetes in the next 10 years, 24.3% were at low risk and the remaining fraction was distributed in slightly elevated, moderate, high and very high risk. All variables influenced the individuals' variance (p < 0.05). The hierarchical clustering and principal component analysis (PCA) revealed that elevated FINDRISC score was strongly associated with: age > 65 years, fasting blood glucose, BMI ? 30 kg/m2 and antihypertensives use. CONCLUTION: We found a high percentage of obesity and overweight, as well as a high risk of cardiometabolic disease and of developing T2D. In addition, in the population studied, the variables that compose the FINDRISC did not influence the highest score in the same way.

Summary: Background: Timely and economic provision of revascularisation procedures is a major healthcare need. We aimed to examine the safety and efficacy of daycase-based lower extremity endovascular revascularisation procedures in patients with peripheral artery disease. Methods: In this systematic review and meta-analysis, we searched MEDLINE and Embase for studies from Jan 01, 2000 through Apr 01, 2024 reporting complications of lower limb endovascular revascularisation procedures with same-day discharge. Eligibility-criteria, complications, and patient characteristics were extracted, methodological quality assessed (adapted Newcastle–Ottawa Scale), and meta-analyses of complications and technical success performed to provide pooled estimates. This study is registered with PROSPERO, CRD42022316466. Findings: Thirty observational studies (17 retrospective, 13 prospective) and 1 RCT reported 2427 minor and 653 major complications after 99,600 daycase procedures (93,344 patients). Eighteen studies reported daycase eligibility-criteria including ‘responsible adult companion’ (78%), ‘proximity to hospital’, and ‘telephone availability’ and excluding unstable and severe co-morbidities, offset coagulation, and severe chronic kidney disease. Pooled incidences of minor (4.7% [95% CI 3.8–5.6%], I2 = 96%) and major (0.64% [95% CI 0.48–0.79%], I2 = 46%) complications were low and technical success high (93% [95% CI 91–96%], I2 = 97%). Most complications were related to the puncture site. Pooled conversion-to-hospitalisation rates and re-admission after discharge were 1.6% (95% CI 1.1–2.2%, I2 = 82%) and 0.11% (95% CI 0.095–0.23%, I2 = 97%), respectively. Meta-regression identified that minor complications decreased since 2000. Male sex and coronary artery disease were associated with more frequent, and higher age and closure device use with less minor complications. Diabetes mellitus and chronic kidney disease were associated with less major complications. Six studies reported complication rates both in daycases and inpatients and there was no significant difference (−0.8% [95% CI −1.9 to 0.3%]). Interpretation: After careful evaluation of eligibility, lower limb angioplasty can be performed safely with high technical success in a daycase setting. Most complications arise from the puncture site and not the procedure itself highlighting the importance of optimal access site management. The heterogeneity between studies warrants standardised monitoring of complications and outcomes. Funding: European Partnership on Metrology, co-financed from European Union’s Horizon Europe Research and Innovation Programme and UK Research and Innovation, and Medical Research Council.

BackgroundActinic keratosis (AK) is a highly prevalent pre-cancerous skin lesion that often leads to cutaneous squamous cell carcinoma. There are different stages of evolution of the disease and several features that characterize keratosis. This study aimed to develop a qualitative and quantitative visual diagnostic tool to facilitate the identification of the characteristics and severity of the main cellular attributes of AK and to show its applicability in evaluating the evolution or treatment through image analysis.MethodsLiterature research on the main scientific databases and in the institute’s database was carried out to gather all the different levels of cellular transformation. To validate the scale, a preliminary characterization study was carried out with 21 subjects who had clinically diagnosed AK lesions to classify the attributes in each skin layer and test the accuracy of the diagnosis of the scale. Afterward, and to show the possibility of a follow-up with a topical treatment, the subjects were divided into two treatment groups, receiving either a cream formulation containing retinoic acid, or a placebo formula. The evaluation was carried out through confocal reflectance microscopy and a digital camera with dermoscopic quality before and after 90 days of treatment.ResultsA table detailing the 18 attributes of AK, and a photographic scale containing RCM images graded by scores established for each characteristic and the frequency of spreading were developed. The results of the validation presented good repeatability, correlation with clinical evaluation, and capacity for differentiating treatments demonstrated by the significant improvement after topical treatment by the reduction of the score for 10 out of the 18 attributes. The preliminary study, evaluated by the detailed transformation scale highlights important differences in the subclinical approach that allows a deeper evaluation of the aspects of the lesion’s re-incidence even after fully treated skin sites.ConclusionThis study brings an innovative method based on RCM, to assist in the quantification of cell transformation level, provide early diagnosis, and deliver a powerful treatment evaluation tool to provide smoother treatment, as well as prevent re-incidence in the cases.

Summary: Background: Studies on DNA methylation following bariatric surgery have primarily focused on blood cells, while it is unclear to which extend it may reflect DNA methylation profiles in specific metabolically relevant organs such as adipose tissue. Here, we investigated whether adipose tissue depots specific methylation changes after bariatric surgery are mirrored in blood. Methods: Using Illumina 850K EPIC technology, we analysed genome-wide DNA methylation in paired blood, subcutaneous and omental visceral AT (SAT/OVAT) samples from nine individuals (N = 6 female) with severe obesity pre- and post-surgery. Findings: The numbers and effect sizes of differentially methylated regions (DMRs) post-bariatric surgery were more pronounced in AT (SAT: 12,865 DMRs from −11.5 to 10.8%; OVAT: 14,632 DMRs from −13.7 to 12.8%) than in blood (9267 DMRs from −8.8 to 7.7%). Cross-tissue DMRs implicated immune-related genes. Among them, 49 regions could be validated with similar methylation changes in blood from independent individuals. Fourteen DMRs correlated with differentially expressed genes in AT post bariatric surgery, including downregulation of PIK3AP1 in both SAT and OVAT. DNA methylation age acceleration was significantly higher in AT compared to blood, but remained unaffected after surgery. Interpretation: Concurrent methylation pattern changes in blood and AT, particularly in immune-related genes, suggest blood DNA methylation mirrors AT's inflammatory state post-bariatric surgery. Funding: The funding sources are listed in the Acknowledgments section.

Introduction: The use of electronic cigarettes (e-cigarettes) has increased in Brazil. Objective: To assess the prevalence of e-cigarette use and the factors associated with its use among college students. Methods: This is a cross-sectional observational study, carried out with undergraduate students from two private colleges. The prevalence of the consumption of e-cigarettes, conventional cigarettes, alcohol and marijuana was evaluated. The motivations for initiating e-cigarette use and the respondents' perceptions about their use were also reported. Results: 518 undergraduate students were evaluated, with a mean age of 23±5.7 years, 64.09% were female and 60.42% were medical students. The prevalence of e-cigarette use was 24.32%, and the highest consumption occurred in medical school. The main motivations for starting the use of e-cigarettes were curiosity (47.70%), and the influence of friends and/or family (31.61%). Advancing age and being employed reduced the chance of using e-cigarettes by 7% and 67%, respectively, while higher family income increased the chance of e-cigarette use by 28%. The use of conventional cigarettes, alcohol and marijuana increased this chance by 6.4; 11.8 and 3.7 times, respectively. Conclusion: The high prevalence of e-cigarette use among undergraduate students stands out. The main reasons to start e-cigarette use were curiosity, and the influence of friends and/or family. Further, e-cigarette use was associated with age, family income, being employed, use of conventional cigarettes, alcohol and marijuana. Due to the high prevalence of e-cigarette use among Brazilian undergraduate students, higher education institutions should initiate awareness campaigns that communicate the health risks linked to their use.

Background Errors associated with failures in filing, actioning and communicating blood test results can lead to delayed and missed diagnoses and patient harm. This study aimed to audit how blood tests in primary care are filed, actioned and communicated in primary care, to identify areas for patient safety improvements.Methods UK primary care clinicians were recruited through the Primary Care Academic CollaboraTive (PACT). PACT members audited 50 recent sets of blood tests from their practice and retrospectively extracted data on blood test result coding, actioning and communication. PACT members received a practice report, showing their own results, benchmarked against other participating practices.Results PACT members from 57 general practices across all four UK nations collected data on 2572 patients who had blood tests in April 2021. In 89.9% (n=2311) they agreed with the initial clinician’s actioning of blood tests; 10.1% disagreed, either partially (7.1%) or fully (3.0%).In 44% of patients (n=1132) an action (eg, ‘make an appointment’) was specified by the filing clinician. This action was carried out in 89.7% (n=1015/1132) of cases; in 6.8% (n=77) the action was not carried out, in 3.5% (n=40) it was unclear. In the 117 cases where the test result had not been actioned 38% (n=45) were felt to be at low risk of harm, 1.7% (n=2) were at high risk of harm, 0.85% (n=1) came to harm.Overall, in 47% (n=1210) of patients there was no evidence in the electronic health records that results had been communicated. Out of 1176 patients with one or more abnormal results there was no evidence of test communication in 30.6% (n=360). There were large variations between practices in rates of actioning and communicating tests.Conclusion This research demonstrates variation in the way blood test results are actioned and communicated, with important patient safety implications.

ContextCOVID-19 induces complex distress across physical, psychological, and social realms and palliative care (PC) has the potential to mitigate this suffering significantly.ObjectivesTo describe the clinical characteristics and outcomes of COVID-19 patients with an indication of PC, compared to patients who had no indication, in different pandemic waves.MethodsThis retrospective multicenter observational cohort included patients from 40 hospitals, admitted from March 2020 to August 2022. Patients who had an indication of palliative care (PC) described in their medical records were included in the palliative care group (PCG), while those who had no such indication in their medical records were allocated to the non-palliative care group (NPCG).ResultsOut of 21,158 patients, only 6.7% had indication for PC registered in their medical records. The PCG was older, had a higher frequency of comorbidities, exhibited higher frailty, and had a higher prevalence of clinical complications and mortality (81.4% vs. 17.7%, p

Introdução: No processo de edificação da Política Nacional de Saúde Integral LGBT+, a Atenção Básica ganha importante destaque, pois deveria funcionar como o contato preferencial dos usuários transgênero (trans). Objetivo: Investigar quais as percepções dos profissionais da Atenção Básica quanto às situações de vulnerabilidade enfrentadas pelas pessoas trans, bem como pesquisar os impedimentos que eles consideram existir na busca dessa população por acesso a esses serviços. Métodos: Utilizou-se uma abordagem qualitativa por meio de entrevistas semiestruturadas com 38 profissionais de saúde atuantes das Estratégias Saúde da Família de dois municípios do interior do estado de São Paulo. O material obtido foi submetido à análise de conteúdo de Bardin. Resultados: Os resultados apontaram para o desconhecimento quanto aos reais empecilhos que dificultam o acesso e seguimento de pessoas trans nos serviços de saúde. Observou-se ainda a manutenção de preconceitos e ideias que reforçam estereótipos ligados ao tema e que se estendem ao exercício da profissão. Isso se relaciona diretamente com a falta da abordagem de assuntos relacionados à sexualidade humana na graduação desses profissionais, além da falta de atualização quanto ao tema, o que impacta a qualidade do serviço que é ofertado à população em estudo. Conclusões: As normativas e portarias já existentes precisam ser efetivamente postas em prática, fazendo-se imperativas a ampliação e difusão do conhecimento a respeito da temática trans no contexto dos serviços públicos de saúde, o que pode servir como base para subsidiar a formação dos profissionais que atuam nesse setor, bem como políticas públicas efetivas.

Objetivo: Descrever a mortalidade materna nas macrorregiões de saúde de Mato Grosso do Sul no período de 2011 a 2019. Métodos: Estudo descritivo e transversal de casos notificados de mortalidade materna no estado de Mato Grosso do Sul e suas macrorregiões de saúde, no período de 2011 a 2019. Foram extraídos por meio do acesso a fonte de dados do Sistema de Informações sobre Mortalidade. Os dados de faixa etária, escolaridade, cor, estado civil, local de ocorrência, causa e período gravídico-puerperal foram armazenados no software Microsoft Excel. A Razão de Mortalidade Materna foi calculada para cada macrorregião. Resultados: Foram identificados 237 óbitos maternos, com 46,0% na macrorregião de Campo Grande, 32,5% em Dourados, 11,4% em Três lagoas e 10,1% em Corumbá. Foram registrados 391.171 nascidos vivos no estado de Mato Grosso do Sul e o coeficiente de mortalidade materna nesse período foi de 60,6/100.000 nascidos vivos. Conclusão: Os números de mortalidade materna se mantem elevados e, o coeficiente de mortalidade materna classificado como muito alto. Apesar dos avanços para a melhoria na assistência obstétrica e a existência de políticas públicas em saúde, o número de mortes que poderiam ser evitadas com o uso de tecnologias simples no nível primário de atenção à saúde para identificação de complicações continua alarmante.

RESUMO Introdução: A medicina de família e comunidade (MFC) é a especialidade preferencial para estar presente na atenção primária à saúde (APS). O padrão ouro de formação de profissionais para a especialidade é a residência médica, momento que ao menos 70% do período de estágio é na APS. Assim, é imprescindível avaliar a qualidade de inserção da residência nesse local. Objetivo: Este estudo teve como objetivo avaliar a qualidade de implementação dos programas de residência médica em MFC na APS. Método: Utilizou-se uma ferramenta desenvolvida para a análise de implementação de residência de MFC na APS em programas pequenos (até dois residentes do segundo ano), médios (de dois a cinco) e grandes (a partir de seis), avaliando de zero a quatro pontos, entre não implantado e totalmente implantado. As notas foram obtidas a partir de entrevista com residentes, preceptores, coordenadores e gestores municipais, considerando a avaliação de quarta geração com análise de Bardin das falas. Resultado: Seis programas foram avaliados, em municípios de 20 mil a 12 milhões de habitantes, com variação de um a 22 residentes do segundo ano por programa, desde insatisfatório (um programa) a totalmente implantado (dois programas). Municípios com maior cobertura de APS apresentaram resultados de implementação melhores. As notas mais baixas foram nos itens “educação permanente” e “educação continuada”, e as mais altas na presença de especialistas em MFC como preceptores. Há diferença de percepção entre os entrevistados considerando as mesmas perguntas. O estudo sugere que municípios com maior investimento na APS também possuem melhores programas de residência, independentemente de o vínculo ser com centros educacionais ou secretarias de saúde. A pandemia de Sars-CoV-2 também dificultou a educação em saúde. Os resultados também foram definidores quando entrevistadas diferentes pessoas, demonstrando ser essencial a análise de quarta geração. Conclusão: Há a necessidade de observar a implementação dos programas de residência na APS para garantir formação de qualidade, e não apenas quantidade para provimento.

O Manual da Alimentação Cardioprotetora para Profissionais da Atenção Básica (MAC) tem objetivo de traduzir as recomendações alimentares das diretrizes sobre o tratamento e prevenção de fatores de risco cardiovascular em uma única estratégia lúdica e compreensiva. Entretanto, não se sabe como e qual o melhor método para implementá-lo na Atenção Primária em Saúde (APS). O objetivo deste artigo é apresentar o protocolo do estudo de implementação do MAC na APS de dois municípios do sudeste do Brasil. Trata-se de um estudo de implementação híbrido tipo II com desenho de ensaio clínico randomizado em cluster. Todos os serviços da APS dos municípios (n=59) serão randomizados (1:1) para o grupo que receberá uma estratégia multifacetada para implementação do MAC, que inclui não só a distribuição do material, mas uma capacitação e Auditoria e Feedback (intervenção) ou para o grupo que inclui apenas a distribuição do material, mimetizando o cenário atual (controle). O desfecho primário de implementação será avaliado a partir da taxa de orientação da Alimentação Cardioprotetora e o desfecho primário de efetividade será avaliado pelo consumo de vegetais dos usuários, em seis meses de seguimento. Os desfechos secundários são: compreensão da orientação por parte dos usuários e dos profissionais, taxa de orientações complementares ao MAC, a percepção da incorporação da orientação na prática clínica dos profissionais, a identificação de barreiras e facilitadores para a implementação do MAC e ainda peso dos usuários. Se positiva, será discutida a ampliação da capacitação para outros municípios brasileiros.

Abstract Background With one in five individuals aged 65 or older living with type 2 diabetes worldwide, it is crucial to acknowledge and address the challenges faced by this population. In this context, our study aims to evaluate the efficacy of a behavioral intervention model delivered through a smart speaker on mental health and diabetes self-care in the elderly with diabetes. Methods This is a single-center, pragmatic, parallel two-arm open randomized clinical trial involving elderly patients with type 2 diabetes. We plan to enroll a total of 112 individuals who will be randomized 1:1 to receive the Smart Speaker EchoDot 3rd Gen device (Amazon Echo®) for home use (intervention arm) or to maintain usual care (control arm). The primary outcome is mental distress, assessed using the 20-item Self Reporting Questionnaire (SRQ-20) after a 12-week intervention period. Secondary outcomes include quality of life, adherence to diabetes self-care behaviors, perception of stress, glycemic control, blood pressure, and lipid profile. Analysis of covariance (ANCOVA) will be used to evaluate the effects of the intervention on the outcomes. Discussion This study assesses the effectiveness of an interactive virtual assistance system for enhancing mental health and glycemic control among elderly individuals with type 2 diabetes. The findings may introduce smart speakers as a valuable tool for promoting diabetes-related self-care in this population. Trial registration ClinicalTrials.gov NCT05329376. Registered on 15 April 2022. Enrollment began on 20 June 2023 and the last update of protocol was on 13 December 2023.

Abstract Background The E-value, a measure that has received recent attention in the comparative effectiveness literature, reports the minimum strength of association between an unmeasured confounder and the treatment and outcome that would explain away the estimated treatment effect. This study contributes to the literature on the applications and interpretations of E-values by examining how the E-value is impacted by data with varying levels of association of unobserved covariates with the treatment and outcome measure when covariate adjustment is applied. We calculate the E-value after using regression and propensity score methods (PSMs) to adjust for differences in observed covariates. Propensity score methods are a common observational research method used to balance observed covariates between treatment groups. In practice, researchers may assume propensity score methods that balance treatment groups across observed characteristics will extend to balance of unobserved characteristics. However, that assumption is not testable and has been shown to not hold in realistic data settings. We assess the E-value when covariate adjustment affects the imbalance in unobserved covariates. Methods Our study uses Monte Carlo simulations to evaluate the impact of unobserved confounders on the treatment effect estimates and to evaluate the performance of the E-Value sensitivity test with the application of regression and propensity score methods under varying levels of unobserved confounding. Specifically, we compare observed and unobserved confounder balance, odds ratios of treatment vs. control, and E-Value sensitivity test statistics from generalized linear model (GLM) regression models, inverse-probability weighted models, and propensity score matching models, over correlations of increasing strength between observed and unobserved confounders. Results We confirm previous findings that propensity score methods – matching or weighting – may increase the imbalance in unobserved confounders. The magnitude of the effect depends on the strength of correlation between the confounder, treatment, and outcomes. We find that E-values calculated after applying propensity score methods tend to be larger when unobserved confounders result in more biased treatment effect estimates. Conclusions The E-Value may misrepresent the size of the unobserved effect needed to change the magnitude of the association between treatment and outcome when propensity score methods are used. Thus, caution is warranted when interpreting the E-Value in the context of propensity score methods.

Abstract Background Adolescence is a period of heightened vulnerability to developing mental health problems, and rates of mental health disorder in this age group have increased in the last decade. Preventing mental health problems developing before they become entrenched, particularly in adolescents who are at high risk, is an important research and clinical target. Here, we report the protocol for the trial of the ‘Building Resilience through Socioemotional Training’ (ReSET) intervention. ReSET is a new, preventative intervention that incorporates individual-based emotional training techniques and group-based social and communication skills training. We take a transdiagnostic approach, focusing on emotion processing and social mechanisms implicated in the onset and maintenance of various forms of psychopathology. Methods A cluster randomised allocation design is adopted with randomisation at the school year level. Five-hundred and forty adolescents (aged 12–14) will be randomised to either receive the intervention or not (passive control). The intervention is comprised of weekly sessions over an 8-week period, supplemented by two individual sessions. The primary outcomes, psychopathology symptoms and mental wellbeing, will be assessed pre- and post-intervention, and at a 1-year follow-up. Secondary outcomes are task-based assessments of emotion processing, social network data based on peer nominations, and subjective ratings of social relationships. These measures will be taken at baseline, post-intervention and 1-year follow-up. A subgroup of participants and stakeholders will be invited to take part in focus groups to assess the acceptability of the intervention. Discussion This project adopts a theory-based approach to the development of a new intervention designed to target the close connections between young people’s emotions and their interpersonal relationships. By embedding the intervention within a school setting and using a cluster-randomised design, we aim to develop and test a feasible, scalable intervention to prevent the onset of psychopathology in adolescence. Trial registration ISRCTN88585916. Trial registration date: 20/04/2023.

Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

In Malawi, the putative origin of a newly described Schistosoma haematobium-mattheei hybrid human schistosome was assessed upon a seminal molecular parasitological survey of cattle. Using miracidia hatch test (MHT) and carcass inspection at slaughter, mean prevalence of bovine schistosomiasis was 49.1% (95% CI: 43.7–54.6%) and 10.3% (95% CI: 6.0–16.2%) respectively, though significant spatial heterogeneity was noted. Approximately 2.0% of infected cattle, and only those from Mangochi District, shed S. haematobium-mattheei and/or S. haematobium in faeces. To quantify schistosome (re)infection dynamics, where a S. haematobium-mattheei hybrid was present, we undertook a novel pilot GPS-datalogging sub-study within a specific herd of cattle (n = 8) on the Lake Malawi shoreline, alongside a praziquantel (40 mg/kg) treatment efficacy spot check. At sub-study baseline, all GPS-tagged cattle had proven daily water contact with the lake. Each animal was patently infected upon MHT, with older animals shedding less miracidia. At one month review, whilst parasitological cure was 100.0%, from six weeks onwards, (re)infection was first noted in the youngest animal. By three-month review, all animals were patently (re)infected though only miracidia of S. mattheei were recovered, albeit in much lower numbers. To conclude, infection with S. mattheei is particularly common in cattle and demonstrates a previously cryptic burden of bovine schistosomiasis. Within Mangochi District, bovine transmission of both S. haematobium-mattheei hybrids and S. haematobium are now incriminated, with unequivocal evidence of contemporary zoonotic spill-over. Future control of urogenital schistosomiasis here in the southern region needs to develop, then successfully integrate, a One Health approach with appropriate mitigating strategies to reduce and/or contain bovine schistosomiasis transmission.

The diversity and prevalence of canine vector-borne pathogens (VBPs) in Bhutan have to date remained unexplored, whilst recent epidemiological surveys in other South Asian nations have found diseases caused by VBPs to be rife in local dog populations. Importantly, many of such VBPs can infect people as well, with a building body of evidence identifying potentially zoonotic rickettsial organisms infecting humans in Bhutan. Given the lack of data on canine pathogens in Bhutan we employed a suite of deep-sequencing metabarcoding methods using Oxford Nanopore Technologies' MinION™ device to holistically characterise the bacterial, apicomplexan and filarial worm blood-borne pathogens of dogs in the country's south. Of the 95 stray, owned and community dogs sampled 78% (95% CI = 69%–85%) were infected with at least one VBP. Pathogen species detected were highly diverse including the bacteria Mycoplasma haemocanis in 16% (95% CI: 10–24%), Ehrlichia canis in 4% (95% CI: 2–10%), Anaplasma platys in 2% (95% CI: 0.5–7%) of dogs as well as the zoonotic species Bartonella clarridgeiae in 1% (95% CI: 0.1–6%), a potentially novel Bartonella spp. and an Ehrlichia chaffeensis-like bacterium, both in 1% (95% CI: 0.1–6%) of dogs. The apicomplexan haemoparasites Hepatozoon canis in 62% (95% CI: 52–71%), Babesia gibsoni in 45% (95% CI: 36–55%) and Babesia vogeli in 3% (95% CI: 1–9%) of dogs were also detected. Finally, 5% (95% CI: 2–12%) of dogs were found to be infected with the filarioid Acanthocheilonema reconditum and 1% (95% CI: 0.1–6%) with zoonotic Dirofilaria sp. hongkongensis. One canine was found positive to the filarioid Setaria tundra, a species normally found infecting cervids. The elucidated diversity of VBP communities highlights the strength of assumption-free diagnostics, such as metabarcoding, in detecting rare, novel, and unexpected pathogens. This approach to identifying pathogen diversity is of critical importance when investigating regions and populations that have thus far been neglected, with the findings aiding the development of future One Health informed strategies for disease control.

Summary: Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: −22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models. Methods: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case–control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions. Findings: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: −17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: −17.9% to 89.6%), and further increased to 80.9% (95% CI: −17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker. Interpretation: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen. Funding: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV.

RESUMO Introdução: A monitoria acadêmica é uma ferramenta complementar à construção do conhecimento dos discentes do ensino superior. Apresenta-se como mecanismo de auxílio e de orientação para os monitorados ao mesmo tempo que desenvolve as habilidades comunicacionais para além dos saberes essenciais do monitor. O presente trabalho tem como objetivo relatar uma experiência de monitoria com diferentes estratégias de ensino e de avaliação por meio de metodologias ativas, aplicando atividades teóricas e práticas interdisciplinares para estudantes de Medicina. Relato de experiência: Este relato de monitoria, realizado em um componente curricular de saúde coletiva da graduação em Medicina de uma universidade pública federal do Rio Grande do Sul, apresenta dados quantitativos e discute os conhecimentos adquiridos com a aplicação das atividades do projeto de ensino. Discussão: Analisaram-se quatro semestres, em que se compararam registros realizados em formulários on-line sem identificação dos respondentes referentes à participação das monitorias de caráter teórico e prático, sendo a maior adesão de participantes nas atividades práticas (42,31% versus 25,55%). Depreenderam-se as principais motivações dos discentes para buscar a monitoria, sendo a elucidação de uma etapa da simulação de pesquisa a mais requisitada. Houve predominância dos valores próximos ao máximo em monitorias práticas em relação às teóricas na avaliação geral delas, sendo considerados três aspectos: importância da atividade; clareza e didática da monitora; esclarecimento de dúvidas. Percebeu-se que o tempo destinado aos encontros variou de forma considerável, sendo mais frequente destinar 60 minutos às atividades teóricas e 30 minutos às atividades práticas. A comparação da proposta de atividades práticas e teóricas aplicadas por meio de metodologias ativas no projeto de monitoria evidenciou o quanto o discente, monitor ou monitorando, beneficia-se do processo de ensino-aprendizagem quando inserido como responsável principal pela própria educação. Conclusão: Na perspectiva da monitora, houve um fortalecimento das próprias competências relacionadas ao saber científico, assim como se observaram um nivelamento da turma em relação aos conteúdos de base e a progressão gradual da aquisição de um raciocínio crítico do estudante da área da saúde.

Multi-host communities are perfect scenarios for the emergence and spread of pathogens, threatening the recovery of endangered, isolated, or inbred populations, such as the brown bear (Ursus arctos) in northwestern Spain. The population recovery in recent years has forced bears to occupy highly anthropized areas, increasing their interaction with human and domestic animals, with potential consequences for global health. During 2022–2023 a survey of parasites, bacteria and viruses shared between wildlife, domestic animals and humans was performed in this population using non-invasive surveillance, i.e., bear fecal samples (n = 73) and sponge-based sampling of trees (n = 42; 14 rubbed trees and 28 control trees). Pathogen detection rates were defined as the percentage of qPCR or culture-positive samples. Generalized linear models were fitted to assess their relationship with environmental variables including dispersion of the human population, and percentage of agricultural and periurban habitats in a 6 km-buffer around each sample. Canine Adenovirus type 1 (45.2%), Giardia spp. (15.1%), Salmonella spp. (12.3%), and extended-spectrum-beta-lactamases (ESBL) Escherichia coli (1.4%) were identified in fecal samples. In contrast, only five sponges from three rubbed and two control trees resulted positive to E. coli (14.3%). The results suggest that several pathogens are common in the Cantabrian brown bear population and that anthropization of the territory modulates their prevalence and richness.The effective design of management programs for bear conservation will require a one-health approach, in which genetic analysis of non-invasive samples can be key tools for the sanitary surveillance at the wildlife-livestock-human interface.

Objective: To investigate whether a combined hip and knee muscle strengthening program is superior to a knee strengthening program for people after lateral patellar dislocation (LPD). Design: Single-blind, superiority, randomized controlled trial with 48 weeks follow-up. Setting: Physiotherapy out-patient clinic. Participants: Forty individuals aged 16 or older, with a history of non-traumatic LPD were randomized to a knee-based strengthening (KBSG) or quadriceps and hip strengthening exercise (HQSG) program (N=40). Inclusion criteria included a positive apprehension sign, pain on palpation along the medial retinaculum, and J sign. Exclusion criteria included restricted range of motion (

Introducción: El cordón umbilical es una estructura de forma espiroidea y es quien comunica el feto a la placenta, dentro de las patologías del mismo está la torsión, una de las más infrecuentes pero con alta mortalidad fetal. Presentación de caso: se trata de un producto de sexo masculino, hijo de madre de 19 años de edad, de 39 semanas de gestación, se le realizó una autopsia en el Instituto Nacional de patología Dr. Sergio Sarita Valdez, evidenciándose torsión de cordón umbilical. Conclusiones: se evidenció durante el procedimiento de autopsia, producto de sexo masculino, de 39 semanas de edad gestacional, se encontró una torsión y una estenosis del cordón umbilical asociado a polihidramnios severo.

Drug repurposing, the process of identifying new uses for existing drugs beyond their original indications, offers significant advantages in terms of reduced development time and costs, particularly in addressing unmet medical needs in rare diseases. Artificial intelligence (AI) has emerged as a transformative force in healthcare, and by leveraging AI technologies, researchers aim to overcome some of the challenges associated with rare diseases. This review presents concrete case studies, as well as pre-existing platforms, initiatives, and companies that demonstrate the application of AI for drug repurposing in rare diseases. Despite representing a modest part of the literature compared to other diseases such as COVID-19 or cancer, the growing interest, and investment in AI for drug repurposing in rare diseases underscore its potential to accelerate treatment availability for patients with unmet medical needs.

To describe the sociodemographic and clinical-epidemiological profile of homeless people affected by tuberculosis in Brazil, from 2015 to 2021. This is a descriptive, population-based epidemiological study, carried out from the tuberculosis notification records in the Brazilian homeless people, available in the Notifiable Diseases Information System. There was a predominance of male people, of mixed race/color, aged between 30 and 49 years, with (in) complete elementary education and who did not receive social benefits. Regarding the clinical-epidemiological aspects, the type of entry as a new case predominated, with the pulmonary form of the disease, directly observed treatment not performed, with loss of follow-up. The prevalence of alcohol and illicit drug use stands out, in addition to the large number of people who used tobacco. This scenario represents a great challenge, since the presence of tuberculosis prevails in this population, especially as a result of numerous risk factors and situations of vulnerability arising from being homeless. Thus, it is necessary to plan and improve actions that consider the specificities of the group, through inter- and intra-sectoral strategies, focusing on the articulation between public health services and social assistance.

Resumen: Objetivo: Analizar mediante el programa de revisión de la medicación, Revisem®, la prevalencia de problemas relacionados con la medicación (PRM) en pacientes de la provincia de Valencia que estaban en tratamiento activo con inhibidores de la bomba de protones (IBP) en 2022. Diseño: Estudio observacional descriptivo y retrospectivo. Material y métodos: Se analizó el historial farmacoterapéutico (HFT) de 295 pacientes siguiendo los criterios propuestos por la Pharmaceutical Care Network Europe, utilizando la plataforma digital Revisem® del Muy Ilustre Colegio Oficial de Farmacéuticos de Valencia (MICOF). Resultados: La edad media de los pacientes fue 81,8 ± 11,1 años y 66,4% fueron mujeres. Se detectó al menos un PRM en 97,3% de los pacientes. De los PRM analizados, 46,9% fueron interacciones, de las cuales 29,7% implicaban un IBP, siendo el omeprazol el de mayor frecuencia. Los PRM con IBP se relacionan de forma significativa con determinadas condiciones del paciente y grupos farmacológicos, como son el sexo femenino, la edad superior a 54 años y la polifarmacia. Conclusiones: La plataforma digital Revisem®, permite la detección de una alta prevalencia de PRM a nivel provincial. La aplicación de nuevas herramientas tecnológicas para detectar la prevalencia de PRM es fundamental para optimizar los tratamientos de los pacientes. Abstract: Objective: To analyze, using the medication review program, Revisem®, the prevalence of drug-related problems (DRP) in patients in the province of Valencia who were on active treatment with proton pump inhibitors (PPI) in 2022. Design: Descriptive and retrospective observational study. Material and methods: The pharmacotherapeutic history of 295 patients was analyzed following the criteria proposed by the Pharmaceutical Care Network Europe, using the Revisem® digital platform of the Muy Ilustre Colegio Oficial de Farmacéuticos (MICOF). Results: The mean age of the patients was 81.8 ± 11.1 years and 66.4% were women. At least one DRP was detected in 97.3% of patients. 46.9% of the DRP analyzed were interactions, of which 29.7% involved a PPI, with omeprazole being the most frequent. DRPs with PPI are significantly related to certain patient conditions and pharmacological groups, such as female sex, age over 54 years and polypharmacy. Conclusions: The application of the Revisem® digital platform allows the detection of a high prevalence of DRP at the provincial level. The application of new technological tools to detect the prevalence of DRP is essential to optimize patient treatments.

A discriminação racial e o racismo ainda são presentes no cotidiano da sociedade, reverberando em vários aspectos na vida da população negra, inclusive no ensino superior, médio e fundamental, onde o preconceito é intenso, e afeta a permanência desse grupo étnico-racial. Diante disso, o objetivo desse artigo analisar as evidências disponíveis na literatura científica sobre experiências de discriminação racial e racismo contra estudantes negros no Brasil. Trata-se de uma revisão integrativa de literatura, a questão norteadora foi embasada pela estratégia PICo, a busca pelos artigos foi realizado nas bases de dados: MEDLINE via PubMed, Web of Science, Scopus e LILACS. Na busca, foi recuperado um quantitativo de 766 publicações, mas depois das análises dos critérios de inclusão e exclusão, e da leitura na íntegra, 12 obras foram incluídas na amostra final. As obras tinham como principais assuntos abordados três temas, sendo eles: Politicas desenvolvidas e implementadas pela a Universidade (41,66%), Impactos da discriminação racial e racismo na vida acadêmica e social (41,66%) e Manifestações de racismo e discriminação e as formas de enfrentamento (16,68%). Assim, o racismo ainda está presente na vida desses estudantes, este fenômeno afeta diretamente o desempenho acadêmico e vida social dos estudantes.

Resumo Introdução: A residência médica é o padrão ouro para formação em medicina de família e comunidade. Na última década houve aumento substancial de vagas sem a avaliação da qualidade dos programas. Objetivo: Este estudo teve como objetivos observar e qualificar a percepção dos preceptores da residência nessa área. Método: Aplicou-se um questionário qualiquantitativo no estado de São Paulo, com análise estatística descritiva e elaboração da matriz FOFA associada à tríade de Donabedian a partir da análise de conteúdo dos entrevistados. Resultado: A amostra foi de 64 preceptores em 27 programas, com mediana de idade de 37 anos e composta de 52% de mulheres. A distribuição mais prevalente é de dois residentes por preceptor, e 67% atuam também com a graduação. Da amostra, 56,7% possuem residência médica e 13,4% são titulados, além de 82% com cursos em preceptoria. A análise qualitativa aponta a formação em preceptoria e o aumento de especialistas como pontos relevantes, mas ainda há a dificuldade com a organização dos serviços e o baixo apoio da gestão municipal. Conclusão: Embora haja preceptores com formação adequada, ainda é necessário seu incremento ante o aumento do número de vagas desproporcional à capacidade instalada. Melhoria das condições estruturais e maior apoio dos municípios serão necessários de acordo com a percepção dos preceptores em medicina de família e comunidade.

Introduction: Although bochdalek hernia is the most common type of congenital diaphragmatic hernia, it is still a rare condition. It can be complicated by the development of secondary pulmonary sequestration, which is subdivided into intralobar pulmonary sequestration and extralobar pulmonary sequestration. Case report: This study describes a case of pulmonary sequestration due to bochdalek hernia in a one-year-old girl, who underwent surgical correction. Discussion: Pulmonary sequestration can be confused with other more frequent pathologies, such as pneumonia or tumors, and diagnosis can be facilitated through the use of vascular imaging techniques, which confirm the diagnosis and show the vascularization of the hernia content.

Covalent hits for drug discovery campaigns are neither fantastic beasts nor mythical creatures, they can be routinely identified through electrophile-first screening campaigns using a suite of different techniques. These include biophysical and biochemical methods, cellular approaches, and DNA-encoded libraries. Employing best practice, however, is critical to success. The purpose of this review is to look at state of the art covalent hit identification, how to identify hits from a covalent library and how to select compounds for medicinal chemistry programmes.

Summary: Background: Tuberculosis (TB) remains a global public health challenge, causing substantial mortality and morbidity. While TB treatment has made significant progress, it often leaves survivors with post-TB sequelae, resulting in long-term health issues. Current healthcare systems and guidelines lack comprehensive strategies to address post-TB sequelae, primarily due to insufficient evidence. This systematic review and meta-analysis aimed to identify effective interventions for preventing post-TB sequelae. Methods: A systematic search was conducted across four databases including PubMed, SCOPUS, Web of Science, and Cochrane Central Register of Controlled Trials from inception to September 22, 2023. Eligible studies reported interventions designed to prevent post-TB sequelae were included. A random effect meta-analysis was conducted where applicable, and heterogeneity between studies was evaluated visually using forest plots and quantitatively using an index of heterogeneity (I2). This study is registered with PROSPERO (CRD42023464392). Findings: From the 2525 unique records screened, 25 studies involving 10,592 participants were included. Different interventions were evaluated for different outcomes. However, only a few interventions were effective in preventing post-TB sequelae. Rehabilitation programs significantly improved lung function (Hedges's g = 0.21; 95% confidence interval (CI): 0.03, 0.39) and prevented neurological sequelae (relative risk (RR) = 0.10; 95% CI: 0.02, 0.42). Comprehensive interventions and cognitive-behavioural therapy significantly reduced the risk of mental health disorders among TB survivors (Hedges's g = −1.89; 95% CI: −3.77, −0.01). In contrast, interventions targeting post-TB liver sequelae, such as vitamin A and vitamin D supplementation and hepatoprotective agents, did not show significant reductions in sequelae (RR = 0.90; 95% CI: 0.52, 1.57). Moreover, adjunctive therapies did not show a significant effect in preventing post-TB neurological sequelae (RR = 0.62, 95% CI: 0.31, 1.24). Interpretation: Rehabilitation programs prevented post-TB lung, neurologic and mental health sequelae, while adjuvant therapies and other interventions require further investigation. Funding: Healy Medical Research Raine Foundation, Curtin School of Population Health and the Australian National Health and Medical Research Council.

Objetivo: A presente pesquisa tem como objetivo fazer uma revisão a respeito do uso de dexmedetomidina (DEX) na sedação pediátrica. Metodologia: Realizou-se a coleta de 11 artigos que tratam da temática, em seguida analisou-se aspectos da respectiva droga, seus possíveis riscos e benefícios da sedação de crianças. Resultados: Identificou-se que a DEX é uma potente agonista, pertencente aos receptores alfa-2 adrenérgicos, que pode ser aplicada em crianças, apresentando como resultado uma eficiente sedação, analgesia e efeito ansiolítico, além de possibilitar uma sedação com muita qualidade. Conclusão: Sua aplicação na pediatria tem sido cada vez mais discutida e mais utilizada corroborando com estudos que têm demonstrado os seus inúmeros benefícios.

A Liga de Emergência é um projeto de extensão universitária, criado em 2003, vinculado ao Departamento de Cirurgia da Faculdade de Medicina e à Pró-reitoria de Extensão da Universidade Federal do Ceará (UFC). Objetivo: relatar a experiência desse projeto, que completou 18 anos de existência em 2021, e seu impacto social por meio da disseminação do conhecimento de emergências médicas, principalmente relacionado ao Suporte Básico de Vida. Metodologia: análise de registros internos ao longo dos anos. Resultado: realização de diversas ações baseadas no tripé acadêmico de ensino, pesquisa e extensão, incluindo cursos, estágios, trabalhos e simulações em emergência. Durante os anos de existência, mais de 100 acadêmicos de medicina já participaram do projeto e cerca de 10.000 pessoas foram capacitadas por meio das atividades de extensão promovidas. Conclusão: acredita-se que o projeto tem grande relevância social, contribuindo para a formação médica em urgência e emergência dos ligantes e para aquisição de importante conhecimento tanto pelo público leigo quanto por acadêmicos e profissionais de diversas áreas da saúde.

Abstract Background Immersive virtual reality (VR) is an innovative strategy for inpatient rehabilitation programs. Using immersive VR in early mobilization protocols has not yet been investigated in the setting of hospitalized patients with acute decompensated heart failure (ADHF), especially to improve perceived dyspnea, a common symptom of heart failure (HF). Methods This is a single-center parallel superiority randomized clinical trial. The study will be conducted at a public teaching hospital in Brazil from January 2023 to January 2024. The sample will include adult patients with ADHF hospitalized for at least 24 h, randomly assigned in a 1:1 ratio to the control (standard early mobilization protocol conducted in the intensive care unit (ICU)) or intervention group (the same standard early mobilization protocol but associated with immersive VR). The primary outcome will be assessing perceived dyspnea, and the secondary outcome will be assessing patient experience. Discussion Using immersive VR in early mobilization protocols in the ICU is expected to improve perceived dyspnea in patients with ADHF as well as patient experience regarding care. This study has the potential to increase patient adherence to early mobilization protocols in the setting of ADHF as well as to promote a positive patient experience. Filling this gap could promote the rational incorporation of technologies in health care. Trial registration This study protocol is in its first version. ClinicalTrials.gov NCT05596292. Registered on 1 December 2022.

Abstract Background Early blood transfusion improves survival in patients with life-threatening bleeding, but the optimal transfusion strategy in the pre-hospital setting has yet to be established. Although there is some evidence of benefit with the use of whole blood, there have been no randomised controlled trials exploring the clinical and cost effectiveness of pre-hospital administration of whole blood versus component therapy for trauma patients with life-threatening bleeding. The aim of this trial is to determine whether pre-hospital leukocyte-depleted whole blood transfusion is better than standard care (blood component transfusion) in reducing the proportion of participants who experience death or massive transfusion at 24 h. Methods This is a multi-centre, superiority, open-label, randomised controlled trial with internal pilot and within-trial cost-effectiveness analysis. Patients of any age will be eligible if they have suffered major traumatic haemorrhage and are attended by a participating air ambulance service. The primary outcome is the proportion of participants with traumatic haemorrhage who have died (all-cause mortality) or received massive transfusion in the first 24 h from randomisation. A number of secondary clinical, process, and safety endpoints will be collected and analysed. Cost (provision of whole blood, hospital, health, and wider care resource use) and outcome data will be synthesised to present incremental cost-effectiveness ratios for the trial primary outcome and cost per quality-adjusted life year at 90 days after injury. We plan to recruit 848 participants (a two-sided test with 85% power, 5% type I error, 1-1 allocation, and one interim analysis would require 602 participants—after allowing for 25% of participants in traumatic cardiac arrest and an additional 5% drop out, the sample size is 848). Discussion The SWiFT trial will recruit 848 participants across at least ten air ambulances services in the UK. It will investigate the clinical and cost-effectiveness of whole blood transfusion versus component therapy in the management of patients with life-threatening bleeding in the pre-hospital setting. Trial registration ISRCTN: 23657907; EudraCT: 2021-006876-18; IRAS Number: 300414; REC: 22/SC/0072, 21 Dec 2021.

Objetivo: O estudo teve como objetivo avaliar fatores associados a danos no glicocálix endotelial de pacientes transplantados hepáticos. Metodologia: Estudo observacional, retrospectivo, desenvolvido no complexo do Hospital Universitário Walter Cantídio (HUWC) e Hospital São Carlos. Foram coletadas amostras biológicas 2 horas após reperfusão do órgão, e foi avaliado o sindecana-1 no sangue. Dados clínicos e laboratoriais, bem como tempo de internação após o transplante foram coletados. Resultados: Foram avaliados 44 pacientes que realizaram transplante hepático ortotópico (THO). Os níveis de sindecana-1 séricos apresentaram mediana de 6,31 (3,69 – 11,44). Foram então formados grupos de pacientes de acordo com o tercis dos níveis de sindecana-1. No intra-operatório, níveis mais altos de sindecana-1 (tercil 3), tiveram relação com hemoglobina (p=0,006), hematócrito (p=0,001), bicarbonato (p=0,029) mais baixos e potássio sérico mais elevado (p=0,042). No pós-operatório o grupo do tercil 3 teve altos níveis de ureia sérica (p=0,023) e creatinina sérica (p=0,032). Além disso, foi observada frequência aumentada de lesão renal aguda (LRA) em 7 dias e 30 dias nos pacientes do tercil 3. Conclusão: Alterações do glicocálix endotelial logo após a cirurgia de pacientes de THO esteve associado com alterações hematológicas do intra-operatório e com alterações renais acompanhada do desenvolvimento de lesão renal aguda no pós-operatório.