Symptom burden, service use and care dissatisfaction among older adults with cancer, cardiovascular disease, respiratory disease, dementia and neurological disease during the last 3 months before death: A pooled analysis of mortality follow-back surveys.

BACKGROUND: Variation in the provision of care and outcomes in the last months of life by cancer and non-cancer conditions is poorly understood. AIMS: (1) To describe patient conditions, symptom burden, practical problems, service use and dissatisfaction with end-of-life care for older adults based on the cause of death. (2) To explore factors related to these variables focussing on the causes of death. DESIGN: Secondary analysis of pooled data using cross-sectional mortality follow-back surveys from three studies: QUALYCARE; OPTCare Elderly; and International Access, Right, and Empowerment 1. SETTING/PARTICIPANTS: Data reported by bereaved relatives of people aged ⩾75 years who died of cancer, cardiovascular disease, respiratory disease, dementia or neurological disease. RESULTS: The pooled dataset contained 885 responses. Overall, service use and circumstances surrounding death differed significantly across causes of death. Bereaved relatives reported symptom severity from moderate to overwhelming in over 30% of cases for all causes of death. Across all causes of death, 28%-38% of bereaved relatives reported some level of dissatisfaction with care. Patients with cardiovascular disease and dementia experienced lower symptom burden and dissatisfaction than those with cancer. The absence of a reliable key health professional was consistently associated with higher symptom burden (p = 0.002), practical problems (p = 0.001) and dissatisfaction with care (p = 0.001). CONCLUSIONS: We showed different trajectories towards death depending on cause. Improving symptom burden and satisfaction in patients at the end-of-life is challenging, and the presence of a reliable key health professional may be helpful.

The rise of home death in the COVID-19 pandemic: a population-based study of death certificate data for adults from 32 countries, 2012-2021.

Background: During the coronavirus 2019 disease (COVID-19) pandemic, health systems had to respond to the needs of COVID-19 patients, while caring for patients with other life-threatening conditions. Pandemics, such as the COVID-19 pandemic, stir global health and mortality patterns. This is likely to include trends in dying places. In this paper, we examine trends in place of death for adults in 32 countries, comparing the initial COVID-19 pandemic years (2020-2021) with the eight years before the pandemic (2012-2019). Methods: Data on place of death for all adults (18 years and over) that died from 1 January 2012 to 31 December 2021 were requested (47 countries approached, 32 included). The classification of place of death varied widely between countries. "Home" was the most common category, the remaining category groups comprised "hospital or health institution", "other defined", and "ill-defined". We analysed place of death data in an aggregate form, by sex, age group, and selected underlying causes of death (cancer, dementia, and COVID-19). Findings: The study included 100.7 million people (51.5% male, 68.0% with ≥70 years), 20.4% died from cancer and 5.8% from dementia; 30.8% of deaths took place at home. The percentage of home deaths rose from 30.1% in 2012-2013 to 30.9% in 2018-2019 and further to 32.2% in the pandemic (2020-2021). Home deaths increased during the pandemic in 23 countries. In most countries the rise was greater in women and cancer; age differences were not consistent. Interpretation: Our study shows that there was a rise in home deaths during the pandemic, but with variability across countries, sex, age, and causes of death. The sex difference observed in most countries may have several explanations, including more engagement of women in discussions about end of life care planning and hospital admission avoidance. A higher rise of home deaths among people dying of cancer may be explained by the more predictable disease trajectory compared to non-malignant conditions, as well as earlier and better integrated palliative care. Funding: This work is part of the EOLinPLACE Project, which has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 948609).

Forecasted Dementia Prevalence in Portugal (2020-2080).

Dementia is a global public health challenge, and its impact on Portugal is yet unclear. This study forecasts dementia prevalence in Portugal until 2080. Using the Gonçalves-Pereira et al (2021) method, we estimated dementia cases among older adults (≥65 years) in the community. Applying age-sex specific prevalence rates of the Gonçalves-Pereira study to population projections for Portugal between 2020-2080, based on the 10/66 Dementia Research Group criteria (10/66 DRG) and the Diagnostic and Statistical Manual of Mental Disorders IV criteria (DSM-IV), to Portugal's population projections (2020-2080) under various growth scenarios (low, medium, and high). We anticipate a more than 2-fold increase in dementia prevalence from 2020 to 2080, both for 10/66 DRG [2.1%-5.0%] and DSM-IV [.8%-2.0%]. By 2080, those aged ≥80 years are projected to constitute 75.0% (vs 59.0% in 2020) of all dementia cases, particularly affecting women. Addressing dementia growth in Portugal calls for a comprehensive global response, while country-level estimates facilitate informed public health planning, policy-making, and resource allocation.

Subsequent correlated changes in complement component 3 and amyloid beta oligomers in the blood of patients with Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) involves the complement cascade, with complement component 3 (C3) playing a key role. However, the relationship between C3 and amyloid beta (Aß) in blood is limited. METHODS: Plasma C3 and Aß oligomerization tendency (AßOt) were measured in 35 AD patients and 62 healthy controls. Correlations with cerebrospinal fluid (CSF) biomarkers, cognitive impairment, and amyloid positron emission tomography (PET) were analyzed. Differences between biomarkers were compared in groups classified by concordances of biomarkers. RESULTS: Plasma C3 and AßOt were elevated in AD patients and in CSF or amyloid PET-positive groups. Weak positive correlation was found between C3 and AßOt, while both had strong negative correlations with CSF Aß42 and cognitive performance. Abnormalities were observed for AßOt and CSF Aß42 followed by C3 changes. DISCUSSION: Increased plasma C3 in AD are associated with amyloid pathology, possibly reflecting a defense response for Aß clearance. Further studies on Aß-binding proteins will enhance understanding of Aß mechanisms in blood.

EOLinPLACE: an international research project to reform the way dying places are classified and understood.

Background: Whenever possible, a person should die where they feel it is the right place to be. There is substantial global variation in home death percentages but it is unclear whether these differences reflect preferences, and there are major limitations in how the place of death is classified and compared across countries. Objectives: EOLinPLACE is an international interdisciplinary research project funded by the European Research Council aiming to create a solid base for a ground-breaking international classification tool that will enable the mapping of preferred and actual places towards death. Design: Mixed-methods observational research. Methods and analysis: We combine classic methods of developing health classifications with a bottom-up participatory research approach, working with international organizations representing patients and informal carers [International Alliance of Patients' Organizations (IAPO) and Eurocarers]. First, we will conduct an international comparative analysis of existing classification systems and routinely collected death certificate data on place of death. Secondly, we will conduct a mixed-methods study (ethnography followed by longitudinal quantitative study) in four countries (the Netherlands, Portugal, Uganda and the United States), to compare the preferences and experiences of patients with life-threatening conditions and their families. Thirdly, based on the generated evidence, we will build a contemporary classification of dying places; assess its content validity through focus groups with patients, carers and other stakeholders; and evaluate it in a psychometric study to examine construct validity, reliability, responsiveness, data quality and interpretability. Ethics: Approved by the ethics committee of the University of Coimbra, Faculty of Medicine (CE-068-2022) and committees in each of the participating countries. Discussion: The findings will provide a deeper understanding of the diversity in individual end-of-life pathways. They will enable key developments such as measurement of progress towards achievement of preferences when care can be planned. The project will open new directions in how to care for the dying. Trial registration: Research Registry UIN 9213.

Patient and Family Preferences About Place of End-of-Life Care and Death: An Umbrella Review.

CONTEXT: The place where people are cared towards the end of their life and die is a complex phenomenon, requiring a deeper understanding. Honoring preferences is critical for the delivery of high-quality care. OBJECTIVES: In this umbrella review we examine and synthesize the evidence regarding preferences about place of end-of-life care and death of patients with life-threatening illnesses and their families. METHODS: Following the Joanna Briggs Institute methodology, we conducted a comprehensive search for systematic reviews in PsycINFO, MEDLINE, EMBASE, CINAHL, Epistemonikos, and PROSPERO without language restrictions. RESULTS: The search identified 15 reviews (10 high-quality, three with meta-analysis), covering 229 nonoverlapping primary studies. Home is the most preferred place of end-of-life care for both patients (11%-89%) and family members (23%-84%). It is also the most preferred place of death (patient estimates from two meta-analyses: 51%-55%). Hospitals and hospice/palliative care facilities are preferred by substantial minorities. Reasons and factors affecting preferences include illness-related, individual, and environmental. Differences between preferred places of care and death are underexplored and the evidence remains inconclusive about changes over time. Congruence between preferred and actual place of death ranges 21%-100%, is higher in studies since 2004 and a meta-analysis shows noncancer patients are at higher risk of incongruence than cancer patients (OR 1.23, 95% CI: 1.01-1.49, I2 = 62%). CONCLUSION: These findings are a crucial starting point to address gaps and enhance strategies to align care with patient and family preferences. To accurately identify patient and family preferences is an important opportunity to change their lives positively.

Feasibility and effectiveness of a two-tiered intervention involving training and a new consultation model for patients with palliative care needs in primary care: A before-after study.

BACKGROUND: Evidence suggests that involving General Practitioners in the care of patients with palliative care needs may improve patient outcomes. AIM: To evaluate whether a two-tiered intervention involving training in palliative care and a new consultation model in primary care for patients with palliative care needs is feasible and could reduce patients' symptom burden. DESIGN: Before-after study including an internal pilot. SETTING/PARTICIPANTS: Nine general practitioners working in a health region in Portugal and 53 patients with palliative care needs from their patient lists were recruited. General Practitioners received training in palliative care and used a new primary palliative care consultation model, with medical consultations every 3 weeks for 12 weeks. The primary outcome was physical symptom burden, self-reported using the Integrated Palliative care Outcome Scale (IPOS) patient version (min.0-max.1000). Secondary outcomes included emotional symptoms (min.0-max.400) and communication/practical issues (min.0-max.300). RESULTS: Of the 35/53 patients completed the 12-week intervention (mean age 72.53 years, SD = 13.45; 54.7% female). All had advanced disease: one third had cancer (n = 13), one third had congestive heart failure (n = 12); others had chronic kidney disease and chronic obstructive pulmonary disease. After the 12 weeks of intervention, there was a reduction in physical symptom burden [mean difference from baseline of 71.42 (95%CI 37.01-105.85) with a medium-large effect size (0.71], and in emotional symptom burden [mean difference 42.86 (95%CI 16.14-69.58), with a medium effect size (0.55)]. No difference was found for communication/practical issues. CONCLUSIONS: Our intervention can be effective in reducing patients' physical and emotional symptoms. TRIAL REGISTRATION: ClinicalTrials.gov ID - NCT05244590. Registration: 14th February 2022.

Non-pharmacological interventions in primary care to improve the quality of life of older patients with palliative care needs: a systematic review of randomised controlled trials.

OBJECTIVES: Our systematic review aimed to summarise non-pharmacological interventions applicable in primary care that improve the quality of life of older patients with palliative care needs. DESIGN: Systematic review. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was patients' quality of life. Secondary outcomes were symptoms relief and patients' well-being measures. METHODS AND ANALYSIS: We searched MEDLINE, EMBASE, PsycINFO, Cochrane and CINAHL up to October 2022 for randomised controlled trials (RCTs). We also handsearched abstract books of relevant congresses and scientific meetings in the last 5 years. Screening, data extraction and quality evaluation (Cochrane risk-of-bias (RoB) V.2.0 tool and Grading of Recommendations, Assessment, Development and Evaluations (GRADE)) were done independently by two reviewers, with disagreements solved by a third reviewer. Findings were narratively synthesised. RESULTS: We identified 4 RCTs, including 268 patients. One study used a broad criteria of palliative care needs ('progressive, life-threatening disease'), two studies focused on advanced cancer and one study on heart failure. The non-pharmacological interventions evaluated were advance care planning conducted by general practitioners (GPs); social worker-aided palliative care; online primary palliative care training for GPs and spiritual history taking by nurses and GPs. No intervention showed a statistically significant impact on quality of life and the evidence was low according to GRADE. CONCLUSION: The results highlight a dearth of evidence on what non-pharmacological interventions can be effectively done in primary care to improve the quality of life of older persons with palliative care needs. The results should be interpreted with caution, as the search more comprehensively covers interventions delivered by GPs. PROSPERO REGISTRATION NUMBER: CRD42020154216.

Optimal blood tau species for the detection of Alzheimer's disease neuropathology: an immunoprecipitation mass spectrometry and autopsy study.

Plasma-to-autopsy studies are essential for validation of blood biomarkers and understanding their relation to Alzheimer's disease (AD) pathology. Few such studies have been done on phosphorylated tau (p-tau) and those that exist have made limited or no comparison of the different p-tau variants. This study is the first to use immunoprecipitation mass spectrometry (IP-MS) to compare the accuracy of eight different plasma tau species in predicting autopsy-confirmed AD. The sample included 123 participants (AD = 69, non-AD = 54) from the Boston University Alzheimer's disease Research Center who had an available ante-mortem plasma sample and donated their brain. Plasma samples proximate to death were analyzed by targeted IP-MS for six different tryptic phosphorylated (p-tau-181, 199, 202, 205, 217, 231), and two non-phosphorylated tau (195-205, 212-221) peptides. NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Binary logistic regressions tested the association between each plasma peptide and autopsy-confirmed AD status. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from the logistic regression models. Odds Ratio (OR) was used to study associations between the different plasma tau species and CERAD and Braak classifications. All tau species were increased in AD compared to non-AD, but p-tau217, p-tau205 and p-tau231 showed the highest fold-changes. Plasma p-tau217 (AUC = 89.8), p-tau231 (AUC = 83.4), and p-tau205 (AUC = 81.3) all had excellent accuracy in discriminating AD from non-AD brain donors, even among those with CDR < 1). Furthermore, p-tau217, p-tau205 and p-tau231 showed the highest ORs with both CERAD (ORp-tau217 = 15.29, ORp-tau205 = 5.05 and ORp-tau231 = 3.86) and Braak staging (ORp-tau217 = 14.29, ORp-tau205 = 5.27 and ORp-tau231 = 4.02) but presented increased levels at different amyloid and tau stages determined by neuropathological examination. Our findings support plasma p-tau217 as the most promising p-tau species for detecting AD brain pathology. Plasma p-tau231 and p-tau205 may additionally function as markers for different stages of the disease.

Discovery of new Schistosoma mansoni aspartyl protease inhibitors by structure-based virtual screening.

BACKGROUND: Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma, with a limited treatment, mainly based on the use of praziquantel (PZQ). Currently, several aspartic proteases genes have already been identified within the genome of Schistosoma species. At least one enzyme encoded from this gene family (SmAP), named SmCD1, has been validated for the development of schistosomicidal drugs, since it has a key role in haemoglobin digestion by worms. OBJECTIVE: In this work, we integrated a structure-based virtual screening campaign, enzymatic assays and adult worms ex vivo experiments aiming to discover the first classes of SmCD1 inhibitors. METHODS: Initially, the 3D-structures of SmCD1, SmCD2 and SmCD3 were generated using homology modelling approach. Using these models, we prioritised 50 compounds from 20,000 compounds from ChemBridge database for further testing in adult worm aqueous extract (AWAE) and recombinant SmCD1 using enzymatic assays. FINDINGS: Seven compounds were confirmed as hits and among them, two compounds representing new chemical scaffolds, named 5 and 19, had IC50 values against SmCD1 close to 100 µM while presenting binding efficiency indexes comparable to or even higher than pepstatin, a classical tight-binding peptide inhibitor of aspartyl proteases. Upon activity comparison against mammalian enzymes, compound 50 was selective and the most potent against the AWAE aspartic protease activity (IC50 = 77.7 µM). Combination of computational and experimental results indicate that compound 50 is a selective inhibitor of SmCD2. Compounds 5, 19 and 50 tested at low concentrations (10 uM) were neither cytotoxic against WSS-1 cells (48 h) nor could kill adult worms ex-vivo, although compounds 5 and 50 presented a slight decrease on female worms motility on late incubations times (48 or 72 h). MAIN CONCLUSION: Overall, the inhibitors identified in this work represent promising hits for further hit-to-lead optimisation.

Development and Upscaling of SiO2@TiO2 Core-Shell Nanoparticles for Methylene Blue Removal.

SiO2@TiO2 core-shell nanoparticles were successfully synthesized via a simple, reproducible, and low-cost method and tested for methylene blue adsorption and UV photodegradation, with a view to their application in wastewater treatment. The monodisperse SiO2 core was obtained by the classical Stöber method and then coated with a thin layer of TiO2, followed by calcination or hydrothermal treatments. The properties of SiO2@TiO2 core-shell NPs resulted from the synergy between the photocatalytic properties of TiO2 and the adsorptive properties of SiO2. The synthesized NPs were characterized using FT-IR spectroscopy, HR-TEM, FE-SEM, and EDS. Zeta potential, specific surface area, and porosity were also determined. The results show that the synthesized SiO2@TiO2 NPs that are hydrothermally treated have similar behaviors and properties regardless of the hydrothermal treatment type and synthesis scale and better performance compared to the SiO2@TiO2 calcined and TiO2 reference samples. The generation of reactive species was determined by EPR, and the photocatalytic activity was evaluated by the methylene blue (MB) removal in aqueous solution under UV light. Hydrothermally treated SiO2@TiO2 showed the highest adsorption capacity and photocatalytic removal of almost 100% of MB after 15 min in UV light, 55 and 89% higher compared to SiO2 and TiO2 reference samples, respectively, while the SiO2@TiO2 calcined sample showed 80%. It was also observed that the SiO2-containing samples showed a considerable adsorption capacity compared to the TiO2 reference sample, which improved the MB removal. These results demonstrate the efficient synergy effect between SiO2 and TiO2, which enhances both the adsorption and photocatalytic properties of the nanomaterial. A possible photocatalytic mechanism was also proposed. Also noteworthy is that the performance of the upscaled HT1 sample was similar to one of the lab-scale synthesized samples, demonstrating the potentiality of this synthesis methodology in producing candidate nanomaterials for the removal of contaminants from wastewater.

α-Synuclein seed amplification assay as a diagnostic tool for parkinsonian disorders.

INTRODUCTION: Synucleinopathies such as Parkinson's disease (PD) and multiple system atrophy (MSA) can be challenging to diagnose due to the symptom overlap with, for example, atypical parkinsonisms like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Seed amplification assays (SAA), developed for the detection of α-synuclein (αSyn) aggregates in CSF, have been successful when used as a biomarker evaluation for synucleinopathies. In this study, we investigated the potential of this assay to not only detect αSyn seeds in CSF, but also discriminate between movement disorders. METHODS: The αSyn-SAA was tested in a Scandinavian cohort composed of 129 CSF samples from patients with PD (n = 55), MSA (n = 27), CBD (n = 7), and PSP (n = 16), as well as healthy controls (HC, n = 24). RESULTS: The αSyn seed amplification assay (αSyn-SAA) was able to correctly identify all PD samples as positive (sensitivity of 100%) while also discriminating the PD group from HC (70.8% specificity, p < 0.0001) and tauopathies [CBD (71% specificity) and PSP (75% specificity), p < 0.0001)]. The αSyn-SAA was also able to identify almost all MSA samples as positive for αSyn aggregation (sensitivity of 92.6%). In general, this assay is able to discriminate between the synucleinopathies and tauopathies analyzed herein (p < 0.0001) despite the overlapping symptoms in these diseases. CONCLUSION: These findings suggest the αSyn-SAA is a useful diagnostic tool for differentiating between different parkinsonian disorders, although further optimization may be needed.

Methods to Discover and Validate Biofluid-Based Biomarkers in Neurodegenerative Dementias.

Neurodegenerative dementias are progressive diseases that cause neuronal network breakdown in different brain regions often because of accumulation of misfolded proteins in the brain extracellular matrix, such as amyloids or inside neurons or other cell types of the brain. Several diagnostic protein biomarkers in body fluids are being used and implemented, such as for Alzheimer's disease. However, there is still a lack of biomarkers for co-pathologies and other causes of dementia. Such biofluid-based biomarkers enable precision medicine approaches for diagnosis and treatment, allow to learn more about underlying disease processes, and facilitate the development of patient inclusion and evaluation tools in clinical trials. When designing studies to discover novel biofluid-based biomarkers, choice of technology is an important starting point. But there are so many technologies to choose among. To address this, we here review the technologies that are currently available in research settings and, in some cases, in clinical laboratory practice. This presents a form of lexicon on each technology addressing its use in research and clinics, its strengths and limitations, and a future perspective.

Percepção de enfermeiros sobre as 3S ­ Smart Safe Shoes: meias para prevenção de quedas / Nurses perception of the 3S - Smart Safe Shoes: socks to prevent falls / Percepción de enfermeros sobre los 3S - Smart Safe Shoes: calcetines para prevenir caídas

Objetivo: analisar a percepção dos enfermeiros sobre o uso das 3S - Smart Safe Shoes na sua fase de protótipo e os resultados da avaliação do seu uso por idosos internados. Método: estudo de carater exploratório, descritivo e misto, entre novembro de 2021 e março de 2022. Incluiu idosos internados com capacidade de deambulação e identificados com risco de queda; e enfermeiros especialistas. Os dados quantitativos foram analisados por estatística descritiva e os qualitativos a partir de análise temática. Resultados: participaram 28 idosos e sete enfermeiros, ambos concordaram que as 3S ­ Smart Safe Shoes são confortáveis. Os enfermeiros consideram que as meias se adaptaram perfeitamente às diferentes regiões anatômicas do pé e que apresentam propriedades antiderrapantes nos pisos testados; e na maioria das situações, permitem uma boa mobilidade dos dedos, em todos os movimentos tibiotársicos (86%). Todos os enfermeiros destacam a facilidade de calçar as meias e consideram que estas devem ser incluídas como um elemento em estratégia de prevenção de quedas. Conclusão: as 3S - Smart Safe Shoes reunem as características necessárias para garantir uma marcha segura em idosos internados e o seu uso deve ser considerado em outros contextos.

Objective: to analyse nurse's perception about 3S - Smart Safe Shoes use in their prototype phase and describe their evaluation about this use by hospitalized elderly patients. Method: exploratory, descriptive and mixed study, between November 2021 and March 2022. It included hospitalized elderly people who were able to walk and identified as being at risk of falling; and specialist nurses. Quantitative data were analyzed using descriptive statistics and qualitative data using thematic analysis. Results: 28 seniors and seven nurses participated, both agreed that the 3S ­ Smart Safe Shoes are comfortable. The nurses consider that the socks adapt perfectly to the different anatomical regions of the foot and that they have non-slip properties on the tested floors; and in most situations, they allow good mobility of the fingers, in all tibiotarsal movements (86%). All nurses highlight the ease of putting on stockings and consider that these should be included as an element in a fall prevention strategy. Conclusion: 3S - Smart Safe Shoes have the necessary characteristics to guarantee a safe gait in hospitalized elderly patients and their use should be considered in other contexts.

A educação permanente em saúde para a enfermagem de cuidados críticos: estudo qualitativo / La educación médica permanente para enfermería de cuidados críticos: estudio cualitativo / The permanent health education for critical care nursing: qualitative study

Objetivo:identificar e analisar apercepção da enfermagem acerca da Educação Permanente em Saúde em unidades de cuidados críticos de um hospital públicomunicipal de São Paulo. Método: pesquisa qualitativa, sendo realizadas 35 entrevistas com a equipe de enfermagem de unidades de terapia intensiva adulto, tratadas porAnálise de Conteúdo,na lógica do arco de Maguerez. Resultados: emergiramduascategorias, ambas elencando a Educação Permanente como necessária, porém falha no contexto de trabalho da enfermagem em cuidados críticos.Conclusões:evidencia-se avalorização das ações de educação notrabalho e que não há neste cenário a educação permanente em saúde propriamente dita,sendo indicada maior atenção da instituição de formaquanti-qualitativa eações focadas nas necessidades da enfermagem de cuidados críticos, sugerindo-seinvestimentosem pesquisas acerca da temática para promoção das práticas de saúde baseadas em evidências.

Objective:to identify and analyze the perception of nursing about continuing education in health in critical care units of a municipal public hospital in São Paulo. Method: qualitative research, with 35 interviews carried out with the nursing team of adult intensive care units, treated by Content Analysis,in the logic of Maguerez's arc.Results:two categories emerged, both listing Continuing Education as necessary, but failing in the context of nursing work in critical care.Conclusionsthe valorization of educational actions at work is evident and that in this scenario there is no permanent health education per se, with greater attention from the institution being indicated in a quantitative and qualitative way and actions focused on the needs of critical care nursing, suggesting investments in research on the topic to promote evidence-based health practices.

Objetivo:identificar y analizar la percepción de enfermería sobre la educación permanente en salud en unidades de cuidados críticos de un hospital públicomunicipal de São Paulo. Método:investigación cualitativa, con 35 entrevistas realizadas al equipo de enfermería de unidades de cuidados intensivos de adultos, tratadas por Análisis de Contenido, en la lógica del arco de Maguerez.Resultados:surgieron dos categorías, ambas enumerando la educación continua como necesaria, pero fracasando en el contexto del trabajo de enfermería en cuidados críticos. Conclusiones: se evidencia la valorización de las acciones educativas en el trabajo y que en este escenario no existe educación en salud permanente per se, siendo indicada una mayor atención por parte de la institución de manera cuantitativa y cualitativa y acciones enfocadas a las necesidades de la enfermería en cuidados críticos, sugiriendo inversiones. en investigaciones sobre el tema para promover prácticas de salud basadas en evidencia.

Contributions of a Rehabilitation Nursing Program in the Self-Care of Women Undergoing Breast Surgery.

BACKGROUND: Although surgical treatments for breast cancer have exhibited advanced interventions, axillary lymph node dissection can limit functionality and compromise women's self-care. This study aims to assess the effectiveness of a rehabilitation nursing program in improving self-care performance in women undergoing breast surgery with axillary lymph node dissection. METHODS: This quantitative, quasi-experimental study involved 48 women recruited from a main hospital between 2018 and 2019. The participants completed a three-month rehabilitation program at home. The evaluation instrument used was the DASH questionnaire. This study was not registered. RESULTS: The functionality of the upper limb ipsilateral to the surgery improved significantly (p < 0.001) after the implementation of the program, influencing the participants' capacity for self-care, including washing/drying their hair, washing their back, and wearing a shirt. The average DASH total score increased from 54.4 to 8.1 after the program. CONCLUSIONS: The rehabilitation nursing program positively influenced the participants' self-care ability. Incorporating rehabilitation nursing programs into breast cancer treatment can improve self-care performance and the overall quality of patients' lives. This study was not registered.

Evaluation of a Dementia Training Course for Staff of a Center of Dementia Care.

INTRODUCTION: Literature shows poor dementia training and competencies among health and social professionals. Due to the growing prevalence of people with dementia and all the related care demands, specialized training is increasingly needed but must be effective in terms of impact on knowledge, behaviors, and attitudes. We aimed to analyze the impact of a first-level dementia training course for staff of a new specialized center for people with dementia, considering the first three levels of Kirkpatrick's evaluation framework, namely, staff reaction (satisfaction), skills and learning (knowledge and dementia attitudes), and behavior changes. METHODS: This is a single-center group pre-post design study of a 12-session online course. An online questionnaire was administered to measure satisfaction, expectations, knowledge/learning, attitudes (Dementia Attitude Scale), and new behaviors/practices. We compared perceived knowledge (Wilcoxon signed-rank test) and attitudes (paired t test). Thematic analysis explored new behaviors/practices. RESULTS: Eighty-five professionals and 1 volunteer were included (median age 31, 92% female). Satisfaction with the training was high (median 4/5). Perceived knowledge improved (median 3-4; p < 0.001). The knowledge test median score was 70.8%. After training, participants showed better attitudes toward dementia (mean 116.5, SD 10.3, to mean 122.2, SD 11.5; p < 0.001). Most (93%) said their behavior/practice changed. Thematic analysis yielded four new behavior/practice dimensions: care provision/interaction, communication, family/caregivers, and self-confidence. CONCLUSIONS: The course improved all dimensions evaluated, suggesting it effectively provides first-level dementia training. This may be transferable to similar settings.

AI-Driven Discovery of SARS-CoV-2 Main Protease Fragment-like Inhibitors with Antiviral Activity In Vitro.

SARS-CoV-2 is the causative agent of COVID-19 and is responsible for the current global pandemic. The viral genome contains 5 major open reading frames of which the largest ORF1ab codes for two polyproteins, pp1ab and pp1a, which are subsequently cleaved into 16 nonstructural proteins (nsp) by two viral cysteine proteases encoded within the polyproteins. The main protease (Mpro, nsp5) cleaves the majority of the nsp's, making it essential for viral replication and has been successfully targeted for the development of antivirals. The first oral Mpro inhibitor, nirmatrelvir, was approved for treatment of COVID-19 in late December 2021 in combination with ritonavir as Paxlovid. Increasing the arsenal of antivirals and development of protease inhibitors and other antivirals with a varied mode of action remains a priority to reduce the likelihood for resistance emerging. Here, we report results from an artificial intelligence-driven approach followed by in vitro validation, allowing the identification of five fragment-like Mpro inhibitors with IC50 values ranging from 1.5 to 241 µM. The three most potent molecules (compounds 818, 737, and 183) were tested against SARS-CoV-2 by in vitro replication in Vero E6 and Calu-3 cells. Compound 818 was active in both cell models with an EC50 value comparable to its measured IC50 value. On the other hand, compounds 737 and 183 were only active in Calu-3, a preclinical model of respiratory cells, showing selective indexes twice as high as those for compound 818. We also show that our in silico methodology was successful in identifying both reversible and covalent inhibitors. For instance, compound 818 is a reversible chloromethylamide analogue of 8-methyl-γ-carboline, while compound 737 is an N-pyridyl-isatin that covalently inhibits Mpro. Given the small molecular weights of these fragments, their high binding efficiency in vitro and efficacy in blocking viral replication, these compounds represent good starting points for the development of potent lead molecules targeting the Mpro of SARS-CoV-2.

[Long-Term Reversible Contraception in Adolescence: The Reality of a Tertiary Pediatric Hospital in Portugal]. / Contraceção Reversível de Longa Duração na Adolescência: A Realidade de um Hospital Pediátrico Terciário em Portugal.

INTRODUCTION: Contraception in adolescence is essential to prevent unwanted pregnancies, abortion and sexually transmitted diseases. The use of longacting reversible contraceptive methods (LARCs) has been highly recommended due to their efficacy since they are user independent methods. The aim of this study was to evaluate the use of LARCs in adolescence in the population of a Childhood and Adolescence Gynecology clinic, and to describe the sociodemographic characteristics of the adolescents as well as previous contraceptive practices. MATERIAL AND METHODS: Retrospective analysis that included adolescents using LARCs, monitored in a Childhood and Adolescence Gynecology clinic of a Portuguese tertiary pediatric hospital, between June 2012 and June 2021. RESULTS: A total of 122 adolescents were included, with a median age of 16 (11 - 18) years and 62.3% (n = 76) were sexually active. The preferred method was the subcutaneous implant, placed in 82.3% (n = 101), followed by the Levonorgestrel-Intrauterine System in 16.4% (n = 20) and the copper intrauterine device in 1.3% (n = 1). The main indications for LARCs were contraceptive needs 90.2% (n = 110), abnormal uterine bleeding during puberty in 14.8% (n = 18), dysmenorrhea in 10.7% (n = 13) and need for amenorrhea in 0.8% (n = 1). The median time of implant use was 20 (1 - 48) months and of the LNG-IUS it was 20 (1 - 36) months. The 12-month adherence rate for both was 76.2% (n = 93). The removal rate for reasons besides the expiration date was 9.8% (n = 12) in adolescents who had implants, and no LNG-IUS or copper intrauterine devices were removed. There were no pregnancies after insertion of LARCs. CONCLUSION: Contraceptive needs were the main reason for choosing LARCs, followed by abnormal uterine bleeding during puberty management and dysmenorrhea. All these factors may contribute to the high rate of satisfaction and continuity of these methods.

Introdução: A contraceção na adolescência tem um papel fundamental na sociedade por prevenir gravidezes indesejadas e infeções sexualmente transmissíveis. O uso de métodos contracetivos reversíveis de longa duração (LARCs) tem vindo a ser recomendado pela sua eficácia e perfil de segurança nesta faixa etária. O objetivo deste estudo foi avaliar a utilização de LARCs na população de uma consulta de Ginecologia da Infância e Adolescência e descrever as características sociodemográficas das adolescentes assim como a prática contracetiva prévia. Material e Métodos: Análise retrospetiva que incluiu as adolescentes utilizadoras de LARCs, acompanhadas na consulta de Ginecologia da Infância e Adolescência de um hospital pediátrico terciário português, no período entre junho de 2012 e junho de 2021. Resultados: Foram incluídas 122 adolescentes, cuja mediana de idades foi 16 (11 ­ 18) anos. Destas, 62,3% (n = 76) eram sexualmente ativas. O método preferencial foi o implante subcutâneo, colocado em 82,3% (n = 101), seguido do sistema intrauterino de Levonorgestrel (SIU-LNG) em 16,4% (n = 20) e o dispositivo intrauterino de cobre em 1,3% (n = 1). As principais indicações para a escolha de LARCs foram desejo contracetivo em 90,2% (n = 110), hemorragia uterina anormal da puberdade em 14,8% (n = 18), dismenorreia em 10,7% (n = 13) e necessidade de amenorreia em 0,8% (n = 1). O tempo mediano de utilização do implante foi 20 (1 ­ 48) meses e do SIU-LNG 20 (1 ­ 36) meses. A taxa de continuidade aos 12 meses para ambos foi de 76,2% (n = 93). A taxa de remoção antes do tempo padronizado foi de 9,8% (n = 12) nas adolescentes que colocaram implante, sendo que não foram removidos SIU-LNG ou dispositivo intrauterino de cobre. Não se registaram gravidezes após a colocação de LARCs. Conclusão: O desejo contracetivo foi o primeiro motivo para a escolha de um LARC seguido do controlo da hemorragia uterina anormal e da dismenorreia. Todos estes fatores poderão contribuir para a elevada taxa de satisfação e continuidade destes métodos.

Preferences about place of end-of-life care and death of patients with life-threatening illnesses and their families: a protocol for an umbrella review.

INTRODUCTION: For most of history, the majority of people died at home surrounded by family. However, the global scenario has progressively changed towards hospital death and more recently in some countries back again towards home, with indication that COVID-19 may have further increased the number of home deaths. It is therefore timely to establish the state-of-the-art about people's preferences for place of end-of-life care and death, to understand the full spectrum of preferences, nuances and commonalities worldwide. This protocol describes the methods for an umbrella review which aims to examine and synthesise the available evidence regarding preferences about place of end-of-life care and death of patients with life-threatening illnesses and their families. METHODS AND ANALYSIS: We will search for relevant systematic reviews (quantitative and/or qualitative) in six databases from inception without language restrictions: PsycINFO, MEDLINE, EMBASE, CINAHL, PROSPERO and Epistemonikos. Following the Joanna Briggs Institute (JBI) methodology for umbrella reviews, eligibility screening, data extraction and quality assessment (using the JBI Critical Appraisal Checklist) will be done by two independent reviewers. We will report the screening process using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. Study double-counting will be reported using the Graphical Representation of Overlap for OVErviews tool. A narrative synthesis will include 'Summary of Evidence' tables to address five review questions (distribution of preferences and reasons, influencing variables, place of care vs place of death, changes over time, congruence between preferred and actual places), grading the evidence on each question using Grading of Recommendations Assessment, Development and Evaluation (GRADE) and/or GRADE-Confidence in the Evidence from Reviews of Qualitative research. ETHICS AND DISSEMINATION: This review does not require ethical approval. The results will be presented at conferences and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022339983.