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.

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.

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.

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.

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.

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.

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.

The needs of children receiving end of life care and the impact of a paediatric palliative care team: a retrospective cohort study.

Published data collected in hospital during the last year of life of children with life-limiting complex chronic conditions (CCC) is scarce, yet critical, for the implementation of paediatric palliative care (PPC). This study aims to describe the last year of life of children with CCC, in terms of clinical characteristics, hospital resources and the impact of referral to a hospital-based PPC team (PPCT). Using a retrospective cohort study, we examined the clinical records of children aged 1-18 years of age with CCC who died in a tertiary hospital between January 2016 and December 2020. Hospital resources utilised in the last year of life, therapies and procedures during the final week of life, decision to limit treatment (DLT), referral to the PPCT and place of death were analysed. Seventy-two patients (60% male) with a median age of 10.1 years were included. Most had ≥ 2 CCC (58%) with cancer as the most common diagnosis (47%). The group with ≥ 3 CCC (n = 23) had longer hospital stays (p = 0.041). Of the 17 patients referred to the PPCT, there was a higher frequency of DLT (94% vs. 40% in non-referred, p < 0.001), greater use of subcutaneous route (53% vs. 0%, p < 0.001), lower frequency of blood transfusions (12% vs. 55%, p = 0.002) and a lower proportion of deaths in the Intensive Care Unit (6% vs. 64%, p < 0.001). CONCLUSIONS: Early implementation of PPC optimises the use of hospital resources, minimises invasive procedures and therapies, and may develop effective and sustainable alternatives which are better suited to the needs of children and families. WHAT IS KNOWN: • In recent years, there has been an increased prevalence of complex chronic condition (CCC), which has led to more specialised and prolonged medical care until the end of life. • There are few paediatric studies on use of hospital resources and the invasiveness of procedures in the last year of life for children. WHAT IS NEW: • This study is one of the few to provide a comprehensive characterisation of the last year of life of children/adolescents with CCC. • Timely referral to a specialised PPC team optimises the use of hospital resources, minimise invasive procedures and develop effective and sustainable alternatives which are better suited to the needs of children and/or families.

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.

SCRN1: A cerebrospinal fluid biomarker correlating with tau in Alzheimer's disease.

INTRODUCTION: Secernin-1 (SCRN1) is a neuronal protein that co-localizes with neurofibrillary tangles in Alzheimer's disease (AD), but not with tau inclusions in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), or Pick's disease. METHODS: We measured SCRN1 concentration in cerebrospinal fluid (CSF) using a novel mass spectrometric parallel reaction monitoring method in three clinical cohorts comprising patients with neurochemically characterized AD (n = 25) and controls (n = 28), clinically diagnosed Parkinson's disease (PD; n = 38), multiple system atrophy (MSA; n = 31), PSP (n = 20), CBD (n = 8), healthy controls (n = 37), and neuropathology-confirmed AD (n = 47). RESULTS: CSF SCRN1 was significantly increased in AD (P < 0.01, fold change = 1.4) compared to controls (receiver operating characteristic area under the curve = 0.78) but not in CBD, PSP, PD, or MSA. CSF SCRN1 positively correlated with CSF total tau (R = 0.78, P = 1.1 × 10-13 ), phosphorylated tau181 (R = 0.64, P = 3.2 × 10-8 ), and Braak stage and negatively correlated with Mini-Mental State Examination score. DISCUSSION: CSF SCRN1 is a candidate biomarker of AD, reflecting tau pathology. HIGHLIGHTS: We developed a parallel reaction monitoring assay to measure secernin-1 (SCRN1) in cerebrospinal fluid (CSF). CSF SCRN1 was increased in Alzheimer's disease compared to healthy controls. CSF SCRN1 remained unchanged in Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, or corticobasal degeneration compared to controls. CSF SCRN1 correlated strongly with CSF phosphorylated tau and total tau. CSF SCRN1 increased across Braak stages and negatively correlated with Mini-Mental State Examination score.

The effects of early rehabilitation on functional exercise tolerance in decompensated heart failure patients: Results of a multicenter randomized controlled trial (ERIC-HF study).

OBJECTIVE: To analyze (1) the effect of an aerobic training program on functional exercise tolerance in decompensated heart failure (DHF) patients; (2) to assess the effects of an aerobic training program on functional independence; and (3) dyspnea during activities of daily living. DESIGN: A randomized controlled clinical trial with follow-up at discharge. SETTINGS: Eight hospitals. Recruitment took place between 9/ 2017 and 3/2019. GROUP ASSIGNMENTS: Patients with DHF who were admitted to the hospital, were randomly assigned to usual rehabilitation care guideline recommended (control group) or aerobic training program (exercise group). MAIN OUTCOME: Functional exercise tolerance was measured with a 6-min walking test at discharge. RESULTS: In total 257 patients with DHF were included, with a mean age of 67 ± 11 years, 84% (n = 205) had a reduced ejection fraction and the hospital stay was 16 ± 10 days. At discharge, patients in the intervention group walked further compared to the control group (278 ± 117m vs 219 ± 115m, p < 0.01) and this difference stayed significant after correcting for confounders (p < 0.01). A significant difference was found favoring the exercise group in functional independence (96 ± 7 vs 93 ± 12, p = 0.02) and dyspnea associated to ADL (13 ± 5 vs 17 ± 7, p < 0.01) and these differences persisted after correcting for baseline values and confounders (functional independence p < 0.01; dyspnea associated with ADL p = 0.02). CONCLUSION: The ERIC-HF program is safe, feasible, and effective in increasing functional exercise tolerance and functional independence in hospitalized patients admitted due to DHF.

Portuguese adolescents with cystic fibrosis and their parents: An intervention proposal for nursing clinical practice.

PURPOSE: Cystic fibrosis is a life-shortening genetic disease. It affects both patient and family with the nurse playing a key role in the monitoring process. This study sought to contribute to enhanced targeted health care to adolescents with cystic fibrosis and their parents by understanding the experiences of living with cystic fibrosis. Based on Afaf Meleis' Transitions Theory (1986) nurses identify the transition experienced by the study participants, thus contributing to the quality of nursing interventions. DESIGN AND METHODS: Two qualitative research studies using data collected through semi-structured interviews were conducted. The Straussian Grounded Theory was applied. The snowball technique was used for recruitment, under the inclusion criteria: adolescents aged between 10 and 21 years; diagnosis of cystic fibrosis for more than one year; and parents of these adolescents. A final sample of 16 adolescents and 14 parents was obtained. RESULTS: Nursing therapeutic interventions acted as a facilitator of the health/illness transition process. Nurses' intervention areas were identified to empower adolescents and their parents with targeted knowledge and abilities to cope with problems. After diagnosis, parents assumed a new role-playing. CONCLUSIONS: Adolescents with cystic fibrosis and their parents experience various transition phases. Nurses can better help identifying the onset, persistence and ending of harmful periods. PRACTICE IMPLICATIONS: Adolescents with cystic fibrosis and their parents experience various transition phases. Nursing therapeutic interventions are cardinal to the health/illness transition.

Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synuclein.

α-synuclein (aSyn) is a major player in Parkinson's disease and a group of other disorders collectively known as synucleinopathies, but the precise molecular mechanisms involved are still unclear. aSyn, as virtually all proteins, undergoes a series of posttranslational modifications during its lifetime, which can affect its biology and pathobiology. We recently showed that glycation of aSyn by methylglyoxal (MGO) potentiates its oligomerization and toxicity, induces dopaminergic neuronal cell loss in mice, and affects motor performance in flies. Small heat-shock proteins (sHsps) are molecular chaperones that facilitate the folding of proteins or target misfolded proteins for clearance. Importantly, sHsps were shown to prevent aSyn aggregation and cytotoxicity. Upon treating cells with increasing amounts of methylglyoxal, we found that the levels of Hsp27 decreased in a dose-dependent manner. Therefore, we hypothesized that restoring the levels of Hsp27 in glycating environments could alleviate the pathogenicity of aSyn. Consistently, we found that Hsp27 reduced MGO-induced aSyn aggregation in cells, leading to the formation of nontoxic aSyn species. Remarkably, increasing the levels of Hsp27 suppressed the deleterious effects induced by MGO. Our findings suggest that in glycating environments, the levels of Hsp27 are important for modulating the glycation-associated cellular pathologies in synucleinopathies.

The burden of serious health-related suffering among cancer decedents: Global projections study to 2060.

BACKGROUND: Palliative care improves outcomes for people with cancer, but in many countries access remains poor. Understanding future needs is essential for effective health system planning in response to global policy. AIM: To project the burden of serious health-related suffering associated with death from cancer to 2060 by age, gender, cancer type and World Bank income region. DESIGN: Population-based projections study. Global projections of palliative care need were derived by combining World Health Organization cancer mortality projections (2016-2060) with estimates of serious health-related suffering among cancer decedents. RESULTS: By 2060, serious health-related suffering will be experienced by 16.3 million people dying with cancer each year (compared to 7.8 million in 2016). Serious health-related suffering among cancer decedents will increase more quickly in low income countries (407% increase 2016-2060) compared to lower-middle, upper-middle and high income countries (168%, 96% and 39% increase 2016-2060, respectively). By 2060, 67% of people who die with cancer and experience serious health-related suffering will be over 70 years old, compared to 47% in 2016. In high and upper-middle income countries, lung cancer will be the single greatest contributor to the burden of serious health-related suffering among cancer decedents. In low and lower-middle income countries, breast cancer will be the single greatest contributor. CONCLUSIONS: Many people with cancer will die with unnecessary suffering unless there is expansion of palliative care integration into cancer programmes. Failure to do this will be damaging for the individuals affected and the health systems within which they are treated.

25-Hydroxycholesterol Effect on Membrane Structure and Mechanical Properties.

Cholesterol is responsible for the plasticity of plasma membranes and is involved in physiological and pathophysiological responses. Cholesterol homeostasis is regulated by oxysterols, such as 25-hydroxycholesterol. The presence of 25-hydroxycholesterol at the membrane level has been shown to interfere with several viruses' entry into their target cells. We used atomic force microscopy to assess the effect of 25-hydroxycholesterol on different properties of supported lipid bilayers with controlled lipid compositions. In particular, we showed that 25-hydroxycholesterol inhibits the lipid-condensing effects of cholesterol, rendering the bilayers less rigid. This study indicates that the inclusion of 25-hydroxycholesterol in plasma membranes or the conversion of part of their cholesterol content into 25-hydroxycholesterol leads to morphological alterations of the sphingomyelin (SM)-enriched domains and promotes lipid packing inhomogeneities. These changes culminate in membrane stiffness variations.

Evaluation of radiographs for the detection of sublumbar lymphadenopathy in dogs.

The purpose of this study was to evaluate radiographs for the detection of sublumbar lymph node (SLN) enlargement. Ultrasound was used to determine SLN size. Twenty-two dogs with anal gland adenocarcinoma or lymphoma were prospectively included, with 16/22 having SLN enlargement on ultrasound. Twenty-one dogs without enlargement were retrospectively included as controls. Three blinded observers evaluated 43 right lateral abdominal radiographs for the presence of SLN enlargement. Sensitivity and specificity of radiographs for the detection of SLN enlargement were 81%/70%, 94%/81%, and 75%/100% for a general practitioner, imaging resident, and radiologist, respectively. Ventral displacement of the colon, a soft tissue opacity in the caudal retroperitoneal space and loss of conspicuity of the ventral margin of the iliopsoas muscle were radiographic findings significantly associated with identification (P-values < 0.05). Markedly enlarged SLNs (> 21.5 mm) were consistently detected radiographically by observers with specialist imaging training. Key clinical message: Radiographic visualization should raise suspicion of neoplastic infiltration of SLN but lack of visualization does not exclude mild to moderate enlargement. Additional imaging such as ultrasound or computed tomography remains important to confirm or exclude sublumbar lymphadenopathy.

Évaluation de radiographies pour la détection de lymphadénopathie sub-lombaire chez des chiens. Le but de la présente étude était d'évaluer des radiographies pour détecter l'augmentation de taille des ganglions sub-lombaires (SLN). L'échographie fut utilisée pour déterminer la taille des SLN. Vingt-deux chiens avec un adénocarcinome des glandes anales ou un lymphome furent inclus prospectivement, avec 16/22 ayant des SLN augmentés lors de l'échographie. Vingt-et-un chiens sans augmentation de taille furent inclus rétrospectivement comme témoins. Trois observateurs ont évalué à l'aveugle 43 radiographies abdominales latérales droites pour la présence d'augmentation des SLN. La sensibilité et la spécificité des radiographies pour la détection d'augmentation des SLN étaient de 81 %/70 %, 94 %/81 % et 75 %/100 % pour un praticien généraliste, un résident en imagerie et un radiologiste, respectivement. Un déplacement ventral du côlon, une opacité des tissus mous dans l'espace rétropéritonéal caudal et une perte de visibilité de la bordure ventrale du muscle iliopsoas furent des trouvailles radiographiques associées significativement avec l'identification (P < 0,05). Des SLN avec une forte augmentation de taille (> 21,5 mm) étaient constamment détectés radiographiquement par des observateurs avec une formation spécialisée en imagerie.Message clinique clé:La visualisation radiographique devrait soulever des soupçons d'infiltration néoplasique des SNL mais le manque de visualisation n'exclu pas une augmentation de taille de légère à modérée. Des analyses en imagerie additionnelles, telles que l'échographie ou la tomodensitométrie, demeurent importantes pour confirmer ou exclure une lymphadénopathie sub-lombaire.(Traduit par Dr Serge Messier).

Do patients, families, and healthcare teams benefit from the integration of palliative care in burn intensive care units? Results from a systematic review with narrative synthesis.

BACKGROUND: Burn units are intensive care facilities specialized in the treatment of patients with severe burns. As burn injuries have a major impact in physical, psychosocial, and spiritual health, palliative care can be a strengthening component of integrated care. AIM: To review and appraise the existing evidence about the integration of palliative care in burn intensive care units with respect to (1) the concept, model and design and (2) the benefits and outcomes of this integration. DESIGN: A systematic review was conducted following PRISMA guidelines. Protocol registered with PROSPERO (CRD42018111676). DATA SOURCES: Five electronic databases were searched (PubMed/NLM, Web of Science, MEDLINE/TR, Ovid, and CINAHL/EBSCO) until May 2019. A narrative synthesis of the findings was constructed. Hawker et al.'s tool was used for quality appraisal. RESULTS: A total of 299 articles were identified, of which five were included for analysis involving a total of 7353 individuals. Findings suggest that there may be benefits from integrating palliative care in burn units, specifically in terms of patients' comfort, decision-making processes, and family care. Multidisciplinary teams may experience lower levels of burden as result of integrating palliative care in burn units. CONCLUSION: This review reflects the challenging setting of burn intensive care units. Evidence from these articles suggests that the integration of palliative care in burn intensive care units improves patients' comfort, decision-making process, and family care. Further research is needed to better understand how the integration of palliative care in burn intensive care units may be fostered and to identify the outcomes of this integration.

Factors associated with older people's emergency department attendance towards the end of life: a systematic review.

Background: Emergency department (ED) attendance for older people towards the end of life is common and increasing, despite most preferring home-based care. We aimed to review the factors associated with older people's ED attendance towards the end of life. Methods: Systematic review using Medline, Embase, PsychINFO, CINAHL and Web of Science from inception to March 2017. Included studies quantitatively examined factors associated with ED attendance for people aged ≥65 years within the last year of life. We assessed study quality using the QualSyst tool and determined evidence strength based on quality, quantity and consistency. We narratively synthesized the quantitative findings. Results: Of 3824 publications identified, 21 were included, combining data from 1 565 187 participants. 17/21 studies were from the USA and 19/21 used routinely collected data. We identified 47 factors and 21 were included in the final model. We found high strength evidence for associations between ED attendance and palliative/hospice care (adjusted effect estimate range: 0.1-0.94); non-white ethnicity (1.03-2.16); male gender (1.04-1.83, except 0.70 in one sub-sample) and rural areas (0.98-1.79). The final model included socio-demographic, illness and service factors, with largest effect sizes for service factors. Conclusions: In this synthesis, receiving palliative care was associated with lower ED attendance in the last year of life for older adults. This has implications for service models for older people nearing the end of life. However, there is limited evidence from European countries and none from low or middle-income countries, which warrants further research.

The impact of population ageing on end-of-life care in Scotland: projections of place of death and recommendations for future service provision.

BACKGROUND: Global annual deaths are rising. It is essential to examine where future deaths may occur to facilitate decisions regarding future service provision and resource allocation. AIMS: To project where people will die from 2017 to 2040 in an ageing country with advanced integrated palliative care, and to prioritise recommendations based on these trends. METHODS: Population-based trend analysis of place of death for people that died in Scotland (2004-2016) and projections using simple linear modelling (2017-2040); Transparent Expert Consultation to prioritise recommendations in response to projections. RESULTS: Deaths are projected to increase by 15.9% from 56,728 in 2016 (32.8% aged 85+ years) to 65,757 deaths in 2040 (45% aged 85+ years). Between 2004 and 2016, proportions of home and care home deaths increased (19.8-23.4% and 14.5-18.8%), while the proportion of hospital deaths declined (58.0-50.1%). If current trends continue, the numbers of deaths at home and in care homes will increase, and two-thirds will die outside hospital by 2040. To sustain current trends, priorities include: 1) to increase and upskill a community health and social care workforce through education, training and valuing of care work; 2) to build community care capacity through informal carer support and community engagement; 3) to stimulate a realistic public debate on death, dying and sustainable funding. CONCLUSION: To sustain current trends, health and social care provision in the community needs to grow to support nearly 60% more people at the end-of-life by 2040; otherwise hospital deaths will increase.