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Background Disordered mineral and bone metabolism is a common complication of chronic kidney disease (CKD). Bone biopsy remains the gold standard tool for evaluating renal osteodystrophy (ROD), but it is an invasive procedure. Despite a growing interest in the ability of newer bone biomarkers to discriminate between different forms of ROD, data on pre-dialysis patients are scarce. Methods A cross-sectional study was conducted in a cohort of 56 patients with CKD Stages 3 and 4. Participants underwent a transiliac bone biopsy after a course of double tetracycline labelling. Circulating levels of Wnt signalling inhibitors sclerostin and Dickkopf-1 (DKK1), soluble receptor activator of nuclear factor-κB ligand (sRANKL) and osteoprotegerin were measured and correlated with histomorphometric analysis results. Results Most patients had abnormal bone histology and low-turnover bone disease was the predominant form of ROD. Characteristics associated with high bone turnover were worse renal function, lower serum calcium and higher intact parathyroid hormone and fibroblast growth factor-23 levels. Patients with low bone turnover, on the other hand, presented with higher sclerostin along with lower DKK1 and sRANKL levels. In the multivariable logistic regression analysis, sclerostin and DKK1 levels were independently associated with low-turnover bone disease. Conclusions Our results suggest that circulating levels of Wnt signalling inhibitors sclerostin and DKK1 are predictive of low-turnover bone disease in patients not yet on dialysis. Further research is needed to assess the performance of these bone turnover biomarkers, compared with histomorphometric analysis, in the diagnosis and treatment monitoring of ROD., Graphical Abstract Graphical Abstract

The transition to motherhood is a deeply personal experience that can have an effect on women’s psychological, social, and spiritual sense of self. This qualitative study explored women’s lived experiences of their transition to motherhood and the role that spirituality plays in the process of transformation. Six women, two with postpartum depression, were interviewed on their experiences of pregnancy, childbirth, early motherhood, and spirituality. Interpretative phenomenological analysis was used to analyze interview data and identify emergent themes in women’s experiences of motherhood. Two superordinate themes emerged—Reality of Motherhood and Motherhood Awakens Spirituality. Spirituality was “centered” in the women’s overall experience of motherhood. The women emphasized the importance of spiritual connections to others and the divine in their understanding of what it means to be a mother. The women with postpartum depression described similar but more intense experiences in their transition to motherhood in comparison to women who did not have postpartum depression. The findings highlight how the experiences of motherhood and spirituality mutually influence each other toward the development of an integrated identity as mother. Clinicians need to attend to the potential positive and negative roles of spirituality in women’s transition to motherhood and intervene early to address any indications of emotional or spiritual struggle in women’s adjustment.

Background: Dementia due to Alzheimer’s disease (AD) is a complex neurodegenerative disorder, which much of heritability remains unexplained. At the clinical level, one of the most common physiological alterations is the slowing of oscillatory brain activity, measurable by electroencephalography (EEG). Relative power (RP) at the conventional frequency bands (i.e., delta, theta, alpha, beta-1, and beta-2) can be considered as AD endophenotypes. Objective: The aim of this work is to analyze the association between sixteen genes previously related with AD: APOE, PICALM, CLU, BCHE, CETP, CR1, SLC6A3, GRIN2 β, SORL1, TOMM40, GSK3 β, UNC5C, OPRD1, NAV2, HOMER2, and IL1RAP, and the slowing of the brain activity, assessed by means of RP at the aforementioned frequency bands. Methods: An Iberian cohort of 45 elderly controls, 45 individuals with mild cognitive impairment, and 109 AD patients in the three stages of the disease was considered. Genomic information and brain activity of each subject were analyzed. Results: The slowing of brain activity was observed in carriers of risk alleles in IL1RAP (rs10212109, rs9823517, rs4687150), UNC5C (rs17024131), and NAV2 (rs1425227, rs862785) genes, regardless of the disease status and situation towards the strongest risk factors: age, sex, and APOE ɛ4 presence. Conclusion: Endophenotypes reduce the complexity of the general phenotype and genetic variants with a major effect on those specific traits may be then identified. The found associations in this work are novel and may contribute to the comprehension of AD pathogenesis, each with a different biological role, and influencing multiple factors involved in brain physiology.

Background:Nurses are the largest regulated group of healthcare professionals involved in palliative care. In 2004, a taskforce of the European Association for Palliative Care (EAPC) launched the ‘Guide for development of palliative nurse education in Europe’ (hereinafter, the EAPC 2004 Guide). No systematic evaluation of its impact in the development of palliative care education was undertaken.Aims:To describe current undergraduate and postgraduate nursing education across Europe; to identify the roles that nurses with different palliative care educational levels have in palliative care; and to assess the uptake of the EAPC 2004 Guide in the development of palliative care nursing in Europe.Design:Descriptive research involving an online survey among nursing experts, and the consultation of national representatives.Setting/participants:A total of 135 nurses (52% response rate) from 25 countries completed the online survey; representatives from 16 countries were consulted.Results:In 14 (56%) countries, palliative care was not identified as a mandatory subject within undergraduate nursing education. The EAPC 2004 Guide is widely known and was/is being used in many countries to promote palliative care nursing education. Large variations were found across and within country responses.Conclusions:Palliative care nursing education varies largely in Europe. The wide awareness and use of the EAPC 2004 Guide show how policy measures can influence the development of palliative care education. Recommendations are built and focus on both fostering the use of this guide and implementing policy measures to ensure that palliative care nursing is recognised and certified as a specialty in all European countries.

Background: Postmenopausal women have an elevated risk of developing cardiovascular diseases, which can be counteracted by conventional exercise regimes or recreational football. Less is known about the impact of exercise programmes based on other team sports. Thus, we examined the effects of recreational team handball on aerobic performance, cardiorespiratory fitness and cardiometabolic health in untrained postmenopausal women. Methods: Sixty-seven participants (age 68 ± 6 years, stature 157 ± 6 cm, body mass 67 ± 10 kg, fat mass 37 ± 7%, VO2peak 25.2 ± 3.6 mL/min/kg, Yo-Yo intermittent endurance level 1 test performance (YYIE1) 230 ± 103 m) with no previous experience of team handball were randomly allocated to either a team handball (THG, n = 41) or a control (CG, n = 26) group. THG performed 2-3 60-min training sessions per week for 16 weeks. YYIE1 performance and cardiometabolic markers were evaluated at baseline and post-intervention. Results: Average attendance during recreational team handball training was 1.9 ± 0.4 sessions per week, with mean heart rates of 76 ± 6%HRmax and 18 ± 9 min (44 ± 20% of total time) played at HR > 80%HRmax. A between-group effect was observed for YYIE1 performance, with a more pronounced improvement in aerobic exercise performance in THG compared to CG (70 ± 62 vs 15 ± 44%; p < 0.001). Within-group improvements (p < 0.05) were observed for THG with regard to VO2peak (7 ± 10%), incremental treadmill test time to exhaustion (TTE) (11 ± 14%), total cholesterol (-3 ± 9%) and low-density lipoprotein cholesterol (-2 ± 14%), with no significant changes in CG except an increase (p < 0.05) in TTE. Post-intervention values were higher for THG vs CG for YYIE1 performance (88%; 406 ± 216 vs 216 ± 75 m) and VO2peak (10%; 27.5 ± 3.8 vs 24.9 ± 3.6 mL/min/kg). Conclusions: Recreational team handball can be used to obtain moderate-to-vigorous aerobic intensities, and just 2 weekly 60-min team handball training sessions for 16 weeks can result in improvements in aerobic performance and in markers of cardiorespiratory fitness in postmenopausal women with no previous experience of the sport. RP is supported by a grant from the Portuguese Foundation for Science and Technology (SFRH/BD/136789/2018). This study is part of the Handball for Health project, which has the support of the Portuguese Handball Federation, the European Handball Federation and Gaia City Hall. We would like to thank all the participants for their committed participation. We would also like to express our gratitude to the students and technicians of the University Institute of Maia and Faculty of Sport, University of Porto, who collaborated in the data collection and provided technical assistance, and to Henrik Holm Andersen from Copenhagen Translation for the language editing.

Predictions of mortality may help in the selection of patients who benefit from intensive care. Endothelial dysfunction is partially responsible for many of the organic dysfunctions in critical illness. Reactive hyperaemia is a vascular response of the endothelium that can be measured by peripheral arterial tonometry (RH-PAT). We aimed to assess if reactive hyperaemia is affected by critical illness and if it correlates with outcomes. Prospective study with a cohort of consecutive patients admitted to an Intensive Care Unit. RH-PAT was accessed on admission and on the 7th day after admission. Early and late survivors were compared to non-survivors. The effect of RH-PAT variation on late mortality was studied by a logistic regression model. The association between RH-PAT and severity scores and biomarkers of organic dysfunction was investigated by multivariate analysis. 86 patients were enrolled. Mean ln(RHI) on admission was 0.580 and was significantly lower in patients with higher severity scores (p

Machado-Joseph disease (MJD/SCA3) is the most common form of dominantly inherited ataxia worldwide. The disorder is caused by an expanded CAG repeat in the ATXN3 gene. Past studies have revealed that the length of the expansion partly explains the disease age at onset (AO) variability of MJD, which is confirmed in this study (Pearson's correlation coefficient R2 = 0.62). Using a total of 786 MJD patients from five different geographical origins, a genome-wide association study (GWAS) was conducted to identify additional AO modifying factors that could explain some of the residual AO variability. We identified nine suggestively associated loci (P < 1 × 10-5). These loci were enriched for genes involved in vesicle transport, olfactory signaling, and synaptic pathways. Furthermore, associations between AO and the TRIM29 and RAG genes suggests that DNA repair mechanisms might be implicated in MJD pathogenesis. Our study demonstrates the existence of several additional genetic factors, along with CAG expansion, that may lead to a better understanding of the genotype-phenotype correlation in MJD. FA and CL were funded by the Fonds de Recherche du Québec–Santé. SM is funded by FCT (CEECIND/00684/2017) and by NORTE-01-0145- FEDER-000008, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). FM and LI are funded by Fundaçao de Amparo a Pesquisa do Estado de São Paulo (FAPESP, 2013/07559-3). MLSP and LBJ were funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq) and by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). GAR holds a Canada Research Chair in Genetics of the Nervous System and the Wilder Penfield Chair in Neurosciences.

Aim: Bone disease after kidney transplant (KT) results from multiple factors, including previous bone and mineral metabolism disturbances and effects of transplant-related medications. New biomolecules have been recently associated with the development and progression of the chronic kidney disease–associated bone and mineral disorder (CKD-MBD). These include sclerostin and the soluble receptor activator of nuclear factor-kB ligand (sRANKL). Methods: To better understand the role of biomarkers in post-transplant bone disease, this study was designed to prospectively evaluate and correlate results from the histomorphometric analysis of bone biopsies after KT with emerging serum biomarkers of the CKD-MBD: sclerostin, Dickkopf-related protein 1 (Dkk-1), sRANKL and osteo-protegerin (OPG). Results: Our data shows a significant increase in plasma levels of bioactive sclerostin after KT accompanied by a significant reduction in plasma levels of Dkk-1, suggesting a promotion of the inhibition of bone formation by osteoblasts through the activation of these inhibitors of the Wnt signaling pathway. In addition, we found a significant increase in plasma levels of free sRANKL after KT accompanied by a significant reduction in plasma levels of its decoy receptor OPG, suggesting an enhanced bone resorption by osteoclasts mediated by this mechanism. Conclusions: Taken together, these results suggest that the loss of bone volume observed after KT could be explain mainly by the inhibition of bone formation mediated by sclerostin accompanied by an enhanced bone resorption mediated by sRANKL.

Acute myeloid leukemia (AML) is a heterogeneous disease with poor prognosis and limited treatment strategies. Determining the role of cell-extrinsic regulators of leukemic cells is vital to gain clinical insights into the biology of AML. Iron is a key extrinsic regulator of cancer, but its systemic regulation remains poorly explored in AML. To address this question, we studied iron metabolism in patients with AML at diagnosis and explored the mechanisms involved using the syngeneic MLL-AF9–induced AML mouse model. We found that AML is a disorder with a unique iron profile, not associated with inflammation or transfusion, characterized by high ferritin, low transferrin, high transferrin saturation (TSAT), and high hepcidin. The increased TSAT in particular, contrasts with observations in other cancer types and in anemia of inflammation. Using the MLL-AF9 mouse model of AML, we demonstrated that the AML-induced loss of erythroblasts is responsible for iron redistribution and increased TSAT. We also show that AML progression is delayed in mouse models of systemic iron overload and that elevated TSAT at diagnosis is independently associated with increased overall survival in AML. We suggest that TSAT may be a relevant prognostic marker in AML.

Background:The prevalence of thyroid dysfunction and autoimmunity in the Portuguese population has not yet been estimated. However, the national prevalence of the metabolic syndrome remains high. The association of thyroid pathology with cardiovascular risk has been addressed but is still unclear. Our study aimed to evaluate the prevalence of thyroid dysfunction and autoimmunity and to assess the associations of thyroid-stimulating hormone and thyroid hormones and antibodies with metabolic syndrome, its components, and other possible determinants in a national sample.Material and Methods:The present study included a subsample of 486 randomly selected participants from a nationwide cross-sectional study sample of 4095 adults. A structured questionnaire was administered on past medical history and socio-demographic and behavioural characteristics. Blood pressure and anthropometric measurements were collected, and the serum lipid profile, glucose, insulin, hs- CRP, TSH, FT4, FT3 and thyroid antibodies were measured.Results:In our sample, the prevalence of hypothyroidism, hyperthyroidism and undiagnosed dysfunction was 4.9%, 2.5% and 72.2%, respectively. Overall, the prevalence of positivity for the thyroid peroxidase and thyroglobulin antibodies was 11.9% and 15.0%, respectively. A positive association was found between free triiodothyronine and metabolic syndrome (OR: 2.019; 95% CI: 1.196, 3.410). Additionally, thyroid peroxidase antibodies had a negative association with metabolic syndrome (OR: 0.465; 95% CI: 0.236, 0.917) and its triglyceride component (OR: 0.321; 95% CI: 0.124, 0.836).Conclusion:The prevalence of undiagnosed thyroid dysfunction and autoimmunity was high. Thyroid peroxidase antibodies were negatively associated with metabolic syndrome and its triglyceride component, whereas the free triiodothyronine level was positively associated with metabolic syndrome.

Dynamic mutations by microsatellite instability are the molecular basis of a growing number of neuromuscular and neurodegenerative diseases. Repetitive stretches in the human genome may drive pathogenicity, either by expansion above a given threshold, or by insertion of abnormal tracts in nonpathogenic polymorphic repetitive regions, as is the case in spinocerebellar ataxia type 37 (SCA37). We have recently established that this neurodegenerative disease is caused by an (ATTTC)n insertion within an (ATTTT)n in a noncoding region of DAB1. We now investigated the mutational mechanism that originated the (ATTTC)n insertion within an ancestral (ATTTT)n . Approximately 3% of nonpathogenic (ATTTT)n alleles are interspersed by AT-rich motifs, contrarily to mutant alleles that are composed of pure (ATTTT)n and (ATTTC)n stretches. Haplotype studies in unaffected chromosomes suggested that the primary mutational mechanism, leading to the (ATTTC)n insertion, was likely one or more T>C substitutions in an (ATTTT)n pure allele of approximately 200 repeats. Then, the (ATTTC)n expanded in size, originating a deleterious allele in DAB1 that leads to SCA37. This is likely the mutational mechanism in three similar (TTTCA)n insertions responsible for familial myoclonic epilepsy. Because (ATTTT)n tracts are frequent in the human genome, many loci could be at risk for this mutational process. We are grateful to the families and individuals who participated in this work. We thank Patricia Ribeiro for technical assistance. This study was financed by Fundo Europeu de Desenvolvimento Regional (FEDER), through the COMPETE 2020 Operational Pro- gram for Competitiveness and Internationalization (POCI) of Portugal 2020, and by the Fundacão para a Ciência e a Tecnologia (FCT) and Ministério da Ciência, Tecnologia e Ensino Superior (Portugal), in the framework of the project POCI-01-0145-FEDER-029255; (PTDC/MED-GEN/29255/2017) to I.S. J.R.L. and C.L.O. were sup- ported by scholarships from PEst-C/SAU/LA0002/2013. S.M. is funded by the project IF/00930/2013/ CP1184/CT0002 from FCT. This work was also funded by the Porto Neurosciences and Neurologic Disease Research Initiative at the Instituto de Investigação e Inovação em Saúde (Norte-01-0145-FEDER- 000008), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTU- GAL 2020 Partnership Agreement with FEDER.

Vitamin D deficiency has been associated with significant changes in dental structures. In children, it can induce enamel and dentin defects, which have been identified as risk factors for caries. This study aimed to assess the association between low serum 25-hydroxyvitamin D (25(OH) D) levels (&lt, 30 ng/mL) and the prevalence of caries in the permanent teeth and mixed dentition of 7-year-old children. A sample of 335 children from the population-based birth cohort Generation XXI (Porto, Portugal) was included. Data on children&rsquo, s demographic and social conditions, health status, dental health behaviours, dental examination including erupted permanent first molars, and blood samples available for vitamin D analysis were collected. Dental outcomes included the presence of caries, including non-cavitated lesions (d1&ndash, 6mft/D1&ndash, 6MFT &gt, 0), and advanced caries (d3&ndash, 6mft/D3&ndash, 6MF &gt, 0). Serum 25(OH) D was measured using a competitive electrochemiluminescence immunoassay protein-binding assay. Bivariate analysis and multivariate logistic regression were used. Advanced caries in permanent teeth was significantly associated with children&rsquo, s vitamin D levels &lt, 30 ng/mL, gastrointestinal disorders, higher daily intake of cariogenic food, and having had a dental appointment at &le, 7 years old. Optimal childhood levels of vitamin D may be considered an additional preventive measure for dental caries in the permanent dentition.

Background Maternal high-caloric nutrition and related gestational diabetes mellitus (GDM) are associated with a high-risk for developing metabolic complications later in life and in their offspring. In contrast, exercise is recognized as a non-pharmacological strategy against metabolic dysfunctions associated to lifestyle disorders. Therefore, we investigated whether gestational exercise delays the development of metabolic alterations in GDM mothers later in life, but also protects 6-week-old male offspring from adverse effects of maternal diet. Methods Female Sprague-Dawley rats were fed with either control (C) or high-fat high-sucrose (HFHS) diet to induce GDM and submitted to gestational exercise during the 3 weeks of pregnancy. Male offspring were sedentary and fed with C-diet. Results Sedentary HFHS-fed dams exhibited increased gestational body weight gain (p

Background The Zika virus (ZIKV) is a flavivirus and the human disease caused by this virus has been described in the Americas in 2015. ZIKV has been identified as an etiological agent of acute exanthematous disease in Brazil. In the same year, an epidemic of microcephaly with images suggestive of congenital infection raised the suspicion of a relationship between these alterations and ZIKV infection. Epidemiological and histopathological studies point to a strong relationship between prenatal Zika virus infection and microcephaly. Newborns with microcephaly, may also present auditory and visual changes, seizures and severe neurodevelopmental impairment. In 2016, the World Health Organization (WHO) declared Zika virus (ZIKV) infection a public health emergency of international concern. Aims Clinical observation in the ambulatory school of ABRAH (Brazilian Association of Recycling and Homeopathy Assistance) of patients with encephalopathy of various origins, using the medicine Helleborus niger as equalizer of the NS (Nervous System), as described in the Complex Systems of Carillo, shows improvement in motor, cognitive and seizure disorders. Based on this observation, we propose to use this method in patients with ZIKV congenital infection. Methodology To evaluate 15 patients in follow-up at the AFR (Fluminense Rehabilitation Association), through homeopathic anamnesis, clinical, diathesic, biotypological and temperamental classification. The Gross Motor Function Classification System (GMFCS) will be used. All patients will receive Helleborus niger 6 Ch daily for 6 months. Results and discussion This study was forwarded to the research ethics committee and will begin in July 2019. Will be evaluated the use of Helleborus niger in patients with congenital infection by ZIKV, as equalizer of NS. The expected result is overall neurological improvement. Conclusion Helleborus niger, probably stimulating self-regulation through uninjured neurological pathways, will promote autopoiesis and construction of new programs of action, and will enable the improvement of patients with congenital ZIKV infection.

Brain waves, measured by electroencephalography (EEG), are a powerful tool in the investigation of neurophysiological traits and a noninvasive and cost-effective alternative in the diagnostic of some neurological diseases. In order to identify novel Quantitative Trait Loci (QTLs) for brain wave relative power (RP), we collected resting state EEG data in five frequency bands (&delta, &theta, &alpha, &beta, 1, and &beta, 2) and genome-wide data in a cohort of 105 patients with late onset Alzheimer&rsquo, s disease (LOAD), 41 individuals with mild cognitive impairment and 45 controls from Iberia, correcting for disease status. One novel association was found with an interesting candidate for a role in brain wave biology, CLEC16A (C-type lectin domain family 16), with a variant at this locus passing the adjusted genome-wide significance threshold after Bonferroni correction. This finding reinforces the importance of immune regulation in brain function. Additionally, at a significance cutoff value of 5 &times, 10&minus, 6, 18 independent association signals were detected. These signals comprise brain expression Quantitative Loci (eQTLs) in caudate basal ganglia, spinal cord, anterior cingulate cortex and hypothalamus, as well as chromatin interactions in adult and fetal cortex, neural progenitor cells and hippocampus. Moreover, in the set of genes showing signals of association with brain wave RP in our dataset, there is an overrepresentation of loci previously associated with neurological traits and pathologies, evidencing the pleiotropy of the genetic variation modulating brain function.

Neck circumference (NC) has been proposed as a simple and practical tool, independently associated with cardiometabolic risk factors. However, the association of NC with inter-muscular adipose tissue (IMAT) is still to be determined. We aimed to examine the association of NC with thigh IMAT, and visceral adipose tissue (VAT) measured with computed tomography (CT) in overweight/obese women. 142 premenopausal overweight and obese Caucasian women participated in this cross-sectional study. NC was measured with an inextensible metallic tape above the thyroid cartilage according to International Society for Advancement of Kinanthropometry protocol. Thigh IMAT and VAT volumes were measured with a single cross-sectional CT. Regarding the covariates, fat mass (FM) was assessed with dual-energy x-ray absorptiometry and physical activity was objectively measured with accelerometry. NC was positively associated with thigh IMAT and VAT volumes (standardized β coefficient: β = 0.45, P-value = ≤0.001, β = 0.60, P = ≤ 0.001; respectively), which persisted after adjusting for age, height, overall FM or moderate-to-vigorous physical activity. Our findings show that NC is associated with thigh IMAT volume in overweight and obese premenopausal Caucasian women, regardless of the amount of lower-body fatness. These results suggest underscoring the relevance of NC as a marker of adipose tissue content in thigh skeletal muscle.

Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is predominantly caused by mutations in genes that encode sarcomere-associated proteins. Effective gene-based diagnosis is critical for the accurate clinical management of patients and their family members. However, the introduction of high-throughput DNA sequencing approaches for clinical diagnostics has vastly expanded the number of variants of uncertain significance, leading to many inconclusive results that limit the clinical utility of genetic testing. More recently, developments in RNA analysis have been improving diagnostic outcomes by identifying new variants that interfere with splicing. This review summarizes recent discoveries of RNA mis-splicing in HCM and provides an overview of research that aims to apply the concept of RNA therapeutics to HCM.

Alzheimer&rsquo, s disease (AD) is the most prevalent cause of dementia, being considered a major health problem, especially in developed countries. Late-onset AD is the most common form of the disease, with symptoms appearing after 65 years old. Genetic determinants of AD risk are vastly unknown, though, &epsilon, 4 allele of the ApoE gene has been reported as the strongest genetic risk factor for AD. The objective of this study was to analyze the relationship between brain complexity and the presence of ApoE &epsilon, 4 alleles along the AD continuum. For this purpose, resting-state electroencephalography (EEG) activity was analyzed by computing Lempel-Ziv complexity (LZC) from 46 healthy control subjects, 49 mild cognitive impairment subjects, 45 mild AD patients, 44 moderate AD patients and 33 severe AD patients, subdivided by ApoE status. Subjects with one or more ApoE &epsilon, 4 alleles were included in the carriers subgroups, whereas the ApoE &epsilon, 4 non-carriers subgroups were formed by subjects without any &epsilon, 4 allele. Our results showed that AD continuum is characterized by a progressive complexity loss. No differences were observed between AD ApoE &epsilon, 4 carriers and non-carriers. However, brain activity from healthy subjects with ApoE &epsilon, 4 allele (carriers subgroup) is more complex than from non-carriers, mainly in left temporal, frontal and posterior regions (p-values &lt, 0.05, FDR-corrected Mann&ndash, Whitney U-test). These results suggest that the presence of ApoE &epsilon, 4 allele could modify the EEG complexity patterns in different brain regions, as the temporal lobes. These alterations might be related to anatomical changes associated to neurodegeneration, increasing the risk of suffering dementia due to AD before its clinical onset. This interesting finding might help to advance in the development of new tools for early AD diagnosis.

Background: Palliative care exists in diverse healthcare settings. Nurses play a crucial role in its provision. Different levels of palliative care provision and education have been recognized in the literature. Therefore, nurses need a set of various competencies to provide high-quality palliative care. Aims: To systematically synthesize the empirical evidence of (1) nursing competencies needed in palliative care and (2) whether these competencies differ across the level of palliative care. Design: Systematic integrative review with thematic synthesis. Prospero: CRD42018114869. Data sources: CINAHL, PubMed, Academic Search Premier, Scopus and Medic databases. Studies on nursing competencies linked to palliative care reported in English, Swedish, Finnish, Spanish, Portuguese or German were considered. Search terms: ‘palliative care or hospice care or end-of-life care’, ‘competency or professional competence or skills’ and ‘nursing’. Articles were independently screened and reviewed by two researchers. Quality appraisal was conducted following Hawker’s criteria. Results: A total of 7454 articles were retrieved, 21 articles were included in the analysis. Six diverse nursing competencies dimensions, namely leadership, communication, collaboration, clinical, ethico-legal and psycho-social and spiritual were identified. The reports rarely defined the level of palliative care and covered a wide array of healthcare settings. Conclusion: Nurses need a wide range of competencies to provide quality palliative care. Few studies focused on which competencies are relevant to a specific level of palliative care. Further research is needed to systematize the nursing competencies and define which nursing competencies are central for different levels of palliative care to enhance palliative care development, education and practice.

(1) Background: half-marathon races are popular among recreational runners, with increases in participation among middle-aged and women. We aimed to determine the effects of two half-marathon training programs on hematological and biochemical markers in middle-aged female recreational runners; (2) Methods: ten women (40 ± 7 years) followed moderate intensity continuous training (MICT), based on running volume below 80% V˙O2max, and another ten women followed high intensity interval training (HIIT) at 80%–100% V˙O2max, with less volume, and combined with eccentric loading exercise. Hematology, plasma osmolality, and plasma markers of metabolic status, muscle damage, inflammatory, and oxidative stress were measured before (S1) and after (S2) training and 24 h after the half-marathon (S3); (3) Results: both training programs had similar moderate effects at S2. However, the acute response at S3 induced different alterations. There was a greater decrease in cholesterol and triglyceride levels in MICT and reductions in markers of damage and inflammation in HIIT. Greater variability in some plasma markers at S3 in MICT suggests that there is inter-individual variability in the response to training; (4) Conclusions: HIIT led to better adaptation to the competition maybe because of the repeated exposure to higher oxygen consumption and eccentric loading exercise.

Introduction The practice and study of pain management pose myriad ethical challenges. There is a consensual opinion that adequate management of pain is a medical obligation rooted in classical Greek practice. However, there is evidence that patients often suffer from uncontrolled and unnecessary pain. This is inconsistent with the leges artis, and its practical implications merit a bioethical analysis. Several factors have been identified as causes of uncontrolled and unnecessary pain, which deprive patients from receiving appropriate treatments that theoretically they have the right to access. Important factors include (with considerable regional, financial, and cultural differences) the following: 1) failure to identify pain as a priority in patient care; 2) failure to establish an adequate physician–patient relationship; 3) insufficient knowledge regarding adequate prescription of analgesics; 4) conflicting notions associated with drug-induced risk of tolerance and fear of addiction; 5) concerns regarding “last-ditch” treatments of severe pain; and 6) failure to be accountable and equitable. Objective The aim of this article was to establish that bioethics can serve as a framework for addressing these challenging issues and, from theoretical to practical approaches, bioethical reflection can contextualize the problem of unrelieved pain. Methods This article is organized into three parts. First, we illustrate that pain management and its undertreatment are indeed ethical issues. The second part describes possible ethical frameworks that can be combined and integrated to better define the ethical issues in pain management. Finally, we discuss possible directions forward to improve ethical decision making in pain management. Discussion We argue that 1) the treatment of pain is an ethical obligation, 2) health science schools, especially medical training institutions, have the duty to teach pain management in a comprehensive fashion, and 3) regulatory measures, which prevent patients from access to opioid treatment as indicated in their cases, are unethical and should be reconsidered. Conclusion Developing an ethical framework for pain management will result in enhanced quality of care, linking the epistemic domains of pain management to their anthropological foundations, thereby making them ethically sound., Video abstract

Background: Communication is present in all encounters in care and of importance to create a caring relation. A good relation between patients, next of kin and health care staff is crucial, not lea ...

Background: Vitamin D (VitD) and parathyroid hormone (PTH) play important roles in calcium metabolism and skeletal homeostasis. Estimates of the VitD status in several European countries show large variations between them. In addition, no national population-based estimate has been published. VitD and PTH may also play important roles in cardiovascular risk, which has been suggested to be associated with metabolic syndrome (MetS) and is very prevalent in Portugal. The goal of our study was to evaluate the prevalence of hypovitaminosis D and its determinants as well as PTH serum level determinants and associations of the 25-hydroxyvitamin D and PTH serum levels with MetS and its individual components in a sample of the Portuguese mainland population. Methods: PORMETS is a national cross-sectional study that includes a total sample of 4095 adults. A subsample, including 500 participants, was randomly selected for the present study. A structured questionnaire was administered to collect information on personal medical histories and socio-demographic and behavioral characteristics. Blood pressure and anthropometrics measurements were performed. Fasting venous samples were collected and PTH and 25-hydroxyvitamin D were measured. VitD adequacy was classified according to the Institute of Medicine, and MetS was classified according to the Joint Interim Statement recommendations. Multiple linear regression and unconditional logistic regression models were used to estimate the associations between the levels of PTH and 25-hydroxyvitamin D and with MetS and its individual components. Results: The prevalence of VitD deficiency was 37.7%, and MetS was present in 191 participants (38.4%). The serum PTH levels showed a positive association (OR: 1.014; 95%CI: 1.002, 1.026) with the waist circumference component of MetS. The serum 25-hydroxyvitamin D levels were negatively associated with MetS (OR: 0.957; 95%CI: 0.922, 0.993) as well as with its blood pressure (OR: 0.949; 95%CI: 0.912, 0.987) and triglycerides (OR: 0.930; 95%CI: 0.892, 0.969) components. Conclusion: This study showed a high national prevalence of hypovitaminosis D. The PTH levels showed a significant positive association with the WC component of MetS, and the VitD levels were negatively associated with the BP and triglycerides components as well as with the MetS. This work was supported by the Insulin Resistance Study Group of the Endocrinology, Diabetes and Metabolism Portuguese Society. Ana Cristina Santos holds a FCT Investigator contract IF/01060/2015.

AIM: Explore the use of transferrin-receptor peptide-functionalized nanoparticles (NPs) targeting blood-brain barrier (BBB) as siRNA carriers to silence P-glycoprotein (P-gp).MATERIALS & METHODS: Permeability experiments were assessed through a developed BBB cell-based model; P-gp mRNA expression was evaluated in vitro; rhodamine 123 permeability was assessed after cell monolayer treatment with siRNA NPs.RESULTS: Beyond their ability to improve siRNA permeability through the BBB by twofold, 96-h post-transfection, functionalized polymeric NPs successfully reduced P-gp mRNA expression up to 52%, compared with nonfunctionalized systems. Subsequently, the permeability of rhodamine 123 through the human BBB model increased up to 27%.CONCLUSION: Developed BBB-targeted NPs induced P-gp downregulation and consequent increase on P-gp substrate permeability, revealing their ability to modulate drug efflux at the BBB.

Introduction Antimicrobial resistance (AMR) is a challenging global and public health issue, raising bioethical challenges, considerations and strategies. Objectives This research protocol presents a conceptual model leading to formulating an empirically based bioethics framework for antibiotic use, AMR and designing ethically robust strategies to protect human health. Methods Mixed methods research will be used and operationalized into five substudies. The bioethical framework will encompass and integrate two theoretical models: global bioethics and ethical decision-making. Results Being a study protocol, this article reports on planned and ongoing research. Conclusions Based on data collection, future findings and using a comprehensive, integrative, evidence-based approach, a step-by-step bioethical framework will be developed for (i) responsible use of antibiotics in healthcare and (ii) design of strategies to decrease AMR. This will entail the analysis and interpretation of approaches from several bioethical theories, including deontological and consequentialist approaches, and the implications of uncertainty to these approaches.

Machado-Joseph disease (MJD/SCA3) is the most common form of dominantly inherited ataxia worldwide. The disorder is caused by an expanded CAG repeat in the ATXN3 gene. Past studies have revealed that the length of the expansion partly explains the disease age at onset (AO) variability of MJD, which is confirmed in this study. Using a total of 786 MJD patients from five different geographical origins, a genome-wide association study (GWAS) was conducted to identify additional AO modifying factors that could explain some of the residual AO variability. We identified nine suggestively associated loci (P < 1 × 10−5). These loci were enriched for genes involved in vesicle transport, olfactory signaling, and synaptic pathways. Furthermore, associations between AO and the TRIM29 and RAG genes suggests that DNA repair mechanisms might be implicated in MJD pathogenesis. Our study demonstrates the existence of several additional genetic factors, along with CAG expansion, that may lead to a better understanding of the genotype-phenotype correlation in MJD.

To investigate whether reactive hyperemia measured by peripheral arterial tonometry correlates with markers of endothelial dysfunction and may be used to identify sepsis in critical illness.A prospective study was performed using a cohort of critically ill patients. Endothelial dysfunction was assessed on admission by quantifying reactive hyperemia-peripheral arterial tonometry and plasma levels of endothelin-1, soluble E-selectin, endocan and syndecan-1. Septic patients were compared to patients without evidence of infection.Fifty-eight septic patients were compared to 28 controls. The natural logarithm of reactive hyperemia-peripheral arterial tonometry was negatively correlated with cardiovascular comorbidities, disease severity and plasma levels of soluble E-selectin (p = 0.024) and syndecan-1 (p0.001). The natural logarithm of reactive hyperemia-peripheral arterial tonometry was lower in septic patients than in controls (0.53 ± 0.48 versus 0.69 ± 0.42, respectively). When adjusted for age, the multivariable model predicted that each 0.1-unit decrease in natural logarithm of reactive hyperemia-peripheral arterial tonometry increased the odds for infection by 14.6%. m.Reactive hyperemia-peripheral arterial tonometry is closely related to soluble E-selectin and syndecan-1, suggesting an association between endothelial activation, glycocalyx degradation and vascular reactivity. Reactive hyperemia-peripheral arterial tonometry appears to be compromised in critically ill patients, especially those with sepsis.Investigar se a hiperemia reativa correlaciona-se com marcadores de disfunção endotelial e pode ser utilizada para identificar sepse na doença crítica.Trata-se de estudo prospectivo em uma coorte de pacientes críticos. A disfunção endotelial foi avaliada quando da admissão, por meio da quantificação de hiperemia por tonometria arterial periférica e níveis plasmáticos de endotelina 1, E-selectina solúvel, endocana e sindecano 1. Os pacientes sépticos foram comparados com pacientes sem evidência de infecção.Cinquenta e oito pacientes sépticos foram comparados com 28 controle. O logaritmo natural da tonometria arterial periférica teve correlação negativa com comorbidades cardiovasculares, severidade da doença e níveis plasmáticos de E-selectina solúvel (p = 0,024) e sindecano 1 (p0,001). O logaritmo natural da tonometria arterial periférica foi mais baixo nos pacientes sépticos quando comparado com os de pacientes controle (0,53 ± 0,48 versus 0,69 ± 0,42, respectivamente) e, quando ajustado à idade, o modelo multivariado predisse que cada 0,1 de diminuição em unidades de logaritmo natural da tonometria arterial periférica levou a aumento de 14,6% na probabilidade de infecção.A hiperemia reativa avaliada por tonometria arterial periférica tem estreita relação com E-selectina solúvel e sindecano 1, o que sugere associação entre ativação endotelial, degradação de glicocálix e reatividade vascular. A hiperemia reativa por tonometria arterial periférica parece estar comprometida em pacientes críticos, especialmente os com sepse.

Faecal calprotectin (FC) is a sensitive and non-invasive marker for gastrointestinal mucosal inflammation [1]. Since Calprotectin is a small calcium-binding protein released by neutrophils (S100 family) as a result of an inflammatory process [2], it is an excellent inflammatory marker to distinguish organic inflammatory bowel disease (IBD) - Crohn’s disease (CD) or Ulcerative Colitis (UC) from functional disease- Irritable Bowel Syndrome (IBS) [1,2]. In pediatric patients, FC is useful for an early diagnosis of IBD significantly reducing the number of invasive procedures in children with gastrointestinal symptoms. Endoscopic procedures are unpleasant for the patient, time-consuming and bear the risk of intestinal perforation. In addition, FC is more sensitive than C-reactive protein (CRP) in reflecting IBD activity [3], being for this reason also used to monitor IBD therapy and to predict relapse in these patients [1,3]. Because of its enormous potential as biomarker, many methods have been developed for its measurement. Although the quantitative enzyme-linked immune sorbent assay (ELISA) is considered the “gold” standard method to quantify FC, there are also immunochromatographic tests that are regularly used. More recently, automated immunoassays have been developed as an alternative, leading to an improved solution in the routine laboratory in view of an exponential increase in workload [4,5]. In our hospital, we have been using a rapid test to measure FC in pediatric samples. As the number of tests for these samples has been increasing in the last years, the possibility to automate this parameter was considered as worth to evaluate. The main purpose of this study was to determine FC levels with an immunoassay test adapted to an automated equipment and compare with a rapid routine test.

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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.

Background: Nurses are the largest professional group in healthcare and those who make more decisions. In 2014, the Committee on Bioethics of the Council of Europe launched the “Guide on the decision-making process regarding medical treatment in end-of-life situations” (hereinafter, Guide), aiming at improving decision-making processes and empowering professionals in making end-of-life decisions. The Guide does not mention nurses explicitly. Objectives: To analyze the ethical principles most valued by nurses working in palliative care when making end-of-life decisions and investigate if they are consistent with the framework and recommendations of the Guide; to identify what disputed/controversial issues are more frequent in these nurses’ current end-of-life care practices. Design: Qualitative secondary analysis. Participants/context: Three qualitative datasets including 32 interviews from previous studies with nurses working in palliative care in Portugal. Ethical consideration: Ethical approval was obtained from the Ethics Research Lab of the Instituto de Bioética (Ethics Research Lab of the Institute of Bioethics) (Ref.04.2015). Ethical procedures are thoroughly described. Findings: All participant nurses referred to autonomy as an ethical principle paramount in end-of-life decision-making. They were commonly involved in end-of-life decision-making. Palliative sedation and communication were the most mentioned disputed/controversial issues. Discussion: Autonomy was highly valued in end-of-life care and decision-making. Nurses expressed major concerns in assessing patients’ preferences, wishes, and promoting advance care planning. Nurses working in palliative care in Portugal were highly involved in end-of-life decision-making. These processes embraced a collective, inclusive approach. Palliative sedation was the most mentioned disputed issue, which is aligned with previous findings. Communication also emerged as a sensitive ethical issue; it is surprising, however, that only three nurses referred to it. Conclusion: While the Guide does not explicitly mention nurses in its content, this study shows that nurses working in palliative care in Portugal are involved in these processes. Further research is needed on nurses’ involvement and practices in end-of-life decision-making.

Background: Making palliative care accessible to all citizens who are in need of this type of care requires effective policies and education. Moreover, healthcare professionals have an ethical and legal responsibility to ensure quality palliative care. Nevertheless, palliative care has had traditionally a limited emphasis in healthcare professionals’ undergraduate education. Aim: To study the current status of palliative care education in nursing undergraduate curricula and compare 2005 and 2015 findings. Design: An online survey was sent to all state schools providing nursing undergraduate education in Portugal ( N = 21). The survey assessed if and how palliative care was included in the curricula, and whether or not national and international recommendations for palliative care nursing education were followed. Further analysis included the content of available curricula/syllabi. Setting/participants: A total of 19 schools completed the survey (90% of response rate). These institutions are geographically dispersed and representative of state nursing educational institutions in Portugal. Results: In 2015, all participant schools integrated palliative care in their curricula; nine schools had palliative care as an independent curricular unit (an 800% increase compared to 2005). While in 2005, only 14 out of 23 (61%) schools included palliative care explicitly in their curricula; in 2015, all 19 participant schools did so. National and international recommendations were followed. Conclusion: The inclusion of palliative care within nursing undergraduate curricula strongly increased from 2005 to 2015. Further research is needed to understand the contribution of education in the access, care provision, quality and development of palliative care in this country.

Background: Ethical decisions are part of contemporary practices in palliative care. The need of making such decisions is associated to higher burnout levels and other work related problems among healthcare professionals. Aims: As part of the project entitled “Decisions in End-of-Life Care in Spain and Portugal” (DELiCaSP), this study aims to (i) identify the most common ethical decisions made by Portuguese palliative care teams and (ii) understand how the making of such decisions relates to burnout. Methods: A mixed methods study was conducted with 9 palliative care teams, using (i) questionnaires of socio-demographic and professional variables, work-related experiences, (ii) the Maslach Burnout Inventory, (iii) interviews and (iv) observations. These teams were geographically dispersed across the country, covering the North, Centrum and South regions, and heterogeneous: Five palliative care units for inpatients; three home care teams; and one hospital support team. A total of 20 interviews and 240 hours of observations were completed until reaching saturation. Results: The most common ethical decisions were related to communication issues (information disclosure of the diagnosis and prognosis), forgoing treatment and sedation. Although perceived as stressful, emotionally demanding and challenging, ethical decisions were not significantly associated with burnout. Conclusions: Making ethical decisions is not associated with higher burnout levels among professionals working in Portuguese palliative care teams. This can be explained by the interprofessional decision-making process followed by these teams, which promotes a sense of shared-decision and team-based empowerment; and by the advanced level of interdisciplinary education in palliative care that these professionals have.

Objectives Depressive symptoms are common in patients with cancer and tend to increase as death approaches. The study aims were to examine the prevalence of depressive symptoms in patients with cancer in their final 24 h, and their association with other symptoms, sociodemographic and care characteristics. Methods A stratified sample of deaths was drawn by Statistics Netherlands. Questionnaires on patient and care characteristics were sent to the physicians (N=6860) who signed the death certificates (response rate 77.8%). Adult patients with cancer with non-sudden death were included (n=1363). Symptoms during the final 24 h of life were assessed on a 1–5 scale and categorised as 1=no, 2–3=mild/moderate and 4–5=severe/very severe. Results Depressive symptoms were registered in 37.6% of the patients. Patients aged 80 years or more had a reduced risk of having mild/moderate depressive symptoms compared with those aged 17–65 years (OR 0.70; 95% CI 0.50 to 0.99). Elderly care physicians were more likely to assess patients with severe/very severe depressive symptoms than patients with no depressive symptoms (OR 4.18; 95% CI 1.48 to 11.76). Involvement of pain specialists/palliative care consultants and psychiatrists/psychologists was associated with more ratings of severe/very severe depressive symptoms. Fatigue and confusion were significantly associated with mild/moderate depressive symptoms and anxiety with severe/very severe symptoms. Conclusions More than one-third of the patients were categorised with depressive symptoms during the last 24 h of life. We recommend greater awareness of depression earlier in the disease trajectory to improve care.

This chapter aims to provide an overview of the ethical framework and decision-making in clinical dementia research, and to analyze and discuss the ethical challenges and issues that can arise when conducting clinical dementia research. Informed consent is the most scrutinized and controversial aspect of clinical research ethics. In clinical dementia research, assessing decision-making capacity may be challenging as the nature and progress of each disease influences decision-making capacity in diverse ways. Persons with dementia represent a vulnerable population deserving special attention when developing, implementing, and evaluating the informed consent process. In this chapter, particular attention will be given to vulnerability categories and how these influence decision-making capacity. Ethical frameworks with a pragmatic contour and implication are needed to protect vulnerable patients from potential harms and ensure their optimal participation in clinical dementia research. In addition, this chapter analyses important ethical challenges and issues in clinical dementia research. If handled thoughtfully, they would not pose insuperable barriers to research. But if they are ignored, they could slow the research process, alienate potential study subjects and cause harm to research participants. Ethical considerations in research involving persons with dementia primarily concern the representation of the interests of the participants with dementia and protection of their vulnerabilities and rights. A core set of ethical questions and recommendations are drawn to aid researchers, institutional review boards and potential research participants in the process of participating in clinical dementia research.

The aim of this study was to analyze electroencephalographic (EEG) background activity in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) by means of multiscale spectral entropy (MSSE). To achieve this goal, five minutes of EEG activity were acquired from 18 cognitive healthy controls, 10 MCI subjects and 32 AD patients. Our results showed statistically significant differences (p-values < 0.05, Kruskal-Wallis test) in MSSE values for all scale factors. Additionally, a 3D receiver operating characteristic (ROC) curve was used to assess the discrimination ability of MSSE among the 3 groups, showing a good three-way discrimination power (volume under the surface of 0.6). These results suggest that MSSE can be a useful measure to characterize neural alterations in AD, even at early stages.

Machado-Joseph disease (MJD, also known as spinocerebellar ataxia 3 or SCA3) is the most common dominant ataxia worldwide, with an overall average prevalence of 1-5/100,000. To this date, two major ancestral lineages have been found throughout the world. In China, the relative frequency of MJD among the SCAs reaches as high as 63%, however, little is known about its mutational origin in this country. We analyzed 50 families with MJD patients in two or more generations to study the hypothesis that new mutational events have occurred in this population. Haplotypes based on 20 SNPs have shown new genetic backgrounds segregating with MJD mutations in our cohort from China. We found the "Joseph-derived" lineage (Joseph lineage with a G variant in rs56268847) to be very common among Chinese MJD patients. Moreover, we estimated the time for the origin of this MJD SNP background based on STR diversity flanking the (CAG)n of ATXN3. It was surprising to find that the Chinese MJD population originated from 8,000 to 17,000 years ago, far earlier than the previous literature reports, which will be an important evidence to explain the origin, spread and founder effects of MJD. This work was supported by the National Key Research and Development Program of China (Nos. 2016YFC0905100 and 2016YFC0901504 to HJ), the National Natural Science Foundation of China (Nos. 81771231 and 81471156 to HJ), the Clinical Research Funds of Xiangya Hospital (2014L03 to HJ), the Clinical and rehabilitation fund of Peking University Weiming Biotech Group (No. xywm2015I10 to HJ), Youth Foundation of Xiangya Hospital (No. 2017Q03 to ZC), and Independent Exploration and Innovation Project of Graduate Students of Central South University (No. 1053320170177 to TL). Moreover, SM is funded by the project IF/00930/2013 from FCT. This article is a result of the project NORTE-01-0145-FEDER-000008, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, and through the European Regional Development Fund (ERDF).

Several outcome measures have been systematically implemented to be used in palliative care. However, routine use in clinical practice is not without ethical challenges, which are not commonly addressed. The objectives of this study are therefore (I) to identify the ethical challenges/issues of outcome measurement in palliative care and (II) to understand how these ethical challenges/issues are addressed in palliative care clinical practice. The study consisted of a systematic review of systematic reviews, which is a type of review that brings together a summary of reviews in one place. We searched PubMed, Web of Science, EBSCOhost searching CINAHL Complete, MEDLINE Complete, Nursing & Allied Health Collection: Comprehensive, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Cochrane Methodology Register, Library, Information Science & Technology Abstracts, MedicLatina, from inception to January 2018. Out of 159 articles screened, only two [2] articles were included for analysis. The main ethical challenge/issue identified in these two reviews was cognitive impairment, particularly in patients with dementia. This challenge was addressed via proxy (family carers or health professionals) reporting outcome measurement. Ethical challenges/issues are poorly addressed in the existing systematic reviews about outcome measurement in palliative care clinical practice. Only two systematic reviews addressed ethical challenges/issues, namely cognitive impairment, particularly in persons with dementia. Further research is needed on this subject and to foster the use of outcome measurement among this vulnerable group of patients.