Ângela Leite

Psychological aspects of pre‐symptomatic testing for Machado–Joseph disease and familial amyloid polyneuropathy type I

Machado–Joseph disease [MJD, also spinocerebellar ataxia type 3 (SCA3)] and familial amyloid polyneuropathy type I (FAP‐I or ATTR V30M) are neurodegenerative disorders, inherited in an autosomal dominant fashion, which have a high prevalence in Portugal, probably due to a founder effect. MJD and FAP‐I are late‐onset diseases, with symptoms emerging usually during adulthood. CGPP, which is the national reference centre for these disorders, has a genetic lab that offers diagnostic, pre‐symptomatic and prenatal testing and an outpatient clinic to counsel and follow relatives at risk for hereditary ataxias, FAP‐I and Huntington disease (HD). The present work is a review of our 10‐year experience with psychological counselling of individuals at risk for MJD and FAP‐I. Persons at risk for FAP‐I may show a better response to pre‐symptomatic testing than those who are at risk for MJD and HD because of the availability of liver transplantation, which may improve their health and life expectancy. Psychological well‐being and specific distress of MJD and FAP‐I test applicants, before undergoing genetic testing (baseline level) and 3 to 6 months after disclosure of test results, have shown a low level of change, both in identified carriers and non‐carriers. A major goal of psychological characterization of at‐risk individuals for MJD and FAP‐I is to determine the factors that influence the uptake of genetic testing.

Mid- and long-term anxiety levels associated with presymptomatic testing of Huntington’s disease, Machado-Joseph disease, and familial amyloid polyneuropathy

Objective: To study anxiety as a variable of the mid- and long-term psychological impact of pre-symptomatic testing for three autosomal dominant late-onset disorders – Huntington’s disease (HD), Machado-Joseph disease (MJD) and familial amyloid polyneuropathy (FAP) TTR V30M – in a Portuguese sample. Methods: This cross-sectional study included 203 participants: 170 (83.7%) underwent pre-symptomatic testing for FAP, 29 (14.3%) for HD, and 4 (2%) for MJD. Of the 203 participants, 73 (36.0%) were asymptomatic carriers, 29 (14.5%) were symptomatic carriers, 9 (4.5%) were diagnosed with FAP and had a liver transplant, and 89 (44.5%) were non-carriers. Most were women (58.1%) and married (66.5%). The anxiety variable was assessed using the Zung Self-Rating Anxiety Scale (SAS). Results: The anxiety scores were higher for symptomatic carriers and for those who underwent psychological support consultations over the years. For symptomatic carriers, the mean scores were superior to 40 points, which reflects clinical anxiety. Conclusion: Although it was not possible to differentiate between the mid- and long-term psychological impacts, this study supports the conclusion that the proximity to the age of symptoms onset might be a trigger for anxiety.

Subjects At-Risk for Genetic Diseases in Portugal: Illness Representations.

This study investigates illness representations of subjects at-risk for 3 autosomal dominant late-onset disorders: Familial Amyloid Polyneuropathy (FAP) TTR V30M, Huntington’s disease (HD) and Machado-Joseph disease (MJD), comparing them with the illness representations of subjects at-risk for Hemochromatosis (HH). The present study included a clinical group that consisted of 213 subjects at genetic risk (FAP, HD and MJD), comprising 174 subjects at-risk for FAP, 34 subjects at-risk for HD and only 5 subjects at-risk for MJD; and the control group consisting of 31 subjects at genetic risk for HH. All subjects at-risk were undergoing the process of genetic counseling to learn their genetic status (carrier or non-carrier). Subjects were assessed through a semi-structured single interview, in order to obtain sociodemographic data and the answer to an open-ended question relating to the illness representation issue: “What does this illness mean to you?/ What is this disease to you?” It was in the subjects’ metaphors that subjects best expressed what they felt regarding the disease and the situation of being at-risk for this disease. Family is their mirror and their source of learning and, therefore, it is inevitable that family is related to the meaning of the disease itself.

Predictors of Subclinical Inflammatory Obesity: Plasma Levels of Leptin, Very Low-Density Lipoprotein Cholesterol and CD14 Expression of CD16+ Monocytes

Objective: Predictors of subclinical inflammatory obesity (SIO) can be important tools for early therapeutic interventions in obesity-related comorbidities. Waist circumference (WC) and BMI have different SIO sensitivity. We aimed to i) identify SIO predictors and ii) investigate whether CD16+ monocytes are associated with BMI- (generally) or WC-defined (centrally) obesity. Methods: Anthropometric and metabolic/endocrine (namely catecholamines, adrenaline and noradrenaline) parameters were evaluated, and CD16+ monocytes were studied by flow cytometry in the peripheral blood from 63 blood donors, and compared and correlated to each other. Multiple linear regression analysis was performed to identify variables that best predict SIO. Results: CD16+ monocyte counts were similar in BMI and WC groups. CD16+ monocytes from centrally obese (CO) showed a more inflammatory pattern, as compared to non-CO subjects. WC was sensitive to lipidemia and, in CO subjects, lipidemia was associated with a more inflammatory phenotype of CD16+ monocytes. These differences were not noticed between BMI groups. Adrenaline was correlated with CD16+ monocyte expansion with a lower inflammatory pattern. Leptin, very low-density lipoprotein cholesterol (VLDL-C), and CD14 expression of CD16+ monocytes were found to be CO predictors. Conclusions: WC-, but not BMI-defined obesity, was associated with a more inflammatory pattern of CD16+ monocytes, without monocyte expansion, suggesting that a monocyte maturation process rather than an independent arise of CD16+ monocytes occurs in CO. Thus, in a population with low cardiovascular risk, leptin, VLDL-C, and CD14 expression of CD16+ monocytes predict CO, constituting a putative tool for screening of SIO.

Illness representations, knowledge and motivation to perform presymptomatic testing for late-onset genetic diseases

Abstract This study addresses the relation between illness representations, knowledge and motivation to perform the presymptomatic testing (PST) of subjects at-risk for Familial Amyloydotic Polyneuropathy (FAP), Huntington’s disease (HD) and Machado–Joseph disease (MJD), compared with subjects at-risk for Hereditary Hemochromatosis (HH). The sample comprised a clinical group of 213 subjects at genetic risk for FAP, HD and MJD, and a comparison group of 31 subjects at genetic risk for HH, that answered three open-ended questions relating illness representations, knowledge about the disease, and motivation to perform PST. People at-risk for FAP, HD and MJD use more metaphors, make more references to the family, are more concerned with the future and feel more out of curiosity and to learn, than for HH. These subjects at-risk correspond to the profile of somatic individual or personhood, wherein the unsubjectivation of the disease can function as a coping mechanism.

Blood Donor Characteristics on Transfusion Outcomes—Should Obesity Be Assessed in Future Clinical Trials?

Blood Donor Characteristics on Transfusion Outcomes—Should Obesity Be Assessed in Future Clinical Trials? To the Editor The work of Chassé and colleagues1 in a recent issue of JAMA Internal Medicine reported that blood donor (BD) characteristics may affect red blood cell (RBC) transfusion outcomes and describes a higher risk of death for recipients of RBC transfusions from young donors and female donors independently of recipient age, sex, and comorbidities. The authors discuss these results, mentioning the healthy donor phenomenon and the blood composition in female sex, not ruling out unknown biological and/or environmental factors. Considered healthier than the general population, BDs present cardiovascular risk factors, particularly, obesity. The health consequences for recipients of blood transfusions or bone marrow transplantation from donors with obesity are unrevealed notwithstanding being expected. The clinical and biological rationale for this hypothesis is based on scientific evidences widely accepted: (1) obesity is an inflammatory disease and “inflamed donors,” apart from showing altered immune cells at genomic, phenotype, and function levels, also have in circulation immunoregulators such as leptin, lipids, extracellular vesicles, microRNAs signaling molecules implicated in adaptive and innate immune activation with a role in obesity and cardiovascular comorbidities2; (2) the signaling of leptin, a proinflammatory cytokine primarily produced by adipocytes proportionally to adiposity and present in higher levels in women, is associated with the occurrence, progression, and prognosis of hematologic malignancies3; (3) low CD34+ cell count has been described in blood harvested from overweight or obese mothers, candidates for stem cell donation of umbilical cord blood units, and in newborns weighing above average.4 Although the composition of immune cells in the allograft may affect the clinical outcomes of patients, the impact of donor weight and/or body mass index on CD34+ cells remains controversial. Central obesity, a more sensitive obesity measurement for inflammation than body mass index, could, partially, explain the contradictory results in the association between body mass index and/or weight and immune cell composition of allograft. Moreover, even leukodepleted, RBC have some residual leukocytes with stem cell function. A population of BD with central obesity prevalence of 57.7%, showed higher inflammatory phenotype pattern of monocytes in central obesity compared with their counterpart.5 The existence of “inflamed” donors is even more important when a significant part of the recipients is immunocompromised. Future clinical trials with vein-to-vein methodology are needed to evaluate if inflammatory obesity matters as a characteristic of donor on clinical outcomes of recipients of blood transfusion and/or hematopoietic stem cell transplantation.

Working with cancer: motivation and job satisfaction

Purpose The purpose of this study is to investigate the motivational factors to work with cancer patients, their repercussions in job satisfaction among Portuguese healthcare professionals and to understand the role of sociodemographic and occupational variables in motivation and job satisfaction. Design/methodology/approach An instrument based on Maslow’s and Herzberg’s theories and developed by Paleologou et al. (2006) was applied to four categories of healthcare professionals. This instrument comprises four work-related motivators (remuneration, achievements, coworkers and job attributes) and a single-item question about job satisfaction. In total, 400 healthcare professionals in a Portuguese oncology hospital participated in this study. Findings Job satisfaction was positively and significantly associated with all motivational factors. Qualifications predicted all motivational factors, although the motivator “coworkers” was also influenced by age. Originality/value Motivation and job satisfaction are related, and some studies investigate the relation between them. However, these constructs are not sufficiently studied among healthcare professionals in oncology hospitals. This study shows that motivational factors to work in a cancer hospital are critical for job satisfaction among healthcare professionals. Moreover, qualifications predicted all motivational factors in this context.

Long-term predictors for psychological outcome of pre-symptomatic testing for late-onset neurological diseases

This longitudinal study aimed at determining predicting variables for middle and long-term psychological disturbance due pre-symptomatic testing (PST) for two late-onset neurological diseases, Huntington disease (HD) and TTR (transthyretin protein) familial amyloid polyneuropathy (FAP) Val30Met (now classified as Val50Met). 196 clinical records of persons who performed PST at least three years ago and answered to the two stages of evaluation (before PST and least 3 years after disclosure of results) were analysed. For this purpose, regression analysis was performed, showing that the Positive Symptom Distress Index (PSDI), psychoticism, somatization and paranoid ideation dimensions assume predictive value in the middle and long-term impact for total anxiety and PSDI. The result of PST was not a relevant predictor. The application of an evaluation instrument of various psychopathological dimensions played a fundamental role in the detection of clinical situations that may arise several years later after PST. Attention should be paid to providing psychological support to persons at-risk who, at the pre-test phase, present some psychopathology indices before pursuing with genetic testing.

Subjects at Risk for Genetic Late-Onset Neurological Diseases: Objective Knowledge

Background/Aims: This study addresses the objective knowledge about the disease of subjects at risk for 3 genetic late-onset neurological diseases (LOND): familial amyloid polyneuropathy (FAP) TTR V30M, Huntington disease (HD), and Machado-Joseph disease (MJD). Methods: Subjects at risk for FAP, HD, and MJD submitted to genetic counseling to know their status (carrier or non-carrier) and subjects at risk for hereditary hemochromatosis (HH), the control group, completed a sociodemographic questionnaire and answered the open-ended question: “What do you know about this disease?.” Results: From 10 categories of answers, references to the disease, quantitative answers, references to the family, and metaphors stood out. References to the disease, references to the family, and metaphors were mentioned more often by subjects at risk for LOND than by subjects at risk for HH (control group). Conclusion: The disease itself and its meaning as well as sick relatives play a key role in the objective knowledge about LOND. Thus, genetic counseling protocols of subjects at risk for LOND should include questions concerning family knowledge and disease experience.