Catania et al. However, several studies reported several facilitators or significant barriers to trial participation [ 35 , 36 ]. Several studies have reported that women were less likely than men to enroll in clinical trials [ 40 , 51 , 52 , 53 , 54 ]. A population-based study found no evident gender differences in clinical trial participation [ 41 ].
Sufficient and clear information, discussion with researchers, possible side effects in clinical trials and potential QoL-related benefits of participating in clinical trials have been reported as factors that are very important for participating in clinical trials.
Sufficient and clear information is a strong motivation to participating in a clinical trial whereas lack of information or explanation is a strong motivation to refuse participation in a clinical trial [ 58 , 59 ].
While it is paramount to ensure that patients can make an adequately informed decision about participation in clinical trials [ 60 ], the consent to participate on a clinical trial often is not adequately informed [ 37 ]. In a study conducted by Mowlabaccus and Jodheea-Jutton, In a study conducted by Godskesen et al. Limited previous information about clinical trials is cited as an important barrier to participation [ 61 ]. Note, however, that providing adequate information to clinical trial participants is not an easy task.
As is the case with patient clinical information, clinical trial information should be concise. Lengthy information can be confusing for patients [ 62 ].
Importantly, it has been cited in literature that patients may have misunderstood the purpose of a clinical trial [ 4 , 64 ] or the potential personal benefit from a clinical trial [ 65 ]. Patients who enter quickly into clinical trial registers may not feel that they fully understood the implications of their clinical trial participation [ 66 ]. Therefore, patients should be given an adequate time frame to consider the information provided [ 4 ].
At any rate, adequate information is a strong factor promoting clinical trial participation. Several studies suggest that patients who participated in clinical trials should be offered the trial results [ 4 , 62 , 67 , 68 , 69 ].
Not receiving results may discourage patients from participating in future trials [ 67 ]. The majority of participants in a survey conducted by Jones et al. In this perspective, Jones et al. Interestingly, Cox et al. Moorcraft et al. The potential distress of hearing bad news is not a sufficient reason for not informing trial participants of the trial results [ 69 ]. Participating in discussions and engaging in shared decision-making processes may improve the participant—research team relationship by creating a research environment in which the patients feel that they are valued and respected.
Trust in researchers is a strong facilitator of clinical trial participation. Establishing trust in health providers and creating a relationship between participants and recruiters can promote participation in clinical trials [ 76 ]. Respondents It seems to be important to participants in clinical trials to be sure that the final beneficiaries of trials are patients rather than commercial pharmaceutical companies [ 77 ]. Furthermore, In the same vein was a study carried out by Burt et al.
Enhancing transparency in the conduction of clinical trials can increase the trust of participants [ 79 ]. The same holds true for the procedure of obtaining informed consent [ 74 ]. Ferrell et al. Most believed that participation would improve or stabilize their illness and quality of life. Pride in participating and hope for a better quality of life are motivations to consent to participating in a clinical trial [ 59 ]. The aforementioned findings are in line with other studies [ 9 , 10 , 14 , 62 , 65 , 71 , 72 , 86 ].
Fears of mistreatment, potential side effects from little-known drugs and exploitation have been reported in literature as strong barriers to clinical trial participation [ 37 , 59 , 87 , 88 , 89 , 90 , 91 ]. More particularly, fears of drug-related side effects have been cited in literature as a major barrier to participating in clinical trials [ 37 , 45 , 92 ].
Several participants in a single-center study conducted in the US by Sood et al. Walsh and Sheridan found that payment is a strong facilitator of participating in clinical trials [ 43 ]. However, Manton et al. Stocks et al. Furthermore, in the context of minority participation, remuneration was found to be important to male participants whereas the researcher-participant relationship was important to female participants [ 94 ].
As the data of our survey were collected from 13 different districts of Greece, the demographics of participants may be representative of the general population, at least to a large extent. This can be regarded as a chief strength of the study. In this survey, the respondents patients came from a broad range of demographics, such as educational background, age, gender, marital status, employment status.
The diversity in our survey may be regarded as one of its strengths. However, while the vast majority of previous studies on the topic of patient views on clinical trial participation have used methods involving disease-specific patient groups groups of patients with the same or similar diagnosis or symptoms , in our study any given medical condition had an equal probability of being involved. As a consequence, the results from this cross-sectional study were subject to limited disease-related bias compared to other studies involving patients with a particular medical condition.
At any rate, there is the potential for response bias. Our respondents might be patients with a particular interest in medical research. These are limitations of our study. Ultimately, consistent with the nature of surveys is the following limitation: Quantitative research cannot capture all dimensions of the phenomenon of interest. Despite these study limitations, the Greek version of the questionnaire can be useful for measuring the patient views of participation in clinical trials in Greece, where quantifying of these views is in its very infancy.
The findings emerged from this study are in line with previous literature. Sufficient and clear information, discussion with researchers, possible side effects in clinical trials and potential QoL-related benefits of participating in clinical trial have been reported as factors that are very important for participating in clinical trials. The datasets used and analysed in this study are available from the corresponding author on reasonable request.
Allison M. Can web 2. Nat Biotechnol. Barriers to participation in clinical trials of cancer: a meta-analysis and systematic review of patient-reported factors. Lancet Oncol. Article PubMed Google Scholar. Ellis PM. Attitudes towards and participation in randomised clinical trials in oncology: a review of the literature.
Ann Oncol. Patient motivations surrounding participation in phase I and phase II clinical trials of cancer chemotherapy. Br J Cancer. Preliminary development of a questionnaire measuring patient views of participation in clinical trials. BMC Res Notes. Quality of informed consent in cancer clinical trials: a cross-sectional survey.
Hope for a cure and altruism are the main motives behind participation in phase 3 clinical cancer trials. Eur J Cancer Care Engl. Perceptions of cancer patients and their physicians involved in phase I trials.
J Clin Oncol. Impact and perceptions of mandatory tumor biopsies for correlative studies in clinical trials of novel anticancer agents. Research biopsies in phase I studies: views and perspectives of participants and investigators. The views of patients and healthy volunteers on participation in clinical trials: an exploratory survey study. Contemp Clin Trials.
Public attitudes toward participation in cancer clinical trials. Phase 0 Clinical Trials: Conceptions and Misconceptions. Cancer J. RStudio Team. Accessed 6 Apr Quatto P, Ripamonti E. R package version 2. Rosseel Y. J Stat Softw. R package version 0. Assessing the inter-rater agreement for ordinal data through weighted indexes. Stat Methods Med Res. Kaiser HF. A second generation little jiffy.
Hutcheson G, Sofroniou N. The Multrivariate Social Scientist. SAGE Publications; Bartlett MS. J R Stat Soc. Using multivariate statistics. Boston: Pearson; Google Scholar. Educ Psychol Meas. Cattel RB. Multivariate Behav Res. Multivariate Data Analysis. While tau-PET binding was tightly associated with MTL subregional atrophy, only tau in Brodmann area 35, entorhinal cortex and the anterior hippocampus was related to memory performance. Importantly, no measure of grey matter volume or thickness was associated with memory performance in cognitively unimpaired individuals.
In contrast, tau-PET binding in the hippocampus, as well as posterior hippocampal atrophy, were both strongly associated with memory in MCI patients. Mediation analyses revealed that atrophy mediated the effect of tau pathology on memory.
Finally, functional connectivity analyses revealed that transentorhinal tau pathology in cognitively unimpaired individuals resulted primarily in reduced MTL—anterior-temporal functional connectivity.
Meanwhile, tau-related reductions in functional connectivity in critical MTL—posterior-medial networks were associated with early subtle memory impairment. The neuropathological literature suggests the earliest cortical neurofibrillary tau tangles accumulate in an area in the anterior MTL that covers the transentorhinal region and part of the entorhinal cortex. Our voxel-wise results show an almost exact replication of their original findings where tau-PET binding could be observed in a region spanning Brodmann area 35 i.
This is also in line with a recent autopsy imaging study combining ex vivo MRI and serial histopathology, which identified an almost identical pattern, 42 as well as a study showing that Braak stage was associated with neuron loss in the subicular end of CA1. These findings suggest that specific regions in the posterior MTL are affected in later disease stages. Hippocampal tau-PET signal never reached the levels of neocortical regions.
One underlying reason might be that tau pathology is particularly accumulating in subiculum and CA1 while other subregions, such as CA2—3 and the dentate gyrus, seem rather spared in non-demented individuals Supplementary Videos 1—3.
Taken together, we found the earliest signs of abnormal tau-PET signal in regions of the anterior-temporal system while progressively more regions of the posterior-medial system became abnormal in later tau-EBM stages. These findings can inform research on disease stage-specific cognitive markers.
Tau binding has recently been shown to be tightly linked to atrophy. In addition, our region of interest analysis revealed that tau pathology was associated with local thickness and volume within regions such as the entorhinal cortex, Brodmann area 35 and the hippocampus.
In addition, while earlier studies used an MTL-tau composite, we used tau-PET signal from individual regions of interest, and the reduced off-target binding of 18 F-RO tau-PET allowed us to analyse the signal from the hippocampus.
In addition to local relationships, we found a robust effect where tau in distant MTL subregions was strongly associated with lower volume of the posterior hippocampus, suggesting remote mechanisms of atrophy in addition to local effects.
This finding was additionally confirmed by our voxel-based morphometry analysis. The relationship between primarily posterior hippocampal atrophy and tau pathology has recently been reported in several studies. Furthermore, a study from our group showed additional evidence for lower posterior hippocampal volume of the subiculum with increased levels of CSF p-Tau.
Earlier work has suggested a tight link between tau, neurodegeneration and cognitive performance. We show that entorhinal, Brodmann area 35 and anterior hippocampal tau-PET binding were related to memory performance in cognitively unimpaired individuals, while only hippocampal tau-PET binding was associated with memory in MCI patients. Critically, while memory was not associated with atrophy in any MTL region in the cognitively unimpaired, posterior hippocampal atrophy mediated the effect of hippocampal tau on memory in MCI patients.
Taken together, this suggests that while tau-related memory impairment might be less dependent on atrophy in early disease stages, it seems to depend on posterior hippocampal atrophy at the MCI stage. Recent work using lesion mapping further strengthens the role of the posterior hippocampus in memory impairment showing that lesions causing amnesia were all functionally connected to an area spanning the posterior hippocampus and parts of the retrosplenial cortex.
Whether there is a qualitative difference between subtle tau-related memory impairment in cognitively unimpaired individuals and tau- and atrophy-related impairment in MCI patients needs to be addressed in future studies using several different memory measures. In addition, reduced MTL-posterior-medial functional connectivity was more consistently associated with memory impairment. In line with these earlier results, the findings of our present study show that increases in tau-PET signal in the transentorhinal and entorhinal region in cognitively unimpaired individuals were mainly associated with reduced MTL-anterior-temporal functional connectivity.
This is in agreement with a recent study that reported a hippocampus-anterior-temporal system disconnection, paired with increased regional hippocampal homogeneity, to be associated with increasing MTL tau-PET signal.
These resulting subcomponents are congruent with recent reports highlighting functional connectivity between the MTL and parietal nodes of the default mode network to be particularly relevant for episodic memory. Future studies focusing on the interactions of specific functional connectivity networks, tau pathology and memory function in independent cohorts of cognitively unimpaired individuals are needed.
First, our identified order of biomarker abnormality in tau-PET SUVR across different subregions is based on cross-sectional measurements instead of longitudinal data. Second, the implementation of the EBM used here assumes one common trajectory for participants. While this might be true, there could still be individuals with non-typical spread of tau. Fourth, while we followed a unique approach using individually derived fine-grained MTL subregions, the resulting regions of interest were in part quite small and challenge the resolution offered by tau-PET.
Fifth, while the tau-PET tracer in our study showed considerably reduced off-target binding in the choroid plexus, 17 tau tracers with even lower choroid plexus binding may be better suited for assessing MTL subregions. Finally, we used ADAS-delayed word recall as a measure of memory performance, which limits our results to a specific memory measure. Given the specificity of tau-related effects on atrophy and functional connectivity in different disease stages, future studies with several different and more specific memory measures are needed to further understand the nature of early tau-related memory impairment.
Taken together, our findings provide an anatomically detailed insight into tau progression across fine-grained MTL subregions and memory-relevant cortical regions in non-demented individuals. While tau pathology might affect memory performance in cognitively unimpaired individuals via reduced functional connectivity in critical MTL-cortical networks, memory impairment in MCI seems to be associated with posterior hippocampal atrophy. The other authors report no competing interests.
Supplementary material is available at Brain online. Correlation of Alzheimer disease neuropathologic changes with cognitive status: A review of the literature. J Neuropathol Exper Neurol. Google Scholar.
Entorhinal tau pathology, episodic memory decline, and neurodegeneration in aging. J Neurosci. Progress in brain research. Progr Brain Res. Ranganath C , Ritchey M. Two cortical systems for memory-guided behaviour. Nat Rev Neurosci. Nat Commun. JAMA Neurol.
Braak H , Braak E. Neurobiol Aging. PET imaging of tau deposition in the aging human brain. Braak H , Tredici KD. From the entorhinal region via the prosubiculum to the dentate fascia: Alzheimer disease-related neurofibrillary changes in the temporal allocortex. Discriminative accuracy of [18 F]flortaucipir positron emission tomography for Alzheimer disease vs other neurodegenerative disorders.
Early tau burden correlates with higher rate of atrophy in transentorhinal cortex. J Alzheimers Dis. Sci Transl Med. Head-to-head comparison of tau positron emission tomography tracers [18F]flortaucipir and [18F]RO Hum Brain Mapping. Appropriate reference region selection of 18F-florbetaben and 18F-flutemetamol beta-amyloid PET expressed in Centiloid. Optimism, motivational coping and well-being: Evidence supporting the importance of flexible goal adjustment. Positive psychology at work: A conceptual review, state-of-practice assessment, and a look ahead.
The Journal of Positive Psychology. Diener E. Culture and subjective well-being. Champaign, IL: Springer; Seligman ME, Csikszentmihalyi M. Positive psychology: An introduction. Netherlands: Springer; Luthans F. Positive organizational behavior: Developing and managing psychological strengths. Luthans F, Youssef CM. Emerging positive organizational behavior. Human, social, and now positive psychological capital management: Investing in people for competitive advantage.
The psychological capital of Chinese workers: Exploring the relationship with performance. Larson M, Luthans F. Potential added value of psychological capital in predicting work attitudes. Experimental analysis of a web-based training intervention to develop positive psychological capital.
The implications of positive psychological capital on employee absenteeism. Social and psychological resources and adaptation. Positive psychological capital: Measurement and relationship with performance and satisfaction. Why entrepreneurs often experience low, not high, levels of stress: The joint effects of selection and psychological capital. Journal of Management. Bandura A. Self-Efficacy: The exercise of control. New York, NY: W. Freeman and Co; Jerusalem M, Schwarzer R.
Self-efficacy as a resource factor in stress appraisal processes. In: Schwarzer R, editor. Self-efficacy: Thought Control of Action. Stajkovic AD, Luthans F. Self-efficacy and work-related performance: A meta-analysis. Psychological capital: Investing and developing positive organizational behavior.
Positive Organizational Behavior. The Oxford handbook of positive psychology. Psychological Capital and beyond. Optimism, coping, and health: assessment and implications of generalized outcome expectancies. Dispositional optimism and physical well-being: The influence of generalized outcome expectancies on health. J PERS. Hope and health. Handbook of social and clinical psychology: The health perspective. Snyder CR. The psychology of hope: You can get there from here. The future of positive psychology: A declaration of independence.
Handbook of positive psychology. Hope theory: Rainbows in the mind. Having the will and finding the way: A review and meta-analysis of hope at work. Great expectations: A meta-analytic examination of optimism and hope. Distinguishing hope and optimism: Two sides of a coin, or two separate coins? Positive expectancies and mental health: Identifying the unique contributions of hope and optimism. Rand KL. Hope and optimism: Latent structures and influences on grade expectancy and academic performance.
A prospective study of hope, optimism, and health. The hope construct, will, and ways: Their relations with self—efficacy, optimism, and general well—being. Pavot W. The assessment of subjective well-being: Successes and shortfalls. The science of subjective well-being. The remarkable changes in the science of subjective well-being. Xu J, Roberts RE. Whistle while you work: A review of the life satisfaction literature.
Tay L, Diener E. Needs and subjective well-being around the world. Health benefits: Meta-analytically determining the impact of well-being on objective health outcomes. Health Psychology Review. Keyes CLM.
The mental health continuum: From languishing to flourishing in life. Maddux JE. Self-efficacy—The power of believing you can. Handbook of Positive Psychology. New York: Oxford University Press; A job-seeking self-efficacy scale for people with physical disabilities: Preliminary development and psychometric testing.
Looking for adolescents' well-being: Self-efficacy beliefs as determinants of positive thinking and happiness. Hampton NZ. Subjective well-being among people with spinal cord injuries: The role of self-efficacy, perceived social support, and perceived health. Discrepancy in illness-related goals and quality of life in chronically ill patients: the role of self-efficacy.
Psychology and Health. Positive Psychology. The scientific and practical explorations of human strengths.
Chronic diseases and depression: the modifying role of psychosocial resources. Self-efficacy, social support, and depression in aging: A longitudinal analysis. Journal of Gerontology. Self-efficacy as a mediator between stressful life events and depressive symptoms. Seeing the glass half full: A review of the causes and consequences of optimism.
Dispositional optimism and coping: A meta-analytic review. Sheldon KM, Lyubomirsky S. How to increase and sustain positive emotion: The effects of expressing gratitude and visualizing best possible selves.
Meta—analysis of the impact of positive psychological capital on employee attitudes, behaviors, and performance. Human Resource Development Quarterly. Impact of positive psychological capital on well-being over time. Goal pursuit, goal adjustment, and affective well-being following lower limb amputation. Self-regulation processes and health: the importance of optimism and goal adjustment. Thus, Greek society as an indicative western world society appears to be homogenized in terms of representations related to exercise, smoking, and the impact of the disease on human life.
This finding may be attributed to the society's exposure to a broad and long-standing unambiguous description of these concepts, a practice that has inevitably led the society to the acceptance of a common meaning for those representations following the concept's shared meanings or shared conceptual maps [ 42 ].
In the context of the exploratory structural model that was tested, the centralities of the categories concerning diet, alcoholic beverage consumption, nightlife, and lifestyle was founded to consist of the same latent variable, suggesting that there is a similar effect of age, gender, and psychopathology on the centralities of the words.
These findings may reveal that these social representations have a comparable level of word homogenization, nevertheless offering the possibility of personalized expression. For example, in a study of climate change, the authors found a common core set of concepts, but there were also many differences in how climate change is framed and conceived by respondents [ 43 ].
The centrality of the words concerning health was founded to be marginally non-significantly loaded on that latent factor showing that social representations about health are affected by the psycho-demographic variables differently than the other four-word groups. This result ties nicely with previous studies wherein sociodemographic variables such as age, gender, education, and socio-economic status, should be taken into account in the study of social representations [ 3 , 11 ].
Also, differences were reported concerning the effect of age, gender, psychopathology, and shame on the centralities of the five-word categories providing insight into how those factors are reflected in the differences of the social representations within the same Greek cultural context. Older respondents were found to give more decentralized words when "Nightlife" was the stimulus word, a finding reflecting the different pace at which people move away from nightlife experiences as they are getting older.
The finding that women provided more centrally positioned words than men in the lifestyle words graph reflects the known fact that women have healthier dietary habits, a higher rate of physical activity, and a lower rate of smoking and obesity than men [ 44 ]. A healthy dietary pattern previously reported relates to decreasing the risk of depression [ 45 ]. Thus one would assume that a similar effect would appear between depression and the centrality of the words selected to describe the social representation of diet.
The present study's findings seem to provide hints towards a different direction since subjects with increased levels of depression were found to choose more centrally positioned words in the diet, giving more decentralized responses when the stimulus word was health. Those findings suggest a higher complexity pattern of the social representations concerning diet and health and the relation with depression disorder and a possible interaction effect with other factors that remain to be demonstrated in future studies.
As reflected in the external shame score, higher feelings of inferiority correspond to more decentralized words to the network graph of lifestyle words category, indicating higher subject's desire to manifest an identity with stronger personal characteristics.
The analogous effect of external shame on the centrality of the words concerning health is not possible to visibly interpreted, suggesting a possible interaction with physical health problems. This factor was not met in our study. The negative feelings associated with what one thinks and feels about oneself are reflected in the internal shame score.
Internal shame score was found to significantly affect the centrality of the words concerning the social representation of nightlife, showing greater subject's insecurity to move away from the social norms describing human activities of entertainment of that kind.
These findings support the notion that shame should be considered as a determinant of health [ 46 ]. The link between extensive alcohol consumption and hostility has been well documented in the literature [ 47 , 48 ], while analogous results also indicate the relation of hostility with eating disorders [ 49 ]. The relations as mentioned above are confirmed as far as the way of expression is concerned since hostility score found to have a significant negative effect on alcohol consumption and diet word categories.
This finding reflects the tendency of a subject with a higher hostility score to stay away from social norms and avoid using mainstream words to describe those representations providing words positioned less centrally in the word graphs of alcohol and diet. Interpersonal sensitivity has been previously reported to be connected with eating disorder symptoms [ 50 ], being also related to higher general morbidity and mortality [ 51 ].
Individuals with higher interpersonal sensitivity were found to provide more decentralized words when the stimulus word was diet indicating a greater distancing from social norms. At the same time, more considerable interpersonal sensitivity was connected to more centrally positioned words concerning health, demonstrating a common-sense agreement on health representation. The literature review did not provide any previous research on free associations following the analysis method of the present study.
Thus, it is essential to describe all the sources of ambiguity with respect to our method of analysis to allow the reader to evaluate the study's findings correctly. Firstly, the concept of the importance of a node in a graph is ill-defined, and that is the reason that many centrality measures have been proposed in the graph theory. The four centrality measures that were computed in the present article are commonly reported in the literature.
Among the four selected centrality indexes, the authoritative centrality index was prefered to be used in the subsequent analysis due to the ease of interpretation. It is not known whether there will be significant differences in the reported findings under a different centrality index choice among the other theoretically available indexes. Concerning the structural equation model, the baseline model's RMSEA fit index was equal to 0,, smaller than 0,, a limit below which the fit indexes are reported to be not very informative [ 52 ], a finding that possibly reflects the overall small correlation among the eight centralities and the psychometric variables Additional file 1 : Table S3.
Additionally, a simple direct effect model was chosen to test the effects of the psycho-demographic variables on word centralities, a non-optimal option since there is strong evidence in the literature that there are significant effects of age and gender on various social groups on psychopathology [ 53 ].
Lastly, various interactions have been suggested between gender, psychopathology, and human habits that were investigated in the present study [ 54 ]. These facts may suggest a richer path model where psychopathology and shame would also regress on age and gender could be more realistic.
However, a model of greater complexity did not acceptably fit our data, suggesting future analogous research to a larger sample. Notwithstanding these shortcomings, the results of this study can give valuable contributions to the construction of social representations about health, illness, and lifestyle behaviours with possible application in the field of health marketing.
Studying how the centrality of a word interacts with the psychopathological state in the general population within the same group of individuals may help researchers objectify "new" scientific and emotional issues associated with the nature and meaning of such representations.
Our study found differences among the central core words and categories provided by individuals with different levels of psychopathology, indicating that the dynamics of social representations are subject to socio-cultural and individual emotional phenomena.
Further work is required to examine whether the reflections of psychopathology on social representations are casual, making also possible an early identification of psychopathological process through the word usage within a group of individuals. Studies in group decision II: differences of positions, differences of opinion and group polarization.
Eur J Soc Psychol. Article Google Scholar. Flick U. Social representations and the social construction of everyday knowledge: theoretical and methodological queries. Soc Sci Inf. Enhancing assessment of social representations by comparing groups with different cultural and demographic characteristics: a case study on pulses.
Food Q Prefer. Health and illness: a social psychological analysis. Joffe H. Social Representations and health psychology. Murray M, Flick U. Social representations of health and illness: qualitative methods and related theories—an introduction. Conceptualisation of health and illness. Psychol Dev Soc. Foster JL. J Health Psychol. Abric J-C. Central system, peripheral system: their functions and roles in the dynamics of social representations.
Papers Soc Rep. Google Scholar. Meier K, Kirchler E. Social representations of the euro in Austria. J Econ Psychol. A central place for meat, but what about pulses? Food Res Int. Focusing the research agenda on burnout in IT: social representations of burnout in the profession. Eur J Inf Syst. Lo Monaco G, Bonetto E. Social representations and culture in food studies. Social representations of wine and culture: a comparison between France and New Zealand.
Food Qual Prefer. Helman C. Culture, health and illness, 5th edn. London: CRC Press; Soc Sci Med. PubMed Article Google Scholar. Wolter R. The structural approach to social representations: bridges between theory and methods. Medicina Universitaria.
0コメント