Perceptions of Hope Among Bereaved Caregivers of Cancer Patients Who Received Early Palliative Care: A Content and Lexicographic Analysis.

BACKGROUND: Oncologists' fear of taking away hope from patients when proposing early palliative care (EPC) is a barrier to the implementation of this model. This study explores hope perceptions among bereaved caregivers of onco-hematologic patients who received EPC. MATERIALS AND METHODS: Open-ended questionnaires were administered to 36 primary caregivers of patients who received EPC (26 solid and 10 hematologic cancer patients; mean age: 51.4 years, range age: 20-74), at 2 cancer centers, 2 months to 3 years after a patient death. Definitions of hope in the caregivers' narratives were analyzed through a directed approach to content analysis. Results were complemented with automated lexicographic analysis. RESULTS: Caregivers perceived hope mainly as resilience and as expectations based on what they were told about the patients' clinical conditions. Their hope was bolstered by trusting relationships with the healthcare teams. EPC interventions were recalled as the major support for hope, both during the illness and after the death of the patient. The automated quantitative lexical analysis provided deeper insights into the links between hope, truth, and trust. CONCLUSIONS: Our findings suggest that telling the truth about an incurable onco-hematologic disease and beginning EPC might be the combination of factors triggering hope in the setting of incurable cancer.

Changes in Cancer Patients' and Caregivers' Disease Perceptions While Receiving Early Palliative Care: A Qualitative and Quantitative Analysis.

BACKGROUND: Little is known about the underlying mechanisms through which early palliative care (EPC) improves multiple outcomes in patients with cancer and their caregivers. The aim of this study was to qualitatively and quantitatively analyze patients' and caregivers' thoughts and emotional and cognitive perceptions about the disease prior to and during the EPC intervention, and in the end of life, following the exposure to EPC. MATERIALS AND METHODS: Seventy-seven patients with advanced cancer and 48 caregivers from two cancer centers participated in semistructured interviews. Their reports were qualitatively and quantitatively analyzed by the means of the grounded theory and a text-analysis program. RESULTS: Participants reported their past as overwhelmed by unmanaged symptoms, with detrimental physical and psychosocial consequences. The EPC intervention allowed a prompt resolution of symptoms and of their consequences and empowerment, an appreciation of its multidimensional approach, its focus on the person and its environment, and the need for EPC for oncologic populations. Patients reported that conversations with the EPC team increased their acceptance of end of life and their expectation of a painless future. Quantitative analysis revealed higher use of Negative Affects (p < .001) and Biological Processes words (p < .001) when discussing the past; Agency words when discussing the present (p < .001); Positive Affects (p < .001), Optimism (p = .002), and Insight Thinking words (p < .001) when discussing the present and the future; and Anxiety (p = .002) and Sadness words (p = .003) when discussing the future. CONCLUSION: Overall, participants perceived EPC to be beneficial. Our findings suggest that emotional and cognitive processes centered on communication underlie the benefits experienced by participants on EPC. IMPLICATIONS FOR PRACTICE: By qualitative and quantitative analyses of the emotional and cognitive perceptions of cancer patients and their caregivers about their experiences before and during EPC interventions, this study may help physicians/nurses to focus on the disease perception by patients/caregivers and the benefits of EPC, as a standard practice. The analysis of words used by patients/caregivers provides a proxy for their psychological condition and support in tailoring an EPC intervention, based on individual needs. This study highlights that the relationship of the triad EPC team/patients/caregivers may rise as a therapeutic tool, allowing increasing awareness and progressive acceptance of the idea of death.

Inhibitory Plasticity: From Molecules to Computation and Beyond.

Synaptic plasticity is the cellular and molecular counterpart of learning and memory and, since its first discovery, the analysis of the mechanisms underlying long-term changes of synaptic strength has been almost exclusively focused on excitatory connections. Conversely, inhibition was considered as a fixed controller of circuit excitability. Only recently, inhibitory networks were shown to be finely regulated by a wide number of mechanisms residing in their synaptic connections. Here, we review recent findings on the forms of inhibitory plasticity (IP) that have been discovered and characterized in different brain areas. In particular, we focus our attention on the molecular pathways involved in the induction and expression mechanisms leading to changes in synaptic efficacy, and we discuss, from the computational perspective, how IP can contribute to the emergence of functional properties of brain circuits.

Brain Activation Patterns Characterizing Different Phases of Motor Action: Execution, Choice and Ideation.

Motor behaviour is controlled by a large set of interacting neural structures, subserving the different components involved in hierarchical motor processes. Few studies have investigated the neural substrate of higher-order motor ideation, i.e. the mental operation of conceiving a movement. The aim of this functional magnetic resonance imaging study was to segregate the neural structures involved in motor ideation from those involved in movement choice and execution. An index finger movement paradigm was adopted, including three different conditions: performing a pre-specified movement, choosing and executing a movement and ideating a movement of choice. The tasks involved either the right or left hand, in separate runs. Neuroimaging results were obtained by comparing the different experimental conditions and computing conjunction maps of the right and left hands for each contrast. Pre-specified movement execution was supported by bilateral fronto-parietal motor regions, the cerebellum and putamen. Choosing and executing finger movement involved mainly left fronto-temporal areas and the anterior cingulate. Motor ideation activated almost exclusively left hemisphere regions, including the inferior, middle and superior frontal regions, middle temporal and middle occipital gyri. These findings show that motor ideation is controlled by a cortical network mainly involved in abstract thinking, cognitive and motor control, semantic and visual imagery processes.

Ranking brain areas encoding the perceived level of pain from fMRI data.

Pain perception is thought to emerge from the integrated activity of a distributed brain system, but the relative contribution of the different network nodes is still incompletely understood. In the present functional magnetic resonance imaging (fMRI) study, we aimed to identify the more relevant brain regions to explain the time profile of the perceived pain intensity in healthy volunteers, during noxious chemical stimulation (ascorbic acid injection) of the left hand. To this end, we performed multi-way partial least squares regression of fMRI data from twenty-two a-priori defined brain regions of interest (ROI) in each hemisphere, to build a model that could efficiently reproduce the psychophysical pain profiles in the same individuals; moreover, we applied a novel three-way extension of the variable importance in projection (VIP) method to summarize each ROI contribution to the model. Brain regions showing the highest VIP scores included the bilateral mid-cingulate, anterior and posterior insular, and parietal operculum cortices, the contralateral paracentral lobule, bilateral putamen and ipsilateral medial thalamus. Most of these regions, with the exception of medial thalamus, were also identified by a statistical analysis on mean ROI beta values estimated using the time course of the psychophysical rating as a regressor at the voxel level. Our results provide the first rank-ordering of brain regions involved in coding the perceived level of pain. These findings in a model of acute prolonged pain confirm and extend previous data, suggesting that a bilateral array of cortical areas and subcortical structures is involved in pain perception.

Early palliative care perceptions by patients with cancer and primary caregivers: metaphorical language.

OBJECTIVE: This article reports on the results of an analysis of metaphorical language used by patients diagnosed with advanced cancer and their caregivers receiving early palliative care (EPC). METHODS: Data were collected through a pen-and-paper questionnaire on respondents' perceptions of the disease, its treatment and their idea of death, before and after receiving EPC. The data were analysed by identifying all metaphorical uses of language, following the 'metaphor identification procedure' proposed by the Praggjelaz Group. RESULTS: Metaphors were used from a variety of semantic fields. EPC was described using spiritual terms, to indicate that this approach was instrumental in 'restoring life', 'producing hope' and making patients feel 'accompanied'. The most recurrent metaphors were those referring to light and salvation; spatial metaphors were used to describe the treatment and the hospital as a 'safe haven' and 'an oasis of peace'. Patients and caregivers were overall consistent in the aforementioned ways of referring to illness and treatment; caregivers were more likely than patients to use war metaphors, although their use overall was rare. CONCLUSIONS: Our results suggest that EPC is perceived positively by patients and their caregivers and provide insights regarding the manner in which EPC could be presented to patients, caregivers and the public.

"When You're Smiling": How Posed Facial Expressions Affect Visual Recognition of Emotions.

Facial imitation occurs automatically during the perception of an emotional facial expression, and preventing it may interfere with the accuracy of emotion recognition. In the present fMRI study, we evaluated the effect of posing a facial expression on the recognition of ambiguous facial expressions. Since facial activity is affected by various factors, such as empathic aptitudes, the Interpersonal Reactivity Index (IRI) questionnaire was administered and scores were correlated with brain activity. Twenty-six healthy female subjects took part in the experiment. The volunteers were asked to pose a facial expression (happy, disgusted, neutral), then to watch an ambiguous emotional face, finally to indicate whether the emotion perceived was happiness or disgust. As stimuli, blends of happy and disgusted faces were used. Behavioral results showed that posing an emotional face increased the percentage of congruence with the perceived emotion. When participants posed a facial expression and perceived a non-congruent emotion, a neural network comprising bilateral anterior insula was activated. Brain activity was also correlated with empathic traits, particularly with empathic concern, fantasy and personal distress. Our findings support the idea that facial mimicry plays a crucial role in identifying emotions, and that empathic emotional abilities can modulate the brain circuits involved in this process.

Caregiver's quality of life in advanced cancer: validation of the construct in a real-life setting of early palliative care.

Introduction: Early palliative care (EPC) improves the quality of life (QoL) of advanced cancer patients and their caregivers. The increasingly widespread use of this care model requires the development of measures supporting its interventions. Although the construct of patient's QoL has been extensively investigated and several QoL measures have been further validated, there is a paucity of data concerning the QoL of the caregiver. In 2018, McDonald and colleagues addressed this issue by interviewing 23 primary caregivers of advanced cancer patients who participated in an EPC randomized clinical trial to understand their perspective on the QoL construct. The Authors identified six major dimensions associated with the construct of caregiver's QoL. The present retrospective study aimed to validate these dimensions on a larger sample and in a real-life EPC setting. Methods: Previously collected reports from 137 primary caregivers of advanced cancer patients on EPC answering questions about their experience with this care model were qualitatively analyzed through a deductive, thematic approach to identify and confirm the six dimensions constituting the construct of interest based on McDonald's and colleagues' results. Results: The six dimensions ("living in the patient's world", "burden of illness and caregiving", "assuming the caregiver role", "renegotiating relationships", "confronting mortality", and "maintaining resilience") were consistently found in the reports from primary caregivers in a real-life EPC setting, confirming to be significant themes associated to their QoL. Conclusion: A definite and recurrent construct of primary caregiver's QoL as described by McDonald and colleagues was also found in a larger sample and in a real-life EPC setting. Thus it may lay the groundwork for the development of a dedicated questionnaire.

Words hurt: common and distinct neural substrates underlying nociceptive and semantic pain.

Introduction: Recent studies have shown that processing semantic pain, such as words associated with physical pain, modulates pain perception and enhances activity in regions of the pain matrix. A direct comparison between activations due to noxious stimulation and processing of words conveying physical pain may clarify whether and to what extent the neural substrates of nociceptive pain are shared by semantic pain. Pain is triggered also by experiences of social exclusion, rejection or loss of significant others (the so-called social pain), therefore words expressing social pain may modulate pain perception similarly to what happens with words associated with physical pain. This event-related fMRI study aims to compare the brain activity related to perceiving nociceptive pain and that emerging from processing semantic pain, i.e., words related to either physical or social pain, in order to identify common and distinct neural substrates. Methods: Thirty-four healthy women underwent two fMRI sessions each. In the Semantic session, participants were presented with positive words, negative pain-unrelated words, physical pain-related words, and social pain-related words. In the Nociceptive session, participants received cutaneous mechanical stimulations that could be either painful or not. During both sessions, participants were asked to rate the unpleasantness of each stimulus. Linguistic stimuli were also rated in terms of valence, arousal, pain relatedness, and pain intensity, immediately after the Semantic session. Results: In the Nociceptive session, the 'nociceptive stimuli' vs. 'non-nociceptive stimuli' contrast revealed extensive activations in SI, SII, insula, cingulate cortex, thalamus, and dorsolateral prefrontal cortex. In the Semantic session, words associated with social pain, compared to negative pain-unrelated words, showed increased activity in most of the same areas, whereas words associated with physical pain, compared to negative pain-unrelated words, only activated the left supramarginal gyrus and partly the postcentral gyrus. Discussion: Our results confirm that semantic pain partly shares the neural substrates of nociceptive pain. Specifically, social pain-related words activate a wide network of regions, mostly overlapping with those pertaining to the affective-motivational aspects of nociception, whereas physical pain-related words overlap with a small cluster including regions related to the sensory-discriminative aspects of nociception. However, most regions of overlap are differentially activated in different conditions.

Stigma of Palliative Care among Patients with Advanced Cancer and Their Caregivers on Early Palliative Care.

The early referral to palliative care (PC) represents a successful value-based model with proven benefits regarding the quality of life and clinical outcomes for advanced cancer patients and their caregivers. Yet, its provision remains typically confined to the last weeks of life as per the historical, late PC model. The stigma according to which PC represents end-of-life care has been identified as the root of the problem. To explore the presence and effects of the stigma in a clinical context, we surveyed 78 patients and 110 caregivers (mean age: 71.7 and 60.7, respectively) on early PC to study what their perception of PC was before their direct experience. The responses were analyzed through a qualitative descriptive approach. The participants explicitly mentioned a lack of knowledge about PC (53% of the sample), which they identified also among physicians and the population (13%); an identification of PC with the late PC model (53%); and a detrimental reaction to the proposal of an early PC referral (83%). However, the participants explicitly mentioned that a direct experience of early PC allowed for an acquired awareness of early PC meaning and benefits (52%), as well as a comprehension of its differences with late PC (34%); the regret for the delayed referral (8%); the perception of the word "palliative" as a barrier (21%); and the belief that early PC should be part of the cancer routine practice (25%). A comprehensive multi-level intervention is necessary for a widespread understanding of the essence of anticipated PC.

Early palliative care versus usual haematological care in multiple myeloma: retrospective cohort study.

OBJECTIVES: Although early palliative care (EPC) is beneficial in acute myeloid leukaemia, little is known about EPC value in multiple myeloma (MM). We compared quality indicators for palliative and end-of-life (EOL) care in patients with MM receiving EPC with those of patients who received usual haematological care (UHC). METHODS: This observational, retrospective study was based on 290 consecutive patients with MM. The following indicators were abstracted: providing psychological support, assessing/managing pain, discussing goals of care, promoting advance care plan, accessing home care services; no anti-MM treatment within 14 and 30 days and hospice length of stay >7 days before death; no cardiopulmonary resuscitation, no intubation, <2 hospitalisations and emergency department visits within 30 days before death. Comparisons were performed using unadjusted and confounder-adjusted regression models. RESULTS: 55 patients received EPC and 231 UHC. Compared with UHC patients, EPC patients had a significantly higher number of quality indicators of care (mean 2.62±1.25 vs 1.12±0.95; p<0.0001)); a significant reduction of pain intensity over time (p<0.01) and a trend towards reduced aggressiveness at EOL, with the same survival (5.3 vs 5.46 years; p=0.74)). CONCLUSIONS: Our data support the value of integrating EPC into MM routine practice and lay the groundwork for future prospective comparative studies.

Gratitude among advanced cancer patients and their caregivers: The role of early palliative care.

Objective: A cancer diagnosis represents a unique trauma, given its life-threatening, multidimensional, and uncertain nature. Gratitude is a construct representing the emotional state that arises when individuals recognize that a benefit has been received as a result of someone else's action or a spiritual entity's intervention. Based on the positive psychological wellbeing, gratitude has been associated with improved health outcomes even in the disease setting. Thus, the models of care that foster gratitude should be adopted in the clinical context. This study aims to explore whether and how gratitude may originate in patients with advanced cancer and their caregivers undergoing early palliative care (EPC). Methods: We analyzed 251 reports from 133 patients and 118 caregivers describing their clinical experience in two EPC units. The sources of gratitude were identified and ranked based on their frequencies. Words expressing gratitude and words referring to communication and spirituality were collected by means of the Linguistic Inquiry and Word Count software and correlated. Results: In total, 123 (92.5%) of 133 patients' and 97 (82.2%) of 118 caregivers' reports, respectively, included explicit or implicit expressions of gratitude. Gratitude was associated specifically with successful physical symptom management, emotional support, improved attitude toward death, better information, humanity, and the familiar environment. The use of words of gratitude in patients' reports was positively correlated with the use of words referring to communication (r = .215, p = .026) and spirituality (r = .612, p <.001). Conclusion: Our results suggest that interventions within the EPC model based on doctor-patient-caregiver communication may allow patients and caregivers to experience a feeling of gratitude, and this may represent a resource to be exploited to improve their physical and psychosocial wellbeing.

Early Palliative Care in Acute Myeloid Leukemia.

BACKGROUND: Several novel targeted therapies seem to improve the outcome of acute myeloid leukemia (AML) patients. Nonetheless, the 5-year survival rate remains below 40%, and the trajectory of the disease remains physically and emotionally challenging, with little time to make relevant decisions. For patients with advanced solid tumors, the integration of early palliative care (EPC) with standard oncologic care a few weeks after diagnosis has demonstrated several benefits. However, this model is underutilized in patients with hematologic malignancies. METHODS: In this article, we analyze the palliative care (PC) needs of AML patients, examine the operational aspects of an integrated model, and review the evidence in favor of EPC integration in the AML course. RESULTS: AML patients have a high burden of physical and psychological symptoms and high use of avoidant coping strategies. Emerging studies, including a phase III randomized controlled trial, have reported that EPC is feasible for inpatients and outpatients, improves quality of life (QoL), promotes adaptive coping, reduces psychological symptoms, and enhances the quality of end-of-life care. CONCLUSIONS: EPC should become the new standard of care for AML patients. However, this raises issues about the urgent development of adequate programs of education to increase timely access to PC.

Different semantic and affective meaning of the words associated to physical and social pain in cancer patients on early palliative/supportive care and in healthy, pain-free individuals.

Early palliative/supportive care (ePSC) is a medical intervention focused on patient's needs, that integrates standard oncological treatment, shortly after a diagnosis of advanced/metastatic cancer. ePSC improves the appropriate management of cancer pain. Understanding the semantic and emotional impact of the words used by patients to describe their pain may further improve its assessment in the ePSC setting. Psycholinguistics assumes that the semantic and affective properties of words affect the ease by which they are processed and comprehended. Therefore, in this cross-sectional survey study we collected normative data about the semantic and affective properties of words associated to physical and social pain, in order to investigate how patients with cancer pain on ePSC process them compared to healthy, pain-free individuals. One hundred ninety patients and 124 matched controls rated the Familiarity, Valence, Arousal, Pain-relatedness, Intensity, and Unpleasantness of 94 words expressing physical and social pain. Descriptive and inferential statistics were performed on ratings in order to unveil patients' semantic and affective representation of pain and compare it with those from controls. Possible effects of variables associated to the illness experience were also tested. Both groups perceived the words conveying social pain as more negative and pain-related than those expressing physical pain, confirming previous evidence of social pain described as worse than physical pain. Patients rated pain words as less negative, less pain-related, and conveying a lower intense and unpleasant pain than controls, suggesting either an adaptation to the pain experience or the role played by ePSC in improving patients' ability to cope with it. This exploratory study suggests that a chronic pain experience as the one experienced by cancer patients on ePSC affects the semantic and affective representation of pain words.

The psycholinguistic and affective structure of words conveying pain.

Despite the flourishing research on the relationships between affect and language, the characteristics of pain-related words, a specific type of negative words, have never been systematically investigated from a psycholinguistic and emotional perspective, despite their psychological relevance. This study offers psycholinguistic, affective, and pain-related norms for words expressing physical and social pain. This may provide a useful tool for the selection of stimulus materials in future studies on negative emotions and/or pain. We explored the relationships between psycholinguistic, affective, and pain-related properties of 512 Italian words (nouns, adjectives, and verbs) conveying physical and social pain by asking 1020 Italian participants to provide ratings of Familiarity, Age of Acquisition, Imageability, Concreteness, Context Availability, Valence, Arousal, Pain-Relatedness, Intensity, and Unpleasantness. We also collected data concerning Length, Written Frequency (Subtlex-IT), N-Size, Orthographic Levenshtein Distance 20, Neighbor Mean Frequency, and Neighbor Maximum Frequency of each word. Interestingly, the words expressing social pain were rated as more negative, arousing, pain-related, and conveying more intense and unpleasant experiences than the words conveying physical pain.

Modulation of neural circuits underlying temporal production by facial expressions of pain.

According to the Scalar Expectancy Theory, humans are equipped with a biological internal clock, possibly modulated by attention and arousal. Both emotions and pain are arousing and can absorb attentional resources, thus causing distortions of temporal perception. The aims of the present single-event fMRI study were to investigate: a) whether observation of facial expressions of pain interferes with time production; and b) the neural network subserving this kind of temporal distortions. Thirty healthy volunteers took part in the study. Subjects were asked to perform a temporal production task and a concurrent gender discrimination task, while viewing faces of unknown people with either pain-related or neutral expressions. Behavioural data showed temporal underestimation (i.e., longer produced intervals) during implicit pain expression processing; this was accompanied by increased activity of right middle temporal gyrus, a region known to be active during the perception of emotional and painful faces. Psycho-Physiological Interaction analyses showed that: 1) the activity of middle temporal gyrus was positively related to that of areas previously reported to play a role in timing: left primary motor cortex, middle cingulate cortex, supplementary motor area, right anterior insula, inferior frontal gyrus, bilateral cerebellum and basal ganglia; 2) the functional connectivity of supplementary motor area with several frontal regions, anterior cingulate cortex and right angular gyrus was correlated to the produced interval during painful expression processing. Our data support the hypothesis that observing emotional expressions distorts subjective time perception through the interaction of the neural network subserving processing of facial expressions with the brain network involved in timing. Within this frame, middle temporal gyrus appears to be the key region of the interplay between the two neural systems.

Pain Mirrors: Neural Correlates of Observing Self or Others' Facial Expressions of Pain.

Facial expressions of pain are able to elicit empathy and adaptive behavioral responses in the observer. An influential theory posits that empathy relies on an affective mirror mechanism, according to which emotion recognition relies upon the internal simulation of motor and interoceptive states triggered by emotional stimuli. We tested this hypothesis comparing representations of self or others' expressions of pain in nineteen young healthy female volunteers by means of functional magnetic resonance imaging (fMRI). We hypothesized that one's own facial expressions are more likely to elicit the internal simulation of emotions, being more strictly related to self. Video-clips of the facial expressions of each volunteer receiving either painful or non-painful mechanical stimulations to their right hand dorsum were recorded and used as stimuli in a 2 × 2 (Self/Other; Pain/No-Pain) within-subject design. During each trial, a 2 s video clip was presented, displaying either the subject's own neutral or painful facial expressions (Self No-Pain, SNP; Self Pain, SP), or the expressions of other unfamiliar volunteers (Others' No-Pain, ONP; Others' Pain, OP), displaying a comparable emotional intensity. Participants were asked to indicate whether each video displayed a pain expression. fMRI signals were higher while viewing Pain than No-Pain stimuli in a large bilateral array of cortical areas including middle and superior temporal, supramarginal, superior mesial and inferior frontal (IFG) gyri, anterior insula (AI), anterior cingulate (ACC), and anterior mid-cingulate (aMCC) cortex, as well as right fusiform gyrus. Bilateral activations were also detected in thalamus and basal ganglia. The Self vs. Other contrast showed signal changes in ACC and aMCC, IFG, AI, and parietal cortex. A significant interaction between Self and Pain [(SP vs. SNP) >(OP vs. ONP)] was found in a pre-defined region of aMCC known to be also active during noxious stimulation. These findings demonstrate that the observation of one's own and others' facial expressions share a largely common neural network, but self-related stimuli induce generally higher activations. In line with our hypothesis, selectively greater activity for self pain-related stimuli was found in aMCC, a medial-wall region critical for pain perception and recognition.

'Mirror pain' in the formalin test: behavioral and 2-deoxyglucose studies.

Subcutaneous injection of a dilute formaldehyde solution (5 or 10%) into a hind paw induced, in the majority of rats, the appearance of 'mirror pain': licking the contralateral untreated hind paw 10-60 min after injection. Contralateral licking activity was much less frequent than the ipsilaterally directed one, but the overall intensities of the two responses were positively correlated. Qualitatively, the two behaviours were similar. Functional activity levels of the lumbar spinal cord, as revealed by the 2-deoxyglucose (2-DG) technique, were increased bilaterally over the first hour after unilateral hind limb formalin injection in unanesthetized, freely moving rats. The enhancement of the [14C]2-DG uptake could be detected both in dorsal and ventral horns, as well as in the gray matter surrounding the central canal, and the anterolateral and dorsolateral funiculi. These metabolic changes may reflect an enhancement of the functional activity of both interneuronal pools and units projecting to supraspinal centers, giving rise to a referred contralateral pain.