In myalgic encephalomyelitis/chronic fatigue syndrome,increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is accompanied by activation of immuno-inflammatory pathways, increased bacterial translocation and autoimmune responses to serotonin (5-HT). Inflammation is known to damage 5-HT neurons while bacterial translocation may drive autoimmune responses. This study has been carried out to examine the autoimmune responses to 5-HT in ME/CFS in relation to inflammation and bacterial translocation.

Methods

We examined 5-HT antibodies in 117 patients with ME/CFS (diagnosed according to the centers for disease control and prevention criteria, CDC) as compared with 43 patients suffering from chronic fatigue (CF) but not fulfilling the CDC criteria and 35 normal controls. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin and the IgA responses to Gram-negative bacteria were measured. Severity of physio-somatic symptoms was measured using the fibromyalgia and chronic fatigue syndrome rating scale (FF scale).

Results

The incidence of positive autoimmune activity against 5-HT was significantly higher (p<0.001) in ME/CFS (61.5%) than in patients with CF (13.9%) and controls (5.7%). ME/CFS patients with 5-HT autoimmune activity displayed higher TNFα, IL-1 and neopterin and increased IgA responses against LPS of commensal bacteria than those without 5-HT autoimmune activity. Anti-5-HT antibody positivity was significantly associated with increased scores on hyperalgesia, fatigue, neurocognitive and autonomic symptoms, sadness and a flu-like malaise.

Discussion

The results show that, in ME/CFS, increased 5-HT autoimmune activity is associated with activation of immuno-inflammatory pathways and increased bacterial translocation, factors which are known to play a role in the onset of autoimmune reactions. 5-HT autoimmune activity could play a role in the pathophysiology of ME/CFS and the onset of physio-somatic symptoms. These results provide mechanistic support for the notion that ME/CFS is a neuro-immune disorder.     

A review and meta-synthesis of qualitative studies on myalgic encephalomyelitis/chronic fatigue syndrome

Objective

To review and synthesize findings across qualitative studies on Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Methods

Articles were systematically reviewed and analyzed within a meta-analytic framework. Analyses included a multi-perspective examination of ME/CFS, as well as a comparative analysis of ME/CFS versus other chronic conditions.

Results

Thirty-four qualitative studies on ME/CFS were included. Findings include three substantive thematic areas that focus on: (1) experiences of people with ME/CFS, (2) experiences of physicians, and (3) themes that intersect both of these groups. For patients, illness development influenced identity, reductions in functioning, and coping. Physician-specific themes described lack of awareness about ME/CFS and recommended improvement in educational resources. Intersecting themes expressed issues with diagnosis creating tensions and fueling the stigmatization of ME/CFS.

Conclusions

Findings indicate multilayered, context-specific experiences and ways in which both people with ME/CFS, as well as those involved in their lives (e.g., family or the medical community), interpret this illness. Future qualitative studies should recognize the various facets of the ME/CFS experience, the network members of people with ME/CFS, and the sociocultural environment through which the illness is understood.

Practice implications

Health care professionals can gain unique insight from patient experiences, allowing for more accurate diagnoses and treatment recommendations.     

The role of changes in activity as a function of perceived available and expended energy in nonpharmacological treatment outcomes for ME/CFS

Nonpharmacological interventions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often emphasize gradual increases in activity to promote improvement in physical functioning and fatigue. The energy envelope theory may provide a framework for understanding the relationship between changes in activity level and outcomes for patients with ME/CFS. This study examined the relationship between energy envelope and changes in activity after nonpharmacological interventions in a sample of 44 adults with ME/CFS. Results showed that those who were within their energy envelope before treatment showed more improvement in physical functioning and fatigue compared with those outside of their energy envelope. These findings suggest that an assessment of perceived available and expended energy could help guide the development of individualized nonpharmacological interventions for people with ME/CFS.     

Biological underpinnings of the commonalities in depression, somatization, and Chronic Fatigue Syndrome

Background

Somatization is a multisomatoform disorder characterized by medically unexplained, functional or psychosomatic symptoms. Similar somatic symptoms are key components of depression and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Methods

This paper reviews the evidence that such symptoms are organically based. We use the term “physio-somatic” to describe these symptoms.

Results

Inflammation, cell-mediated immune (CMI) activation and alterations in the tryptophan catabolite (TRYCAT) pathway are associated with the physio-somatic symptoms of depression, ME/CFS and/or somatization. Proinflammatory cytokines, decreased tryptophan and aberrations in TRYCATs may cause physio-somatic symptoms, such as fatigue, autonomic symptoms, hyperalgesia and somatic presentations.

Conclusions

The data suggest co-ordinated and interacting biological pathways driving the occurrence of physio-somatic symptoms across these three disorders, giving a biologically validated “pathway phenotype”. These data have far-reaching implications for DSM-IV diagnostic conceptualizations of somatization (and ME/CFS) suggesting the presence of an emerging organic explanation. Future research should focus on the role of immune regulation, and co-ordination, of neuronal activity and, through larger data sets, ultimately creating new, biologically validated classification rules. These data have implications for the development of novel therapies utilizing these insights, buttressing the role of psychotherapy in psychosomatic presentations.     

Illness perceptions in patients with fibromyalgia

Objective

Former studies in chronic diseases showed the importance of patients’ beliefs and perceptions. The Revised Illness Perception Questionnaire was developed to assess these illness perceptions. Our goal was to investigate psychometric properties of the IPQ-R for Fibromyalgia Dutch language version (IPQ-R FM-Dlv) and to describe illness perceptions of participants with FM.

Methods

196 patients completed the IPQ-R FM-Dlv. Internal consistency, domain structure and inter domain correlations were calculated and compared to the IPQ-R English language version. Scores were compared with chronic fatigue syndrome (CFS), rheumatoid arthritis (RA), and coronary heart disease (CHD).

Results

Most psychometric properties were comparable to those of the original IPQ-R. Participants showed a lack of understanding of their illness, expected their FM to be chronic and to have a lot of negative consequences on functioning. In 17 out of 24 domains significant differences were found between FM and CFS, RA, and CHD patients.

Conclusion

The IPQ-R FM-Dlv showed acceptable psychometric properties, although some aspects need closer examination. Illness perceptions of FM patients on the Dutch questionnaire were non-comparable to CFS, RA, and CHD patients on the English questionnaire.

Practice implications

The IPQ-R FM-Dlv can be used to assess illness perceptions of Dutch FM patients.     

Learning to cope with chronic illness. Efficacy of a multi-component treatment for people with chronic fatigue syndrome

Objective

The aim of this study was to determine the efficacy of an out-patient, multi-component programme developed for patients with chronic fatigue syndrome (CFS).

Methods

Twenty-two patients were assessed before and after six months of treatment. Findings were compared with 22 individuals on the waiting list. The programme offered medical care as well as information and counselling to help patients to understand, accept and cope with their illness.

Results

At six months, there were significant differences between the groups for fatigue, self-efficacy and anxiety. Overall, 82% of the treated patients reported feeling better and 23% had improved to such a degree that they were discharged from the clinic. The gains were maintained at twelve months.

Conclusion

This programme was found to be both helpful and acceptable and may provide a useful first-line intervention for many patients with CFS.

Practice implications

Short, pragmatic programmes may be as effective as cognitive-behaviour therapy.     

Self-investigation in adolescent chronic fatigue syndrome: Narrative changes and health improvement

Objective

A small-scale intervention study into narrative self-investigation in adolescent chronic fatigue syndrome (CFS).

Method

The self-confrontation method (SCM) is an instrument to assess and change personal life stories. Forty-two adolescents diagnosed with CFS were included and randomly assigned to either 6 or 12 sessions with the SCM. Twenty-five healthy adolescents were assigned to 6 sessions. Outcome was measured directly after the self-investigation procedure at 4 months. Follow-up measurements were made 10 months later. The Checklist Individual Strength and the Child Health Questionnaire were used to measure changes in fatigue, physical and psychosocial functioning.

Results

Self-investigation resulted in significant changes in participants’ narratives. Moreover, after self-investigation there was a significant improvement in fatigue, physical and psychosocial functioning for the adolescents with CFS. The patients who completed 12 sessions improved most. At follow-up, the positive effects were maintained.

Conclusion

Self-investigation enables a move beyond the symptoms of CFS in an individualized, patient centered way. Narrative transformation seems to contribute to improved physical and psychosocial outcome in adolescent CFS.

Practice implications

The SCM allows adolescents to discover (for themselves) factors that might cause or perpetuate their fatigue. The results suggest that self-investigation is a useful instrument in the management of adolescent CFS.     

Differences in Physical and Psychosocial Characteristics Between CFS and Fatigued Non-CFS Patients,a Case-Control Study

Purpose

The main research question is: “Do CFS patients differ from fatigued non-CFS patients with respect to physical, cognitive, behavioral, social, and emotional determinants?” In addition, group differences in relevant outcomes were explored.

Method

Patients who met the Centers for Disease Control (CDC) criteria for CFS were categorized as CFS; these patients were mainly recruited via a large Dutch patient organization. Primary care patients who were fatigued for at least 1 month and up to 2 years but did not meet the CDC criteria were classified as fatigued non-CFS patients. Both groups were matched by age and gender (N?=?192 for each group).

Results

CFS patients attributed their fatigue more frequently to external causes, reported a worse physical functioning, more medical visits, and a lower employment rate. The results of a multiple logistic regression analysis showed that patients who believe that their fatigue is associated with more severe consequences, that their fatigue will last longer and is responsible for more additional symptoms are more likely to be classified as CFS, while patients who are more physically active and have higher levels of “all or nothing behavior” are less likely to be classified as having CFS.

Conclusion

A longitudinal study should explore the predictive value of the above factors for the transition from medically unexplained fatigue to CFS in order to develop targeted interventions for primary care patients with short-term fatigue complaints.

     

Spousal support in a behavior change intervention for cholesterol management

Objective

To evaluate spousal involvement in a nurse-led intervention for patients with high cholesterol in which patients set health goals and spouses learned support strategies.

Methods

Qualitative interviews were conducted with 29 patients and 26 spouses who received the intervention during a trial. Interviews were stratified by patient LDL-C change (better, same, worse). Coded text was content analyzed, and organized into thematic matrices, with columns indicating individuals (spouse or patient) and rows indicating dyads.

Results

Patients and spouses reported no drawbacks to spousal involvement; some patients whose LDL-C did not improve wanted more focus on spouse health. Spouses said that the nurse's expertise and interest were helpful and they were better able to communicate with patients about health. Although the program helped couples work together, spouses with better or same LDL-C talked more about functioning as a unit, whereas those whose partners had worse LDL-C talked more about functioning as individuals.

Conclusion

Although the spousal role was accepted, there were variations in level of involvement. More active spousal involvement might relate to better patient outcomes. For less involved spouses, more focus on their health may improve commitment or involvement.

Practice implications

These findings can inform ways to generate spousal support in future trials.     

Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment

Background

Cytokine disturbances have been suggested to be associated with the Chronic Fatigue Syndrome/Myalgic encephalomyelitis (CFS/ME) for decades.

Methods

Fifty female CFS patients were included in a study on the effect of the interleukin-1-receptor antagonist anakinra or placebo during 4 weeks. EDTA plasma was collected from patients before and directly after treatment. At baseline, plasma samples were collected at the same time from 48 healthy, age-matched female neighborhood controls. A panel of 92 inflammatory markers was determined in parallel in 1 μL samples using a ‘proximity extension assay’ (PEA) based immunoassay. Since Transforming growth factor beta (TGF-β) and interleukin-1 receptor antagonist (IL-1Ra) were not included in this platform, these cytokines were measured with ELISA.

Results

In CFS/ME patients, the ‘normalized protein expression’ value of IL-12p40 and CSF-1 was significantly higher (p value 0.0042 and 0.049, respectively). Furthermore, using LASSO regression, a combination of 47 markers yielded a prediction model with a corrected AUC of 0.73. After correction for multiple testing, anakinra had no effect on circulating cytokines. TGF-β did not differ between patients and controls.

Conclusions

In conclusion, this study demonstrated increased IL-12p40 and CSF-1 concentrations in CFS/ME patients in addition to a set of predictive biomarkers. There was no effect of anakinra on circulating cytokines other than IL-1Ra. Trial Registration: ClinicalTrials.gov Identifier: NCT02108210, Registered April 2014

     

Fatigue communication at the out-patient clinic of Rheumatology

Objective

To describe nurse–patient and rheumatologist–patient interaction in fatigue communication at the rheumatology out-patient clinic.

Methods

Consultations of 20 rheumatoid arthritis (RA) patients with the nurse specialist and the rheumatologist were videotaped and analysed using the Medical Interview Aural Rating Scale (MIARS). Subsequently, patients were asked to fill out a concern questionnaire asking how worried they felt and how satisfied they were with attention given by both healthcare professionals. Finally, patients were interviewed on reasons for being not or not completely satisfied with the care received.

Results

Fatigue was discussed in 42% of the rheumatologists’ consultations and 83% of the nurse specialists’ consultations. RA patients more often used implicit cues instead of explicit concerns related to fatigue. Almost 72% of the patients felt worried about fatigue and in general they were more satisfied with the nurse specialist's attention to fatigue than with the attention from the rheumatologist.

Conclusion

Fatigue is not structurally communicated at the rheumatology out-patient clinic and exploring and acknowledging communication techniques can help patients to express their concerns about fatigue.

Practice implications

Healthcare professionals must recognise fatigue as a severe problem for RA patients and start the conversation on fatigue instead of waiting for the patient to mention fatigue spontaneously.     

Development and preliminary evaluation of a cognitive behavioural approach to fatigue management in people with multiple sclerosis

Objectives

(i) To develop a group-based intervention for the management of multiple sclerosis (MS) fatigue incorporating energy effectiveness and cognitive behavioural approaches and (ii) to undertake a process and preliminary evaluation.

Methods

Drawing upon a literature search, a local model of good practice and the views of service users and health professionals, a manualised group-based fatigue management programme was developed, designed to be delivered by health professionals. A process and preliminary outcome evaluation was undertaken. Sixteen participants attended across two iterations. Participant feedback, obtained via a focus group and evaluation questionnaires, was used to refine the programme. Outcomes were collected pre- and post-programme (including fatigue severity, quality of life, self-efficacy).

Results

Focus group feedback suggested the programme was well received, reflected in high attendance and positive ratings on evaluation questionnaires. At follow-up, despite the small sample size, there were significant improvements in perceived self-efficacy for managing fatigue.

Conclusion

An evidence-based fatigue management intervention has been developed and preliminary findings look promising. In the next phase we will examine whether the programme transfers satisfactorily to other centres and collect data in preparation for a randomised controlled trial (RCT).

Practice implications

Implications for practice will emerge when the results of our RCT are published.     

Conceptualizations of patient empowerment among individuals seeking treatment for diabetes mellitus in an urban, public-sector clinic

Objective

The patient empowerment paradigm has been promoted as a critical component of diabetes care. The present study explores how patients in an urban, public-sector clinic perceive patient empowerment as it applies to their treatment, interactions with clinicians, and self-care behaviors.

Methods

Semi-structured interviews were conducted with 29 individuals and analyzed through an inductive approach.

Results

Patient empowerment was described as taking responsibility for self-care behaviors. Participants reported they that must be internally driven to maintain their self-care regiment, and placed moral value on their performance. Some participants asked questions during healthcare encounters, but fewer reported setting the agenda or making meaningful decisions regarding their care.

Conclusion

Gaps in individuals’ perception of empowerment were identified, along with barriers such as frustration, fatigue, financial concerns, transportation, and scheduling difficulties.

Practice implications

Increasing patient empowerment in socially disadvantaged settings will require careful communication to elicit questions, present all available treatment choices, and encourage individuals to take responsibility without placing blame on them for instances of poor glycemic control.     

Cross-Cultural Study of Information Processing Biases in Chronic Fatigue Syndrome: Comparison of Dutch and UK Chronic Fatigue Patients

Purpose

This study aims to replicate a UK study, with a Dutch sample to explore whether attention and interpretation biases and general attentional control deficits in chronic fatigue syndrome (CFS) are similar across populations and cultures.

Method

Thirty eight Dutch CFS participants were compared to 52 CFS and 51 healthy participants recruited from the UK. Participants completed self-report measures of symptoms, functioning, and mood, as well as three experimental tasks (i) visual-probe task measuring attentional bias to illness (somatic symptoms and disability) versus neutral words, (ii) interpretive bias task measuring positive versus somatic interpretations of ambiguous information, and (iii) the Attention Network Test measuring general attentional control.

Results

Compared to controls, Dutch and UK participants with CFS showed a significant attentional bias for illness-related words and were significantly more likely to interpret ambiguous information in a somatic way. These effects were not moderated by attentional control. There were no significant differences between the Dutch and UK CFS groups on attentional bias, interpretation bias, or attentional control scores.

Conclusion

This study replicated the main findings of the UK study, with a Dutch CFS population, indicating that across these two cultures, people with CFS demonstrate biases in how somatic information is attended to and interpreted. These illness-specific biases appear to be unrelated to general attentional control deficits.

     

Psychoeducation with patients at-risk for schizophrenia—An exploratory pilot study

Objective

To introduce a psychoeducational program for patients of at-risk mental state and its preliminary evaluation.

Methods

The psychoeducational program was designed as a purely informative intervention and consisted of seven 1-h sessions. Sixteen at-risk mental state patients (mean age 26 ± 4.9 years, 12 males/4 females, mean score on prodromal psychopathology (Bonn Scale for Assessment of predictive Basis Symptoms [BSABS-P] 18.6 ± 13.3) were investigated.

Results

Comparisons of means before and after psychoeducation showed a significant reduction in psychopathology and fatalistic LoC as well as an improvement in knowledge, global functioning and various areas of QoL. A qualitative evaluation of the psychoeducational program also showed advantages from patients’ perspectives.

Conclusions

This study provides empirical evidence for benefits of psychoeducation with patients of at-risk mental state for schizophrenia but is exploratory and has some limitations, e.g. the small sample size. Therefore the results have to be replicated in a randomized controlled trial in order to be able to demonstrate conclusively the effectiveness of psychoeducation in the pre-psychotic phase.

Practice implications

Results from this preliminary study suggest that psychoeducation is a promising intervention for patients of at-risk mental state for schizophrenia, and therefore worthy of more investigations.     

Treatment-related and psychosocial variables in explaining physical activity in women three weeks to six months post-treatment of breast cancer

Objective

This study examined treatment-related and psychosocial variables in explaining total and leisure time physical activity in breast cancer survivors three weeks to six months post-treatment.

Methods

A questionnaire was used to measure total and leisure time physical activity and relevant determinants among 464 breast cancer survivors (aged 18–65 years).

Results

Personal control was an important overall determinant in explaining physical activity in breast cancer survivors. The impact of treatment-related variables and psychological functioning depended on the working status of the women. Fatigue and poor body image prevented non-working women from being sufficiently physically active. In working women, chemotherapy and arm problems negatively influenced physical activity, whereas therapy side-effects (headaches, hot flashes, feeling unwell) and poor body image positively influenced physical activity. Social support and coping strategies could not explain post-treatment physical activity levels.

Conclusion

Personal control, treatment-related variables and psychological functioning influenced physical activity after cancer treatment. Relations depended on the working status of the women.

Practice implications

Incorporating self-control methods in physical activity interventions after breast cancer could be helpful. Furthermore, interventions should be tailored to the experienced symptoms (fatigue, arm-problems, body image) and working status of women.     

Risk factors for longer term psychological distress in well-functioning fibromyalgia patients: A prospective study into prognostic factors

Objective

Psychological distress is a key risk factor for long-term complaints in fibromyalgia (FM). Prognostic factors for psychological distress might facilitate an early identification of patients at risk to help prevent long-term dysfunction, especially for the relatively well-functioning patients showing little distress who are usually not considered for treatment. This study hence examines potential prognostic factors in this subgroup.

Methods

Psychological distress, physical functioning, illness cognitions (helplessness, acceptance), pain-avoidance factors (passive pain-coping, fear of pain, hypervigilance), and social factors (social support, social reinforcement) was assessed in 78 low-distress FM patients at baseline and after a mean of 9 months (SD = 3.3).

Results

Baseline physical functioning did not predict changes in psychological distress, whereas a higher level of hypervigilance, less acceptance, and less perceived social support predicted an increase in psychological distress at follow-up.

Conclusion

Illness cognitions, pain-avoidance factors, and social support can be considered as prognostic factors predicting changes in psychological distress in FM. More research is needed to investigate additional factors that could also be implicated (e.g. personality factors, stressful events).

Practice implications

Timely assessment of illness cognitions, pain-avoidance factors, and social support may help identify subgroups of relatively well-functioning FM patients at risk of longer term aggravated psychological distress.     

Using multiple methods to characterize the phenotype of individuals with a family history of major depressive disorder

Background

Unaffected relatives (URs) of individuals with major depressive disorder (MDD) are biologically more vulnerable to depression. We compare healthy URs and controls at the level of phenotype (symptoms and functioning) and endophenotype (negative emotion bias), and further investigate the interrelation between these and the contribution of environmental early life stress.

Methods

URs (n=101), identified using Family History Screen interview methods and matched controls completed written and interview questions assessing symptoms of depression and anxiety, negative cognitive style, life functioning and early life stress. Biases in emotion processing were measured using a facial expression of emotion identification paradigm.

Results

Compared to controls, URs reported higher levels of depression and anxiety, a stronger negative cognitive bias, and poorer functioning and lower satisfaction with life. URs were slower to correctly identify fear and sad facial expressions. A slower response time to identify sad faces was correlated with lower quality of life in the social domain. Early life stress (ELS) did not contribute significantly to any outcome.

Limitations

The methodology relies on accurate reporting of participants' own psychiatric history and that of their family members. The degree of vulnerability varies among URs.

Conclusions

A family history of depression accounts for subtle differences in symptom levels and functioning without a necessary role of ELS. A negative emotion bias in processing emotion may be one vulnerability marker for MDD. Biological markers may affect functioning measures before symptoms at the level of experience.     

Anxiety symptoms among remitted depressed outpatients: Prevalence and association with quality of life and psychosocial functioning

Background

Prior studies of remission from depression have only examined the impact of residual depressive, but not anxiety, symptoms. Given that anxiety comorbidity in currently depressed patients is common and is associated with poorer outcomes, residual anxiety symptoms may play a significant role in remitted patients' well-being and vulnerability to relapse. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined the frequency of residual anxiety symptoms among depressed outpatients in remission based on the HAM-D and associations among residual anxiety, psychosocial functioning and quality of life.

Methods

We interviewed 274 psychiatric outpatients diagnosed with DSM-IV major depressive disorder. Patients completed measures of depression and anxiety symptoms, psychosocial functioning, and quality of life.

Results

Nearly three-quarters of remitted depressed patients endorsed at least one residual anxiety symptom, with a majority experiencing more than one symptom. Anxiety severity was associated with reduced functioning and quality of life across all life domains. Controlling for depression severity, anxiety symptoms were independently related to reduced functioning and quality of life in several domains.

Limitations

We did not assess for specific pre-existing DSM-IV anxiety disorders nor particular treatments patients received, which may have influenced residual anxiety symptoms. Future studies should replicate the results using other measures of remission.

Conclusions

Anxiety symptoms are common in depressed patients in remission, and independently related to reduced functioning and quality of life. Thus, it is important to consider anxiety symptoms in evaluating the completeness of treatment response of depressed patients.     

Different perspectives on communication quality and emotional functioning during routine oncology consultations

Objective

To determine quality of communication in routine oncology consultations from patient, physician, and observer perspectives, and to determine agreement of emotional function content in consultations from these three perspectives.

Methods

In total, 69 consultations were included. Perceived quality of communication and whether or not emotional functioning had been discussed was evaluated with patient- and physician-reported questionnaires. Observer perspective was evaluated by content analysis of audio records of the consultations. Agreement between perspectives was analyzed and means compared using linear mixed models.

Results

The patients’ ratings of communication quality differed significantly from those of both the physician and observer. Observer and physician scores did not differ significantly. Physicians rated emotional functioning as discussed more often than was reported from patient and observer perspectives.

Conclusion

The patients’ view of the quality of communication differed from that of the physician and observer. Whether emotional functioning was discussed or not was also perceived differently by patients, physicians, and observer.

Practice implications

The underpinnings and implications of these results need to be further explored regarding how to move toward a higher degree of shared understanding, where different perspectives are more in alignment, and how to develop more valid methods for evaluating communication.