Patient-reported outcome measures on mental health and psychosocial factors in patients with Brugada syndrome.

AIMS: Brugada syndrome (BrS) is a hereditary arrhythmic disease, associated with sudden cardiac death. To date, little is known about the psychosocial correlates and impacts associated with this disease. The aim of this study was to assess a set of patient-reported psychosocial outcomes, to better profile these patients, and to propose a tailored psychosocial care. METHODS AND RESULTS: Patients were recruited at the European reference Centre for BrS at Universitair Ziekenhuis Brussel, Belgium. Recruitment was undertaken in two phases: phase 1 (retrospective), patients with confirmed BrS, and phase 2 (prospective), patients referred for ajmaline testing who had an either positive or negative diagnosis. BrS patients were compared to controls from the general population. Two hundred and nine questionnaires were analysed (144 retrospective and 65 prospective). Collected patient-reported outcomes were on mental health (12 item General Health Questionnaire; GHQ-12), social support (Oslo Social Support Scale), health-related quality of life, presence of Type-D personality (Type-D Scale; DS14), coping styles (Brief-COPE), and personality dimensions (Ten Item Personality Inventory). Results showed higher mental distress (GHQ-12) in BrS patients (2.53 ± 3.03) than in the general population (P < 0.001) and higher prevalence (32.7%) of Type D personality (P < 0.001) in patients with confirmed Brugada syndrome (BrS +). A strong correlation was found in the BrS + group (0.611, P < 0.001) between DS14 negative affectivity subscale and mental distress (GHQ-12). CONCLUSION: Mental distress and type D personality are significantly more common in BrS patients compared to the general population. This clearly illustrates the necessity to include mental health screening and care as standard for BrS.

Should we include monitors to improve assessment of awareness and pain in unconscious palliatively sedated patients? A case report.

BACKGROUND: Awareness and pain during palliative sedation is typically assessed by observational scales, but the use of such scales has been put into question. CASE PRESENTATION: A woman in her mid-80s was admitted to a palliative care unit, presenting with chronic lymphatic leukemia, depression, and a cerebrovascular accident, with right-sided hemiplegia and aphasia. The patient was unable to eat and was suffering from nausea and vomiting. Before admission, the patient had expressed her desire to discontinue treatment on several occasions. CASE MANAGEMENT: The decision was made to initiate palliative sedation. The patient consented to take part in a study to assess level of comfort and pain using two monitoring devices (NeuroSense monitor and Analgesia Nociception Index monitor). CASE OUTCOME: The patient died 90 h after initiation of palliative sedation. Titration of the medication was challenging and sedation was not deep enough during the first 2 days. Thirteen assessments made with the Ramsay Sedation Scale showed that the patient was considered to be in a deep sleep, while in fact the NeuroSense monitor indicated otherwise. CONCLUSION: This case demonstrates the feasibility and potential advantages of using monitoring devices to objectify assessments of pain and discomfort in palliatively sedated patients.

Comfort in palliative sedation (Compas): a transdisciplinary mixed method study protocol for linking objective assessments to subjective experiences.

BACKGROUND: In case of untreatable suffering at the end of life, palliative sedation may be chosen to assure comfort by reducing the patient's level of consciousness. An important question here is whether such sedated patients are completely free of pain. Because these patients cannot communicate anymore, caregivers have to rely on observation to assess the patient's comfort. Recently however, more sophisticated techniques from the neurosciences have shown that sometimes consciousness and pain are undetectable with these traditional behavioral methods. The aim of this study is to better understand how unconscious palliative sedated patients experience the last days of their life and to find out if they are really free of pain. METHODS: In this study we will observe 40 patients starting with initiation of palliative sedation until death. Assessment of comfort based on behavioral observations will be related with the results from a NeuroSense monitor, an EEG-based monitor used for evaluation of the adequacy of anesthesia and sedation in the operating room and an ECG-based Analgesia Nociception Index (ANI) monitor, which informs about comfort or discomfort condition, based on the parasympathetic tone. An innovative and challenging aspect of this study is its qualitative approach; "objective" and "subjective" data will be linked to achieve a holistic understanding of the study topic. The following data will be collected: assessment of pain/comfort by the patients themselves (if possible) by scoring a Visual Analogue Scale (VAS); brain function monitoring; monitoring of parasympathetic tone; caregivers' assessment (pain, awareness, communication); relatives' perception of the quality of the dying process; assessment by 2 trained investigators using observational scales; video and audio registration. DISCUSSION: Measuring pain and awareness in non-communicative dying patients is both technically and ethically challenging. ANI and EEG have shown to be promising technologies to detect pain that otherwise cannot be detected with the "traditional" methods. Although these technologies have the potential to provide objective quantifiable indicators for distress and awareness in non-communicative patients, strikingly they have not yet been used to check whether the current assessments for non-communicative patients are reliable. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov (Identifier: NCT03273244 ; registration date: 7.9.2017).

Systematic screening for distress in oncology practice using the Distress Barometer: the impact on referrals to psychosocial care.

PURPOSE: This study evaluates how patterns of psychosocial referral of patients with elevated distress differ in a 'systematic screening for distress' condition versus a 'usual practice' condition in ambulatory oncology practice. METHODS: The psychosocial referral process in a 2-week usual practice (N=278) condition was compared with a 2-week 'using the Distress Barometer as a screening instrument' (N=304) condition in an outpatient clinic with seven consulting oncologists. RESULTS: Out of all distressed patients in the usual practice condition, only 5.5% of patients detected with distress were actually referred to psychosocial counselling, compared with 69.1% of patients detected with distress in the condition with systematic screening using the Distress Barometer. Only 3.7% of patients detected with distress in the usual practice condition finally accepted this referral, compared with 27.6% of patients detected with distress in the screening condition. CONCLUSIONS: Using the Distress Barometer as a self-report screening instrument prior to oncological consultation optimises detection of elevated distress in patients, and this results in a higher number of performed and accepted referrals, but cannot by itself guarantee actual psychosocial referral or acceptance of referral. There is not only a problem of poor detection of distress in cancer patients but also a need for better decision-making and communication between oncologists and patients about this issue.

Subjective wellbeing and psychological symptoms of university students during the COVID-19 pandemic: Results of a structured telephone interview in a large sample of university students.

University students are at elevated risk for psychological distress, especially during the COVID-19 pandemic. The aim of this study was to warmly contact our students and investigate the psychological impact of the COVID-19 pandemic on the subjective wellbeing (SWB) and levels of psychological symptoms (such as depressive and anxious feelings) of university students in Belgium. All bachelor and master students of the Vrije Universiteit Brussels (N = 15,475) were invited for a brief structured telephone interview in March, 2021. In total, 7,154 students were assessed by a structured interview, based on the Kessler Psychological Distress Scale (K6) and the Anamnestic Comparative Self-Assessment (ACSA). Compared to a representative sample, students considered their life during the pandemic as less satisfying compared to their life before the pandemic. Overall, all students have suffered from COVID-19 and the measures taken to contain the pandemic. Twenty percent of our sample of 7,154 VUB students scored above the K6 cutoff, indicating a heightened risk for having a diagnosable mental illness severe enough to cause functional limitations and to require treatment. This study highlights the need for psychological support for all students, during the COVID-19 pandemic.

Neurophysiological Assessments During Continuous Sedation Until Death Put Validity of Observational Assessments Into Question: A Prospective Observational Study.

INTRODUCTION: In case of untreatable suffering at the end of life, continuous sedation until death (CSD) may be the only treatment option left. Because these patients cannot communicate anymore, caregivers have to rely on behavioral observation to assess the patient's comfort. Recently, however, a number of studies from the neurosciences have shown that sometimes consciousness and pain are undetectable with these traditional behavioral methods. The aim of this study was to find out if subjective caregiver assessments of consciousness and pain would be confirmed by objective neurophysiological measures. METHODS: In this prospective observational study, we observed patients from the start of palliative sedation until death. Subjective caregiver assessments of level of consciousness and pain based on behavioral observations were compared with objective measures from neurophysiological monitoring devices. RESULTS: We collected and analyzed 108 subjective caregiver assessments in a sample of 12 patients and 32 assessments by traditionally used observational scales. We compared these with objective neurophysiological measures. Sensitivity and specificity of caregivers' subjective assessments of consciousness was 23.6 and 91.1% respectively, with an accuracy of 54.0% and interrater reliability (κ) of 0.13. For pain, this was 0 and 94.79%, respectively, an accuracy of 88%, and an inter-rater reliability (κ) of - 0.063. Agreement between caregivers' subjective assessments and objective neurophysiological measures of consciousness and pain was very poor. CONCLUSIONS: Caregivers' subjective assessment of level of consciousness and pain during CSD is unreliable compared with objective neurophysiological monitoring. Our results suggest that assessments of patient comfort during CSD could have been improved substantially by including objective monitoring of level of consciousness and pain. TRIAL REGISTRATION: The protocol for this observational study has been registered retrospectively at Clinical-Trials.gov (ID NCT03273244).

Cross-national comparability of the WHOQOL-BREF: a measurement invariance approach.

PURPOSE: To evaluate whether the WHOQOL-BREF measures the QOL construct in the same way across nations. METHODS: Students from Flanders, Belgium and Iran completed the WHOQOL-BREF as part of a larger Quality of Life questionnaire. Their responses were compared using a multi-group confirmatory factor analysis. RESULTS: In general, the QOL construct appears rather similar in both cultures; however, participants from both countries seem to respond differently to particular items of the WHOQOL-BREF. Especially for the physical and psychological domain, this is problematic, because none of their indicators works in the same way across samples. CONCLUSIONS: Notwithstanding some limitations of this study, it must be concluded that the WHOQOL-BREF should only be used with great caution in cross-national comparisons.

Attitudes of Professional Caregivers and Family Members Regarding the Use of Monitoring Devices to Improve Assessments of Pain and Discomfort During Continuous Sedation Until Death.

CONTEXT: Assessing consciousness and pain during continuous sedation until death (CSD) by behavior-based observational scales alone has recently been put into question. Instead, the use of monitoring technology has been suggested to make more objective and reliable assessments. Insights into which factors influence attitudes toward using these monitoring devices in a context of CSD is a first step in formulating recommendations to inform future practice. OBJECTIVES: The aim of this study was to find out what influences professional caregivers' and family members' (FMs) attitudes regarding the use of monitors during CSD. METHODS: We conducted semistructured face-to-face interviews with 20 professional caregivers and 15 FMs, who cared for a patient or had an FM, respectively, who took part in a study using monitoring devices. Recruitment took place in an academic hospital, a locoregional hospital, and two nursing homes, all located in Belgium. Two researchers independently analyzed the data, using grounded theory to inductively develop a model that represents the emerging attitude toward use of monitors during CSD. RESULTS: Our model shows that the emerging attitudes toward using monitors during CSD is determined by view on CSD, desire for peace of mind, emotional valence attached to using monitors, and the realization that the sole use of behavior-based observational measures could be unreliable in a CSD context. We identified several facilitators and barriers to inform future implementation strategies. CONCLUSION: Most participants had no objections, and all participants found the use of monitoring devices during CSD feasible and acceptable. We identified a number of facilitators and barriers and suggested that being aware that care can be improved, good communication, shared decision making, and continuing professional education can overcome the identified barriers. We suggest future research would focus on developing implementation strategies and guidelines for introducing objective monitoring devices in diverse palliative care settings.

Axitinib plus avelumab in the treatment of recurrent glioblastoma: a stratified, open-label, single-center phase 2 clinical trial (GliAvAx).

BACKGROUND: No treatment demonstrated to improve survival in patients with recurrent glioblastoma (rGB) in a randomized trial. Combining axitinib with the programmed cell death ligand 1 blocking monoclonal antibody avelumab may result in synergistic activity against rGB. METHODS: Adult patients with rGB following prior surgery, radiation therapy and temozolomide chemotherapy were stratified according to their baseline use of corticosteroids. Patients with a daily dose of ≤8 mg of methylprednisolone (or equivalent) initiated treatment with axitinib (5 mg oral two times per day) plus avelumab (10 mg/kg intravenous every 2 weeks) (Cohort-1). Patients with a higher baseline corticosteroid dose initiated axitinib monotherapy; avelumab was added after 6 weeks of therapy if the corticosteroid dose could be tapered to ≤8 mg of methylprednisolone (Cohort-2). Progression-free survival at 6 months (6-m-PFS%), per immunotherapy response assessment for neuro-oncology criteria, served as the primary endpoint. RESULTS: Between June 2017 and August 2018, 54 patients (27 per cohort) were enrolled and initiated study treatment (median age: 55 years; 63% male; 91% Eastern Cooperative Oncology Group Performance Status 0-1). Seventeen (63%) patients treated in Cohort-2 received at least one dose of avelumab. The 6-m-PFS% was 22.2% (95% CI 6.5% to 37.9%) and 18.5% (95% CI 3.8% to 33.2%) in Cohort-1 and Cohort-2, respectively; median overall survival was 26.6 weeks (95% CI 20.8 to 32.4) in Cohort-1 and 18.0 weeks (95% CI 12.5 to 23.5) in Cohort-2. The best objective response rate was 33.3% and 22.2% in Cohort-1 and Cohort-2, respectively, with a median duration of response of 17.9 and 19.0 weeks. The most frequent treatment-related adverse events were dysphonia (67%), lymphopenia (50%), arterial hypertension and diarrhea (both 48%). There were no grade 5 adverse events. CONCLUSION: The combination of avelumab plus axitinib has an acceptable toxicity profile but did not meet the prespecified threshold for activity justifying further investigation of this treatment in an unselected population of patients with rGB.

Neurocognitive Function, Psychosocial Outcome, and Health-Related Quality of Life of the First-Generation Metastatic Melanoma Survivors Treated with Ipilimumab.

PURPOSE: To assess neurocognitive function (NCF), psychosocial outcome, health-related quality of life (HRQoL), and long-term effects of immune-related adverse events (irAE) on metastatic melanoma survivors treated with ipilimumab (IPI). METHODS: Melanoma survivors were identified within two study populations (N = 104), at a single-center university hospital, and defined as patients who were disease-free for at least 2 years after initiating IPI. Data were collected using 4 patient-reported outcome measures, computerized NCF testing, and a semistructured interview at the start and 1-year follow-up. RESULTS: Out of 18 eligible survivors, 17 were recruited (5F/12M); median age is 57 years (range 33-86); and median time since initiating IPI was 5.6 years (range 2.1-9.3). The clinical interview revealed that survivors suffered from cancer-related emotional distress such as fear of recurrence (N = 8), existential problems (N = 2), survivor guilt (N = 2), and posttraumatic stress disorder (N = 6). The mean EORTC QLQ-C30 Global Score was not significantly different from the European mean of the healthy population. Nine survivors reported anxiety and/or depression (Hospitalization Depression Scale) during the survey. Seven survivors (41%) reported fatigue (Fatigue Severity Scale). Seven patients (41%) had impairment in NCF; only three out of seven survivors had impairment in subjective cognition (Cognitive Failure Questionnaire). Anxiety, depression, fatigue, and neurocognitive symptoms remained stable at the 1-year follow-up. All cases of skin toxicity (N = 8), hepatitis (N = 1), colitis (N = 3), and sarcoidosis (N = 1) resolved without impact on HRQoL. Three survivors experienced hypophysitis; all suffered from persistent fatigue and cognitive complaints 5 years after onset. One survivor who experienced a Guillain-Barré-like syndrome suffered from persisting depression, fatigue, and impairment in NCF. CONCLUSION: A majority of melanoma survivors treated with IPI continue to suffer from emotional distress and impairment in NCF. Timely detection in order to offer tailored care is imperative, with special attention for survivors with a history of neuroendocrine or neurological irAE. The trial is registered with B.U.N. 143201421920.

On the linearity of predefined and self-anchoring Visual Analogue Scales.

Two functional measurement studies were conducted to test the effect of two types of end anchors on the linearity of Visual Analogue Scale (VAS) data. With the first type of end anchors, participants responded to the stimuli using a VAS with predefined end anchors. With the second type, respondents defined the end anchors in terms of their own assumptions, perceptions, goals and values. The results show that VASs can be considered as linear scales and that the type of end anchors used has no effect on the linearity of the VAS data.

Long-term impact of stroke on patients' health-related quality of life.

PURPOSE: This international study aims to examine the size and determinants of the impact of stroke on five-year survivors' health-related quality of life (HRQoL) in four different European countries. METHOD: Patients were recruited consecutively in four European rehabilitation centers. Five years after stroke, the EuroQol-visual analog scale (EQ-VAS) was administered in 226 first-ever stroke patients. Impact of stroke was determined by calculating EQ-VAS z-norm scores (= deviation - expressed in SD - of patients' EQ-VAS level relative to their age-and gender-matched national population norms). Determinants of EQ-VAS z-norm scores were identified using multivariate linear regression analysis. RESULTS: Five years post-stroke, patients' mean EQ-VAS was 63.74 (SD = 19.33). Mean EQ-VAS z-norm score was -0.57 [95%CI: (-0.70)-(-0.42)]. Forty percent of the patients had an EQ-VAS z-norm score <-0.75 SD; 52% had an EQ-VAS z-norm score between -0.75 and +0.75 SD, only 8% scored >+0.75 SD. Higher patients' levels of depression, anxiety and disability were associated with increasingly negative EQ-VAS z-norm scores (adjusted R2 = 0.392). CONCLUSIONS: Five years after stroke, mean HRQoL of stroke survivors showed large variability and was more than ½ SD below population norm. Forty percent had a HRQoL level below, 52% on, and 8% above population norm. The variability could only partially be explained by the variables considered in this study. Longitudinal studies are needed to increase our understanding of the size and determinants of the impact of stroke on the HRQoL of long-term stroke survivors. Implications for rehabilitation The current European concept of stroke rehabilitation is focused on the acute and sub-acute rehabilitation phase, i.e., in the first months after stroke. The results of this study show that at five years after stroke, the mean level of HRQoL of stroke survivors remains below the healthy population level. This finding shows the need for continuation of rehabilitation in the chronic phase. At five years after stroke, higher patients' levels of depression, anxiety and disability were associated with lower scores for HRQoL. This finding implicates that chronic rehabilitation programs should be multi-faceted in order to increase long-term survivors' psychosocial outcomes.

Relating specific emotions to intrinsic motivation: on the moderating role of positive and negative emotion differentiation.

Despite the fact that studies on self-determination theory have traditionally disregarded the explicit role of emotions in the motivation eliciting process, research attention for the affective antecedents of motivation is growing. We add to this emerging research field by testing the moderating role of emotion differentiation -individual differences in the extent to which people can differentiate between specific emotions- on the relationship between twelve specific emotions and intrinsic motivation. To this end, we conducted a daily diary study (N = 72) and an experience sampling study (N = 34). Results showed that the relationship between enthusiasm, cheerfulness, optimism, contentedness, gloominess, miserableness, uneasiness (in both studies 1 and 2), calmness, relaxation, tenseness, depression, worry (only in Study 1) on one hand and intrinsic motivation on the other hand was moderated by positive emotion differentiation for the positive emotions and by negative emotion differentiation for the negative emotions. Altogether, these findings suggest that for people who are unable to distinguish between different specific positive emotions the relationship between those specific positive emotions and intrinsic motivation is stronger, whereas the relationship between specific negative emotions and intrinsic motivation is weaker for people who are able to distinguish between the different specific negative emotions. Theoretical and practical implications are discussed.

Sleepiness phenomics: modeling individual differences in subjective sleepiness profiles.

The present study investigates individual differences in subjective sleepiness profiles during 36 h of sustained wakefulness in a modified constant routine protocol. Twenty-three volunteers (11 females), aged between 18 and 47 yrs (M age = 30.41, SD = 10.26) enrolled in the study. Subjective sleepiness ratings were collected every 2 h by means of visual analogue scales. Circadian rhythmicity was assessed by means of salivary cortisol. Subjective sleepiness data were analyzed using functional principal component analysis (fPCA). Our results show that approximately 80% of the variance is accounted for by three functional components. The first component explains 50.28% of the variance and is characterized by a profile of exclusively positive loadings, representing vertical shifts from the mean sleepiness profile. Scores on this component are positively related to self-reported habitual sleep times and mean slow wave activity (SWA) during wake. Positive scores on the second component (18.40% of the variance) are characterized by a higher than average peak-to-trough amplitude in subjective sleepiness profiles. Participants with higher than average scores on this component show a significantly higher amplitude in salivary cortisol profiles as opposed to participants with lower than average scores. Participants with positive scores on the third component (10.09% of the variance) show higher than average levels of subjective sleepiness during morning hours, a buildup of wake effort occurring later and more afternoon sleepiness after sleep deprivation than negative scorers. Peak levels of salivary cortisol occur significantly later in these participants. Taken together, our results suggest that component 1 represents tonic differences in sleepiness profiles primarily related to mechanisms of sleep homeostasis, component 2 to circadian amplitude differences and component 3 to diurnal preference. However, since the components are additions to a mean profile, each of the three components is likely to correspond to a mixture of multiple physiological parameters, rather than to a single process. The approach shows interesting potential for (1) revealing unidentified physiological processes, (2) testing existing assumptions about regulatory mechanisms at the basis of interindividual variability in sleepiness profiles and (3) the specification of sleepiness phenotypes on a quantitative basis.

Felicitometric hermeneutics: interpreting quality of life measurements.

The use of quality of life (QOL) outcomes in clinical trials is increasing as a number of practical, ethical, methodological, and regulatory reasons for their use have become apparent. It is important, then, that QOL measurements and differences between QOL scores be readily interpretable. We study interpretation in two contexts: when determining QOL and when basing decisions on QOL differences. We consider both clinical situations involving individual patients and research contexts, e.g., randomized clinical trials, involving groups of patients. We note the ethical importance of such understanding: proper interpretation and communication facilitate health care decision making. Communication that facilitates interpretation is of moral significance since better communication can attenuate ethical problems and inform choices. Much of what is communication worthy about QOL assessments is determined by the particular QOL instrument used in the assessment and how it is administered. In practice, these choices will be driven by the purpose of the assessment, but, it is argued, to maximize understanding, we should combine the information garnered from traditional standardized QOL instruments, from individualized QOL assessments, and from a recently proposed dialogic paradigm, where QOL is determined by shared conversation regarding the interpretation of texts. And, while some studies can surely succeed using abbreviated methods of administration (e.g., postal surveys may suffice for certain purposes), we will focus on methods of administration involving interviewer-respondent interaction. We suggest that during the QOL elicitation process, interviewer and respondent should engage in a two-way conversation in order to achieve a shared understanding of the "answers" to QOL "questions" and, finally, to reach a shared interpretation of the individual's QOL.

Comparative sensitivity of outcome variables of a software-based Behavioral Sleep Resistance Task.

Unintentional sleep and performance impairment due to extended wakefulness are often the cause of traffic and work accidents. Therefore, large-scale screening instruments assessing the ability to resist falling asleep during monotonous tasks are needed. The current widespread computer use in industrial and home settings offers the possibility to use software-based instruments as an alternative for expensive hardware interfaces to assess sleep resistance. Therefore, we propose a software-based sleep resistance task based on the procedure of the Oxford SLEep Resistance test (OSLER): the Behavioral Sleep Resistance Task (BSRT). In order to validate this instrument we submitted 36 healthy individuals to four 40-min sleep resistance challenges during a night of extended wakefulness (14, 16, 18 and 20 h). Subjective sleepiness was assessed by means of the Karolinska Sleepiness Scale and a Visual Analogue Scale for sleepiness/alertness and objective sleepiness by means of a 4-min EEG-monitored fixation task. Our results show significant correlations of BSRT hit ratio, error profiles and sleep onset latency variables with subjective sleepiness and of BSRT hit ratio and 3-6 error profiles with High-Beta Central EEG activity. Additionally, using a distribution- and scale-free sensitivity index, we found that subjective sleepiness measures are the most sensitive to the effects of sustained wakefulness, closely followed by the BSRT hit ratio and BSRT error profile 3-6.

The Functional Measurement Experiment Builder suite: two Java-based programs to generate and run functional measurement experiments.

We propose a free, easy-to-use computer program that does not requires prior knowledge of computer programming to generate and run experiments using textual or pictorial stimuli. Although the FM Experiment Builder suite was initially programmed for building and conducting FM experiments, it can also be applied for non-FM experiments that necessitate randomized, single, or multifactorial designs. The program is highly configurable, allowing multilingual use and a wide range of different response formats. The outputs of the experiments are Microsoft Excel compatible .xls files that allow easy copy-paste of the results into Weiss's FM CalSTAT program (2006) or any other statistical package. Its Java-based structure is compatible with both Windows and Macintosh operating systems, and its compactness (< 1 MB) makes it easily distributable over the Internet.