A protocol to differentiate the chondrogenic ATDC5 cell-line for the collection of chondrocyte-derived extracellular vesicles.

Skeletal growth and fracture healing rely on the mineralization of cartilage in a process called endochondral ossification. Chondrocytes firstly synthesize and then modify cartilage by the release of a wide range of particles into their extracellular space. Extracellular vesicles (EVs) are one type of such particles, but their roles in endochondral ossification are yet to be fully understood. It remains a challenge to obtain representative populations of chondrocyte-derived EVs, owing to difficulties both in preserving the function of primary chondrocytes in culture and in applying the serum-free conditions required for EV production. Here, we used the ATDC5 cell-line to recover chondrocyte-derived EVs from early- and late-differentiation stages, representing chondrocytes before and during cartilage mineralization. After screening different culture conditions, our data indicate that a serum-free Opti-MEM-based culture medium preserves chondrocyte identity and function, matrix mineralization and cell viability. We subsequently scaled-up production and isolated EVs from conditioned medium by size-exclusion chromatography. The obtained chondrocyte-derived EVs had typical ultrastructure and expression of classical EV markers, at quantities suitable for downstream experiments. Importantly, chondrocyte-derived EVs from late-differentiation stages had elevated levels of alkaline phosphatase activity. Hence, we established a method to obtain functional chondrocyte-derived EVs before and during cartilage mineralization that may aid the further understanding of their roles in endochondral bone growth and fracture healing.

Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes bone length, regulates cortical and trabecular bone mass, and maintains growth plate architecture and width in a sex- and site-specific manner in mice.

Tartrate-resistant acid phosphatase (TRAP) serum levels reflect osteoclast number, bone remodeling activity, and fracture risk. Deletion or loss of function of TRAP results in short stature in mice and man. Yet, the impact and mechanisms of TRAP for the site- and sex-specific development of bone and cartilage is not well understood. Here, we use a global TRAP knockout (TRAPKO) and wildtype littermate control (WT) mice of both sexes to investigate TRAP as a possible sex- and site-specific regulator of bone and growth plate development. TRAPKO mice of both sexes weighed less and had shorter tibial length than their WT, features that were more accentuated in male than female TRAPKO mice. These changes were not associated with a general reduction in growth as not all organs displayed a proportionally lower mass, and serum IGF-1 was unchanged. Using µCT and site-specificity analysis of the cortical bone revealed wider proximal tibia, a higher trabecular thickness, and lower trabecular separation in male TRAPKO compared to WT mice, an effect not seen in female mice. Histomorphometric analysis revealed that the growth plate height as well as height of terminal hypertrophic chondrocytes were markedly increased, and the number of columns was decreased in TRAPKO mice of both sexes. These effects were more accentuated in female mice. Proliferation and differentiation of bone marrow derived macrophages into osteoclasts, as well as C-terminal cross links were normal in TRAPKO mice of both sexes. Collectively, our results show that TRAP regulates bone and cartilage development in a sex-and site-specific manner in mice.

The level of protein in the maternal murine diet modulates the facial appearance of the offspring via mTORC1 signaling.

The development of craniofacial skeletal structures is fascinatingly complex and elucidation of the underlying mechanisms will not only provide novel scientific insights, but also help develop more effective clinical approaches to the treatment and/or prevention of the numerous congenital craniofacial malformations. To this end, we performed a genome-wide analysis of RNA transcription from non-coding regulatory elements by CAGE-sequencing of the facial mesenchyme of human embryos and cross-checked the active enhancers thus identified against genes, identified by GWAS for the normal range human facial appearance. Among the identified active cis-enhancers, several belonged to the components of the PI3/AKT/mTORC1/autophagy pathway. To assess the functional role of this pathway, we manipulated it both genetically and pharmacologically in mice and zebrafish. These experiments revealed that mTORC1 signaling modulates craniofacial shaping at the stage of skeletal mesenchymal condensations, with subsequent fine-tuning during clonal intercalation. This ability of mTORC1 pathway to modulate facial shaping, along with its evolutionary conservation and ability to sense external stimuli, in particular dietary amino acids, indicate that the mTORC1 pathway may play a role in facial phenotypic plasticity. Indeed, the level of protein in the diet of pregnant female mice influenced the activity of mTORC1 in fetal craniofacial structures and altered the size of skeletogenic clones, thus exerting an impact on the local geometry and craniofacial shaping. Overall, our findings indicate that the mTORC1 signaling pathway is involved in the effect of environmental conditions on the shaping of craniofacial structures.

The role of illness perceptions in delayed care-seeking in heart failure: A mixed-methods study.

BACKGROUND: Unclear illness perceptions are common in heart failure. The self-regulation model of illness behaviour highlights factors that may impact how people with chronic illness choose to cope with or manage their condition and has been used to study pre-hospital delay for stroke and acute myocardial infarction. The principles of self-regulation can be applied in heart failure to help illuminate the link between unclear illness perceptions and sub-optimal symptom self-management. OBJECTIVE: Informed by the self-regulation model of illness behaviour, this study examines the role of illness perceptions in coping responses that lead to delayed care-seeking for heart failure symptoms. DESIGN: Mixed-methods phenomenological study. SETTING(S): Quaternary referral hospital - centre of excellence for cardiovascular care and heart transplantation. PARTICIPANTS: Seventy-two symptomatic patients with heart failure participated in a survey assessing illness perceptions. A subset of fifteen individuals was invited to participate in semi-structured interviews. METHODS: Illness perceptions were assessed using the Brief Illness Perception Questionnaire. In-depth semi-structured interviews were conducted to elicit previous care-seeking experiences and decision-making that led to a passive, or active coping response to worsening symptoms. Descriptive statistics were used to report questionnaire findings, and open-ended responses were grouped into descriptive categories. Interpretative phenomenological analysis was undertaken on interview transcripts. RESULTS: Participants perceived little personal control over their condition and mostly attributed heart failure to lifestyle factors such as diet and lack of activity. Cognitive dissonance between perceived self-identity and heart failure-identity led to a highly emotional response which drove coping towards avoidance strategies and denial. CONCLUSIONS: This study demonstrates the use of the principles of self-regulation in heart failure and offers a framework to understand how patient representations and emotional responses can inform behaviour in illness. Findings highlight the value of empowering patients to take control of their health and the need to help align values (e.g. independence) with behaviours (e.g. actively addressing problems) to facilitate optimal symptom self-management.

Feasibility of Integrating MEditatioN inTO heaRt Disease (the MENTOR Study): A Phase II Randomized Controlled Trial.

BACKGROUND: Comorbid depression and/or anxiety symptoms occur in 25% of patients attending cardiac rehabilitation (CR) programs and are associated with poorer prognosis. There is a need to evaluate psychological interventions, including meditation, that have potential to improve psychological health in CR programs. AIMS: The aim of this study was to determine the feasibility and acceptability of integrating a meditation intervention into an existing Australian CR program for the reduction of depression and anxiety symptoms. METHODS: This was a mixed-methods feasibility randomized controlled trial. Thirty-one patients with CVD and, at a minimum, mild depression and/or anxiety symptoms were randomized to meditation and standard CR or to standard CR alone. A 16-minute guided group meditation was delivered face-to-face once a week for 6 weeks, with daily self-guided meditation practice between sessions. Feasibility outcomes included screening, recruitment, and retention. Semistructured interviews of patients' (n = 10) and health professionals' (n = 18) perspectives of intervention participation and delivery were undertaken to assess acceptability. Between-group differences in depression, anxiety, stress, self-efficacy for mindfulness, and health status at 6 and 12 weeks were also assessed. RESULTS AND CONCLUSION: Meditation was considered feasible, with 83% (12/15) of the intervention group completing an average of 3.13 (SD, 2.56) out of 6 group meditation sessions and 5.28 (SD, 8.50) self-guided sessions. Meditation was considered acceptable by patients, clinicians, and health managers. Between-group differences in the number of CR sessions completed favored the intervention group in per-protocol analyses (intervention group vs control group, 12 vs 9 sessions; P = .014), which suggests that meditation may be useful to improve patients' adherence to exercise-based CR program.

Spatially resolved transcriptomic profiling of degraded and challenging fresh frozen samples.

Spatially resolved transcriptomics has enabled precise genome-wide mRNA expression profiling within tissue sections. The performance of methods targeting the polyA tails of mRNA relies on the availability of specimens with high RNA quality. Moreover, the high cost of currently available spatial resolved transcriptomics assays requires a careful sample screening process to increase the chance of obtaining high-quality data. Indeed, the upfront analysis of RNA quality can show considerable variability due to sample handling, storage, and/or intrinsic factors. We present RNA-Rescue Spatial Transcriptomics (RRST), a workflow designed to improve mRNA recovery from fresh frozen specimens with moderate to low RNA quality. First, we provide a benchmark of RRST against the standard Visium spatial gene expression protocol on high RNA quality samples represented by mouse brain and prostate cancer samples. Then, we test the RRST protocol on tissue sections collected from five challenging tissue types, including human lung, colon, small intestine, pediatric brain tumor, and mouse bone/cartilage. In total, we analyze 52 tissue sections and demonstrate that RRST is a versatile, powerful, and reproducible protocol for fresh frozen specimens of different qualities and origins.

Comparison of six frailty instruments in adults with heart failure: a prospective cohort pilot study.

AIMS: To compare the frailty prevalence and predictive performance of six frailty instruments in adults with heart failure and determine the feasibility of study methods. METHODS AND RESULTS: Prospective cohort pilot study. Adults aged 18 years or older with a confirmed diagnosis of heart failure in Sydney, New South Wales, Australia. The Frailty Phenotype; the Survey of Health, Ageing, and Retirement in Europe Frailty Instrument (SHARE-FI); St Vincent's Frailty instrument; St Vincent's Frailty instrument plus cognition and mood; The Fatigue, Resistance, Ambulation, Illnesses, and Loss of Weight (FRAIL) scale; and the Deficit Accumulation Index (DAI) were compared. Multiple logistic regression was used to develop six frailty instrument models to evaluate the association between each frailty instrument and composite all-cause rehospitalization and mortality at 12 months. One hundred and thirty-one patients were included with a mean age of 54 [± 14(SD)]. Frailty prevalence ranged from 33 to 81%. All instruments except one (the FRAIL scale) appeared to signal an increased odds of rehospitalization and/or mortality, yet these results were non-significant. The six frailty instrument models displayed sensitivity between 88-92% and C-statistic values of 0.71-0.73, suggesting satisfactory discrimination. CONCLUSION: The prevalence of frailty varied across six frailty instruments yet was in the higher range despite a 'younger' heart failure cohort. Further research is required to confirm the psychometric properties of these instruments for routine clinical use in an adequately powered and more diverse heart failure cohort.

Altered developmental programs and oriented cell divisions lead to bulky bones during salamander limb regeneration.

There are major differences in duration and scale at which limb development and regeneration proceed, raising the question to what extent regeneration is a recapitulation of development. We address this by analyzing skeletal elements using a combination of micro-CT imaging, molecular profiling and clonal cell tracing. We find that, in contrast to development, regenerative skeletal growth is accomplished based entirely on cartilage expansion prior to ossification, not limiting the transversal cartilage expansion and resulting in bulkier skeletal parts. The oriented extension of salamander cartilage and bone appear similar to the development of basicranial synchondroses in mammals, as we found no evidence for cartilage stem cell niches or growth plate-like structures during neither development nor regeneration. Both regenerative and developmental ossification in salamanders start from the cortical bone and proceeds inwards, showing the diversity of schemes for the synchrony of cortical and endochondral ossification among vertebrates.

Clinician Estimates of Frailty Compared to Formal Frailty Assessment in Adults With Heart Failure: A Cross-Sectional Analysis.

BACKGROUND: Frailty assessment is recommended for patients with heart failure. Despite the availability of instruments to assess frailty, there are no clear recommendations regarding the optimal instrument to use in a heart failure context. This ambiguity combined with a lack of education and resources, often leads clinicians to rely on subjective estimates of frailty, such as 'the end-of-the-bed' or 'eyeball' test. AIM: To examine the association between clinician-estimated frailty and formal frailty assessment in adults with heart failure. METHODS: Cross-sectional analysis of the FRAilty MEasurement in Heart Failure (FRAME-HF) study. PARTICIPANTS: (1) Adults aged ≥18 years in the outpatient heart failure clinic and cardiology ward; (2) and cardiovascular clinicians (nurses, physicians, and allied-health professionals). Following participant recruitment, cardiovascular clinicians were asked to rate the participant's frailty status based on their routine clinical assessment as either: frail, pre-frail, or non-frail, which was then compared to a formal frailty assessment using a modified version of the Frailty Phenotype. The association between clinician-estimated frailty and formal frailty assessment were examined using a weighted Kappa statistic and Spearman's correlation coefficient. RESULTS: A total of 75 patients and 39 clinicians were recruited, producing 194 paired frailty assessments. Mean age of the patients was 54 (±13) years. Correlation of pooled clinician-estimated frailty to formal frailty was fair (0.52, p=0.00). Correlation was highest between allied-health estimated frailty and formal frailty (0.70, p=0.00). Agreement between pooled clinician-estimated frailty and formal frailty was fair (0.33) and was highest between allied health-estimated frailty and formal frailty (0.45). CONCLUSION: Subjective clinician-estimated frailty is not a reliable replacement for formal frailty assessment in adults with heart failure, underscoring the need for assessment using a valid and reliable instrument.

The relationship between neurocognitive performance and HRV parameters in nurses and non-healthcare participants.

Nurses represent the largest sector of the healthcare workforce, and it is established that they are faced with ongoing physical and mental demands that leave many continuously stressed. In turn, this chronic stress may affect cardiac autonomic activity, which can be non-invasively evaluated using heart rate variability (HRV). The association between neurocognitive parameters during acute stress situations and HRV has not been previously explored in nurses compared to non-nurses and such, our study aimed to assess these differences. Neurocognitive data were obtained using the Mini-Mental State Examination and Cognistat psychometric questionnaires. ECG-derived HRV parameters were acquired during the Trier Social Stress Test. Between-group differences were found in domain-specific cognitive performance for the similarities (p = .03), and judgment (p = .002) domains and in the following HRV parameters: SDNNbaseline, (p = .004), LFpreparation (p = .002), SDNNpreparation (p = .002), HFpreparation (p = .02), and TPpreparation (p = .003). Negative correlations were found between HF power and domain-specific cognitive performance in nurses. In contrast, both negative and positive correlations were found between HRV and domain-specific cognitive performance in the non-nurse group. The current findings highlight the prospective use of autonomic HRV markers in relation to cognitive performance while building a relationship between autonomic dysfunction and cognition.

Frailty Measures in Patients Listed for Lung Transplantation.

BACKGROUND: The study aimed to determine whether the addition of cognitive impairment, depression, or both, to the assessment of physical frailty (PF) is associated with the risk of lung transplant (LTX) waitlist mortality. METHODS: Since March 2013, all patients referred for LTX evaluation underwent PF assessment. Cognition was assessed using the Montreal Cognitive Assessment and depression assessed using the Depression in Medical Illness questionnaire. We assessed the association of 4 composite frailty measures: PF ≥3 of 5 = frail, cognitive frailty (CogF ≥3 of 6 = frail), depressive frailty (DepF ≥3 of 6 = frail), and combined frailty (ComF ≥3 of 7 = frail) with waitlist mortality. RESULTS: The prevalence of PF was 78 (22%), CogF 100 (28%), DepF 105 (29%), and ComF 124 (34%). Waitlist survival in the non-PF group was 94% ± 2% versus 71% ± 7% in the PF group (P < 0.001). Cox proportional hazards regression analysis demonstrated that PF (adjusted hazard ratio [HR], 4.88; 95% confidence interval [CI], 2.06-11.56), mild cognitive impairment (adjusted HR, 3.03; 95% CI, 1.05-8.78), and hypoalbuminemia (adjusted HR, 0.89; 95% CI, 0.82-0.97) were independent predictors of waitlist mortality. There was no significant difference in the area under the curve of the 4 frailty measures. CONCLUSIONS: The addition of cognitive function and depression variables to the PF assessment increased the number of patients classified as frail. However, the addition of these variables does not strengthen the association with LTX waitlist mortality compared with the PF measure.

The Role of Lifestyle and Cardiovascular Risk Factors in Dropout From an Australian Cardiac Rehabilitation Program. A Longitudinal Cohort Study.

BACKGROUND: Cardiac rehabilitation (CR) programs reduce the risk of further cardiac events and improve the ability of people living with cardiovascular disease to manage their symptoms. However, many people who experience a cardiac event do not attend or fail to complete their CR program. Little is known about the characteristics of people who drop out compared to those who complete CR. AIMS: To identify subgroups of patients attending a cardiac rehabilitation program who are more likely to dropout prior to final assessment by (1) calculating the dropout rate from the program, (2) quantifying the association between dropout and socio-demographic, lifestyle, and cardiovascular risk factors, and (3) identifying independent predictors of dropout. METHODS: The study population is from a large metropolitan teaching hospital in Sydney, Australia, and consists of all participants consecutively enrolled in an outpatient CR program between 2006 and 2017. Items assessed included diagnoses and co-morbidities, quality of life (SF-36), psychological health (DASS-21), lifestyle factors and physical assessment. Dropout was defined as failure to complete the outpatient CR program and post CR assessment. RESULTS: Of the 3,350 patients enrolled in the CR program, 784 (23.4%; 95%CI: 22.0-24.9%) dropped out prior to completion. The independent predictors of dropout were smoking (OR 2.4; 95%CI: 1.9-3.0), being separated or divorced (OR 2.0; 95%CI: 1.5-2.6), younger age (<55 years) (OR 1.9; 95%CI: 1.6-2.4), obesity (OR 1.6; 95%CI: 1.3-2.0), diabetes (OR 1.6; 95%CI: 1.3-2.0), sedentary lifestyle (OR 1.3; 95%CI: 1.1-1.6) and depressive symptoms (OR 1.3; 95%CI: 1.1-1.6). CONCLUSION: To improve the CR program completion rate, clinicians need to consider the impact of socio-demographic, lifestyle, and cardiovascular risk factors on their patients' ability to complete CR. Tailored strategies which target the independent predictors of dropout are required to promote adherence to CR programs and thereby potentially reduce long-term cardiovascular risk.

Smart Devices and Wearable Technologies to Detect and Monitor Mental Health Conditions and Stress: A Systematic Review.

Recently, there has been an increase in the production of devices to monitor mental health and stress as means for expediting detection, and subsequent management of these conditions. The objective of this review is to identify and critically appraise the most recent smart devices and wearable technologies used to identify depression, anxiety, and stress, and the physiological process(es) linked to their detection. The MEDLINE, CINAHL, Cochrane Central, and PsycINFO databases were used to identify studies which utilised smart devices and wearable technologies to detect or monitor anxiety, depression, or stress. The included articles that assessed stress and anxiety unanimously used heart rate variability (HRV) parameters for detection of anxiety and stress, with the latter better detected by HRV and electroencephalogram (EGG) together. Electrodermal activity was used in recent studies, with high accuracy for stress detection; however, with questionable reliability. Depression was found to be largely detected using specific EEG signatures; however, devices detecting depression using EEG are not currently available on the market. This systematic review highlights that average heart rate used by many commercially available smart devices is not as accurate in the detection of stress and anxiety compared with heart rate variability, electrodermal activity, and possibly respiratory rate.

Classifying Multi-Level Stress Responses From Brain Cortical EEG in Nurses and Non-Health Professionals Using Machine Learning Auto Encoder.

OBJECTIVE: Mental stress is a major problem in our society and has become an area of interest for many psychiatric researchers. One primary research focus area is the identification of bio-markers that not only identify stress but also predict the conditions (or tasks) that cause stress. Electroencephalograms (EEGs) have been used for a long time to study and identify bio-markers. While these bio-markers have successfully predicted stress in EEG studies for binary conditions, their performance is suboptimal for multiple conditions of stress. METHODS: To overcome this challenge, we propose using latent based representations of the bio-markers, which have been shown to significantly improve EEG performance compared to traditional bio-markers alone. We evaluated three commonly used EEG based bio-markers for stress, the brain load index (BLI), the spectral power values of EEG frequency bands (alpha, beta and theta), and the relative gamma (RG), with their respective latent representations using four commonly used classifiers. RESULTS: The results show that spectral power value based bio-markers had a high performance with an accuracy of 83%, while the respective latent representations had an accuracy of 91%.

Attitudes and practices towards palliative care in chronic heart failure: a survey of cardiovascular nurses and physicians.

BACKGROUND: Heart failure is a chronic condition with various implications for individuals and families. Although the importance of implementing palliative care is recommended in best practice guidelines, implementation strategies are less clear. AIMS: This study sought to; (1) determine Australian and New Zealand cardiovascular nurses and physicians' end of life care attitudes and specialist palliative care referral in heart failure and; (2) determine self-reported delivery of supportive care and attitudes towards service names. METHODS: An electronic survey was emailed to members of four peak bodies and professional networks. Participants were also recruited through social media. Paper-based versions of the survey were completed by attendees of the 66th Cardiac Society of Australia and New Zealand Annual Scientific Meeting, August 2018. FINDINGS: There were 113 completed responses included in the analyses. Participants were nurses (n = 75), physicians (n = 32) and allied health professionals (n = 4). Most (67%) reported they were comfortable with providing end of life care; however, fewer respondents agreed they received support for their dying patients and one-third experienced a sense of failure when heart failure progressed. Most (84-100%) participants agreed they would refer a heart failure patient later in the illness trajectory. There was a more favourable attitude towards the service name 'supportive care' than to 'palliative care'. CONCLUSION: Comfort with end of life discussions is encouraging as it may lead to a greater likelihood of planning future care and identifying palliative care needs. Peer support and supervision may be useful for addressing feelings of failure. The use of needs-based assessment tools, adopting the service name 'supportive care' and further research focusing on primary palliative team-based approach is required to improve palliative care access. IMPACT STATEMENT: Cardiovascular nurses and physicians are comfortable providing end of life care, but referrals to palliative care in the later stages of heart failure persists.

A single educational intervention on heart failure self-care: Extended follow-up from a multisite randomized controlled trial.

BACKGROUND: Heart failure outcomes remain poor, and little is known about the causes and predictors of these outcomes in Lebanon. AIM: The purpose of this article is to report the causes and predictors of the 6- and 12-month readmission and mortality of previously recruited patients to the Family focused Approach to iMprove Heart Failure care In LebanonQualitY intervention (FAMILY) study. METHODS: A multi-site block randomized controlled trial in three tertiary medical centers in Beirut. Initially, participants were randomized to either the control or the intervention group. The latter group, with their family caregivers, received heart failure self-care resources and an educational intervention on self-care and symptom management during their index admission. Participants from the FAMILY study were followed up with through phone calls for readmission and mortality at 6 and 12 months following their hospital discharge. RESULTS: A total of 218 (85%) patients were followed up with for this evaluation. There was a significant difference between the intervention group and the control group in terms of mortality at 6 months (n=18 (16%) versus n=36 (33%); p<0.05) and 12 months (n=29 (26%) versus n=45 (42%); p<0.05) post the index discharge. Mortality at 6 and 12 months was associated with aging, lower body mass index scores and readmission at 30 days post the index admission. Results of a logistic regression for mortality at 6 months showed hypertensive etiology of heart failure and 30-day readmission to be the only significant predictors. CONCLUSION: A single session intervention was associated with lower mortality, even after an extended period of time, possibly mediated by other variables. Future studies should be powered for such outcomes while also addressing the cultural needs and literacy levels of the patients using multi-session trials and more frequent follow-ups.

Discrepancies between proxy estimates and patient reported, health related, quality of life: minding the gap between patient and clinician perceptions in heart failure.

PURPOSE: Health related quality of life (HRQoL) is rarely routinely measured in the clinical setting. In the absence of patient reported data, clinicians rely on proxy and informal estimates to support clinical decisions. This study compares clinician estimates (proxy) with patient reported HRQoL in patients with advanced heart failure and examines factors influencing discrepancies. METHODS: Seventy-five patients with heart failure, (22 females, 53 males) completed the EQ-5D-5L questionnaire. Thirty-nine clinicians (11 medical, 23 nursing, 5 allied health) completed the proxy version (V1) producing 194 dyads. Correlation was assessed using Spearman's rank tests, systematic bias was examined with Bland-Altman analyses. Inter-rater agreement at the domain level, was investigated using linear weighted Kappa statistics while factors influencing the IRG were explored using independent student t-tests, analysis of variance and regression. RESULTS: There was a moderate positive correlation between clinician HRQoL estimates and patient reported utility (r = 0.38; p < .0005). Mean clinician estimates were higher than patient reported utility (0.60 vs 0.54; p = 0.008), with significant underestimation of reported problems apparent in three of the five EQ-5D-5L domains. Patient sex (female), depressed mood and frailty were all associated with an increased inter-rater gap. CONCLUSION: Clinicians in this sample overestimated HRQoL. Factors affecting the inter-rater gap, including sex and depression, support formal HRQoL screening to enhance clinical conversations and decision making. The discrepancy also supports regulatory restriction on the use of expert opinion in the development of QALYs in health economic analysis.

Stress Watch: The Use of Heart Rate and Heart Rate Variability to Detect Stress: A Pilot Study Using Smart Watch Wearables.

Stress is an inherent part of the normal human experience. Although, for the most part, this stress response is advantageous, chronic, heightened, or inappropriate stress responses can have deleterious effects on the human body. It has been suggested that individuals who experience repeated or prolonged stress exhibit blunted biological stress responses when compared to the general population. Thus, when assessing whether a ubiquitous stress response exists, it is important to stratify based on resting levels in the absence of stress. Research has shown that stress that causes symptomatic responses requires early intervention in order to mitigate possible associated mental health decline and personal risks. Given this, real-time monitoring of stress may provide immediate biofeedback to the individual and allow for early self-intervention. This study aimed to determine if the change in heart rate variability could predict, in two different cohorts, the quality of response to acute stress when exposed to an acute stressor and, in turn, contribute to the development of a physiological algorithm for stress which could be utilized in future smartwatch technologies. This study also aimed to assess whether baseline stress levels may affect the changes seen in heart rate variability at baseline and following stress tasks. A total of 30 student doctor participants and 30 participants from the general population were recruited for the study. The Trier Stress Test was utilized to induce stress, with resting and stress phase ECGs recorded, as well as inter-second heart rate (recorded using a FitBit). Although the present study failed to identify ubiquitous patterns of HRV and HR changes during stress, it did identify novel changes in these parameters between resting and stress states. This study has shown that the utilization of HRV as a measure of stress should be calculated with consideration of resting (baseline) anxiety and stress states in order to ensure an accurate measure of the effects of additive acute stress.

A RandomisEd ControLled TrIal of ChEwing Gum to RelieVE Thirst in Chronic Heart Failure (RELIEVE-CHF).

BACKGROUND: Thirst is a common and troublesome symptom of patients with chronic heart failure (CHF). To date, there are no interventions to help alleviate thirst in this cohort. Chewing gum is a novel intervention, which has been tested in people undergoing haemodialysis, also prescribed with a fluid restricted therapy. The aim of this study was to determine the effect of chewing gum on the level of thirst in the short-term (average of 24 hours each day for 4 days) and in the longer-term (Days 7, 14 and 28) individuals with CHF. METHODS: Seventy-one (71) individuals with CHF on oral loop diuretics were randomised to chewing gum (n=36) or control (n=35) for 2 weeks. Both groups were assessed for their level of thirst at Days 1-4, 7, 14 and 28. RESULTS: Significant improvements in the level of thirst of those who received chewing gum compared to the control group at Day 4 (p=0.04) and Day 14 (p=0.02) were observed. CONCLUSION: Chewing gum provided relief from thirst in the short-term and in the longer term. This trial provides important information to inform future clinical trials on ways to relieve thirst.