Molecular regulation of virulence in Legionella pneumophila.

Legionella pneumophila is a gram-negative bacteria found in natural and anthropogenic aquatic environments such as evaporative cooling towers, where it reproduces as an intracellular parasite of cohabiting protozoa. If L. pneumophila is aerosolized and inhaled by a susceptible person, bacteria may colonize their alveolar macrophages causing the opportunistic pneumonia Legionnaires' disease. L. pneumophila utilizes an elaborate regulatory network to control virulence processes such as the Dot/Icm Type IV secretion system and effector repertoire, responding to changing nutritional cues as their host becomes depleted. The bacteria subsequently differentiate to a transmissive state that can survive in the environment until a replacement host is encountered and colonized. In this review, we discuss the lifecycle of L. pneumophila and the molecular regulatory network that senses nutritional depletion via the stringent response, a link to stationary phase-like metabolic changes via alternative sigma factors, and two-component systems that are homologous to stress sensors in other pathogens, to regulate differentiation between the intracellular replicative phase and more transmissible states. Together, we highlight how this prototypic intracellular pathogen offers enormous potential in understanding how molecular mechanisms enable intracellular parasitism and pathogenicity.

Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK.

BACKGROUND: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease. METHODS: We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391). FINDINGS: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22-1·10]; d=0·46 [0·16-0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention. INTERPRETATION: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services. FUNDING: National Institute for Health and Care Research Health Technology Assessment and Motor Neurone Disease Association.

The lived experience of facioscapulohumeral muscular dystrophy: A systematic review and synthesis of the qualitative literature.

INTRODUCTION: In this review we sought to characterize the lived experience of people living with FSHD (pwFSHD) to help clinicians to orient their services to the needs of these individuals. METHODS: Five electronic databases were systematically searched for qualitative research studies containing quotations from pwFSHD. ENhancing Transparency in REporting the Synthesis of Qualitative research and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines informed the methodology. Study quality was assessed using the Critical Appraisal Skills Programme Checklist tool, which measures the methodological quality of qualitative research. Data extracted from included studies were analyzed using thematic synthesis. RESULTS: Ninety-nine pwFSHD took part in the six studies included in this review - from research teams based in two countries. Five descriptive themes emerged: "Engaging with life as symptoms progress"; "The emotional journey"; "A family burden to bear"; "Social connection and disconnection"; and "Tension between visibility and invisibility." From these, two analytical themes were derived: "The emotional challenge of continuing and intensifying adaptation" and "The relational burden of rare disease." DISCUSSION: The lived experience of pwFSHD is characterized by physical, emotional, and social challenges that impact on engagement with life, particularly as symptoms progress. Further research is needed to provide a fuller understanding of the experience of pain in FSHD and of the lived experience of FSHD across cultures.

A pilot randomised controlled trial of acceptance and commitment therapy for medication decision-making and quality of life in women with breast cancer: The ACTION trial.

OBJECTIVE: Non-adherence to adjuvant endocrine therapy (AET) in women with breast cancer is common and associated with medication side-effects and distress. We co-designed an Acceptance and Commitment Therapy intervention (ACTION) to enhance medication decision-making and quality of life (QoL). We undertook a pilot trial of ACTION to inform the feasibility of a phase III trial, and to examine intervention acceptability. METHODS: This was a multi-site, exploratory, two-arm, individually randomised external pilot trial. Women with early breast cancer prescribed AET were randomised (1:1) to receive usual care (UC) or UC + ACTION. The ACTION intervention comprised a remotely delivered one-to-one ACT session followed by three group sessions delivered by clinical psychologists, alongside a website containing ideas for the self-management of side effects. RESULTS: Of the 480 women screened for eligibility, 260 (54.2%) were approached and 79 (30.4%) randomised. 71 (89.9%) women provided data at 3-month and 70 (88.6%) at 6-month 40 women were randomised to receive UC + ACTION and 32 (80.0%) completed the intervention. Most (75.0%) accessed the website at least once. ACTION was acceptable to participants (Borkovec & Nau Scale: mean = 7.8 [SD = 2.7] out of 10). Signals of effectiveness in favour of the UC + ACTION arm were observed for medication adherence (Adherence Starts with Knowledge questionnaire-12), QoL (work and social adjustment scale), health-related QoL (functional assessment of cancer therapy[FACT] general and FACT-ES-19/23), distress (generalised anxiety disorder -7, patient health questionnaire-9) and psychological flexibility (valuing questionnaire). CONCLUSIONS: The ACTION intervention was acceptable to patients. There were promising signals for effectiveness on primary and secondary outcomes. A phase III randomised controlled trial is feasible. TRIAL REGISTRATION: ISRCTN12027752.

Cost-effectiveness of acceptance and commitment therapy for people living with motor neuron disease, and their health-related quality of life.

BACKGROUND: Given the degenerative nature of the condition, people living with motor neuron disease (MND) experience high levels of psychological distress. The purpose of this research was to investigate the cost-effectiveness of acceptance and commitment therapy (ACT), adapted for the specific needs of this population, for improving quality of life. METHODS: A trial-based cost-utility analysis over a 9-month period was conducted comparing ACT plus usual care (n = 97) versus usual care alone (n = 94) from the perspective of the National Health Service. In the primary analysis, quality-adjusted life years (QALYs) were computed using health utilities generated from the EQ-5D-5L questionnaire. Sensitivity analyses and subgroup analyses were also carried out. RESULTS: Difference in costs was statistically significant between the two arms, driven mainly by the intervention costs. Effects measured by EQ-5D-5L were not statistically significantly different between the two arms. The incremental cost-effectiveness was above the £20,000 to £30,000 per QALY gained threshold used in the UK. However, the difference in effects was statistically significant when measured by the McGill Quality of Life-Revised (MQOL-R) questionnaire. The intervention was cost-effective in a subgroup experiencing medium deterioration in motor neuron symptoms. CONCLUSIONS: Despite the intervention being cost-ineffective in the primary analysis, the significant difference in the effects measured by MQOL-R, the low costs of the intervention, the results in the subgroup analysis, and the fact that ACT was shown to improve the quality of life for people living with MND, suggest that ACT could be incorporated into MND clinical services.

Mental health in paediatric and adult myositis-related diseases: current state of research, interventions, and future steps from the MIHRA Psychological Impact Scientific Working Group.

Psychological and emotional well-being are critical aspects of overall health for individuals with chronic rheumatologic conditions. Mental health-related literature, however, predominantly focuses on systemic lupus erythematosus or rheumatoid arthritis, with limited emphasis on idiopathic inflammatory myopathies (IIMs). High proportions of those with juvenile myositis report psychological distress at levels warranting mental health referral. Adults with dermatomyositis diagnosed with depression or anxiety do not receive adequate mental health care. Mental health symptoms in those with IIMs are associated with worse health-related quality of life, medication adherence, and disease outcomes. Despite demonstrated high rates of mental health burden, access to mental health care remains severely lacking.Data related to mental health burden is limited by small sample size, limited generalisability, variable methods of assessment, and inconsistent diagnosis codes to define mental health conditions. Additional research is needed to validate current screening tools in myositis populations. Other relevant measurable factors include disease severity, non-health- and health-related trauma exposure, loneliness, isolation, loss of control, sleep difficulties, fatigue, pain, self-esteem, body image, sexual health, and health inequities. Studiesare needed investigating the efficacy of therapeutic and pharmacologic interventions among patients with myositis who experience depression and anxiety. Currently, knowledge and resources are limited around mental health burden and potential intervention for those living with IIMs. The Myositis International Health & Research Collaborative Alliance (MIHRA) Psychological Impact Scientific Working Group offers a preliminary road map to characterise and prioritise the work ahead to understand baseline mental health burden and compare avenues for intervention.

A randomised controlled trial of acceptance and commitment therapy for improving quality of life in people with muscle diseases.

Abstract. BACKGROUND: Chronic muscle diseases (MD) are progressive and cause wasting and weakness in muscles and are associated with reduced quality of life (QoL). The ACTMuS trial examined whether Acceptance and Commitment Therapy (ACT) as an adjunct to usual care improved QoL for such patients as compared to usual care alone. METHODS: This two-arm, randomised, multicentre, parallel design recruited 155 patients with MD (Hospital and Depression Scale ⩾ 8 for depression or ⩾ 8 for anxiety and Montreal Cognitive Assessment ⩾ 21/30). Participants were randomised, using random block sizes, to one of two groups: standard medical care (SMC) (n = 78) or to ACT in addition to SMC (n = 77), and were followed up to 9 weeks. The primary outcome was QoL, assessed by the Individualised Neuromuscular Quality of Life Questionnaire (INQoL), the average of five subscales, at 9-weeks. Trial registration was NCT02810028. RESULTS: 138 people (89.0%) were followed up at 9-weeks. At all three time points, the adjusted group difference favoured the intervention group and was significant with moderate to large effect sizes. Secondary outcomes (mood, functional impairment, aspects of psychological flexibility) also showed significant differences between groups at week 9. CONCLUSIONS: ACT in addition to usual care was effective in improving QoL and other psychological and social outcomes in patients with MD. A 6 month follow up will determine the extent to which gains are maintained.

Autorepressor PsrA is required for optimal Legionella pneumophila growth in Acanthamoeba castellanii protozoa.

Legionella pneumophila possesses a unique intracellular lifecycle featuring distinct morphological stages that include replicative forms and transmissive cyst forms. Expression of genes associated with virulence traits and cyst morphogenesis is concomitant, and governed by a complex stringent response based-regulatory network and the stationary phase sigma factor RpoS. In Pseudomonas spp., rpoS expression is controlled by the autorepressor PsrA, and orthologs of PsrA and RpoS are required for cyst formation in Azotobacter. Here we report that the L. pneumophila psrA ortholog, expressed as a leaderless monocistronic transcript, is also an autorepressor, but is not a regulator of rpoS expression. Further, the binding site sequence recognized by L. pneumophila PsrA is different from that of Pseudomonas PsrA, suggesting a repertoire of target genes unique to L. pneumophila. While PsrA was dispensable for growth in human U937-derived macrophages, lack of PsrA affected bacterial intracellular growth in Acanthamoeba castellanii protozoa, but also increased the quantity of poly-3-hydroxybutyrate (PHB) inclusions in matured transmissive cysts. Interestingly, overexpression of PsrA increased the size and bacterial load of the replicative vacuole in both host cell types. Taken together, we report that PsrA is a host-specific requirement for optimal temporal progression of L. pneumophila intracellular lifecycle in A. castellanii.

Integrated fiber optic spectrally resolved downwelling irradiance sensor for pushbroom spectrometers.

We present an integrated fiber optic spectrally resolved downwelling irradiance sensor for pushbroom hyperspectral imagers. The system comprises of a cosine corrector and custom fiber patch cables, collecting the ambient light in a large solid angle and feeding it directly to the entrance slit of the spectrometer. The system enables simultaneous measurement of downwelling and upwelling irradiance using the main hyperspectral camera sensor. As a demonstration, the spectral reflectance of a soil sample was measured with a RMSE of 8.4%, a significant improvement on the RMSE of 54% found without correction. At a weight of approximately 10 grams, this system provides a substantial weight saving over standalone incident light sensing instruments.

A randomised controlled trial of acceptance and commitment therapy plus usual care compared to usual care alone for improving psychological health in people with motor neuron disease (COMMEND): study protocol.

BACKGROUND: Motor neuron disease (MND) is a rapidly progressive, fatal neurodegenerative disease that predominantly affects motor neurons from the motor cortex to the spinal cord and causes progressive wasting and weakening of bulbar, limb, abdominal and thoracic muscles. Prognosis is poor and median survival is 2-3 years following symptom onset. Psychological distress is relatively common in people living with MND. However, formal psychotherapy is not routinely part of standard care within MND Care Centres/clinics in the UK, and clear evidence-based guidance on improving the psychological health of people living with MND is lacking. Previous research suggests that Acceptance and Commitment Therapy (ACT) may be particularly suitable for people living with MND and may help improve their psychological health. AIMS: To assess the clinical and cost-effectiveness of ACT modified for MND plus usual multidisciplinary care (UC) in comparison to UC alone for improving psychological health in people living with MND. METHODS: The COMMEND trial is a multi-centre, assessor-blind, parallel, two-arm RCT with a 10-month internal pilot phase. 188 individuals aged ≥ 18 years with a diagnosis of definite, laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis, and additionally the progressive muscular atrophy and primary lateral sclerosis variants, will be recruited from approximately 14 UK-based MND Care Centres/clinics and via self-referral. Participants will be randomly allocated to receive up to eight 1:1 sessions of ACT plus UC or UC alone by an online randomisation system. Participants will complete outcome measures at baseline and at 6- and 9-months post-randomisation. The primary outcome will be quality of life at six months. Secondary outcomes will include depression, anxiety, psychological flexibility, health-related quality of life, adverse events, ALS functioning, survival at nine months, satisfaction with therapy, resource use and quality-adjusted life years. Primary analyses will be by intention to treat and data will be analysed using multi-level modelling. DISCUSSION: This trial will provide definitive evidence on the clinical and cost-effectiveness of ACT plus UC in comparison to UC alone for improving psychological health in people living with MND. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN12655391. Registered 17 July 2017, https://www.isrctn.com/ISRCTN12655391 . PROTOCOL VERSION: 3.1 (10/06/2020).

The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models.

Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here we describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. Our mechanistic studies demonstrate that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. In vivo, S63845 shows potent anti-tumour activity with an acceptable safety margin as a single agent in several cancers. Moreover, MCL1 inhibition, either alone or in combination with other anti-cancer drugs, proved effective against several solid cancer-derived cell lines. These results point towards MCL1 as a target for the treatment of a wide range of tumours.

Non-adherence to COVID-19 containment behaviours: results from an all-Ireland telephone survey.

BACKGROUND: COVID-19 public health measures like handwashing and social distancing can help stem the spread of the virus. Adherence to guidelines varies between individuals. This study aims to identify predictors of non-adherence to social distancing and handwashing guidelines. METHODS: A cross-sectional weekly telephone survey was conducted over eight weeks (11/06/2020-05/08/2020). The sample included adults resident on the island of Ireland (75:25 split between ROI and NI). Data were collected on demographics, threat perceptions, fear of COVID-19, response efficacy and self-efficacy, response cost and social norms, COVID-19 behaviours, mood, loneliness, and self-reported health. RESULTS: 3011 participants were surveyed. Handwashing non-adherers were more likely to be male (OR: 5.2, 95% CI: 2.4 - 11.3), to have higher levels of loneliness (OR: 1.86, 95% CI: 1.1 - 3.1), and higher perceptions of handwashing costs (OR: 3.4, 95% CI: 2.2 - 5.2). Those reporting rarely engaging in social distancing were more likely to be members of lower socioeconomic groups, to be younger (OR: 0.97, 95% CI: 0.96 - 0.98), male (OR: 1.67, 95% CI: 1.1 - 2.5), healthcare workers (OR: 1.98, 95% CI: 1.1 - 3.4), to report lower mood (OR: 1.72, 95% CI: 1.3 - 2.2), were less likely to live in households with people aged under-18 (OR: 0.75, 95% CI: 0.6 - 0.9), and to have lower fear of COVID-19 (OR: 0.79, 95% CI: 0.6 - 0.9). CONCLUSIONS: Non-adherers to handwashing differ to social distancing non-adherers. Public health messages should target specific demographic groups and different messages are necessary to improve adherence to each behaviour.

Supporting adjuvant endocrine therapy adherence in women with breast cancer: the development of a complex behavioural intervention using Intervention Mapping guided by the Multiphase Optimisation Strategy.

BACKGROUND: Adjuvant endocrine therapy (AET) reduces the risk of breast cancer recurrence and mortality. However, up to three-quarters of women with breast cancer do not take AET as prescribed. Existing interventions to support adherence to AET have largely been unsuccessful, and have not focused on the most salient barriers to adherence. This paper describes the process of developing four theory-based intervention components to support adherence to AET. Our aim is to provide an exemplar of intervention development using Intervention Mapping (IM) with guidance from the Multiphase Optimisation Strategy (MOST). METHODS: Iterative development followed the six-stage IM framework with stakeholder involvement. Stage 1 involved a literature review of barriers to adherence and existing interventions, which informed the intervention objectives outlined in Stage 2. Stage 3 identified relevant theoretical considerations and practical strategies for supporting adherence. Stage 4 used information from Stages 1-3 to develop the intervention components. Stages 1-4 informed a conceptual model for the intervention package. Stages 5 and 6 detailed implementation considerations and evaluation plans for the intervention package, respectively. RESULTS: The final intervention package comprised four individual intervention components: Short Message Service to encourage habitual behaviours surrounding medication taking; an information leaflet to target unhelpful beliefs about AET; remotely delivered Acceptance and Commitment Therapy-based guided self-help to reduce psychological distress; and a website to support self-management of AET side-effects. Considerations for implementation within the NHS, including cost, timing and mode of delivery were outlined, with explanation as to how using MOST can aid this. We detail our plans for the final stage of IM which involve feasibility testing. This involved planning an external exploratory pilot trial using a 24-1 fractional factorial design, and a process evaluation to assess acceptability and fidelity of intervention components. CONCLUSIONS: We have described a systematic and logical approach for developing a theoretically informed intervention package to support medication adherence in women with breast cancer using AET. Further research to optimise the intervention package, guided by MOST, has the potential to lead to more effective, efficient and scalable interventions.

Wellbeing, burnout, and safe practice among healthcare professionals: predictive influences of mindfulness, values, and self-compassion.

Poor wellbeing and burnout are significant issues among health-care professionals (HCPs) and may contribute to unsafe practice. In this exploratory study, we aimed to: provide the first investigation of the combined and unique influences of these psychological factors in predicting safe practice; confirm the role played by mindfulness in relation to wellbeing, burnout and safe practice; and investigate whether values and self-compassion predict additional variability above and beyond mindfulness skills. Ninety-eight NHS staff completed measures of wellbeing, burnout, perceived safety of practice, mindfulness, values and self-compassion. Practitioners with higher perceived safety of practice reported higher levels of mindfulness, but not values or self-compassion, particularly lower experiential avoidance and nonjudgmental attitude toward difficult thoughts. Mindfulness explained significant variability in psychological distress (20%), emotional exhaustion (8%), cognitive weariness (10%), patient safety related to oneself (7%), and related to work (8%). Values (obstruction) added unique variance for psychological distress (12%) and physical fatigue (10%). Moreover, self-compassion explained a small yet significant portion of variability in emotional exhaustion. These preliminary findings suggest that mindfulness processes may be associated with perceived safety of practice. The results also indicate that mindfulness-based interventions for HCPs may benefit from the inclusion of values-based action components and self-compassion practices.

Patient and health care professional co-development of an Acceptance and Commitment Therapy intervention to support hormone therapy decision-making and well-being in women with breast cancer.

OBJECTIVES: The aim of this work was to co-develop an Acceptance and Commitment Therapy (ACT) intervention to support medication adherence and quality of life in breast cancer survivors (BCSs). The research approach was intervention co-development. METHODS: The sample consisted of BCS focus groups (n = 24), health care provider (HCP) interviews (n = 10), and a co-development workshop (BCSs, n = 12; HCPs, n = 9).We conducted 6 BCS focus groups and 10 HCP interviews to understand the acceptability of ACT. We co-designed the intervention in a workshop. RESULTS: Participants reported high acceptability of an ACT intervention. BCSs preferred ACT exercises focused on values and self-compassion. Both groups recommended face-to-face intervention delivery, by a clinical psychologist, with a mixture of individual and group sessions. BCSs requested advice on side-effect management. CONCLUSIONS: We effectively used patient and HCP co-design to configure an ACT intervention to support medication adherence and quality of life for BCSs. If feasible and efficacious, this ACT-based intervention could support breast cancer survivorship.

Freeform based hYperspectral imager for MOisture Sensing (FYMOS).

We present FYMOS, an all-aluminum, robust, light weight, freeform based, near infrared hYperspectral imager for MOisture Sensing. FYMOS was designed and built to remotely measure moisture content using spectral features from 0.7-1.7µm integrating an InGaAs sensor. The imaging system, operating at F/2.8, is based on the three-concentric-mirror (Offner) spectrograph configuration providing a spectral resolution of 8 nm optimized for broad spectral coverage with sufficient resolution to make assessments of water levels. To optimize the optical performance, whilst minimizing weight and size, the design incorporates a bespoke freeform blazed grating machined on a commercial 5 axis ultra precision diamond machine. We achieve a 30% improvement on the RMS wavefront error in the spatial and spectral fields compared to a conventional Offner-Chrisp design with similar aperture and the monolithic Primary/Tertiary mirror eases the manufacturing assembly whilst minimizing weight. We demonstrate the performance of FYMOS by measuring the evaporation rate of water on a soil sample and results are processed with a physical multilayer radiative transfer model (MARMIT) to estimate the mean water thickness.

The Unfolding Method to Explore Health-Related Quality of Life Constructs in a Chinese General Population.

OBJECTIVES: Health-related quality of life (HRQOL) is a complicated concept that can be measured using multiple health items. Although HRQOL is closely associated with people's subjective assessment of their own health, a limited number of studies have investigated which health items are considered most important and relevant by the general population. Even fewer empirical studies have investigated how HRQOL is understood in non-Western populations. This study used multidimensional unfolding analysis in a Chinese general population to explore the constructs of HRQOL. METHODS: A scoping review of Chinese generic HRQOL measures and a series of qualitative interviews produced a list of 42 potentially important health items in a Chinese cultural setting; 110 Chinese participants in face-to-face interviews ranked the health items from most important to least important. Responses were coded into a rectangular 110 × 42 matrix, and multidimensional unfolding was conducted to analyze participants' preferences for health items. RESULTS: It was found that demographic characteristics and one's health condition affected views of HRQOL. Meanwhile, 3 health items were considered to be most important across the whole sample: sleep quality, body constitution, and spiritual appearance. CONCLUSION: This study used a novel approach to explore how people coming from a Chinese cultural setting may perceive HRQOL and which aspects of HRQOL are most important to them. The study shows that multidimensional unfolding is a feasible approach to assess preferences in a general population. Future studies using this approach are recommended to further explore the constructs of HRQOL in other general populations.

Investigating the potentially important role of psychological flexibility in adherence to antiretroviral therapy in people living with HIV.

Antiretroviral therapy (ART) has significantly improved immune health and survival rates in HIV, but these outcomes rely on near perfect adherence. While many psychosocial factors are related to sub-optimal adherence, effectiveness of associated interventions are modest or inconsistent. The Psychological Flexibility (PF) model underlying Acceptance and Commitment Therapy (ACT) identifies a core set of broadly applicable transdiagnostic processes that may be useful to explain and improve non-adherence. However, PF has not previously been examined in relation to ART adherence. Therefore, this cross-sectional study (n = 275) explored relationships between PF and intentional/unintentional ART non-adherence in people with HIV. Adults with HIV prescribed ART were recruited online. Participants completed online questionnaires assessing self-reported PF, adherence and emotional and general functioning. Logistic regressions examined whether PF processes were associated with intentional/unintentional non-adherence. Fifty-eight percent of participants were classified as nonadherent according to the Medication Adherence Rating Scale, of which 41.0% reported intentional and 94.0% unintentional non-adherence. Correlations between PF and adherence were small. PF did not significantly explain intentional/unintentional non-adherence after controlling for demographic and disease factors. Further clarification of the utility of PF in understanding ART non-adherence is warranted using prospective or experimental designs in conjunction with more objective adherence measures.

Evidence of objective sleep impairment in nonepileptic attack disorder: A naturalistic prospective controlled study using actigraphy and daily sleep diaries over six nights.

Poor sleep is reported by many with nonepileptic attack disorder (NEAD) with correlations evident between self-reported sleep quality and mood and functional impairment. However, it is contended that self-reported sleep impairment in NEAD is a subjective phenomenon, which represents a general tendency to over-report symptoms or misinterpret bodily states in those with NEAD. The present study was therefore designed to investigate the extent of subjective and objective sleep impairments in those with NEAD. Over six nights we prospectively recorded comparable nightly objective (actigraphy) and subjective (consensus sleep diary) sleep parameters in a sample of 17 people with NEAD, and an age- and gender-matched normative control group (N = 20). Participants recorded daily measures of attacks, dissociation, and mood. Alongside higher subjective sleep impairment, the NEAD group had significantly worse objective sleep on several metrics compared to the normative controls, characterized by disrupted sleep (frequent awakenings and wake after sleep onset, low efficiency). Exploratory analyses using mixed effects models showed that attacks were more likely to occur on days preceded by longer, more restful sleep. This study, which had good ecological validity, evidences the presence of objective sleep impairment in NEAD, suggesting that in patient reports of problems with sleep should be given careful consideration in clinical practice.

Acceptance and commitment therapy for late-life treatment-resistant generalised anxiety disorder: a feasibility study.

BACKGROUND: Generalised anxiety disorder (GAD) is the most common anxiety disorder in older people. First-line management includes pharmacological and psychological therapies, but many do not find these effective or acceptable. Little is known about how to manage treatment-resistant generalised anxiety disorder (TR-GAD) in older people. OBJECTIVES: To examine the acceptability, feasibility and preliminary estimates of the effectiveness of acceptance and commitment therapy (ACT) for older people with TR-GAD. PARTICIPANTS: People aged ≥65 years with TR-GAD (defined as not responding to GAD treatment, tolerate it or refused treatment) recruited from primary and secondary care services and the community. INTERVENTION: Participants received up to 16 one-to-one sessions of ACT, developed specifically for older people with TR-GAD, in addition to usual care. MEASUREMENTS: Co-primary outcomes were feasibility (defined as recruitment of ≥32 participants and retention of ≥60% at follow-up) and acceptability (defined as participants attending ≥10 sessions and scoring ≥21/30 on the satisfaction with therapy subscale). Secondary outcomes included measures of anxiety, worry, depression and psychological flexibility (assessed at 0 and 20 weeks). RESULTS: Thirty-seven participants were recruited, 30 (81%) were retained and 26 (70%) attended ≥10 sessions. A total of 18/30 (60%) participants scored ≥21/30 on the satisfaction with therapy subscale. There was preliminary evidence suggesting that ACT may improve anxiety, depression and psychological flexibility. CONCLUSIONS: There was evidence of good feasibility and acceptability, although satisfaction with therapy scores suggested that further refinement of the intervention may be necessary. Results indicate that a larger-scale randomised controlled trial of ACT for TR-GAD is feasible and warranted.