Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy. METHODS: At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes). RESULTS: Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P = 0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis. CONCLUSIONS: After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.).

Development of a new health-related quality of life measure for people with diabetes who experience hypoglycaemia: the Hypo-RESOLVE QoL.

AIMS/HYPOTHESIS: Valid and reliable patient-reported outcome measures are vital for assessing disease impact, responsiveness to healthcare and the cost-effectiveness of interventions. A recent review has questioned the ability of existing measures to assess hypoglycaemia-related impacts on health-related quality of life for people with diabetes. This mixed-methods project was designed to produce a novel health-related quality of life patient-reported outcome measure in hypoglycaemia: the Hypo-RESOLVE QoL. METHODS: Three studies were conducted with people with diabetes who experience hypoglycaemia. In Stage 1, a comprehensive health-related quality of life framework for hypoglycaemia was elicited from semi-structured interviews (N=31). In Stage 2, the content validity and acceptability of draft measure content were tested via three waves of cognitive debriefing interviews (N=70 people with diabetes; N=14 clinicians). In Stage 3, revised measure content was administered alongside existing generic and diabetes-related measures in a large cross-sectional observational survey to assess psychometric performance (N=1246). The final measure was developed using multiple evidence sources, incorporating stakeholder engagement. RESULTS: A novel conceptual model of hypoglycaemia-related health-related quality of life was generated, featuring 19 themes, organised by physical, social and psychological aspects. From a draft version of 76 items, a final 14-item measure was produced with satisfactory structural (χ2=472.27, df=74, p<0.001; comparative fit index =0.943; root mean square error of approximation =0.069) and convergent validity with related constructs (r=0.46-0.59), internal consistency (α=0.91) and test-retest reliability (intraclass correlation coefficient =0.87). CONCLUSIONS/INTERPRETATION: The Hypo-RESOLVE QoL is a rigorously developed patient-reported outcome measure assessing the health-related quality of life impacts of hypoglycaemia. The Hypo-RESOLVE QoL has demonstrable validity and reliability and has value for use in clinical decision-making and as a clinical trial endpoint. DATA AVAILABILITY: All data generated or analysed during this study are included in the published article and its online supplementary files ( https://doi.org/10.15131/shef. DATA: 23295284.v2 ).

Producing a preference-based quality of LIFE measure to quantify the impact of HYPOGLYCAEMIA on people living with diabetes: A mixed-methods research protocol.

BACKGROUND: Assessment of patient-reported outcome measures (PROMs), including quality of life (QoL), is essential in diabetes research and care. However, a recent review concluded that current hypoglycaemia-specific PROMs have limited evidence of validity, reliability and responsiveness for assessing the impact of hypoglycaemia on QoL in people living with diabetes. None of the PROMs identified could be used directly to inform the cost-effectiveness of treatments and interventions. There is a need for a new hypoglycaemia-specific QoL PROM, which can be used directly to inform economic evaluations. AIMS: This project has three aims: (a) To develop draft PROM content for measuring the impact of hypoglycaemia on QoL in adults with diabetes. (b) To refine the draft content using cognitive debriefing interviews and psychometrics. This will result in a condition-specific PROM that can be used to quantify the impact of hypoglycaemia upon QoL. (c) To generate a preference-based measure (PBM) that will enable utility values to be calculated for economic evaluation. METHODS: A mixed-methods, three-stage design is used: (a) Qualitative interviews will inform the draft PROM content. (b) Cognitive debriefing interview data will be used to refine the draft PROM content. The PROM will be administered in a large-scale survey to enable psychometric validation. Final item selection for the PROM will be informed by psychometric performance, translatability assessment and input from stakeholder groups. (c) A classification system will be generated, comprising a reduced number of items from the PROM. A valuation survey will be conducted to derive a value set for the PBM.

A comprehensive qualitative framework for health-related quality of life in Duchenne muscular dystrophy.

PURPOSE: Duchenne muscular dystrophy (DMD) is a rare x-linked neuromuscular condition predominantly affecting boys and men. There is a paucity of research qualitatively detailing the lived experience of health-related quality of life (HRQoL) for people with DMD. The aim of this study was to identify a comprehensive framework for better understanding HRQoL in DMD. METHODS: Eighteen boys and men (aged 7 to ≥ 40 years) with DMD were recruited from charity Duchenne UK, a DMD support group, and 5 UK National Health Service Trusts. Semi-structured interviews were conducted using a topic guide informed by a review into HRQoL in DMD. Generic, preference-based, patient-reported outcome measures (PROs) were used as prompts. Interviews were audio recorded, transcribed verbatim and analysed using framework analysis. RESULTS: Thirty-seven themes were coded, within seven categories. Six categories were conceptualised as components of HRQoL (autonomy, daily activities, feelings and emotions, identity, physical aspects, social relationships) and one considered an input (healthcare, support, and environment). Three additional themes were used to code feedback on the generic PROs (CHU-9D, EQ-5D, HUI). Social relationships received most coverage in the data and was noted as an omission from the PROs. CONCLUSION: A 30-item framework for HRQoL in DMD has been developed, which was used as input into a new condition-specific HRQoL PRO and preference-based measure: the DMD-QoL. The data has value in its own right in highlighting the lived experience of HRQoL for people with DMD and as a barometer for assessing the content of HRQoL PROs for use in DMD.

Hypothetical versus experienced health state valuation: a qualitative study of adult general public views and preferences.

OBJECTIVES: Responses from hypothetical and experienced valuation tasks of health-related quality of life differ, yet there is limited understanding of why these differences exist, what members of the public think about them, and acceptable resolutions. This study explores public understanding of, opinions on, and potential solutions to differences between hypothetical versus experienced responses, in the context of allocating health resources. METHODS: Six focus groups with 30 members of the UK adult public were conducted, transcribed verbatim, and analysed using framework analysis. Participants self-completed the EQ-5D-5L, before reporting the expected consequences of being in two hypothetical EQ-5D-5L health states for ten years. Second, participants were presented with prior results on the same task from a public (hypothetical) and patient (experienced) sample. Third, a semi-structured discussion explored participants': (1) understanding, (2) opinions, and (3) potential resolutions. RESULTS: Twenty themes emerged, clustered by the three discussion points. Most participants found imagining the health states difficult without experience, with those aligned to mental health harder to understand. Participants were surprised that health resource allocation was based on hypothetical responses. They viewed experienced responses as more accurate, but noted potential biases. Participants were in favour of better informing, but not influencing the public. Other solutions included incorporating other perspectives (e.g., carers) or combining/weighting responses. CONCLUSION: Members of the UK public appear intuitively not to support using potentially uninformed public values to hypothetical health states in the context of health resource allocation. Acceptable solutions involve recruiting people with greater experience, including other/combinations of views, or better informing respondents.

Measuring carer quality of life in Duchenne muscular dystrophy: a systematic review of the reliability and validity of self-report instruments using COSMIN.

INTRODUCTION: Duchenne muscular dystrophy is a rare, progressive, life-limiting genetic neuromuscular condition that significantly impacts the quality of life of informal caregivers. Carer quality of life is measured using heterogeneous self-report scales, yet their suitability for Duchenne remains unclear. This review aimed to identify and evaluate the reliability and validity of quality of life instruments in Duchenne carers. MATERIALS AND METHODS: Systematic searches were conducted in Embase, MEDLINE, CINAHL, PsycINFO, Cochrane Library and Google Scholar. Full research articles reporting data on multiple-item self-report quality of life instruments in informal Duchenne carers were included. Extracted evidence was qualitatively synthesised and evaluated, including risk of bias, against the Consensus-based Standards for the selection of health Measurement Instruments. Duchenne carer collaborators (N = 17) helped rate the instruments' content validity. RESULTS: Thirty-one articles featuring thirty-two quality of life instruments were included. Content validity was rated as "inconsistent" based on very low quality evidence. For Duchenne carer collaborators, the best instrument was PedsQL Family Impact Module. Only one instrument had evidence for structural validity (rated "unsatisfactory") and measurement invariance (rated "satisfactory"). Instruments received "satisfactory" ratings for internal consistency and mixed ratings for construct validity and responsiveness. There was no evidence for reliability, measurement error, or criterion validity. DISCUSSION: Instruments used to measure Duchenne carer quality of life have limited and often inconsistent supportive psychometric evidence. Further work must investigate instruments' measurement properties in Duchenne carers and/or the development of new tools. In the interim, we recommend considering the PedsQL Family Impact Module based on Duchenne carer ratings.

Transforming challenges into opportunities: conducting health preference research during the COVID-19 pandemic and beyond.

The disruptions to health research during the COVID-19 pandemic are being recognized globally, and there is a growing need for understanding the pandemic's impact on the health and health preferences of patients, caregivers, and the general public. Ongoing and planned health preference research (HPR) has been affected due to problems associated with recruitment, data collection, and data interpretation. While there are no "one size fits all" solutions, this commentary summarizes the key challenges in HPR within the context of the pandemic and offers pragmatic solutions and directions for future research. We recommend recruitment of a diverse, typically under-represented population in HPR using online, quota-based crowdsourcing platforms, and community partnerships. We foresee emerging evidence on remote, and telephone-based HPR modes of administration, with further studies on the shifts in preferences related to health and healthcare services as a result of the pandemic. We believe that the recalibration of HPR, due to what one would hope is an impermanent change, will permanently change how we conduct HPR in the future.

Measuring quality of dying, death and end-of-life care for children and young people: A scoping review of available tools.

BACKGROUND: The circumstances and care provided at the end of a child's life have a profound impact on family members. Although assessing experiences and outcomes during this time is challenging, healthcare professionals have a responsibility to ensure high quality of care is provided. AIM: To identify available tools which measure the quality of dying, death and end-of-life care for children and young people; describe the content, and data on validity and reliability of existing tools. DESIGN: Scoping review was conducted following the Arksey and O'Malley methodological framework. DATA SOURCES: Four electronic databases (MEDLINE, EMBASE, CINAHL and PsycINFO) and grey literature were searched for studies published in English (January 2000-June 2021). A review of reference lists and citation searching was also undertaken. Tools needed to include a focus on the 'dying' phase of illness (defined as the last month of life). RESULTS: From 2078 articles, a total of 18 studies, reporting on 11 tools were identified. All tools were completed by primary caregivers or healthcare professionals as 'proxy' assessments; all except one was undertaken after death. Question items about quality of life and preparation for death were found in all tools; items relating to cultural aspects of care, grief and financial costs were less common. Only 6/11 had undergone psychometric testing within a paediatric palliative care setting. CONCLUSIONS: Future research should include ways to adapt, refine and improve existing tools. Assessing their wider application in different clinical and cultural settings and conducting further psychometric assessment represent areas of focus.

Care Starts at Home: Emotional State and Appeals to Altruism may Reduce Demand for Overused Health Services in the UK.

BACKGROUND: Overuse of unnecessary services, screening tests, and treatments is an ongoing problem for national health care systems. Overuse is at least partly driven by patient demand. PURPOSE: This study examined whether altering patients' emotional state and appealing to patient altruism would reduce demand for three commonly overused UK health services. METHODS: In an online experiment, 1,267 UK volunteers were randomized to anxiety, compassion, or neutral conditions before viewing three overuse vignettes. In each vignette, use of the health service was recommended against by the doctor and participants were further randomized to one of three altruism frames, emphasizing the impact of overuse on the self, the self and others locally, or the self and others nationally. Participants rated the likelihood that they would pursue the health service and, assuming that they did not, how long they would be willing-to-wait for it. RESULTS: Altruism frame had a small effect on intentions to use the health service. Those in the local or national (vs. self) frame were 4.7 and 6.1 percentage points, respectively, less likely to ask for the service. Emotion induction had no direct effect on outcomes. However, self-reporting higher levels of anxiety or compassion post-induction was associated with a small, greater likelihood in intentions to ask for the health service or willingness-to-wait, respectively. No interactions between frame and emotion were observed. CONCLUSIONS: As a low-cost initiative, emphasizing the benefits to the self and local or national communities could be embedded in appeals designed to appropriately reduce health care overuse in the UK.

Deriving a Preference-Based Measure for People With Duchenne Muscular Dystrophy From the DMD-QoL.

OBJECTIVES: This study generates a preference-based measure for capturing the quality of life of people with Duchenne muscular dystrophy (DMD) from a new measure of quality of life, DMD-QoL. METHODS: A health state classification system was derived from the DMD-QoL based on psychometric performance of items, factor analysis, and item response theory analysis. Preferences for health states described by the classification system were elicited using an online discrete choice experiment survey with life years as an additional attribute, from members of the UK general population (n = 1043). Discrete choice experiment data was modeled using a conditional fixed-effects logit model and utility estimates were directly anchored on the 1 to 0 full health-dead scale. RESULTS: The health state classification system has 8 dimensions: mobility, difficulty using hands, difficulty breathing, pain, tiredness, worry, participation, and feeling good about yourself. The standard model had mostly statistically significant coefficients and reflected the instrument's monotonic structure. However, 2 dimensions had inconsistent coefficients (where utility increased as health worsened) and a consistent model was estimated that merged adjacent inconsistent severity levels. The best state defined by the classification system has a value of 1 and the worst state has a value of -0.559. CONCLUSION: The modeled results enable DMD-QoL-8D utility values to be generated using DMD-QoL or DMD-QoL-8D data to generate QALYs for people with DMD. QALYs can then be used to inform economic models of the cost-effectiveness of interventions in DMD. Future research comparing the psychometric performance of DMD-QoL-8D to existing generic preference-based measures, including EQ-5D-5L, is recommended.

Valuing child and adolescent health: a qualitative study on different perspectives and priorities taken by the adult general public.

BACKGROUND: Quantitative health preference research has shown that different "perspectives", defined here as who is imagined to be experiencing particular health states, impact stated preferences. This qualitative project aimed to elucidate this phenomenon, within the context of adults' valuation of child and adolescent health states. METHODS: Six focus groups with 30 members of the UK adult public were conducted between December 2019 and February 2020 and analysed using framework analysis. Each focus group had two stages. First, participants individually completed time trade-off tasks and a pairwise task (mirroring a discrete choice experiment without duration) for two EQ-5D-Y health states, assuming a series of perspectives: (a) themselves at current age; (b) another adult; (c) 10-year old child; (d) themselves as a 10-year old child. Second, a semi-structured discussion explored their responses. RESULTS: Participants' views were often heterogeneous, with some common themes. Qualitatively, participants expressed a different willingness to trade-off life years for a 10-year old child versus themselves or another adult, and this differed by the health profile and child imagined. The same health states were often viewed as having a different impact on utility for a 10-year old child than adults. Imagining a 10-year old child is difficult and there is variation in who is imagined. Participants found answering based on their own-adult perspective most acceptable. There were no strong preferences for prioritising child health over working-age adults' health. CONCLUSIONS: If an adult sample is used to value child- and adolescent-specific health states it is important to consider the perspective employed. Members of the adult public provide different responses when different perspectives are used due to differences in the perceived impact of the same health states. If adults are asked to imagine a child, we recommend that sampling is representative for parental status, since this can affect preferences.

The role of response domain and scale label in the quantitative interpretation of patient-reported outcome measure response options.

PURPOSE: Uncertainties exist in how respondents interpret response options in patient-reported outcome measures (PROMs), particularly across different domains and for different scale labels. The current study assessed how respondents quantitatively interpret common response options. METHODS: Members of the general public were recruited to this study via an online panel, stratified by age, gender, and having English as a first language. Participants completed background questions and were randomised to answer questions on one of three domains (i.e. loneliness (negatively phrased), happiness or activities (positively phrased)). Participants were asked to provide quantitative interpretations of response options (e.g. how many times per week is equal to "often") and to order several common response options (e.g. occasionally, sometimes) on a 0-100 slider scale. Chi-squared tests and regression analyses were used to assess whether response options were interpreted consistently across domains and respondent characteristics. RESULTS: Data from 1377 participants were analysed. There was general consistency in quantifying the number of times over the last 7 days to which each response option referred. Response options were consistently assigned a lower value in the loneliness than happiness and activities domains. Individual differences, such as age and English as a second language, explained some significant variation in responses, but less than domain. CONCLUSION: Members of the public quantify common response options in a similar way, but their quantification is not equivalent across domains or every type of respondent. Recommendations for the use of certain scale labels over others in PROM development are provided.

Measuring quality of life in Duchenne muscular dystrophy: a systematic review of the content and structural validity of commonly used instruments.

Duchenne muscular dystrophy (DMD) is an inherited X-linked neuromuscular disorder. A number of questionnaires are available to assess quality of life in DMD, but there are concerns about their validity. This systematic review aimed to appraise critically the content and structural validity of quality of life instruments for DMD. Five databases (EMBASE, MEDLINE, CINAHL, PsycINFO, and Cochrane Library) were searched, with supplementary searches in Google Scholar. We included articles with evidence on the content and/or structural validity of quality of life instruments in DMD, and/or instrument development. Evidence was evaluated against the Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. Fifty five articles featured a questionnaire assessing quality of life in DMD. Forty instruments were extracted and 26 underwent assessment. Forty-one articles contained evidence on content or structural validity (including 37 development papers). Most instruments demonstrated low quality evidence and unsatisfactory or inconsistent validity in DMD, with the majority not featuring direct validation studies in this population. Only KIDSCREEN received an adequate rating for instrument design and a satisfactory result for content validity based on its development, yet, like the majority of PROMs, the measure has not been directly validated for use in DMD. Further research is needed on the validity of quality of life instruments in DMD, including content and structural validity studies in this population.

Disgust propensity has a causal link to the stigmatization of people with cancer.

Disgust-driven stigma may be motivated by an assumption that a stigmatized target presents a disease threat, even in the absence of objective proof. Accordingly, even non-contagious diseases, such as cancer, can become stigmatized by eliciting disgust. This study had two parts: a survey (n = 272), assessing the association between disgust traits and cancer stigma; and an experiment, in which participants were exposed to a cancer surgery (n = 73) or neutral video (n = 68), in order to test a causal mechanism for the abovementioned association. Having a higher proneness to disgust was associated with an increased tendency to stigmatize people with cancer. Further, a significant causal pathway was observed between disgust propensity and awkwardness- and avoidance-based cancer stigma via elevated disgust following cancer surgery exposure. In contrast, those exposed to cancer surgery not experiencing elevated disgust reported less stigma than controls. Exposure-based interventions, which do not elicit disgust, may be profitable in reducing cancer stigma.

Self-disgust mediates the relationship between childhood adversities and psychosis.

OBJECTIVE: Traumatic events in childhood have been implicated in the development of psychosis, but given that trauma is not in itself sufficient to cause psychosis, researchers have started to investigate other psychological constructs potentially involved in explaining this relationship. Given that self-disgust as a transdiagnostic construct plays a role in the development/maintenance of a range of mental health difficulties, the objective of this study was to investigate whether self-disgust mediates the relationship between childhood trauma and psychosis. METHOD: A cross-sectional quantitative study design was used. Seventy-eight participants (Mage  = 37.64 years, SDage  = 11.57 years; 77% women; 88% White Caucasian) who reported experiencing clinical levels of psychosis were recruited using social media. The participants completed online survey measures of childhood trauma, self-disgust, experiences of psychosis, self-esteem, and external shame. The data were analysed using correlation and mediation analyses. RESULTS: Significant indirect effects of childhood trauma on both positive (ß = .17, BC 95% CI [0.06, 0.30]) and negative symptoms (ß = .26, BC 95% CI [0.14, 0.40]) of psychosis via self-disgust were observed. These effects remained despite the inclusion of self-esteem and external shame as control variables in the mediation models. CONCLUSION: This study is the first to show a mediating role for self-disgust in the relationship between childhood trauma and later psychosis. Although the findings should be considered preliminary until strengthened by further research, they nevertheless provide corroboration of the potential utility of self-disgust as a transdiagnostic construct not only from a theoretical perspective, but also from its potential to inform formulation and interventions. PRACTITIONER POINTS: When assessing individuals with psychosis, especially those with a trauma history explore experiences and feelings related to the construct of self-disgust. Such experiences are likely to centre on feelings of repulsion towards the self/need for distance and might also manifest in the content of their psychotic experiences. Individuals with significant levels or experiences of self-disgust are likely to need specific interventions to address these; while interventions seeking to improve positive aspects of their identity might well be useful, they are unlikely to address the specific maladaptive elements of self-disgust. While self-disgust-focused interventions have not been widely researched, limited current evidence suggests cognitive restructuring and affirmation techniques might be useful.

10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer.

BACKGROUND: The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. METHODS: We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. RESULTS: There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). CONCLUSIONS: At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

From hadrons to quarks in neutron stars: a review.

In recent years our understanding of neutron stars has advanced remarkably, thanks to research converging from many directions. The importance of understanding neutron star behavior and structure has been underlined by the recent direct detection of gravitational radiation from merging neutron stars. The clean identification of several heavy neutron stars, of order two solar masses, challenges our current understanding of how dense matter can be sufficiently stiff to support such a mass against gravitational collapse. Programs underway to determine simultaneously the mass and radius of neutron stars will continue to constrain and inform theories of neutron star interiors. At the same time, an emerging understanding in quantum chromodynamics (QCD) of how nuclear matter can evolve into deconfined quark matter at high baryon densities is leading to advances in understanding the equation of state of the matter under the extreme conditions in neutron star interiors. We review here the equation of state of matter in neutron stars from the solid crust through the liquid nuclear matter interior to the quark regime at higher densities. We focus in detail on the question of how quark matter appears in neutron stars, and how it affects the equation of state. After discussing the crust and liquid nuclear matter in the core we briefly review aspects of microscopic quark physics relevant to neutron stars, and quark models of dense matter based on the Nambu-Jona-Lasinio framework, in which gluonic processes are replaced by effective quark interactions. We turn then to describing equations of state useful for interpretation of both electromagnetic and gravitational observations, reviewing the emerging picture of hadron-quark continuity in which hadronic matter turns relatively smoothly, with at most only a weak first order transition, into quark matter with increasing density. We review construction of unified equations of state that interpolate between the reasonably well understood nuclear matter regime at low densities and the quark matter regime at higher densities. The utility of such interpolations is driven by the present inability to calculate the dense matter equation of state in QCD from first principles. As we review, the parameters of effective quark models-which have direct relevance to the more general structure of the QCD phase diagram of dense and hot matter-are constrained by neutron star mass and radii measurements, in particular favoring large repulsive density-density and attractive diquark pairing interactions. We describe the structure of neutron stars constructed from the unified equations of states with crossover. Lastly we present the current equations of state-called 'QHC18' for quark-hadron crossover-in a parametrized form practical for neutron star modeling.

Effect of Partners' Disgust Responses on Psychological Wellbeing in Cancer Patients.

The aim of this study was to explore quantitatively the relationship between disgust responses in cancer patients and their partners, and in turn their relationship to patients' psychological well-being. We recruited 50 participants with heterogeneous cancer diagnoses and their partners from cancer-related groups (e.g., charities). Patients completed questionnaires to determine levels of disgust propensity, disgust sensitivity, self-disgust, and symptoms of anxiety and depression. Disgust propensity and sensitivity were also assessed in their partners. Partners' disgust sensitivity was significantly positively correlated with cancer patients' self-disgust, disgust propensity, and depression. Path analyses suggested that patients' self-disgust plays a role in mediating the effect of partners' disgust sensitivity on patients' psychological well-being. This study provides the first quantitative evidence that psychological well-being in cancer patients is contingent on their partners' sensitivity to disgust, and that patients' self-disgust plays a mediating role. Focusing therapeutically on disgust responses could well be beneficial to people with cancer.

The effect of disgust-related side-effects on symptoms of depression and anxiety in people treated for cancer: a moderated mediation model.

As maladaptive disgust responses are linked to mental health problems, and cancer patients may experience heightened disgust as a result of treatments they receive, we explored the associations between disgust-related side-effects and symptoms of depression and anxiety in people treated for cancer. One hundred and thirty two (83 women, M age = 57.48 years) participants answered questions about their treatments, side-effects, disgust responding, and mental health. Experiencing bowel and/or bladder problems, sickness and/or nausea (referred to here as "core" disgust-related side-effects) was significantly related to greater symptoms of depression and borderline increased anxiety. Further, these links were explained by a moderated mediation model, whereby the effects of core disgust side-effects on depression and anxiety were mediated by (physical and behavioural) self-directed disgust, and disgust propensity moderated the effect of core disgust side-effects on self-disgust. These findings stress the importance of emotional responses, like disgust, in psychological adaptation to the side-effects of cancer treatments.

The revolting self: an interpretative phenomenological analysis of the experience of self-disgust in females with depressive symptoms.

OBJECTIVE: Self-focused disgust has been implicated in depression and other mental health problems. However, "self-disgust" as a psychological concept has never been properly defined and remains particularly enigmatic. A qualitative methodology was used to obtain an informed understanding of self-disgust. METHOD: Nine female participants with clinically relevant depressive symptoms completed semistructured interviews about their understanding and experiences of self-disgust. These were analyzed using Interpretative Phenomenological Analysis. RESULTS: Four superordinate themes emerged: (a) "The subjective experience of self-disgust" revealed how self-disgust was perceived as a consuming, visceral experience with trait and state components; (b) "Origins of the revolting self" covered antecedent factors and the role of others in the genesis of self-disgust; (c) "Consequences of self-disgust" included the psychological and behavioral results of a disgusting self; and (d) "Associated emotional states" described associations between self-disgust and other feeling states. CONCLUSIONS: The current findings suggest self-disgust is a consuming negative psychological phenomenon, associated with depression, problems with eating, physical appearance, interpersonal relationships, and self-persecution. Implications for clinical practice and future research on the topic are discussed.