ABSTRACT
BACKGROUND: The androgen receptor is a tumour suppressor in oestrogen receptor-positive breast cancer. The activity and safety of enobosarm, an oral selective androgen receptor modulator, was evaluated in women with oestrogen receptor (ER)-positive, HER2-negative, and androgen receptor (AR)-positive disease. METHODS: Women who were postmenopausal (aged ≥18 years) with previously treated ER-positive, HER2-negative, locally advanced or metastatic breast cancer with an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled in a randomised, open-label, multicentre, multinational, parallel design, phase 2 trial done at 35 cancer treatment centres in nine countries. Participants were stratified on the setting of immediately preceding endocrine therapy and the presence of bone-only metastasis and randomly assigned (1:1) to 9 mg or 18 mg oral enobosarm daily using an interactive web response system. The primary endpoint was clinical benefit rate at 24 weeks in those with centrally confirmed AR-positive disease (ie, the evaluable population). This trial is registered with ClinicalTrials.gov (NCT02463032). FINDINGS: Between Sept 10, 2015, and Nov 28, 2017, 136 (79%) of 172 patients deemed eligible were randomly assigned to 9 mg (n=72) or 18 mg (n=64) oral enobosarm daily. Of these 136 patients, 102 (75%) patients formed the evaluable population (9 mg, n=50; 18 mg, n=52). The median age was 60·5 years (IQR 52·3-69·3) in the 9 mg group and 62·5 years (54·0-69·3) in the 18 mg group. The median follow-up was 7·5 months (IQR 2·9-14·1). At 24 weeks, 16 (32%, 95% CI 20-47) of 50 in the 9 mg group and 15 (29%, 17-43) of 52 in the 18 mg group had clinical benefit. Six (8%) of 75 patients who received 9 mg and ten (16%) of 61 patients who received 18 mg had grade 3 or grade 4 drug-related adverse events, most frequently increased hepatic transaminases (three [4%] of 75 in the 9 mg group and two [3%] of 61 in the 18 mg group), hypercalcaemia (two [3%] and two [3%]), and fatigue (one [1%] and two [3%]). Four deaths (one in the 9 mg group and three in the 18 mg group) were deemed unrelated to the study drug. INTERPRETATION: Enobosarm has anti-tumour activity in patients with ER-positive, HER2-negative advanced breast cancer, showing that AR activation can result in clinical benefit, supporting further clinical investigation of selective AR activation strategies for the treatment of AR-positive, ER-positive, HER2-negative advanced breast cancer. FUNDING: GTx.
Subject(s)
Anilides , Breast Neoplasms , Female , Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Receptor, ErbB-2/genetics , Receptors, Androgen/genetics , Receptors, Estrogen , AgedABSTRACT
AIM: Colorectal cancer (CRC) patients need CRC-specific dietary guidance, but often lack access to adequate nutritional information and support. This scoping review identified study interventions, online resources, which have been produced to support nutritional care self-management for CRC patients from diagnosis, through treatment and into survivorship and guidelines to underpin these. METHODS: The review was carried out in accordance with the JBI method for Scoping Reviews. Study interventions, online resources that support the self-management of nutrition and diet in CRC patients were eligible for inclusion, along with CRC-specific guidelines. Searches up to February 2023, were carried out via MEDLINE, CINAHL, PsycInfo, Embase, and Web of Science for published literature and ProQuest Dissertations, Theses Global, TRIP Medical Database, and Google search engines for grey literature. Two reviewers independently screened titles and abstracts, and relevant full texts for inclusion. Data were analysed descriptively. RESULTS: Eight study interventions, 74 online resources and three guidelines specifically aimed at CRC patients were included in the review. Study interventions were heterogenous with respect to duration, whether it was personalized, who supported delivery and which guidelines underpinned the intervention. Three study interventions resulted in improved quality of life and one lengthened survival. A total of 36 (48.6%) online resources were produced by UK charity organizations. Most of the included information was for patients after completing treatment. Specific advice for patients with a stoma was lacking. Some of the online resources provided conflicting advice. The three guidelines explained how dietary adjustments can help address symptoms related to cancer or treatment and two provided more specific guidance on making dietary changes, with specific examples of how to tailor dietary advice to patient needs. CONCLUSION: This scoping review of study interventions, online resources, and guidelines highlighted the need for reliable, detailed, and personalized information to help CRC patients to self-manage their nutritional care.
ABSTRACT
BACKGROUND: Nutritional status is compromised long-term following oesophagectomy. Controversy surrounds the optimal route for nutrition support postoperatively and there is wide variation in the use of feeding jejunostomy tubes. METHODS: A retrospective service evaluation was conducted for all consecutive adults who underwent oesophagectomy for a cancer diagnosis within a specialist centre between April 2016 and July 2019 (n = 165). Nutritional and clinical outcomes were compared for patients who received jejunostomy feeding (n = 24), versus those who did not (n = 141). RESULTS: Patients with feeding jejunostomy lost significantly less weight at both 6 and 12 months postoperatively compared to those without jejunostomy (p ≤ 0.001 and p = 0.001, respectively). This remained statistically significant in multiple regression, controlling for age, gender, preoperative tumour staging and adjuvant treatment (p ≤ 0.001 and p = 0.03, respectively). Median length of home enteral feeding was 10 weeks after discharge in the jejunostomy group. We observed minor jejunostomy tube-related complications in four patients (16.7%). Of those readmitted within 90 days of surgery in the non-jejunostomy group, nutritional failure was a factor in 43.2% of these readmissions. "Rescue tube feeding" was required by 8.5% of the non-jejunostomy group within the first postoperative year, including 6.4% within 90 days of surgery. CONCLUSIONS: Use of short-term supplementary jejunal feeding in addition to oral intake after hospital discharge is beneficial for maintaining weight after oesophagectomy. We suggest a future randomised-controlled trial to confirm these findings.
Subject(s)
Enteral Nutrition , Esophagectomy , Jejunostomy , Adult , Humans , Esophagectomy/adverse effects , Jejunostomy/adverse effects , Retrospective Studies , Treatment Outcome , Male , FemaleABSTRACT
BACKGROUND: The present study aims to summarise current knowledge and identify gaps in knowledge and research regarding experience, decision-making and information needs around parenteral nutrition, among people with advanced cancer, and their carers. METHODS: This review was informed by previous methods and guidance on conducting and reporting scoping reviews. A literature search was conducted in March 2021 using Embase, Medline, CINAHL, Google and Web of Science to identify studies that examined the experience, decision-making process and information needs of adults with advanced cancer, and their carers, who were making decisions around commencing and discontinuing parenteral nutrition. There were no date limitations, although only papers published in English were included. RESULTS: Of the 588 papers identified, 12 papers, all qualitative, met the eligibility criteria. Despite the reported negative aspects of home parenteral nutrition, patients and carers felt the benefits outweighed these. There was variability in whether patients and carers felt involved in decisions around commencing parenteral nutrition. No studies specifically addressed information needs. CONCLUSIONS: Research is required to explore the information that patients with advanced cancer, and their carers, need to facilitate their decision-making around commencing and discontinuing parenteral nutrition. We recommend the development of processes for obtaining written informed consent from patients commencing parenteral nutrition to ensure that core topics are discussed on initiation, enabling patients and carers to make informed decisions. Additionally, we recommend development of a national framework to inform patients and carers of the whole discharge process on PN from decision-making to discontinuing PN.
Subject(s)
Neoplasms , Parenteral Nutrition, Home , Adult , Humans , Caregivers , Neoplasms/therapy , Patient Discharge , CognitionABSTRACT
OBJECTIVE: Personalised care requires the identification of modifiable risk factors so that interventions can be implemented rapidly following a gynaecological cancer diagnosis. Our objective was to determine what pre-treatment factors are associated with quality of life (QOL) at baseline (pre-treatment) and 12 months. METHODS: 1222 women with a confirmed diagnosis of endometrial, ovarian, cervical or vulvar cancer from 82 UK NHS hospitals agreed to complete questionnaires at baseline, three and 12 months. Questionnaires included measures of QOL, health, lifestyle, support and self-management. The primary outcome measure was QOL as measured by Quality of Life in Adult Cancer Survivors (QLACS). Sites provided clinical data at baseline, six and 12 months. Linear regression models were constructed to examine the association between baseline characteristics and QOL outcomes. RESULTS: QOL declined between baseline and 3 months, followed by an improvement at 12 months. Baseline (pre-treatment) factors associated with worse QOL at both baseline and 12 months were depression, anxiety, living in a more deprived area and comorbidities which limit daily activities, whereas higher self-efficacy and age of 50+ years were associated with better QOL. CONCLUSIONS: Depression, anxiety and self-efficacy are modifiable risk factors that can impact on QOL. Screening for these, and assessment of whether comorbidities limit daily activities, should be incorporated in a holistic needs assessment and interventions to improve self-efficacy should be made available. Care can then be personalised from the outset to enable all women with a gynaecological cancer the opportunity to have the best QOL.
Subject(s)
Genital Neoplasms, Female , Quality of Life , Adult , Anxiety/etiology , Cohort Studies , Female , Genital Neoplasms, Female/diagnosis , Genital Neoplasms, Female/epidemiology , Genital Neoplasms, Female/therapy , Humans , Middle Aged , Surveys and Questionnaires , United KingdomABSTRACT
PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core Questionnaire (QLQ-C30) is a widely used generic self-report measure of health-related quality of life (HRQOL) for cancer patients. However, no validated voice script for interviewer-led telephone administration was previously available. The aim of this study was to develop a voice script for interviewer administration via telephone. METHODS: Following guidelines from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) PRO Mixed Modes Good Research Practices Task Force, a randomised cross-over equivalence study, including cognitive debriefing, was conducted to assess equivalence between paper and telephone administration modes. Assuming an expected intraclass correlation coefficient (ICC) of 0.70 and a minimally acceptable level of 0.50, a sample size of 63 was required. RESULTS: Cognitive interviews with five cancer patients found the voice script to be clear and understandable. Due to a protocol deviation in the first wave of testing, only 26 patients were available for analyses. A second wave of recruitment was conducted, adding 37 patients (n = 63; mean age 55.48; 65.1% female). Total ICCs for mode comparison ranged from 0.72 (nausea and vomiting, 95% CI 0.48-0.86) to 0.90 (global health status/QoL, 95% CI 0.80-0.95; pain, 95% CI 0.79-0.95; constipation, 95% CI 0.80-0.95). For paper first administration, all ICCs were above 0.70, except nausea and vomiting (ICC 0.55; 95% CI 0.24-0.76) and financial difficulties (ICC 0.60; 95% CI 0.31-0.79). For phone first administration, all ICCs were above 0.70. CONCLUSIONS: The equivalence testing results support the voice script's validity for administration of the QLQ-C30 via telephone.
Subject(s)
Neoplasms , Quality of Life , Female , Health Status , Humans , Male , Middle Aged , Neoplasms/psychology , Quality of Life/psychology , Surveys and Questionnaires , TelephoneABSTRACT
AIM: Nutrition is associated with aetiology and impacts outcomes in colorectal cancer (CRC). This study aimed to explore nutritional symptoms and concerns of patients with CRC and CRC dietetic resource across the UK. METHODS: Study 1 is a descriptive analysis of nutrition-related measures in the ColoRectal Wellbeing (CREW) study, a prospective 5-year longitudinal cohort study of a representative sample of 872 adults with non-metastatic CRC. Study 2 is a descriptive analysis of data collected using a freedom of information request to all UK trusts/boards on dietetic resources for CRC. RESULTS: Study 1 found that 31% of CREW participants wanted more diet and lifestyle advice. At 3 months post-surgery, 10% reported poor appetite. A fifth experienced weight loss and 16% had concerns regarding weight loss 9 months post-surgery. In study 2 just 3% of hospitals providing CRC services had a dedicated CRC dietitian (hepato-pancreato-biliary, 11.1%; head and neck cancer, 14.3%). There was no dietetic outpatient follow-up of CRC patients in 72% of hospitals. CONCLUSIONS: Dietetic resource for patients with CRC is scarce even though weight loss, poor appetite and unmet needs are common and persist over time. Work is needed to embed nutritional care into the management of patients with CRC.
Subject(s)
Colorectal Neoplasms , Nutritional Status , Adult , Colorectal Neoplasms/complications , Diet , Humans , Longitudinal Studies , Prospective StudiesABSTRACT
AIM: Depression experienced by people with colorectal cancer (CRC) is an important clinical problem affecting quality of life. Recognition of depression at key points in the pathway enables timely referral to support. This study aimed to examine depression before and 5 years after surgery to examine its prevalence and identify determinants. METHOD: The ColoREctal Wellbeing (CREW) study is a prospective UK cohort study involving 872 adults with nonmetastatic CRC recruited before surgery with curative intent. Questionnaires completed before surgery and 3, 9, 15, 24, 36, 48 and 60 months after surgery captured socio-demographics and assessed depression (Centre for Epidemiologic Studies Depression Scale, CES-D) and other psychosocial factors. Clinical details were also gathered. We present the prevalence of clinically significant depression (CES-D ≥ 20) over time and its predictors assessed before and 2 years after surgery. RESULTS: Before surgery, 21.0% of the cohort reported CES-D ≥ 20 reducing to 14.7% 5 years after surgery. Presurgery risk factors predicting subsequent depression were clinically significant depression and anxiety, previous mental health service use, low self-efficacy, poor health, having neoadjuvant treatment and low social support. Postsurgery risk factors at 2 years predicting subsequent depression were clinically significant depression, negative affect, cognitive dysfunction, accommodation type and poor health. CONCLUSION: Depression is highly pervasive in people with CRC, exceeding prevalence in the general population across follow-up. Our findings emphasize the need to screen and treat depression across the pathway. Our novel data highlight key risk factors of later depression at important and opportune time points: before surgery and at the end of routine surveillance. Early recognition and timely referral to appropriate support is vital to improve long-term psychological outcomes.
Subject(s)
Colorectal Neoplasms , Quality of Life , Adult , Anxiety , Cohort Studies , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/surgery , Depression/epidemiology , Depression/etiology , Humans , Prevalence , Prospective StudiesABSTRACT
PURPOSE: This systematic review was performed to identify all relevant health-related quality of life (HRQoL) issues associated with COVID-19. METHODS: A systematic literature search was undertaken in April 2020. In four teams of three reviewers each, all abstracts were independently reviewed for inclusion by two reviewers. Using a pre-defined checklist of 93 criteria for each publication, data extraction was performed independently by two reviewers and subsequently compared and discussed. If necessary, a third reviewer resolved any discrepancies. The search was updated in February 2021 to retrieve new publications on HRQoL issues including issues related to the long-term consequences of COVID-19. RESULTS: The search in April 2020 identified 3342 potentially relevant publications, and 339 publications were selected for full-text review and data extraction. We identified 75 distinct symptoms and other HRQoL issues categorized into 12 thematic areas; from general symptoms such as fever, myalgia, and fatigue, to neurological and psychological issues. The updated search revealed three extra issues experienced during active disease and long-term problems with fatigue, psychological issues and impaired cognitive function. CONCLUSION: This first comprehensive systematic review provides a detailed overview of the wide range of HRQoL issues experienced by patients with COVID-19 throughout the course of the disease. It demonstrates the devastating impact of the disease and provides critically important information for clinicians, to enable them to better recognize the disease and to provide knowledge important for treatment and follow-up. The results provided the foundation for the international development of a COVID-19 specific patient-reported HRQoL questionnaire.
Subject(s)
COVID-19/psychology , Quality of Life/psychology , COVID-19/epidemiology , Fatigue , Humans , Pandemics , Patient Reported Outcome Measures , SARS-CoV-2 , Surveys and QuestionnairesABSTRACT
It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate--predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.
Subject(s)
Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/metabolism , Frontal Lobe/metabolism , Nerve Net/metabolism , White Matter/metabolism , Adolescent , Adult , Cross-Sectional Studies , Diffusion Tensor Imaging/methods , Frontal Lobe/pathology , Humans , Male , Middle Aged , Nerve Net/pathology , White Matter/pathology , Young AdultABSTRACT
In humans, both language and fine motor skills are associated with left-hemisphere specialization, whereas visuospatial skills are associated with right-hemisphere specialization. Individuals with autism spectrum conditions (ASC) show a profile of deficits and strengths that involves these lateralized cognitive functions. Here we test the hypothesis that regions implicated in these functions are atypically rightward lateralized in individuals with ASC and, that such atypicality is associated with functional performance. Participants included 67 male, right-handed adults with ASC and 69 age- and IQ-matched neurotypical males. We assessed group differences in structural asymmetries in cortical regions of interest with voxel-based analysis of grey matter volumes, followed by correlational analyses with measures of language, motor and visuospatial skills. We found stronger rightward lateralization within the inferior parietal lobule and reduced leftward lateralization extending along the auditory cortex comprising the planum temporale, Heschl's gyrus, posterior supramarginal gyrus, and parietal operculum, which was more pronounced in ASC individuals with delayed language onset compared to those without. Planned correlational analyses showed that for individuals with ASC, reduced leftward asymmetry in the auditory region was associated with more childhood social reciprocity difficulties. We conclude that atypical cerebral structural asymmetry is a potential candidate neurophenotype of ASC.
Subject(s)
Autistic Disorder/complications , Autistic Disorder/pathology , Cerebral Cortex/pathology , Functional Laterality/physiology , Language Development Disorders/etiology , Acoustic Stimulation , Adolescent , Adult , Brain Mapping , Cognition Disorders/diagnosis , Cognition Disorders/etiology , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Photic Stimulation , Psychiatric Status Rating Scales , Space Perception , Statistics as Topic , Young AdultABSTRACT
BACKGROUND: Informal carers of cancer patients with cachexia face additional challenges to those encountered by informal carers in general because of the central role food and eating play in everyday life. Patient weight loss and anorexia, core features of cancer cachexia, are frequent causes of distress in caregivers. Identification of quality of life issues can inform the development of interventions for both caregivers and patients and facilitate communication with healthcare professionals. AIM: To identify quality of life issues that are relevant to carers of cancer patients with cachexia. DESIGN: A systematic review and thematic synthesis of the qualitative literature were conducted. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: PubMed, ISI Web of Knowledge, EMBASE, MEDLINE, CINAHL, PsycINFO and PsycARTICLES were searched for publications dated from January 1980 to February 2015 using search terms relating to cancer, cachexia, quality of life and carers. Papers written in the English language, featuring direct quotes from the carers of adult patients with any cancer diagnosis and cachexia or problems with weight loss or anorexia, were included. RESULTS: Five themes were extracted from the 16 identified studies. These highlighted the impact on everyday life, the attempts of some carers to take charge, the need for healthcare professional's input, conflict with the patient and negative emotions. CONCLUSION: The complexity of caring for a cancer patient with cachexia translates into a range of problems and experiences for informal carers. By addressing the impact of caring for a patient with cancer cachexia on carers, both caregiver and patient quality of life may improve.
Subject(s)
Cachexia/psychology , Caregivers/psychology , Neoplasms/nursing , Quality of Life , Cachexia/etiology , Health Services Needs and Demand , Humans , Interpersonal Relations , Neoplasms/complications , Neoplasms/psychology , Qualitative ResearchABSTRACT
OBJECTIVES: The objective was to map the experiences and needs of patients presenting with symptoms of suspected cancer in the primary care interval (from when they first present to primary care to their first appointment or referral to a secondary or tertiary level healthcare facility). DESIGN: This was a scoping review. INCLUSION CRITERIA: Studies or reports written in English which included primary data on the primary care interval experiences and/or needs of adult patients presenting with new symptoms of suspected cancer were eligible. Studies which only included patients with secondary or recurring cancer, conference abstracts and reviews were excluded. No date limits were applied. METHODS: The Joanna Briggs Institute method for Scoping Reviews guided screening, report selection and data extraction. At least two independent reviewers contributed to each stage. Medline, CINAHL, PsychInfo, Embase and Web of Science were searched and several grey literature resources. Relevant quantitative findings were qualitised and integrated with qualitative findings. A thematic analysis was carried out. RESULTS: Of the 4855 records identified in the database search, 18 were included in the review, along with 13 identified from other sources. The 31 included studies were published between 2002 and 2023 and most (n=17) were conducted in the UK. Twenty subthemes across four themes (patient experience, interpersonal, healthcare professional (HCP) skills, organisational) were identified. No studies included patient-reported outcome measures. Patients wanted (1) to feel heard and understood by HCPs, (2) a plan to establish what was causing their symptoms, and (3) information about the next stages of the diagnostic process. CONCLUSIONS: Scoping review findings can contribute to service planning as the cancer diagnostic pathway for symptomatic presentation of cancer evolves. The effectiveness of this pathway should be evaluated not only in terms of clinical outcomes, but also patient-reported outcomes and experience, along with the perspectives of primary care HCPs.
Subject(s)
Neoplasms , Adult , Humans , Neoplasms/diagnosis , Health Personnel , Emotions , Patients , Primary Health CareABSTRACT
PURPOSE: The purpose of this systematic review is to better understand access to, acceptance of and adherence to cancer prehabilitation. METHODS: MEDLINE, CINAHL, PsychINFO, Embase, Physiotherapy Evidence Database, ProQuest Medical Library, Cochrane Library, Web of Science and grey literature were systematically searched for quantitative, qualitative and mixed-methods studies published in English between January 2017 and June 2023. Screening, data extraction and critical appraisal were conducted by two reviewers independently using Covidence™ systematic review software. Data were analysed and synthesised thematically to address the question 'What do we know about access, acceptance and adherence to cancer prehabilitation, particularly among socially deprived and minority ethnic groups?' The protocol is published on PROSPERO CRD42023403776 RESULTS: Searches identified 11,715 records, and 56 studies of variable methodological quality were included: 32 quantitative, 15 qualitative and nine mixed-methods. Analysis identified facilitators and barriers at individual and structural levels, and with interpersonal connections important for prehabilitation access, acceptance and adherence. No study reported analysis of facilitators and barriers to prehabilitation specific to people from ethnic minority communities. One study described health literacy as a barrier to access for people from socioeconomically deprived communities. CONCLUSIONS: There is limited empirical research of barriers and facilitators to inform improvement in equity of access to cancer prehabilitation. IMPLICATIONS FOR CANCER SURVIVORS: To enhance the inclusivity of cancer prehabilitation, adjustments may be needed to accommodate individual characteristics and attention given to structural factors, such as staff training. Interpersonal connections are proposed as a fundamental ingredient for successful prehabilitation.
ABSTRACT
PURPOSE: Assessing the health-related quality of life (HRQOL) of cancer patients with cachexia is particularly important because treatments for cachexia are currently aimed at palliation and treatment efficacy must be measured in ways other than survival. The aim of this systematic review was to evaluate HRQOL assessment in cancer patients with cachexia. METHODS: Using guidance from the Centre for Reviews and Dissemination, relevant databases were searched from January 1980 to January 2012 with terms relating to cancer, cachexia and HRQOL for papers including adult cancer patients with cachexia or documented weight loss at baseline. RESULTS: We found one cachexia-specific instrument, the Functional Assessment of Anorexia/Cachexia Therapy, but the tool has not been fully validated, does not cover all the relevant domains and the consensus-based standards for the selection of health status measurement instruments checklist highlighted a number of weaknesses in the methodological quality of the validation study. Sixty-seven studies assessed HRQOL in cachectic or weight-losing cancer patients. Most used generic cancer HRQOL instruments, limiting the amount of useful information they provide. A modified version of the Efficace minimum data checklist demonstrated that the quality of reporting on HRQOL tool use was inadequate in many of the studies. A negative relationship between HRQOL and weight loss was found in 23 of the 27 studies which directly examined this. CONCLUSION: There is a pressing need for a well-designed HRQOL tool for use with this patient group in both clinical trials and clinical practice.
Subject(s)
Anorexia/etiology , Cachexia/etiology , Health Status , Neoplasms/complications , Quality of Life , Anorexia/drug therapy , Cachexia/drug therapy , Humans , Neoplasms/psychology , Treatment OutcomeABSTRACT
BACKGROUND: The LOw RISk DCIS (LORIS) study was set up to compare conventional surgical treatment with active monitoring in women with ductal carcinoma in situ (DCIS). Recruitment to trials with a surveillance arm is known to be challenging, so strategies to maximise patient recruitment, aimed at both patients and recruiting centres, were implemented. METHODS: Women aged ≥ 46 years with a histologically confirmed diagnosis of non-high-grade DCIS were eligible for 1:1 randomisation to either surgery or active monitoring. Prior to randomisation, all eligible women were invited to complete: (1) the Clinical Trials Questionnaire (CTQ) examining reasons for or against participation, and (2) interviews exploring in depth opinions about the study information sheets and film. Women agreeing to randomisation completed validated questionnaires assessing health status, physical and mental health, and anxiety levels. Hospital site staff were invited to communication workshops and refresher site initiation visits to support recruitment. Their perspectives on LORIS recruitment were collected via surveys and interviews. RESULTS: Eighty percent (181/227) of eligible women agreed to be randomised. Over 40% of participants had high anxiety levels at baseline. On the CTQ, the most frequent most important reasons for accepting randomisation were altruism and belief that the trial offered the best treatment, whilst worries about randomisation and the influences of others were the most frequent most important reasons for declining. Most women found the study information provided clear and useful. Communication workshops for site staff improved knowledge and confidence but only about half said they themselves would join LORIS if eligible. The most common recruitment barriers identified by staff were low numbers of eligible patients and patient preference. CONCLUSIONS: Recruitment to LORIS was challenging despite strategies aimed at both patients and site staff. Ensuring that recruiting staff support the study could improve recruitment in similar future trials. TRIAL REGISTRATION: ISRCTN27544579, prospectively registered on 22 May 2014.
Subject(s)
Carcinoma, Intraductal, Noninfiltrating , Female , Humans , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Carcinoma, Intraductal, Noninfiltrating/surgery , Health Status , Patient Selection , Middle AgedABSTRACT
AIM: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) is among the most widely used patient-reported outcome measures in cancer research and practice. It was developed prior to guidance that content should be established directly from patients to confirm it measures concepts of interest and is appropriate and comprehensive for the intended population. This study evaluated the content validity of the QLQ-C30 for use with cancer patients. METHODS: Adults undergoing cancer treatment in Europe and the USA participated in open-ended concept elicitation interviews regarding their functional health, symptoms, side-effects and impacts on health-related quality of life. Thematic analysis was conducted, and similarities across cancer types, disease stages and countries or languages were explored. RESULTS: Interviews with 113 patients with cancer (85 European, 28 USA) including breast, lung, prostate, colorectal and other cancers were conducted between 2016 and 2020. Conceptual saturation was achieved. The most frequently reported concepts were included in the QLQ-C30 conceptual framework. QLQ-C30 items were widely understood across language versions and were relevant to patients across cancer types and disease stages. While several new concepts were elicited such as difficulty climbing steps or stairs, weight loss, skin problems and numbness, many were not widely experienced and/or could be considered sub-concepts of existing concepts. CONCLUSIONS: The QLQ-C30 demonstrates good evidence of content validity for the assessment of functional health, symptom burden and health-related quality of life in patients with localised-to-advanced cancer.
Subject(s)
Neoplasms , Quality of Life , Adult , Male , Humans , Health Status , Surveys and Questionnaires , Neoplasms/therapy , Neoplasms/diagnosis , Patient Reported Outcome MeasuresABSTRACT
Individual differences in cognitive style can be characterized along two dimensions: 'systemizing' (S, the drive to analyze or build 'rule-based' systems) and 'empathizing' (E, the drive to identify another's mental state and respond to this with an appropriate emotion). Discrepancies between these two dimensions in one direction (S>E) or the other (E>S) are associated with sex differences in cognition: on average more males show an S>E cognitive style, while on average more females show an E>S profile. The neurobiological basis of these different profiles remains unknown. Since individuals may be typical or atypical for their sex, it is important to move away from the study of sex differences and towards the study of differences in cognitive style. Using structural magnetic resonance imaging we examined how neuroanatomy varies as a function of the discrepancy between E and S in 88 adult males from the general population. Selecting just males allows us to study discrepant E-S profiles in a pure way, unconfounded by other factors related to sex and gender. An increasing S>E profile was associated with increased gray matter volume in cingulate and dorsal medial prefrontal areas which have been implicated in processes related to cognitive control, monitoring, error detection, and probabilistic inference. An increasing E>S profile was associated with larger hypothalamic and ventral basal ganglia regions which have been implicated in neuroendocrine control, motivation and reward. These results suggest an underlying neuroanatomical basis linked to the discrepancy between these two important dimensions of individual differences in cognitive style.
Subject(s)
Brain Mapping , Brain/anatomy & histology , Cognition/physiology , Empathy/physiology , Adolescent , Adult , Brain/physiology , Humans , Image Interpretation, Computer-Assisted , Magnetic Resonance Imaging , Male , Sex Characteristics , Young AdultABSTRACT
BACKGROUND: We aimed to create a questionnaire to assess the health-related quality of life including functioning, symptoms, and general health status of adult patients with current or previous COVID-19. Here, we report on Phase I and II of the development. METHODS: Internationally recognized methodology for questionnaire development was followed. In Phase I, a comprehensive literature review was performed to identify relevant COVID-19 issues. Decisions for inclusion, exclusion, and data extraction were completed independently in teams of two and then compared. The resulting issues were discussed with health care professionals (HCPs) and current and former COVID-19 patients. The input of HCPs and patients was carefully considered, and the list of issues updated. In Phase II, this updated list was operationalized into items/questions. RESULTS: The literature review yielded 3342 publications, 339 of which were selected for full-text review, and 75 issues were identified. Discussions with 44 HCPs from seven countries and 52 patients from six countries showed that psychological symptoms, worries, and reduced functioning lasted the longest for patients, and there were considerable discrepancies between HCPs and patients concerning the importance of some of the symptoms. The final list included 73 issues, which were operationalized into an 80-item questionnaire. CONCLUSION: The resulting COVID-19 questionnaire covers health-related quality of life issues relevant to COVID-19 patients and is available in several languages. The next steps include testing of the applicability and patients' acceptability of the questionnaire (Phase IIIA) and preliminary psychometric testing (Phase IIIB).
ABSTRACT
The 'self' is a complex multidimensional construct deeply embedded and in many ways defined by our relations with the social world. Individuals with autism are impaired in both self-referential and other-referential social cognitive processing. Atypical neural representation of the self may be a key to understanding the nature of such impairments. Using functional magnetic resonance imaging we scanned adult males with an autism spectrum condition and age and IQ-matched neurotypical males while they made reflective mentalizing or physical judgements about themselves or the British Queen. Neurotypical individuals preferentially recruit the middle cingulate cortex and ventromedial prefrontal cortex in response to self compared with other-referential processing. In autism, ventromedial prefrontal cortex responded equally to self and other, while middle cingulate cortex responded more to other-mentalizing than self-mentalizing. These atypical responses occur only in areas where self-information is preferentially processed and does not affect areas that preferentially respond to other-referential information. In autism, atypical neural self-representation was also apparent via reduced functional connectivity between ventromedial prefrontal cortex and areas associated with lower level embodied representations, such as ventral premotor and somatosensory cortex. Furthermore, the magnitude of neural self-other distinction in ventromedial prefrontal cortex was strongly related to the magnitude of early childhood social impairments in autism. Individuals whose ventromedial prefrontal cortex made the largest distinction between mentalizing about self and other were least socially impaired in early childhood, while those whose ventromedial prefrontal cortex made little to no distinction between mentalizing about self and other were the most socially impaired in early childhood. These observations reveal that the atypical organization of neural circuitry preferentially coding for self-information is a key mechanism at the heart of both self-referential and social impairments in autism.