A hybrid open-top light-sheet microscope for versatile multi-scale imaging of cleared tissues.

Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need for a flexible system that can address imaging applications with varied requirements in terms of resolution, sample size, tissue-clearing protocol, and transparent sample-holder material. Here, we present a 'hybrid' system that combines a unique non-orthogonal dual-objective and conventional (orthogonal) open-top light-sheet (OTLS) architecture for versatile multi-scale volumetric imaging. We demonstrate efficient screening and targeted sub-micrometer imaging of sparse axons within an intact, cleared mouse brain. The same system enables high-throughput automated imaging of multiple specimens, as spotlighted by a quantitative multi-scale analysis of brain metastases. Compared with existing academic and commercial light-sheet microscopy systems, our hybrid OTLS system provides a unique combination of versatility and performance necessary to satisfy the diverse requirements of a growing number of cleared-tissue imaging applications.

Axially swept open-top light-sheet microscopy for densely labeled clinical specimens.

Open-top light-sheet (OTLS) microscopy offers rapid 3D imaging of large optically cleared specimens. This enables nondestructive 3D pathology, which provides key advantages over conventional slide-based histology including comprehensive sampling without tissue sectioning/destruction and visualization of diagnostically important 3D structures. With 3D pathology, clinical specimens are often labeled with small-molecule stains that broadly target nucleic acids and proteins, mimicking conventional hematoxylin and eosin (H&E) dyes. Tight optical sectioning helps to minimize out-of-focus fluorescence for high-contrast imaging in these densely labeled tissues but has been challenging to achieve in OTLS systems due to trade-offs between optical sectioning and field of view. Here we present an OTLS microscope with voice-coil-based axial sweeping to circumvent this trade-off, achieving 2 µm axial resolution over a 750 × 375 µm field of view. We implement our design in a non-orthogonal dual-objective (NODO) architecture, which enables a 10-mm working distance with minimal sensitivity to refractive index mismatches, for high-contrast 3D imaging of clinical specimens.

Health-related quality of life after a diagnosis of bladder cancer: a longitudinal survey over the first year.

OBJECTIVES: To describe the health-related quality of life (HRQoL) of patients in a prospective 12-month observational cohort study of new bladder cancer diagnoses and compare with national cancer and general population surveys. PATIENTS AND METHODS: A prospective UK study in patients with new bladder cancer diagnoses at 13 NHS Trusts. The HRQoL data were collected at 3, 6, 9 and 12 months. Questionnaires used included: the EuroQoL five Dimensions (EQ-5D), European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-30-item core, EORTC QLQ-24-item non-muscle-invasive bladder cancer, and EORTC QLQ-30-item muscle-invasive bladder cancer. Results were compared with the Cancer Quality of Life Survey and Health Survey for England. RESULTS: A total of 349 patients were recruited, 296 (85%) completed the first (baseline) and 233 (67%) the final survey. The patients underwent transurethral resection of bladder tumour (TURBT) ± intravesical therapy (238 patients, 80%), radical cystectomy/radiotherapy (51, 17%) or palliation (seven, 2%). At baseline, patients needing radical treatment reported worse HRQoL including lower social function (74.2 vs 83.8, P = 0.002), increased fatigue (31.5 vs 26.1, P = 0.03) and more future worries (39.2 vs 29.4, P = 0.005) than patients who underwent TURBT. Post-treatment surveys showed no change/improvements for patients who underwent TURBT but deterioration for the radically treated cohort. At final survey, reports were similar to baseline, regardless of treatment. Radically treated patients continued to report poorer HRQoL including issues with body image (23.4 vs 12.5, P = 0.007) and male sexual function (75.8 vs 40.4, P < 0.001) compared to those who underwent TURBT. Radically treated patients reported lower EQ-5D utility scores and more problems with usual activities than the general population. DISCUSSION: Patients undergoing TURBT can be reassured regarding HRQoL following treatment. However, those requiring radical treatment report greater changes in HRQoL with the need for appropriate clinical and supportive care to minimise the impact of treatments.

Nondestructive 3D pathology with analysis of nuclear features for prostate cancer risk assessment.

Prostate cancer treatment decisions rely heavily on subjective visual interpretation [assigning Gleason patterns or International Society of Urological Pathology (ISUP) grade groups] of limited numbers of two-dimensional (2D) histology sections. Under this paradigm, interobserver variance is high, with ISUP grades not correlating well with outcome for individual patients, and this contributes to the over- and undertreatment of patients. Recent studies have demonstrated improved prognostication of prostate cancer outcomes based on computational analyses of glands and nuclei within 2D whole slide images. Our group has also shown that the computational analysis of three-dimensional (3D) glandular features, extracted from 3D pathology datasets of whole intact biopsies, can allow for improved recurrence prediction compared to corresponding 2D features. Here we seek to expand on these prior studies by exploring the prognostic value of 3D shape-based nuclear features in prostate cancer (e.g. nuclear size, sphericity). 3D pathology datasets were generated using open-top light-sheet (OTLS) microscopy of 102 cancer-containing biopsies extracted ex vivo from the prostatectomy specimens of 46 patients. A deep learning-based workflow was developed for 3D nuclear segmentation within the glandular epithelium versus stromal regions of the biopsies. 3D shape-based nuclear features were extracted, and a nested cross-validation scheme was used to train a supervised machine classifier based on 5-year biochemical recurrence (BCR) outcomes. Nuclear features of the glandular epithelium were found to be more prognostic than stromal cell nuclear features (area under the ROC curve [AUC] = 0.72 versus 0.63). 3D shape-based nuclear features of the glandular epithelium were also more strongly associated with the risk of BCR than analogous 2D features (AUC = 0.72 versus 0.62). The results of this preliminary investigation suggest that 3D shape-based nuclear features are associated with prostate cancer aggressiveness and could be of value for the development of decision-support tools. © 2023 The Pathological Society of Great Britain and Ireland.

Visual Assessment of 2-Dimensional Levels Within 3-Dimensional Pathology Data Sets of Prostate Needle Biopsies Reveals Substantial Spatial Heterogeneity.

Prostate cancer prognostication largely relies on visual assessment of a few thinly sectioned biopsy specimens under a microscope to assign a Gleason grade group (GG). Unfortunately, the assigned GG is not always associated with a patient's outcome in part because of the limited sampling of spatially heterogeneous tumors achieved by 2-dimensional histopathology. In this study, open-top light-sheet microscopy was used to obtain 3-dimensional pathology data sets that were assessed by 4 human readers. Intrabiopsy variability was assessed by asking readers to perform Gleason grading of 5 different levels per biopsy for a total of 20 core needle biopsies (ie, 100 total images). Intrabiopsy variability (Cohen κ) was calculated as the worst pairwise agreement in GG between individual levels within each biopsy and found to be 0.34, 0.34, 0.38, and 0.43 for the 4 pathologists. These preliminary results reveal that even within a 1-mm-diameter needle core, GG based on 2-dimensional images can vary dramatically depending on the location within a biopsy being analyzed. We believe that morphologic assessment of whole biopsies in 3 dimension has the potential to enable more reliable and consistent tumor grading.

Long-term care for people treated for cancer during childhood and adolescence.

Worldwide advances in treatment and supportive care for children and adolescents with cancer have resulted in a increasing population of survivors growing into adulthood. Yet, this population is at very high risk of late occurring health problems, including significant morbidity and early mortality. Unique barriers to high-quality care for this group include knowledge gaps among both providers and survivors as well as fragmented health-care delivery during the transition from paediatric to adult care settings. Survivors of childhood and adolescent cancer are at risk for a range of late-occuring side-effects from treatment, including cardiac, endocrine, pulmonary, fertility, renal, psychological, cognitive, and socio-developmental impairments. Care coordination and transition to adult care are substantial challenges, but can be empowering for survivors and improve outcomes, and could be facilitated by clear, effective communication and support for self-management. Resources for adult clinical care teams and primary care providers include late-effects surveillance guidelines and web-based support services.

International variation in childhood cancer mortality rates from 2001 to 2015: Comparison of trends in the International Cancer Benchmarking Partnership countries.

Despite improved survival rates, cancer remains one of the most common causes of childhood death. The International Cancer Benchmarking Partnership (ICBP) showed variation in cancer survival for adults. We aimed to assess and compare trends over time in cancer mortality between children, adolescents and young adults (AYAs) and adults in the six countries involved in the ICBP: United Kingdom, Denmark, Australia, Canada, Norway and Sweden. Trends in mortality between 2001 and 2015 in the six original ICBP countries were examined. Age standardised mortality rates (ASR per million) were calculated for all cancers, leukaemia, malignant and benign central nervous system (CNS) tumours, and non-CNS solid tumours. ASRs were reported for children (age 0-14 years), AYAs aged 15 to 39 years and adults aged 40 years and above. Average annual percentage change (AAPC) in mortality rates per country were estimated using Joinpoint regression. For all cancers combined, significant temporal reductions were observed in all countries and all age groups. However, the overall AAPC was greater for children (-2.9; 95% confidence interval = -4.0 to -1.7) compared to AYAs (-1.8; -2.1 to -1.5) and adults aged >40 years (-1.5; -1.6 to -1.4). This pattern was mirrored for leukaemia, CNS tumours and non-CNS solid tumours, with the difference being most pronounced for leukaemia: AAPC for children -4.6 (-6.1 to -3.1) vs AYAs -3.2 (-4.2 to -2.1) and over 40s -1.1 (-1.3 to -0.8). AAPCs varied between countries in children for all cancers except leukaemia, and in adults over 40 for all cancers combined, but not in subgroups. Improvements in cancer mortality rates in ICBP countries have been most marked among children aged 0 to 14 in comparison to 15 to 39 and over 40 year olds. This may reflect better care, including centralised service provision, treatment protocols and higher trial recruitment rates in children compared to older patients.

Sexual Activity, Function and Dysfunction After a Diagnosis of Bladder Cancer.

BACKGROUND: Sexual dysfunction is common in those affected by cancer and local and radical treatments for Bladder Cancer (BC) can affect sexual function directly. AIM: To evaluate sexual function following a bladder cancer (BC) diagnosis. METHODS: Self-reported sexual function was collected 10 years after a diagnosis of BC as part of a cross-sectional patient reported outcome measure (PROM) survey exploring life after BC diagnosis and treatment. OUTCOMES: Participants completed a combined EORTC QLQ-BLM30 and QLQ-NMIBC24 questionnaire, including questions on sexual activity, intimacy, erectile/ejaculatory function and vaginal dryness. RESULTS: A total of 1796 participants returned a completed survey out of 3279 eligible participants (55%). Of the participants who returned a completed survey, a total of 1530 (85%) participants answered sexual function questions. The median (IQR) age was 75 (70-81). Participants were predominantly men (78%) and married/in civil partnerships (66%). In total, 31% were sexually active. Vaginal dryness was common (66%) in women. Erectile and ejaculatory dysfunction (80% and 58% respectively) were common in men. Compared to TURBT +/- intravesical treatments, those who had radical treatment were less likely to be sexually active (adjusted OR 0.56, 95% CI: 0.44-0.72, P<0.001) and had worse mean scores for intimacy problems (29.1 [radical treatment] vs 12.1, P<0.001), male sexual problems (72.2 [radical treatment] vs 45.7, P<0.001) and overall sexual function (17.1 [radical treatment] vs 20.3, P=0.01). CLINICAL IMPLICATIONS: These findings highlight the magnitude of sexual dysfunction in the BC patient cohort and can help inform patients during the pre-op counselling process and shared decision making prior to BC treatments. STRENGTHS AND LIMITATIONS: This study provides the largest in-depth analysis of sexual activity and function after BC diagnosis and treatment, to date. Limitations include the lack of data on participants' sexual function prior to BC treatment and the heterogeneity with respect to time passed since last BC treatment. CONCLUSION: Sexual dysfunction in BC patients is common and rates appear higher following radical treatments compared to endoscopic. It is important to elicit these problems in clinics to enable counselling and treatment. Jubber I, Rogers Z, Catto JWF, et al. Sexual Activity, Function and Dysfunction After a Diagnosis of Bladder Cancer. J Sex Med 2022;19:1431-1441.

Standardizing the surgical management of benign ovarian tumors in children and adolescents: A best practice Delphi consensus statement.

AIM: No widely agreed consensus protocols exist for the management of benign ovarian tumors (BOT) in children. This presents a substantial risk for suboptimal management. We aimed to generate multispecialty consensus guidance to standardize surgical management and provide a clear follow-up protocol for children with BOTs. METHODS: Prospective two-round confidential e-Delphi consensus survey distributed among multispecialty expert panel; concluded by two semistructured videoconferences. MAIN RESULTS: Consensus was generated on these core outcome sets: preoperative/intraoperative management; follow-up; adolescent gynecology referral. (1) Children with BOTs should receive the same management as other patients with potentially neoplastic lesions: Preoperative discussion at a pediatric oncology multidisciplinary meeting to risk stratify tumors, and management by health professionals with expertise in ovarian-sparing surgery and laparoscopy. (2) Ovarian-sparing surgery for BOTs should be performed wherever possible to maximize fertility preservation. (3) Ovarian masses detected during emergency laparoscopy/laparotomy should be left in situ wherever feasible and investigated appropriately (imaging/tumor markers) before resection. (4) Follow-up should be undertaken for all patients after BOT resection. Patients should be offered referral to adolescent gynecology to discuss fertility implications. CONCLUSION: This best practice Delphi consensus statement emphasizes the importance of managing children with BOTs through a well-defined oncological MDT strategy, in order to optimize risk stratification and allow fertility preservation by ovarian-sparing surgery wherever possible.

Long-term unmet supportive care needs of teenage and young adult (TYA) childhood brain tumour survivors and their caregivers: a cross-sectional survey.

INTRODUCTION: The supportive care needs of long-term childhood brain tumour survivors, now teenagers and young adults (TYAs), and their caregivers are largely unknown. We aimed to describe their supportive care needs and explore associations between needs and quality of life (QoL). METHODS: Participants were recruited from long-term follow-up clinics (in three NHS Trusts in England) and online. Participants included childhood brain tumour survivors, ≥ 5 years from diagnosis, currently aged 13-30, and their primary caregivers. Survivors completed the Supportive Care Needs Survey (SCNS) Short Form and caregivers the SCNS-Partners & Caregivers, alongside validated QoL questionnaires (Peds-FACT-Br and CQOLC). RESULTS: In total, 112 individuals (69 survivors/43 caregivers) participated. Survivors reported on average 9.4 (± 8.5) unmet needs. Needs were greatest in the psychological domain, with anxiety (60.3%), uncertainty about the future (50.7%) and feeling down and depressed (48.5%) most commonly reported. Caregivers reported on average 12.4 (± 12.3) unmet needs. Again, the greatest number of unmet needs was observed in the psychological domain. Many caregivers also reported information needs around financial support/government benefits (42.9%) and possible survivor fertility problems (42.9%). Multivariable linear regression analysis showed that female survivors, unemployed survivors, survivors further away from diagnosis and single caregivers were more likely to report unmet needs. More unmet needs were significantly associated with poorer QoL in survivors and caregivers. CONCLUSION: This research provides leads to improving supportive care and long-term follow-up services. Psychological support represents the biggest gap in care. Understanding unmet needs and recognising what services are required are critical to improving quality of long-term survival.

Stability of health-related quality of life and morbidity burden from 18 months after diagnosis of prostate cancer: results of a UK-wide population-based outcome cohort.

OBJECTIVE: To evaluate the dynamic nature of self-reported health-related quality of life (HRQL) and morbidity burden in men diagnosed with prostate cancer, we performed a follow-up study of the Life After Prostate Cancer Diagnosis (LAPCD) study cohort 12 months after initial survey. METHODS: The LAPCD study collected information from 35,823 men across the UK who were 18-42 months post-diagnosis of prostate cancer. Men who were still alive 12 months later were resurveyed. Generic HRQL (EQ-5D-5L plus self-assessed health rating) and prostate cancer-specific outcomes (EPIC-26) were assessed. Treatment(s) received was self-reported. Previously defined clinically meaningful differences were used to evaluate changes in outcomes over time. RESULTS: A total of 28,450 men across all disease stages completed follow-up surveys (85.8% response). Of the 21,700 included in this study, 89.7% reported no additional treatments since the first survey. This group experienced stable urinary and bowel outcomes, with good function for most men at both time points. On-going poor (but stable) urinary issues were associated with previous surgery. Sexual function scores remained low (mean: 26.8/100). Self-assessed health ratings were stable over time. The largest declines in HRQL and functional outcomes were experienced by men reporting their first active treatment between surveys. DISCUSSION: The results suggest stability of HRQL and most specific morbidities by 18-42 months for men who report no further treatment in the subsequent 12 months. This is reassuring for those with good function and HRQL but re-enforces the need for early intervention and support for men who experience poor outcomes.

The Effect of Antiseizure Medication Administration on Mortality and Early Posttraumatic Seizures in Critically Ill Older Adults with Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Older adults represent an understudied and growing TBI population. Current Brain Trauma Foundation guidelines support prophylactic antiseizure medication (ASM) administration to reduce the risk of early posttraumatic seizures (within 7 days of injury) in patients with severe TBI. Whether ASM decreases mortality or early seizure risk in this population remains unclear. This study addresses the knowledge gap regarding the impact of ASM administration on the risk of seizure or mortality after TBI in patients more than 65 years of age. METHODS: This retrospective cohort study used a publicly available data set from the Medical Information Mart for Intensive Care-III from the Massachusetts Institute of Technology. Our cohort included patients 65 years or older with a primary exposure of early ASM administration with TBI resulting in an intensive care unit (ICU) admission in a level I trauma center from 2001 to 2012. A double-robust inverse propensity scale weighted model on the basis of proportional hazard and logistic regression models was created to assess the association between ASM administration and risk of death within 7 days of admission to the ICU. Secondary outcomes included 30-day mortality and 1-year mortality, early posttraumatic seizures, ICU length of stay, and hospital length of stay. RESULTS: Of 1145 patients 65 years or older with TBI admitted to an ICU, 783 (68.4%) received ASM within the first 24 h. Patients meeting inclusion criteria were predominantly white (83.8%) and were male (52.3%), with a median (interquartile range) age of 81 (74-86) years. TBI severity, classified by Glasgow Coma Score, was predominantly mild (71.2%), followed by moderate (16.8%) and severe (11.3%). Patients who received ASM were less likely to have died at 7 days (adjusted death hazard ratio [HR] = 0.48 [95% confidence interval {CI} 0.28-0.88], P = 0.005), at 30 days (adjusted HR 0.67 [95% CI 0.45-0.99], P = 0.045), and at 1 year (adjusted HR 0.72 [95% CI 0.54-0.97], P = 0.029). Groups were not different in regard to seizure (adjusted seizure odds ratio 1.18 [95% CI 0.61-2.26]) compared with those who did not receive ASM. CONCLUSIONS: Early ASM administration was associated with reduced mortality at 7 days, 30 days, and 1 year but did not decrease the risk of early seizures among older adults who presented with TBI at an ICU. This benefit was observed in mild, moderate, and severe TBI assessed by Glasgow Coma Score on presentation among patients 65 years old and older and suggests broader recommendations for the use of ASM in older adults who present with TBI of any severity at an ICU.

Severity of COVID-19 in children with cancer: Report from the United Kingdom Paediatric Coronavirus Cancer Monitoring Project.

BACKGROUND: Children with cancer are frequently immunocompromised. While children are generally thought to be at less risk of severe SARS-CoV-2 infection than adults, comprehensive population-based evidence for the risk in children with cancer is unavailable. We aimed to produce evidence of the incidence and outcomes from SARS-CoV-2 in children with cancer attending all hospitals treating this population across the UK. METHODS: Retrospective and prospective observational study of all children in the UK under 16 diagnosed with cancer through data collection from all hospitals providing cancer care to this population. Eligible patients tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). The primary end-point was death, discharge or end of active care for COVID-19 for those remaining in hospital. RESULTS: Between 12 March 2020 and 31 July 2020, 54 cases were identified: 15 (28%) were asymptomatic, 34 (63%) had mild infections and 5 (10%) moderate, severe or critical infections. No patients died and only three patients required intensive care support due to COVID-19. Estimated incidence of hospital identified SARS-CoV-2 infection in children with cancer under 16 was 3%. CONCLUSIONS: Children with cancer with SARS-CoV-2 infection do not appear at increased risk of severe infection compared to the general paediatric population. This is reassuring and supports the continued delivery of standard treatment.

Experiences of Support for Sexual Dysfunction in Men With Prostate Cancer: Findings From a U.K.-Wide Mixed Methods Study.

BACKGROUND: Men with prostate cancer (PCa) often experience sexual dysfunction following diagnosis and treatment, yet little is known about the support they receive to deal with this. AIM: To explore men's experiences of support for sexual dysfunction following PCa diagnosis. METHODS: This study included a U.K.-wide survey of men 18-42 months post-diagnosis of PCa, identified through cancer registries. The survey measured sexual function and the extent to which men perceived sexual dysfunction to be a problem (Expanded Prostate Cancer Index Composite-26), access to and experience of medications, devices, and specialist services for sexual dysfunction, and included a free-text question for further comments. Analysis focussed on men who reported poor sexual function, which they considered a moderate or big problem. Descriptive statistics explored the characteristics of men offered intervention and those that found this helpful. Free-text responses were analyzed using thematic analysis. OUTCOME: The main outcome of this study was to assess access to and experience of medications, devices, and specialist services for sexual dysfunction. RESULTS: 39.0% of all survey respondents (13,978/35,823) reported poor sexual function, which they considered a moderate or big problem. 51.7% of these men were not offered any intervention to aid sexual functioning. 71.9% of those offered an intervention reported trying it, of whom 48.7% found the intervention helpful. Men treated with surgery or brachytherapy were most likely to be offered an intervention. Medication was the most commonly offered intervention and 39.3% of those who tried medication found this helpful. Although offered less often, approximately half of the men who tried devices or attended specialist services found the intervention helpful. Free-text responses indicated that barriers to accessing support included inadequate information and support from healthcare professionals, embarrassment, negative views about treatment options, concerns about side effects and safety, and inconsistencies between secondary and primary care. Barriers to continuing use included limited effectiveness of treatments, inadequate ongoing support, and funding constraints. Drivers of sexual recovery included patient proactivity and persistence with trying different treatment options and ongoing support from health professionals. CLINICAL IMPLICATIONS: There is an urgent need to ensure that all men are offered, and have equal access to, sexual care support, with referral to specialist services when required. STRENGTHS & LIMITATIONS: This study presents data from a large, U.K.-wide, population-based study of men with PCa and includes quantitative and qualitative findings. The possibility of non-response bias should, however, be considered. CONCLUSION: There are significant shortcomings in the support offered to U.K. men with sexual dysfunction following diagnosis and treatment for PCa which need to be addressed. Watson E, Wilding S, Matheson L, et al. Experiences of Support for Sexual Dysfunction in Men With Prostate Cancer: Findings From a U.K.-Wide Mixed Methods Study. J Sex Med 2021;18:515-525.

Unmet support needs in teenage and young adult childhood brain tumour survivors and their caregivers: "it's all the aftermath, and then you're forgotten about".

PURPOSE: Teenage and young adult (TYA) survivors of childhood brain tumours and their family caregivers can experience many late effects of treatment that can hamper the transition to living independent lives. Yet, their long-term supportive care needs are largely unknown. We investigated the supportive care needs of TYA survivors and their caregivers and explored the role and perceived use of support. METHODS: Face-to-face semi-structured interviews were conducted with survivors aged 16-30 (n = 11) who were ≥ 5 years after diagnosis and caregivers (n = 11). Interviews were recorded and transcriptions thematically analysed. RESULTS: Four themes emerged: (1) preferences for support and support services (unmet needs). Concerns regarding mental health, employment and financial uncertainty, the desire to live independently, and lack of support were emphasised. (2) Decline in support. Caregivers noted a drop-off in support available when transitioning to adult services. (3) Reasons for not obtaining adequate support. Several barriers to accessing support were raised, including distance and aging out of services. (4) The role of long-term hospital-based follow-up care. Participants highlighted the importance of, and reassurance from, long-term follow-up care but noted a more all-inclusive approach is required. CONCLUSIONS: Even many years after diagnosis, TYA childhood brain tumour survivors and their caregivers continue to have unmet supportive care needs. Both TYA survivors and their caregivers can benefit from support to meet their unique needs and improve long-term quality of life. Understanding unmet needs and recognising what services are required due to the late effects of treatment is critical to improving long-term quality of survival.

Strategies for living well with hormone-responsive advanced prostate cancer-a qualitative exploration.

PURPOSE: Due to recent treatment advances, men are increasingly living longer with advanced prostate cancer (PCa). This study sought to understand men's experiences of living with and adjusting to advanced hormone-responsive PCa and how this influenced their quality of life (QoL), in order to highlight how support could be optimized. METHODS: Participants were recruited through a UK wide survey-the 'Life After Prostate Cancer Diagnosis' study. In-depth telephone interviews were conducted with 24 men (aged 46-77 years) with advanced (stage IV) hormone-responsive PCa diagnosed 18-42 months previously. Thematic analysis was undertaken using a framework approach. RESULTS: Most participants perceived their QoL to be relatively good, which was influenced by the following factors (enablers to 'living well' with PCa): a sense of connectedness to others, engagement in meaningful activities, resources (social, cognitive, financial), ability to manage uncertainty, utilization of adjustment strategies and support, communication and information from health professionals. Barriers to 'living well' with PCa were often the converse of these factors. These also included more troublesome PCa-related symptoms and stronger perceptions of loss and restriction. CONCLUSIONS: In our study, men living with advanced hormone-responsive PCa often reported a good QoL. Exploring the influences on QoL in men with advanced PCa indicates how future interventions might improve the QoL of men who are struggling. Further research is required to develop and test interventions that enhance QoL for these men.

Understanding Barriers to Novel Data Linkages: Topic Modeling of the Results of the LifeInfo Survey.

BACKGROUND: Novel consumer and lifestyle data, such as those collected by supermarket loyalty cards or mobile phone exercise tracking apps, offer numerous benefits for researchers seeking to understand diet- and exercise-related risk factors for diseases. However, limited research has addressed public attitudes toward linking these data with individual health records for research purposes. Data linkage, combining data from multiple sources, provides the opportunity to enhance preexisting data sets to gain new insights. OBJECTIVE: The aim of this study is to identify key barriers to data linkage and recommend safeguards and procedures that would encourage individuals to share such data for potential future research. METHODS: The LifeInfo Survey consulted the public on their attitudes toward sharing consumer and lifestyle data for research purposes. Where barriers to data sharing existed, participants provided unstructured survey responses detailing what would make them more likely to share data for linkage with their health records in the future. The topic modeling technique latent Dirichlet allocation was used to analyze these textual responses to uncover common thematic topics within the texts. RESULTS: Participants provided responses related to sharing their store loyalty card data (n=2338) and health and fitness app data (n=1531). Key barriers to data sharing identified through topic modeling included data safety and security, personal privacy, requirements of further information, fear of data being accessed by others, problems with data accuracy, not understanding the reason for data linkage, and not using services that produce these data. We provide recommendations for addressing these issues to establish the best practice for future researchers interested in using these data. CONCLUSIONS: This study formulates a large-scale consultation of public attitudes toward this kind of data linkage, which is an important first step in understanding and addressing barriers to participation in research using novel consumer and lifestyle data.

Using the Framework Method for the Analysis of Qualitative Dyadic Data in Health Research.

There are an increasing number of qualitative studies which focus on the dyad (couples, families, caregivers-patients, health care professionals-patients). However, there is limited literature regarding qualitative methodology for dyadic analysis when members of the couple have been interviewed separately. The aim of this article is to share the knowledge we gained from undertaking a novel approach to dyadic analysis. We used an adapted version of the Framework method on data gathered in a study exploring the impact of prostate cancer on younger men and their partners. In this article, we examine and reflect on the challenges of this type of analysis and describe how we analyzed the interview data from a dyadic point of view, to share what we learned in the process.

Decision regret in men living with and beyond nonmetastatic prostate cancer in the United Kingdom: A population-based patient-reported outcome study.

OBJECTIVE: Clinical options for managing nonmetastatic prostate cancer (PCa) vary. Each option has side effects associated with it, leading to difficulty in decision-making. This study aimed to assess the relationship between patient involvement in treatment decision-making and subsequent decision regret (DR), and quantify the impact of health-related quality of life (HRQL) outcomes on DR. METHODS: Men living in the United Kingdom, 18 to 42 months after diagnosis of PCa, were identified from cancer registration data and sent a questionnaire. Measures included the Decision Regret Scale (DRS), Expanded Prostate cancer Index Composite short form (EPIC-26), EQ-5D-5L, and an item on involvement in treatment decision-making. Multivariable ordinal regression was utilized, with DR categorized as none, mild, or moderate/severe regret. RESULTS: A total of 17 193 men with stage I-III PCa completed the DRS: 36.6% reported no regret, 43.3% mild regret, and 20.0% moderate/severe regret. The odds of reporting DR were greater if men indicated their views were not taken into account odds ratio ([OR] = 6.42, 95% CI: 5.39-7.64) or were involved "to some extent" in decision-making (OR = 4.63, 95% CI: 4.27-5.02), compared with men who were "definitely" involved. After adjustment, including for involvement, men reporting moderate/big problems with urinary, bowel, or sexual function were more likely to experience regret compared with men with no/small problems. Better HRQL scores were associated with lower levels of DR. CONCLUSIONS: This large-scale study demonstrates the benefit of patient involvement in treatment decision-making for nonmetastatic PCa. However, men experiencing side effects and poorer HRQL report greater DR. Promoting engagement in clinical decision-making represents good practice and may reduce the risk of subsequent regret.

Guidance regarding COVID-19 for survivors of childhood, adolescent, and young adult cancer: A statement from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Childhood, adolescent, and young adult (CAYA) cancer survivors may be at risk for a severe course of COVID-19. Little is known about the clinical course of COVID-19 in CAYA cancer survivors, or if additional preventive measures are warranted. We established a working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) to summarize existing evidence and worldwide recommendations regarding evidence about factors/conditions associated with risk for a severe course of COVID-19 in CAYA cancer survivors, and to develop a consensus statement to provide guidance for healthcare practitioners and CAYA cancer survivors regarding COVID-19.