The Supportive Care Needs of Cancer Patients: a Systematic Review.

Cancer, and the complex nature of treatment, has a profound impact on lives of patients and their families. Subsequently, cancer patients have a wide range of needs. This study aims to identify and synthesise cancer patients' views about areas where they need support throughout their care. A systematic  search of the literature from PsycInfo, Embase and Medline databases was conducted, and a narrative. Synthesis of results was carried out using the Corbin & Strauss "3 lines of work" framework. For each line of work, a group of key common needs were identified. For illness-work, the key needs idenitified were; understanding their illness and treatment options, knowing what to expect, communication with healthcare professionals, and staying well. In regards to everyday work, patients wanted to maintain a sense of normalcy and look after their loved ones. For biographical work, patients commonly struggled with the emotion impact of illness and a lack of control over their lives. Spiritual, sexual and financial problems were less universal. For some types of support, demographic factors influenced the level of need reported. While all patients are unique, there are a clear set of issues that are common to a majority of cancer journeys. To improve care, these needs should be prioritised by healthcare practitioners.

Centralisation of radical cystectomies for bladder cancer in England, a decade on from the 'Improving Outcomes Guidance': the case for super centralisation.

OBJECTIVE: To analyse the impact of centralisation of radical cystectomy (RC) provision for bladder cancer in England, on postoperative mortality, length of stay (LoS), complications and re-intervention rates, from implementation of centralisation from 2003 until 2014. In 2002, UK policymakers introduced the 'Improving Outcomes Guidance' (IOG) for urological cancers after a global cancer surgery commission identified substantial shortcomings in provision of care of RCs. One key recommendation was centralisation of RCs to high-output centres. No study has yet robustly analysed the changes since the introduction of the IOG, to assess a national healthcare system that has mature data on such institutional transformation. PATIENTS AND METHODS: RCs performed for bladder cancer in England between 2003/2004 and 2013/2014 were analysed from Hospital Episode Statistics (HES) data. Outcomes including 30-day, 90-day, and 1-year all-cause postoperative mortality; median LoS; complication and re-intervention rates, were calculated. Multivariable statistical analysis was undertaken to describe the relationship between each surgeon and the providers' annual case volume and mortality. RESULTS: In all, 15 292 RCs were identified. The percentage of RCs performed in discordance with the IOG guidelines reduced from 65% to 12.4%, corresponding with an improvement in 30-day mortality from 2.7% to 1.5% (P = 0.024). Procedures adhering to the IOG guidelines had better 30-day mortality (2.1% vs 2.9%; P = 0.003) than those that did not, and better 1-year mortality (21.5% vs 25.6%; P < 0.001), LoS (14 vs 16 days; P < 0.001), and re- intervention rates (30.0% vs 33.6%; P < 0.001). Each single extra surgery per centre reduced the odds of death at 30 days by 1.5% (odds ratio [OR] 0.985, 95% confidence interval [CI] 0.977-0.992) and 1% at 1 year (OR 0.990, 95% CI 0.988-0.993), and significantly reduced rates of re-intervention. CONCLUSION: Centralisation has been implemented across England since the publication of the IOG guidelines in 2002. The improved outcomes shown, including that a single extra procedure per year per centre can significantly reduce mortality and re-intervention, may serve to offer healthcare planners an evidence base to propose new guidance for further optimisation of surgical provision, and hope for other healthcare systems that such widespread institutional change is achievable and positive.

Histone chaperones ASF1 and NAP1 differentially modulate removal of active histone marks by LID-RPD3 complexes during NOTCH silencing.

Histone chaperones are involved in a variety of chromatin transactions. By a proteomics survey, we identified the interaction networks of histone chaperones ASF1, CAF1, HIRA, and NAP1. Here, we analyzed the cooperation of H3/H4 chaperone ASF1 and H2A/H2B chaperone NAP1 with two closely related silencing complexes: LAF and RLAF. NAP1 binds RPD3 and LID-associated factors (RLAF) comprising histone deacetylase RPD3, histone H3K4 demethylase LID/KDM5, SIN3A, PF1, EMSY, and MRG15. ASF1 binds LAF, a similar complex lacking RPD3. ASF1 and NAP1 link, respectively, LAF and RLAF to the DNA-binding Su(H)/Hairless complex, which targets the E(spl) NOTCH-regulated genes. ASF1 facilitates gene-selective removal of the H3K4me3 mark by LAF but has no effect on H3 deacetylation. NAP1 directs high nucleosome density near E(spl) control elements and mediates both H3 deacetylation and H3K4me3 demethylation by RLAF. We conclude that histone chaperones ASF1 and NAP1 differentially modulate local chromatin structure during gene-selective silencing.

Role of fluorodeoxyglucose positron emission tomography (FDG PET)-computed tomography (CT) in the staging of bladder cancer.

OBJECTIVE: To determine whether to use (18) F-fluorodeoxyglucose positron emission tomography (FDG PET) scans in the preoperative staging of bladder cancer (BC). PATIENTS AND METHODS: In all, 233 patients with muscle-invasive BC (MIBC) or high-risk non-MIBC being considered for radical cystectomy (RC) between 2005 and 2011 had FDG-PET and computed tomography (CT) of the chest, abdomen and pelvis to assess for pelvic lymph node (LN) involvement or distant metastases. Sensitivity and specificity for detecting pelvic LN involvement was determined by comparing the results of the scans to the histopathology reports in patients undergoing RC. These parameters for distant metastases were determined from biopsy results or follow-up imaging. In patients who did not undergo RC, follow-up imaging was used to evaluate the sensitivity and specificity. Patients were excluded from analysis if they either had neoadjuvant chemotherapy or had <10 LNs removed at lymphadenectomy. RESULTS: The PET scan was able to detect metastatic disease outside of the pelvis with a sensitivity of 54% compared with 41% for the staging CT (N = 207). Both scans had similar specificities of 97% and 98%. There were 13 PET avid lesions not visualised on the corresponding staging CT scans. These proved to be metastatic BC (six patients), a synchronous primary colonic cancer (one), colonic adenomas (one), basal cell tumour of the parotid gland (one) and inflammatory lesions (four). The sensitivity and specificity of the CT scans for pelvic LN involvement was 45% and 98%, respectively (N = 93). Using a combination of the PET and CT scan, the sensitivity for detecting metastatic disease in LNs increased to 69% with a 3% reduction in specificity to 95%. CONCLUSIONS: PET when used in conjunction with a standard CT scan provides a small improvement in preoperative staging of BC. However, this advantage is not significant enough to justify the additional cost. Hence we recommend use of dual imaging only in highly selected patients.

Long COVID symptoms and demographic associations: A retrospective case series study using healthcare application data.

Objectives: To investigate long COVID (LC) symptoms self-reported via a digital application. Explore associations between various demographic factors and intensity of LC symptoms. Design: A retrospective case series study. We analysed self-reported symptoms from 1008 individuals with LC between November 30, 2020, and March 23, 2022. Setting: England and Wales. Participants: Individuals with LC using the healthcare application in 31 post-COVID-19 clinics and self-reporting LC symptoms. Main outcome measures: Highest reported LC symptoms, associations with demographic factors and intensity of symptoms. Results: 109 symptom categories were identified, with pain (26.5%), neuropsychological issues (18.4%), fatigue (14.3%) and dyspnoea (7.4%) the most prevalent. The intensity of reported symptoms increased by 3.3% per month since registration. Age groups 68-77 and 78-87 experienced higher symptom intensity (32.8% and 86% higher, respectively) compared to the 18-27 age group. Women reported 9.2% more intense symptoms than men, and non-white individuals with LC reported 23.5% more intense symptoms than white individuals with LC. Higher education levels (national vocational qualification (NVQ) 3 to NVQ 5) were associated with less symptom intensity (27.7%, 62.8% and 44.7% less, respectively) compared to the least educated (NVQ 1-2). People in less deprived areas had less intense symptoms than those in the most deprived area. No significant association was found between index of multiple deprivation (IMD) decile and number of symptoms. Conclusion: Treatment plans must prioritise addressing prevalent LC symptoms; we recommend sustained support for LC clinics. Demographic factors significantly influence symptom severity, underlining the need for targeted interventions. These findings can inform healthcare policies to better manage LC.

Impact of fatigue as the primary determinant of functional limitations among patients with post-COVID-19 syndrome: a cross-sectional observational study.

OBJECTIVES: To describe self-reported characteristics and symptoms of treatment-seeking patients with post-COVID-19 syndrome (PCS). To assess the impact of symptoms on health-related quality of life (HRQoL) and patients' ability to work and undertake activities of daily living. DESIGN: Cross-sectional single-arm service evaluation of real-time user data. SETTING: 31 post-COVID-19 clinics in the UK. PARTICIPANTS: 3754 adults diagnosed with PCS in primary or secondary care deemed suitable for rehabilitation. INTERVENTION: Patients using the Living With Covid Recovery digital health intervention registered between 30 November 2020 and 23 March 2022. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the baseline Work and Social Adjustment Scale (WSAS). WSAS measures the functional limitations of the patient; scores of ≥20 indicate moderately severe limitations. Other symptoms explored included fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), depression (Patient Health Questionnaire-Eight Item Depression Scale), anxiety (Generalised Anxiety Disorder Scale, Seven-Item), breathlessness (Medical Research Council Dyspnoea Scale and Dyspnoea-12), cognitive impairment (Perceived Deficits Questionnaire, Five-Item Version) and HRQoL (EQ-5D). Symptoms and demographic characteristics associated with more severe functional limitations were identified using logistic regression analysis. RESULTS: 3541 (94%) patients were of working age (18-65); mean age (SD) 48 (12) years; 1282 (71%) were female and 89% were white. 51% reported losing ≥1 days from work in the previous 4 weeks; 20% reported being unable to work at all. Mean WSAS score at baseline was 21 (SD 10) with 53% scoring ≥20. Factors associated with WSAS scores of ≥20 were high levels of fatigue, depression and cognitive impairment. Fatigue was found to be the main symptom contributing to a high WSAS score. CONCLUSION: A high proportion of this PCS treatment-seeking population was of working age with over half reporting moderately severe or worse functional limitation. There were substantial impacts on ability to work and activities of daily living in people with PCS. Clinical care and rehabilitation should address the management of fatigue as the dominant symptom explaining variation in functionality.

Gene-specific targeting of the histone chaperone asf1 to mediate silencing.

The histone chaperone Asf1 assists in chromatin assembly and remodeling during replication, transcription activation, and gene silencing. However, it has been unclear to what extent Asf1 could be targeted to specific loci via interactions with sequence-specific DNA-binding proteins. Here, we show that Asf1 contributes to the repression of Notch target genes, as depletion of Asf1 in cells by RNAi causes derepression of the E(spl) Notch-inducible genes. Conversely, overexpression of Asf1 in vivo results in decreased expression of target genes and produces phenotypes that are strongly modified (enhanced and suppressed) by mutations affecting the Notch pathway, but not by mutations in other signaling pathways. Asf1 can be coprecipitated with the DNA-binding protein Su(H) and the corepressor Hairless and interacts directly with two components of this complex, Hairless and SKIP. Thus, in addition to playing more general roles in chromatin dynamics, Asf1 is directed via interactions with sequence-specific complexes to mediate silencing of specific target genes.

Novel Implementation Strategy to Electronically Screen and Signpost Patients to Health Behavior Apps: Mixed Methods Implementation Study (OptiMine Study).

BACKGROUND: Behavior change apps have the potential to provide individual support on a population scale at low cost, but they face numerous barriers to implementation. Electronic health records (EHRs) in acute care hospitals provide a valuable resource for identifying patients at risk, who may benefit from behavior change apps. A novel, emerging implementation strategy is to use digital technologies not only for providing support to help-seeking individuals but also for signposting patients at risk to support services (also called proactive referral in the United States). OBJECTIVE: The OptiMine study aimed to increase the reach of behavior change apps by implementing electronic signposting for smoking cessation and alcohol reduction in a large, at-risk population that was identified through an acute care hospital EHR. METHODS: This 3-phase, mixed methods implementation study assessed the acceptability, feasibility, and reach of electronic signposting to behavior change apps by using a hospital's EHR system to identify patients who are at risk. Phase 1 explored the acceptability of the implementation strategy among the patients and staff through focus groups. Phase 2 investigated the feasibility of using the hospital EHR to identify patients with target risk behaviors and contact them via SMS text message, email, or patient portal. Phase 3 assessed the impact of SMS text messages sent to patients who were identified as smokers or risky drinkers, which signposted them to behavior change apps. The primary outcome was the proportion of participants who clicked on the embedded link in the SMS text message to access information about the apps. The acceptability of the SMS text messages among the patients who had received them was also explored in a web-based survey. RESULTS: Our electronic signposting strategy-using SMS text messages to promote health behavior change apps to patients at risk-was found to be acceptable and feasible and had good reach. The hospital sent 1526 SMS text messages, signposting patients to either the National Health Service Smokefree or Drink Free Days apps. A total of 13.56% (207/1526) of the patients clicked on the embedded link to the apps, which exceeded our 5% a priori success criterion. Patients and staff contributed to the SMS text message content and delivery approach, which were perceived as acceptable before and after the delivery of the SMS text messages. The feasibility of the SMS text message format was determined and the target population was identified by mining the EHR. CONCLUSIONS: The OptiMine study demonstrated the proof of concept for this novel implementation strategy, which used SMS text messages to signpost at-risk individuals to behavior change apps at scale. The level of reach exceeded our a priori success criterion in a non-help-seeking population of patients receiving unsolicited SMS text messages, disconnected from hospital visits. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/23669.

Development, deployment and evaluation of digitally enabled, remote, supported rehabilitation for people with long COVID-19 (Living With COVID-19 Recovery): protocol for a mixed-methods study.

INTRODUCTION: Long COVID-19 is a distressing, disabling and heterogeneous syndrome often causing severe functional impairment. Predominant symptoms include fatigue, cognitive impairment ('brain fog'), breathlessness and anxiety or depression. These symptoms are amenable to rehabilitation delivered by skilled healthcare professionals, but COVID-19 has put severe strain on healthcare systems. This study aims to explore whether digitally enabled, remotely supported rehabilitation for people with long COVID-19 can enable healthcare systems to provide high quality care to large numbers of patients within the available resources. Specific objectives are to (1) develop and refine a digital health intervention (DHI) that supports patient assessment, monitoring and remote rehabilitation; (2) develop implementation models that support sustainable deployment at scale; (3) evaluate the impact of the DHI on recovery trajectories and (4) identify and mitigate health inequalities due to the digital divide. METHODS AND ANALYSIS: Mixed-methods, theoretically informed, single-arm prospective study, combining methods drawn from engineering/computer science with those from biomedicine. There are four work packages (WP), one for each objective. WP1 focuses on identifying user requirements and iteratively developing the intervention to meet them; WP2 combines qualitative data from users with learning from implementation science and normalisation process theory, to promote adoption, scale-up, spread and sustainability of the intervention; WP3 uses quantitative demographic, clinical and resource use data collected by the DHI to determine illness trajectories and how these are affected by use of the DHI; while WP4 focuses on identifying and mitigating health inequalities and overarches the other three WPs. ETHICS AND DISSEMINATION: Ethical approval obtained from East Midlands - Derby Research Ethics Committee (reference 288199). Our dissemination strategy targets three audiences: (1) Policy makers, Health service managers and clinicians responsible for delivering long COVID-19 services; (2) patients and the public; (3) academics. TRIAL REGISTRATION NUMBER: Research Registry number: researchregistry6173.

The multidisciplinary, theory-based co-design of a new digital health intervention supporting the care of oesophageal cancer patients.

OBJECTIVE: Oesophageal cancer patients have complex care needs. Cancer clinical nurse specialists play a key role in coordinating their care but often have heavy workloads. Digital health interventions can improve patient care but there are few examples for oesophageal cancer. This paper aims to describe the multidisciplinary co-design process of a digital health intervention to improve the experience of care and reduce unmet needs among patients with oesophageal cancer. METHODS: A theory-based, multi-disciplinary, co-design approach was used to inform the developmental process of the digital health intervention. Key user needs were elicited using mixed methodology from systematic reviews, focus groups and interviews and holistic need assessments. Overarching decisions were discussed among a core team of patients, carers, health care professionals including oncologists and cancer clinical nurse specialists, researchers and digital health providers. A series of workshops incorporating a summary of findings of key user needs resulted in the development of a minimum viable product. This was further refined after a pilot study based on feedback from end users. RESULTS: The final digital health intervention consists of a mobile app feature for patients and carers connected to a dashboard with supporting additional features for clinical nurse specialist. It contains a one-way messaging function for clinical nurse specialists to communicate with patients, functions for patients to record weight and holistic need assessment results which could be viewed by their clinical nurse specialists as well as a library of informative articles. CONCLUSIONS: The multidisciplinary co-design of a digital health intervention providing support for oesophageal cancer patients and health care professionals has been described. Future studies to establish its impact on patient outcomes are planned.

Mining Electronic Health Records to Promote the Reach of Digital Interventions for Cancer Prevention Through Proactive Electronic Outreach: Protocol for the Mixed Methods OptiMine Study.

BACKGROUND: Digital behavior change interventions have demonstrated effectiveness for smoking cessation and reducing alcohol intake, which ultimately reduce cancer risk. Leveraging electronic health records (EHR) to identify at-risk patients and increasing the reach of digital interventions through proactive electronic outreach provide a novel approach that may increase the number of individuals who engage with evidence-based treatment. OBJECTIVE: This study aims to increase the reach of digital behavior change interventions by implementing a proactive electronic message system for smoking cessation and alcohol reduction among a large, at-risk population identified through an acute hospital EHR. METHODS: This protocol describes a 3-phase, mixed-methods implementation study to assess the acceptability, feasibility, and reach of a proactive electronic message system to digital interventions using a hospital's EHR system to identify eligible patients. In Phase 1, we will conduct focus group discussions with patients and hospital staff to assess the overall acceptability of the electronic message system. In Phase 2, we will conduct a descriptive analysis of the patient population in the hospital EHR regarding target risk behaviors and other person-level characteristics to determine the project's feasibility and potential reach. In Phase 3, we will send proactive messages to patients identified as smokers or risky drinkers. Messages will encourage and provide access to behavior change mobile apps via an embedded link; the primary outcome will be the proportion of participants who click on the link to access information about the apps. RESULTS: At the time of initial protocol submission, data collection was complete, but analysis had not begun. This study was funded by Cancer Research UK from April 2019 to March 2020. Health Research Authority approval was granted in June 2019. CONCLUSIONS: Increasing the reach of digital behavior change interventions can improve population health by reducing the burden of preventable death and disease. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23669.