INTRODUCTION:People from ethnic minorities in the UK face barriers to appropriate mental health care, including cultural stigma, language barriers and discriminatory practices. Culturally competent mental health services are proposed as a way to reduce these disparities, but implementation is limited. AIM:To establish consensus among ethnic minorities, carers, public advisors and health professionals on core components of culturally competent mental health services. METHODS:A three-stage Delphi process was conducted: two survey rounds followed by an online consensus workshop. Participants rated the importance of statements on a 9-point Likert scale covering lived experience, systemic challenges, cultural sensitivity and community-based support. Consensus was prespecified as ≥ 70% participants rating an item as important (scores of 7-9). Free-text responses in Round 1 and workshop discussions informed wording and grouping of recommendations. RESULTS:Sixty-six took part in this study, including 34 service users, 3 carers, 3 public members and 26 professionals. Forty-seven items reached consensus across four sections: lived experience of isolation and stigma living with mental health, systemic challenges for people from ethnic minorities seeking health services support, improving cultural sensitivity and support in services, and community-based support. These were interpreted through four overarching themes in the workshop co-production: understanding mental health in cultural context, raising awareness through community engagement, equipping interpreters and health professionals for inclusive mental health support, and driving systemic change towards collaboration, cultural sensitivity, and continuity of mental health care. CONCLUSIONS:This study co-developed 46 recommendations that can be used as a checklist to support the development, design and delivery of culturally competent mental health services. The findings suggest that improving cultural competence will need system-level and community-informed changes, including stronger peer support, mental health education, advocacy and co-production. The recommendations can guide commissioners and providers when reviewing service pathways and planning improvement work and offer a starting point for piloting and validating a practical checklist for routine use. PATIENT OR PUBLIC CONTRIBUTION:A project advisory group of four patient representatives and three team members met six times, reviewed and piloted survey materials, advised on recruitment, and contributed to analysis and final recommendations.

Background Existing health inequalities and the lack of timely and appropriate support have long been a reality for many ethnic minority individuals living with mental health conditions, even before the pandemic. Limited access to services and the absence of culturally or religiously embedded care have led to increased severity of mental health problems.Objective To explore the complexity of interactions between ethnic minorities and mental health services and their experiences of seeking and receiving mental health support throughout the pandemic.Methods Semi-structured interviews with purposive and snowball sampling of ethnic minorities aged over 18 (n=32) across North East and North West in England were analysed using a framework approach.Findings Five themes were generated. Cultural stigma attached to mental health could lead to fear and reluctance to seek support. Individuals struggled to engage with non-culturally sensitive health services. Instead, they indicated a strong preference for wider community support, which continued through the pandemic despite interrupted health services. A collaboration between mental health services and ethnic minority communities was advocated to shape services to cultural contexts and improve patient-centred service delivery.Conclusions Ethnic minorities with mental health face significant challenges and disparities in seeking and engaging in mental health services. They often seek support from multicultural community settings even though the support is not specifically targeted at addressing mental health issues. Understanding cultural beliefs, religious influences and family and community structures are necessary components of culturally appropriate care.Clinical implications Culturally sensitive mental health services need to be integrated into existing systems through initiating collaborations with ethnic minority communities that tailor services to meet the needs of diverse populations, improving overall engagement and experiences.

Objectives In recent times, the world has witnessed unprecedented challenges, with the COVID-19 pandemic being a major disruptor to various aspects of daily life. This article delves into the profound impact of pandemics on primary care, specifically focussing on changes in antidepressant prescriptions and mental health referrals before, during, and after lockdowns in England, UK. Methods In this retrospective study, we used anonymised individual-level electronic health record data from general practitioner (GP) practices in the North of England, UK. We applied a negative binomial-logit hurdle model and a multinominal logit regression model to assess the impact on antidepressant prescriptions and GP referral types, respectively. Results The initiation of antidepressant prescriptions showed a notable decrease during and post lockdowns, with a minor uptick in ongoing antidepressant prescriptions during the lockdown periods. Over the course of lockdowns and beyond, there was a growing trend of patients being referred to social prescribing interventions. Notably, individuals from ethnic minorities were more inclined to receive fewer medical treatments and more social prescribing interventions. Conclusion The increase in antidepressant prescriptions during the pandemic-related lockdowns was expected due to these challenging circumstances. Reduced referrals to secondary mental health services occurred as online counselling services were deemed inappropriate by some doctors, and patients were hesitant to seek face-to-face help. Notably, there was a rise in social prescribing referrals, emerging as a valuable resource for psychological support amid heightened mental health strain. Additionally, ethnic minority patients were less likely to receive medical treatments but more likely to be referred to social prescribing services. Despite the inevitable negative impacts of the COVID-19 pandemic, these findings highlight the active role of non-clinical support in a social model of health, addressing unmet needs and reducing barriers to mental health care for certain groups.

Background Severe deterioration in mental health and disrupted care provision during the COVID-19 increased unmet needs for mental health. This review aimed to identify changes in mental health services for patients in response to the pandemic and understand the impact of the changes on patients and providers. Methods Following the Cochrane guidance for rapid reviews, Cochrane CENTRAL, MEDLINE, Embase and PsycInfo were searched for empirical studies that investigated models of care, services, initiatives or programmes developed/evolved for patients receiving mental health care during COVID-19, published in English and undertaken in high-income countries. Thematic analysis was conducted to describe the changes and an effect direction plot was used to show impact on outcomes. Results 33 of 6969 records identified were included reporting on patients’ experiences ( n = 24), care providers’ experiences ( n = 7) and mixed of both ( n = 2). Changes reported included technology-based care delivery, accessibility, flexibility, remote diagnostics and evaluation, privacy, safety and operating hours of service provision. These changes had impacts on: (1) care access; (2) satisfaction with telehealth; (3) comparability of telehealth with face-to-face care; (4) treatment effectiveness; (5) continuity of care; (6) relationships between patients and care providers; (7) remote detection and diagnostics in patients; (8) privacy; (9) treatment length and (10) work-life balance. Conclusions A shift to telecommunication technologies had a significant impact on patients and care providers’ experiences of mental health care. Improvements to care access, flexibility, remote forms of care delivery and lengths of operating service hours emerged as crucial changes, which supported accessibility to mental health services, increased attendance and reduced dropouts from care. The relationships between patients and care providers were influenced by service changes and were vastly depending on technological literacy and context of patients and availability and care access ranging from regular contact to a loss of in-person contact. The review also identified an increase in care inequality and a feeling of being disconnected among marginalised groups including homeless people, veterans and ethic minority groups. Telehealth in mental care could be a viable alternative to face-to-face service delivery with effective treatment outcomes. Further research is needed to better understand the impact of the changes identified particularly on underserved populations.

BACKGROUND:Psychiatric medications play a vital role in the management of mental health disorders. However, the COVID-19 pandemic and subsequent lockdown limited access to primary care services, leading to an increase in remote assessment and treatment options to maintain social distancing. This study aimed to investigate the impact of the COVID-19 pandemic lockdown on the use of psychiatric medication in primary care settings.METHODS:We conducted a retrospective claims-based analysis of anonymized monthly aggregate practice-level data on anxiolytics and hypnotics use from 322 general practitioner (GP) practices in the North East of England, where health disparities are known to be higher. Participants were all residents who took anxiolytics and hypnotics from primary care facilities for two financial years, from 2019/20 to 2020/21. The primary outcome was the volume of Anxiolytics and Hypnotics used as the standardized, average daily quantities (ADQs) per 1000 patients. Based on the OpenPrescribing database, a random-effect model was applied to quantify the change in the level and trend of anxiolytics and hypnotics use after the UK national lockdown in March 2020. Practice characteristics extracted from the Fingertips data were assessed for their association with a reduction in medication use following the lockdown.RESULTS:This study in the North East of England found that GP practices in higher health disparate regions had a lower workload than those in less health disparate areas, potentially due to disparities in healthcare utilization and socioeconomic status. Patients in the region reported higher levels of satisfaction with healthcare services compared to the England average, but there were differences between patients living in higher versus less health disparate areas. The study highlights the need for targeted interventions to address health disparities, particularly in higher health disparate areas. The study also found that psychiatric medication use was significantly more common in residents living in higher health disparate areas. Daily anxiolytics and hypnotics use decreased by 14 items per 1000 patients between the financial years 2019/20 and 2020/21. A further nine items per 1000 decreased for higher health disparate areas during the UK national lockdown.CONCLUSIONS:People during the COVID-19 lockdown were associated with an increased risk of unmet psychiatric medication demand, especially for higher health disparate areas that had low-socioeconomic status.

Background: Recurrence of non-muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumour (TURBT). Photodynamic diagnosis (PDD) may reduce recurrence. PDD uses a photosensitiser in the bladder that causes the tumour to fluoresce to guide resection. PDD provides better diagnostic accuracy and allows more complete tumour resection. Objective: To estimate the economic efficiency of PDD-guided TURBT (PDD-TURBT) in comparison to white light-guided TURNT (WL-TURBT) in individuals with a suspected first diagnosis of NMIBC at intermediate or high risk of recurrence on the basis of routine visual assessment before being scheduled for TURBT. Design, setting, and participants: This is a health economic evaluation alongside a pragmatic, open-label, parallel-group randomised trial from a societal perspective. A total of 493 participants (aged >= 16 yr) were randomly allocated to PDD-TURBT (n = 244) or WL-TURBT (n = 249) in 22 UK National Health Service hospitals. Outcome measurements and statistical analysis: Cost effectiveness ratios were based on the use of health care resources associated with PDD-TURBT and WL-TURBT and quality-adjusted life years (QALYs) gained within the trial. Uncertainties in key parameters were assessed using sensitivity analyses. Results and limitations: On the basis of the use of resources driven by the trial protocol, the incremental cost effectiveness of PDD-TURBT in comparison to WL-TURBT was not cost saving. At 3 yr, the total cost was 12 pound 881 for PDD-TURBT and 12 pound 005 for WL-TURBT. QALYs at three years were 2.087 for PDD-TURBT and 2.094 for WL-TURBT. The probability that PDD-TURBT is cost effective was never >30% above the range of societal cost-effectiveness thresholds. Conclusions: There was no evidence of a difference in either costs or QALYs over 3yr follow-up between PDD-TURBT and WL-TURBT in individuals with suspected intermediate- or high-risk NMIBC. PDD-TURBT is not supported for the management of primary intermediate- or high-risk NMIBC. Patient summary: We assessed overall costs for two approaches for removal of bladder tumours in noninvasive cancer and measured quality-adjusted life years gained for each. We found that use of a photosensitiser in the bladder was not more cost effective than use of white light only during tumour removal. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction Cardiovascular disease (CVD) has shown significant health inequalities for people with low socioeconomic status associated with more risk factors. This review was to synthesize interventions that targeted CVD risks and outcomes among socioeconomically disadvantaged populations and to understand the impact associated with these interventions.Sources of data Cochrane CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL were searched for records published in the last decade using a systematic search strategy, complemented by screening the reference lists and citation indexes. Nineteen studies were included and a narrative synthesis with the effect direction plot was undertaken in which studies, interventions, participants and outcomes were examined according to the intervention type focusing on behaviours, lifestyle, education, medication and monitoring.Areas of agreement No universal definition of disadvantaged socioeconomic status was used with common factors relating to racial/ethnic minorities, low income and low or no health insurance. Mixed effects of interventions were reported on clinical outcomes including weight, body mass index, blood pressure, glycated haemoglobin and cholesterol.Areas of controversy Inconsistent effect was reported due to a large variety of settings, participants and intervention components although they are considered necessary to address the complex health needs of socioeconomically disadvantaged populations.Growing points There is inadequate evidence to determine whether any of the intervention types are effective in optimising lipids management for socioeconomically disadvantaged populations.Areas timely for developing research Research is needed with mixed evidence using real world evaluation and lived experience combined with health economic evaluation, on both mental and physical health outcomes.

Introduction Linking routinely collected health care system data records for the same individual across different services and over time has enormous potential for the NHS and its patients. The aims of this data linkage study are to quantify the changes to mental health services utilisation in responses to the COVID-19 pandemic and determine whether these changes were associated with health-related outcomes and wellbeing among people living in the most deprived communities in North East and North Cumbria, England. Methods and analysis We will assemble a retrospective cohort of people having referred or self-referred to NHS-funded mental health services or Improving Access to Psychological Therapies (IAPT) services between 23rd March 2019 and 22nd March 2020 in the most deprived areas in England. We will link together data from retrospective routinely collected healthcare data including local general practitioner (GP) practice data, Hospital Episode Statistics admitted patient care outpatients, and A&E, Community Services Data Set, Mental Health Services Data Set, and Improving Access to Psychological Therapies Data Set. We will use these linked patient-level data to 1) describe the characteristics of the cohort prior to the lockdown; 2) investigate changes to mental health services utilised between multiple time periods of the COVID-19 lockdown including out of lockdown; 3) explore the relationship between these changes and health outcomes/wellbeing and factors that confound and mediate this relationship among this cohort. Strengths and limitations of this study This study comprises a deprived population-based cohort of people having referred or self-referred to NHS-funded secondary mental health services or Improving Access to Psychological Therapies (IAPT) services over an extended period of the lockdown in England (2019–2022). This study will utilise a new longitudinal data resource that will link together detailed data from a cohort of individual participants and retrospective administrative data relating to the use of primary, secondary, and community care services. The study period covers pre-lockdown, different lockdown and post-lockdown, and out of lockdown periods up to March 2022. Routinely collected administrative data contain limited contextual information and represent an underestimate of total health outcomes for these individuals. Routinely collected datasets can often been incomplete or contain missing data, which can make it difficult to accurately analyse the data and draw meaningful conclusions. Intervention and treatment for mental health conditions are not wholly captured across these data sources and may impact health outcomes.

BackgroundCOVID-19 has exacerbated the significant and longstanding mental health inequalities for ethnic minorities, who were less likely to access mental health support in primary care but more likely to end up in crisis care compared to the majority ethnic group. Services were poorly offered and accessed to respond to the increased mental health challenges.AimTo 1) establish evidence on which changes to mental health services provided in response to COVID-19 are beneficial for ethnic minorities who experience mental health difficulties in the North of England, and 2) to inform what and how culturally competent mental health services should be routinely provided.MethodsA mixed methods approach comprising 1) a rapid review to map services and models of care designed or adjusted for mental health during the pandemic, 2) an observational study of retrospective routine data to assess changes to mental health services and associated outcomes, 3) qualitative interviews to understand experiences of seeking care and factors associated with high-quality service provision, and 4) a Delphi study to establish consensus on key features of culturally competent services. From the selected areas in the North of England, adults from ethnic minorities who experience mental health difficulties will be identified from the primary, community and secondary care services and local ethnic minority communities.DiscussionThis study will identify ways to tackle health inequalities and contribute to mental health service recovery post pandemic by providing practice recommendations on equitable and effective services to ensure culturally competent and high-quality care. A list of services and features on what and how mental health services will be provided. Working with study collaborators and public and patient involvement partners, the study findings will be widely disseminated through presentations, conferences and publications and will inform the subsequent funding application for intervention development and evaluation.

BACKGROUND:Around 7500 people are diagnosed with non-muscle-invasive bladder cancer in the UK annually. Recurrence following transurethral resection of bladder tumour is common, and the intensive monitoring schedule required after initial treatment has associated costs for patients and the NHS. In photodynamic diagnosis, before transurethral resection of bladder tumour, a photosensitiser that is preferentially absorbed by tumour cells is instilled intravesically. Transurethral resection of bladder tumour is then conducted under blue light, causing the photosensitiser to fluoresce. Photodynamic diagnosis-guided transurethral resection of bladder tumour offers better diagnostic accuracy than standard white-light-guided transurethral resection of bladder tumour, potentially reducing the chance of subsequent recurrence. OBJECTIVE:The objective was to assess the clinical effectiveness and cost-effectiveness of photodynamic diagnosis-guided transurethral resection of bladder tumour. DESIGN:This was a multicentre, pragmatic, open-label, parallel-group, non-masked, superiority randomised controlled trial. Allocation was by remote web-based service, using a 1 : 1 ratio and a minimisation algorithm balanced by centre and sex. SETTING:The setting was 22 NHS hospitals. PARTICIPANTS:Patients aged ≥ 16 years with a suspected first diagnosis of high-risk non-muscle-invasive bladder cancer, no contraindications to photodynamic diagnosis and written informed consent were eligible. INTERVENTIONS:Photodynamic diagnosis-guided transurethral resection of bladder tumour and standard white-light cystoscopy transurethral resection of bladder tumour. MAIN OUTCOME MEASURES:The primary clinical outcome measure was the time to recurrence from the date of randomisation to the date of pathologically proven first recurrence (or intercurrent bladder cancer death). The primary health economic outcome was the incremental cost per quality-adjusted life-year gained at 3 years. RESULTS:We enrolled 538 participants from 22 UK hospitals between 11 November 2014 and 6 February 2018. Of these, 269 were allocated to photodynamic diagnosis and 269 were allocated to white light. A total of 112 participants were excluded from the analysis because of ineligibility (n = 5), lack of non-muscle-invasive bladder cancer diagnosis following transurethral resection of bladder tumour (n = 89) or early cystectomy (n = 18). In total, 209 photodynamic diagnosis and 217 white-light participants were included in the clinical end-point analysis population. All randomised participants were included in the cost-effectiveness analysis. Over a median follow-up period of 21 months for the photodynamic diagnosis group and 22 months for the white-light group, there were 86 recurrences (3-year recurrence-free survival rate 57.8%, 95% confidence interval 50.7% to 64.2%) in the photodynamic diagnosis group and 84 recurrences (3-year recurrence-free survival rate 61.6%, 95% confidence interval 54.7% to 67.8%) in the white-light group (hazard ratio 0.94, 95% confidence interval 0.69 to 1.28; p = 0.70). Adverse event frequency was low and similar in both groups [12 (5.7%) in the photodynamic diagnosis group vs. 12 (5.5%) in the white-light group]. At 3 years, the total cost was £12,881 for photodynamic diagnosis-guided transurethral resection of bladder tumour and £12,005 for white light. There was no evidence of differences in the use of health services or total cost at 3 years. At 3 years, the quality-adjusted life-years gain was 2.094 in the photodynamic diagnosis transurethral resection of bladder tumour group and 2.087 in the white light group. The probability that photodynamic diagnosis-guided transurethral resection of bladder tumour was cost-effective was never > 30% over the range of society's cost-effectiveness thresholds. LIMITATIONS:Fewer patients than anticipated were correctly diagnosed with intermediate- to high-risk non-muscle-invasive bladder cancer before transurethral resection of bladder tumour and the ratio of intermediate- to high-risk non-muscle-invasive bladder cancer was higher than expected, reducing the number of observed recurrences and the statistical power. CONCLUSIONS:Photodynamic diagnosis-guided transurethral resection of bladder tumour did not reduce recurrences, nor was it likely to be cost-effective compared with white light at 3 years. Photodynamic diagnosis-guided transurethral resection of bladder tumour is not supported in the management of primary intermediate- to high-risk non-muscle-invasive bladder cancer. FUTURE WORK:Further work should include the modelling of appropriate surveillance schedules and exploring predictive and prognostic biomarkers. TRIAL REGISTRATION:This trial is registered as ISRCTN84013636. FUNDING:This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 40. See the NIHR Journals Library website for further project information.

ABSTRACTIntroductionThe COVID-19 pandemic has caused disruptions to mental health services, forcing the rapid implementation of alternative ways of delivering services alongside a greater immediate, and continuously growing, demand across those services. The care and level of mental health service provided are felt to be inadequate to respond to the increasing demand for mental health conditions in the time of the pandemic, leading to an urgent need to learn from service change and consequences to inform solutions and plans to support the NHS post-pandemic plan in the UK. This rapid review aims to understand the changes in mental health services during the pandemic and summarise the impact of these changes on the health outcomes of people with mental health conditions.Methods and analysisCochrane CENTRAL, MEDLINE, EMBASE, and PsycInfowill be searched for eligible studies with key terms indicating mental health AND COVID-19 AND health services. Studies will be included if objective and subjective effects of changes to mental health services in response to COVID-19 are reported on adults with mental health conditions, peer-reviewed and published in the English language. Study selection and data extraction will be undertaken dependently by two reviewers. Evidence will be summarised narratively and in a logic model.Ethics and disseminationEthics approval is not required for this review. A list of interventions/services/models of care delivered to people with mental health conditions will be grouped as “Do”, “Don’t” and “Don’t know” based on the evidence on effectiveness and acceptability. The results will be written for publication in an open-access peer-reviewed journal and disseminated to the public and patients, clinicians, commissioners, funders, and academic conferences.PROSPERO registration numberCRD42022306923Strengths and limitations of this studyThis is a rapid review with a systematic search of literatureEvidence on changes to mental health services and associated health outcomes will be examined to make practice recommendationsThis review will provide the evidence base to inform solutions and plans to support the mental health service provision for the post-pandemic periodSome limitations to the study design include limited to OECD studies, exclusion of non-English studies, publication bias, quality of data, selection bias, and no quality assessment in the rapid evidence review.

BackgroundRecurrence of non–muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis (PDD) provides better diagnostic accuracy and more complete tumor resection and may reduce recurrence. However, there is limited evidence on the longer-term clinical effectiveness and cost-effectiveness of PDD-guided resection.MethodsIn this pragmatic, open-label, parallel-group randomized trial conducted in 22 U.K. National Health Service hospitals, we recruited participants with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence on the basis of routine visual assessment before being listed for TURBT. Participants were assigned (1:1) to PDD-guided TURBT or to standard white light (WL)–guided TURBT. The primary clinical outcome was time to recurrence at 3 years of follow-up, analyzed by modified intention to treat.ResultsA total of 538 participants were enrolled (269 in each group), and 112 participants without histologic confirmation of NMIBC or who had had cystectomy were excluded. After 44 months’ median follow-up, 86 of 209 in the PDD group and 84 of 217 in the WL group had recurrences. The hazard ratio for recurrence was 0.94 (95% confidence interval [CI], 0.69 to 1.28; P=0.70). Three-year recurrence-free rates were 57.8% (95% CI, 50.7 to 64.2) and 61.6% (95% CI, 54.7 to 67.8) in the PDD and WL groups, respectively, with an absolute difference of −3.8 percentage points (95% CI, −13.37 to 5.59) favoring PDD. Adverse events occurred in less than 2% of participants, and rates were similar in both groups, as was health-related quality of life. PDD-guided TURBT was £876 (95% CI, −766 to 2518; P=0.591) more costly than WL-guided TURBT over a 3-year follow-up, with no evidence of a difference in quality-adjusted life years (−0.007; 95% CI, −0.133 to 0.119; P=0.444).ConclusionsPDD-guided TURBT did not reduce recurrence rates, nor was it cost-effective compared with WL at 3 years. (Funded by the National Institute for Health and Care Research Health Technology Assessment program; ISRCTN number, ISRCTN84013636.)

We present a noninvasive Web-based app to help exclude or diagnose myelodysplastic syndrome (MDS), a bone marrow (BM) disorder with cytopenias and leukemic risk, diagnosed by BM examination. A sample of 502 MDS patients from the European MDS (EUMDS) registry (n > 2600) was combined with 502 controls (all BM proven). Gradient-boosted models (GBMs) were used to predict/exclude MDS using demographic, clinical, and laboratory variables. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the models, and performance was validated using 100 times fivefold cross-validation. Model stability was assessed by repeating its fit using different randomly chosen groups of 502 EUMDS cases. AUC was 0.96 (95% confidence interval, 0.95-0.97). MDS is predicted/excluded accurately in 86% of patients with unexplained anemia. A GBM score (range, 0-1) of less than 0.68 (GBM < 0.68) resulted in a negative predictive value of 0.94, that is, MDS was excluded. GBM ≥ 0.82 provided a positive predictive value of 0.88, that is, MDS. The diagnosis of the remaining patients (0.68 ≤ GBM < 0.82) is indeterminate. The discriminating variables: age, sex, hemoglobin, white blood cells, platelets, mean corpuscular volume, neutrophils, monocytes, glucose, and creatinine. A Web-based app was developed; physicians could use it to exclude or predict MDS noninvasively in most patients without a BM examination. Future work will add peripheral blood cytogenetics/genetics, EUMDS-based prospective validation, and prognostication.

Available evidence suggests that in most patients with LR-MDS the risk of death is not related to disease progression but is mainly attributable to non-leukemic death. 2,17 In addition, a proportion of these patients have prolonged survival that precludes the design of clinical trials adopting OS as a primary endpoint. These challenges have resulted in potentially biased assessment of the effectiveness and appropriate use of the available interventions in this patient population. The EUMDS Registry has identified novel meaningful outcome indicators and clinical endpoints, and reliable measures of response to HCI (Figure 4). The results of our analysis indicate that RBCT density is strongly associated with a decreased OS, even at relatively low dose densities. In addition, we observed that an early decrease in platelet count is an independent adverse prognostic indicator in LR-MDS, and combining relative platelet drop and transfusion dependency allows early identification of patients at risk of rapid progression, and may guide early therapeutic interventions, including allogeneic hematopoietic stem cell transplantation or experimental interventions. Taken together, these results indicate that regular RBCT requirement, early platelet count kinetics, and restriction in HRQoL are early independent and meaningful outcome indicators, and reliable measures of effectiveness of therapeutic interventions, evaluated in this set of studies. These findings support the integration of RBCT requirement and HRQoL in the general core outcome sets and in response criteria in patients with LR-MDS, and have important implications for clinical practice and the design of clinical endpoints. Our results strongly support the adoption of freedom from transfusion as a meaningful clinical endpoint in patients with LR-MDS. Anemia is the main determinant of therapeutic intervention in patients with LR-MDS, and ESA are recommended as first-line treatment for patients with symptomatic anemia. 10 The observational studies within the EUMDS Registry showed that the response rate, as well as the capacity of these agents to delay the onset of a regular RBCT need, is most pronounced in RBCT-naive patients. These results identified early initiation of treatment with ESA as a major treatment response indicator, and indicate that ESA should be recommended in LR-MDS patients with symptomatic anemia before starting regular RBCT. After the onset of RBCT dependency, patients with LR-MDS are prone to long-term accumulation of iron. 1,43 The EUMDS Registry studies provided evidence that elevated LPI levels are associated with reduced survival in RBCT dependent patients, whereas iron chelation therapy normalizes LPI levels. These findings suggest that NTBI and LPI may serve as early indicators of iron toxicity and a means to measure the effectiveness of iron chelation therapy in patients with LR-MDS. However, qualified NTBI and LPI are only currently available in specialized laboratories. 44 Large observational cohorts with detailed clinical and laboratory data, like the EUMDS cohort, are the ideal framework in which to identify well defined MDS subtypes that may benefit from novel targeted treatments. An example of such a subtype is MDS with loss of parts of chromosome 5, namely del5q; these patients have a relatively favorable outcome on lenalidomide treatment. In order to identify homogeneous subsets of patients within MDS, preliminary evidence has suggested that recently identified mutations in splicing factors may recognize distinct disease entities within myeloid neoplasms. 45 Splicing modulators are now in pre-clinical testing, and are very likely to lead to the introduction of effective drugs for specific groups of MDS patients. Luspatercept, a specific inhibitor of growth and differentiation factor-11, a member of the transforming growth factor β superfamily, induced substantial improvement of anemia, especially in patients with ring sideroblasts. 46 Characterization of individual cases by new genetic markers (one of the main objectives of the MDS-RIGHT project) will allow refined classification of patients into biological subgroups that are expected to respond differently to therapeutic interventions to guide discontinuation of those interventions that are less effective or less cost-effective. The main question is whether RCT data and retrospective cohort data in selected tertiary care centers are representative of the 'real world' data of the older patients with LR-MDS in the general population. A careful comparison of the 'real world' data and the RCT data will be needed in order to provide a clear answer to these questions. Meanwhile, the current analyses of data collected over 10 years in the EUMDS Registry provides relevant and important information which could help assess prognosis and response to standard interventions in this older patient group.

Iron overload due to red blood cell (RBC) transfusions is associated with morbidity and mortality in lower-risk myelodysplastic syndrome (MDS) patients. Many studies have suggested improved survival after iron chelation therapy (ICT), but valid data are limited. The aim of this study was to assess the effect of ICT on overall survival and hematologic improvement in lower-risk MDS patients in the European MDS registry. We compared chelated patients with a contemporary, non-chelated control group within the European MDS registry, that met the eligibility criteria for starting iron chelation. A Cox proportional hazards model was used to assess overall survival (OS), treating receipt of chelation as a time-varying variable. Additionally, chelated and non-chelated patients were compared using a propensity-score matched model. Of 2,200 patients, 224 received iron chelation. The hazard ratio and 95% confidence interval for OS for chelated patients, adjusted for age, sex, comorbidity, performance status, cumulative RBC transfusions, Revised-International Prognostic Scoring System (IPSS-R), and presence of ringed sideroblasts was 0.50 (0.34-0.74). The propensity-score analysis, matched for age, sex, country, RBC transfusion intensity, ferritin level, comorbidity, performance status, and IPSS-R, and, in addition, corrected for cumulative RBC transfusions and presence of ringed sideroblasts, demonstrated a significantly improved OS for chelated patients with a hazard ratio of 0.42 (0.27-0.63) compared to non-chelated patients. Up to 39% of chelated patients reached an erythroid response. In conclusion, our results suggest that iron chelation may improve OS and hematopoiesis in transfused lower-risk MDS patients. This trial was registered at clinicaltrials.gov identifier: 00600860.

45 In myelodysplastic syndromes (MDS) health-related quality of life (HRQoL) represents a relevant 46 patient-reported outcome, which is essential in individualized therapy planning. Prospective data 47 on HRQoL in lower-risk MDS remain rare. We assessed HRQOL by EQ-5D-questionnaire at initial 48 diagnosis in 1690 consecutive IPSS-Low/Int-1 MDS-patients from the European LeukemiaNet 49 Registry. Impairments were compared with ageand sex-matched EuroQol Group norms. A 50 significant proportion of MDS-patients reported moderate/severe problems in the dimensions 51 pain/discomfort (49.5%), mobility (41.0%), anxiety/depression (37.9%), and usual activities 52 (36.1%). Limitations in mobility, self-care, usual activities, pain/discomfort and EQ-VAS were 53 significantly more frequent in the old, in females, and in those with high co-morbidity burden, low 54 haemoglobin-levels, or red blood cells transfusion-need (p<0.001). In comparison to ageand sex55 matched peers, the proportion of problems in usual activities and anxiety/depression was 56 significantly higher in MDS-patients (p<0.001). MDS-related restrictions in the dimension mobility 57 were most prominent in males, and in older people (p<0.001); in anxiety/depression in female and 58 in younger people (p<0.001); and in EQ-VAS in women and in persons older than 75 years 59 (p<0.05). Patients newly diagnosed with IPSS lower-risk MDS experience a pronounced reduction 60 in HRQoL and a clustering of restrictions in distinct dimensions of HRQoL as compared with 61 reference populations. 62 63 © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Introduction Patient perception and perspective have become relevant in individualised therapy planning in MDS. Thus, integration of patient-reported outcomes (PRO), including health-related quality of life (HRQoL), in studies and in clinical practice is essential. We demonstrated recently pronounced impairments in HRQoL in patients with MDS (Stauder et al., Leukemia 2018). However, longitudinal data on aspects of HRQoL in MDS are rare.

BackgroundSelf-management is recommended for patients with chronic back pain. Health professionals' support for self-management can be more effective when working in partnership with patients. The aim of this study was to investigate the associations between patient-professional partnerships and the self-management of chronic back pain. MethodsAn explanatory sequential mixed methods study was undertaken. Adults with chronic back pain referred to pain management clinics participated at baseline and 3-month follow-up. Their pain severity, partnerships with health professionals and self-management ability were measured. Hierarchical linear regression was undertaken to examine the strength of the associations between partnerships and self-management. A subsample was interviewed about experiences of the impact of patient-professional partnerships on their self-management ability, using a grounded theory approach. ResultsA total of 147 patients were recruited and 103 (70%) patients completed the follow-up. A strong association (p<0.001) was detected between patient-professional partnerships and all dimensions of self-management ability. This was validated by interviews with a subsample of 26 patients. Four themes emerged as follows: connecting with health professionals, being supported through partnerships, feeling positive and making progress towards self-management, and acknowledging the impact but feeling no difference. ConclusionsDeveloping a partnership in care may improve patients' ability to gain knowledge, manage side effects and symptoms and adhere to treatment. It helped strengthen health professionals' support and produce a sense of safety for patients. Guiding health professionals in building partnerships where expectations are acknowledged and tailored information and support are provided could be considered as part of the standard education and training. SignificanceThis study identified and validated strong associations between patient-professional partnerships and self-management. Support for self-management alone may not be sufficient, and building partnerships where patients and professionals work together towards agreed goals make an essential contribution to helping increase patients' ability to self-manage chronic back pain.

Abstract Background Data on causes of death (COD) in patients with lower-risk (LR-MDS) is limited and sometimes conflicting. In contrast to higher-risk MDS, many LR-MDS patients die from conditions associated with advanced age, not directly associated with the underlying disease. Infections and cardiovascular disorders (CVD) have been reported as frequent COD in LR-MDS, but whether the incidence is higher than in age-matched population, is not known. The EUMDS Registry has been collecting prospective observational data on LR-MDS since 2008. The comprehensive clinical and laboratory data provides a unique chance to assess the impact of LR-MDS on survival either by causes related to MDS or indirectly related to MDS by aggravation of co-morbidities. Objectives To assess the impact of MDS and associated co-morbidities on COD in patients with LR-MDS and to evaluate the COD in the whole group and across participating countries. Methods: We evaluated clinical and laboratory data of LR-MDS patients registered in EUMDS registry from 2008 to 2018. Data were obtained by 145 centers from 16 European countries and Israel. MDS related causes of death were defined as infection, bleeding, MDS progression and AML transformation. Overall survival(OS) and relative survival(RS) were estimated using the Stata program 'strel' with age, sex and country specific background obtained from national life tables for the CONCORD program. RS is a standard approach used to take into account competing causes of death by adjusting for the age and sex specific mortality in the general population, estimating the excess mortality in these patients compared to that seen in the general population of each country. Results Overall data on 2235 LR-MDS patients was available in the EUMDS registry. Of these, 822 (36,7%) patients had died at the time of analysis. Median age was 77 years and 65% of the patients were male. Nearly half of them (46.9%) were diagnosed as IPPS low risk. The MDS-Comorbidity Index was low, intermediate and high in 55.7%, 37.5% and 6.8% of patients respectively. The most common COD were those considered as related to MDS 41.7% (Table 1). Deaths due to cardiovascular and pulmonary diseases were reported in 10.1% and 4.9% respectively. Other reasons (e.g. liver, renal failure, second malignancy) were found in 18.2%. In 25% of patients, the precise reason of death remained unknown. The proportion of MDS related COD were different between participating countries with lower rates in Germany (30%), France (31.3%) and higher in Portugal (55%), Greece (55.2%) and Romania (63.1%). Median follow-up was 2.1 years (0.1-10 years). Five-year overall survival in the whole cohort was 47.1% (95% CI: 44.1%-49.9%) and 5-year relative survival (attributed to MDS/AML only) was 59.1% (95% CI:55.4%-62.5%)(Figure 1). One year overall and relative survival was 90.4% (95% CI:89.1%-91.6%) and 94.4% (95% CI:93%-95.5%) respectively. Conclusions: MDS- related complications are the most common causes of death in LR-MDS patients. Comparison of overall and relative survival supports that observation and indicates that excess mortality in LR-MDS patients can be mainly explained by MDS/AML related causes. Interestingly, the strongest influence of MDS/AML attributable deaths was observed during the first year from diagnosis. Disclosures Fenaux: Janssen: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Roche: Honoraria; Otsuka: Honoraria, Research Funding. Stauder:Teva: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Germing:Novartis: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria, Research Funding. de Witte:Novartis: Research Funding; Celgene: Honoraria, Research Funding; Amgen: Consultancy, Research Funding. Smith:Jazz Pharmaceuticals: Research Funding; Johnson & Johnson: Research Funding; Gilead Sciences: Consultancy; Novartis: Research Funding.