Implementing national care guidelines in local authorities in England and Wales: a theory-of-change.

BACKGROUND: The delivery of high-quality services in chronically underfunded social or long-term care systems is a major challenge internationally. National guidelines, developed by the National Institute for Health and Care Excellence, set out how local authorities in England and Wales should fund and provide care based on best available evidence. Theoretical and participatory approaches can usefully inform the design and evaluation of implementation strategies for guidelines. The aim of the study is to develop a Theory-of-Change for how the implementation of these guidelines is expected to lead to impacts from a local authority perspective. METHODS: As part of a comparative case study (The 'Valuing Care Guidelines' study; February 2022 to April 2024) with three local authority sites in England and Wales, we involved altogether 17 participants in two Theory-of-Change online workshops per site, each of 2 hours. Additional data gathered from the same participants as part of the overall study were used to conceptualise and enrich information from the workshops. RESULTS: Participants described the Theory-of-Change map as follows: A wide range of activities (categorised in stages of 'pre-implementation', 'implementation', 'sustainment and scaling') and skills were required to implement guidelines, and achieve long-term organisational sustainability and service delivery outcomes, leading to final impacts for service users and carers. Participants described a co-creation implementation model, led by 'Implementation Support Practitioners', who utilised relational skills to achieve motivation, trust, and confidence at different organisational levels, addressing contextual barriers such as inadequate staffing, lack of resources and of organisational support systems. Consistent use of guidelines by frontline staff could only be achieved if the value of guideline implementation was promoted widely, and if consideration was given to the roles of stakeholders, such as the inspection body, local health care providers, users and carers. CONCLUSIONS: Our study is the first to investigate the implementation of national social care guidelines by local authorities in England and Wales. It generates insights that can guide implementation practice as well as inform the evaluation of future implementation strategies.

Economic Evaluation of Family-Focused Programs When Parents Have a Mental Health Problem: Methodological Considerations.

OBJECTIVES: The nature of adverse effects of parental mental health problems and of the interventions to address them may require specific designs of economic evaluation studies. Nevertheless, methodological guidance is lacking. We aim to understand the broad spectrum of adverse effects from parental mental health problems in children and the economic consequences on an individual and societal level to navigate the design of economic evaluations in this field. METHODS: We conducted a systematic literature search of empirical studies on children's adverse effects from parental mental illness. We clustered types of impact, identified individual and public cost consequences, and illustrated the results in an impact inventory. RESULTS: We found a wide variety of short- and long-term (mental) health impacts, impacts on social functioning and socioeconomic implications for the children individually, and adverse effects on the societal level. Consequently, public costs can occur in various public sectors (eg, healthcare, education), and individuals may have to pay costs privately. CONCLUSIONS: Existing evaluations in this field mostly follow standard methodological approaches (eg, cost-utility analysis using quality-adjusted life-years) and apply a short-time horizon. Our findings suggest applying a long-term time horizon (at least up to early adulthood), considering cost-consequence analysis and alternatives to health-related quality of life and quality-adjusted life-years as outcome measures, and capturing the full range of possible public and private costs.

The clinical value of detecting microcalcifications on a mammogram.

Many breast lesions are associated with microcalcifications that are detectable by mammography. In most cases, radiologists are able to distinguish calcifications usually associated with benign diseases from those associated with malignancy. In addition to their value in the early detection of breast carcinoma and accurate radiological diagnosis, the presence of microcalcifications often affects the extent of surgical intervention. Certain types of microcalcifications are associated with negative genetic and molecular characteristics of the tumor and unfavorable prognosis. Microcalcifications localized in the larger ducts (duct-centric, casting-type microcalcifications) represent an independent negative prognostic marker compared to lesions containing other types of microcalcifications and to non-calcified lesions. In this review, we summarize the theoretical and methodological background for understanding the clinical impact and discuss the diagnostic and prognostic value of microcalcifications detected in the breast by mammography.

What are the current and projected future cost and health-related quality of life implications of scaling up cognitive stimulation therapy?

OBJECTIVES: Cognitive stimulation therapy (CST) is one of the few non-pharmacological interventions for people living with dementia shown to be effective and cost-effective. What are the current and future cost and health-related quality of life implications of scaling-up CST to eligible new cases of dementia in England? METHODS/DESIGN: Data from trials were combined with microsimulation and macrosimulation modelling to project future prevalence, needs and costs. Health and social costs, unpaid care costs and quality-adjusted life years (QALYs) were compared with and without scaling-up of CST and follow-on maintenance CST (MCST). RESULTS: Scaling-up group CST requires year-on-year increases in expenditure (mainly on staff), but these would be partially offset by reductions in health and care costs. Unpaid care costs would increase. Scaling-up MCST would also require additional expenditure, but without generating savings elsewhere. There would be improvements in general cognitive functioning and health-related quality of life, summarised in terms of QALY gains. Cost per QALY for CST alone would increase from £12,596 in 2015 to £19,573 by 2040, which is below the threshold for cost-effectiveness used by the National Institute for Health and Care Excellence (NICE). Cost per QALY for CST and MCST combined would grow from £19,883 in 2015 to £30,906 by 2040, making it less likely to be recommended by NICE on cost-effectiveness grounds. CONCLUSIONS: Scaling-up CST England for people with incident dementia can improve lives in an affordable, cost-effective manner. Adding MCST also improves health-related quality of life, but the economic evidence is less compelling.

Examining the dynamics between young people's mental health, poverty and life chances in six low- and middle-income countries: protocol for the CHANCES-6 study.

PURPOSE: Poverty and poor mental health are closely related and may need to be addressed together to improve the life chances of young people. There is currently little evidence about the impact of poverty-reduction interventions, such as cash transfer programmes, on improved youth mental health and life chances. The aim of the study (CHANCES-6) is to understand the impact and mechanisms of such programmes. METHODS: CHANCES-6 will employ a combination of quantitative, qualitative and economic analyses. Secondary analyses of longitudinal datasets will be conducted in six low- and middle-income countries (Brazil, Colombia, Liberia, Malawi, Mexico and South Africa) to examine the impact of cash transfer programmes on mental health, and the mechanisms leading to improved life chances for young people living in poverty. Qualitative interviews and focus groups (conducted among a subset of three countries) will explore the views and experiences of young people, families and professionals with regard to poverty, mental health, life chances, and cash transfer programmes. Decision-analytic modelling will examine the potential economic case and return-on-investment from programmes. We will involve stakeholders and young people to increase the relevance of findings to national policies and practice. RESULTS: Knowledge will be generated on the potential role of cash transfer programmes in breaking the cycle between poor mental health and poverty for young people, to improve their life chances. CONCLUSION: CHANCES-6 seeks to inform decisions regarding the future design and the merits of investing in poverty-reduction interventions alongside investments into the mental health of young people.

Valuing Alzheimer's disease drugs: a health technology assessment perspective on outcomes.

OBJECTIVES: Due to the nature of Alzheimer's disease (AD), health technology assessment (HTA) agencies might face considerable challenges in choosing appropriate outcomes and outcome measures for drugs that treat the condition. This study sought to understand which outcomes informed previous HTAs, to explore possible reasons for prioritizations, and derive potential implications for future assessments of AD drugs. METHOD: We conducted a literature review of studies that analyzed decisions made in HTAs (across disease areas) in three European countries: England, Germany, and The Netherlands. We then conducted case studies of technology assessments conducted for AD drugs in these countries. RESULTS: Overall, outcomes measured using clinical scales dominated decisions or recommendations about whether to fund AD drugs, or price negotiations. HTA processes did not always allow the inclusion of outcomes relevant to people with AD, their carers, and families. Processes did not include early discussion and agreement on what would constitute appropriate outcome measures and cut-off points for effects. CONCLUSIONS: We conclude that in order to ensure that future AD drugs are valued appropriately and timely, early agreement with various stakeholders about outcomes, outcome measures, and cut-offs is important.

Cost-effectiveness of PoNDER health visitor training for mothers at lower risk of depression: findings on prevention of postnatal depression from a cluster-randomised controlled trial.

BACKGROUND: There is evidence for the cost-effectiveness of health visitor (HV) training to assess postnatal depression (PND) and deliver psychological approaches to women at risk of depression. Whether this approach is cost-effective for lower-risk women is unknown. There is a need to know the cost of HV-delivered universal provision, and how much it might cost to improve health-related quality of life for postnatal women. A sub-study of a cluster-randomised controlled trial in the former Trent region (England) previously investigated the effectiveness of PoNDER HV training in mothers at lower risk of PND. We conducted a parallel cost-effectiveness analysis at 6-months postnatal for all mothers with lower-risk status attributed to an Edinburgh Postnatal Depression Scale (EPDS) score <12 at 6-weeks postnatal. METHODS: Intervention HVs were trained in assessment and cognitive behavioural or person-centred psychological support techniques to prevent depression. Outcomes examined: quality-adjusted life-year (QALY) gains over the period between 6 weeks and 6 months derived from SF-6D (from SF-36); risk-of-depression at 6 months (dichotomising 6-month EPDS scores into lower risk (<12) and at-risk (⩾12). RESULTS: In lower-risk women, 1474 intervention (63 clusters) and 767 control participants (37 clusters) had valid 6-week and 6-month EPDS scores. Costs and outcomes data were available for 1459 participants. 6-month adjusted costs were £82 lower in intervention than control groups, with 0.002 additional QALY gained. The probability of cost-effectiveness at £20 000 was very high (99%). CONCLUSIONS: PoNDER HV training was highly cost-effective in preventing symptoms of PND in a population of lower-risk women and cost-reducing over 6 months.

Access to health care for older people with intellectual disability: a modelling study to explore the cost-effectiveness of health checks.

BACKGROUND: Whilst people with intellectual disability grow older, evidence has emerged internationally about the largely unmet health needs of this specific ageing population. Health checks have been implemented in some countries to address those health inequalities. Evaluations have focused on measuring process outcomes due to challenges measuring quality of life outcomes. In addition, the cost-effectiveness is currently unknown. As part of a national guideline for this population we sought to explore the likely cost-effectiveness of annual health checks in England. METHODS: Decision-analytical Markov modelling was used to estimate the cost-effectiveness of a strategy, in which health checks were provided for older people with intellectual disability, when compared with standard care. The approach we took was explorative. Individual models were developed for a selected range of health conditions, which had an expected high economic impact and for which sufficient evidence was available for the modelling. In each of the models, hypothetical cohorts were followed from 40 yrs. of age until death. The outcome measure was cost per quality-adjusted life-year (QALY) gained. Incremental cost-effectiveness ratios (ICER) were calculated. Costs were assessed from a health provider perspective and expressed in 2016 GBP. Costs and QALYs were discounted at 3.5%. We carried out probabilistic sensitivity analysis. Data from published studies as well as expert opinion informed parameters. RESULTS: Health checks led to a mean QALY gain of 0.074 (95% CI 0.072 to 0.119); and mean incremental costs of £4787 (CI 95% 4773 to 5017). For a threshold of £30,000 per QALY, health checks were not cost-effective (mean ICER £85,632; 95% CI 82,762 to 131,944). Costs of intervention needed to reduce from £258 to under £100 per year in order for health checks to be cost-effective. CONCLUSION: Whilst findings need to be considered with caution as the model was exploratory in that it was based on assumptions to overcome evidence gaps, they suggest that the way health systems deliver care for vulnerable populations might need to be re-examined. The work was carried out as part of a national guideline and informed recommendations about system changes to achieve more equal health care provisions.

Circles of Support and personalization: Exploring the economic case.

Circles of Support aim to enable people with learning disabilities (and others) to live full lives as part of their communities. As part of a wider study of the economic case for community capacity building conducted from 2012 to 2014, we conducted a mixed methods study of five Circles in North West England. Members of these Circles were supporting adults with moderate to profound learning disabilities and provided accounts of success in enabling the core member to live more independent lives with improved social care outcomes within cost envelopes that appeared to be less than more traditional types of support. The Circles also reported success in harnessing community resources to promote social inclusion and improve well-being. This very small-scale study can only offer tentative evidence but does appear to justify more rigorous research into the potential of Circles to secure cost-effective means of providing support to people with learning disabilities than the alternative, which in most cases would have been a long-term residential care placement.

Costs and benefits of scaling psychosocial interventions during the perinatal period in England: A simulation modelling study.

BACKGROUND: Globally, guidance recommends the integration of mental health into maternal and child healthcare to address common maternal mental health problems during the perinatal period. However, implementing this in the real-world requires substantial resource allocations. OBJECTIVE: The aim of this study was to estimate the likely costs and consequences linked to scaling the delivery of treatment (in the form of psychosocial interventions) during the perinatal period. DESIGN: Simulation modelling. SETTING(S): England. METHODS: Costs and consequences were modelled for three scenarios of assumed provision of services, whereby one referred to the projected provision under current government plans, with no additional scaling up of treatment. The other two scenarios referred to additional scaling of treatment: in one scenario, this referred to the provision of treatment by midwives and health visitors trained in the routine enquiry about mental health and delivery of psychosocial interventions; in the other scenario this referred to an expanded provision by primary mental health services. For each scenario and in yearly intervals (covering a ten-year period, 2015 to 2024), unit cots and outcomes were assigned to the activities women were assumed to receive (routine enquiry, assessment, treatment, care coordination). All costs were in 2020 pounds sterling. Data sources for the modelling included: published findings from randomised controlled trials; national unit cost source; national statistics; and expert consultation. RESULTS: If the projected treatment gap was to be addressed, an estimated additional 111,154 (50,031) women would be accessing treatment in 2015 (2024). Estimated total costs (including cost offsets) in the scenario of projected provision under current government plans would be £73.5 million in 2015 and £95.2 million in 2024, whilst quality-adjusted life years gained would be 901 and 928 respectively. Addressing the treatment gap through provision by trained midwives and health visitors could mean additional costs of £7.3 million in 2015 but lower costs of £18.4 million in 2024. The additional quality-adjusted life years gained are estimated at 2096 in 2015 and 1418 in 2024. A scenario in which the treatment gap would be met by primary mental health services was likely to be more costly and delivered less health gains. CONCLUSIONS: Findings from this modelling study suggest that scaling the integration of mental health care into routinely delivered care for women during the perinatal period might be economically viable. REGISTRATION: N/A. TWEETABLE ABSTRACT: Integrating mental health into maternal and child healthcare might generate economic benefits new study by @a_annettemaria and @knappem @CPEC_LSE finds #increasing access to treatment for women with perinatal mental health problems.

Types and aspects of support that young carers need and value, and barriers and enablers to access: the REBIAS-YC qualitative study.

Background: Many children and young people in England provide support to family members who are disabled, have mental or physical ill health, or misuse drugs or alcohol. Providing care can negatively impact children and young people's education, employment, health and social participation, with associated costs. Support is needed to prevent and reduce these negative impacts. The study sought to provide new knowledge and address prior research gaps regarding how best to support young carers from their perspective and that of the people they care for. Objectives: To address the following questions: What types, components or features of services and other support are seen as helpful, valued, and acceptable to young people who look after someone at home and the people they support? Conversely, what is found to be less or unhelpful? What additional support is perceived as needed? What are the barriers experienced by young and young adult carers in seeking and accessing services for themselves or the person they support? What are the barriers and facilitators for practitioners in providing support and services perceived as valued, helpful and needed by young and young adult carers and the people they support? Design and setting: In-depth qualitative methodology using focus groups, in-depth semistructured interviews and workshops in four localities in England. Participants: One hundred and thirty-three carers aged 9-25 years with a range of caring and life circumstances and sociodemographic characteristics. Seventeen adult care recipients (parents) with a range of physical and/or mental healthcare and support needs. Nineteen practitioners from schools, colleges, young carers organisations, voluntary sector services, mental health services, the National Health Service, adult social care and local authority adult and children's social care commissioners. Results: The types and aspects of support that young carers and their families need, and value when received, include: support that reduces or removes their practical and emotional caring responsibilities; support to mitigate the negative impacts of care and help with other life issues; information and advice about services and wider resources and support; someone trusted available to talk to; greater awareness, recognition and understanding; and choice, flexibility, and co-development of plans and solutions. We found a great deal of unmet need for support, and variation in type and quality of support received, including geographically. Limitations: Potential limitations are that we were not able to engage with, or recruit, young carers from some intended subgroups, meaning some perspectives are missing. Partly because of COVID-19 measures during the study, we mainly recruited through young carers organisations and their family projects, although this was balanced by recruitment through schools and extensive outreach and engagement by the collaborating organisations prior to the project starting. Conclusions: Action is now needed to consistently and sustainably implement the types of support that young carers and the people they care for say they need and value. Future work: Future work should include more research from the perspectives of young carers and the people they care for, especially from particularly marginalised groups; and research to understand what works and how to improve implementation of the support needed and valued. Study registration: This study is registered as Current Controlled Trials ISRCTN13478876. https://doi.org/10.1186/ISRCTN13478876. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR129645) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 36. See the NIHR Funding and Awards website for further award information.

Many children and young people in England provide support to family members who are disabled, have mental or physical ill health, or misuse drugs or alcohol. They are sometimes called young or young adult carers. Providing care often brings satisfaction and a sense of pride but can also have negative effects on young people's lives. The study aimed to find out their views about what would best support them and the people they care for. The study asked two important questions: (1) What are the difficulties faced by young carers and the people they support in seeking, accessing and receiving the right type of support at the right times? (2) What services and support do they find helpful, what support would they like, and what needs would it meet? To answer these questions, we held group discussions (focus groups) and in-depth interviews with 133 young carers with a range of caring and life circumstances and 17 parents receiving help from a young carer. We also held workshops with 19 practitioners who are involved in identifying, supporting and funding services for young carers and their families. They told us that the types of support that they and their families need, and value when received, include: support for the people they care for, so they are providing less practical and emotional care support to help with any negative impacts of providing care and with other life issues information and advice about services, wider resources and support someone trusted to talk to greater awareness, recognition and understanding choice, flexibility and working together to develop plans and solutions We found a great deal of unmet need for support, and variation in the type and quality of support received, including across geographical areas. Action is now needed to consistently and sustainably implement the types of support that young carers and their families say they need and value.

Perinatal mental health care in the Italian mental health departments: a national survey.

BACKGROUND: Evidence on the negative outcomes of untreated mental disorders during pregnancy and in the first year after childbirth on women's and children's health has stimulated interest in how to develop and sustain high-quality mental health care during the perinatal period. In Italy, there is a lack of knowledge about how mental health services support women with perinatal mental disorders (PMDs). This study aims to describe the adoption of good practices for the prevention and care of PMDs by the Italian mental health departments (MHDs). METHODS: This is a nationwide cross-sectional survey conducted online using LimeSurvey. Starting from the Ministry of Health Registry's 127 MHDs were invited to participate between February and March, 2023. Characteristics of the participating MHDs were reported as descriptive statistics. RESULTS: One hundred nineteen MHDs participated, with a response rate of 93.7%. Regarding the prevention of PMDs, 69 (58.0%) MHDs offer preconception counseling, whereas only 6 (5.0%) have information material for this purpose. Written integrated care pathways for PMDs are not available in 94 (79.7%) MHDs. A reference professional for psychopharmacological treatment during pregnancy or breastfeeding is available in 55 (46.2%) MHDs, while a specific treatment plan for women with PMDs is adopted by 27 (22.7%) MHDs. Thirty-four (28.6%) MHDs have established an outpatient clinic for PMDs, whereas there are no inpatient psychiatric facilities designed for mothers and infants (mother-baby units). CONCLUSIONS: There is a need to improve the care of women with PMDs in Italy. The provision of pre-conception counseling, integrated care pathways, and specialist skills and facilities for PMDs should be prioritized.

Acceptability, engagement and exploratory outcomes and costs of a co-designed intervention to support children of parents with a mental illness: Mixed-methods evaluation and descriptive analysis.

Children whose parents have a mental illness are much more likely to experience mental health problems and other adverse long-term impacts. Child-centred psychosocial interventions can be effective, but not much is known about how to design and implement them in different settings. A pre-post, mixed methods, single-arm evaluation of a co-designed social support intervention with parents and children (4-18 years) measured parents' mental health (PHQ-9), perceived social support (ENRICHD), parental self-efficacy (PSAM) and children's mental health (SDQ), quality of life (Kidscreen-27), and child service use (CAMHSRI-EU) at baseline and 6 months. Qualitative data were gathered at 6 months to explore parents' and children's experience with the intervention. Twenty-nine parents and 21 children completed baseline and follow-up questionnaires; 22 parents and 17 children participated in interviews. Parents' depression (MD -1.36, SD 8.08), perceived social support (MD 1, SD 5.91), and children's mental health potentially improved, and children's service use and costs potentially reduced (€224.6 vs. €122.2, MD 112.4). Parental self-efficacy was potentially reduced (MD -0.11, SD 3.33). The sample was too small to perform statistical analysis. Favourable themes emerged describing the high satisfaction with the intervention, parents' improved understanding of the impact of their mental health problems on children, and improvements in parent-child relationships. This study contributes to an emerging evidence base for co-designed child-centred interventions to prevent the transgenerational transmission of poor mental health.

Exploring the return-on-investment for scaling screening and psychosocial treatment for women with common perinatal mental health problems in Malawi: Developing a cost-benefit-calculator tool.

This study sought to develop a user-friendly decision-making tool to explore country-specific estimates for costs and economic consequences of different options for scaling screening and psychosocial interventions for women with common perinatal mental health problems in Malawi. We developed a simple simulation model using a structure and parameter estimates that were established iteratively with experts, based on published trials, international databases and resources, statistical data, best practice guidance and intervention manuals. The model projects annual costs and returns to investment from 2022 to 2026. The study perspective is societal, including health expenditure and productivity losses. Outcomes in the form of health-related quality of life are measured in Disability Adjusted Life Years, which were converted into monetary values. Economic consequences include those that occur in the year in which the intervention takes place. Results suggest that the net benefit is relatively small at the beginning but increases over time as learning effects lead to a higher number of women being identified and receiving (cost­)effective treatment. For a scenario in which screening is first provided by health professionals (such as midwives) and a second screening and the intervention are provided by trained and supervised volunteers to equal proportions in group and individual sessions, as well as in clinic versus community setting, total costs in 2022 amount to US$ 0.66 million and health benefits to US$ 0.36 million. Costs increase to US$ 1.03 million and health benefits to US$ 0.93 million in 2026. Net benefits increase from US$ 35,000 in 2022 to US$ 0.52 million in 2026, and return-on-investment ratios from 1.05 to 1.45. Results from sensitivity analysis suggest that positive net benefit results are highly sensitive to an increase in staff salaries. This study demonstrates the feasibility of developing an economic decision-making tool that can be used by local policy makers and influencers to inform investments in maternal mental health.

Economic costs of perinatal depression and anxiety in a lower middle income country: Pakistan.

BACKGROUND: Women's mental health during the perinatal period is a major public health problem in Pakistan. Many challenges and competing priorities prevent progress to address the large treatment gap. Aim To quantify the long-term impacts of untreated perinatal depression and anxiety in economic terms, thus highlighting its overall burden based on country-specific evidence. METHODS: Cost estimates were generated for a hypothetical cohort of women giving birth in 2017, and their children. Women and children experiencing adverse events linked to perinatal mental health problems were modelled over 40 years. Costs assigned to adverse events included were those linked to losses in quantity and quality-of-life, productivity, and healthcare-related expenditure. Present values were derived using a discount rate of 3 %. Data were taken from published cohort studies, as well as from sources of population, economic and health indicators. RESULTS: The total costs were $16.5 billion for the cohort and $2680 per woman giving birth. The by far largest proportion referred to quality-of-life losses ($15.8 billion). Productivity losses and out-of-pocket expenditure made up only a small proportion of the costs, due to low wages and market prices. When the costs of maternal suicide were included, total costs increased to $16.6 billion. LIMITATIONS: Important evidence gaps prevented the inclusion of all cost consequences linked to perinatal mental health problems. CONCLUSIONS: Total national costs are much higher compared with those in other, higher middle-income countries, reflecting the excessive disease burden. This study is an important first step to inform resource allocations.

HER2-low metastases of HER2-negative primary tumors: a single institution analysis of intertumoral and internodal heterogeneity in node-positive breast cancer.

Objective: HER2 status in breast cancer is an essential parameter in individual therapeutic decision-making and is routinely assessed in primary tumors in accordance with international recommendations. Reports of HER2 heterogeneity raise the question of basing treatment decisions on HER2 status in metastases, if present. We investigated the degree and clinical implications of HER2 heterogeneity in lymph node-positive breast cancer. Because of recent recognition of therapeutic opportunities in this group of tumors, we especially focused on cases involving low-level HER2 expression. Methods: The HER2 status of primary tumors and of corresponding lymph node metastases was determined in archived material at the protein and gene levels using the gene- protein assay and interpreted in accordance with 2018 ASCO/CAP criteria. HER2-low status was defined as protein expression levels 1+ or 2+ with negative amplification status. Results: We analyzed a series of 43 cases of primary infiltrating breast cancer, each with at least two axillary nodes harboring macrometastases (>2 mm), in total 206 such nodes. In 7% of cases, we detected intertumoral HER2 heterogeneity. Three of nine HER2-positive primary tumors were associated with HER2-negative metastases. No cases with HER2-negative primary tumors had HER2-positive metastases, but 55% (6/11) of HER2 0 primary tumors had HER2 1+ and/or 2+ metastases, and 19% (3/16) HER2 1+ cases had exclusively HER2 0 metastases. All metastases in HER2 2+ cases showed HER2-low protein expression levels. Internodal HER2 heterogeneity at low protein expression levels (presence of HER2 0, HER2 1+, and/or HER2 2+ metastatic deposits within the same axilla) was seen in 40% (17/43) of cases. We found no statistically significant association between HER2 heterogeneity and other tumor-related parameters. Survival data indicated worse outcomes in the HER2-low group compared with the rest of the cohort. Conclusion: Our results indicate a substantial instability of HER2 protein expression, leading to considerable intertumoral and internodal HER2 heterogeneity in lymph node-positive breast carcinomas. This heterogeneity is particularly relevant in HER2-low tumors in which the corrective effects of HER2 gene copy number analysis definitionally is absent. Our findings suggest that determining HER2 status in metastatic lymph nodes may generate relevant information for therapeutic decision-making.

Potential mechanisms by which cash transfer programmes could improve the mental health and life chances of young people: A conceptual framework and lines of enquiry for research and policy.

Mental health is inextricably linked to both poverty and future life chances such as education, skills, labour market attachment and social function. Poverty can lead to poorer mental health, which reduces opportunities and increases the risk of lifetime poverty. Cash transfer programmes are one of the most common strategies to reduce poverty and now reach substantial proportions of populations living in low- and middle-income countries. Because of their rapid expansion in response to the COVID-19 pandemic, they have recently gained even more importance. Recently, there have been suggestions that these cash transfers might improve youth mental health, disrupting the cycle of disadvantage at a critical period of life. Here, we present a conceptual framework describing potential mechanisms by which cash transfer programmes could improve the mental health and life chances of young people. Furthermore, we explore how theories from behavioural economics and cognitive psychology could be used to more specifically target these mechanisms and optimise the impact of cash transfers on youth mental health and life chances. Based on this, we identify several lines of enquiry and action for future research and policy.

Practices to support co-design processes: A case-study of co-designing a program for children with parents with a mental health problem in the Austrian region of Tyrol.

Forms of collaborative knowledge production, such as community-academic partnerships (CAP), have been increasingly used in health care. However, instructions on how to deliver such processes are lacking. We aim to identify practice ingredients for one element within a CAP, a 6-month co-design process, during which 26 community- and 13 research-partners collaboratively designed an intervention programme for children whose parent have a mental illness. Using 22 published facilitating and hindering factors for CAP as the analytical framework, eight community-partners reflected on the activities which took place during the co-design process. From a qualitative content analysis of the data, we distilled essential practices for each CAP factor. Ten community- and eight research-partners revised the results and co-authored this article. We identified 36 practices across the 22 CAP facilitating or hindering factors. Most practices address more than one factor. Many practices relate to workshop design, facilitation methods, and relationship building. Most practices were identified for facilitating 'trust among partners', 'shared visions, goals and/or missions', 'effective/frequent communication', and 'well-structured meetings'. Fewer practices were observed for 'effective conflict resolution', 'positive community impact' and for avoiding 'excessive funding pressure/control struggles' and 'high burden of activities'. Co-designing a programme for mental healthcare is a challenging process that requires skills in process management and communication. We provide practice steps for delivering co-design activities. However, practitioners may have to adapt them to different cultural contexts. Further research is needed to analyse whether co-writing with community-partners results in a better research output and benefits for participants.

Psychosis Recovery Orientation in Malawi by Improving Services and Engagement (PROMISE) protocol.

Malawi has a population of around 20 million people and is one of the world's most economically deprived nations. Severe mental illness (largely comprising psychoses and severe mood disorders) is managed by a very small number of staff in four tertiary facilities, aided by clinical officers and nurses in general hospitals and clinics. Given these constraints, psychosis is largely undetected and untreated, with a median duration of untreated psychosis (DUP) of around six years. Our aim is to work with people with lived experience (PWLE), caregivers, local communities and health leaders to develop acceptable and sustainable psychosis detection and management systems to increase psychosis awareness, reduce DUP, and to improve the health and lives of people with psychosis in Malawi. We will use the UK Medical Research Council guidance for developing and evaluating complex interventions, including qualitative work to explore diverse perspectives around psychosis detection, management, and outcomes, augmented by co-design with PWLE, and underpinned by a Theory of Change. Planned deliverables include a readily usable management blueprint encompassing education and community supports, with an integrated care pathway that includes Primary Health Centre clinics and District Mental Health Teams. PWLE and caregivers will be closely involved throughout to ensure that the interventions are shaped by the communities concerned. The effect of the interventions will be assessed with a quasi-experimental sequential implementation in three regions, in terms of DUP reduction, symptom remission, functional recovery and PWLE / caregiver impact, with quality of life as the primary outcome. As the study team is focused on long-term impact, we recognise the importance of having embedded, robust evaluation of the programme as a whole. We will therefore evaluate implementation processes and outcomes, and cost-effectiveness, to demonstrate the value of this approach to the Ministry of Health, and to encourage longer-term adoption across Malawi.