21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer.

BACKGROUND: The recurrence score based on the 21-gene breast-cancer assay has been clinically useful in predicting a chemotherapy benefit in hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary lymph-node-negative breast cancer. In women with positive lymph-node disease, the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is unclear. METHODS: In a prospective trial, we randomly assigned women with hormone-receptor-positive, HER2-negative breast cancer, one to three positive axillary lymph nodes, and a recurrence score of 25 or lower (scores range from 0 to 100, with higher scores indicating a worse prognosis) to endocrine therapy only or to chemotherapy plus endocrine (chemoendocrine) therapy. The primary objective was to determine the effect of chemotherapy on invasive disease-free survival and whether the effect was influenced by the recurrence score. Secondary end points included distant relapse-free survival. RESULTS: A total of 5083 women (33.2% premenopausal and 66.8% postmenopausal) underwent randomization, and 5018 participated in the trial. At the prespecified third interim analysis, the chemotherapy benefit with respect to increasing invasive disease-free survival differed according to menopausal status (P = 0.008 for the comparison of chemotherapy benefit in premenopausal and postmenopausal participants), and separate prespecified analyses were conducted. Among postmenopausal women, invasive disease-free survival at 5 years was 91.9% in the endocrine-only group and 91.3% in the chemoendocrine group, with no chemotherapy benefit (hazard ratio for invasive disease recurrence, new primary cancer [breast cancer or another type], or death, 1.02; 95% confidence interval [CI], 0.82 to 1.26; P = 0.89). Among premenopausal women, invasive disease-free survival at 5 years was 89.0% with endocrine-only therapy and 93.9% with chemoendocrine therapy (hazard ratio, 0.60; 95% CI, 0.43 to 0.83; P = 0.002), with a similar increase in distant relapse-free survival (hazard ratio, 0.58; 95% CI, 0.39 to 0.87; P = 0.009). The relative chemotherapy benefit did not increase as the recurrence score increased. CONCLUSIONS: Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease-free survival and distant relapse-free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. (Funded by the National Cancer Institute and others; RxPONDER ClinicalTrials.gov number, NCT01272037.).

Polypharmacy, over-the-counter medications, and aromatase inhibitor adherence in early-stage breast cancer.

PURPOSE: Polypharmacy is associated with negative health outcomes and decreased medication adherence. Polypharmacy is common in cancer populations, but few studies have evaluated the relationship between polypharmacy and aromatase inhibitor (AI) adherence. No studies have evaluated the relationship between over-the-counter (OTC) supplements and AI adherence. Our primary hypothesis was that polypharmacy would be associated with increased risk of premature AI discontinuation. METHODS: This exploratory analysis used data from the Exemestane and Letrozole Pharmacogenetics (ELPh) trial, a prospective, multicenter, randomized controlled trial that enrolled participants from 2005 to 2009. Included patients were female, postmenopausal, with stage 0-III breast cancer, who had completed indicated chemotherapy, surgery, and radiation. Participants were randomized to adjuvant exemestane or letrozole and completed serial clinical examinations and questionnaires for two years. Concomitant medication data were collected prospectively. Cox proportion models were used for statistical analysis of the relationship between polypharmacy, OTCs, medication class, and AI adherence. RESULTS: In the 490 analyzed participants, use of any prescription medications at baseline was associated with decreased risk of premature AI discontinuation (HR 0.56, p = 0.02). Use of selective serotonin reuptake inhibitors (SSRIs) or selective serotonin and norepinephrine reuptake inhibitors (SNRIs) at baseline was associated with decreased risk of premature AI discontinuation (HR 0.67, p = 0.04). Use of any OTCs was not associated with AI discontinuation. CONCLUSION: Baseline use of prescription medications but not OTCs was associated with increased AI persistence. Future research is needed to understand how this can be utilized to promote AI adherence.

Breast Cancer Circulating Tumor Cells: Current Clinical Applications and Future Prospects.

BACKGROUND: Identification and characterization of circulating tumor markers, designated as "liquid biopsies," have greatly impacted the care of cancer patients. Although more recently referring to circulating tumor DNA (ctDNA), the term liquid biopsy initially was coined to refer to any blood-borne biomarker related to malignancy, including circulating tumor cells (CTCs) in blood. In this manuscript, we review the specific state of the art of CTCs in breast cancer. CONTENT: Liquid biopsies might play a clinical role across the entire spectrum of breast cancer, from risk assessment, prevention, screening, and treatment. CTC counts have been shown to carry clear, independent prognostic information in the latter situation. However, the clinical utility of CTCs in breast cancer remains to be determined. Nonetheless, in addition to CTC enumeration, analyses of CTCs provide tumor molecular information representing the entire, often-heterogeneous disease, relatively noninvasively and longitudinally. Technological advances have allowed the interrogation of CTC-derived information, providing renewed hope for a clinical role in disease monitoring and precision oncology. SUMMARY: This narrative review examines CTCs, their clinical validity, and current prospects of clinical utility in breast cancer with the goal of improving patient outcomes.

Equal, equitable or exacerbating inequalities: patterns and predictors of social prescribing referrals in 160 128 UK patients.

BACKGROUND: Social prescribing is growing rapidly globally as a way to tackle social determinants of health. However, whom it is reaching and how effectively it is being implemented remains unclear. AIMS: To gain a comprehensive picture of social prescribing in the UK, from referral routes, reasons, to contacts with link workers and prescribed interventions. METHOD: This study undertook the first analyses of a large database of administrative data from over 160 000 individuals referred to social prescribing across the UK. Data were analysed using descriptive analyses and regression modelling, including logistic regression for binary outcomes and negative binomial regression for count variables. RESULTS: Mental health was the most common referral reason and mental health interventions were the most common interventions prescribed. Between 72% and 85% of social prescribing referrals were from medical routes (primary or secondary healthcare). Although these referrals demonstrated equality in reaching across sociodemographic groups, individuals from more deprived areas, younger adults, men, and ethnic minority groups were reached more equitably via non-medical routes (e.g. self-referral, school, charity). Despite 90% of referrals leading to contact with a link worker, only 38% resulted in any intervention being received. A shortage of provision of community activities - especially ones relevant to mental health, practical support and social relationships - was evident. There was also substantial heterogeneity in how social prescribing is implemented across UK nations. CONCLUSIONS: Mental health is the leading reason for social prescribing referrals, demonstrating its relevance to psychiatrists. But there are inequalities in referrals. Non-medical referral routes could play an important role in addressing inequality in accessing social prescribing and therefore should be prioritised. Additionally, more financial and infrastructural resource and strategic planning are needed to address low intervention rates. Further investment into large-scale data platforms and staff training are needed to continue monitoring the development and distribution of social prescribing.

Fates of Terrigenous Dissolved Organic Carbon in the Gulf of Maine.

A significant amount of organic carbon is transported in dissolved form from soils to coastal oceans via inland water systems, bridging land and ocean carbon reservoirs. However, it has been discovered that the presence of terrigenous dissolved organic carbon (tDOC) in oceans is relatively limited. Therefore, understanding the fates of tDOC in coastal oceans is essential to account for carbon sequestration through land ecosystems and ensure accurate regional carbon budgeting. In this study, we developed a state-of-the-art modeling approach by coupling a land-to-ocean tDOC flux simulation model and a coastal tDOC tracking model to determine the potential fates of tDOC exported from three primary drainage basins in the Gulf of Maine (GoM). According to our findings, over half a year in the GoM, 56.4% of tDOC was mineralized. Biomineralization was responsible for 90% of that amount, with the remainder attributed to photomineralization. Additionally, 37% of the tDOC remained suspended in the GoM, and 6.6% was buried in the marine sediment.

Building common understanding: seeking consensus and defining social prescribing across contexts - a collective commentary on a Delphi study.

Social prescribing has become a global phenomenon. A Delphi study was recently conducted with 48 social prescribing experts from 26 countries to establish global agreement on the definition of social prescribing. We reflect on the use and utility of the outputs of this work, and where we go from here.

Surgeon Factors and Trends Associated With the Use of Subacromial Decompression at the Time of Rotator Cuff Repair.

PURPOSE: Subacromial decompression (SAD) has historically been described as an essential part of the surgical treatment of rotator cuff disorders. However, investigations throughout the 21st century have increasingly questioned the need for routine SAD during rotator cuff repair (RCR). Our purpose was to assess for changes in the incidence of SAD performed during RCR over a 12-year period. In addition, we aimed to characterize surgeon and practice factors associated with SAD use. METHODS: Records from two large tertiary referral systems in the United States from 2010 to 2021 were reviewed. All cases of RCR with and without SAD were identified. The outcome of interest was the proportion of SAD performed during RCR across years and by surgeon. Surgeon-specific characteristics included institution, fellowship training, surgical volume, academic practice, and years in practice. Yearly trends were assessed using binomial logistic regression modeling, with a random effect accounting for surgeon-specific variability. RESULTS: During the study period, 37,165 RCR surgeries were performed by 104 surgeons. Of these cases, 71% underwent SAD during RCR. SAD use decreased by 11%. The multivariable model found that surgeons in academic practice, those with lower surgical volume, and those with increasing years in practice were significantly associated with increased odds of performing SAD. Surgeons with fellowship training were significantly more likely to use SAD over time, with the greatest odds of SAD noted for sports medicine surgeons (odds ratio = 3.04). CONCLUSIONS: Although SAD use during RCR appears to be decreasing, multiple surgeon and practice factors (years in practice, fellowship training, volume, and academic practice) are associated with a change in SAD use. CLINICAL RELEVANCE: These data suggest that early-career surgeons entering practice are likely driving the trend of declining SAD. Despite evidence suggesting limited clinical benefits, SAD remains commonly performed; future studies should endeavor to determine factors associated with practice changes among surgeons.

A Comparison of Early Complication Rates of Endoscopic Carpal Tunnel Release With and Without Resident Involvement.

PURPOSE: The purpose of this study was to compare the complication rates of endoscopic carpal tunnel release (ECTR) relative to orthopedic resident trainee involvement in the procedure. METHODS: All patients undergoing isolated, elective ECTR by two attending surgeons within a 59-month period were analyzed. Cases were categorized as the following according to the degree of resident involvement: ECTR performed by attending with either no resident or a resident as an assistant (group 1), resident performing a portion of the procedure (group 2), and resident performing the entire procedure (group 3). Early postoperative complications and/or intraoperative conversion to an open procedure were the outcomes of interest. We used a noninferiority design, hypothesizing that resident involvement would not be associated with inferior outcomes compared with cases without resident involvement. Multiple logistic regression models, adjusted for patient demographic and surgical characteristics, were fit to assess the relationship between resident involvement groups and complication/conversion outcomes. RESULTS: A total of 1,167 ECTR cases (895 patients) were performed and returned for postoperative follow-up for at least 2 weeks after surgery. Operative time was significantly shorter for group 1 cases versus group 2 and 3 cases. The early postoperative complication and conversion rates were 1.7% and 1.0%, respectively. Superficial infection (1.2%), deep infection (0.3%), and transient neuropraxia (0.3%) occurred infrequently and did not differ relative to resident involvement. No differences in the odds of complication and/or conversion relative to resident involvement were observed. CONCLUSIONS: The results of ECTR performed entirely or in part by attending-supervised resident trainees were not inferior to ECTR performed by an attending surgeon regarding the odds of experiencing complications or conversion to an open procedure. With appropriate supervision, ECTR can be performed safely by orthopedic and plastic surgery residents. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Ruin-of-the-rivers? A global review of run-of-the-river dams.

The classification of a hydropower scheme as run-of-the-river (or run-of-river; ROR) evokes an image of a low-impact installation; however, examination of eight case studies worldwide shows that substantial negative societal and ecological impacts are tied to them, albeit in somewhat different ways. We conclude that ROR dams not only potentially displace communities, disrupt livelihoods, and degrade environments in surrounding areas, but they also divert water from areas of need, impact aquatic ecology through habitat destruction and disruption of fish migrations, emit non-trivial amounts of greenhouse gases over the lifespan of the project, and disrupt streamflow in downstream river sections. While these negative impacts vary on a case-by-case basis, medium and large ROR dams consistently have multiple and cumulative impacts, even when not having appreciable reservoirs. We contend that many impactful dams do not qualify as low-impact ROR projects, despite being defined as such. Such mislabeling is facilitated in part by the ambiguous definition of the term, which risks the ROR concept being used by proponents of impactful structures to downplay their negative effects and thus mislead the public or gain status, including within the Clean Development Mechanism in relation to mitigating climate change.

Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors are effective in germline BRCA1 or BRCA2 (BRCA1/2) mutation-associated metastatic breast cancer. However, studies evaluating PARP inhibitors plus platinum-based chemotherapy in germline BRCA1/2-wildtype triple-negative breast cancer are scarce. A large proportion of germline BRCA1/2-wildtype triple-negative breast cancer shows homologous recombination deficiency (HRD), resulting in a BRCA-like phenotype that might render sensitivity to PARP inhibitors. The S1416 trial assessed the efficacy of cisplatin combined with the PARP inhibitor veliparib in three predefined groups of metastatic breast cancer: germline BRCA1/2-mutated, BRCA-like, and non-BRCA-like. METHODS: S1416 was a randomised, double-blind, placebo-controlled, phase 2 trial conducted at 154 community and academic clinical sites across the USA. Eligible patients aged 18 years or older had metastatic or recurrent triple-negative breast cancer or germline BRCA1/2-associated metastatic or recurrent breast cancer, an Eastern Cooperative Oncology Group performance status of 0-2, and had received up to one line of chemotherapy for metastatic disease. Patients were randomly assigned (1:1) via the National Clinical Trials Network open interactive system with dynamic balancing on number of previous cytotoxic regimens for metastatic disease to receive intravenous cisplatin (75 mg/m2, day 1) combined with either veliparib or matching placebo (300 mg orally twice a day, days 1-14) on a 21-day cycle. Investigators, patients, and the sponsors were masked to treatment assignment; the study statisticians were unmasked. Central testing after ran domisation classified patients as having mutated or wildtype germline BRCA1/2. A biomarker panel established a priori was used to classify patients with wildtype germline BRCA1/2 into BRCA-like and non-BRCA-like phenotype groups, with BRCA-like status based on at least one of the biomarkers: genomic instability score (≥42), somatic BRCA1/2 mutations, BRCA1 promoter methylation, or non-BRCA1/2 homologous recombination repair germline mutations. The primary endpoint was investigator-assessed progression-free survival, analysed separately for the three predefined biomarker groups with a prespecified α value for each analysis. Efficacy analyses were done by intention to treat and included all eligible patients. Safety analyses of toxicities attributed to treatment included all patients who received at least one dose of veliparib or placebo. The study is ongoing and registered with ClinicalTrials.gov, NCT02595905. FINDINGS: Between July 7, 2016, and June 15, 2019, 335 patients were enrolled and randomly assigned. 320 patients (n=162 to cisplatin plus veliparib, all women; and n=158 to cisplatin plus placebo, 157 women and one man) were eligible for efficacy evaluation. 247 patients were classified into the three biomarker groups: germline BRCA1/2-mutated (n=37), BRCA-like (n=101), and non-BRCA-like (n=109). 73 patients could not be classified due to missing biomarker information. Median follow-up was 11·1 months (IQR 5·6-20·8). In the germline BRCA1/2-mutated group, median progression-free survival was 6·2 months (95% CI 2·3-9·2) in the cisplatin plus veliparib group and 6·4 months (4·3-8·2) in the cisplatin plus placebo group (HR 0·79 [95% CI 0·38-1·67]; log-rank p=0·54). In the BRCA-like group, median progression-free survival was 5·9 months (95% CI 4·3-7·8) in the cisplatin plus veliparib group versus 4·2 months (2·3-5·0) in the cisplatin plus placebo group (HR 0·57 [95% CI 0·37-0·88]; p=0·010). In the non-BRCA-like group, median progression-free survival was 4·0 months (95% CI 2·5-4·7) in the cisplatin plus veliparib group versus 3·0 months (2·2-4·4) in the cisplatin plus placebo group (HR 0·89 [95% CI 0·60-1·33]; p=0·57). The most common grade 3 or worse adverse events attributed to treatment were neutropenia (71 [46%] of 155 patients in the cisplatin plus veliparib group vs 29 [20%] of 147 in the cisplatin plus placebo group), leukopenia (42 [27%] vs 11 [7%]), anaemia (35 [23%] vs 12 [8%]), and thrombocytopenia (29 [19%] vs four [3%]). Serious adverse events attributed to treatment occurred in 48 (31%) patients in the cisplatin plus veliparib group and 53 (36%) patients in the cisplatin plus placebo group. Treatment-related adverse events led to death in one patient in the cisplatin plus veliparib group (sepsis) and one patient in the cisplatin plus placebo group (acute kidney injury due to cisplatin plus heart failure from previous doxorubicin exposure). INTERPRETATION: The addition of veliparib to cisplatin significantly improved progression-free survival in patients with BRCA-like metastatic triple-negative breast cancer, but not in patients with non-BRCA-like metastatic breast cancer. PARP inhibitors combined with platinum-based chemotherapy should be explored further in BRCA-like triple-negative breast cancer. FUNDING: National Cancer Institute and National Institute of General Medical Sciences (US National Institutes of Health); AbbVie; Myriad Genetics; the Biomarker, Imaging, and Quality of Life Studies Funding Program (awarded by the National Cancer Institute); and The University of Kansas Cancer Center.

REMARK guidelines for tumour biomarker study reporting: a remarkable history.

In 2005, several experts in tumor biomarker research publishe the REporting recommendations for Tumor MARKer prognostic studies (REMARK) criteria. Coupled with the subsequent Biospecimen Reporting for Improved Study Quality (BRISQ) criteria, these initiatives provide a framework for transparently reporting of the methods of study conduct and analyses.

Thymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226).

BACKGROUND: Some patients with metastatic breast cancer (MBC) stay on endocrine therapy (ET) for years and others progress quickly. Serum thymidine kinase activity (TKa), an indicator of cell-proliferation, is a potential biomarker for monitoring ET and predicting MBC outcome. We have previously reported TKa as being prognostic in MBC in SWOG S0226. Here, new data on progression within 30/60 days post sampling, with a new, FDA approved version of DiviTum®TKa highlighting differences vs. a Research Use Only version is reported. METHODS: 1,546 serum samples from 454 patients were assessed, collected at baseline and at 4 subsequent timepoints during treatment. A new predefined cut-off tested the ability to predict disease progression. A new measuring unit, DuA (DiviTum® unit of Activity) is adopted. RESULTS: A DiviTum®TKa score <250 DuA provides a much lower risk of progression within 30/60 days after blood draw, the negative predictive value (NPV) was 96.7% and 93.5%, respectively. Patients <250 DuA experienced significantly longer progression-free survival and overall survival, demonstrated at baseline and for all time intervals. CONCLUSIONS: DiviTum®TKa provides clinically meaningful information for patients with HR+ MBC. Low TKa levels provide such a high NPV for rapid progression that such patients might forego additional therapy added to single agent ET.Trial registration: NCT00075764.

Global patterns of drought recovery.

Drought, a recurring phenomenon with major impacts on both human and natural systems, is the most widespread climatic extreme that negatively affects the land carbon sink. Although twentieth-century trends in drought regimes are ambiguous, across many regions more frequent and severe droughts are expected in the twenty-first century. Recovery time-how long an ecosystem requires to revert to its pre-drought functional state-is a critical metric of drought impact. Yet the factors influencing drought recovery and its spatiotemporal patterns at the global scale are largely unknown. Here we analyse three independent datasets of gross primary productivity and show that, across diverse ecosystems, drought recovery times are strongly associated with climate and carbon cycle dynamics, with biodiversity and CO2 fertilization as secondary factors. Our analysis also provides two key insights into the spatiotemporal patterns of drought recovery time: first, that recovery is longest in the tropics and high northern latitudes (both vulnerable areas of Earth's climate system) and second, that drought impacts (assessed using the area of ecosystems actively recovering and time to recovery) have increased over the twentieth century. If droughts become more frequent, as expected, the time between droughts may become shorter than drought recovery time, leading to permanently damaged ecosystems and widespread degradation of the land carbon sink.

Integrative clinical genomics of metastatic cancer.

Metastasis is the primary cause of cancer-related deaths. Although The Cancer Genome Atlas has sequenced primary tumour types obtained from surgical resections, much less comprehensive molecular analysis is available from clinically acquired metastatic cancers. Here we perform whole-exome and -transcriptome sequencing of 500 adult patients with metastatic solid tumours of diverse lineage and biopsy site. The most prevalent genes somatically altered in metastatic cancer included TP53, CDKN2A, PTEN, PIK3CA, and RB1. Putative pathogenic germline variants were present in 12.2% of cases of which 75% were related to defects in DNA repair. RNA sequencing complemented DNA sequencing to identify gene fusions, pathway activation, and immune profiling. Our results show that integrative sequence analysis provides a clinically relevant, multi-dimensional view of the complex molecular landscape and microenvironment of metastatic cancers.

Wellbeing while waiting evaluating social prescribing in CAMHS: study protocol for a hybrid type II implementation-effectiveness study.

BACKGROUND: Social prescribing is a mechanism of connecting patients with non-medical forms of support within the community and has been shown to improve mental health and wellbeing in adult populations. In the last few years, it has been used in child and youth settings with promising results. Currently, pathways are being developed for social prescribing in Child and Adolescent Mental Health Services (CAMHS) to support children and young people on treatment waiting lists. The Wellbeing While Waiting study will evaluate whether social prescribing benefits the mental health and wellbeing of children and young people. METHODS: This study utilises an observational, hybrid type II implementation-effectiveness design. Up to ten CAMHS who are developing social prescribing pathways as part of a programme run across England with support from the Social Prescribing Youth Network will participate. Outcomes for children and young people receiving social prescribing whilst on CAMHS waiting lists will be compared to a control group recruited prior to the pathway roll-out. Questionnaire data will be collected at baseline, 3 months and 6 months. Primary outcomes for children and young people are mental health symptoms (including anxiety, depression, stress, emotional and behavioural difficulties). Secondary outcomes include: loneliness, resilience, happiness, whether life is worthwhile, life satisfaction, and service use. An implementation strand using questionnaires and interviews will explore the acceptability, feasibility, and suitability of the pathway, potential mechanisms of action and their moderating effects on the outcomes of interest, as well as the perceived impact of social prescribing. Questionnaire data will be analysed mainly using difference-in-differences or controlled interrupted time series analysis. Interview data will be analysed using reflexive thematic analysis. DISCUSSION: The Wellbeing While Waiting study will provide the first rigorous evidence of the impact of social prescribing for children and young people on waiting lists for mental health treatment. Findings will help inform the prioritisation, commissioning, and running of social prescribing in other CAMHS. To maximise impact, findings will be available on the study website ( https://sbbresearch.org ) and disseminated via national and international networks. TRIAL REGISTRATION: N/A.

Evidence-based Recovery Colleges: developing a typology based on organisational characteristics, fidelity and funding.

PURPOSE: Recovery Colleges (RCs) have been implemented across England with wide variation in organisational characteristics. The purpose of this study is to describe RCs across England in terms of organisational and student characteristics, fidelity and annual spending, to generate a RC typology based on characteristics and to explore the relationship between characteristics and fidelity. METHODS: All RC in England meeting criteria on recovery orientation, coproduction and adult learning were included. Managers completed a survey capturing characteristics, fidelity and budget. Hierarchical cluster analysis was conducted to identify common groupings and generate an RC typology. RESULTS: Participants comprised 63 (72%) of 88 RC in England. Fidelity scores were high (median 11, IQR 9-13). Both NHS and strengths-focussed RCs were associated with higher fidelity. The median annual budget was £200,000 (IQR £127,000-£300,000) per RC. The median cost per student was £518 (IQR £275-£840), cost per course designed was £5,556 (IQR £3,000-£9,416) and per course run was £1,510 (IQR £682-£3,030). The total annual budget across England for RCs is an estimated £17.6 m including £13.4 m from NHS budgets, with 11,000 courses delivered to 45,500 students. CONCLUSION: Although the majority of RCs had high levels of fidelity, there were sufficiently pronounced differences in other key characteristics to generate a typology of RCs. This typology might prove important for understanding student outcomes and how they are achieved and for commissioning decisions. Staffing and co-producing new courses are key drivers of spending. The estimated budget for RCs was less than 1% of NHS mental health spending.

Defining young people's mental health self-care: a systematic review and co-development approach.

Self-care is among the emerging types of mental health support which operate outside traditional services, although the meaning and practice of self-care for young people with mental health difficulties are currently unclear. This systematic review was pre-registered with PROSPERO (CRD42021282510) and investigated conceptualizations of self-care in academic publications which investigated or discussed self-care for young people's mental health or wellbeing. A Patient and Public Involvement (PPI) workshop facilitated young people with experience of mental health difficulties to respond to the identified concepts and co-develop a definition of self-care. Searches in PsycINFO, MEDLINE, Embase, CINAHL Plus, Scopus, Cochrane Library of Systematic Reviews, and gray literature sources resulted in 90 included publications. Content analysis indicated little conceptual consistency, with health and wellness promotion most commonly used to define self-care. The PPI workshop co-developed a definition of mental health self-care, which attendees felt should emphasize an individual process of self-awareness, self-compassion, and specific strategies to work toward emotional balance. This study highlights the gap between current academic understandings of young people's mental health self-care and young people's experience. The presented definition will enable future research to begin from an understanding of self-care which is relevant to young people with experience of mental health difficulties.

A systematic review of shared decision making interventions in child and youth mental health: synthesising the use of theory, intervention functions, and behaviour change techniques.

Reviews around interventions to improve shared decision making (SDM) for child and youth mental health have produced inconclusive findings on what approaches increase participation. Importantly, the previous reviews did not explore the use of theory, as well as mechanisms of change (intervention functions) and active units of change (behaviour change techniques). The aim of this review was to explore these factors and ascertain how, if at all, these contribute to SDM. Five databases were searched up until April 2020. Studies met inclusion criteria if they were: (a) an intervention to facilitate SDM; (b) aimed at children, adolescence, or young people aged up to 25, with a mental health difficulty, or their parents/guardians; and (c) included a control group. Data were extracted on patient characteristics, study design, intervention, theoretical background, intervention functions, behaviour change techniques, and SDM. Quality assessment of the studies was undertaken using the Effective Public Health Practice Project (EPHPP) quality assessment tool. Eight different interventions met inclusion criteria. The role of theory to increase SDM remains unclear. Specific intervention functions, such as 'education' on SDM and treatment options and 'environmental restructuring' using decision aids, are being used in SDM interventions, as well as 'training' for clinicians. Similarly, behaviour change techniques linked to these, such as 'adding objects to the environment', 'discussing pros/cons', and clinicians engaging in 'behavioural practice/rehearsal'. However, as most studies scored low on the quality assessment criteria, as well as a small number of studies included and a low number of behaviour change techniques utilised, links between behaviour change techniques, intervention functions and increased participation remain tentative. Intervention developers and clinicians may wish to consider specific intervention functions and behaviour change techniques to facilitate SDM.

Self-management, self-care, and self-help in adolescents with emotional problems: a scoping review.

This study aimed to review the existing published and grey literature describing the concepts of self-management, self-care, and self-help, and to capture strategies or techniques related to these concepts, for adolescents with emotional problems. Emotional problems are rising amongst adolescents, yet timely access to specialist mental health treatment is limited to those with greater severity of mental health difficulties. Self-management, self-care, and self-help strategies may be used by adolescents with emotional problems both in terms of those waiting for treatment and to prevent relapse. Given the overlap in existing definitions and the lack of clarity around these concepts in an adolescent mental health context, a scoping review of the literature is warranted to provide clarity. Eligible studies were those involving adolescents aged 10 to 19 years with symptoms of emotional problems. Studies referenced self-management, self-care, or self-help, not involving a professional, in this population. Quantitative, qualitative, economic, and mixed methods studies, as well as systematic, scoping, and literature reviews, from 2000 onwards and in the English language, were eligible for inclusion. A systematic search was conducted of both published and grey literature. Databases searched included PsycINFO, Medline, Embase, Web of Science, and CINAHL Plus. Mednar was also searched for unpublished studies and grey literature. Tables  of themes, terms, and associated strategies are presented alongside a thematic analysis of the results. 62 articles were included. These were 20 quantitative studies, 14 systematic reviews, 10 qualitative studies, five review papers, four book chapters, four mixed methods studies, two dissertations, two meta-analyses and one scoping review and systematic review. Most of the included articles referenced self-help (n = 51), followed by self-management (n = 17) and self-care (n = 6). A total of 12 themes were identified from a reflexive thematic analysis of descriptions (and associated strategies) of self-management, self-help, or self-care in included texts. This scoping review provides clarity on the similarities and differences between how these concepts are discussed, and the strategies which are associated with each of these concepts in the relevant literature. Implications for policy and intervention development for adolescents' self-management, self-help, and self-care of their mental health are discussed. There is considerable overlap in both the ways in which these concepts are described, and the strategies or approaches proposed in relation to them, supporting previous research suggesting these strategies should be grouped under a single term, such as "self or community approaches." More research is needed for self-management, self-help, and self-care amongst marginalized groups as these adolescents may have the highest unmet need for mental health support.

The impact of universal, school based, interventions on help seeking in children and young people: a systematic literature review.

Reviews into universal interventions to improve help seeking in young people focus on specific concepts, such as behaviour, do not differentiate between interpersonal and intrapersonal help seeking, and often report on statistical significance, rather than effect size. The aim of this review was to address the gaps highlighted above, to investigate the impact of universal, school-based interventions on help-seeking in children and young people, as well as to explore longer term impact. Four databases were searched. Data were extracted on country of origin, design, participant, school, and intervention characteristics, the help-seeking concept measured (e.g. knowledge, attitude/intention, behaviour), the duration between baseline and each follow-up (if applicable) and effect sizes at each follow-up. Quality assessment of the studies was undertaken using the Effective Public Health Practice Project (EPHPP) quality assessment tool. Overall, 14 different interventions met inclusion criteria. The majority of the studies were rated low in the quality assessment. Three constructs were most frequently reported a) intrapersonal attitudes towards help-seeking, b) interpersonal attitudes towards help-seeking and c) intrapersonal intended help-seeking. Findings around intervention effect were mixed. There was tentative evidence that interventions impacting interpersonal attitudes produced small effect sizes when measured between 3 and 6 months post intervention and that when effect sizes were initially observed intrapersonal attitudes, this remained at 3-6 month follow-up. Further work should pay attention to implementation factors, understanding the core ingredients needed to deliver effective interventions and whether embedding mental health education could help sustain or top up effect sizes from help-seeking interventions.