What helps people to reduce or stop self-harm? A systematic review and meta-synthesis of first-hand accounts.

BACKGROUND: Self-harm is an important public health problem but therapeutic interventions, particularly for people who have a history of multiple repetition, are not always taken up or effective when they are. The aim of this review is to explore first-hand accounts of what helps outside therapy and identify actions and processes, which can support the reduction or cessation of self-harm. METHODS: A systematic review and thematic meta-synthesis of the first-person accounts of what has helped to reduce or stop self-harm reported in primary studies. RESULTS: The meta-synthesis combined 546 participant excerpts from 56 studies. Two over-arching themes were identified: (i) breaking the chain incorporated actions taken to break the link between a person's current psychological or social state and the act of self-harm and (ii) building a new foundation for change captured actions over the longer-term, focusing on practical changes in relationships and in a person's way of life, such as work or living arrangements. CONCLUSIONS: The results emphasize the importance of interpersonal change in reducing or stopping self-harm. While interpersonal factors are acknowledged as important reasons behind self-harm, they are often under-represented in self-management advice and therapeutic interventions that focus on individual psychopathology.

"They have more than enough to do than patch up people like me." Experiences of seeking support for self-harm in lockdown during the COVID-19 pandemic.

WHAT IS KNOWN ON THE SUBJECT?: In the initial months of the pandemic, there was no significant increase in demand for mental health services During the pandemic, there was an increase in people reporting an increase in suicidal thoughts. Understanding of the experience of seeking help for self-harm during lockdown is lacking, in terms of availability and accessibility of support services WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: People who self-harm found that their support structures were significantly impacted by lockdown Lockdown presented relational difficulties for people who self-harm WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Learning about the experience of receiving support from mental health liaison services during lockdown from a first-hand perspective is essential to improving the provision of these services in the future. In times of national crisis, services should be prepared to support clients via alternative means including telephone and online. Public facing messages about service availability should be carefully expressed to minimize misunderstandings. ABSTRACT: Introduction National lockdown caused disruption to health services and third-sector organizations offering support to people who self-harm. Early reports suggested self-harm-related hospital attendances declined. Lack of knowledge related to the availability and accessibility of support provisions for people who self-harm warrants exploration into how they experienced help-seeking during lockdown. Aims This study aimed to explore the experiences of people who self-harm and perspectives on help-seeking. Method We conducted a qualitative study based on telephone and email interviews with 14 people who self-harm in England. Results Participants identified challenges to coping with life in lockdown, emphasizing the role of self-harm. Help-seeking was impeded by feeling like a burden and potential for spreading the virus. People who self-harm exercised self-reliance in response to "stay home" messaging, but some may have struggled without formal support. Online support served an important role in continuity of care during lockdown but could widen inequalities from limited resources and access. Implications for practice Helping mental health liaison nurses to understand the experiences of people who self-harm during lockdown is critical to providing continuing support to this population. Services should consider how and when they communicate changes to their provisions to the public, and the impact this will have on those in need of support.

Valued attributes of professional support for people who repeatedly self-harm: A systematic review and meta-synthesis of first-hand accounts.

Therapeutic interventions are an important adjunct to self-help strategies for people who self-harm. There is little guidance for those offering therapy on the effective components of interventions for people who self-harm. This was a systematic review aiming to identify the factors that contribute to positive experiences of therapy as described by people who have reduced or stopped self-harm. The review followed PRISMA guidelines to locate and synthesize peer-reviewed qualitative studies describing experiences of therapy among people who had reduced or stopped self-harm. Study selection, data extraction, and quality assessment were peer reviewed and conducted for at least two researchers independently. Relevant first-hand quotations were extracted from eligible studies and synthesized using a thematic analysis in collaboration with experts with personal and professional experience of self-harm. Twenty-three studies met eligibility criteria. Themes identified in the reported accounts were arranged under two meta-themes. 'Positive aspects of seeing a professional' identified aspects of professional care that were common to all encounters: the value of sharing, space to talk and reflect, and the boundaries inherent in contact with a professional. 'Positive attributes of individual professionals' depended upon individual characteristics: the ability to build reciprocal trust by being non-judgemental, showing genuine empathic concern, and being confident to talk about and respond directly to self-harm. Our review indicates that therapeutic alliance is perceived as key to effective professional help for self-harm, irrespective of underlying principles of therapy. All forms of therapy should be timely and reliable and centred around the needs of the individual and their experience of self-harm.

Understanding the functions of repeated self-harm: A Q methodology approach.

BACKGROUND: Multiple repetition of self-harm is common and is associated with poor quality of life and with an increased risk of suicide. Treatment outside specialist clinics rarely takes account of what is known about the varied and conflicting reasons for multiple repetition. We aimed to identify ways in which individuals who self-harm make sense of their motivations for repetition. METHODS: In 2018/2019 we recruited 59 participants from NHS services, support organizations in England and via social media into a Q-methodology study. Participants sorted, ranked and commented on 46 separate functions of self-harm according to whether they agreed or disagreed with them as reasons for their own self-harm. The functions were identified from a range of academic sources and first-person accounts. RESULTS: Principal Component Analysis was used to identify four distinct accounts for repeated self-harm: 1) Managing my mental state, 2) Communicating Distress, 3) Distract from suicidal thoughts or feelings and 4) Producing positive feelings. There were no clear links between account and gender or other respondent characteristic, although those who self-harmed most regularly and frequently ('so many times I've lost count') were mostly in Accounts 1 and 4. CONCLUSIONS: This is the first study to use Q methodology to explore reasons for repeated self-harm. The accounts identified can help in personalizing therapy by going beyond models that focus on a single function such as affect regulation or experiential avoidance, while reducing the field to a manageable number of points of view that can be explored in therapy.

Online Resources for People Who Self-Harm and Those Involved in Their Informal and Formal Care: Observational Study with Content Analysis.

Despite recent fears about online influences on self-harm, the internet has potential to be a useful resource, and people who self-harm commonly use it to seek advice and support. Our aim was to identify and describe UK-generated internet resources for people who self-harm, their friends or families, in an observational study of information available to people who search the internet for help and guidance. The different types of advice from different websites were grouped according to thematic analysis. We found a large amount of advice and guidance regarding the management of self-harm. The most detailed and practical advice, however, was limited to a small number of non-statutory sites. A lay person or health professional who searches the web may have to search through many different websites to find practical help. Our findings therefore provide a useful starting point for clinicians who wish to provide some guidance for their patients about internet use. Websites change over time and the internet is in constant flux, so the websites that we identified would need to be reviewed before making any recommendations to patients or their families or friends.

Social prescribing: less rhetoric and more reality. A systematic review of the evidence.

OBJECTIVES: Social prescribing is a way of linking patients in primary care with sources of support within the community to help improve their health and well-being. Social prescribing programmes are being widely promoted and adopted in the UK National Health Service and so we conducted a systematic review to assess the evidence for their effectiveness. SETTING/DATA SOURCES: Nine databases were searched from 2000 to January 2016 for studies conducted in the UK. Relevant reports and guidelines, websites and reference lists of retrieved articles were scanned to identify additional studies. All the searches were restricted to English language only. PARTICIPANTS: Systematic reviews and any published evaluation of programmes where patient referral was made from a primary care setting to a link worker or facilitator of social prescribing were eligible for inclusion. Risk of bias for included studies was undertaken independently by two reviewers and a narrative synthesis was performed. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes of interest were any measures of health and well-being and/or usage of health services. RESULTS: We included a total of 15 evaluations of social prescribing programmes. Most were small scale and limited by poor design and reporting. All were rated as a having a high risk of bias. Common design issues included a lack of comparative controls, short follow-up durations, a lack of standardised and validated measuring tools, missing data and a failure to consider potential confounding factors. Despite clear methodological shortcomings, most evaluations presented positive conclusions. CONCLUSIONS: Social prescribing is being widely advocated and implemented but current evidence fails to provide sufficient detail to judge either success or value for money. If social prescribing is to realise its potential, future evaluations must be comparative by design and consider when, by whom, for whom, how well and at what cost. TRIAL REGISTRATION NUMBER: PROSPERO Registration: CRD42015023501.

Does access to a demand-led evidence briefing service improve uptake and use of research evidence by health service commissioners? A controlled before and after study.

BACKGROUND: The Health and Social Care Act mandated research use as a core consideration of health service commissioning arrangements in England. We undertook a controlled before and after study to evaluate whether access to a demand-led evidence briefing service improved the use of research evidence by commissioners compared with less intensive and less targeted alternatives. METHODS: Nine Clinical Commissioning Groups (CCGs) in the North of England received one of three interventions: (A) access to an evidence briefing service; (B) contact plus an unsolicited push of non-tailored evidence; or (C) unsolicited push of non-tailored evidence. Data for the primary outcome measure were collected at baseline and 12 months using a survey instrument devised to assess an organisations' ability to acquire, assess, adapt and apply research evidence to support decision-making. Documentary and observational evidence of the use of the outputs of the service were sought. RESULTS: Over the course of the study, the service addressed 24 topics raised by participating CCGs. At 12 months, the evidence briefing service was not associated with increases in CCG capacity to acquire, assess, adapt and apply research evidence to support decision-making, individual intentions to use research findings or perceptions of CCG relationships with researchers. Regardless of intervention received, participating CCGs indicated that they remained inconsistent in their research-seeking behaviours and in their capacity to acquire research. The informal nature of decision-making processes meant that there was little traceability of the use of evidence. Low baseline and follow-up response rates and missing data limit the reliability of the findings. CONCLUSIONS: Access to a demand-led evidence briefing service did not improve the uptake and use of research evidence by NHS commissioners compared with less intensive and less targeted alternatives. Commissioners appear well intentioned but ad hoc users of research. Further research is required on the effects of interventions and strategies to build individual and organisational capacity to use research.

Effects of a demand-led evidence briefing service on the uptake and use of research evidence by commissioners of health services: protocol for a controlled before and after study.

BACKGROUND: Clinical Commissioning Groups (CCGs) are mandated to use research evidence effectively to ensure optimum use of resources by the National Health Service (NHS), both in accelerating innovation and in stopping the use of less effective practices and models of service delivery. We intend to evaluate whether access to a demand-led evidence service improves uptake and use of research evidence by NHS commissioners compared with less intensive and less targeted alternatives. METHODS/DESIGN: This is a controlled before and after study involving CCGs in the North of England. Participating CCGs will receive one of three interventions to support the use of research evidence in their decision-making: 1) consulting plus responsive push of tailored evidence; 2) consulting plus an unsolicited push of non-tailored evidence; or 3) standard service unsolicited push of non-tailored evidence. Our primary outcome will be changed at 12 months from baseline of a CCGs ability to acquire, assess, adapt and apply research evidence to support decision-making. Secondary outcomes will measure individual clinical leads and managers' intentions to use research evidence in decision making. Documentary evidence of the use of the outputs of the service will be sought. A process evaluation will evaluate the nature and success of the interactions both within the sites and between commissioners and researchers delivering the service. DISCUSSION: The proposed research will generate new knowledge of direct relevance and value to the NHS. The findings will help to clarify which elements of the service are of value in promoting the use of research evidence. Those involved in NHS commissioning will be able to use the results to inform how best to build the infrastructure they need to acquire, assess, adapt and apply research evidence to support decision-making and to fulfil their statutory duties under the Health and Social Care Act.

Translating research into practice in Leeds and Bradford (TRiPLaB): a protocol for a programme of research.

BACKGROUND: The National Institute for Health Research (NIHR) has funded nine Collaborations for Leadership in Applied Health Research and Care (CLAHRCs). Each CLAHRC is a partnership between higher education institutions (HEIs) and the NHS in nine UK regional health economies. The CLAHRC for Leeds, York, and Bradford comprises two 'research themes' and three 'implementation themes.' One of these implementation themes is Translating Research into Practice in Leeds and Bradford (TRiPLaB). TRiPLaB aims to develop, implement, and evaluate methods for inducing and sustaining the uptake of research knowledge into practice in order to improve the quality of health services for the people of Leeds and Bradford. METHODS: TRiPLaB is built around a three-stage, sequential, approach using separate, longitudinal case studies conducted with collaborating NHS organisations, TRiPLaB will select robust innovations to implement, conduct a theory-informed exploration of the local context using a variety of data collection and analytic methods, and synthesise the information collected to identify the key factors influencing the uptake and adoption of targeted innovations. This synthesis will inform the development of tailored, multifaceted, interventions designed to increase the translation of research findings into practice. Mixed research methods, including time series analysis, quasi-experimental comparison, and qualitative process evaluation, will be used to evaluate the impact of the implementation strategies deployed. CONCLUSION: TRiPLaB is a theory-informed, systematic, mixed methods approach to developing and evaluating tailored implementation strategies aimed at increasing the translation of research-based findings into practice in one UK health economy. Through active collaboration with its local NHS, TRiPLaB aims to improve the quality of health services for the people of Leeds and Bradford and to contribute to research knowledge regarding the interaction between context and adoption behaviour in health services.

xCT expression reduces the early cell cycle requirement for calcium signaling.

Calcium has long been recognized as an important regulator of cell cycle transitions although the mechanisms are largely unknown. A functional genomic screen has identified genes involved in the regulation of early cell cycle progression by calcium. These genes when overexpressed confer the ability to bypass the G1/S arrest induced by Ca(2+)-channel antagonists in mouse fibroblasts. Overexpression of the cystine-glutamate exchanger, xCT, had the greatest ability to evade calcium antagonist-induced cell cycle arrest. xCT carries out the rate limiting step of glutathione synthesis in many cell types and is responsible for the uptake of cystine in most human cancer cell lines. Functional analysis indicates that the cystine uptake activity of xCT overcomes the G1/S arrest induced by Ca(2+)-channel antagonists by bypassing the requirement for calcium signaling. Since cells overexpressing xCT were found to have increased levels and activity of the AP-1 transcription factor in G1, redox stimulation of AP-1 activity accounts for the observed growth of these cells in the presence of calcium channel antagonists. These results suggest that reduced calcium signaling impairs AP-1 activation and that xCT expression may directly affect cell proliferation.

Effective knock down of very high ABCG2 expression by a hammerhead ribozyme.

BACKGROUND: Ribozymes are an effective tool to reduce the mRNA levels of specific target genes. Overexpression of the drug transport protein, ABCG2, has been associated with multidrug resistance in cancer cells. MATERIALS AND METHODS: An expression plasmid encoding a hammerhead ribozyme against the ABCG2 gene was stably transfected into multidrug-resistant MCF7/MX cells that express very high levels of the ABCG2 protein. The effect of the ribozyme was determined by quantitative real-time RT-PCR, Western blot and cytotoxicity assays. RESULTS: The ribozyme reduced ABCG2 mRNA levels to less than 10% of control values, which resulted in the concomitant reduction of ABCG2 protein levels and sensitization of the cells to mitoxantrone and methotrexate. CONCLUSION: The ribozyme used was highly effective in reducing the expression of its target gene, ABCG2, and was able to modulate the associated multidrug-resistant phenotype.

Overexpression of wild-type breast cancer resistance protein mediates methotrexate resistance.

Previously, we have reported that a multidrug-resistant, mitoxantrone (MX)-selected cell line, MCF7/MX, is highly cross-resistant to the antifolate methotrexate (MTX), because of enhanced ATP-dependent drug efflux (E. L. Volk et al., Cancer Res., 60: 3514-3521, 2000). These cells overexpress the breast cancer resistance protein (BCRP), and resistance to MTX as well as to MX was reversible by the BCRP inhibitor, GF120918. These data indicated that BCRP causes the multidrug-resistance phenotype. To further examine the role of this transporter in MTX resistance, and in particular the role of amino acid 482, we analyzed a number of BCRP-overexpressing cell lines. MTX resistance correlated with BCRP expression in all of the cell lines expressing the wild-type transporter, which contains an Arg at position 482. In contrast, little or no cross-resistance was found in the MCF7/AdVp1000 and S1-M1-3.2 and S1-M1-80 cell lines, which contain acquired mutations at this position, R482T and R482G, respectively. Concomitantly, the greatest reduction in MTX accumulation was observed in the MCF7/MX cells (BCRP(Arg)) as compared with cells expressing the Thr and Gly BCRP variants. Furthermore, the reduction in drug accumulation was sensitive to BCRP inhibition by GF120918. In conclusion, we have demonstrated a novel role for BCRP as a mediator of MTX resistance and have provided further evidence for the importance of amino acid 482 in substrate specificity.