Combination of self-harm methods and fatal and non-fatal repetition: A cohort study.

BACKGROUND: Assessment and aftercare for people who self-harm needs to be related to an understanding of risks of adverse outcomes. We aimed to determine whether self-harm by a combination of methods and its early repetition are associated with adverse outcomes - especially non-fatal repetition and suicide. METHOD: 10,829 consecutive general hospital attendances due to self-harm in one large English city were monitored, through scrutiny of Emergency Department attendances, over three years and followed up to determine the incidence of non-fatal repetition. Subsequent deaths, by any cause and by suicide, were determined from national statistical records. RESULTS: 6155 patients accounted for the 10,829 episodes: 72% by self-poisoning, 21% self-injury, and 746 episodes (7%) due to a combination of methods. After a combined-methods index episode, non-fatal repetition (P=0.001) and suicide (P=0.002) occurred sooner and more frequently than it did among those who had self-poisoned. Further hospital attendance due to self-harm within a month was associated with a 3.7-fold (95% CI 2.1-6.4) risk of subsequent suicide. LIMITATIONS: The data exclude self-harm episodes that do not result in a hospital attendance. Index episodes in the study are not generally life-time first episodes so follow-up data are based on an arbitrary start-point. Both of these limitations are common to all studies of this kind. CONCLUSIONS: At psychosocial assessment and the making of aftercare arrangements, combined methods of self-harm or another recent episode should be considered 'red-flag' indicators for attention to care

Combined bezafibrate and medroxyprogesterone acetate: potential novel therapy for acute myeloid leukaemia

Background: The majority of acute myeloid leukaemia (AML) patients are over sixty years of age. With current treatment regimens, survival rates amongst these, and also those younger patients who relapse, remain dismal and novel therapies are urgently required. In particular, therapies that have anti-leukaemic activity but that, unlike conventional chemotherapy, do not impair normal haemopoiesis. Principal Findings: Here we demonstrate the potent anti-leukaemic activity of the combination of the lipid-regulating drug bezafibrate (BEZ) and the sex hormone medroxyprogesterone acetate (MPA) against AML cell lines and primary AML cells. The combined activity of BEZ and MPA (B/M) converged upon the increased synthesis and reduced metabolism of prostaglandin D2 (PGD2) resulting in elevated levels of the downstream highly bioactive, anti-neoplastic prostaglandin 15-deoxy Δ12,14 PGJ2 (15d-PGJ2). BEZ increased PGD2 synthesis via the generation of reactive oxygen species (ROS) and activation of the lipid peroxidation pathway. MPA directed prostaglandin synthesis towards 15d-PGJ2 by inhibiting the PGD2 11β -ketoreductase activity of the aldo-keto reductase AKR1C3, which metabolises PGD2 to 9α11β-PGF2α. B/M treatment resulted in growth arrest, apoptosis and cell differentiation in both AML cell lines and primary AML cells and these actions were recapitulated by treatment with 15d-PGJ2. Importantly, the actions of B/M had little effect on the survival of normal adult myeloid progenitors. Significance: Collectively our data demonstrate that B/M treatment of AML cells elevated ROS and delivered the anti-neoplastic actions of 15d-PGJ2. These observations provide the mechanistic rationale for the redeployment of B/M in elderly and relapsed AML

The feasibility of using the EQ-5D-3L with adults with mild to moderate learning disabilities within a randomized control trial: a qualitative evaluation

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: The datasets used and analysed during the current study are available from the corresponding author on reasonable request. It is not possible to share qualitative data as individuals could be identifiable.Background In trials incorporating a health economic evaluation component, reliable validated measures for health-related quality of life (HRQOL) are essential. The EQ-5D is the preferred measure for cost-effectiveness analysis in UK trials. This paper presents a qualitative evaluation of the use of the EQ-5D-3L in a feasibility randomised control trial with participants who had a mild- to moderate learning disability and type 2 diabetes. Methods Researchers administered the EQ-5D-3L to 82 participants at baseline and 77 at follow-up. After each interview, researchers rated the ease of administering the EQ-5D-3L and made free-text entries on the administration experience. For a subset of 16 interviews, researchers audio-recorded more detailed journal entries. Ease of administration data were analysed using descriptive statistics. Free-text responses were subject to a basic content analysis. The EQ-5D-3L-related journal entries were transcribed, coded and analysed thematically. Results Over half of participants were perceived to experience difficulty answering some or all of the items in the EQ-5D-3L (60% at baseline; 54% at follow-up). Analysis of the free-text entries and audio journals identified four themes that question the use of the EQ-5D-3L in this population. The first theme is related to observations of participant intellectual ability and difficulties, for example, in understanding the wording of the measure. Theme 2 is related to the normalisation of adjustments for impairments, which rendered the measure less sensitive in this population. Theme 3 is related to researcher adaptation and non-standard administration. An overarching fourth theme was identified in that people with learning disabilities were viewed as ‘unreliable witnesses’ by both researchers and supporters. Conclusions It is recommended that the EQ-5D-3L should not be used in isolation to assess health-related quality of life outcomes in trials research in adults with a learning disability. Further research is required to develop and evaluate a version of the EQ-5D appropriate for this population in trials research. It is unrealistic to expect that adjustments to the wording alone will deliver an appropriate measure: supporter or researcher involvement will almost always be required. This requirement needs to be factored into the development and administration guidelines of any new version of the EQ-5D for adults with a learning disability.This work was undertaken by those working on the OK Diabetes study and contributed to the development of the project. OK Diabetes was funded by the National Institute for Health Research Health Technology Assessment Programme [project number 10/102/03]

Evaluating provision of psychological assessment and support in palliative care: A national survey of hospices in England

Objective: Psychological distress is common in palliative care patients. The 2004 National Institute of Healthcare and Excellence (NICE) guidance for supportive and palliative care for adults with cancer, which remains contemporary, recognised that access to psychological support was inconsistent and often inadequate. Their 4-tier model requires multidisciplinary psychological assessment at key points. Implicit is the need for improved training and support for staff and equity in service provision. This survey was designed to determine the levels of self-reported competence amongst healthcare staff in the psychological assessment and screening of patients in adult hospices in England and their awareness of the NICE guidelines. Methods: A short anonymised online questionnaire was sent to 164 hospices to determine perceptions of healthcare professionals (HCPs) on their own competence in screening and assessment of distress, provision of therapies and levels of training and supervision. Results: Responses were received from 140 HCPs in approximately thirty-eight hospices. Key findings included self-reported needs for training and supervision. Over a quarter of nurses (28.8%) and AHPs (27.8%) had no level 2 training, and only half of nurses, AHPs and physicians were aware of the NICE guidelines. Access to level 3 specialist psychological services was lacking and some HCPs felt unable to screen and assess patients for referral to specialist services. Conclusions: Consistent, standardised training in assessment of psychological needs is required to ensuring delivery of high-quality care for psychological needs. Areas for future development identified include essential communication skills and high-quality supervision for those delivering psychotherapeutic interventions

Systems for electronic documentation and sharing of advance care planning preferences: a scoping review

Digital approaches to support advance care planning (ACP) documentation and sharing are increasingly being used, with a lack of research to characterise their design, content, and use. This study aimed to characterise how digital approaches are being used to support ACP documentation and sharing internationally. A scoping review was performed in accordance with the JBI (formerly Joanna Briggs Institute) guidelines and the PRISMA 2020 checklist, prospectively registered on Open Science Framework (https://osf.io/xnrg3). MEDLINE, EMBASE, PsycINFO, ACM Digital, IEEE Xplore and CINAHL were searched in February 2023. Only publications in English, published from 2008 onwards were considered. Eligibility criteria included a focus on ACP and electronic systems. Out of 2,393 records, 34 reports were included, predominantly from the USA (76.5%). ACP documentation is typically stored in electronic health records (EHRs) (67.6%), with a third (32.4%) enabling limited patient access. Non-standard approaches (n = 15;44.1%) were the commonest study design of included reports, with outcome measures focusing on the influence of systems on the documentation (i.e. creation, quantity, quality, frequency or timing) of ACP information (n = 23;67.6%). Digital approaches to support ACP are being implemented and researched internationally with an evidence base dominated by non-standard study designs. Future research is needed to extend outcome measurement to consider aspects of care quality and explore whether the content of existing systems aligns with aspects of care that are valued by patients

Supporting patient access to medicines in community palliative care: on-line survey of health professionals’ practice, perceived effectiveness and influencing factors

Background: Patient access to medicines at home during the last year of life is critical for symptom control, but is thought to be problematic. Little is known about healthcare professionals’ practices in supporting timely medicines access and what influences their effectiveness. The purpose of the study was to evaluate health professionals’ medicines access practices, perceived effectiveness and influencing factors. Methods: On-line questionnaire survey of health care professionals (General Practitioners, Community Pharmacists, community-based Clinical Nurse Specialists and Community Nurses) delivering end-of-life care in primary and community care settings in England. Quantitative data were analysed using descriptive statistics. Results: One thousand three hundred twenty-seven responses were received. All health professional groups are engaged in supporting access to prescriptions, using a number of different methods. GPs remain a predominant route for patients to access new prescriptions in working hours. However, nurses and, increasingly, primary care-based pharmacists are also actively contributing. However, only 42% (160) of Clinical Nurse Specialists and 27% (27) of Community Nurses were trained as prescribers. The majority (58% 142) of prescribing nurses and pharmacists did not have access to an electronic prescribing system. Satisfaction with access to shared patient records to facilitate medicines access was low: 39% (507) were either Not At All or only Slightly satisfied. Out-of-hours specialist cover was reported by less than half (49%; 656) and many General Practitioners and pharmacists lacked confidence advising about out-of-hours services. Respondents perceived there would be a significant improvement in pain control if access to medicines was greater. Those with shared records access reported significantly lower pain estimates for their caseload patients. Conclusions: Action is required to support a greater number of nurses and pharmacists to prescribe end-of-life medicines. Solutions are also required to enable shared access to patient records across health professional groups. Coverage and awareness of out-of-hours services to access medicines needs to be improved

Practitioner insights as a means of setting a context for conservation

A key obstacle to conservation success is the tendency of conservation professionals to tackle each challenge individually rather than collectively and in context. We sought to prioritize barriers to conservation previously described in the conservation literature. We undertook an online survey of 154 practitioners from over 70 countries to ascertain the most important barriers to conservation they faced. We used statistical analyses to identify the key impediments to conservation success and to examine whether these were affected by organizational attributes. Twenty‐one barriers were identified. The importance ascribed to those was influenced by continent of operation and organization size, but not by organization age or autonomy (from larger parent organizations). We found the most important barriers to consider when undertaking conservation action were wider issues (e.g., population growth, consumerism, favoring development, and industrial‐scale activity), operating environment (e.g., lack of political will, ineffective law enforcement, weak governments, corruption, safety and security), community attributes (e.g., dynamics, conflicts, and education levels), and the way conservation is undertaken (overconfidence, lack of funding, and externally set agendas). However, we advise against applying a one‐size‐fits‐all approach. We propose that conservationists account for the complex socioecological systems they operate in if they are to achieve success

Mechanistic Systems Modeling to Improve Understanding and Prediction of Cardiotoxicity Caused by Targeted Cancer Therapeutics

Tyrosine kinase inhibitors (TKIs) are highly potent cancer therapeutics that have been linked with serious cardiotoxicity, including left ventricular dysfunction, heart failure, and QT prolongation. TKI-induced cardiotoxicity is thought to result from interference with tyrosine kinase activity in cardiomyocytes, where these signaling pathways help to control critical processes such as survival signaling, energy homeostasis, and excitation–contraction coupling. However, mechanistic understanding is limited at present due to the complexities of tyrosine kinase signaling, and the wide range of targets inhibited by TKIs. Here, we review the use of TKIs in cancer and the cardiotoxicities that have been reported, discuss potential mechanisms underlying cardiotoxicity, and describe recent progress in achieving a more systematic understanding of cardiotoxicity via the use of mechanistic models. In particular, we argue that future advances are likely to be enabled by studies that combine large-scale experimental measurements with Quantitative Systems Pharmacology (QSP) models describing biological mechanisms and dynamics. As such approaches have proven extremely valuable for understanding and predicting other drug toxicities, it is likely that QSP modeling can be successfully applied to cardiotoxicity induced by TKIs. We conclude by discussing a potential strategy for integrating genome-wide expression measurements with models, illustrate initial advances in applying this approach to cardiotoxicity, and describe challenges that must be overcome to truly develop a mechanistic and systematic understanding of cardiotoxicity caused by TKIs

Problem-solving therapy rather than treatment as usual for adults after self-harm: a pragmatic, feasibility, randomised controlled trial (the MIDSHIPS trial)

Background: Non-fatal self-harm is one of the commonest reasons for adults’ emergency hospital attendance. Although strongly associated with fatal and non-fatal repetition, there is weak evidence about effective interventions—and no clear NICE guidance or clinical consensus concerning aftercare. We examined the practicability of a definitive trial to evaluate problem-solving therapy (PST) to reduce repetition of self-harm; MIDSHIPS is a single-centre, parallel-group, individually randomised controlled feasibility trial comparing treatment-as-usual (TAU) alone to TAU plus up to six sessions of brief problem-solving therapy (PST) with adults who had recently attended hospital because of self-harm. Objectives were to adapt the intervention for a UK setting, train therapists, recruit and randomise patients, deliver PST under supervision, and establish comparative outcomes, assessed blindly. Methods: We adapted the problem-solving intervention from an earlier trial and trained a mental-health nurse to deliver it. Adult patients attending the general hospital for self-harm were recruited while undergoing psychosocial assessment by the mental health team, and 62 were randomly allocated (32 TAU, 30 PST). The primary outcome assessed repeat hospital attendance due to further self-harm 6 months post-randomisation. Secondary outcomes included participant-reported outcomes and service use at 3 and 6 months post-randomisation. Results: The recruitment period had to be extended and 710 patients screened in order to establish a trial sample of the planned size (N = 62). A quarter of participants allocated to PST did not undertake the therapy offered; those who received PST attended a median of three sessions. Secondary outcomes were established for 49 (79%) participants at 6 months; all participants’ hospital records were retrieved. Repetition of self-harm leading to hospital presentation occurred in 19 of the 62 participants (30.6%, 95% CI 19.2%, 42.1%) within 6 months of randomisation. Promising differential rates of self-harm were observed with an event rate of 23.3% (95% CI 8.2%, 38.5%) in the PST arm; and 37.5% (95% CI 20.7%, 54.3%) in TAU. Economic findings were also encouraging, with a small QALY gain (0.0203) in the PST arm together with less reported use of the NHS in the PST arm (average £2120) than with TAU-only (£2878). Conclusions: The feasibility trial achieved its objectives despite considerable difficulties with recruitment—adapting the PST, training a therapist, recruiting patients who had recently self-harmed, delivering the therapy, and establishing primary and secondary outcomes. These data provide a robust platform for a definitive multicentre randomised controlled trial of brief problem-solving therapy after hospital attendance due to self-harm. Trial registration: Identification number and URL: ISRCTN54036115 http://www.isrctn.com/search?q=midships. Registered: 13 January 201