Approaches to improving mental health care for autistic children and young people: a systematic review and meta-analysis.

Autistic children and young people (CYP) experience mental health difficulties but face many barriers to accessing and benefiting from mental health care. There is a need to explore strategies in mental health care for autistic CYP to guide clinical practice and future research and support their mental health needs. Our aim was to identify strategies used to improve mental health care for autistic CYP and examine evidence on their acceptability, feasibility, and effectiveness. A systematic review and meta-analysis were carried out. All study designs reporting acceptability/feasibility outcomes and empirical quantitative studies reporting effectiveness outcomes for strategies tested within mental health care were eligible. We conducted a narrative synthesis and separate meta-analyses by informant (self, parent, and clinician). Fifty-seven papers were included, with most investigating cognitive behavioral therapy (CBT)-based interventions for anxiety and several exploring service-level strategies, such as autism screening tools, clinician training, and adaptations regarding organization of services. Most papers described caregiver involvement in therapy and reported adaptations to communication and intervention content; a few reported environmental adjustments. In the meta-analyses, parent- and clinician-reported outcomes, but not self-reported outcomes, showed with moderate certainty that CBT for anxiety was an effective treatment compared to any comparison condition in reducing anxiety symptoms in autistic individuals. The certainty of evidence for effectiveness, synthesized narratively, ranged from low to moderate. Evidence for feasibility and acceptability tended to be positive. Many identified strategies are simple, reasonable adjustments that can be implemented in services to enhance mental health care for autistic individuals. Notable research gaps persist, however.

Implementation strategies for telemental health: a systematic review.

BACKGROUND: The COVID-19 pandemic resulted in a rapid shift from traditional face-to-face care provision towards delivering mental health care remotely through telecommunications, often referred to as telemental health care. However, the manner and extent of telemental health implementation have varied considerably across settings and areas, and substantial barriers are encountered. There is, therefore, a need to identify what works best for service users and staff and establish the key mechanisms for efficient integration into routine care. OBJECTIVE: We aimed to identify investigations of pre-planned strategies reported in the literature intended to achieve or improve effective and sustained implementation of telemental health approaches (including video calls, telephone calls, text messaging platforms or a combination of any of these approaches with face-to-face care), and to evaluate how different strategies influence implementation outcomes. METHODS: A systematic review was conducted, with five databases searched for any relevant literature published between January 2010 and July 2021. Studies were eligible if they took place in specialist mental health services and focused on pre-planned strategies to achieve or improve the delivery of mental health care through remote communication between mental health professionals or between mental health professionals and service users, family members, unpaid carers, or peer supporters. All included studies were quality-assessed. Data were synthesised using the Expert Recommendations for Implementing Change (ERIC) compilation of implementation strategies and the taxonomy of implementation outcomes. RESULTS: A total of 14 studies were identified as meeting the inclusion criteria from a total of 14,294 records of which 338 were assessed at full text. All ERIC implementation strategies were used by at least one study, the most commonly reported being 'Train and educate stakeholders'. All studies reported using a combination of several implementation strategies, with the mean number of strategies used per study of 3.5 (range 2-6), many of which were reported to result in an improvement in implementation over time. Few studies specifically investigated a single implementation strategy and its associated outcomes, making conclusions regarding the most beneficial strategy difficult to draw. CONCLUSIONS: Using a combination of implementation strategies appears to be a helpful method of supporting the implementation of telemental health. Further research is needed to test the impact of specific implementation strategies on implementation outcomes.

Development and implementation of a postgraduate medical education-wide initiative in quality improvement and patient safety.

BACKGROUND: Quality improvement and patient safety (QIPS) have been assigned a higher profile in CanMEDS 2015, CanMEDS-Family Medicine 2017 and new accreditation standards, prompting an initiative at Dalhousie University to create a vision for integrating QIPS into postgraduate medical education. OBJECTIVE: The purpose of this study is to describe the implementation of a QIPS strategy across residency education at Dalhousie University. METHODS: A QIPS task force was formed, and a literature review and needs assessment survey were completed. A needs assessment survey was distributed to all Dalhousie residency programme directors. 12 programme directors were interviewed individually to collect additional feedback. The results were used to develop a 'road map' of recommendations with a graduated timeline. RESULTS: A task force report was released in February 2018. 46 recommendations were developed with a timeframe and responsible party identified for each. Implementation of the QIPS strategy is underway, and evaluation and challenges faced will be described. CONCLUSIONS: We have developed a multiyear strategy that is available to provide guidance and support to all programmes in QIPS. The development and implementation of this QIPS framework may serve as a template for other institutions who seek to integrate these competencies into residency training.

Current state of the evidence on community treatments for people with complex emotional needs: a scoping review.

BACKGROUND: Improving the quality of care in community settings for people with 'Complex Emotional Needs' (CEN-our preferred working term for services for people with a "personality disorder" diagnosis or comparable needs) is recognised internationally as a priority. Plans to improve care should be rooted as far as possible in evidence. We aimed to take stock of the current state of such evidence, and identify significant gaps through a scoping review of published investigations of outcomes of community-based psychosocial interventions designed for CEN. METHODS: We conducted a scoping review with systematic searches. We searched six bibliographic databases, including forward and backward citation searching, and reference searching of relevant systematic reviews. We included studies using quantitative methods to test for effects on any clinical, social, and functioning outcomes from community-based interventions for people with CEN. The final search was conducted in November 2020. RESULTS: We included 226 papers in all (210 studies). Little relevant literature was published before 2000. Since then, publications per year and sample sizes have gradually increased, but most studies are relatively small, including many pilot or uncontrolled studies. Most studies focus on symptom and self-harm outcomes of various forms of specialist psychotherapy: most result in outcomes better than from inactive controls and similar to other specialist psychotherapies. We found large evidence gaps. Adaptation and testing of therapies for significant groups (e.g. people with comorbid psychosis, bipolar disorder, post-traumatic stress disorder, or substance misuse; older and younger groups; parents) have for the most part only reached a feasibility testing stage. We found little evidence regarding interventions to improve social aspects of people's lives, peer support, or ways of designing effective services. CONCLUSIONS: Compared with other longer term mental health problems that significantly impair functioning, the evidence base on how to provide high quality care for people with CEN is very limited. There is good evidence that people with CEN can be helped when specialist therapies are available and when they are able to engage with them. However, a much more methodologically robust and substantial literature addressing a much wider range of research questions is urgently needed to optimise treatment and support across this group.

Video feedback parent-infant intervention for mothers experiencing enduring difficulties in managing emotions and relationships: A randomised controlled feasibility trial.

OBJECTIVES: Parents experiencing mental health difficulties consistent with "personality disorder", often related to a history of complex trauma, may face increased challenges in parent-child relationships and child socioemotional development. There are no published randomised controlled trials (RCTs) evaluating perinatal parent-child interventions for this population. We evaluated the feasibility and acceptability of undertaking an RCT of the video feedback intervention for positive parenting adapted for perinatal mental health (VIPP-PMH). DESIGN: Feasibility study incorporating a pilot RCT. METHODS: Mothers with enduring difficulties in managing emotions and relationships, consistent with a "personality disorder", and their 6- to 36-month old infants were randomly allocated to receive six sessions of VIPP-PMH (n = 20) or usual care alone (n = 14). RESULTS: 76% of eligible mothers consented to participate. Intervention uptake and completion rates were 95% (≥1 VIPP-PMH session) and 70% (6 sessions), respectively. Follow-up rates were 85% at month 5 and 65% at month 8 post-baseline. Blinded observer-ratings of maternal sensitivity in parent-child interaction favoured the intervention group at month 5 (RR = 1.94, 95% CI 0.67-5.63) and month 8 (RR = 1.91, 95% CI 0.68-5.33). Small changes over time in self-rated parenting confidence and stress favoured the intervention group. There were no clear intervention effects on maternal non-intrusiveness or mental health, or on child behaviour problems, emotional functioning, or self-regulation. CONCLUSIONS: An RCT of VIPP-PMH is feasible and acceptable to implement with mothers experiencing difficulties consistent with perinatal "personality disorder". A fully powered definitive RCT should be undertaken.

A qualitative study of experiences of NHS mental healthcare workers during the Covid-19 pandemic.

BACKGROUND: The Covid-19 pandemic has imposed extraordinary strains on healthcare workers. But, in contrast with acute settings, relatively little attention has been given to those who work in mental health settings. We aimed to characterise the experiences of those working in English NHS secondary mental health services during the first wave of the pandemic. METHODS: The design was a qualitative interview-based study. We conducted semi-structured, remote (telephone or online) interviews with 35 members of staff from NHS secondary (inpatient and community) mental health services in England. Analysis was based on the constant comparative method. RESULTS: Participants reported wide-ranging changes in the organisation of secondary mental health care and the nature of work in response to the pandemic, including pausing of all services deemed to be "non-essential", deployment of staff across services to new and unfamiliar roles, and moves to remote working. The quality of participants' working life was impaired by increasing levels of daily challenge associated with trying to provide care in trying and constrained circumstances, the problems of forging new ways of working remotely, and constraints on ability to access informal support. Participants were confronted with difficult dilemmas relating to clinical decision-making, prioritisation of care, and compromises in ability to perform the therapeutic function of their roles. Other dilemmas centred on trying to balance the risks of controlling infection with the need for human contact. Many reported features of moral injury linked to their perceived failures in providing the quality or level of care that they felt service users needed. They sometimes sought to compensate for deficits in care through increased advocacy, taking on additional tasks, or making exceptions, but this led to further personal strain. Many experienced feelings of grief, helplessness, isolation, distress, and burnout. These problems were compounded by sometimes poor communication about service changes and by staff feeling that they could not take time off because of the potential impact on others. Some reported feeling poorly supported by organisations. CONCLUSIONS: Mental health workers faced multiple adversities during the pandemic that were highly consequential for their wellbeing. These findings can help in identifying targets for support.

Randomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosis.

BACKGROUND: Critically ill patients with impaired neutrophil phagocytosis have significantly increased risk of nosocomial infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) improves phagocytosis by neutrophils ex vivo. This study tested the hypothesis that GM-CSF improves neutrophil phagocytosis in critically ill patients in whom phagocytosis is known to be impaired. METHODS: This was a multicentre, phase IIa randomised, placebo-controlled clinical trial. Using a personalised medicine approach, only critically ill patients with impaired neutrophil phagocytosis were included. Patients were randomised 1:1 to subcutaneous GM-CSF (3 µg/kg/day) or placebo, once daily for 4 days. The primary outcome measure was neutrophil phagocytosis 2 days after initiation of GM-CSF. Secondary outcomes included neutrophil phagocytosis over time, neutrophil functions other than phagocytosis, monocyte HLA-DR expression and safety. RESULTS: Thirty-eight patients were recruited from five intensive care units (17 randomised to GM-CSF). Mean neutrophil phagocytosis at day 2 was 57.2% (SD 13.2%) in the GM-CSF group and 49.8% (13.4%) in the placebo group, p=0.73. The proportion of patients with neutrophil phagocytosis≥50% at day 2, and monocyte HLA-DR, appeared significantly higher in the GM-CSF group. Neutrophil functions other than phagocytosis did not appear significantly different between the groups. The most common adverse event associated with GM-CSF was fever. CONCLUSIONS: GM-CSF did not improve mean neutrophil phagocytosis at day 2, but was safe and appeared to increase the proportion of patients with adequate phagocytosis. The study suggests proof of principle for a pharmacological effect on neutrophil function in a subset of critically ill patients.

Insufficient glucocorticoid signaling and elevated inflammation in coronary heart disease patients with comorbid depression.

Coronary heart disease (CHD) and depression are very common and often co-existing disorders. In addition to psychological and social morbidity, depression exacerbates adverse cardiac outcomes in CHD patients. Inflammation has been proposed as one of the mechanisms involved in the association between these two debilitating diseases. Therefore, the present study aimed to evaluate inflammatory responses as well as to investigate the pathophysiological mechanisms underlying the putative inflammatory activation in CHD patients with and without depression, by assessing the function of two important biological factors regulating inflammation, the hypothalamus-pituitary-adrenal (HPA) axis and the glucocorticoid receptor (GR). Eighty-three CHD patients with (n=28) and without (n=55) comorbid depression were recruited from primary care services in South London. Depression status was assessed by means of Clinical Interview Schedule Revised for diagnosis of depression, and Beck Depression Inventory for the presence of depressive symptoms. Serum C-reactive protein (CRP), plasma vascular endothelial growth factor (VEGF), and plasma and salivary cortisol were measured using commercially available ELISA kits. Gene expression of GR and interleukin-6 (IL-6) were conducted via qPCR. GR sensitivity was evaluated in vitro in isolated peripheral blood mononuclear cells using the dexamethasone inhibition of lipopolysaccharide-stimulated IL-6 levels. Serum levels of kynurenine pathway metabolites were measured using high performance liquid chromatography. Our results show that CHD patients with depression had higher levels of CRP, IL-6 gene expression, and VEGF compared with CHD non-depressed, as well as lower plasma and saliva cortisol levels. The CHD depressed group also exhibited a reduction in GR expression and sensitivity. Finally, tryptophan levels were significantly lower in patients with depression, who also showed an increased kynurenine/tryptophan ratio. In conclusion, CHD patients with depression had elevated levels of inflammation in the context of HPA axis hypoactivity, GR resistance, and increased activation of the kynurenine pathway. Reduced cortisol bioavailability and attenuated glucocorticoid responsiveness due to decreased expression and sensitivity of GR may lead to insufficient glucocorticoid signaling and thus elevation of inflammation in these patients.

Approaches to improving mental healthcare for autistic people: systematic review.

BACKGROUND: Autistic people have a high likelihood of developing mental health difficulties but a low chance of receiving effective mental healthcare. Therefore, there is a need to identify and examine strategies to improve mental healthcare for autistic people. AIMS: To identify strategies that have been implemented to improve access, experiences of care and mental health outcomes for autistic adults, and to examine evidence on their acceptability, feasibility and effectiveness. METHOD: A co-produced systematic review was conducted. MEDLINE, PsycINFO, CINHAL, medRxiv and PsyArXiv were searched. We included all study designs reporting acceptability or feasibility outcomes and empirical quantitative study designs reporting effectiveness outcomes. Data were synthesised using a narrative approach. RESULTS: A total of 30 articles were identified. These included 16 studies of adapted mental health interventions, eight studies of service improvements and six studies of bespoke mental health interventions developed for autistic people. There was no conclusive evidence on effectiveness. However, most bespoke and adapted approaches appeared to be feasible and acceptable. Identified adaptations appeared to be acceptable and feasible, including increasing knowledge and detection of autism, providing environmental adjustments and communication accommodations, accommodating individual differences and modifying the structure and content of interventions. CONCLUSION: Many identified strategies are feasible and acceptable, and can be readily implemented in services with the potential to make mental healthcare more suitable for autistic people, but important research gaps remain. Future research should address these and investigate a co-produced package of service improvement measures.

Mother and clinician experiences of a trial of a video feedback parent-infant intervention for mothers experiencing difficulties consistent with 'personality disorder': A qualitative interview study.

OBJECTIVES: We explored mothers' and clinicians' experiences of a video feedback intervention adapted for perinatal 'personality disorder' (VIPP-PMH) and the acceptability of a randomised controlled trial (RCT) examining its effectiveness. DESIGN: In-depth qualitative interviews with participants from a two-phase feasibility study of the VIPP-PMH intervention. Participants were mothers experiencing enduring difficulties in managing emotions and relationships, consistent with a 'personality disorder', and their 6- to 36-month-old children. METHODS: Forty-four qualitative interviews were conducted, including all nine mothers receiving VIPP-PMH during the pilot phase, 25 of the 34 mothers participating in the RCT (14 allocated to the VIPP-PMH arm and 9 from the control arm), 11 of the 12 clinicians delivering VIPP-PMH and one researcher. Interview data were thematically analysed. RESULTS: Mothers described feeling motivated to take part in the research and understood the need for randomisation. Research visits were largely experienced positively, with some suggestions for improvement in questionnaire timing and accessibility. Almost all mothers initially felt anxious about being filmed, but reported positive experiences of the intervention, particularly valuing its non-judgemental, positive and child-focussed nature, their supportive relationship with the therapist and the insights they gained on their child. CONCLUSIONS: The findings indicate the likely feasibility and acceptability of undertaking a future definitive RCT of the VIPP-PMH intervention in this population. In designing a future trial, a positive and non-judgemental therapeutic relationship will be important to allay mothers' anxieties about being filmed, and careful consideration should be given to the timing and accessibility of questionnaires used.

Qualitative study of candidacy and access to secondary mental health services during the COVID-19 pandemic.

Candidacy, a construct describing how people's eligibility for care is negotiated between themselves and services, has received limited attention in the context of mental health care. In addition, candidacy research has only rarely studied the views of carers and health professionals. In this article, we use concepts relating to candidacy to enable a theoretically informed examination of experiences of access to secondary mental health services during the first wave of the COVID-19 pandemic in England. We report a qualitative study of the views and experiences of service users, carers, and healthcare professionals. Analysis of 65 in-depth interviews was based on the constant comparative method. We found that wide-ranging service changes designed to address the imperatives of the pandemic were highly consequential for people's candidacy. Macro-level changes, including increased emphasis on crisis and risk management and adapted risk assessment systems, produced effects that went far beyond restrictions in the availability of services: they profoundly re-structured service users' identification of their own candidacy, including perceptions of what counted as a problem worthy of attention and whether they as individuals needed, deserved, and were entitled to care. Services became less permeable, such that finding a point of entry to those services that remained open required more work of service users and carers. Healthcare professionals were routinely confronted by complex decisions and ethical dilemmas about provision of care, and their implicit judgements about access may have important implications for equity. Many of the challenges of access exposed by the pandemic related to pre-existing resource deficits and institutional weaknesses in care for people living with mental health difficulties. Overall, these findings affirm the value of the construct of candidacy for explaining access to mental healthcare, but also enable deepened understanding of the specific features of candidacy, offering enduring learning and implications for policy and practice.

Remote care for mental health: qualitative study with service users, carers and staff during the COVID-19 pandemic.

OBJECTIVES: To explore the experiences of service users, carers and staff seeking or providing secondary mental health services during the COVID-19 pandemic. DESIGN: Qualitative interview study, codesigned with mental health service users and carers. METHODS: We conducted semistructured, telephone or online interviews with a purposively constructed sample; a lived experience researcher conducted and analysed interviews with service users. Analysis was based on the constant comparison method. SETTING: National Health Service (NHS) secondary mental health services in England between June and August 2020. PARTICIPANTS: Of 65 participants, 20 had either accessed or needed to access English secondary mental healthcare during the pandemic; 10 were carers of people with mental health difficulties; 35 were members of staff working in NHS secondary mental health services during the pandemic. RESULTS: Experiences of remote care were mixed. Some service users valued the convenience of remote methods in the context of maintaining contact with familiar clinicians. Most participants commented that a lack of non-verbal cues and the loss of a therapeutic 'safe space' challenged therapeutic relationship building, assessments and identification of deteriorating mental well-being. Some carers felt excluded from remote meetings and concerned that assessments were incomplete without their input. Like service users, remote methods posed challenges for clinicians who reported uncertainty about technical options and a lack of training. All groups expressed concern about intersectionality exacerbating inequalities and the exclusion of some service user groups if alternatives to remote care are lost. CONCLUSIONS: Though remote mental healthcare is likely to become increasingly widespread in secondary mental health services, our findings highlight the continued importance of a tailored, personal approach to decision making in this area. Further research should focus on which types of consultations best suit face-to-face interaction, and for whom and why, and which can be provided remotely and by which medium.

Structured Psychological Support for people with personality disorder: feasibility randomised controlled trial of a low-intensity intervention.

BACKGROUND: National guidance cautions against low-intensity interventions for people with personality disorder, but evidence from trials is lacking. AIMS: To test the feasibility of conducting a randomised trial of a low-intensity intervention for people with personality disorder. METHOD: Single-blind, feasibility trial (trial registration: ISRCTN14994755). We recruited people aged 18 or over with a clinical diagnosis of personality disorder from mental health services, excluding those with a coexisting organic or psychotic mental disorder. We randomly allocated participants via a remote system on a 1:1 ratio to six to ten sessions of Structured Psychological Support (SPS) or to treatment as usual. We assessed social functioning, mental health, health-related quality of life, satisfaction with care and resource use and costs at baseline and 24 weeks after randomisation. RESULTS: A total of 63 participants were randomly assigned to either SPS (n = 33) or treatment as usual (n = 30). Twenty-nine (88%) of those in the active arm of the trial received one or more session (median 7). Among 46 (73%) who were followed up at 24 weeks, social dysfunction was lower (-6.3, 95% CI -12.0 to -0.6, P = 0.03) and satisfaction with care was higher (6.5, 95% CI 2.5 to 10.4; P = 0.002) in those allocated to SPS. Statistically significant differences were not found in other outcomes. The cost of the intervention was low and total costs over 24 weeks were similar in both groups. CONCLUSIONS: SPS may provide an effective low-intensity intervention for people with personality disorder and should be tested in fully powered clinical trials.

Biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia (VAPrapid2): a randomised controlled trial and process evaluation.

BACKGROUND: Ventilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations of IL-1ß and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion of ventilator-associated pneumonia. The VAPrapid2 trial aimed to determine whether measurement of bronchoalveolar lavage fluid IL-1ß and IL-8 could effectively and safely improve antibiotic stewardship in patients with clinically suspected ventilator-associated pneumonia. METHODS: VAPrapid2 was a multicentre, randomised controlled trial in patients admitted to 24 ICUs from 17 National Health Service hospital trusts across England, Scotland, and Northern Ireland. Patients were screened for eligibility and included if they were 18 years or older, intubated and mechanically ventilated for at least 48 h, and had suspected ventilator-associated pneumonia. Patients were randomly assigned (1:1) to biomarker-guided recommendation on antibiotics (intervention group) or routine use of antibiotics (control group) using a web-based randomisation service hosted by Newcastle Clinical Trials Unit. Patients were randomised using randomly permuted blocks of size four and six and stratified by site, with allocation concealment. Clinicians were masked to patient assignment for an initial period until biomarker results were reported. Bronchoalveolar lavage was done in all patients, with concentrations of IL-1ß and IL-8 rapidly determined in bronchoalveolar lavage fluid from patients randomised to the biomarker-based antibiotic recommendation group. If concentrations were below a previously validated cutoff, clinicians were advised that ventilator-associated pneumonia was unlikely and to consider discontinuing antibiotics. Patients in the routine use of antibiotics group received antibiotics according to usual practice at sites. Microbiology was done on bronchoalveolar lavage fluid from all patients and ventilator-associated pneumonia was confirmed by at least 104 colony forming units per mL of bronchoalveolar lavage fluid. The primary outcome was the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage. Data were analysed on an intention-to-treat basis, with an additional per-protocol analysis that excluded patients randomly assigned to the intervention group who defaulted to routine use of antibiotics because of failure to return an adequate biomarker result. An embedded process evaluation assessed factors influencing trial adoption, recruitment, and decision making. This study is registered with ISRCTN, ISRCTN65937227, and ClinicalTrials.gov, NCT01972425. FINDINGS: Between Nov 6, 2013, and Sept 13, 2016, 360 patients were screened for inclusion in the study. 146 patients were ineligible, leaving 214 who were recruited to the study. Four patients were excluded before randomisation, meaning that 210 patients were randomly assigned to biomarker-guided recommendation on antibiotics (n=104) or routine use of antibiotics (n=106). One patient in the biomarker-guided recommendation group was withdrawn by the clinical team before bronchoscopy and so was excluded from the intention-to-treat analysis. We found no significant difference in the primary outcome of the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage in the intention-to-treat analysis (p=0·58). Bronchoalveolar lavage was associated with a small and transient increase in oxygen requirements. Established prescribing practices, reluctance for bronchoalveolar lavage, and dependence on a chain of trial-related procedures emerged as factors that impaired trial processes. INTERPRETATION: Antibiotic use remains high in patients with suspected ventilator-associated pneumonia. Antibiotic stewardship was not improved by a rapid, highly sensitive rule-out test. Prescribing culture, rather than poor test performance, might explain this absence of effect. FUNDING: UK Department of Health and the Wellcome Trust.

Psychological Support for Personality (PSP) versus treatment as usual: study protocol for a feasibility randomized controlled trial of a low intensity intervention for people with personality disorder.

BACKGROUND: Previous research has demonstrated the clinical effectiveness of long-term psychological treatment for people with some types of personality disorder. However, the high intensity and cost of these interventions limit their availability. Lower-intensity interventions are increasingly being offered to people with personality disorder, but their clinical and cost effectiveness have not been properly tested in experimental studies. We therefore set out to develop a low intensity intervention for people with personality disorder and to test the feasibility of conducting a randomized controlled trial to compare the clinical effectiveness of this intervention with that of treatment as usual (TAU). METHODS: A two-arm, parallel-group, single-blind, randomized controlled trial of Psychological Support for Personality (PSP) versus TAU for people aged over 18 years, who are using secondary care mental health services and have personality disorder. We will exclude people with co-existing organic or psychotic mental disorders (dementia, bipolar affective disorder, delusional disorder, schizophrenia, schizoaffective disorder, or schizotypal disorder), those with cognitive or language difficulties that would preclude them from providing informed consent or compromise participation in study procedures, and those who are already receiving psychological treatment for personality disorder. Participants will be randomized via a remote system in a ratio of PSP to TAU of 1:1. Randomization will be stratified according to the referring team and gender of the participant. A single follow-up assessment will be conducted by masked researchers 24 weeks after randomization to assess mental health (using the Warwick and Edinburgh Well-Being Schedule), social functioning (using the Work and Social Adjustment Scale), health-related quality of life (EQ-5D-5 L), incidence of suicidal behavior, satisfaction with care (Client Satisfaction Questionnaire), and resource use and costs using a modified version of the Adult Service Use Schedule. In addition to this, each participant will be asked to complete the patient version of the Clinical Global Impression Scale. Feasibility and acceptability will primarily be judged by study recruitment rate and engagement and retention in treatment. The analysis will focus principally on descriptive data on the rate of recruitment, characteristics of participants, attrition, adherence to therapy, and follow-up. We will explore the distribution of study outcomes to investigate assumptions of normality in order to plan the analysis and sample size of a future definitive trial. DISCUSSION: Most people with personality disorder do not currently receive evidence-based interventions. While a number of high intensity psychological treatments have been shown to be effective, there is an urgent need to develop effective low intensity approaches to help people unable to use existing treatments. PSP is a low intensity intervention for individuals, which was developed following extensive consultation with users and providers of services for people with personality disorder. This study aims to examine the feasibility of a randomized trial of PSP compared to TAU for people with personality disorder. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN14994755 . Registered on 18 July 2017.

Effectiveness of biomarker-based exclusion of ventilator-acquired pneumonia to reduce antibiotic use (VAPrapid-2): study protocol for a randomised controlled trial.

BACKGROUND: Ventilator-acquired pneumonia (VAP) is a common reason for antimicrobial therapy in the intensive care unit (ICU). Biomarker-based diagnostics could improve antimicrobial stewardship through rapid exclusion of VAP. Bronchoalveloar lavage (BAL) fluid biomarkers have previously been shown to allow the exclusion of VAP with high confidence. METHODS/DESIGN: This is a prospective, multi-centre, randomised, controlled trial to determine whether a rapid biomarker-based exclusion of VAP results in fewer antibiotics and improved antimicrobial management. Patients with clinically suspected VAP undergo BAL, and VAP is confirmed by growth of a potential pathogen at [≥] 10(4) colony-forming units per millilitre (CFU/ml). Patients are randomised 1:1, to either a 'biomarker-guided recommendation on antibiotics' in which BAL fluid is tested for IL-1ß and IL-8 in addition to routine microbiology testing, or to 'routine use of antibiotics' in which BAL undergoes routine microbiology testing only. Clinical teams are blinded to intervention until 6 hours after randomisation, when biomarker results are reported to the clinician. The primary outcome is a change in the frequency distribution of antibiotic-free days (AFD) in the 7 days following BAL. Secondary outcome measures include antibiotic use at 14 and 28 days; ventilator-free days; 28-day mortality and ICU mortality; sequential organ failure assessment (SOFA) at days 3, 7 and 14; duration of stay in critical care and the hospital; antibiotic-associated infections; and antibiotic-resistant pathogen cultures up to hospital discharge, death or 56 days. A healthcare-resource-utilisation analysis will be calculated from the duration of critical care and hospital stay. In addition, safety data will be collected with respect to performing BAL. A sample size of 210 will be required to detect a clinically significant shift in the distribution of AFD towards more patients having fewer antibiotics and therefore more AFD. DISCUSSION: This trial will test whether a rapid biomarker-based exclusion of VAP results in rapid discontinuation of antibiotics and therefore improves antibiotic management in patients with suspected VAP. TRIAL REGISTRATION: ISRCTN65937227 . Registered on 22 August 2013. ClinicalTrials.gov, NCT01972425 . Registered on 24 October 2013.

Lessons from a pilot and feasibility randomised trial in depression (Blood pressure Rapid Intensive Lowering And Normal Treatment for Mood and cognition in persistent depression (BRILiANT mood study)).

BACKGROUND: The blood pressure rapid intensive lowering and normal treatment for mood and cognition in persistent depression (BRILiANT mood study) was devised as a pilot study to investigate the feasibility and safety of intensive blood pressure lowering as treatment for persistent mood and cognitive symptoms in older adults with major depressive disorder and to assess the availability of this population for recruitment. In addition, the relationship between reduced blood pressure and the change in cerebral blood flow and mood was to be investigated. METHODS: A single centre pilot randomised controlled trial (RCT), with two parallel groups of intensive or normal treatment for hypertension, recruiting from primary and secondary care and newspaper advert, with an aim of recruiting 66 participants, was observed in this study. At the end of the recruitment period, in order to explore the reasons for failure to recruit to target, surveys were developed and issued to those involved in recruitment. RESULTS: Recruitment rates were lower than expected which led to the study being expanded to further areas and opened to self-referral via advertisement. However, because of better management of hypertension due to changes in the UK Quality and Outcomes Framework guidelines for blood pressure treatment, few eligible patients were identified and the study closed at the end of the recruitment period, with 13 participants consenting, but 12 failing screening resulting in one recruited participant. CONCLUSIONS: Overall, the BRILiANT mood study was found not to be feasible, and results suggest that the expected patient population no longer exists. To overcome such recruitment difficulties, a prompt commencement of a study after funding so no relevant care changes occur might help prevent similar problems in future studies. In addition, self-referral, in this case via advertisement in papers, may be a useful tool to increase response rate. When recruiting in primary care, direct access to primary care databases, in a secure and anonymised way, may enable more effective screening. Ultimately, the BRILiANT mood study was shown not to be feasible; this was a useful conclusion from this pilot study. TRIAL REGISTRATION: ISRCTN 64524251; UKCRN Portfolio No: 13284.