• The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): a randomised placebo-controlled trial

  Cheshire, Jack; Gibbon, Simon D. (2022)

  BackgroundData from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted.MethodsMulticentre, double-blind, placebo-controlled trial. We aimed to recruit 222 inpatients with severe BPD aged 18 or over, who had failed to respond to other antipsychotic medications. We randomly allocated participants on a 1:1 ratio to receive up to 400 mg of clozapine per day or an inert placebo using a remote web-based randomisation service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at 6 months. Secondary outcomes included self-harm, aggression, resource use and costs, side effects and adverse events. We used a modified intention to treat analysis (mITT) restricted to those who took one or more dose of trial medication, using a general linear model fitted at 6 months adjusted for baseline score, allocation group and site.ResultsThe study closed early due to poor recruitment and the impact of the COVID-19 pandemic. Of 29 study participants, 24 (83%) were followed up at 6 months, of whom 21 (72%) were included in the mITT analysis. At 6 months, 11 (73%) participants assigned to clozapine and 6 (43%) of those assigned to placebo were still taking trial medication. Adjusted difference in mean total ZAN-BPD score at 6 months was -3.86 (95% Confidence Intervals = -10.04 to 2.32). There were 14 serious adverse events; 6 in the clozapine arm and 8 in the placebo arm of the trial. There was little difference in the cost of care between groups.InterpretationWe recruited insufficient participants to test the primary hypothesis. The study findings highlight problems in conducting placebo-controlled trials of clozapine and in using clozapine for people with BPD, outside specialist inpatient mental health units.Trial registrationISRCTN18352058. https://doi.org/10.1186/ISRCTN18352058.
• Automated virtual reality therapy to treat agoraphobic avoidance and distress in patients with psychosis (gameChange): a multicentre, parallel-group, single-blind, randomised, controlled trial in England with mediation and moderation analyses

  O'Regan, Eileen; Jones, Julia; Martin, Jennifer L.; Hollis, Chris P. (2022)

  BACKGROUNDAutomated delivery of psychological therapy using immersive technologies such as virtual reality (VR) might greatly increase the availability of effective help for patients. We aimed to evaluate the efficacy of an automated VR cognitive therapy (gameChange) to treat avoidance and distress in patients with psychosis, and to analyse how and in whom it might work.METHODSWe did a parallel-group, single-blind, randomised, controlled trial across nine National Health Service trusts in England. Eligible patients were aged 16 years or older, with a clinical diagnosis of a schizophrenia spectrum disorder or an affective diagnosis with psychotic symptoms, and had self-reported difficulties going outside due to anxiety. Patients were randomly assigned (1:1) to either gameChange VR therapy plus usual care or usual care alone, using a permuted blocks algorithm with randomly varying block size, stratified by study site and service type. gameChange VR therapy was provided in approximately six sessions over 6 weeks. Trial assessors were masked to group allocation. Outcomes were assessed at 0, 6 (primary endpoint), and 26 weeks after randomisation. The primary outcome was avoidance of, and distress in, everyday situations, assessed using the self-reported Oxford Agoraphobic Avoidance Scale (O-AS). Outcome analyses were done in the intention-to-treat population (ie, all participants who were assigned to a study group for whom data were available). We performed planned mediation and moderation analyses to test the effects of gameChange VR therapy when added to usual care. This trial is registered with the ISRCTN registry, 17308399.FINDINGSBetween July 25, 2019, and May 7, 2021 (with a pause in recruitment from March 16, 2020, to Sept 14, 2020, due to COVID-19 pandemic restrictions), 551 patients were assessed for eligibility and 346 were enrolled. 231 (67%) patients were men and 111 (32%) were women, 294 (85%) were White, and the mean age was 37·2 years (SD 12·5). 174 patients were randomly assigned to the gameChange VR therapy group and 172 to the usual care alone group. Compared with the usual care alone group, the gameChange VR therapy group had significant reductions in agoraphobic avoidance (O-AS adjusted mean difference -0·47, 95% CI -0·88 to -0·06; n=320; Cohen's d -0·18; p=0·026) and distress (-4·33, -7·78 to -0·87; n=322; -0·26; p=0·014) at 6 weeks. Reductions in threat cognitions and within-situation defence behaviours mediated treatment outcomes. The greater the severity of anxious fears and avoidance, the greater the treatment benefits. There was no significant difference in the occurrence of serious adverse events between the gameChange VR therapy group (12 events in nine patients) and the usual care alone group (eight events in seven patients; p=0·37).INTERPRETATIONAutomated VR therapy led to significant reductions in anxious avoidance of, and distress in, everyday situations compared with usual care alone. The mediation analysis indicated that the VR therapy worked in accordance with the cognitive model by reducing anxious thoughts and associated protective behaviours. The moderation analysis indicated that the VR therapy particularly benefited patients with severe agoraphobic avoidance, such as not being able to leave the home unaccompanied. gameChange VR therapy has the potential to increase the provision of effective psychological therapy for psychosis, particularly for patients who find it difficult to leave their home, visit local amenities, or use public transport.FUNDINGNational Institute of Health Research Invention for Innovation programme, National Institute of Health Research Oxford Health Biomedical Research Centre.
• Factors influencing the efficacy of an online behavioural intervention for children and young people with tics: Process evaluation of a randomised controlled trial

  Khan, Kareem; Hollis, Chris P.; Hall, Charlotte L.; Davies, E. Bethan; Glazebrook, Cris (2022)

  The Online Remote Behavioural Intervention for Tics (ORBIT) trial found that an internet-delivered, therapist-supported, and parent-assisted Exposure and Response Prevention (ERP) intervention reduced tic severity and improved clinical outcomes. This process evaluation aimed to explore mechanisms of impact and factors influencing efficacy. Participants were 112 children with a tic disorder and their parents randomised to the active intervention arm of the ORBIT trial. Child engagement was assessed by usage metrics and parent engagement by chapter completion. Experiences of the digital intervention were explored by semi-structured interviews. Outcomes (3-months post randomisation) were change in tic severity and overall clinical improvement. Tic severity reduced from baseline to 3-month follow-up and 36% were rated as much improved clinically. Greater tic severity at baseline predicted reduction in tic severity. Parental engagement was the only independent predictor of clinical improvement. There were no statistically significant mediators or moderators of the relationship between level of child engagement and outcome. From the qualitative findings, child participants appreciated working together with parents on the intervention and participants found the intervention engaging. ORBIT may be an effective and acceptable intervention for children and young people with tic disorders, with parental engagement being a key factor in successful outcomes.
• Virtual reality (VR) therapy for patients with psychosis: satisfaction and side effects

  O'Regan, Eileen; Jones, Julia

  BACKGROUNDAutomated virtual reality therapies are being developed to increase access to psychological interventions. We assessed the experience with one such therapy of patients diagnosed with psychosis, including satisfaction, side effects, and positive experiences of access to the technology. We tested whether side effects affected therapy.METHODSIn a clinical trial 122 patients diagnosed with psychosis completed baseline measures of psychiatric symptoms, received gameChange VR therapy, and then completed a satisfaction questionnaire, the Oxford-VR Side Effects Checklist, and outcome measures.RESULTS79 (65.8%) patients were very satisfied with VR therapy, 37 (30.8%) were mostly satisfied, 3 (2.5%) were indifferent/mildly dissatisfied, and 1 (0.8%) person was quite dissatisfied. The most common side effects were: difficulties concentrating because of thinking about what might be happening in the room (n = 17, 14.2%); lasting headache (n = 10, 8.3%); and the headset causing feelings of panic (n = 9, 7.4%). Side effects formed three factors: difficulties concentrating when wearing a headset, feelings of panic using VR, and worries following VR. The occurrence of side effects was not associated with number of VR sessions, therapy outcomes, or psychiatric symptoms. Difficulties concentrating in VR were associated with slightly lower satisfaction. VR therapy provision and engagement made patients feel: proud (n = 99, 81.8%); valued (n = 97, 80.2%); and optimistic (n = 96, 79.3%).CONCLUSIONSPatients with psychosis were generally very positive towards the VR therapy, valued having the opportunity to try the technology, and experienced few adverse effects. Side effects did not significantly impact VR therapy. Patient experience of VR is likely to facilitate widespread adoption.
• Experiences of people with multiple sclerosis at work: Towards the understanding of the needs for a job retention vocational rehabilitation intervention

  das Nair, Roshan (2022)

  BACKGROUNDSupporting people with multiple sclerosis (MS) at work can be challenging due to the unpredictable nature and myriad of disease-related symptoms, and issues related to the work environment.OBJECTIVETo explore, amongst people with MS in employment, their experiences of and need for vocational rehabilitation (VR), and perceived barriers and facilitators to implementing VR.METHODSWe conducted 20 semi-structured interviews with people with MS, employers, and healthcare professionals. Interviews were audio-recorded, transcribed, and analysed using the framework method.RESULTSWe identified nine themes reflecting the main MS symptoms (e.g. cognition, fatigue), and environmental factors such as support provided at work (e.g. change of working hours) and workplace characteristics. Providing support tailored to the individual's needs and early intervention were seen as important attributes for the intervention. The barriers identified referred to lack of resources and confidentiality issues; however, having flexibility in the content and delivery of the intervention were seen as facilitators.CONCLUSIONThe impact of environmental factors (e.g. attitudes towards disability) on employment difficulties is equal to or greater than disease-related factors. Environmental changes in the attitudes of co-workers and workplace flexibility can enable people with MS to remain in work for longer.
• Posttraumatic growth and recovery among a sample of Egyptian mental health service users: a phenomenological study

  Ng, Fiona; Slade, Mike (2022)

  BACKGROUNDDelivery of recovery-oriented mental health practice is fundamental to personal recovery. Yet, there is lack of service users' accounts on what constitutes mental health recovery in Egypt.OBJECTIVESThe aim of this study was to explore mental health recovery meaning informed by people with personal experience of recovery.METHODSA phenomenological research design was used. Semi-structured qualitative interviews were conducted with 17 adult community-dwelling individuals who identified as recovered/recovering from mental health issues. An inductive thematic analysis approach was used to analyses participants' responses.RESULTSParticipants predominately reported personal and functional definitions of mental health recovery. Posttraumatic growth was the strongest theme comprising: relation to others, spirituality, new possibilities, identity & strengths, and appreciation of life. Themes of acceptance and forgiveness, functional and clinical recovery, and finding hope were also identified.CONCLUSIONSThis is the first study to explore mental health recovery meaning among a sample of people with lived experience of mental health issues in Egypt. Findings suggest that developing and implementing psychosocial interventions to support posttraumatic growth among people with mental health issues is a priority.
• Character strength-focused positive psychotherapy on acute psychiatric wards: A feasibility and acceptability study

  Slade, Mike (2022)

  OBJECTIVEA manualized single-session positive psychotherapy intervention was developed and tested on acute psychiatric wards.METHODSParticipants were invited in 2018-2019 to identify positive experiences, link them to a personal character strength, and plan a strengths-based activity. The intervention's feasibility was evaluated through fidelity to session components, character strengths identification, and activity completion. Acceptability was evaluated with self-reported pre- and postsession mood ratings, a postsession helpfulness rating, and narrative feedback.RESULTSParticipants (N=70) had complex and severe mental health conditions. In 18 group sessions, 89% of components were delivered with fidelity; 80% of the participants identified a character strength, of whom 71% identified a strengths-based activity, and 58% completed the activity. The mean±SD helpfulness rating (N=23) was 8.5±1.5 (on a 10-point Likert scale), and positive mood significantly increased postsession (5.9 presession vs. 7.2 postsession).CONCLUSIONSPositive psychotherapy is feasible in challenging inpatient settings, and service users with severe and complex mental health conditions find it helpful.
• Automated virtual reality cognitive therapy (gameChange) in inpatient psychiatric wards: Qualitative study of staff and patient views using an implementation framework

  Jones, Julia (2022)

  BACKGROUNDAutomated virtual reality (VR) therapy could allow a greater number of patients to receive evidence-based psychological therapy. The aim of the gameChange VR therapy is to help patients overcome anxious avoidance of everyday social situations. gameChange has been evaluated with outpatients, but it may also help inpatients prepare for discharge from psychiatric hospital.OBJECTIVEThe aim of this study is to explore the views of patients and staff on the provision of VR therapy on psychiatric wards.METHODSFocus groups or individual interviews were conducted with patients (n=19) and National Health Service staff (n=22) in acute psychiatric wards. Questions were derived from the nonadoption, abandonment, and challenges to the scale-up, spread, and sustainability framework. Expectations of VR therapy were discussed, and participants were then given the opportunity to try out the gameChange VR therapy before they were asked questions that focused on opinions about the therapy and feasibility of adoption.RESULTSThere was great enthusiasm for the use of gameChange VR therapy on psychiatric wards. It was considered that gameChange could help build confidence, reduce anxiety, and "bridge that gap" between the differences of being in hospital and being discharged to the community. However, it was reflected that the VR therapy may not suit everyone, especially if they are acutely unwell. VR on hospital wards for entertainment and relaxation was also viewed positively. Participants were particularly impressed by the immersive quality of gameChange and the virtual coach. It was considered that a range of staff groups could support VR therapy delivery. The staff thought that implementation would be facilitated by having a lead staff member, having ongoing training accessible, and involving the multidisciplinary team in decision-making for VR therapy use. The most significant barrier to implementation identified by patients and staff was a practical one: access to sufficient, private space to provide the therapy.CONCLUSIONSPatients and staff were keen for VR to be used on psychiatric wards. In general, patients and staff viewed automated VR therapy as possible to implement within current care provision, with few significant barriers other than constraints of space. Patients and staff thought of many further uses of VR on psychiatric wards. The value of VR therapy on psychiatric wards now requires systematic evaluation.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)RR2-10.2196/20300.
• Typology of content warnings and trigger warnings: Systematic review

  Charles, Ashleigh; Hare-Duke, Laurie; Nudds, Hannah; Llewellyn-Beardsley, Joy; Rennick-Egglestone, Stefan; Ng, Fiona; Yeo, Caroline; Slade, Mike (2022)

  Content and trigger warnings give information about the content of material prior to receiving it. Different typologies of content warnings have emerged across multiple sectors, including health, social media, education and entertainment. Benefits arising from their use are contested, with recent empirical evidence from educational sectors suggesting they may raise anxiety and reinforce the centrality of trauma experience to identity, whilst benefits relate to increased individual agency in making informed decisions about engaging with content. Research is hampered by the absence of a shared inter-sectoral typology of warnings. The aims of this systematic review are to develop a typology of content warnings and to identify the contexts in which content warnings are used. The review was pre-registered (ID: CRD42020197687, URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020197687) and used five sources: electronic databases covering multiple sectors (n = 19); table of contents from multi-sectoral journals (n = 5), traditional and social media websites (n = 53 spanning 36 countries); forward and backward citation tracking; and expert consultation (n = 15). In total, 6,254 documents were reviewed for eligibility and 136 documents from 32 countries were included. These were synthesised to develop the Narrative Experiences Online (NEON) content warning typology, which comprises 14 domains: Violence, Sex, Stigma, Disturbing content, Language, Risky behaviours, Mental health, Death, Parental guidance, Crime, Abuse, Socio-political, Flashing lights and Objects. Ten sectors were identified: Education, Audio-visual industries, Games and Apps, Media studies, Social sciences, Comic books, Social media, Music, Mental health, and Science and Technology. Presentation formats (n = 15) comprised: education materials, film, games, websites, television, books, social media, verbally, print media, apps, radio, music, research, DVD/video and policy document. The NEON content warning typology provides a framework for consistent warning use and specification of key contextual information (sector, presentation format, target audience) in future content warning research, allowing personalisation of content warnings and investigation of global sociopolitical trends over time.
• Understanding factors that affect wellbeing in trans people "later" in transition: a qualitative study

  Aldridge, Zoe; Thorne, Nat; Marshall, Ellen; English, Cara; Yip, Andrew K. T.; Nixon, Elena; Bouman, Walter P.; Arcelus, Jon (2022)

  PURPOSEAlthough cross-sectional studies have demonstrated that trans people present with lower quality of life and wellbeing than the general population, few studies have explored the factors associated with this, particularly in those who have medically transitioned some time ago. This paper aims to fill the gap in the literature on what factors are associated with wellbeing in trans people who initiated medical transition some time ago.METHODSThis study used semi-structured one-to-one interviews with 23 participants to investigate the factors that impact upon the wellbeing of trans people who had initiated Gender Affirming Medical Treatment five or more years ago. The content of the interviews were analysed with an inductive, grounded theory approach to identify common themes within them.RESULTSThe four themes identified include some consistencies with cisgender populations (while being viewed through the lens of trans experience), as well as those more specific to the trans experience. Together these themes were: Interactions with healthcare services; Seeking societal acceptance; Quality of social support; The 'double-edged sword' of media and social media. Each of the themes identifies a factor that participants highlighted as impacting, either positively or negatively, on their wellbeing.CONCLUSIONSThe results highlight the importance of social support, protective legislations, awareness of trans issues in the general public, and the need of improving the knowledge held by non-specialist healthcare providers.
• Psychological treatments for depression and anxiety in dementia and mild cognitive impairment

  Orrell, Martin (2022)

  BACKGROUNDExperiencing anxiety and depression is very common in people living with dementia and mild cognitive impairment (MCI). There is uncertainty about the best treatment approach. Drug treatments may be ineffective and associated with adverse effects. Guidelines recommend psychological treatments. In this updated systematic review, we investigated the effectiveness of different psychological treatment approaches.OBJECTIVESPrimary objective To assess the clinical effectiveness of psychological interventions in reducing depression and anxiety in people with dementia or MCI. Secondary objectives To determine whether psychological interventions improve individuals' quality of life, cognition, activities of daily living (ADL), and reduce behavioural and psychological symptoms of dementia, and whether they improve caregiver quality of life or reduce caregiver burden.SEARCH METHODSWe searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE, Embase, four other databases, and three trials registers on 18 February 2021.SELECTION CRITERIAWe included randomised controlled trials (RCTs) that compared a psychological intervention for depression or anxiety with treatment as usual (TAU) or another control intervention in people with dementia or MCI.DATA COLLECTION AND ANALYSISA minimum of two authors worked independently to select trials, extract data, and assess studies for risk of bias. We classified the included psychological interventions as cognitive behavioural therapies (cognitive behavioural therapy (CBT), behavioural activation (BA), problem-solving therapy (PST)); 'third-wave' therapies (such as mindfulness-based cognitive therapy (MBCT)); supportive and counselling therapies; and interpersonal therapies. We compared each class of intervention with control. We expressed treatment effects as standardised mean differences or risk ratios. Where possible, we pooled data using a fixed-effects model. We used GRADE methods to assess the certainty of the evidence behind each result.MAIN RESULTSWe included 29 studies with 2599 participants. They were all published between 1997 and 2020. There were 15 trials of cognitive behavioural therapies (4 CBT, 8 BA, 3 PST), 11 trials of supportive and counselling therapies, three trials of MBCT, and one of interpersonal therapy. The comparison groups received either usual care, attention-control education, or enhanced usual care incorporating an active control condition that was not a specific psychological treatment. There were 24 trials of people with a diagnosis of dementia, and five trials of people with MCI. Most studies were conducted in community settings. We considered none of the studies to be at low risk of bias in all domains.  Cognitive behavioural therapies (CBT, BA, PST) Cognitive behavioural therapies are probably slightly better than treatment as usual or active control conditions for reducing depressive symptoms (standardised mean difference (SMD) -0.23, 95% CI -0.37 to -0.10; 13 trials, 893 participants; moderate-certainty evidence). They may also increase rates of depression remission at the end of treatment (risk ratio (RR) 1.84, 95% CI 1.18 to 2.88; 2 studies, with one study contributing 2 independent comparisons, 146 participants; low-certainty evidence). We were very uncertain about the effect of cognitive behavioural therapies on anxiety at the end of treatment (SMD -0.03, 95% CI -0.36 to 0.30; 3 trials, 143 participants; very low-certainty evidence). Cognitive behavioural therapies probably improve patient quality of life (SMD 0.31, 95% CI 0.13 to 0.50; 7 trials, 459 participants; moderate-certainty evidence) and activities of daily living at end of treatment compared to treatment as usual or active control (SMD -0.25, 95% CI -0.40 to -0.09; 7 trials, 680 participants; moderate-certainty evidence). Supportive and counselling interventions Meta-analysis showed that supportive and counselling interventions may have little or no effect on depressive symptoms in people with dementia compared to usual care at end of treatment (SMD - .05, 95% CI -0.18 to 0.07; 9 trials, 994 participants; low-certainty evidence). We were very uncertain about the effects of these treatments on anxiety, which was assessed only in one small pilot study. Other interventions There were very few data and very low-certainty evidence on MBCT and interpersonal therapy, so we were unable to draw any conclusions about the effectiveness of these interventions.AUTHORS' CONCLUSIONSCBT-based treatments added to usual care probably slightly reduce symptoms of depression for people with dementia and MCI and may increase rates of remission of depression. There may be important effect modifiers (degree of baseline depression, cognitive diagnosis, or content of the intervention). CBT-based treatments probably also have a small positive effect on quality of life and activities of daily living. Supportive and counselling interventions may not improve symptoms of depression in people with dementia. Effects of both types of treatment on anxiety symptoms are very uncertain. We are also uncertain about the effects of other types of psychological treatments, and about persistence of effects over time. To inform clinical guidelines, future studies should assess detailed components of these interventions and their implementation in different patient populations and in different settings.
• Feasibility, acceptability and costs of nurse-led Alpha-Stim cranial electrostimulation to treat anxiety and depression in university students

  Morriss, Richard K. (2022)

  BACKGROUND: Only a relatively low proportion of university students seek help for anxiety and depression disorders, partly because they dislike current drug and psychological treatment options and would prefer home-based care. The aim of this study is to determine the feasibility, acceptability and cost utility of Alpha-Stim cranial electrostimulation (CES) delivered through a nurse led primary care clinic as a daily treatment for anxiety and depression symptoms by the student at home in contrast to usual primary care. METHOD: Feasibility and acceptability of a nurse led clinic offering Alpha-Stim CES in terms of the take up and completion of the six-week course of Alpha-Stim CES. Change in score on the GAD-7 and PHQ-9 as measures of anxiety and depression symptoms at baseline and at 8 weeks following a course of Alpha-Stim CES. Similar evaluation in a non-randomised control group attending a family doctor over the same period. Cost-utility analysis of the nurse led Alpha-Stim CES and family doctor pathways with participants failing to improve following further NICE Guideline clinical care (facilitated self-help and cognitive behaviour therapy). RESULTS: Of 47 students (mean age 22.1, years, 79% female opting for Alpha-Stim CES at the nurse-led clinic 46 (97.9%) completed a 6-week daily course. Forty-seven (47) students comprised a comparison group receiving usual family doctor care. Both Alpha-Stim CES and usual family doctor care were associated with large effect size reductions in GAD-7 and PHQ-9 scores from baseline to 8 weeks. There were no adverse effects and only one participant showed a clinically important deterioration in the Alpha-Stim group. In the cost utility analysis, Alpha-Stim CES was a cheaper option than usual family doctor care under all deterministic or probabilistic assumptions. CONCLUSION: Nurse delivered Alpha-Stim CES may be a feasible, acceptable and cheaper way of providing greater choice and home-based care for some university students seeking help from primary care with new presentations of anxiety and depression.
• The economic burden of dementia in low- and middle-income countries (LMICs): a systematic review

  Stephan, Blossom C. M. (2022)

  INTRODUCTIONMore than two-thirds of people with dementia live in low- and middle-income countries (LMICs), resulting in a significant economic burden in these settings. In this systematic review, we consolidate the existing evidence on the cost of dementia in LMICs.METHODSSix databases were searched for original research reporting on the costs associated with all-cause dementia or its subtypes in LMICs. The national-level dementia costs inflated to 2019 were expressed as percentages of each country's gross domestic product (GDP) and summarised as the total mean percentage of GDP. The risk of bias of studies was assessed using the Larg and Moss method.RESULTSWe identified 14 095 articles, of which 24 studies met the eligibility criteria. Most studies had a low risk of bias. Of the 138 LMICs, data were available from 122 countries. The total annual absolute per capita cost ranged from US$590.78 for mild dementia to US$25 510.66 for severe dementia. Costs increased with the severity of dementia and the number of comorbidities. The estimated annual total national costs of dementia ranged from US$1.04 million in Vanuatu to US$195 billion in China. The average total national expenditure on dementia estimated as a proportion of GDP in LMICs was 0.45%. Indirect costs, on average, accounted for 58% of the total cost of dementia, while direct costs contributed 42%. Lack of nationally representative samples, variation in cost components, and quantification of indirect cost were the major methodological challenges identified in the existing studies.CONCLUSIONThe estimated costs of dementia in LMICs are lower than in high-income countries. Indirect costs contribute the most to the LMIC cost. Early detection of dementia and management of comorbidities is essential for reducing costs. The current costs are likely to be an underestimation due to limited dementia costing studies conducted in LMICs, especially in countries defined as low- income.PROSPERO REGISTRATION NUMBERThe protocol was registered in the International Prospective Register of Systematic Reviews database with registration number CRD42020191321.
• Progressing towards blood based diagnostic RNA biomarkers for dementia with lewy bodies

  Rajkumar, Anto P. (2022)

  Prevalence of Dementia with Lewy bodies (DLB) is second only to Alzheimer's disease (AD) among people with neurodegenerative dementia. Accurate distinction between these two most common subtypes of dementia is essential because they differ in their prognosis, neuropsychiatric symptoms, pharmacological management, 1 and sensitivity to medication adverse effects. Misdiagnosing DLB as AD, and prescribing an antipsychotic medication for treating persistent visual hallucinations and associated challenging behaviours may lead to life-threatening adverse events. Moreover, DLB leads to earlier institutionalisation and mortality, more severe neuropsychiatric symptoms, higher costs and more carers’ burden than AD. Currently, there are only three indicative biomarkers helping to diagnose DLB, 1) reduced dopamine transporter uptake in basal ganglia, visualised by Single-Photon Emission Computed Tomography or Positron Emission Tomography, 2) low uptake 123iodine-Meta-iodobenzylguanidine myocardial scintigraphy, and 3) polysomnography confirming rapid eye movement sleep without atonia. 2 These indicative biomarkers are not routinely used in most clinical settings because of costs, equipment availability or concerns over feasibility. There is an urgent clinical need for discovering reliable blood-based biomarkers that can aid differentiating DLB from AD. Such blood-based diagnostic biomarkers hold promise for rapid clinical adoption and for facilitating early diagnosis and accurate subtyping of dementia.
• Clinical utility of cerebrospinal fluid Aβ42 and tau measures in diagnosing mild cognitive impairment in early onset dementia

  Junaid, Kehinde (2022)

  BACKGROUNDThe differentiation of a preclinical or prodromal Alzheimer's disease (AD) is challenging particularly in patients with early onset Alzheimer's or related dementias (EOARD). We report our experience on diagnostic lumbar puncture to diagnose EOARD at a tertiary neurocognitive referral center in Nottingham, England from March 2018 to October 2020.OBJECTIVETo assess amyloid-β42 (Aβ42), total tau, and Thr181-phosphorylated tau (p-tau) measurements in the cerebrospinal fluid (CSF) in patients with mild cognitive impairment (MCI) and in relation to their follow-up cognitive performance.METHODSThirty participants aged 32-68 years old (mean 59 years; 57% female) were included. Clinical diagnosis was based on clinical presentation, neurocognitive profile, neuroradiological features (MRI, FDG-PET CT) and CSF Aβ42, total tau, and p-tau measurements.RESULTSPatients with MCI who progressed to AD (prodromal AD) had significantly higher CSF total (797.63 pg/ml) and p-tau (82.31 pg/ml), and lower Aβ42 levels (398.94 pg/ml) in comparison to their counterparts with stable MCI (total tau 303.67 pg/ml, p-tau 43.56 pg/ml, Aβ42 873.44 pg/ml) (p <  0.01 for CSF total and p-tau measures and p <  0.0001 for CSF Aβ42 measures). None of the CSF biomarkers correlated with any of the cognitive performance measures. Principal component analysis confirmed that the clinical diagnosis of MCI secondary to AD, namely prodromal AD (as per NIA-AA criteria) in younger adults, was associated with decreased CSF Aβ42.CONCLUSIONIn early onset AD, low levels of CSF Aβ42 appear to be more sensitive than total and p-tau measures in differentiating AD MCI from other forms of dementia. Further work on larger samples of EOARD in clinical practice will address the cost effectiveness of making an earlier diagnosis.
• Olfactory stimulation for people with dementia: A rapid review

  Dening, Tom (2022)

  There is a growing interest in using olfactory (smell) stimulation in dementia care. This study aims to extend current knowledge by synthesising the evidence on the efficacy of interventions using olfactory stimulation for people with dementia and to assess the effects of different types of odours and administration methods using a mixed methods approach. The rapid review was conducted based on searches in six electronic databases. A narrative approach was applied to assess 20 studies included in the review. Fourteen studies used a quasi-experimental design, five studies used an experimental design and one was a case study. High heterogeneity was found on odours and methods of application used, with the majority of studies administering lavender oil using a diffuser. Mixed results were reported on the benefits of olfactory stimulation on responsive behaviours and cognitive function. Although the evidence available is limited, encouraging results were found regarding olfactory stimulation and increased sleep duration, food intake and improved balance. It was not possible to draw any overall conclusion in relation to the effect of olfactory stimulation. However, this review shows promising results that support further investigation of olfactory stimulation as a nonpharmacological intervention for people with dementia. The review is limited due to the low to moderate quality of studies included. Furthermore, the broad range of approaches was employed, and comparison between the studies was difficult. Further high-quality mixed method studies using robust and detailed protocols are needed to clarify the effects of olfactory stimuli and any other factors that may influence the responses of people with dementia.
• The COVID-19 pandemic and its impact on tic symptoms in children and young people: A prospective cohort study

  Hall, Charlotte L.; Khan, Kareem; Brown, Beverley J.; Hollis, Chris P. (2022)

  To understand how children and young people with tic disorders were affected by COVID-19, we compared pre and during pandemic scores on the Yale Global Tic Severity Scale (YGTSS). Participants were young people (N = 112; male:78%; 9–17 years) randomised to the control arm of the “ORBIT-Trial” (ISRCTN70758207, ClinicalTrials.gov-NCT03483493). For this analysis, the control arm was split into two groups: one group was followed up to 12-months’ post-randomisation before the pandemic started (pre-COVID group, n = 44); the other group was impacted by the pandemic at the 12-month follow-up (during-COVID group, n = 47). Mixed effects linear regression modelling was conducted to explore differences in YGTSS at 6- and 12-months post-randomisation. There were no significant differences in tic symptom or severity between participants who were assessed before and during COVID-19. This finding was not influenced by age, gender, symptoms of anxiety or autism spectrum disorder. Thus, the COVID-19 pandemic did not significantly impact existing tic symptoms. (PsycInfo Database Record (c) 2022 APA, all rights reserved) (Source: journal abstract)
• Current pharmacological treatments for ADHD

  Groom, Madeleine J.; Cortese, Samuele (2022)

  Attention-Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental condition associated with impaired function and increased risk of poor outcomes in children, young people and adults with the condition. Currently approved pharmacological treatments for ADHD include a range of stimulant (methylphenidate, amphetamine) and nonstimulant (atomoxetine, guanfacine, clonidine) medications. All have been shown to be effective in treating the symptoms of ADHD and improving other functional outcomes including quality of life, academic performance, rates of accidents and injuries, and do not appear to be associated with significant adverse outcomes or side effects. In this chapter, we review medications for ADHD by summarising the mechanisms of action of each of the two main classes of compounds (stimulants and nonstimulants), the formulations of the most commonly prescribed medications within each class, their efficacy in treating ADHD symptoms and other outcomes, and other factors that influence treatment decisions including side effects and tolerability, comorbidities and medical history. We conclude with a summary of the treatment decisions made by clinicians and suggest some next steps for research. Further research is needed to understand the mechanisms of action of these medications and how exactly they improve symptoms, and to examine their effects on commonly occurring comorbidities.
• Characteristics of alcohol recovery narratives: Systematic review and narrative synthesis

  Jones, Katy A.; Llewellyn-Beardsley, Joy; Rennick-Egglestone, Stefan (2022)

  BACKGROUND AND AIMSNarratives of recovery from alcohol misuse have been analysed in a range of research studies. This paper aims to produce a conceptual framework describing the characteristics of alcohol misuse recovery narratives that are in the research literature, to inform the development of research, policy, and practice.METHODSSystematic review was conducted following PRISMA guidelines. Electronic searches of databases (Ovid MEDLINE, EMBASE, CINHAL, PsychInfo, AMED and SCOPUS), grey literature, and citation searches for included studies were conducted. Alcohol recovery narratives were defined as "first-person lived experience accounts, which includes elements of adversity, struggle, strength, success, and survival related to alcohol misuse, and refer to events or actions over a period of time". Frameworks were synthesised using a three-stage process. Sub-group analyses were conducted on studies presenting analyses of narratives with specific genders, ages, sexualities, ethnicities, and dual diagnosis. The review was prospectively registered (PROSPERO CRD42021235176).RESULTS32 studies were included (29 qualitative, 3 mixed-methods, 1055 participants, age range 17-82years, 52.6% male, 46.4% female). Most were conducted in the United States (n = 15) and Europe (n = 11). No included studies analysed recovery narratives from lower income countries. Treatment settings included Alcoholic Anonymous (n = 12 studies), other formal treatment, and 'natural recovery'. Eight principle narrative dimensions were identified (genre, identity, recovery setting, drinking trajectory, drinking behaviours, stages, spirituality and religion, and recovery experience) each with types and subtypes. All dimensions were present in most subgroups. Shame was a prominent theme for female narrators, lack of sense of belonging and spirituality were prominent for LGBTQ+ narrators, and alienation and inequality were prominent for indigenous narrators.CONCLUSIONSReview provides characteristics of alcohol recovery narratives, with implications for both research and healthcare practice. It demonstrated knowledge gaps in relation to alcohol recovery narratives of people living in lower income countries, or those who recovered outside of mainstream services.PROTOCOL REGISTRATIONProspero registration number: CRD42020164185.
• A randomised controlled trial investigating the clinical and cost-effectiveness of Alpha-Stim AID cranial electrotherapy stimulation (CES) in patients seeking treatment for moderate severity depression in primary care (Alpha-Stim-D Trial)

  Patel, Shireen; Boutry, Clement; Patel, Priya; Craven, Michael P.; Guo, Boliang; Butler, Debbie; Higton, Fred; McNaughton, Rebecca; Briley, Paul M.; Nixon, Neil L.; et al. (2022)

  BACKGROUNDMajor depression is the second leading cause of years lost to disability worldwide and is a leading contributor to suicide. However, first-line antidepressants are only fully effective for 33%, and only 40% of those offered psychological treatment attend for two sessions or more. Views gained from patients and primary care professionals are that greater treatment uptake might be achieved if people with depression could be offered alternative and more accessible treatment options. Although there is evidence that the Alpha-Stim Anxiety Insomnia and Depression (AID) device is safe and effective for anxiety and depression symptoms in people with anxiety disorders, there is much less evidence of efficacy in major depression without anxiety. This study investigates the effectiveness of the Alpha-Stim AID device, a cranial electrotherapy stimulation (CES) treatment that people can safely use independently at home. The device provides CES which has been shown to increase alpha oscillatory brain activity, associated with relaxation.METHODSThe aim of this study is to investigate the clinical and cost-effectiveness of Alpha-Stim AID in treatment-seeking patients (aged 16 years upwards) with moderate to moderately severe depressive symptoms in primary care. The study is a multi-centre parallel-group, double-blind, non-commercial, randomised controlled superiority trial. The primary objective of the study is to examine the clinical efficacy of active daily use of 8 weeks of Alpha-Stim AID versus sham Alpha-Stim AID on depression symptoms at 16 weeks (8 weeks after the end of treatment) in people with moderate severity depression. The primary outcome is the 17-item Hamilton Depression Rating Scale at 16 weeks. All trial and treatment procedures are carried out remotely using videoconferencing, telephone and postal delivery considering the COVID-19 pandemic restrictions.DISCUSSIONThis study is investigating whether participants using the Alpha-Stim AID device display a reduction in depressive symptoms that can be maintained over 8 weeks post-treatment. The findings will help to determine whether Alpha-Stim AID should be recommended, including being made available in the NHS for patients with depressive symptoms.TRIAL REGISTRATIONISRTCN ISRCTN11853110 . Registered on 14 August 2020.

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