Applied Research Collaboration Research Articles

Associations between physical multimorbidity patterns and common mental health disorders in middle-aged adults: A prospective analysis using data from the UK Biobank.

BackgroundWe aimed to identify specific patterns of physical multimorbidity, defined as the presence of two or more physical long-term conditions, and to examine the extent to which these specific patterns could predict future incident and persistent common mental health disorders (CMDs) in middle-aged adults enrolled in the UK Biobank.MethodsWe assessed prospective associations between physical multimorbidity status at the baseline assessment (2006–2010) and depression and anxiety ‘caseness’ according to the Patient Health Questionnaire (PHQ)-9 and the Generalised Anxiety Disorder Assessment (GAD)-7 at the follow-up assessment (2016) in 154,367 middle-aged adults enrolled in the UK Biobank (median age: 57 years, interquartile range = 50–62 years, 56.5% female, mean duration of follow-up: 7.6 years, standard deviation = 0.87). Patterns of physical multimorbidity were identified using exploratory factor analysis. Logistic regression was used to assess prospective associations between physical multimorbidity patterns at baseline and both incident and persistent depression and anxiety at follow-up.FindingsCompared to those with no physical multimorbidity, having two (adjusted odds ratio (aOR) =1.41, 95%CI 1.32 to 1.53), three (aOR = 1.94, 95%CI 1.76 to 2.14), four (aOR = 2.38, 95%CI 2.07 to 2.74), and five or more (aOR = 2.89, 95%CI 2.42 to 3.45) physical conditions was prospectively associated with incident depression at follow-up in a dose response manner. Similar trends emerged for incident anxiety, persistent depression, and persistent anxiety, but associations were strongest for incident CMDs. Regarding specific patterns of physical MM, the respiratory pattern (aOR = 3.23, 95%CI 2.44 to 4.27) and the pain/gastrointestinal pattern (aOR = 2.19, 95%CI 1.92 to 2.50) emerged as the strongest predictors of incident depression. Similar results emerged for incident anxiety.InterpretationThese findings highlight patterns of physical multimorbidity with the poorest prognosis for both emerging and persisting depression and anxiety. These findings might have significant implications for the implementation of integrated mental and physical healthcare and facilitate the development of targeted preventative interventions and treatment for those with physical multimorbidity.FundingAR is supported by Guy's Charity grant number EIC180702; JAT is funded by Medical Research Council (MRC) number MR/SO28188/1; AD is funded by Guy's Charity grant number EIC180702 and MRC grant number MR/SO28188/1. JD is part supported by the ESRC Centre for Society and Mental Health at King's College London (ES/S012567/1), grants from the ESRC (ES/S002715/1), by the Health Foundation working together with the Academy of Medical Sciences, for a Clinician Scientist Fellowship, and by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London and the National Institute for Health Research (NIHR) Applied Research Collaboration South London (NIHR ARC South London) at King's College Hospital NHS Foundation Trust. The views expressed are those of the author[s] and not necessarily those of the ESRC, NIHR, the Department of Health and Social Care or King's College London.

Mitigating the impacts of COVID-19: where are the mental health trials?

Mitigating the impacts of COVID-19: where are the mental health trials?

931-P: Supporting Physical Activity in Children with Type 1 Diabetes: A Survey of Health Care Professionals

Background: The risk of some of the co-morbidities associated with type 1 diabetes (T1D) can be mitigated through physical activity. Despite benefits, research shows that children and adolescents with T1D are not meeting recommended levels of physical activity. Health Care Professionals (HCPs) have an important role in supporting and encouraging children and adolescents to be physically active. Therefore it is important to understand the perspectives of HCPs in relation to understanding physical activity behaviours in children and adolescents, prior to designing interventions to support physical activity. Methods: An online mixed methods survey of HCPs in England and Wales. Respondents were asked questions about how they support physical activity in the clinic and their perceptions of barriers/enablers of physical activity. Quantitative data were analysed descriptively, qualitative data were analysed using a combined deductive framework and inductive thematic analysis using the Capability, Opportunity, Motivation model of behaviour (COM-B). Results: Responses were received from 114 individual HCPs, representing 45% of paediatric diabetes units in England and Wales. Results show that HCPs felt that the promotion of physical activity is important in their clinic (90%) and advise children and adolescents to increase levels of physical activity (88%). Many respondents (43%) felt there was lack of education opportunities for HCPs on this topic. Qualitative responses highlighted three key areas of behaviour that might be a barrier to physical activity in their patients: (1) psychological capacity (i.e., fear of hypoglycaemia and lack of understanding of how to manage insulin and glucose levels), (2) physical opportunity (i.e., time, cost, and access to resources), and (3) social opportunity (i.e., family, school, and peer support). Conclusion: This understanding will help develop future interventions to support physical activity in children and adolescents with T1D. Disclosure E. Cockcroft: None. P. Narendran: Speaker’s Bureau; Self; Novo Nordisk Inc., Sanofi. E. Wooding: None. R. C. Andrews: None. Funding National Institute for Health Research Applied Research Collaboration South West Peninsula (to E.C.)

The challenges and opportunities of mental health data sharing in the UK

The challenges and opportunities of mental health data sharing in the UK

P118 Co-design of a model Fracture Liaison Service consultation: a Delphi survey with patients and clinicians

Abstract Background/Aims Fracture Liaison Services (FLSs) are recommended to deliver best practice in secondary fracture prevention. As part of the iFraP (Improving uptake of Fracture Prevention drug Treatments) research programme this study aimed to 1) co-design content for a ‘model FLS consultation’ and 2) gain consensus on the appropriateness of osteoporosis clinical guidelines in the context of FLSs. Methods Three rounds of modified Delphi survey were sent to patients with osteoporosis and/or fragility fractures, carers, and clinicians. Participants were presented with potential consultation content derived from an evidence synthesis of current guidelines, frameworks and theories of shared decision-making, communication and medicine adherence, and stakeholder consultation. Participants were asked to rate their perception of the importance of each statement on a 5-point Likert scale and elaborate using free-text boxes. In Round 2, participants were shown mean scores of importance from Round 1. Statements identified as of ‘low importance’ at the end of Rounds 1 and 2 were discussed by the study team, including patient contributors, and were removed or amended. In Round 3, participants were asked whether the statement was ‘essential’ or ‘optional’ in a time-limited FLS consultation. Percentage agreement with each statement was ranked. The threshold for ‘essential’ versus ‘optional’ was determined by the study team. Results 391 invitations to participate were sent, with 72, 49, and 52 responders to Rounds 1, 2 and 3 respectively. Throughout Rounds 1-3 participants considered 122 statements. By Round 3, 81 statements were deemed essential, with an additional 14 optional statements. Essential statements were distilled into 18 recommendations constituting the ‘model FLS consultation’. Statements related to stages of the consultation, including: introductions; gather information; consider therapeutic options; elicit patient perceptions; establish shared decision-making preferences; share information about condition and treatment; check understanding; and signpost next steps. There was consensus that FLS clinicians should discuss the benefits and risks of oral and intravenous bisphosphonates and denosumab. Optional consultation content included a statement suggesting clinicians should observe the patient to look for signs of fractures in their spine, with free-text responses suggesting that FLS clinicians may not ‘be best qualified’ to perform physical examinations. Removed statements included those relating to the discussion of Hormone Replacement Therapy, Raloxifene and Teriparatide, with free-text statements suggesting that ‘specialists’ (e.g. Rheumatologists) should discuss these medications. Additionally, statements that described the potential consequences of fracture (e.g. ‘the clinician should explain that one in ten patients with a hip fracture will die within 12 months of fracture.’) were removed. Free-text comments described these statements as potentially ‘scary’. Conclusion The Delphi survey has informed iFraP intervention development by highlighting essential and optional FLS consultation content. Findings also provide insight into aspects of current osteoporosis clinical guidelines deemed appropriate in nurse/allied health professional led FLSs. Disclosure L. Bullock: None. C. Jinks: Grants/research support; CJ is part funded by the NIHR Applied Research Collaboration (ARC) West Midlands. F. Crawford-Manning: Grants/research support; FCM is part funded by the NIHR Clinical Research Network Scholar Programme. S. Leyland: None. J. Fleming: None. E.M. Clark: None. E. Cottrell: None. J. Edwards: Grants/research support; JE is an NIHR Academic Clinical Lecturer in Primary Care (CL-2016-10-003). Z. Paskins: Grants/research support; ZP is funded by the NIHR, Clinician Scientist Award (CS-2018-18-ST2-010)/NIHR Academy.

P117 Exploring experiences of Fracture Liaison Services and perceptions of a new decision tool to support patient and clinician decisions: a focus group study

Abstract Background/Aims The iFraP study (Improving uptake of Fracture Prevention Treatments) is developing a computerised decision-support tool to support clinician decision-making, risk communication and informed patient decision-making in Fracture Liaison Service (FLS) consultations. To inform iFraP intervention development, this study explored 1) patient and clinician experiences of FLSs and 2) perspectives towards the new iFraP tool. Methods Four focus groups and supplementary interviews included 9 FLS clinicians, 7 General Practitioners (GPs), and 8 patients who recently attended an FLS consultation. Theoretically-informed thematic analysis was conducted to facilitate understanding of current FLS practice, potential intervention acceptability and possible barriers to, and facilitators of, implementation. Results FLS clinicians and GPs suggested that FLSs worked well to identify patients at high risk of future fracture and to recommend medication. FLS clinicians were confident in their role and felt their consultations were person-centred and addressed information needs. However, some FLS clinicians described communicating risk as difficult and gave examples of when they are uncertain whether medication should be recommended (e.g. patient with osteopenic bone mineral density). FLS clinicians had varying perceptions of their roles in discussing medications, with some not viewing this as their responsibility; whereas GPs reported that medication discussions were an important aspect of the FLS clinician role. When medication recommendations (and discussion) were delivered, the setting varied across services including face-to-face in clinic or at the patient’s home, by letter, or by telephone. On the whole, patients reflected positively on their FLS appointment. However, some patients described unmet information needs, such as risk of future fractures, potential benefits and risks of medications, and information about follow-up.Many FLS clinicians and GPs reflected upon the potential value of the tool, including the inclusion of visual images to facilitate understanding of fracture risk, and to promote consistent messages across FLSs and between primary and secondary care. Barriers to intervention implementation were also identified. Clinicians expressed concern that evidence-based Cates plots to support explanations of medication effectiveness may make patients believe medications are not ‘worthwhile’. This suggests that clinicians prioritised promotion of medication adherence over informed decision-making, highlighting that the goal of FLS clinicians and iFraP may not align. Furthermore, concern was expressed that use of a computerised tool may detract from the clinician-patient relationship. Conclusion These novel findings illustrate the experience of FLS consultations from three perspectives. They highlight FLS clinicians’ clinical decision-support needs and patients’ unmet need for clear information that addresses their medication concerns. Overall, the iFraP intervention was viewed as acceptable, with the potential to support clinicians’ decision-making and to facilitate informed decision-making. Differences in FLS configuration and a move to more remote consulting may mean the intervention needs to be adaptable to different settings to address barriers to implementation. Disclosure L. Bullock: None. C. Jinks: Grants/research support; CJ is part funded by the NIHR Applied Research Collaboration (ARC) West Midlands. A. Hawarden: Grants/research support; AH is a NIHR funded Academic Clinical Fellow. F. Crawford-Manning: Grants/research support; FCM is part funded by the NIHR Clinical Research Network Scholar Programme. S. Leyland: None. J. Fleming: None. E.M. Clark: None. E. Cottrell: None. J. Edwards: Grants/research support; JE is an NIHR Academic Clinical Lecturer in Primary Care (CL-2016-10-003). Z. Paskins: Grants/research support; ZP is funded by the NIHR, Clinician Scientist Award (CS-2018-18-ST2-010)/NIHR Academy.

Measuring therapeutic engagement in finnish adult acute psychiatric in-patient care units using the finnish version of therapeutic engagement questionnaire (TEQ)

IntroductionThe Therapeutic Engagement Questionnaire (TEQ) has been developed and validated in partnership with service users (SUs), registered mental health nurses (RMHNs) and nurse academics in the UK in accordance with psychometric theory. The TEQ is highly relevant and useful to clinical practice. The TEQ measures therapeutic engagement (TE) in two contexts - 1-1 interactions between SUs and RMHNs, as well as the overall environment and atmosphere of the units - from the perspective of both SUs and RMHNs. The TEQ has been translated into Finnish by two expert panels and was pre-tested and validated in ten adult acute psychiatric in-patient units in two hospitals in Finland.ObjectivesTo measure TE in Finnish adult acute in-patient psychiatric settings from the perspectives of both SUs and RMHNs.MethodsThe Finnish version of the TEQ (Hoidollinen yhteistyö) will be completed by RMHNs and SUs in 15 adult acute psychiatric in-patient units. Nine of the units are within the University Hospital and six in a municipal psychiatric hospital. The data will be collected within a 3-month period (October - December 2020). The coordinating nurse of each unit will organise the operational side of the study including obtaining consent from SUs. The nurses will participate in the survey via Webropol which includes nurses’ consent. Sociodemographic information will be collected from the SUs and nurses.ResultsThe results of the measurement study will be reported at the 29th European Congress of Psychiatry.ConclusionsThe conclusions of the measurement study will be reported at the 29th European Congress of Psychiatry.Conflict of interestThis study is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration South London (NIHR ARC South London).

The Prevalence of Multimorbidity and Associations With Clinical Outcomes Among Middle Aged People in Golestan, Iran: A Longitudinal Cohort Study

Background: As the populations of lower- and middle-income countries (LMICs) age, multimorbidity is increasing. There is little research on epidemiology and consequences of multimorbidity in LMICs. Methods: The Golestan Cohort Study recruited participants aged 40-75 years free of any gastrointestinal cancer between January 2004 and June 2008. Baseline data were collected on demographics, medications, self-reported illness, tobacco and alcohol consumption, physical activity, and clinical measurements were taken. Participants were followed up annually and hospital admissions and deaths were recorded. Multimorbidity was categorised as: count of conditions, or as two or more conditions, and the association with death within ten years of study entry was investigated using multivariable logistic regression. Further associations of multimorbidity with survival and hospitalisations were explored using Cox models and Poisson logistic regression models respectively. Findings: Of the original 50,045 individuals, 2,162 were removed because of missing baseline data or incorrect follow up date entered. A further 2,297 participants were removed from the complete case analysis due to loss to follow up; these participants were included in the survival analysis.During 10 years of follow up 5,411 participants died and 17,855 were hospitalised at least once. Odds of death increased with increasing number of conditions, after controlling for age, sex, education, wealth, physical activity, smoking history, and BMI. Compared to no conditions, the odds ratio (OR) for death for people with two or more conditions was 1.99 (95% CI 1.86 - 2.12, p<0.001) and even higher for people with four or more conditions (OR 3.57; 95% CI 3.12-4.08, p <0.001). Number of hospital admissions also significantly increased with number of conditions after adjustment for demographic and behavioural risk factors. Interpretation: This is one of the first studies to report on longitudinal effects of multimorbidity in a LMIC, and shows that the long terms effects of multimorbidity on mortality and hospitalisation, are just as detrimental as in high income countries. This should have major impact on health policy and planning in the years to come, and resources and global health funds need to be aimed at improving health system preparedness in LMICs to treat this patient group. Funding Statement: MDW acknowledges support from the NIHR Newcastle Biomedical Research Centre. TM is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) West Midlands. This report presents independent research funded by the National Institute for Health Research (NIHR). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This was a secondary analysis of de-identified participant data. The initial study was approved by the ethics committee of the Digestive Diseases Research Institute, Tehran, University of Medical Sciences (OHRP-IRB-00001641). Before participation, a written informed consent was obtained from each participant, allowing investigators to use anonymised data for future analysis.

Risk factors for suicide in prisons: a systematic review and meta-analysis

SummaryBackgroundRates of suicide among people in prison are elevated compared with people of similar age and sex who are living in the community. Improving assessments and interventions to reduce suicide risk requires updated evidence on risk factors. We aimed to examine risk factors associated with suicide in prisoners.MethodsWe did an updated systematic review and meta-analysis of risk factors for suicide among people in prison. We searched five biblographic databases for articles published between Jan 1, 2006, and Aug 13, 2020, and one database for articles published between Jan 1, 1973, and Aug 13, 2020. Eligible studies reported risk factors in individuals who died by suicide while in prison and in controls from the general prison population. Two reviewers independently extracted data for each study using a standardised form. We calculated random-effects pooled odds ratios (ORs) for the association of suicide with demographical, clinical, criminological, and institutional risk factors, and investigated heterogeneity using subgroup and meta-regression analyses. This systematic review is registered with PROSPERO, CRD42020137979.FindingsWe identified 8041 records through our searches, and used 77 eligible studies from 27 countries, including 35 351 suicides, in the main analysis. The strongest clinical factors associated with suicide were suicidal ideation during the current period in prison (OR 15·2, 95% CI 8·5–27·0), a history of attempted suicide (OR 8·2, 4·4–15·3), and current psychiatric diagnosis (OR 6·4, 3·6–11·1). Institutional factors associated with suicide included occupation of a single cell (OR 6·8, 2·3–19·8) and having no social visits (OR 1·9, 1·5–2·4). Criminological factors included remand status (OR 3·6, 3·1–4·1), serving a life sentence (OR 2·4, 1·3–4·6), and being convicted of a violent offence, in particular homicide (OR 3·1, 2·2–4·2).InterpretationSeveral modifiable risk factors, such as psychiatric diagnosis, suicidal ideation during the current period in prison, and single-cell occupancy, are associated with suicide among people in prison. Preventive interventions should target these risk factors and include improved access to evidence-based mental health care. Understanding other factors associated with suicide might improve risk stratification and resource allocation in prison services.FundingWellcome Trust, National Institute for Health Research Applied Research Collaboration Oxford and Thames Valley.

End-of-life care during COVID-19: opportunities and challenges for community nursing.

BB is funded by the National Institute for Health Research (NIHR) School for Primary Care Research. SB is supported by the NIHR Applied Research Collaboration East of England (ARC EoE) programme.

Impact of Poverty and Family Adversity on Adolescent Health: A Multi-Trajectory Analysis Using the UK Millennium Cohort Study

Background: Children exposed to poverty and family adversities including domestic violence, parental mental ill health and parental alcohol misuse may experience poor outcomes across the life course. However, the complex interrelationships between these exposures in childhood are unclear. We therefore assessed the clustering of trajectories of household poverty and family adversities and their impacts on adolescent health outcomes. Methods: We used longitudinal data from the UK Millennium Cohort study on 11564 children followed to age 14 years. Family adversities included parent reported domestic violence and abuse, mental ill health and frequent alcohol use. We used a group-based multi-trajectory cluster model to identify trajectories of poverty and family adversity for children. We assessed associations of these trajectories with child physical, mental and behavioural outcomes at age 14 years using multivariable logistic regression, adjusting for confounders. Findings: Six trajectories were identified: low poverty and family adversity (43·2%), persistent parental alcohol use (7·7%), persistent domestic violence and abuse (3·4%), persistent parental mental ill health (11·9%), persistent poverty (22·6%) and persistent poverty and parental mental ill health (11·1%). Compared with children exposed to low poverty and adversity, children in the persistent adversity trajectory groups experienced worse outcomes; those exposed to persistent parental mental ill health and poverty were particularly at increased risk of socioemotional behavioural problems (adjusted odds ratio 6·4; 95% CI 5·0 – 8·3), cognitive disability (aOR 2·1; CI 1·5 – 2·8), drug experimentation (aOR 2·8; CI 1·8 – 4·2) and obesity (aOR 1·8; CI 1·3 – 2·5). Interpretation: In a contemporary UK cohort, persistent poverty and/or persistent parental mental ill health affects over four in ten children. The combination of both affects one in ten children and is strongly associated with adverse child outcomes, particularly poor child mental health. Funding Information: This work was funded by the National Institute for Health Research (NIHR) Policy Research Programme (ORACLE: OveRcoming Adverse ChiLdhood Experiences, Grant reference number NIHR200717); and the National Institute for Health Research (NIHR) Applied Research Collaboration South London (NIHR ARC South London) at King’s College Hospital NHS Foundation Trust. DTR is supported by the NIHR School for Public Health Research, the NIHR Public Health Policy Research and by the Medical Research Council (MRC) on a Clinician Scientist Fellowship (MR/P008577/1). VSS is supported by the Swedish Research Council for Health, Working Life and Welfare (FORTE) [2016-07148; 2020-00274]. Professors Kaner and Howard are supported by NIHR Senior Investigator awards and Prof Kaner is Director of the NIHR Applied Research Collaboration for the North East and North Cumbria. The views expressed in this publication are those of the authors and not necessarily those of the NIHR, MRC or FORTE. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: Ethical approval for each wave of the MCS was granted by NHS Multicenter Research Ethics Committees. No further ethical approval was required for this secondary analysis of MCS data.

Evaluating the Impacts of Tiered Restrictions Introduced in England, During October and December 2020 on COVID-19 Cases: A Synthetic Control Study

Background: In 2020, a second wave of COVID-19 cases unevenly affected places in England leading to the introduction of a tiered system with different restrictions implemented geographically. Whilst previous research has examined the impact of national lockdowns on transmission, there has been limited research examining the marginal effect of differences in localised restrictions or how these effects vary by deprivation. Methods: We examined how Tier 3 restrictions affected COVID-19 case rates, and how these effects varied by level of deprivation, using data on weekly reported cases for 7201 neighbourhoods in England and adjusting these for changing case-detection rates. We identified areas that entered Tier 3 restrictions in October and December, constructed a synthetic control group of places under Tier 2 restrictions, and compared changes in weekly infections over a 4-week period. We used interaction analysis to estimate whether this effect varied by level of deprivation and the prevalence of a new variant (B.1.1.7). Results: The introduction of Tier 3 restrictions in October and December was associated with a 14% (95% CI 10% to 19%) and 20% (95% CI 13% to 29%) reduction in infections respectively, compared to the rates expected with Tier 2 restrictions only. The effects were similar across levels of deprivation and by the prevalence of the new variant. Interpretation: Compared to Tier 2 restrictions, additional restrictions on hospitality and meeting outdoors introduced in Tier 3 areas in England had a moderate effect on transmission and these restrictions did not appear to increase inequalities in COVID-19 cases.Funding Statement: BB, XZ are supported by the National Institute for Health Research(NIHR) Gastrointestinal Health Protection Research Unit. BB is also supported by the NIHR Applied Research Collaboration North West Coast (ARC NWC). GO is supported by the NIHR School for Public Health Research. IB is supported by NIHR Senior Investigator award. The viewsexpressed in this publication are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social.Declaration of Interests: None to declare.

Effectiveness of a task-sharing collaborative care model for identification and management of depressive symptoms in patients with hypertension attending public sector primary care clinics in South Africa: pragmatic parallel cluster randomised controlled trial.

BackgroundWe tested the real-world effectiveness of a collaborative task-sharing model on depressive symptom reduction in hypertensive Primary Health Care (PHC) patients in South Africa. MethodA pragmatic parallel cluster randomised trial in 20 clinics in the Dr Kenneth Kaunda district, North West province. PHC clinics were stratified by sub-district and randomised in a 1:1 ratio. Control clinics received care as usual (CAU), involving referral to PHC doctors and/or mental health specialists. Intervention clinics received CAU plus enhanced mental health training and a lay counselling referral service. Participant inclusion criteria were ≥ 18 years old, Patient Health Questionnaire-9 (PHQ-9) score ≥ 9 and receiving hypertension medication. Primary superiority outcome was ≥ 50% reduction in PHQ-9 score at 6 months. Statistical analyses comprised mixed effects regression models and a non-inferiority analysis. Trial registration number: NCT 02425124. ResultsBetween April 2015 and October 2015, 1043 participants were enrolled (504 intervention and 539 control); 82% were women; half were ≥ 55 years. At 6 and 12 months follow-up, 91% and 89% of participants were interviewed respectively. One control group participant committed suicide. There was no significant difference in the primary outcome between intervention (N=256/456) and control (N=232/492) groups (55.9% versus 50.9%; adjusted risk difference = -0.04 ([95% CI = -0.19; 0.11], p = 0.6). The difference in PHQ-9 scores was within the defined equivalence limits at 6 and 12 months for the non-inferiority analysis. LimitationsThe trial was limited by low exposure to depression treatment by trial participants and by observed co-intervention in control clinics ConclusionsIncorporating lay counselling services within collaborative care models does not produce superior nor inferior outcomes to models with specialist only counselling services. FundingThis work was supported by the UK Department for International Development [201446] as well as the National Institute of Mental Health, United States of America, grant number 1R01MH100470-01. Graham Thornicroft is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) South London at King's College London and King's College Hospital NHS Foundation Trust.

Culturally Tailored Interventions for People Affected by Dementia: A Systematic Review and Conceptual Model About Implementation

Background: Dementia prevalence is higher in low- and middle-income countries (LMICs) and some minority ethnic (ME) groups but these groups are less likely to receive interventions. Methods: In this systematic review, we searched 11 electronic databases from inception to May 26th, 2019. We included non-drug cognitive, psychological or social interventions for people with dementia and their family carers tailored to people in LMICs and ME groups, and provided details of how they were culturally tailored. We assessed study quality and conducted a narrative synthesis of the acceptability, feasibility and effectiveness of culturally tailored interventions, distinguishing between evidence-based interventions, culturally adapted for a new setting and newly developed, culturally tailored interventions with no existing evidence base. This study was registered with PROSPERO: CRD42019133090. Findings: Our searches retrieved 40,558 results of which 23 were eligible for inclusion. Evidence-based, multicomponent interventions adapted for Latino carers were acceptable, feasible and effective in the US and Columbia. Interventions developed for carers in India were effective there but not in other LMICs. Culturally adapted Cognitive Stimulation Therapy was acceptable and feasible to people with dementia in Sub-Saharan Africa. Adaptations were made to peripheral intervention components with core therapeutic components unchanged. Interpretation: We propose a conceptual model based on our findings to aid implementation of culturally appropriate treatments for people affected by dementia in LMICs and ME groups. Evidence-based interventions need to be adapted for culturally different settings with therapeutic components retained, and tested for acceptability, feasibility and evidence that they remain effective. Full effectiveness trials are then unnecessary. Funding Statement: National Institute for Health Research Applied Research Collaboration North Thames and Alzheimer’s Society. Declaration of Interests: None.

Streamlining follicular monitoring during controlled ovarian stimulation: a data-driven approach to efficient IVF care in the new era of social distancing.

STUDY QUESTIONWhat is the optimal follicular tracking strategy for controlled ovarian stimulation (COS) in order to minimise face-to-face interactions?SUMMARY ANSWERAs data from follicular tracking scans on Days 5, 6 or 7 of stimulation are the most useful to accurately predict trigger timing and risk of over-response, scans on these days should be prioritised if streamlined monitoring is necessary.WHAT IS KNOWN ALREADYBritish Fertility Society guidance for centres restarting ART following coronavirus disease 2019 (COVID-19) pandemic-related shutdowns recommends reducing the number of patient visits for monitoring during COS. Current evidence on optimal monitoring during ovarian stimulation is sparse, and protocols vary significantly. Small studies of simplifying IVF therapy by minimising monitoring have reported no adverse effects on outcomes, including live birth rate. There are opportunities to learn from the adaptations necessary during these extraordinary times to improve the efficiency of IVF care in the longer term.STUDY DESIGN, SIZE, DURATIONA retrospective database analysis of 9294 ultrasound scans performed during monitoring of 2322 IVF cycles undertaken by 1875 women in a single centre was performed. The primary objective was to identify when in the IVF cycle the data obtained from ultrasound are most predictive of both oocyte maturation trigger timing and an over-response to stimulation. If a reduced frequency of clinic visits is needed due to COVID-19 precautions, prioritising attendance for monitoring scans on the most predictive cycle days may be prudent.PARTICIPANTS/MATERIALS, SETTING, METHODSThe study comprised anonymised retrospective database analysis of IVF/ICSI cycles at a tertiary referral IVF centre. Machine learning models are used in combining demographic and follicular tracking data to predict cycle oocyte maturation trigger timing and over-response. The primary outcome was the day or days in cycle from which scan data yield optimal model prediction performance statistics. The model for predicting trigger day uses patient age, number of follicles at baseline scan and follicle count by size for the current scan. The model to predict over-response uses age and number of follicles of a given size.MAIN RESULTS AND THE ROLE OF CHANCEThe earliest cycle day for which our model has high accuracy to predict both trigger day and risk of over-response is stimulation Day 5. The Day 5 model to predict trigger date has a mean squared error 2.16 ± 0.12 and to predict over-response an area under the receiver operating characteristic curve 0.91 ± 0.01.LIMITATIONS, REASONS FOR CAUTIONThis is a retrospective single-centre study and the results may not be generalisable to centres using different treatment protocols. The results are derived from modelling, and further clinical validation studies will verify the accuracy of the model.WIDER IMPLICATIONS OF THE FINDINGSFollicular tracking starting at Day 5 of stimulation may help to streamline the amount of monitoring required in COS. Previous small studies have shown that minimal monitoring protocols did not adversely impact outcomes. If IVF can safely be made less onerous on the clinic’s resources and patient’s time, without compromising success, this could help to reduce burden-related treatment drop-out.STUDY FUNDING/COMPETING INTEREST(S)F.P.C. acknowledges funding from the NIHR Applied Research Collaboration Wessex. The authors declare they have no competing interests in relation to this work.TRIAL REGISTRATION NUMBERN/A.

Effects of liraglutide and semaglutide on stroke subtypes in patients with type 2 diabetes: a post hoc analysis of the LEADER, SUSTAIN 6 and PIONEER 6 trials

Abstract Introduction Diabetes is an independent risk factor for stroke, with approximately a two-fold excess risk in people with versus those without diabetes. Accumulating evidence suggests glucagon-like peptide-1 (GLP-1) analogues (including liraglutide and semaglutide) may reduce the risk of stroke in patients with type 2 diabetes (T2D). Purpose We examined the effect of liraglutide and semaglutide on stroke and its subtypes based on pooled data from LEADER, SUSTAIN 6 and PIONEER 6. Methods LEADER (NCT01179048), SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716) were global randomised cardiovascular (CV) outcomes trials of liraglutide, subcutaneous semaglutide and oral semaglutide, respectively, in patients with T2D at high CV risk. In this post hoc analysis, we evaluated the effect of these GLP-1 analogue treatments (pooled) on time to first occurrence of all strokes and subtypes of stroke. Ischaemic stroke was subcategorised according to the TOAST classification, based on aetiology by an external blinded reviewer. A Cox proportional hazards model stratified by trial with pooled treatment as a factor was used to examine treatment effects. Results Across the three trials, 216/7907 (2.7%) patients in the GLP-1 analogue group and 262/7913 (3.3%) in the placebo group had a stroke. The risk of first occurrence of all strokes was significantly reduced in the GLP-1 analogue versus placebo group (HR 0.82, 95% CI 0.68–0.98; p=0.030). Treatment effects were consistent across stroke subtypes: ischaemic (HR 0.84, 95% CI 0.69–1.02; p=0.08), haemorrhagic (HR 0.72, 95% CI 0.42–1.22; p=0.22) and undetermined (HR 0.71, 95% CI 0.32–1.60; p=0.41; Figure 1). Across TOAST subcategories, there was a trend that GLP-1 analogue treatment had the greatest benefit versus placebo in small vessel occlusion strokes compared with large artery disease or cardioembolic strokes; however, no statistically significant effects were found in any subcategory. Conclusion In this post hoc analysis of the LEADER, SUSTAIN 6 and PIONEER 6 trials, GLP-1 analogue treatment reduced the risk of stroke in patients with T2D and high CV risk, with an indication using TOAST criteria of the strongest effect on stroke caused by small vessel occlusion. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novo Nordisk A/S. WDS is supported by the NIHR Exeter Clinical Research Facility. MAJ is supported by the NIHR SW Peninsula Applied Research Collaboration. This abstract does not necessarily reflect the views of the NIHR, the Exeter Clinical Research Facility, the NHS or the UK Department of Health.

CCopeY: A Mixed-Methods Co-Produced Study on the Mental Health Status and Coping Strategies of Young People During COVID-19 Lockdown in the UK

Background: Young people’s mental health during COVID-19 pandemic has been identified as a priority. However, studies to date are largely simple surveys and lacking any meaningful involvement from patients and the public in their design, planning and delivery. The study aim was to examine the mental health status and coping strategies of young people (aged 16-24) during and after COVID-19 lockdown using co-production methodology. Methods: We utilised a sequential co-produced mixed methods design. Participants were aged 16-24 and lived in the UK. The primary outcome was mental health status, measured using Patient Health Questionnaire (PHQ-9), anxiety coronavirus impact sub-scale (CIS) and reported self-harm. Predictors included sociodemographic variables, coping strategies (Brief COPE), sleep (Sleep Condition Indicator), personality traits (Ten-Item Personality Inventory) and optimism (Life-Orientation Test - Revised). Semi-structured interviews were also conducted with a purposive sample of survey participants. The study was registered with COVID MINDS. Results: Seven-hundred and ninety-six participants (mean age 19.6 [SD 2.7]) took part in the first survey in April 2020. Survey data showed 26.6% had poor mental health and 10% had self-harmed since lockdown. Young people identifying as Black/Black British ethnicity in our study had the highest increased odds of experiencing poor mental health. Logistic regression showed behavioural disengagement, self-blame and substance misuse coping strategies, negative affect, sleep problems and reduced conscientiousness were all significantly associated with poor mental health. Eighteen participants were followed up and interviewed. There were three main interlinking themes: (1) pre-existing and developed helpful coping strategies employed during lockdown, (2) mental health difficulties worsened during lockdown and (3) the need for mental health and non-mental health support during and after lockdown. Interpretation: To our knowledge this is the first sequential co-produced mixed methods study to examine mental health status and coping strategies of young people during COVID-19 lockdown. On average, young people’s mental health has significantly worsened since lockdown, and dysfunctional coping strategies are associated with this. However, young people have found innovative and adaptive ways to cope, including distraction and having a good routine. Going forward, appropriate and effective mental health support adapted to lockdown conditions is needed to help young people during and after lockdown.Trial Registration: The study was registered with COVID MINDS.Funding Statement: NIHR Patient Safety Translational Research Centre programme grant (Ref: PSTRC-2016-004) and Institute of Global Health Innovation. We are also grateful for support from the National Institute for Health Research (NIHR) under the Applied Research Collaboration (ARC) programme for North West London. and the Imperial NIHR Biomedical Research Centre. Declaration of Interests: PA received funding from Dr Foster Ltd (a wholly owned subsidiary of Telstra Health). AB received funding from Dr Foster Ltd and Medtronic. All other authors declare no competing interests.Ethics Approval Statement: This study was approved by the Imperial Research Ethics committee (ICREC ref: 20IC914) on 20/04/2020.

Genetic Risk of Clozapine Induced Leukopenia and Neutropenia: A Genome-Wide Association Study

Background: Antipsychotics can improve psychotic symptoms, but treatment responses vary widely. Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is also associated with several adverse effects such as metabolic syndrome and leukopenia. The mechanism of clozapine induced leukopenia (CIL) has not yet been fully elucidated. Genetic factors are likely to play an important role in the molecular basis, but most investigations have focused on individuals of European ancestry. In this manuscript, we report the first genome-wide association study (GWAS) of CIL and clozapine induced neutropenia (CIN) in a Chinese population. Methods: We performed a GWAS in up to 1,879 patients (225 CIL cases with WBC < 4,000 mm−3, including 43 CIN cases with ANC < 1500 mm−3, and 1654 controls) of Chinese descent. Data from common and rare single nucleotide polymorphisms (SNPs) were tested for association. We also performed a trans-ancestry meta-analysis with GWAS results of European individuals from the Clozapine Induced Agranulocytosis Consortium (CIAC). Findings: We identified several novel loci reaching the threshold of genome-wide significance level (P < 5 × 10−8). Three novel loci were associated with CIL while six were associated with CIN. We identified two T cell related genes in this study (TRAC and TRAT1). We also observed that one locus with evidence close to genome-wide significance (P = 5·08 × 10−8) was near the HLA-B gene in the major histocompatibility complex region in the trans-ancestry meta-analysis. Interpretation: Our results provide novel understanding of potential genetic and immune mechanisms for CIL and CIN. Funding Statement: This work was supported by the National Key RD Shanghai Youth Top-notch Talent Support Program to J.C., Shanghai Mental Health Center (2016-fx-02), Shanghai Municipal Commission of Science and Technology (17JC1402900, 17490712200, 18DZ2260200), Shanghai Municipal Health Commission (ZK2015B01, 201540114), Scientific Research and Development Fund of Shanghai Jiao Tong University (19X150010012), Shanghai Municipal Science and Technology Major Project (2018SHZDZX05), Innovative Research Team of High-Level Local Universities in Shanghai and Shanghai Clinical Research Center for Mental Health (19MC1911100). R.S. is part-funded by: i) the National Institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King’s College London; ii) a Medical Research Council (MRC) Mental Health Data Pathfinder Award to King’s College London; iii) an NIHR Senior Investigator Award; iv) the National Institute for Health Research (NIHR) Applied Research Collaboration South London (NIHR ARC South London) at King’s College Hospital NHS Foundation Trust. Declaration of Interests: We declare that we have no conflicts of interest. Ethics Approval Statement: In accordance with the principles in Declaration of Helsinki, the study was approved by the Ethics Committee at the Bio-X Institutes of Shanghai Jiao Tong University and the written informed consent was obtained from each participant. It is confirmed that the research complied with the Guidance of the Ministry of Science and Technology (MOST) for the Review and Approval of Human Genetic Resources.

Risk Factors for Excess Deaths Among Older Adults Without Confirmed COVID-19 During Lockdown: A Retrospective Cohort Study

Background: Besides deaths directly attributable to COVID-19, many excess deaths occurred during ‘lockdown’, the range of societal responses to the initial wave of the COVID-19 pandemic. Data regarding these excess deaths is sparse, but necessary in order to avoid them in future waves. We investigated what factors contributed to excess deaths of older patients during the initial 2020 lockdown beyond those attributable to confirmed COVID-19. We hypothesized that both physical diseases and mental disorders would contribute.Methods: We did a retrospective cohort study using data from the electronic clinical records from Cambridge and Peterborough NHS Foundation Trust (CPFT), UK (catchment area population ~ 0.86 million). Eligible patients were aged 65 years or over at baseline with at least 14 days’ follow-up, excluding patients diagnosed with confirmed or suspected SARS-CoV-2 infection. We defined a cohort exposed to COVID-19 lockdown comprising patients recorded in CPFT between March 23, 2020 and May 19, 2020, and compared their mortality with an cohort recorded in CPFT between January 13, 2020 and 10 March, 2020, unexposed to lockdown. We used Cox regression to estimate the association between risk factors and death. Controlled covariates included social demographic factors, smoking status, mental comorbidities, and physical comorbidities.Findings: In the two cohorts, 3,073 subjects were exposed to lockdown and 4,372 subjects were unexposed; the cohorts were followed up for an average of 74 days and 78 days, respectively. After controlling for confounding by sociodemographic factors, smoking status, mental comorbidities, and physical comorbidities, dementia patients suffered an additional 53% risk of death (HR = 1.53, 95% CI = 1.02-2.31), and patients with severe mental illness suffered an additional 123% risk of death (HR = 2.23, 95% CI = 1.42-3.49). No significant additional death risks were identified from physical comorbidities.Interpretation: During lockdown people with dementia or severe mental illness had a higher risk of excess death. This study suggests that such patients require additional support during a societal response to this and similar epidemics/pandemics. These data could inform future health service responses and policymaking to help prevent avoidable excess death during future outbreaks of similar infectious diseases.Funding Statement: SC’s, PBJ’s, and RNC’s research was supported by the Medical Research Council (grant MC_PC_17213 to RNC). PBJ is funded through the NIHR Applied Research Collaboration (ARC) East of England. This research was supported in part by the UK National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. Declaration of Interests: SC, EFE, PQ, and JRL declare no conflict of interest with this work. PBJ is a scientific advisory board member for Janssen and Recordati. BRU is clinical director for older people’s and adult community services at CPFT. He is clinical director of the Windsor Unit at Fulbourn Hospital (CPFT), which delivers clinical trials in dementia/mild cognitive impairment for academic and commercial organisations without personal benefit, and is the clinical lead for dementia for the NIHR Clinical Research Network (CRN) in the East of England. His salary is part-funded by the NIHR CRN. He has been principal investigator on trials for Axovant, Lilly, and EIP Pharma; his institution has benefited from payment for research carried out but he has not personally received any money. His wife is the lead for mental health for Suffolk Clinical Commissioning Group. RNC consults for Campden Instruments Ltd and receives royalties from Cambridge University Press, Cambridge Enterprise, and Routledge.Ethics Approval Statement: NHS Research Ethics 17/EE/0442

Management of chronic cardiometabolic conditions and mental health during COVID-19

Management of chronic cardiometabolic conditions and mental health during COVID-19