Relationships between sodium, fats and carbohydrates on blood pressure, cholesterol and HbA1c: an umbrella review of systematic reviews.

Background: The relationship between nutrition and health is complex and the evidence to describe it broad and diffuse. This review brings together evidence for the effect of nutrients on cardiometabolic risk factors. Methods: An umbrella review identified systematic reviews of randomised controlled trials and meta-analyses estimating the effects of fats, carbohydrates and sodium on blood pressure, cholesterol and haemoglobin A1c (HbA1c). Medline, Embase, Cochrane Library and Science Citation Index were search through 26 May 2020, with supplementary searches of grey literature and websites. English language systematic reviews and meta-analyses were included that assessed the effect of sodium, carbohydrates or fat on blood pressure, cholesterol and HbA1c. Reviews were purposively selected using a sampling framework matrix. The quality of evidence was assessed with A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR2) checklist, evidence synthesised in a narrative review and causal pathways diagram. Results: Forty-three systematic reviews were included. Blood pressure was significantly associated with sodium, fibre and fat. Sodium, fats and carbohydrates were significantly associated with cholesterol. Monounsaturated fat, fibre and sugars were associated with HbA1c. Conclusion: Multiple relationships between nutrients and cardiometabolic risk factors were identified and summarised in an accessible way for public health researchers. The review identifies associations, inconsistencies and gaps in evidence linking nutrition to cardiometabolic health.

Factors within the clinical encounter that impact upon risk assessment within child and adolescent mental health services: a rapid realist synthesis.

Background: Risk assessment is a key process when a child or adolescent presents at risk for self-harm or suicide in a mental health crisis or emergency. Risk assessment by a healthcare professional should be included within a biopsychosocial assessment. However, the predictive value of risk-screening tools for self-harm and suicide in children and adolescents is consistently challenged. A review is needed to explore how best to undertake risk assessment and the appropriate role for tools/checklists within the assessment pathway. Aims: To map research relating to risk assessment for child and adolescent mental health and to identify features that relate to a successful risk assessment. Objectives: To review factors within the clinical encounter that impact upon risk assessments for self-harm and suicide in children and adolescents: i. to conduct a realist synthesis to understand mechanisms for risk assessment, why they occur and how they vary by context ii. to conduct a mapping review of primary studies/reviews to describe available tools of applicability to the UK. Data sources: Databases, including MEDLINE, PsycINFO®, EMBASE, CINAHL, HMIC, Science and Social Sciences Citation Index and the Cochrane Library, were searched (September 2021). Searches were also conducted for reports from websites. Review methods: A resource-constrained realist synthesis was conducted exploring factors that impact upon risk assessments for self-harm and suicide. This was accompanied by a mapping review of primary studies/reviews describing risk-assessment tools and approaches used in UK child and adolescent mental health. Following piloting, four reviewers screened retrieved records. Items were coded for the mapping and/or for inclusion in the realist synthesis. The review team examined the validity and limitations of risk-screening tools. In addition, the team identified structured approaches to risk assessment. Reporting of the realist synthesis followed RAMESES guidelines. Results: From 4084 unique citations, 249 papers were reviewed and 41 studies (49 tools) were included in the mapping review. Eight reviews were identified following full-text screening. Fifty-seven papers were identified for the realist review. Findings highlight 14 explanations (programme theories) for a successful risk assessment for self-harm and suicide. Forty-nine individual assessment tools/approaches were identified. Few tools were developed in the UK, specifically for children and adolescents. These lacked formal independent evaluation. No risk-screening tool is suitable for risk prediction; optimal approaches incorporate a relationship of trust, involvement of the family, where appropriate, and a patient-centred holistic approach. The objective of risk assessment should be elicitation of information to direct a risk formulation and care plan. Limitations: Many identified tools are well-established but lack scientific validity, particularly predictive validity, or clinical utility. Programme theories were generated rapidly from a survey of risk assessment. Conclusions: No single checklist/approach meets the needs of risk assessment for self-harm and suicide. A whole-system approach is required, informed by structured clinical judgement. Useful components include a holistic assessment within a climate of trust, facilitated by family involvement. Study registration: This study is registered as PROSPERO CRD42021276671. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR135079) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 1. See the NIHR Funding and Awards website for further award information.

When young people up to 18 years of age present to health services, having tried to poison themselves, take an overdose or injure themselves, a health professional needs to work out whether this is likely to happen again (risk assessment). Lists of questions or things to look for (risk screening) have proved unreliable. Thorough discussion with the child or teenager may be helpful but takes much time. How can a health professional best use time spent with a young person to prevent further harm and make sure that they get the treatment that they need? This review focuses on young persons who use health services in the UK. Included studies report how health professionals work out whether young people are likely to harm themselves; either how to handle the overall discussion or to use memory aids or checklists (known as tools) to help the discussion. Tools developed in the USA many years ago have not been tested well enough with UK populations. Recent approaches within the UK are used inconsistently. Young persons do not like how they are assessed. Health professionals may use methods that have not been shown to work or use tools differently from how they were designed. This review identified 14 ways to help a young person have valued discussions with a health professional. Health professionals should not simply 'tick boxes'; tools should help them gain a full picture, including input from other family members. Health professionals should create a trusted relationship where the young person feels respected and heard. Tools should not label someone 'at risk' but should support care that reduces the risk of further harm. Health professionals should gather good-quality information that includes asking about thoughts of suicide. Staff should be supported by training, guidance and feedback from experienced colleagues.

Reducing unplanned hospital admissions from care homes: a systematic review.

Background: Care homes predominantly care for older people with complex health and care needs, who are at high risk of unplanned hospital admissions. While often necessary, such admissions can be distressing and provide an opportunity cost as well as a financial cost. Objectives: Our objective was to update a 2014 evidence review of interventions to reduce unplanned admissions of care home residents. We carried out a systematic review of interventions used in the UK and other high-income countries by synthesising evidence of effects of these interventions on hospital admissions; feasibility and acceptability; costs and value for money; and factors affecting applicability of international evidence to UK settings. Data sources: We searched the following databases in December 2021 for studies published since 2014: Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews; Cumulative Index to Nursing and Allied Health Literature; Health Management Information Consortium; Medline; PsycINFO; Science and Social Sciences Citation Indexes; Social Care Online; and Social Service Abstracts. 'Grey' literature (January 2022) and citations were searched and reference lists were checked. Methods: We included studies of any design reporting interventions delivered in care homes (with or without nursing) or hospitals to reduce unplanned hospital admissions. A taxonomy of interventions was developed from an initial scoping search. Outcomes of interest included measures of effect on unplanned admissions among care home residents; barriers/facilitators to implementation in a UK setting and acceptability to care home residents, their families and staff. Study selection, data extraction and risk of bias assessment were performed by two independent reviewers. We used published frameworks to extract data on intervention characteristics, implementation barriers/facilitators and applicability of international evidence. We performed a narrative synthesis grouped by intervention type and setting. Overall strength of evidence for admission reduction was assessed using a framework based on study design, study numbers and direction of effect. Results: We included 124 publications/reports (30 from the UK). Integrated care and quality improvement programmes providing additional support to care homes (e.g. the English Care Homes Vanguard initiatives and hospital-based services in Australia) appeared to reduce unplanned admissions relative to usual care. Simpler training and staff development initiatives showed mixed results, as did interventions aimed at tackling specific problems (e.g. medication review). Advance care planning was key to the success of most quality improvement programmes but do-not-hospitalise orders were problematic. Qualitative research identified tensions affecting decision-making involving paramedics, care home staff and residents/family carers. The best way to reduce end-of-life admissions through access to palliative care was unclear in the face of inconsistent and generally low-quality evidence. Conclusions: Effective implementation of interventions at various stages of residents' care pathways may reduce unplanned admissions. Most interventions are complex and require adaptation to local contexts. Work at the interface between health and social care is key to successful implementation. Limitations: Much of the evidence identified was of low quality because of factors such as uncontrolled study designs and small sample size. Meta-analysis was not possible. Future work: We identified a need for improved economic evidence and the evaluation of integrated care models of the type delivered by hospital-based teams. Researchers should carefully consider what is realistic in terms of study design and data collection given the current context of extreme pressure on care homes. Study registration: This study is registered as PROSPERO database CRD42021289418. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (award number NIHR133884) and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 18. See the NIHR Journals Library website for further project information.

Older people living in care homes often have complex health problems such as dementia and frailty, and they may need to be taken to hospital at short notice. This can lead to them being admitted for further tests and treatment. We know that some of these unplanned hospital admissions might be avoided if health and social care services worked together to meet residents' needs. We looked for published research on methods (interventions) used in health and social care to reduce these admissions. Interventions could be carried out by care home staff, general practitioners, nurses, paramedics or other specialists individually or in teams. We asked which interventions have been evaluated, how strong is the evidence that they work and how acceptable they are to care home residents, family carers and staff. We also looked for information on how easy or difficult they are to implement and whether they represent good value for money. We included 124 research studies (30 from the UK). We found that integrated care programmes linking care homes with general practitioners and community services can be effective but need time and support (such as extra money and specialist staff) to implement them. Quality improvement programmes and training to improve staff skills may also reduce admissions. For care home residents nearing the end of life, advance care planning and palliative care can ensure that wishes are followed and avoid potentially burdensome admissions to hospital. Hospital-based teams providing 'outreach' services to care homes have been evaluated in Australia and could be suitable for UK research. We found limited evidence on interventions involving paramedics and on 'value for money'. We found many barriers to implementing new services in the UK, particularly staff shortages and high staff turnover, together with care homes closing down or changing ownership. Successful interventions have often been based on existing services and relationships.

Delivery of public health interventions by the ambulance sector: a scoping review.

BACKGROUND: With millions of unscheduled patient contacts every year and increasing call outs clustered around the most deprived communities, it is clear the ambulance sector could have a role to play in improving population health. However, the application and value of a public health approach within the ambulance sector has not been comprehensively explored. A scoping review was undertaken to explore the role of the ambulance sector in the delivery of public health interventions and what impact this has on population health and ambulance sector outcomes. METHODS: A search strategy was developed on MEDLINE and translated to other major medical and health related bibliographic databases (Embase; CINAHL; HMIC; Science and Social Sciences Citation Index; Cochrane Library) to identify literature published since 2000 in OECD countries. Targeted grey literature, reference list, and citation searching was also carried out. Search results were downloaded to Microsoft Excel and screened by three reviewers according to pre-determined inclusion / exclusion criteria. Data from included studies, such as the type of activity noted within the paper, the population involved and the public health approach that was utilised, was extracted from within the paper using a data extraction form and narratively synthesised. RESULTS: Fifty-two references were included in the final review (37 database searching; 9 reference list searching; 6 grey literature). Included articles were categorised according to the relevant public health domains and subdomains as articulated by the UK Faculty of Public Health: 1. Health improvement domain: Public health education and advice (Health promotion sub-domain) (n=13) Emergency Services personnel providing vaccines (Disease prevention sub-domain) (n=1) 2. Health care public health domain Paramedicine (Service delivery sub-domain) (n=30) Screening tools and referral pathways used by the ambulance sector (Service delivery sub-domain) (n=28) Health intelligence using ambulance sector data (population health management sub-domain) (n=26) Of note, some domains (e.g. health protection) returned nil results. DISCUSSION: The scoping review demonstrates the breadth of public health related activities in which the ambulance sector is involved. However, an overemphasis on demand management outcomes precludes definitive conclusions on the impact of ambulance sector-led public health initiatives on public health outcomes. Future evaluations of public health initiatives should incorporate wider health system perspectives beyond the immediately apparent remit of the ambulance sector.

Factors which facilitate or impede patient engagement with pulmonary and cardiac rehabilitation: a rapid evaluation mapping review.

Background: There is a considerable body of systematic review evidence considering the effectiveness of rehabilitation programmes on clinical outcomes. However, much less is known about effectively engaging and sustaining patients in rehabilitation. There is a need to understand the full range of potential intervention strategies. Methods: We conducted a mapping review of UK review-level evidence published 2017-21. We searched MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health (CINAHL) and conducted a narrative synthesis. Included reviews reported factors affecting commencement, continuation or completion of cardiac or pulmonary rehabilitation, or an intervention to facilitate these factors. Study selection was undertaken independently by two reviewers. Results: In total, we identified 20 review papers that met our inclusion criteria. There was a bias towards reviews considering cardiac rehabilitation, with these numbering 16. An additional 11 unpublished interventions were also identified through internet searching of key websites. The reviews included 60 identifiable UK primary studies that considered factors which affected attendance at rehabilitation; 42 considered cardiac rehabilitation and 18 considering pulmonary rehabilitation. They reported on factors from the patients' point of view, as well as the views of professionals involved in referral or treatment. It was more common for factors to be reported as impeding attendance at rehabilitation rather than facilitating it. We grouped the factors into patient perspective (support, culture, demographics, practical, health, emotions, knowledge/beliefs and service factors) and professional perspective (knowledge: staff and patient, staffing, adequacy of service provision and referral from other services, including support and wait times). We found considerably fewer reviews (n = 3) looking at interventions to facilitate participation in rehabilitation. Although most of the factors affecting participation were reported from a patient perspective, most of the identified interventions were implemented to address barriers to access in terms of the provider perspective. The majority of access challenges identified by patients would not therefore be addressed by the identified interventions. The more recent unevaluated interventions implemented during the COVID-19 pandemic may have the potential to act on some of the patient barriers in access to services, including travel and inconvenient timing of services. Conclusions: The factors affecting commencement, continuation or completion of cardiac or pulmonary rehabilitation consist of a web of complex and interlinked factors taking into consideration the perspectives of the patients and the service providers. The small number of published interventions we identified that aim to improve access are unlikely to address the majority of these factors, especially those identified by patients as limiting their access. Better understanding of these factors will allow future interventions to be more evidence based with clear objectives as to how to address the known barriers to improve access. Limitations: Time limitations constrained the consideration of study quality and precluded the inclusion of additional searching methods such as citation searching and contacting key authors. This may have implications for the completeness of the evidence base identified. Future work: High-quality effectiveness studies of promising interventions to improve attendance at rehabilitation, both overall and for key patient groups, should be the focus moving forward. Funding: This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HSDR programme or the Department of Health. Study registration: The study protocol is registered with PROSPERO [CRD42022309214].

While we know quite a lot about what makes rehabilitation for heart (cardiac) or lung (pulmonary) conditions effective, less is known about how to engage people with these services and how to encourage them to continue to attend. We have looked at what studies have already been done to summarise the factors that affect whether someone chooses to attend rehabilitation and what is being tried to improve rates of attendance. We were particularly interested in people who are less likely to attend for rehabilitation. We searched in research databases for studies published since 2017 that included UK patients and services. We found 17 relevant summary papers which included a total of 52 UK studies. Most of these papers looked at the factors that affect attendance at rehabilitation, with far fewer studies considering ways to improve attendance. There were more studies looking at rehabilitation for cardiac than pulmonary conditions. Whether someone attended rehabilitation was affected by factors such as whether they felt supported, cultural and personal factors, practical factors such as travel and access, plus patient health, emotions, knowledge and beliefs about rehabilitation services. From a staff perspective, knowledge (staff and patient), staffing levels, level of service provision, and referral from other services were believed to affect attendance. We found a few studies where changes had been made to try to improve access including a number of studies of online delivery of rehabilitation services during COVID-19. Our summary of the factors that affect attendance at rehabilitation may be helpful to inform services about what changes they should make in the future to improve levels of attendance.

Exploring the relationship between working from home, mental and physical health and wellbeing: a systematic review.

Background: Understanding the impact of working from home on health and wellbeing is of great interest to employers and employees alike, with a strong need for up-to-date guidance. The aim of this systematic review was to identify, appraise and synthesise existing research evidence that explores the impact of home working on health and wellbeing outcomes for working people and health inequalities in the population. Methods: We conducted a systematic review of qualitative, quantitative and observational studies. We searched databases, reference lists and UK grey literature and completed citation searching of included papers. We extracted and tabulated key data from the included papers and synthesised narratively. Factors associated with the health and wellbeing of people working at home reported in the literature were displayed by constructing mind maps of each individual factor which had been identified. The findings were combined with an a priori model to develop a final model, which was validated in consultation with stakeholders. Results: Of 96 studies which were found to meet the inclusion criteria for the review, 30 studies were published before the COVID-19 pandemic and a further 66 were published during the pandemic. The quality of evidence was limited by the study designs employed by the authors, with the majority of studies being cross-sectional surveys (n = 59). For the most part, for studies which collected quantitative data, measures were self-reported. The largest volume of evidence identified consisted of studies conducted during the COVID-19 pandemic which looked at factors which influence the relationship between working from home and measures relating to mental health and wellbeing. Fifteen studies which considered the potential for working at home to have different effects for different subgroups suggested that working at home may have more negative consequences during the COVID-19 pandemic for women and in particular, mothers. There was very little evidence on age (two studies), ethnicity (one study), education or income (two studies) in terms of moderating home working effects, and very limited evidence from before the COVID-19 pandemic. The concept of enforced working from home and having 'no choice' was reported in only one paper prior to the pandemic and two papers reporting on working from home as a result of COVID-19. However, the concept of lack of choice around working from home was implicit in much of the literature - even though it was not directly measured. There were no clear patterns of wellbeing measures which changed from positive to negative association (or vice versa) during the pandemic. Limitations: The quality of the evidence base was very much limited by study designs, particularly for studies published during the COVID-19 pandemic, with the majority of studies consisting of data collected by cross-sectional surveys (often online). Due to the rapidly expanding nature of the evidence on this topic, it is possible that new studies were published after the final citation searches were conducted. Discussion: The evidence base for the factors which influence the relationship between home working and health-related outcomes has expanded significantly as a result of the need for those whose work could be done from home to work at home during the COVID-19 pandemic. Our findings suggest that there are factors relating to the external context, the role of employers and the circumstances of the employee which contribute to determining whether someone works at home and what the associated impacts on health and wellbeing may be. Learning from the COVID-19 lockdown experience will be important to inform future policy on home and hybrid working. Future work: There is a need for better-quality studies of the health impact of home working, in particularly studies which recruit a range of participants who are representative of the working population and which are designed to minimise sampling/recruitment biases and response biases. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (project reference 18/93 PHR Public Health Review Team) and will be published in full in Public Health Research; Vol. 11, No. 4. See the NIHR Journals Library website for further project information. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Study registration: This study is registered as PROSPERO 2021 CRD42021253474.

INTRODUCTION: Working from home is becoming more common and has increased due to the COVID-19 pandemic. However, the impact of working at home on the health of home workers and the general population remains unclear. METHODS: We looked for research which had been undertaken to help to understand the impact of home working on people's health. One researcher summarised the findings of each paper in tables, and these were checked by a second researcher. These were then drawn together into a final diagram to summarise the findings of all the relevant studies. RESULTS: We found 96 papers and reports: 30 published before the COVID-19 pandemic and 66 published during the pandemic. This shows that the number of studies in this area has increased significantly as a result of home working due to COVID-19 lockdowns. The largest volume of studies we found were conducted during the pandemic and looked at measures of wellbeing and mental health. Lack of choice over whether to work from home was also considered in respect to wellbeing. Further measures linked to the home-work environment included feeling in control of time, lack of commuting to work, more time with the family, lower work/family conflict, and spaces shared with others. Openness to new ways of living was also included. Fifteen studies suggested overall that working at home may have more negative consequences during the COVID-19 pandemic for women and, in particular, mothers. There was very little evidence to tell us how a person's age, ethnicity, education or income might affect their health when working from home. CONCLUSIONS: Many factors determine whether someone works at home, and the effects on their health and wellbeing. These are related to what is happening in the world, the employer and type of job, and the circumstances of the employee.

Systematic review of time lag between antibiotic use and rise of resistant pathogens among hospitalized adults in Europe.

Background: Antimicrobial resistance (AMR) causes substantial health and economic burden to individuals, healthcare systems and societies globally. Understanding the temporal relationship between antibiotic consumption and antibiotic resistance in hospitalized patients can better inform antibiotic stewardship activities and the time frame for their evaluation. Objectives: This systematic review examined the temporal relationship between antibiotic use and development of antibiotic resistance for 42 pre-defined antibiotic and pathogen combinations in hospitalized adults in Europe. Methods: Searches in MEDLINE, Embase, Cochrane Library and NIHR Centre for Reviews and Dissemination were undertaken from 2000 to August 2021. Pathogens of interest were Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecium, CoNS, Pseudomonas aeruginosa and Acinetobacter baumannii complex. Results: Twenty-eight ecological studies and one individual-level study were included. Ecological studies were predominantly retrospective in design (19 studies) and of reasonable (20 studies) to high (8 studies) methodological quality. Of the eight pathogens of interest, no relevant data were identified for S. pneumoniae and CoNS. Across all pathogens, the time-lag data from the 28 ecological studies showed a similar pattern, with the majority of studies reporting lags ranging from 0 to 6 months. Conclusions: Development of antibiotic resistance for the investigated antibiotic/pathogen combinations tends to occur over 0 to 6 months following exposure within European hospitals. This information could inform planning of antibiotic stewardship activities in hospital settings.

Rehabilitation medicine in palliative care of chronic neurological conditions.

BACKGROUND: People living with long-term neurological conditions (LTNC) often require palliative care. Rehabilitation medicine specialists often coordinate the long-term care of these patients. OBJECTIVE: The aim of the present review was to undertake systematic literature searches to identify the evidence on palliative care for people with LTNC to guide rehabilitation medicine specialists caring for these patients in the UK. METHODS: We searched for evidence for (1) discussion of end of life, (2) planning for end-of-life care, (3) brief specialist palliative care interventions, (4) support for family and carers, (5) training of rehabilitation medicine specialists in palliative care, and (6) commissioning of services. The databases searched were MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, NHS Economic Evaluation Database and Health Technology Assessment Database. Evidence was assimilated using a simplified version of the Grading of Recommendations Assessment, Development and Evaluation method. RESULTS: We identified 2961 records through database searching for neurological conditions and 1261 additional records through database searches for specific symptoms. We removed duplicate records and conference presentations. We screened 3234 titles and identified 330 potentially relevant abstracts. After reading the abstracts we selected 34 studies for inclusion in the evidence synthesis. CONCLUSIONS: From the evidence reviewed we would like to recommend that we move forward by establishing a closer working relationship with specialists in palliative care and rehabilitation medicine and explore the implications for cross-specialty training.

What influences decisions to transfer older care-home residents to the emergency department? A synthesis of qualitative reviews.

BACKGROUND: care home residents aged over 65 have disproportionate rates of emergency department (ED) attendance and hospitalisation. Around 40% attendances may be avoidable, and hospitalisation is associated with harms. We synthesised the evidence available in qualitative systematic reviews of different stakeholders' experiences of decisions to transfer residents to the ED. METHODS: six electronic databases, references and citations of included reviews and relevant policy documents were searched. Reviews of qualitative studies exploring factors that influenced care home staff, medical practitioners, residents' family or residents' experiences and factors influencing decisions to transfer residents to the ED were included. Thematic analysis was used to synthesise findings. RESULTS: six previous reviews were included, which synthesised the findings of 34 primary studies encompassing 152 care home residents, 283 resident family members or carers and 447 care home staff. Of the primary studies, 19 were conducted in the North America, seven in Australia, five were conducted in Scandinavia, two in the United Kingdom and one in Holland. Three themes were identified: (i) power dynamics between residents, family members, care home staff and health care professionals (external to the care home) influence decisions; (ii) admission can be necessary; however, (iii) some decisions may be driven by factors other than clinical need. CONCLUSION: transfer decisions are complex and are determined not just by changes in health status interventions aimed at reducing avoidable transfers need to address the key role family members have in transfer decisions, the medical legal fears of care home staff and barriers to accessing community services.

Factors associated with increased Emergency Department transfer in older long-term care residents: a systematic review.

The proportion of adults older than 65 years is rapidly increasing. Care home residents in this age group have disproportionate rates of transfer to the Emergency Department (ED) and around 40% of attendances might be avoidable. We did a systematic review to identify factors that predict ED transfer from care homes. Six electronic databases were searched. Observational studies that provided estimates of association between ED attendance and variables at a resident or care home level were included. 26 primary studies met the inclusion criteria. Seven common domains of factors assessed for association with ED transfer were identified and within these domains, male sex, age, presence of specific comorbidities, polypharmacy, rural location, and care home quality rating were associated with likelihood of ED transfer. The identification of these factors provides useful information for policy makers and researchers intending to either develop interventions to reduce hospitalisations or use adjusted rates of hospitalisation as a care home quality indicator.

Factors that influence mental health of university and college students in the UK: a systematic review.

BACKGROUND: Worsening mental health of students in higher education is a public policy concern and the impact of measures to reduce transmission of COVID-19 has heightened awareness of this issue. Preventing poor mental health and supporting positive mental wellbeing needs to be based on an evidence informed understanding what factors influence the mental health of students. OBJECTIVES: To identify factors associated with mental health of students in higher education. METHODS: We undertook a systematic review of observational studies that measured factors associated with student mental wellbeing and poor mental health. Extensive searches were undertaken across five databases. We included studies undertaken in the UK and published within the last decade (2010-2020). Due to heterogeneity of factors, and diversity of outcomes used to measure wellbeing and poor mental health the findings were analysed and described narratively. FINDINGS: We included 31 studies, most of which were cross sectional in design. Those factors most strongly and consistently associated with increased risk of developing poor mental health included students with experiences of trauma in childhood, those that identify as LGBTQ and students with autism. Factors that promote wellbeing include developing strong and supportive social networks. Students who are prepared and able to adjust to the changes that moving into higher education presents also experience better mental health. Some behaviours that are associated with poor mental health include lack of engagement both with learning and leisure activities and poor mental health literacy. CONCLUSION: Improved knowledge of factors associated with poor mental health and also those that increase mental wellbeing can provide a foundation for designing strategies and specific interventions that can prevent poor mental health and ensuring targeted support is available for students at increased risk.

The Incidence and Costs of Adverse Events Associated with Antidepressants: Results from a Systematic Review, Network Meta-Analysis and Multi-Country Economic Model.

Purpose: There is variation in the safety profile of antidepressants. Rates of adverse events along with the costs of treating them can be an important factor influencing the choice of depression treatment. This study sought to estimate the comparative safety of commonly prescribed antidepressants, and how the costs of treating these varied across European countries. Methods: A systematic literature review was conducted (in Medline, Embase, PsycINFO and CENTRAL) to identify placebo-controlled trials reporting rates of at least one type of sexual dysfunction, weight change, insomnia, anxiety, and anhedonia. Eight antidepressants were considered: duloxetine, escitalopram, fluoxetine, paroxetine, sertraline, trazodone, venlafaxine, and vortioxetine. This evidence was synthesised via Bayesian random effects network meta-analyses to provide comparative estimates of safety. A systematic search identified country-specific costs of managing depression and adverse events of antidepressants. Evidence on costs and safety was combined in an economic model to provide country-specific costs for Bulgaria, the Czech Republic, Greece, Hungary, Italy, Romania, Slovakia, Portugal, and Poland. Results: Trazodone had the lowest rates of both insomnia (odds ratio 0.66, 95% credible interval 0.31 to 1.38) and anxiety (0.13, <0.01 to 1.80). All antidepressants were associated with increased rates of sexual dysfunction relative to placebo. Weight change was largest for fluoxetine (kg change -1.01, -1.40 to -0.60) and sertraline (-1.00, -1.36 to -0.65), although heterogeneity was extreme for this outcome. No evidence was identified for anhedonia. Total costs were lowest for trazodone in all nine of the countries evaluated. This was primarily due to reduced rates of treatment discontinuation. Conclusion: Trazodone generally had the best safety profile of the antidepressants evaluated. This led to healthcare costs being lowest for trazodone in all nine European countries, emphasising the importance of considering rates of adverse events when choosing a pharmacological treatment to treat symptoms of depression.

A systematic review case study of urgent and emergency care configuration found citation searching of Web of Science and Google Scholar of similar value.

BACKGROUND: Supplementary search methods, including citation searching, are essential if systematic reviews are to avoid producing biased conclusions. Little evidence exists on how to prioritise databases for citation searching or to establish whether using multiple sources is beneficial. OBJECTIVES: A systematic review examining urgent and emergency care reconfiguration was used to investigate the utility of citation searching on Web of Science (WOS) and/or Google Scholar (GS). METHODS: This case study investigated numbers of studies, additional studies and unique studies retrieved from both sources. In addition, the time to search, the ease of adding references to reference management software and obtaining abstracts of studies for screening are briefly considered. RESULTS: WOS retrieved 62 references after deduplication of the results, 52 being additional references not retrieved during the database searching. GS retrieved 134 unique references with 63 additional references. WOS and GS retrieved the same three additional included studies. WOS was less time intensive to search given the facility to restrict to English language papers and availability of abstracts. CONCLUSIONS: In a single systematic review case study, citation searching was required to identify all included studies. Citation searching on WOS is more efficient, where a subscription is available. Both databases identified the same studies but GS required additional time to remove non-English language studies and locate abstracts.

The impact of hypoglycaemia in children and adolescents with type 1 diabetes on parental quality of life and related outcomes: A systematic review.

This systematic review aims to summarize and critically evaluate the current evidence regarding the impact of hypoglycaemia in children and adolescents with type 1 diabetes on parental quality of life. MEDLINE, PsycINFO, CINAHL, and the Cochrane Library were searched. Inclusion criteria were: 1) quantitative design, 2) included parents of children or adolescents with type 1 diabetes, 3) assessment of hypoglycemia in children/adolescents with type 1 diabetes, 4) assessment of parent quality of life (or related domains of life), and 5) analysis of the relationship(s) between the child's hypoglycaemia and parents' quality of life. The data were summarised in accordance with Synthesis Without Meta-Analysis Guidelines. Twelve studies were included, reporting data from 1895 parents across six countries. Ten studies were cross-sectional; two included prospective data. Evidence suggested that greater frequency and severity of hypoglycemia was associated with greater parental fear of hypoglycemia, emotional distress and family burden. Children's hypoglycaemia has a negative impact on the well-being of parents, but there is an absence of evidence regarding the impact on their overall quality of life. Research into the hypoglycaemia-specific quality of life of parents is needed to explore the impact on various areas, such as social and physical dimensions.

Recognition of risk and prevention in safeguarding of children and young people: a mapping review and component analysis of service development interventions aimed at health and social care professionals.

BACKGROUND: The term 'safeguarding' covers the protection of health, wellbeing and human rights. Effective safeguarding enables people (particularly children, young adults and other vulnerable people) to live free from fear of abuse, harm or neglect. The UK Children Act 2004 required key agencies, including health and social care providers, to consider the need to safeguard children and promote their welfare. Within a larger evidence synthesis project, we sought to identify and map service development interventions (excluding provision of training) aimed at improving awareness of safeguarding and identifying at-risk children and young people in health and social care settings. METHODS: We searched fourteen health and social care databases from 2004 (date of Children Act) to October 2019 and updated the review via a citation search in March 2021. Studies of any design were eligible if they described or evaluated an intervention (other than training) aimed at health or social care professionals in the United Kingdom and designed to improve recognition of risk in the context of safeguarding children and young people. Studies with no intervention (e.g. qualitative studies) were included to explain why interventions work or fail to work. Included studies were summarised using narrative synthesis. Risk of bias of included studies and overall strength of evidence were assessed using standard methods. We used a 5-item checklist ("TIDieR-Lite") to map intervention components. RESULTS: Thirty-nine publications were included, of which 31 dealt with service developments, six with use of data and two with other initiatives. Promising service development initiatives include liaison nurses, assessment clinics, secondment, joint protocols and a 'hub and spoke' model. Initiatives involving use of routine data appeared promising and unlikely to generate significant additional costs. However, the quality of the evidence was generally low, with a shortage of controlled and long-term studies. CONCLUSIONS: Health and social care services wishing to improve awareness of child safeguarding issues may benefit from looking beyond high-quality training provision. Future research should focus on service-relevant outcomes and ensure the active involvement of young people and their families/carers.

Is working in later life good for your health? A systematic review of health outcomes resulting from extended working lives.

BACKGROUND: Work, rather than unemployment, is recognised as being good for health, but there may be an age when the benefits are outweighed by adverse impacts. As countries around the world increase their typical retirement age, the potential effect on population health and health inequalities requires scrutiny. METHODS: We carried out a systematic review of literature published since 2011 from developed countries on the health effects of employment in those over 64 years of age. We completed a narrative synthesis and used harvest plots to map the direction and volume of evidence for the outcomes reported. We followed the Preferred Reporting Items for Systematic Reviews (PRISMA) checklist in our methods and reporting. RESULTS: We identified seventeen relevant studies, which were of cohort or cross-sectional design. The results indicate evidence of beneficial or neutral effects from extended working on overall health status and physical health for many employees, and mixed effects on mental health. The benefits reported however, are most likely to be for males, those working part-time or reducing to part-time, and employees in jobs which are not low quality or low reward. CONCLUSIONS: Extending working life (particularly part time) may have benefits or a neutral effect for some, but adverse effects for others in high demand or low reward jobs. There is the potential for widening health inequalities between those who can choose to reduce their working hours, and those who need to continue working full time for financial reasons. There is a lack of evidence for effects on quality of life, and a dearth of interventions enabling older workers to extend their healthy working life.

The impact of hypoglycaemia on quality of life outcomes among adults with type 1 diabetes: A systematic review.

Hypoglycaemia is a common barrier to optimal glycaemic management and often feared among adults with type 1 diabetes. The aim of this systematic review was to summarize current evidence regarding the impact of hypoglycaemia on quality of life (QoL) and related outcomes. Electronic searches of MEDLINE, PsycINFO, CINAHL, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were conducted. Peer-reviewed empirical studies investigating the relationship between hypoglycaemia and QoL were eligible for inclusion. Thirty studies met the inclusion criteria. Extracted data was summarized in a narrative synthesis according to Synthesis Without Meta-Analysis guidelines. None of the studies examined the impact of hypoglycaemia on general QoL. There was no association between hypoglycaemia and diabetes-specific QoL in four of the 30 studies. Severe hypoglycaemia was associated with greater fear of hypoglycaemia and diabetes distress, and lower general emotional well-being, but not with depression, anxiety, or health status. Self-treated hypoglycaemia was associated with greater fear of hypoglycaemia. With the exception of fear of hypoglycaemia, this review shows mixed associations between hypoglycaemia and psychological outcomes. Further research is needed to investigate the impact of hypoglycaemia on other domains of QoL.

Schizophrenia Treatment with Second-Generation Antipsychotics: A Multi-Country Comparison of the Costs of Cardiovascular and Metabolic Adverse Events and Weight Gain.

PURPOSE: Cardiovascular and metabolic adverse events are costly to treat, and their incidence is increased amongst people with schizophrenia, with different rates observed for second-generation antipsychotics. To inform treatment choice, this study sought to estimate the lifetime costs associated with antipsychotic choice, and how these costs varied across European countries. METHODS: Systematic searches were conducted to identify evidence on effectiveness and costs. A Markov model was developed to assess the costs of ten antipsychotics: aripiprazole, brexpiprazole, cariprazine, lumateperone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone and ziprasidone. Costs were obtained for seven countries: Italy, Hungary, France, Slovenia, Spain, Sweden and the UK. The costs considered were adverse events (including diabetes, myocardial infarction, stroke and weight gain), drug costs, relapse, treatment discontinuation and schizophrenia management. Two adult populations were modelled; initiating either acute or maintenance treatment, with a lifetime horizon for both. RESULTS: Lurasidone was associated with the lowest lifetime costs amongst patients initiating acute treatment compared to all other atypical antipsychotics considered. The second lowest costs were for ziprasidone. These results were observed for all seven countries. The main drivers of cost differences were rates of diabetes and cardiovascular diseases, which were lowest for lurasidone, followed by ziprasidone then lumateperone. Costs for managing weight gain were lowest for lurasidone and ziprasidone. Similar results were observed for patients initiating maintenance treatment. CONCLUSION: Diabetes and cardiovascular events are large drivers of lifetime costs for people with schizophrenia. Lurasidone is predicted to have the lowest rates of these adverse events, and so the lowest costs amongst patients initiating acute treatment in seven European countries compared to nine other antipsychotics. Future research should investigate the individual costs of relapse management, including differences in the costs and proportions of hospitalizations.

Modelling approaches for histology-independent cancer drugs to inform NICE appraisals: a systematic review and decision-framework.

BACKGROUND: The first histology-independent marketing authorisation in Europe was granted in 2019. This was the first time that a cancer treatment was approved based on a common biomarker rather than the location in the body at which the tumour originated. This research aims to explore the implications for National Institute for Health and Care Excellence appraisals. METHODS: Targeted reviews were undertaken to determine the type of evidence that is likely to be available at the point of marketing authorisation and the analyses required to support National Institute for Health and Care Excellence appraisals. Several challenges were identified concerning the design and conduct of trials for histology-independent products, the greater levels of heterogeneity within the licensed population and the use of surrogate end points. We identified approaches to address these challenges by reviewing key statistical literature that focuses on the design and analysis of histology-independent trials and by undertaking a systematic review to evaluate the use of response end points as surrogate outcomes for survival end points. We developed a decision framework to help to inform approval and research policies for histology-independent products. The framework explored the uncertainties and risks associated with different approval policies, including the role of further data collection, pricing schemes and stratified decision-making. RESULTS: We found that the potential for heterogeneity in treatment effects, across tumour types or other characteristics, is likely to be a central issue for National Institute for Health and Care Excellence appraisals. Bayesian hierarchical methods may serve as a useful vehicle to assess the level of heterogeneity across tumours and to estimate the pooled treatment effects for each tumour, which can inform whether or not the assumption of homogeneity is reasonable. Our review suggests that response end points may not be reliable surrogates for survival end points. However, a surrogate-based modelling approach, which captures all relevant uncertainty, may be preferable to the use of immature survival data. Several additional sources of heterogeneity were identified as presenting potential challenges to National Institute for Health and Care Excellence appraisal, including the cost of testing, baseline risk, quality of life and routine management costs. We concluded that a range of alternative approaches will be required to address different sources of heterogeneity to support National Institute for Health and Care Excellence appraisals. An exemplar case study was developed to illustrate the nature of the assessments that may be required. CONCLUSIONS: Adequately designed and analysed basket studies that assess the homogeneity of outcomes and allow borrowing of information across baskets, where appropriate, are recommended. Where there is evidence of heterogeneity in treatment effects and estimates of cost-effectiveness, consideration should be given to optimised recommendations. Routine presentation of the scale of the consequences of heterogeneity and decision uncertainty may provide an important additional approach to the assessments specified in the current National Institute for Health and Care Excellence methods guide. FURTHER RESEARCH: Further exploration of Bayesian hierarchical methods could help to inform decision-makers on whether or not there is sufficient evidence of homogeneity to support pooled analyses. Further research is also required to determine the appropriate basis for apportioning genomic testing costs where there are multiple targets and to address the challenges of uncontrolled Phase II studies, including the role and use of surrogate end points. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 76. See the NIHR Journals Library website for further project information.

In May 2017, the US Food and Drug Administration granted the first approval for a cancer treatment based on a common biomarker rather than the location in the body at which the tumour originated (the tumour site); that is, a site-agnostic or 'histology-independent' indication was granted. Research from the National Institute for Health and Care Excellence suggests that there are approximately 20 technologies currently in development for histology-independent indications. The first marketing authorisation was granted in Europe in 2019. Histology-independent treatments have the potential to have important effects in patient populations for whom there are currently limited or no available treatment options. However, it is also important to ensure that the use of these treatments in the NHS is supported by systematic and robust assessments of clinical evidence (i.e. how well the medicine or treatment works) and economic evidence (i.e. the medicine's value for money). These assessments are undertaken by the National Institute for Health and Care Excellence, usually for treatments targeting specific tumours sites. However, a histology-independent marketing authorisation would probably include many tumour sites and it is not possible for the National Institute for Health and Care Excellence to conduct a separate assessment for each tumour site for which the treatment could be beneficial. As a result, the National Institute for Health and Care Excellence needs to consider how these products can be appropriately assessed without creating unnecessary delays in patient access. This research explores the extent to which the National Institute for Health and Care Excellence's existing approaches for assessing clinical and economic value can be applied to histology-independent indications, and any changes that might be required. We explore the nature and amount of evidence that is typically available at the point of initial marketing authorisation and develop recommendations to establish the evidence and analyses required to help inform the National Institute for Health and Care Excellence's decisions. We use case studies to highlight possible challenges and to explore ways that these challenges might be addressed. This research will help to inform future National Institute for Health and Care Excellence policy on how to appraise cancer drugs with histology-independent indications. It will also inform the development of guidance for those developing these treatments to help their understanding of the clinical effectiveness and cost-effectiveness assessments that will be required to inform the National Institute for Health and Care Excellence's appraisals.

A systematic review of meta-analyses assessing the validity of tumour response endpoints as surrogates for progression-free or overall survival in cancer.

BACKGROUND: Tumour response endpoints, such as overall response rate (ORR) and complete response (CR), are increasingly used in cancer trials. However, the validity of response-based surrogates is unclear. This systematic review summarises meta-analyses assessing the association between response-based outcomes and overall survival (OS), progression-free survival (PFS) or time-to-progression (TTP). METHODS: Five databases were searched to March 2019. Meta-analyses reporting correlation or regression between response-based outcomes and OS, PFS or TTP were summarised. RESULTS: The systematic review included 63 studies across 20 cancer types, most commonly non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and breast cancer. The strength of association between ORR or CR and either PFS or OS varied widely between and within studies, with no clear pattern by cancer type. The association between ORR and OS appeared weaker and more variable than that between ORR and PFS, both for associations between absolute endpoints and associations between treatment effects. CONCLUSIONS: This systematic review suggests that response-based endpoints, such as ORR and CR, may not be reliable surrogates for PFS or OS. Where it is necessary to use tumour response to predict treatment effects on survival outcomes, it is important to fully reflect all statistical uncertainty in the surrogate relationship.