Thromboprophylaxis during pregnancy and the puerperium: a systematic review and economic evaluation to estimate the value of future research.

Background: Pharmacological prophylaxis to prevent venous thromboembolism is currently recommended for women assessed as being at high risk of venous thromboembolism during pregnancy or in the 6 weeks after delivery (the puerperium). The decision to provide thromboprophylaxis involves weighing the benefits, harms and costs, which vary according to the individual's venous thromboembolism risk. It is unclear whether the United Kingdom's current risk stratification approach could be improved by further research. Objectives: To quantify the current decision uncertainty associated with selecting women who are pregnant or in the puerperium for thromboprophylaxis and to estimate the value of one or more potential future studies that would reduce that uncertainty, while being feasible and acceptable to patients and clinicians. Methods: A decision-analytic model was developed which was informed by a systematic review of risk assessment models to predict venous thromboembolism in women who are pregnant or in the puerperium. Expected value of perfect information analysis was used to determine which factors are associated with high decision uncertainty and should be the target of future research. To find out whether future studies would be acceptable and feasible, we held workshops with women who have experienced a blood clot or have been offered blood-thinning drugs and surveyed healthcare professionals. Expected value of sample information analysis was used to estimate the value of potential future research studies. Results: The systematic review included 17 studies, comprising 19 unique externally validated risk assessment models and 1 internally validated model. Estimates of sensitivity and specificity were highly variable ranging from 0% to 100% and 5% to 100%, respectively. Most studies had unclear or high risk of bias and applicability concerns. The decision analysis found that there is substantial decision uncertainty regarding the use of risk assessment models to select high-risk women for antepartum prophylaxis and obese postpartum women for postpartum prophylaxis. The main source of decision uncertainty was uncertainty around the effectiveness of thromboprophylaxis for preventing venous thromboembolism in women who are pregnant or in the puerperium. We found that a randomised controlled trial of thromboprophylaxis in obese postpartum women is likely to have substantial value and is more likely to be acceptable and feasible than a trial recruiting women who have had a previous venous thromboembolism. In unselected postpartum women and women following caesarean section, the poor performance of risk assessment models meant that offering prophylaxis based on these models had less favourable cost effectiveness with lower decision uncertainty. Limitations: The performance of the risk assessment model for obese postpartum women has not been externally validated. Conclusions: Future research should focus on estimating the efficacy of pharmacological thromboprophylaxis in pregnancy and the puerperium, and clinical trials would be more acceptable in women who have not had a previous venous thromboembolism. Study registration: This study is registered as PROSPERO CRD42020221094. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR131021) and is published in full in Health Technology Assessment; Vol. 28, No. 9. See the NIHR Funding and Awards website for further award information.

Women who are pregnant or who have given birth in the previous 6 weeks are at increased risk of developing blood clots that can cause serious illness or death. Small doses of blood thinners given by injection are safe in pregnancy and can reduce the risk of blood clots, but they can slightly increase the risk of bleeding. Healthcare professionals use risk assessment tools to decide if a woman is at high risk of blood clots and should be offered blood thinners. We wanted to find out what research would be useful to help them make better decisions. We reviewed previous research to establish which risk assessment tools are best at predicting who will have a blood clot. We then created a mathematical model to predict what would happen when using different risk assessment tools to decide who should be offered blood thinners, both during pregnancy and after giving birth. We found that there was a lot of uncertainty about which women should be offered blood thinners. This was mainly because there have only been a few small studies comparing blood thinners to no treatment in pregnant women or women who have recently given birth. We estimated the value of future studies comparing blood thinners to no treatment, in groups of women with different risk factors, by predicting what information we would gain and how this would be used to improve decisions about using blood thinners. To find out whether these studies would be acceptable and feasible, we held workshops with women who have experienced a blood clot or have been offered blood thinners and surveyed healthcare professionals. We found that a study in obese women who have recently given birth would have substantial value and may be more acceptable than a study in pregnant women with a previous blood clot.

Understanding interventions and outcomes in supported employment and individual placement support: A qualitative evidence synthesis.

BACKGROUND: Economically developed economies continue to display large and long-standing disability employment gaps. Train-then-place activation models have traditionally dominated efforts to support non-working disabled people to gain employment but recently there has been increasing interest in place-then-train Supported Employment (SE) activation models. OBJECTIVE: Evidence regarding the effectiveness of SE approaches is growing. However, authors have called for greater understanding of the mechanisms underpinning these interventions. We therefore carried out a systematic review of qualitative research to understand the processes operating. METHODS: We carried out a systematic review of qualitative research around SE interventions carried out in developed countries since 2000 in any population excepting those with severe mental illness. We used thematic synthesis and logic modelling methods and assessed the quality of the body of literature. RESULTS: We identified and included 13 relevant source studies containing qualitative data. Key aspects of the programmes reported were the nature of the support, the employment advisor, and the type of employment. Influencing factors were client-related, employer and employment-related, programme-related, and system-related. Effects beyond the gaining of employment included a changed attitude to work, different outlook, increased skills and/or confidence. Suggested longer-term impacts were on health and wellbeing, financial security, independence, contribution to society and sense of belonging. CONCLUSIONS: This review adds to the growing evidence regarding the value of SE interventions for disabled people. It adds insights regarding the key elements of the programmes, and suggests outcomes beyond the measures typically considered within quantitative studies.

Covariates of success in quitting smoking: a systematic review of studies from 2008 to 2021 conducted to inform the statistical analyses of quitting outcomes of a hospital-based tobacco dependence treatment service in the United Kingdom.

Background: Smoking cessation interventions are being introduced into routine secondary care in the United Kingdom (UK), but there are person and setting-related factors that could moderate their success in quitting smoking. This review was conducted as part of an evaluation of the QUIT hospital-based tobacco dependence treatment service ( https://sybics-quit.co.uk). The aim of the review was to identify a comprehensive set of variables associated with quitting success among tobacco smokers contacting secondary healthcare services in the UK who are offered support to quit smoking and subsequently set a quit date. The results would then be used to inform the development of a statistical analysis plan to investigate quitting outcomes. Methods: Systematic literature review of five electronic databases. Studies eligible for inclusion investigated quitting success in one of three contexts: (a) the general population in the UK; (b) people with a mental health condition; (c) quit attempts initiated within a secondary care setting. The outcome measures were parameters from statistical analysis showing the effects of covariates on quitting success with a statistically significant (i.e., p-value <0.05) association. Results: The review identified 29 relevant studies and 14 covariates of quitting success, which we grouped into four categories: demographics (age; sex; ethnicity; socio-economic conditions; relationship status, cohabitation and social network), individual health status and healthcare setting (physical health, mental health), tobacco smoking variables (current tobacco consumption, smoking history, nicotine dependence; motivation to quit; quitting history), and intervention characteristics (reduction in amount smoked prior to quitting, the nature of behavioural support, tobacco dependence treatment duration, pharmacological aids). Conclusions: In total, 14 data fields were identified that should be considered for inclusion in datasets and statistical analysis plans for evaluating the quitting outcomes of smoking cessation interventions initiated in secondary care contexts in the UK. PROSPERO registration: CRD42021254551 (13/05/2021).

Stop smoking interventions are being incorporated as a systematic and opt-out component of secondary care services in the UK's National Health Service (NHS), driven by the NHS's Long Term Plan. This review was conducted as part of an evaluation of the QUIT hospital-based tobacco dependence treatment service ( https://sybics-quit.co.uk). To support the development of statistical analyses to find out what affects smokers' success in quitting smoking after contacting the service, research was needed to identify what characteristics of the individual smokers and the healthcare setting might be important for success in quitting. The main purpose of the review was to support the development of a statistical analysis plan of quitting outcomes. We looked at academic papers published between 2008 and 2021 that estimated the influence of different factors on success in quitting smoking. The results of the review summarise the list of factors that previous studies have found to have an influence on quitting outcomes. The list of factors was used to inform discussions with the service about what data fields it would be important for the service to collect because that data could be important for helping the service to understand variation in quitting outcomes.

Cost-effectiveness of therapeutics for COVID-19 patients: a rapid review and economic analysis.

Background: Severe acute respiratory syndrome coronavirus 2 is the virus that causes coronavirus disease 2019. Over six million deaths worldwide have been associated with coronavirus disease 2019. Objective: To assess the cost-effectiveness of treatments used for the treatment of coronavirus disease 2019 in hospital or used in the community in patients with coronavirus disease 2019 at high risk of hospitalisation. Setting: Treatments provided in United Kingdom hospital and community settings. Methods: Clinical effectiveness estimates were taken from the coronavirus disease-network meta-analyses initiative and the metaEvidence initiative. A mathematical model was constructed to explore how the interventions impacted on patient health, measured in quality-adjusted life-years gained. The costs associated with treatment, including those of hospital care, were also estimated and used to form a cost per quality-adjusted life-year gained value which was compared with thresholds published by the National Institute for Health and Care Excellence. Estimates of cost-effectiveness compared against current standard of care were produced in both the hospital and community settings at three different levels of efficacy: mean, low and high. Public list prices were used for interventions with neither confidential patient access schemes nor confidential list prices considered. Results incorporating confidential pricing data were provided to the National Institute for Health and Care Excellence appraisal committee. Results: The treatments were estimated to be clinically effective although not all reached statistical significance. All treatments in the hospital setting, or community, were estimated to plausibly have a cost per quality-adjusted life-year gained value below National Institute for Health and Care Excellence's thresholds when compared with standard of care. However, almost all drugs could plausibly have cost per quality-adjusted life-years above National Institute for Health and Care Excellence's thresholds. However, there is considerable uncertainty in the results as the prevalent severe acute respiratory syndrome coronavirus 2 variant, vaccination status, history of being infected with severe acute respiratory syndrome coronavirus 2 and standard of care have all evolved since the pivotal studies were conducted which could have significant impact on the efficacy of each drug. For drugs used in high-risk patients in the community setting, the proportion of people at high risk who need hospital admission was a large driver of the cost per quality-adjusted life-year. Limitations: No studies were identified that were conducted in current conditions. This may be a large limitation as the severe acute respiratory syndrome coronavirus 2 variant changes. No head-to-head studies of interventions were identified. Conclusions: The results produced could be informative to decision-makers, although conclusions regarding the most clinical - and cost-effectiveness of each intervention should be tentative due to the evolving nature of the decision problem and, in this report, the use of list prices only. Comparisons between interventions should also be treated with caution due to potentially large heterogeneity between studies. Future work: Research assessing the relative clinical effectiveness of interventions within head-to-head studies in current conditions would be beneficial. Contemporary information related to the probability of hospital admission and death for patients at high risk in the community would improve the precision of the estimates generated. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR135564) and will be published in full in Health Technology Assessment; Vol. 27, No. 14. See the NIHR Journals Library website for further project information.

Coronavirus disease 2019 is an infectious disease that can cause death and long-term ill-health. Treatments exist that can be provided in hospital to reduce the number of deaths from coronavirus disease 2019. Treatments also exist which can be provided in the community for people at high risk of needing to be admitted to hospital to reduce the number of admissions and to reduce the number of deaths from coronavirus disease 2019. However, the value for money of these treatments has not been estimated. We took the clinical effectiveness of nine treatments from published literature sources and built a model that estimated the value for money of six treatments compared with care without these treatments. Three treatments were excluded due to confidential prices. The results of the model showed that many treatments in a hospital setting had estimates of cost-effectiveness that would normally be seen to be good value for money using the thresholds published by the National Institute of Health and Care Excellence. The same was true for some treatments in a community setting. However, it is also possible that these treatments are not good value for money. The benefit of the drugs and value for money is highly uncertain as studies trying to estimate the gain have been done with (1) previous variants of the virus causing coronavirus disease 2019 being widespread, (2) where the proportion of people who have had vaccinations or who had previously had coronavirus disease 2019 is low and (3) where standard treatment was that when coronavirus disease 2019 was first identified, and not the drugs used now. Because of these differences, and the unknown price of some interventions, we cannot confidently say which (if any) treatments help patients the most, or which treatment represents the best value for money. Further research, in current conditions, would improve the accuracy of our answers.

Risk assessment models for venous thromboembolism in pregnancy and in the puerperium: a systematic review.

OBJECTIVES: To assess the comparative accuracy of risk assessment models (RAMs) to identify women during pregnancy and the early postnatal period who are at increased risk of venous thromboembolism (VTE). DESIGN: Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: MEDLINE, Embase, Cochrane Library and two research registers were searched until February 2021. ELIGIBILITY CRITERIA: All validation studies that examined the accuracy of a multivariable RAM (or scoring system) for predicting the risk of developing VTE in women who are pregnant or in the puerperium (within 6 weeks post-delivery). DATA EXTRACTION AND SYNTHESIS: Two authors independently selected and extracted data. Risk of bias was appraised using PROBAST (Prediction model Risk Of Bias ASsessment Tool). Data were synthesised without meta-analysis. RESULTS: Seventeen studies, comprising 19 externally validated RAMs and 1 internally validated model, met the inclusion criteria. The most widely evaluated RAMs were the Royal College of Obstetricians and Gynaecologists guidelines (six studies), American College of Obstetricians and Gynecologists guidelines (two studies), Swedish Society of Obstetrics and Gynecology guidelines (two studies) and the Lyon score (two studies). In general, estimates of sensitivity and specificity were highly variable with sensitivity estimates ranging from 0% to 100% for RAMs that were applied to antepartum women to predict antepartum or postpartum VTE and 0% to 100% for RAMs applied postpartum to predict postpartum VTE. Specificity estimates were similarly diverse ranging from 28% to 98% and 5% to 100%, respectively. CONCLUSIONS: Available data suggest that external validation studies have weak designs and limited generalisability, so estimates of prognostic accuracy are very uncertain. PROSPERO REGISTRATION NUMBER: CRD42020221094.

Realist inquiry into Maternity care @ a Distance (ARM@DA): realist review protocol.

INTRODUCTION: One of the most commonly reported COVID-19-related changes to all maternity services has been an increase in the use of digital clinical consultations such as telephone or video calling; however, the ways in which they can be optimally used along maternity care pathways remain unclear. It is imperative that digital service innovations do not further exacerbate (and, ideally, should tackle) existing inequalities in service access and clinical outcomes. Using a realist approach, this project aims to synthesise the evidence around implementation of digital clinical consultations, seeking to illuminate how they can work to support safe, personalised and appropriate maternity care and to clarify when they might be most appropriately used, for whom, when, and in what contexts? METHODS AND ANALYSIS: The review will be conducted in four iterative phases, with embedded stakeholder involvement: (1) refining the review focus and generating initial programme theories, (2) exploring and developing the programme theories in light of evidence, (3) testing/refining the programme theories and (4) constructing actionable recommendations. The review will draw on four sources of evidence: (1) published literature (searching nine bibliographic databases), (2) unpublished (grey) literature, including research, audit, evaluation and policy documents (derived from Google Scholar, website searches and e-thesis databases), (3) expertise contributed by service user and health professional stakeholder groups (n=20-35) and (4) key informant interviews (n=12). Included papers will consist of any study design, in English and from 2010 onwards. The review will follow the Realist and Meta-narrative Evidence Synthesis Evolving Standards quality procedures and reporting guidance. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the University of Nottingham, Faculty of Medicine and Health Sciences Ethics Committee (FMHS 426-1221). Informed consent will be obtained for all key informant interviews. Findings will be disseminated in a range of formats relevant to different audiences. PROSPERO REGISTRATION NUMBER: CRD42021288702.

Understanding the current nutritional management for people with amyotrophic lateral sclerosis - A mapping review.

BACKGROUND & AIMS: Poor nutritional outcomes are observed in people with Amyotrophic Lateral Sclerosis (pwALS) including weight loss and poor dietary intake. Surveys of healthcare professionals have highlighted the lack of evidence and knowledge regarding nutritional management of ALS throughout the disease course. Furthermore, national evidence-based guidance is lacking. This mapping review aims to understand the structure and input of nutritional management services for pwALS. METHODS: Systematic searches were conducted across eight electronic databases to identify qualitative and quantitative research on structure and input of nutritional care in ALS. Supplementary searches included grey literature, citation and reference list searching of included studies and key reviews, web searching and contacting experts and organisations that provide ALS services to identify guidelines. Study selection and data extraction were undertaken independently by at least two reviewers. Data was synthesised using a narrative approach. RESULTS: One hundred and nine documents were identified. These consisted of journal articles, guidelines and related documents that contributed evidence towards mapping of nutritional management of pwALS. No evidence on commissioning of nutritional care was identified. Guidelines provided high-level overviews and gave general guidance or recommendations for care; however, these typically focused on gastrostomy with limited guidance on broader aspects, including oral nutrition support. Evidence from primary studies found nutritional care delivery in ALS consisted of multiple types of nutritional management, at different time points during the disease course and involving a range of professionals. There was little evidence relating to proactive nutritional care. Details of healthcare setting, number of professionals involved in care, team composition and how services were delivered in community settings were sparse. Although the role of the speech and language therapist in swallowing assessment and provision of advice on the management of swallowing difficulties was consistent; there was limited evidence on care provided by dietitians. In addition, a small number of studies reported on the use of screening tools. Overall, evidence was consistent that weight management, including monitoring of weight change by professionals and patients, was central and recommended that this should be part of nutritional assessment and follow-up. CONCLUSIONS: The evidence identified in this mapping review has highlighted the requirement for further primary research providing specific details on how nutritional management of pwALS is structured and delivered.

Qualitative Review on Domains of Quality of Life Important for Patients, Social Care Users, and Informal Carers to Inform the Development of the EQ-HWB.

OBJECTIVES: To identify the themes to inform the content of a new generic measure, the EQ-HWB (EQ Health and Wellbeing), that can be used in economic evaluation across health, social care, and public health, based on the views of users and beneficiaries of these services including informal carers. METHODS: A qualitative review was undertaken. Systematic and citation searches were undertaken focusing on qualitative evidence of the impact on quality of life from reviews for selected health conditions, informal carers, social care users, and primary qualitative work used in the development of selected measures. A subset of studies was included in the review. Framework analysis and synthesis were undertaken based on a conceptual model. RESULTS: A total of 42 reviews and 24 primary studies were selected for inclusion in the review. Extraction and synthesis resulted in 7 high-level themes (with subthemes): (1) feelings and emotions (sadness, anxiety, hope, frustration, safety, guilt/shame); (2) cognition (concentration, memory, confusion, thinking clearly); (3) self-identity (dignity/respect, self-esteem); (4) "coping, autonomy, and control" relationships; (5) social connections (loneliness, social engagement, stigma, support, friendship, belonging, burden); (6) physical sensations (pain, discomfort, sleep, fatigue); and (7) activity (self-care, meaningful activities, mobility, communication, hearing, vision). Apart from physical sensations, most of the other themes and subthemes were relevant across both health and social care, including for informal carers. CONCLUSIONS: The findings from this broad review identified themes that go beyond health and that are relevant to patients, informal carers, and social care users. The themes and subthemes informed the domains for the EQ-HWB.

Diagnostic accuracy of conventional oral examination for detecting oral cavity cancer and potentially malignant disorders in patients with clinically evident oral lesions: Systematic review and meta-analysis.

This systematic review evaluates the diagnostic accuracy of conventional oral examination (COE) versus incisional or excisional biopsy for the diagnosis of malignant and/or dysplastic lesions in patients with clinically evident lesions. Searches were conducted across five electronic databases from inception to January 2020. Meta-analyses were undertaken, where appropriate. Among 18 included studies, 14 studies were included in the meta-analysis, giving summary estimates for COE of 71% sensitivity and 85% specificity for the diagnosis of dysplastic and/or malignant lesions. The pooled diagnostic accuracy of identifying malignant-only lesions was reported in seven studies, giving a pooled estimate of 88% sensitivity and 81% specificity. Diagnostic accuracy of different types of dental/medical professionals in identifying dysplastic or malignant lesions gave varying estimates of sensitivity and specificity across three studies. Further research is needed to improve the diagnostic accuracy of COE for early detection of dysplastic and malignant oral lesions.

Changes in quality of life following hypoglycaemia in adults with type 2 diabetes: A systematic review of longitudinal studies.

AIM: To conduct a systematic review of published studies reporting on the longitudinal impacts of hypoglycaemia on quality of life (QoL) in adults with type 2 diabetes. METHOD: Database searches with no restrictions by language or date were conducted in MEDLINE, Cochrane Library, CINAHL and PsycINFO. Studies were included for review if they used a longitudinal design (e.g. cohort studies, randomised controlled trials) and reported on the association between hypoglycaemia and changes over time in patient-reported outcomes related to QoL. RESULTS: In all, 20 longitudinal studies published between 1998 and 2020, representing 50,429 adults with type 2 diabetes, were selected for review. A descriptive synthesis following Synthesis Without Meta-analysis guidelines indicated that self-treated symptomatic hypoglycaemia was followed by impairments in daily functioning along with elevated symptoms of generalised anxiety, diabetes distress and fear of hypoglycaemia. Severe hypoglycaemic events were associated with reduced confidence in diabetes self-management and lower ratings of perceived health over time. Frequent hypoglycaemia was followed by reduced energy levels and diminished emotional well-being. There was insufficient evidence, however, to conclude that hypoglycaemia impacted sleep quality, depressive symptoms, general mood, social support or overall diabetes-specific QoL. CONCLUSIONS: Longitudinal evidence in this review suggests hypoglycaemia is a common occurrence among adults with type 2 diabetes that impacts key facets in the physical and psychological domains of QoL. Nonetheless, additional longitudinal research is needed-in particular, studies targeting diverse forms of hypoglycaemia, more varied facets of QoL and outcomes assessed using hypoglycaemia-specific measures.

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

OBJECTIVE: To conduct a systematic review to examine associations between hypoglycemia and quality of life (QoL) in children and adolescents with type 1 diabetes. METHODS: Four databases (Medline, Cochrane Library, CINAHL, PsycINFO) were searched systematically in November 2019 and searches were updated in September 2021. Studies were eligible if they included children and/or adolescents with type 1 diabetes, reported on the association between hypoglycemia and QoL (or related outcomes), had a quantitative design, and were published in a peer-reviewed journal after 2000. A protocol was registered the International Prospective Register of Systematic Reviews (PROSPERO; CRD42020154023). Studies were evaluated using the Joanna Briggs Institute's critical appraisal tool. A narrative synthesis was conducted by outcome and hypoglycemia severity. RESULTS: In total, 27 studies met inclusion criteria. No hypoglycemia-specific measures of QoL were identified. Evidence for an association between SH and (domains) of generic and diabetes-specific QoL was too limited to draw conclusions, due to heterogenous definitions and operationalizations of hypoglycemia and outcomes across studies. SH was associated with greater worry about hypoglycemia, but was not clearly associated with diabetes distress, depression, anxiety, disordered eating or posttraumatic stress disorder. Although limited, some evidence suggests that more recent, more frequent, or more severe episodes of hypoglycemia may be associated with adverse outcomes and that the context in which hypoglycemia takes places might be important in relation to its impact. CONCLUSIONS: There is insufficient evidence regarding the impact of hypoglycemia on QoL in children and adolescents with type 1 diabetes at this stage. There is a need for further research to examine this relationship, ideally using hypoglycemia-specific QoL measures.

Risk assessment models for venous thromboembolism in hospitalised adult patients: a systematic review.

INTRODUCTION: Hospital-acquired thrombosis accounts for a large proportion of all venous thromboembolism (VTE), with significant morbidity and mortality. This subset of VTE can be reduced through accurate risk assessment and tailored pharmacological thromboprophylaxis. This systematic review aimed to determine the comparative accuracy of risk assessment models (RAMs) for predicting VTE in patients admitted to hospital. METHODS: A systematic search was performed across five electronic databases (including MEDLINE, EMBASE and the Cochrane Library) from inception to February 2021. All primary validation studies were eligible if they examined the accuracy of a multivariable RAM (or scoring system) for predicting the risk of developing VTE in hospitalised inpatients. Two or more reviewers independently undertook study selection, data extraction and risk of bias assessments using the PROBAST (Prediction model Risk Of Bias ASsessment Tool) tool. We used narrative synthesis to summarise the findings. RESULTS: Among 6355 records, we included 51 studies, comprising 24 unique validated RAMs. The majority of studies included hospital inpatients who required medical care (21 studies), were undergoing surgery (15 studies) or receiving care for trauma (4 studies). The most widely evaluated RAMs were the Caprini RAM (22 studies), Padua prediction score (16 studies), IMPROVE models (8 studies), the Geneva risk score (4 studies) and the Kucher score (4 studies). C-statistics varied markedly between studies and between models, with no one RAM performing obviously better than other models. Across all models, C-statistics were often weak (<0.7), sometimes good (0.7-0.8) and a few were excellent (>0.8). Similarly, estimates for sensitivity and specificity were highly variable. Sensitivity estimates ranged from 12.0% to 100% and specificity estimates ranged from 7.2% to 100%. CONCLUSION: Available data suggest that RAMs have generally weak predictive accuracy for VTE. There is insufficient evidence and too much heterogeneity to recommend the use of any particular RAM. PROSPERO REGISTRATION NUMBER: Steve Goodacre, Abdullah Pandor, Katie Sworn, Daniel Horner, Mark Clowes. A systematic review of venous thromboembolism RAMs for hospital inpatients. PROSPERO 2020 CRD42020165778. Available from https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=165778https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=165778.

Identifying the evidence base of interventions supporting mental health nurses to cope with stressful working environments: A scoping review.

AIM: To scope the evidence on interventions used to help mental health nurses cope with stressful working environments. BACKGROUND: Nursing managers may implement interventions to support mental health nurses cope in their role. However, the evidence supporting these interventions has not been recently reviewed. METHODS: A scoping review was conducted which entailed searching and selecting potential studies, undertaking data extraction and synthesis. RESULTS: Eighteen studies published since 2000 were identified. They employed different designs, ten used quasi-experimental methods. Interventions involving active learning appeared beneficial, for example stress reduction courses and mindfulness. However, small sample sizes, short follow-up periods and variation in outcome measures make it difficult to identify the optimum interventions. No studies have considered cost-effectiveness. CONCLUSION: There is some evidence that mental health nurses benefit from interventions to help them cope with stressful working environments. However, higher quality research is needed to establish the effectiveness and cost-effectiveness of different interventions. IMPLICATIONS FOR NURSING MANAGEMENT: Managers should provide opportunities and encourage mental health nurses to engage in active learning interventions, for example mindfulness to help them cope with stressful working environments. Nurses also want managers to address organisational issues; however, no research on these types of interventions was identified.

The suitability of patient-reported outcome measures used to assess the impact of hypoglycaemia on quality of life in people with diabetes: a systematic review using COSMIN methods.

AIMS/HYPOTHESIS: It is generally accepted that hypoglycaemia can negatively impact the quality of life (QoL) of people living with diabetes. However, the suitability of patient-reported outcome measures (PROMs) used to assess this impact is unclear. The aim of this systematic review was to identify PROMs used to assess the impact of hypoglycaemia on QoL and examine their quality and psychometric properties. METHODS: Systematic searches (MEDLINE, EMBASE, PsycINFO, CINAHL and The Cochrane Library databases) were undertaken to identify published articles reporting on the development or validation of hypoglycaemia-specific PROMs used to assess the impact of hypoglycaemia on QoL (or domains of QoL) in adults with diabetes. A protocol was developed and registered with PROSPERO (registration no. CRD42019125153). Studies were assessed for inclusion at title/abstract stage by one reviewer. Full-text articles were scrutinised where considered relevant or potentially relevant or where doubt existed. Twenty per cent of articles were assessed by a second reviewer. PROMS were evaluated, according to COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines, and data were extracted independently by two reviewers against COSMIN criteria. Assessment of each PROM's content validity included reviewer ratings (N = 16) of relevance, comprehensiveness and comprehensibility: by researchers (n = 6); clinicians (n = 6); and adults with diabetes (n = 4). RESULTS: Of the 214 PROMs used to assess the impact of hypoglycaemia on QoL (or domains of QoL), seven hypoglycaemia-specific PROMS were identified and subjected to full evaluation: the Fear of Hypoglycemia 15-item scale; the Hypoglycemia Fear Survey; the Hypoglycemia Fear Survey version II; the Hypoglycemia Fear Survey-II short-form; the Hypoglycemic Attitudes and Behavior Scale; the Hypoglycemic Confidence Scale; and the QoLHYPO questionnaire. Content validity was rated as 'inconsistent', with most as '(very) low' quality, while structural validity was deemed 'unsatisfactory'. Other measurement properties (e.g. reliability) varied, and evidence gaps were apparent across all PROMs. None of the identified studies addressed cross-cultural validity or measurement error. Criterion validity and responsiveness were not assessed due to the lack of a 'gold standard' measure of the impact of hypoglycaemia on QoL against which to compare the PROMS. CONCLUSIONS/INTERPRETATION: None of the hypoglycaemia-specific PROMs identified had sufficient evidence to demonstrate satisfactory validity, reliability and responsiveness. All were limited in terms of content and structural validity, which restricts their utility for assessing the impact of hypoglycaemia on QoL in the clinic or research setting. Further research is needed to address the content validity of existing PROMs, or the development of new PROM(s), for the purpose of assessing the impact of hypoglycaemia on QoL. PROSPERO REGISTRATION: CRD42019125153.

What are the cost-savings and health benefits of improving detection and management for six high cardiovascular risk conditions in England? An economic evaluation.

OBJECTIVES: To estimate the cost savings and health benefits of improving detection of individuals at high risk of cardiovascular disease (CVD) in England, to determine to which patient subgroups these benefits arise, and to compare different strategies for subsequent management. DESIGN: An economic analysis using the School for Public Health Research CVD Prevention Model. SETTING: England 2018. PARTICIPANTS: Adults aged 16 and older with one or more high cardiovascular risk conditions, including hypertension, diabetes, non-diabetic hyperglycaemia, atrial fibrillation, chronic kidney disease and high cholesterol. INTERVENTIONS: Detection of 100% of individuals with CVD high risk conditions compared with current levels of detection in England. Detected individuals are assumed to be managed either according to current levels of care or National Institute of Health and Care Excellence (NICE) guidelines. MAIN OUTCOME MEASURES: Incremental and cumulative costs, savings, quality adjusted life years (QALYs), CVD cases, and net monetary benefit, from a UK NHS and Personal Social Services perspective. RESULTS: £68 billion could be saved, 4.9 million QALYs gained and 3.4 million cases of CVD prevented over 25 years if all individuals in England with the six CVD high risk conditions were diagnosed and subsequently managed at current levels. Additionally, if all detected individuals were managed according to NICE guidelines, total savings would be £61 billion, 8.1 million QALYs would be gained and 5.2 million CVD cases prevented. Most benefits come from detection of high cholesterol in the short term and diabetes in the long term. CONCLUSIONS: Substantial cost savings and health benefits would accrue if all individuals with conditions that increase CVD risk could be diagnosed, with detection of undiagnosed diabetes producing greatest benefits. Ensuring all conditions are managed according to NICE guidelines would further increase health benefits. Projected cost-savings could be invested in developing acceptable and cost-effective solutions for improving detection and management.

Learning across the UK: a review of public health systems and policy approaches to early child development since political devolution.

BACKGROUND: Giving children the best start in life is critical for their future health and wellbeing. Political devolution in the UK provides a natural experiment to explore how public health systems contribute to children's early developmental outcomes across four countries. METHOD: A systematic literature review and input from a stakeholder group was used to develop a public health systems framework. This framework then informed analysis of public health policy approaches to early child development. RESULTS: A total of 118 studies met the inclusion criteria. All national policies championed a 'prevention approach' to early child development. Political factors shaped divergence, with variation in national conceptualizations of child development ('preparing for life' versus 'preparing for school') and pre-school provision ('universal entitlement' or 'earned benefit'). Poverty and resourcing were identified as key system factors that influenced outcomes. Scotland and Wales have enacted distinctive legislation focusing on wider determinants. However, this is limited by the extent of devolved powers. CONCLUSION: The systems framework clarifies policy complexity relating to early child development. The divergence of child development policies in the four countries and, particularly, the explicit recognition in Scottish and Welsh policy of wider determinants, creates scope for this topic to be a tracer area to compare UK public health systems longer term.

Interventions to promote oral nutritional behaviours in people living with neurodegenerative disorders of the motor system: A systematic review.

BACKGROUND & AIMS: Weight loss is common in people with neurodegenerative diseases of the motor system (NDMS), such as Parkinson's disease and Amyotrophic Lateral Sclerosis, and is associated with reduced quality of life, functional ability and survival. This systematic review aims to identify interventions and intervention components (i.e. behaviour change techniques [BCTs] and modes of delivery [MoDs]) that are associated with increased effectiveness in promoting oral nutritional behaviours that help people with NDMS to achieve a high calorie diet. METHODS: Eight electronic databases including MEDLINE and CINAHL were searched from inception to May 2018. All interventions from included studies were coded for relevant BCTs and MoDs. Methodological quality of studies was assessed using the Cochrane risk of bias tool. RESULTS: Fourteen studies were included. Of these, eight studies reported interventions to assist with swallowing difficulties and six studies reported interventions targeting dietary content. Beneficial effects in managing swallowing difficulties were observed with video assisted swallowing therapy, lung volume recruitment and swallowing management clinics with outpatient support. In contrast, studies reporting effectiveness of chin down posture, use of thickened liquids and respiratory muscle training were inconclusive. Positive effects in interventions targeting dietary content included the use of food pyramid tools, individualised nutritional advice with nutritional interventions, electronic health applications, face-to-face dietary counselling and high fat, high carbohydrate and milk whey protein supplements. Individualised nutritional advice with weekly phone contact did not appear to be effective. Most frequently coded BCTs were 'instructions on how to perform the behaviour', 'self-monitoring' and 'behavioural practice/rehearsal'. Most commonly identified MoDs were 'human, face-to-face' and 'somatic therapy'. However, the robustness of these findings are low due to the small number of studies, small sample sizes and large between-study variability. CONCLUSIONS: Despite the limited evidence, these findings may help inform the development of more effective interventions to promote oral nutritional behaviours in people with NDMS. However, further research is needed to demonstrate which interventions, or intervention components, yield most benefit.

Different strategies for pharmacological thromboprophylaxis for lower-limb immobilisation after injury: systematic review and economic evaluation.

BACKGROUND: Thromboprophylaxis can reduce the risk of venous thromboembolism (VTE) during lower-limb immobilisation, but it is unclear whether or not this translates into meaningful health benefit, justifies the risk of bleeding or is cost-effective. Risk assessment models (RAMs) could select higher-risk individuals for thromboprophylaxis. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of different strategies for providing thromboprophylaxis to people with lower-limb immobilisation caused by injury and to identify priorities for future research. DATA SOURCES: Ten electronic databases and research registers (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, the Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluation Database, Science Citation Index Expanded, ClinicalTrials.gov and the International Clinical Trials Registry Platform) were searched from inception to May 2017, and this was supplemented by hand-searching reference lists and contacting experts in the field. REVIEW METHODS: Systematic reviews were undertaken to determine the effectiveness of pharmacological thromboprophylaxis in lower-limb immobilisation and to identify any study of risk factors or RAMs for VTE in lower-limb immobilisation. Study quality was assessed using appropriate tools. A network meta-analysis was undertaken for each outcome in the effectiveness review and the results of risk-prediction studies were presented descriptively. A modified Delphi survey was undertaken to identify risk predictors supported by expert consensus. Decision-analytic modelling was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained of different thromboprophylaxis strategies from the perspectives of the NHS and Personal Social Services. RESULTS: Data from 6857 participants across 13 trials were included in the meta-analysis. Thromboprophylaxis with low-molecular-weight heparin reduced the risk of any VTE [odds ratio (OR) 0.52, 95% credible interval (CrI) 0.37 to 0.71], clinically detected deep-vein thrombosis (DVT) (OR 0.40, 95% CrI 0.12 to 0.99) and pulmonary embolism (PE) (OR 0.17, 95% CrI 0.01 to 0.88). Thromboprophylaxis with fondaparinux (Arixtra®, Aspen Pharma Trading Ltd, Dublin, Ireland) reduced the risk of any VTE (OR 0.13, 95% CrI 0.05 to 0.30) and clinically detected DVT (OR 0.10, 95% CrI 0.01 to 0.94), but the effect on PE was inconclusive (OR 0.47, 95% CrI 0.01 to 9.54). Estimates of the risk of major bleeding with thromboprophylaxis were inconclusive owing to the small numbers of events. Fifteen studies of risk factors were identified, but only age (ORs 1.05 to 3.48), and injury type were consistently associated with VTE. Six studies of RAMs were identified, but only two reported prognostic accuracy data for VTE, based on small numbers of patients. Expert consensus was achieved for 13 risk predictors in lower-limb immobilisation due to injury. Modelling showed that thromboprophylaxis for all is effective (0.015 QALY gain, 95% CrI 0.004 to 0.029 QALYs) with a cost-effectiveness of £13,524 per QALY, compared with thromboprophylaxis for none. If risk-based strategies are included, it is potentially more cost-effective to limit thromboprophylaxis to patients with a Leiden thrombosis risk in plaster (cast) [L-TRiP(cast)] score of ≥ 9 (£20,000 per QALY threshold) or ≥ 8 (£30,000 per QALY threshold). An optimal threshold on the L-TRiP(cast) receiver operating characteristic curve would have sensitivity of 84-89% and specificity of 46-55%. LIMITATIONS: Estimates of RAM prognostic accuracy are based on weak evidence. People at risk of bleeding were excluded from trials and, by implication, from modelling. CONCLUSIONS: Thromboprophylaxis for lower-limb immobilisation due to injury is clinically effective and cost-effective compared with no thromboprophylaxis. Risk-based thromboprophylaxis is potentially optimal but the prognostic accuracy of existing RAMs is uncertain. FUTURE WORK: Research is required to determine whether or not an appropriate RAM can accurately select higher-risk patients for thromboprophylaxis. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017058688. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

People who have their leg immobilised in a plaster cast or brace following an injury are at risk of developing a blood clot. Sometimes the clot can break up and lodge in the lungs, which can make the person seriously ill. Drugs that thin the blood (anticoagulants) can reduce the risk of blood clots, but they carry a small risk of serious bleeding. This study analysed all published trials of anticoagulants for people with leg immobilisation and found that, without treatment, there was a 1­2% risk of a serious blood clot. This risk was roughly halved by using anticoagulant treatment. These estimates were used in a simulation model of patient treatment and it was found that the benefit of anticoagulants in reducing blood clots (in terms of length and quality of life) outweighed the risks of bleeding. Next, all published studies of risk assessment tools were analysed. Risk assessment tools can be used to predict who is most likely to get a blood clot. There were only a few studies and they had significant weaknesses. The risk assessment tools in the simulation model were evaluated and it was found that the most cost-effective approach was to use a risk assessment tool to select approximately half of the patients for treatment (those at higher risk), while not treating those at lower risk. Treating only the higher-risk patients would be a cost-effective use of NHS resources, compared with treating nobody. Treating everybody, compared with just treating higher-risk patients, would improve outcomes for some patients but would not be a cost-effective use of NHS resources. This study suggests that anticoagulant drugs are an effective and potentially cost-effective way of preventing blood clots in people with leg immobilisation due to injury. Research is needed to determine whether or not risk assessment tools can accurately predict who needs anticoagulant drugs and who does not.

Meeting the review family: exploring review types and associated information retrieval requirements.

BACKGROUND AND OBJECTIVES: The last decade has witnessed increased recognition of the value of literature reviews for advancing understanding and decision making. This has been accompanied by an expansion in the range of methodological approaches and types of review. However, there remains uncertainty over definitions and search requirements beyond those for the 'traditional' systematic review. This study aims to characterise health related reviews by type and to provide recommendations on appropriate methods of information retrieval based on the available guidance. METHODS: A list of review types was generated from published typologies and categorised into 'families' based on their common features. Guidance on information retrieval for each review type was identified by searching pubmed, medline and Google Scholar, supplemented by scrutinising websites of review producing organisations. RESULTS: Forty-eight review types were identified and categorised into seven families. Published guidance reveals increasing specification of methods for information retrieval; however, much of it remains generic with many review types lacking explicit requirements for the identification of evidence. CONCLUSIONS: Defining review types and utilising appropriate search methods remain challenging. By familiarising themselves with a range of review methodologies and associated search methods, information specialists will be better equipped to select suitable approaches for future projects.