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Context: Advance care planning (ACP) is a comprehensive procedure aimed at helping individuals understand and articulate their values, life goals, and preferences concerning future medical treatment. Despite extensive research on ACP in populations with terminal illnesses, dementia, and those in long-term care, there is a lack of focus on its impact among older adults without life-limiting conditions. Objectives: To investigate the effectiveness, acceptability, and feasibility of ACP for older adults without life-limiting conditions. Methods: We searched 11 electronic databases, spanning from inception to November 2023, complemented by extensive grey literature and reference searches. Rigorous quality assessments were conducted using the Mixed Methods Appraisal Tool (MMAT). Our approach adopted a dynamic convergent mixed-methods design, incorporating thematic and narrative synthesis. Findings: From over 12,600 citations, a total of 16 studies, comprising four randomised controlled trials (RCTs), nine qualitative studies, and three mixed methods studies met the inclusion criteria. Limited findings indicate that ACP interventions are generally effective in improving document completion rates and reducing hospital readmissions. Acceptability and feasibility of these interventions were high, although significantly influenced by cultural and religious factors. Limitations: Evidence supporting the effectiveness, acceptability, and feasibility of ACP in reducing unplanned hospital admissions in older adults without life-limiting conditions was limited. We excluded observations based on unwell older people, though some material with unclear distinctions may have been included. Quality assessments revealed that one of four RCTs had a high risk of bias, three had unclear risks; all nine qualitative studies had low risk; and one of three mixed methods studies had low risk while two had unclear risks. Implications: Further targeted research is necessary to assess the intervention’s value for this population. Rigorous real-world evidence studies involving older adults without life-limiting conditions and their proxies is crucial to enabling providers to tailor ACPs to diverse populations, whilst respecting individuals’ religious and cultural beliefs.

Background: To inform radiofrequency electromagnetic field (RF-EMF) exposure guidelines the World Health Organization (WHO) is bringing together evidence on RF-EMF in relation to health outcomes prioritised for evaluation by experts in this field. Given this, a network of topic experts and methodologists have conducted a series of systematic reviews collecting, assessing, and synthesising data of relevance to these guidelines. Here we present a systematic review of the effect of RF-EMF exposure on adverse pregnancy outcomes in human observational studies which follows the WHO handbook for guideline development and the COSTER conduct guidelines. Methods: We conducted a broad, sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; and the EMF Portal. Grey literature searches were also conducted through relevant databases (including OpenGrey), organisational websites and via consultation of RF-EMF experts. We included quantitative human observational studies on the effect of RF-EMF exposure in adults’ preconception or pregnant women on pre-term birth, small for gestational age (SGA; associated with intrauterine growth restriction), miscarriage, stillbirth, low birth weight (LBW) and congenital anomalies. In blinded duplicate, titles and abstracts then full texts were screened against eligibility criteria. A third reviewer gave input when consensus was not reached. Citation chaining of included studies was completed. Two reviewers’ data extracted and assessed included studies for risk of bias using the Office of Health Assessment and Translation (OHAT) tool. Random effects meta-analyses of the highest versus the lowest exposures and dose–response meta-analysis were conducted as appropriate and plausible. Two reviewers assessed the certainty in each body of evidence using the OHAT GRADE tool. Results: We identified 18 studies in this review; eight were general public studies (with the general public as the population of interest) and 10 were occupational studies (with the population of interest specific workers/workforces).General public studies.From pairwise meta-analyses of general public studies, the evidence is very uncertain about the effects of RF-EMF from mobile phone exposure on preterm birth risk (relative risk (RR) 1.14, 95% confidence interval (CI): 0.97–1.34, 95% prediction interval (PI): 0.83–1.57; 4 studies), LBW (RR 1.14, 95% CI: 0.96–1.36, 95% PI: 0.84–1.57; 4 studies) or SGA (RR 1.13, 95% CI: 1.02–1.24, 95% PI: 0.99–1.28; 2 studies) due to very low-certainty evidence. It was not feasible to meta-analyse studies reporting on the effect of RF-EMF from mobile phone exposure on congenital anomalies or miscarriage risk. The reported effects from the studies assessing these outcomes varied and the studies were at some risk of bias. No studies of the general public assessed the impact of RF-EMF exposure on stillbirth.Occupational studies.In occupational studies, based on dose–response meta-analyses, the evidence is very uncertain about the effects of RF-EMF amongst female physiotherapists using shortwave diathermy on miscarriage due to very low-certainty evidence (OR 1.02 95% CI 0.94–1.1; 2 studies). Amongst offspring of female physiotherapists using shortwave diathermy, the evidence is very uncertain about the effects of RF-EMF on the risk of congenital malformations due to very low-certainty evidence (OR 1.4, 95% CI 0.85 to 2.32; 2 studies). From pairwise meta-analyses, the evidence is very uncertain about the effects of RF-EMF on the risk of miscarriage (RR 1.06, 95% CI 0.96 to 1.18; very low-certainty evidence), pre-term births (RR 1.19, 95% CI 0.32 to 4.37; 3 studies; very low-certainty evidence), and low birth weight (RR 2.90, 95% CI: 0.69 to 12.23; 3 studies; very low-certainty evidence). Results for stillbirth and SGA could not be pooled in meta-analyses. The results from the studies reporting these outcomes were inconsistent and the studies were at some risk of bias. Discussion: Most of the evidence identified in this review was from general public studies assessing localised RF-EMF exposure from mobile phone use on female reproductive outcomes. In occupational settings, each study was of heterogenous whole-body RF-EMF exposure from radar, short or microwave diathermy, surveillance and welding equipment and its effect on female reproductive outcomes. Overall, the body of evidence is very uncertain about the effect of RF-EMF exposure on female reproductive outcomes.Further prospective studies conducted with greater rigour (particularly improved accuracy of exposure measurement and using appropriate statistical methods) are required to identify any potential effects of RF-EMF exposure on female reproductive outcomes of interest.

Background: The World Health Organization (WHO) is bringing together evidence on radiofrequency electromagnetic field (RF-EMF) exposure in relation to health outcomes, previously identified as priorities for research and evaluation by experts in the field, to inform exposure guidelines. A suite of systematic reviews have been undertaken by a network of topic experts and methodologists to collect, assess and synthesise data relevant to these guidelines. Following the WHO handbook for guideline development and the COSTER conduct guidelines, we systematically reviewed the evidence on the potential effects of RF-EMF exposure on male fertility in human observational studies. Methods: We conducted a broad and sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; Web of Science and EMF Portal. We also conducted searches of grey literature through relevant databases including OpenGrey, and organisational websites and consulted RF-EMF experts. We hand searched reference lists of included study records and for citations of these studies. We included quantitative human observational studies on the effect of RF-EMF exposure in adult male participants on infertility: sperm concentration; sperm morphology; sperm total motility; sperm progressive motility; total sperm count; and time to pregnancy. Titles and abstracts followed by full texts were screened in blinded duplicate against pre-set eligibility criteria with consensus input from a third reviewer as required. Data extraction from included studies was completed by two reviewers, as was risk of bias assessment using the Office of Health Assessment and Translation (OHAT) tool. We conducted a dose–response meta-analysis as possible and appropriate. Certainty of the evidence was assessed by two reviewers using the OHAT GRADE tool with input from a third reviewer as required. Results: We identified nine studies in this review; seven were general public studies (with the general public as the population of interest) and two were occupational studies (with specific workers/workforces as the population of interest).General public studies.Duration of phone use: The evidence is very uncertain surrounding the effects of RF-EMF on sperm concentration (10/6 mL) (MD (mean difference) per hour of daily phone use 1.6 106/mL, 95 % CI −1.7 to 4.9; 3 studies), sperm morphology (MD 0.15 percentage points of deviation of normal forms per hour, 95 % CI −0.21 to 0.51; 3 studies), sperm progressive motility (MD −0.46 percentage points per hour, 95 % CI −1.04 to 0.13; 2 studies) and total sperm count (MD per hour −0.44 106/ejaculate, 95 % CI −2.59 to 1.7; 2 studies) due to very low-certainty evidence. Four additional studies reported on the effect of mobile phone use on sperm motility but were unsuitable for pooling; only one of these studies identified a statistically significant effect. All four studies were at risk of exposure characterisation and selection bias; two of confounding, selective reporting and attrition bias; three of outcome assessment bias and one used an inappropriate statistical method.Position of phone: There may be no or little effect of carrying a mobile phone in the front pocket on sperm concentration, total count, morphology, progressive motility or on time to pregnancy.Of three studies reporting on the effect of mobile phone location on sperm total motility and, or, total motile count, one showed a statistically significant effect. All three studies were at risk of exposure characterisation and selection bias; two of confounding, selective reporting and attrition bias; three of outcome assessment bias and one used inappropriate statistical method.RF-EMF Source: One study indicates there may be little or no effect of computer or other electric device use on sperm concentration, total motility or total count. This study is at probably high risk of exposure characterisation bias and outcome assessment bias.Occupational studies.With only two studies of occupational exposure to RF-EMF and heterogeneity in the population and exposure source (technicians exposed to microwaves or seamen exposed to radar equipment), it was not plausible to statistically pool findings. One study was at probably or definitely high risk of bias across all domains, the other across domains for exposure characterisation bias, outcome assessment bias and confounding. Discussion: The majority of evidence identified was assessing localised RF-EMF exposure from mobile phone use on male fertility with few studies assessing the impact of phone position. Overall, the evidence identified is very uncertain about the effect of RF-EMF exposure from mobile phones on sperm outcomes. One study assessed the impact of other RF-EMF sources on male fertility amongst the general public and two studies assessed the impact of RF-EMF exposure in occupational cohorts from different sources (radar or microwave) on male fertility.Further prospective studies conducted with greater rigour (in particular, improved accuracy of exposure measurement and appropriate statistical method use) would build the existing evidence base and are required to have greater certainty in any potential effects of RF-EMF on male reproductive outcomes. Prospero Registration: CRD42021265401 (SR3A)

Abstract Background Unpaid carers of older people, and older unpaid carers, experience a range of adverse outcomes. Supporting carers should therefore be a public health priority. Our understanding of what works to support carers could be enhanced if future evaluations prioritise under-researched interventions and outcomes. To support this, we aimed to: map evidence about interventions to support carers, and the outcomes evaluated; and identify key gaps in current evidence. Methods Evidence gap map review methods were used. Searches were carried out in three bibliographic databases for quantitative evaluations of carer interventions published in OECD high-income countries between 2013 and 2023. Interventions were eligible if they supported older carers (50 + years) of any aged recipient, or any aged carers of older people (50 + years). Findings 205 studies reported across 208 publications were included in the evidence map. The majority evaluated the impact of therapeutic and educational interventions on carer burden and carers’ mental health. Some studies reported evidence about physical exercise interventions and befriending and peer support for carers, but these considered a limited range of outcomes. Few studies evaluated interventions that focused on delivering financial information and advice, pain management, and physical skills training for carers. Evaluations rarely considered the impact of interventions on carers’ physical health, quality of life, and social and financial wellbeing. Very few studies considered whether interventions delivered equitable outcomes. Conclusion Evidence on what works best to support carers is extensive but limited in scope. A disproportionate focus on mental health and burden outcomes neglects other important areas where carers may need support. Given the impact of caring on carers’ physical health, financial and social wellbeing, future research could evaluate interventions that aim to support these outcomes. Appraisal of whether interventions deliver equitable outcomes across diverse carer populations is critical.

Objective International trials can be challenging to operationalise due to incompatibilities between country-specific policies and infrastructures. The aim of this systematic review was to identify the operational complexities of conducting international trials and identify potential solutions for overcoming them.Design Systematic review.Data sources Medline, Embase and Health Management Information Consortium were searched from 2006 to 30 January 2023.Eligibility criteria All studies reporting operational challenges (eg, site selection, trial management, intervention management, data management) of conducting international trials were included.Data extraction and synthesis Search results were independently screened by at least two reviewers and data were extracted into a proforma.Results 38 studies (35 RCTs, 2 reports and 1 qualitative study) fulfilled the inclusion criteria. The median sample size was 1202 (IQR 332–4056) and median number of sites was 40 (IQR 13–78). 88.6% of studies had an academic sponsor and 80% were funded through government sources. Operational complexities were particularly reported during trial set-up due to lack of harmonisation in regulatory approvals and in relation to sponsorship structure, with associated budgetary impacts. Additional challenges included site selection, staff training, lengthy contract negotiations, site monitoring, communication, trial oversight, recruitment, data management, drug procurement and distribution, pharmacy involvement and biospecimen processing and transport.Conclusions International collaborative trials are valuable in cases where recruitment may be difficult, diversifying participation and applicability. However, multiple operational and regulatory challenges are encountered when implementing a trial in multiple countries. Careful planning and communication between trials units and investigators, with an emphasis on establishing adequately resourced cross-border sponsorship structures and regulatory approvals, may help to overcome these barriers and realise the benefits of the approach.Open science framework registration number osf-registrations-yvtjb-v1.

Summary: Background: Based on real-world data, we developed a 10-year prediction model to estimate the burden among patients with depression from the public healthcare system payer's perspective to inform early resource planning in Hong Kong. Methods: We developed a Markov cohort model with yearly cycles specifically capturing the pathway of treatment-resistant depression (TRD) and comorbidity development along the disease course. Projected from 2023 to 2032, primary outcomes included costs of all-cause and psychiatric care, and secondary outcomes were all-cause deaths, years of life lived, and quality-adjusted life-years. Using the territory-wide electronic medical records, we identified 25,190 patients aged ≥10 years with newly diagnosed depression from 2014 to 2016 with follow-up until 2020 to observe the real-world time-to-event pattern, based on which costs and time-varying transition inputs were derived using negative binomial modelling and parametric survival analysis. We applied the model as both closed cohort, which studied a fixed cohort of incident patients in 2023, and open cohort, which introduced incident patients by year from 2014 to 2032. Utilities and annual new patients were from published sources. Findings: With 9217 new patients in 2023, our closed cohort model projected the 10-year cumulative costs of all-cause and psychiatric care to reach US$309.0 million and US$58.3 million, respectively, with 899 deaths (case fatality rate: 9.8%) by 2032. In our open cohort model, 55,849–57,896 active prevalent cases would cost more than US$322.3 million and US$60.7 million, respectively, with more than 943 deaths annually from 2023 to 2032. Fewer than 20% of cases would live with TRD or comorbidities but contribute 31–54% of the costs. The greatest collective burden would occur in women aged above 40, but men aged above 65 and below 25 with medical history would have the highest costs per patient-year. The key cost drivers were relevant to the early disease stages. Interpretation: A limited proportion of patients would develop TRD and comorbidities but contribute to a high proportion of costs, which necessitates appropriate attention and resource allocation. Our projection also demonstrates the application of real-world data to model long-term costs and mortality, which aid policymakers anticipate foreseeable burden and undertake budget planning to prepare for the care need in alternative scenarios. Funding: Research Impact Fund from the University Grants Committee, Research Grants Council with matching fund from the Hong Kong Association of Pharmaceutical Industry (R7007-22).

Background: Unpaid care is a critical source of support for people with health and social care needs. Unpaid carers are a group facing increasing demands and are at risk of adverse outcomes. Objectives: To assess the breadth of evidence on older carers/carers of older people in UK cohort studies. Methods: Using scoping review methods, we developed a targeted search strategy in three bibliographic databases (Medline, PsycInfo and CINAHL) for studies reporting carer characteristics and outcomes. Data were mapped using Evidence for Policy and Practice Information (EPPI) Reviewer, a web-based programme for managing and analysing data in reviews. The impacts of caring were explored and synthesised. Findings: Eighty-five studies were included. Where studies examined the impact of caring, outcomes were typically health-related; findings were inconsistent. Fewer studies reported the socioeconomic, disability-related, quality of life, or social impacts of caring. Fewer than half of studies reported subgroup analyses or care recipient information, and only five studies stratified carers’ outcomes by a measure of socioeconomic status. Limitations: Relying on data from observational studies means that key outcomes or caring pathways may be overlooked due to data collection methods. We therefore cannot infer causation/reverse causation regarding caring and carer outcomes. Implications: Our work highlights specific gaps in evidence regarding the social, economic, health and quality of life outcomes for carers. We also suggest methodological considerations to improve our understanding of care recipients, carers’ trajectories, and those at greatest risk of adverse outcomes. This information is vital to the development of research design, policies and interventions to support carers’ wellbeing.

BackgroundPeople experiencing homelessness co-occurring with substance use or offending ('severe and multiple disadvantage' SMD) often have high levels of poor oral health and related health behaviours (particularly, substance use, smoking, poor diet). This systematic review aimed to assess the effectiveness and cost-effectiveness of interventions in adults experiencing SMD to improve oral health and related health behaviours.Methods and findingsFrom inception to February 2023, five bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, and Scopus) and grey literature were searched. Two researchers independently screened the search results. Randomized controlled trials (RCTs), comparative studies and economic evaluations were included that reported outcomes on oral health and the related health behaviours. Risk of bias was assessed and results narratively synthesized. Meta-analyses were performed where appropriate. This review was registered with PROSPERO (reg. no: CRD42020202416). Thirty-eight studies were included (published between 1991 and 2023) with 34 studies reporting about effectiveness. Most studies reported on substance use (n = 30). Interventions with a combination of housing support with substance use and mental health support such as contingent work therapy appeared to show some reduction in substance use in SMD groups. However, meta-analyses showed no statistically significant results. Most studies had short periods of follow-up and high attrition rates. Only one study reported on oral health; none reported on diet. Three RCTs reported on smoking, of which one comprising nicotine replacement with contingency management showed improved smoking abstinence at 4 weeks compared to control. Five studies with economic evaluations provided some evidence that interventions such as Housing First and enhanced support could be cost-effective in reducing substance use.ConclusionThis review found that services such as housing combined with other healthcare services could be effective in improving health behaviours, particularly substance use, among SMD groups. Gaps in evidence also remain on oral health improvement, smoking, and diet. High quality studies on effectiveness with adequate power and retention are needed to address these significant health challenges in SMD populations.

Objectives Among people experiencing severe and multiple disadvantage (SMD), poor oral health is common and linked to smoking, substance use and high sugar intake. Studies have explored interventions addressing oral health and related behaviours; however, factors related to the implementation of these interventions remain unclear. This mixed-methods systematic review aimed to synthesise evidence on the implementation and sustainability of interventions to improve oral health and related health behaviours among adults experiencing SMD.Methods Bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, EBSCO, Scopus) and grey literature were searched from inception to February 2023. Studies meeting the inclusion criteria were screened and extracted independently by two researchers. Quality appraisal was undertaken, and results were synthesised using narrative and thematic analyses.Results Seventeen papers were included (published between 1995 and 2022). Studies were mostly of moderate quality and included views from SMD groups and service providers. From the qualitative synthesis, most findings were related to aspects such as trust, resources and motivation levels of SMD groups and service providers. None of the studies reported on diet and none included repeated offending (one of the aspects of SMD). From the quantitative synthesis, no difference was observed in programme attendance between the interventions and usual care, although there was some indication of sustained improvements in participation in the intervention group.Conclusion This review provides some evidence that trust, adequate resources and motivation levels are potentially important in implementing interventions to improve oral health and substance use among SMD groups. Further research is needed from high quality studies and focusing on diet in this population.PROSPERO registration number CRD42020202416.

Objectives To identify prognostic models for melanoma survival, recurrence and metastasis among American Joint Committee on Cancer stage I and II patients postsurgery; and evaluate model performance, including overall survival (OS) prediction.Design Systematic review and narrative synthesis.Data sources Searched MEDLINE, Embase, CINAHL, Cochrane Library, Science Citation Index and grey literature sources including cancer and guideline websites from 2000 to September 2021.Eligibility criteria Included studies on risk prediction models for stage I and II melanoma in adults ≥18 years. Outcomes included OS, recurrence, metastases and model performance. No language or country of publication restrictions were applied.Data extraction and synthesis Two pairs of reviewers independently screened studies, extracted data and assessed the risk of bias using the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies checklist and the Prediction study Risk of Bias Assessment Tool. Heterogeneous predictors prevented statistical synthesis.Results From 28 967 records, 15 studies reporting 20 models were included; 8 (stage I), 2 (stage II), 7 (stages I–II) and 7 (stages not reported), but were clearly applicable to early stages. Clinicopathological predictors per model ranged from 3–10. The most common were: ulceration, Breslow thickness/depth, sociodemographic status and site. Where reported, discriminatory values were ≥0.7. Calibration measures showed good matches between predicted and observed rates. None of the studies assessed clinical usefulness of the models. Risk of bias was high in eight models, unclear in nine and low in three. Seven models were internally and externally cross-validated, six models were externally validated and eight models were internally validated.Conclusions All models are effective in their predictive performance, however the low quality of the evidence raises concern as to whether current follow-up recommendations following surgical treatment is adequate. Future models should incorporate biomarkers for improved accuracy.PROSPERO registration number CRD42018086784.

Objectives Horizon scanning (HS) is a method used to examine signs of change and may be used in foresight practice. HS methods used for the identification of innovative medicinal products cannot be applied in medical technologies (MedTech) due to differences in development and regulatory processes. The aim of this study is to identify HS and other methodologies used for MedTech foresight in support to healthcare decision-making.Method A mapping review was performed. We searched bibliographical databases including MEDLINE, Embase, Scopus, Web of Science, IEEE Xplore and Compendex Engineering Village and grey literature sources such as Google, CORE database and the International HTA database. Our searches identified 8888 records. After de-duplication, and manual and automated title, abstracts and full-text screening, 49 papers met the inclusion criteria and were data extracted.Results Twenty-five single different methods were identified, often used in combination; of these, only three were novel (appearing only once in the literature). Text mining or artificial intelligence solutions appear as early as 2012, often practised in patent and social media sources. The time horizon used in scanning was not often justified. Some studies regarded experts both as a source and as a method. Literature searching remains one of the most used methods for innovation identification. HS methods were vaguely reported, but often involved consulting with experts and stakeholders.Conclusion Heterogeneous methodologies, sources and time horizons are used for HS and foresight of MedTech innovation with little or no justification provided for their use. This review revealed an array of known methods being used in combination to overcome the limitations posed by single methods. The review also revealed inconsistency in methods reporting, with a lack of any consensus regarding best practice. Greater transparency in methods reporting and consistency in methods use would contribute to increased output quality to support informed timely decision-making.

Background: Malnutrition worsens the health of frail older adults. Current treatments for malnutrition may include prescribed oral nutritional supplements, which are multinutrient products containing macronutrients and micronutrients. Objective: To assess the effectiveness and cost-effectiveness of oral nutritional supplements (with or without other dietary interventions) in frail older people who are malnourished or at risk of malnutrition. Data sources: MEDLINE, EMBASE, Cochrane Library, Scopus, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and grey literature were searched from inception to 13 September 2021. Review methods: A systematic review and meta-analysis was conducted to evaluate the effectiveness and cost-effectiveness of oral nutritional supplements in frail older people (aged ≥ 65 years) who are malnourished or at risk of malnutrition (defined as undernutrition as per National Institute for Health and Care Excellence guidelines). Meta-analysis and network meta-analysis were undertaken, where feasible, along with a narrative synthesis. A cost-effectiveness review was reported narratively. A de novo model was developed using effectiveness evidence identified in the systematic review to estimate the cost-effectiveness of oral nutritional supplements. Results: Eleven studies (n = 822 participants) were included in the effectiveness review, six of which were fully or partly funded by industry. Meta-analyses suggested positive effects of oral nutritional supplements compared with standard care for energy intake (kcal) (standardised mean difference 1.02, 95% confidence interval 0.15 to 1.88; very low quality evidence) and poor mobility (mean difference 0.03, p

Objectives We consider expert opinion and its incorporation into a planned meta-analysis as a way of adjusting for anticipated publication bias. We conduct an elicitation exercise among eligible British Gynaecological Cancer Society (BGCS) members with expertise in gynaecology.Design Expert elicitation exercise.Setting BGCS.Participants Members of the BGCS with expertise in gynaecology.Methods Experts were presented with details of a planned prospective systematic review and meta-analysis, assessing overall survival for the extent of excision of residual disease (RD) after primary surgery for advanced epithelial ovarian cancer. Participants were asked views on the likelihood of different studies (varied in the size of the study population and the RD thresholds being compared) not being published. Descriptive statistics were produced and opinions on total number of missing studies by sample size and magnitude of effect size estimated.Results Eighteen expert respondents were included. Responders perceived publication bias to be a possibility for comparisons of RD 1 cm) are likely to be impacted by publication bias, but this is unlikely to attenuate effect estimates in meta-analyses.

Abstract Background Surgical interventions for the treatment of stress urinary incontinence (SUI) in women are commonly employed following the failure of minimally invasive therapies. Due to the limited information available on the relative cost-effectiveness of available surgeries for treating SUI, a de novo economic analysis was conducted to assess costs and effects of all relevant surgeries. To inform the economic analysis, the objective of this review was to identify and assess the quality of existing economic evaluation studies on different surgical interventions for the treatment of SUI in women. Methods The following databases were searched during the review process: Medical Literature Analysis and Retrieval System Online (MEDLINE), MEDLINE In-Process, Excerpta Medica Database (Embase), National Health Service Economic Evaluation Database (NHS EED), and Health Management Information Consortium and Cost-Effectiveness Analysis Registry (CEA registry). The key criteria for inclusion were that the study population included women with SUI and that the surgical interventions considered were utilised as either a primary or a follow-up surgery. The review included only full economic evaluations. Studies were quality assessed using the Drummond checklist for economic evaluations. No quantitative synthesis of the results by meta-analysis was conducted due to the high methodological heterogeneity. Results Twenty-six economic evaluations were included, of which 13 were model-based analyses. Surgical treatments assessed most frequently were mid-urethral slings and open and laparoscopic colposuspension. There were some differences in the methodological approaches taken, including differences in type of economic analysis, perspective, time horizon, types of resource use, and costs and outcomes that were included in the analysis. The majority of studies conducted a cost-utility analysis from a health system perspective and applied a time horizon of between 1 and 5 years. The cost-effectiveness results suggest that single-incision mini-sling and mid-urethral slings are among the most cost-effective options. Conclusions The review has shown that methods used for the economic evaluation of surgical treatments for SUI vary widely in terms of study design, analysis type, compared alternatives, time horizon, costing methodologies and effect outcomes. Future economic evaluation studies on surgical treatments for SUI may be improved by the application of available guidelines. Systematic review registration Registered in PROSPERO in 2016, CRD42016049339

BackgroundThere is need to consider the value of soft intelligence, leveraged using accessible natural language processing (NLP) tools, as a source of analyzed evidence to support public health research outputs and decision-making. ObjectiveThe aim of this study was to explore the value of soft intelligence analyzed using NLP. As a case study, we selected and used a commercially available NLP platform to identify, collect, and interrogate a large collection of UK tweets relating to mental health during the COVID-19 pandemic. MethodsA search strategy comprised of a list of terms related to mental health, COVID-19, and lockdown restrictions was developed to prospectively collate relevant tweets via Twitter’s advanced search application programming interface over a 24-week period. We deployed a readily and commercially available NLP platform to explore tweet frequency and sentiment across the United Kingdom and identify key topics of discussion. A series of keyword filters were used to clean the initial data retrieved and also set up to track specific mental health problems. All collated tweets were anonymized. ResultsWe identified and analyzed 286,902 tweets posted from UK user accounts from July 23, 2020 to January 6, 2021. The average sentiment score was 50%, suggesting overall neutral sentiment across all tweets over the study period. Major fluctuations in volume (between 12,622 and 51,340) and sentiment (between 25% and 49%) appeared to coincide with key changes to any local and/or national social distancing measures. Tweets around mental health were polarizing, discussed with both positive and negative sentiment. Key topics of consistent discussion over the study period included the impact of the pandemic on people’s mental health (both positively and negatively), fear and anxiety over lockdowns, and anger and mistrust toward the government. ConclusionsUsing an NLP platform, we were able to rapidly mine and analyze emerging health-related insights from UK tweets into how the pandemic may be impacting people’s mental health and well-being. This type of real-time analyzed evidence could act as a useful intelligence source that agencies, local leaders, and health care decision makers can potentially draw from, particularly during a health crisis.

Background: The World Health Organization (WHO) is bringing together evidence on radiofrequency electromagnetic field (RF-EMF) exposure in relation to health outcomes, previously identified as priorities for evaluation by experts in the field, to inform exposure guidelines. A suite of systematic reviews are being undertaken by a network of topic experts and methodologists in order to collect, assess and synthesise data relevant to these guidelines. Here, we present the protocol for the systematic review on the effect of exposure to RF on adverse reproductive outcomes (human observational studies), also referred to as Systematic Review (SR) 3 within the series of systematic reviews currently being commissioned. Objectives: Following the WHO handbook for guideline development and the COSTER conduct guidelines, we will systematically review the effect of RF-EMF exposure on both male fertility (SR3A) and adverse pregnancy outcomes (SR3B) in human observational studies. Herein we adhere to the PRISMA-P reporting guidelines. Data sources: We will conduct a broad search for potentially relevant records relevant for both reviews within the following bibliographic databases: MEDLINE; Embase; and EMF Portal. We will also conduct searches of grey literature through relevant databases and organisational websites. RF-EMF experts will also be consulted. We will hand search citation and reference lists of included study records. Study eligibility criteria: We will include quantitative human observational studies on the effect of RF-EMF exposure: (in SR3A) in adult male participants on infertility, sperm morphology, concentration or total sperm count or motility; and (in SR3B) in preconception adults or pregnant women on preterm birth, small for gestational age (associated with intrauterine growth restriction), miscarriage, stillbirth and congenital anomalies. Study appraisal and synthesis methods: Titles, abstracts and then full texts will be screened in blinded duplicate against eligibility criteria with input from a third reviewer as required. Data extraction from included studies will be completed by two reviewers as will risk of bias assessment using the Office of Health Assessment and Translation (OHAT) tool. If appropriate we will undertake meta-analysis to pool effect measures and explore heterogeneity using sub-group analyses or meta-regression as feasible. We will conduct sensitivity analysis to assess the impact of any assumptions made throughout the review process. The OHAT methodology, based on the GRADE guidelines for evidence assessment, will be used to evaluate the certainty of evidence per outcome and to conclude the level of evidence of a health effect. Conclusion: This manuscript details the protocols for two systematic reviews. The aims of publishing details of both protocols are to: pre-specify their scope and methods; reduce the impact of reviewer bias; promote transparency and replicability; and improve the review process. Prospero registration: CRD42021265401 (SR3A), CRD42021266268 (SR3B).

To facilitate effective targeted COVID-19 vaccination strategies, it is important to understand reasons for vaccine hesitancy where uptake is low. Artificial intelligence (AI) techniques offer an opportunity for real-time analysis of public attitudes, sentiments, and key discussion topics from sources of soft-intelligence, including social media data. In this work, we explore the value of soft-intelligence, leveraged using AI, as an evidence source to support public health research. As a case study, we deployed a natural language processing (NLP) platform to rapidly identify and analyse key barriers to vaccine uptake from a collection of geo-located tweets from London, UK. We developed a search strategy to capture COVID-19 vaccine related tweets, identifying 91,473 tweets between 30 November 2020 and 15 August 2021. The platform's algorithm clustered tweets according to their topic and sentiment, from which we extracted 913 tweets from the top 12 negative sentiment topic clusters. These tweets were extracted for further qualitative analysis. We identified safety concerns; mistrust of government and pharmaceutical companies; and accessibility issues as key barriers limiting vaccine uptake. Our analysis also revealed widespread sharing of vaccine misinformation amongst Twitter users. This study further demonstrates that there is promising utility for using off-the-shelf NLP tools to leverage insights from social media data to support public health research. Future work to examine where this type of work might be integrated as part of a mixed-methods research approach to support local and national decision making is suggested.

BackgroundThe 2020 COVID-19 pandemic prompted the rapid implementation of new and existing digital technologies to facilitate access to health and care services during physical distancing. Older people may be disadvantaged in that regard if they are unable to use or have access to smartphones, tablets, computers, or other technologies. ObjectiveIn this study, we synthesized evidence on the impact of digital technologies on older adults’ access to health and social services. MethodsWe conducted an umbrella review of systematic reviews published from January 2000 to October 2019 using comprehensive searches of 6 databases. We looked for reviews in a population of adults aged ≥65 years in any setting, reporting outcomes related to the impact of technologies on access to health and social care services. ResultsA total of 7 systematic reviews met the inclusion criteria, providing data from 77 randomized controlled trials and 50 observational studies. All of them synthesized findings from low-quality primary studies, 2 of which used robust review methods. Most of the reviews focused on digital technologies to facilitate remote delivery of care, including consultations and therapy. No studies examined technologies used for first contact access to care, such as online appointment scheduling. Overall, we found no reviews of technology to facilitate first contact access to health and social care such as online appointment booking systems for older populations. ConclusionsThe impact of digital technologies on equitable access to services for older people is unclear. Research is urgently needed in order to understand the positive and negative consequences of digital technologies on health care access and to identify the groups most vulnerable to exclusion.

Background: Malignant melanoma is the fifth most common cancer in the UK, with rates continuing to rise, resulting in considerable burden to patients and the NHS. Objectives: The objectives were to evaluate the effectiveness and cost-effectiveness of current and alternative follow-up strategies for stage IA and IB melanoma. Review methods: Three systematic reviews were conducted. (1) The effectiveness of surveillance strategies. Outcomes were detection of new primaries, recurrences, metastases and survival. Risk of bias was assessed using the Cochrane Collaboration’s Risk-of-Bias 2.0 tool. (2) Prediction models to stratify by risk of recurrence, metastases and survival. Model performance was assessed by study-reported measures of discrimination (e.g. D-statistic, Harrel’s c-statistic), calibration (e.g. the Hosmer–Lemeshow ‘goodness-of-fit’ test) or overall performance (e.g. Brier score, R2). Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). (3) Diagnostic test accuracy of fine-needle biopsy and ultrasonography. Outcomes were detection of new primaries, recurrences, metastases and overall survival. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies–2 (QUADAS–2) tool. Review data and data from elsewhere were used to model the cost-effectiveness of alternative surveillance strategies and the value of further research. Results: (1) The surveillance review included one randomised controlled trial. There was no evidence of a difference in new primary or recurrence detected (risk ratio 0.75, 95% confidence interval 0.43 to 1.31). Risk of bias was considered to be of some concern. Certainty of the evidence was low. (2) Eleven risk prediction models were identified. Discrimination measures were reported for six models, with the area under the operating curve ranging from 0.59 to 0.88. Three models reported calibration measures, with coefficients of ≥ 0.88. Overall performance was reported by two models. In one, the Brier score was slightly better than the American Joint Committee on Cancer scheme score. The other reported an R2 of 0.47 (95% confidence interval 0.45 to 0.49). All studies were judged to have a high risk of bias. (3) The diagnostic test accuracy review identified two studies. One study considered fine-needle biopsy and the other considered ultrasonography. The sensitivity and specificity for fine-needle biopsy were 0.94 (95% confidence interval 0.90 to 0.97) and 0.95 (95% confidence interval 0.90 to 0.97), respectively. For ultrasonography, sensitivity and specificity were 1.00 (95% confidence interval 0.03 to 1.00) and 0.99 (95% confidence interval 0.96 to 0.99), respectively. For the reference standards and flow and timing domains, the risk of bias was rated as being high for both studies. The cost-effectiveness results suggest that, over a lifetime, less intensive surveillance than recommended by the National Institute for Health and Care Excellence might be worthwhile. There was considerable uncertainty. Improving the diagnostic performance of cancer nurse specialists and introducing a risk prediction tool could be promising. Further research on transition probabilities between different stages of melanoma and on improving diagnostic accuracy would be of most value. Limitations: Overall, few data of limited quality were available, and these related to earlier versions of the American Joint Committee on Cancer staging. Consequently, there was considerable uncertainty in the economic evaluation. Conclusions: Despite adoption of rigorous methods, too few data are available to justify changes to the National Institute for Health and Care Excellence recommendations on surveillance. However, alternative strategies warrant further research, specifically on improving estimates of incidence, progression of recurrent disease; diagnostic accuracy and health-related quality of life; developing and evaluating risk stratification tools; and understanding patient preferences. Study registration: This study is registered as PROSPERO CRD42018086784. Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol 25, No. 64. See the NIHR Journals Library website for further project information.

Background Eating, drinking and swallowing difficulties (EDSD) are common in children with neurodisability, and have physical and non-physical causes. EDSD have substantial impacts on the child and family. Little is currently documented about what advice is usually given by professionals, including the interventions commonly used, and what informally constitutes ‘best clinical practice’. We aimed to identify current UK practice of parent-delivered interventions for EDSD for children with neurodisability, and the outcomes valued by professionals and parents.Methods Two populations were sampled: health professionals working with children and young people (aged 0–18 years) with neurodisability who experience EDSD (n=421); parents of children with neurodisability aged up to 12 years who experience EDSD (n=359). Questionnaires were developed based on the findings from updates of three systematic reviews, a mapping review of interventions used with this population, and in consultation with health professionals and parents. The questionnaires were distributed through UK health professional and parent networks and mainstream and specialist schools.Results Diverse professional groups, including speech and language therapists, occupational therapists, paediatricians and dietitians, support children with EDSD and neurodisability. A range of parent-delivered interventions, such as food and drink modification, positioning and modification of mealtime environment, were recommended by health professionals and are used by and acceptable to parents. Health professionals thought the interventions were effective but parents’ views were less consistent. Both health professionals and parents rated better general health and improved nutrition as the most important outcomes.Conclusions These survey findings outline current UK practice of parent-delivered interventions for EDSD in young children with neurodisability. The survey suggests key outcomes to measure in assessing the effectiveness of interventions. Further research is now needed to fully evaluate the effectiveness of interventions and move towards an evidence-based approach to best practice.

Objectives To identify and map evidence about the consequences of unpaid caring for all carers of older people, and effective interventions to support this carer population.Design A rapid review of systematic reviews, focused on the consequences for carers of unpaid caring for older people, and interventions to support this heterogeneous group of carers. Reviews of carers of all ages were eligible, with any outcome measures relating to carers’ health, and social and financial well-being. Searches were conducted in MEDLINE, PsycInfo and Epistemonikos (January 2000 to January 2020). Records were screened, and included systematic reviews were quality appraised. Summary data were extracted and a narrative synthesis produced.Results Twelve systematic reviews reporting evidence about the consequences of caring for carers (n=6) and assessing the effectiveness of carer interventions (n=6) were included. The review evidence typically focused on mental health outcomes, with little information identified about carers’ physical, social and financial well-being. Clear estimates of the prevalence and severity of carer outcomes, and how these differ between carers and non-carers, were absent. A range of interventions were identified, but there was no strong evidence of effectiveness. In some studies, the choice of outcome measure may underestimate the full impact of an intervention.Conclusions Current evidence fails to fully quantify the impacts that caring for older people has on carers’ health and well-being. Information on social patterning of the consequences of caring is absent. Systematic measurement of a broad range of outcomes, with comparison to the general population, is needed to better understand the true consequences of caring. Classification of unpaid caring as a social determinant of health could be an effective lever to bring greater focus and support to this population. Further work is needed to develop and identify suitable interventions in order to support evidence-based policymaking and practice.

Abstract Background Atrial fibrillation (AF) represents the most common sustained cardiac arrhythmia. A service evaluation was carried out at an anticoagulation clinic in Newcastle upon-Tyne to explore the efficacy of introducing self-testing of anticoagulation status for AF patients on warfarin. The analysis presented aims to assess the potential cost savings and clinical outcomes associated with introducing self-testing at a clinic in the Northeast of England, and to determine the cost-effectiveness of a redesigned treatment pathway including genetic testing and self-testing components. Methods Questionnaires were administered to individuals participating in the service evaluation to understand the patient costs associated with clinical monitoring (139 patients), and quality-of-life before and after the introduction of self-testing (varying numbers). Additionally, data on time in therapeutic range (TTR) were captured at multiple time points to identify any change in outcome. Finally, an economic model was developed to assess the cost-effectiveness of introducing a redesigned treatment pathway, including genetic testing and self-testing, for AF patients. Results The average cost per patient of attending the anticoagulation clinic was £16.24 per visit (including carer costs). Costs were higher amongst patients tested at the hospital clinic than those tested at the community clinic. Improvements in quality-of-life across all psychological topics, and improved TTR, were seen following the introduction of self-testing. Results of the cost-effectiveness analysis showed that the redesigned treatment pathway was less costly and more effective than current practice. Conclusions Allowing AF patients on warfarin to self-test, rather than attend clinic to have their anticoagulation status assessed, has the potential to reduce patient costs. Additionally, self-testing may result in improved quality-of-life and TTR. Introducing genetic testing to guide patient treatment based on sensitivity to warfarin, and applying this in combination with self-testing, may also result in improved patient outcomes and reduced costs to the health service in the long-term.

Abstract Background Carbapenemase-producing Enterobacteriaceae (CPE), bacteria which are resistant to the carbapenem class of antibiotics, present an urgent public health risk. The objective of this study was to assess the potential costs and consequences of implementing a testing strategy involving a polymerase chain reaction (PCR)-based diagnostic test for CPE amongst high risk patients upon admission to UK hospitals, to replace the current culture-based testing strategy. Methods A decision-analytic model was developed to estimate the expected medical care costs associated with a PCR testing strategy for CPE compared with the current culture testing strategy, and to consider the consequences, in terms of the diagnostic accuracy and associated cost implications, of each approach. The modelled population were patients admitted to hospital at high risk of colonisation with CPE, with model pathways for current practice based on those described in the Public Health England (PHE) toolkit for CPE testing. Costs were estimated from a UK National Health Service (NHS) perspective, with outcomes presented in terms of percentage of samples identified as true positive, false positive, true negative and false negative following each method of testing. Results Results indicated that the PCR testing strategy led to an estimated cost saving of £462 per patient for a 5-day hospital stay. For all sensitivity analyses conducted, PCR testing resulted in an expected cost saving. Potential cost savings approached £850 per patient for the sensitivity analysis assuming a 15-day hospital stay, indicating that PCR testing results in greater cost savings as length of stay increases. Fewer false positive, and more true negative, cases were identified with the PCR testing strategy in all analyses conducted. Conclusions This economic analysis gives an insight into the potential cost savings that could be made by the UK NHS through the introduction of a PCR-based diagnostic testing strategy to replace current recommended culture-based methods for the detection of CPE. Savings are due primarily to a faster time to result with PCR, meaning that CPE-free patients are not isolated unnecessarily. Therefore, a PCR-based diagnostic may aid appropriate use of isolation resource.

Objectives A clear understanding of whether increases in longevity are spent in good health is necessary to support ageing, health and care-related policy.Design We conducted a systematic review to update and summarise evidence on trends in health expectancies, in Organisation for Economic Co-operation and Development (OECD) high-income countries.Data sources Four electronic databases (MEDLINE, 1946–19 September 2019; Embase 1980–2019 week 38; Scopus 1966–22 September 2019, Health Management Information Consortium, 1979–September 2019), and the UK Office for National Statistics website (November 2019).Eligibility criteria English language studies published from 2016 that reported trends in healthy, active and/or disability-free life expectancy in an OECD high-income country.Data extraction and synthesis Records were screened independently by two researchers. Study quality was assessed using published criteria designed to identify sources of bias in studies reporting trends, and evidence summarised by narrative synthesis.Findings Twenty-eight publications from 11 countries were included, covering periods from 6 to 40 years, between 1970 and 2017. In most countries, gains in healthy and disability-free life expectancy do not match the growth in total life expectancy. Exceptions were demonstrated for women in Sweden, where there were greater gains in disability-free years than life expectancy. Gains in healthy and disability-free life expectancy were greater for men than women in most countries except the USA (age 85), Japan (birth), Korea (age 65) and Sweden (age 77).Conclusion An expansion of disability in later life is evident in a number of high-income countries, with implications for the sustainability of health and care systems. The recent COVID-19 pandemic may also impact health expectancies in the longer term.

Background: Eating, drinking and swallowing difficulties are common in young children with neurodisability. These difficulties may lead to inadequate calorie intake, which affects a child’s nutrition, growth and general physical health. Objective: To examine which interventions are available that can be delivered at home by parents to improve eating, drinking and swallowing in young children with neurodisability and are suitable for investigation in pragmatic trials. Design: This was a mixed-methods study that included focus groups, surveys, an update of published systematic reviews of interventions, a systematic review of measurement properties of existing tools, evidence mapping, evidence synthesis, a Delphi survey and stakeholder workshops. Setting: The study was carried out in NHS hospitals, community services, family homes and schools. Participants: Parents of children who had neurodisability and eating, drinking and swallowing difficulties. Professionals from health and education. Young people with eating, drinking and swallowing difficulties or young people who had previously experienced eating, drinking and swallowing difficulties. Data sources: Literature reviews; national surveys of parents and professionals; focus groups with parents, young people and professionals; and stakeholder consultation workshops. Review methods: An update of published systematic reviews of interventions (searched July–August 2017), a mapping review (searched October 2017) and a systematic review of measurement properties using COnsensus-based Standards for the Selection of health status Measurement INstruments (COSMIN) methodology (searched May 2018). Results: Significant limitations of the available research evidence regarding interventions and tools to measure outcomes were identified. A total of 947 people participated: 400 parents, 475 health professionals, 62 education professionals and 10 young people. The survey showed the wide range of interventions recommended by NHS health professionals, with parents and professionals reporting variability in the provision of these interventions. Parents and professionals considered 19 interventions as relevant because they modified eating, drinking and swallowing difficulties. Parents and professionals considered 10 outcomes as important to measure (including Nutrition, Growth and Health/safety); young people agreed that these were important outcomes. Stakeholder consultation workshops identified that project conclusions and recommendations made sense, were meaningful and were valued by parents and professionals. Parents and health professionals were positive about a proposed Focus on Early Eating, Drinking and Swallowing (FEEDS) toolkit of interventions that, through shared decision-making, could be recommended by health professionals and delivered by families. Limitations: The national surveys included large numbers of parents and professionals but, as expected, these were not representative of the UK population of parents of children with eating, drinking and swallowing difficulties. Owing to the limitations of research evidence, pragmatic decisions were made about interventions that might be included in future research and outcomes that might be measured. For instance, the reviews of research found only weak or poor evidence to support the effectiveness of interventions. The review of outcome measures found only limited low-level evidence about their psychometric properties. Conclusions: Opportunities and challenges for conducting clinical trials of the effectiveness of the FEEDS toolkit of interventions are described. Parents and professionals thought that implementation of the toolkit as part of usual NHS practice was appropriate. However, this would first require the toolkit to be operationalised through development as a complex intervention, taking account of constituent interventions, delivery strategies, implementation and manualisation. Subsequently, an evaluation of its clinical effectiveness and cost-effectiveness could be undertaken using appropriate research methods. Future work: Initial steps include FEEDS toolkit development and evaluation of its use in clinical practice, and identification of the most robust methods to measure valued outcomes, such as Nutrition and Growth. Trial registration: Current Controlled Trials ISRCTN10454425. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 22. See the NIHR Journals Library website for further project information.

Objectives Frailty is typically assessed in older populations. Identifying frailty in adults aged under 60 years may also have value, if it supports the delivery of timely care. We sought to identify how frailty is measured in younger populations, including evidence of the impact on patient outcomes and care.Design A rapid review of primary studies was conducted.Data sources Four databases, three sources of grey literature and reference lists of systematic reviews were searched in March 2020.Eligibility criteria Eligible studies measured frailty in populations aged under 60 years using experimental or observational designs, published after 2000 in English.Data extraction and synthesis Records were screened against review criteria. Study data were extracted with 20% of records checked for accuracy by a second researcher. Data were synthesised using a narrative approach.Results We identified 268 studies that measured frailty in samples that included people aged under 60 years. Of these, 85 studies reported evidence about measure validity. No measures were identified that were designed and validated to identify frailty exclusively in younger groups. However, in populations that included people aged over and under 60 years, cumulative deficit frailty indices, phenotype measures, the FRAIL Scale, the Liver Frailty Index and the Short Physical Performance Battery all demonstrated predictive validity for mortality and/or hospital admission. Evidence of criterion validity was rare. The extent to which measures possess validity across the younger adult age (18–59 years) spectrum was unclear. There was no evidence about the impact of measuring frailty in younger populations on patient outcomes and care.Conclusions Limited evidence suggests that frailty measures have predictive validity in younger populations. Further research is needed to clarify the validity of measures across the adult age spectrum, and explore the utility of measuring frailty in younger groups.

Background and objectiveLoneliness is associated with increased rates of morbidity and mortality, and is a growing public health concern in later life. This study aimed to produce an evidence-based estimate of the prevalence of loneliness amongst older people (aged 60 years and above).Study design and settingSystematic review and random-effects meta-analysis of observational studies from high income countries 2008 to 2020, identified from searches of five electronic databases (Medline, EMBASE, PsychINFO, CINAHL, Proquest Social Sciences Premium Collection). Studies were included if they measured loneliness in an unselected population.ResultsThirty-nine studies reported data on 120,000 older people from 29 countries. Thirty-one studies were suitable for meta-analysis. The pooled prevalence estimate of loneliness was 28.5% (95%CI: 23.9% - 33.2%). In twenty-nine studies reporting loneliness severity, the pooled prevalence was 25.9% (95%CI: 21.6% - 30.3%) for moderate loneliness and 7.9% (95%CI: 4.8% - 11.6%) for severe loneliness (z = -6.1, p < 0.001). Similar pooled prevalence estimates were observed for people aged 65-75 years (27.6%, 95%CI: 22.6% - 33.0%) and over 75 years (31.3%, 95%CI: 21.0% - 42.7%, z = 0.64, p = 0.52). Lower levels of loneliness were reported in studies from Northern Europe compared to South and Eastern Europe.ConclusionsLoneliness is common amongst older adults affecting approximately one in four in high income countries. There is no evidence of an increase in the prevalence of loneliness with age in the older population. The burden of loneliness is an important public health and social problem, despite severe loneliness being uncommon.Prospero registrationCRD42017060472.

Background: One-fifth of all disabled children have mobility limitations. Early provision of powered mobility for very young children (aged

Background: This study aimed to identify and examine systematic review evidence of health and social care interventions for the community-dwelling older population regarding unplanned hospital admissions, timely hospital discharge and patient well-being. Methods: A meta-review was conducted using Joanna Briggs and PRISMA guidance. A search strategy was developed: eight bibliographic medical and social science databases were searched, and references of included studies checked. Searches were restricted to OECD countries and to systematic reviews published between January 2013–March 2018. Data extraction and quality appraisal was undertaken by one reviewer with a random sample screened independently by two others. Results: Searches retrieved 21,233 records; using data mining techniques, we identified 8,720 reviews. Following title and abstract and full-paper screening, 71 systematic reviews were included: 62 quantitative, seven qualitative and two mixed methods reviews. There were 52 reviews concerned with healthcare interventions and 19 reviews concerned with social care interventions. This meta-review summarises the evidence and evidence gaps of nine broad types of health and social care interventions. It scrutinises the presence of research in combined health and social care provision, finding it lacking in both definition and detail given. This meta-review debates the overlap of some of the person-centred support provided by community health and social care provision. Research recommendations have been generated by this process for both primary and secondary research. Finally, it proposes that research recommendations can be delivered on an ongoing basis if meta-reviews are conducted as living systematic reviews. Conclusions: This meta-review provides evidence of the effect of health and social care interventions for the community-dwelling older population and identification of evidence gaps. It highlights the lack of evidence for combined health and social care interventions and for the impact of social care interventions on health care outcomes. Registration: PROSPERO ID CRD42018087534; registered on 15 March 2018.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD.Methods and findingsWe conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83-2.76, p < 0.001, I2 99%). T2DM data were from 12 studies, with 22.8 million individuals followed up for a median of 10 years (IQR 6.4 to 16.9) experiencing 72,792 liver events. Fourteen studies were included in the meta-analysis of obesity (BMI > 30 kg/m2) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12-1.28, p < 0.001, I2 87%). There was also evidence to suggest that lipid abnormalities (low high-density lipoprotein and high triglycerides) and hypertension were both independently associated with incident severe liver disease. Significant study heterogeneity observed in the meta-analyses and possible under-publishing of smaller negative studies are acknowledged to be limitations, as well as the potential effect of competing risks on outcome.ConclusionsIn this review, we observed that T2DM is associated with a greater than 2-fold increase in the risk of developing severe liver disease. As the incidence of diabetes and obesity continue to rise, using these findings to improve case finding for people at high risk of liver disease will allow for effective management to help address the increasing morbidity and mortality from liver disease.Trial registrationPROSPERO CRD42018115459.

Abstract Background Intra-arterial thrombectomy is the gold standard treatment for large artery occlusive stroke. However, the evidence of its benefits is almost entirely based on trials delivered by experienced neurointerventionists working in established teams in neuroscience centres. Those responsible for the design and prospective reconfiguration of services need access to a comprehensive and complementary array of information on which to base their decisions. This will help to ensure the demonstrated effects from trials may be realised in practice and account for regional/local variations in resources and skill-sets. One approach to elucidate the implementation preferences and considerations of key experts is a Delphi survey. In order to support commissioning decisions, we aimed using an electronic Delphi survey to establish consensus on the options for future organisation of thrombectomy services among physicians with clinical experience in managing large artery occlusive stroke. Methods A Delphi survey was developed with 12 options for future organisation of thrombectomy services in England. A purposive sampling strategy established an expert panel of stroke physicians from the British Association of Stroke Physicians (BASP) Clinical Standards and/or Executive Membership that deliver 24/7 intravenous thrombolysis. Options with aggregate scores falling within the lowest quartile were removed from the subsequent Delphi round. Options reaching consensus following the two Delphi rounds were then ranked in a final exercise by both the wider BASP membership and the British Society of Neuroradiologists (BSNR). Results Eleven stroke physicians from BASP completed the initial two Delphi rounds. Three options achieved consensus, with subsequently wider BASP (97%, n = 43) and BSNR members (86%, n = 21) assigning the highest approval rankings in the final exercise for transferring large artery occlusive stroke patients to nearest neuroscience centre for thrombectomy based on local CT/CT Angiography. Conclusions The initial Delphi rounds ensured optimal reduction of options by an expert panel of stroke physicians, while subsequent ranking exercises allowed remaining options to be ranked by a wider group of experts within stroke to reach consensus. The preferred implementation option for thrombectomy is investigating suspected acute stroke patients by CT/CT Angiography and secondary transfer of large artery occlusive stroke patients to the nearest neuroscience (thrombectomy) centre.

Abstract Background National guidance on preventing type 2 diabetes mellitus (T2DM) in the UK recommends low-intensity lifestyle interventions for individuals with intermediate categories of hyperglycaemia defined in terms of impaired fasting glucose (IFG) or ‘at-risk’ levels of HbA1c. In a recent systematic review of economic evaluations of such interventions, most studies had evaluated intensive trial-based lifestyle programmes in participants with impaired glucose tolerance (IGT). This study examines the costs and effects of different intensity lifestyle programmes and metformin in participants with different categories of intermediate hyperglycaemia. Methods We developed a decision tree and Markov model (50-year horizon) to compare four approaches, namely (1) a low-intensity lifestyle programme based on current NICE guidance, (2) a high-intensity lifestyle programme based on the US Diabetes Prevention Program, (3) metformin, and (4) no intervention, modelled for three different types of intermediate hyperglycaemia (IFG, IGT and HbA1c). A health system perspective was adopted and incremental analysis undertaken at an individual and population-wide level, taking England as a case study. Results Low-intensity lifestyle programmes were the most cost-effective (£44/QALY, £195/QALY and £186/QALY compared to no intervention in IGT, IFG and HbA1c, respectively). Intensive lifestyle interventions were also cost-effective compared to no intervention (£2775/QALY, £6820/QALY and £7376/QALY, respectively, in IGT, IFG and HbA1c). Metformin was cost-effective relative to no intervention (£5224/QALY, £6842/QALY and £372/QALY in IGT, IFG and HbA1c, respectively), but was only cost-effective relative to other treatments in participants identified with HbA1c. At a willingness-to-pay threshold of £20,000/QALY, low- and high-intensity lifestyle programmes were cost-effective 98%, 99% and 98% and 81%, 81% and 71% of the time in IGT, IFG and HbA1c, respectively. An England-wide programme for 50–59 year olds could reduce T2DM incidence by

Background: Flexible, integrated models of service delivery are being developed to meet the changing demands of an ageing population. To underpin the spread of innovative models of care across the NHS, summaries of the current research evidence are needed. This report focuses exclusively on care homes and reviews work in four specific areas, identified as key enablers for the NHS England vanguard programme. Aim: To conduct a rapid synthesis of evidence relating to enhancing health in care homes across four key areas: technology, communication and engagement, workforce and evaluation. Objectives: (1) To map the published literature on the uses, benefits and challenges of technology in care homes; flexible and innovative uses of the nursing and support workforce to benefit resident care; communication and engagement between care homes, communities and health-related organisations; and approaches to the evaluation of new models of care in care homes. (2) To conduct rapid, systematic syntheses of evidence to answer the following questions. Which technologies have a positive impact on resident health and well-being? How should care homes and the NHS communicate to enhance resident, family and staff outcomes and experiences? Which measurement tools have been validated for use in UK care homes? What is the evidence that staffing levels (i.e. ratio of registered nurses and support staff to residents or different levels of support staff) influence resident outcomes? Data sources: Searches of MEDLINE, CINAHL, Science Citation Index, Cochrane Database of Systematic Reviews, DARE (Database of Abstracts of Reviews of Effects) and Index to Theses. Grey literature was sought via Google™ (Mountain View, CA, USA) and websites relevant to each individual search. Design: Mapping review and rapid, systematic evidence syntheses. Setting: Care homes with and without nursing in high-income countries. Review methods: Published literature was mapped to a bespoke framework, and four linked rapid critical reviews of the available evidence were undertaken using systematic methods. Data were not suitable for meta-analysis, and are presented in narrative syntheses. Results: Seven hundred and sixty-one studies were mapped across the four topic areas, and 65 studies were included in systematic rapid reviews. This work identified a paucity of large, high-quality research studies, particularly from the UK. The key findings include the following. (1) Technology: some of the most promising interventions appear to be games that promote physical activity and enhance mental health and well-being. (2) Communication and engagement: structured communication tools have been shown to enhance communication with health services and resident outcomes in US studies. No robust evidence was identified on care home engagement with communities. (3) Evaluation: 6 of the 65 measurement tools identified had been validated for use in UK care homes, two of which provide general assessments of care. The methodological quality of all six tools was assessed as poor. (4) Workforce: joint working within and beyond the care home and initiatives that focus on staff taking on new but specific care tasks appear to be associated with enhanced outcomes. Evidence for staff taking on traditional nursing tasks without qualification is limited, but promising. Limitations: This review was restricted to English-language publications after the year 2000. The rapid methodology has facilitated a broad review in a short time period, but the possibility of omissions and errors cannot be excluded. Conclusions: This review provides limited evidential support for some of the innovations in the NHS vanguard programme, and identifies key issues and gaps for future research and evaluation. Future work: Future work should provide high-quality evidence, in particular experimental studies, economic evaluations and research sensitive to the UK context. Study registration: This study is registered as PROSPERO CRD42016052933, CRD42016052933, CRD42016052937 and CRD42016052938. Funding: The National Institute for Health Research Health Services and Delivery Research programme.

Background: Urinary incontinence in women is a distressing condition that restricts quality of life and results in a large economic burden to both the NHS and women themselves. Objective: To evaluate the clinical effectiveness, safety and cost-effectiveness of surgical treatment for stress urinary incontinence (SUI) in women and explore women’s preferences. Design: An evidence synthesis, a discrete choice experiment (DCE) and an economic decision model, with a value-of-information (VOI) analysis. Nine surgical interventions were compared. Previous Cochrane reviews for each were identified and updated to include additional studies. Systematic review methods were applied. The outcomes of interest were ‘cure’ and ‘improvement’. Both a pairwise and a network meta-analysis (NMA) were conducted for all available surgical comparisons. A DCE was undertaken to assess the preferences of women for treatment outcomes. An economic model assessed the cost-effectiveness of alternative surgeries and a VOI analysis was undertaken. Results: Data from 175 studies were included in the effectiveness review. The majority of included studies were rated as being at high or unclear risk of bias across all risk-of-bias domains. The NMA, which included 120 studies that reported data on ‘cure’ or ‘improvement’, showed that retropubic mid-urethral sling (MUS), transobturator MUS, traditional sling and open colposuspension were more effective than other surgical procedures for both primary outcomes. The results for other interventions were variable. In general, rate of tape and mesh exposure was higher after transobturator MUS than after retropubic MUS or single-incision sling, whereas the rate of tape or mesh erosion/extrusion was similar between transobturator MUS and retropubic MUS. The results of the DCE, in which 789 women completed an anonymous online questionnaire, indicate that women tend to prefer surgical treatments associated with no pain or mild chronic pain and shorter length of hospital stay as well as those treatments that have a smaller risk for urinary symptoms to reoccur after surgery. The cost-effectiveness results suggest that, over a lifetime, retropubic MUS is, on average, the least costly and most effective surgery. However, the high level of uncertainty makes robust estimates difficult to ascertain. The VOI analysis highlighted that further research around the incidence rates of complications would be of most value. Limitations: Overall, the quality of the clinical evidence was low, with limited data available for the assessment of complications. Furthermore, there is a lack of robust evidence and significant uncertainty around some parameters in the economic modelling. Conclusions: To our knowledge, this is the most comprehensive assessment of published evidence for the treatment of SUI. There is some evidence that retropubic MUS, transobturator MUS and traditional sling are effective in the short to medium term and that retropubic MUS is cost-effective in the medium to long term. The VOI analysis highlights the value of further research to reduce the uncertainty around the incidence rates of complications. There is a need to obtain robust clinical data in future work, particularly around long-term complication rates. Study registration: This study is registered as PROSPERO CRD42016049339. Funding: The National Institute for Health Research Health Technology Assessment programme.

Diagnostic testing remains the backbone of the coronavirus disease 2019 (COVID-19) response, supporting containment efforts to mitigate the outbreak. The severity of this crisis and increasing capacity issues associated with polymerase chain reaction (PCR)-based testing, accelerated the development of diagnostic solutions to meet demands for mass testing. The National Institute for Health Research (NIHR) Innovation Observatory is the national horizon scanning organization in England. Since March, the Innovation Observatory has applied advanced horizon scanning methodologies and tools to compile a diagnostic landscape, based upon data captured for molecular (MDx) and immunological (IDx) based diagnostics (commercialized/in development), for the diagnosis of SARS-CoV-2. In total we identified and tracked 1608 diagnostics, produced by 1045 developers across 54 countries. Our dataset shows the speed and scale in which diagnostics were produced and provides insights into key periods of development and shifts in trends between MDx and IDx solutions as the pandemic progressed. Stakeholders worldwide required timely and detailed intelligence to respond to major challenges, including testing capacity and regulatory issues. Our intelligence assisted UK stakeholders with assessing priorities and mitigation options throughout the pandemic. Here we present the global evolution of diagnostic innovations devised to meet changing needs, their regulation and trends across geographical regions, providing invaluable insights into the complexity of the COVID-19 phenomena.

The amount of grey literature and 'softer' intelligence from social media or websites is vast. Given the long lead-times of producing high-quality peer-reviewed health information, this is causing a demand for new ways to provide prompt input for secondary research. To our knowledge, this is the first review of automated data extraction methods or tools for health-related grey literature and soft data, with a focus on (semi)automating horizon scans, health technology assessments (HTA), evidence maps, or other literature reviews. We searched six databases to cover both health- and computer-science literature. After deduplication, 10% of the search results were screened by two reviewers, the remainder was single-screened up to an estimated 95% sensitivity; screening was stopped early after screening an additional 1000 results with no new includes. All full texts were retrieved, screened, and extracted by a single reviewer and 10% were checked in duplicate. We included 84 papers covering automation for health-related social media, internet fora, news, patents, government agencies and charities, or trial registers. From each paper, we extracted data about important functionalities for users of the tool or method; information about the level of support and reliability; and about practical challenges and research gaps. Poor availability of code, data, and usable tools leads to low transparency regarding performance and duplication of work. Financial implications, scalability, integration into downstream workflows, and meaningful evaluations should be carefully planned before starting to develop a tool, given the vast amounts of data and opportunities those tools offer to expedite research.

Background: Approximately 9000 new cases of head and neck squamous cell cancers (HNSCCs) are treated by the NHS each year. Chemoradiation therapy (CRT) is a commonly used treatment for advanced HNSCC. Approximately 90% of patients undergoing CRT require nutritional support via gastrostomy or nasogastric tube feeding. Long-term dysphagia following CRT is a primary concern for patients. The effect of enteral feeding routes on swallowing function is not well understood, and the two feeding methods have, to date (at the time of writing), not been compared. The aim of this pilot randomised controlled trial (RCT) was to compare these two options. Methods: This was a mixed-methods multicentre study to establish the feasibility of a RCT comparing oral feeding plus pre-treatment gastrostomy with oral feeding plus as-required nasogastric tube feeding in patients with HNSCC. Patients were recruited from four tertiary centres treating cancer and randomised to the two arms of the study (using a 1 : 1 ratio). The eligibility criteria were patients with advanced-staged HNSCC who were suitable for primary CRT with curative intent and who presented with no swallowing problems. Main outcome measures: The primary outcome was the willingness to be randomised. A qualitative process evaluation was conducted alongside an economic modelling exercise. The criteria for progression to a Phase III trial were based on a hypothesised recruitment rate of at least 50%, collection of outcome measures in at least 80% of those recruited and an economic value-of-information analysis for cost-effectiveness. Results: Of the 75 patients approached about the trial, only 17 consented to be randomised [0.23, 95% confidence interval (CI) 0.13 to 0.32]. Among those who were randomised, the compliance rate was high (0.94, 95% CI 0.83 to 1.05). Retention rates were high at completion of treatment (0.94, 95% CI 0.83 to 1.05), at the 3-month follow-up (0.88, 95% CI 0.73 to 1.04) and at the 6-month follow-up (0.88, 95% CI 0.73 to 1.04). No serious adverse events were recorded in relation to the trial. The qualitative substudy identified several factors that had an impact on recruitment, many of which are amenable to change. These included organisational factors, changing cancer treatments and patient and clinician preferences. A key reason for the differential recruitment between sites was the degree to which the multidisciplinary team gave a consistent demonstration of equipoise at all patient interactions at which supplementary feeding was discussed. An exploratory economic model generated from published evidence and expert opinion suggests that, over the 6-month model time horizon, pre-treatment gastrostomy tube feeding is not a cost-effective option, although this should be interpreted with caution and we recommend that this should not form the basis for policy. The economic value-of-information analysis indicates that additional research to eliminate uncertainty around model parameters is highly likely to be cost-effective. Study limitations: The recruitment issues identified for this cohort may not be applicable to other populations undergoing CRT. There remains substantial uncertainty in the economic evaluation. Conclusions: The trial did not meet one of the three criteria for progression, as the recruitment rate was lower than hypothesised. Once patients were recruited to the trial, compliance and retention in the trial were both high. The implementation of organisational and operational measures can increase the numbers recruited. The economic analysis suggests that further research in this area is likely to be cost-effective. Future work: The implementation of organisational and operational measures can increase recruitment. The appropriate research question and design of a future study needs to be identified. More work is needed to understand the experiences of nasogastric tube feeding in patients undergoing CRT. Trial registration: Current Controlled Trials ISRCTN48569216. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 16. See the NIHR Journals Library website for further project information.

BackgroundBrazil has sought to use economic evaluation to support healthcare decision-making processes. While a number of health economic evaluations (HEEs) have been conducted, no study has systematically reviewed the quality of Brazilian HEE. The objective of this systematic review was to provide an overview regarding the state of HEE research and to evaluate the number, characteristics, and quality of reporting of published HEE studies conducted in a Brazilian setting.MethodsWe systematically searched electronic databases (MEDLINE, EMBASE, Latin American, and Caribbean Literature on Health Sciences Database, Scientific Electronic Library Online, NHS Economic Evaluation Database, health technology assessment Database, Bireme, and Biblioteca Virtual em Saúde Economia da Saúde); citation indexes (SCOPUS, Web of Science), and Sistema de Informação da Rede Brasileira de Avaliação de Tecnologia em Saúde. Partial and full HEEs published between 1980 and 2013 that referred to a Brazilian setting were considered for inclusion.ResultsIn total, 535 studies were included in the review, 36.8% of these were considered to be full HEE. The category of healthcare technologies more frequently assessed were procedures (34.8%) and drugs (28.8%) which main objective was treatment (72.1%). Forty-four percent of the studies reported their funding source and 36% reported a conflict of interest. Overall, the full HEE quality of reporting was satisfactory. But some items were generally poorly reported and significant improvement is required: (1) methods used to estimate healthcare resource use quantities and unit costs, (2) methods used to estimate utility values, (3) sources of funding, and (4) conflicts of interest.ConclusionA steady number of HEE have been published in Brazil since 1980. To improve their contribution to inform national healthcare policy efforts need to be made to enhance the quality of reporting of HEEs and promote improvements in the way HEEs are designed, implemented (i.e., using sound methods for HEEs) and reported.

Background: Hyperhidrosis is uncontrollable excessive sweating that occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. The management of hyperhidrosis is uncertain and variable. Objective: To establish the expected value of undertaking additional research to determine the most effective interventions for the management of refractory primary hyperhidrosis in secondary care. Methods: A systematic review and economic model, including a value-of-information (VOI) analysis. Treatments to be prescribed by dermatologists and minor surgical treatments for hyperhidrosis of the hands, feet and axillae were reviewed; as endoscopic thoracic sympathectomy (ETS) is incontestably an end-of-line treatment, it was not reviewed further. Fifteen databases (e.g. CENTRAL, PubMed and PsycINFO), conference proceedings and trial registers were searched from inception to July 2016. Systematic review methods were followed. Pairwise meta-analyses were conducted for comparisons between botulinum toxin (BTX) injections and placebo for axillary hyperhidrosis, but otherwise, owing to evidence limitations, data were synthesised narratively. A decision-analytic model assessed the cost-effectiveness and VOI of five treatments (iontophoresis, medication, BTX, curettage, ETS) in 64 different sequences for axillary hyperhidrosis only. Results and conclusions: Fifty studies were included in the effectiveness review: 32 randomised controlled trials (RCTs), 17 non-RCTs and one large prospective case series. Most studies were small, rated as having a high risk of bias and poorly reported. The interventions assessed in the review were iontophoresis, BTX, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland (e.g. laser, microwave). There is moderate-quality evidence of a large statistically significant effect of BTX on axillary hyperhidrosis symptoms, compared with placebo. There was weak but consistent evidence for iontophoresis for palmar hyperhidrosis. Evidence for other interventions was of low or very low quality. For axillary hyperhidrosis cost-effectiveness results indicated that iontophoresis, BTX, medication, curettage and ETS was the most cost-effective sequence (probability 0.8), with an incremental cost-effectiveness ratio of £9304 per quality-adjusted life-year. Uncertainty associated with study bias was not reflected in the economic results. Patients and clinicians attending an end-of-project workshop were satisfied with the sequence of treatments for axillary hyperhidrosis identified as being cost-effective. All patient advisors considered that the Hyperhidrosis Quality of Life Index was superior to other tools commonly used in hyperhidrosis research for assessing quality of life. Limitations: The evidence for the clinical effectiveness and safety of second-line treatments for primary hyperhidrosis is limited. This meant that there was insufficient evidence to draw conclusions for most interventions assessed and the cost-effectiveness analysis was restricted to hyperhidrosis of the axilla. Future work: Based on anecdotal evidence and inference from evidence for the axillae, participants agreed that a trial of BTX (with anaesthesia) compared with iontophoresis for palmar hyperhidrosis would be most useful. The VOI analysis indicates that further research into the effectiveness of existing medications might be worthwhile, but it is unclear that such trials are of clinical importance. Research that established a robust estimate of the annual incidence of axillary hyperhidrosis in the UK population would reduce the uncertainty in future VOI analyses. Study registration: This study is registered as PROSPERO CRD42015027803. Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: Recent policy and guidance has focused on chemotherapy services being offered closer to home, but the clinical and economic implications of this are uncertain. Objectives: To compare the impact of delivering intravenous chemotherapy in different settings on a range of outcomes, including quality of life, safety and costs. Design: Multimethods approach: systematic review of clinical effectiveness, qualitative and cost-effectiveness studies; description of the patient pathway and brief survey of current provision; and development of a decision model to explore aspects of cost-effectiveness. Setting: Provision of intravenous chemotherapy. Participants: Chemotherapy patients. Interventions: Setting in which chemotherapy was administered (home, community or outpatient). Outcome measures: Safety, quality of life, preference, satisfaction, opinions/experiences, social functioning, clinical outcomes, costs and resource/organisational issues. Data sources: Sixteen electronic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched from inception to October 2013 for published and unpublished studies. Review methods: Two reviewers independently screened potentially relevant studies, extracted data and quality assessed the included studies. Study validity was evaluated using appropriate quality assessment tools. Clinical effectiveness and cost-effectiveness studies were summarised narratively, and qualitative studies were synthesised using meta-ethnography. Results: Of the 67 eligible studies, 25 were comparative, with nine including a concurrent economic evaluation. Although some of the 10 randomised trials were designed to minimise avoidable biases, slow recruitment rates and non-participation of eligible patients for setting-related reasons meant that trial sample sizes were small and populations were inherently biased to favour the home or community settings. There was little evidence to suggest differences between settings in terms of quality of life, clinical outcomes, psychological outcomes or adverse events. All nine economic evaluations were judged as having low or uncertain quality, providing limited evidence to draw overall conclusions. Most were cost–consequence analyses, presenting cost outcomes alongside trial results but deriving no summary measure of benefit. Poor resource use reporting and use of different perspectives across settings made results difficult to compare. Seventeen qualitative studies (450 participants) were judged as moderate to good quality, although all compared new or proposed services with existing outpatient facilities and biased samples were used. The three main lines of argument were barriers to service provision, satisfaction with chemotherapy and making compromises to maintain normality. Most patients made explicit trade-offs between the time and energy required for outpatient chemotherapy, which reduced quality of life, and an increased sense of safety. A patient pathway was described, informed by expert advice and a brief survey of NHS and private providers, which identified wide variation in the ways in which home and community chemotherapy was delivered. Considering limitations of the available data and variation in provision, cost-effectiveness modelling results were not robust and were viewed as exploratory only; the results were highly unstable. Conclusions: Primary studies comparing settings for administering intravenous chemotherapy appear difficult to conduct. Consequently, few robust conclusions can be made about the clinical effectiveness and cost-effectiveness. Qualitative studies indicate that the patient time and energy required for outpatient chemotherapy reduces quality of life. A nested randomised controlled trial within a larger observational cohort of patients is proposed to enhance recruitment and improve generalisability of results. Future economic evaluations require detailed patient characteristic, resource use, cost and quality-of-life data, although their results are likely to have limited generalisability. Study registration: This study is registered as PROSPERO CRD42013004851. Funding: The National Institute for Health Research Health Services and Delivery Research programme.

Background: There has been growing interest in the NHS over recent years in the use of enhanced recovery programmes for elective surgery to deliver productivity gains through reduced length of stay, fewer postoperative complications, reduced readmissions and improved patient outcomes. Objectives: To evaluate the clinical effectiveness and cost-effectiveness of enhanced recovery programmes for patients undergoing elective surgery in acute hospital settings. To identify and critically describe key factors associated with successful adoption, implementation and sustainability of enhanced recovery programmes in UK settings. To summarise existing knowledge about patient experience of enhanced recovery programmes in UK settings. Data sources: Eight databases, including Database of Abstracts of Reviews and Effects, International Prospective of Systematic Reviews, NHS Economic Evaluation Database and MEDLINE, were searched from 1990 to March 2013 without language restrictions. Relevant reports and guidelines and reference lists of retrieved articles were scanned to identify additional studies. Review methods: Systematic reviews, randomised controlled trials (RCTs), economic evaluations, and UK NHS cost analysis studies were included if they evaluated the impact of enhanced recovery programmes on any health- and cost-related outcomes. Eligible studies included patients undergoing elective surgery in an acute hospital setting. Implementation case studies and surveys of patient experience in a UK setting were also eligible for inclusion. Quality assessment of systematic reviews, RCTs and economic evaluations was based on existing Centre for Reviews and Dissemination processes. All stages of the review process were performed by one researcher and checked by a second with discrepancies resolved by consensus. The type and range of evidence precluded meta-analysis and we therefore performed a narrative synthesis, differentiating between clinical effectiveness and cost-effectiveness, implementation case studies and evidence on patient experience. Results: Seventeen systematic reviews of varying quality were included in this report. Twelve additional RCTs were included; all were considered at high risk of bias. Most of the evidence focused on colorectal surgery. Fourteen innovation case studies and 15 implementation case studies undertaken in NHS settings were identified and provide descriptions of factors critical to the success of an enhanced recovery programme. Ten relevant economic evaluations were identified evaluating costs and outcomes over short time horizons. Despite the plethora of studies, robust evidence was sparse. Evidence for colorectal surgery suggests that enhanced recovery programmes may reduce hospital stays by 0.5–3.5 days compared with conventional care. There were no significant differences in reported readmission rates. Other surgical specialties showed greater variation in reported reductions in length of stay reflecting the limited evidence identified. Limitations: Findings relating to other clinical outcomes, cost-effectiveness, implementation and patient experience were hampered by a lack of robust evidence and poor reporting. Conclusions: There is consistent, albeit limited, evidence that enhanced recovery programmes may reduce length of patient hospital stay without increasing readmission rates. The extent to which managers and clinicians considering implementing enhanced recovery programmes can realise reductions and cost savings will depend on length of stays achieved under their existing care pathway. RCTs comparing an enhanced recovery programme with conventional care continue to be conducted and published. Further single-centre RCTs of this kind are not a priority. Rather, what is needed is improved collection and reporting of how enhanced recovery programmes are implemented, resourced and experienced in NHS settings. Funding: The National Institute for Health Research Health Services and Delivery Research programme.

Background: There is currently no standard practice for the monitoring of patients receiving treatment for osteoporosis. Repeated dual-energy X-ray absorptiometry (DXA) is commonly used for monitoring treatment response, but it has its limitations. Bone turnover markers have advantages over DXA as they are non-invasive, relatively cheap and can detect changes in bone turnover rates earlier. However, they do have disadvantages, particularly high within- and between-patient variability. The ability of bone turnover markers to identify treatment non-responders and predict future fracture risk has yet to be established. Objectives: We aimed to determine the clinical effectiveness, test accuracy, reliability, reproducibility and cost-effectiveness of bone turnover markers for monitoring the response to osteoporosis treatment. Data sources: We searched 12 electronic databases (including MEDLINE, EMBASE, The Cochrane Library and trials registries) without language restrictions from inception to March 2012. We hand-searched three relevant journals for the 12 months prior to May 2012, and websites of five test manufacturers and the US Food and Drug Administration (FDA). Reference lists of included studies and relevant reviews were also searched. Review methods: A systematic review of test accuracy, clinical utility, reliability and reproducibility, and cost-effectiveness of two formation and two resorption bone turnover markers, in patients being treated for osteoporosis with any of bisphosphonate [alendronate (Fosamax®, MSD), risedronate (Actonel®, Warner Chilcott Company), zolendronate (Zometa®, Novartis)], raloxifene (Evista®, Eli Lilly and Company Ltd), strontium ranelate (Protelos®, Servier Laboratories Ltd), denosumab (Prolia®, Amgen Ltd) or teriparatide (Forsteo®, Eli Lilly and Company Ltd), was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Given the breadth of the review question, a range of study designs and outcome measures were eligible. The development of a decision model was planned to determine the cost-effectiveness of bone turnover markers for informing changes in patient management if clinical effectiveness could be established. Results: Forty-two studies (70 publications) met the inclusion criteria; none evaluated cost-effectiveness. Only five were randomised controlled trials (RCTs); these assessed only the impact of bone marker monitoring on aspects of adherence. No RCTs evaluated the effectiveness of bone turnover marker monitoring on treatment management. One trial suggested that feedback of a good response decreased non-persistence [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.53 to 0.95], and feedback of a poor response increased non-persistence (HR 2.22, 95% CI 1.27 to 3.89); it is not clear whether or not the trial recruited a population representative of that seen in clinical practice. Thirty-three studies reported results of some assessment of test accuracy, mostly correlations between changes in bone turnover and bone mineral density. Only four studies reported on intra- or interpatient reliability and reproducibility in treated patients. Overall, the results were inconsistent and inconclusive, owing to considerable clinical heterogeneity across the studies and the generally small sample sizes. As clinical effectiveness of bone turnover monitoring could not be established, a decision-analytic model was not developed. Conclusions: There was insufficient evidence to inform the choice of which bone turnover marker to use in routine clinical practice to monitor osteoporosis treatment response. The research priority is to identify the most promising treatment–test combinations for evaluation in subsequent, methodologically sound, RCTs. In order to determine whether or not bone turnover marker monitoring improves treatment management decisions, and ultimately impacts on patient outcomes in terms of reduced incidence of fracture, RCTs are required. Given the large number of potential patient population–treatment–test combinations, the most promising combinations would initially need to be identified in order to ensure that any RCTs focus on evaluating those strategies. As a result, the research priority is to identify these promising combinations, by either conducting small variability studies or initiating a patient registry to collect standardised data. Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: During the COVID-19 pandemic ‘social distancing’ has highlighted the need to minimise loneliness and isolation among older adults (aged 50+). We wanted to know what remotely delivered befriending, social support and low intensity psychosocial interventions may help to alleviate social isolation and loneliness and how they work. Methods: We followed a systematic ‘review of reviews’ approach. Searches of 11 databases from the fields of health, social care, psychology and social science were undertaken during April 2020. Reviews meeting our PICOS criteria were included if they focussed on the evaluation of remote interventions to reduce levels of social isolation or loneliness in adults aged 50+ and were critically appraised using AMSTAR2. Narrative synthesis was used at a review and study level to develop a typology of intervention types and their effectiveness. Intervention Component Analysis (ICA) and Qualitative Comparative Analysis (QCA) were used at a study level to explore the characteristics of successful interventions. Results: We synthesised evidence from five systematic reviews and 18 primary studies. Remote befriending, social support and low intensity psychosocial interventions took the form of: (i) supported video-communication; (ii) online discussion groups and forums; (iii) telephone befriending; (iv) social networking sites; and (v) multi-tool interventions. The majority of studies utilised the first two approaches, and were generally regarded positively by older adults, although with mixed evidence around effectiveness. Focussing on processes and mechanisms, using ICA and QCA, we found that the interventions that were most successful in improving social support: (i) enabled participants to speak freely and to form close relationships; (ii) ensured participants have shared experiences/characteristics; (iii) included some form of pastoral guidance. Conclusions: The findings highlight a set of intervention processes that should be incorporated into interventions, although they do not lead us to recommend specific modes of support, due to the heterogeneity of interventions.

Background: During the 2020 COVID-19 pandemic, millions of older adults are advised to avoid contact with those outside their household. ‘Social distancing’ has highlighted the need to minimise loneliness and isolation through the provision of remotely delivered befriending, social support and low intensity psychosocial interventions. We wanted to know what interventions are effective and how they work to help inform decisions about different approaches. Methods: We followed a systematic ‘review of reviews’ approach and included systematic reviews focussed on the effectiveness or implementation of remote interventions to reduce levels of social isolation or loneliness in adults aged 50+. Searches of 11 databases were undertaken during April 2020 and eligible reviews were critically appraised using AMSTAR2. Narrative synthesis was used at a review and study level to develop a typology of intervention types and their effectiveness. Intervention Component Analysis (ICA) and Qualitative Comparative Analysis (QCA) were used at a study level to explore the characteristics of successful interventions. Results: We synthesised evidence from five systematic reviews and 18 primary studies. Remote befriending, social support and low intensity psychosocial interventions took the form of: (i) supported video-communication; (ii) online discussion groups and forums; (iii) telephone befriending; (iv) social networking sites; and (v) multi-tool interventions. The majority of studies utilised the first two approaches, and were generally regarded positively by older adults, although with mixed quantitative evidence around effectiveness. Focussing on processes and mechanisms, using ICA and QCA, we found that the interventions that were most effective in improving social support: (i) enabled participants to speak freely and to form close relationships; (ii) ensured participants have shared experiences/characteristics; (iii) included some form of pastoral guidance. Conclusions: The findings highlight a set of intervention processes that should be incorporated into interventions, although they do not lead us to recommend particular modes of remote support.