The Association between Blood Test Trends and Undiagnosed Cancer: A Systematic Review and Critical Appraisal.

Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient's individual baseline and important changes within the normal range. We aimed to review the published literature to understand the association between blood test trends and undiagnosed cancer. MEDLINE and EMBASE were searched until 15 May 2023 for studies assessing the association between blood test trends and undiagnosed cancer. We used descriptive summaries and narratively synthesised studies. We included 29 articles. Common blood tests were haemoglobin (24%, n = 7), C-reactive protein (17%, n = 5), and fasting blood glucose (17%, n = 5), and common cancers were pancreatic (29%, n = 8) and colorectal (17%, n = 5). Of the 30 blood tests studied, an increasing trend in eight (27%) was associated with eight cancer types, and a decreasing trend in 17 (57%) with 10 cancer types. No association was reported between trends in 11 (37%) tests and breast, bile duct, glioma, haematological combined, liver, prostate, or thyroid cancers. Our review highlights trends in blood tests that could facilitate the identification of individuals at increased risk of undiagnosed cancer. For most possible combinations of tests and cancers, there was limited or no evidence.

The association between restricted activity and patient outcomes in older adults: systematic literature review and meta-analysis.

BACKGROUND: Restricted activity is a potential early marker of declining health in older adults. Previous studies of this association with patient outcomes have been inconclusive. This review aimed to evaluate the extent to which restricted activity is associated with decline in health. METHODS: A search was conducted for studies including people over 65 years old which investigated the association between measures of restricted activity and hospitalisation, cognitive decline, and mortality. Following data extraction by two reviewers, eligible studies were summarised using Inverse Variance Heterogeneity meta-analysis. RESULTS: The search identified 8,434 unique publications, with 11 eligible studies. Three measures of restricted activity were identified: bed rest, restricted movement, and dependency for activities of daily living (ADL). Three studies looked at hospitalisations, with two finding a significant association with bed rest or restricted movement and one showing no evidence of an association. Restricted activity was associated with a significant increase in mortality across all three measures (bed rest odds ratio [OR] 6.34, 95%CI 2.51-16.02, I2 = 76%; restricted movement OR 5.38 95%CI 2.60-11.13, I2 = 69%; general ADL dependency OR 4.65 95%CI 2.25-9.26, I2 = 84%). The significant heterogeneity observed could not be explained by restricting the analysis by length of follow-up, or measure of restricted activity. No meta-analysis was conducted on the limited evidence for cognitive decline outcomes. CONCLUSIONS: Limited studies have considered the prognostic value of restricted activity in terms of predicting future declining health. Current evidence suggests restricted activity is associated with hospitalisation and mortality, and therefore could identify a group for whom early intervention might be possible.

Accuracy of prenatal and postnatal biomarkers for estimating gestational age: a systematic review and meta-analysis.

Background: Knowledge of gestational age (GA) is key in clinical management of individual obstetric patients, and critical to be able to calculate rates of preterm birth and small for GA at a population level. Currently, the gold standard for pregnancy dating is measurement of the fetal crown rump length at 11-14 weeks of gestation. However, this is not possible for women first presenting in later pregnancy, or in settings where routine ultrasound is not available. A reliable, cheap and easy to measure GA-dependent biomarker would provide an important breakthrough in estimating the age of pregnancy. Therefore, the aim of this study was to determine the accuracy of prenatal and postnatal biomarkers for estimating gestational age (GA). Methods: Systematic review prospectively registered with PROSPERO (CRD42020167727) and reported in accordance with the PRISMA-DTA. Medline, Embase, CINAHL, LILACS, and other databases were searched from inception until September 2023 for cohort or cross-sectional studies that reported on the accuracy of prenatal and postnatal biomarkers for estimating GA. In addition, we searched Google Scholar and screened proceedings of relevant conferences and reference lists of identified studies and relevant reviews. There were no language or date restrictions. Pooled coefficients of correlation and root mean square error (RMSE, average deviation in weeks between the GA estimated by the biomarker and that estimated by the gold standard method) were calculated. The risk of bias in each included study was also assessed. Findings: Thirty-nine studies fulfilled the inclusion criteria: 20 studies (2,050 women) assessed prenatal biomarkers (placental hormones, metabolomic profiles, proteomics, cell-free RNA transcripts, and exon-level gene expression), and 19 (1,738,652 newborns) assessed postnatal biomarkers (metabolomic profiles, DNA methylation profiles, and fetal haematological components). Among the prenatal biomarkers assessed, human chorionic gonadotrophin measured in maternal serum between 4 and 9 weeks of gestation showed the highest correlation with the reference standard GA, with a pooled coefficient of correlation of 0.88. Among the postnatal biomarkers assessed, metabolomic profiling from newborn blood spots provided the most accurate estimate of GA, with a pooled RMSE of 1.03 weeks across all GAs. It performed best for term infants with a slightly reduced accuracy for preterm or small for GA infants. The pooled RMSEs for metabolomic profiling and DNA methylation profile from cord blood samples were 1.57 and 1.60 weeks, respectively. Interpretation: We identified no antenatal biomarkers that accurately predict GA over a wide window of pregnancy. Postnatally, metabolomic profiling from newborn blood spot provides an accurate estimate of GA, however, as this is known only after birth it is not useful to guide antenatal care. Further prenatal studies are needed to identify biomarkers that can be used in isolation, as part of a biomarker panel, or in combination with other clinical methods to narrow prediction intervals of GA estimation. Funding: The research was funded by the Bill and Melinda Gates Foundation (INV-000368). ATP is supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the NIHR Biomedical Research Centre funding scheme. The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, the Department of Health, or the Department of Biotechnology. The funders of this study had no role in study design, data collection, analysis or interpretation of the data, in writing the paper or the decision to submit for publication.

The diagnostic accuracy of cardiac ultrasound for acute myocardial ischemia in the emergency department: a systematic review and meta-analysis.

BACKGROUND: Chest pain is responsible for millions of visits to the emergency department (ED) annually. Cardiac ultrasound can detect ischemic changes, but varying accuracy estimates have been reported in previous studies. We synthetized the available evidence to yield more precise estimates of the accuracy of cardiac ultrasound for acute myocardial ischemia in patients with chest pain in the ED and to assess the effect of different clinical characteristics on test accuracy. METHODS: A systematic search for studies assessing the diagnostic accuracy of cardiac ultrasound for myocardial ischemia in the ED was conducted in MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Web of Science, two trial registries and supplementary methods, from inception to December 6th, 2022. Prospective cohort, cross-sectional, case-control studies and randomized controlled trials (RCTs) that included data on diagnostic accuracy were included. Risk of bias was assessed with the QUADAS-2 tool and a bivariate hierarchical model was used for meta-analysis with paired Forest and SROC plots used to present the results. Subgroup analyses was conducted on clinically relevant factors. RESULTS: Twenty-nine studies were included, with 5043 patients. The overall summary sensitivity was 79.3% (95%CI 69.0-86.8%) and specificity was 87.3% (95%CI 79.9-92.2%), with substantial heterogeneity. Subgroup analyses showed increased sensitivity in studies where ultrasound was conducted at ED admission and increased specificity in studies that excluded patients with previous heart disease, when the target condition was acute coronary syndrome, or when final chart review was used as the reference standard. There was very low certainty in the results based on serious risk of bias and indirectness in most studies. CONCLUSIONS: Cardiac ultrasound may have a potential role in the diagnostic pathway of myocardial ischemia in the ED; however, a pooled accuracy must be interpreted cautiously given substantial heterogeneity and that important patient and test characteristics affect its diagnostic performance. PROTOCOL REGISTRATION: PROSPERO (CRD42023392058).

Brain health measurement: a scoping review.

OBJECTIVES: Preservation of brain health is an urgent priority for the world's ageing population. The evidence base for brain health optimisation strategies is rapidly expanding, but clear recommendations have been limited by heterogeneity in measurement of brain health outcomes. We performed a scoping review to systematically evaluate brain health measurement in the scientific literature to date, informing development of a core outcome set. DESIGN: Scoping review. DATA SOURCES: Medline, APA PsycArticles and Embase were searched through until 25 January 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they described brain health evaluation methods in sufficient detail in human adults and were in English language. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened titles, abstracts and full texts for inclusion and extracted data using Covidence software. RESULTS: From 6987 articles identified by the search, 727 studies met inclusion criteria. Study publication increased by 22 times in the last decade. Cohort study was the most common study design (n=609, 84%). 479 unique methods of measuring brain health were identified, comprising imaging, cognitive, mental health, biological and clinical categories. Seven of the top 10 most frequently used brain health measurement methods were imaging based, including structural imaging of grey matter and hippocampal volumes and white matter hyperintensities. Cognitive tests such as the trail making test accounted for 286 (59.7%) of all brain health measurement methods. CONCLUSIONS: The scientific literature surrounding brain health has increased exponentially, yet measurement methods are highly heterogeneous across studies which may explain the lack of clinical translation. Future studies should aim to develop a selected group of measures that should be included in all brain health studies to aid interstudy comparison (core outcome set), and broaden from the current focus on neuroimaging outcomes to include a range of outcomes.

Integrated palliative care in oncology: a protocol for a realist synthesis.

INTRODUCTION: Emerging evidence suggests improved quality of life, reduced symptom burden and lower health services costs when integrated palliative care and cancer care are implemented. Integrated palliative care aims to achieve care continuity by integrating organisational, administrative and clinical services involved in patient care networks. However, integrated palliative care for cancer is not common practice. This project, therefore, aims to understand how integrated palliative care and cancer care works in different healthcare settings (inpatient/outpatient), and for which groups of people (at what stage of the cancer journey), so we can develop guidance for optimal delivery. METHODS AND ANALYSIS: We will conduct a realist synthesis to develop a programme theory of how integrated palliative care in cancer works, for whom and in what contexts to achieve improved symptom management and quality of life for patients and their families.This realist synthesis will follow the five stages outlined by Pawson: (1) locating existing theories, (2) searching for evidence, (3) article selection, (4) extracting and organising data and (5) synthesising the evidence and drawing conclusions. We will work closely with our expert stakeholder group, which includes health and social care professionals providing palliative care and oncology; management and policy groups and members of the public and patients. We will adhere to RAMESES quality standards for undertaking a realist synthesis. ETHICS AND DISSEMINATION: Ethics approval for this project is not required.The realist synthesis will develop a programme theory that provides clarity on the optimal delivery of palliative care for adults with cancer. We will use the programme theory to coproduce guidance and user-friendly outputs, working with stakeholders to inform delivery of best practice. Findings will inform further research in integrated palliative care and cancer. Stakeholder engagement will assist in the dissemination of our findings. PROSPERO REGISTRATION NUMBER: CRD42023389791.

Adequacy of clinical guideline recommendations for patients with low-risk cancer managed with monitoring: systematic review.

OBJECTIVES: The aim of this systematic review was to summarize national and international guidelines that made recommendations for monitoring patients diagnosed with low-risk cancer. It appraised the quality of guidelines and determined whether the guidelines adequately identified patients for monitoring, specified which tests to use, defined monitoring intervals, and stated triggers for further intervention. It then assessed the evidence to support each recommendation. STUDY DESIGN AND SETTING: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses, we searched PubMed and Turning Research into Practice databases for national and international guidelines' that were written in English and developed or updated between 2012 and 2023. Quality of individual guidelines was assessed using the AGREE II tool. RESULTS: Across the 41 published guidelines, 48 different recommendations were identified: 15 (31%) for prostate cancer, 11 (23%) for renal cancer, 6 (12.5%) for thyroid cancer, and 10 (21%) for blood cancer. The remaining 6 (12.5%) were for brain, gastrointestinal, oral cavity, bone and pheochromocytoma and paraganglioma cancer. When combining all guidelines, 48 (100%) stated which patients qualify for monitoring, 31 (65%) specified which tests to use, 25 (52%) provided recommendations for surveillance intervals, and 23 (48%) outlined triggers to initiate intervention. Across all cancer sites, there was a strong positive trend with higher levels of evidence being associated with an increased likelihood of a recommendation being specific (P = 0.001) and the evidence for intervals was based on expert opinion or other guidance. CONCLUSION: With the exception of prostate cancer, the evidence base for monitoring low-risk cancer is weak and consequently recommendations in clinical guidelines are inconsistent. There is a lack of direct evidence to support monitoring recommendations in the literature making guideline developers reliant on expert opinion, alternative guidelines, or indirect or nonspecific evidence.

Disparities in COVID-19 mortality amongst the immunosuppressed: A systematic review and meta-analysis for enhanced disease surveillance.

BACKGROUND: Effective disease surveillance, including that for COVID-19, is compromised without a standardised method for categorising the immunosuppressed as a clinical risk group. METHODS: We conducted a systematic review and meta-analysis to evaluate whether excess COVID-associated mortality compared to the immunocompetent could meaningfully subdivide the immunosuppressed. Our study adhered to UK Immunisation against infectious disease (Green Book) criteria for defining and categorising immunosuppression. Using OVID (EMBASE, MEDLINE, Transplant Library, and Global Health), PubMed, and Google Scholar, we examined relevant literature between the entirety of 2020 and 2022. We selected for cohort studies that provided mortality data for immunosuppressed subgroups and immunocompetent comparators. Meta-analyses, grey literature and any original works that failed to provide comparator data or reported all-cause or paediatric outcomes were excluded. Odds Ratios (OR) and 95% confidence intervals (CI) of COVID-19 mortality were meta-analysed by immunosuppressed category and subcategory. Subgroup analyses differentiated estimates by effect measure, country income, study setting, level of adjustment, use of matching and publication year. Study screening, extraction and bias assessment were performed blinded and independently by two researchers; conflicts were resolved with the oversight of a third researcher. PROSPERO registration number is CRD42022360755. FINDINGS: We identified 99 unique studies, incorporating data from 1,542,097 and 56,248,181 unique immunosuppressed and immunocompetent patients with COVID-19 infection, respectively. Compared to immunocompetent people (pooled OR, 95%CI), solid organ transplants (2.12, 1.50-2.99) and malignancy (2.02, 1.69-2.42) patients had a very high risk of COVID-19 mortality. Patients with rheumatological conditions (1.28, 1.13-1.45) and HIV (1.20, 1.05-1.36) had just slightly higher risks than the immunocompetent baseline. Case type, setting income and mortality data matching and adjustment were significant modifiers of excess immunosuppressed mortality for some immunosuppressed subgroups. INTERPRETATION: Excess COVID-associated mortality among the immunosuppressed compared to the immunocompetent was seen to vary significantly across subgroups. This novel means of subdivision has prospective benefit for targeting patient triage, shielding and vaccination policies during periods of high disease transmission.

Effects of community-based interventions for stillbirths in sub-Saharan Africa: a systematic review and meta-analysis.

Background: Sub-Saharan Africa (SSA) alone contributed to 42% of global stillbirths in 2019, and the rate of stillbirth reduction has remained slow. There has been an increased uptake of community-based interventions to combat stillbirth in the region, but the effects of these interventions have been poorly assessed. Our objectives were to examine the effect of community-based interventions on stillbirth in SSA. Methods: In this systematic review and meta-analysis, we searched eight databases (MEDLINE [OvidSP], Embase [OvidSP], Cochrane Central Register of Controlled Trials, Global Health, Science Citation Index and Social Science Citation index [Web of Science Core Collection], CINAHL [EBSCOhost] and Global Index Medicus) and four grey literature sources from January 1, 2000 to July 7, 2023 for relevant studies from SSA. Community-based interventions targeting stillbirths solely or as part of complex interventions, with or without hospital interventions were included, while hospital-only interventions, microcredit schemes and maternity waiting home interventions were excluded. Study quality was assessed using the Cochrane risk of bias and National Heart, Lung and Blood Institute's tools. The study outcome was odds of stillbirth in intervention versus control communities. Pooled odds ratios (ORs) were estimated using random-effects models, and subgroup analyses were performed by intervention type and strategies. Publication bias was evaluated by funnel plot and Egger's test. This study is registered with PROSPERO, CRD42021296623. Findings: Of the 4223 records identified, seventeen studies from fifteen SSA countries were eligible for inclusion. One study had four arms (community only, hospital only, community and hospital, and control arms), so information was extracted from each arm. Analysis of 13 of the 17 studies which had community-only intervention showed that the odds of stillbirth did not vary significantly between community-based intervention and control groups (OR 0.96; 95% CI 0.78-1.17, I2 = 57%, p ≤ 0.01, n = 63,884). However, analysis of four (out of five) studies that included both community and health facility components found that in comparison with community only interventions, this combination strategy significantly reduced the odds of stillbirth by 17% (OR 0.83; 95% CI 0.79-0.87, I2 = 11%, p = 0.37, n = 244,868), after excluding a study with high risk of bias. The quality of the 17 studies were graded as poor (n = 2), fair (n = 9) and good (n = 6). Interpretation: Community-based interventions alone, without strengthening the quality and capacity of health facilities, are unlikely to have a substantial effect on reducing stillbirths in SSA. Funding: Nuffield Department of Population Health, Balliol College, the Clarendon Fund, Medical Research Council.

Psychometric Performance of Generic Childhood Multi-Attribute Utility Instruments in Preterm and Low Birthweight Populations: A Systematic Review.

BACKGROUND: Individuals born preterm (gestational age < 37 weeks) and/or at low birthweight (<2500 g) are at increased risk of health impairments from birth to adulthood. This review aimed to evaluate the psychometric performance of generic childhood-specific or childhood-compatible multi-attribute utility instruments (MAUIs) in preterm and/or low birthweight (PLB) populations. METHODS: Searches covered seven databases, including studies that targeted childhood (aged < 18 years) and/or adult (≥18 years) PLB populations; provided psychometric evidence for generic childhood-specific or compatible MAUI(s) (any language version); and published in English. Eighteen psychometric properties were evaluated using a four-part criteria rating system. Data syntheses identified psychometric evidence gaps and summarised the psychometric assessment methods/results. RESULTS: A total of 42 studies were included, generating 178 criteria rating outputs across four MAUIs: 17D, CHSCS-PS, HUI2, and HUI3. Moreover, 64.0% of outputs concerned the HUI3 MAUI, and 38.2% related to known-group validity. There was no evidence for five psychometric properties. Only 6.7% of outputs concerned reliability and proxy-child agreement. No MAUI outperformed others across all properties. The frequently applied HUI2 and HUI3 lacked content validity evidence. CONCLUSIONS: This psychometric evidence catalogue should inform the selection of MAUI(s) suited to the specific aims of applications targeting PLB populations. Further psychometric research is warranted to address the gaps in psychometric evidence.

The multifaceted consequences and economic costs of child anxiety problems: A systematic review and meta-analysis.

Background: Over a quarter of people have an anxiety disorder at some point in their life, with many first experiencing difficulties during childhood or adolescence. Despite this, gaps still exist in the current evidence base of the multiple consequences of childhood anxiety problems and their costs. Methods: A systematic review of Medline, PsycINFO, EconLit and the National Health Service Economic Evaluation Database was conducted for longitudinal and economic studies reporting on the association between childhood anxiety problems and at least one individual-, family- or societal-level outcome or cost. All studies were synthesised narratively. For longitudinal studies, 'effect direction' was used as a common metric, with random effects meta-analysis undertaken where possible. Results: Eighty-three studies met inclusion criteria and were synthesised narratively. We identified 788 separate analyses from the longitudinal studies, which we grouped into 15 overarching outcome domains. Thirteen of the studies were incorporated into 13 meta-analyses, which indicated that childhood anxiety disorders were associated with future anxiety, mood, behaviour and substance disorders. Narrative synthesis also suggested associations between anxiety problems and worse physical health, behaviour, self-harm, eating, relationship, educational, health care, employment, and financial outcomes. 'Effect direction' was conflicting in some domains due to a sparse evidence base. Higher economic costs were identified for the child, their families, healthcare providers and wider society, although evidence was limited and only covered short follow-up periods, up to a maximum of 2 years. Total annual societal costs per anxious child were up to £4040 (2021 GBP). Conclusions: Childhood anxiety problems are associated with impaired outcomes in numerous domains, and considerable economic costs, which highlight the need for cost-effective interventions and policies to tackle them. More economic evidence is needed to inform models of the long-term, economic-related, consequences of childhood anxiety problems.

Types, reporting and acceptability of community-based interventions for stillbirth prevention in sub-Saharan Africa (SSA): a systematic review.

Background: Community-based interventions are increasingly being implemented in Sub-Saharan Africa (SSA) for stillbirth prevention, but the nature of these interventions, their reporting and acceptability are poorly assessed. In addition to understanding their effectiveness, complete reporting of the methods, results and intervention acceptability is essential as it could potentially reduce research waste from replication of inadequately implemented and unacceptable interventions. We conducted a systematic review to investigate these aspects of community-based interventions for preventing stillbirths in SSA. Methods: In this systematic review, eight databases (MEDLINE(OvidSP), Embase (OvidSP), Cochrane Central Register of Controlled Trials, Global Health, Science Citation Index and Social Science Citation index (Web of Science Core Collection), CINAHL (EBSCOhost) and Global Index Medicus) and four grey literature sources were searched from January 1, 2000 to July 7, 2023 for relevant quantitative and qualitative studies from SSA (PROSPERO-CRD42021296623). Following deduplication, abstract screening and full-text review, studies were included if the interventions were community-based with or without a health facility component. The main outcomes were types of community-based interventions, completeness of intervention reporting using the TIDier (Template for Intervention Description and replication) checklist, and themes related to intervention acceptability identified using a theoretical framework. Study quality was assessed using the Cochrane risk of bias and National Heart, Lung and Blood Institute's tools. Findings: Thirty-nine reports from thirty-four studies conducted in 18 SSA countries were eligible for inclusion. Four types of interventions were identified: nutritional, infection prevention, access to skilled childbirth attendants and health knowledge/behaviour of women. These interventions were implemented using nine strategies: mHealth (defined as the use of mobile and wireless technologies to support the achievement of health objectives), women's groups, community midwifery, home visits, mass media sensitisation, traditional birth attendant and community volunteer training, community mobilisation and transport vouchers. The completeness of reporting using the TIDier checklist varied across studies with a very low proportion of the included studies reporting the intervention intensity, dosing, tailoring and modification. The quality of the included studies were graded as poor (n = 6), fair (n = 14) and good (n = 18). Though interventions were acceptable, only 4 (out of 7) studies explored women's perceptions, mostly focusing on perceived intervention effects and how they felt, omitting key constructs like ethicality, opportunity cost and burden of participation. Interpretation: Different community-based interventions have been tried and evaluated for stillbirth prevention in SSA. The reproducibility and implementation scale-up of these interventions may be limited by incomplete intervention descriptions in the published literature. To strengthen impact, it is crucial to holistically explore the acceptability of these interventions among women and their families. Funding: Clarendon/Balliol/NDPH DPhil scholarship for UGA. MN is funded by a Medical Research Council Transition Support Award (MR/W029294/1).

Primary care micro-teams: an international systematic review of patient and healthcare professional perspectives.

BACKGROUND: International trends have shifted to creating large general practices. There is an assumption that interdisciplinary teams will increase patient accessibility and provide more cost-effective, efficient services. Micro-teams have been proposed to mitigate for some potential challenges of practice expansion, including continuity of care. AIM: To review available literature and examine how micro-teams are described, and identify opportunities and limitations for patients and practice staff. DESIGN AND SETTING: This was an international systematic review of studies published in English. METHOD: Databases (MEDLINE, EMBASE, CINAHL, Cochrane Library, and Scopus) and grey literature were searched. Studies were included if they provided evidence about implementation of primary care micro-teams. Framework analysis was used to synthesise identified literature. The research team included a public contributor co-applicant. The authors conducted stakeholder discussions with those with and without experience of micro-team implementation. RESULTS: Of the 462 studies identified, 24 documents met the inclusion criteria. Most included empirical data from healthcare professionals, describing micro-team implementation. Results included characteristics of the literature; micro-team description; range of ways micro-teams have been implemented; reported outcomes; and experiences of patients and staff. CONCLUSION: The organisation of primary care has potential impact on the nature and quality of patient care, safety, and outcomes. This review contributes to current debate about care delivery and how this can impact on the experiences and outcomes of patients and staff. This analysis identifies several key opportunities and challenges for future research, policy, and practice.

The usage of data in NHS primary care commissioning: a realist review.

BACKGROUND: Primary care has been described as the 'bedrock' of the National Health Service (NHS) accounting for approximately 90% of patient contacts but is facing significant challenges. Against a backdrop of a rapidly ageing population with increasingly complex health challenges, policy-makers have encouraged primary care commissioners to increase the usage of data when making commissioning decisions. Purported benefits include cost savings and improved population health. However, research on evidence-based commissioning has concluded that commissioners work in complex environments and that closer attention should be paid to the interplay of contextual factors and evidence use. The aim of this review was to understand how and why primary care commissioners use data to inform their decision making, what outcomes this leads to, and understand what factors or contexts promote and inhibit their usage of data. METHODS: We developed initial programme theory by identifying barriers and facilitators to using data to inform primary care commissioning based on the findings of an exploratory literature search and discussions with programme implementers. We then located a range of diverse studies by searching seven databases as well as grey literature. Using a realist approach, which has an explanatory rather than a judgemental focus, we identified recurrent patterns of outcomes and their associated contexts and mechanisms related to data usage in primary care commissioning to form context-mechanism-outcome (CMO) configurations. We then developed a revised and refined programme theory. RESULTS: Ninety-two studies met the inclusion criteria, informing the development of 30 CMOs. Primary care commissioners work in complex and demanding environments, and the usage of data are promoted and inhibited by a wide range of contexts including specific commissioning activities, commissioners' perceptions and skillsets, their relationships with external providers of data (analysis), and the characteristics of data themselves. Data are used by commissioners not only as a source of evidence but also as a tool for stimulating commissioning improvements and as a warrant for convincing others about decisions commissioners wish to make. Despite being well-intentioned users of data, commissioners face considerable challenges when trying to use them, and have developed a range of strategies to deal with 'imperfect' data. CONCLUSIONS: There are still considerable barriers to using data in certain contexts. Understanding and addressing these will be key in light of the government's ongoing commitments to using data to inform policy-making, as well as increasing integrated commissioning.

Immunogenicity and seroefficacy of 10-valent and 13-valent pneumococcal conjugate vaccines: a systematic review and network meta-analysis of individual participant data.

Background: Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. Methods: In this systematic-review and network meta-analysis, we searched the Cochrane Library, Embase, Global Health, Medline, clinicaltrials.gov and trialsearch.who.int up to February 17, 2023 with no language restrictions. Studies were eligible if they presented data comparing the immunogenicity of either PCV7, PCV10 or PCV13 in head-to-head randomised trials of young children under 2 years of age, and provided immunogenicity data for at least one time point after the primary vaccination series or the booster dose. Publication bias was assessed via Cochrane's Risk Of Bias due to Missing Evidence tool and comparison-adjusted funnel plots with Egger's test. Individual participant level data were requested from publication authors and/or relevant vaccine manufacturers. Outcomes included the geometric mean ratio (GMR) of serotype-specific IgG and the relative risk (RR) of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Seroefficacy was defined as the RR of seroinfection. We also estimated the relationship between the GMR of IgG one month after priming and the RR of seroinfection by the time of the booster dose. The protocol is registered with PROSPERO, ID CRD42019124580. Findings: 47 studies were eligible from 38 countries across six continents. 28 and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. GMRs comparing PCV13 vs PCV10 favoured PCV13 for serotypes 4, 9V, and 23F at 1 month after primary vaccination series, with 1.14- to 1.54- fold significantly higher IgG responses with PCV13. Risk of seroinfection prior to the time of booster dose was lower for PCV13 for serotype 4, 6B, 9V, 18C and 23F than for PCV10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Two-fold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (RR 0.46, 95% CI 0.23-0.96). Interpretation: Serotype-specific differences were found in immunogenicity and seroefficacy between PCV13 and PCV10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These findings could be used to compare PCVs and optimise vaccination strategies. Funding: The NIHR Health Technology Assessment Programme.

Meta-review of the barriers and facilitators to women accessing perinatal mental healthcare.

Perinatal mental health (PMH) problems are common and can have an adverse impact on women and their families. However, research suggests that a substantial proportion of women with PMH problems do not access care. OBJECTIVES: To synthesise the results from previous systematic reviews of barriers and facilitators to women to seeking help, accessing help, and engaging in PMH care, and to suggest recommendations for clinical practice and policy. DESIGN: A meta-review of systematic reviews. REVIEW METHODS: Seven databases were searched and reviewed using a Preferred Reporting Items for Systematic Reviews and Meta Analyses search strategy. Studies that focused on the views of women seeking help and accessing PMH care were included. Data were analysed using thematic synthesis. Assessing the Methodological Quality of Systematic Reviews-2 was used to assess review methodology. To improve validity of results, a qualitative sensitivity analysis was conducted to assess whether themes remained consistent across all reviews, regardless of their quality rating. RESULTS: A total of 32 reviews were included. A wide range of barriers and facilitators to women accessing PMH care were identified. These mapped across a multilevel model of influential factors (individual, healthcare professional, interpersonal, organisational, political and societal) and across the care pathway (from decision to consult to receiving care). Evidence-based recommendations to support the design and delivery of PMH care were produced based on identified barriers and facilitators. CONCLUSION: The identified barriers and facilitators point to a complex interplay of many factors, highlighting the need for an international effort to increase awareness of PMH problems, reduce mental health stigma, and provide woman-centred, flexible care, delivered by well trained and culturally sensitive primary care, maternity, and psychiatric health professionals. PROSPERO REGISTRATION NUMBER: CRD42019142854.

Digital undergraduate medical education and patient and carer involvement: a rapid systematic review of current practice.

BACKGROUND: Involving patients and carers in medical students' learning aims to centralise the perspective of healthcare users and supports our future medical workforce in the development of key skills. Medical schools are increasingly using digital technology for teaching and it is timely to understand how to maintain patient and carer involvement in this context. METHODS: Ovid MEDLINE, Ovid EMBASE and medRxiv were searched in October 2020 and reference lists of key articles were hand searched. Eligible studies reported authentic patient or carer involvement in undergraduate medical education where technology was also used. Study quality was assessed by the Mixed Methods Appraisal Tool (MMAT). Levels of patient or carer involvement were assessed using Towle et al.'s (2010) taxonomy, from Level 1 (lowest level) to Level 6 (highest level). RESULTS: Twenty studies were included in this systematic review. In 70% of studies, patients and carers featured in video or web-based case scenarios with no interaction between healthcare users and students. The remaining 30% of studies reported real-time interactions between students and patients via remote clinical encounters. Digital teaching sessions involving patients or carers were perceived to be valuable by students and educators, and increased student engagement, patient-centred attitudes, clinical knowledge, and communication skills. No studies reported the perspective of patients or carers. DISCUSSION: Digital technology has not yet driven higher levels of patient and carer involvement in medical training. "Live" interactions between students and patients are becoming more common but challenges need addressing to ensure positive experiences for all involved. Future teaching should enhance the role of patients and carers in medical education and support them to overcome any potential barriers to doing so remotely.

Systematic Review of the Psychometric Performance of Generic Childhood Multi-attribute Utility Instruments.

BACKGROUND: Childhood multi-attribute utility instruments (MAUIs) can be used to measure health utilities in children (aged ≤ 18 years) for economic evaluation. Systematic review methods can generate a psychometric evidence base that informs their selection for application. Previous reviews focused on limited sets of MAUIs and psychometric properties, and only on evidence from studies that directly aimed to conduct psychometric assessments. OBJECTIVE: This study aimed to conduct a systematic review of psychometric evidence for generic childhood MAUIs and to meet three objectives: (1) create a comprehensive catalogue of evaluated psychometric evidence; (2) identify psychometric evidence gaps; and (3) summarise the psychometric assessment methods and performance by property. METHODS: A review protocol was registered with the Prospective Register of Systematic Reviews (PROSPERO; CRD42021295959); reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline. The searches covered seven academic databases, and included studies that provided psychometric evidence for one or more of the following generic childhood MAUIs designed to be accompanied by a preference-based value set (any language version): 16D, 17D, AHUM, AQoL-6D, CH-6D, CHSCS-PS, CHU9D, EQ-5D-Y-3L, EQ-5D-Y-5L, HUI2, HUI3, IQI, QWB, and TANDI; used data derived from general and/or clinical childhood populations and from children and/or proxy respondents; and were published in English. The review included 'direct studies' that aimed to assess psychometric properties and 'indirect studies' that generated psychometric evidence without this explicit aim. Eighteen properties were evaluated using a four-part criteria rating developed from established standards in the literature. Data syntheses identified psychometric evidence gaps and summarised the psychometric assessment methods/results by property. RESULTS: Overall, 372 studies were included, generating a catalogue of 2153 criteria rating outputs across 14 instruments covering all properties except predictive validity. The number of outputs varied markedly by instrument and property, ranging from 1 for IQI to 623 for HUI3, and from zero for predictive validity to 500 for known-group validity. The more recently developed instruments targeting preschool children (CHSCS-PS, IQI, TANDI) have greater evidence gaps (lack of any evidence) than longer established instruments such as EQ-5D-Y, HUI2/3, and CHU9D. The gaps were prominent for reliability (test-retest, inter-proxy-rater, inter-modal, internal consistency) and proxy-child agreement. The inclusion of indirect studies (n = 209 studies; n = 900 outputs) increased the number of properties with at least one output of acceptable performance. Common methodological issues in psychometric assessment were identified, e.g., lack of reference measures to help interpret associations and changes. No instrument consistently outperformed others across all properties. CONCLUSION: This review provides comprehensive evidence on the psychometric performance of generic childhood MAUIs. It assists analysts involved in cost-effectiveness-based evaluation to select instruments based on the application-specific minimum standards of scientific rigour. The identified evidence gaps and methodological issues also motivate and inform future psychometric studies and their methods, particularly those assessing reliability, proxy-child agreement, and MAUIs targeting preschool children.

Facility-based stillbirth review processes used in different countries across the world: a systematic review.

Background: Facility-based stillbirth review provides opportunities to estimate incidence, evaluate causes and risk factors for stillbirths, and identify any issues related to the quality of pregnancy and childbirth care which require improvement. Our aim was to systematically review all types and methods of facility-based stillbirth review processes used in different countries across the world, to examine how stillbirth reviews in facility settings are being conducted worldwide and to identify the outcomes of implementing the reviews. Moreover, to identify facilitators and barriers influencing the implementation of the identified facility-based stillbirth reviews processes by conducting subgroup analyses. Methods: A systematic review of published literature was conducted by searching MEDLINE (OvidSP) [1946-present], EMBASE (OvidSP) [1974-present], WHO Global Index Medicus (globalindexmedicus.net), Global Health (OvidSP) [1973-2022 Week 8] and CINAHL (EBSCOHost) [1982-present] from their inception until 11 January, 2023. For unpublished or grey literature, the WHO databases, Google Scholar and ProQuest Dissertations & Theses Global were searched, as well as hand searching the reference lists of included studies. MESH terms encompassing "∗Clinical Audit", "∗Perinatal Mortality", "Pregnancy Complications", and "Stillbirth" were used with Boolean operators. Studies that used a facility-based review process or any approach to evaluate care prior to stillbirth, and explained the methods used were included. Reviews and editorials were excluded. Three authors (YYB, UGA, and DBT) independently screened and extracted data, and assessed the risk of bias using an adapted JBI's Checklist for Case Series. A logic model was used to inform the narrative synthesis. The review protocol was registered with PROSPERO, CRD42022304239. Findings: A total of 68 studies from 17 high-income (HICs) and 22 low-and-middle-income countries (LMICs) met the inclusion criteria from a total of 7258 identified records. These were stillbirth reviews conducted at different levels: district, state, national, and international. Three types were identified: audit, review, and confidential enquiry, but not all desired components were included in most processes, which led to a mismatch between the description of the type and the actual method used. Routine data from hospital records was the most common data source for identifying stillbirths, and case assessment was based on stillbirth definition in 48 out of 68 studies. Hospital notes were the most common source of information about care received and causes/risk factors for stillbirth. Short-term and medium-term outcomes were reported in 14 studies, but impact of the review process on reducing stillbirth, which is more difficult to establish, was not reported in any study. Facilitators and barriers in implementing a successful stillbirth review process identified from 14 studies focused on three main themes: resources, expertise, and commitment. Interpretation: This systematic review's findings identified that there is a need for clear guidelines on how to measure the impact of implementation of changes based on outputs of stillbirth reviews and methods to enable effective dissemination of learning points in the future and promoting them through training platforms. In addition, there is a need to develop and adopt a universal definition of stillbirth to facilitate meaningful comparison of stillbirth rates between regions. The key limitation of this review is that while using a logic model for narrative synthesis was deemed most appropriate for this study, sequence of implementing a stillbirth review in the real world is not linear, and assumptions are often not met. Therefore, the logic model proposed in this study should be interpreted with flexibility when designing a stillbirth review process. The generated learnings from the stillbirth review processes inform the action plans and allow facilities to consider where the changes should happen to improve the quality of care in the facilities, enabling positive short-term and medium-term outcomes. Funding: Kellogg College, University of Oxford, Clarendon Fund, University of Oxford, Nuffield Department of Population Health, University of Oxford and Medical Research Council (MRC).

Systematic review of economic evaluations of varicella vaccination programmes.

OBJECTIVES: This study carried out a systematic literature review of economic evaluations of varicella vaccination programmes from the earliest publication to the present day, including programmes in the workplace and in special risk groups as well as universal childhood vaccination and catch up programmes. METHODS: Articles published from 1985 until 2022 were sourced from PubMed/Medline, Embase, Web of Science, NHSEED and Econlit. Eligible economic evaluations, which included posters and conference abstracts, were identified by two reviewers who scrutinised each other's selections at both title and abstract and full report stages. The studies are described in terms of their methodological characteristics. Their results are aggregated by type of vaccination programme and the nature of the economic outcome. RESULTS: A total of 2575 articles were identified of which 79 qualified as economic evaluations. A total of 55 studies focused on universal childhood vaccination, 10 on the workplace and 14 on high risk groups. Twenty-seven studies reported estimates of incremental cost per quality-adjusted life year (QALY) gained, 16 reported benefit-cost ratios, 20 reported cost-effectiveness outcomes in terms of incremental cost per event or life saved and 16 reported cost-cost offset results. Most studies of universal childhood vaccination reported an increase in overall costs to health services, but often a reduction in cost from a societal perspective. CONCLUSIONS: The evidence surrounding the cost-effectiveness of varicella vaccination programmes remains sparse with contrasting conclusions in some areas. Future research should particularly aim to encompass the impact of universal childhood vaccination programmes on herpes zoster among adults.