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The Oxford Royal College of General Practitioners Clinical Informatics Digital Hub: Protocol to develop extended COVID-19 surveillance and trial platforms
Background: Routinely recorded primary care data have been used for many years by sentinel networks for surveillance. More recently, real world data have been used for a wider range of research projects to support rapid, inexpensive clinical trials. Because the partial national lockdown in the United Kingdom due to the coronavirus disease (COVID-19) pandemic has resulted in decreasing community disease incidence, much larger numbers of general practices are needed to deliver effective COVID-19 surveillance and contribute to in-pandemic clinical trials. Objective: The aim of this protocol is to describe the rapid design and development of the Oxford Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) and its first two platforms. The Surveillance Platform will provide extended primary care surveillance, while the Trials Platform is a streamlined clinical trials platform that will be integrated into routine primary care practice. Methods: We will apply the FAIR (Findable, Accessible, Interoperable, and Reusable) metadata principles to a new, integrated digital health hub that will extract routinely collected general practice electronic health data for use in clinical trials and provide enhanced communicable disease surveillance. The hub will be findable through membership in Health Data Research UK and European metadata repositories. Accessibility through an online application system will provide access to study-ready data sets or developed custom data sets. Interoperability will be facilitated by fixed linkage to other key sources such as Hospital Episodes Statistics and the Office of National Statistics using pseudonymized data. All semantic descriptors (ie, ontologies) and code used for analysis will be made available to accelerate analyses. We will also make data available using common data models, starting with the US Food and Drug Administration Sentinel and Observational Medical Outcomes Partnership approaches, to facilitate international studies. The Surveillance Platform will provide access to data for health protection and promotion work as authorized through agreements between Oxford, the Royal College of General Practitioners, and Public Health England. All studies using the Trials Platform will go through appropriate ethical and other regulatory approval processes. Results: The hub will be a bottom-up, professionally led network that will provide benefits for member practices, our health service, and the population served. Data will only be used for SQUIRE (surveillance, quality improvement, research, and education) purposes. We have already received positive responses from practices, and the number of practices in the network has doubled to over 1150 since February 2020. COVID-19 surveillance has resulted in tripling of the number of virology sites to 293 (target 300), which has aided the collection of the largest ever weekly total of surveillance swabs in the United Kingdom as well as over 3000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology samples. Practices are recruiting to the PRINCIPLE (Platform Randomised trial of INterventions against COVID-19 In older PeopLE) trial, and these participants will be followed up through ORCHID. These initial outputs demonstrate the feasibility of ORCHID to provide an extended national digital health hub. Conclusions: ORCHID will provide equitable and innovative use of big data through a professionally led national primary care network and the application of FAIR principles. The secure data hub will host routinely collected general practice data linked to other key health care repositories for clinical trials and support enhanced in situ surveillance without always requiring large volume data extracts. ORCHID will support rapid data extraction, analysis, and dissemination with the aim of improving future research and development in general practice to positively impact patient care.
Medications that reduce emergency hospital admissions: An overview of systematic reviews and prioritisation of treatments
Background: Rates of emergency hospitalisations are increasing in many countries, leading to disruption in the quality of care and increases in cost. Therefore, identifying strategies to reduce emergency admission rates is a key priority. There have been large-scale evidence reviews to address this issue; however, there have been no reviews of medication therapies, which have the potential to reduce the use of emergency health-care services. The objectives of this study were to review systematically the evidence to identify medications that affect emergency hospital admissions and prioritise therapies for quality measurement and improvement. Methods: This was a systematic review of systematic reviews. We searched MEDLINE, PubMed, the Cochrane Database of Systematic Reviews & Database of Abstracts of Reviews of Effects, Google Scholar and the websites of ten major funding agencies and health charities, using broad search criteria. We included systematic reviews of randomised controlled trials that examined the effect of any medication on emergency hospital admissions among adults. We assessed the quality of reviews using AMSTAR. To prioritise therapies, we assessed the quality of trial evidence underpinning meta-analysed effect estimates and cross-referenced the evidence with clinical guidelines. Results: We identified 140 systematic reviews, which included 1968 unique randomised controlled trials and 925,364 patients. Reviews contained 100 medications tested in 47 populations. We identified high-to moderate-quality evidence for 28 medications that reduced admissions. Of these medications, 11 were supported by clinical guidelines in the United States, the United Kingdom and Europe. These 11 therapies were for patients with heart failure (angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, aldosterone receptor antagonists and digoxin), stable coronary artery disease (intensive statin therapy), asthma exacerbations (early inhaled corticosteroids in the emergency department and anticholinergics), chronic obstructive pulmonary disease (long-acting muscarinic antagonists and long-acting beta-2 adrenoceptor agonists) and schizophrenia (second-generation antipsychotics and depot/maintenance antipsychotics). Conclusions: We identified 11 medications supported by strong evidence and clinical guidelines that could be considered in quality monitoring and improvement strategies to help reduce emergency hospital admission rates. The findings are relevant to health systems with a large burden of chronic disease and those managing increasing pressures on acute health-care services.
Influenza and Respiratory Virus Surveillance, Vaccine Uptake, and Effectiveness at a Time of Cocirculating COVID-19: Protocol for the English Primary Care Sentinel System for 2020-2021 (Preprint)
BACKGROUND The Oxford–Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) are commencing their 54th season of collaboration at a time when SARS-CoV-2 infections are likely to be cocirculating with the usual winter infections. OBJECTIVE The aim of this study is to conduct surveillance of influenza and other monitored respiratory conditions and to report on vaccine uptake and effectiveness using nationally representative surveillance data extracted from primary care computerized medical records systems. We also aim to have general practices collect virology and serology specimens and to participate in trials and other interventional research. METHODS The RCGP RSC network comprises over 1700 general practices in England and Wales. We will extract pseudonymized data twice weekly and are migrating to a system of daily extracts. First, we will collect pseudonymized, routine, coded clinical data for the surveillance of monitored and unexpected conditions; data on vaccine exposure and adverse events of interest; and data on approved research study outcomes. Second, we will provide dashboards to give general practices feedback about levels of care and data quality, as compared to other network practices. We will focus on collecting data on influenza-like illness, upper and lower respiratory tract infections, and suspected COVID-19. Third, approximately 300 practices will participate in the 2020-2021 virology and serology surveillance; this will include responsive surveillance and long-term follow-up of previous SARS-CoV-2 infections. Fourth, member practices will be able to recruit volunteer patients to trials, including early interventions to improve COVID-19 outcomes and point-of-care testing. Lastly, the legal basis for our surveillance with PHE is Regulation 3 of the Health Service (Control of Patient Information) Regulations 2002; other studies require appropriate ethical approval. RESULTS The RCGP RSC network has tripled in size; there were previously 100 virology practices and 500 practices overall in the network and we now have 322 and 1724, respectively. The Oxford–RCGP Clinical Informatics Digital Hub (ORCHID) secure networks enable the daily analysis of the extended network; currently, 1076 practices are uploaded. We are implementing a central swab distribution system for patients self-swabbing at home in addition to in-practice sampling. We have converted all our primary care coding to Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) coding. Throughout spring and summer 2020, the network has continued to collect specimens in preparation for the winter or for any second wave of COVID-19 cases. We have collected 5404 swabs and detected 623 cases of COVID-19 through extended virological sampling, and 19,341 samples have been collected for serology. This shows our preparedness for the winter season. CONCLUSIONS The COVID-19 pandemic has been associated with a groundswell of general practices joining our network. It has also created a permissive environment in which we have developed the capacity and capability of the national primary care surveillance systems and our unique public health institute, the RCGP and University of Oxford collaboration.
Validity and timeliness of cancer diagnosis data collected during a prospective cohort study and reported by the English and Welsh cancer registries: a retrospective, comparative analysis
Background: Cancer places a high burden on society and health-care systems. Cancer research requires high-quality data, which is resource-intensive to obtain. Using administrative datasets such as cancer registries could improve the efficiency of cancer studies if data were valid and timely. We aimed to compare the validity and timeliness of diagnostic cancer data on-site during the SYMPLIFY study to that obtained from the cancer registries of England and Wales. Methods: Cancer data were collected from 5461 participants across 44 hospital sites during a prospective observational study in England and Wales, SYMPLIFY (ISRCTN10226380). Linked cancer data were obtained from Digital Health and Care Wales (DHCW), the Welsh Cancer Intelligence and Surveillance Unit (WCISU), and the English National Cancer Registration Dataset (NCRD) and Rapid Cancer Registration Dataset (RCRD), regularly between April, 2022, and September, 2023. The primary objectives of the study were to evaluate the validity (via assessment of the proportion of completed data fields and concordance with SYMPLIFY sites), and timeliness of the data in all datasets, for all cancers diagnosed within 9 months of study enrolment. Data fields investigated were cancer site via International Classification of Disease, 10th Revision (ICD-10) code; cancer morphology via International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3) morphology histology code and broad morphological grouping; overall stage; and TNM classification. Findings: For data collected between April, 2022, and September, 2023, completeness at the last data cut available for each dataset ranged from 84% to 100% for ICD-O-3 morphology, from 43% to 100% for overall stage, and from 74% to 83% for TNM stage. The concordance between SYMPLIFY data and NCRD was 96% (95% CI 92–98) for ICD-10, 60% (53–66) for ICD-O-3 morphology, 83% (78–88) for ICD-O-3 broad morphology groupings, 73% (67–78) for stage, and 51% (44–59) for TNM; and with WCISU was 89% (95% CI 81–94) for ICD-10, 63% (53–73) for ICD-O-3 morphology, 80% (70–87) for ICD-O-3 broad morphology groupings, 83% (74–90) for overall stage, and 49% (38–61) for TNM stage. Concordance between SYMPLIFY and RCRD was 95% (95% CI 92–98) for ICD-10, 67% (60–74) for ICD-O-3 morphology, 85% (79–90) for ICD-O-3 broad morphology groupings, and 73% (65–80) for overall stage; and between SYMPLIFY and DHCW was 96% (91–99) for ICD-10, 74% (64–83) for ICD-O-3 morphology, 84% (75–91) for ICD-O-3 broad morphology groupings, and 87% (74–95) for stage. The SYMPLIFY dataset reached completion at 12 months post-enrolment in November, 2022, compared with 13 months for NCRD in December, 2023. RCRD and DHCW reached completion at 13 months and 15 months post-enrolment, in December, 2022, and February, 2023, respectively. Interpretation: We report similar completeness of data fields, concordance, and timeliness between on-site and centrally collected cancer outcomes data. Our findings suggest that central registry data can help alleviate the resource burden in clinical trials and improve cancer research. Cancer registries might need additional resources to provide data for registry-based trials at scale. Funding: GRAIL Bio UK.
Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study (update)
Objective: To quantify the predictive value of unexpected weight loss for cancer according to patient's age, sex, smoking status, and concurrent clinical features (symptoms, signs, and abnormal blood test results). Design: Diagnostic accuracy study (update). Setting: Data from Clinical Practice Research Datalink electronic health records linked to the National Cancer Registration and Analysis Service in primary care, England. Participants: 326 240 adults (≥18 years) with a code for unexpected weight loss from 1 January 2000 to 31 December 2019. Main outcome measures: Cancer diagnosis in the six months after the earliest weight loss code (index date). Codes for additional clinical features were identified in the three months before to one month after the index date. Diagnostic accuracy measures included positive and negative likelihood ratios, positive predictive values, and diagnostic odds ratios. Results: Of 326 240 adults with unexpected weight loss, 184 270 (56.5%) were women, 176 508 (54.1%) were aged ≥60 years, and 176 053 (54.0%) were ever smokers. 15 624 (4.8%) had a diagnosis of cancer within six months of the index date, of whom 15 051 (96.3%) were aged ≥50 years. The positive predictive value for cancer was above the 3% threshold recommended by the National Institute for Health and Care Excellence for urgent investigation in men aged ≥50 years and women aged ≥60 years. 17 additional clinical features were associated with cancer in younger men with unexpected weight loss, and eight in women. Positive likelihood ratios in men ranged from 1.43 (95% confidence interval 1.30 to 1.58) for fatigue to 21.00 (8.59 to 51.37) for rectal mass, and in women from 1.28 (1.16 to 1.41) for back pain to 19.46 (12.69 to 29.85) for pelvic mass. Abnormal blood test results associated with cancer included low albumin (positive likelihood ratio 3.24, 3.13 to 3.35) and raised platelets (3.48, 3.35 to 3.62), total white cell count (3.01, 2.89 to 3.14), and C reactive protein (3.13, 3.05 to 3.20). However, no normal blood test result in isolation ruled out cancer. Clinical features co-occurring with unexpected weight loss were associated with multiple cancer sites. Conclusion: The risk of cancer in younger adults with unexpected weight loss presenting to primary care is <3% and does not merit investigation under current UK guidelines. However, in men aged ≥50 years, women aged ≥60 years, and younger patients with concurrent clinical features, the risk of cancer warrants referral for invasive investigation. Clinical features typically associated with specific cancer sites are markers of several cancer types when they occur with unexpected weight loss.
Cultivating Doctors’ Gut Feeling: Experience, Temporality and Politics of Gut Feelings in Family Medicine
For the past decade, within family medicine there has been a focus on cultivating doctors gut feelings as ‘a way of knowing’ in cancer diagnostics. In this paper, building on interviews with family doctors in Oxford shire, UK we explore the embodied and temporal dimensions of clinical reasoning and how the cultivation of doctors’ gut feelings is related to hierarchies of medical knowledge, professional training, and doctors’ fears of litigation. Also, we suggest that the introduction of gut feeling in clinical practice is an attempt to develop a theory of clinical reasoning that fits the biopolitics of our contemporary. The turn towards predictive medicine and the values introduced by accelerated diagnostic regimes, we conclude, introduce a need for situated and embodied modes of reading bodies. We contribute theoretically by framing our analysis within a sensorial anthropology approach.
Building the case for the use of gut feelings in cancer referrals: Perspectives of patients referred to a non-specific symptoms pathway
Background Gut feelings may be useful when dealing with uncertainty, which is ubiquitous in primary care. Both patients and GPs experience this uncertainty but patients' views on gut feelings in the consultation have not been explored. Aim To explore patients' perceptions of gut feelings in decision making, and to compare these perceptions with those of GPs. Design and setting Qualitative interviews with 21 patients in Oxfordshire, UK. Method Patients whose referral to a cancer pathway was based on their GP's gut feeling were invited to participate. Semi-structured interviews were conducted from November 2019 to January 2020, face to face or over the telephone. Data were analysed with a thematic analysis and mind-mapping approach. Results Some patients described experiencing gut feelings about their own health but often their willingness to share this with their GP was dependent on an established doctor-patient relationship. Patients expressed similar perspectives on the use of gut feelings in consultations to those reported by GPs. Patients saw GPs' gut feelings as grounded in their experience and generalist expertise, and part of a process of evidence gathering. Patients suggested that GPs were justified in using gut feelings because of their role in arranging access to investigations, the difficult 'grey area' of presentations, and the time- and resource-limited nature of primary care. When GPs communicated that they had a gut feeling, some saw this as an indication that they were being taken seriously. Conclusion Patients accepted that GPs use gut feelings to guide decision making. Future research on this topic should include more diverse samples and address the areas of concern shared by patients and GPs.
GPs’ use of gut feelings when assessing cancer risk: A qualitative study in UK primary care
Background The use of gut feelings to guide clinical decision making in primary care has been frequently described but is not considered a legitimate reason for cancer referral. Aim To explore the role that gut feeling plays in clinical decision making in primary care. Design and setting Qualitative interview study with 19 GPs in Oxfordshire, UK. Method GPs who had referred patients to a cancer pathway based on a gut feeling as a referral criterion were invited to participate. Interviews were conducted between November 2019 and January 2020, and transcripts were analysed using the one sheet of paper method. Results Gut feeling was seen as an essential part of decision making that facilitated appropriate and timely care. GPs distanced their gut feelings from descriptions that could be seen as unscientific, describing successful use as reliant on experience and clinical knowledge. This was especially true for patients who fell within a ‘grey area’ where clinical guidelines did not match the GP’s assessment of cancer risk, either because the guidance inadequately represented or did not include the patient’s presentation. GPs sought to legitimise their gut feelings by gathering objective clinical evidence, careful examination of referral procedures, and consultation with colleagues. Conclusion GPs described their gut feelings as important to decision making in primary care and a necessary addition to clinical guidance. The steps taken to legitimise their gut feelings matched that expected in good clinical practice.
A systematic review and thematic synthesis of qualitative studies exploring GPs' and nurses' perspectives on discussing weight with patients with overweight and obesity in primary care
Guidelines and evidence suggest primary care clinicians should give opportunistic interventions to motivate weight loss, but these rarely occur in practice. We sought to examine why by systematically reviewing qualitative research examining general practitioners' (‘GPs’) and nurses' views of discussing weight with patients. We systematically searched English language publications (1945-2018) to identify qualitative interview and focus group studies. Thematic methods were used to synthesise the findings from these papers. We synthesised the studies by identifying second-order themes (explanations offered by the original researchers) and third-order constructs (new explanations which went beyond those in the original publications). Quality assessment using the Joanna Briggs checklist was undertaken. We identified 29 studies (>601 GPs, nurses and GP trainees) reporting views on discussing weight with patients. Key second-order themes were lack of confidence in treatments and patients' ability to make changes, stigma, interactional difficulty of discussing the topic and a belief of a wider societal responsibility needed to deal with patients with overweight and obesity. The third-order analytical theme was that discussions about weight were not a priority, and other behavioural interventions, including those relating to smoking, often took precedent. GPs and nurses reported that noting body mass index measurements at every consultation alongside a framework to deliver interventions would likely increase the frequency and perceived efficacy of behavioural weight interventions. GPs and nurses acknowledge the importance of obesity as a health issue, but this is insufficient, particularly amongst GPs, for them to construe this as a medical problem to address with patients in consultations. Strategies to implement clinical guidelines need to make tackling obesity a clinical priority. Training to overcome interactional difficulties, regular weighing of patients and changing expectations and understanding of weight loss interventions are also probably required.
The GLANCE study: Patients’ and GPs’ views on the use of gut feelings for cancer in primary care
Objectives: Gut feelings, often described as a sense of alarm or reassurance for a patient’s health that may not be based on clinical evidence, are increasingly recognised as a feature of primary care practice. Studies have shown they help avoid missed diagnoses in disease areas including respiratory tract infections, heart disease, and cancer. Their use, however, in clinical decision making is contentious due to concerns over their subjectivity and difficulties in rationalising, articulating, and incorporating them into standardised medical practice. Our objective is to explore what GPs’ and patients’ gut feeling about cancer is, and how the transformation of feeling into gut feeling is shaped by particular terrains of experiences, fields of practices and sociocultural contexts. We investigate this through exploring GPs’ and patients experiences of using gut feelings for cancer suspicion, their understanding of what constitutes gut feelings, and the acceptability of using gut feelings as a referral criterion. Method: Recruitment began in October 2019 and is ongoing. Interview participants were identified from the Suspected CANcer (SCAN) Pathway database. Patients who were referred either entirely or partly based on a gut feeling and attended their first clinic visit within a year of the start of recruitment were contacted with a patient information leaflet and an invitation to take part in an interview. GPs who had referred at least one patient to the SCAN pathway were also sent an information leaflet and invitation to take part. We did not require GPs to have referred based on a gut feeling in an attempt to gain a range of views on the topic. Up to 50 interviews will be conducted, 25 patient and 25 GP interviews. Interviews will transcribed verbatim and analysed thematically using the NVivo software package. Results: To date, 13 patient and 10 GP interviews have been conducted, including two patients who were diagnosed with cancer through the SCAN Pathway. Initial results suggest that both GPs and patients are supportive of the use of gut feelings for cancer and see it as a manifestation of accumulated clinical expertise. GPs found SCAN useful because it provides a route to diagnosis for patients with no localising symptoms, who previously would have been referred to multiple organ specific two-week-wait pathways until a cause for their symptoms was found. GPs have described gut feeling as a sense that something is not right with the clinical picture, while patients have drawn an analogy between gut feeling and an immediate sense of dislike that may occur when meeting someone for the first time. Patients also acknowledged that GPs operate under uncertainty and as such felt that gut feelings are an important diagnostic tool. Conclusions: To the best of our knowledge, this is the first study that has discussed gut feelings for cancer with both clinicians and patients. Furthermore, that our participants have recently either been referred, or had the option to make a referral, based on a gut feeling for cancer lends a unique perspective and relevance to the discussions. Initial results suggest that gut feelings are experienced by patients and clinicians, and both are supportive of its use in primary care. Further data will be collected during January 2020, and understanding, use, and the risks and benefits of using gut feelings for the suspicion of cancer will be explored during the full analysis of the data.
Feasibility and Acceptability of Community Coronavirus Disease 2019 Testing Strategies (FACTS) in a University Setting.
BackgroundDuring the coronavirus disease 2019 (COVID-19) pandemic in 2020, the UK government began a mass severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing program. This study aimed to determine the feasibility and acceptability of organized regular self-testing for SARS-CoV-2.MethodsThis was a mixed-methods observational cohort study in asymptomatic students and staff at University of Oxford, who performed SARS-CoV-2 antigen lateral flow self-testing. Data on uptake and adherence, acceptability, and test interpretation were collected via a smartphone app, an online survey, and qualitative interviews.ResultsAcross 3 main sites, 551 participants (25% of those invited) performed 2728 tests during a follow-up of 5.6 weeks; 447 participants (81%) completed at least 2 tests, and 340 (62%) completed at least 4. The survey, completed by 214 participants (39%), found that 98% of people were confident to self-test and believed self-testing to be beneficial. Acceptability of self-testing was high, with 91% of ratings being acceptable or very acceptable. A total of 2711 (99.4%) test results were negative, 9 were positive, and 8 were inconclusive. Results from 18 qualitative interviews with students and staff revealed that participants valued regular testing, but there were concerns about test accuracy that impacted uptake and adherence.ConclusionsThis is the first study to assess feasibility and acceptability of regular SARS-CoV-2 self-testing. It provides evidence to inform recruitment for, adherence to, and acceptability of regular SARS-CoV-2 self-testing programs for asymptomatic individuals using lateral flow tests. We found that self-testing is acceptable and people were able to interpret results accurately.
Death audits and reviews for reducing maternal, perinatal and child mortality
Background: The United Nations' Sustainable Development Goals (SDGs) include reducing the global maternal mortality rate to less than 70 per 100,000 live births and ending preventable deaths of newborns and children under five years of age, in every country, by 2030. Maternal and perinatal death audit and review is widely recommended as an intervention to reduce maternal and perinatal mortality, and to improve quality of care, and could be key to attaining the SDGs. However, there is uncertainty over the most cost-effective way of auditing and reviewing deaths: community-based audit (verbal and social autopsy), facility-based audits (significant event analysis (SEA)) or a combination of both (confidential enquiry). Objectives: To assess the impact and cost-effectiveness of different types of death audits and reviews in reducing maternal, perinatal and child mortality. Search methods: We searched the following from inception to 16 January 2019: CENTRAL, Ovid MEDLINE, Embase OvidSP, and five other databases. We identified ongoing studies using ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, and searched reference lists of included articles. Selection criteria: Cluster-randomised trials, cluster non-randomised trials, controlled before-and-after studies and interrupted time series studies of any form of death audit or review that involved reviewing individual cases of maternal, perinatal or child deaths, identifying avoidable factors, and making recommendations. To be included in the review, a study needed to report at least one of the following outcomes: perinatal mortality rate; stillbirth rate; neonatal mortality rate; mortality rate in children under five years of age or maternal mortality rate. Data collection and analysis: We used standard Cochrane Effective Practice and Organisation of Care (EPOC) group methodological procedures. Two review authors independently extracted data, assessed risk of bias and assessed the certainty of the evidence using GRADE. We planned to perform a meta-analysis using a random-effects model but included studies were not homogeneous enough to make pooling their results meaningful. Main results: We included two cluster-randomised trials. Both introduced death review and audit as part of a multicomponent intervention, and compared this to current care. The QUARITE study (QUAlity of care, RIsk management, and TEchnology) concerned maternal death reviews in hospitals in West Africa, which had very high maternal and perinatal mortality rates. In contrast, the OPERA trial studied perinatal morbidity/mortality conferences (MMCs) in maternity units in France, which already had very low perinatal mortality rates at baseline. The OPERA intervention in France started with an outreach visit to brief obstetricians, midwives and anaesthetists on the national guidelines on morbidity/mortality case management, and was followed by a series of perinatal MMCs. Half of the intervention units were randomised to receive additional support from a clinical psychologist during these meetings. The OPERA intervention may make little or no difference to overall perinatal mortality (low certainty evidence), however we are uncertain about the effect of the intervention on perinatal mortality related to suboptimal care (very low certainty evidence).The intervention probably reduces perinatal morbidity related to suboptimal care (unadjusted odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.95; 165,353 births; moderate-certainty evidence). The effect of the intervention on stillbirth rate, neonatal mortality, mortality rate in children under five years of age, maternal mortality or adverse effects was not reported. The QUARITE intervention in West Africa focused on training leaders of hospital obstetric teams using the ALARM (Advances in Labour And Risk Management) course, which included one day of training about conducting maternal death reviews. The leaders returned to their hospitals, established a multidisciplinary committee and started auditing maternal deaths, with the support of external facilitators. The intervention probably reduces inpatient maternal deaths (adjusted OR 0.85, 95% CI 0.73 to 0.98; 191,167 deliveries; moderate certainty evidence) and probably also reduces inpatient neonatal mortality within 24 hours following birth (adjusted OR 0.74, 95% CI 0.61 to 0.90; moderate certainty evidence). However, QUARITE probably makes little or no difference to the inpatient stillbirth rate (moderate certainty evidence) and may make little or no difference to the inpatient neonatal mortality rate after 24 hours, although the 95% confidence interval includes both benefit and harm (low certainty evidence). The QUARITE intervention probably increases the percent of women receiving high quality of care (OR 1.87, 95% CI 1.35 - 2.57, moderate-certainty evidence). The effect of the intervention on perinatal mortality, mortality rate in children under five years of age, or adverse effects was not reported. We did not find any studies that evaluated child death audit and review or community-based death reviews or costs. Authors' conclusions: A complex intervention including maternal death audit and review, as well as development of local leadership and training, probably reduces inpatient maternal mortality in low-income country district hospitals, and probably slightly improves quality of care. Perinatal death audit and review, as part of a complex intervention with training, probably improves quality of care, as measured by perinatal morbidity related to suboptimal care, in a high-income setting where mortality was already very low. The WHO recommends that maternal and perinatal death reviews should be conducted in all hospitals globally. However, conducting death reviews in isolation may not be sufficient to achieve the reductions in mortality observed in the QUARITE trial. This review suggests that maternal death audit and review may need to be implemented as part of an intervention package which also includes elements such as training of a leading doctor and midwife in each hospital, annual recertification, and quarterly outreach visits by external facilitators to provide supervision and mentorship. The same may also apply to perinatal and child death reviews. More operational research is needed on the most cost-effective ways of implementing maternal, perinatal and paediatric death reviews in low- and middle-income countries.
Death audits and reviews for reducing maternal, perinatal and child mortality
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the impact and cost-effectiveness of different types of death review in reducing maternal, perinatal and child mortality.
Opportunistic smoking cessation interventions for people accessing financial support settings: A scoping review
Aim: The aim of this work was to systematically scope the evidence on opportunistic tobacco smoking cessation interventions for people accessing financial support settings. Methods: We searched MEDLINE, Embase, PsycINFO and the Cochrane Tobacco Addiction Group specialized register to 21 March 2023. We duplicate screened 20% of titles/abstracts and all full texts. We included primary studies investigating smoking cessation interventions delivered opportunistically to people who smoked tobacco, within settings offering support for problems caused by financial hardship, for example homeless support services, social housing and food banks. Data were charted by one reviewer, checked by another and narratively synthesized. Results: We included 25 studies conducted in a range of financial support settings using qualitative (e.g. interviews and focus groups) and quantitative (e.g. randomized controlled trials, surveys and single arm intervention studies) methodologies. Evidence on the acceptability and feasibility of opportunistic smoking cessation advice was investigated among both clients and providers. Approximately 90% of service providers supported such interventions; however, lack of resources, staff training and a belief that tobacco smoking reduced illicit substance use were perceived barriers. Clients welcomed being asked about smoking and offered assistance to quit and expressed interest in interventions including the provision of nicotine replacement therapy, e-cigarettes and incentives to quit smoking. Six studies investigated the comparative effectiveness of opportunistic smoking cessation interventions on quitting success, with five comparing more to less intensive interventions, with mixed results. Conclusions: Most studies investigating opportunistic smoking cessation interventions in financial support settings have not measured their effectiveness. Where they have, settings, populations, interventions and findings have varied. There is more evidence investigating acceptability, with promising results.
Associations of BMI with COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination in England: a population-based cohort study
Background: A high BMI has been associated with a reduced immune response to vaccination against influenza. We aimed to investigate the association between BMI and COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination by using a large, representative population-based cohort from England. Methods: In this population-based cohort study, we used the QResearch database of general practice records and included patients aged 18 years or older who were registered at a practice that was part of the database in England between Dec 8, 2020 (date of the first vaccination in the UK), to Nov 17, 2021, with available data on BMI. Uptake was calculated as the proportion of people with zero, one, two, or three doses of the vaccine across BMI categories. Effectiveness was assessed through a nested matched case-control design to estimate odds ratios (OR) for severe COVID-19 outcomes (ie, admission to hospital or death) in people who had been vaccinated versus those who had not, considering vaccine dose and time periods since vaccination. Vaccine effectiveness against infection with SARS-CoV-2 was also investigated. Multivariable Cox proportional hazard models estimated the risk of severe COVID-19 outcomes associated with BMI (reference BMI 23 kg/m2) after vaccination. Findings: Among 9 171 524 participants (mean age 52 [SD 19] years; BMI 26·7 [5·6] kg/m2), 566 461 tested positive for SARS-CoV-2 during follow-up, of whom 32 808 were admitted to hospital and 14 389 died. Of the total study sample, 19·2% (1 758 689) were unvaccinated, 3·1% (287 246) had one vaccine dose, 52·6% (4 828 327) had two doses, and 25·0% (2 297 262) had three doses. In people aged 40 years and older, uptake of two or three vaccine doses was more than 80% among people with overweight or obesity, which was slightly lower in people with underweight (70–83%). Although significant heterogeneity was found across BMI groups, protection against severe COVID-19 disease (comparing people who were vaccinated vs those who were not) was high after 14 days or more from the second dose for hospital admission (underweight: OR 0·51 [95% CI 0·41–0·63]; healthy weight: 0·34 [0·32–0·36]; overweight: 0·32 [0·30–0·34]; and obesity: 0·32 [0·30–0·34]) and death (underweight: 0·60 [0·36–0·98]; healthy weight: 0·39 [0·33–0·47]; overweight: 0·30 [0·25–0·35]; and obesity: 0·26 [0·22–0·30]). In the vaccinated cohort, there were significant linear associations between BMI and COVID-19 hospitalisation and death after the first dose, and J-shaped associations after the second dose. Interpretation: Using BMI categories, there is evidence of protection against severe COVID-19 in people with overweight or obesity who have been vaccinated, which was of a similar magnitude to that of people of healthy weight. Vaccine effectiveness was slightly lower in people with underweight, in whom vaccine uptake was also the lowest for all ages. In the vaccinated cohort, there were increased risks of severe COVID-19 outcomes for people with underweight or obesity compared with the vaccinated population with a healthy weight. These results suggest the need for targeted efforts to increase uptake in people with low BMI (<18·5 kg/m2), in whom uptake is lower and vaccine effectiveness seems to be reduced. Strategies to achieve and maintain a healthy weight should be prioritised at the population level, which could help reduce the burden of COVID-19 disease. Funding: UK Research and Innovation and National Institute for Health Research Oxford Biomedical Research Centre.
Adiposity and the first-onset of diagnosed mental illnesses: a population-based cohort study of 10 million UK adults
Background: Whether both high and low BMI are risk factors for mental illnesses is unclear, especially serious mental illnesses. Experimental evidence suggests that metabolic pathways might mediate the association, but this is uncertain. To examine associations between BMI and the first-onset of diagnosed mental illnesses with assessment for mediating effects of cardiometabolic disorders. Methods: Using the UK Clinical Practice Research Datalink (2000–2022), individuals ≥ 18 years with a recorded BMI assessment were included. Diagnosed mental illnesses were ascertained via clinical diagnoses, referrals to mental health services, or psychotropic prescriptions. Restricted cubic splines and Cox proportional hazard models estimated associations between BMI and incident mental illnesses. Mediation analyses assessed the mediating role of cardiometabolic disorders and biomarkers. Results: The study population included 10,465,562 adults (mean BMI 26.8 kg/m2, standard deviation 5.5). Compared to those with a healthy BMI (18.5–25.0 kg/m2), individuals with severe obesity (≥ 40 kg/m2) had higher risks for depression (HR 1.32; 95% CI 1.31–1.33), anxiety (1.12; 1.10–1.13), bulimia nervosa (1.38; 1.20–1.58), other unspecified eating disorders (OUD) (2.04; 1.91–2.17), bipolar disorder (1.44; 1.36–1.54), schizophrenia (2.02; 1.91–2.15) and other psychoses (1.40; 1.28–1.53), but a lower risk for anorexia nervosa (0.45; 0.42–0.49). Individuals with underweight (< 18.5 kg/m2) were at increased risks of depression (1.28; 1.27–1.29), anxiety (1.26; 1.24–1.27), anorexia nervosa (3.88; 3.77–4.01), bulimia nervosa (1.52; 1.37–1.68), OUD (4.50; 4.33–4.67), schizophrenia (1.46; 1.35–1.56), and other psychoses (1.22; 1.10–1.35), with no association with bipolar disorder. Associations were stronger in women, younger adults, and Asian populations. Cardiometabolic diseases did not mediate associations, but LDL, triglycerides, HbA1c demonstrated partial mediation (indirect effect: 0.2%-15%). Conclusions: Individuals with severe obesity and underweight had increased risk of common and serious mental illnesses, especially in women, younger individuals, and Asian populations. Associations were not mediated by cardiometabolic diseases but partially by biomarkers.
A Ketogenic Diet for Treatment-Resistant Depression: A Randomized Clinical Trial.
IMPORTANCE: Preclinical evidence and case reports suggest potential therapeutic benefits of ketogenic diets (KDs) in the treatment of depression, but evidence from well-controlled randomized clinical trials (RCTs) is lacking. OBJECTIVE: To assess the efficacy of a KD compared with a control diet in adults with treatment-resistant depression (TRD). DESIGN, SETTING, AND PARTICIPANTS: This RCT was conducted between February 22 and June 15, 2024. Participants aged 18 to 65 years with TRD and a score of 15 or greater on the 9-item Patient Health Questionnaire (PHQ-9) from across the UK were included. INTERVENTION: Participants were randomized 1:1 to one of two 6-week dietary interventions: (1) KD of prepared foods providing less than 30 g of carbohydrates per day with weekly individual dietetic support or (2) a control (phytochemical [phyto]) diet with vouchers to purchase 1 extra serving of vegetables or fruit and replace saturated fats with unsaturated fats, with equal dietetic support. The last follow-up was at 12 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the between-group difference in change in PHQ-9 score from baseline to week 6. Secondary outcomes included PHQ-9 score at 12 weeks, depression remission, anxiety, anhedonia, cognitive impairment, quality of life, and functional outcomes. RESULTS: The study included 88 participants (mean [SD] age, 42.1 [13.1] years; 61 women [69%]): 44 in the KD group and 44 in the phyto diet group. Depression severity decreased markedly in both groups; the mean (SD) change in PHQ-9 score from baseline to week 6 was -10.5 (7.0) in the KD group and -8.3 (5.1) in the phyto group. The mean between-group differences in PHQ-9 score at 6 and 12 weeks were -2.18 (95% CI, -4.33 to -0.03; P = .05; Cohen d, -0.68; 95% CI -1.35 to -0.01) and -1.85 (95% CI, -4.04 to 0.33; P = .10; Cohen d, -0.58; 95% CI, -1.26 to 0.10), respectively. There were no differences in secondary outcomes between the KD and phyto groups. No serious adverse events occurred. CONCLUSIONS AND RELEVANCE: In this RCT, a KD had antidepressant benefits compared with a well-matched control diet at 6 weeks. However, the clinical relevance is uncertain, as the mean effect size compared with the control was modest and not evident in secondary analyses. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06091163.