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The ultimate goal of value-based laboratory medicine is maximizing the effectiveness of laboratory tests in improving patient outcomes, optimizing resources and minimizing unnecessary costs. This approach abandons the oversimplified notion of test volume and cost, in favor of emphasizing the clinical utility and quality of diagnostic tests in the clinical decision-making. Several key elements characterize value-based laboratory medicine, which can be summarized in some basic concepts, such as organization of in vitro diagnostics (including appropriateness, integrated diagnostics, networking, remote patient monitoring, disruptive innovations), translation of laboratory data into clinical information and measurable outcomes, sustainability, reimbursement, ethics (e.g., patient empowerment and safety, data protection, analysis of big data, scientific publishing). Education and training are also crucial, along with considerations for the future of the profession, which will be largely influenced by advances in automation, information technology, artificial intelligence, and regulations concerning in vitro diagnostics. This collective opinion paper, composed of summaries from presentations given at the two-day European Federation of Laboratory Medicine (EFLM) Strategic Conference "A vision to the future: value-based laboratory medicine" (Padova, Italy; September 23-24, 2024), aims to provide a comprehensive overview of value-based laboratory medicine, projecting the profession into a more clinically effective and sustainable future., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Patient engagement when providing patient access to health data results from an interaction between the available tools and individual capabilities. The recent digital advancements of the healthcare field have altered the manifestation and importance of patient engagement. However, a comprehensive assessment of what factors contribute to patient engagement remain absent. In this review article, we synthesised the most frequently discussed factors that can foster patient engagement with their health data., Methods: A scoping review was conducted in MEDLINE, Embase, and Google Scholar. Relevant data were synthesized within 7 layers using a thematic analysis: (1) social and demographic factors, (2) patient ability factors, (3) patient motivation factors, (4) factors related to healthcare professionals' attitudes and skills, (5) health system factors, (6) technological factors, and (7) policy factors., Results: We identified 5801 academic and 200 Gy literature records, and included 292 (4.83%) in this review. Overall, 44 factors that can affect patient engagement with their health data were extracted. We extracted 6 social and demographic factors, 6 patient ability factors, 12 patient motivation factors, 7 factors related to healthcare professionals' attitudes and skills, 4 health system factors, 6 technological factors, and 3 policy factors., Conclusions: Improving patient engagement with their health data enables the development of patient-centered healthcare, though it can also exacerbate existing inequities. While expanding patient access to health data is an important step towards fostering shared decision-making in healthcare and subsequently empowering patients, it is important to ensure that these developments reach all sectors of the community., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Pathogenic BRCA1 or BRCA2 germline mutations contribute to hereditary breast, ovarian, prostate, and pancreatic cancer. Paradoxically, bi-allelic inactivation of BRCA1 or BRCA2 (bBRCA1/2) is embryonically lethal and decreases cellular proliferation. The compensatory mechanisms that facilitate oncogenesis in bBRCA1/2 tumors remain unclear., Methods: We identified recurrent genetic alterations enriched in human bBRCA1/2 tumors and experimentally validated if these improved proliferation in cellular models. We analyzed mutations and copy number alterations (CNAs) in bBRCA1/2 breast and ovarian cancer from the TCGA and ICGC. We used Fisher's exact test to identify CNAs enriched in bBRCA1/2 tumors compared to control tumors that lacked evidence of homologous recombination deficiency. Genes located in CNA regions enriched in bBRCA1/2 tumors were further screened by gene expression and their effects on proliferation in genome-wide CRISPR/Cas9 screens. A set of candidate genes was functionally validated with in vitro clonogenic survival and functional assays to validate their influence on proliferation in the setting of bBRCA1/2 mutations., Results: We found that bBRCA1/2 tumors harbor recurrent large-scale genomic deletions significantly more frequently than histologically matched controls (n = 238 cytobands in breast and ovarian cancers). Within the deleted regions, we identified 277 BRCA1-related genes and 218 BRCA2-related genes that had reduced expression and increased proliferation in bBRCA1/2 but not in wild-type cells in genome-wide CRISPR screens. In vitro validation of 20 candidate genes with clonogenic proliferation assays validated 9 genes, including RIC8A and ATMIN (ATM-Interacting protein). We identified loss of RIC8A, which occurs frequently in both bBRCA1/2 tumors and is synthetically viable with loss of both BRCA1 and BRCA2. Furthermore, we found that metastatic homologous recombination deficient cancers acquire loss-of-function mutations in RIC8A. Lastly, we identified that RIC8A does not rescue homologous recombination deficiency but may influence mitosis in bBRCA1/2 tumors, potentially leading to increased micronuclei formation., Conclusions: This study provides a means to solve the tumor suppressor paradox by identifying synthetic viability interactions and causal driver genes affected by large-scale CNAs in human cancers., (© 2024. The Author(s).)

Background: Digital therapeutic Sleepio has proven effective in improving sleep quality and decreasing symptoms of anxiety. The National Institute for Health and Care Excellence (NICE) guidance recommends Sleepio as an alternative treatment to usual sleep hygiene education and hypnotic medications. General practitioners (GPs) play a critical role in the adoption of digital therapeutics in patient care. Previous interventions did not adopt theoretical frameworks to systematically understand GPs behaviour toward referring patients to digital therapeutics., Objectives: This study aimed to report the systematic and comprehensive development of an intervention to encourage GPs to refer insomnia patients to Sleepio, using the Behaviour Change Wheel (BCW)., Methods: The eight steps outlined in the BCW were followed to develop an intervention. The Capability Opportunity Motivation-Behaviour Self-Evaluation Questionnaire (COM-B-Qv1) was adopted to understand GPs perceived facilitators and barriers to refer insomnia patients to Sleepio. The Behaviour Change Technique Taxonomy Version 1 (BCTv1) was thereafter used to identify possible strategies that could be used to facilitate changes in GPs' behaviour in relation to Sleepio., Results: The BCW design process resulted in the identification of five intervention functions, three policy categories and five behaviour change techniques (BCTs) as potential active components for an intervention. The intervention includes providing GPs with an orientation about using Sleepio to improve their knowledge and confidence, sending visual reminders to GPs to recommend Sleepio to their patients, providing ongoing technical support., Conclusion: The BCW can be successfully applied through a systematic process to understand the drivers of GPs' behaviour and to develop an intervention that can encourage them to refer insomnia patients to Sleepio., (© 2024. The Author(s).)

Aim: To explore how to help make online consultation notes easier for patient audiences to understand., Background: Most patients in England will soon be able to access all new prospective entries (including free-text) within their online primary care health record via the NHS App or other online services., Method: We conducted interviews and focus group discussions with 26 patients from underserved communities. Participants responded to vignettes about fictional patient consultation scenarios and assessed the clarity of corresponding simulated records. Participants were then asked to identify potential comprehension issues, offensive content, or anxiety triggers., Results: Most participants struggled to understand a large proportion of simulated notes, particularly medical acronyms, clinician shorthand, and non-clinical abbreviations. Participants also identified issues that may cause unintended offence or additional anxiety. Participants considered that most patients will struggle to fully understand the content of their consultation notes in their current format. They made a number of suggestions about how this service may be improved to meet the needs of patient audiences and maintain positive patient-clinician relationships., Conclusion: Opening up online record access to include patient audiences necessitates a significant cultural shift in the way that consultation notes are written and used. To maximise NHS investment in this policy and avoid worsening health inequalities, it is essential to ensure that all patients can understand and access the benefits of online access to their notes. To do this, clinicians need to be supported to manage the challenges of writing for patient audiences, while continuing to maintain effective clinical care., (© British Journal of General Practice 2024.)

Purpose: Nearly all published ophthalmology-related Big Data studies rely exclusively on International Classification of Diseases (ICD) billing codes to identify patients with particular ocular conditions. However, inaccurate or nonspecific codes may be used. We assessed whether natural language processing (NLP), as an alternative approach, could more accurately identify lens pathology., Design: Database study comparing the accuracy of NLP versus ICD billing codes to properly identify lens pathology., Methods: We developed an NLP algorithm capable of searching free-text lens exam data in the electronic health record (EHR) to identify the type(s) of cataract present, cataract density, presence of intraocular lenses, and other lens pathology. We applied our algorithm to 17.5 million lens exam records in the Sight Outcomes Research Collaborative (SOURCE) repository. We selected 4314 unique lens-exam entries and asked 11 clinicians to assess whether all pathology present in the entries had been correctly identified in the NLP algorithm output. The algorithm's sensitivity at accurately identifying lens pathology was compared with that of the ICD codes., Results: The NLP algorithm correctly identified all lens pathology present in 4104 of the 4314 lens-exam entries (95.1%). For less common lens pathology, algorithm findings were corroborated by reviewing clinicians for 100% of mentions of pseudoexfoliation material and 99.7% for phimosis, subluxation, and synechia. Sensitivity at identifying lens pathology was better for NLP (0.98 [0.96-0.99] than for billing codes (0.49 [0.46-0.53])., Conclusions: Our NLP algorithm identifies and classifies lens abnormalities routinely documented by eye-care professionals with high accuracy. Such algorithms will help researchers to properly identify and classify ocular pathology, broadening the scope of feasible research using real-world data., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Research on age-progression facial morphing interventions for smoking cessation has not investigated the effect of different instructions for intervention delivery. The objective of this pilot study was to investigate the influence of two instruction types used to deliver the intervention on efficacy of the intervention., Method: Women were recruited and randomly allocated to an age-progression intervention session with (i) neutral instructions; (ii) instructions designed to reassure; or (iii) a condition that controlled for participant engagement ("control"). The conditions were delivered in a one-time procedure, after which primary (quitting intentions) and secondary (cigarettes/week, quit attempts) outcomes were measured immediately post-intervention, and at 1 and 3 months., Results: Seventy-two women (M = 25.7; SD = 0.9) were recruited and randomly allocated to condition (Neutral n = 27, Reassuring n = 22, Control n = 23). Quitting intentions were higher in the Reassuring versus Control arm (3 months post-intervention, F = 4.37, p = 0.016, 95% CI [0.231, 2.539], eta 2  = 0.11); quit attempts were greater in the two intervention arms (58%) versus Control (1-month post-intervention, 15%) (χ 2  = 9.83, p < 0.05, OR 1.00 [0.28, 3.63])., Conclusions: Findings highlight the importance of optimising instructions to enhance intervention efficacy., Trial Registration: clinicaltrials.gov Record: NCT03749382., (© 2024. The Author(s).)

To evaluate immune responses to COVID-19 vaccines in adults aged 50 years and older, spike protein (S)-specific antibody concentration, avidity, and function (via angiotensin-converting enzyme 2 (ACE2) inhibition surrogate neutralization and antibody dependent cellular phagocytosis (ADCP)), as well as S-specific T cells were quantified via activation induced marker (AIM) assay in response to two-dose series. Eighty-four adults were vaccinated with either: mRNA/mRNA (mRNA-1273 and/or BNT162b2); ChAdOx1-S/mRNA; or ChAdOx1-S/ChAdOx1-S. Anti-S IgG concentrations, ADCP scores and ACE2 inhibiting antibody concentrations were highest at one-month post-second dose and declined by four-months post-second dose for all groups. mRNA/mRNA and ChAdOx1-S/mRNA schedules had significantly higher antibody responses than ChAdOx1-S/ChAdOx1-S. CD8 + T-cell responses one-month post-second dose were associated with increased ACE2 surrogate neutralization. Antibody avidity (total relative avidity index) did not change between one-month and four-months post-second dose and did not significantly differ between groups by four-months post-second dose. In determining COVID-19 correlates of protection, a measure that considers both antibody concentration and avidity should be considered., (© 2024. The Author(s).)

Introduction: The prevalence of gestational diabetes mellitus (GDM) is rising in the UK and is associated with maternal and neonatal complications. National Institute for Health and Care Excellence guidance advises first-line management with healthy eating and physical activity which is only moderately effective for achieving glycaemic targets. Approximately 30% of women require medication with metformin and/or insulin. There is currently no strong evidence base for any particular dietary regimen to improve outcomes in GDM. Intermittent low-energy diets (ILEDs) are associated with improved glycaemic control and reduced insulin resistance in type 2 diabetes and could be a viable option in the management of GDM. This study aims to test the safety, feasibility and acceptability of an ILED intervention among women with GDM compared with best National Health Service (NHS) care., Method and Analysis: We aim to recruit 48 women with GDM diagnosed between 24 and 30 weeks gestation from antenatal clinics at Wythenshawe and St Mary's hospitals, Manchester Foundation Trust, over 13 months starting in November 2022. Participants will be randomised (1:1) to ILED (2 low-energy diet days/week of 1000 kcal and 5 days/week of the best NHS care healthy diet and physical activity advice) or best NHS care 7 days/week until delivery of their baby. Primary outcomes include uptake and retention of participants to the trial and adherence to both dietary interventions. Safety outcomes will include birth weight, gestational age at delivery, neonatal hypoglycaemic episodes requiring intervention, neonatal hyperbilirubinaemia, admission to special care baby unit or neonatal intensive care unit, stillbirths, the percentage of women with hypoglycaemic episodes requiring third-party assistance, and significant maternal ketonaemia (defined as ≥1.0 mmol/L). Secondary outcomes will assess the fidelity of delivery of the interventions, and qualitative analysis of participant and healthcare professionals' experiences of the diet. Exploratory outcomes include the number of women requiring metformin and/or insulin., Ethics and Dissemination: Ethical approval has been granted by the Cambridge East Research Ethics Committee (22/EE/0119). Findings will be disseminated via publication in peer-reviewed journals, conference presentations and shared with diabetes charitable bodies and organisations in the UK, such as Diabetes UK and the Association of British Clinical Diabetologists., Trial Registration Number: NCT05344066., Competing Interests: Competing interests: Michelle Harvie has coauthored three self-help books for the public to follow intermittent diets. All author proceeds are paid directly to the charity Prevent Breast Cancer (registered charity number 1109839) to fund breast cancer research., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To describe the experiences and opinions of general practitioners (GPs) in England regarding patients having access to their full online GP health records., Design: Convenience sample, online survey., Participants: 400 registered GPs in England., Main Outcome Measures: Investigators measured GPs' experiences and opinions about online record access (ORA), including patient care and their practice., Results: A total of 400 GPs from all regions of England responded. A minority (130, 33%) believed ORA was a good idea. Most GPs believed a majority of patients would worry more (364, 91%) or find their GP records more confusing than helpful (338, 85%). Most GPs believed a majority of patients would find significant errors in their records (240, 60%), would better remember their care plan (280, 70%) and feel more in control of their care (243, 60%). The majority believed they will/already spend more time addressing patients' questions outside of consultations (357, 89%), that consultations will/already take significantly longer (322, 81%) and that they will be/already are less candid in their documentation (289, 72%) after ORA. Nearly two-thirds of GPs believed ORA would increase their litigation (246, 62%)., Conclusions: Similar to clinicians in other countries, GPs in our sample were sceptical of ORA, believing patients would worry more and find their records more confusing than helpful. Most GPs also believed the practice would exacerbate work burdens. However, the majority of GPs in this survey also agreed there were multiple benefits to patients having online access to their primary care health records. The findings of this survey also contribute to a growing body of contrastive research from countries where ORA is advanced, demonstrating clinicians are sceptical while studies indicate patients appear to derive multiple benefits., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Remote (digital and/or telephone) access and consultation models are being driven by national policy with the goal being that the National Health Service operate on a remote-first (digital-first) basis by 2029. Previous research has suggested that remote methods of access to care and consulting may act to widen health inequalities for certain patients and/or groups such as those from ethnic minorities. South Asian (SA) patients comprise the largest ethnic minority group in England. Understanding the experiences and needs of this group is critical to ensuring that general practice can deliver equitable, quality health care., Methods: Qualitative study. 37 participants (from Indian, Pakistani and/or Bangladeshi background) were recruited to take part in either in-person preferred language focus groups or remote semistructured interviews in the English language. Thematic analysis was conducted to identify themes in the qualitative data., Findings: Three major interlinked themes were identified: (1) reduced access, (2) reduced patient choice and (3) quality and safety concerns. The findings highlight access issues split by (i) general issues with appointment access via any remote means and (ii) specific issues related to language barriers creating additional barriers to access and care. Some patients valued the convenience of remote access but also raised concerns regarding appointment availability and reduced patient choice. Face-to-face consultations were preferable but less available. The findings underscore how participants perceived remote care to be of lesser quality and less safe. Concerns were greatest for those with limited English proficiency (LEP), with the removal of non-verbal aspects of communication and 'hands-on' care leading to perceptions of reduced psycho-social safety., Conclusion: SA patients' experiences of remote-led primary care access and care delivery were negative with only a minority viewing it positively and for certain limited scenarios. Face-to-face models of care remain the preferred mode of consultation, particularly for those with LEP. Hybrid models of access offer patients the greatest choice, and are likely to meet the varying needs of the South-Asian patient population going forwards. The remote first approach to primary care may be achievable as a service ideal, but its limitations need to be recognised and accounted for to ensure that primary care can be an equitable service, both now and in the future., Public Contribution: Members of the public were involved in all phases of research in the study. This included co-working in partnership throughout the study including, reviewing patient-facing documents, recruiting participants, data facilitation, translation work, interpretation of the data and co-authors on this manuscript. The key to the success of our study was collaborative teamwork, which involved experienced members of the public with SA cultural knowledge working together with and integral to the research team for all components., (© 2024 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

While research on the effects of patient access to health records is increasing, a basic understanding of the spread of patient-accessible electronic health records worldwide is lacking. In this survey of healthcare experts with professional and personal experience from 29 countries, we explored the state of patient online record access (ORA). We asked participants whether ORA exists in their country and which information is available through it. Experts in all polled countries reported having some national access to health records, with 6 (21%) countries providing exclusively paper-based records and 23 (79%) countries having ORA. Overview of test/lab results and prescription/medication lists were the most commonly available information. Free-text clinical notes were accessible in less than half of the surveyed countries (12, 41%). We will continue to map the state of patient ORA, focusing on traditionally underrepresented countries.

Background and Objectives: Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC)., Methods: We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults < 25 years between November 2020-May 2021 and phase 2 enrolled children < 10 years between June 2021-May 2022 in BC. Participants completed electronic surveys and self-collected finger-prick dried blood spot (DBS) samples. Samples were tested for immunoglobulin G antibodies against ancestral spike protein (S). Descriptive statistics from survey data were reported and two multivariable analyses were conducted to evaluate factors associated with seropositivity., Results: A total of 2864 participants were enrolled, of which 95/2167 (4.4%) participants were S-seropositive in phase 1 across all ages, and 61/697 (8.8%) unvaccinated children aged under ten years were S-seropositive in phase 2. Overall, South Asian participants had a higher seropositivity than other ethnicities (13.5% vs. 5.2%). Of 156 seropositive participants in both phases, 120 had no prior positive SARS-CoV-2 test. Young infants and young adults had the highest reported seropositivity rates (7.0% and 7.2% respectively vs. 3.0-5.6% across other age groups)., Conclusions: SARS-CoV-2 seropositivity among unvaccinated children and young adults was low in May 2022, and South Asians were disproportionately infected. This work demonstrates the need for improved diagnostics and reporting strategies that account for age-specific differences in pandemic dynamics and acceptability of testing mechanisms., (© 2024. The Author(s).)

Introduction: Long-term conditions are a major burden on health systems. One way to facilitate more research and better clinical care among patients with long-term conditions is to collect accurate data on their daily symptoms (patient-generated health data) using wearable technologies. Whilst evidence is growing for the use of wearable technologies in single conditions, there is less evidence of the utility of frequent symptom tracking in those who have more than one condition., Aims: To explore patient views of the acceptability of collecting daily patient-generated health data for three months using a smartwatch app., Methods: Watch Your Steps was a longitudinal study which recruited 53 patients to track over 20 symptoms per day for a 90-day period using a study app on smartwatches. Semi-structured interviews were conducted with a sub-sample of 20 participants to explore their experience of engaging with the app., Results: In a population of older people with multimorbidity, patients were willing and able to engage with a patient-generated health data app on a smartwatch. It was suggested that to maintain engagement over a longer period, more 'real-time' feedback from the app should be available. Participants did not seem to consider the management of more than one condition to be a factor in either engagement or use of the app, but the presence of severe or chronic pain was at times a barrier., Conclusion: This study has provided preliminary evidence that multimorbidity was not a major barrier to engagement with patient-generated health data via a smartwatch symptom tracking app., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: WGD has received consultancy fees from Google., (© The Author(s) 2024.)

Patients' online record access (ORA) is growing worldwide. In some countries, including the United States and Sweden, access is advanced with patients obtaining rapid access to their full records on the web including laboratory and test results, lists of prescribed medications, vaccinations, and even the very narrative reports written by clinicians (the latter, commonly referred to as "open notes"). In the United States, patient's ORA is also available in a downloadable form for use with other apps. While survey studies have shown that some patients report many benefits from ORA, there remain challenges with implementation around writing clinical documentation that patients may now read. With ORA, the functionality of the record is evolving; it is no longer only an aide memoire for doctors but also a communication tool for patients. Studies suggest that clinicians are changing how they write documentation, inviting worries about accuracy and completeness. Other concerns include work burdens; while few objective studies have examined the impact of ORA on workload, some research suggests that clinicians are spending more time writing notes and answering queries related to patients' records. Aimed at addressing some of these concerns, clinician and patient education strategies have been proposed. In this viewpoint paper, we explore these approaches and suggest another longer-term strategy: the use of generative artificial intelligence (AI) to support clinicians in documenting narrative summaries that patients will find easier to understand. Applied to narrative clinical documentation, we suggest that such approaches may significantly help preserve the accuracy of notes, strengthen writing clarity and signals of empathy and patient-centered care, and serve as a buffer against documentation work burdens. However, we also consider the current risks associated with existing generative AI. We emphasize that for this innovation to play a key role in ORA, the cocreation of clinical notes will be imperative. We also caution that clinicians will need to be supported in how to work alongside generative AI to optimize its considerable potential., (©Charlotte Blease, John Torous, Brian McMillan, Maria Hägglund, Kenneth D Mandl. Originally published in JMIR Medical Education (https://mededu.jmir.org), 04.01.2024.)

Background: Dementia affects ability to remember, think, or make decisions that interfere with doing everyday activities. There is no cure, therefore any prevention or delay of the onset is of importance. This study aims to investigate the association between zoster and influenza vaccinations and the risk of developing dementia., Methods: We conducted a retrospective population-based cohort study using electronic health records from 1469 general practices contributing to the Clinical Practice Research Datalink (CPRD) Aurum database with linked hospital episode statistics (HES) and Office for National Statistics (ONS) mortality records. We built two 'matched cohorts': zoster vaccine (854,745 exposed individuals) matched with 8.8 million comparators without a history of zoster vaccination, and influenza vaccine (742,487 exposed individuals) matched with 7.12 million comparators without a history of vaccination as another comparator group. The cohorts were then followed to assess the association of exposure (vaccine) with outcome (dementia diagnosis)., Results: Zoster vaccination was associated with a lower risk of dementia diagnosis (adjusted hazard ratio (HR) 0.78 with 95% CI: 0.77-0.79), Alzheimer's diagnosis (adjusted HR 0.91 with 95% CI: 0.89-0.92 and other types of dementia (adjusted HR 0.71 with 95% CI: 0.69-0.72). Influenza vaccination also was associated with a slightly reduced hazard of dementia risk (adjusted HR 0.96 with 95% CI: 0.94-0.97)., Conclusion: Both zoster vaccine for prevention of shingles / herpes zoster and influenza vaccine to prevent influenza were associated with diminished risk of dementia, with the zoster association appearing more pronounced., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Internationally, patient-accessible electronic health records (PAEHRs) are increasingly being implemented. Despite reported benefits to patients, the innovation has prompted concerns among health care professionals (HCPs), including the possibility that access incurs a "dumbing down" of clinical records. Currently, no review has investigated empirical evidence of whether and how documentation changes after introducing PAEHRs., Objective: This paper presents the protocol for a scoping review examining potential subjective and objective changes in HCPs documentation after using PAEHRs., Methods: This scoping review will be carried out based on the framework of Arksey and O'Malley. Several databases will be used to conduct a literature search (APA PsycInfo, CINAHL, PubMed, and Web of Science Core Collection). Authors will participate in screening identified papers to explore the research questions: How do PAEHRs affect HCPs' documentation practices? and What subjective and objective changes to the clinical notes arise after patient access? Only studies that relate to actual use experiences, and not merely prior expectations about PAEHRs, will be selected in the review. Data abstraction will include but will not be limited to publication type, publication year, country, sample characteristics, setting, study aim, research question, and conclusions. The Mixed Methods Appraisal Tool will be used to assess the quality of the studies included., Results: The results from this scoping review will be presented as a narrative synthesis structured along the key themes of the corpus of evidence. Additional data will be prepared in charts or tabular format. We anticipate the results to be presented in a scoping review at a later date. They will be disseminated at scientific conferences and through publication in a peer-reviewed journal., Conclusions: This is the first scoping review that considers potential change in documentation after implementation of PAEHRs. The results can potentially help affirm or refute prior opinions and expectations among various stakeholders about the use of PAEHRs and thereby help to address uncertainties. Results may help to provide guidance to clinicians in writing notes and thus have immediate practical relevance to care. In addition, the review will help to identify any substantive research gaps in this field of research. In the longer term, our findings may contribute to the development of shared documentation guidelines, which in turn are central to improving patient communication and safety., International Registered Report Identifier (irrid): PRR1-10.2196/46722., (©Eva Meier-Diedrich, Gail Davidge, Maria Hägglund, Anna Kharko, Camilla Lyckblad, Brian McMillan, Charlotte Blease, Julian Schwarz. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 28.08.2023.)

Background: NHS England have announced plans to enable all adult patients to have full prospective access to their primary care record by default. Despite this, little is known about the views and experiences of primary care staff regarding patients' online records access (ORA)., Aim: To examine the views and experiences of primary care staff regarding patients having online access to their primary care health record, and how this service could be supported and improved., Design and Setting: A qualitative study of a purposive sample of 30 primary care staff in England., Method: Online semi-structured interviews with primary care staff were conducted between December 2021 and March 2022. Verbatim transcripts were analysed inductively using thematic analysis., Results: Most staff agreed with the principle of patient access to online health records but had mixed feelings regarding the potential benefits and drawbacks of applying this in practice. Staff identified opportunities for improving patient engagement, health literacy, and efficiencies in some administrative workloads, as well as concerns about maintaining the clinical integrity of patient records and ensuring that staff and patient safety and wellbeing are protected., Conclusion: Participants acknowledged that ORA may transform the purpose and function of the record and that ORA has potential to instigate a significant cultural shift in primary care, changing how staff work and relate to patients. This underlines the need for additional staff training and support to expand capability and capacity to adapt practice and enhance patient engagement with, and understanding of, their health records., (© The Authors.)

The social identity approach to leadership argues that leaders' capacity to influence and inspire others is grounded in a shared sense of social identity (or 'us-ness') that those leaders create, advance, represent, and embed for the groups they lead. The approach therefore argues that a key task for leaders is to develop insights and skills of (social) identity leadership that allow them to motivate and mobilize groups and transform them into a potent social and organizational force. In contrast to other approaches and programs which focus on leaders' leader identity (their 'I-ness'), the 5R leadership development program supports the development of leaders' social identity by raising awareness of the importance of social identity ('we-ness') for leadership and taking leaders through structured activities that help them build engaged and inclusive teams. The present research assessed the benefits of facilitated and learner self-directed versions of the 5R program (Ns = 27, 22 respectively) relative to a no-treatment control (N = 27). Results (including those of an intention-to-treat analysis; N = 76) indicated that, relative to leaders in the control condition, those who participated in both forms of 5R reported large increases in identity leadership knowledge, as well as medium-sized increases in both team engagement (a compound factor comprised of team identification, team OCB, team efficacy, and work engagement) and 'teamfulness' (comprised of team reflexivity, team psychological safety, team goal clarity, and inclusive team climate). We reflect on the importance of teamfulness for leadership and team functioning and on the value of programs that help leaders develop this., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Intellectual property pertaining to the 5R Leadership Development Program is asserted, owned, and licensed by the University of Queensland. The university and its agents have a commercial as well as an intellectual interest in this program. The fourth author is the Director of Identify Leadership which is formally licensed to deliver 5R. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Haslam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Competing interests: None declared.

Background: Mobile health (mHealth) apps have great potential to support the management of chronic conditions. Despite widespread acceptance of mHealth apps by the public, health care providers (HCPs) are reluctant to prescribe or recommend such apps to their patients., Objective: This study aimed to classify and evaluate interventions aimed at encouraging HCPs to prescribe mHealth apps., Methods: A systematic literature search was conducted to identify studies published from January 1, 2008, to August 5, 2022, using 4 electronic databases: MEDLINE, Scopus, CINAHL, and PsycINFO. We included studies that evaluated interventions encouraging HCPs to prescribe mHealth apps. Two review authors independently assessed the eligibility of the studies. The "National Institute of Health's quality assessment tool for before-and-after (pretest-posttest design) studies with no control group" and "the mixed methods appraisal tool (MMAT)" were used to assess the methodological quality. Owing to high levels of heterogeneity between interventions, measures of practice change, specialties of HCPs, and modes of delivery, we conducted a qualitative analysis. We adopted the behavior change wheel as a framework for classifying the included interventions according to intervention functions., Results: In total, 11 studies were included in this review. Most of the studies reported positive findings, with improvements in a number of outcomes, including increased knowledge of mHealth apps among clinicians, improved self-efficacy or confidence in prescribing, and an increased number of mHealth app prescriptions. On the basis of the behavior change wheel, 9 studies reported elements of environmental restructuring such as providing HCPs with lists of apps, technological systems, time, and resources. Furthermore, 9 studies included elements of education, particularly workshops, class lectures, individual sessions with HCPs, videos, or toolkits. Furthermore, training was incorporated in 8 studies using case studies or scenarios or app appraisal tools. Coercion and restriction were not reported in any of the interventions included. The quality of the studies was high in relation to the clarity of aims, interventions, and outcomes but weaker in terms of sample size, power calculations, and duration of follow-up., Conclusions: This study identified interventions to encourage app prescriptions by HCPs. Recommendations for future research should consider previously unexplored intervention functions such as restrictions and coercion. The findings of this review can help inform mHealth providers and policy makers regarding the key intervention strategies impacting mHealth prescriptions and assist them in making informed decisions to encourage this adoption., (©Ohoud Alkhaldi, Brian McMillan, Noha Maddah, John Ainsworth. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 27.02.2023.)

Background: In 2022, NHS England announced plans to ensure that all adult primary care patients in England would have full online access to new data added to their general practitioner (GP) record. However, this plan has not yet been fully implemented. Since April 2020, the GP contract in England has already committed to offering patients full online record access on a prospective basis and on request. However, there has been limited research into UK GPs' experiences and opinions about this practice innovation., Objective: This study aimed to explore the experiences and opinions of GPs in England about patients' access to their full web-based health record, including clinicians' free-text summaries of the consultation (so-called "open notes")., Methods: In March 2022, using a convenience sample, we administered a web-based mixed methods survey of 400 GPs in the United Kingdom to explore their experiences and opinions about the impact on patients and GPs' practices to offer patients full online access to their health records. Participants were recruited using the clinician marketing service Doctors.net.uk from registered GPs currently working in England. We conducted a qualitative descriptive analysis of written responses ("comments") to 4 open-ended questions embedded in a web-based questionnaire., Results: Of 400 GPs, 224 (56%) left comments that were classified into 4 major themes: increased strain on GP practices, the potential to harm patients, changes to documentation, and legal concerns. GPs believed that patient access would lead to extra work for them, reduced efficiency, and increased burnout. The participants also believed that access would increase patient anxiety and incur risks to patient safety. Experienced and perceived documentation changes included reduced candor and changes to record functionality. Anticipated legal concerns encompassed fears about increased litigation risks and lack of legal guidance to GPs about how to manage documentation that would be read by patients and potential third parties., Conclusions: This study provides timely information on the views of GPs in England regarding patient access to their web-based health records. Overwhelmingly, GPs were skeptical about the benefits of access both for patients and to their practices. These views are similar to those expressed by clinicians in other countries, including Nordic countries and the United States before patient access. The survey was limited by the convenience sample, and it is not possible to infer that our sample was representative of the opinions of GPs in England. More extensive, qualitative research is required to understand the perspectives of patients in England after experiencing access to their web-based records. Finally, further research is needed to explore objective measures of the impact of patient access to their records on health outcomes, clinician workload, and changes to documentation., (©Charlotte Blease, John Torous, Zhiyong Dong, Gail Davidge, Catherine DesRoches, Anna Kharko, Andrew Turner, Ray Jones, Maria Hägglund, Brian McMillan. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.02.2023.)

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: During the development of this article, CB, TD, and LS worked at OpenNotes (www.opennotes.org), an education, research, and advocacy unit at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have the following interests to declare: The authors declare no conflicts of interest.

Background: Current evidence supports the use of wearable trackers by people with cardiometabolic conditions. However, as the health benefits are small and confounded by heterogeneity, there remains uncertainty as to which patient groups are most helped by wearable trackers., Objective: This study examined the effects of wearable trackers in patients with cardiometabolic conditions to identify subgroups of patients who most benefited and to understand interventional differences., Methods: We obtained individual participant data from randomized controlled trials of wearable trackers that were conducted before December 2020 and measured steps per day as the primary outcome in participants with cardiometabolic conditions including diabetes, overweight or obesity, and cardiovascular disease. We used statistical models to account for clustering of participants within trials and heterogeneity across trials to estimate mean differences with the 95% CI., Results: Individual participant data were obtained from 9 of 25 eligible randomized controlled trials, which included 1481 of 3178 (47%) total participants. The wearable trackers revealed that over the median duration of 12 weeks, steps per day increased by 1656 (95% CI 918-2395), a significant change. Greater increases in steps per day from interventions using wearable trackers were observed in men (interaction coefficient -668, 95% CI -1157 to -180), patients in age categories over 50 years (50-59 years: interaction coefficient 1175, 95% CI 377-1973; 60-69 years: interaction coefficient 981, 95% CI 222-1740; 70-90 years: interaction coefficient 1060, 95% CI 200-1920), White patients (interaction coefficient 995, 95% CI 360-1631), and patients with fewer comorbidities (interaction coefficient -517, 95% CI -1188 to -11) compared to women, those aged below 50, non-White patients, and patients with multimorbidity. In terms of interventional differences, only face-to-face delivery of the tracker impacted the effectiveness of the interventions by increasing steps per day., Conclusions: In patients with cardiometabolic conditions, interventions using wearable trackers to improve steps per day mostly benefited older White men without multimorbidity., Trial Registration: PROSPERO CRD42019143012; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=143012., (©Alexander Hodkinson, Evangelos Kontopantelis, Salwa S Zghebi, Christos Grigoroglou, Brian McMillan, Harm van Marwijk, Peter Bower, Dialechti Tsimpida, Charles F Emery, Mark R Burge, Hunter Esmiol, Margaret E Cupples, Mark A Tully, Kaberi Dasgupta, Stella S Daskalopoulou, Alexandra B Cooke, Ayorinde F Fayehun, Julie Houle, Paul Poirier, Thomas Yates, Joseph Henson, Derek R Anderson, Elisabeth B Grey, Maria Panagioti. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 30.08.2022.)

Objective: To assess the diagnostic Read code usage for 18 conditions by examining their frequency and diversity in UK primary care between 2000 and 2013., Design: Population-based cohort study SETTING: 684 UK general practices contributing data to the Clinical Practice Research Datalink (CPRD) GOLD., Participants: Patients with clinical codes for at least one of asthma, chronic obstructive pulmonary disease, diabetes, hypertension (HT), coronary heart disease, atrial fibrillation (AF), heart failure, stroke, hypothyroidism, chronic kidney disease, learning disability (LD), depression, dementia, epilepsy, severe mental illness (SMI), osteoarthritis, osteoporosis and cancer., Primary and Secondary Outcome Measures: For the frequency ranking of clinical codes, canonical correlation analysis was applied to correlations of clinical code usage of 1, 3 and 5 years. Three measures of diversity (Shannon entropy index of diversity, richness and evenness) were used to quantify changes in incident and total clinical codes., Results: Overall, all examined conditions, except LD, showed positive monotonic correlation. HT, hypothyroidism, osteoarthritis and SMI codes' usage had high 5-year correlation. The codes' usage diversity remained stable overall throughout the study period. Cancer, diabetes and SMI had the highest richness (code lists need time to define) unlike AF, hypothyroidism and LD. SMI (high richness) and hypothyroidism (low richness) can last for 5 years, whereas cancer and diabetes (high richness) and LD (low richness) only last for 2 years., Conclusions: This is an under-reported research area and the findings suggest the codes' usage diversity for most conditions remained overall stable throughout the study period. Generated mental health code lists can last for a long time unlike cardiometabolic conditions and cancer. Adopting more consistent and less diverse coding would help improve data quality in primary care. Future research is needed following the transfer to the Systematised Nomenclature of Medicine Clinical Terms (SNOMED CT) coding., Competing Interests: Competing interests: DMA reports research grants from Abbvie, Almirall, Celgene, Eli Lilly, Novartis, UCB and the Leo Foundation., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

COVID-19 emergency use authorizations and approvals for vaccines were achieved in record time. However, there remains a need to develop additional safe, effective, easy-to-produce, and inexpensive prevention to reduce the risk of acquiring SARS-CoV-2 infection. This need is due to difficulties in vaccine manufacturing and distribution, vaccine hesitancy, and, critically, the increased prevalence of SARS-CoV-2 variants with greater contagiousness or reduced sensitivity to immunity. Antibodies from eggs of hens (immunoglobulin Y; IgY) that were administered the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were developed for use as nasal drops to capture the virus on the nasal mucosa. Although initially raised against the 2019 novel coronavirus index strain (2019-nCoV), these anti-SARS-CoV-2 RBD IgY surprisingly had indistinguishable enzyme-linked immunosorbent assay binding against variants of concern that have emerged, including Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529). This is different from sera of immunized or convalescent patients. Culture neutralization titers against available Alpha, Beta, and Delta were also indistinguishable from the index SARS-CoV-2 strain. Efforts to develop these IgY for clinical use demonstrated that the intranasal anti-SARS-CoV-2 RBD IgY preparation showed no binding (cross-reactivity) to a variety of human tissues and had an excellent safety profile in rats following 28-day intranasal delivery of the formulated IgY. A double-blind, randomized, placebo-controlled phase 1 study evaluating single-ascending and multiple doses of anti-SARS-CoV-2 RBD IgY administered intranasally for 14 days in 48 healthy adults also demonstrated an excellent safety and tolerability profile, and no evidence of systemic absorption. As these antiviral IgY have broad selectivity against many variants of concern, are fast to produce, and are a low-cost product, their use as prophylaxis to reduce SARS-CoV-2 viral transmission warrants further evaluation., Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT04567810, identifier NCT04567810., Competing Interests: GY, TH, AY, and KB are affiliated with Sutro Biopharma, Inc; NO-H with Charles River Laboratories, Inc; JR, with Linear Clinical Research. Ltd; and BM with Bravado Pharmaceuticals, Inc. DM-R is named on a patent filed for composition and methods for passive immunization against viral infections such as SARS-CoV-2. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Frumkin, Lucas, Scribner, Ortega-Heinly, Rogers, Yin, Hallam, Yam, Bedard, Begley, Cohen, Badger, Abbasi, Dye, McMillan, Wallach, Bricker, Joshi, Boon, Pokhrel, Kraemer, Lee, Kargotich, Agochiya, John and Mochly-Rosen.)

Helicobacter pylori infects the gastric mucosa of a large number of humans. Although asymptomatic in the vast majority of cases, H pylori infection can lead to the development of peptic ulcers gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Using a variety of mechanisms, H pylori locally suppresses the function of the host immune system to establish chronic infection. Systemic immunomodulation has been observed in both clinical and pre-clinical studies, which have demonstrated that H pylori infection is associated with reduced incidence of inflammatory diseases, such as asthma and Crohn's disease. The introduction of immunotherapies in the arsenal of anti-cancer drugs has revealed a new facet of H pylori -induced immune suppression. In this review, we will describe the intimate interactions between H pylori and its host, and formulate hypothtyeses describing the detrimental impact of H pylori infection on the efficacy of cancer immunotherapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Oster, Vaillant, McMillan and Velin.)

We investigate the diagnostic accuracy and predictive value of finger prick capillary dried blood spot (DBS) samples tested by a quantitative multiplex anti-immunoglobulin G (IgG) assay to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies after infection or vaccination. This cross-sectional study involved participants ( n  = 6,841) from several serological surveys conducted in nonhospitalized children and adults throughout 2020 and 2021 in British Columbia (BC), Canada. Analysis used paired DBS and serum samples from a subset of participants ( n  = 642) prior to vaccination to establish signal thresholds and calculate diagnostic accuracy by logistic regression. Discrimination of the logistic regression model was assessed by receiver operator curve (ROC) analysis in an n  = 2,000 bootstrap of the paired sample ( n  = 642). The model was cross-validated in a subset of vaccinated persons ( n  = 90). Unpaired DBS samples ( n  = 6,723) were used to evaluate anti-IgG signal distributions. In comparison to paired serum, DBS samples from an unvaccinated population possessed a sensitivity of 79% (95% confidence interval [95% CI]: 58 to 91%) and specificity of 97% (95% CI: 95 to 98%). ROC analysis found that DBS samples accurately classify SARS-CoV-2 seroconversion at an 88% percent rate (area under the curve [AUC] = 88% [95% CI: 80 to 95%]). In coronavirus disease 2019 (COVID-19) vaccine dose one or two recipients, the sensitivity of DBS testing increased to 97% (95% CI: 83 to 99%) and 100% (95% CI: 88 to 100%). Modeling found that DBS testing possesses a high positive predictive value (98% [95% CI: 97 to 98%]) in a population with 75% seroprevalence. We demonstrate that DBS testing should be considered to reliably detect SARS-CoV-2 seropositivity from natural infection or vaccination. IMPORTANCE Dried blood spot samples have comparable diagnostic accuracy to serum collected by venipuncture when tested by an electrochemiluminescent assay for antibodies and should be considered to reliably detect seropositivity following SARS-CoV-2 infection and/or vaccination.

Introduction: Cardiovascular disease (CVD) remains one of the leading causes of preventable death in Europe, therefore any opportunity to intervene and improve care should be maximised. Known CVD risk factors are routinely collected in the emergency department (ED), yet they are often not acted on. If the risk factors have prognostic value and a pathway can be created, then this would provide more holistic care for patients and reduce health system inefficiency., Methods and Analysis: In this mixed-methods study, we will use quantitative methods to investigate the prognostic characteristics of routinely collected data for long-term CVD outcomes, and qualitative methods to investigate how to use and implement this knowledge. The quantitative arm will use a database of approximately 21 000 chest pain patient episodes with a mean follow-up of 7.3 years. We will use Cox regression to evaluate the prognostic characteristics of routinely collected ED data for long-term CVD outcomes. We will also use a series of semi-structured interviews to co-design a prototype care pathway with stakeholders via thematic analysis. To enable the development of prototypes, themes will be structured into a logic model consisting of situation, inputs, outputs and mechanism., Ethics and Dissemination: This work has been approved by Research Ethics Committee (Wales REC7) and the Human Research Authority under reference 19/WA/0312 and 19/WA/0311. It has also been approved by the Confidentiality Advisory Group reference 19/CAG/0209. Dissent recorded in the NHS' opt-out scheme will be applied to the dataset by NHS Digital. This work will be disseminated through peer-review publication, conference presentation and a public dissemination strategy., Trial Registration Number: ISRCTN41008456., Protocol Version: V.1.0-7 June 2021., Competing Interests: Competing interests: RB has consulted for Siemens, Roche, Beckman, Singulex, LumiraDx and Abbott., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Helicobacter pylori (H. pylori) colonizes the human gastric mucosa with a high worldwide prevalence. Currently, H. pylori is eradicated by the use of antibiotics. However, elevated antibiotic resistance suggests new therapeutic strategies need to be envisioned: one approach being prophylactic vaccination. Pre-clinical and clinical data show that a urease-based vaccine is efficient in decreasing H. pylori infection through the mobilization of T helper (Th) cells, especially Th17 cells. Th17 cells produce interleukins such as IL-22 and IL-17, among others, and are key players in vaccine efficacy. Recently, granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing Th17 cells have been identified., Aim: This study explores the possibility that GM-CSF plays a role in the reduction of H. pylori infection following vaccination., Results: We demonstrate that GM-CSF + IL-17 + Th17 cells accumulate in the stomach mucosa of H. pylori infected mice during the vaccine-induced reduction of H. pylori infection. Secondly, we provide evidence that vaccinated GM-CSF deficient mice only modestly reduce H. pylori infection. Conversely, we observe that an increase in GM-CSF availability reduces H. pylori burden in chronically infected mice. Thirdly, we show that GM-CSF, by acting on gastric epithelial cells, promotes the production of βdefensin3, which exhibits H. pylori bactericidal activities., Conclusion: Taken together, we demonstrate a key role of GM-CSF, most probably originating from Th17 cells, in the vaccine-induced reduction of H. pylori infection., (© 2022 The Authors. Helicobacter published by John Wiley & Sons Ltd.)

Objective: In this study, we determined whether Helicobacter pylori ( H. pylori ) infection dampens the efficacy of cancer immunotherapies., Design: Using mouse models, we evaluated whether immune checkpoint inhibitors or vaccine-based immunotherapies are effective in reducing tumour volumes of H. pylori -infected mice. In humans, we evaluated the correlation between H. pylori seropositivity and the efficacy of the programmed cell death protein 1 (PD-1) blockade therapy in patients with non-small-cell lung cancer (NSCLC)., Results: In mice engrafted with MC38 colon adenocarcinoma or B16-OVA melanoma cells, the tumour volumes of non-infected mice undergoing anticytotoxic T-lymphocyte-associated protein 4 and/or programmed death ligand 1 or anti-cancer vaccine treatments were significantly smaller than those of infected mice. We observed a decreased number and activation status of tumour-specific CD8 + T cells in the tumours of infected mice treated with cancer immunotherapies independent of the gut microbiome composition. Additionally, by performing an in vitro co-culture assay, we observed that dendritic cells of infected mice promote lower tumour-specific CD8 + T cell proliferation. We performed retrospective human clinical studies in two independent cohorts. In the Dijon cohort, H. pylori seropositivity was found to be associated with a decreased NSCLC patient survival on anti-PD-1 therapy. The survival median for H. pylori seropositive patients was 6.7 months compared with 15.4 months for seronegative patients (p=0.001). Additionally, in the Montreal cohort, H. pylori seropositivity was found to be associated with an apparent decrease of NSCLC patient progression-free survival on anti-PD-1 therapy., Conclusion: Our study unveils for the first time that the stomach microbiota affects the response to cancer immunotherapies and that H. pylori serology would be a powerful tool to personalize cancer immunotherapy treatment., Competing Interests: Competing interests: FG received honoraria for oral communication from Lilly, Sanofi, Amgen, and is an advisory board of Merck Serono, Amgen and Sanofi. The remaining authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The objective was to assess the prognostic value of hypertension detected in the emergency department (ED)., Methods: The ED presents a unique opportunity to predict long-term cardiovascular disease (CVD) outcomes with its potential for high-footfall, and large-scale routine data collection applied to underserved patient populations. A systematic review and meta-analyses were conducted to assess the prognostic performance and feasibility of ED-measured hypertension as a risk factor for long-term CVD outcomes. We searched MEDLINE and Embase databases and gray literature sources. The target populations were undifferentiated ED patients. The prognostic factor of interest was hypertension. Feasibility outcomes included prevalence, reliability, and follow-up attendance. Meta-analyses were performed for feasibility using a random effect and exact likelihood., Results: The searches identified 1072 studies after title and abstract review, 53 studies had their full text assessed for eligibility, and 26 studies were included. Significant heterogeneity was identified, likely due to the international populations and differing study design. The meta-analyses estimate of prevalence for ED-measured hypertension was 0.31 (95% confidence interval  0.25-0.37). ED hypertension was persistent outside the ED (FE estimate of 0.50). The proportion of patients attending follow-up was low with an exact likelihood estimate of 0.41. Three studies examined the prognostic performance of hypertension and demonstrated an increased risk of long-term CVD outcomes., Conclusion: Hypertension can be measured feasibly in the ED and consequently used in a long-term cardiovascular risk prediction model. There is an opportunity to intervene in targeted individuals, using routinely collected data., (© 2021 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

The purpose of this study was to evaluate the performance of machine learning algorithms to predict trabeculectomy surgical outcomes. Preoperative systemic, demographic and ocular data from consecutive trabeculectomy surgeries from a single academic institution between January 2014 and December 2018 were incorporated into models using random forest, support vector machine, artificial neural networks and multivariable logistic regression. Mean area under the receiver operating characteristic curve (AUC) and accuracy were used to evaluate the discrimination of each model to predict complete success of trabeculectomy surgery at 1 year. The top performing model was optimized using recursive feature selection and hyperparameter tuning. Calibration and net benefit of the final models were assessed. Among the 230 trabeculectomy surgeries performed on 184 patients, 104 (45.2%) were classified as complete success. Random forest was found to be the top performing model with an accuracy of 0.68 and AUC of 0.74 using 5-fold cross-validation to evaluate the final optimized model. These results provide evidence that machine learning models offer value in predicting trabeculectomy outcomes in patients with refractory glaucoma., (© 2022. The Author(s).)

Objectives: A substantial reduction in self-harm recorded in primary care occurred during the first wave of COVID-19 but effects on primary care management of self-harm are unknown. Our objectives were to examine the impact of COVID-19 on clinical management within 3 months of an episode of self-harm., Design: Retrospective cohort study., Setting: UK primary care., Participants: 4238 patients with an index episode of self-harm recorded in UK primary care during the COVID-19 first-wave period (10 March 2020-10 June 2020) compared with 48 739 patients in a prepandemic comparison period (10 March-10 June, 2010-2019)., Outcome Measures: Using data from the UK Clinical Practice Research Datalink, we compared cohorts of patients with an index self-harm episode recorded during the prepandemic period versus the COVID-19 first-wave period. Patients were followed up for 3 months to capture subsequent general practitioner (GP)/practice nurse consultation, referral to mental health services and psychotropic medication prescribing. We examined differences by gender, age group and Index of Multiple Deprivation quintile., Results: Likelihood of having at least one GP/practice nurse consultation was broadly similar (83.2% vs 80.3% in the COVID-19 cohort). The proportion of patients referred to mental health services in the COVID-19 cohort (4.2%) was around two-thirds of that in the prepandemic cohort (6.1%). Similar proportions were prescribed psychotropic medication within 3 months in the prepandemic (54.0%) and COVID-19 first-wave (54.9%) cohorts., Conclusions: Despite the challenges experienced by primary healthcare teams during the initial COVID-19 wave, prescribing and consultation patterns following self-harm were broadly similar to prepandemic levels. We found no evidence of widening of digital exclusion in terms of access to remote consultations. However, the reduced likelihood of referral to mental health services warrants attention. Accessible outpatient and community services for people who have self-harmed are required as the COVID-19 crisis recedes and the population faces new challenges to mental health., Competing Interests: Competing interests: NK reports grants and personal fees from the UK Department of Health and Social Care, the National Institute of Health Research (NIHR), the National Institute for Health and Care Excellence (NICE) and the Healthcare Quality and Improvement Partnership, outside the submitted work; works with NHS England on national quality improvement initiatives for suicide and self-harm; is a member of the advisory group for the National Suicide Prevention Strategy of the Department of Health and Social Care; has chaired NICE guideline committees for Self-harm and Depression; and is currently the Topic Advisor for the new NICE Guidelines for self-harm. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Appearance-related interventions to promote healthy behaviour have been found effective to communicate health risks. The current study aimed to explore women smokers' experiences of age-progression software showing the effects of smoking on the face., Methods: A qualitative design was implemented, utilizing both individual interviews and focus groups within a critical realist framework. Fifteen, 19-52 year-old women smokers were administered an age-progression intervention. All participants responded to the intervention, engaged in semi-structured interviews, and were invited back to attend one of three focus groups. Data were analysed using inductive thematic analysis., Results: Four main themes were identified: Health versus Appearance, Shock Reaction, Perceived Susceptibility, and Intention to Quit. Participants found the intervention useful, voicing need for a comprehensive approach that includes both appearance and health. Despite increases in appearance-based apps which could diminish impact, women's accounts of shock induced by the aged smoking-morphed images were similar to previous work conducted more than ten years previously., Conclusions: The study provides novel insights in how women smokers currently perceive, and react to, an age-progression intervention for smoking cessation., Innovation: Findings emphasise the implementation of this intervention type accompanied by health information in a range of patient settings., Competing Interests: None to declare., (© 2022 The Authors.)

Netgun capture is a commonly used capture method for mule deer (Odocoileus hemionus) in North America. Mortalities during netgun captures are generally low, and most often caused by direct trauma and occasionally fatal capture myopathy. Capture is a stressful event for a wild animal, and subclinical capture myopathy is difficult to measure. The use of tranquilizers during netgun capture is not widespread. We compared physiologic variables from 250 netgun-captured deer (57 males and 193 females) that did or did not receive midazolam and azaperone (mean, 0.14 mg/kg; SD, 0.02 mg/kg; range, 0.08-0.21 mg/kg) at time of capture and before transporting to a processing location, with the goal of evaluating whether drug administration would improve or worsen the physiologic state of the animal. Deer were captured in association with management activities between December 2018 and March 2020, with 132 deer receiving midazolam and azaperone at time of capture. Variables recorded included chase times, time from capture to arrival at the processing location, time from capture to release, serial rectal temperatures, heart rates, respiratory rates, body condition, age, sex, O2 administration, creatine kinase, aspartate aminotransferase, packed cell volume, red blood cell concentration, and hemoglobin, as well as serial venous pH, pCO2, HCO3-, and base excess. All animals were collared with GPS tracking devices and monitored after release. There was no difference in survival after capture between deer that did or did not receive midazolam and azaperone. All animals experienced severe metabolic lactic acidosis, which generally worsened with increasing chase time, highlighting the critical importance of limiting chase times during captures. Drug administration did not influence the degree of metabolic acidosis; however, it appeared to have a favorable effect on several stress-related indices, including rectal temperature, heart rate, respiratory rate, and packed cell volume., (© Wildlife Disease Association 2022.)

Introduction: People living with multiple long-term conditions (multimorbidity) (MLTC-M) experience an accumulating combination of different symptoms. It has been suggested that these symptoms can be tracked longitudinally using consumer technology, such as smartphones and wearable devices., Aim: The aim of this study was to investigate longitudinal user engagement with a smartwatch application, collecting survey questions and active tasks over 90 days, in people living with MLTC-M., Methods: 'Watch Your Steps ' was a prospective observational study, administering multiple questions and active tasks over 90 days. Adults with more than one clinician-diagnosed long-term conditions were loaned Fossil® Sport smartwatches, pre-loaded with the study app. Around 20 questions were prompted per day.Daily completion rates were calculated to describe engagement patterns over time, and to explore how these varied by patient characteristics and question type., Results: Fifty three people with MLTC-M took part in the study. Around half were male ( = 26; 49%) and the majority had a white ethnic background ( n = 45; 85%). About a third of participants engaged with the smartwatch app nearly every day. The overall completion rate of symptom questions was 45% inter-quartile range (IQR 23-67%) across all study participants. Older patients and those with greater MLTC-M were more engaged, although engagement was not significantly different between genders., Conclusion: It was feasible for people living with MLTC-M to report multiple symptoms per day over 3 months. User engagement appeared as good as other mobile health studies that recruited people with single health conditions, despite the higher daily data entry burden., Competing Interests: Declaration of conflicting interest: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: WGD has received consultancy fees from Abbvie and Google., (© The Author(s) 2021.)

Pathogenic germline mutations in the RAD51 paralog genes RAD51C and RAD51D, are known to confer susceptibility to ovarian and triple-negative breast cancer. Here, we investigated whether germline loss-of-function variants affecting another RAD51 paralog gene, RAD51B, are also associated with breast and ovarian cancer. Among 3422 consecutively accrued breast and ovarian cancer patients consented to tumor/germline sequencing, the observed carrier frequency of loss-of-function germline RAD51B variants was significantly higher than control cases from the gnomAD population database (0.26% vs 0.09%), with an odds ratio of 2.69 (95% CI: 1.4-5.3). Furthermore, we demonstrate that tumors harboring biallelic RAD51B alteration are deficient in homologous recombination DNA repair deficiency (HRD), as evidenced by analysis of sequencing data and in vitro functional assays. Our findings suggest that RAD51B should be considered as an addition to clinical germline testing panels for breast and ovarian cancer susceptibility., (© 2021. The Author(s).)

Background: Patients presenting with chest pain represent a large proportion of attendances to emergency departments. In these patients clinicians often consider the diagnosis of acute myocardial infarction (AMI), the timely recognition and treatment of which is clinically important. Clinical prediction models (CPMs) have been used to enhance early diagnosis of AMI. The Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid is currently in clinical use across Greater Manchester. CPMs have been shown to deteriorate over time through calibration drift. We aim to assess potential calibration drift with T-MACS and compare methods for updating the model., Methods: We will use routinely collected electronic data from patients who were treated using TMACS at two large NHS hospitals. This is estimated to include approximately 14,000 patient episodes spanning June 2016 to October 2020. The primary outcome of acute myocardial infarction will be sourced from NHS Digital's admitted patient care dataset. We will assess the calibration drift of the existing model and the benefit of updating the CPM by model recalibration, model extension and dynamic updating. These models will be validated by bootstrapping and one step ahead prequential testing. We will evaluate predictive performance using calibrations plots and c-statistics. We will also examine the reclassification of predicted probability with the updated TMACS model., Discussion: CPMs are widely used in modern medicine, but are vulnerable to deteriorating calibration over time. Ongoing refinement using routinely collected electronic data will inevitably be more efficient than deriving and validating new models. In this analysis we will seek to exemplify methods for updating CPMs to protect the initial investment of time and effort. If successful, the updating methods could be used to continually refine the algorithm used within TMACS, maintaining or even improving predictive performance over time., Trial Registration: ISRCTN number: ISRCTN41008456., (© 2021. The Author(s).)

PRMT5 is an essential arginine methyltransferase and a therapeutic target in MTAP-null cancers. PRMT5 uses adaptor proteins for substrate recruitment through a previously undefined mechanism. Here, we identify an evolutionarily conserved peptide sequence shared among the three known substrate adaptors (CLNS1A, RIOK1, and COPR5) and show that it is necessary and sufficient for interaction with PRMT5. We demonstrate that PRMT5 uses modular adaptor proteins containing a common binding motif for substrate recruitment, comparable with other enzyme classes such as kinases and E3 ligases. We structurally resolve the interface with PRMT5 and show via genetic perturbation that it is required for methylation of adaptor-recruited substrates including the spliceosome, histones, and ribosomal complexes. Furthermore, disruption of this site affects Sm spliceosome activity, leading to intron retention. Genetic disruption of the PRMT5-substrate adaptor interface impairs growth of MTAP-null tumor cells and is thus a site for development of therapeutic inhibitors of PRMT5., Competing Interests: Declaration of interests Materials related to this article are in a provisional patent application by the Broad Institute. W.R.S. is a board or scientific advisory board (SAB) member and holds equity in Peloton Therapeutics, Ideaya Biosciences, Civetta Therapeutics, and Bluebird bio; has consulted for Array, Astex, Dynamo Therapeutics, Ipsen, Merck Pharmaceuticals, PearlRiver Therapeutics, Sanofi, Scorpion Therapeutics, and Servier; and receives research funding from Pfizer Pharmaceuticals, Merck Pharmaceuticals, Ideaya Biosciences, and Deerfield Management. B.J.M. is an employee and equity holder of Tango Therapeutics. D. Porter is an employee and equity holder of Cedilla Therapeutics. A.J.A. has consulted for Oncorus Inc., Arrakis Therapeutics, and Merck & Company and has research funding from Mirati Therapeutics and Deerfield Management., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Precis: In a trio of prospective studies, the iCare rebound tonometer demonstrated significantly lower test-retest variability than Goldmann tonometry with good interoperator and interdevice reproducibility, supporting its value in monitoring intraocular pressure (IOP) changes over time., Purpose: The purpose of this study was to characterize intraoperator and interoperator and interdevice reliability of IOP measurements with rebound tonometry (RT, ic100)., Methods: Three prospective cross-sectional studies were conducted in distinct sample of adult patients with established glaucoma, suspected glaucoma, or no glaucoma at the West Virginia University Eye Institute. Participants in study 1 underwent 5 RT measurements in one randomly selected eye and 5 Goldmann tonometry measurements in the fellow eye by 1 operator; intraoperator variability was compared using the F test. In study 2, 3 operators each obtained 3 RT measurements in participants in randomized operator order. In study 3, a single operator collected 3 measurements each with 3 RTs in randomized device order. Between-operator and between-device reproducibility were characterized using intraclass correlation coefficients (ICCs)., Results: Overall, 28, 19, and 25 subjects participated in the 3 respective studies. Within-subject variance across subjects was 0.757 in RT measurements and 2.471 in Goldmann measurements (P=0.0035). Interoperator reproducibility of RT measurements was good in both eyes [ICC for right eyes 0.78, 95% confidence interval (CI): 0.60-0.85; ICC for left eyes 0.75, 95% CI: 0.50-0.83]. Interdevice reproducibility of RT measurements was good approaching excellent (ICC for right eyes 0.87, 95% CI: 0.83-0.90; ICC for left eyes 0.89, 95% CI: 0.86-0.91)., Conclusions: The RT's lower measurement variability and good interoperator and interdevice reproducibility suggest that it can characterize IOP changes over time more robustly than Goldmann tonometry, aiding clinicians in assessing the effectiveness of glaucoma therapy and the consistency of IOP control., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Activities of daily living and quality of life (QOL) are hindered by upper extremity (UE) impairments experienced by individuals with multiple sclerosis (iMS). The Nine-Hole Peg Test (9-HPT) is most frequently used to measure UE function. However, it does not measure peoples' ability to perform routine tasks in daily life and may not be useful in iMS who cannot pick up the pegs utilized in the 9-HPT. Therefore, we evaluated three measures to explore a more comprehensive assessment of UE function: Upper Extremity Function Scale (UEFS), Action Research Arm Test (ARAT), and the 9-HPT. The objectives were to quantitatively assess the relationship between these measures of UE function, understand if the measures correlate with QOL as calculated by the MS Quality of Life-54 (MSQOL-54), and to determine differences in the measures based on employment status., Methods: 112 (79 female) iMS were prospectively recruited for this descriptive correlational study. Inclusion criteria were as follows: confirmed diagnosis of MS or clinically isolated syndrome, age ≥ 18 years, and ability to self-consent. All statistical analyses including Spearman's correlation coefficient ( r s ) and Kruskal-Wallis tests were performed using SPSS., Results: A moderate correlation ( r s = -0.51; p < 0.001) was found between the ARAT and 9-HPT scores for the more impaired hand. Likewise, a moderate correlation was found between UEFS and the physical health composite scores (PHCSs) of MSQOL-54 ( r s = -0.59; p < 0.001). Finally, performances on ARAT, 9-HPT, and UEFS differed between the employed individuals and those on long-term disability ( p = 0.007, p < 0.001, and p = 0.001)., Conclusion: The UEFS moderately correlated with the QOL measure, and considering the UESF is a patient-reported outcome, it could be used to complement routinely captured measures of assessing UE function. Further study is warranted to determine which measure, or combination of measures, is more sensitive to changes in UE function over time., Competing Interests: Dr. Levin has received educational and/or consulting funding from Biogen Idec, Pendopharm, and Sanofi Genzyme. Dr. Zucker-Levin, Dr. Saini, Dr. Donkers, Benjamin McMillan, and Pawan Kumar have no conflicts of interest., (Copyright © 2021 Aman Saini et al.)

Helicobacter pylori (Hp) colonizes the human gastric mucosa with a high worldwide prevalence. Currently, Hp can be eradicated by the use of antibiotics. Due to the increase of antibiotic resistance, new therapeutic strategies need to be devised: one such approach being prophylactic vaccination. Pre-clinical and clinical data showed that a urease-based vaccine is efficient in decreasing Hp infection through the mobilization of T helper (Th)-dependent immune effectors, including eosinophils. Preliminary data have shown that upon vaccination and subsequent Hp infection, eosinophils accumulate in the gastric mucosa, suggesting a possible implication of this granulocyte subset in the vaccine-induced reduction of Hp infection. In our study, we confirm that activated eosinophils, expressing CD63, CD40, MHCII and PD-L1 at their cell surface, infiltrate the gastric mucosa during vaccine-induced reduction of Hp infection. Strikingly, we provide evidence that bone marrow derived eosinophils efficiently kill Hp in vitro, suggesting that eosinophils may participate to the vaccine-induced reduction of Hp infection. However, conversely to our expectations, the absence of eosinophils does not decrease the efficacy of this Hp vaccine in vivo. Indeed, vaccinated mice that have been genetically ablated of the eosinophil lineage or that have received anti-Sialic acid-binding immunoglobulin-like lectin F eosinophil-depleting antibodies, display a lower Hp colonization when compared to their eosinophil sufficient counterparts. Although the vaccine induces similar urease-specific humoral and Th responses in both eosinophil sufficient and deficient mice, a decreased production of anti-inflammatory cytokines, such as IL-10, TGFβ, and calgranulin B, was specifically observed in eosinophil depleted mice. Taken together, our results suggest that gastric eosinophils maintain an anti-inflammatory environment, thus sustaining chronic Hp infection. Because eosinophils are one of the main immune effectors mobilized by Th2 responses, our study strongly suggests that the formulation of an Hp vaccine needs to include an adjuvant that preferentially primes Hp-specific Th1/Th17 responses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)