Crystal Structure of a Full-Length Human Tetraspanin Reveals a Cholesterol-Binding Pocket.

Tetraspanins comprise a diverse family of four-pass transmembrane proteins that play critical roles in the immune, reproductive, genitourinary, and auditory systems. Despite their pervasive roles in human physiology, little is known about the structure of tetraspanins or the molecular mechanisms underlying their various functions. Here, we report the crystal structure of human CD81, a full-length tetraspanin. The transmembrane segments of CD81 pack as two largely separated pairs of helices, capped by the large extracellular loop (EC2) at the outer membrane leaflet. The two pairs of helices converge at the inner leaflet to create an intramembrane pocket with additional electron density corresponding to a bound cholesterol molecule within the cavity. Molecular dynamics simulations identify an additional conformation in which EC2 separates substantially from the transmembrane domain. Cholesterol binding appears to modulate CD81 activity in cells, suggesting a potential mechanism for regulation of tetraspanin function.

Molecular basis for substrate recruitment to the PRMT5 methylosome.

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.

An Age-Progression Intervention for Smoking Cessation: A Pilot Study Investigating the Influence of Two Sets of Instructions on Intervention Efficacy.

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], eta2 = 0.11); quit attempts were greater in the two intervention arms (58%) versus Control (1-month post-intervention, 15%) (χ2 = 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.

A tail of two sites: a bipartite mechanism for recognition of notch ligands by mind bomb E3 ligases.

Mind bomb (Mib) proteins are large, multi-domain E3 ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. This ubiquitination step marks the ligand proteins for epsin-dependent endocytosis, which is critical for in vivo Notch receptor activation. We present here crystal structures of the substrate recognition domains of Mib1, both in isolation and in complex with peptides derived from Notch ligands. The structures, in combination with biochemical, cellular, and in vivo assays, show that Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membrane proximal region and the other near the C terminus. Together, these studies provide insights into the mechanism of ubiquitin transfer by Mind bomb E3 ligases, illuminate a key event in ligand-induced activation of Notch receptors, and identify a potential target for therapeutic modulation of Notch signal transduction in disease.

The association of herpes zoster and influenza vaccinations with the risk of developing dementia: a population-based cohort study within the UK Clinical Practice Research Datalink.

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.

Patient Online Record Access in English Primary Care: Qualitative Survey Study of General Practitioners' Views.

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.

Association Between Patient Factors and the Effectiveness of Wearable Trackers at Increasing the Number of Steps per Day Among Adults With Cardiometabolic Conditions: Meta-analysis of Individual Patient Data From Randomized Controlled Trials.

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_record.php?RecordID=143012.

Patients' Adoption of Electronic Personal Health Records in England: Secondary Data Analysis.

BACKGROUND: In England, almost all general practices (GPs) have implemented GP online services such as electronic personal health records (ePHRs) that allow people to schedule appointments, request repeat prescriptions, and access parts of their medical records. The overall adoption rate of GP online services has been low, reaching just 28% in October 2019. In a previous study, Abd-Alrazaq et al adopted a model to assess the factors that influence patients' use of GP online services in England. According to the previous literature, the predictive power of the Abd-Alrazaq model could be improved by proposing new associations between the existing variables in the model. OBJECTIVE: This study aims to improve the predictive power of the Abd-Alrazaq model by proposing new relationships between the existing variables in the model. METHODS: The Abd-Alrazaq model was amended by proposing new direct, mediating, moderating, and moderated mediating effects. The amended model was examined using data from a previous study, which were collected by a cross-sectional survey of a convenience sample of 4 GPs in West Yorkshire, England. Structural equation modeling was used to examine the theoretical model and hypotheses. RESULTS: The new model accounted for 53% of the variance in performance expectancy (PE), 76% of the variance in behavioral intention (BI), and 49% of the variance in use behavior (UB). In addition to the significant associations found in the previous study, this study found that social influence (SI) and facilitating conditions (FCs) are associated with PE directly and BI indirectly through PE. The association between BI and UB was stronger for younger women with higher levels of education, income, and internet access. The indirect effects of effort expectancy (EE), perceived privacy and security (PPS), and SI on BI were statistically stronger for women without internet access, patients with internet access, and patients without internet access, respectively. The indirect effect of PPS on BI was stronger for patients with college education or diploma than for those with secondary school education and lower, whereas the indirect effect of EE on BI was stronger for patients with secondary school education or lower than for those with college education or a diploma. CONCLUSIONS: The predictive power of the Abd-Alrazaq model improved by virtue of new significant associations that were not examined before in the context of ePHRs. Further studies are required to validate the new model in different contexts and to improve its predictive power by proposing new variables. The influential factors found in this study should be considered to improve patients' use of ePHRs.

Predicting visual function after an ocular bee sting.

PURPOSE: To report a case of toxic optic neuropathy caused by an ocular bee sting. METHODS: Case report and literature review. RESULTS: A 44-year-old female presented with no light perception vision 2 days after a corneal bee sting in her right eye. She was found to have diffuse cornea edema with overlying epithelial defect and a pinpoint penetrating laceration at 6 o'clock. There was an intense green color to the cornea. The pupil was fixed and dilated with an afferent pupillary defect. A small hyphema was seen, and a dense white cataract had formed. A diagnosis of toxic endophthalmitis with associated toxic optic neuropathy was made. The patient underwent pars plana vitrectomy and lensectomy with anterior chamber washout. She was also placed on systemic broad-spectrum antibiotics. She had noted clinical improvement over the course of her hospitalization and was discharged with light perception vision. A corneal opacity precluded viewing of the fundus. We utilized ganzfeld electroretinography and flash visual evoked potentials (2 and 10 Hz) to assess the visual function. Both tests were normal and predicted improvement following restorative surgery. She underwent a secondary lens implantation with penetrating keratoplasty 7 months later. This was followed by an epiretinal membrane peel 1 year after the bee sting. Her best corrected visual acuity improved to 20/80. CONCLUSION: Toxic endophthalmitis and toxic optic neuropathy can be complications of ocular bee sting. We discuss the management of this rare occurrence and the role of electroretinographic testing and visual evoked potentials in predicting visual outcome.

Primary Care Patient Records in the United Kingdom: Past, Present, and Future Research Priorities.

This paper briefly outlines the history of the medical record and the factors contributing to the adoption of computerized records in primary care in the United Kingdom. It discusses how both paper-based and electronic health records have traditionally been used in the past and goes on to examine how enabling patients to access their own primary care record online is changing the form and function of the patient record. In addition, it looks at the evidence for the benefits of Web-based access and discusses some of the challenges faced in this transition. Finally, some suggestions are made regarding the future of the patient record and research questions that need to be addressed to help deepen our understanding of how they can be used more beneficially by both patients and clinicians.

Structure of human POFUT1, its requirement in ligand-independent oncogenic Notch signaling, and functional effects of Dowling-Degos mutations.

Protein O-fucosyltransferase-1 (POFUT1), which transfers fucose residues to acceptor sites on serine and threonine residues of epidermal growth factor-like repeats of recipient proteins, is essential for Notch signal transduction in mammals. Here, we examine the consequences of POFUT1 loss on the oncogenic signaling associated with certain leukemia-associated mutations of human Notch1, report the structures of human POFUT1 in free and GDP-fucose bound states, and assess the effects of Dowling-Degos mutations on human POFUT1 function. CRISPR-mediated knockout of POFUT1 in U2OS cells suppresses both normal Notch1 signaling, and the ligand-independent signaling associated with leukemogenic mutations of Notch1. Normal and oncogenic signaling are rescued by wild-type POFUT1 but rescue is impaired by an active-site R240A mutation. The overall structure of the human enzyme closely resembles that of the Caenorhabditis elegans protein, with an overall backbone RMSD of 0.93 Å, despite primary sequence identity of only 39% in the mature protein. GDP-fucose binding to the human enzyme induces limited backbone conformational movement, though the side chains of R43 and D244 reorient to make direct contact with the fucose moiety in the complex. The reported Dowling-Degos mutations of POFUT1, except for M262T, fail to rescue Notch1 signaling efficiently in the CRISPR-engineered POFUT1-/- background. Together, these studies identify POFUT1 as a potential target for cancers driven by Notch1 mutations and provide a structural roadmap for its inhibition.

Cost effectiveness of using cognitive screening tests for detecting dementia and mild cognitive impairment in primary care.

INTRODUCTION: We estimated the cost effectiveness of different cognitive screening tests for use by General Practitioners (GPs) to detect cognitive impairment in England. METHODS: A patient-level cost-effectiveness model was developed using a simulated cohort that represents the elderly population in England (65 years and older). Each patient was followed over a lifetime period. Data from published sources were used to populate the model. The costs include government funded health and social care, private social care and informal care. Patient health benefit was measured and valued in Quality Adjusted Life Years (QALYs). RESULTS: Base-case analyses found that adopting any of the three cognitive tests (Mini-Mental State Examination, 6-Item Cognitive Impairment Test or GPCOG (General Practitioner Assessment of Cognition)) delivered more QALYs for patients over their lifetime and made savings across sectors including healthcare, social care and informal care compared with GP unassisted judgement. The benefits were due to early access to medications. Among the three cognitive tests, adopting the GPCOG was considered the most cost-effective option with the highest Incremental Net Benefit (INB) at the threshold of £30 000 per QALY from both the National Health Service and Personal Social Service (NHS PSS) perspective (£195 034 per 1000 patients) and the broader perspective that includes private social care and informal care (£196 251 per 1000 patients). Uncertainty was assessed in both deterministic and probabilistic sensitivity analyses. CONCLUSIONS: Our analyses indicate that the use of any of the three cognitive tests could be considered a cost-effective strategy compared with GP unassisted judgement. The most cost-effective option in the base-case was the GPCOG. Copyright © 2016 John Wiley & Sons, Ltd.

'Getting it write' in a new era of patient online access to primary care health records.

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.

Generative Language Models and Open Notes: Exploring the Promise and Limitations.

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.

"Test-Retest Reliability of Intraocular Pressure Measurements with Office-Based versus Home-Based Rebound Tonometers".

PRCIS: Intraocular pressure (IOP) measurements obtained with the HOME2 rebound tonometer are interchangeable with measurements obtained using the office-based IC100 and IC200 rebound tonometers, making characterization of circadian IOP achievable with no inter-device sources of variability. PURPOSE: To evaluate test-retest reliability between intraocular pressure (IOP) measurements obtained with a home rebound tonometer operated by patients and those obtained with office rebound tonometers operated by experienced clinical staff. METHODS: Following training and practice with a home rebound tonometer (iCare HOME2) in a randomly selected eye, patients with established or suspected open-angle glaucoma underwent IOP measurement in the fellow eye as follows in randomized order: 3 good quality measurements with the iCare IC100 operated by experienced clinical staff, 3 good quality measurements with the iCare IC200 operated by experienced clinical staff, and 3 good quality measurements with the HOME2 operated by the subject. The Shrout-Fleisch intraclass correlation coefficient ICC (2,1) was the measure of reliability utilized based on the model using two-way random effects, absolute agreement, and single measurement. RESULTS: Thirty eyes of 30 patients were evaluated. The Pearson correlation coefficient (r) for IOP measurements taken with the IC100 and HOME2 was 0.97, with the IC200 and HOME2 was 0.96, and with the IC100 and IC200 was 0.97. Test-retest reliability between HOME2 and IC100 (ICC 0.90), HOME2 and IC200 (ICC 0.92), and IC100 and IC200 (ICC 0.94) all reflected excellent test-retest reliability. CONCLUSION: The test-retest reliability of IOP measurements taken by patients using the iCare HOME2 self-tonometer compared with IOP measurements taken by trained operators using the iCare IC100 and IC200 tonometers was uniformly excellent (ICCs all ≥0.9). These findings indicate that these three devices should be considered interchangeable for the clinical assessment of circadian IOP.

Exploring potential drivers of patient engagement with their health data through digital platforms: A scoping review.

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.

Mapping Patients' Online Record Access Worldwide: Preliminary Results from an International Survey of Healthcare Experts.

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.

Experiences and opinions of general practitioners with patient online record access: an online survey in England.

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.