Prevalence of orthostatic intolerance in long covid clinic patients and healthy volunteers: A multicenter study.

Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.

Challenges to implementing electronic trial data collection in primary care: a qualitative study.

BACKGROUND: Within-consultation recruitment to primary care trials is challenging. Ensuring procedures are efficient and self-explanatory is the key to optimising recruitment. Trial recruitment software that integrates with the electronic health record to support and partially automate procedures is becoming more common. If it works well, such software can support greater participation and more efficient trial designs. An innovative electronic trial recruitment and outcomes software was designed to support recruitment to the Runny Ear randomised controlled trial, comparing topical, oral and delayed antibiotic treatment for acute otitis media with discharge in children. A qualitative evaluation investigated the views and experiences of primary care staff using this trial software. METHODS: Staff were purposively sampled in relation to site, role and whether the practice successfully recruited patients. In-depth interviews were conducted using a flexible topic guide, audio recorded and transcribed. Data were analysed thematically. RESULTS: Sixteen staff were interviewed, including GPs, practice managers, information technology (IT) leads and research staff. GPs wanted trial software that automatically captures patient data. However, the experience of getting the software to work within the limited and complex IT infrastructure of primary care was frustrating and time consuming. Installation was reliant on practice level IT expertise, which varied between practices. Although most had external IT support, this rarely included supported for research IT. Arrangements for approving new software varied across practices and often, but not always, required authorisation from Clinical Commissioning Groups. CONCLUSIONS: Primary care IT systems are not solely under the control of individual practices or CCGs or the National Health Service. Rather they are part of a complex system that spans all three and is influenced by semi-autonomous stakeholders operating at different levels. This led to time consuming and sometimes insurmountable barriers to installation at the practice level. These need to be addressed if software supporting efficient research in primary care is to become a reality.

The impact of governance in primary health care delivery: a systems thinking approach with a European panel.

BACKGROUND: Enhancing primary health care (PHC) is considered a policy priority for health systems strengthening due to PHC's ability to provide accessible and continuous care and manage multimorbidity. Research in PHC often focuses on the effects of specific interventions (e.g. physicians' contracts) in health care outcomes. This informs narrowly designed policies that disregard the interactions between the health functions (e.g. financing and regulation) and actors involved (i.e. public, professional, private), and their impact in care delivery and outcomes. The purpose of this study is to analyse the interactions between PHC functions and their impact in PHC delivery, particularly in providers' behaviour and practice organisation. METHODS: Following a systems thinking approach with data obtained through a three-round European Delphi process, we developed a framework that captures (1) the interactions between PHC functions by analysing correlations between PHC characteristics of participating countries, (2) how actors involved shaped these interactions by identifying the actor and level of devolution (or fragmentation) in the analysis, and (3) their potential effect on care delivery by exploring panellists' opinions. RESULTS: A total of 59 panellists from 24 countries participated in the first round and 76% of the initial panellists (22 countries) completed the last round. Findings show correlations between governance, financing and regulation based on their degree of decentralisation. This is supported by panellists, who agreed that the actors involved in health system governance determine the type of PHC financing (e.g. ownership or payment mechanisms) and regulation (e.g. competences or gatekeeping), and this may impact care delivery and outcomes. Governance in our framework is an overarching function whose impact in PHC delivery is mediated through the degree of decentralisation (both delegation and devolution) of PHC financing and regulation. CONCLUSIONS: The application of this approach in policy implementation assessment intends to uncover limitations due to poor accountability and commitment to shared objectives. Its application in the design of health strategies helps foresee (and prevent) undesired or unexpected effects of narrow interventions. This approach will assist in the development of the realistic and long-term policies required for health systems strengthening.

What gives rise to clinician gut feeling, its influence on management decisions and its prognostic value for children with RTI in primary care: a prospective cohort study.

BACKGROUND: The objectives were to identify 1) the clinician and child characteristics associated with; 2) clinical management decisions following from, and; 3) the prognostic value of; a clinician's 'gut feeling something is wrong' for children presenting to primary care with acute cough and respiratory tract infection (RTI). METHODS: Multicentre prospective cohort study where 518 primary care clinicians across 244 general practices in England assessed 8394 children aged ≥3 months and < 16 years for acute cough and RTI. The main outcome measures were: Self-reported clinician 'gut feeling'; clinician management decisions (antibiotic prescribing, referral for acute admission); and child's prognosis (reconsultation with evidence of illness deterioration, hospital admission in the 30 days following recruitment). RESULTS: Clinician years since qualification, parent reported symptoms (illness severity score ≥ 7/10, severe fever < 24 h, low energy, shortness of breath) and clinical examination findings (crackles/ crepitations on chest auscultation, recession, pallor, bronchial breathing, wheeze, temperature ≥ 37.8 °C, tachypnoea and inflamed pharynx) independently contributed towards a clinician 'gut feeling that something was wrong'. 'Gut feeling' was independently associated with increased antibiotic prescribing and referral for secondary care assessment. After adjustment for other associated factors, gut feeling was not associated with reconsultations or hospital admissions. CONCLUSIONS: Clinicians were more likely to report a gut feeling something is wrong, when they were more experienced or when children were more unwell. Gut feeling is independently and strongly associated with antibiotic prescribing and referral to secondary care, but not with two indicators of poor child health.

Possible Sources of Bias in Primary Care Electronic Health Record Data Use and Reuse.

BACKGROUND: Enormous amounts of data are recorded routinely in health care as part of the care process, primarily for managing individual patient care. There are significant opportunities to use these data for other purposes, many of which would contribute to establishing a learning health system. This is particularly true for data recorded in primary care settings, as in many countries, these are the first place patients turn to for most health problems. OBJECTIVE: In this paper, we discuss whether data that are recorded routinely as part of the health care process in primary care are actually fit to use for other purposes such as research and quality of health care indicators, how the original purpose may affect the extent to which the data are fit for another purpose, and the mechanisms behind these effects. In doing so, we want to identify possible sources of bias that are relevant for the use and reuse of these type of data. METHODS: This paper is based on the authors' experience as users of electronic health records data, as general practitioners, health informatics experts, and health services researchers. It is a product of the discussions they had during the Translational Research and Patient Safety in Europe (TRANSFoRm) project, which was funded by the European Commission and sought to develop, pilot, and evaluate a core information architecture for the learning health system in Europe, based on primary care electronic health records. RESULTS: We first describe the different stages in the processing of electronic health record data, as well as the different purposes for which these data are used. Given the different data processing steps and purposes, we then discuss the possible mechanisms for each individual data processing step that can generate biased outcomes. We identified 13 possible sources of bias. Four of them are related to the organization of a health care system, whereas some are of a more technical nature. CONCLUSIONS: There are a substantial number of possible sources of bias; very little is known about the size and direction of their impact. However, anyone that uses or reuses data that were recorded as part of the health care process (such as researchers and clinicians) should be aware of the associated data collection process and environmental influences that can affect the quality of the data. Our stepwise, actor- and purpose-oriented approach may help to identify these possible sources of bias. Unless data quality issues are better understood and unless adequate controls are embedded throughout the data lifecycle, data-driven health care will not live up to its expectations. We need a data quality research agenda to devise the appropriate instruments needed to assess the magnitude of each of the possible sources of bias, and then start measuring their impact. The possible sources of bias described in this paper serve as a starting point for this research agenda.

The impact of a diagnostic decision support system on the consultation: perceptions of GPs and patients.

BACKGROUND: Clinical decision support systems (DSS) aimed at supporting diagnosis are not widely used. This is mainly due to usability issues and lack of integration into clinical work and the electronic health record (EHR). In this study we examined the usability and acceptability of a diagnostic DSS prototype integrated with the EHR and in comparison with the EHR alone. METHODS: Thirty-four General Practitioners (GPs) consulted with 6 standardised patients (SPs) using only their EHR system (baseline session); on another day, they consulted with 6 different but matched for difficulty SPs, using the EHR with the integrated DSS prototype (DSS session). GPs were interviewed twice (at the end of each session), and completed the Post-Study System Usability Questionnaire at the end of the DSS session. The SPs completed the Consultation Satisfaction Questionnaire after each consultation. RESULTS: The majority of GPs (74%) found the DSS useful: it helped them consider more diagnoses and ask more targeted questions. They considered three user interface features to be the most useful: (1) integration with the EHR; (2) suggested diagnoses to consider at the start of the consultation and; (3) the checklist of symptoms and signs in relation to each suggested diagnosis. There were also criticisms: half of the GPs felt that the DSS changed their consultation style, by requiring them to code symptoms and signs while interacting with the patient. SPs sometimes commented that GPs were looking at their computer more than at them; this comment was made more often in the DSS session (15%) than in the baseline session (3%). Nevertheless, SP ratings on the satisfaction questionnaire did not differ between the two sessions. CONCLUSIONS: To use the DSS effectively, GPs would need to adapt their consultation style, so that they code more information during rather than at the end of the consultation. This presents a potential barrier to adoption. Training GPs to use the system in a patient-centred way, as well as improvement of the DSS interface itself, could facilitate coding. To enhance patient acceptability, patients should be informed about the potential of the DSS to improve diagnostic accuracy.

Improving the Diagnosis and Treatment of Urinary Tract Infection in Young Children in Primary Care: Results from the DUTY Prospective Diagnostic Cohort Study.

PURPOSE: Up to 50% of urinary tract infections (UTIs) in young children are missed in primary care. Urine culture is essential for diagnosis, but urine collection is often difficult. Our aim was to derive and internally validate a 2-step clinical rule using (1) symptoms and signs to select children for urine collection; and (2) symptoms, signs, and dipstick testing to guide antibiotic treatment. METHODS: We recruited acutely unwell children aged under 5 years from 233 primary care sites across England and Wales. Index tests were parent-reported symptoms, clinician-reported signs, urine dipstick results, and clinician opinion of UTI likelihood (clinical diagnosis before dipstick and culture). The reference standard was microbiologically confirmed UTI cultured from a clean-catch urine sample. We calculated sensitivity, specificity, and area under the receiver operator characteristic (AUROC) curve of coefficient-based (graded severity) and points-based (dichotomized) symptom/sign logistic regression models, and we then internally validated the AUROC using bootstrapping. RESULTS: Three thousand thirty-six children provided urine samples, and culture results were available for 2,740 (90%). Of these results, 60 (2.2%) were positive: the clinical diagnosis was 46.6% sensitive, with an AUROC of 0.77. Previous UTI, increasing pain/crying on passing urine, increasingly smelly urine, absence of severe cough, increasing clinician impression of severe illness, abdominal tenderness on examination, and normal findings on ear examination were associated with UTI. The validated coefficient- and points-based model AUROCs were 0.87 and 0.86, respectively, increasing to 0.90 and 0.90, respectively, by adding dipstick nitrites, leukocytes, and blood. CONCLUSIONS: A clinical rule based on symptoms and signs is superior to clinician diagnosis and performs well for identifying young children for noninvasive urine sampling. Dipstick results add further diagnostic value for empiric antibiotic treatment.

Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people.

BACKGROUND: Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H. pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. This is an update of Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive patients. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003840. DOI: 10.1002/14651858.CD003840.pub4. OBJECTIVES: To assess the proportion of peptic ulcers healed and the proportion of participants who remained free from relapse with eradication therapy against placebo or other pharmacological therapies in H. pylori-positive people.To assess the proportion of participants that achieved complete relief of symptoms and improvement in quality of life scores.To compare the incidence of adverse effects/drop-outs (total number for each drug) associated with the different treatments.To assess the proportion of participants in whom successful eradication was achieved. SEARCH METHODS: In this update, we identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1950 to March 2016) and Ovid EMBASE (1980 to March 2016). To identify further relevant trials, we handsearched reference lists from trials selected by electronic searching, and published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology). The search was last updated in March 2016. We contacted members of Cochrane Upper GI and Pancreatic Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: We analysed randomised controlled trials of short- and long-term treatment of peptic ulcer disease in H. pylori-positive adults. Participants received at least one week of H. pylori eradication compared with ulcer healing drug, placebo or no treatment. Trials were included if they reported assessment from two weeks onwards. DATA COLLECTION AND ANALYSIS: We collected data on ulcer healing, recurrence, relief of symptoms and adverse effects. We calculated the risk ratio (RR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with Review Manager software (RevMan 5.3) based on intention-to-treat analysis as far as possible. MAIN RESULTS: A total of 55 trials were included for one or more outcomes for this review.In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 participants, RR of ulcer persisting = 0.66, 95% confidence interval (CI) 0.58 to 0.76; 381/2286 (adjusted proportion: 12.4%) in eradication therapy plus UHD versus 304/1624 (18.7%) in UHD; low quality evidence) and no treatment (two trials, 207 participants, RR 0.37, 95% CI 0.26 to 0.53; 30/125 (adjusted proportion: 21.7%) in eradication therapy versus 48/82 (58.5%) in no treatment; low quality evidence).In gastric ulcer healing, the differences were imprecise between eradication therapy and UHD (15 trials, 1974 participants, RR 1.23, 95% CI 0.90 to 1.68; 220/1192 (adjusted proportion: 16.0%) in eradication therapy plus UHD versus 102/782 (13.0%) in UHD; very low quality evidence). In preventing duodenal ulcer recurrence the differences were imprecise between maintenance therapy with H.pylori eradication therapy and maintenance therapy with UHD (four trials, 319 participants, RR of ulcer recurring 0.73; 95% CI 0.42 to 1.25; 19/159 (adjusted proportion: 11.9%) in eradication therapy versus 26/160 (16.3%) in UHD; very low quality evidence), but eradication therapy was superior to no treatment (27 trials 2509 participants, RR 0.20, 95% CI 0.15 to 0.26; 215/1501 (adjusted proportion: 12.9%) in eradication therapy versus 649/1008 (64.4%) in no treatment; very low quality evidence).In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (12 trials, 1476 participants, RR 0.31, 95% CI 0.22 to 0.45; 116/697 (adjusted proportion: 16.3%) in eradication therapy versus 356/679 (52.4%) in no treatment; very low quality evidence). None of the trials reported proportion of people with gastric ulcer not healed after initial therapy between H.pylori eradication therapy and no active treatment or the proportion of people with recurrent gastric ulcer or peptic ulcers during maintenance therapy between H.pylori eradication therapy and ulcer healing drug therapy. AUTHORS' CONCLUSIONS: Adding a one to two-week course of H. pylori eradication therapy is an effective treatment for people with H. pylori-positive duodenal ulcer when compared to ulcer healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer healing drug. However, confidence intervals were wide and significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment, and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out.

Feasibility and acceptability of TRANSFoRm to improve clinical trial recruitment in primary care.

BACKGROUND: Recruitment of study participants is a challenging process for health professionals and patients. The Translational Medicine and Patient Safety in Europe (TRANSFoRm) clinical trial tools enable automated identification, recruitment and follow-up in clinical trials, potentially saving time, effort and costs for all parties involved. OBJECTIVES: This study evaluates the acceptability and feasibility of TRANSFoRm to improve clinical trial recruitment in primary care. METHODS: A feasibility study was conducted in three general practices in Poland. Participants were physicians and patients with gastro-oesophageal reflux disease. Semi-structured interviews were held to obtain feedback about the usefulness, ease of use and overall experience with the TRANSFoRm tools and to identify potential usability issues. Data were analysed thematically. RESULTS: A total of 5 physicians and 10 patients participated in the study. Physicians were satisfied with the usefulness of the system, as it enabled easier and faster identification, recruitment and follow-up of patients compared with existing methods. Patients found the TRANSFoRm apps easy to use to report patient outcomes. However, they also felt that the apps may not be useful for patients with limited exposure to smartphone and web technologies. Two main usability issues were identified: physicians could not access the result of the randomization at the end of each visit, and participants could not locate the follow-up reminder email. CONCLUSIONS: This study provides new evidence on the acceptability and feasibility of TRANSFoRm to enable automated identification, recruitment and follow-up of study participants in primary care trials. It also helps to better understand and address users' requirements in eHealth-supported clinical research.

The value of structured data elements from electronic health records for identifying subjects for primary care clinical trials.

BACKGROUND: An increasing number of clinical trials are conducted in primary care settings. Making better use of existing data in the electronic health records to identify eligible subjects can improve efficiency of such studies. Our study aims to quantify the proportion of eligibility criteria that can be addressed with data in electronic health records and to compare the content of eligibility criteria in primary care with previous work. METHODS: Eligibility criteria were extracted from primary care studies downloaded from the UK Clinical Research Network Study Portfolio. Criteria were broken into elemental statements. Two expert independent raters classified each statement based on whether or not structured data items in the electronic health record can be used to determine if the statement was true for a specific patient. Disagreements in classification were discussed until 100 % agreement was reached. Statements were also classified based on content and the percentages of each category were compared to two similar studies reported in the literature. RESULTS: Eligibility criteria were retrieved from 228 studies and decomposed into 2619 criteria elemental statements. 74 % of the criteria elemental statements were considered likely associated with structured data in an electronic health record. 79 % of the studies had at least 60 % of their criteria statements addressable with structured data likely to be present in an electronic health record. Based on clinical content, most frequent categories were: "disease, symptom, and sign", "therapy or surgery", and "medication" (36 %, 13 %, and 10 % of total criteria statements respectively). We also identified new criteria categories related to provider and caregiver attributes (2.6 % and 1 % of total criteria statements respectively). CONCLUSIONS: Electronic health records readily contain much of the data needed to assess patients' eligibility for clinical trials enrollment. Eligibility criteria content categories identified by our study can be incorporated as data elements in electronic health records to facilitate their integration with clinical trial management systems.

Early diagnostic suggestions improve accuracy of family physicians: a randomized controlled trial in Greece.

BACKGROUND: In a recent randomized controlled trial, providing UK family physicians with 'early support' (possible diagnoses to consider before any information gathering) was associated with diagnosing hypothetical patients on computer more accurately than control. Another group of physicians, who gathered information, gave a diagnosis, and subsequently received a list of possible diagnoses to consider ('late support'), were no more accurate than control, despite being able to change their initial diagnoses. OBJECTIVE: To replicate the UK study findings in another country with a different primary health care system. METHODS: All study materials were translated into Greek. Greek family physicians were randomly allocated to one of three groups: control, early support and late support. Participants saw nine scenarios in random order. After reading some information about the patient and the reason for encounter, they requested more information to diagnose. The main outcome measure was diagnostic accuracy. RESULTS: One hundred fifty Greek family physicians participated. The early support group was more accurate than control [odds ratio (OR): 1.67 (1.21-2.31)]. Like their UK counterparts, physicians in the late support group rarely changed their initial diagnoses after receiving support. The pooled OR for the early support versus control comparison from the meta-analysis of the UK and Greek data was 1.40 (1.13-1.67). CONCLUSION: Using the same methodology with a different sample of family physicians in a different country, we found that suggesting diagnoses to consider before physicians start gathering information was associated with more accurate diagnoses. This constitutes further supportive evidence of a generalizable effect of early support.

Evidence-based rules from family practice to inform family practice; the learning healthcare system case study on urinary tract infections.

BACKGROUND: Analysis of encounter data relevant to the diagnostic process sourced from routine electronic medical record (EMR) databases represents a classic example of the concept of a learning healthcare system (LHS). By collecting International Classification of Primary Care (ICPC) coded EMR data as part of the Transition Project from Dutch and Maltese databases (using the EMR TransHIS), data mining algorithms can empirically quantify the relationships of all presenting reasons for encounter (RfEs) and recorded diagnostic outcomes. We have specifically looked at new episodes of care (EoC) for two urinary system infections: simple urinary tract infection (UTI, ICPC code: U71) and pyelonephritis (ICPC code: U70). METHODS: Participating family doctors (FDs) recorded details of all their patient contacts in an EoC structure using the ICPC, including RfEs presented by the patient, and the FDs' diagnostic labels. The relationships between RfEs and episode titles were studied using probabilistic and data mining methods as part of the TRANSFoRm project. RESULTS: The Dutch data indicated that the presence of RfE's "Cystitis/Urinary Tract Infection", "Dysuria", "Fear of UTI", "Urinary frequency/urgency", "Haematuria", "Urine symptom/complaint, other" are all strong, reliable, predictors for the diagnosis "Cystitis/Urinary Tract Infection" . The Maltese data indicated that the presence of RfE's "Dysuria", "Urinary frequency/urgency", "Haematuria" are all strong, reliable, predictors for the diagnosis "Cystitis/Urinary Tract Infection". The Dutch data indicated that the presence of RfE's "Flank/axilla symptom/complaint", "Dysuria", "Fever", "Cystitis/Urinary Tract Infection", "Abdominal pain/cramps general" are all strong, reliable, predictors for the diagnosis "Pyelonephritis" . The Maltese data set did not present any clinically and statistically significant predictors for pyelonephritis. CONCLUSIONS: We describe clinically and statistically significant diagnostic associations observed between UTIs and pyelonephritis presenting as a new problem in family practice, and all associated RfEs, and demonstrate that the significant diagnostic cues obtained are consistent with the literature. We conclude that it is possible to generate clinically meaningful diagnostic evidence from electronic sources of patient data.

Extension of the primary care research object model (PCROM) as clinical research information model (CRIM) for the "learning healthcare system".

BACKGROUND: Patient data from general practices is already used for many types of epidemiological research and increasingly, primary care systems to facilitate randomized clinical trials. The EU funded project TRANSFoRm aims to create a "Learning Healthcare System" at a European level that is able to support all types of research using primary care data, to recruit patients and follow patients in clinical studies and to improve diagnosis and therapy. The implementation of such a Learning Healthcare System needs an information model for clinical research (CRIM), as an informational backbone to integrate aspects of primary care with clinical trials and database searches. METHODS: Workflow descriptions and corresponding data objects of two clinical use cases (Gastro-Oesophageal Reflux Disease and Type 2 Diabetes) were described in UML activity diagrams. The components of activity diagrams were mapped to information objects of PCROM (Primary Care Research Object Model) and BRIDG (Biomedical Research Integrated Domain Group) and evaluated. The class diagram of PCROM was adapted to comply with workflow descriptions. RESULTS: The suitability of PCROM, a primary care information model already used for clinical trials, to act as an information model for TRANSFoRm was evaluated and resulted in its extension with 14 new information object types, two extensions of existing objects and the introduction of two new high-ranking concepts (CARE area and ENTRY area). No PCROM component was redundant. Our result illustrates that in primary care based research an important but underestimated portion of research activity takes place in the area of care (e.g. patient consultation, screening, recruitment and response to adverse events). The newly introduced CARE area for care-related research activities accounts for this shift and includes Episode of Care and Encounter as two new basic elements. In the ENTRY area different aspects of data collection were combined, including data semantics for observations, assessment activities, intervention activities and patient reporting to enable case report form (CRF) based data collection combined with decision support. CONCLUSIONS: Research with primary care data needs an extended information model that covers research activities at the care site which are characteristic for primary care based research and the requirements of the complicated data collection processes.

Pathophysiological Mechanisms in Long COVID: A Mixed Method Systematic Review.

INTRODUCTION: Long COVID (LC) is a global public health crisis affecting more than 70 million people. There is emerging evidence of different pathophysiological mechanisms driving the wide array of symptoms in LC. Understanding the relationships between mechanisms and symptoms helps in guiding clinical management and identifying potential treatment targets. METHODS: This was a mixed-methods systematic review with two stages: Stage one (Review 1) included only existing systematic reviews (meta-review) and Stage two (Review 2) was a review of all primary studies. The search strategy involved Medline, Embase, Emcare, and CINAHL databases to identify studies that described symptoms and pathophysiological mechanisms with statistical analysis and/or discussion of plausible causal relationships between mechanisms and symptoms. Only studies that included a control arm for comparison were included. Studies were assessed for quality using the National Heart, Lung, and Blood Institute quality assessment tools. RESULTS: 19 systematic reviews were included in Review 1 and 46 primary studies in Review 2. Overall, the quality of reporting across the studies included in this second review was moderate to poor. The pathophysiological mechanisms with strong evidence were immune system dysregulation, cerebral hypoperfusion, and impaired gas transfer in the lungs. Other mechanisms with moderate to weak evidence were endothelial damage and hypercoagulation, mast cell activation, and auto-immunity to vascular receptors. CONCLUSIONS: LC is a complex condition affecting multiple organs with diverse clinical presentations (or traits) underpinned by multiple pathophysiological mechanisms. A 'treatable trait' approach may help identify certain groups and target specific interventions. Future research must include understanding the response to intervention based on these mechanism-based traits.

Effect of on-demand vs continuous prescription of proton pump inhibitors on symptom burden and quality of life: results of a real-world randomized controlled trial in primary care patients with gastroesophageal reflux disease.

OBJECTIVES: This study aimed to assess the impact of on-demand versus continuous prescribing of proton pump inhibitors (PPIs) on symptom burden and health-related quality of life in patients with gastroesophageal reflux disease (GERD) presenting to primary care. METHODS: Thirty-six primary care centres across Europe enrolled adult GERD patients from electronic health records. Participants were randomised to on-demand or continuous PPI prescriptions and were followed for 8 weeks. PPI intake, symptom burden, and quality of life were compared between the two groups using mixed-effect regression analyses. Spearman's correlation was used to assess the association between changes in PPI dose and patient-reported outcomes. RESULTS: A total of 488 patients (median age 51 years, 58% women) completed the initial visit, with 360 attending the follow-up visit. There was no significant difference in PPI use between the continuous and on-demand prescription groups (b=.57, 95%CI:0.40-1.53), although PPI use increased in both groups (b = 1.33, 95%CI:0.65 - 2.01). Advice on prescribing strategy did not significantly affect patient-reported outcomes. Both symptom burden (Reflux Disease Questionnaire, b=-0.61, 95%CI:-0.73 - -0.49) and quality of life (12-item Short Form Survey physical score b = 3.31, 95%CI:2.17 - 4.45) improved from baseline to follow-up in both groups. Increased PPI intake correlated with reduced reflux symptoms (n = 347, ρ=-0.12, p = 0.02) and improved quality of life (n = 217, ρ = 0.16, p = 0.02). CONCLUSION: In real-world settings, both continuous and on-demand PPI prescriptions resulted in similar increases in PPI consumption with no difference in treatment effects. Achieving an adequate PPI dose to alleviate reflux symptom burden improves quality of life in GERD patients. EudraCT number 2014-001314-25.

Continuous and on-demand prescription increase in proton pump inhibitor consumption equally in real-world settings and did not result in different outcomes.Reaching a sufficient dose of proton pump inhibitor to reduce reflux symptom burden improves quality of life in patients with gastroesophageal reflux disease.

ROAD2H: Development and evaluation of an open-source explainable artificial intelligence approach for managing co-morbidity and clinical guidelines.

Introduction: Clinical decision support (CDS) systems (CDSSs) that integrate clinical guidelines need to reflect real-world co-morbidity. In patient-specific clinical contexts, transparent recommendations that allow for contraindications and other conflicts arising from co-morbidity are a requirement. In this work, we develop and evaluate a non-proprietary, standards-based approach to the deployment of computable guidelines with explainable argumentation, integrated with a commercial electronic health record (EHR) system in Serbia, a middle-income country in West Balkans. Methods: We used an ontological framework, the Transition-based Medical Recommendation (TMR) model, to represent, and reason about, guideline concepts, and chose the 2017 International global initiative for chronic obstructive lung disease (GOLD) guideline and a Serbian hospital as the deployment and evaluation site, respectively. To mitigate potential guideline conflicts, we used a TMR-based implementation of the Assumptions-Based Argumentation framework extended with preferences and Goals (ABA+G). Remote EHR integration of computable guidelines was via a microservice architecture based on HL7 FHIR and CDS Hooks. A prototype integration was developed to manage chronic obstructive pulmonary disease (COPD) with comorbid cardiovascular or chronic kidney diseases, and a mixed-methods evaluation was conducted with 20 simulated cases and five pulmonologists. Results: Pulmonologists agreed 97% of the time with the GOLD-based COPD symptom severity assessment assigned to each patient by the CDSS, and 98% of the time with one of the proposed COPD care plans. Comments were favourable on the principles of explainable argumentation; inclusion of additional co-morbidities was suggested in the future along with customisation of the level of explanation with expertise. Conclusion: An ontological model provided a flexible means of providing argumentation and explainable artificial intelligence for a long-term condition. Extension to other guidelines and multiple co-morbidities is needed to test the approach further.

The TARGET cohort study protocol: a prospective primary care cohort study to derive and validate a clinical prediction rule to improve the targeting of antibiotics in children with respiratory tract illnesses.

BACKGROUND: Children with respiratory tract infections are the single most frequent patient group to make use of primary care health care resources. The use of antibiotics remains highly prevalent in young children, but can lead to antimicrobial resistance as well as reinforcing the idea that parents should re-consult for similar symptoms. One of the main drivers of indiscriminate antimicrobial use is the lack of evidence for, and therefore uncertainty regarding, which children are at risk of poor outcome. This paper describes the protocol for the TARGET cohort study, which aims to derive and validate a clinical prediction rule to identify children presenting to primary care with respiratory tract infections who are at risk of hospitalisation. METHODS/DESIGN: The TARGET cohort study is a large, multicentre prospective observational study aiming to recruit 8,300 children aged ≥3 months and <16 years presenting to primary care with a cough and respiratory tract infection symptoms from 4 study centres (Bristol, London, Oxford and Southampton). Following informed consent, symptoms, signs and demographics will be measured. In around a quarter of children from the Bristol centre, a single sweep, dual bacterial-viral throat swab will be taken and parents asked to complete a symptom diary until the child is completely well or for 28 days, whichever is sooner. A review of medical notes including clinical history, re-consultation and hospitalisations will be undertaken. Multivariable logistic regression will be used to identify the independent clinical predictors of hospitalisation as well as the prognostic significance of upper respiratory tract microbes. The clinical prediction rule will be internally validated using various methods including bootstrapping. DISCUSSION: The clinical prediction rule for hospitalisation has the potential to help identify a small group of children for hospitalisation and a much larger group where hospitalisation is very unlikely and antibiotic prescribing would be less warranted. This study will also be the largest natural history study to date of children presenting to primary care with acute cough and respiratory tract infections, and will provide important information on symptom duration, re-consultations and the microbiology of the upper respiratory tract.

An ontological treatment of clinical prediction rules implementing the Alvarado score.

A lack of acceptance has hindered the widespread adoption and implementation of clinical prediction rules (CPRs). The use of clinical decision support systems (CDSSs) has been advocated as one way of facilitating a broader dissemination and validation of CPRs. This requires computable models of clinical evidence based on open standards rather than closed proprietary content. The on-going TRANSFoRm project has developed ontological models of CPRs suitable for providing CPR based decision support. This paper presents a description of the design and implementation of the ontology model for CPRs that has been proposed. The conceptual validity of the ontology is discussed using the example of a specific CPR in the form of the Alvarado Score for acute appendicitis. We demonstrate how the model is used to query the structure of this particular rule, providing a computable representation suitable for CPRs in general.