Search

Abstract Aim To describe where clinical information is contemporarily and commonly found in UK primary care, what is favoured by clinicians, and whether this is (1) publicly funded (2) has commercial potential conflicts of interest. Design and setting A mixed methods study, consisting of (1) site visits to general practices in Scotland, (2) online questionnaire, focused on UK general practice (3) analysis of materials cited by professionals. Methods Data about sources of clinical information used was obtained verbally, visually and via search histories on computers from visits. This was used to inform a questionnaire in which primary care clinicians in the four nations of the UK were invited to participate. This obtained data about the information sources used and preferred by clinicians. This information was searched for data about funding and conflicts of interest. Results Over 2022, four practices were visited. 337 clinicians, 280 of whom were general practitioners completed an online questionnaire. 136 different resources were identified. These were mainly websites but sources of information included colleagues, either in practice or through online networks, apps, local guidelines, health charities, and learning resources aimed at GPs. Of these, 70 were not publicly funded, and were a mixture of membership organisations, charities, or sponsored venues. Conclusions Primary care clinicians obtain information for themselves and patients from a wide variety of sources. Funding is from a variety of sources and some contain advertising and/or sponsorship, risking commercial bias. Protocol Pre-published at https://osf.io/wrzqk .

Abstract Background Self-reported health is a widely used health indicator in surveys and questionnaires. The measure gained attention when research identified its association with mortality in the 1970s and 1980s. The measure is also associated with morbidity and other health outcomes such as the utilisation of health services. Self-reported health is a particularly useful measure for young people because this age group is generally clinically healthy. However, it is known that many chronic conditions have long latency periods that are initiated early in life. Because of its predictive nature, self-reported health can be used to estimate young people’s current and future health. Despite its widespread use, however, self-reported health remains a poorly understood concept. This paper presents the protocol for a systematic review that will identify and synthesise qualitative studies that investigate the factors that are considered by young people when they assess their health, and when they talk about health overall. Methods The population of the review is young people aged 10–24 years, with or without health conditions. We will search the databases of MEDLINE (Ovid®), PsycINFO (APA PsycNet), ProQuest Sociology Collection, and Web of Science Core Collection™. We will also utilise techniques of reference checking and forward citation searching, as this strategy has been shown to result in a higher number of high-quality studies in social science systematic reviews. Google Scholar and Google Search were used during preliminary searches; Google Scholar will be utilised for forward citation searching. We will include studies written in English, German, or Finnish; there will be no lower date limit. One reviewer will screen all citations. A second reviewer will independently screen a sample of 20% of the abstracts. Data will be extracted by one researcher, two other researchers will independently review all data extracted, and quality appraisal will be completed by the first reviewer. We will utilise the Quality Framework for the appraisal of included articles and thematic synthesis of qualitative studies. Discussion The results of this systematic review will improve the understanding of the factors that are considered during the self-assessments of health; this will improve the interpretation of the results of quantitative research. Also, an improved understanding of the conceptualisation of health will inform the development of health policies and interventions that support young people’s health. Systematic review registration PROSPERO CRD42022367519.

Background: Diagnostic blood tests have the potential to identify lung cancer in people at high risk. We assessed the cost-effectiveness of a lung cancer screening intervention, using the EarlyCDT®-Lung Test (ECLS) with subsequent X-ray and low-dose chest CT scans (LDCT) for patients with a positive test result, compared to both usual care and LDCT screening for the target population. Methods: We conducted a model-based lifetime analysis from a UK NHS and personal social services perspective. We estimated incremental net monetary benefit (NMB) for the ECLS intervention compared to no screening and to LDCT screening. Results: The incremental NMB of ECLS intervention compared to no screening was GBP 33,179 (95% CI: −GBP 81,396, GBP 147,180) and GBP 140,609 (95% CI: −GBP 36,255, GBP 316,612), respectively, for a cost-effectiveness threshold of GBP 20,000 and GBP 30,000 per quality-adjusted life year. The same figures compared with LDCT screening were GBP 162,095 (95% CI: GBP 52,698, GBP 271,735) and GBP 52,185 (95% CI: −GBP 115,152, GBP 219,711). Conclusions: The ECLS intervention is the most cost-effective screening alternative, with the highest probability of being cost-effective, when compared to no screening or LDCT screening. This result may change with modifications of the parameters, suggesting that the three alternatives considered in the main analysis are potentially cost-effective.

Background The place of tonsillectomy in the management of sore throat in adults remains uncertain. Objectives To establish the clinical effectiveness and cost-effectiveness of tonsillectomy, compared with conservative management, for tonsillitis in adults, and to evaluate the impact of alternative sore throat patient pathways. Design This was a multicentre, randomised controlled trial comparing tonsillectomy with conservative management. The trial included a qualitative process evaluation and an economic evaluation. Setting The study took place at 27 NHS secondary care hospitals in Great Britain. Participants A total of 453 eligible participants with recurrent sore throats were recruited to the main trial. Interventions Patients were randomised on a 1 : 1 basis between tonsil dissection and conservative management (i.e. deferred surgery) using a variable block-stratified design, stratified by (1) centre and (2) severity. Main outcome measures The primary outcome measure was the total number of sore throat days over 24 months following randomisation. The secondary outcome measures were the number of sore throat episodes and five characteristics from Sore Throat Alert Return, describing severity of the sore throat, use of medications, time away from usual activities and the Short Form questionnaire-12 items. Additional secondary outcomes were the Tonsil Outcome Inventory-14 total and subscales and Short Form questionnaire-12 items 6 monthly. Evaluation of the impact of alternative sore throat patient pathways by observation and statistical modelling of outcomes against baseline severity, as assessed by Tonsil Outcome Inventory-14 score at recruitment. The incremental cost per sore throat day avoided, the incremental cost per quality-adjusted life-year gained based on responses to the Short Form questionnaire-12 items and the incremental net benefit based on costs and responses to a contingent valuation exercise. A qualitative process evaluation examined acceptability of trial processes and ramdomised arms. Results There was a median of 27 (interquartile range 12–52) sore throats over the 24-month follow-up. A smaller number of sore throats was reported in the tonsillectomy arm [median 23 (interquartile range 11–46)] than in the conservative management arm [median 30 (interquartile range 14–65)]. On an intention-to-treat basis, there were fewer sore throats in the tonsillectomy arm (incident rate ratio 0.53, 95% confidence interval 0.43 to 0.65). Sensitivity analyses confirmed this, as did the secondary outcomes. There were 52 episodes of post-operative haemorrhage reported in 231 participants undergoing tonsillectomy (22.5%). There were 47 re-admissions following tonsillectomy (20.3%), 35 relating to haemorrhage. On average, tonsillectomy was more costly and more effective in terms of both sore throat days avoided and quality-adjusted life-years gained. Tonsillectomy had a 100% probability of being considered cost-effective if the threshold for an additional quality-adjusted life year was £20,000. Tonsillectomy had a 69% probability of having a higher net benefit than conservative management. Trial processes were deemed to be acceptable. Patients who received surgery were unanimous in reporting to be happy to have received it. Limitations The decliners who provided data tended to have higher Tonsillectomy Outcome Inventory-14 scores than those willing to be randomised implying that patients with a higher burden of tonsillitis symptoms may have declined entry into the trial. Conclusions The tonsillectomy arm had fewer sore throat days over 24 months than the conservative management arm, and had a high probability of being considered cost-effective over the ranges considered. Further work should focus on when tonsillectomy should be offered. National Trial of Tonsillectomy IN Adults has assessed the effectiveness of tonsillectomy when offered for the current UK threshold of disease burden. Further research is required to define the minimum disease burden at which tonsillectomy becomes clinically effective and cost-effective. Trial registration This trial is registered as ISRCTN55284102. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/146/06) and is published in full in Health Technology Assessment; Vol. 27, No. 31. See the NIHR Funding and Awards website for further award information. Plain language summary Tonsillectomy is an operation to take out the pair of tonsil glands at the back of the throat. It is an option for adults who suffer from repeated, severe sore throats. Adults who have a tonsillectomy say that they get fewer sore throats afterwards, but it is not clear whether or not they would have got better over time without the operation. There is pressure on doctors to limit the number of tonsillectomies carried out. At the same time, emergency hospital admissions for adults with severe throat infections have been increasing. NAtional Trial of Tonsillectomy IN Adults aimed to find out whether tonsillectomy is an effective and worthwhile treatment for repeated severe sore throats or whether patients would be better off treated without an operation. A total of 453 patients from 27 hospitals in Great Britain took part in the study. Patients were assigned at random to receive either tonsillectomy or conservative management (treatment as needed from their general practitioner). We measured how many sore throats patients had in the next 2 years by sending them text messages every week. We asked about the impact of their sore throats on their quality of life and time off work, and looked at the costs of treatment. We also interviewed 47 patients, general practitioners and hospital staff about their experiences of tonsillectomy and NAtional Trial of Tonsillectomy IN Adults. The typical patient in the tonsillectomy arm had 23 days of sore throat compared with 30 days of sore throat in the conservative management arm. Tonsillectomy resulted in higher quality of life. We looked to see whether or not it was only those with the most severe sore throats who benefited from tonsillectomy, but we found that patients with more or less severe sore throats at the start all did better with tonsillectomy. Patients who had a tonsillectomy were happy to have undertaken this. Our findings suggest a clear benefit of tonsillectomy using modest additional NHS resources for adults with repeated severe sore throats. Scientific summary Background Sore throats cost the NHS over £120M per annum, including ≈ £60M for general practitioner (GP) consultations and medical therapy. The place of tonsillectomy in the management of sore throat remains uncertain. Objectives Clinical To establish the clinical effectiveness of tonsillectomy, compared with conservative management, for tonsillitis in adults. To report the number of adverse events (AEs), visits to the GP/walk-in clinic/accident and emergency, prescriptions issued and additional interventions required to manage sore throats and related events through weekly Sore Throat Alert Return (STAR) response data and primary care patient records. To adjust the estimate of effectiveness in the light of other baseline covariates, including severity of tonsillitis. To evaluate the impact of alternative sore throat patient pathways by observation and statistical modelling of outcomes. To assess to what extent trial participants were representative of the total population of sore throat patients referred to ear, nose and throat (ENT) clinics. To inform future research. Qualitative process evaluation To examine the acceptability of the trial, treatments and unforeseen consequences from the perspective of participants and stakeholders, including ENT staff and GPs. Economic evaluation To compare costs incurred by the NHS, Personal and Social Services (PSS) and participants to manage recurrent sore throats in adults. To compare quality-adjusted life-years (QALYs) using the area-under-the-curve method based on Short Form questionnaire-6 Dimension (SF-6D) scores derived from longitudinal Short Form questionnaire-12 items (SF-12) responses throughout the study and during self-reported sore throat episodes. To compare the cost-effectiveness measured in terms of the incremental: cost per sore throat day avoided cost per QALY gained net benefit – estimated based on self-reported number of sore throat days and responses to a contingent valuation questionnaire administered at baseline asking participants’ willingness to pay (WTP) to avoid a sore throat day. Methods Design A multicentre, randomised controlled trial comparing the effectiveness of tonsillectomy for recurrent sore throat with that of non-surgical conservative management in a 1 : 1 ratio over a 24-month period. Surgeons, participants and site staff could not be blinded to the allocated procedure. The main trial began following the completion of a feasibility study and included a qualitative process evaluation, as well as an economic evaluation. The design, conduct and reporting of the trial were informed by patients. Crossover of participants between arms was permitted. Interventions Tonsil dissection: dissection of the palatine tonsils preferably within 6 weeks, and no more than 8 weeks, following randomisation (dissection method at the discretion of the participating centres). Conservative (non-surgical) management (i.e. deferred surgery): participants entering the conservative management arm were asked to defer surgery for up to 24 months on the understanding that they would be reviewed at 12 months. Setting and participants A total of 453 patients were recruited to the main trial from 27 NHS secondary care hospitals in Great Britain. Eligible patients were identified via general ENT referrals and established sore throat-specific referral pathways, some of which were run by ENT nurse practitioners. Inclusion criteria Aged ≥16 years. Recurrent sore throats that fulfil current Scottish Intercollegiate Guidelines Network (SIGN) guidance for elective tonsillectomy. Exclusion criteria Previous tonsillectomy. Listed directly (i.e. added to waiting list without prior elective ENT outpatient appointment) during emergency admission (e.g. owing to peritonsillar abscess/quinsy). Primary sleep breathing disorder. Suspected malignancy. Tonsilloliths (as primary referral). Pregnant or breastfeeding. Bleeding diathesis (including haemophilia, sickle cell disease and platelet dysfunction). Therapeutic anticoagulation. Inability to complete self-reported questionnaires and sore throat returns. Main outcome measures Primary outcome The primary outcome measure was the total number of sore throat days over the 24 months following randomisation. The number of sore throat days was collected by a database that was designed for use in the trial (the STAR database). This database allowed participants to respond weekly to alerts by providing the number of sore throats that they had experienced in the previous 7 days (between 0 and 7 sore throat days). From the beginning of the trial, participants were able to choose their preferred method for receiving these alerts: e-mail, text message or interactive voice response (IVR) via telephone. Secondary outcomes A participant who had suffered from a sore throat in the past week (i.e. sore throat days >0) was asked to provide information on the severity of the sore throat(s) and additional data for health economics and other secondary outcomes in a STAR questionnaire. Quality-of-life data, reported as the SF-12 physical component score (PCS) and mental component score (MCS) and additional symptoms of tonsillitis, were collected every 6 months. The impact of alternative NHS sore throat pathways was measured by observation and statistical modelling of outcomes. The extent to which trial participants represented the total population of sore throat patients referred to ENT clinics was assessed through analysis of site screening logs. Adverse events Information regarding the AEs related to the trial intervention was collected during telephone calls at 1 and 2 weeks post tonsillectomy; all tonsillectomy arm serious adverse events (SAEs) were recorded throughout the duration of the trial for all participants. Economic evaluation The cost-effectiveness of tonsillectomy compared with conservative management was evaluated by estimating the total costs incurred by the NHS and PSS, and averaging these costs across participants in each trial arm. Three different analyses were undertaken: (1) a cost-effectiveness analysis (CEA), (2) a cost–utility analysis (CUA) and (3) a cost–benefit analysis (CBA). All three analyses measured costs using the same methodology but differed in their measure of effectiveness. An incremental cost-effectiveness ratio was estimated for the CEA and the CUA by dividing the difference in average total costs by the difference in average total effects. The CEA estimated the incremental cost per sore throat day avoided. The number of sore throat days was derived from the primary outcome data. The CUA estimated the incremental cost per QALY gained. QALYs were derived using the SF-6D algorithm, which estimates utility values based on responses to the SF-12, which was administered at baseline and 6, 12, 18 and 24 months post randomisation and at the time of a sore throat episode. The CBA estimated the incremental net benefit, comparing costs and benefits in monetary terms. Participants’ WTP values, estimated from the contingent valuation study, were multiplied by participants’ self-reported number of sore throat days to estimate the reduction in patient benefits in monetary terms; from this costs were subtracted to give the net benefit. Qualitative process evaluation Qualitative and cognitive interviews were carried out by researchers from Newcastle University for the feasibility study, pilot and main trial. Interviews were held with adult patients with acute tonsillitis who had been referred to ENT outpatient clinics for recurrent sore throats, ENT staff who were working at a National Trial of Tonsillectomy IN Adults (NATTINA) trial site and GPs. These interviews addressed the acceptability of the trial/treatments, unforeseen consequences from the perspective of participants and how patient experience may shape future research. Statistical analysis The primary statistical analysis was carried out on an intention-to-treat (ITT) basis, retaining patients in their randomised arms and including protocol violator and ineligible patients. Patients randomised to conservative management were asked to commit to ‘deferred surgery’. We anticipated that a number of patients would take the opportunity to switch to surgery. We also undertook sensitivity analyses, including a per-treatment (as treated) and a per-protocol analysis. The cumulative total number of sore throat days reported on a patient level was provided separately for each randomised arm. Negative binomial regression was used to compare these, adjusting for stratification variables (baseline severity as a fixed effect and site as a random effect). The summary comparative statistic reported is the incident rate ratio (IRR). The analysis took account of incomplete weekly returns by use of an exposure variable included in the model. The analysis of secondary outcomes followed a broadly similar strategy to the primary outcome. Analyses were adjusted for baseline severity and site, and repeated measures were analysed using random-effects models with appropriate error structure. Results Primary outcome The participants in this trial reported a median of 27 [interquartile range (IQR) 12–52] sore throats over the full 24 months of follow-up. Fewer sore throats were reported in the tonsillectomy arm (median 23, IQR 11–46) than in the conservative management arm (median 30, IQR 14–65). When the primary outcome (total sore throats) was compared between the two randomised arms on an ITT basis, a reduction in sore throats was seen in the tonsillectomy arm. The tonsillectomy arm had 0.53 [IRR, 95% confidence interval (CI) 0.43 to 0.65] times the total sore throat days over the 24-month period than those in the conservative management arm. Sensitivity analyses on the ITT population confirmed this result. The analysis of the per-protocol population of 224 participants had, on average, a greater reduction in the number of sore throats, with patients in the tonsillectomy arm having 0.42 (IRR 95% CI 0.31 to 0.55) times the total score throats compared with the conservative management arm. Around 25% of participants did not receive the treatment that they were randomised to, which meant that some opted not to receive a tonsillectomy and some opted to cross to tonsillectomy. There is evidence to suggest that those with larger numbers of sore throats following randomisation were more likely to either opt for or remain in the tonsillectomy arm. Conversely, those with slightly smaller numbers of sore throats following randomisation were more likely to remain in conservative management or opt out of the tonsillectomy arm. Despite these crossovers, the ITT, per-protocol and per-treated analyses all confirmed that there was a significant reduction in total sore throats for those randomised to tonsillectomy. Secondary outcome measures The benefits of tonsillectomy were also seen in the secondary outcome measures. Tonsillectomy Outcome Inventory-14 (TOI-14) scores improved in both arms, but show a greater improvement in the tonsillectomy arm than the conservative management arm, where at 12 months the difference between the mean scores was –13.17 units (95% CI –17.41 to –8.92 units), indicating a reduction in symptoms. The SF-12 MCS and SF-12 PCS also show significant and beneficial differences in favour of the tonsillectomy arm over time [SF-12 MCS scores 3.71 units higher (95% CI 2.10 to 5.47) and SF-12 PCS 2.77 units higher (95% CI 0.30 to 5.23) in the tonsillectomy arm than the conservative management arm]. Adverse events There were 52 episodes of post-operative haemorrhage reported in 231 participants undergoing tonsillectomy (22.5%). Of these episodes, 35 were reported as SAEs: 8 as mild events, 22 as moderate events and 5 as severe events. No deaths were reported. Seventeen episodes were recorded as AEs, for which patients did not attend hospital. All episodes of bleeding were managed conservatively with no returns to theatre. Economic evaluation On average, tonsillectomy was more costly and more effective than conservative management. In the CEA, the incremental cost to avoid a sore throat episode was £24 per sore throat day. From the contingent valuation, the mean WTP to avoid a sore throat day was £43 (95% CI £2 to £100). In the CUA, tonsillectomy had an 87% probability of being considered cost-effective at a £5000 threshold for an additional QALY; this increased to 100% as the threshold values for an additional QALY increased. In the CBA, tonsillectomy had a 69% probability of having a higher net benefit than conservative management. Qualitative study Trial processes were deemed as acceptable, with only a few sites experiencing barriers to treatment. The use of technology to collect data was particularly well received. However, there were some challenges with recruitment, particularly for staff who lacked equipoise. ENT staff alluded to having to negotiate surgery dates with patients, which, at times, meant that they had to deviate from trial protocols. Some patients did not fully understand the process of randomisation. Patients who had received surgery were unanimous in reporting to be happy to have undertaken this, despite the challenging recovery period. Limitations There was some evidence that those with the most severe extent of disease were reluctant to enter the study (around 5 points higher scores overall on the TOI-14). Some symptoms may not be a result of tonsillitis. Not all patients were offered, or chose, to watch the trial recruitment video. The ITT analysis is likely to offer a conservative underestimate of the true impact of tonsillectomy in reducing sore throat days, as a result of patients crossing over to receive tonsillectomy. A challenge of the economic evaluation was the progressive loss of data over the 24-month follow-up. Conclusions Tonsillectomy in adults is a clinically effective intervention. It was more costly but had a high probability of being considered cost-effective over the range of analyses conducted. Participants with recurrent tonsillitis, who met current UK NHS guidelines to undergo tonsillectomy, suffered significantly fewer sore throat days over 24 months than similar participants treated conservatively. How should health services react? Pre-NATTINA, UK guidelines were a translation of level 1 evidence in children, applied to adults. Access to tonsillectomy in the UK was governed by application of national guidance, which is predicated on a qualifying number of episodes of tonsillitis. NATTINA participants in the tonsillectomy arm reported, on average, fewer healthcare contacts, fewer sore throat days and higher QALYs than those in the conservative management arm. Within the UK, tonsillectomy is listed as a ‘procedure of limited clinical value’ (The Royal College of Surgeons of England. Procedures of Limited Clinical Value: Royal College of Surgeons Briefing. London: The Royal College of Surgeons of England; 2011). To the best of our knowledge, NATTINA is the first definitive trial to demonstrate that tonsillectomy performed according to the current UK national guidelines is effective for patients, and the probability of it being considered cost-effective is high. Guideline reassessment, in particular how guidelines translate into healthcare commissioning, is called for. How should practitioners and patients respond to these findings? We have identified communication issues at the primary–secondary care interface in our qualitative work. There is, therefore, a need to convert the findings of NATTINA into a practical decision support tool for patients and surgeons. Implications for research (in priority order) The top research priority to emerge from NATTINA is to determine the optimum timing of tonsillectomy in adults with recurrent acute tonsillitis. Work is required also to optimise metrics for disease burden severity, and to exploit the novel real-time data collection methods elaborated in NATTINA. There is also a need to better understand optimum treatment strategies, including oral steroids, for tonsillitis in primary care. Trial registration This trial is registered as ISRCTN55284102. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/146/06) and is published in full in Health Technology Assessment; Vol. 27, No. 31. See the NIHR Funding and Awards website for further award information.

Abstract Background Air pollution is associated with poor health; though it is unclear whether this association is stronger for ethnic minorities compared to the rest of the population. This study uses longitudinal data to investigate the spatial–temporal effect of air pollution on individuals’ reported health and its variation by ethnicity in the United-Kingdom (UK). Methods Longitudinal individual-level data from Understanding Society: the UK Household Longitudinal Study including 67,982 adult individuals with 404,264 repeated responses over 11 years (2009–2019) were utilized and were linked to yearly concentrations of NO2, SO2, and particulate-matter (PM10, PM2.5) pollution once at the local authority and once at the census Lower Super Output Area (LSOA) of residence for each individual. This allows for analysis at two geographical scales over time. The association between air pollution and individuals’ health (Likert scale: 1–5, Excellent to poor) and its variation by ethnicity was assessed using three-level mixed-effects ordered logistic models. Analysis distinguished between spatial (between areas) and temporal (across time within each area) effects of air pollution on health. Results Higher concentrations of NO2, SO2, PM10, and PM2.5 pollution were associated with poorer health. Decomposing air pollution into between (spatial: across local authorities or LSOAs) and within (temporal: across years within each local authority or LSOA) effects showed a significant between effect for NO2 and SO2 pollutants at both geographical scales, while a significant between effect for PM10 and PM2.5 was shown only at the LSOAs level. No significant within effects were detected at an either geographical level. Indian, Pakistani/Bangladeshi, Black/African/Caribbean and other ethnic groups and non-UK-born individuals reported poorer health with increasing concentrations of NO2, SO2, PM10, and PM2.5 pollutants in comparison to the British-white and UK-born individuals. Conclusion Using longitudinal data on individuals’ health linked with air pollution data at two geographical scales (local authorities and LSOAs), this study supports the presence of a spatial–temporal association between air pollution and poor self-reported health, which is stronger for ethnic minorities and foreign-born individuals in the UK, partly explained by location-specific differences. Air pollution mitigation is necessary to improve individuals’ health, especially for ethnic minorities who are affected the most.

Background Air pollution is associated with poor health and higher mortality. However, studies that link high spatial resolution air pollution data for several pollutants to individual-level data over prolonged period (>10 years) and assess multiple health outcomes are limited. In this study, we investigated the association between 16-years exposure to air pollution and all-cause and cause-specific (cardiovascular, respiratory, cancer, infectious, and mental/behavioural disorders) mortality and hospital admissions in Scotland. Methods Individual-level data from the “Scottish Longitudinal Study” for 202,237 individuals (2002-2017) were linked to yearly concentrations of NO2, SO2, PM10, and PM2.5 pollutants at 1-Km2 spatial resolution using the individual’s residential postcode. The association between air pollution and mortality and hospital admissions was examined using Cox Proportional-Hazards and multilevel mixed-effects negative binomial models, respectively. Results Increasing concentrations of PM2.5, PM10, and NO2 pollutants were associated with higher rates of all-cause, cardiovascular, respiratory, cancer, and infectious mortality and hospital admissions. Mortality from respiratory diseases increased by 6.2% (95%CI=2.8%-9.6%), 2.5% (95%CI=0.5%-4.5%), and 1.2% (95%CI=0.5%-1.9%) per 1 µg/m3 increase in PM2.5, PM10 and NO2 pollutants, respectively. Exposure to SO2 was mainly linked to mental/behavioural disorders mortality (HR=1.05; 95%CI=1.02-1.07) and respiratory hospital admissions (IRR=1.02; 95%CI=1.01-1.03). Conclusions This study revealed a positive association between air pollution and mortality and hospital admissions in Scotland. Interventions on air pollution through stricter environmental regulations could help ease the mortality and hospital admission burden, for both physical and mental illness.

Abstract Background A common challenge for randomised controlled trials (RCTs) is recruiting enough participants to be adequately powered to answer the research question. Recruitment has been set as a priority research area in trials to improve recruitment and thereby reduce wasted resources in conducted trials that fail to recruit sufficiently. Methods We conducted a systematic mixed studies review to identify the factors associated with recruitment to RCTs in general practice. On September 8, 2020, English language studies were identified from MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and CENTRAL databases for published studies. NTIS and OpenGrey were searched for grey literature, and BMC Trials was hand searched. A narrative synthesis was conducted for qualitative studies and a thematic synthesis for qualitative studies. Results Thirty-seven studies met the inclusion criteria. These were of different study types (10 cross-sectional, 5 non-randomised studies of interventions, 2 RCTs, 10 qualitative and 10 mixed methods). The highest proportion was conducted in the UK (48%). The study quality was generally poor with 24 (65%) studies having major concerns. A complex combination of patient, practitioner or practice factors, and patient, practitioner or practice recruitment were assessed to determine the possible associations. There were more studies of patients than of practices or practitioners. Conclusions For practitioners and patients alike, a trial that is clinically relevant is critical in influencing participation. Competing demands are given as an important reason for declining participation. There are concerns about randomisation relating to its impact on shared decision-making and not knowing which treatment will be assigned. Patients make decisions about whether they are a candidate for the trial even when they objectively fulfil the eligibility criteria. General practice processes, such as difficulties arranging appointments, can hinder recruitment, and a strong pre-existing doctor-patient relationship can improve recruitment. For clinicians, the wish to contribute to the research enterprise itself is seldom an important reason for participating, though clinicians reported being motivated to participate when the research could improve their clinical practice. One of the few experimental findings was that opportunistic recruitment resulted in significantly faster recruitment compared to systematic recruitment. These factors have clear implications for trial design. Methodologically, recruitment research of practices and practitioners should have increased priority. Higher quality studies of recruitment are required to find out what actually works rather than what might work. Trial registration PROSPERO CRD42018100695. Registered on 03 July 2018.

Abstract Background Targeted lung cancer screening is effective in reducing mortality by upwards of twenty percent. However, screening is not universally available and uptake is variable and socially patterned. Understanding screening behaviour is integral to designing a service that serves its population and promotes equitable uptake. We sought to review the literature to identify barriers and facilitators to screening to inform the development of a pilot lung screening study in Scotland. Methods We used Arksey and O’Malley’s scoping review methodology and PRISMA-ScR framework to identify relevant literature to meet the study aims. Qualitative, quantitative and mixed methods primary studies published between January 2000 and May 2021 were identified and reviewed by two reviewers for inclusion, using a list of search terms developed by the study team and adapted for chosen databases. Results Twenty-one articles met the final inclusion criteria. Articles were published between 2003 and 2021 and came from high income countries. Following data extraction and synthesis, findings were organised into four categories: Awareness of lung screening, Enthusiasm for lung screening, Barriers to lung screening, and Facilitators or ways of promoting uptake of lung screening. Awareness of lung screening was low while enthusiasm was high. Barriers to screening included fear of a cancer diagnosis, low perceived risk of lung cancer as well as practical barriers of cost, travel and time off work. Being health conscious, provider endorsement and seeking reassurance were all identified as facilitators of screening participation. Conclusions Understanding patient reported barriers and facilitators to lung screening can help inform the implementation of future lung screening pilots and national lung screening programmes.

Abstract Introduction Targeted lung cancer screening is effective in reducing lung cancer and all‐cause mortality according to major trials in the United Kingdom and Europe. However, the best ways of implementing screening in local communities requires an understanding of the population the programme will serve. We undertook a study to explore the views of those potentially eligible for, and to identify potential barriers and facilitators to taking part in, lung screening, to inform the development of a feasibility study. Methods Men and women aged 45–70, living in urban and rural Scotland, and either self‐reported people who smoke or who recently quit, were invited to take part in the study via research agency Taylor McKenzie. Eleven men and 14 women took part in three virtual focus groups exploring their views on lung screening. Focus group transcripts were transcribed and analysed using thematic analysis, assisted by QSR NVivo. Findings Three overarching themes were identified: (1) Knowledge, awareness and acceptability of lung screening, (2) Barriers and facilitators to screening and (3) Promoting screening and implementation ideas. Participants were largely supportive of lung screening in principle and described the importance of the early detection of cancer. Emotional and psychological concerns as well as system‐level and practical issues were discussed as posing barriers and facilitators to lung screening. Conclusions Understanding the views of people potentially eligible for a lung health check can usefully inform the development of a further study to test the feasibility and acceptability of lung screening in Scotland. Patient or Public Contribution The LUNGSCOT study has convened a patient advisory group to advise on all aspects of study development and implementation. Patient representatives commented on the focus group study design, study materials and ethics application, and two representatives read the focus group transcripts.

Objective To understand: if professionals, citizens and patients can locate UK healthcare professionals’ statements of declarations of interests, and what citizens understand by these.Design The study sample included two groups of participants in three phases. First, healthcare professionals working in the public domain (health professional participants, HPP) were invited to participate. Their conflicts and declarations of interest were searched for in publicly available data, which the HPP checked and confirmed as the ‘gold standard’. In the second phase, laypeople, other healthcare professionals and healthcare students were invited to complete three online tasks. The first task was a questionnaire about their own demographics. The second task was questions about doctors’ conflicts of interest in clinical vignette scenarios. The third task was a request for each participant to locate and describe the declarations of interest of one of the named healthcare professionals identified in the first phase, randomly assigned. At the end of this task, all lay participants were asked to indicate willingness to be interviewed at a later date. In the third phase, each lay respondent who was willing to be contacted was invited to a qualitative interview to obtain their views on the conflicts and declaration of interest they found and their meaning.Setting Online, based in the UK.Participants 13 public-facing health professionals, 379 participants (healthcare professionals, students and laypeople), 21 lay interviewees.Outcome measures (1) Participants’ level of trust in professionals with variable conflicts of interest, as expressed in vignettes, (2) participants’ ability to locate the declarations of interest of a given well-known healthcare professional and (3) laypeoples’ understanding of healthcare professionals declarations and conflicts of interest.Results In the first phase, 13 health professionals (HPP) participated and agreed on a ‘gold standard’ of their declarations. In the second phase, 379 citizens, patients, other healthcare professionals and students participated. Not all completed all aspects of the research. 85% of participants thought that knowing about professional declarations was definitely or probably important, but 76.8% were not confident they had found all relevant information after searching. As conflicts of interest increased in the vignettes, participants trusted doctors less. Least trust was associated with doctors who had not disclosed their conflicts of interest. 297 participants agreed to search for the HPP ‘gold standard’ declaration of interest, and 169 reported some data. Of those reporting any findings, 61 (36%) located a relevant link to some information deemed fit for purpose, and 5 (3%) participants found all the information contained in the ‘gold standard’. In the third phase, qualitative interviews with 21 participants highlighted the importance of transparency but raised serious concerns about how useful declarations were in their current format, and whether they could improve patient care. Unintended consequences, such as the burden for patients and professionals to use declarations were identified, with participants additionally expressing concerns about professional bias and a lack of insight over conflicts. Suggestions for improvements included better regulation and organisation, but also second opinions and independent advice where conflicts of interest were suspected.Conclusion Declarations of interest are important and conflicts of interest concern patients and professionals, particularly in regard to trust in decision-making. If declarations, as currently made, are intended to improve transparency, they do not achieve this, due to difficulties in locating and interpreting them. Unintended consequences may arise if transparency alone is assumed to provide management of conflicts. Increased trust resulting from transparency may be misplaced, given the evidence on the hazards associated with conflicts of interest. Clarity about the purposes of transparency is required. Future policies may be more successful if focused on reducing the potential for negative impacts of conflicts of interest, rather than relying on individuals to locate declarations and interpret them.Trial registration number The protocol was pre-registered at https://osf.io/e7gtq.

Abstract Background Lung cancer is the most common cause of cancer death in the UK. Low-dose computed tomography (LDCT) screening has been shown to identify lung cancer at an earlier stage. A risk stratified approach to LDCT referral is recommended. Those at higher risk of developing lung cancer (aged 55 + , smoker, deprived area) are least likely to participate in such a programme and, therefore, it is necessary to understand the barriers they face and to develop pathways for implementation in order to increase uptake. Methods A 2-phased co-design process was employed to identify ways to further increase opportunity for uptake of a lung cancer screening programme, using a risk indicator for LDCT referral, amongst people who could benefit most. Participants were members of the public at high risk from developing lung cancer and professionals who may provide or signpost to a future lung cancer screening programme. Phase 1: interviews and focus groups, considering barriers, facilitators and pathways for provision. Phase 2: interactive offline booklet and online surveys with professionals. Qualitative data was analysed thematically, while descriptive statistics were conducted for quantitative data. Results In total, ten barriers and eight facilitators to uptake of a lung cancer screening programme using a biomarker blood test for LDCT referral were identified. An additional four barriers and four facilitators to provision of such a programme were identified. These covered wider themes of acceptability, awareness, reminders and endorsement, convenience and accessibility. Various pathway options were evidenced, with choice being a key facilitator for uptake. There was a preference (19/23) for the provision of home test kits but 7 of the 19 would like an option for assistance, e.g. nurse, pharmacist or friend. TV was the preferred means of communicating about the programme and fear was the most dominant barrier perceived by members of the public. Conclusion Co-design has provided a fuller understanding of the barriers, facilitators and pathways for the provision of a future lung cancer screening programme, with a focus on the potential of biomarker blood tests for the identification of at-risk individuals. It has also identified possible solutions and future developments to enhance uptake, e.g. Embedding the service in communities, Effective communication, Overcoming barriers with options. Continuing the process to develop these solutions in a collaborative way helps to encourage the personalised approach to delivery that is likely to improve uptake amongst groups that could benefit most.

Abstract Background Recruiting participants to a clinical study is a resource-intensive process with a high failure rate. The Scottish Health Research Register (SHARE) provides recruitment support service which helps researchers recruit participants by searching patients’ Electronic Health Records (EHRs). The current study aims to evaluate the performance of SHARE in participant recruitment. Methods Recruitment projects eligible for evaluation were those that were conducted for clinical trials or observational studies and finished before 2020. For analysis of recruitment data, projects with incomplete data were excluded. For each project we calculated, from SHARE records, 1) the fraction of the participants recruited through SHARE as a percentage of the number requested by researchers (percentage fulfilled), 2) the percentage of the potential candidates provided by SHARE to researchers that were actually recruited (percentage provided and recruited), 3) the percentage of the participants recruited through SHARE of all the potentially eligible candidates identified by searching registrants’ EHRs (percentage identified and recruited). Research teams of the eligible projects were invited to participate in an anonymised online survey. Two metrics were derived from research teams’ responses, including a) the fraction of the recruited over the study target number of participants (percentage fulfilled), and b) the percentage of the participants recruited through SHARE among the candidates received from SHARE (percentage provided and recruited). Results Forty-four projects were eligible for inclusion. Recruitment data for 24 projects were available (20 excluded because of missingness or incompleteness). Survey invites were sent to all the eligible research teams and received 12 responses. Analysis of recruitment data shows the overall percentage fulfilled was 34.2% (interquartile 13.3–45.1%), the percentage provided and recruited 29.3% (interquartile 20.6–52.4%) and percentage identified and recruited 4.9% (interquartile 2.6–10.2%). Based on the data reported by researchers, percentage fulfilled was 31.7% (interquartile 5.8–59.6%) and percentage provided and recruited was 20.2% (interquartile 8.2–31.0%). Conclusions SHARE may be a valuable resource for recruiting participants for some clinical studies. Potential improvements are to expand the registrant base and to incorporate more data generated during patients’ different health care encounters into the candidate-searching step.

Abstract Background The information given to people considering taking part in a trial needs to be easy to understand if those people are to become, and then remain, trial participants. However, there is a tension between providing comprehensive information and providing information that is comprehensible. User-testing is one method of developing better participant information, and there is evidence that user-tested information is better at informing participants about key issues relating to trials. However, it is not clear if user-testing also leads to changes in the rates of recruitment in trials, compared to standard trial information. As part of a programme of research, we embedded ‘studies within a trial’ (SWATs) across multiple ongoing trials to see if user-tested materials led to better rates of recruitment. Methods Seven ‘host’ trials included a SWAT evaluation and randomised their participants to receive routine information sheets generated by the research teams, or information sheets optimised through user-testing. We collected data on trial recruitment and analysed the results across these trials using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised in a host trial following an invitation to take part. Results Six SWATs (n=27,805) provided data on recruitment. Optimised participant information sheets likely result in little or no difference in recruitment rates (7.2% versus 6.8%, pooled odds ratio = 1.03, 95% CI 0.90 to 1.19, p-value = 0.63, I 2 = 0%). Conclusions Participant information sheets developed through user testing did not improve recruitment rates. The programme of work showed that co-ordinated testing of recruitment strategies using SWATs is feasible and can provide both definitive and timely evidence on the effectiveness of recruitment strategies. Trial registration Healthlines Depression (ISRCTN14172341) Healthlines CVD (ISRCTN27508731) CASPER (ISRCTN02202951) ISDR (ISRCTN87561257) ECLS (NCT01925625) REFORM (ISRCTN68240461) HeLP Diabetes (ISRCTN02123133)

Objective To understand arrangements for healthcare organisations’ declarations of staff interest in Scotland and England in the context of current recommendations.Design Cross-sectional study of a random selection of National Health Service (NHS) hospital registers of interest by two independent observers in England, all NHS Boards in Scotland and a random selection of Clinical Commissioning Groups (CCGs) in England.Setting NHS Trusts in England (NHSE), NHS Boards in Scotland, CCGs in England, and private healthcare organisations.Participants Registers of declarations of interest published in a random sample of 67 of 217 NHS Trusts, a random sample of 15 CCGs of in England, registers held by all 14 NHS Scotland Boards and a purposeful selection of private hospitals/clinics in the UK.Main outcome measures Adherence to NHSE guidelines on declarations of interests, and comparison in Scotland.Results 76% of registers published by Trusts did not routinely include all declaration of interest categories recommended by NHS England. In NHS Scotland only 14% of Boards published staff registers of interest. Of these employee registers (most obtained under Freedom of Information), 27% contained substantial retractions. In England, 96% of CCGs published a Gifts and Hospitality register, with 67% of CCG staff declaration templates and 53% of governor registers containing full standard NHS England declaration categories. Single organisations often held multiple registers lacking enough information to interpret them. Only 35% of NHS Trust registers were organised to enable searching. None of the private sector organisations studied published a comparable declarations of interest register.Conclusion Despite efforts, the current system of declarations frequently lacks ability to meaningfully obtain complete healthcare professionals’ declaration of interests.

Purpose Risk factor-based models struggle to accurately predict the development of cardiovascular disease (CVD) at the level of the individual. Ways of identifying people with low predicted risk who will develop CVD would allow stratified advice and support informed treatment decisions about the initiation or adjustment of preventive medication, and this is the aim of this prospective cohort study.Participants The Tayside Screening for Cardiac Events (TASCFORCE) study recruited men and women aged≥40 years, free from known CVD, with a predicted 10-year risk of coronary heart disease

The linkage of Electronic Medical Records, Administrative and other data sources is highly valuable for research and health system monitoring. Once linked, combined resources can be analyzed to provide the answers to a variety of health questions that otherwise could not be answered. However, legislative and administrative barriers, including lengthy processes for data sharing agreements, may preclude timely linkage which is a key requirement during pandemics. Objective To develop a method using a patient’s health trajectory to probabilistically link primary care Electronic Medical Record (EMR) data with administrative and other data, without the need to transfer large datasets or identifiable information. To determine the legislative feasibility, accuracy and validity of this linkage process. Study Design Identify data strings that do not directly identify patients and could be used as unique linkage variables. The data strings, which we are calling dataprints, are sufficiently similar over time in different databases. One example in Ontario, Canada, is the pattern of submitted health claims. For every patient seen by a family physician, there exists a unique pattern of dates/billing codes/diagnoses over time. These unique patterns are reasonably similar in EMR and administrative datasets. We will apply an algorithm which turns the string in the selected dataprints to an irreversibly hashed code for each person. The hashed code and no additional information will be provided by both data controllers to a trusted-third party who will determine which records match and send a mapping table to both. This enables analyses to be run in parallel, without divulging any direct person identifiers. Dataset Individuals contained in the University of Toronto Practice Based Research Network (UTOPIAN). Outcome Measures Linkage quality will be assessed by the number of true matches and represented by sensitivity, specificity and positive and negative predictive values. Results The method will be evaluated against a validated, deterministically linked reference standard at North York General Hospital using de-identified EMR and hospital data. Results will inform processes to enable analyses across datasets while adhering to privacy legislation.

Although machine learning has permeated many disciplines, the convergence of causal methods and machine learning remains sparse in the existing literature. Our aim was to formulate a marginal structural model in which we envisioned hypothetical (i.e. counterfactual) dynamic treatment regimes using a combination of drug therapies to manage diabetes: metformin, sulfonylurea and SGLT-2. We were interested in estimating “diabetes care provision” in next calendar year using a composite measure of chronic disease prevention and screening elements. We demonstrated the application of dynamic treatment regimes using the National Diabetes Action Canada Repository in which we applied a collection of mainstream statistical learning algorithms. We generated an ensemble of statistical learning algorithms using the SuperLearner based on the following base learners: (i) least absolute shrinkage and selection operator, (ii) ridge regression, (iii) elastic net, (iv) random forest, (v) gradient boosting machines, (vi) neural network. Each statistical learning algorithm was fitted using the pseudo-population with respect to the marginalization of the time-dependent confounding process. The covariate balance was assessed using the longitudinal (i.e. cumulative-time product) stabilized weights with calibrated restrictions. Our results indicated that the treatment drop-in cohorts (with respect to metformin, sulfonylurea and SGLT-2) may improve diabetes care provision in relation to treatment naïve cohort. As a clinical utility, we hope that this article will facilitate discussions around the prevention of adverse chronic outcomes associated with diabetes through the improvement of diabetes care provisions in primary care.

Abstract Background Trials often struggle to achieve their target sample size with only half doing so. Some researchers have turned to Electronic Health Records (EHRs), seeking a more efficient way of recruitment. The Scottish Health Research Register (SHARE) obtained patients’ consent for their EHRs to be used as a searching base from which researchers can find potential participants. However, due to the fact that EHR data is not complete, sufficient or accurate, a database search strategy may not generate the best case-finding result. The current study aims to evaluate the performance of a case-based reasoning method in identifying participants for population-based clinical studies recruiting through SHARE, and assess the difference between its resultant cohort and the original one deriving from searching EHRs. Methods A case-based reasoning framework was applied to 119 participants in nine projects using two-fold cross-validation, with records from a further 86,292 individuals used for testing. A prediction score for study participation was derived from the diagnosis, procedure, pharmaceutical prescription, and laboratory test results attributes of each participant. Evaluation was conducted by calculating Area Under the ROC Curve and information retrieval metrics for the ranking list of the test set by prediction score. We compared the most likely participants as identified by searching a database to those ranked highest by our model. Results The average ROCAUC for nine projects was 81% indicating strong predictive ability for these data. However, the derived ranking lists showed lower predictive performance, with only 21% of the persons ranked within top 50 positions being the same as identified by searching databases. Conclusions Case-based reasoning is may be more effective than a database search strategy for participant identification for clinical studies using population EHRs. The lower performance of ranking lists derived from case-based reasoning means that patients identified as highly suitable for study participation may still not be recruited. This suggests that further study is needed into improvements in the collection and curation of population EHRs, such as use of free text data to aid reliable identification of people more likely to be recruited to clinical trials.

Abstract The evidence base available to trialists to support trial process decisions—e.g. how best to recruit and retain participants, how to collect data or how to share the results with participants—is thin. One way to fill gaps in evidence is to run Studies Within A Trial, or SWATs. These are self-contained research studies embedded within a host trial that aim to evaluate or explore alternative ways of delivering or organising a particular trial process. SWATs are increasingly being supported by funders and considered by trialists, especially in the UK and Ireland. At some point, increasing SWAT evidence will lead funders and trialists to ask: given the current body of evidence for a SWAT, do we need a further evaluation in another host trial? A framework for answering such a question is needed to avoid SWATs themselves contributing to research waste. This paper presents criteria on when enough evidence is available for SWATs that use randomised allocation to compare different interventions.

Background Recent studies suggest an association between ambient air pollution and mental well-being, though evidence is mostly fragmented and inconclusive. Research also suffers from methodological limitations related to study design and moderating effect of key demographics (e.g., ethnicity). This study examines the effect of air pollution on reported mental well-being in United Kingdom (UK) using spatial-temporal (between-within) longitudinal design and assesses the moderating effect of ethnicity. Methods Data for 60,146 adult individuals (age:16+) with 349,748 repeated responses across 10-data collection waves (2009–2019) from “Understanding-Society: The-UK-Household-Longitudinal-Study” were linked to annual concentrations of NO2, SO2, PM10, and PM2.5 pollutants using the individuals’ place of residence, given at the local-authority and at the finer Lower-Super-Output-Areas (LSOAs) levels; allowing for analysis at two geographical scales across time. The association between air pollution and mental well-being (assessed through general-health-questionnaire-GHQ12) and its modification by ethnicity and being non-UK born was assessed using multilevel mixed-effect logit models. Results Higher odds of poor mental well-being was observed with every 10μg/m3 increase in NO2, SO2, PM10 and PM2.5 pollutants at both LSOAs and local-authority levels. Decomposing air pollution into spatial-temporal (between-within) effects showed significant between, but not within effects; thus, residing in more polluted local-authorities/LSOAs have higher impact on poor mental well-being than the air pollution variation across time within each geographical area. Analysis by ethnicity revealed higher odds of poor mental well-being with increasing concentrations of SO2, PM10, and PM2.5 only for Pakistani/Bangladeshi, other-ethnicities and non-UK born individuals compared to British-white and natives, but not for other ethnic groups. Conclusion Using longitudinal individual-level and contextual-linked data, this study highlights the negative effect of air pollution on individuals’ mental well-being. Environmental policies to reduce air pollution emissions can eventually improve the mental well-being of people in UK. However, there is inconclusive evidence on the moderating effect of ethnicity.

Background: Previous work identifies conservative family behaviour amongst Pakistanis in the United Kingdom relative to natives, including earlier marriages, fewer dissolutions, and higher fertility. However, few studies have investigated how fertility and partnership are intertwined and interdependent. Objective: Our aims are, first, to identify differences between the family trajectories of Pakistanis and natives and, second, to determine if patterns are consistent across immigrant generations. Finally, we aim to identify how family trajectories vary across birth cohorts and education levels. Methods: We apply multichannel sequence analysis (MCSA) to data from the UK Household Longitudinal Study. We first use clustering methods to group similar individuals and then apply multinomial logistic regression to calculate the probability of belonging to a cluster based on individual characteristics. Results: The Pakistani population exhibits a higher likelihood of entering a direct marriage and having large families compared to natives. Cohabitation is rare amongst Pakistani population. These patterns have changed little between immigrant generations. Degree-level education is associated with a higher likelihood of adopting behaviours typical to ancestral natives; however, the effects are not large enough to indicate convergence. Contribution: We demonstrate the need to investigate partnership and fertility trajectories simultaneously and show the value of MCSA for identifying differences between migrant groups. The results improve our understanding of family formation patterns of Pakistani immigrants and their descendants in the United Kingdom.

Objectives Multimorbidity—the co-occurrence of at least two chronic diseases in an individual—is an important public health challenge in ageing societies. The vast majority of multimorbidity research takes a cross-sectional approach, but longitudinal approaches to understanding multimorbidity are an emerging research area, being encouraged by multiple funders. To support development in this research area, the aim of this study is to scope the methodological approaches and substantive findings of studies that have investigated longitudinal multimorbidity trajectories.Design We conducted a systematic search for relevant studies in four online databases (Medline, Scopus, Web of Science and Embase) in May 2020 using predefined search terms and inclusion and exclusion criteria. The search was complemented by searching reference lists of relevant papers. From the selected studies, we systematically extracted data on study methodology and findings and summarised them in a narrative synthesis.Results We identified 35 studies investigating multimorbidity longitudinally, all published in the last decade, and predominantly in high-income countries from the Global North. Longitudinal approaches employed included constructing change variables, multilevel regression analysis (eg, growth curve modelling), longitudinal group-based methodologies (eg, latent class modelling), analysing disease transitions and visualisation techniques. Commonly identified risk factors for multimorbidity onset and progression were older age, higher socioeconomic and area-level deprivation, overweight and poorer health behaviours.Conclusion The nascent research area employs a diverse range of longitudinal approaches that characterise accumulation and disease combinations and to a lesser extent disease sequencing and progression. Gaps include understanding the long-term, life course determinants of different multimorbidity trajectories, and doing so across diverse populations, including those from low-income and middle-income countries. This can provide a detailed picture of morbidity development, with important implications from a clinical and intervention perspective.

Rationale Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up.Approach The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for ‘data-enabled clinical trials’. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation.Reflection Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a ‘route map’ to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution.Discussion EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial’s specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR’s funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.

Abstract Background Randomised controlled trials (RCTs) are frequently unable to recruit sufficient numbers of participants. This affects the trial’s ability to answer the proposed research question, wastes resources and can be unethical. RCTs within a general practice setting are increasingly common and similarly face recruitment challenges. The aim of the proposed review is to identify factors that are associated with recruitment rates to RCTs in a general practice setting. These results will be used in further research to predict recruitment to RCTs. Methods/design The electronic databases Medline, EMBASE, Cochrane Database of Systematic Reviews, NTIS and OpenGrey will be searched for relevant articles with no limit on the date of publication. BMC Trials will be manually searched for the past 5 years. Both quantitative and qualitative studies will be included if they have studied recruitment within a general practice RCT. Only English language publications will be included. Screening, quality assessment and data extraction will be conducted by two review authors not blinded to study characteristics. Disagreement will be resolved by discussion and the involvement of a third review author if required. A narrative synthesis of the studies included will be performed. Discussion The review will, for the first time, systematically synthesise existing research on factors associated with recruitment rates to RCTs in general practice. By identifying research gaps to be prioritised in further research, it will be of interest to academics. It will also be of value to clinical trialists who are involved in the complex task of improving trial recruitment. Our team will use the findings to inform a prediction model of trial recruitment using machine learning. Systematic review registration PROSPERO, CRD42018100695. Registered on 03 July 2018.

PURPOSE: The Translational Research and Patients safety in Europe (TRANSFoRm) project aims to integrate primary care with clinical research whilst improving patient safety. The TRANSFoRm International Research Readiness survey (TIRRE) aims to demonstrate data use through two linked data studies and by identifying clinical data repositories and genetic databases or disease registries prepared to participate in linked research. METHOD: The TIRRE survey collects data at micro-, meso- and macro-levels of granularity; to fulfil data, study specific, business, geographical and readiness requirements of potential data providers for the TRANSFoRm demonstration studies. We used descriptive statistics to differentiate between demonstration-study compliant and non-compliant repositories. We only included surveys with >70% of questions answered in our final analysis, reporting the odds ratio (OR) of positive responses associated with a demonstration-study compliant data provider. RESULTS: We contacted 531 organisations within the Eurpean Union (EU). Two declined to supply information; 56 made a valid response and a further 26 made a partial response. Of the 56 valid responses, 29 were databases of primary care data, 12 were genetic databases and 15 were cancer registries. The demonstration compliant primary care sites made 2098 positive responses compared with 268 in non-use-case compliant data sources [OR: 4.59, 95% confidence interval (CI): 3.93–5.35, p < 0.008]; for genetic databases: 380:44 (OR: 6.13, 95% CI: 4.25–8.85, p < 0.008) and cancer registries: 553:44 (OR: 5.87, 95% CI: 4.13–8.34, p < 0.008). CONCLUSIONS: TIRRE comprehensively assesses the preparedness of data repositories to participate in specific research projects. Multiple contacts about hypothetical participation in research identified few potential sites.

BackgroundAdherence to medicines is low for a variety of reasons, including the cost borne by patients. Some jurisdictions publicly fund medicines for the general population, but many jurisdictions do not, and such policies are contentious. To our knowledge, no trials studying free access to a wide range of medicines have been conducted.Methods and findingsWe randomly assigned 786 primary care patients who reported not taking medicines due to cost between June 1, 2016 and April 28, 2017 to either free distribution of essential medicines (n = 395) or to usual medicine access (n = 391). The trial was conducted in Ontario, Canada, where hospital care and physician services are publicly funded for the general population but medicines are not. The trial population was mostly female (56%), younger than 65 years (83%), white (66%), and had a low income from wages as the primary source (56%). The primary outcome was medicine adherence after 2 years. Secondary outcomes included control of diabetes, blood pressure, and low-density lipoprotein (LDL) cholesterol in patients taking relevant treatments and healthcare costs over 2 years. Adherence to all appropriate prescribed medicines was 38.7% in the free distribution group and 28.6% in the usual access group after 2 years (absolute difference 10.1%; 95% confidence interval (CI) 3.3 to 16.9, p = 0.004). There were no statistically significant differences in control of diabetes (hemoglobin A1c 0.27; 95% CI -0.25 to 0.79, p = 0.302), systolic blood pressure (-3.9; 95% CI -9.9 to 2.2, p = 0.210), or LDL cholesterol (0.26; 95% CI -0.08 to 0.60, p = 0.130) based on available data. Total healthcare costs over 2 years were lower with free distribution (difference in median CAN$1,117; 95% CI CAN$445 to CAN$1,778, p = 0.006). In the free distribution group, 51 participants experienced a serious adverse event, while 68 participants in the usual access group experienced a serious adverse event (p = 0.091). Participants were not blinded, and some outcomes depended on participant reports.ConclusionsIn this study, we observed that free distribution of essential medicines to patients with cost-related nonadherence substantially increased adherence, did not affect surrogate health outcomes, and reduced total healthcare costs over 2 years.Trial registrationClinicalTrials.gov NCT02744963.

In a clinical setting, biomarkers are typically measured and evaluated as biological indicators of a physiological state. Population based reference ranges, known as 'static' or 'normal' reference ranges, are often used as a tool to classify a biomarker value for an individual as typical or atypical. However, these ranges may not be informative to a particular individual when considering changes in a biomarker over time since each observation is assessed in isolation and against the same reference limits. To allow early detection of unusual physiological changes, adaptation of static reference ranges is required that incorporates within-individual variability of biomarkers arising from longitudinal monitoring in addition to between-individual variability. To overcome this issue, methods for generating individualised reference ranges are proposed within a Bayesian framework which adapts successively whenever a new measurement is recorded for the individual. This new Bayesian approach also allows the within-individual variability to differ for each individual, compared to other less flexible approaches. However, the Bayesian approach usually comes with a high computational cost, especially for individuals with a large number of observations, that diminishes its applicability. This difficulty suggests that a computational approximation may be required. Thus, methods for generating individualised adaptive ranges by the use of a time-efficient approximate Expectation-Maximisation (EM) algorithm will be presented which relies only on a few sufficient statistics at the individual level.

Introduction Trials often struggle to achieve their target sample size with only half doing so. Some researchers have turned to Electronic Health Records (EHRs), seeking a more efficient way of recruitment. The Scottish Health Research Register (SHARE) obtained patients’ consent for their EHRs to be used as a searching base from which researchers can find potential participants. However, due to the fact that EHR data is not complete, sufficient or accurate, a database search strategy may not generate the best case-finding result. Objectives and Approach A retrospective study was conducted to evaluate the performance of a case-based reasoning method in identifying participants for population-based clinical studies which had recruited through SHARE. A case-based reasoning framework was applied to nine studies with 119 total participants using two-fold cross-validation. Records of 30,000 random individuals were also merged with each test set to simulate the real-world recruitment setting. A prediction score for study participation was generated for each one in the test set through comparison of their diagnosis, procedure, pharmaceutical prescription, and laboratory test results attributes and those of the participants of a particular study. Evaluation was conducted by calculating Area Under the ROC Curve and information retrieval metrics for the ranking list of the test set by prediction score. We also compared the most likely participants as identified by searching a database to those ranked highest by our model. Results The average ROCAUC for nine projects was 81% indicating strong predictive ability. However, the derived ranking lists showed lower predictive performance. 21% of the persons ranked within top 50 positions being the same as identified by searching databases. Conclusion / Implications Case-based reasoning may be more effective than database search strategy for participant identification. This hypothesis requires a prospective study for further validation. The lower performance of ranking lists suggests improvements are needed in the collection and curation of EHRs.

Background: Inconclusive evidence supporting referrals from health professionals to gym-based exercise programmes has raised concern for the roll-out of such schemes, and highlights the importance of developing links between healthcare settings and community-based opportunities to improve physical activity (PA) levels. Aim: This study aimed to identify methods, and explore barriers and facilitators, of connecting primary care patients with PA opportunities from the perspectives of both health professionals (HPs) and patients, using the example of jogscotland. Design & setting: An exploratory study utilising semi-structured interviews with primary care patients (n = 14) and HPs (n = 14) from one UK NHS board was conducted. Method: Patient and HP transcripts were analysed separately using thematic analysis. Potential methods of connection were identified. The Capability, Opportunity, Motivation, behavioural (COM-B) model and theoretical domains framework (TDF) were employed to facilitate identification of barriers and facilitators for connecting primary care to community jogscotland groups. Results: Three methods of connecting patients to community-based groups were identified: informal passive signposting, informal active signposting, and formal referral or prescribing. Barriers and facilitators for patient connection fell into five TDF domains for HPs and two COM-B model components for patients. Conclusion: For patients, HPs raising the topic of PA can help to justify, facilitate, and motivate action to change. The workload associated with connecting patients with community-based opportunities is central to implementation by HPs. Integrative resource solutions and social support for patients can provide a greater variety of PA options and the vital information and support for connecting with local opportunities, such as jogscotland.

BACKGROUND:Starting in the late 1990s, the pharmaceutical industry sought to increase prescribing of opioids for chronic non-cancer pain. Influencing the content of clinical practice guidelines may have been one strategy industry employed. In this study we assessed potential risk of bias from financial conflicts of interest with the pharmaceutical industry in guidelines for opioid prescribing for chronic non-cancer pain published between 2007 and 2013, the peak of opioid prescribing. METHODS:We used the Guideline Panel Review (GPR) to appraise the guidelines included in the 2014 systematic review and critical appraisal by Nuckols et al. These were English language opioid prescribing guidelines for adults with chronic non-cancer pain published between July 2007 and July 2013, the peak of opioid prescribing. The GPR assigns red flags to items known to introduce potential bias from financial conflicts of interest. We operationalized the GPR by creating specific definitions for each red flag. Two reviewers independently evaluated each guideline. Disagreements were resolved with discussion. We also compared our score to the critical appraisal scores for overall quality from the study by Nuckols et al. RESULTS:We appraised 13 guidelines, which received 43 red flags in total. Guidelines had 3.3 red flags on average (out of a possible seven) with range from one to six. Four guidelines had missing information, so red flags may be higher than reported. The guidelines with the highest and second highest scores for overall quality in the 2014 critical appraisal by Nuckols et al. had five and three red flags, respectively. CONCLUSION:Our findings reveal that the guidelines for opioid prescribing chronic non-cancer pain from 2007 to 2013 were at risk of bias because of pervasive conflicts of interest with the pharmaceutical industry and a paucity of mechanisms to address bias. Even highly-rated guidelines examined in a 2014 systematic review and critical appraisal had many red flags.

BackgroundAir-pollution and weather exposure beyond certain thresholds have serious effects on public health. Yet, there is lack of information on wider aspects including the role of some effect modifiers and the interaction between air-pollution and weather. This article aims at a comprehensive review and narrative summary of literature on the association of air-pollution and weather with mortality and hospital admissions; and to highlight literature gaps that require further research.MethodsWe conducted a scoping literature review. The search on two databases (PubMed and Web-of-Science) from 2012 to 2020 using three conceptual categories of "environmental factors", "health outcomes", and "Geographical region" revealed a total of 951 records. The narrative synthesis included all original studies with time-series, cohort, or case cross-over design; with ambient air-pollution and/or weather exposure; and mortality and/or hospital admission outcomes.ResultsThe final review included 112 articles from which 70 involved mortality, 30 hospital admission, and 12 studies included both outcomes. Air-pollution was shown to act consistently as risk factor for all-causes, cardiovascular, respiratory, cerebrovascular and cancer mortality and hospital admissions. Hot and cold temperature was a risk factor for wide range of cardiovascular, respiratory, and psychiatric illness; yet, in few studies, the increase in temperature reduced the risk of hospital admissions for pulmonary embolism, angina pectoris, chest, and ischemic heart diseases. The role of effect modification in the included studies was investigated in terms of gender, age, and season but not in terms of ethnicity.ConclusionAir-pollution and weather exposure beyond certain thresholds affect human health negatively. Effect modification of important socio-demographics such as ethnicity and the interaction between air-pollution and weather is often missed in the literature. Our findings highlight the need of further research in the area of health behaviour and mortality in relation to air-pollution and weather, to guide effective environmental health precautionary measures planning.

Abstract Background Written participant information materials are important for ensuring that potential trial participants receive necessary information so that they can provide informed consent. However, such materials are frequently long and complex, which may negatively impact patient understanding and willingness to participate. Improving readability, ease of comprehension and presentation may assist with improved participant recruitment. The Systematic Techniques for Assisting Recruitment to Trials (MRC START) study aimed to develop and evaluate interventions to improve trial recruitment. This study aimed to assess the effectiveness of an optimised participant information brochure and cover letter developed by MRC START regarding response and participant recruitment rates. Methods We conducted a study within a trial (SWAT) embedded in the EarlyCDT Lung Cancer Scotland (ECLS) trial that aimed to assess the effectiveness of a new test in reducing the incidence of patients with late-stage lung cancer at diagnosis compared with standard care. Potential participants approached for ECLS were randomised to receive the original participant information brochure and accompanying letter (control group) or optimised versions of these materials which had undergone user testing and a process of re-writing, re-organisation and professional graphic design (intervention group). The primary outcome was the number of patients recruited to ECLS. The secondary outcome was the proportion of patients expressing an interest in participating in ECLS. Results In total, 2262 patients were randomised, 1136 of whom were sent the intervention materials and 1126 of whom were sent the control materials. The proportion of patients enrolled and randomised into ECLS was 180 of 1136 (15.8%) in the intervention group and 176 of 1126 (15.6%) in the control group (OR = 1.016, 95% CI, 0.660 to 1.564). The proportion of patients who positively responded to the invitation was 224 of 1136 (19.7%) in the intervention group and 205 of 1126 (18.2%) in the control group (OR = 1.103, 95% CI, 0.778 to 1.565). Conclusions Optimised patient information materials made little difference to the proportion of patients positively responding to a trial invitation or to the proportion subsequently randomised to the host trial. Trial registration ClinicalTrials.gov, NCT01925625. Registered on 15 August 2015. Study Within A Trial, SWAT-23. Registered on 12 April 2016.

Abstract Background Lung cancer is the second most common cancer and the leading cause of cancer death for both men and women. Although low-dose CT (LDCT) is recommended for lung cancer screening in high-risk populations and may decrease lung cancer mortality, there is a need to improve the accuracy of lung cancer screening to decrease over-diagnosis and morbidity. Blood and serum-based biomarkers, including EarlyCDT-lung and microRNA based biomarkers, are promising adjuncts to LDCT in lung cancer screening. We evaluated the diagnostic performance of EarlyCDT-lung, micro-RNA signature classifier (MSC), and miR-test, and their impact on lung cancer-related mortality and all-cause mortality. Methods References were identified using searches of PubMed, EMBASE, and Ovid Medline® from January 2000 to November 2015. Phase three or greater studies in the English language evaluating the diagnostic performance of EarlyCDT-lung, MSC, and miR-test were selected for inclusion. Results Three phase 3 studies were identified, one evaluating EarlyCDT-lung, one evaluating miR-Test, and one evaluating MSC respectively. No phase 4 or 5 studies were identified. All three biomarker assays show promise for the detection of lung cancer. MSC shows promise when used in conjunction with LDCT for lung cancer detection, achieving a positive likelihood ratio of 18.6 if both LDCT and MSC are positive, and a negative likelihood ratio of 0.03 if both LDCT and MSC are negative. However, there is a paucity of high-quality studies that can guide clinical implementation. Conclusions There is currently no high quality evidence to support or guide the implementation of these biomarkers in clinical practice. Reports of further research at stages four and five for these, and other promising methods, is required.

Abstract Background Arteriosclerosis (arterial stiffening) is associated with future cardiovascular events, with this effect postulated to be due to its effect on cardiac afterload, atherosclerosis (plaque formation) progression or both, but with limited evidence examining these early in disease formation. The aim of the current study is to examine the association between arteriosclerosis, atherosclerosis and ventricular remodelling in a population at low-intermediate cardiovascular risk. Methods One thousand six hundred fifty-one subjects free of clinical cardiovascular disease and with a

Abstract Background Recent evidence suggests that screening with low dose computed tomography (LDCT) scans significantly reduces mortality from lung cancer. However, optimal methods to identify potentially eligible patients in primary care are not known. Using brief electronic screening forms administered prior to a primary care visit is a strategy to identify high risk, asymptomatic patients eligible for LDCT screening. The objective of this study was to compare the acceptability and feasibility of using brief electronic versus paper screening forms to identify eligible patients at high risk of developing lung cancer in primary care. Methods A mixed method pilot comparative study was conducted in primary care. Practices were allocated to an electronic form (e-form) group or a paper-based form (p-form) group. Allocation was randomly assigned for the first practice then by alternation. Patients in the e-form practices completed forms at home via the web or in the waiting room on a tablet. Patients in p-form practices completed forms in waiting rooms. Interviews were conducted with patients, administrators, and primary care physicians (PCPs) about their experiences. Results Six of 30 (20%) eligible practices agreed to participate. Over the 16-week study period, a total of 831 of an expected 1442 patients (58%) aged 55–74 years were enrolled; 573/690 (83%) patients in the e-form group and 258/752 (34%) in the p-form group. Of the 573 participants in the e-form group, 335 (58%) completed forms via the web; 238 (29%) did so via tablet. Twenty-four interviews were conducted with 15 patients, 5 administrative staff and 4 PCPs. Patients were willing to discuss lung cancer screening eligibility with their PCP. Staff members expressed low administrative burden except for an extra step to link appointment information to patient demographics to identify eligible patients. PCPs indicated that forms were reminders to discuss smoking cessation. PCPs in the e-form group reported that patients asked questions about screening. Conclusion There was fairly low uptake by primary care practices. For e-forms to be feasible in practice workflow, electronic medical record software needs to link appointment information with patient eligibility requirements. The use of brief pre-consultation electronic screening forms for LDCT eligibility encouraged PCPs to discuss smoking cessation with patients.

Abstract Background Common foot problems are independent risk factors for falls in older people. There is evidence that podiatry can prevent falls in community-dwelling populations. The feasibility of implementing a podiatry intervention and trial in the care home population is unknown. To inform a potential future definitive trial, we performed a pilot randomised controlled trial to assess: (i) the feasibility of a trial of a podiatry intervention to reduce care home falls, and (ii) the potential direction and magnitude of the effect of the intervention in terms of number of falls in care home residents. Methods Informed by Medical Research Council guidance on developing and evaluating complex interventions, we conducted a single blind, pilot randomised controlled trial in six care homes in the East of Scotland. Participants were randomised to either: (i) a three month podiatry intervention comprising core podiatry care, foot and ankle exercises, orthoses and footwear provision or (ii) usual care. Falls-related outcomes (number of falls, time to first fall) and feasibility-related outcomes (recruitment, retention, adherence, data collection rates) were collected. Secondary outcomes included: generic health status, balance, mobility, falls efficacy, and ankle joint strength. Results 474 care home residents were screened. 43 (9.1%) participants were recruited: 23 to the intervention, 20 to control. Nine (21%) participants were lost to follow-up due to declining health or death. It was feasible to deliver the trial elements in the care home setting. 35% of participants completed the exercise programme. 48% reported using the orthoses ‘all or most of the time’. Completion rates of the outcome measures were between 93% and 100%. No adverse events were reported. At the nine month follow-up period, the intervention group per-person fall rate was 0.77 falls vs. 0.83 falls in the control group. Conclusions A podiatry intervention to reduce falls can be delivered to care home residents within a pilot randomised controlled trial of the intervention. Although not powered to determine effectiveness, these preliminary data provide justification for a larger trial, incorporating a full process evaluation, to determine whether this intervention can significantly reduce falls in this high-risk population. Trial registration ClinicalTrials.gov identifier: NCT02178527 ; Date of registration: 17 June 2014.

People with serious mental illness die 10-25 years sooner than people without these conditions. Multiple challenges to accessing and benefitting from healthcare have been identified amongst this population, including a lack of coordination between mental health services and general health services. It has been identified in other conditions such as diabetes that accurate documentation of diagnosis in the primary care chart is associated with better quality of care. It is suspected that if a patient admitted to the hospital with serious mental illness is then discharged without adequate identification of their diagnosis in the primary care setting, follow up (such as medication management and care coordination) may be more difficult. We identified cohorts of patients with schizophrenia and bipolar disorder who accessed care through the North York Family Health Team (a group of 77 family physicians in Toronto, Canada) and North York General Hospital (a large community hospital) between January 1, 2012 and December 31, 2014. We identified whether labeling for these conditions was concordant between the two settings and explored predictors of concordant labeling. This was a retrospective cross-sectional study using de-identified data from the Health Databank Collaborative, a linked primary care-hospital database. We identified 168 patients with schizophrenia and 370 patients with bipolar disorder. Overall diagnostic concordance between primary care and hospital records was 23.2% for schizophrenia and 15.7% for bipolar disorder. Concordance was higher for those with multiple (2+) inpatient visits (for schizophrenia: OR 2.42; 95% CI 0.64-9.20 and for bipolar disorder: OR 8.38; 95% CI 3.16-22.22). Capture-recapture modeling estimated that 37.4% of patients with schizophrenia (95% CI 20.7-54.1) and 39.6% with bipolar disorder (95% CI 25.7-53.6) had missing labels in both settings when adjusting for patients' age, sex, income quintiles and co-morbidities. In this sample of patients accessing care at a large family health team and community hospital, concordance of diagnostic information about serious mental illness was low. Interventions should be developed to improve diagnosis and continuity of care across multiple settings.

Many health systems and research institutes are interested in supplementing their traditional analyses of linked data with machine learning (ML) and other artificial intelligence (AI) methods and tools. However, the availability of individuals who have the required skills to develop and/or implement ML/AI is a constraint, as there is high demand for ML/AI talent in many sectors. The three organizations presenting are all actively involved in training and capacity building for ML/AI broadly, and each has a focus on, and/or discrete initiatives for, particular trainees. P. Alison Paprica, Vector Institute for artificial intelligence, Institute for Clinical Evaluative Sciences, University of Toronto, Canada. Alison is VP, Health Strategy and Partnerships at Vector, responsible for health strategy and also playing a lead role in “1000AIMs” – a Vector-led initiative in support of the Province of Ontario’s \$30 million investment to increase the number of AI-related master’s program graduates to 1,000 per year within five years. Frank Sullivan, University of St Andrews Scotland. Frank is a family physician and an associate director of HDRUK@Scotland. Health Data Research UK \url{https://hdruk.ac.uk/} has recently provided funding to six sites across the UK to address challenging healthcare issues through use of data science. A 50 PhD student Doctoral Training Scheme in AI has also been announced. Each site works in close partnership with National Health Service bodies and the public to translate research findings into benefits for patients and populations. Yin Aphinyanaphongs – INTREPID NYU clinical training program for incoming clinical fellows. Yin is the Director of the Clinical Informatics Training Program at NYU Langone Health. He is deeply interested in the intersection of computer science and health care and as a physician and a scientist, he has a unique perspective on how to train medical professionals for a data drive world. One version of this teaching process is demonstrated in the INTREPID clinical training program. Yin teaches clinicians to work with large scale data within the R environment and generate hypothesis and insights. The session will begin with three brief presentations followed by a facilitated session where all participants share their insights about the essential skills and competencies required for different kinds of ML/AI application and contributions. Live polling and voting will be used at the end of the session to capture participants’ view on the key learnings and take away points. The intended outputs and outcomes of the session are: • Participants will have a better understanding of the skills and competencies required for individuals to contribute to AI applications in health in various ways • Participants will gain knowledge about different options for capacity building from targeted enhancement of the skills of clinical fellows, to producing large number of applied master’s graduates, to doctoral-level training After the session, the co-leads will work together to create a resource that summarizes the learnings from the session and make them public (though publication in a peer-reviewed journal and/or through the IPDLN website)

Introduction Diabetes Action Canada is developing a data repository and registry of potential research participants to support research, QI, and service to improve diabetes care. Central to the repository are pseudonymised linkable electronic medical records (EMRs) from family practices that are participating in the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Objectives and Approach We sought to develop an information governance process that would engender the trust of patients and the health care professionals (HCPs) that their EMR data were being managed responsibly in the best interests of patients living with diabetes. Following an extensive literature review, we developed a principles-based governance framework and operational model, with a strong focus on patient participation in the governance process. We recruited patients through our pre-existing patient advisory circles and physicians through our partners in CPCSSN. In January 2018, we held a training workshop for Research Governing Committee (RGC) members. Results We identified eight values-based principles to guide our governance process: transparency; accountability; following the rule of law; integrity of purpose, science and ethics; participation and inclusiveness; impartiality and independence; effectiveness; efficiency and responsiveness; and reflexivity and continuous quality improvement of process. Patients represent 50% of RGC members and HCPs 20%. Patient members provide their perspectives on: goals and outcomes of the research; the benefits and burdens among people living with diabetes; and the communication preferences of patients around recruitment. HCPs provide a deep understanding of the settings and systems in which care is provided to ensure contextual integrity of the research. Two researchers and one person with bioethics expertise provide technical and ethics perspectives on data requests. Conclusion/Implications Governance must go beyond legal compliance to ensure a ’social licence’ for the use of the data. In part, we address this through our guiding principles, our emphasis on patient and healthcare provider perspectives, and focus on research that is scientifically sound, ethically robust and in the public interest.

BACKGROUND:High quality primary care is fundamental to achieving health for all. Research priority setting is a key facilitator of improving how research activity responds to concrete needs. There has never before been an attempt to identify international primary care research priorities, in order to guide resource allocation and to enhance global primary care. This study aimed to identify a list of top 10 primary care research priorities, as identified by members of the public, health professionals working in primary care, researchers, and policymakers. METHODS:We adapted the James Lind Alliance Priority Setting Partnership process, to conduct multiple rounds of stakeholder recruitment and prioritization. The study included an online survey conducted in three languages, followed by an in-person priority setting exercise involving primary care stakeholders from 13 countries. FINDINGS:Participants identified a list of top 10 international primary care research priorities. These were focused on diverse topics such as enhancing use of information and communication technology, and improving integration of indigenous communities' knowledge in the design of primary care services. The main limitations of the study related to challenges in engaging an adequate diversity and number of appropriate stakeholders, particularly members of the public, in aggregating the diverse set of responses into coherent categories representative of the participants' perspectives and in adequately representing the diversity of submitted responses while ensuring research priorities on the final list are sufficiently actionable to guide resource allocation. CONCLUSIONS:The top 10 identified research priorities have the potential to guide research resource allocation, supporting funding agencies and initiatives to promote global primary care research and practice.

Background: Secondary skin infection is common during eczema exacerbations and many children are treated with antibiotics when this is suspected, although there is little high-quality evidence to justify this practice. Objective: To determine the clinical effectiveness of oral and topical antibiotics, in addition to standard treatment with emollients and topical corticosteroids, in children with clinically infected eczema. Design: Multicentre randomised, double-blind, placebo-controlled trial. Setting: General practices and dermatology clinics in England, Wales and Scotland. Participants: Children (aged 3 months to

Table of content P3 Medial longitudinal arch development of school children Jasper W.K. Tong, Veni P. Kong P4 Is measuring the subtalar joint reliable? Lily Sze, Susie Gale, John Veto, Carla McArdle P5 Comparison of turning gait biomechanics between able‐bodied and unilateral transtibial amputee participants Thanaporn Tunprasert, Victoria Bradley, Siobhan Strike P6 Comparison of walking gait biomechanics between able‐bodied and unilateral transtibial amputee participants using a new model of energy‐storage‐and‐return (ESAR) prosthetic Thanaporn Tunprasert, Victoria Bradley, Siobhan Strike P7 An observational study of in‐shoe plantar and dorsal pressures of skilled downhill skiers on a dry ski slope Robert Ashford, Roozbeth Naemi, Nachiappan Chocklingam, Xavi de Blasc P8 If the shoe fits: a footwear choice toolkit informed by social science methodologies Lisa Farndon, Vicki Robinson, Emily Nicholls P9 The identification of emotions from gait Tabitha Birch, Ivan Birch P11 Experience of foot problems in patients with systemic lupus erythematosus Simon Otter, Sunil Kumar, Peter Gow, Nicola Dalbeth, Michael Corkill, Kevin Davies, Sam Panthakalam, Maheswaran Rohan, Keith Rome P14 Negative pressure wound therapy for the management of foot wounds in the diabetic population: a review of the literature Chloe Egan, Lisa Chandler P15 Lower limb vascular assessment in diabetes: a multifaceted assessment of objective screening techniques Peta Tehan, Vivienne Chuter, Jennifer Sonter, Sean Lanting P16 Improving outcomes for diabetes foot complications Lorna Hicks P17 Acupuncture… an alternative or adjunctive treatment option for diabetes‐related neuropathic pain? Christopher Joyce, David Watterson, Caroline McIntosh P18 “My back is in agony” – A cross‐sectional study into the relationship between musculoskeletal complaints and a whole body postural risk assessment in podiatry students Christopher Joyce, Nigel Roberts P19 Swabs of the treatment couches: Does the material type and texture of podiatric treatment couches increase microorganism contamination? Jacqueline Forss, Chrystalla Charalambous, Jack Kirby, Oluwakemi Ojo P20 Does increased exudate viscosity effect the absorption rate of exudate into four different wound dressings? Jacqueline Forss, Sarah Caukill, Jacqueline Capon, Radiance Fong, Louis Loy P21 An investigation into the microbial load of a 40 °C and 60 °C wash Matthew Diment, Madeleine Murray, Mairghread Ellis, Carla McArdle P23 The sensitivity and specificity of the toe brachial index in detecting peripheral arterial disease: a systematic review and meta‐analysis Peta Tehan, Vivienne Chuter, Christopher Oldmeadow P24 Medicines management activities and non‐medical prescribing within podiatry and physiotherapy: an integrative review of the literature Nicola Carey, Karen Stenner, Heather Gage, Jane Brown, Peter Williams, Simon Otter, Ann Moore, Jude Edwards, Freda Mold, Molly Courtenay A7.2 Non‐invasive vascular assessment in the foot with Diabetes: Diagnostic accuracy of ankle brachial index, toe brachial index and continuous wave Doppler Peta Tehan, Alan Bray, Vivienne Chuter A7.5 The efficacy of dressings on post nail surgery phenolised wounds Pamela Hindmoor B7.1 Cross‐sectional study investigating the role of proximal and distal factors in the development of patellofemoral joint pain Craig Gwynne, Sarah Curran B7.2 Podiatrist's interpretation and use of evidence in MSK practice Andy Bridgen B7.4 Predictors of falling in older podiatry patients – findings from the REFORM study Caroline Fairhurst, Dr Joy Adamson, Belen Corbacho Martin, Sarah Cockayne, Prof Catherine Hewitt, Kate Hicks, Anne‐Maree Keenan, Lorraine Loughrey‐Green, Hylton Menz, Anthony Redmond, Sara Rodgers, Jude Watson, David Torgerson, Robin Hull, Sarah Lamb, Caroline McIntosh, Wesley Vernon, Lisa Farndon B7.5 The REFORM study: Insole preference, requirements and compliance of podiatry patient's aged 65 and over and at risk of falling Lorraine Loughrey‐Green, Sarah Cockayne, Anthony Redmond, Anne‐Maree Keenan, Sara Rodgers, Lisa Farndon, Wesley Vernon, David Torgerson, Caroline Fairhurst, Jude Watson, Hylton Menz, Sarah Lamb, Robin Hull B7.6 A podiatry intervention to reduce falls in care home residents is feasible and demonstrates benefits: results from PIRFECT, a feasibility randomised controlled trial Gavin Wylie, Zoe Young, Brian Williams, Frank Sullivan, Hylton Menz, Simon Ogston, Jacqui Morris C7.1 A survey exploring footwear habits in people with stroke and people with Parkinson's Cathy Bowen, Dorit Kunkel, Mark Cole, Margaret Donovan‐Hall, Ruth Pickering, Malcolm Burnett, Dan Bader, Judy Robison, Louis Mamode, Ann Ashburn C7.2 Painful foot osteoarthritis; a common symptom in a common pathology? Peter McQueen, Maxine Daniels, Michael Doherty, Nigel Arden, Cathy Bowen C7.4 Clinical diagnosis of symptomatic forefoot neuroma in the general population: Delphi based recommendations Charlotte Dando, Lindsey Cherry, Cathy Bowen C7.5 The development and implementation of a Clinical Quality Improvement Framework suitable for use in community services Nichola Stefanou C7.6 The REFORM study ‐ methodological considerations in running a cohort randomised controlled trial within a podiatry patient caseload Sarah Cockayne, Joy Adamson, Caroline Fairhurst, Catherine Hewitt, Anne‐Maree Keenan, Sally Lamb, Lorraine Loughrey‐Green, Caroline McIntosh, Hylton Menz, Anthony Redmond, Sara Rodgers, Wesley Vernon, Jude Watson, Lisa Farndon, Belen Corbacho, Robin Hull, David Torgerson A31 Jewel in the crown: Exploring the factors contributing to the development and impact of foot problems in Systemic Sclerosis (SSc) Begonya Alcacer‐Pitarch, Anthony Redmond, Maya Buch, Anne‐Maree Keenan

OBJECTIVE: To systematically review the literature on the implementation of e-health to identify: (1) barriers and facilitators to e-health implementation, and (2) outstanding gaps in research on the subject. METHODS: MEDLINE, EMBASE, CINAHL, PSYCINFO and the Cochrane Library were searched for reviews published between 1 January 1995 and 17 March 2009. Studies had to be systematic reviews, narrative reviews, qualitative metasyntheses or meta-ethnographies of e-health implementation. Abstracts and papers were double screened and data were extracted on country of origin; e-health domain; publication date; aims and methods; databases searched; inclusion and exclusion criteria and number of papers included. Data were analysed qualitatively using normalization process theory as an explanatory coding framework. FINDINGS: Inclusion criteria were met by 37 papers; 20 had been published between 1995 and 2007 and 17 between 2008 and 2009. Methodological quality was poor: 19 papers did not specify the inclusion and exclusion criteria and 13 did not indicate the precise number of articles screened. The use of normalization process theory as a conceptual framework revealed that relatively little attention was paid to: (1) work directed at making sense of e-health systems, specifying their purposes and benefits, establishing their value to users and planning their implementation; (2) factors promoting or inhibiting engagement and participation; (3) effects on roles and responsibilities; (4) risk management, and (5) ways in which implementation processes might be reconfigured by user-produced knowledge. CONCLUSION: The published literature focused on organizational issues, neglecting the wider social framework that must be considered when introducing new technologies.

Background Recruitment to trials in primary care is often difficult, particularly when practice staff need to identify study participants with acute conditions during consultations. The Scottish Acute Recruitment Management Application (SARMA) system is linked to general practice electronic medical record (EMR) systems and is designed to provide recruitment support to multi-centre trials by screening patients against trial inclusion criteria and alerting practice staff if the patient appears eligible. For patients willing to learn more about the trial, the software allows practice staff to send the patient's contact details to the research team by text message. Aim To evaluate the ability of the software to support trial recruitment. Design of study Software evaluation embedded in a randomised controlled trial. Setting Five general practices in Tayside and Fife, Scotland. Methods SARMA was used to support recruitment to a feasibility trial (the Response to Oral Agents in Diabetes, or ROAD trial) looking at users of oral therapy in diabetes. The technical performance of the software and its utility as a recruitment tool were evaluated. Results The software was successfully installed at four of the five general practices and recruited 11 of the 29 participants for ROAD (other methods were letter and direct invitation by a practice nurse) and had a recruitment return of 35% (11 of 31 texts sent led to a recruitment). Screen failures were relatively low (7 of 31 referred). Practice staff members were positive about the system. Conclusion An automated recruitment tool can support primary care trials in Scotland and has the potential to support recruitment in other jurisdictions. It offers a low-cost supplement to other trial recruitment methods and is likely to have a much lower screen failure rate than blanket approaches such as mailshots and newspaper campaigns.

Objectives General practitioners are increasingly required to practice in a paperless environment and to collect clinical data electronically on electronic patient record (EPR) systems. A principal step in meeting general practice information needs continues to be the establishment of disease registers and consequently the identification of patient populations within primary care databases is a prerequisite. This study aims to identify and validate the optimal search strategy for coronary heart disease (CHD). Methods A multiple logistic regression model for the identification of CHD patients was developed in one site using electronic data, the receiver operating characteristic (ROC) curve and Bayesian statistics. The model was tested on two trial sites. Results Young male CHD patients are more easily identified by generic searches than older females. The optimal search strategy for CHD was found to be the diagnostic code for CHD, nitrate and digoxin but this was dependent on the disease description, age and sex of the study population and the coding system used within the database. Diagnostic code for CHD identified 80.6% (95% confidence interval (CI) 77-83%), 90.0% (CI 88-92%) and 95.9% (CI 94-97%) of local, national and international definitions respectively, with 100% positive predictive values (PPVs) for all definitions. Conclusion Generic queries may inadvertently perpetuate inequalities in health care. Queries should be bespoke and mindful of the conceptualisation of disease by the clinicians recording these data.

Objective To conduct a technical appraisal and qualitative interviews with short message service (SMS - mobile phone text message) users in mainstream health care. Design Observation of service usage followed by in-depth semi-structured interviews. Setting A National Health Service (NHS) general practice in Scotland. Participants One hundred and eighty patients registered. Main outcome measures Service utilisation and patients' views. Results It was technically feasible to open up access to mainstream NHS general practice services using SMS for appointment booking, repeat prescription ordering, clinical enquiries and remote access to the core clinical summary. Conclusion Patients were able to use SMS services responsibly and found automation of prescription ordering particularly useful. Service utilisation was modest and did not adversely impact on the workload of general practitioners (GPs) or their staff.