Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Tonsillectomy is regularly performed in adults with acute tonsillitis, but with scarce evidence. A reduction in tonsillectomies has coincided with an increase in acute adult hospitalisation for tonsillitis complications. We aimed to assess the clinical effectiveness and cost-effectiveness of conservative management versus tonsillectomy in patients with recurrent acute tonsillitis. METHODS: This pragmatic multicentre, open-label, randomised controlled trial was conducted in 27 hospitals in the UK. Participants were adults aged 16 years or older who were newly referred to secondary care otolaryngology clinics with recurrent acute tonsillitis. Patients were randomly assigned (1:1) to receive tonsillectomy or conservative management using random permuted blocks of variable length. Stratification by recruiting centre and baseline symptom severity was assessed using the Tonsil Outcome Inventory-14 score (categories defined as mild 0-35, moderate 36-48, or severe 49-70). Participants in the tonsillectomy group received elective surgery to dissect the palatine tonsils within 8 weeks after random assignment and those in the conservative management group received standard non-surgical care during 24 months. The primary outcome was the number of sore throat days collected during 24 months after random assignment, reported once per week with a text message. The primary analysis was done in the intention-to-treat (ITT) population. This study is registered with the ISRCTN registry, 55284102. FINDINGS: Between May 11, 2015, and April 30, 2018, 4165 participants with recurrent acute tonsillitis were assessed for eligibility and 3712 were excluded. 453 eligible participants were randomly assigned (233 in the immediate tonsillectomy group vs 220 in the conservative management group). 429 (95%) patients were included in the primary ITT analysis (224 vs 205). The median age of participants was 23 years (IQR 19-30), with 355 (78%) females and 97 (21%) males. Most participants were White (407 [90%]). Participants in the immediate tonsillectomy group had fewer days of sore throat during 24 months than those in the conservative management group (median 23 days [IQR 11-46] vs 30 days [14-65]). After adjustment for site and baseline severity, the incident rate ratio of total sore throat days in the immediate tonsillectomy group (n=224) compared with the conservative management group (n=205) was 0·53 (95% CI 0·43 to 0·65; <0·0001). 191 adverse events in 90 (39%) of 231 participants were deemed related to tonsillectomy. The most common adverse event was bleeding (54 events in 44 [19%] participants). No deaths occurred during the study. INTERPRETATION: Compared with conservative management, immediate tonsillectomy is clinically effective and cost-effective in adults with recurrent acute tonsillitis. FUNDING: National Institute for Health Research.

Emulating a Target Trial Using Primary-Care Electronic Health Records: Sodium-Glucose Cotransporter 2 Inhibitor Medications and Hemoglobin A1c.

Substantial effort has been dedicated to conducting randomized controlled experiments to generate clinical evidence for diabetes treatment. Randomized controlled experiments are the gold standard for establishing cause and effect. However, due to their high cost and time commitment, large observational databases such as those comprised of electronic health record (EHR) data collected in routine primary care may provide an alternative source with which to address such causal objectives. We used a Canadian primary-care data repository housed at the University of Toronto (Toronto, Ontario, Canada) to emulate a randomized experiment. We estimated the effectiveness of sodium-glucose cotransporter 2 inhibitor (SGLT-2i) medications for patients with diabetes using hemoglobin A1c (HbA1c) as a primary outcome and marker for glycemic control from 2018 to 2021. We assumed an intention-to-treat analysis for prescribed treatment, with analyses based on the treatment assigned rather than the treatment eventually received. We defined the causal contrast of interest as the net change in HbA1c (percent) between the group receiving the standard of care versus the group receiving SGLT-2i medication. Using a counterfactual framework, marginal structural models demonstrated a reduction in mean HbA1c level with the initiation of SGLT-2i medications. These findings provided effect sizes similar to those from earlier clinical trials on assessing the effectiveness of SGLT-2i medications.

Personalised lung cancer risk stratification and lung cancer screening: do general practice electronic medical records have a role?

BACKGROUND: In the United Kingdom (UK), cancer screening invitations are based on general practice (GP) registrations. We hypothesize that GP electronic medical records (EMR) can be utilised to calculate a lung cancer risk score with good accuracy/clinical utility. METHODS: The development cohort was Secure Anonymised Information Linkage-SAIL (2.3 million GP EMR) and the validation cohort was UK Biobank-UKB (N = 211,597 with GP-EMR availability). Fast backward method was applied for variable selection and area under the curve (AUC) evaluated discrimination. RESULTS: Age 55-75 were included (SAIL: N = 574,196; UKB: N = 137,918). Six-year lung cancer incidence was 1.1% (6430) in SAIL and 0.48% (656) in UKB. The final model included 17/56 variables in SAIL for the EMR-derived score: age, sex, socioeconomic status, smoking status, family history, body mass index (BMI), BMI:smoking interaction, alcohol misuse, chronic obstructive pulmonary disease, coronary heart disease, dementia, hypertension, painful condition, stroke, peripheral vascular disease and history of previous cancer and previous pneumonia. The GP-EMR-derived score had AUC of 80.4% in SAIL and 74.4% in UKB and outperformed ever-smoked criteria (currently the first step in UK lung cancer screening pilots). DISCUSSION: A GP-EMR-derived score may have a role in UK lung cancer screening by accurately targeting high-risk individuals without requiring patient contact.

Intranasal steroid use and COVID-19 mortality among patients with asthma and COPD: A retrospective cohort study.

BACKGROUND: Systemic corticosteroids have been widely used for treating patients with severe acute respiratory distress syndrome. Inhaled corticosteroids may have a protective effect for treating acute coronavirus disease 2019 (COVID-19); however, little is known about the potential effect of intranasal corticosteroids (INCS) on COVID-19 outcomes and severity. OBJECTIVE: To assess the impact of prior long-term INCS exposure on COVID-19 mortality among patients with chronic respiratory disease and in the general population. METHODS: A retrospective cohort study was conducted. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between INCS exposure and all-cause and COVID-19 mortality, adjusted by age, sex, deprivation, exacerbations in the last year, and comorbidities. RESULTS: Exposure to INCS did not have a significant association with COVID-19 mortality among the general population or cohorts with chronic obstructive pulmonary disease or asthma, with HRs of 0.8 (95% CI, 0.6-1.0, P = .06), 0.6 (95% CI, 0.3-1.1, P = .1), and 0.9 (95% CI, 0.2-3.9, P = .9), respectively. Exposure to INCS was, however, significantly associated with reduction in all-cause mortality in all groups, which was 40% lower (HR, 0.6 [95% CI, 0.5-0.6, P < .001]) among the general population, 30% lower (HR, 0.7; 95% CI, 0.6-0.8, P < .001) among patients with chronic obstructive pulmonary disease, and 50% lower (HR, 0.5; 95% CI, 0.3-0.7, P = .003) among patients with asthma. CONCLUSION: The role of INCS in COVID-19 is still unclear, but exposure to INCS does not adversely affect COVID-19 mortality. Further studies are needed to explore the association between their use and inflammatory activation, viral load, angiotensin-converting enzyme 2 gene expression, and outcomes, exploring different types and doses of INCS.

Long-term exposure to air pollution and mortality in Scotland: A register-based individual-level longitudinal study.

BACKGROUND: Air pollution is associated with several adverse health outcomes. However, heterogeneity in the size of effect estimates between cohort studies for long-term exposures exist and pollutants like SO2 and mental/behavioural health outcomes are little studied. This study examines the association between long-term exposure to multiple ambient air pollutants and all-cause and cause-specific mortality from both physical and mental illnesses. METHODS: We used individual-level administrative data from the Scottish-Longitudinal-Study (SLS) on 202,237 individuals aged 17 and older, followed between 2002 and 2017. The SLS dataset was linked to annual concentrations of NO2, SO2, and particulate-matter (PM10, PM2.5) pollution at 1 km2 spatial resolution using the individuals' residential postcode. We applied survival analysis to assess the association between air pollution and all-cause, cardiovascular, respiratory, cancer, mental/behavioural disorders/suicides, and other-causes mortality. RESULTS: Higher all-cause mortality was associated with increasing concentrations of PM2.5, PM10, NO2, and SO2 pollutants. NO2, PM10, and PM2.5 were also associated with cardiovascular, respiratory, cancer and other-causes mortality. For example, the mortality hazard from respiratory diseases was 1.062 (95%CI = 1.028-1.096), 1.025 (95%CI = 1.005-1.045), and 1.013 (95%CI = 1.007-1.020) per 1 µg/m3 increase in PM2.5, PM10 and NO2 pollutants, respectively. In contrast, mortality from mental and behavioural disorders was associated with 1 µg/m3 higher exposure to SO2 pollutant (HR = 1.042; 95%CI = 1.015-1.069). CONCLUSION: This study revealed an association between long-term (16-years) exposure to ambient air pollution and all-cause and cause-specific mortality. The results suggest that policies and interventions to enhance air quality would reduce the mortality hazard from cardio-respiratory, cancer, and mental/behavioural disorders in the long-term.

The spatial-temporal effect of air pollution on individuals' reported health and its variation by ethnic groups in the United Kingdom: a multilevel longitudinal analysis.

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.

Statin-associated immune-mediated necrotizing myositis in Native Americans.

OBJECTIVES: Statin-associated immune-mediated necrotizing myopathy (IMNM) and idiopathic inflammatory myositis (IIM) are myopathies with overlapping features. This study compared the manifestations of IMNM to IIM in Native Americans. METHOD: Twenty-one Native American patients with inflammatory myopathy (IM) were characterized as to diabetes mellitus, hyperlipidaemia, statin exposure, myopathy diagnosis, muscle histology, autoimmune and myositis-specific autoantibodies, therapy and outcome. RESULTS: IM consisted of 52.4% IMNM, 42.9% IIM and 4.8% metabolic myopathy. IMNM vs IIM patients were older [61.6 years (s.d. 9.8) vs 39.8 (14.3)], diabetes mellitus (100% vs 55.6%), hyperlipidaemia (100% vs 33.3%), statin-exposure (100% vs 22.2%), creatine kinase [CK; 11 780 IU (s.d. 7064) vs 1707 (1658)], anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) antibodies (85.7% vs 11.1%) and necrotizing IM (81.8% vs 11.1%), but shorter disease duration [26.2 months (s.d. 395) vs 78.4 (47.9)], RP (9.1% vs 55.6%), cutaneous manifestations (0% vs 55.6%), ANA (18.2% vs 66.7%) or any autoantibody (18.2% vs 88.9%) (all P < 0.05). MRI abnormalities, histologic IM, myositis-specific autoantibodies, pulmonary hypertension, oesophageal dysfunction, interstitial lung disease, disability and persistently elevated CK were similar. IMNM vs IIM was treated more with IVIG (72.7% vs 11.1%; P = 0.009) and less with antimetabolites (45.5% vs 88.9%; P = 0.05) and rituximab (18.2% vs 55.6%; P = 0.09). CONCLUSIONS: IMNM may occur in Native Americans and is associated with diabetes mellitus, hyperlipidaemia, statin use and older age and is characterized by marked CK elevation, necrotizing myopathy and anti-HMGCR antibodies with few cutaneous or vascular manifestations.

Understanding patient barriers and facilitators to uptake of lung screening using low dose computed tomography: a mixed methods scoping review of the current literature.

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.

Optimizing the implementation of lung cancer screening in Scotland: Focus group participant perspectives in the LUNGSCOT study.

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.

Intraarticular injection of the interphalangeal joint for therapy of digital mucoid cysts.

Mucoid cysts are associated with osteoarthritis (OA) of the digital joints and frequently recur after needle drainage, injection, or surgical ablation. This study determined whether intraarticular injection of the adjacent interphalangeal joint rather than the cyst itself might be effective in resolving digital mucoid cysts. Using paired case series design and sterile technique, 25 consecutive OA digital joints with an adjacent mucoid cyst underwent dorsal non-transtendinous intraarticular injection with a 25-gauge needle and 20-mg triamcinolone acetonide, followed by puncture and manual expression of cyst fluid. Patient pain was measured with the 10-cm Visual Analogue Pain Scale prior to the procedure and at 6 months. Cyst resolution was determined at 6 months and 3 years. The subjects were 61.0 ± 7.7 years old and 60% (15/25) female. Mucoid cysts were adjacent to 19 distal interphalangeal, 3 metacarpophalangeal, and 3 interphalangeal joints. Pre-procedural pain was 4.7 ± 1.0; procedural pain was 6.2 ± 0.6 cm, and post-procedural pain at 6 months was 1.2 ± 0.8 cm (74.5% reduction, 95% CI of difference: 3.0 < 3.5 < 4.0 (p < 0.0001)). 84% (21/25) of the cysts resolved at 6 months; however, 60% (15/25) of the mucoid cysts recurred within 3 years and required retreatment (14 adjacent joints re-injected and 1 ablative cyst surgery). No complications were noted. Intraarticular corticosteroid injection using a dorsal non-transtendinous approach of the joint adjacent to a mucoid cyst is effective resolving cysts and reducing pain at 6 months; however, 60% of mucoid cysts reoccur within 3 years and may require reinjection or surgery.Trial registration: This was not a clinical trial.

Increasing uptake to a lung cancer screening programme: building with communities through co-design.

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.

Adherence at 2 years with distribution of essential medicines at no charge: The CLEAN Meds randomized clinical trial.

BACKGROUND: Adherence 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 FINDINGS: We 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. CONCLUSIONS: In 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 REGISTRATION: ClinicalTrials.gov NCT02744963.

Can we achieve better recruitment by providing better information? Meta-analysis of 'studies within a trial' (SWATs) of optimised participant information sheets.

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, I2 = 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).

Earlier diagnosis of lung cancer in a randomised trial of an autoantibody blood test followed by imaging.

The EarlyCDT-Lung test is a high-specificity blood-based autoantibody biomarker that could contribute to predicting lung cancer risk. We report on the results of a phase IV biomarker evaluation of whether using the EarlyCDT-Lung test and any subsequent computed tomography (CT) scanning to identify those at high risk of lung cancer reduces the incidence of patients with stage III/IV/unspecified lung cancer at diagnosis compared with the standard clinical practice at the time the study began.The Early Diagnosis of Lung Cancer Scotland (ECLS) trial was a randomised controlled trial of 12 208 participants at risk of developing lung cancer in Scotland in the UK. The intervention arm received the EarlyCDT-Lung test and, if test-positive, low-dose CT scanning 6-monthly for up to 2 years. EarlyCDT-Lung test-negative and control arm participants received standard clinical care. Outcomes were assessed at 2 years post-randomisation using validated data on cancer occurrence, cancer staging, mortality and comorbidities.At 2 years, 127 lung cancers were detected in the study population (1.0%). In the intervention arm, 33 out of 56 (58.9%) lung cancers were diagnosed at stage III/IV compared with 52 out of 71 (73.2%) in the control arm. The hazard ratio for stage III/IV presentation was 0.64 (95% CI 0.41-0.99). There were nonsignificant differences in lung cancer and all-cause mortality after 2 years.ECLS compared EarlyCDT-Lung plus CT screening to standard clinical care (symptomatic presentation) and was not designed to assess the incremental contribution of the EarlyCDT-Lung test. The observation of a stage shift towards earlier-stage lung cancer diagnosis merits further investigations to evaluate whether the EarlyCDT-Lung test adds anything to the emerging standard of low-dose CT.

Early experience with an opt-in research register - Scottish Health Research Register (SHARE): a multi-method evaluation of participant recruitment performance.

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.

Over-use of thyroid testing in Canadian and UK primary care in frequent attenders: A cross-sectional study.

BACKGROUND: Thyroid-stimulating hormone (TSH) is a common test used to detect and monitor clinically significant hypo- and hyperthyroidism. Population-based screening of asymptomatic adults for thyroid disorders is not recommended. OBJECTIVE: The research objectives were to determine patterns of TSH testing in Canadian and English primary care practices, as well as patient and physician practice characteristics associated with testing TSH for primary care patients with no identifiable indication. METHODS: In this 2-year cross-sectional observational study, Canadian and English electronic medical record databases were used to identify patients and physician practices. Cohorts of patients aged 18 years or older, without identifiable indications for TSH testing, were generated from these databases. Analyses were performed using a random-effects logistic regression to determine patient and physician practice characteristics associated with increased testing. We determined the proportion of TSH tests performed concurrently with at least one common screening blood test (lipid profile or hemoglobin A1c). Standardised proportions of TSH test per family practice were used to examine the heterogeneity in the populations. RESULTS: At least one TSH test was performed in 35.97% (N = 489 663) of Canadian patients and 29.36% (N = 1 030 489) of English patients. Almost all TSH tests in Canada and England (95.69% and 99.23% respectively) were within the normal range (0.40-5.00 mU/L). A greater number of patient-physician encounters was the strongest predictor of TSH testing. It was determined that 51.40% of TSH tests in Canada and 76.55% in England were performed on the same day as at least one other screening blood test. There was no association between the practice size and proportion of asymptomatic patients tested. CONCLUSIONS: This comparative binational study found TSH patterns suggestive of over-testing and potentially thyroid disorder screening in both countries. There may be significant opportunities to improve the appropriateness of TSH ordering in Canada and England and therefore improve the allocation of limited system resources.

Efficient identification of patients eligible for clinical studies using case-based reasoning on Scottish Health Research register (SHARE).

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.

Podiatry interventions to prevent falls in older people: a systematic review and meta-analysis.

BACKGROUND: foot problems are independent risk factors for falls in older people. Podiatrists diagnose and treat a wide range of problems affecting the feet, ankles and lower limbs. However, the effectiveness of podiatry interventions to prevent falls in older people is unknown. This systematic review examined podiatry interventions for falls prevention delivered in the community and in care homes. METHODS: systematic review and meta-analysis. We searched multiple electronic databases with no language restrictions. Randomised or quasi-randomised-controlled trials documenting podiatry interventions in older people (aged 60+) were included. Two reviewers independently applied selection criteria and assessed methodological quality using the Cochrane Risk of Bias tool. TiDieR guidelines guided data extraction and where suitable statistical summary data were available, we combined the selected outcome data in pooled meta-analyses. RESULTS: from 35,857 titles and 5,201 screened abstracts, nine studies involving 6,502 participants (range 40-3,727) met the inclusion criteria. Interventions were single component podiatry (two studies), multifaceted podiatry (three studies), or multifactorial involving other components and referral to podiatry component (four studies). Seven studies were conducted in the community and two in care homes. Quality assessment showed overall low risk for selection bias, but unclear or high risk of detection bias in 4/9 studies. Combining falls rate data showed significant effects for multifaceted podiatry interventions compared to usual care (falls rate ratio 0.77 [95% CI 0.61, 0.99]); and multifactorial interventions including podiatry (falls rate ratio: 0.73 [95% CI 0.54, 0.98]). Single component podiatry interventions demonstrated no significant effects on falls rate. CONCLUSIONS: multifaceted podiatry interventions and multifactorial interventions involving referral to podiatry produce significant reductions in falls rate. The effect of multi-component podiatry interventions and of podiatry within multifactorial interventions in care homes is unknown and requires further trial data. PROSPERO REGISTRATION NUMBER: CRD42017068300.

Antiviral treatment for Bell's palsy (idiopathic facial paralysis).

BACKGROUND: Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. This review was first published in 2001 and most recently updated in 2015. Since a significant benefit of corticosteroids for the early management of Bell's palsy has been demonstrated, the main focus of this update, as in the previous version, was to determine the effect of adding antivirals to corticosteroid treatment. We undertook this update to integrate additional evidence and to better assess the robustness of findings, taking risk of bias fully into account. OBJECTIVES: To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy. SEARCH METHODS: We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS in July 2019. We reviewed the bibliographies of the identified trials and contacted trial authors to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) or quasi-RCTs of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that followed-up participants for less than three months. DATA COLLECTION AND ANALYSIS: We independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures. We performed sensitivity analyses excluding trials at high or unclear risk of bias in at least five domains, and reported these data as the primary analyses. MAIN RESULTS: Fourteen trials, including 2488 participants, met the inclusion criteria. Most were small, and most were at high or unclear risk of bias in multiple domains. We included four new studies at this update.Incomplete recoveryA combination of antivirals and corticosteroids may have little or no effect on rates of incomplete recovery in people with Bell's palsy compared to corticosteroids alone (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.38 to 1.74; 3 trials, N = 766; random-effects; low-certainty evidence). We excluded 10 trials that were at high or unclear risk of bias in several domains from this analysis and limited all analyses to studies at lower risk of bias. Recovery rates were better in participants receiving corticosteroids alone than antivirals alone (RR 2.69, 95% CI 0.73 to 10.01; 2 trials, N = 667; random-effects), but the result was imprecise and allowed for the possibility of no effect. The rate of incomplete recovery was lower with antivirals plus corticosteroids than with placebo or no treatment (RR 0.56, 95% CI 0.42 to 0.76; 2 trials, N = 658; random-effects). Antivirals alone had no clear effect on incomplete recovery rates compared with placebo, but the result was imprecise (RR 1.10, 95% CI 0.87 to 1.40; 2 trials, N = 658; fixed-effect). For people with severe Bell's palsy (House-Brackmann score of 5 and 6, or equivalent on other scales), we found that the combination of antivirals and corticosteroids had no clear effect on incomplete recovery at month six compared to corticosteroids alone, although the result was again imprecise (RR 0.82, 95% CI 0.57 to 1.17; 2 trials, N = 98; random-effects).Motor synkinesis or crocodile tearsAntivirals plus corticosteroids reduced the proportion of participants who experienced these long-term sequelae from Bell's palsy compared to placebo plus corticosteroids (RR 0.56, 95% CI 0.36 to 0.87; 2 trials, N = 469; fixed-effect; moderate-certainty evidence). Antivirals plus corticosteroids reduced long-term sequelae compared to placebo but there was no clear difference in this outcome with antivirals alone compared to placebo.Adverse events Adverse event data were available in four studies providing data on 1592 participants. None of the four comparisons showed clear differences in adverse events between treatment and comparison arms (very low-certainty evidence); for the comparison of antivirals plus corticosteroids and corticosteroids alone in studies at lower risk of bias, the RR was 1.17 (95% CI 0.81 to 1.69; 2 trials, N = 656; fixed-effect; very low-certainty evidence). AUTHORS' CONCLUSIONS: The combination of antivirals and corticosteroids may have little or no effect on rates of incomplete recovery in comparison to corticosteroids alone in Bell's palsy of various degrees of severity, or in people with severe Bell's palsy, but the results were very imprecise. Corticosteroids alone were probably more effective than antivirals alone and antivirals plus corticosteroids were more effective than placebo or no treatment. There was no clear benefit from antivirals alone over placebo.The combination of antivirals and corticosteroids probably reduced the late sequelae of Bell's palsy compared with corticosteroids alone. Studies also showed fewer episodes of long-term sequelae in corticosteroid-treated participants than antiviral-treated participants.We found no clear difference in adverse events from the use of antivirals compared with either placebo or corticosteroids, but the evidence is too uncertain for us to draw conclusions.An adequately powered RCT in people with Bell's palsy that compares different antiviral agents may be indicated.

Primary care providers' views on a future lung cancer screening program.

BACKGROUND: The National Lung Screening Trial demonstrated that screening with low-dose computed tomography significantly reduces mortality from lung cancer in high-risk individuals. OBJECTIVE: To describe the role preferences and information needs of primary care providers (PCPs) in a future organized lung cancer screening program. METHODS: We purposively sampled PCPs from diverse health regions of Ontario and from different practice models including family health teams and community health centres. We also recruited family physicians with a leadership role in cancer screening. We used focus groups and a nominal group process to identify informational priorities. Two analysts systematically applied a coding scheme to interview transcripts. RESULTS: Four groups were held with 34 providers and administrative staff [28 (82%) female, 21 (62%) physicians, 7 (20%) other health professionals and 6 (18%) administrative staff]. PCPs and staff were generally positive about a potential lung cancer screening program but had variable views on their involvement. Informational needs included evidence of potential benefits and harms of screening. Most providers preferred that a new program be modelled on positive features of an existing breast cancer screening program. Lung cancer screening was viewed as a new opportunity to counsel patients about smoking cessation. CONCLUSIONS: The development of a future lung cancer screening program should consider the wide variability in the roles that PCPs preferred. An explicit link to existing smoking cessation programs was seen as essential. As providers had significant information needs, learning materials and opportunities should be developed with them.