Discovery of potent inhibitors of α-synuclein aggregation using structure-based iterative learning.

Machine learning methods hold the promise to reduce the costs and the failure rates of conventional drug discovery pipelines. This issue is especially pressing for neurodegenerative diseases, where the development of disease-modifying drugs has been particularly challenging. To address this problem, we describe here a machine learning approach to identify small molecule inhibitors of α-synuclein aggregation, a process implicated in Parkinson's disease and other synucleinopathies. Because the proliferation of α-synuclein aggregates takes place through autocatalytic secondary nucleation, we aim to identify compounds that bind the catalytic sites on the surface of the aggregates. To achieve this goal, we use structure-based machine learning in an iterative manner to first identify and then progressively optimize secondary nucleation inhibitors. Our results demonstrate that this approach leads to the facile identification of compounds two orders of magnitude more potent than previously reported ones.

UK clinicians' attitudes towards the application of molecular diagnostics to guide antibiotic use in ICU patients with pneumonias: a quantitative study.

BACKGROUND: Molecular diagnostic tests may improve antibiotic prescribing by enabling earlier tailoring of antimicrobial therapy. However, clinicians' trust and acceptance of these tests will determine their application in practice. OBJECTIVES: To examine ICU prescribers' views on the application of molecular diagnostics in patients with suspected hospital-acquired and ventilator-associated pneumonia (HAP/VAP). METHODS: Sixty-three ICU clinicians from five UK hospitals completed a cross-sectional questionnaire between May 2020 and July 2020 assessing attitudes towards using molecular diagnostics to inform initial agent choice and to help stop broad-spectrum antibiotics early. RESULTS: Attitudes towards using molecular diagnostics to inform initial treatment choices and to stop broad-spectrum antibiotics early were nuanced. Most (83%) were positive about molecular diagnostics, agreeing that using results to inform broad-spectrum antibiotic prescribing is good practice. However, many (58%) believed sick patients are often too unstable to risk stopping broad-spectrum antibiotics based on a negative result. CONCLUSIONS: Positive attitudes towards the application of molecular diagnostics to improve antibiotic stewardship were juxtapositioned against the perceived need to initiate and maintain broad-spectrum antibiotics to protect unstable patients.

Using Generative Modeling to Endow with Potency Initially Inert Compounds with Good Bioavailability and Low Toxicity.

In the early stages of drug development, large chemical libraries are typically screened to identify compounds of promising potency against the chosen targets. Often, however, the resulting hit compounds tend to have poor drug metabolism and pharmacokinetics (DMPK), with negative developability features that may be difficult to eliminate. Therefore, starting the drug discovery process with a "null library", compounds that have highly desirable DMPK properties but no potency against the chosen targets, could be advantageous. Here, we explore the opportunities offered by machine learning to realize this strategy in the case of the inhibition of α-synuclein aggregation, a process associated with Parkinson's disease. We apply MolDQN, a generative machine learning method, to build an inhibitory activity against α-synuclein aggregation into an initial inactive compound with good DMPK properties. Our results illustrate how generative modeling can be used to endow initially inert compounds with desirable developability properties.

Multiplexed Digital Characterization of Misfolded Protein Oligomers via Solid-State Nanopores.

Misfolded protein oligomers are of central importance in both the diagnosis and treatment of Alzheimer's and Parkinson's diseases. However, accurate high-throughput methods to detect and quantify oligomer populations are still needed. We present here a single-molecule approach for the detection and quantification of oligomeric species. The approach is based on the use of solid-state nanopores and multiplexed DNA barcoding to identify and characterize oligomers from multiple samples. We study α-synuclein oligomers in the presence of several small-molecule inhibitors of α-synuclein aggregation as an illustration of the potential applicability of this method to the development of diagnostic and therapeutic methods for Parkinson's disease.

Structure-Based Discovery of Small-Molecule Inhibitors of the Autocatalytic Proliferation of α-Synuclein Aggregates.

The presence of amyloid fibrils of α-synuclein is closely associated with Parkinson's disease and related synucleinopathies. It is still very challenging, however, to systematically discover small molecules that prevent the formation of these aberrant aggregates. Here, we describe a structure-based approach to identify small molecules that specifically inhibit the surface-catalyzed secondary nucleation step in the aggregation of α-synuclein by binding to the surface of the amyloid fibrils. The resulting small molecules are screened using a range of kinetic and thermodynamic assays for their ability to bind α-synuclein fibrils and prevent the further generation of α-synuclein oligomers. This study demonstrates that the combination of structure-based and kinetic-based drug discovery methods can lead to the identification of small molecules that selectively inhibit the autocatalytic proliferation of α-synuclein aggregates.

Perceptions and Practicalities Influencing Pre-exposure Prophylaxis Adherence Among Men Who Have Sex with Men in England.

PrEP is highly effective for HIV prevention but requires adequate adherence. In this paper we use the perceptions and practicalities approach (PAPA) to identify factors that influenced PrEP adherence using qualitative data from the PROUD study. From February 2014 to January 2016, we interviewed 41 gay, bisexual and other men-who-have-sex-with-men and one trans woman who were enrolled in the study. We purposively recruited participants for interview based on trial arm allocation, adherence and sexual risk behaviours. The interviews were conducted in English, audio-recorded, transcribed, coded and analysed using framework analysis. Participants in general were highly motivated to use and adhere to PrEP, and this was linked to strong perceptions of personal necessity for PrEP as they felt at risk of HIV and viewed PrEP as highly effective. On the other hand, concerns about side effects and HIV resistance did inhibit PrEP initiation and adherence although this was uncommon. Practical factors such as daily routine, existing habitual pill-taking and pill storage impacted adherence. Drug and alcohol use rarely caused participants to miss doses. These findings indicate that using the principals of PAPA to unpick influencers of PrEP use, could help tailor adherence support in PrEP programmes.

Medication adherence in adult Chinese patients with asthma: role of illness perceptions and medication beliefs.

OBJECTIVE: This study aimed to investigate the relationship between illness perceptions, medication beliefs, and self-reported adherence to inhaled corticosteroid (ICS) therapy in adult Chinese patients with asthma. METHODS: A cross-sectional survey was conducted in the asthma outpatient clinic of Zhongshan Hospital, Fudan University (Shanghai, China) between October 2018 and September 2019. Illness perceptions, medication beliefs, and medication adherence were assessed using validated scales, specifically the Medication Adherence Report Scale for Asthma, Beliefs about Medicines Questionnaire -Specific, and the Brief Illness Perception Questionnaire. Spearman correlation and multiple logistic regression were used to determine the relationship among these factors. Results: A total of 234 patients were included in this study. Of this group, 99 (42.3%) participants were non-adherent to their ICS medication. Medication adherence correlated negatively with 'illness identity' (perceived symptom), 'emotional response' (perceived emotional effect) and concerns about medication (r=-0.16, -0.16 and -0.15, respectively, p < 0.05). After adjusting for illness perceptions, medication beliefs and demographics, beliefs about the necessity of medication (odds ratio [OR]: 1.14, 95% confidence interval [CI]: 1.01-1.30), and emotional response to the disease (OR: 0.89, 95% CI: 0.80-0.99) were significantly associated with medication adherence in patients with asthma. CONCLUSION: Beliefs about the necessity of medication and emotional response to the illness have a strong influence on self-reported medication adherence in adult patients with asthma in China. Interventions targeted adherence improvement among patients with asthma may be tailored to the individual's baseline perceptions and medication beliefs, and focus on modifying inaccurate illness perceptions and medication beliefs as the main targets.

Determinants of Knowledge About Dietary Supplements Among Polish Internet Users: Nationwide Cross-sectional Study.

BACKGROUND: An accurate understanding of dietary supplements (DS) is a prerequisite for informed decisions regarding their intake. However, there is a need for studies on this understanding among the public based on validated research tools. OBJECTIVE: This study aims to assess the knowledge about DS among Polish internet users with no medical education and to identify its determinants and design an appropriate predictive model. METHODS: The study protocol was prospectively registered with a statistical analysis plan. Polish users of a web-based health service and a social networking service were administered a survey consisting of the recently developed questionnaire on knowledge about DS, the questionnaire on trust in advertising DS, the beliefs about medicines questionnaire, and several other health-related single-item measures and sociodemographic questions. The results were subjected to general linear modeling. RESULTS: A total of 6273 participants were included. Of the 17 yes or no questions in the questionnaire of knowledge about DS, the mean number of correct responses was 9.0 (95% CI 8.9-9.1). Health service users performed worse than social networking users by 2.3 points (95% CI 2.1-2.5) in an analysis adjusted for potential confounders. Internet users had fewer true beliefs about DS if they presented higher trust in their advertising (adjusted ß=-.37; 95% CI -.39 to -.34), used DS (adjusted ß=-.14; 95% CI -.17 to -.12), experienced their positive effect (adjusted ß=-.16; 95% CI -.18 to -.13), were older or younger than 35 years (adjusted ß=-.14; 95% CI -.17 to -.12), expressed interest in the topic of DS (adjusted ß=-.10; 95% CI -.13 to -.08), reported getting information about the products from friends (adjusted ß=-.13; 95% CI -.15 to -.11), and believed that medicines are harmful (adjusted ß=-.12; 95% CI -.15 to -.10). The proposed 5-predictor model could explain 31.2% of the variance in knowledge about DS. The model appeared resistant to overfitting and was able to forecast most of the observed associations. CONCLUSIONS: Polish internet users with no medical education exhibit some false beliefs regarding DS. Trusting the advertising of DS appears to conflict with knowledge about them. There is an urgent need for effective web-based educational campaigns on DS and the promotion of advertising literacy. After the proposed predictive model is externally validated, it may help identify the least informed target audience.

Patients' adherence-related beliefs about inhaled steroids: application of the Chinese version of the Beliefs about Medicines Questionnaire-specific in patients with asthma.

Objective: The main objective of the present study is to evaluate the psychometric properties of the Chinese version of Beliefs about Medicines Questionnaire-specific among asthma patients; and to assess the association between patients' belief and adherence to inhaled corticosteroid therapy. Methods: A cross-sectional survey was carried out in the asthma clinic of Zhongshan Hospital, to Fudan University (Shanghai, China) between April 2016 and March 2018. The Beliefs about Medicines Questionnaire-specific was translated into Chinese according to international guidelines. Internal consistency, test-retest reliability, and confirmatory factor analysis were calculated to validate the Beliefs about Medicines Questionnaire-specific. The relationship between the adherence and the belief subscale were assessed using Kruskal-Wallis test. Results: Two hundred and seventeen patients were recruited in this study. The Beliefs about Medicines Questionnaire-specific was deemed reliable based on the results of Cronbach's alpha coefficient and test-retest intraclass correlation coefficient (ICC, ICC= 0.759). Confirmatory factor analysis showed acceptable model fit for the two-factor model. Patients' compliance was closely related to their belief about inhaled corticosteroid. The adherence rates were highest for the accepting groups, and lowest for the skeptical groups. Higher adherence was significantly associated with higher necessity-concerns differential (p = .001) and lower concern (p = .004). Conclusions: The Chinese version of the Beliefs about Medicines Questionnaire-specific can be used as a reliable tool by the clinicians to identify beliefs and behaviors of individual to improve adherence in Chinese patients.

Reliability and validation of Swedish translation of Beliefs about Medication Specific (BMQ-Specific) and Brief Illness Perception Questionnaire (B-IPQ) for use in adolescents with attention-deficit hyperactivity disorder.

Objectives: The purpose of this study was to assess the reliability and validity of Swedish translations of the Beliefs about Medicines Questionnaire-Specific (BMQ-Specific) and Brief Illness Perception Questionnaire (B-IPQ) for use in adolescents with ADHD.Methods: Forward and backward translations of the BMQ-Specific and B-IPQ scales to Swedish were conducted and reviewed by adolescents with ADHD and professionals. The validity and reliability of both questionnaires were investigated in a cross-sectional study of 101 adolescents (13-17 years) on a long-term prescription of ADHD medication recruited from two child and adolescent psychiatric outpatient clinics in Sweden.Results: Regarding the BMQ-Specific, principal component analysis (PCA) loadings confirmed the previously defined components of Specific-Necessity and Specific-Concern. The PCA for B-IPQ revealed two components, the first one, B-IPQ Consequences, captured questions regarding perceptions of the implication of having ADHD (items 1, 2, 5, 6 and 8) and the second one, B-IPQ-Control, the perceptions of the capability to manage the ADHD disorder (items 3, 4 and 7). The Cronbach alpha coefficients for BMQ-Specific-Necessity scale was α = 0.80, for BMQ-Specific-Concern scale α = 0.75, B-IPQ Consequences α = 0.74 and for B-IPQ-Control α = 0.44.Conclusions: The present results prove the Swedish translation of BMQ-Specific and B-IPQ to be valid and reliable for utilization in adolescents with ADHD. The PCA confirmed the original components for BMQ-Specific and the recent findings of two main B-IPQ components describing emotional and cognitive implications versus the capability for self-care maintenance of ADHD.

Ensuring continuity of patient care across the healthcare interface: Telephone follow-up post-hospitalization.

AIMS: To implement pharmacist-led, postdischarge telephone follow-up (TFU) intervention and to evaluate its impact on rehospitalization parameters in polypharmacy patients, via comparison with a well-matched control group. METHOD: Pragmatic, prospective, quasi-experimental study. Intervention patients were matched by propensity score techniques with a control group. Guided by results from a pilot study, clinical pharmacists implemented TFU intervention, added to routine integrated medicines management service. RESULTS: Using an intention to treat approach, reductions in 30- and 90-day readmission rates for intervention patients compared with controls were 9.9% [odds ratio = 0.57; 95% confidence interval (CI): 0.36-0.90; P < 0.001] and 15.2% (odds ratio = 0.53; 95% CI: 0.36-0.79; P = 0.021) respectively. Marginal mean time to readmission was 70.9 days (95% CI: 66.9-74.9) for intervention group compared with 60.1 days (95% CI: 55.4-64.7) for controls. Mean length of hospital stay compared with control was (8.3 days vs. 6.7 days; P < 0.001). Benefit: cost ratio for 30-day readmissions was 29.62, and 23.58 for 90-day interval. Per protocol analyses gave more marked improvements. In intervention patients, mean concern scale score, using Beliefs about Medicine Questionnaire, was reduced 3.2 (95% CI: -4.22 to -2.27; P < 0.001). Mean difference in Medication Adherence Report Scale was 1.4 (22.7 vs. 24.1; P < 0.001). Most patients (83.8%) reported having better control of their medicines after the intervention. CONCLUSIONS: Pharmacist-led postdischarge structured TFU intervention can reduce 30- and 90-day readmission rates. Positive impacts were noted on time to readmission, length of hospital stay upon readmission, healthcare costs, patient beliefs about medicines, patient self-reported adherence and satisfaction.

A Review of Portable Electronic Spirometers: Implications for Asthma Self-Management.

PURPOSE OF REVIEW: Although portable electronic spirometers allow for at-home lung function monitoring, a comprehensive review of these devices has not yet been conducted. We conducted a systematic search and review of commercially available portable electronic spirometers designed for asthma patient use. RECENT FINDINGS: All devices (N = 16) allowed for monitoring of basic lung function parameters, but only 31% provided in-app videos on how to perform breathing maneuvers. Most devices (63%) provided graphical representations of lung function results, but only 44% gave immediate feedback on the quality of the breathing maneuver. Several devices (25%) were FDA-approved and cost ranged from US$99 to $1390. Information on data security (63%), measurement accuracy (50%), and association with patient outcomes (0%) was commonly limited. This review found that providers' ability to make informed decisions about whether asthma patients may benefit from portable electronic spirometers is limited due to lack of patient outcome data.

Predictors of nonadherence in children and adolescents with epilepsy: A multimethod assessment approach.

BACKGROUND: There is a lack of a standardized tool for adherence measurement in patients with epilepsy. Studies in children with epilepsy have reported adherence in 50-96.5%. The primary objective of this study was to identify predictors of nonadherence to antiepileptic drugs (AEDs) using two different methods in Jordanian children and adolescents with epilepsy. METHODS: Participants included 63 children and adolescents with epilepsy and their primary caregivers. Adherence measures included a subjective approach (using parent and child self-reports via Medication Adherence Report Scale (MARS)) and an objective method (measuring plasma levels of AEDs coupled with the application of population pharmacokinetic models to predict AED concentrations in the children). The Beliefs about Medicines Questionnaire (BMQ) was used to examine the association beliefs about medicines with nonadherence in the participating patients. RESULTS: Measuring AEDs in plasma samples captured the highest percentage of nonadherence (36.2%). No significant agreement was found between the AED plasma level method and both the MARS (parent) and MARS (child). The overall nonadherence (combined methods) to AED therapy in children with epilepsy was 44.4%. Logistic regression analysis indicated that children with longer duration of disease were more likely (odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.16-2.04) to be classified as nonadherent as were children whose parents have lower AED Necessity scores (OR: 0.68, 95% CI: 0.53-0.87) and higher AED Concerns (OR: 1.6, 95% CI: 1.26-2.04) as measured by the BMQ. CONCLUSION: The use of a multimethod approach for assessing adherence increases sensitivity for detection of nonadherence to AEDs. Disease duration and parental necessity beliefs and concerns assessed by the BMQ-specific questionnaire were significant predictors of nonadherence to the AED therapy. The need for the development and implementation of interventions that can be employed to improve adherence within this pediatric population has been highlighted by the high levels of nonadherence identified.

A Review of Electronic Devices to Assess Inhaler Technique.

PURPOSE OF REVIEW: Multiple electronic devices exist that provide feedback on the accuracy of patient inhaler technique. Our purpose is to describe the inhaler technique feedback provided by these devices, including specific technique steps measured, how feedback is displayed, target of feedback (patient, provider, researcher), and compatibility with inhaler type (metered-dose inhaler [MDI], diskus, etc.). RECENT FINDINGS: We identified eight devices that provide feedback on inhaler technique. Only one device assessed all evidence-based MDI technique steps. Most devices provide limited real-time feedback to patients, if any feedback at all. Technologies to assess inhaler technique are advancing and hold great potential for improving patient inhaler technique. Many devices are limited in their ability to detect all evidence-based technique steps and provide real-time user-friendly feedback to patients and providers. Usability tests with patients and providers could identify ways to improve these devices to improve their utility in clinical settings.

How to Screen for Non-Adherence to Antihypertensive Therapy.

The quality of assessment of non-adherence to treatment in hypertensive is poor. Within this review, we discuss the different methods used to assess adherence to blood-pressure-lowering medications in hypertension patients. Subjective reports such as physicians' perceptions are inaccurate, and questionnaires completed by patients tend to overreport adherence and show a low diagnostic specificity. Indirect objective methods such as pharmacy database records can be useful, but they are limited by the robustness of the recorded data. Electronic medication monitoring devices are accurate but usually track adherence to only a single medication and can be expensive. Overall, the fundamental issue with indirect objective measures is that they do not fully confirm ingestion of antihypertensive medications. Detection of antihypertensive medications in body fluids using liquid chromatography-tandem mass spectrometry is currently, in our view, the most robust and clinically useful method to assess non-adherence to blood-pressure-lowering treatment. It is particularly helpful in patients presenting with resistant, refractory or uncontrolled hypertension despite the optimal therapy. We recommend using this diagnostic strategy to detect non-adherence alongside a no-blame approach tailoring support to address the perceptions (e.g. beliefs about the illness and treatment) and practicalities (e.g. capability and resources) influencing motivation and ability to adhere.

Determinants of adherence to disease modifying anti-rheumatic drugs in White British and South Asian patients with rheumatoid arthritis: a cross sectional study.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic inflammatory disease causing joint damage, disability, and reduced life expectancy. Highly effective drugs are now available for the treatment of RA. However, poor adherence to drug regimens remains a significant barrier to improving clinical outcomes in RA. Poor adherence has been shown to be linked to patients' beliefs about medicines with a potential impact on adherence. These beliefs are reported to be different between ethnic groups. The purpose of this study was to identify potential determinants of adherence to disease modifying anti-rheumatic drugs (DMARDs) including an assessment of the influence of beliefs about medicines and satisfaction with information provided about DMARDs and compare determinants of adherence between RA patients of White British and South Asian. METHODS: RA patients of either White British (n = 91) or South Asian (n = 89) origin were recruited from secondary care. Data were collected via questionnaires on patients': (1) self-reported adherence (Medication Adherence Report Scale-MARS); (2) beliefs about medicines (Beliefs about Medicines Questionnaire-BMQ); (3) illness perceptions (Illness Perceptions Questionnaire-IPQ) and (4) satisfaction with information about DMARDs (Satisfaction with Information about Medicines questionnaire-SIMS). In addition, clinical and demographic data were collected. RESULTS: The results revealed that socio-demographic factors only explained a small amount of variance in adherence whereas illness representations and treatment beliefs were more substantial in explaining non-adherence to DMARDs. Patients' self-reported adherence was higher in White British than South Asian patients (median 28 (interquartile range 26-30) vs median 26 (interquartile range 23-30) respectively; P = 0.013, Mann-Whitney test). Patients who reported lower adherence were more dissatisfied with the information they had received about their DMARDs (P < 0.001, Spearman correlation, SIMS action and usage subscale; P < 0.001, Spearman correlation, SIMS potential problems subscale) and had more negative beliefs about their DMARDs and were related to ethnicity with South Asian patients having more negative views about medicines. CONCLUSIONS: Socio-demographic factors were found to explain a small amount of variance in adherence. Illness representations and treatment beliefs were more important in explaining non-adherence to DMARDs. Clinicians managing South Asian patients with RA need to be aware that low adherence may be linked to negative beliefs about medicines and illness representations of RA.

Bayesian Optimization in the Latent Space of a Variational Autoencoder for the Generation of Selective FLT3 Inhibitors.

The process of drug design requires the initial identification of compounds that bind their targets with high affinity and selectivity. Advances in generative modeling of small molecules based on deep learning are offering novel opportunities for making this process faster and cheaper. Here, we propose an approach to achieve this goal, where predictions of binding affinity are used in conjunction with the Junction Tree Variational Autoencoder (JTVAE) whose latent space is used to facilitate the efficient exploration of the chemical space using a Bayesian optimization strategy. The exploration identifies small molecules predicted to have both high affinity and high selectivity by using an objective function that optimizes the binding to the target while penalizing the binding to off-targets. The framework is demonstrated for FMS-like tyrosine kinase 3 (FLT3) and shown to predict small molecules with predicted affinity and selectivity comparable to those of clinically approved drugs for this target.

Behavioral Science: Enhancing Our Approach to the Development of Effective Additional Risk Minimization Strategies.

Additional risk minimization strategies may be required to assure a positive benefit-risk balance for some therapeutic products associated with serious adverse drug reactions/risks of use, without which these products may be otherwise unavailable to patients. The goals of risk minimization strategies are often fundamentally to influence the behavior of healthcare professionals (HCPs) and/or patients and can include appropriate patient selection, provision of education and counselling, appropriate medication use, adverse drug reaction monitoring, and adoption of other elements to assure safe use, such as pregnancy prevention. Current approaches to additional risk minimization strategy development rely heavily on information provision, without full consideration of the contextual factors and multi-level influences on patient and HCP behaviors that impact adoption and long-term adherence to these interventions. Application of evidence-based behavioral science methods are urgently needed to improve the quality and effectiveness of these strategies. Evidence from the fields of adherence, health promotion, and drug utilization research underscores the value and necessity for using established behavioral science frameworks and methods if we are to achieve clinical safety goals for patients. The current paper aims to enhance additional risk minimization strategy development and effectiveness by considering how a behavioral science approach can be applied, drawing from evidence in understanding of engagement with pharmaceutical medicines as well as wider public health interventions for patients and HCPs.

Supporting people with type 2 diabetes in effective use of their medicine through mobile health technology integrated with clinical care (SuMMiT-D pilot): results of a feasibility randomised trial.

BACKGROUND: The purpose of this 6-month intervention pilot feasibility randomised trial was to test sending brief messages using mobile phones to promote self-management through taking medication as prescribed to people with type 2 diabetes. This was to inform the design and conduct of a future large-scale United Kingdom-based clinical trial and establish the feasibility of recruitment, the technology used, follow-up, and data collection. METHODS: A multicentre individually randomised, controlled parallel group trial in primary care, recruiting adults (≥ 35 years) with type 2 diabetes in England. Consenting participants were randomly allocated to receive short message system text messages up to four times a week, or usual care, for a period of 6 months; messages contained behavioural change techniques targeting medication use. The primary outcome was the rate of recruitment to randomisation of participants to the trial with a planned rate of 22 participants randomised per month. The study also aimed to establish the feasibility of follow-up at 6 months, with an aim of retaining more than 80% of participants. Data, including patient-reported measures, were collected at baseline and the end of the 6-month follow-up period, and a notes review was completed at 24 months. RESULTS: The trial took place between 26 November 2018 and 30 September 2019. In total 209 participants were randomly allocated to intervention (n = 103) or usual care (n = 106). The maximum rate of monthly recruitment to the trial was 60-80 participants per month. In total, 12,734 messages were sent to participants. Of these messages, 47 were identified as having failed to be sent by the service provider. Participants sent 2,864 messages to the automated messaging system. Baseline data from medical records were available for > 90% of participants with the exception of cholesterol (78.9%). At 6 months, a further HbA1c measurement was reported for 67% of participants. In total medical record data were available at 6 months for 207 (99.0%) of participants and completed self-report data were available for 177 (84.7%) of participants. CONCLUSION: The feasibility of a large-scale randomised evaluation of brief message intervention for people with type 2 diabetes appears to be high using this efficient design. Failure rate of sending messages is low, rapid recruitment was achieved among people with type 2 diabetes, clinical data is available on participants from routine medical records and self-report of economic measures was acceptable. TRIAL REGISTRATION: ISCTRN ISRCTN13404264. Registered on 10 October 2018.

Health and illness beliefs in adults with tuberculosis infection during the COVID-19 pandemic in the UK.

Background: COVID-19 disrupted the TB prevention programme in the UK, especially for TB infection (TBI) care. We explore whether experience of the COVID-19 pandemic impacted on patients' perceptions of TBI and its treatment. Methods: Semi-structured interviews were conducted as part of the Research to Improve Detection and Treatment of TBI (RID-TB) programme, exploring perceptual and practical barriers to TBI treatment. Nineteen people diagnosed with TBI were interviewed between August 2020 and April 2021. Recordings were transcribed and analysed using a constant comparative approach, allowing for a dynamic and iterative exploration of themes. Themes are organised using the Perceptions and Practicalities Approach. Findings: Some participants perceived TBI as a risk factor for increased susceptibility to COVID-19, while some thought that treatment for TBI might protect against COVID-19 or mitigate its effects. Adaptations to TB services (e.g., remote follow-up) and integrated practices during the COVID-19 restrictions (e.g., medication being posted) addressed some practical barriers to TBI treatment. However, we identified beliefs about TBI and COVID-19 that are likely to act as barriers to engagement with TBI treatment, including: interpreting service delays as an indication of TBI not being serious enough for treatment and concerns about contracting COVID-19 in TB clinics. Interpretation: COVID-19 and TBI service delays influence people's perceptions and practical barriers to TBI treatment adherence. Failure to address these beliefs may lead to people's concerns about their treatment not being fully addressed. Utilised service adaptations like remote consultations to address practical barriers may be relevant beyond COVID-19. Funding: NIHR RID-TB Program (RP-PG-0217-20009).