First SARS-CoV-2 Omicron infection as an effective immune booster among mRNA vaccinated individuals: final results from the first phase of the PRIBIVAC randomised clinical trial.

BACKGROUND: Understanding how SARS-CoV-2 breakthrough infections impacts the breadth of immune responses against existing and pre-emergent SARS-CoV-2 strains is needed to develop an evidence-based long-term immunisation strategy. METHODS: We performed a randomised, controlled trial to assess the immunogenicity of homologous (BNT162b2) versus heterologous (mRNA-1273) booster vaccination in 100 BNT162b2-vaccinated infection-naïve individuals enrolled from October 2021. Post hoc analysis was performed to assess the impact of SARS-CoV-2 infection on humoral and cellular immune responses against wild-type SARS-CoV-2 and/or Omicron subvariants. FINDINGS: 93 participants completed the study at day 360. 71% (66/93) of participants reported first SARS-CoV-2 Omicron infection by the end of the study with similar proportions of infections between homologous and heterologous booster groups (72.3% [34/47] vs 69.6% [32/46]; p = 0.82). Mean wildtype SARS-CoV-2 anti-S-RBD antibody level was significantly higher in heterologous booster group compared with homologous group at day 180 (14,588 IU/mL; 95% CI, 10,186-20,893 vs 7447 IU/mL; 4646-11,912; p = 0.025). Participants who experienced breakthrough infections during the Omicron BA.1/2 wave had significantly higher anti-S-RBD antibody levels against wildtype SARS-CoV-2 and antibody neutralisation against BA.1 and pre-emergent BA.5 compared with infection-naïve participants. Regardless of hybrid immunity status, wildtype SARS-CoV-2 anti-S-RBD antibody level declined significantly after six months post-booster or post-SARS-CoV-2 infection. INTERPRETATION: Booster vaccination with mRNA-1273 was associated with significantly higher antibody levels compared with BNT162b2. Antibody responses are narrower and decline faster among uninfected, vaccinated individuals. Boosters may be more effective if administered shortly before infection outbreaks and at least six months after last infection or booster. FUNDING: Singapore NMRC, USFDA, MRC.

Laborie Optilume® Drug-coated balloon may lower the re-treatment rate post-intervention for challenging urethral stricture disease in long-term follow-up: A prospective cohort study.

BACKGROUND: Urethral stricture disease is a common and at times unsatisfying condition that can lead to complications severely impacting a patient's quality of life. Open urethroplasty remains the gold standard treatment; however, it is an invasive and highly specialized procedure. Strictures between 2 to 4 cm in length have been shown to recur at a rate of 50% within 12 months, a rate that typically decreases with each subsequent treatment. The Laborie Optilume drug-coated balloon (DCB) is the first of its kind developed for adjunct treatment of urethral strictures in men. The DCB initially treats the stricture through balloon dilatation and subsequently aims to prevent recurrence via the localized application of Paclitaxel. Our study assesses the safety and efficacy of the DCB in an Australian population with strictures exceeding 2 cm who have undergone at least two prior procedures for urethral stricture disease. METHODS: Patients were prospectively recruited from November 2019 to September 2021. International prostate symptom score (IPSS), IPSS quality of life (QOL) and voiding parameters were collected at baseline, and again at 1, 6, 12 and 18 months. The drug coated balloon was applied by a single consultant urologist under rigid cystoscope with shallow direct vision internal urethrotomy with a cold knife prior to application of the DCB. RESULTS: 17 patients were recruited with an average of 7.7 prior urethral procedures for recurrent stricture disease. 76% were stricture free at 30 months follow-up. There were improvements in almost all parameters including max flow, average flow, IPSS and IPSS QOL scores at 12 and 24 months. There were no complications. CONCLUSION: The DCB is a safe and effective method at reducing the rates of recurrence for high-risk stricture disease and can delay or prevent the need for urethroplasty in what remains a very challenging cohort of patients.

Epidemiology and clinical relevance of persistent bacteraemia in patients with Gram-negative bloodstream infection: a retrospective cohort study.

OBJECTIVES: The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI. METHODS: We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2-5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders. RESULTS: In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29-2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24-1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism. CONCLUSIONS: Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia.

Association between infectious diseases consultation and mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

OBJECTIVES: Data supporting routine infectious diseases (ID) consultation in Gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases. METHODS: Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1-10 days after the first positive blood culture was treated as a time-varying exposure. RESULTS: Of 30,159 patients with GN-BSI across 53 hospitals, 11,013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7-76.1%, interquartile range 19.6-41.1%). 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully-adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted HR 0.82, 95% CI 0.77-0.88, p < 0.0001; translating to absolute risk reduction of -3.8% or NNT of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source). CONCLUSIONS: Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes.

Patient-centred pathology reporting improves patient experience and understanding of disease in prostate cancer care.

Introduction and Objectives: Patient-centred (PC) and holistic care improves patient satisfaction and health outcomes. We sought to investigate the benefit of utilising a PC pathology report in patients undergoing radical prostatectomy (RP) for prostate cancer (PCa). Our study aimed to evaluate and compare patient understanding of their PCa diagnosis after RP, upon receiving either a standard histopathology report or a personalised and PC report (PCR). Moreover, we evaluated knowledge retention at 4 weeks after the initial consultation. Methods: We invited patients undergoing RP at three metropolitan Urology clinics to participate in our randomised controlled study. Patients were randomised to receive either a PCR or standard pathology report. Patient satisfaction questionnaires (Perceived Efficacy in Patient-Physician Interactions [PEPPI], Consultation and Relational Empathy [CARE] and Communication Assessment Tool [CAT]) and a knowledge test were conducted within 72 h of the initial appointment and again at 4 weeks. Accurate recollection of Gleason grade group (GGG) and extracapsular extension (ECE) were classified as 'correct'. Baseline demographic data included age, education, marital and employment status, pre-op prostate specific antigen (PSA) and clinical stage. Baseline data were tested for differences between groups using the Student's t test, chi-squared test or Fisher's exact test depending on whether data were continuous, categorical or sparse. Comparison of correctly answered 'knowledge' questions was analysed using chi-squared test. A significance level of p ≤ 0.05 was used. Results: Data from 62 patients were analysed (30 standard vs. 32 PCR). No significant differences in baseline demographics were found between groups. Both groups reported high levels of satisfaction with their healthcare experiences in all domains of patient-physician rapport, empathy and communication. There were no significant differences between groups in PEPPI (p = 0.68), CAT (p = 0.39) and CARE (p = 0.66) scores, at baseline and 4 weeks. Ninety-three per cent of patients who received the PCR understood the report while 90% felt the report added to their understanding of their PCa. Regarding patient knowledge, the PCR group had significantly more correct answers on GGG and ECE as compared with the standard report group at baseline and 4 weeks (p < 0.001 and 0.001, respectively). Conclusions: Our findings demonstrate that PC pathology reports improve patient knowledge and understanding of their PCa that is retained for at least 4 weeks after initial receipt of results.

Follow-up blood cultures do not reduce mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

OBJECTIVES: The utility of follow-up blood cultures (FUBCs) in patients with Gram-negative bloodstream infection (GN-BSI) is controversial. Observational studies have suggested significant mortality benefit but may be limited by single-centre designs, immortal time bias, and residual confounding. We examined the impact of FUBCs on mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario, Canada. METHODS: Adult patients with GN-BSI hospitalized between April 2017 and December 2021 were included. Primary outcome was all-cause mortality within 30 days. FUBC was treated as a time-varying exposure. Secondary outcomes were 90-day mortality, length of stay, and number of days alive and out of hospital at 30 and 90 days. RESULTS: Thirty-four thousand one hundred patients were included; 8807 (25.8%) patients received FUBC, of which 966 (11.0%) were positive. Median proportion of patients receiving FUBC was 18.8% (interquartile range, 10.0-29.7%; range, 0-66.1%) across 101 hospitals; this correlated with positivity and contamination rate. Eight hundred ninety (10.1%) patients in the FUBC group and 2263 (8.9%) patients in the no FUBC group died within 30 days. In the fully adjusted model, there was no association between FUBC and mortality (hazard ratio, 0.97; 95% CI, 0.90-1.04). Patients with FUBC had significantly longer length of stay (median, 11 vs. 7 days; adjusted risk ratio, 1.18; 95% CI, 1.16-1.21) and fewer number of days alive and out of hospital at 30 and 90 days. DISCUSSION: FUBC collection in patients with GN-BSI varies widely across hospitals and may be associated with prolonged hospitalization without clear survival benefit. Residual confounding may be present given the observational design. Clear benefit should be demonstrated in a randomized trial before widespread adoption of routine FUBC.

Evaluating the impact of a SIMPlified LaYered consent process on recruitment of potential participants to the Staphylococcus aureus Network Adaptive Platform trial: study protocol for a multicentre pragmatic nested randomised clinical trial (SIMPLY-SNAP trial).

INTRODUCTION: Informed consent forms (ICFs) for randomised clinical trials (RCTs) can be onerous and lengthy. The process has the potential to overwhelm patients with information, leading them to miss elements of the study that are critical for an informed decision. Specifically, overly long and complicated ICFs have the potential to increase barriers to trial participation for patients with mild cognitive impairment, those who do not speak English as a first language or among those with lower medical literacy. In turn, this can influence trial recruitment, completion and external validity. METHODS AND ANALYSIS: SIMPLY-SNAP is a pragmatic, multicentre, open-label, two-arm parallel-group superiority RCT, nested within a larger trial, the Staphylococcus aureus Network Adaptive Platform (SNAP) trial. We will randomise potentially eligible participants of the SNAP trial 1:1 to a full-length ICF or a SIMPlified LaYered (SIMPLY) consent process where basic information is summarised with embedded hyperlinks to supplemental information and videos. The primary outcome is recruitment into the SNAP trial. Secondary outcomes include patient understanding of the clinical trial, patient and research staff satisfaction with the consent process, and time taken for consent. As an exploratory outcome, we will also compare measures of diversity (eg, gender, ethnicity), according to the consent process randomised to. The planned sample size will be 346 participants. ETHICS AND DISSEMINATION: The study has been approved by the ethics review board (Sunnybrook Health Sciences Research Ethics Board) at sites in Ontario. We will disseminate study results via the SNAP trial group and other collaborating clinical trial networks. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06168474; www. CLINICALTRIALS: gov).

The CONFIRM trial protocol: the utility of prostate-specific membrane antigen positron emission tomography/computed tomography in active surveillance for prostate cancer.

OBJECTIVES: Primary objectives: To determine the additive value of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the risk stratification of men with newly diagnosed prostate cancer (PCa) who would have otherwise been deemed suitable for active surveillance (AS). Specifically, we aim to determine if PSMA PET/CT can detect a cohort of men on AS that are in fact high risk and likely to experience unfavourable outcomes should they remain on their current treatment pathway. SECONDARY OBJECTIVES: to determine the additive value of PSMA PET/CT to repeat multiparametric magnetic resonance imaging (mpMRI) of the prostate and explore whether a confirmatory biopsy may be avoided in men with a negative PSMA PET/CT and a negative repeat mpMRI of the prostate (Prostate Imaging-Reporting and Data System score of <3). Furthermore, to develop a nomogram combining clinical, imaging and biomarker data to predict the likelihood of failure on AS in men with high-risk features. Also, a blood sample will be taken to perform a Prostate Health Index test at the time of confirmatory biopsy. Furthermore, a portion of this blood will be stored at a biobank for up to 5 years if a follow-up study on molecular biomarkers and genetic assays in this cohort of men is indicated, based on the results from the CONFIRM trial. PATIENTS AND METHODS: The CONFIRM trial is a prospective, multicentre, pre-test/post-test, cohort study across Victoria, Australia, involving men with newly diagnosed low-risk PCa with high-risk features, considered suitable for AS and undergoing confirmatory biopsy. The trial's goal is to provide high-quality evidence to establish whether PSMA PET/CT has a role in risk-stratifying men deemed suitable for AS despite having high-risk feature(s). RESULTS: The CONFIRM trial will measure the proportion of men deemed unsuitable for ongoing AS based on pathological upgrading and multidisciplinary team recommendation due to PSMA PET/CT scan and PSMA-targeted confirmatory biopsy. Additionally, the positive and negative predictive values, sensitivity, and specificity of PSMA PET/CT will be calculated in isolation and combined with repeat mpMRI of the prostate. CONCLUSIONS: This trial will provide robust prospective data to determine if PSMA-PET/CT and standard of care (prostate biopsy ± repeat mpMRI) can improve diagnostic certainty in men undergoing confirmatory biopsy for low-grade PCa with high-risk features.

Variant-specific IgA protects against Omicron infection.

BACKGROUND: The emergence of rapidly evolving SARS-CoV-2 variants, coupled with waning vaccine-induced immunity, has contributed to the rise of vaccine breakthrough infections. It is crucial to understand how vaccine-induced protection is mediated. METHODS: We examined two prospective cohorts of mRNA-vaccinated-and-boosted individuals during the Omicron wave of infection in Singapore. RESULTS: We found that, individuals, who remain uninfected over the follow-up period, had a higher variant-specific IgA, but not IgG, antibody response at 1-month post booster vaccination, compared with individuals who became infected. CONCLUSIONS: We conclude that IgA may have a potential contributory role in protection against Omicron infection.

Comparison of 18F-based PSMA radiotracers with [68Ga]Ga-PSMA-11 in PET/CT imaging of prostate cancer-a systematic review and meta-analysis.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) has become an increasingly established imaging modality in the staging of prostate cancer (PCa). Numerous PSMA-based tracers are currently available, however, there is a lack of consensus on the optimal radiotracer(s) for PSMA PET/CT. This study aims to investigate whether Fluorine-18 (18F)-labelled PSMA PET/CT is significantly different from Gallium-68 (68Ga) in primary diagnosis and/or secondary staging of prostate cancer following biochemical recurrence. METHODS: A critical review of MEDLINE, EMBASE, PubMed and Web of Science databases was performed in May 2023 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Studies that directly compared 18F-based PSMA radiotracers and [68Ga]Ga-PSMA-11 in terms of the normal organ SUV or the lesion SUV or the detection rate were assessed. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). RESULTS: Twenty-four studies were analysed. [18F]DCFPyL and [18F]PSMA-1007 were the two most commonly studied 18F based PSMA tracers. [18F]JK-PSMA-7, [18F]rhPSMA-7, [18F]AlF-PSMA-11 were the new tracers evaluated in a limited number of studies. Overall, [18F]DCFPyL was observed to have a similar lesion detection rate to [68Ga]Ga-PSMA-11 with no increase in false positive rates. [18F]PSMA-1007 was found to have a greater local lesion detection rate because of its predominant hepatobiliary excretory route. However, [68Ga]Ga-PSMA-11 was observed to have a similar local lesion detection rate in studies that administer patients with furosemide prior to the scan. In addition, [18F]PSMA-1007 was found to have a significant number of benign bone uptakes. CONCLUSIONS: [18F]DCFPyL was observed to be similar to [68Ga]Ga-PSMA-11. [18F]PSMA-1007 was observed to be less preferrable to [68Ga]Ga-PSMA-11 due to its high benign bone uptakes. Overall, there was not enough evidence in differentiating the radiotracers based on their clinical impacts.

Are we enrolling the right patients? A scoping review of external validity and generalizability of clinical trials in bloodstream infections.

BACKGROUND: Having a representative population in randomized clinical trials (RCTs) improves external validity and generalizability of trial results. There are limited data examining differences between RCT-enrolled and real-world populations in bloodstream infections (BSI). OBJECTIVES: We conducted a scoping review aiming to review studies assessing generalizability of BSI RCT populations, to identify sub-groups that have been systematically under-represented and to explore approaches to improve external validity of future RCTs. SOURCES: MEDLINE, Embase, and Cochrane Library databases were searched for terms related to external validity or generalizability, BSI, and clinical trials in papers published up to 1 August 2023. Studies comparing enrolled versus nonenrolled patients, or papers discussing external validity or generalizability in the context of BSI RCTs were included. CONTENT: Sixteen papers were included in the final review. Five compared RCT-enrolled and nonenrolled participants from the same source population. There were significant differences between the two groups in all studies, with nonenrolled patients having a greater comorbidity burden and consistently worse outcomes including mortality. We identified several barriers to improving generalizability of RCT populations and outlined potential approaches to reduce these barriers, such as alternative/simplified consent processes, streamlining eligibility criteria and follow-up procedures, quota-based sampling techniques, and ensuring diversity in site and study team selection. IMPLICATIONS: Study cohorts in BSI RCTs are not representative of the general BSI patient population. As we increasingly adopt large pragmatic trials in infectious diseases, it is important to recognize the importance of maximizing generalizability to ensure that our research findings are of direct relevance to our patients.

Evaluating the use of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in the workup of Staphylococcus aureus bacteraemia: a cost-utility analysis.

OBJECTIVES: The use of positron emission tomography/computed tomography (PET/CT) in the evaluation of patients with Staphylococcus aureus bacteraemia can improve the diagnosis of infectious foci and guide clinical management. We aimed to evaluate the cost-utility of PET/CT among adults hospitalized with Staphylococcus aureus bacteraemia. METHODS: A cost-utility analysis was conducted from the healthcare payer perspective using a probabilistic Markov cohort model assessing three diagnostic strategies: (a) PET/CT in all patients, (b) PET/CT in high-risk patients only, and (c) routine diagnostic workup. Primary outcomes were quality-adjusted life years (QALYs), costs in Canadian dollars, and an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analyses were conducted to evaluate parameter uncertainty. RESULTS: Routine workup resulted in an average of 16.64 QALYs from the time of diagnosis at a lifetime cost of $209 060/patient. This was dominated by PET/CT in high-risk patients (i.e. greater effectiveness at lower costs) with average 16.88 QALYs at a cost of $199 552. Compared with PET/CT in high-risk patients only, PET/CT for all patients cost on average $11 960 more but resulted in 0.14 more QALYs, giving an incremental cost-effectiveness ratio of $83 500 (cost per additional QALY gained); however, there was a high degree of uncertainty comparing these two strategies. At a willingness-to-pay threshold of $50 000/QALY, PET/CT in high-risk patients was the most cost-effective strategy in 58.6% of simulations vs. 37.9% for PET/CT in all patients. DISCUSSION: Our findings suggest that a strategy of using PET/CT in high-risk patients is more cost-effective than no PET/CT. Randomized controlled trials should be conducted to evaluate the use of PET/CT in different patient groups.

Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors.

CONTEXT: Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external and internal factors) contribute significantly to the development of BC. Therefore, establishing a clear understanding of these risk factors is the key to prevention. OBJECTIVE: To perform an up-to-date systematic review of BC's epidemiology and external risk factors. EVIDENCE ACQUISITION: Two reviewers (I.J. and S.O.) performed a systematic review using PubMed and Embase in January 2022 and updated it in September 2022. The search was restricted to 4 yr since our previous review in 2018. EVIDENCE SYNTHESIS: Our search identified 5177 articles and a total of 349 full-text manuscripts. GLOBOCAN data from 2020 revealed an incidence of 573 000 new BC cases and 213 000 deaths worldwide in 2020. The 5-yr prevalence worldwide in 2020 was 1 721 000. Tobacco smoking and occupational exposures (aromatic amines and polycyclic aromatic hydrocarbons) are the most substantial risk factors. In addition, correlative evidence exists for several risk factors, including specific dietary factors, imbalanced microbiome, gene-environment risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. CONCLUSIONS: We present a contemporary overview of the epidemiology of BC and the current evidence for BC risk factors. Smoking and specific occupational exposures are the most established risk factors. There is emerging evidence for specific dietary factors, imbalanced microbiome, gene-external risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. Further high-quality evidence is required to confirm initial findings and further understand cancer prevention. PATIENT SUMMARY: Bladder cancer is common, and the most substantial risk factors are smoking and workplace exposure to suspected carcinogens. On-going research to identify avoidable risk factors could reduce the number of people who get bladder cancer.

Unlocking the DOOR-how to design, apply, analyse, and interpret desirability of outcome ranking endpoints in infectious diseases clinical trials.

BACKGROUND: Desirability of outcome ranking (DOOR) outcomes, with or without response adjusted for antibiotic risk (RADAR), are increasingly used in infectious diseases randomized clinical trials (RCTs), with the advantage of being able to combine multiple clinical outcomes and antibiotic duration in a single metric. However, it remains poorly understood, and there is considerable heterogeneity in its use. OBJECTIVES: In this scoping review, we explain how to design, use and analyse a DOOR endpoint, and highlight several pitfalls and potential improvements that can be made to DOOR/RADAR. SOURCES: The Ovid MEDLINE database was searched for terms related to DOOR in English-language articles published up to 31 December 2022. Articles discussing DOOR methodology and/or reporting clinical trial analyses (as either primary, secondary, or post-hoc analysis) using a DOOR outcome were included. CONTENT: Seventeen articles were included in the final review, of which nine reported DOOR analyses of 12 RCTs. Eight articles discussed DOOR methodology. We synthesised information from these articles and discuss (a) how to develop a DOOR scale, (b) how to conduct a DOOR/RADAR analysis, (c) use in clinical trials, (d) use of alternative tiebreakers apart from RADAR, (e) partial credit analyses, and (f) criticisms and pitfalls of DOOR/RADAR. IMPLICATIONS: DOOR is an important innovation for RCTs in infectious diseases. We highlight potential areas of methodological improvement for future research. There remains considerable heterogeneity in its implementation, and further collaborative efforts, with a more diverse range of perspectives, should be made to develop consensus scales for use in prospective studies.

Compliance with face mask use during the COVID-19 pandemic: a community observational study in Singapore.

Introduction: Widespread mask use is an important intervention for control of the coronavirus disease 2019 pandemic. However, data on the factors affecting mask use are lacking. In this observational study, we evaluated the proportion of and factors influencing face mask use and related hygiene practices. Methods: We observed randomly selected members from the public in 367 venues across Singapore, and recorded the proportion of individuals with full compliance with mask use and mask hygiene (hand hygiene before and after touching the mask or face). Logistic regression analyses were used to determine variables associated with mask and hand hygiene compliance. Results: We made 3,821 observations - 2,149 (56.2%) females, 3,569 (93.4%) adults (≥21 years), 212 (5.5%) children (6-20 years) and 40 (1.0%) children (2-5 years). The overall full compliance rate (correct mask use), poor compliance rate (incorrect mask use) and absent mask use were 84.5%, 12.9% and 2.6%, respectively. The factors - male gender, fabric mask usage and crowded indoor venues - were associated with lower mask compliance. Face or mask touching behaviour was observed in 10.7% and 13.7% of individuals observed, respectively. Only one individual performed hand hygiene before and after touching the mask. Conclusion: The rate of mask compliance was high, probably due to legislation mandating mask usage. However, specific factors and crowded indoor venues associated with lower mask compliance were identified. We also noted an issue with the absence of hand hygiene before and after face or mask touching. These issues may benefit from targeted public health messaging.