Johan L Severens

Introduction: Immunocompromised individuals have suboptimal COVID-19 vaccine responses and may continue physically distancing to avoid COVID-19. The EAGLE Study aimed to quantify physical distancing behaviours and associations with health-related quality of life (HRQoL) and related measures in immunocompromised adults. Methods: EAGLE was a cross-sectional, observational online survey study of US and UK immunocompromised adults, children and those children’s caregivers, with adult analyses reported here. Multichannel enrolment and self-reported data collection occurred from December 2022 to June 2023. Immunocompromising diagnosis confirmation using medical records was requested from a randomly selected subset. Physical distancing (in past 4 weeks) was measured using the Physical Distancing Scale for COVID-19 Avoidance (PDS-C19). HRQoL and related measures were the 12-item Short Form Health Survey version 2 (SF-12v2) (includes Short-Form 6-Dimensions), Quality of Life Disease Impact Scale-7-item (QDIS-7), Direct Measure of Loneliness, EQ-5D-5L, Hospital Anxiety and Depression Scale and Work Productivity and Activity Impairment plus Classroom Impairment Questions: Specific Health Problem (WPAI+CIQ:SHP). Associations between PDS-C19 and HRQoL and related measures were assessed using Pearson correlation, linear regression (potential confounders-adjusted) and preliminary structural equation modelling (SEM). Results: 2320 immunocompromised adults fully completed the survey. Confirmation of diagnosis was requested from 27% and confirmed for 90% of responders. 68% of participants reported moderate to high physical distancing. Physical distancing had low correlations with SF-12v2-measured HRQoL domains (range |r|=0.18 to 0.39) and medium correlations with QDIS-7 (r=0.78) and WPAI+CIQ:SHP-measured activity impairment (r=0.68) and presenteeism (r=0.51). In SEM, direct PDS-C19 relationships explained most activity correlations: QDIS, β=0.46 (SE=0.02); activity impairment, β=0.40 (0.02); presenteeism, β=0.29 (0.04). Unstandardised PDS-C19 confounder-adjusted linear regression coefficients were similar to those of SEM. Conclusions: Over 3 years after COVID-19 emergence, a disproportionate number of immunocompromised adults reported substantially physically distancing to avoid COVID-19. Higher physical distancing intensities were associated with greater HRQoL impairments, suggesting such challenges coexist as ongoing concerns for immunocompromised adults.

Background: Immunocompromised individuals are known to respond inadequately to SARS-CoV-2 vaccines, placing them at high risk of severe or fatal COVID-19. Thus, immunocompromised individuals and their caregivers may still practice varying degrees of social or physical distancing to avoid COVID-19. However, the association between physical distancing to avoid COVID-19 and quality of life has not been comprehensively evaluated in any study. Objective: We aim to measure physical distancing behaviors among immunocompromised individuals and the association between those behaviors and person-centric outcomes, including health-related quality of life (HRQoL) measures, health state utilities, anxiety and depression, and work and school productivity impairment. Methods: A patient-informed protocol was developed to conduct the EAGLE Study, a large cross-sectional, observational study, and this paper describes that protocol. EAGLE is designed to measure distancing behaviors and outcomes in immunocompromised individuals, including children (aged ≥6 mo) and their caregivers, and nonimmunocompromised adults in the United States and United Kingdom who report no receipt of passive immunization against COVID-19. We previously developed a novel self- and observer-reported instrument, the Physical Distancing Scale for COVID-19 Avoidance (PDS-C19), to measure physical distancing behavior levels cross-sectionally and retrospectively. Using an interim or a randomly selected subset of the study population, the PDS-C19 psychometric properties will be assessed, including structural validity, internal consistency, known-group validity, and convergent validity. Associations (correlations) will be assessed between the PDS-C19 and validated HRQoL-related measures and utilities. Structural equation modeling and regression will be used to assess these associations, adjusting for potential confounders. Participant recruitment and data collection took place from December 2022 to June 2023 using direct-to-patient channels, including panels, clinician referral, patient advocacy groups, and social media, with immunocompromising diagnosis confirmation collected and assessed for a randomly selected 25% of immunocompromised participants. The planned total sample size is 3718 participants and participant-caregiver pairs. Results will be reported by immunocompromised status, immunocompromising condition category, country, age group, and other subgroups. Results: All data analyses and reporting were planned to be completed by December 2023. Results are planned to be submitted for publication in peer-reviewed journals in 2024-2025. Conclusions: This study will quantify immunocompromised individuals’ physical distancing behaviors to avoid COVID-19 and their association with HRQoL as well as health state utilities. International Registered Report Identifier (IRRID): RR1-10.2196/52643

BACKGROUND Immunocompromised individuals are known to respond inadequately to SARS-CoV-2 vaccines, placing them at high risk of severe or fatal COVID-19. Thus, immunocompromised individuals and their caregivers may still practice varying degrees of social or physical distancing to avoid COVID-19. However, the association between physical distancing to avoid COVID-19 and quality of life has not been comprehensively evaluated in any study. OBJECTIVE We aim to measure physical distancing behaviors among immunocompromised individuals and the association between those behaviors and person-centric outcomes, including health-related quality of life (HRQoL) measures, health state utilities, anxiety and depression, and work and school productivity impairment. METHODS A patient-informed protocol was developed to conduct the EAGLE Study, a large cross-sectional, observational study, and this paper describes that protocol. EAGLE is designed to measure distancing behaviors and outcomes in immunocompromised individuals, including children (aged ≥6 mo) and their caregivers, and nonimmunocompromised adults in the United States and United Kingdom who report no receipt of passive immunization against COVID-19. We previously developed a novel self- and observer-reported instrument, the Physical Distancing Scale for COVID-19 Avoidance (PDS-C19), to measure physical distancing behavior levels cross-sectionally and retrospectively. Using an interim or a randomly selected subset of the study population, the PDS-C19 psychometric properties will be assessed, including structural validity, internal consistency, known-group validity, and convergent validity. Associations (correlations) will be assessed between the PDS-C19 and validated HRQoL-related measures and utilities. Structural equation modeling and regression will be used to assess these associations, adjusting for potential confounders. Participant recruitment and data collection took place from December 2022 to June 2023 using direct-to-patient channels, including panels, clinician referral, patient advocacy groups, and social media, with immunocompromising diagnosis confirmation collected and assessed for a randomly selected 25% of immunocompromised participants. The planned total sample size is 3718 participants and participant-caregiver pairs. Results will be reported by immunocompromised status, immunocompromising condition category, country, age group, and other subgroups. RESULTS All data analyses and reporting were planned to be completed by December 2023. Results are planned to be submitted for publication in peer-reviewed journals in 2024-2025. CONCLUSIONS This study will quantify immunocompromised individuals’ physical distancing behaviors to avoid COVID-19 and their association with HRQoL as well as health state utilities. INTERNATIONAL REGISTERED REPORT RR1-10.2196/52643

Objective: To assess the determinants of the participation rate in breast cancer screening programs by conducting a systematic review of reviews. Methods: We conducted a systematic search in PubMed via Medline, Scopus, Embase, and Cochrane identifying the literature up to April 2019. Out of 2258 revealed unique abstracts, we included 31 reviews, from which 25 were considered as systematic. We applied the Walsh & McPhee Systems Model of Clinical Preventive Care to systematize the determinants of screening participation. Results: The reviews, mainly in high-income settings, reported a wide range for breast cancer screening participation rate: 16–90%. The determinants of breast cancer screening participation were simple low-cost interventions such as invitation letters, basic information on screening, multiple reminders, fixed appointments, prompts from healthcare professionals, and healthcare organizational factors (e.g. close proximity to screening facility). More complex interventions (such as face-to-face counselling or home visits), mass media or improved access to transport should not be encouraged by policy makers unless other information appears. The repeated participation in mammography screening was consistently high, above 62%. Previous positive experience with screening influenced the repeated participation in screening programs. The reviews were inconsistent in the use of terminology related to breast cancer screening participation, which may have contributed to the heterogeneity in the reported outcomes. Conclusions: This study shows that consistent findings of systematic reviews bring more certainty into the conclusions on the effects of simple invitation techniques, fixed appointments and prompts, as well as healthcare organizational factors on promoting participation rate in screening mammography.

Disutility allows to identify how much population values intervention-related harms contributing to knowledge on the benefits/harms ratio of cancer screening programs. This systematic review evaluates disutility related to cancer screening applying a utility theory framework. Using a predefined protocol, Embase, Medline Ovid, Web of Science, Cochrane, Google scholar and supplementary sources were systematically searched. The framework grouped disutilities associated with breast, cervical, lung, colorectal, and prostate cancer screening programs into the screening, diagnostic work up, and treatment phases. We assessed the quality of included studies according to the relevance to target population, risk of bias, appropriateness of measure and the time frame. Out of 2840 hits, we included 38 studies, of which 27 measured (and others estimated) disutilities. Around 70% of studies had medium to high-level quality. Measured disutilities and Quality Adjusted Life Years loss were 0–0.03 and 0–0.0013 respectively in screening phases. Both disutilities and Quality Adjusted Life Years loss had similar ranges in diagnostic work up (0–0.26), and treatment (0.09–0.27) phases. We found no measured disutilities available for lung cancer screening and—little evidence for disutilities in treatment phase. Almost 40% of the estimated disutility values were above the range of measured ones. Cancer screening programs led to low disutities related to screening phase, and low to moderate disutilities related to diagnostic work up and treatment phases. These disutility values varied by the measurement instrument applied, and were higher in studies with lower quality. The estimated disutility values comparing to the measured ones tended to overestimate the harms.

Background: Routine magnetic resonance (MR) imaging for local staging of prostate cancer is controversial, due to moderate staging performance. However, MR imaging may be beneficial in a subgroup of patients with clinically localized prostate cancer. Objective: To define the patient group in which local staging of prostate cancer using MR imaging is useful for treatment outcome. Methods: We used a decision analytic model based on data found in the literature to define the patient subgroup which may benefit from local staging with MR imaging. We applied the threshold approach to calculate the threshold where direct surgery and surgery after MR imaging (surgery–MR imaging threshold) result in equal utility. Additionally, we calculated the threshold where direct radiation and radiation after MR imaging (MR imaging–radiotherapy threshold) result in equal utility. Results: We found that the surgery–MR imaging threshold was at a probability of 45% of having stage ≧T₃ disease. The MR imaging–radiotherapy threshold was at a prior probability of 81% of having stage ≧T₃ disease. Conclusions: The application of the threshold approach indicated that MR imaging should be limited to patients with an intermediate–high risk of having stage T₃ disease.