Enrollment and Retention of Participants in Remote Digital Health Studies: Scoping Review and Framework Proposal

BACKGROUND Digital technologies are increasingly used in health research to collect real-world data from wider populations. A new wave of digital health studies relies primarily on digital technologies to conduct research entirely remotely. Remote digital health studies hold promise to significant cost and time advantages over traditional, in-person studies. However, such studies have been reported to typically suffer from participant attrition, the sources for which are still largely understudied. OBJECTIVE To contribute to future remote digital health study planning, we present a conceptual framework and hypotheses for study enrollment and completion. The framework introduces 3 participation criteria that impact remote digital health study outcomes: (1) participant motivation profile and incentives or nudges, (2) participant task complexity, and (3) scientific requirements. The goal of this study is to inform the planning and implementation of remote digital health studies from a person-centered perspective. METHODS We conducted a scoping review to collect information on participation in remote digital health studies, focusing on methodological aspects that impact participant enrollment and retention. Comprehensive searches were conducted on the PubMed, CINAHL, and Web of Science databases, and additional sources were included in our study from citation searching. We included digital health studies that were fully conducted remotely, included information on at least one of the framework criteria during recruitment, onboarding or retention phases of the studies, and included study enrollment or completion outcomes. Qualitative analyses were performed to synthesize the findings from the included studies. RESULTS We report qualitative findings from 37 included studies that reveal high values of achieved median participant enrollment based on target sample size calculations, 128% (IQR 100%-234%), and median study completion, 48% (IQR 35%-76%). Increased median study completion is observed for studies that provided incentives or nudges to extrinsically motivated participants (62%, IQR 43%-78%). Reducing task complexity for participants in the absence of incentives or nudges did not improve median study enrollment (103%, IQR 102%-370%) or completion (43%, IQR 22%-60%) in observational studies, in comparison to interventional studies that provided more incentives or nudges (median study completion rate of 55%, IQR 38%-79%). Furthermore, there were inconsistencies in measures of completion across the assessed remote digital health studies, where only around half of the studies with completion measures (14/27, 52%) were based on participant retention throughout the study period. CONCLUSIONS Few studies reported on participatory factors and study outcomes in a consistent manner, which may have limited the evidence base for our study. Our assessment may also have suffered from publication bias or unrepresentative study samples due to an observed preference for participants with digital literacy skills in digital health studies. Nevertheless, we find that future remote digital health study planning can benefit from targeting specific participant profiles, providing incentives and nudges, and reducing study complexity to improve study outcomes

Frequency-based rare diagnoses as a novel and accessible approach for studying rare diseases in large datasets: a cross-sectional study

BACKGROUND Up to 8% of the general population have a rare disease, however, for lack of ICD-10 codes for many rare diseases, this population cannot be generically identified in large medical datasets. We aimed to explore frequency-based rare diagnoses (FB-RDx) as a novel method exploring rare diseases by comparing characteristics and outcomes of inpatient populations with FB-RDx to those with rare diseases based on a previously published reference list. METHODS Retrospective, cross-sectional, nationwide, multicenter study including 830,114 adult inpatients. We used the national inpatient cohort dataset of the year 2018 provided by the Swiss Federal Statistical Office, which routinely collects data from all inpatients treated in any Swiss hospital. Exposure: FB-RDx, according to 10% of inpatients with the least frequent diagnoses (i.e.1.decile) vs. those with more frequent diagnoses (deciles 2-10). Results were compared to patients having 1 of 628 ICD-10 coded rare diseases. PRIMARY OUTCOME In-hospital death. SECONDARY OUTCOMES 30-day readmission, admission to intensive care unit (ICU), length of stay, and ICU length of stay. Multivariable regression analyzed associations of FB-RDx and rare diseases with these outcomes. RESULTS 464,968 (56%) of patients were female, median age was 59 years (IQR: 40-74). Compared with patients in deciles 2-10, patients in the 1. were at increased risk of in-hospital death (OR 1.44; 95% CI: 1.38, 1.50), 30-day readmission (OR 1.29; 95% CI 1.25, 1.34), ICU admission (OR 1.50; 95% CI 1.46, 1.54), increased length of stay (Exp(B) 1.03; 95% CI 1.03, 1.04) and ICU length of stay (1.15; 95% CI 1.12, 1.18). ICD-10 based rare diseases groups showed similar results: in-hospital death (OR 1.82; 95% CI 1.75, 1.89), 30-day readmission (OR 1.37; 95% CI 1.32, 1.42), ICU admission (OR 1.40; 95% CI 1.36, 1.44) and increased length of stay (OR 1.07; 95% CI 1.07, 1.08) and ICU length of stay (OR 1.19; 95% CI 1.16, 1.22). CONCLUSION(S) This study suggests that FB-RDx may not only act as a surrogate for rare diseases but may also help to identify patients with rare disease more comprehensively. FB-RDx associate with in-hospital death, 30-day readmission, intensive care unit admission, and increased length of stay and intensive care unit length of stay, as has been reported for rare diseases

Health and social behaviour through pandemic phases in Switzerland : regional time-trends of the COVID-19 Social Monitor panel study

Background Switzerland has a liberal implementation of Coronavirus mitigation measures compared to other European countries. Since March 2020, measures have been evolving and include a mixture of central and federalistic mitigation strategies across three culturally diverse language regions. The present study investigates a hypothesised heterogeneity in health, social behavior and adherence to mitigation measures across the language regions by studying pre-specified interaction effects. Our findings aim to support the communication of regionally targeted mitigation strategies and to provide evidence to address longterm population-health consequences of the pandemic by accounting for different pandemic contexts and cultural aspects. Methods We use data from from the COVID-19 Social Monitor, a longitudinal population-based online survey. We define five mitigation periods between March 2020 and May 2021. We use unadjusted and adjusted logistic regression models to investigate a hypothesized interaction effect between mitigation periods and language regions on selected study outcomes covering the domains of general health and quality of life, mental health, loneliness/isolation, physical activity, health care use and adherence to mitigation measures. Results We analyze 2,163 (64%) participants from the German/Romansh-speaking part of Switzerland, 713 (21%) from the French-speaking part and 505 (15%) from the Italian-speaking part. We found evidence for an interaction effect between mitigation periods and language regions for adherence to mitigation measures, but not for other study outcomes (social behavior, health). The presence of poor quality of life, lack of energy, no physical activity, health care use, and the adherence to mitigation measures changed similarly over mitigation periods in all language regions. Discussion As the pandemic unfolded in Switzerland, also health and social behavior changed between March 2020 to May 2021. Changes in adherence to mitigation measures differ between language regions and reflect the COVID-19 incidence patterns in the investigated mitigation periods, with higher adherence in regions with previously higher incidence. Targeted communcation of mitigation measures and policy making should include cultural, geographical and socioeconomic aspects to address yet unknown long-term population health consequences caused by the pandemic

Swiss chiropractic practice-based research network and musculoskeletal pain cohort pilot study: protocol of a nationwide resource to advance musculoskeletal health services research

INTRODUCTION Musculoskeletal (MSK) pain conditions, a leading cause of global disability, are usually first managed in primary care settings such as medical, physiotherapy, and chiropractic community-based practices. While chiropractors often treat MSK conditions, there is limited real-world evidence on the topic of health service outcomes among patients receiving this type of care. A nationwide Swiss chiropractic practice-based research network (PBRN) and MSK pain patient cohort study will have potential to monitor the epidemiological trends of MSK pain conditions and contribute to healthcare quality improvement. The primary aims of this protocol are to (1) describe the development of an MSK-focused PBRN within the Swiss chiropractic setting, and (2) describe the methodology of the first nested study to be conducted within the PBRN-an observational prospective patient cohort pilot study. METHODS AND ANALYSIS This initiative is conceptualised with two distinct phases. Phase I focuses on the development of the Swiss chiropractic PBRN, and will use a cross-sectional design to collect information from chiropractic clinicians nationwide. Phase II will recruit consecutive patients aged 18 years or older with MSK pain from community-based chiropractic practices participating in the PBRN into a prospective chiropractic cohort pilot study. All data collection will occur through electronic surveys offered in the three Swiss official languages (German, French, Italian) and English. Surveys will be provided to patients prior to their initial consultation in clinics, 1 hour after initial consultation, and at 2, 6 and 12 weeks after initial consultation. ETHICS AND DISSEMINATION Ethics approval has been obtained from the independent research ethics committee of Canton Zurich (BASEC-Nr: 2021-01479). Informed consent will be obtained electronically from all participants. Findings will be reported to stakeholders after each study phase, presented at local and international conferences, and disseminated through peer-reviewed publications. STUDY PRE-REGISTRATION Phase I-Swiss chiropractic PBRN (ClinicalTrials.gov identifier: NCT05046249); Phase 2-Swiss chiropractic cohort (Swiss ChiCo) pilot study (ClinicalTrials.gov identifier: NCT05116020)

The Swiss chiropractic practice-based research network: a population-based cross-sectional study to inform future musculoskeletal research

The Swiss chiropractic practice-based research network (PBRN) is a nationwide project developed in collaboration with patients, clinicians, and academic stakeholders to advance musculoskeletal epidemiologic research. The aim of this study was to describe the clinician population recruited and representativeness of this PBRN to inform future collaboration. A population-based cross-sectional study was performed. PBRN clinician characteristics were described and factors related to motivation (operationalised as VAS score ≥ 70) to participate in a subsequent patient cohort pilot study were assessed. Among 326 eligible chiropractors, 152 enrolled in the PBRN (47% participation). The PBRN was representative of the larger Swiss chiropractic population with regards to age, language, and geographic distribution. Of those enrolled, 39% were motivated to participate in a nested patient cohort pilot study. Motivation was associated with age 40 years or older versus 39 years or younger (OR 2.3, 95% CI 1.0-5.2), and with a moderate clinic size (OR 2.4, 95% CI 1.1-5.7) or large clinic size (OR 2.8, 95% CI 1.0-7.8) versus solo practice. The Swiss chiropractic PBRN has enrolled almost half of all Swiss chiropractors and has potential to facilitate collaborative practice-based research to improve musculoskeletal health care quality.Trial registration: Swiss chiropractic PBRN (ClinicalTrials.gov identifier: NCT05046249); Swiss chiropractic cohort (Swiss ChiCo) pilot study (ClinicalTrials.gov identifier: NCT05116020)

Methodological heterogeneity biases physical activity metrics derived from the Actigraph GT3X in multiple sclerosis: A rapid review and comparative study

BACKGROUND Physical activity (PA) is reduced in persons with multiple sclerosis (MS), though it is known to aid in symptom and fatigue management. Methods for measuring PA are diverse and the impact of this heterogeneity on study outcomes is unclear. We aimed to clarify this impact by comparing common methods for deriving PA metrics in MS populations. METHODS First, a rapid review of existing literature identified methods for calculating PA in studies which used the Actigraph GT3X in populations with MS. We then compared methods in a prospective study on 42 persons with MS [EDSS 4.5 (3.5-6)] during a voluntary course of inpatient neurorehabilitation. Mixed-effects linear regression identified methodological factors which influenced PA measurements. Non-parametric hypothesis tests, correlations, and agreement statistics assessed overall and pairwise differences between methods. RESULTS In the rapid review, searches identified 421 unique records. Sixty-nine records representing 51 eligible studies exhibited substantial heterogeneity in methodology and reporting practices. In a subsequent comparative study, multiple methods for deriving six PA metrics (step count, activity counts, total time in PA, sedentary time, time in light PA, time in moderate to vigorous PA), were identified and directly compared. All metrics were sensitive to methodological factors such as the selected preprocessing filter, data source (vertical vs. vector magnitude counts), and cutpoint. Additionally, sedentary time was sensitive to wear time definitions. Pairwise correlation and agreement between methods varied from weak (minimum correlation: 0.15, minimum agreement: 0.03) to perfect (maximum correlation: 1.00, maximum agreement: 1.00). Methodological factors biased both point estimates of PA and correlations between PA and clinical assessments. CONCLUSIONS Methodological heterogeneity of existing literature is high, and this heterogeneity may confound studies which use the Actigraph GT3X. Step counts were highly sensitive to the filter used to process raw accelerometer data. Sedentary time was particularly sensitive to methodology, and we recommend using total time in PA instead. Several, though not all, methods for deriving light PA and moderate to vigorous PA yielded nearly identical results. PA metrics based on vertical axis counts tended to outperform those based on vector magnitude counts. Additional research is needed to establish the relative validity of existing methods

Differences in COVID-19 vaccination uptake in the first 12 months of vaccine availability in Switzerland : a prospective cohort study

Widespread vaccination uptake has been shown to be crucial in controlling the COVID-19 pandemic and its consequences on healthcare infrastructures. Infection numbers, hospitalisation rates and mortality can be mitigated if large parts of the population are being vaccinated. However, one year after the introduction of COVID-19 vaccines, a substantial share of the Swiss population still refrains from being vaccinated

Factors associated with material deprivation in persons with multiple sclerosis in Switzerland: Cross-sectional data from the Swiss Multiple Sclerosis Registry.

BACKGROUND Multiple sclerosis (MS) impacts education, future career pathways and working capability and therefore may negatively impact the financial situation of persons with MS (pwMS) in Switzerland. We therefore investigated the financial situation and its influencing sociodemographic and disease-specific factors of pwMS compared to the general Swiss population with focus on material deprivation (MD). METHODS Data on the financial situation of pwMS were collected via a specific questionnaire added to the regular, semi-annual follow-up assessments of the Swiss Multiple Sclerosis Registry. Questions were taken in an unmodified format from the standardized "Statistics on Income and Living Conditions" (SILC) questionnaire 2019 of the Federal Statistical Office of Switzerland which evaluates the financial situation of the general Swiss population, enabling a direct comparison of pwMS with the general Swiss population. RESULTS PwMS were 1.5 times more frequently affected by MD than the general Swiss population (6.3% of pwMS versus 4.2% of the general Swiss population) which was confirmed in a multivariable logistic regression analysis of pooled SILC and Swiss Multiple Sclerosis Registry (SMSR) data. High symptom burden, having only mandatory schooling, well as having a pending disability insurance application (as opposed to no application or receiving benefits) were associated with a higher odds of MD whereas higher education, older age, having a Swiss citizenship, living with a spouse or a partner or being currently employed were independently associated with a lower odds of MD. CONCLUSION MS has a negative impact on the financial situation and is associated with MD. PwMS with a high symptom burden at the transition from work force to receiving disability benefits appeared to be vulnerable for MD. Higher education, older age, having a Swiss citizenship, living with a spouse or a partner or being currently employed were independently associated with a lower odds of MD

Biphasic decay kinetics suggest progressive slowing in turnover of latently HIV-1 infected cells during antiretroviral therapy

BACKGROUND: Mathematical models based on kinetics of HIV-1 plasma viremia after initiation of combination antiretroviral therapy (cART) inferred HIV-infected cells to decay exponentially with constant rates correlated to their strength of virus production. To further define in vivo decay kinetics of HIV-1 infected cells experimentally, we assessed infected cell-classes of distinct viral transcriptional activity in peripheral blood mononuclear cells (PBMC) of five patients during 1 year after initiation of cART RESULTS: In a novel analytical approach patient-matched PCR for unspliced and multiply spliced viral RNAs was combined with limiting dilution analysis at the single cell level. This revealed that HIV-RNA+ PBMC can be stratified into four distinct viral transcriptional classes. Two overlapping cell-classes of high viral transcriptional activity, suggestive of a virion producing phenotype, rapidly declined to undetectable levels. Two cell classes expressing HIV-RNA at low and intermediate levels, presumably insufficient for virus production and occurring at frequencies exceeding those of productively infected cells matched definitions of HIV-latency. These cells persisted during cART. Nevertheless, during the first four weeks of therapy their kinetics resembled that of productively infected cells. CONCLUSIONS: We have observed biphasic decays of latently HIV-infected cells of low and intermediate viral transcriptional activity with marked decreases in cell numbers shortly after initiation of therapy and complete persistence in later phases. A similar decay pattern was shared by cells with greatly enhanced viral transcriptional activity which showed a certain grade of levelling off before their disappearance. Thus it is conceivable that turnover/decay rates of HIV-infected PBMC may be intrinsically variable. In particular they might be accelerated by HIV-induced activation and reactivation of the viral life cycle and slowed down by the disappearance of such feedback-loops after initiation of cART