Longitudinal Assessment of Seasonal Impacts and Depression Associations on Circadian Rhythm Using Multimodal Wearable Sensing: Retrospective Analysis.

BACKGROUND: Previous mobile health (mHealth) studies have revealed significant links between depression and circadian rhythm features measured via wearables. However, the comprehensive impact of seasonal variations was not fully considered in these studies, potentially biasing interpretations in real-world settings. OBJECTIVE: This study aims to explore the associations between depression severity and wearable-measured circadian rhythms while accounting for seasonal impacts. METHODS: Data were sourced from a large longitudinal mHealth study, wherein participants' depression severity was assessed biweekly using the 8-item Patient Health Questionnaire (PHQ-8), and participants' behaviors, including sleep, step count, and heart rate (HR), were tracked via Fitbit devices for up to 2 years. We extracted 12 circadian rhythm features from the 14-day Fitbit data preceding each PHQ-8 assessment, including cosinor variables, such as HR peak timing (HR acrophase), and nonparametric features, such as the onset of the most active continuous 10-hour period (M10 onset). To investigate the association between depression severity and circadian rhythms while also assessing the seasonal impacts, we used three nested linear mixed-effects models for each circadian rhythm feature: (1) incorporating the PHQ-8 score as an independent variable, (2) adding seasonality, and (3) adding an interaction term between season and the PHQ-8 score. RESULTS: Analyzing 10,018 PHQ-8 records alongside Fitbit data from 543 participants (n=414, 76.2% female; median age 48, IQR 32-58 years), we found that after adjusting for seasonal effects, higher PHQ-8 scores were associated with reduced daily steps (ß=-93.61, P<.001), increased sleep variability (ß=0.96, P<.001), and delayed circadian rhythms (ie, sleep onset: ß=0.55, P=.001; sleep offset: ß=1.12, P<.001; M10 onset: ß=0.73, P=.003; HR acrophase: ß=0.71, P=.001). Notably, the negative association with daily steps was more pronounced in spring (ß of PHQ-8 × spring = -31.51, P=.002) and summer (ß of PHQ-8 × summer = -42.61, P<.001) compared with winter. Additionally, the significant correlation with delayed M10 onset was observed solely in summer (ß of PHQ-8 × summer = 1.06, P=.008). Moreover, compared with winter, participants experienced a shorter sleep duration by 16.6 minutes, an increase in daily steps by 394.5, a delay in M10 onset by 20.5 minutes, and a delay in HR peak time by 67.9 minutes during summer. CONCLUSIONS: Our findings highlight significant seasonal influences on human circadian rhythms and their associations with depression, underscoring the importance of considering seasonal variations in mHealth research for real-world applications. This study also indicates the potential of wearable-measured circadian rhythms as digital biomarkers for depression.

Barriers, opportunities, and potential costs of expanding HIV support services.

Experiencing housing instability, food insecurity, and financial stress can negatively impact retention in care and treatment adherence for people living with HIV. Expanding services that support socioeconomic needs could help improve HIV outcomes. Our objective was to investigate barriers, opportunities, and costs of expanding socioeconomic support programs. Semi-structured interviews were conducted with organizations serving U.S. Ryan White HIV/AIDS Program clients. Costs were estimated from interviews, organization documents, and city-specific wages. Organizations reported complex patient, organization, program, and system challenges as well as several opportunities for expansion. The average one-year per-person cost for engaging new clients was $196 for transportation, $612 for financial aid, $650 for food aid, and $2498 for short-term housing (2020 USD). Understanding potential expansion costs is important for funders and local stakeholders. This study provides a sense of magnitude for costs to scale-up programs to better meet socioeconomic needs of low-income patients living with HIV.

Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.

BACKGROUND: Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features. OBJECTIVE: We aimed to address these 3 challenges to inform future work in stratified analyses. METHODS: Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model. RESULTS: We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression. CONCLUSIONS: This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.

Remote Assessment of Disease and Relapse in Major Depressive Disorder (RADAR-MDD): recruitment, retention, and data availability in a longitudinal remote measurement study.

BACKGROUND: Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks. A key question for the field is the extent to which participants can adhere to research protocols and the completeness of data collected. We aimed to describe drop out and data completeness in a naturalistic multimodal longitudinal RMT study, in people with a history of recurrent MDD. We further aimed to determine whether those experiencing a depressive relapse at baseline contributed less complete data. METHODS: Remote Assessment of Disease and Relapse - Major Depressive Disorder (RADAR-MDD) is a multi-centre, prospective observational cohort study conducted as part of the Remote Assessment of Disease and Relapse - Central Nervous System (RADAR-CNS) program. People with a history of MDD were provided with a wrist-worn wearable device, and smartphone apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks, and cognitive assessments. Participants were followed-up for a minimum of 11 months and maximum of 24 months. RESULTS: Individuals with a history of MDD (n = 623) were enrolled in the study,. We report 80% completion rates for primary outcome assessments across all follow-up timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. In total, 110 participants had > 50% data available across all data types. CONCLUSIONS: RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible. We found comparable levels of data availability in active and passive forms of data collection, demonstrating that both are feasible in this patient group.

Investigating the impact of COVID-19 lockdown on adults with a recent history of recurrent major depressive disorder: a multi-Centre study using remote measurement technology.

BACKGROUND: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes a clinical illness Covid-19, has had a major impact on mental health globally. Those diagnosed with major depressive disorder (MDD) may be negatively impacted by the global pandemic due to social isolation, feelings of loneliness or lack of access to care. This study seeks to assess the impact of the 1st lockdown - pre-, during and post - in adults with a recent history of MDD across multiple centres. METHODS: This study is a secondary analysis of an on-going cohort study, RADAR-MDD project, a multi-centre study examining the use of remote measurement technology (RMT) in monitoring MDD. Self-reported questionnaire and passive data streams were analysed from participants who had joined the project prior to 1st December 2019 and had completed Patient Health and Self-esteem Questionnaires during the pandemic (n = 252). We used mixed models for repeated measures to estimate trajectories of depressive symptoms, self-esteem, and sleep duration. RESULTS: In our sample of 252 participants, 48% (n = 121) had clinically relevant depressive symptoms shortly before the pandemic. For the sample as a whole, we found no evidence that depressive symptoms or self-esteem changed between pre-, during- and post-lockdown. However, we found evidence that mean sleep duration (in minutes) decreased significantly between during- and post- lockdown (- 12.16; 95% CI - 18.39 to - 5.92; p <  0.001). We also found that those experiencing clinically relevant depressive symptoms shortly before the pandemic showed a decrease in depressive symptoms, self-esteem and sleep duration between pre- and during- lockdown (interaction p = 0.047, p = 0.045 and p <  0.001, respectively) as compared to those who were not. CONCLUSIONS: We identified changes in depressive symptoms and sleep duration over the course of lockdown, some of which varied according to whether participants were experiencing clinically relevant depressive symptoms shortly prior to the pandemic. However, the results of this study suggest that those with MDD do not experience a significant worsening in symptoms during the first months of the Covid - 19 pandemic.

Defining a Novel Role for the Coxsackievirus and Adenovirus Receptor in Human Adenovirus Serotype 5 Transduction In Vitro in the Presence of Mouse Serum.

Human adenoviral serotype 5 (HAdV-5) vectors have predominantly hepatic tropism when delivered intravascularly, resulting in immune activation and toxicity. Coagulation factor X (FX) binding to HAdV-5 mediates liver transduction and provides protection from virion neutralization in mice. FX is dispensable for liver transduction in mice lacking IgM antibodies or complement, suggesting that alternative transduction pathways exist. To identify novel factor(s) mediating HAdV-5 FX-independent entry, we investigated HAdV-5 transduction in vitro in the presence of serum from immunocompetent C57BL/6 or immunocompromised mice lacking IgM antibodies (Rag 2-/- and NOD-scid-gamma [NSG]). Sera from all three mouse strains enhanced HAdV-5 transduction of A549 cells. While inhibition of HAdV-5-FX interaction with FX-binding protein (X-bp) inhibited transduction in the presence of C57BL/6 serum, it had negligible effect on the enhanced transduction observed in the presence of Rag 2-/- or NSG serum. Rag 2-/- serum also enhanced transduction of the FX binding-deficient HAdV-5HVR5*HVR7*E451Q (AdT*). Interestingly, Rag 2-/- serum enhanced HAdV-5 transduction in a FX-independent manner in CHO-CAR and SKOV3-CAR cells (CHO or SKOV3 cells transfected to stably express human coxsackievirus and adenovirus receptor [CAR]). Additionally, blockade of CAR with soluble HAdV-5 fiber knob inhibited mouse serum-enhanced transduction in A549 cells, suggesting a potential role for CAR. Transduction of HAdV-5 KO1 and HAdV-5/F35 (CAR binding deficient) in the presence of Rag 2-/- serum was equivalent to that of HAdV-5, indicating that direct interaction between HAdV-5 and CAR is not required. These data suggest that FX may protect HAdV-5 from neutralization but has minimal contribution to HAdV-5 transduction in the presence of immunocompromised mouse serum. Alternatively, transduction occurs via an unidentified mouse serum protein capable of bridging HAdV-5 to CAR.IMPORTANCE The intravascular administration of HAdV-5 vectors can result in acute liver toxicity, transaminitis, thrombocytopenia, and injury to the vascular endothelium, illustrating challenges yet to overcome for HAdV-5-mediated systemic gene therapy. The finding that CAR and potentially an unidentified factor present in mouse serum might be important mediators of HAdV-5 transduction highlights that a better understanding of the complex biology defining the interplay between adenovirus immune recognition and cellular uptake mechanisms is still required. These findings are important to inform future optimization and development of HAdV-5-based adenoviral vectors for gene therapy.

Similar perspectives on prostate cancer screening value and new guidelines across patient demographic and PSA level subgroups: A qualitative study.

BACKGROUND: In 2012, the United States Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA)-based prostate cancer screening for all men. OBJECTIVE: To inform educational materials addressing patient questions and concerns about the 2012 USPSTF guidelines, we sought to: (i) characterize patient perceptions about prostate cancer screening benefits, harms and recommendations against screening, and (ii) compare perceptions across race, age and PSA level subgroups. METHODS: We conducted qualitative interviews with a sample of 26 men from the Minneapolis Veterans Affairs Health Care System, stratified by race (African American, other), age (50-69, 70-84) and PSA level (documented PSA level ≥4 in Veterans Health Administration electronic medical records vs no such documentation). We used an inductive approach informed by grounded theory to analyse transcribed interviews. RESULTS: Most men in all subgroups expressed misperceptions about the benefits of prostate cancer screening and had difficulty identifying harms associated with screening. In all subgroups, reactions to recommendations against screening ranged from unconditionally receptive to highly resistant. Some men in every subgroup initially resistant to the idea said they would accept a recommendation to discontinue screening from their provider. CONCLUSIONS: Given the similarity of perceptions and reactions across subgroups, materials targeted by race, age and PSA level may not be necessary. Efforts to inform decision making about prostate cancer screening should address misperceptions about benefits and lack of awareness of harms. Provider perspectives and recommendations may play a pivotal role in shaping patient reactions to new guidelines.

A mixed methods study of emotional exhaustion: Energizing and depleting work within an innovative healthcare team.

This mixed methods study documents emotional exhaustion experiences among care team members during the development of an innovative team approach for caring for adults with serious illness. A mixed methods study design was employed to examine depleting work experiences that may produce emotional exhaustion, and energizing aspects of the work that may increase meaningfulness of work, thus reducing emotional exhaustion. The population studied included team members involved in care for adults with serious illness (n = 18). Team members were surveyed quarterly over an 18-month period using the Maslach Burnout Inventory (MBI). The MBI measures burnout, defined as the inability to continue work because of the interactional toll of the work. Analyses of MBI data show that although overall levels of burnout are low, 89% of team members reported moderate/high levels of emotional exhaustion during at least one survey period. In order to understand the kinds of work experiences that may produce or ameliorate emotional exhaustion, qualitative interviews were also conducted with team members at the end of the 18-month period. Major qualitative findings indicate that disputes within the team, environmental pressures, and standardisation of meaningful work leave team members feeling depleted. Having authentic relationships with patients, working as a team, believing in the care model, and practicing autonomy and creativity help team members to restore their emotional energy. Supports for team members' well-being are critical for continued innovation. We conclude with recommendations for improving team members' well-being.

Improving chronic disease care by adding laypersons to the primary care team: a parallel randomized trial.

BACKGROUND: Improving the quality and efficiency of chronic disease care is an important goal. OBJECTIVE: To test whether patients with chronic disease working with lay "care guides" would achieve more evidence-based goals than those receiving usual care. DESIGN: Parallel-group randomized trial, stratified by clinic and conducted from July 2010 to April 2012. Patients were assigned in a 2:1 ratio to a care guide or usual care. Patients, providers, and persons assessing outcomes were not blinded to treatment assignment. (ClinicalTrials.gov: NCT01156974). SETTING: 6 primary care clinics in Minnesota. PATIENTS: Adults with hypertension, diabetes, or heart failure. INTERVENTION: 2135 patients were given disease-specific information about standard care goals and asked to work toward goals for 1 year, with or without the help of a care guide. Care guides were 12 laypersons who received brief training about these diseases and behavior change. MEASUREMENTS: The primary end point for each patient was change in percentage of goals met 1 year after enrollment. RESULTS: The percentage of goals met increased in both the care guide and usual care groups (changes from baseline, 10.0% and 3.9%, respectively). Patients with care guides achieved more goals than usual care patients (82.6% vs. 79.1%; odds ratio, 1.31 [95% CI, 1.16 to 1.47]; P < 0.001); reduced unmet goals by 30.1% compared with 12.6% for usual care patients; and improved more than usual care patients in meeting several individual goals, including not using tobacco. Estimated cost was $286 per patient per year. LIMITATIONS: Providers' usual care may have been influenced by contact with care guides. Last available data in the electronic health record were used to assess end points. CONCLUSION: Adding care guides to the primary care team can improve care for some patients with chronic disease at low cost.

miRNA-21 is dysregulated in response to vein grafting in multiple models and genetic ablation in mice attenuates neointima formation.

AIMS: The long-term failure of autologous saphenous vein bypass grafts due to neointimal thickening is a major clinical burden. Identifying novel strategies to prevent neointimal thickening is important. Thus, this study aimed to identify microRNAs (miRNAs) that are dysregulated during neointimal formation and determine their pathophysiological relevance following miRNA manipulation. METHODS AND RESULTS: We undertook a microarray approach to identify dysregulated miRNAs following engraftment in an interpositional porcine graft model. These profiling experiments identified a number of miRNAs which were dysregulated following engraftment. miR-21 levels were substantially elevated following engraftment and these results were confirmed by quantitative real-time PCR in mouse, pig, and human models of vein graft neointimal formation. Genetic ablation of miR-21 in mice or grafted veins dramatically reduced neointimal formation in a mouse model of vein grafting. Furthermore, pharmacological knockdown of miR-21 in human veins resulted in target gene de-repression and a significant reduction in neointimal formation. CONCLUSION: This is the first report demonstrating that miR-21 plays a pathological role in vein graft failure. Furthermore, we also provided evidence that knockdown of miR-21 has therapeutic potential for the prevention of pathological vein graft remodelling.

Differential effects of professional leaders on health care teams in chronic disease management groups.

BACKGROUND: Leadership by health care professionals is likely to vary because of differences in the social contexts within which they are situated, socialization processes and societal expectations, education and training, and the way their professions define and operationalize key concepts such as teamwork, collaboration, and partnership. This research examines the effect of the nurse and physician leaders on interdependence and encounter preparedness in chronic disease management practice groups. PURPOSE: The aim of this study was to examine the effect of complementary leadership by nurses and physicians involved in jointly producing a health care service on care team functioning. METHODOLOGY: The design is a retrospective observational study based on survey data. The unit of analysis is heart failure care groups in U.S. Veterans Health Administration medical centers. Survey and administrative data were collected in 2009 from 68 Veterans Health Administration medical centers. Key variables include nurse and physician leadership, interdependence, psychological safety, coordination, and encounter preparedness. Reliability and validity of survey measures were assessed with exploratory factor analysis and Cronbach alphas. Multivariate analyses tested hypotheses. FINDINGS: Professional leadership by nurses and physicians is related to encounter preparedness by different paths. Nurse leadership is associated with greater team interdependence, and interdependence is positively associated with respect. Physician leadership is positively associated with greater psychological safety, respect, and shared goals but is not associated with interdependence. Respect is associated with involvement in learning activities, and shared goals are associated with coordination. Coordination and involvement in learning activities are positively associated with encounter preparedness. PRACTICE IMPLICATIONS: By focusing on increasing interdependence and a constructive climate, nurse and physician leaders have the opportunity to increase care coordination and involvement in learning activities.

Examining the surgical stress effects (SSE) framework in practice: A qualitative assessment of perceived sources and consequences of intraoperative stress in surgical teams.

BACKGROUND: Surgical adverse events persist despite extensive improvement efforts. Emotional and behavioral responses to stressors may influence intraoperative performance, as illustrated in the surgical stress effects (SSE) framework. However, the SSE has not been assessed using "real world" data. METHODS: We conducted semi-structured interviews with all surgical team roles at one midwestern VA hospital and elicited narratives involving intraoperative stress. Two coders inductively identified codes from transcripts. The team identified themes among codes and assessed concordance with the SSE framework. RESULTS: Throughout 28 interviews, we found surgical stress was ubiquitous, associated with a variety of factors, including adverse events. Stressors often elicited frustration, anger, fear, and anxiety; behavioral reactions to negative emotions frequently were perceived to degrade individual/team performance and compromise outcomes. Narratives were consistent with the SSE framework and support adding a process outcome (efficiency) and illustrating how adverse events can feedback and acutely increase job demands and stress. CONCLUSION: This qualitative study describes narratives of intraoperative stress, finding they are consistent with the SSE while also allowing minor improvements to the current framework.

Engagement With a Remote Symptom-Tracking Platform Among Participants With Major Depressive Disorder: Randomized Controlled Trial.

BACKGROUND: Multiparametric remote measurement technologies (RMTs), which comprise smartphones and wearable devices, have the potential to revolutionize understanding of the etiology and trajectory of major depressive disorder (MDD). Engagement with RMTs in MDD research is of the utmost importance for the validity of predictive analytical methods and long-term use and can be conceptualized as both objective engagement (data availability) and subjective engagement (system usability and experiential factors). Positioning the design of user interfaces within the theoretical framework of the Behavior Change Wheel can help maximize effectiveness. In-app components containing information from credible sources, visual feedback, and access to support provide an opportunity to promote engagement with RMTs while minimizing team resources. Randomized controlled trials are the gold standard in quantifying the effects of in-app components on engagement with RMTs in patients with MDD. OBJECTIVE: This study aims to evaluate whether a multiparametric RMT system with theoretically informed notifications, visual progress tracking, and access to research team contact details could promote engagement with remote symptom tracking over and above the system as usual. We hypothesized that participants using the adapted app (intervention group) would have higher engagement in symptom monitoring, as measured by objective and subjective engagement. METHODS: A 2-arm, parallel-group randomized controlled trial (participant-blinded) with 1:1 randomization was conducted with 100 participants with MDD over 12 weeks. Participants in both arms used the RADAR-base system, comprising a smartphone app for weekly symptom assessments and a wearable Fitbit device for continuous passive tracking. Participants in the intervention arm (n=50, 50%) also had access to additional in-app components. The primary outcome was objective engagement, measured as the percentage of weekly questionnaires completed during follow-up. The secondary outcomes measured subjective engagement (system engagement, system usability, and emotional self-awareness). RESULTS: The levels of completion of the Patient Health Questionnaire-8 (PHQ-8) were similar between the control (67/97, 69%) and intervention (66/97, 68%) arms (P value for the difference between the arms=.83, 95% CI -9.32 to 11.65). The intervention group participants reported slightly higher user engagement (1.93, 95% CI -1.91 to 5.78), emotional self-awareness (1.13, 95% CI -2.93 to 5.19), and system usability (2.29, 95% CI -5.93 to 10.52) scores than the control group participants at follow-up; however, all CIs were wide and included 0. Process evaluation suggested that participants saw the in-app components as helpful in increasing task completion. CONCLUSIONS: The adapted system did not increase objective or subjective engagement in remote symptom tracking in our research cohort. This study provides an important foundation for understanding engagement with RMTs for research and the methodologies by which this work can be replicated in both community and clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04972474; https://clinicaltrials.gov/ct2/show/NCT04972474. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/32653.

Care guides: an examination of occupational conflict and role relationships in primary care.

BACKGROUND: Improving the efficiency and effectiveness of primary care treatment of patients with chronic illness is an important goal in reforming the U.S. health care system. Reducing occupational conflicts and creating interdependent primary care teams is crucial for the effective functioning of new models being developed to reorganize chronic care. Occupational conflict, role interdependence, and resistance to change in a proof-of-concept pilot test of one such model that uses a new kind of employee in the primary care office, a "care guide," were analyzed. Care guides are lay individuals who help chronic disease patients and their providers achieve standard health goals. PURPOSE: The aim of this study was to examine the development of occupational boundaries, interdependence of care guides and primary care team members, and acceptance by clinic employees of this new kind of health worker. METHODOLOGY/APPROACH: A mixed methods, pilot study was conducted using qualitative analysis; clinic, provider, and patient surveys; administrative data; and multivariate analysis. Qualitative analysis examined the emergence of the care guide role. Administrative data and surveys were used to examine patterns of interdependence between care guides, physicians, team members, and clinic staff; obtain physician evaluations of the care guide role; and evaluate the effect of care guides on patient perceptions of care coordination and follow-up. FINDINGS: Evaluation of implementation of the care guide model showed that (a) the care guide scope of practice was clearly defined; (b) interdependent relationships between care guides and providers were formed; (c) relational triads consisting of patient, care guide, and physician were created; (d) patients and providers were supported in managing chronic disease; and (e) resistance to this model among traditional employees was minimized. PRACTICE IMPLICATIONS: The feasibility of implementing a new care model for chronic disease management in the primary care setting, identifying factors associated with a positive organizational experience, was shown in this study.

Understanding the Subjective Experience of Long-term Remote Measurement Technology Use for Symptom Tracking in People With Depression: Multisite Longitudinal Qualitative Analysis.

BACKGROUND: Remote measurement technologies (RMTs) have the potential to revolutionize major depressive disorder (MDD) disease management by offering the ability to assess, monitor, and predict symptom changes. However, the promise of RMT data depends heavily on sustained user engagement over extended periods. In this paper, we report a longitudinal qualitative study of the subjective experience of people with MDD engaging with RMTs to provide insight into system usability and user experience and to provide the basis for future promotion of RMT use in research and clinical practice. OBJECTIVE: We aimed to understand the subjective experience of long-term engagement with RMTs using qualitative data collected in a longitudinal study of RMTs for monitoring MDD. The objectives were to explore the key themes associated with long-term RMT use and to identify recommendations for future system engagement. METHODS: In this multisite, longitudinal qualitative research study, 124 semistructured interviews were conducted with 99 participants across the United Kingdom, Spain, and the Netherlands at 3-month, 12-month, and 24-month time points during a study exploring RMT use (the Remote Assessment of Disease and Relapse-Major Depressive Disorder study). Data were analyzed using thematic analysis, and interviews were audio recorded, transcribed, and coded in the native language, with the resulting quotes translated into English. RESULTS: There were 5 main themes regarding the subjective experience of long-term RMT use: research-related factors, the utility of RMTs for self-management, technology-related factors, clinical factors, and system amendments and additions. CONCLUSIONS: The subjective experience of long-term RMT use can be considered from 2 main perspectives: experiential factors (how participants construct their experience of engaging with RMTs) and system-related factors (direct engagement with the technologies). A set of recommendations based on these strands are proposed for both future research and the real-world implementation of RMTs into clinical practice. Future exploration of experiential engagement with RMTs will be key to the successful use of RMTs in clinical care.

Multilingual markers of depression in remotely collected speech samples: A preliminary analysis.

BACKGROUND: Speech contains neuromuscular, physiological and cognitive components, and so is a potential biomarker of mental disorders. Previous studies indicate that speaking rate and pausing are associated with major depressive disorder (MDD). However, results are inconclusive as many studies are small and underpowered and do not include clinical samples. These studies have also been unilingual and use speech collected in controlled settings. If speech markers are to help understand the onset and progress of MDD, we need to uncover markers that are robust to language and establish the strength of associations in real-world data. METHODS: We collected speech data in 585 participants with a history of MDD in the United Kingdom, Spain, and Netherlands as part of the RADAR-MDD study. Participants recorded their speech via smartphones every two weeks for 18 months. Linear mixed models were used to estimate the strength of specific markers of depression from a set of 28 speech features. RESULTS: Increased depressive symptoms were associated with speech rate, articulation rate and intensity of speech elicited from a scripted task. These features had consistently stronger effect sizes than pauses. LIMITATIONS: Our findings are derived at the cohort level so may have limited impact on identifying intra-individual speech changes associated with changes in symptom severity. The analysis of features averaged over the entire recording may have underestimated the importance of some features. CONCLUSIONS: Participants with more severe depressive symptoms spoke more slowly and quietly. Our findings are from a real-world, multilingual, clinical dataset so represent a step-change in the usefulness of speech as a digital phenotype of MDD.

Long-term participant retention and engagement patterns in an app and wearable-based multinational remote digital depression study.

Recent growth in digital technologies has enabled the recruitment and monitoring of large and diverse populations in remote health studies. However, the generalizability of inference drawn from remotely collected health data could be severely impacted by uneven participant engagement and attrition over the course of the study. We report findings on long-term participant retention and engagement patterns in a large multinational observational digital study for depression containing active (surveys) and passive sensor data collected via Android smartphones, and Fitbit devices from 614 participants for up to 2 years. Majority of participants (67.6%) continued to remain engaged in the study after 43 weeks. Unsupervised clustering of participants' study apps and Fitbit usage data showed 3 distinct engagement subgroups for each data stream. We found: (i) the least engaged group had the highest depression severity (4 PHQ8 points higher) across all data streams; (ii) the least engaged group (completed 4 bi-weekly surveys) took significantly longer to respond to survey notifications (3.8 h more) and were 5 years younger compared to the most engaged group (completed 20 bi-weekly surveys); and (iii) a considerable proportion (44.6%) of the participants who stopped completing surveys after 8 weeks continued to share passive Fitbit data for significantly longer (average 42 weeks). Additionally, multivariate survival models showed participants' age, ownership and brand of smartphones, and recruitment sites to be associated with retention in the study. Together these findings could inform the design of future digital health studies to enable equitable and balanced data collection from diverse populations.

Unintended consequences of implementing a national performance measurement system into local practice.

BACKGROUND: Although benefits of performance measurement (PM) systems have been well documented, there is little research on negative unintended consequences of performance measurement systems in primary care. To optimize PM systems, a better understanding is needed of the types of negative unintended consequences that occur and of their causal antecedents. OBJECTIVES: (1) Identify unintended negative consequences of PM systems for patients. (2) Develop a conceptual framework of hypothesized relationships between PM systems, facility-level variables (local implementation strategies, primary care staff attitudes and behaviors), and unintended negative effects on patients. DESIGN, PARTICIPANTS, APPROACH: Qualitative study design using dissimilar cases sampling. A series of 59 in-person individual semi-structured interviews at four Veterans Health Administration (VHA) facilities was conducted between February and July 2009. Participants included members of primary care staff and facility leaders. Sites were selected to assure variability in the number of veterans served and facility scores on national VHA performance measures. Interviews were recorded, transcribed and content coded to identify thematic categories and relationships. RESULTS: Participants noted both positive effects and negative unintended consequences of PM. We report three negative unintended consequences for patients. Performance measurement can (1) lead to inappropriate clinical care, (2) decrease provider focus on patient concerns and patient service, and (3) compromise patient education and autonomy. We also illustrate examples of negative consequences on primary care team dynamics. In many instances these problems originate from local implementation strategies developed in response to national PM definitions and policies. CONCLUSIONS: Facility-level strategies undertaken to implement national PM systems may result in inappropriate clinical care, can distract providers from patient concerns, and may have a negative effect on patient education and autonomy. Further research is needed to ascertain how features of centralized PM systems influence whether measures are translated locally by facilities into more or less patient-centered policies and processes.

'Trying to fly the plane while we were building it'. Applying a learning health systems approach to evaluate early-stage barriers and facilitators to implementing primary care transformation: a qualitative study.

OBJECTIVE: A learning health system (LHS) uses data to generate evidence and answer questions required to continually improve system performance and patient care. Given the complexities of practice transformation, an area where LHS is particularly important is the study of primary care transformation (PCT) as PCT generates several practice-level questions that require study where the findings can be readily implemented. In May 2019, a large integrated health delivery system in Minnesota began implementation of a population management PCT in two of its 40 primary care clinics. In this model of care, patients are grouped into one of five service bundles based on their complexity of care; patient appointment lengths and services provided are then tailored to each service bundle. The objective of this study was to examine the use of a LHS in PCT by utilising the Consolidated Framework for Implementation Research (CFIR) to categorise implementation lessons from the initial two PCT clinics to inform further implementation of the PCT within the health system. DESIGN: This was a formative evaluation in which semistructured qualitative interviews were carried out. Observational field notes were also taken. Inductive coding of the data was performed and resultant codes were mapped to the CFIR. SETTING: Two suburban primary care clinics in the Twin Cities, Minnesota. PARTICIPANTS: Twenty-two care team members from the first two clinics to adopt the PCT. RESULTS: Seventeen codes emerged to describe care team members' perceived implementation influences. Codes occurred in each of the five CFIR domains (intervention characteristics, outer setting, inner setting, characteristics of individuals and process), with most codes occurring in the 'inner setting' domain. CONCLUSIONS: Using an LHS approach to determine early-stage implementation influences is key to guiding further PCT implementation, understanding modifications that need to be made and additional research that needs to occur.