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Major depressive disorder (MDD) is defined by an array of symptoms that make it challenging to understand the condition at a population level. Subtyping offers a way to unpick this phenotypic diversity for improved disorder characterisation. We aimed to identify depression subtypes longitudinally using the Inventory of Depressive Symptomatology: Self-Report (IDS-SR). A secondary analysis of a two-year cohort study called Remote Assessment of Disease and Relapse in Major Depressive Disorder (RADAR-MDD), which collected data every three months from patients with a history of recurrent MDD in the United Kingdom, the Netherlands, and Spain (N = 619). We used latent class and latent transition analysis to identify subtypes at baseline, determined their consistency at 6- and 12-month follow-ups, and examined transitions over time. We identified a 4-class solution: (1) severe with appetite decrease, (2) severe with appetite increase, (3) moderate severity and (4) low severity. These same classes were identified at 6- and 12-month follow-ups, and participants tended to remain in the same class over time. We found no statistically significant differences between the two severe subtypes regarding baseline clinical and sociodemographic characteristics. Our findings emphasize severity differences over symptom types, suggesting that current subtyping methods provide insights akin to existing severity measures. When examining transitions, participants were most likely to remain in their respective classes over 1-year, indicating chronicity rather than oscillations in depression severity. Future work recommendations are made. [ABSTRACT FROM AUTHOR]

BackgroundSleep problems tend to vary according to the course of the disorder in individuals with mental health problems. Research in mental health has associated sleep pathologies with depression. However, the gold standard for sleep assessment, polysomnography (PSG), is not suitable for long-term, continuous monitoring of daily sleep, and methods such as sleep diaries rely on subjective recall, which is qualitative and inaccurate. Wearable devices, on the other hand, provide a low-cost and convenient means to monitor sleep in home settings. ObjectiveThe main aim of this study was to devise and extract sleep features from data collected using a wearable device and analyze their associations with depressive symptom severity and sleep quality as measured by the self-assessed Patient Health Questionnaire 8-item (PHQ-8). MethodsDaily sleep data were collected passively by Fitbit wristband devices, and depressive symptom severity was self-reported every 2 weeks by the PHQ-8. The data used in this paper included 2812 PHQ-8 records from 368 participants recruited from 3 study sites in the Netherlands, Spain, and the United Kingdom. We extracted 18 sleep features from Fitbit data that describe participant sleep in the following 5 aspects: sleep architecture, sleep stability, sleep quality, insomnia, and hypersomnia. Linear mixed regression models were used to explore associations between sleep features and depressive symptom severity. The z score was used to evaluate the significance of the coefficient of each feature. ResultsWe tested our models on the entire dataset and separately on the data of 3 different study sites. We identified 14 sleep features that were significantly (P

BackgroundRheumatoid arthritis (RA) is characterized by recurrent fluctuations in symptoms such as joint pain, swelling, and stiffness. Remote measurement technologies (RMTs) offer the opportunity to track symptoms continuously and in real time; therefore, they may provide a more accurate picture of RA disease activity as a complement to prescheduled general practitioner appointments. Previous research has shown patient interest in remote symptom tracking in RA and has provided evidence for its clinical validity. However, there is a lack of co-design in the current development of systems, and the features of RMTs that best promote optimal engagement remain unclear. ObjectiveThis study represents the first in a series of work that aims to develop a multiparametric RMT system for symptom tracking in RA. The objective of this study is to determine the important outcomes for disease management in patients with RA and how these can be best captured via remote measurement. MethodsA total of 9 patients (aged 23-77 years; mean 55.78, SD 17.54) with RA were recruited from King’s College Hospital to participate in two semistructured focus groups. Both focus group discussions were conducted by a facilitator and a lived-experience researcher. The sessions were recorded, transcribed, independently coded, and analyzed for themes. ResultsThematic analysis identified a total of four overarching themes: important symptoms and outcomes in RA, management of RA symptoms, views on the current health care system, and views on the use of RMTs in RA. Mobility and pain were key symptoms to consider for symptom tracking as well as symptom triggers. There is a general consensus that the ability to track fluctuations and transmit such data to clinicians would aid in individual symptom management and the effectiveness of clinical care. Suggestions for visually capturing symptom fluctuations in an app were proposed. ConclusionsThe findings support previous work on the acceptability of RMT with RA disease management and address key outcomes for integration into a remote monitoring system for RA self-management and clinical care. Clear recommendations for RMT design are proposed. Future work will aim to take these recommendations into a user testing phase.

Background: Comprehensive medication management (CMM) is a service provided by clinical pharmacists. CMM aims to optimize pharmacotherapy outcomes by ensuring patients' medications are indicated, effective, safe, and patients are able to adhere to the prescribed medication regimen and take the medications as intended. The goal of CMM is to optimize patients' medications to ensure they are meeting their medication and health‐related goals. Objective: The objective of this project is to evaluate facilitators and barriers to integrating CMM during transitions of care (ToC) at Federally Qualified Health Centers (FQHCs). Design: Semistructured qualitative interviews were conducted with 22 key informants identified through purposive sampling at three FQHCs. Interviews were coded and analyzed deductively using a modified Consolidated Framework for Implementation Research (CFIR) adapted for ToC. Key Results: Thirty‐nine codes were identified across all CFIR constructs, including the addition of a new construct, "Patient characteristics." Major facilitators included the perceived advantage and feasibility of the intervention, standardization of ToC processes, and organizational buy‐in. Major barriers included health information technology system limitations, communication barriers with discharge facilities, technical and staffing challenges in applying criteria to identify patients for CMM, and low patient throughput. Conclusions: Identifying early‐stage barriers and facilitators are key to maximize facilitators and address barriers to support successful implementation. The findings of this work are being used to guide project adaptations to better integrate CMM into the ToC processes. [ABSTRACT FROM AUTHOR]

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 (β=–93.61, P <.001), increased sleep variability (β=0.96, P <.001), and delayed circadian rhythms (ie, sleep onset: β=0.55, P =.001; sleep offset: β=1.12, P <.001; M10 onset: β=0.73, P =.003; HR acrophase: β=0.71, P =.001). Notably, the negative association with daily steps was more pronounced in spring (β of PHQ-8 × spring = –31.51, P =.002) and summer (β of PHQ-8 × summer = –42.61, P <.001) compared with winter. Additionally, the significant correlation with delayed M10 onset was observed solely in summer (β 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Remote measurement technologies, such as smartphones and wearable devices, can improve treatment outcomes for depression through enhanced illness characterization and monitoring. However, little is known about digital outcomes that are clinically meaningful to patients and clinicians. Moreover, if these technologies are to be successfully implemented within treatment, stakeholders' views on the barriers to and facilitators of their implementation in treatment must be considered. Objective: This study aims to identify clinically meaningful targets for digital health research in depression and explore attitudes toward their implementation in psychological services. Methods: A grounded theory approach was used on qualitative data from 3 focus groups of patients with a current diagnosis of depression and clinicians with >6 months of experience with delivering psychotherapy (N=22). Results: Emerging themes on clinical targets fell into the following two main categories: promoters and markers of change. The former are behaviors that participants engage in to promote mental health, and the latter signal a change in mood. These themes were further subdivided into external changes (changes in behavior) or internal changes (changes in thoughts or feelings) and mapped with potential digital sensors. The following six implementation acceptability themes emerged: technology-related factors, information and data management, emotional support, cognitive support, increased self-awareness, and clinical utility. Conclusions: The promoters versus markers of change differentiation have implications for a causal model of digital phenotyping in depression, which this paper presents. Internal versus external subdivisions are helpful in determining which factors are more susceptible to being measured by using active versus passive methods. The implications for implementation within psychotherapy are discussed with regard to treatment effectiveness, service provision, and patient and clinician experience. [ABSTRACT FROM AUTHOR]

Background: Multi-parametric remote measurement technologies (RMTs) comprise smartphone apps and wearable devices for both active and passive symptom tracking. They hold potential for understanding current depression status and predicting future depression status. However, the promise of using RMTs for relapse prediction is heavily dependent on user engagement, which is defined as both a behavioral and experiential construct. A better understanding of how to promote engagement in RMT research through various in-app components will aid in providing scalable solutions for future remote research, higher quality results, and applications for implementation in clinical practice. Objective: The aim of this study is to provide the rationale and protocol for a 2-armed randomized controlled trial to investigate the effect of insightful notifications, progress visualization, and researcher contact details on behavioral and experiential engagement with a multi-parametric mobile health data collection platform, Remote Assessment of Disease and Relapse (RADAR)–base. Methods: We aim to recruit 140 participants upon completion of their participation in the RADAR Major Depressive Disorder study in the London site. Data will be collected using 3 weekly tasks through an active smartphone app, a passive (background) data collection app, and a Fitbit device. Participants will be randomly allocated at a 1:1 ratio to receive either an adapted version of the active app that incorporates insightful notifications, progress visualization, and access to researcher contact details or the active app as usual. Statistical tests will be used to assess the hypotheses that participants using the adapted app will complete a higher percentage of weekly tasks (behavioral engagement: primary outcome) and score higher on self-awareness measures (experiential engagement). Results: Recruitment commenced in April 2021. Data collection was completed in September 2021. The results of this study will be communicated via publication in 2022. Conclusions: This study aims to understand how best to promote engagement with RMTs in depression research. The findings will help determine the most effective techniques for implementation in both future rounds of the RADAR Major Depressive Disorder study and, in the long term, clinical practice. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To understand responses of primary care clinics to inclusion in a tiered total cost of care insurance benefit design. STUDY DESIGN: We used a qualitative design beginning with longitudinal analysis of administrative data on consumer clinic choice, clinic tier placement, and clinic actions, followed by in-depth interviews with key informants from clinics, administering health plans, and program administrators. METHODS: We collected data via semistructured interviews with purposively sampled key informants selected from clinics that prospectively reduced prices to move to, or remain in, a tier with lower cost sharing. Data from interview transcripts were coded using qualitative coding software and analyzed for thematic responses. RESULTS: Our findings suggest that clinics respond to the incentives in the tiered cost-sharing benefit design. Two motivations cited by clinics are (1) concern over developing a reputation as a high-cost clinic and (2) concern about the possible loss of patients due to higher cost sharing. Some clinics have agreed to price reductions or risk-sharing arrangements to move to, or remain in, a tier with lower cost sharing. Clinic informants reported that price reductions alone are not scalable. They sought greater transparency in tier assignment and increased data sharing to help them reduce costly or unnecessary utilization. CONCLUSIONS: Managers of primary care clinics respond to a tiered benefit design that holds them accountable for total cost of care. They respond by offering price discounts and expressing interest in reducing costly referrals and unnecessary use of services. [ABSTRACT FROM AUTHOR]

U.S. clinical guidelines recommend that prior to screening for prostate cancer with Prostate Specific Antigen (PSA), men should have an informed discussion about the potential benefits and harms of screening. Prostate cancer disproportionately affects Black men. To understand how White and Black men reacted to a draft educational pamphlet about the benefits and harms of PSA screening, we conducted race-specific focus groups at a midwestern VA medical center in 2013 and 2015. White and Black men who had been previously screened reviewed the draft pamphlet using a semistructured focus group facilitator guide. Forty-four men, ages 55–81, participated in four White and two Black focus groups. Three universal themes were: low baseline familiarity with prostate cancer, surprise and resistance to the recommendations not to test routinely, and negative emotions in response to ambiguity. Discussions of benefits and harms of screening, as well as intentions for exercising personal agency in prevention and screening, diverged between White and Black focus groups. Discussion in White groups highlighted the potential benefits of screening, minimized the harms, and emphasized personal choice in screening decisions. Participants in Black groups devoted almost no discussion to benefits, considered harms significant, and emphasized personal and collective responsibility for preventing cancer through diet, exercise, and alternative medicine. Discussion in Black groups also included the role of racism and discrimination in healthcare and medical research. These findings contribute to our understanding of how men's varied perspectives and life experiences affect their responses to prostate cancer screening information. [ABSTRACT FROM AUTHOR]

Modern printing toners represent a prime example of subvisible particles that can be easily transferred to hands, clothing, and other surfaces. To explore the potential evidentiary value of toner particles, toner samples were collected from known printer cartridges and characterized by various microanalytical techniques to establish the properties most useful for recognition, identification, and comparison. Environmental samples (i.e., dust) were then collected from various locations at varying distances from toner‐based printers, using both tape lifts and carbon adhesive stubs, to assess the possibility of detecting toner. By light microscopy, toner can be recognized on the basis of particle size and shape, as well as color. Further examination of the micromorphology in the field emission scanning electron microscope reveals characteristic morphologies and differences in surface texture and shape among toner sources. Raman spectroscopy provides chemical identification of the pigment (or pigment class) and, in some cases, also permits identification of the polymer component. While black and blue pigment chemistry remained constant among toner varieties that were studied (copper phthalocyanine and carbon black), variation in yellow and magenta pigments was observed. Analysis of dust samples collected from various environments demonstrated that while toner is consistently detectable in close proximity to printers (within 2 feet), it also can be detected in dust collected in nearby rooms. This research demonstrates that toner particles can be located, characterized, and discriminated, using a suite of microanalytical methods that are applicable to forensic casework. [ABSTRACT FROM AUTHOR]

Modern printing toners represent a prime example of subvisible particles that can be easily transferred to hands, clothing, and other surfaces. To explore the potential evidentiary value of toner particles, toner samples were collected from known printer cartridges and characterized by various microanalytical techniques to establish the properties most useful for recognition, identification, and comparison. Environmental samples (i.e., dust) were then collected from various locations at varying distances from toner‐based printers, using both tape lifts and carbon adhesive stubs, to assess the possibility of detecting toner. By light microscopy, toner can be recognized on the basis of particle size and shape, as well as color. Further examination of the micromorphology in the field emission scanning electron microscope reveals characteristic morphologies and differences in surface texture and shape among toner sources. Raman spectroscopy provides chemical identification of the pigment (or pigment class) and, in some cases, also permits identification of the polymer component. While black and blue pigment chemistry remained constant among toner varieties that were studied (copper phthalocyanine and carbon black), variation in yellow and magenta pigments was observed. Analysis of dust samples collected from various environments demonstrated that while toner is consistently detectable in close proximity to printers (within 2 feet), it also can be detected in dust collected in nearby rooms. This research demonstrates that toner particles can be located, characterized, and discriminated, using a suite of microanalytical methods that are applicable to forensic casework. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of access to outdoor space and buildings and social or community events on elders' perceived disconnectedness. Method: Data were from a representative survey conducted as part of an age-friendly community initiative in a large midwestern city in the United States. Hierarchical logistic regression was employed to examine the relationships between environment, engagement, and connection. Results: Having access to ramps to enter buildings reduced the odds of perceived disconnectedness by 79%, participation in social or community events reduced the odds of perceived disconnectedness by 83%. The odds of perceived disconnectedness for elders "not sure" of their access to public buildings were around 6 times that of those without access, holding all else constant. Discussion: Ensuring access to ramps to enter buildings, disseminating information about the accessibility of parks and buildings, and social or community events may reduce elders' perceived disconnectedness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

The corporate wellness industry is diversifying and now includes legacy wellness companies, divisions of health plans or delivery systems, and new technology-focused solution enterprises. We conducted in-depth interviews with leaders in the industry to understand the changes in its supply side, the drivers of these changes, future trends, and their implications for employers and policy makers. Three key trends emerged from the interviews: The industry is expanding and becoming increasingly diverse and competitive; wellness companies are redefining their business models to promote a culture of health; and the value proposition of employee wellness programs is shifting from a return on investment to a new idea: value on investment. Our findings clarify wellness companies' innovations, their contributions to population health improvement efforts, and the need for additional evidence to demonstrate the value of the new generation of wellness products and services. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression. Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3). Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T"F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T"F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T"F35++ were less prevalent than Ad5 neutralising antibodies. Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer. [ABSTRACT FROM AUTHOR]

Targeted delivery of biological agents selective for atherosclerotic plaques may provide a useful tool for treatment and/or imaging of atherosclerosis. However, there are no naturally occurring viral vectors which are suitable for this. The commonly used gene transfer vectors adenovirus 5 (Ad5) and adeno-associated virus 2 (AAV2) have a broad tropism and inefficiently transduce vascular cells following systemic administration. Therefore there is a requirement for the development of vectors with a high specificity for atherosclerotic tissue. By insertion of atherosclerotic plaque targeting peptides into the viral capsids it may be possible to create retargeted plaque-specific vectors. Previously, phage display in ApoE-/- mice identified several peptides that selectively bind to atherosclerotic plaques 1. We therefore engineered 3 peptides [CAPGPSPSKC, CNHRYMQMC (thought to bind a putative TIMP2 receptor (1)) and CQEPTRLKC] into the capsid of both Ad5 and AAV2 (CQE in Ad only). Modified viruses expressing the LacZ reporter gene were produced and their targeting capacity was then tested in vitro. Transduction of human, murine and rat endothelial cells with peptide-modified Ads was between 2 and 20 fold higher than controls (p<0.05), whereas transduction of non-endothelial HeLa cells was not significantly different (p>0.1). CNH-modified AAV transduction of murine endothelial cell lines was between 10 and 100 fold higher than controls (p<0.05) and transduction was mediated through a proteasome-insensitive pathway, suggesting that the peptide insertion alters both the receptor and trafficking pathway of the virus. In addition, the CNH-modified Ad and AAV vectors both transduced cells expressing the putative CNH receptor, membrane type 1 matrix metalloproteinase (MT1-MMP) significantly higher than control cells.The modified AAV vectors were further characterized in vivo in an ApoE-/- mouse model of atherosclerosis. scAAV vectors with the eGFP reporter gene were delivered systemically. 28 days post-infusion of 6×109 virus particles/mouse, real-time PCR (Taqman) was used to detect the amount of virus in tissues. Compared to control AAV2, substantially higher levels (10-100 fold) of both the peptide-modified viruses were detected in the brachiocephalic artery (site of unstable atheroscerotic plaque) and aorta, with reduced levels in all other organs examined, including liver, spleen, lungs and heart.These results suggest that the tropism of these AAV2 vectors has been substantially altered to create atherosclerotic plaque targeted vectors which will be useful for targeted gene delivery to atherosclerotic tissue.Molecular Therapy (2006) 13, S11–S11; doi: 10.1016/j.ymthe.2006.08.037 [ABSTRACT FROM AUTHOR]

Purpose How to effectively integrate pharmacists into team-based models of care to maximize the benefit they bring to patients and care teams, especially during times of primary care transformation (PCT), remains unknown. The objective of this study was to identify barriers and facilitators when integrating pharmacist-provided comprehensive medication management (CMM) services into a health system's team-based PCT using the Consolidated Framework for Implementation Research (CFIR). Methods Semistructured qualitative interviews were carried out with 22 care team members regarding their perceptions of the implementation of CMM in the PCT. Transcripts were coded to identify CMM implementation barriers and facilitators, and resulting codes were mapped to corresponding CFIR domains and constructs. Results Fifteen codes emerged that were labeled as either a barrier or a facilitator to implementing CMM in the PCT. Facilitators were the perception of CMM as an invaluable resource, precharting, tailored appointment lengths, insurance coverage, increased pharmacy presence, enhanced team-based care, location of CMM, and identification of CMM advocates. Barriers included limited clinic leadership involvement, a need for additional resources, CMM pharmacists not always feeling part of the core team, understanding of and training around CMM's role in the PCT, changing mindsets to utilize resources such as CMM more frequently, underutilization of CMM, and CMM scheduling. Conclusion Clinical pharmacists providing CMM represent a valuable interdisciplinary care team member who can help improve healthcare quality and access to primary care. Identifying and addressing implementation barriers and facilitators early during PCT rollout is critical to the success of team-based services such as CMM and becoming a learning health system. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)