Tear Proteins Altered in Patients with Persistent Eye Pain after Refractive Surgery: Biomarker Candidate Discovery.

Some patients develop persistent eye pain after refractive surgery, but factors that cause or sustain pain are unknown. We tested whether tear proteins of patients with pain 3 months after surgery differ from those of patients without pain. Patients undergoing refractive surgery (laser in situ keratomileusis or photorefractive keratectomy ) were recruited from 2 clinics, and tears were collected 3 months after surgery. Participants rated their eye pain using a numerical rating scale (NRS, 0-10; no pain-worst pain) at baseline, 1 day, and 3 months after surgery. Using tandem mass tag proteomic analysis, we examined tears from patients with pain [NRS ≥ 3 at 3 months (n = 16)] and patients with no pain [NRS ≤ 1 at 3 months (n = 32)] after surgery. A subset of proteins (83 of 2748 detected, 3.0%) were associated with pain 3 months after surgery. High-dimensional statistical models showed that the magnitude of differential expression was not the only important factor in classifying tear samples from pain patients. Models utilizing 3 or 4 proteins had better classification performance than single proteins and represented differences in both directions (higher or lower in pain). Thus, patterns of protein differences may serve as biomarkers of postsurgical eye pain as well as potential therapeutic targets.

Aging-related alterations in mechanistic target of rapamycin signaling promote platelet hyperreactivity and thrombosis.

BACKGROUND: Aging is an independent risk factor for the development of cardiovascular, thrombotic, and other chronic diseases. However, mechanisms of platelet hyperactivation in aging remain poorly understood. OBJECTIVES: Here, we examine whether and how aging alters intracellular signaling in platelets to support platelet hyperactivity and thrombosis. METHODS: Quantitative mass spectrometry with tandem mass tag labeling systematically measured protein phosphorylation in platelets from healthy aged (>65 years) and young human (<45 years) subjects. The role of platelet mechanistic target of rapamycin (mTOR) in aging-induced platelet hyperreactivity was assessed using pharmacologic mTOR inhibition and a platelet-specific mTOR-deficient mouse model (mTORplt-/-). RESULTS: Quantitative phosphoproteomics uncovered differential site-specific protein phosphorylation within mTOR, Rho GTPase, and MAPK pathways in platelets from aged donors. Western blot confirmed constitutive activation of the mTOR pathway in platelets from both aged humans and mice, which was associated with increased aggregation compared with that in young controls. Inhibition of mTOR with either Torin 1 in aged humans or genetic deletion in aged mice reversed platelet hyperreactivity. In a collagen-epinephrine pulmonary thrombosis model, aged wild-type (mTORplt+/+) mice succumbed significantly faster than young controls, while time to death of aged mTORplt-/- mice was similar to that of young mTORplt+/+ mice. Mechanistically, we noted increased Rac1 activation and levels of mitochondrial reactive oxygen species in resting platelets from aged mice, as well as increased p38 phosphorylation upstream of thromboxane generation following agonist stimulation. CONCLUSION: Aging-related changes in mTOR phosphorylation enhance Rac1 and p38 activation to enhance thromboxane generation, platelet hyperactivity, and thrombosis.

Disparities in telemedicine use among Native Hawaiian and Pacific Islander individuals insured through Medicaid.

States have implemented policy changes to increase access to telemedicine services for individuals receiving Medicaid benefits. Native Hawaiian and Pacific Islander (NHPI) individuals experienced disproportionate harms from COVID-19 and have long experienced disparities in health care access compared with other racial and ethnic groups, making the issue of telemedicine access particularly salient for NHPI individuals on Medicaid. Utilizing 100% 2020-2021 Medicaid claims, we compared trends in telemedicine use between NHPI and non-Hispanic White individuals on Medicaid in Washington State and conducted a decomposition analysis to identify drivers of underlying disparities. In both years, NHPI individuals were 38%-39% less likely to use any telemedicine than White individuals after adjusting for patient- and area-level characteristics. Decomposition analysis revealed that most of this difference was due to differential effects of characteristics, rather than group differences in characteristics. Namely, several characteristics that were associated with increased telemedicine use had more muted associations for NHPI vs White individuals, such as English as the primary spoken language and female sex. These findings suggest the presence of limited acceptability of or group-specific barriers to telemedicine for NHPI individuals, including potential discrimination in being offered telemedicine visits. These issues should be understood and mitigated through close collaboration between health care leaders and NHPI communities.

Factors associated with primary care physician turnover in the VA.

Objectives: To quantify the association between primary care team workload satisfaction and primary care physician (PCP) turnover and examine potential mediation of workplace climate factors using survey and administrative data. Study Design: Longitudinal observational study using data from 2008 to 2016. Methods: The outcome variable was PCP turnover. The main explanatory variable was satisfaction with amount of workload. We included 7 additional workplace climate measures (eg, satisfaction with direct supervision) as mediators. We included characteristics of PCPs (eg, PCP years of experience, gender), salary, and clinic factors (eg, urban vs rural geography, community vs hospital based) as covariates. Results: US Department of Veterans Affairs (VA) PCPs working at 787 VA primary care clinics nationally were recruited for this study. Over the 9-year study period, 8362 unique PCPs were employed in the VA. The unadjusted mean quarterly turnover rate was 1.83%, and the mean (SD) workload satisfaction score was 3.58 ( 0.24) on a 5-point Likert scale over the study period. In adjusted analysis, a 1-point increase in workload satisfaction was associated with a decrease of 0.73 (95% CI, 0.36-1.10) percentage points in the probability of turnover in a calendar quarter. In the mediation analysis, we found that workload satisfaction impacted turnover through only 1 of the 7 workplace climate measures: satisfaction with direction by senior managers. Conclusions: Our study findings highlight the key role that achieving primary care workload satisfaction can play in reducing PCP turnover. Identification of direction by senior managers as an underlying mechanism is an important finding for strategic planning to mitigate PCP turnover.

Identifying Patterns of Primary Care In-Person and Telemedicine Use in the Veterans Health Administration: A Latent Class Analysis.

BACKGROUND: The Veterans Health Administration increased synchronous telemedicine (video and telephone visits) in primary care in response to the COVID-19 pandemic. OBJECTIVE: Our objective was to determine veteran use patterns of in-person and telemedicine primary care when all modalities were available. DESIGN: A retrospective cohort analysis. We performed a latent class analysis of primary care visits over a 1-year period to identify veteran subgroup (i.e., class) membership based on amount of primary care use and modality used. Then, we used multinomial logistic regression with a categorical outcome to identify patient characteristics associated with class identification. PARTICIPANTS: A random national sample consisting of 564,580 primary care empaneled veterans in June 2021. MAIN MEASURES: Latent class membership. KEY RESULTS: We identified three latent classes: those with few primary care visits that were predominantly telephone-based (45%), intermediate number of visits of all modalities (50%), and many visits of all modalities (5%). In an adjusted model, characteristics associated with the "few" visits class, compared to the intermediate class, were older age, male sex, White race, further driving distance to primary care, higher Gagne, optimal internet speed, and unmarried status (OR 1.002, 1.52, 1.13, 1.004, 1.04, 1.05, 1.06, respectively; p < .05). Characteristics associated with membership in the "many" visits class, compared to the intermediate class, were Hispanic race, higher JEN Frailty Index and Gagne (OR 1.12, 1.11, 1.02, respectively; p < .05), and higher comorbidity by Care Assessment Need score quartile (Q2 1.73, Q3 2.80, Q4 4.12; p < 0.05). CONCLUSIONS: Veterans accessing primary care in-person or via telemedicine do so primarily in three ways: (1) few visits, predominantly telephone; (2) intermediate visits, all modalities, (3) many visits, all modalities. We found no groups of veterans receiving a majority of primary care through video.

Factors Associated With Use of the Preventive Health Inventory in US Veterans.

Importance: The COVID-19 pandemic caused significant declines in the quality of preventive and chronic disease care. The Veterans Health Administration (VHA) used the Preventive Health Inventory (PHI), a multicomponent care management intervention, to catch up on care disrupted by the pandemic. Objective: To identify key factors associated with PHI use. Design, Setting, and Participants: This cohort study of veterans receiving primary care used administrative data from national VHA primary care clinics for February 1, 2021, through February 1, 2022. Exposure: Patient PHI receipt. Main Outcomes and Measures: The main outcomes were patient, practitioner, and clinic factors associated with PHI receipt. Binomial generalized linear models with fixed effects for clinic were used to analyze factors associated with receipt of PHI. Least absolute shrinkage and selection operator procedures were used for variable selection. Results: A total of 4 358 038 veterans (mean [SD] age, 63.7 [16.0] years; 90% male; 76% non-Hispanic White) formed the study cohort, of whom 389 757 (9%) received the PHI. Veterans who received the PHI had higher mean Care Assessment Need (CAN) scores, which indicate the likelihood of hospitalization or death within 1 year (mean [SD], 51.9 [28.6] vs 47.2 [28.6]; standardized mean difference [SMD], -0.16). They were also more likely to live in urban areas (77% vs 64%; SMD, 0.28) and have a shorter drive distance to primary care (mean [SD], 13.2 [12.4] vs 15.7 [14.6] miles; SMD, 0.19). The mean outpatient use was higher among PHI recipients compared with non-PHI recipients (mean [SD], 18.4 [27.8] vs 15.1 [24.1] visits; SMD, -0.13). In addition, veterans with primary care practitioners with higher caseloads were more likely to receive the PHI (mean [SD], 778 [231] vs 744 [249] patients; SMD, -0.14), and they were more likely to be seen at larger clinics (mean [SD], 9670 [6876] vs 8786 [6892] patients; SMD, -0.13). Prior outpatient use and CAN score were associated with PHI receipt in the final model. Conclusions and Relevance: In this cohort study of the VHA's PHI, patients with higher CAN scores and more outpatient use in the previous year were more likely to receive the PHI. This study identifies potential intervention points to improve care coordination for veterans.

Efficacy of the Canadian CT Head Rule in Patients Presenting to the Emergency Department with Minor Head Injury.

Introduction: Approximately, one in three computed tomography (CT) scans performed for head injury may be avoidable. We evaluate the efficacy of the Canadian CT head rule (CCHR) on head CT imaging in minor head injury (MHI) and its association of Glasgow Coma Scale (GCS) and structural abnormality. Materials and methods: We conducted a prospective cross-sectional study from May 2018 to October 2019 in the Department of Emergency Medicine, Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla, Kerala. The CCHR is applied to patients with MHIs (GCS 13-15) after initial stabilization and it is ascertained, if they require a non-contrast CT head and imaging is done. For those who do not require CT head as per the CCHR are excluded from this study. After imaging the patients who have a positive finding on CT head are admitted and followed up if they underwent any neurosurgical intervention, those with no findings in CT head are discharged from the hospital. A total of 203 patients were included during study period. Results: A total of 203 patients were included in study with mean age of 49.5 years. Approximately, 70% (142) were male. Sensitivity of CCHR for predicting positive CT finding in the present study sample was 68% and specificity was 42.5%. Conclusion: Canadian CT head rule is a useful tool in the Emergency Department for predicting the requirement of CT in patients with MHI. Canadian CT head rule can reduce the number of CT scans ordered following MHI in ED, thus improving the healthcare costs. How to cite this article: Reddy A, Poonthottathil F, Jonnakuti R, Thomas R. Efficacy of the Canadian CT Head Rule in Patients Presenting to the Emergency Department with Minor Head Injury. Indian J Crit Care Med 2024;28(2):148-151.

Defining and Improving Outcomes Measurement for Virtual Care: Report from the VHA State-of-the-Art Conference on Virtual Care.

Virtual care, including synchronous and asynchronous telehealth, remote patient monitoring, and the collection and interpretation of patient-generated health data (PGHD), has the potential to transform healthcare delivery and increase access to care. The Veterans Health Administration (VHA) Office of Health Services Research and Development (HSR&D) convened a State-of-the-Art (SOTA) Conference on Virtual Care to identify future virtual care research priorities. Participants were divided into three workgroups focused on virtual care access, engagement, and outcomes. In this article, we report the findings of the Outcomes Workgroup. The group identified virtual care outcome areas with sufficient evidence, areas in need of additional research, and areas that are particularly well-suited to be studied within VHA. Following a rigorous process of literature review and consensus, the group focused on four questions: (1) What outcomes of virtual care should we be measuring and how should we measure them?; (2) how do we choose the "right" care modality for the "right" patient?; (3) what are potential consequences of virtual care on patient safety?; and (4) how can PGHD be used to benefit provider decision-making and patient self-management?. The current article outlines key conclusions that emerged following discussion of these questions, including recommendations for future research.

Automated Reminders Enhance Mailed Fecal Immunochemical Test Completion Among Veterans: a Randomized Controlled Trial.

BACKGROUND: The Veterans Affairs (VHA) is working to establish a population-based colorectal cancer screening program for average-risk patients using mailed fecal immunochemical testing (FIT). However, low response rates to mailed FIT may hinder success. Key features of mailed FIT programs, including the use of reminders, differ among various national programs, with limited evidence among veterans. OBJECTIVE: We sought to test whether using reminders, either via telephone call or text message, was effective in improving mailed FIT response rates. DESIGN: We conducted a prospective, randomized quality improvement trial ( ClinicalTrials.gov NCT05012007). Veterans who had not returned a FIT within 2 weeks of receiving the kit were randomized to one of three groups: (1) control (no reminder); (2) an automated telephone call reminder; or (3) an automated text message reminder. PARTICIPANTS: A total of 2658 veterans enrolled at VA Puget Sound Health Care System who were aged 45-75 and had an average risk of colorectal cancer. INTERVENTIONS: A single automated telephone call or text message reminder prompting veterans to return the FIT kit. MAIN MEASURES: Our primary outcome was FIT return at 90 days and our secondary outcome was FIT return at 180 days. KEY RESULTS: Participant average age was 62 years, 88% were men, and 66% White. At 90 days, both the phone and text reminder interventions had higher FIT return rates compared to control (intention-to-treat results (ITT): control 28%, phone 39%, text 38%; p<0.001). At 180 days, FIT kit return remained higher in the reminder interventions (ITT: control 32%, phone 42%, text 40%; p<0.001). CONCLUSIONS: Automated reminders increased colorectal cancer screening completion among average-risk veterans. An automated phone call or text message was equally effective. VHA facilities seeking to implement a mailed FIT program should consider using phone or text reminders, depending on available resources.

The amniotic fluid proteome changes across gestation in humans and rhesus macaques.

Amniotic fluid is a complex biological medium that offers protection to the fetus and plays a key role in normal fetal nutrition, organogenesis, and potentially fetal programming. Amniotic fluid is also critically involved in longitudinally shaping the in utero milieu during pregnancy. Yet, the molecular mechanism(s) of action by which amniotic fluid regulates fetal development is ill-defined partly due to an incomplete understanding of the evolving composition of the amniotic fluid proteome. Prior research consisting of cross-sectional studies suggests that the amniotic fluid proteome changes as pregnancy advances, yet longitudinal alterations have not been confirmed because repeated sampling is prohibitive in humans. We therefore performed serial amniocenteses at early, mid, and late gestational time-points within the same pregnancies in a rhesus macaque model. Longitudinally-collected rhesus amniotic fluid samples were paired with gestational-age matched cross-sectional human samples. Utilizing LC-MS/MS isobaric labeling quantitative proteomics, we demonstrate considerable cross-species similarity between the amniotic fluid proteomes and large scale gestational-age associated changes in protein content throughout pregnancy. This is the first study to compare human and rhesus amniotic fluid proteomic profiles across gestation and establishes a reference amniotic fluid proteome. The non-human primate model holds promise as a translational platform for amniotic fluid studies.

Automated Opt-Out vs Opt-In Patient Outreach Strategies for Breast Cancer Screening: A Randomized Clinical Trial.

Importance: Optimal strategies for population-based outreach for breast cancer screening remain unknown. Objective: To evaluate the effect on breast cancer screening of an opt-out automatic mammography referral strategy compared with an opt-in automated telephone message strategy. Design, Setting, and Participants: This pragmatic randomized clinical trial was conducted from April 2022 to January 2023 at a single Veterans Affairs (VA) medical center. Participants were female veterans aged 45 to 75 years who were eligible for breast cancer screening and enrolled in VA primary care. Intervention: Veterans were randomized 1:1 to receive either an automatic mammography referral (opt-out arm) or an automated telephone call with an option for mammography referral (opt-in arm). Main Outcomes and Measures: The primary outcome was completed mammography 100 days after outreach. Secondary outcomes were scheduled or completed mammography by 100 days after outreach and referrals canceled if mammography was not scheduled within 90 days. Both intention-to-treat analyses and a restricted analysis were conducted. The restricted analysis excluded veterans who were unable to be reached by telephone (eg, a nonworking number) or who were found to be ineligible after randomization (eg, medical record documentation of recent mammography). Results: Of 883 veterans due for mammography (mean [SD] age, 59.13 [8.24] years; 656 [74.3%] had received prior mammography), 442 were randomized to the opt-in group and 441 to the opt-out group. In the intention-to-treat analysis, there was no significant difference in the primary outcome of completed mammography at 100 days between the opt-out and opt-in groups (67 [15.2%] vs 66 [14.9%]; P = .90) or the secondary outcome of completed or scheduled mammography (84 [19%] vs 106 [24.0%]; P = .07). A higher number of referrals were canceled in the opt-out group compared with the opt-in group (104 [23.6%] vs 24 [5.4%]; P < .001). The restricted analysis demonstrated similar results except more veterans completed or scheduled mammography within 100 days in the opt-out group compared with the opt-in group (102 of 388 [26.3%] vs 80 of 415 [19.3%]; P = .02). Conclusions and Relevance: In this randomized clinical trial, an opt-out population-based breast cancer screening outreach approach compared with an opt-in approach did not result in a significant difference in mammography completion but did lead to substantially more canceled mammography referrals, increasing staff burden. Trial Registration: ClinicalTrials.gov Identifier: NCT05313737.

Unraveling the role of TGFß signaling in thoracic aortic aneurysm and dissection using Fbn1 mutant mouse models.

Although abnormal TGFß signaling is observed in several heritable forms of thoracic aortic aneurysms and dissections including Marfan syndrome, its precise role in aortic disease progression is still disputed. Using a mouse genetic approach and quantitative isobaric labeling proteomics, we sought to elucidate the role of TGFß signaling in three Fbn1 mutant mouse models representing a range of aortic disease from microdissection (without aneurysm) to aneurysm (without rupture) to aneurysm and rupture. Results indicated that reduced TGFß signaling and increased mast cell proteases were associated with microdissection. In contrast, increased abundance of extracellular matrix proteins, which could be reporters for positive TGFß signaling, were associated with aneurysm. Marked reductions in collagens and fibrillins, and increased TGFß signaling, were associated with aortic rupture. Our data indicate that TGFß signaling performs context-dependent roles in the pathogenesis of thoracic aortic disease.

MicroRNA137-loaded lipid nanoparticles regulate synaptic proteins in the prefrontal cortex.

Genome-wide association studies indicate that allele variants in MIR137, the host gene of microRNA137 (miR137), confer an increased risk of schizophrenia (SCZ). Aberrant expression of miR137 and its targets, many of which regulate synaptic functioning, are also associated with an increased risk of SCZ. Thus, miR137 represents an attractive target aimed at correcting the molecular basis for synaptic dysfunction in individuals with high genetic risk for SCZ. Advancements in nanotechnology utilize lipid nanoparticles (LNPs) to transport and deliver therapeutic RNA. However, there remains a gap in using LNPs to regulate gene and protein expression in the brain. To study the delivery of nucleic acids by LNPs to the brain, we found that LNPs released miR137 cargo and inhibited target transcripts of interest in neuroblastoma cells. Biodistribution of LNPs loaded with firefly luciferase mRNA remained localized to the mouse prefrontal cortex (PFC) injection site without circulating to off-target organs. LNPs encapsulating Cre mRNA preferentially co-expressed in neuronal over microglial or astrocytic cells. Using quantitative proteomics, we found miR137 modulated glutamatergic synaptic protein networks that are commonly dysregulated in SCZ. These studies support engineering the next generation of brain-specific LNPs to deliver RNA therapeutics and improve symptoms of central nervous system disorders.

Learning from national implementation of the Veterans Affairs Clinical Resource Hub (CRH) program for improving access to care: protocol for a six year evaluation.

BACKGROUND: The Veterans Affairs (VA) Clinical Resource Hub (CRH) program aims to improve patient access to care by implementing time-limited, regionally based primary or mental health staffing support to cover local staffing vacancies. VA's Office of Primary Care (OPC) designed CRH to support more than 1000 geographically disparate VA outpatient sites, many of which are in rural areas, by providing virtual contingency clinical staffing for sites experiencing primary care and mental health staffing deficits. The subsequently funded CRH evaluation, carried out by the VA Primary Care Analytics Team (PCAT), partnered with CRH program leaders and evaluation stakeholders to develop a protocol for a six-year CRH evaluation. The objectives for developing the CRH evaluation protocol were to prospectively: 1) identify the outcomes CRH aimed to achieve, and the key program elements designed to achieve them; 2) specify evaluation designs and data collection approaches for assessing CRH progress and success; and 3) guide the activities of five geographically dispersed evaluation teams. METHODS: The protocol documents a multi-method CRH program evaluation design with qualitative and quantitative elements. The evaluation's overall goal is to assess CRH's return on investment to the VA and Veterans at six years through synthesis of findings on program effectiveness. The evaluation includes both observational and quasi-experimental elements reflecting impacts at the national, regional, outpatient site, and patient levels. The protocol is based on program evaluation theory, implementation science frameworks, literature on contingency staffing, and iterative review and revision by both research and clinical operations partners. DISCUSSION: Health systems increasingly seek to use data to guide management and decision-making for newly implemented clinical programs and policies. Approaches for planning evaluations to accomplish this goal, however, are not well-established. By publishing the protocol, we aim to increase the validity and usefulness of subsequent evaluation findings. We also aim to provide an example of a program evaluation protocol developed within a learning health systems partnership.

Characterization of extracellular matrix deposited by segmental trabecular meshwork cells.

PURPOSE: Biophysical and biochemical attributes of the extracellular matrix are major determinants of cell fate in homeostasis and disease. Ocular hypertension and glaucoma are diseases where the trabecular meshwork tissue responsible for aqueous humor egress becomes stiffer accompanied by changes in its matrisome in a segmental manner with regions of high or low flow. Prior studies demonstrate these alterations in the matrix are dynamic in response to age and pressure changes. The underlying reason for segmentation or differential response to pressure and stiffening are unknown. This is largely due to a lack of appropriate models (in vitro or ex vivo) to study this phenomena. METHODS: Primary trabecular meshwork cells were isolated from segmental flow regions, and cells were cultured for 4 weeks in the presence or absence or dexamethasone to obtain cell derived matrices (CDM). The biomechanical attributes of the CDM, composition of the matrisome, and incidence of crosslinks were determined by atomic force microscopy and mass spectrometry. RESULTS: Data demonstrate that matrix deposited by cells from low flow regions are stiffer and exhibit a greater number of immature and mature crosslinks, and that these are exacerbated in the presence of steroid. We also show a differential response of high or low flow cells to steroid via changes observed in the matrix composition. However, no correlations were observed between elastic moduli and presence or absence of mature and immature crosslinks in the CDMs. CONCLUSION: Regardless of a direct correlation between matrix stiffness and crosslinks, we observed distinct differences in the composition and mechanics of the matrices deposited by segmental flow cells. These results suggest distinct differences in cellular identify and likely a basis for mechanical memory post isolation and culture. Nevertheless, we conclude that although a mechanistic basis for matrix stiffness was undetermined in this study, it is a viable tool to study cell-matrix interactions and further our understanding of trabecular meshwork pathobiology.

A Postcard Primer Prior to Mailed Fecal Immunochemical Test Among Veterans: a Randomized Controlled Trial.

BACKGROUND: Mailed fecal immunochemical testing (FIT) programs are increasingly utilized for population-based colorectal cancer (CRC) screening. Advanced notifications (primers) are one behavioral designed feature of many mailed FIT programs, but few have tested this feature among Veterans. OBJECTIVE: To determine if an advanced notification, a primer postcard, increases completion of FIT among Veterans. DESIGN: This is a prospective, randomized quality improvement trial to evaluate a postcard primer prior to a mailed FIT versus mailed FIT alone. PARTICIPANTS: A total of 2404 Veterans enrolled for care at a large VA site that were due for average-risk CRC screening. INTERVENTION: A written postcard sent 2 weeks in advance of a mailed FIT kit that contained information on CRC screening and completing a FIT. MAIN MEASURES: Our primary outcome was FIT completion at 90 days, and our secondary outcome was FIT completion at 180 days. KEY RESULTS: Overall, unadjusted mailed FIT return rates were similar among control vs. primer arms at 90 days (27% vs. 29%, p = 0.11). Our adjusted analysis found a primer postcard did not increase FIT completion compared to mailed FIT alone (OR 1.14 (0.94, 1.37)). CONCLUSIONS: Though primers are often a standard part of mailed FIT programs, we did not find an increase in FIT completion with mailed postcard primers among Veterans. Given the overall low mailed FIT return rates, testing different ways to improve return rates is essential to improving CRC screening.

Proteomic profiling of retina and retinal pigment epithelium combined embryonic tissue to facilitate ocular disease gene discovery.

To expedite gene discovery in eye development and its associated defects, we previously developed a bioinformatics resource-tool iSyTE (integrated Systems Tool for Eye gene discovery). However, iSyTE is presently limited to lens tissue and is predominantly based on transcriptomics datasets. Therefore, to extend iSyTE to other eye tissues on the proteome level, we performed high-throughput tandem mass spectrometry (MS/MS) on mouse embryonic day (E)14.5 retina and retinal pigment epithelium combined tissue and identified an average of 3300 proteins per sample (n = 5). High-throughput expression profiling-based gene discovery approaches-involving either transcriptomics or proteomics-pose a key challenge of prioritizing candidates from thousands of RNA/proteins expressed. To address this, we used MS/MS proteome data from mouse whole embryonic body (WB) as a reference dataset and performed comparative analysis-termed "in silico WB-subtraction"-with the retina proteome dataset. In silico WB-subtraction identified 90 high-priority proteins with retina-enriched expression at stringency criteria of ≥ 2.5 average spectral counts, ≥ 2.0 fold-enrichment, false discovery rate < 0.01. These top candidates represent a pool of retina-enriched proteins, several of which are associated with retinal biology and/or defects (e.g., Aldh1a1, Ank2, Ank3, Dcn, Dync2h1, Egfr, Ephb2, Fbln5, Fbn2, Hras, Igf2bp1, Msi1, Rbp1, Rlbp1, Tenm3, Yap1, etc.), indicating the effectiveness of this approach. Importantly, in silico WB-subtraction also identified several new high-priority candidates with potential regulatory function in retina development. Finally, proteins exhibiting expression or enriched-expression in the retina are made accessible in a user-friendly manner at iSyTE ( https://research.bioinformatics.udel.edu/iSyTE/ ), to allow effective visualization of this information and facilitate eye gene discovery.

Identifying Individual and Clinic Characteristics Associated With Primary Care Provider Turnover During Implementation of the Veterans Health Administration Patient-Centered Medical Home.

Understanding which factors predict primary care provider (PCP) turnover can help organizations prepare for PCP shortages. We conducted a retrospective cohort study of Veteran Health Administration PCPs between 2012 and 2016. We analyzed whether 7 domains of the patient centered medical home (PCMH) implementation-including access, care coordination, comprehensiveness, self-management support, communication, shared decision-making, and team-based care-were associated with PCP turnover. We found that 2 domains of PCMH (access and self-management) were associated with lower turnover, which may reflect that practice cultures that support these characteristics may lower PCP turnover.