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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Phosphoproteomic quantitation and causal analysis reveal pathways in GPVI/ITAM-mediated platelet activation programs.

Platelets engage cues of pending vascular injury through coordinated adhesion, secretion, and aggregation responses. These rapid, progressive changes in platelet form and function are orchestrated downstream of specific receptors on the platelet surface and through intracellular signaling mechanisms that remain systematically undefined. This study brings together cell physiological and phosphoproteomics methods to profile signaling mechanisms downstream of the immunotyrosine activation motif (ITAM) platelet collagen receptor GPVI. Peptide tandem mass tag (TMT) labeling, sample multiplexing, synchronous precursor selection (SPS), and triple stage tandem mass spectrometry (MS3) detected >3000 significant (false discovery rate < 0.05) phosphorylation events on >1300 proteins over conditions initiating and progressing GPVI-mediated platelet activation. With literature-guided causal inference tools, >300 site-specific signaling relations were mapped from phosphoproteomics data among key and emerging GPVI effectors (ie, FcRγ, Syk, PLCγ2, PKCδ, DAPP1). Through signaling validation studies and functional screening, other less-characterized targets were also considered within the context of GPVI/ITAM pathways, including Ras/MAPK axis proteins (ie, KSR1, SOS1, STAT1, Hsp27). Highly regulated GPVI/ITAM targets out of context of curated knowledge were also illuminated, including a system of >40 Rab GTPases and associated regulatory proteins, where GPVI-mediated Rab7 S72 phosphorylation and endolysosomal maturation were blocked by TAK1 inhibition. In addition to serving as a model for generating and testing hypotheses from omics datasets, this study puts forth a means to identify hemostatic effectors, biomarkers, and therapeutic targets relevant to thrombosis, vascular inflammation, and other platelet-associated disease states.

Home Telehealth in the Veterans Health Administration: Trends and Correlates of Length of Enrollment from 2010 to 2017.

BACKGROUND: Home telehealth (HT) programs enable communication and remote monitoring of patient health data between clinician visits, with the goal of improving chronic disease self-management and outcomes. The Veterans Health Administration (VHA) established one of the earliest HT programs in the country in 2003; however, little is known about how these services have been utilized and expanded over the last decade. OBJECTIVE: To describe trends in use of VHA's HT program from 2010 through 2017 and correlates of length of enrollment in HT services. DESIGN: Retrospective observational cohort study. PARTICIPANTS: Patients enrolled in HT between January 1, 2010 and December 31, 2017. MAIN MEASURES: We described the number and characteristics of patients enrolled in HT, including the chronic conditions managed. We also identified length of HT enrollment and examined patient and facility characteristics associated with longer enrollment. KEY RESULTS: The total number of patients enrolled in HT was 402,263. At time of enrollment, half were >65 years old, 91% were male, and 59.3% lived in urban residences. The most common conditions addressed by HT were hypertension (28.8%), obesity (23.9%), and diabetes (17.0%). The median time to disenrollment in HT was 261 days (8.6 months) but varied by chronic condition. In a multivariable Cox proportional hazards model, covariates associated with higher likelihood of staying enrolled were older age, male gender, non-Hispanic Black race/ethnicity, lower neighborhood socioeconomic status, living in a more rural setting, and a greater burden of comorbidities per the Gagne index. CONCLUSIONS: Across 8 years, over 400,000 veterans engaged in HT services for chronic disease management and over half remained in the program for longer than 8 months. Our work provides a real-world evaluation of HT service expansion in the VHA. Additional studies are necessary to identify optimal enrollment duration and patients most likely to benefit from HT services.

Identifying and Prioritizing Workplace Climate Predictors of Burnout Among VHA Primary Care Physicians.

OBJECTIVE: Burnout, or job-related stress, affects more than half of all US physicians, with primary care physicians (PCPs) experiencing some of the highest rates in medicine. Our study analyzes national survey data to identify and prioritize workplace climate predictors of burnout among PCPs within a large integrated health system. DESIGN: Observational study of annual survey data from the Veterans Health Administration (VHA) All Employee Survey (AES) for 2013-2017. AES response rate ranged from 56 to 60% during the study period. Independent and dependent variables were measured from separate random samples. In total, 8,456 individual-level responses among PCPs at 110 VHA practice sites were aggregated at the facility level by reporting year. We used the semi-automated LASSO procedure to identify workplace climate measures that were more influential in predicting burnout and assessed relative importance using the Shapely value decomposition. PARTICIPANTS: VHA employees that self-identify as PCPs. MAIN MEASURES: Dependent variables included two dichotomous measures of burnout: emotional exhaustion and depersonalization. Independent measures included 30 survey measures related to dimensions of workplace climate (e.g., workload, leadership, satisfaction). RESULTS: We identified seven influential workplace climate predictors of emotional exhaustion and nine predictors of depersonalization. With few exceptions, higher agreement/satisfaction scores for predictors were associated with a lower likelihood of burnout. The majority of explained variation in emotional exhaustion was attributable to perceptions of workload (32.6%), organization satisfaction (28.2%), and organization support (19.4%). The majority of explained variation in depersonalization was attributable to workload (25.3%), organization satisfaction (22.9%), and connection to VHA mission (20.7%). CONCLUSION: Identifying the relative importance of workplace climate is important for the allocation of health organization resources to mitigate and prevent burnout within the PCP workplace. In a context of limited resources, efforts to reduce perceived workload and improve organization satisfaction may represent the biggest leverage points for health organizations to address physician burnout.

Platelet proteome dynamics in hibernating 13-lined ground squirrels.

Hibernating mammals undergo a dramatic drop in temperature and blood flow during torpor, yet avoid stasis blood clotting through mechanisms that remain unspecified. The effects of hibernation on hemostasis are especially complex, as cold temperatures generally activate platelets, resulting in platelet clearance and cold storage lesions in the context of blood transfusion. With a hibernating body temperature of 4°C-8°C, 13-lined ground squirrels (Ictidomys tridecemlineatus) provide a model to study hemostasis as well as platelet cold storage lesion resistance during hibernation. Here, we quantified and systematically compared proteomes of platelets collected from ground squirrels at summer (active), fall (entrance), and winter (topor) to elucidate how molecular-level changes in platelets may support hemostatic adaptations in torpor. Platelets were isolated from a total of 11 squirrels in June, October, and January. Platelet lysates from each animal were digested with trypsin prior to 11-plex tandem mass tag (TMT) labeling, followed by LC-MS/MS analysis for relative protein quantification. We measured >700 proteins with significant variations in abundance in platelets over the course of entrance, torpor, and activity-including systems of proteins regulating translation, secretion, metabolism, complement, and coagulation cascades. We also noted species-specific differences in levels of hemostatic, secretory, and inflammatory regulators in ground squirrel platelets relative to human platelets. Altogether, we provide the first ever proteomic characterization of platelets from hibernating animals, where systematic changes in metabolic, hemostatic, and other proteins may account for physiological adaptations in torpor and also inform translational effort to improve cold storage of human platelets for transfusion.

Saturation oxygenation pressure index: a non-invasive bedside measure for severity of respiratory disease in neonates on CPAP.

The treatment of respiratory distress in neonates ranges from non-invasive continuous positive airway pressure (CPAP) to advanced invasive mechanical ventilation. Monitoring on CPAP is often done by calculating oxygenation after blood gas analysis which is an invasive procedure. Saturation oxygen pressure index (SOPI) is a simple, non-invasive, bedside tool to monitor the severity of respiratory illness in neonates on CPAP. This study was aimed at validation of SOP index against AaDO2 and determine the cut-off values of SOPI for A-aDO2 of 70, 85 and100. This was a prospective observational study on 126 neonates with respiratory distress and treated with CPAP. The correlation between SOPI and A-aDO2 was validated using Bootstrap method. There was a significant positive correlation between SOPI and A-aDO2 with the Spearman correlation coefficient (rho) being 0.815 (p = 0). The mean coefficient of correlation after Bootstrap was 0.827 (p value < 0.0001). SOPI values of 1.52, 1.57 and 1.6 predicted A-aDO2 value of 70, 85 and 100 with a sensitivity of above 80% and specificity above 90%, respectively.Conclusion: SOPI has a significant positive correlation of 82.7% against A-aDO2 and can be a valuable tool to assess respiratory distress in neonates without arterial blood gas. What is Known: • Saturation oxygen pressure index (SOPI) is a non-invasive monitoring tool for neonates on N-CPAP. • SOPI has a good correlation with AaDO2. What is New: • Correlation of SOPI with AaDO2 is now validated. • Values between 1.52 and 1.88 indicate clinically useful range of AaDO2 for escalation of respiratory support from CPAP.

MS/MS in silico subtraction-based proteomic profiling as an approach to facilitate disease gene discovery: application to lens development and cataract.

While the bioinformatics resource-tool iSyTE (integrated Systems Tool for Eye gene discovery) effectively identifies human cataract-associated genes, it is currently based on just transcriptome data, and thus, it is necessary to include protein-level information to gain greater confidence in gene prioritization. Here, we expand iSyTE through development of a novel proteome-based resource on the lens and demonstrate its utility in cataract gene discovery. We applied high-throughput tandem mass spectrometry (MS/MS) to generate a global protein expression profile of mouse lens at embryonic day (E)14.5, which identified 2371 lens-expressed proteins. A major challenge of high-throughput expression profiling is identification of high-priority candidates among the thousands of expressed proteins. To address this problem, we generated new MS/MS proteome data on mouse whole embryonic body (WB). WB proteome was then used as a reference dataset for performing "in silico WB-subtraction" comparative analysis with the lens proteome, which effectively identified 422 proteins with lens-enriched expression at ≥ 2.5 average spectral counts, ≥ 2.0 fold enrichment (FDR < 0.01) cut-off. These top 20% candidates represent a rich pool of high-priority proteins in the lens including known human cataract-linked genes and many new potential regulators of lens development and homeostasis. This rich information is made publicly accessible through iSyTE (https://research.bioinformatics.udel.edu/iSyTE/), which enables user-friendly visualization of promising candidates, thus making iSyTE a comprehensive tool for cataract gene discovery.

Events Associated With Changes in Reliance on the Veterans Health Administration Among Medicare-eligible Veterans.

OBJECTIVES: We can learn something about how Veterans value the Veterans Health Administration (VHA) versus community providers by observing Veterans' choices between VHA and Medicare providers after they turn 65. For a cohort of Veterans who were newly age-eligible for Medicare, we estimated the change in VHA reliance (VHA outpatient visits divided by total VHA and Medicare visits) associated with specific events: receiving a life-threatening diagnosis, having a Medicare-paid hospitalization, or moving further from the VHA. RESEARCH DESIGN: A longitudinal cohort study of VHA and Medicare administrative data. SUBJECTS: A total of 5932 VHA users who completed a health survey in 1999 and became age-eligible for Medicare from 1998 to 2000 were followed through 2016. PRINCIPAL FINDINGS: More Veterans chose to rely on the VHA than Medicare (64% vs. 36.%). For a VHA-reliant Veteran, a Medicare-paid hospital stay was associated with a decrease of 7.8 percentage points (pps) (P<0.001) in VHA reliance in the subsequent 12 months, but by 36 months reliance increased to near prehospitalization levels (-1.5 pps; P=0.138). Moving further from the VHA, or receiving a diagnosis of cancer, heart failure, or renal failure had no significant association with subsequent VHA reliance; however, a diagnosis of dementia was associated with a decrease in VHA reliance (-8.6 pps; P=0.026). CONCLUSIONS: A significant majority of newly Medicare-eligible VHA users voted with their feet in favor of sustaining the VHA as a provider of comprehensive medical care for Veterans. These VHA-reliant Veterans maintained their reliance even after receiving a life-threatening diagnosis, and after experiencing Medicare-provided hospital care.

Association of the Patient-Centered Medical Home Implementation with Chronic Disease Quality in Patients with Multimorbidity.

BACKGROUND: The patient-centered medical home (PCMH) was established in part to improve chronic disease management, yet evidence is limited for effects on patients with multimorbidity. OBJECTIVE: To examine the association of Patient-Aligned Care Team (PACT) implementation, the Veterans Health Administration (VA) PCMH model, and care quality for multimorbid patients enrolled in VA primary care from 2012 to 2014. DESIGN: Retrospective cohort. PATIENTS: 318,764 multimorbid (> 3 chronic diseases) patients receiving care in 917 clinics. MAIN MEASURES: PCMH implementation was measured using the PACT Implementation Progress Index (PI2) for clinics in 2012. The PI2 is a validated composite measure of administrative and survey data with higher scores associated with greater care quality. Quality outcomes from 2013 to 2014 were assessed from External Peer Review Program (EPRP) metrics. Outcomes included preventative care, chronic disease management, and mental health and substance use metrics. We used generalized estimating equations to model associations adjusting for patient and clinic characteristics. We also examined associations for a subgroup with > 5 chronic diseases. KEY RESULTS: For one-third of metrics (5/15), greater implementation of PACT in 2012 was associated with higher predicted probability of meeting the quality metric in 2013-2014. This association persisted for only two metrics (diabetic glycemic control, P < 0.001; lipid control in ischemic heart disease, P = 0.02) among patients with > 5 chronic diseases. CONCLUSIONS: Multimorbid patients engaged in care from clinics with higher PCMH implementation received higher quality care across several quality domains, but this association was reduced in patients with > 5 chronic diseases.

Association of the Implementation of the Patient-Centered Medical Home with Quality of Life in Patients with Multimorbidity.

BACKGROUND: The patient-centered medical home (PCMH) has clinical benefits for chronic disease care, but the association with patient-reported outcomes such as health-related quality of life (HRQoL) is unexplored in patients with multimorbidity (two or more chronic diseases). OBJECTIVE: To examine if greater clinic-level PCMH implementation was associated with higher HRQoL in multimorbid adults. DESIGN: A retrospective cohort study. PARTICIPANTS: Twenty-two thousand ninety-five multimorbid patients who received primary care at 944 Veterans Health Administration (VHA) clinics. MAIN MEASURES: Our exposure was the Patient Aligned Care Team Implementation Progress Index (PI2) for the clinic in 2012, a previously validated composite measure of PCMH implementation. Higher PI2 scores indicate better performance within eight PCMH domains. Outcomes were patient-reported HRQoL measured by the physical and mental component scores (PCS and MCS) from the Short Form-12 patient experiences survey in 2013-2014. Interaction of the outcomes with total hospitalizations and primary care visit count was also examined. Generalized estimating equations were used for main models after adjusting for patient and clinic characteristics. RESULTS: The cohort average age was 68 years, mostly male (96%), and had an average of 4.4 chronic diagnoses. Compared with patients seen at the lowest scoring clinics for PCMH implementation, care in the highest scoring clinics was associated with a higher adjusted marginal mean PCS (42.3 (95% CI 41.3-43.4) versus 40.3 (95% CI 39.1-41.5), P = 0.01), but a lower MCS (35.2 (95% CI 34.4-36.1) versus 36.0 (95% CI 35.3-36.8), P = 0.17). Patients with prior hospitalizations seen in clinics with higher compared with lower PI2 scores had a 2.7 point greater MCS (95% CI 0.6-4.8; P = 0.01). CONCLUSIONS: Multimorbid patients seen in clinics with greater PCMH implementation reported higher physical HRQoL, but lower mental HRQoL. The association between PCMH implementation and mental HRQoL may depend on complex interactions with disease severity and prior hospitalizations.

Use of Chronic Care Management Among Primary Care Clinicians.

The Centers for Medicare and Medicade Services (CMS) initiated chronic care management (CCM) codes to reimburse clinicians for coordination activities, but little is known about uptake over time. We find that primary care clinicians drove increasing use over 4 years-a trend that may reflect either new coordination activities or new reimbursements for existing activities. That 5% of chronic care management was denied by Medicare underscores the need for future work evaluating facilitators and barriers to use. Such insight is especially vital given the large number of eligible beneficiaries that have not received chronic care management to date, as well as the limited number of clinicians who currently deliver these services.