Chronic Disease Management through Clinical Video Telehealth on Health Care Utilization, and Mortality in the Veterans Health Administration: A Retrospective Cohort Study.

Background: Chronic health diseases such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DM) affect 6 in 10 Americans and contribute to 90% of the $4.1 trillion health care expenditures. The objective of this study was to measure the effect of clinical video telehealth (CVT) on health care utilization and mortality. A retrospective cohort study of Veterans ≥65 years with CHF, COPD, or DM was conducted. Measures: Veterans using CVT were matched 1:3 on demographic characteristics to Veterans who did not use CVT. Outcomes included 1-year incidence of ED visits, inpatient admissions, and mortality, reported as adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: Final analytical cohorts included 22,280 Veterans with CHF, 51,872 Veterans with COPD, and 170,605 Veterans with DM. CVT utilization was associated with increased ED visits for CHF (aOR: 1.24; 95% CI: 1.15-1.34), COPD (aOR: 1.20; 95% CI: 1.14-1.26), and DM (aOR: 1.07; 95% CI: 1.00-1.10). For CHF, there was no difference between CVT utilization and inpatient admissions (aOR: 0.98; 95% CI 0.91-1.05) or mortality (aOR: 1.03; 95% CI: 0.93-1.15). For COPD, CVT was associated with increased inpatient admissions (aOR: 1.08; 95% CI: 1.02-1.13) and mortality (aOR: 1.36; 95% CI: 1.25-1.48). For DM, CVT utilization was associated with lower risk of inpatient admissions (aOR: 0.83; 95% CI: 0.80-0.86) and mortality (aOR: 0.89; 95% CI: 0.84-0.95). Conclusions: CVT use as an alternative care site might serve as an early warning system, such that this mechanism may indicate when an in-person assessment is needed for potential exacerbation of conditions. Although inpatient and mortality varied, ED utilization was higher with CVT. Exploring pathways accessing clinical care through CVT, and how CVT is directly or indirectly associated with immediate and long-term clinical outcomes would be valuable.

National Survey of the Bone Densitometry Evaluation Process Within an Integrated Healthcare System.

BACKGROUND: To assess the current state of bone mineral density evaluation services via dual energy x-ray absorptiometry (DXA) provided to Veterans with fracture risk through the development and administration of a nationwide survey of facilities in the Veterans Health Administration. METHODOLOGY: The Bone Densitometry Survey was developed by convening a Work Group of individuals with expertise in bone densitometry and engaging the Work Group in an iterative drafting and revision process. Once completed, the survey was beta tested, administered through REDCap, and sent via e-mail to points of contact at 178 VHA facilities. RESULTS: Facility response rate was 31 % (56/178). Most DXA centers reported positively to markers of readiness for their bone densitometers: less than 10 years old (n=35; 63 %); in "excellent" or "good" condition (n=44; 78 %, 32 % and 46 %, respectively); and perform phantom calibration (n=43; 77 %). Forty-one DXA centers (73 %) use intake processes that have been shown to reduce errors. Thirty-seven DXA centers (66 %) reported their technologists receive specialized training in DXA, while 14 (25 %) indicated they receive accredited training. Seventeen DXA centers (30 %) reported performing routine precision assessment. CONCLUSIONS: Many DXA centers reported using practices that meet minimal standards for DXA reporting and preparation; however, the lack of standardization, even within an integrated healthcare system, indicates an opportunity for quality improvement to ensure consistent high quality bone mineral density evaluation of Veterans.

Secure Messaging Intervention in Patients Starting New Antidepressant to Promote Adherence: Pilot Randomized Controlled Trial.

BACKGROUND: There are a range of effective pharmacological and behavioral treatments for depression. However, approximately one-third of patients discontinue antidepressants within the first month of treatment and 44% discontinue them by the third month of treatment. The major reasons reported for discontinuation were side effect burden, patients experiencing that the medications were not working, and patients wanting to resolve their depression without using medication. OBJECTIVE: This study tested the acceptability, feasibility, and preliminary effectiveness of an SMS messaging intervention designed to improve antidepressant adherence and depression outcomes in veterans. The intervention specifically targeted the key reasons for antidepressant discontinuation. For example, the secure message included reminders that it can take up to 6 weeks for an antidepressant to work, or prompts to call their provider should the side effect burden become significant. METHODS: This pilot was a 3-armed randomized controlled trial of 53 veterans undergoing depression treatment at the Iowa City Veterans Affairs Health Care System. Veterans starting a new antidepressant were randomized to secure messaging only (SM-Only), secure messaging with coaching (SM+Coach), or attention control (AC) groups. The intervention lasted 12 weeks with follow-up assessments of key outcomes at 6 and 12-weeks. This included a measure of antidepressant adherence, depressive symptom severity, and side effect burden. RESULTS: The 2 active interventions (SM-Only and SM+Coach) demonstrated small to moderate effect sizes (ESs) in improving antidepressant adherence and reducing side effect burden. They did not appear to reduce the depressive symptom burden any more than in the AC arm. Veteran participants in the SM arms demonstrated improved medication adherence from baseline to 12 weeks on the Medication Adherence Rating Scale compared with those in the AC arm, who had a decline in adherence (SM-Only: ES=0.09; P=.19; SM+Coach: ES=0.85; P=.002). Depression scores on the 9-Item Patient Health Questionnaire decreased for all 3 treatment arms, although the decline was slightly larger for the SM-Only (ES=0.32) and the SM+Coach (ES=0.24) arms when compared with the AC arm. The 2 intervention arms indicated a decrease in side effects on the Frequency, Intensity, and Burden of Side Effects Ratings, whereas the side effect burden for the AC arm increased. These differences indicated moderate ES (SM-Only vs AC: ES=0.40; P=.07; SM+Coach: ES=0.54; P=.07). CONCLUSIONS: A secure messaging program targeting specific reasons for antidepressant discontinuation had small-to-moderate ES in improving medication adherence. Consistent with prior research, the intervention that included brief synchronic meetings with a coach appeared to have a greater benefit than the SMS-alone intervention. Veterans consistently engaged with the SMS messaging in both treatment arms throughout the study period. They additionally provided feedback on which texts were most helpful, tending to prefer messages providing overall encouragement rather than specific wellness recommendations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03930849; https://clinicaltrials.gov/study/NCT03930849.

Fabrication of Protein Macromolecular Frameworks (PMFs) and Their Application in Catalytic Materials.

The construction of three-dimensional (3D) array materials from nanoscale building blocks has drawn significant interest because of their potential to exhibit collective properties and functions arising from the interactions between individual building blocks. Protein cages such as virus-like particles (VLPs) have distinct advantages as building blocks for higher-order assemblies because they are extremely homogeneous in size and can be engineered with new functionalities by chemical and/or genetic modification. In this chapter, we describe a protocol for constructing a new class of protein-based superlattices, called protein macromolecular frameworks (PMFs). We also describe an exemplary method to evaluate the catalytic activity of enzyme-enclosed PMFs, which exhibit enhanced catalytic activity due to the preferential partitioning of charged substrates into the PMF.

Effect of Chronic Disease Home Telehealth Monitoring in the Veterans Health Administration on Healthcare Utilization and Mortality.

BACKGROUND: The high prevalence of chronic diseases, including congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DM), accounts for a large burden of cost and poor health outcomes in US hospitals, and home telehealth (HT) monitoring has been proposed to improve outcomes. OBJECTIVE: To measure the association between HT initiation and 12-month inpatient hospitalizations, emergency department (ED) visits, and mortality in veterans with CHF, COPD, or DM. DESIGN: Comparative effectiveness matched cohort study. PATIENTS: Veterans aged 65 years and older treated for CHF, COPD, or DM. MAIN MEASURES: We matched veterans initiating HT with veterans with similar demographics who did not use HT (1:3). Our outcome measures included a 12-month risk of inpatient hospitalization, ED visits, and all-cause mortality. KEY RESULTS: A total of 139,790 veterans with CHF, 65,966 with COPD, and 192,633 with DM were included in this study. In the year after HT initiation, the risk of hospitalization was not different in those with CHF (adjusted odds ratio [aOR] 1.01, 95% confidence interval [95%CI] 0.98-1.05) or DM (aOR 1.00, 95%CI 0.97-1.03), but it was higher in those with COPD (aOR 1.15, 95%CI 1.09-1.21). The risk of ED visits was higher among HT users with CHF (aOR 1.09, 95%CI 1.05-1.13), COPD (1.24, 95%CI 1.18-1.31), and DM (aOR 1.03, 95%CI 1.00-1.06). All-cause 12-month mortality was lower in those initiating HT monitoring with CHF (aOR 0.70, 95%CI 0.67-0.73) and DM (aOR 0.79, 95%CI 0.75-0.83), but higher in COPD (aOR 1.08, 95%CI 1.00-1.16). CONCLUSIONS: The initiation of HT was associated with increased ED visits, no change in hospitalizations, and lower all-cause mortality in patients with CHF or DM, while those with COPD had both higher healthcare utilization and all-cause mortality.

Engagement in Primary Prevention Program among Rural Veterans With Osteoporosis Risk.

A primary osteoporosis prevention program using a virtual bone health team (BHT) was implemented to comanage the care of rural veterans in the Mountain West region of the United States. The BHT identified, screened, and treated rural veterans at risk for osteoporosis using telephone and United States Postal Service communications. Eligibility was determined by regular use of Veterans Health Administration primary care, age 50 or older, and evidence of fracture risk. This study was conducted to identify demographic and clinical factors associated with the acceptance of osteoporosis screening and the initiation of medication where indicated. A cross-sectional cohort design (N = 6985) was utilized with a generalized estimating equation and logit link function to account for facility-level clustering. Fully saturated and reduced models were fitted using backward selection. Less than a quarter of eligible veterans enrolled in BHT's program and completed screening. Factors associated with a lower likelihood of clinic enrollment included being of older age, unmarried, greater distance from VHA services, having a copayment, prior fracture, or history of rheumatoid arthritis. A majority of veterans with treatment indication started medication therapy (N = 453). In this subpopulation, Fisher's exact test showed a significant association between osteoporosis treatment uptake and a history of two or more falls in the prior year, self-reported parental history of fracture, current smoking, and weight-bearing exercise. The BHT was designed to reduce barriers to screening; however, for this population cost and travel continue to limit engagement. The remarkable rate of medication initiation notwithstanding, low enrollment reduces the impact of this primary prevention program, and findings pertaining to fracture, smoking, and exercise imply that health beliefs are an important contributing factor. Efforts to identify and address barriers to osteoporosis screening and treatment, such as clinical factors, social determinants of health, and health beliefs, may pave the way for effective implementation of population bone health care delivery systems. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Evaluation of a Test to Stay Strategy in Transitional Kindergarten Through Grade 12 Schools - Los Angeles County, California, August 16-October 31, 2021.

On July 12, 2021, the California Department of Public Health updated COVID-19 school guidance, allowing a Test to Stay (TTS) strategy to increase access to in-person learning* (1). The TTS strategy enabled unvaccinated students, exposed in school to a person infected with SARS-CoV-2 (the virus that causes COVID-19), to remain in school while under quarantine, if both the infected person and the exposed person wore masks correctly and consistently throughout the exposure. To stay in school during the quarantine period, the exposed student must remain asymptomatic, wear a mask at school, and undergo twice weekly testing for SARS-CoV-2. To date, few studies have evaluated the impact of TTS on transmission (2-4). This study evaluated a TTS strategy implemented by Los Angeles County Department of Public Health (LAC DPH). During September 20-October 31, 2021, among 78 school districts, one half permitted TTS; in total, 432 (21%) of 2,067 schools adopted TTS. TTS schools did not experience increases in COVID-19 incidence among students after TTS implementation, and in 20 identified outbreaks in TTS schools,† no tertiary transmission was identified. The ratio of student COVID-19 incidence in TTS districts to that in non-TTS districts was similar before and after TTS adoption (rate ratio = 0.5). Non-TTS schools lost an estimated 92,455 in-person school days during September 20-October 31 while students were in quarantine, compared with no lost days among quarantined students in TTS schools. Non-TTS schools cited resource-related reasons for not adopting TTS; 75% of these schools were in LAC's most disadvantaged neighborhoods. Preliminary data from LAC suggest that a school-based TTS strategy does not increase school transmission of SARS-CoV-2, and might greatly reduce loss of in-person school days; however, TTS might have barriers to implementation and require resources that are not available for some schools. Continued efforts to simplify school quarantine strategies might help to ensure that all students have access to safe in-person education. Although vaccination remains the leading public health recommendation to protect against COVID-19 for persons aged ≥5 years, schools might consider TTS as an option for allowing students with a school exposure who are not fully vaccinated to remain in the classroom as an alternative to home quarantine.

Delivering fracture prevention services to rural US veterans through telemedicine: a process evaluation.

An informatics-driven population bone health clinic was implemented to identify, screen, and treat rural US Veterans at risk for osteoporosis. We report the results of our implementation process evaluation which demonstrated BHT to be a feasible telehealth model for delivering preventative osteoporosis services in this setting. PURPOSE: An established and growing quality gap in osteoporosis evaluation and treatment of at-risk patients has yet to be met with corresponding clinical care models addressing osteoporosis primary prevention. The rural bone health tea m (BHT) was implemented to identify, screen, and treat rural Veterans lacking evidence of bone health care and we conducted a process evaluation to understand BHT implementation feasibility. METHODS: For this evaluation, we defined the primary outcome as the number of Veterans evaluated with DXA and a secondary outcome as the number of Veterans who initiated prescription therapy to reduce fracture risk. Outcomes were measured over a 15-month period and analyzed descriptively. Qualitative data to understand successful implementation were collected concurrently by conducting interviews with clinical personnel interacting with BHT and BHT staff and observations of BHT implementation processes at three site visits using the Promoting Action on Research Implementation in Health Services (PARIHS) framework. RESULTS: Of 4500 at-risk, rural Veterans offered osteoporosis screening, 1081 (24%) completed screening, and of these, 37% had normal bone density, 48% osteopenia, and 15% osteoporosis. Among Veterans with pharmacotherapy indications, 90% initiated therapy. Qualitative analyses identified barriers of rural geography, rural population characteristics, and the infrastructural resource requirement. Data infrastructure, evidence base for care delivery, stakeholder buy-in, formal and informal facilitator engagement, and focus on teamwork were identified as facilitators of implementation success. CONCLUSION: The BHT is a feasible population telehealth model for delivering preventative osteoporosis care to rural Veterans.

Virus-Like Particles (VLPs) as a Platform for Hierarchical Compartmentalization.

Hierarchically self-assembled structures are common in biology, but it is often challenging to design and fabricate synthetic analogs. The archetypal cell is defined by hierarchically organized multicompartmentalized structures with boundaries that delineate the interior from exterior environments and is an inspiration for complex functional materials. Here, we have demonstrated an approach to the design and construction of a nested protein cage system that can additionally incorporate the packing of other functional macromolecules and exhibit some of the features of a minimal synthetic cell-like material. We have demonstrated a strategy for controlled co-packaging of subcompartments, ferritin (Fn) cages, together with active cellobiose-hydrolyzing ß-glycosidase enzyme macromolecules, CelB, inside the sequestered volume of the bacteriophage P22 capsid. Using controlled in vitro assembly, we were able to modulate the stoichiometry of Fn cages and CelB encapsulated inside the P22 to control the degree of compartmentalization. The co-encapsulated enzyme CelB showed catalytic activity even when packaged at high total macromolecular concentrations comparable to an intracellular environment. This approach could be used as a model to create synthetic protein-based protocells that can confine smaller functionalized proto-organelles and additional macromolecules to support a range of biochemical reactions.

Utility of accumulated opioid supply days and individual patient factors in predicting probability of transitioning to long-term opioid use: An observational study in the Veterans Health Administration.

Initial supply days dispensed to new users is strongly predictive of future long-term opioid use (LTO). The objective was to examine whether a model integrating additional clinical variables conferred meaningful improvement in predicting LTO, beyond a simple approach using only accumulated supply. Three cohorts were created using Veteran's Health Administration data based on accumulated supply days during the 90 days following opioid initiation: (a) <30 days, (b) ≥30 days, (c) ≥60 days. A base, unadjusted probability of subsequent LTO (days 91-365) was calculated for each cohort, along with an associated risk range based on midpoint values between cohorts. Within each cohort, log-binomial regression modeled the probability of subsequent LTO, using demographic, diagnostic, and medication characteristics. Each patient's LTO probability was determined using their individual characteristic values and model parameter estimates, where values falling outside the cohort's risk range were considered a clinically meaningful change in predictive value. Base probabilities for subsequent LTO and associated risk ranges by cohort were as follows: (a) 3.92% (0%-10.75%), (b) 17.59% (10.76%-28.05%), (c) 38.53% (28.06%-47.55%). The proportion of patients whose individual probability fell outside their cohort's risk range was as follows: 1.5%, 4.6%, and 9.2% for cohorts 1, 2, and 3, respectively. The strong relationship between accumulated supply days and future LTO offers an opportunity to leverage electronic healthcare records for decision support in preventing the initiation of inappropriate LTO through early intervention. More complex models are unlikely to meaningfully guide decision making beyond the single variable of accumulated supply days.

Trends in Hospitalization, Management, and Clinical Outcomes Among Veterans With Critical Limb Ischemia.

BACKGROUND: Contemporary patterns in management and outcomes of critical limb ischemia among United States veterans are unknown. METHODS: We used Veterans Health Administration data to identify patients admitted for critical limb ischemia between 2005 and 2014. We examined temporal trends in incidence, management, and outcomes. RESULTS: A total of 20 938 veterans with critical limb ischemia were hospitalized between 2005 and 2014. Mean age was 67.8 years. Incidence decreased from 0.3 to 0.24 per 1000 persons from 2005 to 2013, P<0.01. During the study period, there was a temporal increase in use of revascularization within 90 days of hospitalization-endovascular (11.2% in 2005 to 18.4% in 2014), surgical (23.8% in 2005 to 26.4% in 2014), and hybrid (6.2% in 2005 to 13.1% in 2014, P value for trend <0.01). Statin prescriptions increased from 47.4% in 2005 to 60.9% in 2014 (P value for trend <0.01). There was a significant decline in risk-adjusted mortality (11.8% in 2005 to 9.7% in 2014) and major amputation (19.8% in 2005 to 12.9% in 2014; P value for trend <0.01 for both) at 90 days. In adjusted analyses, revascularization was associated with a lower risk of mortality (RR, 0.45 [95% CI, 0.41-0.50]; P<0.001) and major amputation at 90 days (RR, 0.23 [95% CI, 0.21-0.26]; P<0.001). Nearly half of the patients who underwent amputation did not receive an invasive vascular procedure within the preceding 90 days. There was large site-level variation in the use of revascularization (median rate, 41.7% [interquartile range, 12.5%-53.2%]). Differences in patient case-mix explained only 8% of site-level variation in receipt of revascularization. CONCLUSIONS: Over the past decade, use of revascularization increased among veterans with critical limb ischemia, which was accompanied by a reduction in mortality and major amputation. However, opportunities to further improve care in this high-risk population still remain.

Factors Associated With Osteoporosis Care of Men Hospitalized for Hip Fracture: A Retrospective Cohort Study.

Rates of postfracture DXA and pharmacotherapy appear to be declining despite their known benefits in fracture reduction. We sought to identify factors associated with osteoporosis care among male veterans aged 50 years and older after hip fracture and to evaluate trends in rates of care with an observational cohort design using US Department of Veterans Affairs' (VA) inpatient, pharmacy, and outpatient encounters and Centers for Medicare and Medicaid Services outpatient pharmacy claims (2007 to 2014) from men aged 50 years and older treated for hip fracture (N = 7317). We used the Cox proportional hazards model with random effects for the admitting facility. A sensitivity analysis was performed for a subset of patients aged 65 to 99 dually enrolled in Medicare ( N = 5821). Overall, approximately 13% of patients had evidence of osteoporosis care within one year of fracture. In the adjusted model, rural residence was associated with lower likelihood of care, and several comorbidities were associated with higher likelihood of receiving care. In sensitivity analyses of patients dually enrolled in Medicare, rural residence remained associated with lower likelihood of osteoporosis care. Overall rates of care decreased over time, but rates of DXA in the VA remained stable. These findings highlight the ongoing problem of low rates of postfracture care among a population with the highest risk of future fracture and its associated morbidity and mortality. The rural disparity in care and differences in rates of care across healthcare delivery systems illustrates the importance of healthcare delivery systems in promoting pharmacotherapy and DXA after sentinel events. Because the VA removes a majority of cost barriers to care, this integrated healthcare system may outperform the private sector in access to care. However, declining rates of pharmacotherapy imply knowledge gaps that undermine quality care. © 2019 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Cargo Retention inside P22 Virus-Like Particles.

Viral protein cages, with their regular and programmable architectures, are excellent platforms for the development of functional nanomaterials. The ability to transform a virus into a material with intended structure and function relies on the existence of a well-understood model system, a noninfectious virus-like particle (VLP) counterpart. Here, we study the factors important to the ability of P22 VLP to retain or release various protein cargo molecules depending on the nature of the cargo, the capsid morphology, and the environmental conditions. Because the interaction between the internalized scaffold protein (SP) and the capsid coat protein (CP) is noncovalent, we have studied the efficiency with which a range of SP variants can dissociate from the interior of different P22 VLP morphologies and exit by traversing the porous capsid. Understanding the types of cargos that are either retained or released from the P22 VLP will aid in the rational design of functional nanomaterials.

In Vivo Packaging of Protein Cargo Inside of Virus-Like Particle P22.

Protein cages are ubiquitous in nature and have been manipulated to encapsulate a range of nonnative cargos including organic, inorganic, and small molecules. Many protein cages are derived from virus capsids that have been rendered noninfectious through the preferential production and use of proteins that are solely involved in capsid assembly, but which do not encapsulate genetic material and therefore do not contribute to infectivity. Here, we describe the production of protein cargo(s) encapsulated inside of P22 virus-like particles (VLPs), derived from bacteriophage P22. This is achieved via genetic fusion of the cargo to a scaffolding protein, which becomes encapsulated in the P22 VLP during templated assembly of the protein cage.

Templated Assembly of a Functional Ordered Protein Macromolecular Framework from P22 Virus-like Particles.

Bottom-up construction of mesoscale materials using biologically derived nanoscale building blocks enables engineering of desired physical properties using green production methods. Virus-like particles (VLPs) are exceptional building blocks due to their monodispersed sizes, geometric shapes, production ease, proteinaceous composition, and our ability to independently functionalize the interior and exterior interfaces. Here a VLP, derived from bacteriophage P22, is used as a building block for the fabrication of a protein macromolecular framework (PMF), a tightly linked 3D network of functional protein cages that exhibit long-range order and catalytic activity. Assembly of PMFs was electrostatically templated, using amine-terminated dendrimers, then locked into place with a ditopic cementing protein that binds to P22. Long-range order is preserved on removal of the dendrimer, leaving a framework material composed completely of protein. Encapsulation of ß-glucosidase enzymes inside of P22 VLPs results in formation of stable, condensed-phase materials with high local concentration of enzymes generating catalytically active PMFs.

Epidemiology of lower extremity peripheral artery disease in veterans.

OBJECTIVE: The objective of this study was to describe the epidemiology, clinical features, outcomes, and predictors of mortality in veterans with peripheral artery disease (PAD). METHODS: We used national data from the Veterans Health Administration from fiscal years 2009 to 2011 to identify patients with a new diagnosis of PAD. Within this cohort, we describe characteristics of the patients, use of recommended medications, and clinical outcomes during a 3-year follow-up (fiscal year 2014). We used Cox proportional hazards regression to examine predictors of mortality and adverse limb outcomes (amputation and hospitalization for critical limb ischemia [CLI]) during follow-up. RESULTS: A total of 175,865 patients with a new diagnosis of PAD were included. The mean age was 69.9 years; 97.8% were male, and 67.7% were white. Nearly 77% of patients had hypertension, 46.5% had diabetes, 23% had chronic obstructive pulmonary disease, and 12.9% had renal failure. A prescription for statins was filled by 60.8%, and 34.9% received high-intensity statins within 90 days of PAD diagnosis. At 1 year, 2.6% underwent revascularization, 1.3% developed CLI, and 1.1% underwent amputation. During a median follow-up of 3.8 years, a total of 28.6% patients died (6.7% at 1 year), and 3.7% developed a limb outcome (2.0% at 1 year). Predictors of mortality included advanced age, comorbidities, and CLI or amputation at presentation. In contrast, prescription with statins was associated with lower mortality. Similar findings were present with regard to predictors of adverse limb outcomes, except that older age was associated with a lower risk of amputation or CLI. CONCLUSIONS: We found that veterans with PAD have a high prevalence of comorbid conditions and have a significant risk of mortality and limb loss. A substantial proportion of veterans with PAD are not prescribed recommended medications, especially statin therapy. Our data highlight important opportunities for improving care of veterans with PAD.

Risk for Prolonged Opioid Use Following Total Knee Arthroplasty in Veterans.

BACKGROUND: Patients undergoing total knee arthroplasty (TKA) may be at risk for prolonged postsurgical opioid use due to a high prevalence of persistent postsurgical pain (20%) and high rates of presurgical opioid use. METHODS: The current study uses a Veterans Health Administration sample of 6653 Veterans who underwent TKA in the fiscal year 2014 that did not require surgical revision during the subsequent year. RESULTS: Sixty percent of the sample had used an opioid in the year prior to surgery, including 20% who were on long-term opioid use at the time of surgery (defined as 90+ days of continuous use) and 40% with any other opioid use in the year prior to surgery. In patients on long-term opioids at the time of surgery, 69% received opioids for at least 6 months and 57% for at least 12 months after TKA. In patients not on long-term opioids at the time of TKA, only 4% received opioids for at least 6 months and 2% for at least 12 months after TKA. Differing risk factors for prolonged opioid use 12 months after TKA were identified in these 2 cohorts (ie, those who were and were not receiving long-term opioids at TKA). CONCLUSION: These findings suggest that the greatest risk for prolonged opioid use after TKA is preoperative opioid use.

Modular Self-Assembly of Protein Cage Lattices for Multistep Catalysis.

The assembly of individual molecules into hierarchical structures is a promising strategy for developing three-dimensional materials with properties arising from interaction between the individual building blocks. Virus capsids are elegant examples of biomolecular nanostructures, which are themselves hierarchically assembled from a limited number of protein subunits. Here, we demonstrate the bio-inspired modular construction of materials with two levels of hierarchy: the formation of catalytically active individual virus-like particles (VLPs) through directed self-assembly of capsid subunits with enzyme encapsulation, and the assembly of these VLP building blocks into three-dimensional arrays. The structure of the assembled arrays was successfully altered from an amorphous aggregate to an ordered structure, with a face-centered cubic lattice, by modifying the exterior surface of the VLP without changing its overall morphology, to modulate interparticle interactions. The assembly behavior and resultant lattice structure was a consequence of interparticle interaction between exterior surfaces of individual particles and thus independent of the enzyme cargos encapsulated within the VLPs. These superlattice materials, composed of two populations of enzyme-packaged VLP modules, retained the coupled catalytic activity in a two-step reaction for isobutanol synthesis. This study demonstrates a significant step toward the bottom-up fabrication of functional superlattice materials using a self-assembly process across multiple length scales and exhibits properties and function that arise from the interaction between individual building blocks.