US Veterans Affairs Research Articles

Individual species and cumulative mixture relationships of 24-hour urine metal concentrations with DNA methylation age variables in older men

BackgroundGlobally, toxic metal exposures are a well-recognized risk factor for many adverse health outcomes. DNA methylation-based measures of biological aging are predictive of disease, but have poorly understood relationships with metal exposures. ObjectiveWe performed a pilot study examining the relationships of 24-h urine metal concentrations with three novel DNA methylation-based measures of biological aging: DNAmAge, GrimAge, and PhenoAge. MethodsWe utilized a previously established urine panel of five common metals [arsenic (As), cadmium (Cd), lead (Pb), manganese (Mn), and mercury (Hg)] found in a subset of the elderly US Veterans Affairs Normative Aging Study cohort (N = 48). The measures of DNA methylation-based biological age were calculated using CpG sites on the Illumina HumanMethylation450 BeadChip. Bayesian Kernel Machine Regression (BKMR) was used to determine metals most important to the aging outcomes and the relationship of the cumulative metal mixture with the outcomes. Individual relationships of important metals with the biological aging outcomes were modeled using fully-adjusted linear models controlling for chronological age, renal function, and lifestyle/environmental factors. ResultsMn was selected as important to PhenoAge. A 1 ng/mL increase in urine Mn was associated with a 9.93-year increase in PhenoAge (95%CI: 1.24, 18.61, p = 0.03). The cumulative urine metal mixture was associated with increases in PhenoAge. Compared to a model where each metal in the mixture is set to its 50th percentile value, every one-unit increase of the cumulative mixture with each metal at its 70th percentile was associated with a 2.53-year increase in PhenoAge (95%CI: 0.10, 4.96, P<0.05). ConclusionOur results add novel evidence that metals detected in urine are associated with increases in biological aging and suggest that these DNA methylation-based measures may be useful for identifying individuals at-risk for diseases related to toxic metal exposures. Further research is necessary to confirm these findings more broadly.

Preoperative Disability in US Veterans.

Using the 12-item World Health Organization Disability Assessment Schedule (WHODAS-12), we measured the prevalence of disability in all eligible patients during a 4-month period who were presenting for preoperative evaluation at a US Veterans Affairs hospital. Overall disability was at least moderate in more than half of these patients (total n = 472 at Durham, NC). Two of the 6 WHODAS domains, "Getting Around" and "Participation in Society," contributed most to the overall scores-25% and 20%, respectively. Further studies are needed to determine the impact of domain-specific disabilities on postoperative outcomes and to identify potential interventions to address these vulnerabilities.

Trends in Health Care–Associated Infection Prevention Practices in US Veterans Affairs Hospitals From 2005 to 2017

Health care-associated infection (HAI) is associated with substantial harm. To reduce HAI, the largest integrated health care system in the United States-the Veterans Health Administration-was an early adopter of infection prevention policies and initiatives. Whether these efforts translated into increased use of practices to prevent HAI in Veterans Affairs (VA) hospitals is unknown. To evaluate changes over time in infection prevention practices and the perception of the importance of infection prevention to hospital leadership. For this survey study, every 4 years between 2005 and 2017, infection preventionists were surveyed at all VA hospitals on use of practices associated with common HAIs, including central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), ventilator-associated pneumonia (VAP), and (beginning in 2013) Clostridioides difficile infection. Data analysis was performed from February 1, 2019, to July 1, 2019. Reported regular use of key infection prevention practices and perceived importance of infection prevention to hospital leadership. Between 2005 and 2017, 320 total surveys were completed with response rates ranging from 59% (73 of 124) in 2017 to 80% (95 of 119) in 2005. Use of 12 different infection prevention practices increased. Since 2013, 92% (69 of 75) to 100% of VA hospitals reported regular use of key infection prevention practices for C difficile infection and CLABSI. In contrast, adoption of many practices to prevent CAUTI, although increasing, have lagged. Despite reported increases in the use of some practices for VAP such as semirecumbent positioning (89% [79 of 89] in 2005 vs 97% [61 of 63] in 2017, P = .007 for trend) and subglottic secretion drainage (23% [19 of 84] in 2005 vs 65% [40 of 62] in 2017, P < .001), use of other key practices such as daily interruptions of sedation (85% [55 of 65] in 2009 vs 87% [54 of 62] in 2017, P = .66) and early mobilization (81% [52 of 64] in 2013 vs 82% [51 of 62] in 2017, P = .88) has not increased. Antibiotic stewardship programs are now reported in nearly every VA hospital (97% [71 of 73]); however, some hospitals report practices for microbiologic testing for HAIs (eg, 22% [16 of 72] report routine urine culture testing in 2017) that could also contribute to antibiotic overuse. From 2005 to 2017, reported use of 12 different infection prevention practices increased in VA hospitals. Areas for continued improvement of infection prevention practices appear to include CAUTI, certain VAP practices, and diagnostic stewardship for HAI. The reported adoption of many infection prevention practices in VA hospitals was higher than in non-VA hospitals. As hospitals continue to merge and health systems become increasingly integrated, these successes could help inform patient safety broadly.

Effectiveness of Elbasvir/Grazoprevir in patients with hepatitis C virus genotype 1 infection and chronic kidney disease in the United States veterans population

Background & aimsRandomized controlled trials of EBR/GZR have reported high treatment efficacy, safety and tolerability in patients undergoing dialysis. However, real world effectiveness data for EBR/GZR in this population is lacking. We evaluated the effectiveness of EBR/GZR in an HCV-infected population with all stages of CKD including dialysis compared with control patients with estimated glomerular filtration rate (eGFR) ≥60 in the US Department of Veterans Affairs (VA). MethodsWe conducted a retrospective cohort study of patients with chronic HCV genotype 1 infection with EBR/GZR prescriptions dispensed during February 1, 2016–August 31, 2017 in 128 VA Medical Centers. We collected patient information regarding history of dialysis, end stage renal disease (ESRD), and/or eGFR values. We measured SVR based on undetectable HCV RNA at least 4 weeks after the completion of treatment. We examined SVR rates by CKD stage compared to control patients and within patient subgroups using logistic regression models. ResultsWe identified 5961 patients (42.5% genotype 1a, 55.0% genotype 1b) who met eligibility criteria and completed a EBR/GZR treatment course (≥11 weeks). Approximately 73.2% (n = 4361) had eGFR ≥60 who served as control patients, 14.4% (n = 860) had Stage 3 CKD, and 12.4% (n = 740) had Stage 4–5 CKD or ESRD. Of patients with Stage 4–5 CKD/ESRD, 76.1% underwent dialysis (n = 563). The overall SVR was 96.7% in all patients, 96.4% for eGFR≥60, 98.3% in Stage 3 CKD, and 96.5% in Stage 4–5 CKD/ESRD. No statistically significant differences were found in the SVR rates in patients with or without dialysis in the Stage 4–5 CKD/ESRD patients (adjusted OR 0.91; 95% CI 0.56–1.47 and OR 1.74; 95% CI 0.63–4.81) compared with those with eGFR≥60. ConclusionWe found EBR/GZR was effective in patients with HCV GT1 infection regardless of CKD severity or receipt of dialysis in the US VA population.

Assessing the prior event rate ratio method via probabilistic bias analysis on a Bayesian network.

Background: Unmeasured confounders are commonplace in observational studies conducted using real‐world data. Prior event rate ratio (PERR) adjustment is a technique shown to perform well in addressing such confounding. However, it has been demonstrated that, in some circumstances, the PERR method actually increases rather than decreases bias. In this work, we seek to better understand the robustness of PERR adjustment. Methods: We begin with a Bayesian network representation of a generalized observational study, which is subject to unmeasured confounding. Previous work evaluating PERR performance used Monte Carlo simulation to calculate joint probabilities of interest within the study population. Here, we instead use a Bayesian networks framework. Results: Using this streamlined analytic approach, we are able to conduct probabilistic bias analysis (PBA) using large numbers of combinations of parameters and thus obtain a comprehensive picture of PERR performance. We apply our methodology to a recent study that used the PERR in evaluating elderly‐specific high‐dose (HD) influenza vaccine in the US Veterans Affairs population. That study obtained an HD relative effectiveness of 25% (95% CI: 2%‐43%) against influenza‐ and pneumonia‐associated hospitalization, relative to standard‐dose influenza vaccine. In this instance, we find that the PERR‐adjusted result is more like to underestimate rather than to overestimate the relative effectiveness of the intervention. Conclusions: Although the PERR is a powerful tool for mitigating the effects of unmeasured confounders, it is not infallible. Here, we develop some general guidance for when a PERR approach is appropriate and when PBA is a safer option.

Incidence of Second Primary Malignancies and Association with Treatment in US Veterans with Multiple Myeloma

Background: In the recent decade, there have been dramatic improvements in multiple myeloma (MM) survival, owing principally to developments in therapeutic options. However, these developments have also raised concerns as to increase in second primary malignancies (SPMs) attributable to these therapies. For example, a Swedish study showed an increased risk of developing acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) in MM patients (11.51 fold), along with 1.19-fold increased risk of non-hematologic malignancies. However, it is presently unclear whether this increase is related to therapy or other factors such as host, environment or behavioral patterns. Here, we study incidence of SPM and association with demographics, exposure, and therapy in a large population in the US Veterans Affairs (VA) healthcare system. Methods: We used the VA's nationwide Corporate Data Warehouse to identify patients diagnosed with MM from 1999 to 2017, as well as their age, race, therapy at induction, stem-cell transplant status, and exposure status. For each patient, we identified the first SPM after MM treatment initiation using the VA Central Cancer Registry. We excluded patients who had records of malignancies prior to MM treatment initiation. Results: We identified 14,261 patients meeting the inclusion criteria, of whom 552 (3.9%) had SPMs, consistent with prior literature. Median age at MM diagnosis was 69.22 years overall (95% CI 51.98-84.76), 66.7 years (52.03-83.86) for those with SPM, and 69.32 years (51.99-) for those without SPM. Median age at diagnosis of SPM was 70.2 years (55.43-86.75). Median time from MM treatment initiation to SPM was 2.38 years (0.09-9.37). Of the 552 observed SPMs, 69 (12.4%) were hematologic (25 MDS, 19 lymphoma, 15 acute leukemia, 6 chronic leukemia, 4 MPN) while 84.5% (466) were oncologic. Prostate cancer was the most common SPM (n=125, 22.6%). We did not observe statistically significant differences in incidence of SPM by smoking status (4.1% among current/former smokers vs 3.7% among never smokers; P=0.347), or Agent Orange exposure (4.2% among those exposed vs 3.8% among those not exposed; P=0.476). We also examined the relationship of common treatments to SPM. SPM is more common among those exposed to lenalidomide (4.3% vs 3.4%, p=0.003), bortezomib (4.8 vs 3.3%, p&lt;0.001), and transplant (7.5% vs 3.5%, p&lt;0.001). Considering only therapy at induction, SPMs occur among 3.3% of those receiving lenalidomide/dexamethasone (Rd), 4.0% of those receiving bortezomib/dexamethasone (Vd), and 4.5% of those receiving RVd (p=0.11). Among those who also received transplant, SPM occurs in 6.0%, 6.6%, and 8.7% of those receiving Rd, Vd, and RVd, respectively (p=0.49). And, among those who did not receive transplant, SPM occurs in 3.1%, 3.5%, and 3.7% of cases, respectively (p=0.52). Conclusion: In comparison to data from the VA Central Cancer Registry on cancer incidence at the VA in general, the incidence of SPM (3.9%) that we report among MM patients is substantially higher than the overall incidence of malignancy in the VA (0.78%). Moreover, we find that common risk factors for developing malignancy, including smoking status and exposure to Agent Orange, are not significantly associated with developing SPM after MM diagnosis. In contrast, we find that therapy utilization, particularly transplant, is associated with significant increases in susceptibility to SPM. Better understanding of these risk factors is needed to appropriately assess the tradeoff of decreased myeloma-related mortality, but potentially increased risk of secondary malignancies with common myeloma therapy options. Disclosures Yellapragada: Novartis: Employment, Other: Spouse Employment ; Celgene: Research Funding; BMS: Research Funding; Takeda: Research Funding. Munshi:Abbvie: Consultancy; Adaptive: Consultancy; Adaptive: Consultancy; Amgen: Consultancy; Amgen: Consultancy; Celgene: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Takeda: Consultancy; Oncopep: Consultancy; Oncopep: Consultancy; Abbvie: Consultancy.

Development of a Clinical Decision Aid for Chiropractic Management of Common Conditions Causing Low Back Pain in Veterans: Results of a Consensus Process

ObjectiveThe purpose of this study was to develop a clinical decision aid for chiropractic management of common conditions causing low back pain (LBP) in veterans receiving treatment in US Veterans Affairs (VA) health care facilities. MethodsA consensus study using an online, modified Delphi technique and Research Electronic Data Capture web application was conducted among VA doctors of chiropractic. Investigators reviewed the scientific literature pertaining to diagnosis and treatment of nonsurgical, neuromusculoskeletal LBP. Thirty seed statements summarizing evidence for chiropractic management, a graphical stepped management tool outlining diagnosis-informed treatment approaches, and support materials were then reviewed by an expert advisory committee. Email notifications invited 113 VA chiropractic clinicians to participate as Delphi panelists. Panelists rated the appropriateness of the seed statements and the stepped process on a 1-to-9 scale using the RAND/University of California, Los Angeles methodology. Statements were accepted when both the median rating and 80% of all ratings occurred within the highly appropriate range. ResultsThirty-nine panelists (74% male) with a mean (standard deviation) age of 46 (11) years and clinical experience of 17 (11) years participated in the study. Accepted statements addressed included (1) essential components of chiropractic care, (2) treatments for conditions causing or contributing to LBP, (3) spinal manipulation mechanisms, (4) descriptions and mechanisms of commonly used chiropractic interventions, and (5) a graphical stepped clinical management tool. ConclusionThis study group produced a chiropractic clinical decision aid for LBP management, which can be used to support evidence-based care decisions for veterans with LBP.

Tobacco smoking and death from prostate cancer in US veterans.

Cigarette smoking is a risk factor for mortality in several genitourinary cancers, likely due to accumulation of carcinogens in urine. However, in prostate cancer (PC) the link has been less studied. We evaluated differences in prostate cancer-specific mortality (PCSM) between current smokers, past smokers, and never smokers diagnosed with PC. This was a retrospective cohort study of PCSM in men diagnosed with PC between 2000 and 2015 treated in the US Veterans Affairs health care system, using competing risk regression analyses. The cohort included 73,668 men (current smokers: 22,608 (30.7%), past smokers: 23,695 (32.1%), and never smokers: 27,365 (37.1%)). Median follow-up was 5.9 years. Current smoker patients were younger at presentation (median age current: 63, never: 66; p < 0.001), and had more advanced disease stage (stage IV disease current: 5.3%, never: 4.3%; p < 0.04). The 10-year incidence of PCSM was 5.2%, 4.8%, and 4.5% for current, past, and never smokers, respectively. On competing risk regression, current smoking was associated with increased PCSM (subdistribution hazard ratio: 1.14, 95% confidence interval: (1.05-1.24), p = 0.002), whereas past smoking was not. Hierarchical regression suggests that this increased risk was partially attributable to tumor characteristics. Smoking at the time of diagnosis is associated with a higher risk of dying from PC as well as other causes of death. In contrast, past smoking was not associated with PCSM suggesting that smoking may be a modifiable risk factor. PC diagnosis may be an important opportunity to discuss smoking cessation.

Factors Influencing the Effectiveness of Allopurinol in Achieving and Sustaining Target Serum Urate in a US Veterans Affairs Gout Cohort.

To assess factors associated with the ability to achieve and maintain target serum urate (SU) with allopurinol in patients with gout. We used US Veterans Affairs (VA) databases from 2002-2012. Eligible patients had ≥ 1 inpatient or ≥ 2 outpatient visits with a diagnostic code for gout, filled a new index allopurinol prescription, had at least 1 posttreatment SU level measured, and met the 12-month observability rule. Treatment successes were defined as the achievement of postindex SU < 6 mg/dl (success 1) and postindex SU < 6 mg/dl that was sustained (success 2). Of the 198,839 unique patients with allopurinol use, 41,153 unique patients (with 47,072 episodes) and 17,402 unique patients (with 18,323 episodes) were eligible for analyses for success 1 and success 2; 42% each achieved (success 1) or achieved and maintained postindex SU < 6 mg/dl (success 2). In multivariable-adjusted models, factors associated with significantly higher odds of both outcomes were older age, normal body mass index, Deyo-Charlson index score of 0, rheumatologist as the main provider rather than non-rheumatologist, midwestern US location for the healthcare facility, a lower hospital bed size, military service connection for medical conditions of 50% or more (a measure of healthcare access priority), longer distance to the nearest VA facility, and lower preindex SU. We identified novel factors associated with maintaining SU < 6 mg/dl based on a theoretical model. Several potentially modifiable factors can be targeted by individual/provider/systems interventions for improving successful achievement and maintenance of target SU in patients with gout.

Medication decision-making for patients with renal insufficiency in inpatient and outpatient care at a US Veterans Affairs Medical Centre: a qualitative, cognitive task analysis

BackgroundMany studies identify factors that contribute to renal prescribing errors, but few examine how healthcare professionals (HCPs) detect and recover from an error or potential patient safety concern. Knowledge of...

Active Surveillance for Norovirus in a US Veterans Affairs Patient Population, Houston, Texas, 2015-2016.

BackgroundNorovirus is a leading cause of acute gastroenteritis (AGE); however, few data exist on endemic norovirus disease burden among adults. Candidate norovirus vaccines are currently in development for all ages, and robust estimates of norovirus incidence among adults are needed to provide baseline data.MethodsWe conducted active surveillance for AGE among inpatients at a Veterans Affairs (VA) hospital in Houston, Texas. Patients with AGE (≥3 loose stools, ≥2 vomiting episodes, or ≥1 episode of both loose stool and vomiting, within 24 hours) within 10 days of enrollment and non-AGE control patients were enrolled. Demographic data and clinical characteristics were collected. Stool samples were tested using the FilmArray gastrointestinal panel; virus-positives were confirmed by real-time reverse transcription polymerase chain reaction and genotyped by sequencing.ResultsFrom November 2, 2015 through November 30, 2016, 147 case patients and 19 control patients were enrolled and provided a stool specimen. Among case patients, 139 (95%) were male and 70 (48%) were aged ≥65 years. Norovirus was the leading viral pathogen detected (in 16 of 20 virus-positive case patients) and accounted for 11% of all AGE cases. No viral pathogens were detected among control patients. Incidence of norovirus-associated hospitalization was 20.3 cases/100 000 person-years and was similar among those aged <65 and ≥65 years.ConclusionsThis active surveillance platform employed screening and enrollment of hospitalized VA patients meeting a standardized AGE case definition, as well as non-AGE control patients. Data from this study highlight the burden of norovirus in a VA inpatient population and will be useful in policy considerations of a norovirus vaccine.

Lactate Predicts Both Short- and Long-Term Mortality in Patients With and Without Sepsis.

Objective:To measure the relationship between lactate and mortality in hospital inpatients. Main outcomes of interest were 3-day, 30-day, and 1-year all-cause mortality.Design:Retrospective cohort study, October 2011 to September 2013.Setting:University-affiliated US Veterans Affairs Hospital.Patients:All inpatients with lactate level measured during the study period.Measurements:Analysis of peak lactate level (mmol/L) during the most recent admission for patients who died, and peak lactate level during an admission for surviving patients. Covariates including sepsis, ICU admission, code blue and rapid response calls, medical vs surgical ward, liver disease, kidney disease, and hospice status were recorded.Results:In total, 3325 inpatients were included; 564 patients had sepsis. Median lactate 1.7 mmol/L (interquartile range [IQR] 1.2-2.6). The 3-day, 30-day, and 1-year mortality were 2.5%, 10%, and 24%, respectively. A lactate level cutoff of ⩾4 mmol/L had best test characteristics (sensitivity 52.4%, specificity 91.4%) to predict increased 3-day mortality. Unadjusted risk ratio of death in 3 days for lactate ⩾4 was 10.3 (95% confidence interval [CI] 6.8-15.7). Patients with sepsis had a consistently higher risk of death compared with patients without sepsis for any given level of lactate. Adjusted odds ratio (OR) of 3-day mortality for lactate ⩾4 was 7.6 (95% CI 4.6-12.5); 30-day mortality was 2.6 (95% CI 1.9-3.6); and 1-year mortality was 1.8 (95% CI 1.4-2.6). Lactates in the normal range (<1.7) were also independently associated with 30-day and 1-year mortality.Conclusions:Lactate predicts risk of death in all patients, although patients with sepsis have a higher mortality for any given lactate level. We report the novel finding that serum lactate, including normal values, is associated with long-term mortality.

Facilitators and Barriers to Implementation of a Peer Support Intervention for Patients with Chronic Pain: A Qualitative Study.

Pain self-management information and support, delivered by peers, are a potentially useful approach to help patients who are struggling to manage their chronic pain. Before implementation into clinical settings, it is important to understand factors that may influence the success of implementation. The purpose of this study was to explore facilitators and barriers to implementation of peer support for chronic pain. Semistructured interviews were conducted with clinicians who provide care to patients with chronic pain, regarding their perceptions of the proposed peer support intervention. A single US Veterans Affairs Medical Center. Using maximum variation sampling, 15 providers were interviewed (11 women, four men). Clinicians' disciplines included primary care, physical therapy, nursing, clinical psychology, social work, and pharmacy. Findings indicated that clinicians 1) had an overall positive perception of the intervention; 2) had specific intervention outcomes they wanted for patients; 3) anticipated that the intervention could positively influence their role; 4) anticipated barriers to intervention participation and maintenance; and 5) had concerns regarding peer coach selection. Findings are discussed in the context of the Consolidated Framework for Implementation Research. Understanding clinician perceptions of a peer support intervention is critical for successful implementation. The feedback collected in this study will facilitate implementation of the intervention on a broader scale, allowing more patients to benefit.

1825. Electronic Measure of Unnecessary Antimicrobial Use in US Veterans Affairs Medical Centers

BackgroundAntimicrobial inappropriateness is highly contextual and dynamic, depending not only on the patient’s disease condition but also the information available at the time. To estimate the extent to which antimicrobials could theoretically be decreased with antimicrobial stewardship, we sought to capture unnecessary inpatient antimicrobial use in context over time as manifested in the electronic health record in Veterans Affairs (VA).MethodsWe extracted antimicrobial use, administrative, admission, and laboratory data from all acute care VA medical centers between 2010 and 2016. Information present during Choice (hospital day [HD] 1–3), Change (HD 4–5), Completion (HD 6–7), and Post-completion (thereafter) was used to determine context. All antimicrobial use without any documented infection was considered unnecessary (admission, discharge, or otherwise). Choice Anti-MRSA agents were considered unnecessary in cellulitis without history of or current positive culture for MRSA. Choice HOMDR agents were unnecessary in cellulitis without history of positive culture for ceftriaxone-resistant Gram-negative rods. Also unnecessary were broad-spectrum antimicrobials (anti-methicillin-resistant Staphylococcus aureus [MRSA] and hospital-onset multidrug-resistant [HOMDR] organisms antimicrobials as defined by the National Healthcare Safety Network) administered without evidence of multidrug-resistant organisms existed during Change and Completion time frames.ResultsFigure 1 demonstrates the distribution of facility proportions of unnecessary antimicrobials of different classes over time. Table 1 illustrates the percentage of unnecessary antimicrobials administered during choice, change, completion, and post-completion time-frames. ConclusionBy this measure, unnecessary anti-MRSA and HOMDR use has been decreasing in VA over time. The bulk of unnecessary use is empiric but there is a substantial proportion that is used for longer stays, during which time more information was likely present. More research is necessary to determine how well these simple rules correlate with clinical determinations of appropriateness. Also ICD-10-CM was implemented in October 2015, which may have introduced an ascertainment bias.Disclosures V. Stevens, Pfizer, Inc.: Grant Investigator, Research grant.

1864. Implementation of the National Healthcare Safety Network’s (NHSN) Antimicrobial Use Option in the US Veterans Affairs (VA) Medical Facilities

BackgroundInappropriate or unnecessary use of antibiotics exacerbates antimicrobial resistance and can lead to adverse clinical outcomes. To address this issue, NHSN created the Antimicrobial Use (AU) Option to report antimicrobial use within acute care facilities. A pilot program was started to implement AU reporting in VA in 2013.MethodsWith support from VA Antimicrobial Stewardship Task Force and NHSN, we deployed one team to focus on implementation and another on technical aspects. We used an iterative recruitment approach with four cohorts to date (Tiers), starting with highly engaged facilities with strong stewardship infrastructure. Our implementation approach (Figure 1) was based on the Promoting Action on Research Implementation (PARiHS) framework for successful implementation of evidence into clinical practice. We evaluated our implementation with focus groups conducted using Skype chat to collect feedback from participants about the implementation process. Group 1 contained six participants from Tiers 1 and 2. Group 2 had three participants from Tiers 3 and 4. Questions were constructed using the PARiHS framework (Table 1). An implementation team member conducted interviews, monitored the discussion, then coded major themes of responses. ResultsTo date, there are over 90 facilities reporting AU to NHSN. Major themes to responses are summarized in Table 1. Overall, focus group participants were supportive of the program, but there were differences between early and later adopters.ConclusionA coordinated, centralized approach to facilitating implementation of NHSN AU reporting has been successful so far. Major themes from focus group responses did differ in some categories depending on tier in a way that appears concordant with the theory diffusion of innovation, e.g., early tiers were enthusiastic despite a lack of institutional support while later tiers reported being motivated by regulatory requirements and had solid institutional support. More research would further inform how to efficiently implement complex programs in large systems.Disclosures All authors: No reported disclosures.

1875. How Many Different Antimicrobial Regimens Are There and Which Are Emerging and Declining?

BackgroundAntimicrobial regimens evolve with changing recommendations and emerging practice patterns. We sought to explore the diversity of these patterns and to identify which inpatient regimens may be emerging in US Veterans Affairs medical centers (VAMC).MethodsWe extracted antimicrobial use and admission data from all acute care VA medical centers between 2005 and 2016. A regimen was defined as all unique antimicrobials and their routes given in a day to a single patient. We applied smoothing to account for intended discontinuation and intermittent dosing due to clearance. We described the distribution of regimens among VAMCs using the Gini index (a Gini index of 0 would mean all regimens were equally frequent and 1 would mean that one regimen dominated all others). We calculated the rank percentile of all regimens. We also used the absolute change in rank percentile between years 2005 and 2016 of the regimen used to describe emerging and declining regimens.ResultsThere were 55,767 distinct regimens. Table 1 describes the Gini index and its decomposition among VAMCs. Overlap accounts for most of the inequality present because regimens are shared between VAMCs. Approximately 20% of the inequality present can be accounted for by variation between VAMCs. Table 2 describes the top 10 rising and the top 10 declining regimens. ConclusionWhile there was a large number of distinct regimens, there was a relative handful of antimicrobial regimens dominated—most of which were commonly present among VAMCs (as manifest by the Gini “overlap” percent). Most regimens in the top 10 were broad-spectrum IV agents, with PO levofloxacin and doxycycline being notable standouts. IV vancomycin, which was the single most common regimen in 2005, decreased markedly. Linezolid and mixed PO metronidazole agents appear to be on the decline.Disclosures V. Stevens, Pfizer, Inc.: Grant Investigator, Research grant.

Androgen deprivation therapy is associated with decreased second primary lung cancer risk in the United States veterans with prostate cancer.

OBJECTIVESWe investigated whether androgen deprivation therapy (ADT) in prostate cancer patients was associated with a decreased risk for second primary lung cancer in US veterans.METHODSProstate cancer diagnoses in the US Veterans Affairs Cancer Registry between 1999 and 2008 were identified. Use of hormonal therapy and diagnoses of second primary lung cancer were determined from the registry. Synchronous prostate and lung cancers, defined as 2 diagnoses made within 1 year, were excluded from the analysis. Cancer-free survival was estimated using the Kaplan-Meier method and hazard ratios were estimated using Cox proportional hazard models.RESULTSAmong the 63,141 identified patients with prostate cancer, 18,707 subjects were eligible for the study. Hormonal therapy was used in 38% of patients and the median follow-up period was 28 months. ADT use was associated with longer lung cancer-free survival in prostate cancer patients (log-rank p=0.01). After adjusting for age, race, smoking and prostate cancer stage, ADT use was associated with decreased lung cancer risk by 15, 21, and 24% after 1, 2, and 3 years, respectively.CONCLUSIONSADT in prostate cancer patients may be associated with decreased second primary lung cancer risk among US veterans.

No Association Between Screening for Hepatocellular Carcinoma and Reduced Cancer-Related Mortality in Patients With Cirrhosis

Screening patients with cirrhosis for hepatocellular carcinoma (HCC) has been recommended. We conducted a matched case-control study within the US Veterans Affairs (VA) health care system to determine whether screening by abdominal ultrasonography (USS) and/or by measuring serum level of α-fetoprotein (AFP) was associated with decreased cancer-related mortality in patients with cirrhosis. We defined cases (n= 238) as patients with cirrhosis who died of HCC from January 1, 2013 through August 31, 2015 and had been in VA care with a diagnosis of cirrhosis for at least 4 years before the diagnosis of HCC. We matched each case to 1 control (n= 238), defined as a patient with cirrhosis who did not die of HCC and had been in VA care for at least 4 years before the date of the matched case's HCC diagnosis. Controls were matched to cases by year of cirrhosis diagnosis, race and ethnicity, age, sex, etiology of cirrhosis, Model for End-Stage Liver Disease score, and VA medical center. We identified all USS and serum AFP tests performed within 4 years before the date of HCC diagnosis in cases or the equivalent index date in controls and determined by chart extraction (blinded to case or control status) whether these tests were performed for screening. There were no significant differences between cases and controls in the proportions of patients who underwent screening USS (52.9% vs 54.2%), screening measurement of serum AFP (74.8% vs 73.5%), screening USS or measurement of serum AFP (81.1% vs 79.4%), or screening USS and measurement of serum AFP (46.6% vs 48.3%) within 4 years before the index date, with or without adjusting for potential confounders. There also was no difference in receipt of these screening tests within 1, 2, or 3 years before the index date. In a matched case-control study of the VA health care system, we found that screening patients with cirrhosis for HCC by USS, measurement of serum AFP, either test, or both tests was not associated with decreased HCC-related mortality. We encourage additional case-control studies to evaluate the efficacy of screening for HCC in other health care systems, in which available records are sufficiently detailed to enable identification of the indication for USS and AFP tests.

Prescribing Trends in US Active Duty Service Members With Posttraumatic Stress Disorder: A Population-Based Study From 2007-2013.

The US Veterans Affairs (VA)/Department of Defense (DoD) Posttraumatic Stress Disorder (PTSD) Clinical Practice Guidelines provide evidence-based pharmacologic treatment recommendations. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are considered first-line medications. Benzodiazepines are relatively contraindicated with a warning that they may cause harm. This population-based study is the first to describe prescribing patterns for active duty service members (ADSMs) diagnosed with PTSD. Health-care-related administrative DoD data from federal fiscal years 2007 through 2013 identified ADSMs with PTSD using ICD-9 codes. Prescription frequencies for antidepressants, benzodiazepines, antipsychotics, anticonvulsants, and other psychotropic medications were calculated for each year. Between 2007 and 2013, ADSMs with a PTSD diagnosis increased from 16,931 to 70,942. SSRI or SNRI prescribing decreased from 55.4% in 2007 to 41.8% in 2010 before increasing to 54.9% in 2013. Benzodiazepine prescribing was stable between 20.9% and 22.3% through 2010 before increasing to 24.7% by 2013. Antipsychotic prescribing declined from 22.6% in 2007 to 14.6% in 2013, driven by a decrease in low-dose quetiapine (≤ 300 mg/d) prescribing, which declined from 19.1% in 2007 to 8.2% in 2013. The increase in SSRI or SNRI prescribing after 2010 and the overall increase in prazosin and decrease in low-dose quetiapine prescribing all suggest increased concordance with the VA/DoD PTSD Clinical Practice Guidelines. The decline in SSRI prescribing up to 2010 is not concordant. The increase in benzodiazepine prescribing, a trend opposite that observed in the VA, is concerning.

Prognostic Role of p16 in Nonoropharyngeal Head and Neck Cancer.

Previous studies have reported conflicting information regarding the prognostic role of p16 in nonoropharyngeal head and neck squamous cell carcinoma (HNSCC). Using the US Veterans Affairs database, we analyzed 1448 patients with locoregionally advanced HNSCC and known p16 status diagnosed between 2005 and 2015 and treated with surgery, radiotherapy, or chemoradiotherapy. Tumor p16 status was determined through manual review of pathology reports of primary tumor specimens. Oropharyngeal (n = 1061) or nonoropharyngeal (n = 387; hypopharyngeal, laryngeal, or oral cavity) tumor site was determined from tumor registry data and manually reviewed for accuracy. We used multivariable Cox regression to analyze the effect of p16 status on overall survival (OS), cancer-specific survival (CSS), and competing mortality (CM) for oropharyngeal or nonoropharyngeal tumor sites. All statistical tests were two-sided. In multivariable models adjusting for treatment, stage, age, comorbidity, and body mass index, patients with p16-positive tumors had improved OS, CSS, and CM compared with patients with p16-negative tumors in both oropharyngeal (OS: hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.40 to 0.71, P < .001; CSS: HR = 0.50, 95% CI = 0.35 to 0.73, P < .001; CM: HR = 0.59, 95% CI = 0.38 to 0.93, P = .02) and nonoropharyngeal primary sites (OS: HR = 0.41, 95% CI = 0.25 to 0.69, P < .001; CSS: HR = 0.37, 95% CI = 0.18 to 0.77, P = .008; CM: HR = 0.46, 95% CI = 0.23 to 0.95, P = .04). The prognostic impact of p16 status did not statistically significantly differ by primary tumor site for OS, CSS, or CM (Pinteraction > .05). Our findings support the hypothesis that p16 has a similar prognostic role in both nonoropharyngeal and oropharyngeal cancer. Consideration should be given to increased testing for p16 in laryngeal, hypopharyngeal, and oral cavity primaries.