Association of peripheral artery disease with life-space mobility restriction and mortality in community-dwelling older adults.

OBJECTIVE: Symptomatic peripheral artery disease (PAD) impairs walking, but data on the impact of PAD on community mobility is limited. Life-space mobility measures the distance, frequency, and assistance needed as older adults move through geographic areas extending from their bedroom (life-space mobility score: 0) to beyond their town (life-space mobility score: 120). We evaluated the association of PAD with longitudinal life-space mobility trajectory. METHODS: Participants were part of the University of Alabama at Birmingham Study of Aging, a longitudinal study of community-dwelling older adults who were observed from 2001 to 2009. We limited our analysis to those who survived at least 6 months (N = 981). PAD was based on self-report with verification by physician report and hospital records. Our primary outcome was life-space mobility score assessed every 6 months. A multilevel change model (mixed model) was used to determine the association between PAD and life-space mobility trajectory during a median 7.9 years of follow-up. RESULTS: Participants had a mean age of 75.7 (standard deviation, 6.7) years; 50.5% were female, and 50.4% were African American. PAD prevalence was 10.1%, and 57.1% of participants with PAD died. In participants with both PAD and life-space restriction, defined as life-space mobility score <60, we observed the highest mortality (73.1%). In a multivariable adjusted mixed effects model, participants with PAD had a more rapid decline in life-space mobility by -1.1 (95% confidence interval [CI], -1.9 to -0.24) points per year compared with those without PAD. At 5-year follow-up, model-adjusted mean life-space mobility was 48.1 (95% CI, 43.5-52.7) and 52.4 (95% CI, 50.9-53.8) among those with and without PAD, respectively, corresponding to a restriction in independent life-space mobility at the level of one's neighborhood. CONCLUSIONS: Life-space mobility is a novel patient-centered measure of community mobility, and PAD is associated with significant life-space mobility decline among community-dwelling older adults. Further study is needed to mechanistically confirm these findings and to determine whether better recognition and treatment of PAD alter the trajectory of life-space mobility.

Association of Statin Dose With Amputation and Survival in Patients With Peripheral Artery Disease.

BACKGROUND: Statin dose guidelines for patients with peripheral artery disease (PAD) are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality. METHODS: Using an observational cohort study design and a validated algorithm, we identified patients with incident PAD (2003-2014) in the national Veterans Affairs data. Highest statin intensity exposure (high-intensity versus low-to-moderate-intensity versus antiplatelet therapy but no statin use) was determined within 1 year of diagnosis of PAD. Outcomes of interest were lower extremity amputations and death. The association of statin intensity with incident amputation and mortality was assessed with Kaplan-Meier plots, Cox proportional hazards modeling, propensity score-matched analysis, and sensitivity and subgroup analyses, as well, to reduce confounding. RESULTS: In 155 647 patients with incident PAD, more than a quarter (28%) were not on statins. Use of high-intensity statins was lowest in patients with PAD only (6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident amputation and mortality risk declined significantly with any statin use in comparison with the antiplatelet therapy-only group. In adjusted Cox models, the high-intensity statin users were associated with lower amputation risk and mortality in comparison with antiplatelet therapy-only users (hazard ratio, 0.67; 95% confidence interval, 0.61-0.74 and hazard ratio, 0.74; 95% confidence interval, 0.70-0.77, respectively). Low-to-moderate-intensity statins also had significant reductions in the risk of amputation and mortality (hazard ratio amputation, 0.81; 95% confidence interval, 0.75- 0.86; hazard ratio death, 0.83; 95% confidence interval, 0.81-0.86) in comparison with no statins (antiplatelet therapy only), but effect size was significantly weaker than the high-intensity statins (P<0.001). The association of high-intensity statins with lower amputation and death risk remained significant and robust in propensity score-matched, sensitivity, and subgroup analyses. CONCLUSIONS: Statins, especially high-intensity formulations, are underused in patients with PAD. This is the first population-based study to show that high-intensity statin use at the time of PAD diagnosis is associated with a significant reduction in limb loss and mortality in comparison with low-to-moderate-intensity statin users, and patients treated only with antiplatelet medications but not with statins, as well.

High hemoglobin A1c associated with increased adverse limb events in peripheral arterial disease patients undergoing revascularization.

OBJECTIVE: Diabetes and peripheral arterial disease (PAD) are independently associated with increased risk of amputation. However, the effect of poor glycemic control on adverse limb events has not been studied. We examined the effects of poor glycemic control (high hemoglobin A1c level) on the risk of amputation and modified major adverse limb events (mMALEs) after lower extremity revascularization. METHODS: Patients undergoing PAD revascularization who had hemoglobin A1c (HbA1c) levels available within 6 months were identified in the Veterans Affairs database of 2003 to 2014 (N = 26,799). The diagnosis of preoperative diabetes mellitus (PreopDM) was defined using diabetes diagnosis codes and evidence of treatment. Amputation and mMALE risk was compared for HbA1c levels using Kaplan-Meier analysis. Cox proportional hazards models were created to assess the effect of high HbA1c levels on amputation and mMALE (adjusted for age, gender, race, socioeconomic status, comorbidities, cholesterol levels, creatinine concentration, suprainguinal or infrainguinal procedure, open or endovascular procedure, severity of PAD, year of cohort entry, and medications) for all patients and stratified by PreopDM. RESULTS: High HbA1c levels were present in 33.2% of the cohort, whereas 59.9% had PreopDM. Amputations occurred in 4359 (16.3%) patients, and 10,580 (39.5%) had mMALE. Kaplan-Meier curves showed the worst outcomes in patient with PreopDM and high HbA1c levels. In the Cox model, incremental HbA1c levels of 6.1% to 7.0%, 7.1% to 8.0%, and >8% were associated with 26% (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.15-1.39), 53% (HR, 1.53; 95% CI, 1.37-1.7), and 105% (HR, 2.05; 95% CI, 1.87-2.26) higher risk of amputation, respectively. Similarly, the risk of mMALE also increased by 5% (HR, 1.05; 95% CI, 0.99-1.11), 21% (HR, 1.21; 95% CI, 1.13-1.29), and 33% (HR, 1.33, 95% CI, 1.25-1.42) with worsening HbA1c levels of 6.1% to 7.0%, 7.1% to 8.0%, and >8%, respectively (vs HbA1c ≤6.0%). In stratified analysis by established PreopDM, the relative risk of amputation or mMALE was much higher with poor glycemic control (HbA1c >7.0%) in patients without PreopDM. CONCLUSIONS: PAD patients with worse perioperative glycemic control have a significantly higher risk of amputation and mMALE. Incremental increases in HbA1c levels are associated with higher hazards of adverse limb outcomes independent of PreopDM status. Poor glycemic control (HbA1c >7.0%) in patients without a PreopDM diagnosis carries twice the relative risk of amputation and mMALE than in those with good glycemic control. These results suggest that screening of diabetic status and better management of glycemic control could be a target for improvement of perioperative and long-term outcomes in PAD patients.

The association of comorbid depression with mortality and amputation in veterans with peripheral artery disease.

OBJECTIVE: Peripheral artery disease (PAD) is an increasing health concern with rising incidence globally. Previous studies have shown an association between PAD incidence and depression. The objective of the study was to determine the association of comorbid depression with PAD outcomes (amputation and all-cause mortality rates) in veterans. METHODS: An observational retrospective cohort of 155,647 patients with incident PAD (2003-2014) from nationwide U.S. Veterans Health Administration hospitals was conducted using the national Veterans Affairs Corporate Data Warehouse. Depression was measured using concurrent International Classification of Diseases, Ninth Revision diagnosis codes 6 months before or after PAD diagnosis. The main outcomes were incident major amputation and all-cause mortality. Crude associations were assessed with Kaplan-Meier plots. The effects of depression adjusted for covariates were analyzed using Cox proportional hazards models. RESULTS: Depression was present in 16% of the cohort, with the occurrence of 9517 amputations and 63,287 deaths (median follow-up, 5.9 years). Unadjusted hazard ratios (HRs) of comorbid depression for amputations and all-cause mortality were 1.32 (95% confidence interval [CI], 1.25-1.39) and 1.02 (95% CI, 0.99-1.04), respectively. After adjustment for covariates in Cox regression models, a diagnosis of comorbid depression at the time of PAD diagnosis was associated with a 13% higher amputation (HR, 1.13; 95% CI, 1.07-1.19) and 17% higher mortality (HR, 1.17; 95% CI, 1.14-1.20) risk compared with patients with no depression. On stratification by use of antidepressants, depressed patients not taking antidepressants had a 42% higher risk of amputation (HR, 1.42; 95% CI, 1.27-1.58) compared with those without depression. Patients taking antidepressants for depression still had increased risk of amputation but only 10% higher compared with those without depression (HR, 1.10; 95% CI, 1.03-1.17). Interestingly, patients taking antidepressants for other indications also had a higher risk of amputation compared with those not having depression or not taking antidepressants (HR, 1.08; 95% CI, 1.03-1.14). Having any diagnosis of depression or the need for antidepressants increased the mortality risk by 18% to 25% in the PAD cohort compared with those without depression and not taking antidepressants for any other indication. CONCLUSIONS: PAD patients with comorbid depression have a significantly higher risk of amputation and mortality than PAD patients without depression. Furthermore, untreated depression was associated with an increased amputation risk in the PAD population, more so than depression or other mental illness being treated by antidepressants. The underlying mechanisms for causality, if any, remain to be determined. The association of antidepressant treatment use with amputation risk should prompt further investigations into possible mechanistic links between untreated depression and vascular dysfunction.

Prevalence and risk factors of post-acute sequelae of COVID-19 among United States Veterans.

PURPOSE: To better understand Post-Acute Sequelae of COVID-19 (PASC) in the Veteran population, this study aims to determine the prevalence of PASC and identify risk factors associated with its development. METHODS: This retrospective cohort study included 363,825 Veterans that tested positive for COVID-19 between February 1, 2020, and September 30, 2022. The primary outcome was the development of PASC 30-180 days following an acute infection with SARS-CoV-2. Multivariate logistic regression was utilized to examine factors associated with PASC. RESULTS: Of the 363,825 Veterans included in the analysis, 164,315 (45%) displayed symptoms of PASC. The Veterans in this analysis were predominantly male, non-Hispanic White, under the age of 65 years old, and lived in an urban residence. The strongest predictors for PASC included Non-Hispanic Black or African American race compared to Non-Hispanic White race (aOR=1.14), being between the ages of 50 and 64 compared to ages 50 and below (aOR=1.80), diabetes (aOR=8.46), and severe acute infection (aOR=1.42). CONCLUSION: Results demonstrate potential health inequities for vulnerable individuals, as well as increased risk for individuals with pre-existing comorbidities. The prevalence of PASC provides estimates for future health care utilization. The risk factors identified can aid public health interventions to reduce the burden of PASC.

Development of Portable Electronic Health Record Based Algorithms to Identify Individuals with Diabetic Retinopathy.

Objectives: To develop, validate and implement algorithms to identify diabetic retinopathy (DR) cases and controls from electronic health care records (EHR)s. Methods : We developed and validated EHR-based algorithms to identify DR cases and individuals with type I or II diabetes without DR (controls) in three independent EHR systems: Vanderbilt University Medical Center Synthetic Derivative (VUMC), the VA Northeast Ohio Healthcare System (VANEOHS), and Massachusetts General Brigham (MGB). Cases were required to meet one of three criteria: 1) two or more dates with any DR ICD-9/10 code documented in the EHR, or 2) at least one affirmative health-factor or EPIC code for DR along with an ICD9/10 code for DR on a different day, or 3) at least one ICD-9/10 code for any DR occurring within 24 hours of an ophthalmology exam. Criteria for controls included affirmative evidence for diabetes as well as an ophthalmology exam. Results: The algorithms, developed and evaluated in VUMC through manual chart review, resulted in a positive predictive value (PPV) of 0.93 for cases and negative predictive value (NPV) of 0.97 for controls. Implementation of algorithms yielded similar metrics in VANEOHS (PPV=0.94; NPV=0.86) and lower in MGB (PPV=0.84; NPV=0.76). In comparison, use of DR definition as implemented in Phenome-wide association study (PheWAS) in VUMC, yielded similar PPV (0.92) but substantially reduced NPV (0.48). Implementation of the algorithms to the Million Veteran Program identified over 62,000 DR cases with genetic data including 14,549 African Americans and 6,209 Hispanics with DR. Conclusions/Discussion: We demonstrate the robustness of the algorithms at three separate health-care centers, with a minimum PPV of 0.84 and substantially improved NPV than existing high-throughput methods. We strongly encourage independent validation and incorporation of features unique to each EHR to enhance algorithm performance for DR cases and controls.

Adaptive selection at G6PD and disparities in diabetes complications.

Diabetes complications occur at higher rates in individuals of African ancestry. Glucose-6-phosphate dehydrogenase deficiency (G6PDdef), common in some African populations, confers malaria resistance, and reduces hemoglobin A1c (HbA1c) levels by shortening erythrocyte lifespan. In a combined-ancestry genome-wide association study of diabetic retinopathy, we identified nine loci including a G6PDdef causal variant, rs1050828 -T (Val98Met), which was also associated with increased risk of other diabetes complications. The effect of rs1050828 -T on retinopathy was fully mediated by glucose levels. In the years preceding diabetes diagnosis and insulin prescription, glucose levels were significantly higher and HbA1c significantly lower in those with versus without G6PDdef. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, participants with G6PDdef had significantly higher hazards of incident retinopathy and neuropathy. At the same HbA1c levels, G6PDdef participants in both ACCORD and the Million Veteran Program had significantly increased risk of retinopathy. We estimate that 12% and 9% of diabetic retinopathy and neuropathy cases, respectively, in participants of African ancestry are due to this exposure. Across continentally defined ancestral populations, the differences in frequency of rs1050828 -T and other G6PDdef alleles contribute to disparities in diabetes complications. Diabetes management guided by glucose or potentially genotype-adjusted HbA1c levels could lead to more timely diagnoses and appropriate intensification of therapy, decreasing the risk of diabetes complications in patients with G6PDdef alleles.

The Social, Demographic, and Clinical Predictors of COVID-19 Severity: a Model-based Analysis of United States Veterans.

PURPOSE: This study aims to identify the contributions of individual and community social determinants of health (SDOH), demographic, and clinical factors in COVID-19 disease severity through a model-based analysis. METHODS: This national cross-sectional study focused on hospitalization among those tested for COVID-19 and use of intensive care, analyzing data on 220,848 Veterans tested between February 20, 2020 and October 20, 2021. Multiple logistic regression models were constructed using backwards elimination. The predictive value of each model was assessed with a c-statistic. RESULTS: Those hospitalized were older, more likely to be male, of Black or Asian race, have an income less than $39,999, live in an urban residence, and have medical comorbidities. The strongest predictors for hospitalization included Gini inequality index, race, income, heart failure, chronic kidney disease (CKD), and chronic obstructive pulmonary disease (COPD). For intensive care, Asian race, rural residence, COPD, and CKD were the strongest predictors. C-statistics were c = 0.749 for hospitalization and c = 0.582 for ICU admission. CONCLUSIONS: A combination of clinical, demographic, individual and community SDOH factors predict COVID-19 hospitalization with good predictive ability and can inform risk stratification, discharge planning, and public health interventions. Racial disparities were not explained by social or clinical factors. Intensive care models had low discriminative power and may be better explained by other characteristics.

Space-time clustering of COVID-19 cases in the United States veteran population.

PURPOSE: To assess the distribution and clustering of coronavirus disease 2019 (COVID-19) testing and incidence over space and time, U.S. Department of Veteran's Affairs (VA) data were used to describe where and when veterans experienced highest proportions of test positivity. METHODS: Data for 6,342,455 veterans who utilized VA services between January 1, 2018, and September 30, 2021, were assessed for COVID-19 testing and test positivity. Testing and positivity proportions by county were mapped and focused-cluster tests identified significant clustering around VA facilities. Spatial cluster analysis also identified where and when veterans experienced highest proportions of test positivity. RESULTS: Within the veterans study population and our time window, 21.3% received at least one COVID-19 test, and 20.4% of those tested had at least one positive test. There was statistically significant clustering of testing around VA facilities, revealing regional variation in testing practices. Veterans experienced highest test positivity proportions between November 2020 and January 2021 in a cluster of states in the Midwest, compared to those who received testing outside of the identified cluster (RR: 3.45). CONCLUSIONS: Findings reflect broad regional trends in COVID-19 positivity which can inform VA policy and resource allocation. Additional analysis is needed to understand patterns during Delta and Omicron variant periods.

Annual Foot Exams are Associated with Reduced Incident Amputation among Older Veterans with Diabetes.

We conducted a secondary data analysis to evaluate the association between annual foot exams and incident lower extremity amputations (LEA) among older veterans with diabetes during FY2007-FY2014. Older Veterans with at least one primary care provider visit each year (N = 664,162) and at least one foot exam each year (N = 72,892) and the overlap were identified from the 5 years prior to the study period of interest (FY2002-FY2006 (N = 71,122)). After excluding incident LEA related to cancer and trauma, 71,018 veterans (mean age +/- SD, % male) were included in the final cohort, which was followed from FY2007-FY2014 to evaluate the influence of subsequent annual foot exams and incident LEA. Consistent annual foot exams were protective for incident LEA in older veterans with diabetes, adjusted OR was 0.85 (97% CI: 0.74-0.96). Results indicate that adherence to annual foot exam guidelines can reduce incident LEA in older veterans with diabetes.

Increased Risk of Incident Diabetes Among Individuals With Latent Tuberculosis Infection.

OBJECTIVE: In cross-sectional U.S. studies, patients with diabetes had twice the prevalence of latent tuberculosis infection (LTBI) compared with those without diabetes. However, whether LTBI contributes to diabetes risk is unknown. We used longitudinal data to determine if LTBI is associated with increased diabetes incidence. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study among U.S. Veterans receiving care in the Veterans Health Administration from 2000 to 2015. Eligibility included all patients without preexisting diabetes who received a tuberculin skin test (TST) or interferon-γ release assay (IGRA). We excluded patients with a history of active TB and those diagnosed with diabetes before or within 2 years after LTBI testing. Patients were followed until diabetes diagnosis, death, or 2015. LTBI was defined as TST or IGRA positive. Incident diabetes was defined by use of ICD-9 codes in combination with a diabetes drug prescription. RESULTS: Among 574,113 eligible patients, 5.3% received both TST/IGRA, 79.1% received TST only, and 15.6% received IGRA only. Overall, 6.6% had LTBI, and there were 2,535,149 person-years (PY) of follow-up after LTBI testing (median 3.2 years). The diabetes incidence rate (per 100,000 PY) was greater in patients with LTBI compared with those without (1,012 vs. 744; hazard ratio [HR] 1.4 [95% CI 1.3-1.4]). Increased diabetes incidence persisted after adjustment for covariates (adjusted HR [aHR] 1.2 [95% CI 1.2-1.3]) compared with those without LTBI. Among patients with LTBI, diabetes incidence was similar in those treated for LTBI compared with those who were not treated (aHR 1.0 [95% CI 0.9-1.1]). CONCLUSIONS: Comprehensive longitudinal data indicate that LTBI is associated with increased diabetes incidence. These results have implications for people with LTBI, ∼25% of the global population.

A Web-Based, Provider-Driven Mobile App to Enhance Patient Care Coordination Between Dialysis Facilities and Hospitals: Development and Pilot Implementation Study.

BACKGROUND: We piloted a web-based, provider-driven mobile app (DialysisConnect) to fill the communication and care coordination gap between hospitals and dialysis facilities. OBJECTIVE: This study aimed to describe the development and pilot implementation of DialysisConnect. METHODS: DialysisConnect was developed iteratively with focus group and user testing feedback and was made available to 120 potential users at 1 hospital (hospitalists, advanced practice providers [APPs], and care coordinators) and 4 affiliated dialysis facilities (nephrologists, APPs, nurses and nurse managers, social workers, and administrative personnel) before the start of the pilot (November 1, 2020, to May 31, 2021). Midpilot and end-of-pilot web-based surveys of potential users were also conducted. Descriptive statistics were used to describe system use patterns, ratings of multiple satisfaction items (1=not at all; 3=to a great extent), and provider-selected motivators of and barriers to using DialysisConnect. RESULTS: The pilot version of DialysisConnect included clinical information that was automatically uploaded from dialysis facilities, forms for entering critical admission and discharge information, and a direct communication channel. Although physicians comprised most of the potential users of DialysisConnect, APPs and dialysis nurses were the most active users. Activities were unevenly distributed; for example, 1 hospital-based APP recorded most of the admissions (280/309, 90.6%) among patients treated at the pilot dialysis facilities. End-of-pilot ratings of DialysisConnect were generally higher for users versus nonusers (eg, "I can see the potential value of DialysisConnect for my work with dialysis patients": mean 2.8, SD 0.4, vs mean 2.3, SD 0.6; P=.02). Providers most commonly selected reduced time and energy spent gathering information as a motivator (11/26, 42%) and a lack of time to use the system as a barrier (8/26, 31%) at the end of the pilot. CONCLUSIONS: This pilot study found that APPs and nurses were most likely to engage with the system. Survey participants generally viewed the system favorably while identifying substantial barriers to its use. These results inform how best to motivate providers to use this system and similar systems and inform future pragmatic research in care coordination among this and other populations.

Effectiveness of a Web-Based Provider Communications Platform in Reducing Hospital Readmissions Among Patients Receiving Dialysis: A Pilot Pre-Post Study.

Rationale & Objective: Suboptimal care coordination between dialysis facilities and hospitals is an important driver of 30-day hospital readmissions among patients receiving dialysis. We examined whether the introduction of web-based communications platform ("DialysisConnect") was associated with reduced hospital readmissions. Study Design: Pilot pre-post study. Setting & Participants: A total of 4,994 index admissions at a single hospital (representing 2,419 patients receiving dialysis) during the study period (January 1, 2019-May 31, 2021). Intervention: DialysisConnect was available to providers at the hospital and 4 affiliated dialysis facilities (=intervention facilities) during the pilot period (November 1, 2020-May 31, 2021). Outcomes: The primary outcome was 30-day readmission; secondary outcomes included 30-day emergency department visits and observation stays. Interrupted time series and linear models with generalized estimating equations were used to assess pilot versus prepilot differences in outcomes; difference-in-difference analyses were performed to compare these differences between intervention versus control facilities. Sensitivity analyses included a third, prepilot/COVID-19 period (March 1, 2020-October 31, 2020). Results: There was no statistically significant difference in the monthly trends in the 30-day readmissions pilot versus prepilot periods (-0.60 vs -0.13, P = 0.85) for intervention facility admissions; the difference-in-difference estimate was also not statistically significant (0.54 percentage points, P = 0.83). Similar analyses including the prepilot/COVID-19 period showed that, despite a substantial drop in admissions at the start of the pandemic, there were no statistically significant differences across the 3 periods. The age-, sex-, race-, and comorbid condition-adjusted, absolute pilot versus prepilot difference in readmissions rate was 1.8% (-3.7% to 7.3%); similar results were found for other outcomes. Limitations: Potential loss to follow-up and pandemic effects. Conclusions: In this pilot, the introduction of DialysisConnect was not associated with reduced hospital readmissions. Tailored care coordination solutions should be further explored in future, multisite studies to improve the communications gap between dialysis facilities and hospitals.

Long-term metformin treatment and risk of peripheral neuropathy in older Veterans.

AIM: Our objective was to assess whether increased duration of metformin therapy is associated with incident peripheral neuropathy (PN) in older Veterans with diabetes. METHODS: Using national Veterans Affairs registry data from 2002 to 2015, we examined Veterans (50 + years) with diabetes. Long-term metformin therapy was defined as prescription ≥ 500 mg/day, filled for ≥ 6 consecutive months. Metformin therapy duration was examined both as continuous and categorical measures. Incident PN was defined by medical chart review. We estimated unadjusted and adjusted (variables selecteda priori)odds ratios (OR) and 95% confidence intervals (CI) using logistic regression. RESULTS: The study included n = 210,004 individuals (mean ± SD: age: 66.2 ± 8.4 yrs, 96% male) prescribed metformin for 47.0 ± 34.0 months. Nineteen percent developed PN during follow-up. After adjusting for age, body mass index, duration of time receiving health care within the VA, smoking status, alcohol abuse, and vitamin B12 testing and treatment, the number of months of metformin treatment was associated with elevated odds for incident PN (aOR (metformin treatment - continuous) = 1.009 (95% CI = 1.009, 1.010); aOR (metformin treatment - categorical (ref: 6-<18 months): 18-<44.1 months = 1.57 (1.51-1.63), 44.1-<61 months = 2.05 (1.97-2.14), 61 + months = 2.69 (2.58-2.79), all p-values < 0.0001). CONCLUSION: Our study suggests that Veterans treated for at least 18 months with metformin are approximately 2-3 times more likely to develop PN than those treated at least six, but<18 months. Future studies are needed to determine whether the association we found may be due to a decline in vitamin B12 status following metformin initiation.

Weight Trends in Veterans With and Without Diabetes, 2000 to 2014.

OBJECTIVE: The aim of this study was to assess weight trends and diabetes prevalence among US veterans. METHODS: Information from the Veterans Affairs Informatics and Computing Infrastructure Corporate Data Warehouse was used to construct data sets that included demographic data, diabetes status, and weight observations for males and females. Secular and longitudinal trends in mean weight were analyzed. RESULTS: A total of 4,527,865 patients born from 1915 to 1984 with weight data during 2000 to 2014 were included; 36.8% had diabetes. Mean weight at baseline was higher in men and women with diabetes (97 kg and 88 kg, respectively) than in men and women without diabetes (86 kg and 76 kg, respectively). Mean weight increased from 2000 to 2014 (P < 0.001) at rates of 0.36 kg/y in women without diabetes, 0.28 kg/y in men with diabetes, 0.25 kg/y in men without diabetes, and 0.22 kg/y in women with diabetes. Weight decreased in those born before 1940, was stable in those born between 1940 and 1949, and increased in those born since 1950. CONCLUSIONS: Among contemporary veterans, women without diabetes are gaining weight more rapidly than women with diabetes or men. Younger veterans are gaining weight more rapidly than older veterans. Further efforts are needed to prevent weight gain in veterans, especially among women.

Race and Socioeconomic Status Independently Affect Risk of Major Amputation in Peripheral Artery Disease.

BACKGROUND: Black race has been shown to be a risk factor for amputation in peripheral artery disease (PAD); however, race has been argued to be a marker for socioeconomic status (SES) rather than true disparity. The aim of this study is to study the impact of race and SES on amputation risk in PAD patients. METHODS AND RESULTS: Patients with incident PAD in the national Veterans Affairs Corporate Data Warehouse were identified from 2003 to 2014 (N=155 647). The exposures were race and SES (measured by median income in residential ZIP codes). The outcome was incident major amputation. Black veterans were significantly more likely to live in low-SES neighborhoods and to present with advanced PAD. Black patients had a higher amputation risk in each SES stratum compared with white patients. In Cox models (adjusting for covariates), black race was associated with a 37% higher amputation risk compared with white race (hazard ratio: 1.37; 95% confidence interval, 1.30-1.45), whereas low SES was independently predictive of increased risk of amputation (hazard ratio: 1.12; 95% confidence interval, 1.06-1.17) and showed no evidence of interaction with race. In predicted amputation risk analysis, black race and low SES continued to be significant risk factors for amputation regardless of PAD presentation. CONCLUSIONS: Black race significantly increases the risk of amputation within the same SES stratum compared with white race and has an independent effect on limb loss after controlling for comorbidities, severity of PAD at presentation, and use of medications.

Serious Fall Injury History and Adverse Health Outcomes After Initiating Hemodialysis Among Older U.S. Adults.

Background: Although older adults with predialysis chronic kidney disease are at higher risk for falls, the prognostic significance of a serious fall injury prior to dialysis initiation has not been well described in the end-stage renal disease population. Methods: We examined the association between a serious fall injury in the year prior to starting hemodialysis and adverse health outcomes in the year following dialysis initiation using a retrospective cohort study of U.S. Medicare beneficiaries ≥ 67 years old who initiated dialysis in 2010-2012. Serious fall injuries were defined using diagnostic codes for falls plus an injury (fracture, joint dislocation, or head injury). Health outcomes, defined as time-to-event variables within the first year of dialysis, included four outcomes: a subsequent serious fall injury, hospital admission, post-acute skilled nursing facility (SNF) utilization, and mortality. Results: Among this cohort of 81,653 initiating hemodialysis, 2,958 (3.6%) patients had a serious fall injury in the year prior to hemodialysis initiation. In the first year of dialysis, 7.6% had a subsequent serious fall injury, 67.6% a hospitalization, 30.7% a SNF claim, and 26.1% died. Those with versus without a serious fall injury in the year prior to hemodialysis initiation were at higher risk (hazard ratio, 95% confidence interval) for a subsequent serious fall injury (2.65, 2.41-2.91), hospitalization (1.11, 1.06-1.16), SNF claim (1.40, 1.30-1.50), and death (1.14, 1.06-1.22). Conclusions: For older adults initiating dialysis, a history of a serious fall injury may provide prognostic information to support decision making and establish expectations for life after dialysis initiation.

Long-term Metformin Therapy and Monitoring for Vitamin B12 Deficiency Among Older Veterans.

OBJECTIVE: To examine the association between long-term metformin therapy and serum vitamin B12 monitoring. DESIGN: Retrospective cohort study. SETTING: A single Veterans Affairs Medical Center (VAMC), 2002-2012. PARTICIPANTS: Veterans 50 years or older with either type 2 diabetes and long-term metformin therapy (n = 3,687) or without diabetes and no prescription for metformin (n = 13,258). MEASUREMENTS: We determined diabetes status from outpatient visits, and defined long-term metformin therapy as a prescription ≥500 mg/d for at least six consecutive months. We estimated the proportion of participants who received a serum B12 test and used multivariable logistic regression, stratified by age, to evaluate the association between metformin use and serum B12 testing. RESULTS: Only 37% of older adults with diabetes receiving metformin were tested for vitamin B12 status after long-term metformin prescription. The mean B12 concentration was significantly lower in the metformin-exposed group (439.2 pg/dL) compared to those without diabetes (522.4 pg/dL) (P = .0015). About 7% of persons with diabetes receiving metformin were vitamin B12 deficient (<170 pg/dL) compared to 3% of persons without diabetes or metformin use (P = .0001). Depending on their age, metformin users were two to three times more likely not to receive vitamin B12 testing compared to those without metformin exposure, after adjusting for sex, race and ethnicity, body mass index, and number of years treated at the VAMC. CONCLUSION: Long-term metformin therapy is significantly associated with lower serum vitamin B12 concentration, yet those at risk are often not monitored for B12 deficiency. Because metformin is first line therapy for type 2 diabetes, clinical decision support should be considered to promote serum B12 monitoring among long-term metformin users for timely identification of the potential need for B12 replacement.