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      Temporal Trends in Incidence Rates of Lower Extremity Amputation and Associated Risk Factors Among Patients Using Veterans Health Administration Services From 2008 to 2018

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          Key Points

          Question

          What are the temporal trends of lower extremity amputation (LEA) among US veterans and what risk factors are associated with the changes?

          Findings

          In this cohort study of 6 493 141 veterans using Veterans Health Administration services, rates of LEA increased between 2008 and 2018. Changes in demographic composition and lower smoking rates were associated with a reduction in LEA incidence rates, but these reductions were more than offset by increased rates of diabetes, peripheral artery disease, and chronic kidney disease.

          Meaning

          These findings suggest that strategies targeting prevention of diabetes, peripheral artery disease, and chronic kidney disease, as well as further reduction in smoking rates, might contribute to reducing the burden of LEA.

          Abstract

          This cohort study examines temporal trends and risk factors associated with lower extremity amputation among veterans using Veterans Health Administration services.

          Abstract

          Importance

          Lower extremity amputation (LEA) is associated with significant morbidity and mortality. However, national temporal trends of LEA incidence rates among US veterans and associated factors have not been well characterized.

          Objective

          To describe the temporal trends of LEA, characterize associated risk factors, and decompose the associations of these risk factors with changes in temporal trends of LEA among US veterans using Department of Veteran Affairs (VA) services between 2008 and 2018.

          Design, Setting, and Participants

          This cohort study used VA data from 2008 to 2018 to estimate incidence rates of LEA among veterans using VA services. Cox regression models were used to identify risk factors associated with LEA. Decomposition analyses estimated the associations of changes in prevalence of risk factors with changes in LEA rates. Data were analyzed from October 1, 2007, to September 30, 2018.

          Main Outcomes and Measures

          Toe, transmetatarsal, below-knee, or above-knee LEA.

          Results

          A total of 6 493 141 veterans were included (median [interquartile range] age, 64 [54-76] years; 6 060 390 [93.4%] men). Veterans were studied for a median (interquartile range) of 10.9 (5.6-11.0) years. Between 2008 and 2018, rates of LEA increased from 12.89 (95% CI, 12.53-13.25) LEA per 10 000 persons to 18.12 (95% CI, 17.70-18.54) LEA per 10 000 persons, representing a net increase of 5.23 (95% CI, 4.68-5.78) LEA per 10 000 persons. Between 2008 and 2018, toe amputation rates increased by 3.24 (2.89-3.59) amputations per 10 000 persons, accounting for 62.0% of the total increase in LEA rates. Transmetatarsal amputations increased by 1.54 (95% CI, 1.27-1.81) amputations per 10 000 persons; below-knee amputation rates increased by 0.81 (95% CI, 0.56-1.05) amputations per 10 000 persons; and above-knee amputation rates decreased by 0.37 (95% CI, 0.14-0.59) amputations per 10 000 persons. Compared with men, women had decreased risk of any LEA (hazard ratio [HR], 0.34 [95% CI, 0.31-0.37]). Factors associated with increased risk of any LEA included Black race (HR, 1.25 [95% CI, 1.21-1.28]) or another non-White race (ie, Asian, Latino, or other; HR, 2.36 [95% CI, 2.30-2.42]), obesity (HR, 1.59 [95% CI, 1.55-1.63]), diabetes (HR, 6.38 [95% CI, 6.22-6.54]), chronic kidney disease (CKD; eg, CKD stage 5: HR, 3.94 [95% CI, 3.22-4.83]), and smoking status (eg, current smoking: HR, 1.97 [95% CI, 1.92-2.03]). Decomposition analyses suggested that while changes in demographic composition, primarily driven by increased proportion of women veterans, associated with a decrease of 0.18 (95% CI, 0.14-0.22) LEA per 10 000 persons, and decreases in smoking rates, associated with a decrease of 0.88 (95% CI, 0.79-0.97) LEA per 10 000 persons. However, these were overwhelmed by increased rates of diabetes, associated with an increase of 1.86 (95% CI, 1.72-1.99) LEA per 10 000 persons; peripheral arterial disease, associated with an increase of 1.53 (95% CI, 1.41-1.65) LEA per 10 000 persons; CKD, associated with an increase of 1.45 (95% CI, 1.33-1.57) LEA per 10 000 persons; and other clinical factors, including body mass index, cancer, cardiovascular disease, cerebrovascular disease, chronic lung disease, dementia, and hypertension, associated with an increase of 1.45 (95% CI, 1.33-1.57) LEA per 10 000 persons.

          Conclusions and Relevance

          This cohort study found that incidence rates of LEA among veterans using VA services increased between 2008 and 2018. Efforts aimed at reducing burden of LEA should target the reduction of diabetes, peripheral arterial disease, and CKD at the individual and population levels.

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          Most cited references44

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          Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                22 January 2021
                January 2021
                22 January 2021
                : 4
                : 1
                : e2033953
                Affiliations
                [1 ]Clinical Epidemiology Center, Department of Veterans Affairs, St Louis Health Care Systems, St Louis, Missouri
                [2 ]Veterans Research and Education Foundation of St Louis, St Louis, Missouri
                [3 ]Department of Epidemiology and Biostatistics, College for Public Health and Social Justice, St Louis University, St Louis, Missouri
                [4 ]Section of Vascular Surgery, Department of Surgery, School of Medicine, Washington University in St Louis, St Louis, Missouri
                [5 ]Department of Surgery, Veterans Affairs St Louis Health Care System, St Louis, Missouri
                [6 ]Division of Nephrology, School of Medicine, Washington University in St Louis, St Louis, Missouri
                [7 ]Department of Medicine, School of Medicine, Washington University in St Louis, St Louis, Missouri
                [8 ]Nephrology Section, Medicine Service, Department of Veteran Affairs St Louis Health Care System, St Louis, Missouri
                [9 ]Institute for Public Health, Washington University in St Louis, St Louis, Missouri
                Author notes
                Article Information
                Accepted for Publication: November 25, 2020.
                Published: January 22, 2021. doi:10.1001/jamanetworkopen.2020.33953
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Cai M et al. JAMA Network Open.
                Corresponding Author: Ziyad Al-Aly, MD, VA St Louis Health Care System, 915 N Grand Blvd, 151-JC, St Louis, MO 63106 ( zalaly@ 123456gmail.com ).
                Author Contributions: Dr Al-Aly had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Cai, Gibson, Zayed, Al-Aly.
                Acquisition, analysis, or interpretation of data: Cai, Xie, Bowe, Zayed, Li, Al-Aly.
                Drafting of the manuscript: Cai, Zayed, Al-Aly.
                Critical revision of the manuscript for important intellectual content: All authors.
                Statistical analysis: Cai, Bowe, Al-Aly.
                Obtained funding: Al-Aly.
                Administrative, technical, or material support: Zayed, Al-Aly.
                Supervision: Zayed, Al-Aly.
                Conflict of Interest Disclosures: None.
                Funding/Support: This study was funded by the US Department of Veterans Affairs and the Institute for Public Health at Washington University in St Louis, Missouri (Dr Al-Aly).
                Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Disclaimer: The contents do not represent the views of the US Department of Veterans Affairs or the US government.
                Article
                zoi201030
                10.1001/jamanetworkopen.2020.33953
                7823225
                33481033
                9d8ad6dd-8eba-45e4-9c81-2dd406431e05
                Copyright 2021 Cai M et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 23 May 2020
                : 25 November 2020
                Categories
                Research
                Original Investigation
                Online Only
                Surgery

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