Incidence Of Lower Extremity Amputations Research Articles

Risk Factors for Lower Extremity Amputation in Patients with End-Stage Kidney Disease: A Nationwide Cohort Study.

Individuals with end-stage kidney disease (ESKD) on dialysis are at a high risk of developing foot ulcerations and undergoing subsequent lower extremity amputation (LEA), which can exert significant impacts on their quality of life and contribute to rising healthcare costs. We aimed to identify risk factors associated with LEA in patients with ESKD to predict LEA progression and eventually prevent it. We used 18 years (2002-2019) of data from the Korean National Health Insurance Service (KNHIS). Data were collected from patients with ESKD who underwent renal replacement therapy (RRT) and had no history of amputation caused by trauma or toxins. The risk factors were compared between patients with or without LEA. We collected data from 220,838 patients newly diagnosed with ESKD, including 6348 in the LEA group and 214,490 in the non-LEA group. The total incidence of LEA was 2.9%. Older age, male gender, lower income, non-metropolitan residence, diabetes mellitus, dialysis treatment (compared to kidney transplantation), microvascular disease, peripheral vascular disease, endovascular procedure, and endovascular operation were associated with an increased risk of LEA. Thus, individuals with ESKD who are at a higher risk for LEA should be closely monitored, and kidney transplantation should be considered as a preventative measure.

Impact of Diabetic Foot Multidisciplinary Unit on Incidence of Lower-Extremity Amputations by Diabetic Foot.

One of the most devastating complications of diabetes is diabetes-related foot disease (DFD), which is a priority for public health systems. The 2016-2020 Catalonia Health Plan aimed to reduce the incidence of total and major lower-extremity amputations (LEAs) due to DFD by 10% in the population aged 45-74 years. The aim of the present study was to compare the incidence of LEA-DFD 5 years before and after the creation of the Diabetic Foot Multidisciplinary Unit at our Hospital. We prospectively collected all cases of LEA-DFD performed at Vall d'Hebron University Hospital from 1 January 2016 to 31 December 2020. Cases of LEA-DFD performed from 1 January 2011 to 31 December 2015 were retrospectively reviewed. The incidence of LEA-DFD between these periods was compared. A total of 457 LEAs due to DFD were performed in 316 patients. We observed a reduction of 27.9% [CI: 23.7-32.1%] in the incidence of total LEA in the 2016-2020 period in comparison with the period 2011-2016 (0.8 ± 0.1 vs. 1.1 ± 0.3 per 10.000 inhabitants/year, p < 0.001), as well as a reduction of 49.3% [CI: 44.6-53.9%] in the incidence of major LEA-DFD (0.15 ± 0.1 vs. 0.30 ± 0.1 per 10.000 inhabitants/year, p < 0.001). The implementation of a Diabetic Foot Multidisciplinary Unit resulted in a significant reduction in the rate of amputations due to DFD in the population with diabetes in North Barcelona.

Incidence of Lower Extremity Amputation in Romania: A Nationwide 5-Year Cohort Study, 2015-2019.

Background and Objectives: The primary objective of this study was to investigate the incidence of lower extremity amputations (LEAs) in a representative population from Romania, in both diabetic and non-diabetic adults, including trauma-related amputations. The secondary objective was to evaluate the trends in LEAs and the overall ratio of major-to-minor amputations. Material and Methods: The study was retrospective and included data from the Romanian National Hospital Discharge Records, conducted between 1 January 2015 and 31 December 2019. Results: The overall number of cases with LEAs was 88,102, out of which 38,590 were aterosclerosis-related LEAs, 40,499 were diabetes-related LEAs, and 9013 were trauma-related LEAs, with an ascending trend observed annually for each of these categories. Of the total non-traumatic amputations, 51.2% were in patients with diabetes. Most LEAs were in men. The total incidence increased from 80.61/100,000 in 2015 to 98.15/100,000 in 2019. Conclusions: Our study reported a 21% increase in total LEAs, 22.01% in non-traumatic LEAs, and 19.65% in trauma-related amputation. The minor-to-major amputation ratio increased over the study period in patients with diabetes. According to these findings, it is estimated that currently, in Romania, there is one diabetes-related amputation every hour and one non-traumatic amputation every 30 min.

1369-P: The Natural Trends in Incidence of Lower Extremity Amputations in South Korea, 2003–2021

Introduction: National data in incidence of lower extremity amputations in the population of South Korea is lacking. Diabetes mellitus is a major risk factor for lower extremity amputations. The prevalence of diabetes mellitus is increasing faster than previously estimated in South Korea. Therefore, we investigated the trend of lower extremity amputations not only in people with diabetes, but also in the total (medically documented) population. Method: We gathered and analyzed the data of the medically documented population, aged 20 years or older, from the Korean Health Insurance Service claims database between 2003 and 2021. Results: Since 2003, incidence of lower extremity amputations among the total population has steadily increased, more than doubling by 2021 (6.8 to 14.5 amputations per 100,000 of population). The contribution of diabetes mellitus on lower extremity amputation has also elevated from 47% in 2003 to 70% in 2021. During the study period, the incidence of lower extremity amputations was consistently higher by more than three times in men (21.6) than in women (7.3), amputations per 100,000 of population in 2021. When foot amputations were classified by lower extremity parts, the proportion of major amputations (above ankle) has decreased slightly. In the last 10 years, the frequency and proportion of three or more repeated foot amputations has reduced (431 (9.2%) to 207 (4.1%)). Conclusion: We reported the increasing trend of lower extremity amputation between 2003 and 2021 according to the increase in the prevalence of diabetes mellitus in South Korea. Among all lower extremity amputations, the major amputations and multiple amputations, 3 or more times, are decreasing. Disclosure J.Jeon: None. K.Lee: None. N.Kim: None. J.Back: None. N.Lee: None. S.Han: None. H.Kim: None. D.Kim: None. T.Kim: None. S.An: None.

Evaluation of the Effectiveness of Remote Foot Temperature Monitoring for Prevention of Amputation in a Large Integrated Health Care System

OBJECTIVEWe evaluated the effectiveness of remote foot temperature monitoring (RTM) in the Veterans Affairs health care system.RESEARCH DESIGN AND METHODSWe conducted a retrospective cohort study that included 924 eligible patients enrolled in RTM between 2019 and 2021 who were matched up to 3:1 to 2,757 nonenrolled comparison patients. We used conditional Cox regression to estimate adjusted cause-specific hazard ratios (aHRs) and corresponding 95% CIs for lower-extremity amputation (LEA) as the primary outcome and all-cause hospitalization and death as secondary outcomes.RESULTSRTM was not associated with LEA incidence (aHR 0.92, 95% CI 0.62–1.37) or all-cause hospitalization (aHR 0.97, 95% CI 0.82–1.14) but was inversely associated (reduced risk) with death (aHR 0.63, 95% CI 0.49–0.82).CONCLUSIONSThis study does not provide support that RTM reduces the risk of LEA or all-cause hospitalization in individuals with a history of diabetic foot ulcer. Randomized controlled trials can overcome important limitations.

Quantifying the incidence of lower limb amputation in people with and without diabetes in Wales between 2008–2018

BackgroundThere is variance in the incidence of lower extremity amputation across and within countries including within the UK. National data shows up to a fourfold variance in the amputation rate throughout the regions of England and differences in amputation incidence have been reported in Scotland and Ireland. Lower extremity amputation rate has yet to be documented within Wales. The aim of this cohort study was to examine trends in diabetes and non-diabetes related lower extremity amputation incidence within the Welsh population and to examine the influence of diabetes on the relative risk of amputation. Materials and MethodsAll first-time amputations between 2008-2018 were extracted from SAIL, a repository of all routine medical data of residents of Wales. People with diabetes were identified using an algorithm utilising data from several clinical and non-clinical sources. Crude and direct age and sex adjusted incidences were estimated over time. ResultsOver the period 3505 major amputations and 4335 minor amputations occurred. The diabetes population greater than 17 years of age increased by 29.4% from 143,595 in 2008 to 206,818 in 2018. There was a statistically significant rate reduction in major amputation in both populations. In the diabetes population the number of major amputations reduced from 6.9 [5.5–8.5]/10 000 person years (PY) in 2008 to 4.9 [5.4–6.2]/10 000 PY in 2018. However, for major amputation, the risk of incident amputation in people with diabetes was 7.3 fold higher [7.1–7.5] than those without diabetes. The relative risk of minor amputation for those with diabetes was higher at 11.9 [11.8 –1.01]. There was no reduction in this risk over the period. ConclusionThis study found that rates of major amputation decreased over the study period but the risk of amputation for persons with diabetes remained substantial. As the population with diabetes increases so do crude rates of amputation, providing a substantial financial and societal cost to the Welsh Population.

Lower extremity amputations (LEAs) in a tertiary hospital in Togo: a retrospective analysis of clinical, biological, radiological, and therapeutic aspects

BackgroundWe analysed the clinical, biological, radiological profiles, and therapeutic patterns of the patients who underwent a surgical lower extremity amputation (LEA) in Togo from 2010 to 2020.MethodsRetrospective analysis of clinical files of adult patients who underwent an LEA at a single centre (Sylvanus Olympio Teaching Hospital) from 1st January 2010 to 31st December 2020. Data were analysed by CDC Epi Info Version 7 and Microsoft Office Excel 2013 software.ResultsWe included 245 cases. The mean age was 59.62 years (15.22 SD) (range: 15–90 years). The sex ratio was 1.99. The medical history of diabetes mellitus (DM) was found in 143/222 (64.41%) files. The amputation level found in 241/245 (98.37%) files was the leg in 133/241 (55.19%) patients, the knee in 14/241 (5.81%), the thigh in 83/241 (34.44%), and the foot in 11/241 (4.56%). The 143 patients with DM who underwent LEA had infectious and vascular diseases. Patients with previous LEAs were more likely to have the same limb affected than the contralateral one. The odds of trauma as an indication for LEA were twice as high in patients younger than 65 years compared to the older (OR = 2.095, 95% CI = 1.050–4.183). The mortality rate after LEA was 17/238 (7.14%). There was no significant difference between age, sex, presence or absence of DM, and early postoperative complications (P = 0.77; 0.96; 0.97). The mean duration of hospitalization marked in 241/245 (98.37%) files was 36.30 (1–278) days (36.20 SD). Patients with LEAs due to trauma had a significantly longer hospital admission than those with non-traumatic indications, F (3,237) = 5.505, P = 0.001.ConclusionsCompared to previous decades, from 2010 to 2020, the average incidence of LEAs for all causes at Sylvanus Olympio Teaching Hospital (Lomé, Togo) decreased while the percentage of patients with DM who underwent LEAs increased. This setting imposes a multidisciplinary approach and information campaigns to prevent DM, cardiovascular diseases, and relative complications.

A database study on incidence and trends in traumatic lower-extremity amputations in the United States

Background: There is minimal focus on traumatic lower-extremity amputations due to their relatively low incidence, but they often come with a higher morbidity and mortality than their upper extremity counterparts. The purpose of this study was to evaluate the incidence and trends of lower extremity amputations in the United States over 10 yr. Methods: The National Electronic Injury Surveillance System (NEISS) was queried from 2008 to 2017 for lower-extremity amputations presenting to United States emergency departments. Date of presentation, age at presentation, amputated appendage, disposition, and cause of the amputation were reported and used for statistical analysis. Results: From 2008 to 2017, 393 patients were reported to have sustained lower-extremity amputations within the NEISS database with an estimated total of 11,475 patients sustaining a lower-extremity amputation over the past 10 yr and an incidence of 2.2 per 100,000 person-years. The incidence of lower-extremity amputations is highest in those under 5 years old. Lawnmowers were the most common mechanism of injury in all age groups. Discussion: Due to the high morbidity and mortality associated with these injuries, it is prudent to follow the trends in lower-extremity amputations. This is particularly important in promoting awareness and prevention of the more common mechanisms such as lawnmower incidents. Level of Evidence: Level IV.

Temporal trends in major, minor and recurrent lower extremity amputations in people with and without diabetes in Belgium from 2009 to 2018

AimsThis study assessed temporal trends in the incidence of lower extremity amputations (LEA) in Belgium from 2009 to 2018, and subsequent secondary amputation rates. MethodsNationwide data on LEA were collected. Sex- and age-adjusted annual incidence rates were calculated. Time trends were analysed in negative binomial models. The incidence of secondary interventions, defined as either any ipsilateral reamputation or any contralateral amputation, was studied with death as competing risk. Results41 304 amputations were performed (13 247 major, 28 057 minor). In individuals with diabetes, the amputation rate (first amputation per patient per year) decreased from 143.6/100.000 person-years to 109.7 (IRR 0.97 per year, 95 %CI 0.96–0.98, p < 0.001). The incidence of major LEAs decreased from 56.2 to 30.7 (IRR 0.93, 95 %CI 0.91–0.94, p < 0.001); the incidence of minor amputations showed a non-significant declining trend in women (54.3 to 45.0/100 000 person years, IRR 0.97 per year, 95 %CI 0.96–0.99), while this remained stable in men with diabetes (149.2 to 135.3/100 000 person years, IRR 1.00 per year, 95 %CI 0.98–1.01). In individuals without diabetes, the incidence of major amputation didn’t change significantly, whereas minor amputation incidence increased (8.0 to 10.6, IRR 1.04, 95 %CI 1.03–1.05, p < 0.001). In individuals with diabetes, one-year secondary intervention rates were high (31.3% after minor, 18.4% after major LEA); the incidence of secondary amputations didn’t change. ConclusionsA significant decline in the incidence rate of major LEA was observed in people with diabetes. This decline was not accompanied by a significant rise in minor LEA. The incidence of secondary interventions remained stable.

Pay-for-performance and continuity of care synergistically reduced amputation of lower extremity in patients with diabetes: a population-based cohort study

sBackgroundDiabetic foot is a common and costly complication of diabetes. No existing study has looked at the effect of continuity of care on amputations of diabetes (DM) patients while considering pay-for-performance (P4P) participation. We investigated the impact of the P4P program and the continuity of care index (COCI) on the incidence of lower extremity amputations (LEA) among diabetics in Taiwan.MethodsThis was a population-based cohort study using insurance claims data from 1997 to 2013. We selected 15,650 DM patients in the P4P program along with age- and sex-matched non-P4P participants at a 1:4 ratio. Time-weighted average (TWA) of the COCI was calculated and included in the time-dependent Cox proportional hazard models to examine the impact of P4P and COCI on the risk of LEA, while controlling for individual and area level characteristics.ResultsDuring four-year follow-up, 1816 subjects experienced LEA. The cumulative LEA hazard rate of the P4P group (n = 153) was significantly lower than that of the non-P4P group (n = 1663) (hazard ratio = 0.37, 95% CI = 0.31–0.43, p < 0.0001, by log-rank test). In the time-dependent Cox proportional hazard model, the adjusted hazard ratios (aHR) for the P4P group was 0.35, (p < 0.0001). With the low COCI (< 0.50) group as the reference, the aHR of LEA was 0.49 (p < 0.0001) for the middle COCI group, (p < 0.0001), and the aHR of LEA for the high COCI (≥ 0.80) group was 0.23 (p < 0.0001).ConclusionsParticipating in the P4P program and increasing COCI might reduce the risk of amputation for DM patients, independently and synergistically.

Time trends (2001\u20132019) and sex differences in incidence and in-hospital mortality after lower extremity amputations among patients with type 1 diabetes in Spain

BackgroundWe examined trends in incidence (2001–2019), clinical characteristics, and in-hospital outcomes following major and minor lower extremity amputations (LEAs) among type 1 diabetes mellitus (T1DM) patients in Spain and attempted to identify sex differences.MethodsRetrospective cohort study using data from the Spanish National Hospital Discharge Database. We estimated the incidence of the LEA procedure stratified by type of LEA. Joinpoint regression was used to estimate incidence trends, and logistic regression was used to estimate factors associated with in-hospital mortality (IHM).ResultsLEA was coded in 6011 patients with T1DM (66.4% minor and 33.6% major). The incidence of minor LEA decreased by 9.55% per year from 2001 to 2009 and then increased by 1.50% per year, although not significantly, through 2019. The incidence of major LEA decreased by 13.39% per year from 2001 to 2010 and then remained stable through 2019. However, incidence increased in men (26.53% per year), although not significantly, from 2017 to 2019. The adjusted incidence of minor and major LEA was higher in men than in women (IRR 3.01 [95% CI 2.64–3.36] and IRR 1.85 [95% CI 1.31–2.38], respectively). Over the entire period, for those who underwent a minor LEA, the IHM was 1.58% (2.28% for females and 1.36% for males; p = 0.045) and for a major LEA the IHM was 8.57% (10.52% for females and 7.59% for males; p = 0.025).IHM after minor and major LEA increased with age and the presence of comorbid conditions such as peripheral arterial disease, ischemic heart disease or chronic kidney disease. Female sex was associated with a higher IHM after major LEA (OR 1.37 [95% CI 1.01–1.84]).ConclusionsOur data show a decrease in incidence rates for minor and major LEA in men and women with T1DM and a slight, albeit insignificant, increase in major LEA in men with T1DM in the last two years of the study. The incidence of minor and major LEA was higher in men than in women. Female sex is a predictor of IHM in patients with T1DM following major LEA.

Diabetes and other vascular risk factors in association with the risk of lower extremity amputation in chronic limb-threatening ischemia: a prospective cohort study

BackgroundPatients with diabetes are at increased risk of developing chronic limb-threatening ischemia (CLTI) due to peripheral arterial disease, and this often results in lower extremity amputation (LEA). Little is known of the interaction between diabetes and other vascular risk factors in affecting the risk of CLTI.MethodsWe investigated the association of diabetes, and its interaction with hypertension, body mass index (BMI) and smoking, with the risk of LEA due to CLTI in the population-based Singapore Chinese Health Study. Participants were interviewed at recruitment (1993–1998) and 656 incident LEA cases were identified via linkage with nationwide hospital database through 2017. Multivariate-adjusted Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% CIs for the associations.ResultsThe HR (95% CI) for LEA risk was 13.41 (11.38–15.79) in participants with diabetes compared to their counterparts without diabetes, and the risk increased in a stepwise manner with duration of diabetes (P for trend < 0.0001). Hypertension and increased BMI independently increased LEA risk in those without diabetes but did not increase the risk in those with diabetes (P for interaction with diabetes ≤ 0.0006). Conversely, current smoking conferred a risk increment of about 40% regardless of diabetes status.ConclusionsAlthough diabetes conferred more than tenfold increase in risk of LEA, hypertension and increased BMI did not further increase LEA risk among those with diabetes, suggesting a common mechanistic pathway for these risk factors. In contrast, smoking may act via an alternative pathway and thus confer additional risk regardless of diabetes status.

1447 Trends in Lower Extremity Amputation Incidence in European Union 15+ Countries 1990-2017

Abstract Aim To assess trends in lower extremity amputation (LEA) incidence in European Union (EU15+) countries for the years 1990-2017. Method This was an observational study using data obtained from the 2017 Global Burden of Disease (GBD) Study. Age standardised incidence rates (ASIRs) for LEA (stratified into toe amputation, and LEA proximal to toes) were extracted from the GBD Results Tool (http://ghdx.healthdata.org/gbd-results-tool) for EU15+ countries for each of the years 1990-2017. Trends were analysed using Joinpoint regression analysis. Results Between 1990 and 2017, variable trends in the incidence of LEA were observed in EU15+ countries. For LEAs proximal to toes, increasing trends were observed in six of 19 countries and decreasing trends in nine of 19 countries, with four countries showing varying trends between sexes. For toe amputation, increasing trends were observed in eight of 19 countries and decreasing trends in eight of 19 countries for both sexes, with three countries showing varying trends between sexes. Australia had the highest ASIRs for both sexes in all LEAs at all time points, with steadily increasing trends. The USA observed the greatest reduction in all LEAs in both sexes over the time period analysed (LEAs proximal to toes: female patients 22.93%, male patients 29.76%; toe amputation: female patients 29.93%, male patients 32.67%). The greatest overall increase in incidence was observed in Australia. Conclusions Variable trends in LEA incidence were observed across EU15+ countries. These trends do not reflect previously observed reductions in incidence of PAOD over the same time period.

A Comparative Analysis of Lower Extremity Amputations and Socioeconomic Determinants Before and During the Coronavirus Disease 2019 State of Emergency in Patients Presenting With Acute Limb Ischemia

A noticeable increase occurred in lower extremity amputations (LEAs) during the coronavirus disease 2019 (COVID-19) pandemic. A previous study from our institution showed that patients with acute limb ischemia (ALI) had presented with advanced ALI during the COVID-19 Massachusetts state of emergency (SOE). In the present study, we investigated patients who had undergone amputation for ALI during the SOE compared with the same period in 2019. We considered the socioeconomic elements, presentation delay, and medical comorbidities as risk factors leading to a greater incidence of LEAs during the SOE.

O48 Incongruous trends in peripheral arterial disease and amputation in Australia

Abstract Introduction We aimed to compare the incidence trends for peripheral arterial disease (PAD) and lower extremity amputation (LEA) in Australia with European Union (EU) 15+ countries. Method For the years 1990–2017, we extracted PAOD and LEA incidence data from the Global Burden of Disease (GBD) Study and compared trends across EU15+ countries (19 countries with similar health expenditure—including Australia, the US and the UK). Result In 2017, the age-standardised incidence rate (ASIR) for PAOD was lower in Australia than any other EU15+ country for males (90.0/100,000) and third lowest in females (99.9/100,000) (only females in Norway and Spain had lower 2017 ASIRs for PAD). However for LEA, the 2017 ASIRs were higher in Australia for both sexes than in any other EU15+ country (male 119.8/100,000, female 78.0/100,000). Furthermore, contrasting and anomalous time trends in the incidence of PAOD and LEA were observed in Australia between 1990–2017. The PAOD ASIR decreased over the 28-year period for both males (-16.5%) and females (-17.4%), whereas the LEA ASIR increased over the same time period for both sexes (males +12.5%, females +10.3%). Given the frequency with which LEAs are precipitated by PAOD, these divergent trends were unexpected, especially within a developed country such as Australia. Conclusion Our data raises the concern that the true incidence of PAOD in Australia is under-diagnosed, with at-risk patients potentially being recognised late in the disease-process, manifesting as high amputation rates relative to countries with similar health expenditure. Take-home Message Australia has anomalous trends in amputation and peripheral arterial disease when compared with other countries with similar health expenditure. Our data raises the concern that the true incidence of PAOD in Australia is under-diagnosed, with at-risk patients potentially being recognised late in the disease-process, manifesting as high amputation rates relative to countries with similar health expenditure.

Vascular Diagnostic and Surgical Treatments Before Lower Limb Amputations in Patients with Arterial Vascular Diseases: A Population Based Study from 2013 to 2015 in Germany

Patients with peripheral artery disease (PAD) have an increased risk of lower limb amputation. Given the international wide variance in major amputations, the high mortality rates and follow up costs as well as the significantly reduced quality of life of patients with amputations, vascular diagnostics and vascular surgery treatments are of great importance for lower limb preservation in patients with PAD. This study examines these guideline based procedures in patients before a first lower limb amputation and PAD. This was a retrospective longitudinal study. Data from a large German statutory health insurance scheme were examined on patients with first amputation of lower extremities and PAD between 2013 and 2015 (incidence). Pre-defined vascular diagnostic and vascular surgical procedures were considered, as specified by guidelines within inpatient and outpatient care in a defined time before lower limb amputation. The overall estimated incidence of lower extremity amputations in the total population was 0.12% from 2013 to 2015. Of these, 51.7% had PAD; 81.8% of patients received at least one vascular diagnostic measure and 61.0% a vascular surgery procedure before the lower extremity amputation. There were only minor variations in the use of diagnostic or surgical treatments between patients with major and minor amputation. In total, 63.9% of patients had vascular surgery before the incident major amputation compared with 60.0% of patients with a minor amputation. Noticeable regional differences were found ranging from 91% (Berlin) to 67% (Bremen) regarding diagnostic procedures provided before amputation, and from 83% (Hamburg) to 55% (Saxony-Anhalt) regarding vascular surgery before amputations. Of patients with PAD, 18.2% did not receive a vascular diagnostic examination before amputation as specified in the guidelines, which reflects an underuse of health services. In one third of patients who did not receive vascular surgery, major amputation probably could have been avoided.

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

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

Annual Foot Exams and Incident Amputation

Diabetes-related lower extremity amputations (LEA) are high cost and high prevalence. Individuals with complications such as neuropathy, foot deformity, history of diabetic foot ulcer or LEA increased morbidity and mortality.1 Current national recommend a foot exam for individuals with diabetes annually or more often depending on risk for LEA.2, The purpose of this pilot study was to examine the relationship between annual foot exams and incident lower extremity amputation in a large Veteran cohort. We conducted a secondary analysis of a national VA Diabetes administrative dataset registry for Veterans with diabetes aged 65 and older during the period of fiscal year 2002-2014 (n=1,544,654; mean age 77.6 years; 97.9 % male). Using logistic regression, we examined the association between annual foot exams and incident LEA. Our analysis was adjusted for demographics, comorbidities, and LEA foot risk. The study included 18,759 (1.21%) Veterans with incident LEA and foot exams, 2,234 (0.14%) Veterans with incident LEA without foot exams. Median age range was 65-75 years old. Gangrene, osteomyelitis, foot ulcers, and neuropathy were the covariates with the highest risk of incident LEA with foot exam. Foot exams did not reduce the risk of LEA when examining Veterans with incident LEA (unadjusted OR of 1.62 (CI 1.56 - 1.69), p<.0001 and adjusted OR was 1.77 (CI 1.69 -1.86), p<.0001. Annual foot exams were not protective for LEA in Veterans with foot exams and incident LEA. Additional research is warranted to examine this relationship considering the effect of early intervention on LEA risk.

Evaluation of Neuropathy, Glycemic Control, and Revascularization as Risk Factors for Future Lower Extremity Amputation among Diabetic Patients

Diabetes mellitus is a major risk factor for progression to lower extremity amputation (LEA) due to progressive neuropathy and glycemia-induced vasculopathy. In this study, we evaluated risk factors for incident LEA type 2 diabetics during a randomized controlled trial and extended post-trial follow-up. The Action to Control Cardiovascular Risk in Diabetes trial randomized 10,251 type 2 diabetics to intensive glycemic control (Hemoglobin A1c (HbA1c) target <6.0%) versus standard glycemic control (HbA1c target 7.0-7.9%). Using backward elimination logistic regression models, we examined relationships between neuropathy using the Michigan Neuropathy Screening Instrument (MNSI) and glycemic control and incident LEA during the clinical trial and subsequent follow-up. 9,746 patients were followed for a mean of 7.9 +/-3.1 (median 8.9) years after randomization. Ninety-eight (1%) participants underwent an incident LEA during the trial or post-trial follow-up period. Baseline demographics and traditional risk factors were examined by incident amputation status. Multivariable models revealed that abnormal 10 gm filament test (HR 4.50, 95% CI 2.92-6.95, P<0.0001), presence of ulceration (HR 4.22, 95% CI 1.65-10.8, P=0.0004), abnormal appearance on foot examination (HR 4.75, 95% CI 2.30-9.83, P<0.0001), and mean postrandomization HbA1c (HR 1.65, 95% CI 1.35-2.00, P<0.0001) were strongly predictive of LEA when accounting for other common risk factors for amputation. In this post hoc analysis of a large randomized controlled population of diabetic patients, we found that components of the MNSI score including presence of ulceration, abnormal appearance of the foot, and 10 gm filament monofilament scoring were strongly predictive of LEA. This adds a valuable clinical tool in the risk stratification of diabetic patients for LEA.

Canagliflozin impedes ischemic hind-limb recovery in the setting of diabetes.

There is a reported increased incidence of lower extremity amputations in individuals with diabetes who are treated with canagliflozin (an SGLT2 receptor inhibitor). It is unclear whether this is an unintended consequence of therapy, or whether canagliflozin can affect peripheral limb perfusion in the setting of underling arterial malperfusion. To evaluate this we explored the effect of canagliflozin on tissue recovery following unilateral hind-limb ischemia (HLI). Adult wildtype (+/+) and diabetic (db/db) mice were maintained on 8 weeks of a regular chow diet, or a chow diet containing canagliflozin (200 mg/kg). Following HLI, hind-limb appearance, function, and Doppler perfusion were serially evaluated. Gastrocnemius muscle fiber size and microvessel density were also evaluated 21 days following HLI. We observed that db/db that received a diet containing canagliflozin had significantly worse hind-limb function and appearance scores compared to both db/db mice that received a regular diet and +/+ mice that received a canagliflozin diet. At post-HLI day 21, db/db mice that received a canagliflozin diet also had decreased Doppler perfusion, gastrocnemius muscle fiber size, and microvessel density compared to +/+ mice that received a canagliflozin diet. These findings indicate that canagliflozin appears to impede ischemic peripheral tissue recovery and warrant further clinical investigation in individuals with diabetes and a history of peripheral artery disease.