To assess whether the risk of subsequent lower-limb amputations and death following an initial toe amputation among individuals with diabetes has changed over time and varies by demographic characteristics and geographic region. RESEARCH DESIGN AND METHODSUsing Veterans Health Administration (VHA) electronic medical records from 1 October 2004 to 30 September 2016, we determined risk of subsequent ipsilateral minor and major amputation within 1 year after an initial toe/ray amputation among veterans with diabetes. To assess changes in the annual rate of subsequent amputation over time, we estimated age-adjusted incidence of minor and major subsequent ipsilateral amputation for each year, separately for African Americans (AAs) and whites. Geographic variation was assessed across VHA markets (n 5 89) using log-linear Poisson regression models adjusting for age and ethnoracial category. RESULTSAmong 17,786 individuals who had an initial toe amputation, 34% had another amputation on the same limb within 1 year, including 10% who had a major ipsilateral amputation. Median time to subsequent ipsilateral amputation (minor or major) was 36 days. One-year risk of subsequent major amputation decreased over time, but risk of subsequent minor amputation did not. Risk of subsequent major ipsilateral amputation was higher in AAs than whites. After adjusting for age and ethnoracial category, 1-year risk of major subsequent amputation varied fivefold across VHA markets. CONCLUSIONSNearly one-third of individuals require reamputation following an initial toe amputation, although risks of subsequent major ipsilateral amputation have decreased over time. Nevertheless, risks remain particularly high for AAs and vary substantially geographically.

Little is known about the population genetics of water balance. A recent meta-genome-wide association study on plasma sodium concentration identified novel loci of high biological plausibility, yet heritability of the phenotype has never been convincingly shown in European ancestry. The present study linked the Vietnam Era Twin Registry with the Department of Veterans Affairs VistA patient care clinical database. Participants ( n = 2,370, 59.6% monozygotic twins and 40.4% dizygotic twins) had a median of seven (interquartile range: 3−14) plasma sodium determinations between October 1999 and March 2017. Heritability of the mean plasma sodium concentration among all twins was 0.41 (95% confidence interval: 0.35−0.46) and 0.49 (95% confidence interval: 0.43−0.54) after exclusion of 514 twins with only a single plasma sodium determination. Heritability among Caucasian ( n = 1,958) and African-American ( n = 268) twins was 0.41 (95% confidence interval: 0.34−0.47) and 0.36 (95% confidence interval: 0.17−0.52), respectively. Exclusion of data from twins who had been prescribed medications known to impact systemic water balance had no effect. The ability of the present study to newly detect substantial heritability across multiple racial groups was potentially a function of the cohort size and relatedness, exclusion of sodium determinations confounded by elevated plasma glucose and/or reduced glomerular filtration rate, transformation of plasma sodium for the independent osmotic effect of plasma glucose, and use of multiple laboratory determinations per individual over a period of years. Individual-level plasma sodium concentration exhibited longitudinal stability (i.e., individuality); the degree to which individual-level means differed from the population mean was substantial, irrespective of the number of determinations. In aggregate, these data establish the heritability of plasma sodium concentration in European ancestry and corroborate its individuality.

Objective: Hormone therapy (HT) is used by menopausal women to treat vasomotor symptoms. Venous thromboembolism (VTE) is an important risk of HT use, and more knowledge on the comparative safety of different estrogenic compounds is useful for women who use HT for these symptoms. The objective was to compare the risk of VTE among users of oral conjugated equine estrogen (CEE), oral estradiol (E2) and transdermal E2, in a cohort of women Veterans.Methods: This retrospective cohort study included all women Veterans aged 40-89 years, using CEE or E2, without prior VTE, between 2003 and 2011. All incident VTE events were adjudicated. Time-to-event analyses using a time-varying HT exposure evaluated the relative VTE risk between estrogen subtypes, with adjustment for age, race, and BMI, with stratification for prevalent vs. incident use of HT.

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The 0 to 10 numeric rating scale (NRS) of pain intensity is a standard outcome in randomized controlled trials (RCTs) of pain treatments. For individuals taking analgesics, there may be a disparity between “observed” pain intensity (the NRS, irrespective of concurrent analgesic use), and “underlying” pain intensity (what the NRS would be had concurrent analgesics not been taken). Using a contemporary causal inference framework, we compare analytic methods that can potentially account for concurrent analgesic use, first in statistical simulations, and second in analyses of real (non-simulated) data from an RCT of lumbar epidural steroid injections (LESI). The default analytic method was ignoring analgesic use, which is the most common approach in pain RCTs. Compared to ignoring analgesic use and other analytic methods, simulations showed that a quantitative pain and analgesia composite outcome based on adding 1.5 points to observed pain intensity for those who were taking an analgesic (the QPAC1.5) optimized power and minimized bias. Analyses of real RCT data supported the results of the simulations, showing greater power with analysis of the QPAC1.5 as compared to ignoring analgesic use and most other methods examined. We propose alternative methods that should be considered in the analysis of pain RCTs.