Thomas G. Travison

Estimating the prevalence of limb loss in the United States: 2005 to 2050.

OBJECTIVE To estimate the current prevalence of limb loss in the United States and project the future prevalence to the year 2050. DESIGN Estimates were constructed using age-, sex-, and race-specific incidence rates for amputation combined with age-, sex-, and race-specific assumptions about mortality. Incidence rates were derived from the 1988 to 1999 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, corrected for the likelihood of reamputation among those undergoing amputation for vascular disease. Incidence rates were assumed to remain constant over time and applied to historic mortality and population data along with the best available estimates of relative risk, future mortality, and future population projections. To investigate the sensitivity of our projections to increasing or decreasing incidence, we developed alternative sets of estimates of limb loss related to dysvascular conditions based on assumptions of a 10% or 25% increase or decrease in incidence of amputations for these conditions. SETTING Community, nonfederal, short-term hospitals in the United States. PARTICIPANTS Persons who were discharged from a hospital with a procedure code for upper-limb or lower-limb amputation or diagnosis code of traumatic amputation. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Prevalence of limb loss by age, sex, race, etiology, and level in 2005 and projections to the year 2050. RESULTS In the year 2005, 1.6 million persons were living with the loss of a limb. Of these subjects, 42% were nonwhite and 38% had an amputation secondary to dysvascular disease with a comorbid diagnosis of diabetes mellitus. It is projected that the number of people living with the loss of a limb will more than double by the year 2050 to 3.6 million. If incidence rates secondary to dysvascular disease can be reduced by 10%, this number would be lowered by 225,000. CONCLUSIONS One in 190 Americans is currently living with the loss of a limb. Unchecked, this number may double by the year 2050.

Adverse events associated with testosterone administration.

BACKGROUND Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied. METHODS Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group. RESULTS A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load. CONCLUSIONS In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy. (ClinicalTrials.gov number, NCT00240981.)

Opioids versus antidepressants in postherpetic neuralgia A randomized, placebo-controlled trial

Background Tricyclic antidepressants (TCA) provide less than satisfactory pain relief for postherpetic neuralgia (PHN), and the role of opioids is controversial. Objective To compare the analgesic and cognitive effects of opioids with those of TCA and placebo in the treatment of PHN. Methods Seventy-six patients with PHN were randomized in a double-blind, placebo-controlled, crossover trial. Each subject was scheduled to undergo three treatment periods (opioid, TCA, and placebo), approximately 8 weeks’ duration each. Doses were titrated to maximal relief or intolerable side effects. The primary outcome measures were pain intensity (0 to 10 scale), pain relief (0 to 100%), and cognitive function. Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication. Results Fifty patients completed two periods, and 44 patients completed all three. Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg. Opioids and TCA reduced pain (1.9 and 1.4) more than placebo (0.2;p < 0.001), with no appreciable effect on any cognitive measure. The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%;p < 0.001). More patients completing all three treatments preferred opioids (54%) than TCA (30%;p = 0.02). Conclusions Opioids effectively treat PHN without impairing cognition. Opioids and TCA act via independent mechanisms and with varied individual effect.

Reference Ranges for Testosterone in Men Generated Using Liquid Chromatography Tandem Mass Spectrometry in a Community-Based Sample of Healthy Nonobese Young Men in the Framingham Heart Study and Applied to Three Geographically Distinct Cohorts

CONTEXT Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men. METHODS TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study. RESULTS In a reference sample of 456 men, mean (sd), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes. CONCLUSION Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.

Functional Outcomes Following Trauma-Related Lower-Extremity Amputation

BACKGROUND The principal aims of this study were to examine functional outcomes following trauma-related lower-extremity amputation and to compare outcomes according to the amputation levels. We hypothesized that above-the-knee amputations would result in less favorable outcomes than would through-the-knee or below-the-knee amputations. A secondary aim was to examine the factors, in addition to amputation level, that influence outcome, including the type of soft-tissue coverage, selected patient characteristics, and the technological sophistication of the prosthetic device. METHODS A cohort of 161 patients who had undergone an above-the-ankle amputation at a trauma center within three months following the injury was followed prospectively at three, six, twelve, and twenty-four months after the injury. The Sickness Impact Profile, a self-reported measure of functional status, was used as the principal measure of outcome. Secondary outcomes included pain; degree of independence in transfers, walking, and climbing stairs; self-selected walking speed; and the physicians satisfaction with the clinical, functional, and cosmetic recovery of the limb. Longitudinal multivariate regression techniques were used to determine whether outcomes differed according to the level of amputation after we controlled for covariates. RESULTS There was no significant difference in the scores on the Sickness Impact Profile between the patients treated with above-the-knee and those treated with below-the-knee amputation. However, patients with a below-the-knee amputation performed better than did patients with an above-the-knee amputation on the timed test for walking speed (p = 0.04). Patients with a through-the-knee amputation had worse regression-adjusted Sickness Impact Profile scores (p = 0.05) and slower self-selected walking speeds (p = 0.004) than did patients with either a below-the-knee or an above-the-knee amputation. Differences according to the level of amputation were most pronounced for physical function. In general, physicians were less satisfied with the clinical, cosmetic, and functional recovery of the patients with a through-the-knee amputation. Except for problems encountered with insufficient gastrocnemius coverage of the stump in many patients with a through-the-knee amputation, neither the soft-tissue coverage nor the technological sophistication of the prosthesis correlated with outcome. CONCLUSIONS Severe disability accompanies above-the-ankle lower-extremity amputation following trauma, regardless of the level of amputation. Clinicians should critically evaluate the need for a through-the-knee amputation in patients with a traumatic injury. The results of this study also underscore the need for controlled studies that examine the relationship between the type and fit of prosthetic devices and functional outcomes.

Effectiveness of Multicomponent Nonpharmacological Delirium Interventions: A Meta-analysis

IMPORTANCE Delirium, an acute disorder with high morbidity and mortality, is often preventable through multicomponent nonpharmacological strategies. The efficacy of these strategies for preventing subsequent adverse outcomes has been limited to small studies to date. OBJECTIVE To evaluate available evidence on multicomponent nonpharmacological delirium interventions in reducing incident delirium and preventing poor outcomes associated with delirium. DATA SOURCES PubMed, Google Scholar, ScienceDirect, and the Cochrane Database of Systematic Reviews from January 1, 1999, to December 31, 2013. STUDY SELECTION Studies examining the following outcomes were included: delirium incidence, falls, length of stay, rate of discharge to a long-term care institution (institutionalization), and change in functional or cognitive status. DATA EXTRACTION AND SYNTHESIS Two experienced physician reviewers independently and blindly abstracted data on outcome measures using a standardized approach. The reviewers conducted quality ratings based on the Cochrane risk-of-bias criteria for each study. MAIN OUTCOMES AND MEASURES We identified 14 interventional studies. The results for outcomes of delirium incidence, falls, length of stay, and institutionalization were pooled for the meta-analysis, but heterogeneity limited our meta-analysis of the results for change in functional or cognitive status. Overall, 11 studies demonstrated significant reductions in delirium incidence (odds ratio [OR], 0.47; 95% CI, 0.38-0.58). Four randomized or matched trials reduced delirium incidence by 44% (OR, 0.56; 95% CI, 0.42-0.76). The rate of falls decreased significantly among intervention patients in 4 studies (OR, 0.38; 95% CI, 0.25-0.60); in 2 randomized or matched trials, the rate of falls was reduced by 64% (OR, 0.36; 95% CI, 0.22-0.61). Length of stay and institutionalization also trended toward decreases in the intervention groups, with a mean difference of -0.16 (95% CI, -0.97 to 0.64) day shorter and the odds of institutionalization 5% lower (OR, 0.95; 95% CI, 0.71-1.26). Among higher-quality randomized or matched trials, length of stay trended -0.33 (95% CI, -1.38 to 0.72) day shorter, and the odds of institutionalization trended 6% lower (OR, 0.94; 95% CI, 0.69-1.30). CONCLUSIONS AND RELEVANCE Multicomponent nonpharmacological delirium prevention interventions are effective in reducing delirium incidence and preventing falls, with a trend toward decreasing length of stay and avoiding institutionalization. Given the current focus on prevention of hospital-based complications and improved cost-effectiveness of care, this meta-analysis supports the use of these interventions to advance acute care for older persons.

Testosterone Suppresses Hepcidin in Men: A Potential Mechanism for Testosterone-Induced Erythrocytosis

CONTEXT The mechanisms by which testosterone increases hemoglobin and hematocrit are unknown. OBJECTIVE The aim was to test the hypothesis that testosterone-induced increase in hematocrit is associated with suppression of the iron regulatory peptide hepcidin. PARTICIPANTS Healthy younger men (ages 19-35 yr; n = 53) and older men (ages 59-75 yr; n = 56) were studied. METHODS Weekly doses of testosterone enanthate (25, 50, 125, 300, and 600 mg) were administered over 20 wk, whereas endogenous testosterone was suppressed by monthly GnRH agonist administration. Blood and serum parameters from each individual were measured at wk 0, 1, 2, 4, 8, and 20. Longitudinal analyses were performed to examine the relationship between hepcidin, hemoglobin, hematocrit, and testosterone while controlling for potential confounders. RESULTS High levels of testosterone markedly suppressed serum hepcidin within 1 wk. Hepcidin suppression in response to testosterone administration was dose-dependent in older men and more pronounced than in young men, and this corresponded to a greater rise in hemoglobin in older men. Serum hepcidin levels at 4 and 8 wk were predictive of change in hematocrit from baseline to peak levels. CONCLUSION Testosterone administration is associated with suppression of serum hepcidin. Greater increases in hematocrit in older men during testosterone therapy are related to greater suppression of hepcidin.

Does Erectile Dysfunction Contribute to Cardiovascular Disease Risk Prediction beyond the Framingham Risk Score

OBJECTIVES This study was designed to determine whether erectile dysfunction (ED) predicts cardiovascular disease (CVD) beyond traditional risk factors. BACKGROUND Both ED and CVD share pathophysiological mechanisms and often co-occur. It is unknown whether ED improves the prediction of CVD beyond traditional risk factors. METHODS This was a prospective, population-based study of 1,709 men (of 3,258 eligible) age 40 to 70 years. The ED data were measured by self-report. Subjects were followed for CVD for an average follow-up of 11.7 years. The association between ED and CVD was examined using the Cox proportional hazards regression model. The discriminatory capability of ED was examined using C statistics. The reclassification of CVD risk associated with ED was assessed using a method that quantifies net reclassification improvement. RESULTS Of the prospective population, 1,057 men with complete risk factor data who were free of CVD and diabetes at baseline were included. During follow-up, 261 new cases of CVD occurred. We found ED was associated with CVD incidence controlling for age (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.05 to 1.90), age and traditional CVD risk factors (HR: 1.41, 95% CI: 1.05 to 1.90), as well as age and Framingham risk score (HR: 1.40, 95% CI: 1.04 to 1.88). Despite these significant findings, ED did not significantly improve the prediction of CVD incidence beyond traditional risk factors. CONCLUSIONS Independent of established CVD risk factors, ED is significantly associated with increased CVD incidence. Nonetheless, ED does not improve the prediction of who will and will not develop CVD beyond that offered by traditional risk factors.

Erectile Dysfunction and Mortality

INTRODUCTION Erectile dysfunction (ED) and cardiovascular disease (CVD) share pathophysiological mechanisms and often co-occur. Yet it is not known whether ED provides an early warning for increased CVD or other causes of mortality. AIM We sought to examine the association of ED with all-cause and cause-specific mortality. METHODS Prospective population-based study of 1,709 men (of 3,258 eligible) aged 40-70 years. ED was measured by self-report. Subjects were followed for a mean of 15 years. Hazard ratios (HR) were calculated using the Cox proportional hazards regression model. MAIN OUTCOME MEASURES Mortality due to all causes, CVD, malignant neoplasms, and other causes. RESULTS Of 1,709 men, 1,284 survived to the end of 2004 and had complete ED and age data. Of 403 men who died, 371 had complete data. After adjustment for age, body mass index, alcohol consumption, physical activity, cigarette smoking, self-assessed health, and self-reported heart disease, hypertension, and diabetes, ED was associated with HRs of 1.26 (95% confidence interval [CI] 1.01-1.57) for all-cause mortality, and 1.43 (95% CI 1.00-2.05) for CVD mortality. The HR for CVD mortality associated with ED is of comparable magnitude to HRs of some conventional CVD risk factors. CONCLUSIONS These findings demonstrate that ED is significantly associated with increased all-cause mortality, primarily through its association with CVD mortality.

Lean mass and not fat mass is associated with male proximal femur strength.

Obesity is suspected to confer protection against fracture, but evidence is mixed. We examined proximal femur geometry and body composition measures in a diverse group of 1171 men (30–79 yr of age). Analyses showed that nonbone lean mass, but not fat mass, is independently associated with measures of proximal femur density, axial and bending strength, and resistance to buckling.