Abstract Ziegler-Graham K, MacKenzie EJ, Ephraim PL, Travison TG, Brookmeyer R. 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.
Abstract
Background:
Reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men.
Objective:
To establish harmonized reference ranges for total testosterone in men ...that can be applied across laboratories by cross-calibrating assays to a reference method and standard.
Population:
The 9054 community-dwelling men in cohort studies in the United States and Europe: Framingham Heart Study; European Male Aging Study; Osteoporotic Fractures in Men Study; and Male Sibling Study of Osteoporosis.
Methods:
Testosterone concentrations in 100 participants in each of the four cohorts were measured using a reference method at Centers for Disease Control and Prevention (CDC). Generalized additive models and Bland-Altman analyses supported the use of normalizing equations for transformation between cohort-specific and CDC values. Normalizing equations, generated using Passing-Bablok regression, were used to generate harmonized values, which were used to derive standardized, age-specific reference ranges.
Results:
Harmonization procedure reduced intercohort variation between testosterone measurements in men of similar ages. In healthy nonobese men, 19 to 39 years, harmonized 2.5th, 5th, 50th, 95th, and 97.5th percentile values were 264, 303, 531, 852, and 916 ng/dL, respectively. Age-specific harmonized testosterone concentrations in nonobese men were similar across cohorts and greater than in all men.
Conclusion:
Harmonized normal range in a healthy nonobese population of European and American men, 19 to 39 years, is 264 to 916 ng/dL. A substantial proportion of intercohort variation in testosterone levels is due to assay differences. These data demonstrate the feasibility of generating harmonized reference ranges for testosterone that can be applied to assays, which have been calibrated to a reference method and calibrator.
We cross-calibrated cohort-specific assays to a reference method at CDC and generated harmonized reference ranges for circulating testosterone levels in men, including age-adjusted reference ranges.
To describe clinical characteristics and risk factors associated with coronavirus disease 2019 (COVID-19) in long-stay nursing home residents.
Retrospective cohort study (March 16, 2020 to May 8, ...2020).
Academic long-term chronic care facility (Boston, MA).
Long-term care residents.
Patient characteristics and clinical symptoms were obtained via electronic medical records and Minimum Data Set. Staff residence was inferred by zip codes. COVID-19 infection was confirmed by polymerase chain reaction testing using nasopharyngeal swabs. Residents were followed until discharge from facility, death, or up to 21 days. Risks of COVID-19 infection were modeled by generalized estimating equation to estimate the relative risk (RR) and 95% confidence intervals (CI) of patient characteristics and staff community of residence.
Overall 146 of 389 (37.5%) long-stay residents tested positive for COVID-19. At the time of positive test, 66 of 146 (45.5%) residents were asymptomatic. In the subsequent illness course, the most common symptom was anorexia (70.8%), followed by delirium (57.6%). During follow-up, 44 (30.1%) of residents with COVID-19 died. Mortality increased with frailty (16.7% in pre-frail, 22.2% in moderately frail, and 50.0% in frail; P < .001). The proportion of residents infected with COVID-19 varied across the long-term care units (range: 0%‒90.5%). In adjusted models, male sex (RR 1.80, 95% CI 1.07, 3.05), bowel incontinence (RR 1.97, 95% CI 1.10, 3.52), and staff residence remained significant predictors of COVID-19. For every 10% increase in the proportion of staff living in a high prevalence community, the risk of testing positive increased by 6% (95% CI 1.04, 1.08).
Among long-term care residents diagnosed with COVID-19, nearly one-half were asymptomatic at the time of diagnosis. Predictors of COVID-19 infection included male sex, bowel incontinence, and staff residence in a community with a high burden of COVID-19. Universal testing of patients and staff in communities with high COVID-19 rates is essential to mitigate outbreaks.
Abstract Introduction As the relationship between delirium and long-term cognitive decline has not been well-explored, we evaluated this association in a prospective study. Methods SAGES is an ...ongoing study involving 560 adults age 70 years or more without dementia scheduled for major surgery. Delirium was assessed daily in the postoperative period using the Confusion Assessment Method. General Cognitive Performance (GCP) and the Informant Questionnaire for Cognitive Decline in the Elderly were assessed preoperatively then repeatedly out to 36 months. Results On average, patients with postoperative delirium had significantly lower preoperative cognitive performance, greater immediate (1 month) impairment, equivalent recovery at 2 months, and significantly greater long-term cognitive decline relative to the nondelirium group. Proxy reports corroborated the clinical significance of the long-term cognitive decline in delirious patients. Discussion Cognitive decline after surgery is biphasic and accelerated among persons with delirium. The pace of long-term decline is similar to that seen with mild cognitive impairment.
Background.
The mechanisms by which testosterone increases hemoglobin and hematocrit remain unclear.
Methods.
We assessed the hormonal and hematologic responses to testosterone administration in a ...clinical trial in which older men with mobility limitation were randomized to either placebo or testosterone gel daily for 6 months.
Results.
The 7%–10% increase in hemoglobin and hematocrit, respectively, with testosterone administration was associated with significantly increased erythropoietin (EPO) levels and decreased ferritin and hepcidin levels at 1 and 3 months. At 6 months, EPO and hepcidin levels returned toward baseline in spite of continued testosterone administration, but EPO levels remained nonsuppressed even though elevated hemoglobin and hematocrit higher than at baseline, suggesting a new set point. Consistent with increased iron utilization, soluble transferrin receptor (sTR) levels and ratio of sTR/log ferritin increased significantly in testosterone-treated men. Hormonal and hematologic responses were similar in anemic participants. The majority of testosterone-treated anemic participants increased their hemoglobin into normal range.
Conclusions.
Testosterone-induced increase in hemoglobin and hematocrit is associated with stimulation of EPO and reduced ferritin and hepcidin concentrations. We propose that testosterone stimulates erythropoiesis by stimulating EPO and recalibrating the set point of EPO in relation to hemoglobin and by increasing iron utilization for erythropoiesis.
Context:
Testosterone's effects on muscle strength and physical function in older men have been inconsistent; its effects on muscle power and fatigability have not been studied.
Objective:
To ...determine the effects of testosterone administration for 3 years in older men on muscle strength, power, fatigability and physical function
Study Design:
In this double-blind, placebo-controlled, randomized trial, healthy men ≥60 years with total testosterone 100–400 ng/dL or free testosterone <50 pg/mL, were randomized to 7.5-g 1% testosterone or placebo gel daily for 3 years.
Outcomes:
Loaded and unloaded stair-climbing power, muscle strength, power, and fatigability in leg press and chest press exercises, and lean mass at baseline, 6, 18, and 36 months.
Results:
The groups were similar at baseline. Testosterone administration for 3 years was associated with significantly greater performance in unloaded and loaded stair-climbing power than placebo (mean (95% CI) estimated between-group difference 10.7W (-4.0,25.5; P=0.026) and 22.4W (4.6,40.3) P=0.027), respectively. Changes in chest press strength (estimated mean difference 16.3N (95% CI 5.5,27.1; P<0.001) and power (mean (95%CI) difference 22.5W (7.5,37.5); P<0.001), and leg press power were significantly greater in men randomized to testosterone than in those randomized to placebo. Lean body mass significantly increased more in the testosterone group.
Conclusion:
Compared to placebo, testosterone replacement in older men for 3 years was associated with modest but significantly greater improvements in stair-climbing power, muscle mass and power. Clinical meaningfulness of these treatment effects and their impact on disability in older adults with functional limitations remains to be studied.
Androgen deprivation therapy (ADT), a cornerstone of treatment for patients with locally advanced and metastatic prostate cancer, is associated with many adverse effects, including osteoporosis, ...sexual dysfunction, fatigue, and vasomotor symptoms. It is also associated with loss of muscle mass and increased adiposity. This change in body composition is likely the inciting event in the development of insulin resistance, an independent risk factor for diabetes mellitus and cardiovascular disease. Although the occurrence of insulin resistance during ADT has been reported, it remains unclear whether this insulin resistance is primarily hepatic or muscular. Similarly, the mechanisms that lead to insulin resistance also remain unknown. The ADT & Metabolism Study was designed to address these knowledge gaps, as the elucidation of the predominant site of insulin resistance will allow prevention strategies and the use of targeted, tissue-specific insulin-sensitizing agents in patients undergoing ADT. This prospective, mechanistic, single-center, 24-week, observational cohort study will enroll treatment-naïve adult men with prostate cancer about to undergo surgical or medical ADT for at least 24 weeks (ADT group; n = 50) and a control group of men who had undergone radical prostatectomy and are in remission (non-ADT group, n = 25). The primary outcome is to determine the site of insulin resistance (skeletal muscle or liver) using frequent sampling oral glucose tolerance test at baseline and 12 and 24 weeks after commencement of ADT (ADT group) or after enrollment in the study (non-ADT group). Secondary outcomes will assess changes in hepatic and intramyocellular fat (using magnetic resonance spectroscopy), inflammatory markers, adipokines, free fatty acids, and changes in body composition (assessed using dual-energy x-ray absorptiometry) and their correlation with the development of insulin resistance. Exploratory outcomes will include changes in muscle performance, physical function, physical activity, vitality, and sexual drive.
Abstract
Background
Nutritional supplementation and physical activity have been shown to positively influence muscle mass and strength in older adults. The efficacy of long-term nutritional ...supplementation in combination with physical activity in older adults remains unclear.
Methods
Mobility-limited (short physical performance battery SPPB ≤9) and vitamin D insufficient (serum 25(OH) D 9–24 ng/mL) older adults were recruited for this study. All subjects participated in a physical activity program. Subjects were randomized to consume a daily nutritional supplement (150 kcal, 20 g whey protein, 800 IU vitamin D, 119 mL beverage) or placebo (30 kcal, nonnutritive, 119 mL). In a prespecified secondary analysis, we examined total-body composition (dual energy X-ray absorptiometry), thigh composition (computed tomography), and muscle strength, power, and quality before and after the 6-month intervention.
Results
One hundred and forty-nine subjects were randomized into the study mean (standard deviation, SD) age 78.5 (5.4) years; 46.3% female; mean (SD) short physical performance battery 7.9 (1.2); mean (SD) vitamin D 18.7 (6.4) ng/mL. After the intervention period both groups demonstrated improvements in muscle strength, body composition, and thigh composition. Nutritional supplementation lead to further losses of intermuscular fat (p = .049) and increased normal muscle density (p = .018).
Conclusions
Six months of physical activity resulted in improvements in body composition, subcutaneous fat, intermuscular fat, and strength measures. The addition of nutritional supplementation resulted in further declines in intermuscular fat and improved muscle density compared to placebo. These results suggest nutritional supplementation provides additional benefits to mobility-limited older adults undergoing exercise training.
ClinicalTrials.gov Identifier: NCT01542892
In a randomized trial involving men with hypogonadism and preexisting or a risk of cardiovascular disease, testosterone therapy was noninferior to placebo with respect to major adverse cardiac events.
IMPORTANCE: Delirium is a common, serious, and potentially preventable problem for older adults, associated with adverse outcomes. Coupled with its preventable nature, these adverse sequelae make ...delirium a significant public health concern; understanding its economic costs is important for policy makers and health care leaders to prioritize care. OBJECTIVE: To evaluate current 1-year health care costs attributable to postoperative delirium in older patients undergoing elective surgery. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included 497 patients from the Successful Aging after Elective Surgery (SAGES) study, an ongoing cohort study of older adults undergoing major elective surgery. Patients were enrolled from June 18, 2010, to August 8, 2013. Eligible patients were 70 years or older, English-speaking, able to communicate verbally, and scheduled to undergo major surgery at 1 of 2 Harvard-affiliated hospitals with an anticipated length of stay of at least 3 days. Eligible surgical procedures included total hip or knee replacement; lumbar, cervical, or sacral laminectomy; lower extremity arterial bypass surgery; open abdominal aortic aneurysm repair; and open or laparoscopic colectomy. Data were analyzed from October 15, 2019, to September 15, 2020. EXPOSURES: Major elective surgery and hospitalization. MAIN OUTCOMES AND MEASURES: Cumulative and period-specific costs (index hospitalization, 30-day, 90-day, and 1-year follow-up) were examined using Medicare claims and extensive clinical data. Total inflation-adjusted health care costs were determined using data from Medicare administrative claims files for the 2010 to 2014 period. Delirium was rated using the Confusion Assessment Method. We also examined whether increasing delirium severity was associated with higher cumulative and period-specific costs. Delirium severity was measured with the Confusion Assessment Method–Severity long form. Regression models were used to determine costs associated with delirium after adjusting for patient demographic and clinical characteristics. RESULTS: Of the 566 patients who were eligible for the study, a total of 497 patients (mean SD age, 76.8 5.1 years; 281 women 57%; 461 White participants 93%) were enrolled after exclusion criteria were applied. During the index hospitalization, 122 patients (25%) developed postoperative delirium, whereas 375 (75%) did not. Patients with delirium had significantly higher unadjusted health care costs than patients without delirium (mean SD cost, $146 358 $140 469 vs $94 609 $80 648). After adjusting for relevant confounders, the cumulative health care costs attributable to delirium were $44 291 (95% CI, $34 554-$56 673) per patient per year, with the majority of costs coming from the first 90 days: index hospitalization ($20 327), subsequent rehospitalizations ($27 797), and postacute rehabilitation stays ($2803). Health care costs increased directly and significantly with level of delirium severity (none-mild, $83 534; moderate, $99 756; severe, $140 008), suggesting an exposure-response relationship. The adjusted mean cumulative costs attributable to severe delirium were $56 474 (95% CI, $40 927-$77 440) per patient per year. Extrapolating nationally, the health care costs attributable to postoperative delirium were estimated at $32.9 billion (95% CI, $25.7 billion-$42.2 billion) per year. CONCLUSIONS AND RELEVANCE: These findings suggest that the economic outcomes of delirium and severe delirium after elective surgery are substantial, rivaling costs associated with cardiovascular disease and diabetes. These results highlight the need for policy imperatives to address delirium as a large-scale public health issue.
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