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ABSTRACT: SummaryAmong community-dwelling older men, compared to those without Parkinson’s disease (PD), over approximately 5years, those
with baseline PD had a significantly greater rate of annualized total hip bone loss (−1.1% vs. 0.4%), proportion of incident
non-spine fractures (14.9% vs. 7.2%) and mortality (34.8% vs. 9.5%).
IntroductionThe objective of this study was to examine the association of Parkinson’s disease (PD) with bone loss and fractures in older
men.
MethodsThis prospective cohort study analyzed data from 5,937 community dwelling men aged ≥65years at six clinical centers of the
Osteoporotic Fractures in Men (MrOS) Study. At baseline and visit two (mean interval 4.6 +/−0.4 SD years), community-diagnosed
PD was ascertained by self-report and hip bone mineral density (BMD) was measured using dual energy x-ray absorptiometry (DXA).
Incident fractures were self-reported. Fractures and deaths were centrally adjudicated.
ResultsAt baseline, 46 (0.8%) men had PD. Age-adjusted mean annualized total hip bone loss was greater in men with vs. those without
PD (−1.08% vs. −0.36%, p < 0.001). 15.2% of men with PD and 7.2% of men without PD experienced an incident non-spine fracture (age-adjusted HR 2.4,
95%CI 1.1–5.0). 34.8% of men with PD and 9.5% of men without PD died during follow-up (age-adjusted HR 3.5, 95%CI 2.2–5.5).
Associations of PD with bone loss, fractures and mortality were modestly altered by additional individual adjustment for possible
confounders.
ConclusionsIn community-dwelling older men, PD was associated with increased bone loss, fractures and mortality. In addition to implementing
fall prevention measures, clinicians should consider osteoporosis screening in older men with PD.
Osteoporosis International 04/2012; 19(9):1277-1282. · 4.58 Impact Factor
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A. Ishani,
M. Paudel,
B. C. Taylor,
E. Barrett-Connor,
S. Jamal,
M. Canales,
M. Steffes, H. A. Fink,
E. Orwoll,
S. R. Cummings,
K. E. Ensrud,
for the Osteoporotic Fractures in Men (MrOS) Study Group
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ABSTRACT: SummaryOlder men with reduced renal function are at increased risk of hip bone loss. Given the robustness of this association across
different measures and a growing body of literature, our findings indicate that clinicians should take into account renal
function when evaluating older men for osteoporosis risk and bone loss. Future randomized controlled trials should test whether
interventions in this high risk population are effective in preventing bone loss and decreasing fracture incidence.
IntroductionStudies examining whether kidney impairment, not requiring dialysis, is associated with osteoporosis have reported conflicting
results.
MethodsWe tested the hypothesis that reduced renal function in older men as manifested by higher concentrations of cystatin C or
lower levels of estimated glomerular filtration rate (eGFR) is associated with higher rates of bone loss. We measured serum
cystatin C, serum creatinine and total hip bone mineral density (BMD) at baseline in a cohort of 404 older men enrolled in
the Osteoporotic Fractures in Men (MrOS) Study and followed them prospectively for an average of 4.4years for changes in
BMD. Associations between renal function and change in hip BMD were examined using linear regression.
ResultsIn multivariable analysis, the mean rate of decline in total hip BMD showed an increase in magnitude with higher cystatin
C concentration (mean annualized percent change −0.29, −0.34, −0.37 and −0.65% for quartiles 1 to 4; p for trend=0.004). Similarly,
adjusted rates of hip bone loss were higher among men with lower eGFR as defined by the modification of diet in renal disease
formula (mean annualized percent change −0.58, −0.39, −0.37, and −0.31 for quartiles 1 to 4; p for trend=0.02), but not among
men with lower eGFR as defined by the Cockcroft–Gault formula (mean annualized percent change −0.47, −0.44, −0.31 and −0.43
for quartiles 1 to 4; p for trend=0.48).
ConclusionsOlder men with reduced renal function are at increased risk of hip bone loss. Our findings suggest that health care providers
should consider renal function when evaluating older men for risk factors for bone loss and osteoporosis.
Osteoporosis International 04/2012; 19(11):1549-1556. · 4.58 Impact Factor
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ABSTRACT: We used a microsimulation model to estimate the threshold body weights at which screening bone densitometry is cost-effective. Among women aged 55-65 years and men aged 55-75 years without a prior fracture, body weight can be used to identify those for whom bone densitometry is cost-effective. INTRODUCTION: Bone densitometry may be more cost-effective for those with lower body weight since the prevalence of osteoporosis is higher for those with low body weight. Our purpose was to estimate weight thresholds below which bone densitometry is cost-effective for women and men without a prior clinical fracture at ages 55, 60, 65, 75, and 80 years. METHODS: We used a microsimulation model to estimate the costs and health benefits of bone densitometry and 5 years of fracture prevention therapy for those without prior fracture but with femoral neck osteoporosis (T-score ≤ -2.5) and a 10-year hip fracture risk of ≥3%. Threshold pre-test probabilities of low BMD warranting drug therapy at which bone densitometry is cost-effective were calculated. Corresponding body weight thresholds were estimated using data from the Study of Osteoporotic Fractures (SOF), the Osteoporotic Fractures in Men (MrOS) study, and the National Health and Nutrition Examination Survey (NHANES) for 2005-2006. RESULTS: Assuming a willingness to pay of $75,000 per quality adjusted life year (QALY) and drug cost of $500/year, body weight thresholds below which bone densitometry is cost-effective for those without a prior fracture were 74, 90, and 100 kg, respectively, for women aged 55, 65, and 80 years; and were 67, 101, and 108 kg, respectively, for men aged 55, 75, and 80 years. CONCLUSIONS: For women aged 55-65 years and men aged 55-75 years without a prior fracture, body weight can be used to select those for whom bone densitometry is cost-effective.
Osteoporosis International 02/2012; · 4.58 Impact Factor
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Y Slinin,
M L Paudel,
B C Taylor, H A Fink,
A Ishani,
M T Canales,
K Yaffe,
E Barrett-Connor,
E S Orwoll,
J M Shikany,
E S Leblanc,
J A Cauley,
K E Ensrud
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ABSTRACT: To test the hypothesis that lower 25-hydroxyvitamin D [25(OH)D] levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline.
We measured 25(OH)D and assessed cognitive function using the Modified Mini-Mental State Examination (3MS) and Trail Making Test Part B (Trails B) in a cohort of 1,604 men enrolled in the Osteoporotic Fractures in Men Study and followed them for an average of 4.6 years for changes in cognitive function.
In a model adjusted for age, season, and site, men with lower 25(OH)D levels seemed to have a higher odds of cognitive impairment, but the test for trend did not reach significance (impairment by 3MS: odds ratio [OR] 1.84, 95% confidence interval [CI] 0.81-4.19 for quartile [Q] 1; 1.41, 0.61-3.28 for Q2; and 1.18, 0.50-2.81 for Q3, compared with Q4 [referent group; p trend = 0.12]; and impairment by Trails B: OR 1.66, 95% CI 0.98-2.82 for Q1; 0.96, 0.54-1.69 for Q2; and 1.30, 0.76-2.22 for Q3, compared with Q4 [p trend = 0.12]). Adjustment for age and education further attenuated the relationships. There was a trend for an independent association between lower 25(OH)D levels and odds of cognitive decline by 3MS performance (multivariable OR 1.41, 95% CI 0.89-2.23 for Q1; 1.28, 0.84-1.95 for Q2; and 1.06, 0.70-1.62 for Q3, compared with Q4 [p = 0.10]), but no association with cognitive decline by Trails B.
We found little evidence of independent associations between lower 25-hydroxyvitamin D level and baseline global and executive cognitive function or incident cognitive decline.
Neurology 11/2009; 74(1):33-41. · 8.31 Impact Factor
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ABSTRACT: We examined the rate of clinical vertebral fractures, and the circumstances associated with the fractures, in a cohort of 5,995 US older men. Fractures were more common in the most elderly men, and were usually associated with falls and other low-energy trauma.
Little is known about clinical vertebral fractures in older men. We postulated that clinical vertebral fractures occur with falls, affect men with osteoporosis, and are more common as age increases.
Five thousand nine hundred and ninety-five men aged > or =65 years were followed prospectively for an average of 4.7 years. Men with incident clinical vertebral fractures were compared to controls.
One percent (n = 61) sustained incident clinical vertebral fractures (2.2/1,000 person-years). The rate of fracture rose with age (0.7% in men 65-69 years and 5% > or =85 years). Fractured men were more likely frail (8.2% vs. 2.2%), more often fell (36.1% vs. 21%) and had lower total hip and lumbar spine BMD (all p values < or =0.002). In 73.8% of cases fractures were precipitated by no known trauma or by low-energy trauma, including falls in 57.3% Fractures were thoracic in 33% and lumbar in 56%. Men with an incident vertebral fracture were more likely to be osteoporotic (13% vs. 2%, p < 0.0001), but most men with incident fractures did not have osteoporosis.
Incident clinical vertebral fractures were relatively common in older men and the rate increased after age 80 years. Fractures were usually associated with minimal trauma, most commonly a fall.
Osteoporosis International 05/2008; 19(5):615-23. · 4.58 Impact Factor
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ABSTRACT: Systematic review.
To evaluate effectiveness and adverse effects of botulinum toxin (BTX) for treatment of urinary incontinence (UI) due to detrusor overactivity (DO).
Randomized controlled trials published in English before November 2006 were included if they enrolled subjects with UI caused by DO and reported incontinence outcomes.
Three trials totaling 104 subjects with DO refractory to antimuscarinic treatment were included. Two BTX-A trials enrolled primarily patients with NDO secondary to spinal cord injury (SCI) (93%). BTX-A decreased daily UI episodes compared to placebo but the reductions were only significantly different at a few of the time intervals during 24 weeks of follow-up. BTX-A was superior in reducing daily UI episodes in SCI subjects compared to intravesical resiniferatoxin at 12 and 18 months after injections. A small crossover study found BTX-B significantly more effective than placebo in reducing weekly UI episodes in subjects with predominately idiopathic DO. Adverse events (AEs) in BTX-A-treated subjects included urinary tract infection, pain at the injection site, hematuria and autonomic dysreflexia. Four subjects treated with BTX-B reported autonomic AEs.
BTX may improve UI for subjects with refractory DO. The preferred dose and type of BTX is not known. Long-term efficacy and safety remain unclear and require conduct of larger RCT using standardized and validated clinical outcomes measures.
Spinal Cord 09/2007; 45(8):535-41. · 1.80 Impact Factor
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ABSTRACT: To determine whether older women with abdominal aortic calcification had a greater cardiovascular and all-cause mortality, as such data are limited in older adults.
Prospective cohort study with a mean follow-up of 13 years.
Community-based sample with four US clinical centres.
A total of 2056 women aged > or =65 years with abdominal aortic calcification assessed on baseline radiographs.
Mortality rate (all, cardiovascular, cancer or other cause) adjudicated from death certificates and hospital records.
The prevalence of abdominal aortic calcification increased with age, ranging from 60% at age 65-69 years to 96% at 85 years and older. Participants with aortic calcification were more likely to die during follow-up of any cause (47% vs. 27%) or a cardiovascular-specific cause (18% vs. 11%, both P < 0.001) than those without aortic calcification. In age-adjusted analyses, aortic calcification was associated with a greater rate of all-cause and cause-specific mortality (cardiovascular, cancer, and other, all P < or = 0.01). In analyses adjusted for age and cardiovascular risk factors, aortic calcification was associated with an increased rate of all-cause mortality (HR: 1.37, 95% CI: 1.15-1.64), and noncardiovascular noncancer mortality (HR: 1.57, 95% CI: 1.17-2.11). The associations between aortic calcification and cancer mortality (HR: 1.44, 95% CI: 1.00-2.08) or cardiovascular mortality (HR: 1.18, 95% CI: 0.88-1.57) showed a similar pattern without reaching statistical significance, but was slightly stronger for mortality from coronary heart disease (HR: 1.53, 95% CI: 0.91-2.56).
Abdominal aortic calcification in older women is associated with increased mortality. Future research should examine potential mechanisms for this association.
Journal of Internal Medicine 03/2007; 261(3):238-44. · 5.48 Impact Factor
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K A Faulkner,
J A Cauley,
J M Zmuda,
D P Landsittel,
A B Newman,
S A Studenski,
M S Redfern,
K E Ensrud, H A Fink,
N E Lane,
M C Nevitt
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ABSTRACT: The purpose of this study was to examine the relationships of vitamin D supplementation and serum concentrations of vitamin D metabolites and parathyroid hormone (PTH) with neuromuscular function and falls in older community-dwelling women.
We examined these relationships using a 4-year prospective multi-center study among 9,526 community-dwelling women enrolled in the Study of Osteoporotic Fractures (median age: 70 years; interquartile range: 67-75) and a subset of 389 women (97%) out of 400 who were randomly selected from the entire cohort for serum measures. Measurements included: vitamin D supplementation, serum 25-hydroxyvitamin D(3) [25(OH)D(3)], serum 1,25-dihydroxyvitamin D(3) [1,25(OH) (2)D(3)], and serum intact parathyroid hormone (iPTH); grip and quadriceps strength, chair-stand time, walking speed, reaction time, and balance-walk time (including changes in grip strength, chair-stand time, walking speed and balance-walk time over approximately 3.7 years); and incident fall rates (number of falls/woman-years).
In 9,526 women, vitamin D supplementation was not associated with any measures of neuromuscular function, change in neuromuscular function, or fall rates (p>0.01 for all). In a subgroup of 389 women, there was a trend of higher 25(OH)D(3) concentration with slightly weaker grip strength (p=0.007), and women in the fourth quartile of 1,25(OH)(2)D(3) had a faster chair-stand time (p=0.017) than women in the first quartile; still, in general, concentrations of 25(OH)D(3), 1,25(OH)(2)D(3), and iPTH were not associated with either neuromuscular function or changes in neuromuscular function (p>0.05 for all). However, higher 1,25(OH)(2)D(3) concentration was associated with lower fall rates (p=0.039).
Higher 1,25(OH)(2)D(3) concentration is associated with a lower fall risk in older community-dwelling women, but vitamin D supplementation, and 25(OH)D(3) and iPTH concentrations are not associated with either neuromuscular function or falls.
Osteoporosis International 02/2006; 17(9):1318-28. · 4.58 Impact Factor
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ABSTRACT: Lower levels of endogenous sex steroids or declines in these hormones may contribute to the increased rates of bone loss observed in older adults experiencing weight loss. We hypothesized that among older men with weight loss, higher rates of bone loss at the hip would be observed in men with lower baseline bioavailable sex steroids or those with greater declines in these hormones.
To test this hypothesis, body weight, hip bone mineral density (BMD) using dual energy x-ray absorptiometry and endogenous sex steroids in paired serum samples by sensitive immunoassays were measured at a baseline and at a second examination that was held an average of 1.8 years later in 1267 older men enrolled in the Osteoporotic Fractures in Men (MrOS) study.
Men experiencing weight loss had higher rates of hip bone loss than those with stable weight or weight gain within each quartile of baseline sex steroid level [p values for test of trend across weight change categories <0.010 within each quartile of bioavailable estradiol and testosterone and <0.060 within each quartile of sex hormone-binding globulin (SHBG)]. Results were similar when a change in sex steroids was substituted for baseline sex steroids in the analyses. Among men with weight loss, the rate of decline in total hip BMD showed a stepwise increase in magnitude with decreasing baseline bioavailable estradiol (p value for trend <0.040), with increasing baseline SHBG (p value for trend<0.030) and with greater decreases in bioavailable testosterone from baseline (p value for trend <0.001).
These findings support the hypothesis that the impact of weight loss in older men on rates of hip bone loss may be increased by the presence of a sex steroid insufficiency.
Osteoporosis International 01/2006; 17(9):1329-36. · 4.58 Impact Factor
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ABSTRACT: To determine the efficacy and safety of trazodone in the treatment of erectile dysfunction (ED) in a meta-analysis.
The data sources used were Medline and the Cochrane Library databases (January 1966 to May 2002), bibliographies of retrieved articles and review articles, and conference proceedings and abstracts. Trials were eligible for inclusion in the review if they included men with ED, compared trazodone with a control, were randomized, of > or = 7 days' duration and assessed clinically relevant outcomes. Two reviewers independently evaluated study quality and extracted data in a standardized fashion.
Six trials (comprising 396 men) met the inclusion criteria; they consisted of heterogeneous populations, were small, brief and in some cases methodologically weak. Three of the six trials showed an apparently clinically meaningful benefit of trazodone for ED compared with placebo, the differences being statistically significant in two. In pooled results, trazodone monotherapy appeared more likely than placebo to lead to a 'positive treatment response', although this difference was not statistically significant (37% vs 20%; relative benefit increase, 1.6; 95% confidence interval, CI, 0.8-3.3). Subgroup analyses suggested that men with psychogenic ED might be more likely to benefit from trazodone than those with mixed or physiological ED. The efficacy of trazodone also appeared greater at higher doses (150-200 vs 50 mg/day). Men randomized to trazodone were not significantly more likely than those receiving placebo to withdraw for any reason or for an adverse event, or to have specific adverse events, but wide CIs could not exclude a greater risk of these adverse outcomes with trazodone. Specific adverse events with trazodone included dry mouth (19%), sedation (16%), dizziness (16%) and fatigue (15%).
Trazodone may be helpful in men with ED, possibly more so at higher doses, and in men with psychogenic ED. Future high-quality trials should compare trazodone with placebo and other therapies in men with depression and psychogenic ED.
BJU International 09/2003; 92(4):441-6. · 2.84 Impact Factor
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ABSTRACT: Evidence-based medicine is an important way of allowing the reader to judge clearly whether a treatment has a place in a particular condition, and to see what faults were present in the various trials of its efficacy. It is often rather unsettling to read in a meta-analysis or in a systematic literature review how poorly constructed many trials are. The authors from Minneapolis have carried out such a study into the use of trazodone in male erectile dysfunction. They draw attention to the poor quality of many of the trials and give their reasons for this observation. They suggest that trazodone may be helpful in men with this condition, possibly at higher doses and in men with psychogenic erectile dysfunction.OBJECTIVE
To determine the efficacy and safety of trazodone in the treatment of erectile dysfunction (ED) in a meta-analysis.METHODS
The data sources used were Medline and the Cochrane Library databases (January 1966 to May 2002), bibliographies of retrieved articles and review articles, and conference proceedings and abstracts. Trials were eligible for inclusion in the review if they included men with ED, compared trazodone with a control, were randomized, of ≥ 7 days’ duration and assessed clinically relevant outcomes. Two reviewers independently evaluated study quality and extracted data in a standardized fashion.RESULTSSix trials (comprising 396 men) met the inclusion criteria; they consisted of heterogeneous populations, were small, brief and in some cases methodologically weak. Three of the six trials showed an apparently clinically meaningful benefit of trazodone for ED compared with placebo, the differences being statistically significant in two. In pooled results, trazodone monotherapy appeared more likely than placebo to lead to a ‘positive treatment response’, although this difference was not statistically significant (37% vs 20%; relative benefit increase, 1.6; 95% confidence interval, CI, 0.8–3.3). Subgroup analyses suggested that men with psychogenic ED might be more likely to benefit from trazodone than those with mixed or physiological ED. The efficacy of trazodone also appeared greater at higher doses (150–200 vs 50 mg/day). Men randomized to trazodone were not significantly more likely than those receiving placebo to withdraw for any reason or for an adverse event, or to have specific adverse events, but wide CIs could not exclude a greater risk of these adverse outcomes with trazodone. Specific adverse events with trazodone included dry mouth (19%), sedation (16%), dizziness (16%) and fatigue (15%).CONCLUSION
Trazodone may be helpful in men with ED, possibly more so at higher doses, and in men with psychogenic ED. Future high-quality trials should compare trazodone with placebo and other therapies in men with depression and psychogenic ED.
BJU International 08/2003; 92(4):441 - 446. · 2.84 Impact Factor
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ABSTRACT: Relatively little is known about outcomes following clinical osteoporotic fractures at nonhip, nonvertebral skeletal sites. To address this issue, we prospectively assessed post-fracture disability at multiple skeletal sites in a population of 909 older (aged 55-81 years), community-dwelling women with low femoral neck bone mineral density who had experienced a fracture while enrolled in the Fracture Intervention Trial (FIT). FIT is a randomized, double-masked, placebo-controlled trial that was designed to determine the effect of alendronate on fracture incidence, and the current study was conducted as a secondary analysis of FIT data. Following incident clinical fractures, FIT participants were followed prospectively for assessment of site-specific, fracture-related disability. Measures of disability were self-reported days hospitalized or confined to bed because of the fracture ('bed days') and days of reduced usual activities because of the fracture ('limited activity days'). Of fracture types evaluated, those of the hip resulted in the highest percentage of subjects with any bed days or limited activity days after fracture (94% with any bed days and 100% with any limited activity days), though the mean number of bed days and limited activity days appeared highest after lumbar vertebral fractures (25.8 mean bed days and 158.5 mean limited activity days). Substantial disability also was reported after fractures of thoracic vertebrae, humerus, distal forearm, ankle and foot. Within fracture types, post-fracture disability was highly variable, ranging from none to more than 6 months.
Osteoporosis International 02/2003; 14(1):69-76. · 4.58 Impact Factor
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ABSTRACT: Relatively little is known about outcomes following clinical osteoporotic fractures at nonhip, nonvertebral skeletal sites.
To address this issue, we prospectively assessed post-fracture disability at multiple skeletal sites in a population of 909
older (aged 55–81 years), community-dwelling women with low femoral neck bone mineral density who had experienced a fracture
while enrolled in the Fracture Intervention Trial (FIT). FIT is a randomized, double-masked, placebo-controlled trial that
was designed to determine the effect of alendronate on fracture incidence, and the current study was conducted as a secondary
analysis of FIT data. Following incident clinical fractures, FIT participants were followed prospectively for assessment of
site-specific, fracture-related disability. Measures of disability were self-reported days hospitalized or confined to bed
because of the fracture (`bed days') and days of reduced usual activities because of the fracture (`limited activity days').
Of fracture types evaluated, those of the hip resulted in the highest percentage of subjects with any bed days or limited
activity days after fracture (94% with any bed days and 100% with any limited activity days), though the mean number of bed
days and limited activity days appeared highest after lumbar vertebral fractures (25.8 mean bed days and 158.5 mean limited
activity days). Substantial disability also was reported after fractures of thoracic vertebrae, humerus, distal forearm, ankle
and foot. Within fracture types, post-fracture disability was highly variable, ranging from none to more than 6 months.
Osteoporosis International 12/2002; 14(1):69-76. · 4.58 Impact Factor
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ABSTRACT: Abdominal palpation during physical examination is an important means of detecting abdominal aortic aneurysm (AAA), but limited information is available on its accuracy.
Two hundred subjects (aged 51-88 years), 99 with and 101 without AAA as determined by previous ultrasound, each underwent physical examination of the abdomen by 2 internists who were blinded to each other's findings and to the ultrasound diagnosis.
The overall accuracy of abdominal palpation for detecting AAA was as follows: sensitivity, 68% (95% confidence interval [CI], 60%-76%); specificity, 75% (95% CI, 68%-82%); positive likelihood ratio, 2.7 (95% CI, 2.0-3.6); negative likelihood ratio 0.43 (95% CI, 0.33-0.56). Interobserver pair agreement for AAA vs no AAA between the first and second examinations was 77% (kappa = 0.53). Sensitivity increased with AAA diameter, from 61% for AAAs of 3.0 to 3.9 cm, to 69% for AAAs of 4.0 to 4.9 cm, 72% for AAAs of 4.0 cm or larger, and 82% for AAAs of 5.0 cm or larger. Sensitivity in subjects with an abdominal girth less than 100 cm (40-in waistline) was 91% vs 53% for girth of 100 cm or greater (P<.001). When girth was 100 cm or greater and the aorta was palpable, sensitivity was 82%. When girth was less than 100 cm and the AAA was 5.0 cm or larger, sensitivity was 100% (12 examinations). Factors independently associated with correct examination findings included AAA diameter (odds ratio [OR], 1.95 per centimeter increase; 95% CI, 1.06-3.58); abdominal girth (OR, 0.90 per centimeter increase; 95% CI, 0.87-0.94); and the examiner's assessment that the abdomen was not tight (OR, 2.68; 95% CI, 1.17-6.13).
Abdominal palpation has only moderate overall sensitivity for detecting AAA, but appears to be highly sensitive for diagnosis of AAAs large enough to warrant elective intervention in patients who do not have a large girth. Abdominal palpation has good sensitivity even in patients with a large girth if the aorta is palpable.
Archives of Internal Medicine 03/2000; 160(6):833-6. · 11.46 Impact Factor
