Search

Background: Medication use is a potentially reversible cause of urinary incontinence (UI). The objective of this longitudinal cohort study was to evaluate whether self-reported UI in community-dwelling older women is associated with the use of different classes of antihypertensive agents., Methods: The sample consisted of 959 black and white women aged 72-81 years without baseline (Year 1) UI from the Health, Aging, and Body Composition Study. Use of any antihypertensive from 10 drug classes (ie, alpha blockers [central], alpha blockers [peripheral], angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, beta blockers, calcium channel blockers, diuretics [loop], diuretics [potassium-sparing], diuretics [thiazide], and vasodilators) was determined during Year 3 in-person interviews. The number of unique antihypertensive agents used and the standardized daily dosage were also examined. Self-reported UI, operationally defined as leaking urine at least weekly during the previous 12 months, was assessed at Year 4 visits., Results: A total of 197 women (20.5%) reported UI at Year 4. Although any antihypertensive use, number of agents used, and standardized daily dosage at Year 3 were not associated with UI at Year 4, use of one particular drug class-peripheral alpha blockers (ie, doxazosin, prazosin, and terazosin)-was associated with fourfold greater odds of UI (adjusted odds ratio = 4.47; 95% confidence interval = 1.79-11.21; p = .0014). Further, in post hoc analyses, these odds nearly doubled in those also taking loop diuretics (adjusted odds ratio = 8.81; 95% confidence interval = 1.78-43.53; p = .0076)., Conclusion: In community-dwelling older women, peripheral alpha blocker use was associated with UI, and the odds nearly doubled when used with loop diuretics.

Purpose: Little research has been conducted on the epidemiology of urinary incontinence in individuals with type 2 diabetes. We examined prevalence, incidence and risk factors for urinary incontinence among women with type 2 diabetes in the NHS (Nurses' Health Study) and NHS II., Materials and Methods: We obtained urinary incontinence information at study baseline (2000 in NHS and 2001 in NHS II) and 2 followup periods (2002 and 2004 in the NHS, and 2003 and 2005 in the NHS II). Among women with type 2 diabetes we calculated the prevalence of urinary incontinence for 9,994 women with baseline urinary incontinence information, and urinary incontinence incidence rates for 4,331 women with no urinary incontinence at baseline and urinary incontinence information during followup. Multivariable adjusted odds ratios and relative risks were estimated for associations between possible risk factors and urinary incontinence., Results: The prevalence of at least monthly urinary incontinence was 48% and at least weekly urinary incontinence was 29% among women with type 2 diabetes, and the corresponding incidence rates were 9.1 and 3.4 per 100 person-years, respectively. White race, higher body mass index, higher parity, lower physical activity, current postmenopausal hormone use and diuretic use were risk factors for prevalent and incident urinary incontinence in this study, and hysterectomy, vascular disease and longer duration of diabetes were associated with increased odds of prevalent urinary incontinence only. Increasing age and microvascular complications were associated with a greater risk of frequent urinary incontinence., Conclusions: Urinary incontinence was common in this study of women with type 2 diabetes. We identified multiple risk factors for urinary incontinence in these women, several of which suggest ways to reduce urinary incontinence., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Aims: To identify, in subjects with overactive bladder (OAB), differences in brain activity between those who maintained and those who lost bladder control during functional magnetic resonance imaging (fMRI) of the brain with simultaneous urodynamics., Methods: Secondary analysis of a cohort of older women (aged >60) with proven urgency urinary incontinence, who, in the scanner, either developed detrusor overactivity and incontinence (the "DO group") or did not (the "no DO" group). A priori hypothesis: during urgency provoked by bladder filling, without DO, activity in regions related to continence control is diminished in the DO group; specifically (1a) less activation in supplementary motor area (SMA) and (1b) less deactivation in prefrontal cortex (PFC) and parahippocampal complex (PH). We also explored phenotypic (clinical and urodynamic) differences between the groups., Results: During urgency preceding DO, the DO group showed stronger activation in SMA and adjacent regions (hypothesis 1a rejected), and less deactivation in PH but no significant difference in PFC (hypothesis 1b partially accepted). These subjects were older, with more changes in brain's white matter, decreased tolerance of bladder filling and greater burden of incontinence., Conclusions: (1) In older women with OAB, brain activity in the SMA is greater among those with more easily elicitable DO, suggesting a compensatory response to failure of control elsewhere. (2) OAB is heterogeneous; one possible phenotype shows severe functional impairment attributable partly to age-related white matter changes. (3) Functional brain imaging coupled with urodynamics may provide CNS markers of impaired continence control in subjects with OAB., (Copyright © 2012 Wiley Periodicals, Inc.)

The patient-centered medical home is a rapidly growing concept in reforming American health care. It has spread from its origins in primary care pediatrics to family practice and, more recently, into internal medicine. This review article describes how primary care geriatricians can obtain certification from the National Committee for Quality Assurance (NCQA) for a patient-centered medical home that includes some of the features unique to geriatrics.

Objective: To estimate the association between long-term caffeine intake and risk of urinary incontinence (UI) progression over 2 years among women with moderate UI., Methods: We conducted a prospective cohort study in 21,564 women with moderate UI enrolled in the Nurses' Health Study and Nurses' Health Study II. Incontinence progression was identified from questionnaires during 2 years of follow-up. Baseline caffeine intake (ie, average intake during the previous year) and change in caffeine intake during the 4 years before baseline were measured using food frequency questionnaires. Odds ratios (ORs) for incontinence progression according to caffeine intake were calculated for each cohort separately, and then for both cohorts combined., Results: The percentage of women with UI progression was similar across categories of baseline level of caffeine intake and change in caffeine intake before baseline. For example, percentages were 21% compared with 22% comparing 450 mg or more to less than 150 mg of caffeine per day (adjusted OR 0.87, 95% confidence interval 0.70-1.08). Comparing women with increased caffeine intake to those with stable caffeine intake, percentages with progression were 22% compared with 20% (OR 1.08, 95% confidence interval 0.95-1.22). Results were similar in separate analyses of urge and stress UI., Conclusion: Long-term caffeine intake over 1 year was not associated with risk of UI progression over 2 years among women with moderate incontinence, although we could not examine acute effects of caffeine. Improved understanding of the effect of caffeine on the bladder is needed to better-advise women with incontinence about caffeine intake., Level of Evidence: II.

Objectives: To compare outcomes and measures of efficiency for hospitalized elderly adults managed by geriatricians with those managed by other physicians., Design: Secondary data analysis using a system that integrates clinical and financial information for inpatient and outpatient services delivered throughout the University of Pittsburgh Medical Center (UPMC). Propensity scores were developed based on participant sociodemographic and clinical characteristics and used to match participants based on the attending physician's specialty (geriatrician, n = 701; nongeriatrician, n = 11,549). Multivariate analyses using generalized estimating equations methods were performed., Setting: Two UPMC hospitals in Pittsburgh, Pennsylvania., Participants: Patients aged 65 and older admitted in 2002 in a medical diagnosis-related group (DRG)., Measurements: Outcomes (inpatient mortality, 30-day mortality, readmission) and efficiency measures (length of stay, total costs, and surplus, which is the difference between hospital costs and payment received for an admission)., Results: Elderly adults managed by geriatricians were significantly older (P < .001) and more likely to be male (P < .001) and had more diagnoses (P < .001). Propensity scores successfully balanced characteristics managed by the two groups. Patients of geriatricians had shorter length of stay (P < .001), lower costs per admission (P < .001), and greater surplus (P < .001) with no differences in outcomes. In multivariate analyses, there were not significant differences in outcomes, but patients of geriatricians had significantly shorter length of stay and lower costs per admission and generated more surplus for the hospitals., Conclusion: Geriatricians were more efficient than other physicians in managing hospitalized elderly adults with medical DRGs frequently managed by geriatricians. This efficiency did not compromise patient outcomes., (© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.)

Objectives: To examine screening strategies for osteoporosis and fractures for treatment of long-term care residents., Design: Cross-sectional analysis to examine screening strategies for treatment., Setting: Assisted living and skilled care facilities., Participants: Two hundred two frail women aged 65 and older (mean 85), excluding those receiving bisphosphonates., Measurements: Clinical fractures of the hip or spine (Clin Fx); Clin Fx or bone mineral density (BMD); Clin Fx, BMD, or vertebral fractures (VF) assessed according to dual-energy X-ray absorptiometry-based vertebral fracture assessments; fracture risk algorithm using femoral neck BMD (FRAX-FN); fracture risk algorithm using body mass index (FRAX-BMI); or Clin Fx or heel ultrasound (heel US)., Results: Treatment eligibility ranged from 17% (Clin Fx) to 98% (FRAX-BMI). VFs were found in 47%, 74% of which were silent. Criteria with Clin Fx, BMD, or VF identified 73% of study participants for treatment. FRAX-FN suggested treatment in 81% but would have missed approximately 10% of individuals with silent VFs. Clin Fx or heel US suggested that 39% of participants were eligible for treatment., Conclusion: Long-term care residents eligible for osteoporosis treatment ranged from fewer than 20% to roughly all residents depending on screening criteria. VFs are common and identify a subset of residents missed by conventional BMD scans or FRAX-FN. A reasonable clinical approach could consider treatment for those with Clin Fx of the hip or spine, radiological evidence of a VF, or osteoporosis according to BMD classification. Prospective studies are needed to determine optimal screening strategies for treatment in this cohort., (© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.)

Androgen deprivation therapy (ADT) has become the cornerstone of treatment for both advanced and nonmetastatic prostate cancer. The presence of a nontraumatic vertebral fracture (VF) identifies a patient who has clinical osteoporosis. Vertebral fracture analysis (VFA), a dual-energy X-ray absorptiometry (DXA)-based technology identifies VFs in conjunction with a standard bone mineral density (BMD) examination. The objective of this study was to determine if VFA would increase the diagnosis of osteoporosis in men with prostate cancer on ADT. One hundred sixteen men aged ≥ 60yrs with nonmetastatic prostate cancer receiving ADT for ≥ 6mos underwent DXA of the spine, hip, and 1/3 distal radius, VFA, and conventional vertebral X-rays. Approximately 40% of the men had clinically defined osteoporosis. The use of conventional DXA criteria (spine and hip) alone resulted in the misdiagnosis of approx 75% of patients. VFA and addition of the 1/3 distal radius site performed by DXA both increased the rate of diagnosis and reduced the misclassification of osteoporosis in men with prostate cancer, compared with conventional DXA criteria alone. Analysis indicated that VFA assessment of mild, moderate, and severe fractures from all readable vertebrae (T5-L4) had a kappa statistic, sensitivity, and specificity of 0.92, 100%, and 95%, respectively, with semiquantitative radiography. Men with prostate cancer on ADT should be screened for osteoporosis at the initiation of therapy, and evaluation should include DXA of the 1/3 distal radius in addition to the spine and hip, as well as evaluation for VFs., (Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Objective: We investigated the relation between total fluid intake and incident urinary incontinence in the Nurses' Health Study cohorts., Study Design: We measured daily fluid intake using food frequency questionnaires among 65,167 women, who were 37-79 years old, without urinary incontinence at study baseline (2000-2001). Women reported incontinence incidence on questionnaires during 4 years of follow-up evaluation. Multivariable-adjusted hazard ratios and 95% confidence intervals were calculated with Cox proportional hazards models., Results: We found no association between total fluid intake and risk of incident incontinence (hazard ratio, 1.04; 95% confidence interval, 0.98-1.10; comparing top vs bottom quintile of fluid intake). In analyses of incontinence type, total fluid intake was not associated with risks of incident stress, urgency, or mixed incontinence., Conclusion: No significant risk of incident urinary incontinence was found with higher fluid intake in women. These findings suggest that women should not restrict their fluid intake to prevent incontinence development., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Purpose: Although caffeine consumption is common and generally believed to affect bladder function, little is known about caffeine intake and incident urinary incontinence., Materials and Methods: We performed a prospective cohort study in 65,176 women 37 to 79 years old without incontinence in the Nurses' Health Study and the Nurses' Health Study II. Incident incontinence was identified from questionnaires during 4 years of followup. Caffeine intake was measured using food frequency questionnaires administered before incontinence development. The multivariate adjusted relative risk of the relation between caffeine intake and incontinence risk as well as attributable risk were calculated., Results: Caffeine was not associated with incontinence monthly or more. However, there was a modest, significantly increased risk of incontinence at least weekly in women with the highest (greater than 450 mg) vs the lowest (less than 150 mg) daily intake (RR 1.19, 95% CI 1.06-1.34) and a significant trend of increasing risk with increasing intake (p for trend = 0.01). This risk appeared focused on incident urgency incontinence (greater than 450 vs less than 150 mg daily, RR 1.34, 95% CI 1.00-1.80, p for trend = 0.05) but not on stress or mixed incontinence (p for trend = 0.75 and 0.19, respectively). The attributable risk of urgency incontinence associated with high caffeine intake was 25%., Conclusions: Findings suggest that high but not lower caffeine intake is associated with a modest increase in the incidence of frequent urgency incontinence. A fourth of the cases with the highest caffeine consumption would be eliminated if high caffeine intake were eliminated. Confirmation of these findings in other studies is needed before recommendations can be made., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Evidence suggests that race affects the prevalence and incidence of urinary incontinence (UI) in women. But little is known about racial differences in the rates of remission, improvement, and progression of UI in women., Objective: We sought to compare changes in UI frequency over two years among Asian, black, and white women with UI., Methods: Participants in the Nurses' Health Study and the Nurses' Health Study II responded to mailed questionnaires (in 2000 and 2002, and 2001 and 2003, respectively), giving information on race and the frequency of UI. Prospective analyses were conducted over two years from data gathered on 57,900 women, ages 37 to 79, who had at least monthly UI at baseline., Results: Over the two two-year study periods, black women were significantly more likely than white women to report remission of UI (14% versus 9%, respectively), and Asian women were significantly more likely than white women to report less frequent UI (40% versus 31%, respectively). Improvement was more common in older black women than in older white women, but rates of improvement were comparable between younger black and younger white women. Black women were less likely than white women to report more frequent UI at follow-up (30% versus 34%, respectively), and, after adjusting for health and lifestyle factors, the difference was borderline statistically significant., Conclusions: Changes in the frequency of UI appear to vary by race, even after adjustment for risk factors. These findings may account for some of the previously observed differences in UI prevalence across racial groups. Although UI is a common condition in women of all races, nurses and other clinicians should be aware that its presentation may vary according to race. Such an understanding could increase clinicians' confidence in discussing UI with patients, reducing the possibility that the condition goes unrecognized., Keywords: epidemiology, progression, race, remission, urinary incontinence.

Objectives: To evaluate whether use of certain medications with potential urological effects is associated with development of incident urinary incontinence in community-resident older women., Design: Longitudinal cohort study., Setting: Pittsburgh, PA, and Memphis, TN., Participants: Nine hundred fifty-nine healthy black and white women aged 65 and older enrolled in the Health, Aging and Body Composition Study without baseline (Year 1) self-reported urinary incontinence., Measurements: Use of alpha blockers, anticholinergics, central nervous system medications (opioids, benzodiazepines, antidepressants, antipsychotics), diuretics (thiazide, loop, potassium sparing), and estrogen (all dosage forms) was determined during Year 3 interviews. Self-reported incident (≥ weekly) incontinence in during the previous 12 months was assessed at Year 4 interviews., Results: Overall, 20.5% of these women reported incident incontinence at Year 4 (3 years from baseline). The most common medication used with potential urological activity was a thiazide diuretic (24.3%), followed by estrogen (22.2%); alpha blockers were the least commonly used (2.3%). Multivariable logistic regression analyses revealed that current users of alpha blockers (adjusted odds ratio (AOR)=4.98, 95% confidence interval (CI)=1.96-12.64) and estrogen (AOR=1.60, 95% CI=1.08-2.36) had a greater risk of urinary incontinence than nonusers. There was no greater risk (P>.05) of urinary incontinence with the current use of anticholinergics, central nervous system medications, or diuretics. No statistically significant race-by-medication use interactions were found (all P>.05)., Conclusion: These results corroborate earlier reports that, in elderly women, use of alpha blockers or estrogens is associated with risk of self-reported incident urinary incontinence., (© 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.)

Evidence from longitudinal studies in community-dwelling elderly links complaints of urgency and urinary incontinence with structural white matter changes known as white matter hyperintensities (WMH). How WMH might lead to incontinence remains unknown, since information about how they relate to neural circuits involved in continence control is lacking. The aim of this study was to investigate the role of WMH in altered brain activity in older women with urgency incontinence. In a cross-sectional study, we measured WMH, globally and in specific white matter tracts, and correlated them with regional brain activity measured by fMRI (combined with simultaneous urodynamic monitoring) during bladder filling and reported 'urgency'. We postulated that increase in global WMH burden would be associated with changes (either attenuation or reinforcement) in responses to bladder filling in brain regions involved in bladder control. Secondly, we proposed that such apparent effects of global WMH burden might be specifically related to the burden in a few critical white matter pathways. The results showed that regional activations (e.g. medial/superior frontal gyrus adjacent to dorsal ACG) and deactivations (e.g. perigenual ACG adjacent to ventromedial prefrontal cortex) became more prominent with increased global WMH burden, suggesting that activity aimed at suppressing urgency was augmented. Secondary analyses confirmed that the apparent effect of global WMH burden might reflect the presence of WMH in specific pathways (anterior thalamic radiation and superior longitudinal fasciculus), thus affecting connections between key regions and suggesting possible mechanisms involved in continence control., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: We calculated incidence rates of urinary incontinence by incontinence frequency and type over 4 years in Asian, black, and white women in the United States., Study Design: Prospective analyses included 76,724 participants aged 37-79 years in the Nurses' Health Study cohorts with no incontinence at baseline., Results: The 4-year incidence of incontinence at least monthly was higher in white women (7.3/100 person-years) compared with Asian (5.7/100 person-years; P = .003) and black women (4.8/100 person-years; P < .001). The incidence of at least weekly stress incontinence was significantly lower in black compared with white women (0.1 vs 0.8 per 100 person-years; P < .001). The difference between black and white women in the incidence of any incontinence and stress incontinence remained significant after adjusting for known risk factors (P < .001 for both)., Conclusion: Urinary incontinence incidence differs by race. Studies to confirm these results and better understand underlying mechanisms are needed., (Copyright 2010 Mosby, Inc. All rights reserved.)

Purpose: We investigated the relationship between experimental neuroimaging and self-reported urinary incontinence measures., Materials and Methods: We evaluated 14 functionally independent, community dwelling women older than 60 years with moderate to severe urgency urinary incontinence. All underwent detailed clinical assessment (3-day bladder diary, 24-hour pad test and quality of life assessment), urodynamic testing and functional brain scanning. Brain activity during reported urgency was assessed using a method that combines functional magnetic resonance imaging with simultaneous urodynamic monitoring during repeat bladder filling/emptying cycles. We used the statistical parametric mapping program SPM2 (http://www.fil.ion.ucl.ac.uk/spm/spm2.html) to correlate brain activity with relevant clinical covariates, including the number of urgency incontinent episodes, amount of urine leakage and psychological burden as assessed by the Urge Impact Scale questionnaire., Results: Activity in rostral and subgenual anterior cingulate gyrus, insula, inferior frontal gyrus, orbitofrontal cortex, dorsal and posterior cingulate gyrus, parahippocampus, cuneus and parts of parietotemporal lobe correlated positively with daytime incontinence frequency and urine loss. Different brain regions correlated with the psychological burden and the associations were inverse, that is precuneus/cuneus and posterior cingulate gyrus, and superior temporal, supramarginal and transverse gyrus., Conclusions: As provoked by bladder filling, regional brain activity in the setting of self-reported urgency correlates significantly with incontinence severity in daily life and the associated psychological burden. Thus, observations made under experimental conditions correlate with patient real-life experience and suggest neural correlates of urgency incontinence symptoms that could serve as potential targets for future investigations.

Loss of bladder control (urge incontinence) is common in elderly; the cause is usually unknown. Functional imaging has revealed the brain network controlling responses to bladder filling. Age-related changes in this network might predispose to urge incontinence. We sought such changes in 10 continent, healthy women aged 30-79 years who underwent fMRI while fluid (approximately 20 ml) was repeatedly infused into and withdrawn from the bladder. Data were collected in 4 measurement blocks with progressively increasing bladder volumes and were analyzed by SPM2, using the contrast infuse-withdraw to quantify response to bladder infusion. Effective connectivity was examined by physiophysiological interaction (PhPI; see interpretation in Supplementary Material), with right insula (RI) and dorsal anterior cingulate cortex (dACC) as seed regions. Dependence on age and bladder volume (= block number) was assessed. Bladder infusion evoked expected activations. Activation decreased with age in bilateral insula and dACC. PhPI revealed connectivity with RI and dACC in regions that included bilateral putamen and R pontine micturition center. Interaction (connectivity) tended to increase with age in regions including L insula, L paracentral lobule and PAG. Consistent with a special role in maintaining continence, medial prefrontal cortex (mPFC) showed a trend to deactivation on bladder infusion that became more prominent in old age, and a trend to negative interaction (connectivity) that weakened significantly with age. Thus, with increasing age, weaker signals in the bladder control network as a whole and/or changes in mPFC function or connecting pathways may be responsible for the development of urge incontinence.

Purpose: Recent data in postmenopausal women indicate that current and past use of exogenous hormones is related to urinary incontinence risk. Little is known about exogenous hormones and risk of urinary incontinence in younger women. We investigated the association between oral contraceptive pills and incident urinary incontinence in premenopausal women enrolled in the Nurses' Health Study II., Materials and Methods: Participants reported use of oral contraceptive pills from 1989 to 2001. Among 21,864 premenopausal women 37 to 54 years old reporting no urinary incontinence in 2001 we identified 749 with incident urinary incontinence at least weekly between 2001 and 2003. Odds ratios and 95% confidence intervals were estimated using multivariable logistic regression., Results: Women who had ever used oral contraceptive pills had a statistically significant 27% (95% CI 1-59) increased odds of experiencing urinary incontinence at least weekly compared with those who never used oral contraceptive pills. In women with 10 or more years of use the odds ratio increased to 1.48 (95% CI 1.13-1.95). Ever using oral contraceptive pills was specifically associated with urgency urinary incontinence (OR 2.48, 95% CI 1.07-5.76) rather than stress urinary incontinence (OR 1.04, 95% CI 0.78-1.40). Although we had limited information on urinary tract infection, control for urinary tract infection did not alter these findings., Conclusions: Use of oral contraceptive pills may be associated with a modest increase in the odds of urinary incontinence among premenopausal women. However, this is one of the first reports of such an association and, thus, further research is needed to confirm our findings and investigate possible mechanisms.

During the next several decades, the aging of the "baby boom" generation in the United States will result in a dramatic increase in the number of patients aged 65 and older seeking medical care, but current projections suggest that the shortage of geriatrics-trained specialists will only worsen during this time period. As a result, the care of elderly patients will largely fall to other types of physicians. Consequently, it is imperative that medical school training include exposure to the basic skills needed to care safely for older adults. This goal is challenging, because the number of geriatric medicine faculty in most academic medical centers is small, and multiple other medical specialties are also vying for time in a busy medical school curriculum. Whether a 3-day course conducted during the third year of medical school could teach basic principles of geriatric medicine in a time- and manpower-effective manner was explored. It was found that even this brief exposure to geriatrics could have meaningful effects on student knowledge of and comfort with geriatrics.

Objective: The objective of the study was to examine the association of hormone therapy with incident urinary incontinence (UI) in postmenopausal women aged 37-54 years in the Nurses' Health Study II., Study Design: Participants reported use of hormone therapy, including hormone type, on biennial questionnaires from 1989 to 2001. Among 7341 postmenopausal women reporting no UI in 2001, we identified 1026 women who developed UI at least monthly between 2001 and 2003. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Women currently using hormone therapy had 1.39-fold (95% CI, 1.16-1.67) increased odds of incident UI, compared with women who never used hormone therapy. ORs were similar in current users of oral estrogen alone (OR, 1.35, 95% CI, 1.03-1.78) and oral estrogen with progestin (OR, 1.37, 95% CI, 1.13-1.67)., Conclusion: These findings suggest an increased risk of UI associated with use of postmenopausal hormone therapy in younger postmenopausal women.

Purpose: To improve the understanding of the etiological relation between type 2 diabetes and urinary incontinence, we examined associations between diabetes and urinary incontinence type in 71,650 women 37 to 79 years old in the Nurses' Health Study and the Nurses' Health Study II., Materials and Methods: From 1976 to 2000 in the Nurses' Health Study and 1989 to 2001 in the Nurses' Health Study II participants reported diagnoses of type 2 diabetes. Women with incident urinary incontinence at least weekly were identified from 2000 to 2002 in the Nurses' Health Study and 2001 to 2003 in the Nurses' Health Study II. We pooled data from the 2 cohorts, and estimated odds ratios and 95% confidence intervals using multivariable logistic regression adjusting for age, parity, body mass index, smoking, hysterectomy, functional limitations, menopausal status, postmenopausal hormone use, incontinence promoting medications and study cohort., Results: The incidence of at least weekly urinary incontinence was 5.3% (3,612 of 67,984) among women without type 2 diabetes and 8.7% (318 of 3,666) among women with diabetes. Overall the multivariable adjusted odds of incident urinary incontinence were increased 20% (OR 1.2, 95% CI 1.0-1.3, p = 0.01) among women with vs without type 2 diabetes. This increase appeared largely explained by significantly greater odds of urge urinary incontinence (OR 1.4, 95% CI 1.0-1.9, p = 0.03). There was no apparent association between diabetes and stress (p = 0.3) or mixed (p = 0.6) urinary incontinence, although confidence intervals were somewhat wide., Conclusions: Our findings suggest that type 2 diabetes may especially influence urge urinary incontinence. Further research is needed to confirm this finding and identify pathways linking these conditions.

Objectives: To examine the epidemiology of urinary incontinence (UI) in older women., Design: Prospective study., Setting: Nurses' Health Study., Participants: Incidence of UI was determined in 23,792 women aged 54 to 79 without UI at baseline. Progression or remission of UI was determined in 28,813 women with UI at least monthly at baseline., Measurements: UI was ascertained according to questionnaires in 2000 and 2002. Rates of incident UI and progression or remission of prevalent UI were calculated. Logistic regression was used to estimate relative risks of UI associated with risk factors., Results: In women with no urine leakage at baseline, 9.2% reported leakage at least monthly after 2 years. For women with leakage at least weekly, the incidence was 3.6%; of these cases, stress UI had the highest incidence, followed by mixed and urge UI. Relationships between UI and age differed for stress UI, which decreased with age (relative risk (RR)=0.63, 95% confidence interval (CI)=0.43-0.92 for aged 70-79 vs 54-59), and urge and mixed UI, which increased with age (RR=2.28, 95% CI=1.09-4.75 and RR=2.11, 95% CI=1.24-3.61, respectively). For prevalent UI in 2000, 32.1% of subjects with leakage once a month progressed to leakage at least once a week over follow-up. Only 8.9% with frequent leakage in 2000 reported improvement to monthly leakage or less, with 2.0% having complete remission., Conclusion: The incidence of UI is high in older women, and progression from occasional to frequent leaking is common. Urge UI, for which there are limited effective treatments, increases with age, thus research on UI prevention in older women is particularly important.

Overall body fat and central adiposity may reflect different mechanisms leading to urinary incontinence (UI). We examined the associations of BMI and waist circumference with incident UI, including the independent associations of BMI and waist circumference with UI type, among women aged 54-79 years in the Nurses' Health Study. Study participants reported their height in 1976 and their weight and waist circumference in 2000. From 2000 to 2002, we identified 6,790 women with incident UI at least monthly among 35,754 women reporting no UI in 2000. Type of incontinence was determined on questionnaires sent to cases with at least weekly incontinence. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression. There were highly significant trends of increasing risk of UI with increasing BMI and waist circumference (P for trend <0.001 for both). Multivariable RRs of developing at least monthly UI were 1.66 (95% CI 1.45-1.91) comparing women with a BMI of > or =35 kg/m(2) to women with BMI 21-22.9 kg/m(2) and 1.72 (95% CI 1.53-1.95) comparing women in extreme quintiles of waist circumference. When BMI and waist circumference were included in models simultaneously, BMI was associated with urge and mixed UI (P for trend 0.003 and 0.03, respectively), but not stress UI (P for trend 0.77). Waist circumference was associated only with stress UI (P for trend <0.001). These results suggest that women who avoid high BMI and waist circumference may have a lower risk of UI development.

Purpose: While strenuous, high impact activity may provoke urinary incontinence, little is known about relations with moderate physical activity. We examined recreational activity and incident urinary incontinence in middle-aged women., Materials and Methods: This is a prospective study of women 37 to 54 years old in the Nurses' Health Study II. Repeated physical activity reports from 1989 to 2001 were averaged to estimate long-term activity levels. From 2001 to 2003 we identified 4,081 incident cases with at least monthly urinary incontinence. Incontinence type was further determined among cases with at least weekly urinary incontinence. Multivariable logistic regression models were used to estimate adjusted relative risks of urinary incontinence across quantiles of physical activity. To determine whether relations were mediated by body mass index, separate models were constructed that excluded and included body mass index as a covariate., Results: The risk of at least monthly urinary incontinence decreased with increasing quintiles of moderate physical activity (RR 0.80, 95% CI 0.72-0.89 comparing extreme quintiles). For stress and urge urinary incontinence, women with the most physical activity had lower rates of incontinence than those with less activity. RRs were 0.75 (95% CI 0.59-0.96 for top vs bottom quartile) for stress urinary incontinence and 0.53 (95% CI 0.31-0.90) for urge urinary incontinence. After adjustment for body mass index, the overall association with at least monthly incontinence attenuated, but remained significant (RR 0.89, 95% CI 0.80-0.99 comparing extreme quintiles)., Conclusions: Long-term, moderate physical activity was inversely associated with urinary incontinence. The role of exercise in weight maintenance may partly explain this association.

The regions of the supraspinal network that controls urinary bladder behavior are well known, but little is known about their interconnections. We tested the feasibility of using physiophysiological interaction to explore the effective connections of the network and to seek disease-related differences in connectivity. This was a secondary analysis of fMRI data obtained from women aged 26-85 years, 11 with urge urinary incontinence and 10 with normal bladder function. In each subject, fMRI BOLD images were obtained during a period with full bladder and strong bladder sensation (without detrusor overactivity) while repeatedly infusing and withdrawing a small amount of liquid in and out of the bladder. Regions of interest included right insula (RI) and anterior cingulate gyrus (ACG), both consistently involved in bladder control. Other regions effectively connected to them were identified by significant correlation between their fMRI signal and the interaction RIxACG. Among normal subjects, many regions involved in bladder control were effectively connected with RI/ACG, including frontotemporal and sensorimotor cortex, forebrain, midbrain and pontine regions. The sign of the correlation with RIxACG was near-uniformly positive, perhaps suggesting mainly inhibitory connections. Among urge-incontinent subjects, the effective connectivity was shifted to a parieto-temporal complex, while the sign of the correlation was predominantly negative, perhaps consistent with excitation (recruitment) of accessory pathways in an attempt to maintain bladder control. Thus, physiophysiological interaction yields potentially important information about the connectivity of the bladder control network and its changes in disease.

Objectives: To determine the effect of biofeedback (BFB) therapy on psychological burden of urge urinary incontinence (UI) and whether prior depression or current depressive symptoms affect older women's response to BFB., Design: Secondary analysis of an ongoing trial., Setting: Academic medical center., Participants: Forty-two community-dwelling women aged 60 and older with urge UI., Intervention: BFB and behavioral training in urge suppression provided over 8 weeks., Measurements: UI frequency on 3-day bladder diary, psychological burden assessed using Urge Impact Scale (URIS-24) total and subscale scores, history of depression, and depressive symptoms on the Mental Component Subscale (MCS) of the Medical Outcomes Study 36-item Short Form Survey (SF-36). Age and chronic conditions were included as covariates., Results: BFB improved UI (by 45%, P=.001) and psychological burden (P=.001 for total URIS-24 score and for all three of its subscales; P=.01 for SF36-MCS). However, although the magnitude of UI improvement was equivalent for those with and without a history of depression, improvement in psychological outcomes was twice as great in those with a history of depression, especially on the perception of control subscale, and improvement was not related to baseline depressive symptoms., Conclusion: In older women with urge UI, BFB significantly improves psychological burden, especially in those with a history of depression, in whom psychological burden is linked to change in perception of control. Psychological factors are relevant outcome measures for UI, and these data suggest that focusing on UI frequency alone may have underestimated BFB's efficacy and additional therapeutic benefits.

Aim: To identify age-related changes in the normal brain/bladder control system, and differences between urge incontinence in younger and older women, as shown by brain responses to bladder filling; and to use age, bladder volume, urge incontinence and detrusor overactivity (DO) as probes to reveal control system function. Functional MRI was used to examine regional brain responses to bladder infusion in 21 females (26-85 years): 11 "cases" with urge incontinence and DO (proven previously) and 10 normal "controls". Responses and their age dependence were determined at small and large bladder volumes, in whole brain and in regions of interest representing right insula and anterior cingulate (ACG). In "controls", increasing bladder volume/sensation led to increasing insular responses; with increasing age, insular responses became weaker. In younger "cases", ACG responded abnormally strongly at large bladder volumes/strong sensation. Elderly "cases" showed strong ACG responses even at small bladder volume but more moderate responses at larger volumes; if DO occurred, pontine micturition center (PMC) activation did not increase., Conclusion: Among normal "controls", increasing age leads to decreased responses in brain regions involved in bladder control, including right insula, consistent with its role in mapping normal bladder sensations. Strong ACG activation occurs in urge-incontinent "cases" and may be a sign of urgency, indicating recruitment of alternative pathways when loss of bladder control is feared. Easier ACG provocation in older "cases" reflects lack of physiological reserve or different etiology. ACG responses seem associated with PMC inhibition: reduced ACG activity accompanies failure of inhibition (DO).

Objective: The objective of the study was to describe changes in urinary incontinence in middle-aged women., Study Design: A prospective analysis of 64,650 women aged 36-55 years in the Nurses' Health Study II. Participants reported urine leaking in 2001 and 2003. Two-year incidence and remission proportions were estimated., Results: The 2-year incidence of incontinence was 13.7%. Incidence generally increased through age 50 years and then declined slightly in older women. Among women with incident incontinence at least weekly, the incidence of stress incontinence increased through age 50 years (2-year incidence 1.7%), and the incidence of urge incontinence was stable across age groups (2-year incidence 0.4%). Also, a minority (38%) mentioned leaking to their physician. Complete remission of symptoms occurred in 13.9% of women with incontinence at baseline., Conclusion: We found that incontinence occurs frequently in middle-aged women. Yet few women mentioned incontinence to their physicians; thus, it may be important to initiate conversations about urinary symptoms even among younger patients.

Background: Influenza causes significant morbidity and mortality in long-term care facilities. Immunization of health care workers has been shown to reduce the impact of influenza in this setting, yet few studies address improvement efforts aimed at long-term care staff immunization., Objective: To determine the feasibility of achieving and sustaining high rates of staff influenza immunization for a community-based long-term care facility., Methods: A needs analysis was conducted to determine the organizational and individual level barriers to influenza vaccination of staff. Systems changes, educational interventions, and reminders were implemented based on the barriers assessment. Staff immunization rates were calculated over a 10-year period from 1996 to 2006., Results: Organizational and individual barriers were identified and targeted. Using data from 1996 and 1997 as a baseline, staff immunization rates improved from 54% to 55% to between 74% and 95% over the past 4 years., Conclusions: Achieving and sustaining high staff influenza immunization rates is possible in a community-based long-term care facility with an involved quality improvement team and medical director.

Aims: To test whether nerve growth factor (NGF) concentration in human bladder urothelium/suburothelium is related to detrusor overactivity (DO), bladder sensation, detrusor contractility, or other aspects of lower urinary tract function., Materials and Methods: Concentration of NGF was measured (using ELISA) in superficial bladder biopsies from 27 women (mean age 52 years, range 22-82) after comprehensive video-urodynamics and bladder diary. Approximately half (12/27) showed clear DO and half did not., Results: There was no evidence for increased NGF concentration in subjects with DO (association negative by Mann-Whitney test, P = 0.23). NGF was not significantly associated with two measures of detrusor contractility (Spearman's r = -0.29, P = 0.17; r = -0.20, P = 0.33); nor with four measures inversely related to sensation: volume at strong desire to void and maximum capacity on cystometry (r = -0.13, P = 0.53; r = -0.23, P = 0.28), and maximum voided volume and mean daytime voided volume on bladder diary (r = -0.29, P = 0.16; r = -0.16, P = 0.44). It was significantly associated with 24-hr urine output on bladder diary (Spearman's r = -0.55, P = 0.004)., Conclusions: Elevated NGF levels in human urothelium/suburothelium are not strongly associated with DO, detrusor contractility or increased bladder sensation. NGF levels are lower in subjects with higher 24-hr urine output. This observation is consistent with a role for NGF in an active process (trafficking) involved in bladder filling.

Aims: To determine normative data for lower urinary tract function in asymptomatic continent women without detrusor overactivity (DO) across the age span., Methods: Healthy female volunteers aged > or =20 years were recruited from the community. Comprehensive assessment included bladder diary, physical examination, uroflowmetry, and video-urodynamics. Continent women without history of frequent urgency and without DO were selected. Data on bladder storage, voiding and urethral sphincter function, urine output and frequency are presented for pre-, peri-, and postmenopausal women., Results: Twenty-four asymptomatic women (mean age 50.2 years, range 22-80 years) met the inclusion criteria, including 7 pre- (29.2 years), 7 peri- (48.8 years), and 10 postmenopausal (66.0 years) women. For all subjects, maximum single voided volume in bladder diary was 500 ml and maximum cystometric capacity was 580 ml (median values). Strong desire to void (SDV) was reported at 287, 366, and 425 ml for pre-, peri-, and postmenopausal groups, respectively. The maximum flow rate was 25, 32, and 23 ml/sec in uroflowmetry and 23, 24, and 18 ml/sec in pressure-flow study, respectively. Median post-void residual volume (PVR) was below 20 ml in all groups. At maximum flow rate subjects voided with detrusor pressures of 29, 26, and 24 cm H(2)O, respectively. Maximum urethral closure pressure was 94, 74, and 42 cm H(2)O, respectively., Conclusions: We provide normative data on bladder function in asymptomatic, continent, pre-, peri-, and postmenopausal women without DO.

Purpose: We examined the relationship of DO and aging, and bladder function in female volunteers., Materials and Methods: We recruited 85 cognitively competent, fully functional female volunteers who were 22 to 90 years old (median age 54) with and without symptoms suggestive of DO. Comprehensive assessment included a bladder diary, uroflowmetry and videourodynamics. We examined predefined urodynamic and diary variables for associations with DO and age, summarizing results in the 3 subgroups no DO, intermediate DO and clinically relevant DO., Results: Compared to women without DO those with DO showed a decrease in maximum cystometric capacity (558 vs 448 ml), mean daytime voided volume (260 vs 175 ml) and volume at strong desire to void (363 vs 283 ml) but an increase in maximum isovolumetric pressure (41 vs 64 cm H2O) and maximum detrusor pressure during involuntary contraction (intermediate and relevant DO 22 and 37 cm H2O, respectively). The positive association between increased detrusor contraction strength and DO was present at younger ages but absent in older subjects. Maximum urethral closure pressure and detrusor contraction strength decreased significantly with age., Conclusions: From young adulthood to old age DO appears to affect bladder function parameters. It is associated with decreased bladder capacity and increased bladder sensation. Moreover, in younger adults DO is also associated with increased detrusor contraction strength, which is an association not seen in older individuals. This age associated loss of muscle function may be related to sarcopenia, implying that different treatments may be appropriate in older adults.

Objectives: To identify age-associated changes in female lower urinary tract function across a wide age spectrum, controlling for detrusor overactivity (DO)., Design: Secondary analysis of a cross-sectional study of DO and aging. Eligible volunteers were stratified by age group and presence of DO., Setting: Community-based volunteers, evaluated in research laboratory., Participants: Eighty-five ambulatory, nondemented, community-dwelling female volunteers, with and without bladder symptoms suggestive of DO, recruited by advertising, mean age 54 (range 22-90); 75% Caucasian, 21% African American., Measurements: Comprehensive assessment included bladder diary, uroflowmetry, and detailed videourodynamics. Predefined urodynamic and diary variables were examined for association with age and DO. Mean values of these variables were calculated for subgroups aged 20 to 39, 40 to 59, and 60 and older (14 subjects > or =70)., Results: Maximum urethral closure pressure, detrusor contraction strength, and urine flow rate declined significantly with age (P<.001, P<.001, P=.006, respectively), regardless of whether DO was present. Most elderly individuals continued to empty their bladder almost completely, with normal voiding frequency. Mean number of nocturnal voids was less than one in all age groups. Bladder capacity did not decrease with age (mean 522 mL in oldest group) but was smaller in subjects with DO. Bladder sensation diminished significantly with age (P<.001) but was stronger in subjects with DO., Conclusion: Female bladder and urethral function appear to deteriorate throughout adult life, whether DO is present or not. Specifically, detrusor contractility, bladder sensation, and urethral pressure decline. The common belief that bladder capacity shrinks with age may be related to DO rather than to aging itself.

Objective: The purpose of this study was to identify risk factors for urinary incontinence in middle-aged women., Study Design: We conducted a cross-sectional analysis of 83,355 Nurses' Health Study II participants. Since 1989, women have provided health information on mailed questionnaires; in 2001, at the ages 37 to 54 years, information on urinary incontinence was requested. We examined adjusted odds ratios of incontinence using logistic regression., Results: Forty-three percent of the women reported incontinence. After adjustment, black (odds ratio, 0.49; 95% CI, 0.40-0.60) and Asian-American women (odds ratio, 0.57; 95% CI, 0.46-0.72) were at reduced odds of severe incontinence compared with white women. Increased age, body mass index, parity, current smoking, type 2 diabetes mellitus, and hysterectomy all were associated positively with incontinence. Women who were aged 50 to 54 years had 1.81 times the odds of severe incontinence compared with women who were <40 years old (95% CI, 1.66-1.97); women with a body mass index of > or =30 kg/m2 had 3.10 times the odds of severe incontinence compared with a body mass index of 22 to 24 kg/m2 (95% CI, 2.91-3.30)., Conclusion: Urinary incontinence is highly prevalent among these middle-aged women. Potential risk factors include age, race/ethnicity, body mass index, parity, smoking, diabetes mellitus, and hysterectomy.

Context: Although androgen deprivation therapy (ADT) for prostate cancer is associated with bone loss, little is known about when this bone loss occurs., Objective: We postulated that men on ADT would experience the greatest bone loss acutely after initiation of ADT., Design and Setting: We conducted a 12-month prospective study at an academic medical center., Patients or Other Participants: We studied 152 men with prostate cancer (30 with acute ADT, < 6 months; 50 with chronic ADT, > or = 6 months; and 72 with no ADT) and 43 healthy age-matched controls., Main Outcome Measures: We assessed bone mineral density (BMD) of the hip, wrist, total body, and spine; body composition; and markers of bone turnover., Results: After 12 months, men receiving acute ADT had a significant reduction in BMD of 2.5 +/- 0.6% at the total hip, 2.4 +/- 1.0% at the trochanter, 2.6 +/- 0.5% at the total radius, 3.3 +/- 0.5% at the total body, and 4.0 +/- 1.5% at the posteroanterior spine (all P < 0.05). Men with chronic ADT had a 2.0 +/- 0.6% reduction in BMD at the total radius (P < 0.05). Healthy controls and men with prostate cancer not receiving ADT had no significant reduction in BMD. Both use and duration of ADT were associated with change in bone mass at the hip (P < 0.05). Men receiving acute ADT had a 10.4 +/- 1.7% increase in total body fat and a 3.5 +/- 0.5% reduction in total body lean mass at 12 months, whereas body composition did not change in men with prostate cancer on chronic ADT or in healthy controls (P < 0.05). Markers of bone formation and resorption were elevated in men receiving acute ADT after 6 and 12 months compared with the other men with prostate cancer and controls (P < 0.05). Men in the highest tertile of bone turnover markers at 6 months had the greatest loss of bone density at 12 months., Conclusions: Men with prostate cancer who are initiating ADT have a 5- to 10-fold increased loss of bone density at multiple skeletal sites compared with either healthy controls or men with prostate cancer who are not on ADT, placing them at increased risk of fracture. Bone loss is maximal in the first year after initiation of ADT, suggesting initiation of early preventive therapy.

Purpose: Our aim was to determine the effect of hormone replacement on physical performance measures, functional ability, physical activity, falls, and cognitive function in elderly women., Subjects and Methods: Following a 3-month, open-label, run-in phase, we randomized 373 community-dwelling women aged 65 years and older to receive conjugated equine estrogen 0.625 mg/day plus or minus medroxyprogesterone 2.5 mg/day vs placebo for 3 years in a double-blind fashion. We assessed time to rise from a chair, timed walking, balance, Instrumental Activities of Daily Living, Physical Activity Scale of the Elderly, Folstein Mini-Mental State Examination, and falls., Results: Over 3 years, except for balance scores, performance measures declined significantly (all P<.05). There were no significant mean differences between women on hormone replacement versus placebo for rising time (0.1, -0.5 to 0.7 seconds [mean, 95% confidence interval]), walking normal (0.0, -0.4 to 0.4 seconds), and walking fast (0.2, -0.1 to 0.6 seconds). There were no significant mean differences between the two groups for the Instrumental Activities of Daily Living (0.1, -0.1 to 0.3 points), Physical Activity Scale of the Elderly (-3, -15 to 8 points), Folstein Mini-Mental State Examination (-0.1, -0.3 to 0.3 points), or the proportion of participants reporting falls (-1, -11 to 9%)., Conclusion: In elderly women, hormone replacement had no statistically significant effect on cognition or balance, nor did it prevent the age-related decline in physical measures of mobility, ability to rise from a chair, self-reported activities of daily living, physical activity scores, or falls.

Purpose: In older adults detrusor overactivity (DO) is almost as common in continent individuals as in those with urge incontinence (UUI). Thus, UUI likely reflects the contribution of additional factors. We postulated that of functionally independent individuals in whom transient causes were excluded those in whom DO was accompanied by UUI would be more likely to have smaller functional bladder capacity, less warning and less ability to avert urine loss in the face of DO., Materials and Methods: While blinded to continence status, we reviewed the records of all 52 cognitively intact and nonobstructed volunteers older than 65 years who had DO associated with urgency during urodynamic testing and had been asked to try to prevent leakage for 2 minutes. Of these individuals 31 were continent at home., Results: In patients with UI mean functional bladder capacity +/- SD was smaller (313 +/- 153 vs 390 +/- 178 ml, p = 0.06) and warning was briefer (87 +/- 81 vs 120 +/- 116 ml), although the association with warning was less impressive (p = 0.14). The ability to forestall leakage for at least 2 minutes correlated strongly with being continent at home (p < 0.002). For continence detrusor suppression at the onset of DO was more important than sphincter contraction., Conclusions: Urge incontinence in older adults involves more than simply the presence of DO. Physical function, cognitive function and medications are already known to be important for continence. Our data suggest that functional bladder capacity and the ability to suppress involuntary contraction (and possibly warning) are also potentially important covariates. These factors may represent additional potential targets for behavioral and pharmacological therapy.

Unlabelled: This study examined the effect of hormone replacement, alendronate, or combination therapy on hip structural geometry in 373 postmenopausal women over 3 years. We found that antiresorptive agents alone or in combination result in improvement in parameters of hip structural geometry and BMD. These data provide additional information regarding potential mechanisms for fracture reduction with antiresorptive therapy., Introduction: Fracture reduction is only partially explained by increased BMD. The aim of this study was to examine changes in structural geometry of the hip, derived from DXA in postmenopausal women after treatment with antiresorptive agents., Materials and Methods: This was a double-blind, placebo-controlled, randomized clinical trial of 373 women over the age of 65 years, who were randomized to hormone replacement therapy, alendronate, combination therapy, or placebo for 3 years. The outcomes included the DXA-derived hip structure analysis program by Beck, which is an engineering interpretation of the DXA data. The indices included cross-sectional area, section modulus (a measure of bending strength), outer diameter, cortical thickness, and buckling ratio (an index of cortical bone stability). Properties were measured in cross-sectional regions traversing the femur at the narrowest point on the femoral neck, the intertrochanteric region, and the proximal shaft., Results: In the femoral neck, improvement in the hip structure analysis indices were generally significantly greater with combination therapy than either monotherapy; increases were also greater at the intertrochanter compared with hormone replacement therapy. For example, the section modulus at the intertrochanter and narrow neck increased 10.6% and 10.3%, respectively, with combination therapy, 9.1% and 7.3% with alendronate, 5.8% and 6.9% with hormone replacement therapy, and 3.4% and 3.2% with placebo (p < 0.01 across the four groups). Buckling ratio increased, suggesting decreased stability in the placebo group, whereas there was either no change or significant improvements (p < 0.05) in each active treatment group., Conclusions: We conclude that changes in the distribution of bone mass underlying the improvements in density with antiresorptive agents in combination or alone have positive effects on structural strength and stability at the proximal femur. This study provides additional information on the potential mechanisms for fracture reduction with antiresorptive agents.

Background: The purpose of this study was to determine if vitamin D supplementation, 400-800 IU daily, could effectively treat vitamin D deficiency and insufficiency over 3 months., Methods: To test this hypothesis, we conducted a cross-sectional survey followed by a 3-month, open-label run-in phase prior to a randomized clinical trial. We enrolled 573 community-dwelling women age 65 or older, 373 of whom completed the run-in phase. All women received a daily multivitamin containing 400 IU of vitamin D and one to two calcium supplements containing 200 IU of vitamin D. We assessed bone mineral metabolism (including 25-hydroxyvitamin D and parathyroid hormone), markers of bone turnover, and bone mineral density., Results: Of the 553 screened participants who had baseline vitamin D levels available, 16% had vitamin D deficiency (serum vitamin D < 10 ng/ml) and 48% had vitamin D insufficiency (serum vitamin D between 10 and 20 ng/ml). Only 36% of participants had normal vitamin D levels (serum vitamin D > or = 20 ng/ml). Baseline vitamin D intake was negatively associated with serum parathyroid hormone (r = -0.29, p <.0001), and not associated with bone mineral density or bone resorption. Vitamin D deficiency was associated with decreased physical activity and slower gait. Of the 373 women who completed the run-in phase and received treatment with a multivitamin and vitamin D-containing calcium supplement, vitamin D deficiency decreased from 16% at baseline to 0% at 3 months, and vitamin D insufficiency decreased from 48% at baseline to 20% at 3 months (p <.001)., Conclusions: We conclude that vitamin D deficiency and insufficiency, which are common among ambulatory, community-dwelling elderly women, can be normalized in 80% of patients over 3 months with vitamin D supplementation of 400-800 IU/d.

Elderly women on combination therapy with alendronate and hormone replacement for osteoporosis have greater gains in bone mass than those on monotherapy. It is not known whether early changes in markers can predict the long-term changes in bone density with therapy. We assessed bone density and biochemical markers of bone turnover [urine N-telopeptide cross-linked collagen type 1 (NTx), serum bone-specific alkaline phosphatase, and osteocalcin] every 6 months for 3 yr in a double-blind, placebo-controlled, randomized clinical trial. After a 3-month run-in phase, 373 community-dwelling, elderly women were randomized to 1) alendronate, 2) hormone replacement therapy, 3) combination therapy with alendronate and hormone replacement therapy, or 4) placebo. Women on active treatment with the greatest decrease in markers of bone turnover at 6 months had the greatest increases in spine and hip bone density at 3 yr. The response to alendronate was generally associated with greater reductions in markers than the response to hormone replacement and was associated with greater increases in bone density at the spine and hip. Those in the tertile with the greatest decrease in urinary NTx had a 10.1% increase in spine bone density and a 6.1% increase in hip bone density compared with those in the lowest tertile, who had a 5.9% increase in spine bone density and a 2.1% increase in hip bone density. In women on active treatment, the area under the receiver operator curve for a 6-month change in markers to predict a response in bone mineral density at 3 yr was highest for urine NTx (range, 75-78%) and lowest for osteocalcin (range, 60-66%). We conclude that short-term changes in biochemical markers of bone turnover at 6 months predict bone density changes at the spine and hip at 3 yr in elderly women on alendronate, hormone replacement therapy, or combination therapy.

Purpose: Clinical studies indicate that detrusor contractility decreases in old age and the dense band pattern with caveolar depletion represents the ultrastructural norm of the aged human detrusor. We performed animal studies to explore the hypothesis that lowering estrogen induces the dense band pattern with estrogen replacement restoring usual sarcolemmal appearance and increasing caveolar number., Materials and Methods: Newborn, young (1-month-old) and middle-aged (13 to 14-month-old) female rats were studied. Middle-aged animals were evaluated 4 months after sham operation or ovariectomy (OVx) with OVx rats receiving placebo or 25% 17beta-estradiol (E2) capsules for 1 week prior to sacrifice. Electron microscopy was used to evaluate sarcolemmal structure and quantify caveolar numbers in bladder muscle cells. Caveolae were also assessed by measuring caveolin-1 protein., Results: Alternating electron dense and thinner zones with abundant caveolae were present in bladder sarcolemma from middle-aged animals. Newborn and OVx sarcolemma showed many ultrastructural features of the dense band pattern with fewer caveolae present per micro sarcolemma or per muscle cell compared with sham operated middle-aged controls. E2 replacement decreased the dense band pattern and increased caveolar numbers in OVx animals. Caveolin-1 protein levels underwent similar changes following maturation, OVx and E2 replacement, while alpha-smooth muscle actin remained unchanged., Conclusions: Prolonged estrogen withdrawal results in sarcolemmal changes in middle-aged animals, similar to the dense pattern observed in newborns. Estrogen replacement decreases the dense pattern, while increasing caveolar numbers and caveolin-1 protein. It remains to be seen whether estrogen influences caveolar depletion and/or contractility in human bladders.

Aims: Impaired detrusor contractility is common in older adults. One aspect, detrusor contraction strength during voiding, can be measured by the isovolumetric detrusor pressure attained if flow is interrupted mechanically (a stop test). Because interruption is awkward in practice, however, simple indices or nomograms based on measurements made during uninterrupted voiding are an appealing alternative. We investigated whether such methods, originally developed for males, might be applicable in female subjects, and attempted to identify a single best method., Methods: We compared stop-test isovolumetric pressures with estimates based on pressure-flow studies in a group of elderly women suffering from urge incontinence. Measurements were made pre- and post-treatment with placebo or oxybutynin, allowing investigation of test-retest reliability and responsiveness to small changes of contractility., Results: Existing methods of estimating detrusor contraction strength from pressure-flow studies, including the Schäfer contractility nomogram and the projected isovolumetric pressure PIP, greatly overestimate the isovolumetric pressure in these female patients. A simple modification provides a more reliable estimate, PIP(1), equal to p(det.Qmax) + Q(max) (with pressure in cmH(2)O and Q(max) in ml/sec). Typically PIP(1) ranges from 30 to 75 cmH(2)O in this population of elderly urge-incontinent women. PIP(1), however, is less responsive to a small change in contraction strength than the isovolumetric pressure measured by mechanical interruption., Conclusions: The parameter PIP(1) is simple to calculate from a standard pressure-flow study and may be useful for clinical assessment of detrusor contraction strength in older females. For research, however, a mechanical stop test still remains the most reliable and responsive method. The Schäfer contractility nomogram and related parameters such as DECO and BCI are not suitable for use in older women., (Copyright 2004 Wiley-Liss, Inc.)

To determine if bone mineral density (BMD) substantially influences health-related behaviors in men at risk for osteoporosis, we surveyed 102 men who were participating in a study of prostate cancer and bone loss. Subjects included 68 men with prostate cancer, 44 of whom were hypogonadal on androgen deprivation therapy, and 34 healthy age-matched controls without prostate cancer. At least 6 mo after an initial evaluation, assessment of BMD, and osteoporosis information session, men were administered a questionnaire regarding their healthrelated behaviors. We found that men with osteopenia were 4 times as likely (13%) and men with osteoporosis were more than 10 times as likely (41%) to start taking bisphosphonates compared to men with a normal bone mass (3%, p < 0.0001). Men with low bone mass were more likely to begin taking calcium (p < 0.05) and vitamin D supplements (p < 0.05). Hypogonadal men were 10 times as likely to begin using bisphosphonates (34%) compared to the control group (3%, p < 0.0001) and twice as likely to begin using calcium supplements (57% vs 24%, p < 0.05). Caffeine consumption, alcohol consumption, dietary calcium intake, exercise, and smoking habits were not different in men with osteoporosis or those who were hypogonadal compared to controls. We conclude that men with low bone mass and hypogonadism were more likely to start using bisphosphonates, calcium supplements, and vitamin D supplements after having a bone density test. However, they were not more likely to make significant health-related lifestyle changes after obtaining the results of their bone mass.

Context: Therapy with individual antiresorptive agents has been shown to be effective for prevention and treatment of postmenopausal osteoporosis, but whether combination antiresorptive therapy with hormones and bisphosphonates is safe or efficacious or how these agents compare in elderly women is unknown., Objective: To determine whether hormone replacement and the bisphosphonate alendronate sodium in combination are efficacious and safe, and how they compare with monotherapy in community-dwelling elderly women., Design: Randomized, double-blind, placebo-controlled, clinical trial., Setting and Participants: Five hundred seventy-three community-dwelling women age 65 years or older were screened: 485 completed screening and 373 (aged 65 to 90 years) were randomized following a 3-month, open-label, run-in phase with hormone replacement and alendronate placebo. The trial was conducted at a single academic US medical center from January 1996 to May 2001., Interventions: Participants were randomly assigned in a 2 x 2 factorial design to receive hormone replacement (conjugated equine estrogen, 0.625 mg/d, with or without medroxyprogesterone, 2.5 mg/d) and alendronate, 10 mg daily, both agents, or neither. All participants received calcium and vitamin D supplements., Main Outcome Measures: Annualized change in bone mineral density of the hip and spine and occurrence of adverse events., Results: Bone mineral density at 3 years was significantly greater at all femoral and vertebral sites in women treated with combination therapy than with monotherapy, with mean (SD) increases of 5.9% (3.8) at the total hip, 10.4% (5.4) at the posteroanterior lumbar spine, and 11.8% (6.8) at the lateral lumbar spine. Mean (SD) increases in bone mass at the hip in women treated with alendronate alone were significantly greater than in those treated with hormone replacement therapy alone (4.2% [3.8] vs 3.0% [4.9]; P<.05, respectively), and alendronate resulted in more responders to therapy. All therapies were well tolerated and participant retention was 90% at 3 years., Conclusions: Combination therapy with hormone replacement and alendronate was efficacious and well tolerated in this cohort. Alendronate was superior to hormone replacement, and combination therapy was superior to either therapy alone. Combination therapy may represent an option for women with more severe disease or for those who have failed to achieve an adequate response to monotherapy.

Purpose: Impaired detrusor contractility has an important role in geriatric voiding dysfunction but there are many competing methods of measurement. We compared the performance of 3 methods of measuring detrusor contraction strength to identify the best one., Materials and Methods: We retrospectively analyzed urodynamics data on 84 females 53 years old or older. All had urge incontinence and were enrolled in a placebo controlled oxybutynin trial. Stop tests (voluntary interruption, mechanical interruption and continuous mechanical occlusion of flow) were performed on each subject., Results: At baseline the voluntary stop test measured lower mean isovolumetric detrusor pressure +/- SD than the mechanical and continuous methods (31.2 +/- 16.0 versus 47.2 +/- 26.5 and 48.7 +/- 24.4 cm. water, respectively). The latter 2 values also correlated highly (r = 0.87). Followup data on 76 women confirmed these results. Based on baseline and followup values in the 20 women who received placebo the continuous occlusion test showed highest test-retest reliability (r = 0.9, p <0.01), followed by the mechanical (r = 0.69, p = 0.01) and voluntary (r = 0.67, p <0.01) stop tests. Treatment with oxybutynin decreased isovolumetric detrusor pressure in all 3 stop tests by up to 6 cm. water. However, the decrease was statistically significant only for the continuous occlusion test., Conclusions: To assess detrusor contraction strength in elderly females with urge incontinence the mechanical stop and continuous occlusion tests are acceptable but the continuous occlusion test has better reliability and better detects slight drug induced changes. Voluntary stop tests greatly underestimate detrusor isovolumetric pressure and should no longer be used.

Purpose: We studied the ultrastructure of intrinsic detrusor innervation in long-standing neurogenic bladder dysfunction in the human., Materials and Methods: Endoscopic or open detrusor biopsies were obtained from 15 female and 31 male patients 7 to 96 years old who had hyperreflexic neurogenic bladder dysfunction for less than 1 to 43 years. Of the patients 9 had meningomyelocele, 25 had spinal cord injury and 12 had a brain disorder. Changes in intrinsic detrusor nerves were evaluated by electron microscopy qualitatively and quantitatively according to predefined criteria., Results: Axonal degeneration was observed in 44 of the 45 biopsies with discernible intrinsic nerves. Structurally normal axons were 5(1/2) or 4 times more common in brain disorder than meningomyelocele or spinal cord injury group biopsies (median 33%, 6%, 8%, respectively). Axonal regeneration, not encountered in nonneuropathic dysfunctional detrusors, was observed in restricted distribution in most biopsies (76%) and was independent of the duration of neurogenic bladder dysfunction. Axon sprouts were observed in 17 biopsies (38%), and copeptidergic axons formed 20% (median per biopsy) of discernible axon profiles in contrast to less than 1% in normal detrusor. Activated Schwann cells were observed in all but 1 biopsy. The axonal changes were not associated with the level or degree of spinal cord lesion in patients with meningomyelocele or spinal cord injury., Conclusions: Combined degeneration and regeneration is the characteristic change in intrinsic nerves of detrusor in upper motoneuron neurogenic bladder dysfunction. The observed changes offer the possibility of clinically recognizing neuropathic contribution to a dysfunctional detrusor, as well as the potential to distinguish its spinal versus supraspinal etiology.

Purpose: We standardize procedures for ultrastructural study of detrusor smooth muscle and intrinsic nerves in neurogenic bladder dysfunction in the human, and present an overview of the findings., Materials and Methods: The study included 18 female and 33 male patients 7 to 96 years old. They had neurogenic bladder dysfunction with hyperreflexia for less than 1 to 43 years, resulting from upper motoneuron lesions (spinal cord injury 25, brain disorder 17) or combined upper and lower motoneuron deficit (meningomyelocele 9). Endoscopic or open bladder biopsies were processed for ultrastructural study of detrusor smooth muscle and intrinsic neural elements. Qualitative morphologic criteria of muscle cell arrangement, degeneration and cell-cell contacts, as well as those of degeneration and regeneration of intrinsic neural elements are defined., Results: Five biopsies from the brain disorder group had insufficient smooth muscle and were excluded from study. The remaining 46 biopsies were evaluated by electron microscopy, and all displayed the complete dysjunction pattern of detrusor overactivity. Most displayed degeneration and regeneration of intrinsic axons but disproportionately limited muscle cell degeneration, irrespective of detrusor contractility. The brain disorder group biopsies displayed many more ultrastructurally normal axons than the meningomyelocele and spinal cord injury group biopsies (median 33% versus 8% or less)., Conclusions: Upper motoneuron neurogenic bladder dysfunction in humans is associated with intrinsic neuromuscular defects in the detrusor. Ultrastructural features of these defects suggest morphologic markers that not only may distinguish neuropathic from nonneuropathic bladder dysfunction, but also may point to the anatomical level of the neurogenic deficit.

Purpose: We describe the ultrastructure of detrusor smooth muscle in long-standing neurogenic bladder dysfunction in the human., Materials and Methods: Detrusor biopsies were obtained from (15 female and 31 male) patients 7 to 96 years old with neurogenic bladder dysfunction for less than 1 to 43 years. Of the patients 9 had meningomyelocele, 25 spinal cord injury and 12 brain disorder. Urodynamically, all patients had detrusor hyperreflexia (neurogenic detrusor overactivity) in addition to bladder outlet obstruction in 4, impaired detrusor contractility in 19, decreased bladder compliance in 4, and detrusor-sphincter dyssynergia in 24. Ultrastructural changes in detrusor, including those associated with detrusor overactivity, impaired detrusor contractility and bladder outlet obstruction, were evaluated qualitatively and quantitatively., Results: Intermediate junctions of muscle cells were absent or reduced in 45 biopsies, which instead had dominant intimate cell appositions with much narrower junctional gaps. A greater than 2 intimate cell apposition-to-intermediate junction ratio was present in 45 biopsies (98%), and intimate cell apposition linked chains of 5 muscle cells or greater in all biopsies (100%). Muscle cell degeneration was observed in 34 biopsies from 20 of 27 patients (74%) with normal contractility and 14 of 19 (74%) with impaired detrusor contractility. No particular changes were associated with functional bladder outlet obstruction due to detrusor-sphincter dyssynergia., Conclusions: The ultrastructural complete dysjunction pattern is a feature of hyperreflexia as well as nonneuropathic detrusor overactivity of various etiology. A greater than 2 intimate cell apposition-to-intermediate junction ratio had 98% sensitivity but its specificity remains to be determined. The lack of relationship between muscle cell degeneration and detrusor contractility probably reflects limitations of urodynamic measurement of contractility in patients with spinal cord injury and meningomyelocele.

Portable ultrasound assessment of postmicturition bladder for residual urine volume is rapid, accurate, and precise. However, other cystic pelvic pathologic conditions may present as a false-positive finding on the ultrasound. We describe two cases in which the residual urine was falsely detected as being elevated due to unsuspected pregnancy., (Copyright 2003 Wiley-Liss, Inc.)

Objectives: To validate the Memorial Delirium Assessment Scale (MDAS) as a measure of delirium severity in a cohort of patients aged 65 and older; to examine the association between severity of delirium and patient outcomes; and to examine the association between psychomotor variants of delirium and each of those outcomes., Design: Prospective assessment of sample., Setting: Hospital., Participants: One hundred twenty-two older patients (mean age +/- standard deviation = 79 +/- 8) who had undergone acute hip fracture surgery., Measurements: We used standardized instruments to assess prefracture activities of daily living (ADLs), ambulatory status, cognition, and living situation. Postoperatively, each patient was interviewed daily. Delirium was diagnosed using the Confusion Assessment Method (CAM), and delirium severity was measured using the MDAS. The MDAS was also used to categorize the psychomotor types of delirium into "purely hypoactive" or "any hyperactivity." Telephone or face-to-face interviews were conducted at 1 and 6 months to assess survival, ADL function, ambulatory status, and living situation., Results: Of 122 patients, 40% developed CAM-defined delirium. Delirious patients had higher average MDAS scores than nondelirious patients (11.7 vs 2.4, P <.0001). We used the median of the average MDAS score to classify patients into mild or severe delirium. Severe delirium was generally associated with worse outcomes than was mild delirium, and the associations reached statistical significance for nursing home placement or death at 6 months (52% vs 17%, P =.009). Additionally, patients who did not meet full CAM criteria for delirium experienced worse outcomes if they had some symptoms of delirium than if they had no or few symptoms (nursing home placement or death at 6 months: 27% vs 0%, P =.001). Surprisingly, these patients with subsyndromal delirium who did not fulfill CAM criteria for delirium but demonstrated significant delirium symptoms, had outcomes similar to or worse than those with mild CAM-defined delirium. Pure hypoactive delirium accounted for 71% (34/48) of cases and was less severe than was delirium with any hyperactivity (average MDAS score 10.6 vs 14.8, P =.007). In our cohort, patients with pure hypoactive delirium had better outcomes than did those with any hyperactivity (nursing home placement or death at 1 month: 32% vs 79%, P =.003); this difference persisted after adjusting for severity., Conclusion: In this study of delirium in older hip fracture patients, the MDAS, a continuous severity measure, was a useful adjunct to the CAM, a dichotomous diagnostic measure. In patients with CAM-defined delirium, severe delirium was generally associated with worse outcomes than was mild delirium. In patients who did not fulfill CAM criteria, subsyndromal delirium was associated with worse outcomes than having few or no symptoms of delirium. Patients with subsyndromal delirium had outcomes similar to patients with mild delirium, suggesting that a dichotomous approach to diagnosis and management may be inappropriate. Pure hypoactive delirium was more common than delirium with any hyperactive features, tended to be milder, and was associated with better outcomes even after adjusting for severity. Future studies should confirm our preliminary associations and examine whether treatment to reduce the severity of delirium symptoms can improve outcomes after hip fracture repair.